Lattice Transformation from 2D to Quasi 1D and Phonon Properties of Exfoliated ZrS2 and ZrSe2.

Recent reports on thermal and thermoelectric properties of emerging 2D materials have shown promising results. Among these materials are Zirconium-based chalcogenides such as zirconium disulfide (ZrS2 ), zirconium diselenide (ZrSe2 ), zirconium trisulfide (ZrS3 ), and zirconium triselenide (ZrSe3 ). Here, the thermal properties of these materials are investigated using confocal Raman spectroscopy. Two different and distinctive Raman signatures of exfoliated ZrX2 (where X = S or Se) are observed. For 2D-ZrX2 , Raman modes are in alignment with those reported in literature. However, for quasi 1D-ZrX2 , Raman modes are identical to exfoliated ZrX3 nanosheets, indicating a major lattice transformation from 2D to quasi-1D. Raman temperature dependence for ZrX2 are also measured. Most Raman modes exhibit a linear downshift dependence with increasing temperature. However, for 2D-ZrS2 , a blueshift for A1g mode is detected with increasing temperature. Finally, phonon dynamics under optical heating for ZrX2 are measured. Based on these measurements, the calculated thermal conductivity and the interfacial thermal conductance indicate lower interfacial thermal conductance for quasi 1D-ZrX2 compared to 2D-ZrX2 , which can be attributed to the phonon confinement in 1D. The results demonstrate exceptional thermal properties for Zirconium-based materials, making them ideal for thermoelectric device applications and future thermal management strategies.

The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol.

PURPOSE: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. METHODS: A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. RESULTS: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. CONCLUSION: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

Effect of the timing of second molar bonding on the duration of the mandibular arch levelling: a randomized clinical trial.

INTRODUCTION: This study investigated the effect of the timing of second molar bonding on the time required for the levelling of the mandibular dental arch. TRIAL DESIGN: Single-centre two-arm parallel randomized clinical trial using random permuted blocks. Allocation concealment was achieved through sealed envelopes. There was blinding in outcome assessment, but not of patient or operator. METHODS: Thirty-six patients (12-18 years old) with mild to moderate crowding and fully erupted mandibular second molars were assigned randomly (1:1 ratio) in two groups. Group A started fixed orthodontic treatment by bracket bonding in both jaws. Initial wire was 0.014" NiTi. Lower second molar tubes were bonded at the time of 0.016" x 0.022" NiTi wire placement. Group B was same as Group A, but second lower molars were bonded at the first appointment. Placement of the 0.017" x 0.025" stainless steel wire in the mandibular arch was considered the primary endpoint of the trial, indicating the completion of the levelling phase. The days required from bonding to the endpoint comprised the main outcome. Non-parametric statistics were applied. RESULTS: There were two dropouts in each group. The compared groups had similar baseline characteristics regarding age, sex, overjet, overbite, space in the dental arch, average Curve of Spee (CoS), and maximum CoS. Group A tended to require more days for levelling (median: 203 days) than Group B (median: 168 days). However, this difference was not statistically significant (P = 0.128). From the tested occlusal factors, only initial overjet was found to be moderately associated with the days required to complete levelling of the mandibular arch (r = 0.45, P = 0.009). CONCLUSIONS: In the frame of the current study, the duration of the levelling phase of orthodontic treatment with fixed appliances was not affected by the timing of second molar inclusion in the appliance. Future research could aim in cases with deep CoS to generalize the present findings and in larger sample sizes.

Success of palatal implants or mini-screws placed median or paramedian for the reinforcement of anchorage during orthodontic treatment: a systematic review.

