Fabrication and evaluation of ribavirin-loaded electrospun nanofibers as an antimicrobial wound dressing.

Background: Skin is regarded as an essential first line of defense against harmful pathogens and it hosts an ecosystem of microorganisms that create a widely diverse skin microbiome. In chronic wounds, alterations in the host-microbe interactions occur forming polymicrobial biofilms that hinder the process of wound healing. Ribavirin, an antiviral drug, possesses antimicrobial activity, especially against Pseudomonas aeruginosa and Candida albicans, which are known as the main opportunistic pathogens in chronic wounds. Rationale: In this study, electrospun nanofiber systems loaded with ribavirin were developed as a potential wound dressing for topical application in chronic wounds. Ribavirin was chosen in this study owing to the emerging cases of antimicrobial (antibiotics and antifungal) resistance and the low attempts to discover new antimicrobial agents, which encouraged the repurposing use of current medication as an alternative solution in case of resistance to the available agents. Additionally, the unique mechanism of action of ribavirin, i.e., perturbing the bacterial virulence system without killing or stopping their growth and rendering the pathogens disarmed, might be a promising choice to prevent drug resistance. Cyclodextrin (CD) was utilized to formulate ribavirin as an electrospun nanofibers delivery system to enhance the absorption and accelerate the release of ribavirin for topical use. Results: The results demonstrated a successful ribavirin nanofibers fabrication that lacked beads and pores on the nanofibrous surfaces. Ribavirin underwent a physical transformation from crystalline to amorphous form, as confirmed by X-ray diffraction analysis. This change occurred due to the molecular dispersion after the electrospinning process. Additionally, the CD enhanced the encapsulation efficiency of ribavirin in the nanofibers as observed from the drug-loading results. Polyvinylpyrrolidone (PVP) and CD increased ribavirin released into the solution and the disintegration of fibrous mats which shrank and eventually dissolved into a gel-like substance as the ribavirin-loaded fibers began to break down from their border toward the midpoint. Cytotoxicity of ribavirin and CD was evaluated against human dermal fibroblasts (HFF-1) and the results showed a relatively safe profile of ribavirin upon 24-hour cell exposure, while CD was safe within 24- and 48-hour. Conclusion: This study provides valuable insights into the potential application of our nanofibrous system for treating chronic wounds; however, further antimicrobial and in-vivo studies are required to confirm its safety and effectiveness.

Validation and Application of Screen-Printed Microchip for Potentiometric Determination of Metformin Hydrochloride in Tablet Dosage Form.

Metformin is an oral biguanides hypoglycaemic agent, which used to lower the blood glucose levels in people with type 2 diabetes mellitus. Many analytical techniques have been used to quantify the drug in different pharmaceutical dosage forms; however, most of these methods have limited throughput in the quality control application. A disposable potentiometric microsensor responsive to metformin has recently been reported. For the first time, herein, this method of analysis has been validated according to IUPAC recommendations and successfully applied in the determination of metformin drug in some dosage form. Different drug formulations of metformin hydrochloride have been collected from the local pharmaceutical stores in Saudi Arabia and analysed using the validated microchip-based method of analysis. Subsequently, the results of this study showed that the validated method was linear, specific, precise, and accurate. The linear range was 1 × 10-1-1 × 10-5 mol L-1 and the correlation coefficient was 0.999. The limit of detection was 2.89 × 10-6 mol L-1, and the limit of quantification was 8.77 × 10-6 mol L-1. This method demonstrated high precision, with an RSD% of less than 2.22%. The accuracy of this method was obtained by comparing the recovery percentage with percentage values less than 5%. The results obtained showed that there was no significant difference between the references, label, and recovery of less than 5%.

Association between Gingival Phenotype and Periodontal Disease Severity-A Comparative Longitudinal Study among Patients Undergoing Fixed Orthodontic Therapy and Invisalign Treatment.

