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Muhammad Sikandar,1 Muhammad Harris Shoaib,1 Rabia Ismail Yousuf,1 Farrukh Rafiq Ahmed,1 Fatima Ramzan Ali,1,2 Muhammad Talha Saleem,1 Kamran Ahmed,1 Sana Sarfaraz,3 Sabahat Jabeen,1 Fahad Siddiqui,1 Tazeen Husain,1 Faaiza Qazi,1 Muhammad Suleman Imtiaz1 1Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan; 2Jinnah College of Pharmacy, Sohail University, Karachi, 74000, Pakistan; 3Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, PakistanCorrespondence: Muhammad Harris Shoaib, Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi, 75270, Pakistan, Email harrisshoaib2000@yahoo.com; mhshoaib@uok.edu.pkPurpose: Halloysite nanotubes (HNTs) are a versatile and highly investigated clay mineral due to their natural availability, low cost, strong mechanical strength, biocompatibility, and binding properties. The present work explores its role for retarding and controlling the drug release from the composite polymer matrix material.Methods: For this purpose, nanocomposite films comprising propranolol HCl and different concentrations of HNTs were formulated using the “solution casting method”. The menthol in a concentration of 1% w/v was used as a permeation enhancer, and its effect on release and permeation was also determined. Quality characteristics of the nanocomposite were determined, and in vitro release and permeation studies were performed using the Franz diffusion system. The data was analyzed using various mathematical models and permeation parameters. Optimized formulation was also subjected to skin irritation test, FTIR, DSC, and SEM study. Systemic absorption and disposition of propranolol HCl from the nanocomposites were predicted using the GastroPlus TCAT® model.Results: The control in drug release rate was associated with the higher concentration of HNTs. F8 released 50% of propranolol within 8 hours (drug, HNTs ratio, 1:2). The optimized formulation (F6) with drug: HNTs (2:1), exhibited drug release 80% in 4 hours, with maximum flux of 145.812 μg/cm2hr. The optimized formulation was found to be a non-irritant for skin with a shelf life of 35.46 months (28– 30 ℃). The in silico model predicted Cmax, Tmax, AUCt, and AUCinf as 32.113 ng/mL, 16.58 h, 942.34 ng/mL×h, and 1102.9 ng/mL×h, respectively.Conclusion: The study demonstrated that HNTs could be effectively used as rate controlling agent in matrix type transdermal formulations.Keywords: halloysite nanotube, transdermal, nanocomposite, controlled release, GastroPlus

OBJECTIVE: The study evaluated the effect of Sapindus mukorossi (SM) extract as a final root canal irrigant on sealer penetration (SP) in dentinal tubules and microleakage. MATERIALS AND METHODS: Samples were selected based on inclusion and exclusion criteria. An access opening in all samples was performed and the working length was decided using pro taper for canal finishing along with constant irrigation. Specimens were randomly divided into 3 groups. Group 1 was irrigated with 3 ml of 17% EDTA; group 2 was irrigated with SM irrigant and group 3 samples were irrigated with 0.9% saline. After obturation, samples were vertically placed in 1% methylene blue dye cut in half longitudinally, and viewed under a stereomicroscope. Analysis of SP in the dentinal tubule was assessed using scanning electron microscopy (SEM). For microleakage assessment, mean and standard deviation were reported and One-Way ANOVA was applied. SP was compared using Kruskal-Wallis' test. For inspecting the interaction between SM/EDTA and NaOCl, Fisher's exact test was applied. No statistically significant difference between microleakage in any of the tested groups was observed. The control group showed minimum leakage as compared to EDTA and SM. RESULTS: The results displayed that there was no significant difference, (p=0.67), between dentinal tubule SP at 2 mm. A significant difference between dentinal tubule SP among groups at 5 mm was observed (p<0.05). CONCLUSIONS: SM ethanolic extract showed comparable outcomes of smear layer removal and sealer penetration to 17% EDTA, as a final irrigant in root canal cleaning. Therefore, SM has the potential to be used as an adjuvant final irrigant in conjunction with NaOCl. [ABSTRACT FROM AUTHOR]