Objectives: To assess the failure rates of palatal implants and palatal mini-screws, independently and comparatively, used for supplementing anchorage during orthodontic treatment. Protocol and registration: The protocol was not registered prior to the study. This study was not registered in any publicly assessable database. Materials and methods: Screening for inclusion eligibility, quality assessment of studies, and data extraction was performed independently by two authors. The electronic databases MEDLINE, EMBASE, and CENTRAL, as well as unpublished literature, were searched with no restrictions on publication date or language using detailed strategies. The main outcome assessed was palatal implant or mini-screw failure. Randomized controlled trials were evaluated according to the Cochrane risk of bias tool. Prospective and retrospective studies were graded employing the adjusted predetermined criteria of Bondemark. Results: Twenty-seven studies satisfied the inclusion criteria. Four were RCTs of low risk of bias, 12 were prospective (2 low, 7 unclear, 3 high risk of bias) and 11 were retrospective studies (6 unclear, 5 high risk of bias). Only one retrospective study assessed both palatal implants and mini-screws. Seventeen studies, including the four RCTs, assessed solely palatal implants and nine studies palatal mini-screws. The median failure risk of palatal implants was 6.0 per cent (range: 0.0-26.1%) and of mini-screws 6.1 per cent (range: 0.0-33.3%). The median follow-up period was 17.9 months for palatal implants and 6 months for mini-screws. Limitations: Significant clinical and methodological heterogeneity among studies and highly variable outcomes. Conclusions: Both palatal implants and mini-screws have quite low failure rates that are also comparable, though the median follow-up period of palatal implants was quite larger. Therefore, in regular orthodontic cases, the choice between anchoring devices may rely on other factors, such as costs, patient comfort, personal preferences, familiarity with the device, and insertion procedures.

Valproic acid for agitation in the intensive care unit: an observational study of psychiatric consults.

BACKGROUND: Agitation is a common clinical problem encountered in the intensive care unit (ICU). Treatment options are based on clinical experience and sparse quality literature. AIM: The aim of this study was to describe the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU, identify predictors of response to VPA and evaluate the independent effect of VPA on agitation compared to standard of care (SOC). METHOD: This retrospective single center observational study evaluated adult patients admitted to the ICU for whom a psychiatric consultation was requested for agitation management, with agitation defined as a Richmond Agitation Sedation Score of 2 or greater. A descriptive analysis of the proportion of agitation-free patients per day of follow-up, the incidence of agitation-related-events, as well as the evolution of co-medications use over time are presented. A logistic regression model was used to assess predictors of VPA response, defined as being agitation-free on Day 7 and generalized estimating equations were used to evaluate the independent effect of VPA as adjuvant therapy for agitation in the critically ill. RESULTS: One hundred seventy-five patients were included in the study with 78 receiving VPA. The percentage of agitation-free patients on VPA was 6.5% (5/77) on Day 1, 14.1% (11/78) on Day 3 and 39.5% (30/76) on Day 7. Multivariate regression model for clinical and demographic variables identified female gender as predictor of response on Day 7 (OR 6.10 [1.18-31.64], p = 0.03). The independent effect of VPA was non-significant when compared to SOC. CONCLUSION: Although VPA used as adjuvant treatment was associated with a decrease in agitation, its effect when compared to SOC did not yield significant results.

Preformed Stainless-Steel Crowns: Their Effects on Oral Hygiene Maintenance and Gingival Health - A Prospective Original Research.

The stainless-steel crown (SSC) is a durable restoration and has several indications for use in primary teeth such as following a pulpotomy/pulpectomy, fractured teeth, teeth with developmental defects, or large multi-surface caries lesions where amalgam is likely to fail. Due to its durability and a lifespan like the primary tooth, it could well be the gold standard in restorative care. SSCs protect the crown from fracture, reduce the possibility for leakage, and ensure a biological seal. However, the placement of the SSC should follow a meticulous technique. There are some clinical situations where the SSC may fail, leading to plaque accumulation and gingivitis. This could be secondary to improper crimping of crown margins, which lead to poorly adapted SSC. In some clinical situations, ledge formation under the crown or failure to clean excess cement can contact the gingiva and cause gingival inflammation. This study was carried out on 41 children between the ages of 4 and 10 in Al Qassim region to study the effects of SSCs on gingiva and oral hygiene. The study also aims to establish the correlation between SSC adaptation and post-insertion inflammation. The plaque and gingival index were recorded at 3 months' post SSC insertion. Clinical examination was undertaken, and gingival index (Loe and Silness 1967) and plaque index (Silness and Loe 1967) were used to record gingival health and plaque accumulation, respectively. The result for post-inflammation and SSC adaptation showed that there was no statistically significant difference in post-insertion inflammation and crown adaptation (P value = 0.216). The result for pre-operative inflammation and post-operative inflammation shows that there is no significant difference in post-inflammation and adaptation (P value = 0.47). We found that oral hygiene care had a heightening effect and oral hygiene maintenance plays a key role in preventing gingival inflammation irrespective of the SSC adaptation over short periods of time (3 months).

Client's satisfaction with healthcare services received at the hospital outpatients department and the primary healthcare facilities in Al-Qassim, Saudi Arabia: A review of service users' satisfaction.