This longitudinal study aimed to compare the association between gingival phenotype (thin vs. thick) and periodontal disease severity in patients undergoing fixed orthodontic therapy (FOT) and Invisalign treatment over a six-month follow-up period. Clinical periodontal parameters, including full mouth plaque score (FMPS), full mouth bleeding score (FMBS), gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), gingival recession (GR), keratinized tissue width (KTW), transgingival probing, and gingival biotype assessment, were recorded at baseline and 6 months into treatment for both orthodontic groups and a control group. Statistical analysis evaluated differences in parameters between groups and across time points. In the thick phenotype, both Invisalign and FOT groups showed a significant mean reduction in FMPS (baseline to 6 months) by -24.8707 and -12.3489, respectively (p < 0.05). The gingival index decreased significantly for both groups, with Invisalign and FOT showing reductions of -0.83355 and -1.10409, respectively (p < 0.05). FMBS (baseline to 6 months) decreased significantly for Invisalign and FOT, with mean differences of -9.10298 and -12.6579 (p < 0.05). Probing pocket depth (baseline to 6 months) was also significantly reduced for both Invisalign and FOT groups while CAL showed non-significant differences in both groups (p > 0.05). Similar changes were seen in the thin phenotype too. This study highlights the positive influence of both Invisalign and fixed orthodontic therapy on periodontal health, particularly in patients with thin and thick gingival biotypes. These findings, with significant reductions in key periodontal parameters, offer valuable insights to guide orthodontic treatment decisions and enhance patient outcomes.

Pharmacist management of atrial fibrillation in UK primary care: a cross-sectional study.

Background: Atrial Fibrillation (AF) increases the risk of stroke by a factor of five, leading a significant cost burdens on healthcare system. Pharmacists, especially those based in a primary care environment are well placed to support patients in this therapeutic area. Objectives: To assess primary care pharmacists' actual knowledge on the management of AF symptoms and anticoagulation. Furthermore, to investigate the resources used by pharmacists. Methods: A cross-sectional study using survey was conducted, targeting UK-based registered pharmacists employed within primary care settings. Quantitative data were analysed utilising descriptive univariate and bivariate statistics. Results: 349 pharmacists completed the adapted 19-questions of the pharmacists' knowledge. Out of a maximum of 19 points, the mean score was 14.34 ± 2.2 (75 ± 11.6%). The questionnaire revealed several significant gaps in pharmacists' knowledge. Most of the surveyed pharmacists (62.8%) reported that they used sources of information to support their consultations. Half reported that they used the National Institute for Health and Care Excellence (NICE) guidance (52.4%) and the British National Formulary (BNF) (50.7%). Conclusions: Primary care pharmacists are knowledgeable about AF and its management; however, some gaps exist which may require addressing. Although pharmacists use a variety of information resources, it is the traditional resources that remain the most frequently used.

Development and evaluation of sildenafil/glycyrrhizin-loaded nanofibers as a potential novel buccal delivery system for erectile dysfunction.

Erectile dysfunction (ED) is a growing health condition that needs safe and effective therapy. One of the main common treatments is sildenafil which is used in clinics for managing erectile dysfunction by enhancing the blood supply to the penis. In the current study, sildenafil was formulated as nanofibers and mixed with the root extract of Glycyrrhiza glabra (glycyrrhizin) as a natural sweetener to be administrated in the buccal cavity for enhanced drug bioavailability, rapid drug absorption and improved patient compliance. The formulated dual-loaded nanofibers were evaluated by measuring diameter, disintegration, drug loading efficiency, drug release profile, and in vitro cell viability assessment. The results showed that the sildenafil/glycyrrhizin-loaded fibers had a diameter of 0.719 ± 0.177 µm and lacked any beads and pores formation on their surfaces. The drug loading and encapsulation efficiency for sildenafil were measured as 52 ± 7 µg/mg and 67 ± 9 %, respectively, while they were 290 ± 32 µg/mg and 94 ± 10 %, respectively, for glycyrrhizin. The release rate of sildenafil and glycyrrhizin demonstrated a burst release in the first minute, followed by a gradual increment until a complete release after 120 min. The in vitro cell viability evaluation exhibited that the application of sildenafil and glycyrrhizin is safe upon 24-hour treatment on human skin fibroblast cells at all used concentrations (i.e., ≤ 1,000 and 4,000 µg/mL, respectively). However, the application of sildenafil-glycyrrhizin combination (in a ratio of 1:4) demonstrated more than 80 % cell viability at concentrations of ≤ 250 and 1000 µg/mL, respectively, following 24-hour cell exposure. Therefore, sildenafil/glycyrrhizin dual-loaded PVP nanofibers showed a potential buccal therapeutic approach for erectile dysfunction management.

