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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]

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.

Nematode eggs are pervasive pathogens that infect billions of people and livestock every year. Adult parasitic nematode worms can be distinguished based on their size and morphology. However, their eggs, particularly their species Ascaris lumbricoides and Ascaris suum cannot be identified from each other. Identifying eggs of helminths from wastewater and sludge is important from a public health perspective to minimize the spread of Ascaris infections. Numerous methods exist for nematode identification, from a morphological-based approach to high throughput sequencing technology. However, these techniques are not consistent and often laborious and time-consuming. In this study, we demonstrate that non-invasive real-time identification of eggs is possible based on their intrinsic fluorescence. Using confocal microscopy, we investigate the autofluorescence properties of five species of nematode eggs and observe clear differences between genus and for the first time their species in sludge samples. This non-invasive imaging technique could lead to better understanding of these species and may assist in early control of diseases.

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release., Competing Interests: The authors have declared that no competing interests exist.

To evaluate and compare the pharmacokinetic (PK) characteristics of a newly developed oral osmotically controlled drug delivery system of Eperisone 150 mg tablets with Eperisone immediate release (IR) marketed tablet brand as a reference formulation. It was a single dose, two treatment, two sequence, randomized, crossover study, involving 12 healthy human subjects. A modified, sensitive LC-ESI-MS/MS method was developed and validated as per FDA guidelines for estimation of Eperisone in plasma using a simple extraction and quick protein precipitation method. Non-compartmental pharmacokinetic model was used for PK analysis. Results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. The bio-analytical method used for estimating drug plasma concentration was found to be simple, selective, linear, accurate and precise with 0.01 ng/ml as limit of detection. The comparative PK analysis revealed an insignificant difference in AUC 0-∞, AUC 0-t, V z /F, Cl/F and t 1/2λz , whereas a significant difference in C max , T max and MTTs were found. The relative bioavailability of Eperisone osmotic tablet was 109.7%. The osmotic controlled release drug formulation was found to release Eperisone for an extended period with less inter individual fluctuation in pharmacokinetic variables.

Propolis is a potent anti-microbial and natural anti-inflammatory by-product obtained from the beehive. Studies have demonstrated the superior biocompatibility and anti-microbial properties of propolis as compared to calcium hydroxide. However, its effect on postoperative endodontic pain is unknown. Therefore, this study aimed to investigate the impact of Chinese propolis paste as an intracanal medicament on postoperative endodontic pain intensities compared with calcium hydroxide (control) at different time intervals in necrotic teeth with periapical radiolucency. Eighty patients with single-rooted necrotic teeth with visible periapical radiolucency were recruited and randomly allocated to either the calcium hydroxide or propolis groups. After chemo-mechanical preparation and intracanal medicament insertion, patients were given the VAS (visual analogue scale) to record pain scores. Inter-group data were compared and analyzed using two-way repeated measure ANOVA (Bonferroni test). A p -value of < 0.025 was considered significant. In total, >78% of the patients experienced no or only mild post-operative pain in both the groups at all time intervals, without any significant difference in pain scores between the two groups ( p > 0.025). An overall flare-up rate of 14.8% was found. The results suggest that either of these medicaments can be used as an inter-appointment medication for the prevention of postoperative pain in necrotic cases.