The emergence of drug-resistant strains of Mycobacterium tuberculosis has become a significant public health problem and has led to a setback in efforts to end tuberculosis (TB) worldwide. The longer duration, heavier pill load, and higher toxicity profile of DR-TB regimens compared to those for drug-susceptible TB (DS-TB) lead to reduced adherence and worse treatment results, including mortality. This study was conducted to estimate treatment outcomes and adverse effects in patients with drug-resistant TB patients on bedaquiline-containing regimen. Patients after the pre-treatment evaluation were enrolled for bedaquiline-containing regimen. These patients were followed up for 18 months and the final outcome was assessed along with the adverse effects. It was found that 49 (84.4%) patients achieved culture conversion by three months and 54 (93.1%) achieved culture conversion by six months, 52 (83.81%) patients had favourable outcomes (cured, treatment completed) and 10 patients had unfavourable outcomes (died, lost to follow-up, failed). Coupled with gradually increasing trends of success rates from 2012, lesser failure rates and lesser concerns regarding grave adverse effects are a silver lining along the cloud of increasing burden and widening resistance patterns. More funding has to be directed towards ensuring adherence and finding high-risk individuals in order to expedite the achievement of sustainable development (SDG) goals.

This study aimed to assess the effects of low-temperature stress on two tomato cultivars (S-22 and PKM-1) treated with 24-epibrassinolide (EBL) and selenium (Se) by determining the changes in the proteomics profiles, growth biomarkers, biochemical parameters, and physiological functions. The growth parameters, photosynthetic traits, and activity of nitrate reductase in the S-22 and PKM-1 plants were markedly reduced by exposure to low temperatures. However, the combined application of EBL and Se under different modes significantly enhanced the aforementioned parameters under stress and non-stress conditions. Exposure to low temperatures increased the activities of the antioxidant enzymes (catalase, peroxidase, and superoxide dismutase) and the proline content of leaves, which were further enhanced by treatment with Se and EBL in both varieties. This research sheds light on the potential for employing exogenous EBL and Se as crucial biochemical tactics to assist tomato plants in surviving low-temperature stress. Moreover, the differentially expressed proteins that were involved in plant metabolism following the combined application of EBL and Se under low-temperature stress were additionally identified. Functional analysis revealed that the Q54YH4 protein plays an active role against plant stressors. The conserved regions in the protein sequences were analyzed for assessing the reliability of plant responses against the external application of EBL and Se under low temperatures.

Aim: The article aims to describe the technique of designing and fabricating ear prosthesis with the integration of computeraided design and computer-aided manufacturing (CAD/CAM) versus a conventional method. Background: The use of rapid prototyping for prosthesis fabrication preceded by the generation of ear prosthesis design utilising the computed tomography data of the patient are recent advance technologies. Case description: A 6-year-old boy came with congenitally missing right ear. The healthy left ear was mirrored and printed using the 3-dimensional (3D) printer. Since there was a tissue remnant on the affected side of the patient’s ear, the printed ear model was copied in wax. The incorporation of CAD/CAM eliminated the conventional technique involving impression taking of normal ear as a model. Thus, fabrication procedure was simplified, ensuring rapid production. Conclusion: The dimension, shape, and anatomic contour of the ear prosthesis were quite similar to those of the normal ear. This outcome suggested that using the CAD/CAM system to fabricate ear prosthesis from computed tomography data is a practical technique which can be used in a clinical setting. Clinical significance: Rapid prototyping techniques used in this case gave the highest possible level of accuracy in size, shape, and position of the prosthesis. It also decreased the patient appointments and fabrication time compared to the conventional technique.

Introduction: Acute facial nerve palsy secondary to neuroendocrine adenoma of the middle ear (NAME) is a rare disorder. There is only one case report in the literature describing similar findings. Case Report: A 50-year-old man initially presented to ENT clinic with a right-sided middle ear mass and normal facial nerve function. Over the next six days, he developed House-Brackmann grade II facial paralysis. He underwent urgent surgical exploration of the tympanic cavity and excision of the middle ear mass via a post-auricular approach. Histopathological and immunohistochemical analysis revealed NAME. Three weeks after the surgery, facial nerve function returned to normal. No recurrence was found at a 3-year follow-up. Conclusion: Acute onset facial palsy induced by NAME is an extremely rare disorder. For a patient already affected by hearing impairment resulted from middle ear mass, facial weakness can have a significant additional detrimental impact on their wellbeing. The early complete excision of tumor is recommended not only as a curative treatment but also restoration of facial function.