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils.

BACKGROUND: Due to its volatility, photostability, and gastrointestinal toxicity, Perillyl Alcohol (POH), a monoterpenoid component of various plant species, is a chemotherapeutic drug with insufficient efficacy. Many naturally occurring bioactive compounds have well-known antiproliferative properties, including sefsol, jojoba, tea tree, and moringa oils. OBJECTIVE: This study sought to develop an oil-based Self Nanoemulsifying Drug Delivery System (SNEDDS) using tween 80 as the surfactant and Dimethyl Sulfoxide (DMSO) or Polyethylene Glycol (PEG) 400 as the cosurfactant; the oils were used in a range of 10-20% to boost POH's anticancer efficacy. METHODS: The formulations' size, charge, and impact on the viability of glioma cell lines, ANGM-CSS and A172, were evaluated. RESULTS: The developed SNEDDS formulations ranged from 3 nm to 362 nm in size, with electronegative surface charges between 5.05 and 17.0 mV and polydispersity indices between 0.3 and 1.0. CONCLUSION: The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required.

Evaluation of the Milled and Three-Dimensional Digital Manufacturing, 10-Degree and 20-Degree Preparation Taper, Groove and Box Auxiliary Retentive Features, and Conventional and Resin-Based Provisional Cement Type on the Adhesive Failure Stress of 3 mm Short Provisional Crowns.

BACKGROUND This study evaluated the effects of milling (CADCAM), 3D printing, preparation taper angles (10-degree and 20-degree), auxiliary retentive features (groove and box), and provisional cement types (conventional and resin-based) on the adhesive failure stress of 3-mm short provisional crowns (PC). The research was motivated by the need to understand how digital dentistry technologies impact the retention and durability of provisional crowns. MATERIAL AND METHODS A total of 160 working models (3D-printed) and PCs [80 milled (CopraTemp)/80 printed (Asiga)] were fabricated from two 10- and 20-degree typodont master models and two 20-degree 3D-printed master models (groove and box), simulating a 3 mm high all-ceramic short PC. After provisional cementation with conventional (Kerr TempBond) and resin-based (ProviTemp) cements, 16 subgroups (n=10 each) underwent thermocycling (10 000 cycles; 5-55°C) and pull-off tests on a universal testing machine. Statistical analysis was performed using one-way ANOVA and post hoc Tukey test. RESULTS Conventional cement failed at lower stress for milled (47.68 to 73.54) and printed (48.40 to 77.91) as compared to resin cement for milled (104.2 to 137.27) and printed (184.85 to 328.84), respectively, with significant differences. Increased taper and groove decreased failure load except for the printed PC/resin cement combination. Use of proximal box preparation increased retention significantly. Except for 20-degree taper cemented with conventional cement, the differences in auxiliary retentive features for milled and printed provisional crowns were statistically significant at P≤0.05. CONCLUSIONS 3D-printed PC, resin-based cement, 10-degree taper, and proximal box preparation were associated with higher retention than milled, conventional cements, 20-degree taper, and vertical groove.

Influence of Chairside Simulated Adjustment (Finishing and Polishing) Protocol and Chlorhexidine Mouthwash Immersion on Color Stability and Translucency of 2 and 3 Preshaded Multilayered Monolithic Zirconia.