Background: Wnt signaling is a cellular pathway involved in embryogenesis, development, and neoplasia. Wnt-pathway activation may accelerate prostate cancer androgen-independent growth and mediate antiandrogen resistance. Since 10-20% of advanced prostate cancers harbor Wnt-activating mutations, we aimed to characterize the clinical features and response to novel antiandrogens in such patients., Objective: To determine whether men with metastatic castration-resistant prostate cancer (mCRPC) who harbor Wnt-pathway mutations have poorer responses to first-line novel hormonal therapies: abiraterone/enzalutamide., Design, Setting, and Participants: Patients with mCRPC who received first-line abiraterone or enzalutamide were retrospectively evaluated. Using tumor DNA analyses, we queried for activating mutations in CTNNB1 or inactivating mutations in APC or RNF43, all of which are predicted to stimulate Wnt signaling. Presence or absence of at least one Wnt-activating alteration was correlated with clinical-pathologic characteristics and treatment outcomes., Outcome Measurements and Statistical Analysis: Time to prostate-specific antigen (PSA) progression, overall survival (OS), and PSA response were measured. Cox regression models were used to test associations between Wnt status and clinical-pathologic outcomes; Kaplan-Meier and log-rank analyses were used to compare time-to-event endpoints., Results and Limitations: Of 137 patients evaluated, 11% (n=15) had tumor DNA analysis showing at least one Wnt-stimulating alteration. Patients with Wnt-activating mutations had numerically fewer T3/T4 tumors than Wnt wild-type patients (31% vs 51%), but were otherwise generally balanced. Median time to PSA progression on first-line abiraterone/enzalutamide was shorter in Wnt-activated patients (6.5 vs 9.6mo, hazard ratio [HR] 2.34, p=0.003), as was OS (23.6 vs 27.7mo, HR 2.28, p=0.01). PSA responses were numerically worse in Wnt-activated patients (53% vs 75%, p=0.12). Presence of Wnt-activating alterations (adjusted HR [aHR] 2.33, p=0.007) and use of previous chemotherapy (aHR 1.83, p=0.004) were both independently associated with increased hazard of progression., Conclusions: Patients with somatic Wnt-pathway activating mutations have worse outcomes to first-line abiraterone/enzalutamide than Wnt wild-type patients. Our data suggest that additional genomically informed therapies are needed for this relevant subset of mCRPC patients., Patient Summary: In this report, we retrospectively examined outcomes of metastatic prostate cancer patients with or without Wnt-pathway mutations who received abiraterone or enzalutamide for the first time, in order to examine whether these mutations affect the prognosis. Our study suggested that patients who have Wnt-pathway activating mutations derived less benefit from abiraterone and enzalutamide when compared to patients without these mutations. We conclude that Wnt-pathway mutations might decrease the effectiveness of abiraterone and enzalutamide, and we propose that the Wnt pathway might be a good therapeutic target for these patients, in order to potentially reverse or prolong resistance to abiraterone and enzalutamide in men with Wnt mutations., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The present research work elucidates the photocatalytic effect of titania on liquid crystal based sensor used to detect sodium arsenate in water. The titania nanoparticles with an average size of 18-20 nm were synthesized by hydrothermal method and calcined up to 500 °C to obtain pure anatase phase. The catalytic activity of titania nanoparticles was enhanced by surface modification with (3-aminopropyl) trimethoxysilane. The sensing experiment was performed under visible light irradiation while keeping the concentration of substrate, analyte, the thickness of the liquid crystal layer, temperature and pH values constant. In addition, span 80 (a non-ionic surfactant) was used to obtain homeotropic alignment of liquid crystals. The TiO₂ nanoparticles gave dark to bright texture within 53 min while the functionalized titania responded in less than 25 min under similar sensing condition. The detection results showed that the functionalized titania nanoparticles possess greater photocatalytic activity under visible light and enhanced the sensing response than unfunctionalized titania nanoparticles.

Background: Pathogenic mutations in genes mediating homologous recombination (HR) DNA repair are present in 20-30% of men with metastatic castrate-resistant prostate cancer (mCRPC). Radium-223 is a bone-seeking α-emitter that induces double-strand DNA breaks, thereby killing cancer cells in the bone microenvironment., Objective: To evaluate the potential impact of germline or somatic HR-deficiency (HRD) mutations on radium-223 efficacy in mCRPC with bone metastasis., Design, Setting, and Participants: This is a retrospective single-institution study. Medical records of 190 mCRPC patients for whom germline and/or somatic DNA sequencing data were available were reviewed. Of these patients, 28 had received standard-of-care radium-223 at Johns Hopkins between February 2013 and February 2018., Outcome Measurements and Statistical Analysis: Alkaline phosphatase (ALP) responses and time-to-ALP-progression were the coprimary endpoints. Prostate-specific antigen (PSA) responses, overall survival (OS), and time to next systemic therapy were also evaluated., Results and Limitations: Of the 28 patients included, 10 men (35.7%) had a germline/somatic HRD mutation (three in BRCA2, and one each in ATM, ATR, CHEK2, FANCG, FANCI, FANCL, and PALB2) and 18 (64.3%) did not. Men with HRD mutations (HRD+) had numerically lower ages (66 vs 73yr, p=0.25), more soft-tissue metastases (50% vs 38%, p=0.43), and higher baseline ALP levels (130 vs 108 U/l, p=0.84). Compared with HRD(-) men, HRD(+) patients showed greater ALP responses (80% vs 39%, p=0.04), longer time to ALP progression (median10.4 vs 5.8mo, hazard ratio [HR] 6.4, p=0.005), and a trend toward longer OS (median 36.9 vs 19.0mo, HR 3.3, p=0.11). PSA responses (0% vs 0%, p>0.99) and time to next systemic therapy (HR 1.5, p=0.39) were similar between the two groups. Results are limited by the retrospective nature of the analysis and the small sample size., Conclusions: In this exploratory study, bone-metastatic CRPC patients with inactivating HRD mutations demonstrated significantly improved ALP responses and time to ALP progression. These results should motivate prospective validation of the "synthetic lethality" hypothesis between HRD mutations and radium-223 activity., Patient Summary: In this report, we retrospectively examined outcomes to metastatic prostate cancer in patients with and without DNA repair mutations who received radium-223, a therapy that kills cancer cells by causing direct DNA damage. Our study suggested that patients who have inherited or acquired DNA repair gene mutations derived greater benefit from radium-223 when compared with patients without these mutations. We concluded that radium-223 might have an important role in this setting; however, prospective studies are needed to confirm whether DNA repair mutations truly make radium-223 work better or not., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)