Brassinosteroids and hydrogen peroxide (H2O2) are extensively used to combat several environmental factors, including heavy metal stress in plants, but their cumulative impact on the maintenance of copper (Cu) homeostasis in plants could not be dissected at elevated level. This study was executed to explore the roles of 24-epibrassinolide (EBL; foliar) and H2O2 (root dipping) in resilience of tomato (Solanum lycopersicum L.) plants to Cu stress. The cumulative effect of EBL and H2O2 in tomato plants grown under Cu stress (10 or 100 mg kg−1 soil) were assessed. Roots of 20 d old plants were submerged in 0.1 mM of H2O2 solution for 4 h and subsequently transplanted in the soil-filled earthen pots and at 30 day after transplantation (DAT), the plants were sprinkled with deionized water (control), and/or 10−8 M EBL and plant performances were evaluated at 40 DAT. High Cu (100 mg kg−1 soil) concentration considerably reduced photosynthetic efficacy, cell viability, and plant growth, and deformed chloroplast ultrastructure and root morphology with altered stomatal behavior, but boosted the activity of antioxidant enzymes, proline content and electrolyte leakage in the leaves of tomato. Moreover, EBL and H2O2 implemented through distinct modes improved photosynthetic efficiency, modified chloroplast ultrastructure, stomatal behavior, root structure, cell viability and production of antioxidants and proline (osmolyte) that augmented resilience of tomato plants to Cu stress. This study revealed the potential of EBL and H2O2 applied through distinct mode could serve as an effective strategy to reduce Cu-toxicity in tomato crop.

Judaism and Christianity are the revealed religions like Islam. The major common factor of this resemblance is the belief in Oneness of Allah. This belief establishes the foundations for tolerance in social and communal life through which fair justice and equality can be achieved in the society. There are important points to be noted here, that if international community can be made united and an international political body can be established and could tackle the issue of law and order. Then why the followers of Sharīʿah (revealed law)i.e. Jews, Christian and Muslims cannot be unite. Unfortunately, if this doctrine could not establish, the world cannot be achieved tolerance and harmony. These revealed religions had given the concept of religious tolerance which is substantiate by the teachings of Hazrat Ibrahim (A.S), Hazrat Musa (A.S), Hazrat Esa (A.S) and Hazrat Muhammad (SAW) . The teachings of all these prophets were based on unity, justice, tolerance, peace and standard morals. The article Sheds lights the importance of peace in the world and need to understand the real teachings of revealed laws in Bible and Qur’ān, and highlights the importance of interfaith- dialogue among Book-keepers, also analyses the life of Holy Prophet (SAW) and Caliphate Era with reference to tolerance and harmony. It is also tried to give suggestions’ and recommendations for the solutions of contemporary problems of mankind.

High temperature is a serious threat to crop production. Brassinosteroids (BRs), a group of plant steroidal hormones, can reduce effects of abiotic stresses. The present study was aimed to study the potency of brassinosteroids on high temperature induced changes in Indian mustard (Brassica juncea L.) for effects on growth, chlorophyll, photosynthesis, photosystem II, antioxidant system and proline. Surface sterilized seeds of Indian mustard were sown in pots, grown for 21 days and treated with double distilled water or 0.01 µM of 28-homobrassinolide. Treated plants, after 24 h, were exposed to 30°C or 40°C for 48 h. One set of plants were kept at ambient temperature, 25°C, as the control. Plants were harvested at 30 days stage of growth to assess the various parameters. Plants exposed to 40°C had a decline in growth, leaf water potential, chlorophyll, photosynthetic rate, and activities of carbonic anhydrase (E.C.4.2.1.1) and nitrate reductase (E.C.1.6.1.1). The 28-homobrassinolide alone improved growth and photosynthesis responses along with various enzymes activities. Treatment of plants with HBL prior to exposure to 40°C, partially reduced damage and completely controlled damage when exposure was to 30°C. Levels of the antioxidative enzymes catalase (E.C.1.11.1.6), peroxidase (E.C.1.11.1.7), and superoxide dismutase (E.C.1.15.1.1), and the level of proline increased in response to 30 or 40°C and were further enhanced in the presence of 28-homobrassinolide. Plants grown under high temperature had increased levels of H2O2; application of HBL before temperature treatment decreased H2O2 content compared to the control. Elevated levels of antioxidative enzymes and proline might be responsible for conferring tolerance to high temperature stress in Indian mustard and overcome the loss of productivity of the crop.