BACKGROUND Preshaded monolithic zirconia (MLZ) is reported to have high translucency. This study aimed to assess the effect of chlorhexidine gluconate (ChG) mouthwash on color and translucency parameter (TP) of 2 different preshaded MLZ dental ceramics after clinical adjustment. MATERIAL AND METHODS Two MLZ disk-shaped specimens [NPM (Nacera Pearl Multi-Shade) (n=72) and CZM (Ceramill Zolid FX Multilayer)] (n=72) were simulated for clinical adjustment, finished, and polished using 2 adjustment kits [recommended kit, third-party kit: Diasynt Plus and SUN (n=12 each)] and later immersed in ChG mouthwash (Avohex) for 2 weeks. Difference in color (ΔE) and TP (Y) were calculated using the CIELab formula after measuring the coordinates (Lab) with a colorimeter. Individual changes in color and TP were assessed on the Clinical acceptance (perceptible) threshold (CAT/CPT) and Translucency perception threshold (TPT), respectively. Differences between the 2 ceramics were assessed using one-way ANOVA and post hoc tests, with all differences considered significant at P<0.05. RESULTS NPM and CZM differed in color at baseline despite having the same Vita shade combination. Between the 2 preshaded MLZ ceramics, NPM showed significant changes in color when adjusted with a third-party kit. Chlorhexidine produced changes in color and TP that were designated as clinically perceptible (ΔE=1.0 to 3.3) on the CAT/CPT and TPT scales, irrespective of the adjustment kit used. ChG produced the least or no changes in glazed MLZ specimens. CONCLUSIONS ChG mouthwash, whenever prescribed for preshaded MLZ restoration, should be adjusted prior to final glazing to avoid clinical adjustments that adversely affects color and translucency of the restoration.

Retraction: Lymphangioma: A Rare Benign Cystic Pancreatic Lesion.

[This retracts the article DOI: 10.7759/cureus.21056.].

Development of progesterone electrospun nanofibers to coat Arabin pessaries as a dual preventive and therapeutic approach for preterm labor.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

Temperature rise in photopolymerized adhesively-bonded resin composite: A thermography study.

OBJECTIVES: To assess visually and quantitatively the contributions of the adhesive layer photopolymerization and the subsequent resin composite increment to spatio-temporal maps of temperature at five different cavity locations, subjected to two irradiance curing protocols: standard and ultra-high. METHODS: Caries-free molars were used to obtain 40, 2 mm thick dentin slices, randomly assigned to groups (n = 5). These slices were incorporated within 3D-printed model cavites, 4 mm deep, restored with Adhese® Universal bonding agent and 2 mm thick Tetric® Powerfill resin composite, and photocured sequentially, as follows: G1: control-empty cavity; G2: adhesive layer; G3 composite layer with no adhesive; and G4 composite layer with adhesive. The main four groups were subdivided based on two curing protocols, exposed either to standard 10 s (1.2 W/cm2) or Ultra high 3 s (3 W/cm2) irradiance modes using a Bluephase PowerCure LCU. Temperature maps were obtained, via a thermal imaging camera, and numerically analyzed at 5 locations. The data were analyzed using two-way ANOVA followed by multiple one-way ANOVA, independent t-tests and Tukey post-hoc tests (α = 0.05). Tmax, ΔT, Tint (integrated area under the curve) and time-to-reach-maximum-temperature were evaluated. RESULTS: Two-way ANOVA showed that there was no significant interaction between light-curing time and location on the measured parameters (p > 0.05), except for the time-to-reach-maximum-temperature (p < 0.05). Curing the adhesive layer alone with the 10 s protocol resulted in a significantly increased pulpal roof temperature compared to 3 s cure (p < 0.05). Independent T-tests between G3 and G4, between 3 s and 10 s, confirmed that the adhesive agent caused no significant increases (p > 0.05) on the measured parameters. The ultra-high light-curing protocol significantly increased ΔT in composite compared to 10 s curing (p < 0.05). SIGNIFICANCE: When the adhesive layer was photocured alone in a cavity, with a 2 mm thick dentin floor, the exothermal release of energy resulted in higher temperatures with a 10 s curing protocol, compared to a 3 s high irradiance. But when subsequently photocuring a 2 mm layer of composite, the resultant temperatures generated at pulpal roof location from the two curing protocols were similar and therefore there was no increased hazard to the dental pulp from the immediately prior adhesive photopolymerization, cured via the ultra-high irradiation protocol.

Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.

Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls. Meta-analyses were then performed with these two Saudi MI studies and the CardioGRAMplusC4D and UK BioBank GWAS as controls. Meta-analyses of the two Saudi MI studies resulted in 17 SNPs with genome-wide significance. Meta-analyses of all 4 studies revealed 66 loci with genome-wide significance levels of p < 5 × 10-8. All of these variants, except rs2764203, have previously been reported as MI-associated loci or to have high linkage disequilibrium with known loci. One SNP association in Shisa family member 5 (SHISA5) (rs11707229) was evident at a much higher frequency in the Saudi MI populations (> 12% MAF). In conclusion, our results replicated many MI associations, whereas in Saudi-only GWAS (meta-analyses), several new loci were implicated that require future validation and functional analyses.