OBJECTIVES: To assess the level of satisfaction expressed for services rendered in the public health sector to clients who were seen at outpatient departments (OPDs) and primary healthcare (PHC) facilities in Al-Qassim Health Cluster in Saudi Arabia. METHODS: This study used a comparative cross-sectional study design, and data were obtained as secondary data from The Patient's Experience Platform. Data analysis was carried out using Stata (version 16), and the significance level was 5%. RESULTS: In comparing the mean satisfaction in 9 domains, statistically significantly higher means for the PHC facilities than the OPDs were seen across 7 domains: patients navigating health facilities (p=0.008), nursing services (p<0.001), physicians' services (p=0.004), radiological services (p<0.001), personal issues (p=0.003), the pharmacy (p=0.005), and general experience (p=0.036). CONCLUSION: This study's findings are significant. They indicate that client satisfaction with services at PHC facilities was significantly higher than with services at hospital OPDs in Al-Qassim region. This underscores the need to improve the quality of services provided at OPDs to bring them to the same level as those provided by PHC facilities. Policymakers and implementers should, therefore, sustain efforts to make OPDs and PHC facilities more desirable for clients.

Laparoscopic Management of Inguinal Hernia: A Systematic Review and Updated Network Meta-Analysis of Randomized Controlled Trials.

Various surgical approaches for inguinal hernia repair have been outlined in medical literature. In most cases, these lesions are repaired by general surgeons. A variety of surgical techniques for the treatment of inguinal hernias have been documented in the medical literature. In 2018, the European Hernia Society (EHS) recommended laparo-endoscopic repair as a preferred approach for adults. This method involves a combination of laparoscopic and endoscopic techniques for hernia repair. The goal of this systematic review is to conduct a thorough examination of the total extraperitoneal vs. transabdominal preperitoneal comparison in inguinal hernia repair, with an emphasis on randomized controlled trials (RCTs). It also intends to conduct a trial sequential analysis (TSA) in order to determine whether more trials and investigations are required or whether there is sufficient evidence to draw a firm conclusion. The study's systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and December 2023. The meta-analysis was carried out using Resource Manager Revman version 5.4.1 (Revman International, Inc., New York City, New York). After a review of the studies was done, ten studies were selected to be used in conducting the systematic review and meta-analysis. The recurrence rate of TEP treatment was found to be slightly lower than transabdominal preperitoneal (TAPP). The two techniques did not differ in terms of postoperative complications; however, TEP had a marginally lower rate of postoperative pain. Further, the study revealed that there was a decreased risk of wound infections, seromas, and hematomas with total extraperitoneal (TEP) as opposed to transabdominal preperitoneal (TAPP). TEP also reduced the amount of recovery time needed. After conducting successful hernia treatments, total extraperitoneal and transabdominal preperitoneal both had low rates of complications and recurrence. Based on the information obtained from the study analysis, this meta-analysis provides evidence for the efficacy of TAPP and TEP techniques in the management of inguinal hernias. Though there was a statistically significant difference while applying both methods in the treatment of hernia (p=0.001), TEPs have been shown to have a lower recurrence rate than TAPPs. Similarly, the TEP method has been revealed to have a slight reduction in postoperative pain compared to transabdominal preperitoneal. However, the two techniques have been shown to have no significant difference in postoperative complications. Further, laparoscopic procedures have proved to be a little bit safer and more effective than open procedures. This has been shown by reduced risk of wound infection, hematoma, seroma, and decreased sensibility while using this method. It accelerated the healing process as well. Thus, depending on the needs of the patients and the experience level of the surgeons responsible for the treatments, inguinal hernias can be repaired using either transabdominal preperitoneal or total extraperitoneal techniques since both treatment techniques have generally minimal chance of complications or recurrence as both have proved to safer method.

Biochemical and thermodynamic properties of de novo synthesized urease from Vicia sativa seeds with enhanced industrial applications.

Urease is one of the most significant enzymes in the industry. The objective of this research was to isolate and partially purify urease from Vicia sativa seeds with urease characterization. With a 6.4 % yield, the purification fold was 9.0. By using chromatography, it was determined that the isolated urease had a molecular weight of 55 kDa. The maximum urease activity was found following a 60-s incubation period at 40 °C and pH 8. The activity of urease was significantly boosted by a mean of calcium, barium, DL-dithiothreitol, Na2EDTA, and citrate (16.9, 26.6, 18.6, 13.6, and 31 %), respectively. But nickel and mercury caused inhibitory effects and completely inhibited urease activity, indicating the presence of a thiol (-SH) group in the enzyme active site. The Arrhenius plot was used to analyze the thermodynamic constants of activation, Ea, ΔH*, ΔG*, and ΔS*. The results showed that the values were 30 kJ/mol, 93.14 kJ/mol, 107.17 kJ/mol/K, and -40.80 J/mol/K, respectively. The significance of urease extraction from various sources may contribute to our understanding of the metabolism of urea in plants. The current report has novelty as it explained for the first time the kinetics and thermodynamics of hydrolysis of urea and inactivation of urease from V. sativa seeds.