This study was designed to assess the combined effect of both aluminium and salt stress on the processes and molecules pertinent to these stresses and to establish relationship between these two stresses on the basis of photosynthetic attributes and antioxidant enzymes in wheat cultivars. Seven different varieties of wheat grown under environmentally controlled conditions. At 10 days stage of growth, plants were treated with NaCl (100 or 150 mM) and/or Al (05 or 10 mM) through soil. At 30 days stage, treatment of Al and salt stress alone showed the similar deteriorating response in terms of photosynthetic traits and LWP whereas, electrolyte leakage, lipid peroxidation, H2O2 content along with enzymes of antioxidant and proline content varied in different varieties of wheat. Moreover, the combination of Al and salt stress further increased the antioxidant enzymes and proline accumulation. However, salt stress restrict the uptake of Al by roots in significant manner under combine treatment of Al and salt stress. The pattern of tolerance was observed on the basis of enhanced antioxidant system and proline accumulation and cultivar LOK-1 and 502 showed maximum and minimum tolerance respectively against the combination of salt and aluminium stress.

Abstract Background In South Asia, it is estimated that 80% of patients choose to attend a private facility for their healthcare needs. Although patients generally believe that the private-sector provides high quality services, private diagnostic laboratories are largely unregulated and little is known about the accuracy of results provided. This study assesses the accuracy of sputum smear microscopy for pulmonary tuberculosis diagnosis in private laboratories operating in Karachi, Pakistan. A novel evaluation methodology was designed in which patient-actors submitted sputum specimens spiked with cultured Mycobacterium tuberculosis (Mtb) for testing such that laboratories were not aware that they were being assessed. Methods Smear-negative sputum specimens from Indus Hospital TB Program patients were collected and combined with an attenuated, cultured Mtb strain to create Mtb-spiked samples; for negative standards, no Mtb was added to the smear-negative sputum specimens. Seven of the largest private laboratories across Karachi were chosen for evaluation and were sent six Mtb-spiked and one Mtb-negative sputum specimens. Patient-actors pretending to be laboratory customers submitted these specimens to each laboratory for testing over a three day period. Results Only three laboratories accurately classified all the Mtb-spiked specimens which were submitted. A further three misclassified all the Mtb-spiked specimens as smear-negative, thus providing the ‘patients’ with false negative results. Conclusions TB sputum smear microscopy services are highly variable across private laboratories and are often of extremely poor quality. Engagement, capacity building and rigorous monitoring of standards at private laboratories are of vital importance for the control of TB. Our findings, while specific for TB diagnostic tests, could be symptomatic of other tests performed in private laboratories and warrant further investigation.

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (F pred ) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of F pred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of F pred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents., 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 Elsevier B.V. All rights reserved.)