Awareness, Knowledge, and Attitude Towards Urinary Tract Infections: An Appraisal From Saudi Arabia.

Introduction Urinary tract infections (UTIs) are a common global health issue, yet awareness and knowledge about UTIs among the general population can vary widely. This study aimed to assess the awareness, knowledge, and attitudes regarding UTIs among Saudi Arabian citizens residing in Al-Ahsa, Saudi Arabia. Methods A descriptive cross-sectional study was conducted among Saudi Arabian citizens aged 18 and above residing in Alhassa. A structured questionnaire was used to collect data on participants' awareness, knowledge, attitudes, and experiences related to UTIs. Data were analyzed using IBM® SPSS® Statistics. Results The study included 445 participants, predominantly males, with 279 (62.7%) and a range of educational backgrounds. Approximately 302 (70.1%) of the participants were aware of UTIs. However, misconceptions about the definition of UTI and its risk factors were common. Most participants recognized bacteria as the primary cause of UTIs, with 261 (58.7%) identifying this factor. Symptoms such as painful urination were recognized by 390 participants, which is a significant proportion. When experiencing UTI symptoms, 285 (66.1%) indicated they would go to the hospital. Significant associations were found between awareness, knowledge, and socio-demographic factors. Conclusion This study highlights the need for increased awareness and knowledge about UTIs among Saudi Arabian citizens in Alhassa. Tailored educational interventions are essential to correct misconceptions, promote accurate risk factor awareness, and encourage appropriate management strategies. Public health campaigns can contribute to reducing the burden of UTIs in the community.

Alkaptonuria Diagnosis Following a Discectomy: A Case Report.

Alkaptonuria is a rare genetic disorder characterized by the excessive production of homogentisic acid, leading to the formation and deposition of pigment polymers throughout the body. It is extremely rare, affecting only around one in 100,000 individuals. Despite the normal life expectancy, it can cause severe morbidities. Alkaptonuria is typically managed supportively with pain medication, dietary modifications, and surgical interventions, which are considered to be the gold standard of therapy. Here we present a case of a 33-year-old male with no previous medical or surgical history who presented with severe acute back pain radiating to the left leg. Genetic testing confirmed a homozygous pathogenic variant for alkaptonuria. This case highlights the challenges in diagnosing alkaptonuria, emphasizing the significance of early detection, and clinical evaluation for improved outcomes. Furthermore, it underscores the need to consider alkaptonuria as a multidimensional disease, necessitating further research to enhance our understanding and develop effective management. Therefore, this study serves as an opportunity for future trials and studies aimed at digging deeper into the intricacies of alkaptonuria to increase our understanding and establish comprehensive management plans for affected individuals.

Green Synthesis of Silver Nanoparticles Using Jacobaea maritima and the Evaluation of Their Antibacterial and Anticancer Activities.

Much attention has been gained on green silver nanoparticles (green-AgNPs) in the medical field due to their remarkable effects against multi-drug resistant (MDR) microorganisms and targeted cancer treatment. In the current study, we demonstrated a simple and environment-friendly (i.e., green) AgNP synthesis utilizing Jacobaea maritima aqueous leaf extract. This leaf is well-known for its medicinal properties and acts as a reducing and stabilizing agent. Nanoparticle preparation with the desired size and shape was controlled by distinct parameters; for instance, temperature, extract concentration of salt, and pH. The characterization of biosynthesized AgNPs was performed by the UV-spectroscopy technique, dynamic light scattering, scanning electron microscopy, X-ray diffraction, and Fourier-transform infrared. The successful formation of AgNPs was confirmed by a surface plasmon resonance at 422 nm using UV-visible spectroscopy and color change observation with a particle size of 37± 10 nm and a zeta potential of -10.9 ± 2.3 mV. SEM further confirmed the spherical size and shape of AgNPs with a size varying from 28 to 52 nm. Antibacterial activity of the AgNPs was confirmed against all Gram-negative and Gram-positive bacterial reference and MDR strains that were used in different inhibitory rates, and the highest effect was on the E-coli reference strain (MIC = 25 µg/mL). The anticancer study of AgNPs exhibited an IC50 of 1.37 µg/mL and 1.98 µg/mL against MCF-7 (breast cancer cells) and A549 (lung cancer cells), respectively. Therefore, this green synthesis of AgNPs could have a potential clinical application, and further in vivo study is required to assess their safety and efficacy.