Ferula sinkiangensis (Chou-AWei, Chinese Ferula): Traditional Uses, Phytoconstituents, Biosynthesis, and Pharmacological Activities.

Ferula is the third largest genus of the Apiaceae family, its species are utilized as a remedy for diverse ailments all over the world. F. sinkiangensis K. M. Shen (Chou-AWei, Chinese Ferula) is mainly found in Xin-jiang Uygur Autonomous Region, China. Traditionally, it is utilized for treating various illnesses such as digestive disorders, rheumatoid arthritis, wound infection, baldness, bronchitis, ovarian cysts, intestinal worms, diarrhea, malaria, abdominal mass, cold, measles, and bronchitis. It can produce different classes of metabolites such as sesquiterpene coumarins, steroidal esters, lignans, phenylpropanoids, sesquiterpenes, monoterpenes, coumarins, organic acid glycosides, and sulfur-containing compounds with prominent bioactivities. The objective of this work is to point out the reported data on F. sinkiangensis, including traditional uses, phytoconstituents, biosynthesis, and bioactivities. In the current work, 194 metabolites were reported from F. sinkiangensis in the period from 1987 to the end of 2022. Nevertheless, future work should be directed to conduct in vivo, mechanistic, and clinical assessments of this plant`s metabolites to confirm its safe usage.

Safety and efficacy of elbasvir/grazoprevir in patients infected with hepatitis C virus genotype 4 in Qassim region of Saudi Arabia.

Objective: Untreated hepatitis C virus (HCV) infection can lead to cirrhosis, hepatocellular cancer, and even death and also increases liver diseases. The elbasvir/grazoprevir (EBR-GZR) treatment regimen when given in HCV genotype (GT) 1 and GT4 infection for 8 or 12 weeks showed a high sustained virolgical response (SVR) rates in different populations. This study was assessed the effectiveness as well as safety of EBR-GZR in 12 week treatment regimen in HCV GT4-infected treatment-naïve Saudi patients. Methods: This study conducted from June 2017 and December 2020 on Saudi HCV patients infected with GT4. Treatment protocol was given for 12 weeks in treatment-naive HCV GT4 infected cirrhotic and non-cirrhotic participants which were later followed for a total of 24 weeks for safety and efficacy of EBR-GZR. Results: We analyzed data of 54 participants with HCV GT 4 infection. Mean age was (53.46 ± 14.94) Treatment regimen was given to 14 cirrhotic (F4) and 40 non-cirrhotic (F0-F3). SVR was seen in 98.1% of participants with tolerable side effects and improved model for end stage liver disease (MELD) scores as fall in percentage seen from 18.5% to 14.8% in participants with MELD > 10. Conclusion: This retrospective study confirms that EBR-GZR for 12 weeks is a safe and effective treatment regimen in HCV GT4 patients in studied Saudi population. Treatment completion was followed by high SVR12 rates with improvement in prognostic markers of liver disease in participants with compensated cirrhosis. In short, the EBR-GZR combination showed efficacy in achieving the SVR12 in Child-Pugh B cirrhotic and non-cirrhotic population with a favorable safety profile.

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling.