The emergence of COVID-19 caused a significant global threat, affecting populations worldwide. Its impact extended beyond just physical health, as it inflicted severe damage and challenges to individuals' well-being, leading to a deterioration in mental health. The lived experiences of patients hold a paramount position to explore and understand their perception of care which can ultimately strengthen the health system's delivery domain. This study explores the lived experiences of patients in the isolation ward, their recovery, and the quality of care being provided in the hospital and its effects on their mental health., Study Design: A phenomenological qualitative study using in-depth interviews., Methods: We conducted 11 in-depth interviews of COVID-19 patients admitted to the isolation ward of the public hospitals of Peshawar, Pakistan. Participants who stayed for a minimum of 10 days in an isolation ward were included in this study. Interviews were transcribed and analyzed using NVivo 12 software and generated five themes through inductive analysis., Results: Five themes emerged from the participants' lived experiences: Heading towards the hospital, Health Care Quality, Impact on Mental Health, Recovering from COVID-19 and Back on one's feet . These included all the positive and negative lived experiences. Socio-environmental factors along with their experiences of the disease itself and with the healthcare providers guided their reaction which was important conciliators in their experiences during the pandemic., Conclusion: Based on the findings, the environment of isolation had a major influence on the mental well-being of the individuals involved. Considering the important role of the ward environment in shaping patient experiences and outcomes prompts a reevaluation of healthcare practices and policies. By addressing these factors healthcare systems can strive for greater effectiveness, resilience, and compassion in managing the pandemic's impact on patient care., Competing Interests: No known competing interests were reported by all the authors contributing to this research, either financially or in personal relationships that could potentially impact the reported findings., (© 2024 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Currently, traditional and newer molecular and mass spectrometry techniques of identifying bacteria from biological samples requires lengthy sample preparation, growth and labelling/staining assays. Thus, there is a pressing clinical need for an adjunct method that accurately identifies bacteria in real time. Here we report on the evaluation of confocal microscopy for the identification of clinically important and multi-drug resistant (MDR) bacteria in real time, using their intrinsic fluorescence features, i.e., emission spectra and fluorescence lifetime. The results demonstrate that difference in emission spectra and fluorescence lifetimes can be used as a fingerprint for identification of 12 bacterial species and MDR strains in real-time. Photostability or time-traces of bacteria demonstrated that these parameters could be used for tracking and recording without a need for labelling. Further, dilution experiments demonstrated that using intrinsic fluorescence S. aureus, Klebsiella pneumoniae and Escherichia coli bacteria can be detected and identified at clinically relevant concentrations as low as 2 × 10 2  CFU/mL. This non-invasive, non-labelling optical methodology may serve as the basis for development of a device that would quickly and accurately identify bacteria in biological samples. Thus, this intrinsic fluorescence technique would provide clinicians information, within minutes from sampling, to base accurate and specific treatments for patients., (Copyright © 2023 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The detection and identification of biomolecules are essential in the modern era of medical diagnostics. Several approaches have been established, but they have significant limitations such as laborious and time-consuming sample preparation, analysis, and the need to use external probes which provide adequate but not desired levels of accuracy and sensitivity. Herein, we have explored successfully a non-invasive technique to detect and identifybiomolecules such as amino acids and proteins by utilizing their intrinsic fluorescence. The developed confocal microscopy method revealed high and photostable emission counts of these biomolecules including amino acids (tryptophan, phenylalanine, tyrosine, proline, histidine, cysteine, aspartic acid, asparagine, isoleucine, lysine, glutamic acid, arginine) and proteins (HSA, BSA) when they are excited with a green laser. The fluorescence lifetime of the samples enabled the identification and distinction of known and blind samples of biomolecules from each other. The developed optical technique is straightforward, non-destructive and does not require laborious labeling to identify specific proteins, and may serve as the basis for the development of a device that would quickly and accurately identify proteins at an amino acid level. Therefore, this approach would open an avenue for precise detection in imaging and at the same time increases our understanding of chemical dynamics at the molecular level., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: A SeDeM expert tool-driven I-optimal mixture design has been used to develop a directly compressible multiparticulate based extended release minitablets for gastro-retentive drug delivery systems using loxoprofen sodium as a model drug. Methods: Powder blends were subjected to stress drug-excipient compatibility studies using FTIR, thermogravimetric analysis, and DSC. SeDeM diagram expert tool was utilized to assess the suitability of the drug and excipients for direct compression. The formulations were designed using an I-optimal mixture design with proportions of methocel K100M, ethocel 10P and NaHCO 3 as variables. Powder was compressed into minitablets and encapsulated. After physicochemical evaluation lag-time, floating time, and drug release were studied. Heckel analysis for yield pressure and accelerated stability studies were performed as per ICH guidelines. The in silico PBPK Advanced Compartmental and Transit model of GastroPlus™ was used for predicting in vivo pharmacokinetic parameters. Results: Drug release follows first-order kinetics with fickian diffusion as the main mechanism for most of the formulations; however, a few formulations followed anomalous transport as the mechanism of drug release. The in-silico -based pharmacokinetic revealed relative bioavailability of 97.0%. Discussion: SeDeM expert system effectively used in QbD based development of encapsulated multiparticulates for once daily administration of loxoprofen sodium having predictable in-vivo bioavailability., 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 Rauf-ur-Rehman, Shoaib, Ahmed, Yousuf, Siddiqui, Saleem, Qazi, Khan, Irshad, Bashir, Naz, Farooq and Mahmood.)