Evaluation of the Effects of Digital Manufacturing, Preparation Taper, Cement Type, and Aging on the Color Stability of Anterior Provisional Crowns Using Colorimetry.

BACKGROUND Replicating the 3-dimensional (3D) color of natural teeth in artificial substitutes is challenging. Fixed dental prosthodontics require aesthetic, color-stable provisional restorations. Recent milling and 3D printing digital manufacturing techniques offer improved outcomes. This study assesses color stability in various digital manufacturing methods, tapers, and aging effects on anterior provisional resin restorations. MATERIAL AND METHODS Two all-ceramic tooth preparations on typodont teeth with 10° and 20° tapers were converted into experimental dies. Forty temporary crowns were manufactured using 3D printing and computer-aided design/computer-aided manufacturing (milling). Within these 2 groups, 10 crowns were cemented using a regular and clear provisional cement. All samples were thermocycled to simulate clinical use of 6 months. Color difference formula (CIEDE2000) indicated changes between before and after cementation (ΔE00) and between after cementation and after thermocycling (ΔE00[II]). The color change was considered significant in terms of clinically perceptible (ΔE00 ≤0.62) and acceptable (ΔE00 ≤2.62) changes. One-way ANOVA (P value of less than 0.05) calculated overall differences, which were established using a Fisher post hoc test. RESULTS Crowns cemented with clear cement showed fewer color changes irrespective of the manufacturing technique or taper. Notably, only the 10° 3D-printed crown with clear cement had an imperceptible color change at the pre-/post-cementation phase. Meanwhile, the 10° and 20° milled crowns with regular cement exhibited unacceptable color changes after thermocycling. CONCLUSIONS For long­term temporization in the aesthetic zone, properly optimized 3D-printed provisional restorations cemented with clear cement had better color stability.

Incorporation of Perillyl Alcohol into Lipid-Based Nanocarriers Enhances the Antiproliferative Activity in Malignant Glioma Cells.

Perillyl alcohol (PA), a naturally existing monocyclic terpene related to limonene, is characterized by its poor aqueous solubility and very limited bioavailability. Its potential anti-cancer activity against malignant glioma has been reported. The aim was to develop PA-loaded lipid-based nanocarriers (LNCs), and to investigate their anti-cancer activity against two different brain cell lines. Non-medicated and PA-loaded LNCs were prepared and characterized. The mechanism of cytotoxic activity of PA was conducted using a molecular docking technique. The cell viabilities against A172 and ANGM-CSS cells were evaluated. The results revealed that the average particle size of the prepared LNCs ranged from 248.67 ± 12.42 to 1124.21 ± 12.77 nm, the polydispersity index was 0.418 ± 0.043-0.509 ± 0.064, while the zeta potential ranged from -36.91 ± 1.31 to -15.20 ± 0.96 mV. The molecular docking studies demonstrated that the drug had binding activity to human farnesyltransferase. Following exposure of the two glioblastoma cell lines to the PA-loaded nanoformulations, MTS assays were carried out, and the data showed a far lower half-maximal inhibitory concentration in both cell lines when compared to pure drug and non-medicated nanocarriers. These results indicate the potential in vitro antiproliferative activity of PA-loaded LNCs. Therefore, the prepared PA-loaded nanocarriers could be used to enhance drug delivery across the blood-brain barrier (BBB) in order to treat brain cancer, especially when formulated in a suitable dosage form. The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound's distribution and effects within the brain.

Bronchodilator reversibility testing in morbidly obese non-smokers: fluticasone/salmeterol efficacy versus salbutamol bronchodilator.