Hyperglycemia, as a hallmark of the metabolic malady diabetes mellitus, has been an overwhelming healthcare burden owing to its high rates of comorbidity and mortality, as well as prospective complications affecting different body organs. Available therapeutic agents, with α-glucosidase inhibitors as one of their cornerstone arsenal, control stages of broad glycemia while showing definitive characteristics related to their low clinical efficiency and off-target complications. This has propelled the academia and industrial section into discovering novel and safer candidates. Herein, we provided a thorough computational exploration of identifying candidates from the marine-derived Aspergillus terreus isolates. Combined structural- and ligand-based approaches using a chemical library of 275 metabolites were adopted for pinpointing promising α-glucosidase inhibitors, as well as providing guiding insights for further lead optimization and development. Structure-based virtual screening through escalating precision molecular docking protocol at the α-glucosidase canonical pocket identified 11 promising top-docked hits, with several being superior to the market drug reference, acarbose. Comprehensive ligand-based investigations of these hits' pharmacokinetics ADME profiles, physiochemical characterizations, and obedience to the gold standard Lipinski's rule of five, as well as toxicity and mutagenicity profiling, proceeded. Under explicit conditions, a molecular dynamics simulation identified the top-stable metabolites: butyrolactone VI (SK-44), aspulvinone E (SK-55), butyrolactone I 4''''-sulfate (SK-72), and terrelumamide B (SK-173). They depicted the highest free binding energies and steadiest thermodynamic behavior. Moreover, great structural insights have been revealed, including the advent of an aromatic scaffold-based interaction for ligand-target complex stability. The significance of introducing balanced hydrophobic/polar moieties, like triazole and other bioisosteres of carboxylic acid, has been highlighted across docking, ADME/Tox profiling, and molecular dynamics studies for maximizing binding interactions while assuring safety and optimal pharmacokinetics for targeting the intestinal-localized α-glucosidase enzyme. Overall, this study provided valuable starting points for developing new α-glucosidase inhibitors based on nature-derived unique scaffolds, as well as guidance for prospective lead optimization and development within future pre-clinical and clinical investigations.

Incidence and Risk Factors for Retinal Detachment Following Cataract Surgery at a Tertiary Center in Jeddah, Saudi Arabia.

Introduction The incidence of retinal detachment in the general population is 0.08%, it has been reported to reach 0.7% or higher following cataract surgery. One of the most important risk factors for retinal detachment is posterior capsular rupture during cataract surgery. Additional risk factors include high myopia, history of ocular trauma, young age, male sex, and diabetes. In this study, we aimed to investigate the incidence and risk factors of retinal detachment following cataract surgery in patients treated at our hospital. Materials and methods This retrospective cohort study was conducted at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. The medical records of 365 patients (365 eyes) who underwent cataract surgery from 2017 to 2021 were reviewed. Results The average age of the 365 patients was 63 years, and 47.7% (n=174) of patients were male. The incidence of retinal detachment was 3.3% (n=12). The risk of RD was 2.8 times higher for the right eye than for the left eye. The incidence of RD was significantly more in eyes with intraoperative posterior capsular rupture, zonular dehiscence, corneal trauma, and surgery combined with anterior vitrectomy than in other eyes. The most common complication of cataract surgery is corneal edema, which was observed in 22.7% of the eyes; our analysis revealed a significant relationship between corneal edema and the duration of surgery. Conclusion In our study, we highlighted the higher incidence of retinal detachment compared to those in other studies; most cases occurred one month postoperatively.

Evaluation of oral health-related quality of life and its association with mental health status of patients with type 2 diabetes mellitus in the post-COVID-19 pandemic era: A study from Central Saudi Arabia.

Background and objectives: The association between oral and mental health is reciprocal, in which poor oral health may lead to several mental health issues, especially among patients with diabetes. The present study evaluated oral health-related quality of life (OHRQOL) and its association with mental health conditions among patients with type 2 diabetes mellitus (T2DM) in central Saudi Arabia. Methods: The Arabic version of the Oral Health Impact Profile-14 (OHIP-14) questionnaire and the Depression, Anxiety, and Stress Scale-21 Items (DASS-21) were used to assess the OHRQOL and mental health status of patients with diabetes. We utilized logistic regression analysis to identify the predictors of poor OHRQOL, and Spearman's correlation test to identify any correlations between OHIP-14 and overall DASS-21 scores, as well as each subscale. Results: Of the 677 patients included in the present study, 52.7% had a poor OHRQOL, which was significantly higher (positive association) among patients with a longer duration of diabetes (adjusted odds ratio [AOR] = 3.31; 95% confidence interval [CI] = 1.96-4.17) and those who did not periodically monitor their oral health (AOR = 2.85; 95% CI = 1.76-3.89). Some forms (mild, moderate, severe, or extremely severe) of depression, anxiety, and stress were observed in 59.7, 71.1, and 67.1% of the participants, respectively. Furthermore, we found that the total OHRQOL scores had a significant positive association with depression (AOR = 2.32, 95% CI = 1.34-3.71, p = 0.001), anxiety (AOR = 1.81, 95% CI = 1.22-2.79, p = 0.003), and stress (AOR = 1.43, 95% CI = 1.14-2.19, p = 0.026). Conclusion: The results of the present study suggest the importance of appropriate and targeted health education programs for T2DM patients to ensure periodic dental examinations and oral health. Additionally, we recommend counseling sessions for all T2DM patients with trained healthcare providers to improve their mental health status during follow-up visits at outpatient diabetes care centers.