This study describes an efficient antimicrobial drug delivery system composed of iron oxide magnetic nanoparticles (Fe 3 O 4 NPs) coated by an MOF-199 network. Then, the prepared vancomycin (VAN)-loaded carrier was fully packed in a lattice of beta-cyclodextrin (BCD). For cell adhesion, beta-cyclodextrin has been functionalized with guanidine (Gn) groups within in situ synthetic processes. Afterward, drug loading efficiency and the release patterns were investigated through precise analytical methods. Confocal microscopy has shown that the prepared cargo (formulated as [VAN@Fe 3 O 4 /MOF-199]BCD-Gn) could be attached to the Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) bacterial cells in a higher rate than the individual VAN. The presented system considerably increased the antibacterial effects of the VAN with a lower dosage of drug. The cellular experiments such as the zone of inhibition and optical density (OD 600 ) have confirmed the enhanced antibacterial effect of the designed cargo. In addition, the MIC/MBC (minimum inhibitory and bactericidal concentrations) values have been estimated for the prepared cargo compared to the individual VAN, revealing high antimicrobial potency of the VAN@Fe 3 O 4 /MOF-199]BCD-Gn cargo.

Objective:  The removal of residual pulpal debris (RPD) from the root canal walls, especially in necrotic teeth is important for successful endodontic outcome. The aim of this study was to evaluate the RPD removal efficacy of handpiece mounted continuous irrigation with simultaneous root canal preparation from the apical third of root canals as compared to conventional syringe irrigation (SI)., Materials and Methods:  Ninety extracted teeth were randomly divided into three groups: SI; handpiece mounted continuous irrigation (CI); and both syringe and continuous irrigation (CI+SI). After root canal preparation, roots were sectioned at 1 (a), 3 (b) and 5 (c) mm from apex and prepared for Hematoxylin-Eosin staining. Sections were microscopically examined for presence of RPD., Statistical Analysis:  Intergroup difference in average percentage of RPD at different root levels was calculated by using analysis of variance test (ANOVA). Tuckey test was used for pairwise comparison., Results:  ANOVA showed significant difference between all three groups ( p < 0.05). SI group showed a significantly higher percentage of RPD as compared with CI and CI+ SI groups at all root levels ( p < 0.01). At root level a, CI showed a significantly higher percentage of RPD as compared with CI+SI ( p < 0.01)., Conclusion:  Handpiece mounted CI during rotary instrumentation showed a significant reduction in RPD as compared with conventional syringe irrigation. This technique was found to be an effective method for an enhanced root canal debridement., Competing Interests: None declared., (European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Fluorescent nanoparticles (NPs) have been increasingly studied as contrast agents for better understanding of biological processes at the cellular and molecular level. However, their use as bioimaging tools is strongly dependent on their optical emission as well as their biocompatibility. This work reports the fabrication and characterization of silk fibroin (SF) coated magnesium oxide (MgO) nanospheres, containing oxygen, Cr 3+ and V 2+ related optical defects, as a nontoxic and biodegradable hybrid platform for bioimaging applications. The MgO-SF spheres demonstrated enhanced emission efficiency compared to noncoated MgO NPs. Furthermore, SF sphere coating was found to overcome agglomeration limitations of the MgO NPs. The hybrid nanospheres were investigated as an in vitro bioimaging tool by recording their cellular uptake, trajectories, and mobility in human skin keratinocytes cells (HaCaT), human glioma cells (U87MG) and breast cancer cells (MCF7). Enhanced cellular uptake and improved intracellular mobilities of MgO-SF spheres compared to MgO NPs was demonstrated in three different cell lines. Validated infrared and bright emission of MgO-SF NP indicate their prospects for in vivo imaging. The results identify the potential of the hybrid MgO-SF nanospheres for bioimaging. This study may also open new avenues to optimize drug delivery through biodegradable silk and provide noninvasive functional imaging feedback on the therapeutic processes through fluorescent MgO.