A positive response in reversibility testing is widely used to diagnose patients with airway limitations. However, despite its simple procedure, it doesn't accurately reflect the exact airway irreversibility. This study aimed to investigate the efficacy of a bronchodilation reversibility test using salbutamol and fluticasone/salmeterol combination in obese non-smoker subjects.The study included patients without a history of obstructive lung disease or bronchodilators. A sub-classification of patients based on body mass index (BMI) was carried out into normal (< 24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI ≥ 30). Spirometry measurements were performed before and after salbutamol or fluticasone/salmeterol administration.The study included 415 (49.9% male) patients with a mean age of 40.92 ± 10.86 years. Obese subjects showed a high prevalence of restrictive patterns (23.4%), with non-significantly lower spirometric values compared to normal and overweight subjects (p > 0.05). The magnitude of bronchodilation, as identified by spirometry, following fluticasone/salmeterol was higher in all participants, with a significant increase in obese subjects with a p-value of 0.013, 0.002, and 0.035 for FEV1, FEV1% predicted, and FEV1/FVC, respectively.Fluticasone/salmeterol combination increases FEV1, FEV1% of predicted, and FEV1/FVC ratio than the conventional test using salbutamol inhaler, and it can be a potential candidate for assessment of airway obstruction using reversibility test, especially among the obese population.

Awareness of isotretinoin use and safety in Saudi Arabia: A nationwide cross-sectional study.

Introduction: Acne is a prevalent skin condition that affects numerous adolescents and adults worldwide. The most effective treatment for acne is isotretinoin, but its usage is associated with a wide range of adverse effects, and regular monitoring is necessary. Hence, appropriate usage with awareness of potential side effects is crucial. This study aimed to assess the knowledge and awareness of isotretinoin use and safety among individuals with acne in Saudi Arabia. Methods: A national cross-sectional survey was conducted through an online self-administered questionnaire distributed via social media platforms. The questionnaire consisted of 27 questions in multiple-choice and Likert scale formats, covering demographics, patient awareness of isotretinoin use and side effects, satisfaction with clinical consultation and information provided. Descriptive statistics were used to summarize data. Results: 1315 participants completed the survey, of which most were female (74.1%), single (67.5%), and aged 18-25 years (48.9%). Dryness and teratogenicity were the most commonly known side effects of isotretinoin use (85.5% and 64.9% respectively). However, most participants were unaware of other side effects, such as psychiatric disorders (62.9%), altered liver enzyme concentrations (65.2%), hyperlipidemia (68.1%), anemia (92.4%), and decreased platelet count (96%). Moreover, 36% of sexually active females initiated isotretinoin without contraception. Regarding satisfaction with the information provided during clinical consultation, 63.2% of participants were very satisfied or satisfied. Doctors were the primary source of information (86.8%), followed by the internet (17.8%). Only 45% were informed to avoid blood donation during and after treatment for at least two months. Conclusion: The study highlights the significance of providing patients with comprehensive information about the potential side effects of isotretinoin, including the need to use contraception and avoid blood donation during and after treatment. Effective communication between physicians and patients is critical in ensuring the safe and effective use of isotretinoin.

Factors Related to Relapse of Congenital Talipes Equinovarus (CTEV) After the Ponseti Method.

BACKGROUND: Congenital talipes equinovarus (CTEV) is one of the common congenital disorders in pediatric orthopedic practice that affects a large group of children.It is a combination of four parts of deformity that affect either a single foot or both feet. Our aim in this study is to estimate the prevalence and incidence of CTEV and to evaluate the risk factors that lead to relapse in some children to avoid relapse in future and complex surgical interventions, as well as to improve the final outcome. MATERIALS AND METHODS: A retrospective cohort study for the cases of CTEV was conducted to estimate the prevalence of relapse in children with CTEV after management by the Ponseti method and to evaluate the risk factors that lead to recurrence. RESULT: The study includes 103 patients with CTEV, and only 22 patients had relapse. The prevalence rate of relapsed cases was 20.4%, and the incidence was 42 per thousand. The average number of casts applied was 4.05 ± 1.37. The average severity of the deformity that was measured by the Pirani score was 4.97 ± 1.21. The most common atypical presentation of CTEV was associated with developmental dysplasia of the hip (DDH), followed by myelomeningocele (MMC). CONCLUSION: The only significant factors in the study were the Pirani score and non-compliance of the brace with p < 0.05. There was not any significance in the correction of the deformity by Ponseti between idiopathic and non-idiopathic CTEV based on the number of casts and the Pirani score. The dynamic foot brace can be the solution for the high recurrence rate, yet more studies are needed in the future.