Polyaromatic hydrocarbons (PAHs), such as pyrene, benzo[a]pyrene, phenanthrene, and anthracene induce toxic, carcinogenic, and mutagenic effects on living organisms and are considered as primary pollutants. Traditional methods for their identification are often laborious and time-consuming and do not account for the heterogeneous nature of their distribution. Here we present confocal microscopy as a rapid and accurate technique for direct analysis of PAHs in soil samples without the complexity of sample pre-processing which might delay results for several days. The method uses the intrinsic fluorescence of PAHs for detection and their emission spectra for the identification of different PAHs. A clear difference was observed in the fluorescence spectral properties of phenanthrene, pyrene and naphthalene in real-time environmental samples. The post-processing of confocal scans obtained in the detection stage of PAHs was completed through the application of ImageJ software. Intrinsic fluorescence-based detections of PAHs may open new avenues in terms of rapid detection and identification of PAHs in heterogeneous complex soil samples., Competing Interests: Declaration of competing interest There is no conflict of interest between authors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives:  The current study aimed to assess the impact of factors such as age, gender, and the tooth type on postoperative endodontic pain in necrotic teeth with symptomatic periapical periodontitis and radiolucency dressed randomly with either calcium hydroxide or propolis paste., Materials and Methods:  The standard chemomechanical root canal preparation of 80 teeth was performed by the primary investigator. The intracanal medicaments were inserted by the secondary operator. Patients self-recorded their postoperative endodontic pain intensity with the help of visual analog scale at 4, 12, 24 (day 2), 48 (day 3), and 72 (day 4) hours. During analysis, patients (68/80) were grouped according to gender, age, and the tooth type., Statistical Analysis:  Mann-Whitney's U test was applied for mean pain score comparison between genders and between tooth type. Kruskal-Wallis' test was applied for mean pain score comparison between the age groups., Results:  No significant difference ( p > 0.05) in pain scores was found between the age groups and between the tooth types. Males had significantly higher pain scores as compared with females at days 2 ( p = 0.035), 3 ( p = 0.023), and 4 ( p = 0.020)., Conclusion:  The results suggested that there was no impact of age and tooth types on postoperative endodontic pain., Competing Interests: None declared., (European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The objective was to develop eperisone HCl sustained-release pellets through extrusion spheronization technique and to determine the influence of different hydrophobic (polymeric based and wax-based) and hydrophilic (polymeric based) matrix former on the release of eperisone HCl (BCS class I drug) and on pellet sphericity. The pellet formulations consisted of different hydrophobic and hydrophilic matrix formers like HPMC K4M (10-20%) HPMC K15M (10%), EC (7cps) (10-20%), Carnauba wax (10-20%), Compritol ATO 888 (10-20%), Glyceryl monostearate (10%), lactose and microcrystalline cellulose. The initial burst release of the drug from matrix pellet formulations was effectively controlled by coating with 5% EC (ethylcellulose) dispersion. The dissolution profile and drug release kinetics of coated pellet formulations were determined at both acidic and basic pH medium. SEM (Scanning electron microscope) technique was used to determine the surface morphology and cross-section of F5 and F7 pellet formulation. The mechanism of drug release of coated formulation followed non-Fickian diffusion. FTIR spectroscopy was conducted and no drug and excipients interaction was observed. The results had shown that optimized coated formulation was F5 and F7 which effectively extend the drug release for 12 hours.

This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R 2  > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8-1.25. The AUC 0-t and AUC 0-∞ of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The C max of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the T max of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.