Synergistic Benefits: Exploring the Anti-Virulence Effects of Metformin/Vildagliptin Antidiabetic Combination against Pseudomonas aeruginosa via Controlling Quorum Sensing Systems.

The repurposing of drugs is one of the most competent strategies for discovering new antimicrobial agents. Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPI-4) that is used effectively in combination with metformin to control blood glucose levels in diabetic patients. This study was designed to evaluate the anti-virulence activities of this combination against one of the most clinically important pathogens, Pseudomonas aeruginosa. The current findings show a significant ability of the vildagliptin-metformin combination to diminish biofilm formation, bacterial motility, and the production of virulent extracellular enzymes and pyocyanin pigment. Furthermore, this drug combination significantly increased the susceptibility of P. aeruginosa to oxidative stress, indicating immunity enhancement in the eradication of bacterial cells. In compliance with the in vitro findings, the histopathological photomicrographs of mice showed a considerable protective effect of the metformin-vildagliptin combination against P. aeruginosa, revealing relief of inflammation due to P. aeruginosa-induced pathogenesis. P. aeruginosa mainly employs quorum sensing (QS) systems to control the production of its huge arsenal of virulence factors. The anti-virulence activities of the metformin-vildagliptin combination can be interrupted by the anti-QS activities of both metformin and vildagliptin, as both exhibited a considerable affinity to QS receptors. Additionally, the metformin-vildagliptin combination significantly downregulated the expression of the main three QS-encoding genes in P. aeruginosa. These findings show the significant anti-virulence activities of metformin-vildagliptin at very low concentrations (10, 1.25 mg/mL, respectively) compared to the concentrations (850, 50 mg/mL, respectively) used to control diabetes.

Antimicrobial Potential of Different Isolates of Chaetomium globosum Combined with Liquid Chromatography Tandem Mass Spectrometry Chemical Profiling.

The antimicrobial resistance of pathogenic microorganisms against commercial drugs has become a major problem worldwide. This study is the first of its kind to be carried out in Egypt to produce antimicrobial pharmaceuticals from isolated native taxa of the fungal Chaetomium, followed by a chemical investigation of the existing bioactive metabolites. Here, of the 155 clinical specimens in total, 100 pathogenic microbial isolates were found to be multi-drug resistant (MDR) bacteria. The Chaetomium isolates were recovered from different soil samples, and wild host plants collected from Egypt showed strong inhibitory activity against MDR isolates. Chaetomium isolates displayed broad-spectrum antimicrobial activity against C. albicans, Gram-positive, and Gram-negative bacteria, with inhibition zones of 11.3 to 25.6 mm, 10.4 to 26.0 mm, and 10.5 to 26.5 mm, respectively. As a consecutive result, the minimum inhibitory concentration (MIC) values of Chaetomium isolates ranged from 3.9 to 62.5 µg/mL. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis was performed for selected Chaetomium isolates with the most promising antimicrobial potential against MDR bacteria. The LC-MS/MS analysis of Chaetomium species isolated from cultivated soil at Assuit Governate, Upper Egypt (3), and the host plant Zygophyllum album grown in Wadi El-Arbaein, Saint Katherine, South Sinai (5), revealed the presence of alkaloids as the predominant bioactive metabolites. Most detected bioactive metabolites previously displayed antimicrobial activity, confirming the antibacterial potential of selected isolates. Therefore, the Chaetomium isolates recovered from harsh habitats in Egypt are rich sources of antimicrobial metabolites, which will be a possible solution to the multi-drug resistant bacteria tragedy.

Tailoring and optimization of a honey-based nanoemulgel loaded with an itraconazole-thyme oil nanoemulsion for oral candidiasis.

The use of essential oil-based nanoemulsions (NEs) has been the subject of extensive research on a variety of conditions affecting the oral cavity. NEs are delivery methods that improve the solubility and distribution of lipid medicines to the intended areas. Because of their antibacterial and antifungal properties, itraconazole and thyme oil-based self-nanoemulsifying drug delivery systems (ItZ-ThO-SNEDDS) were created to protect oral health against oral microorganisms. The ItZ-ThO-SNEDDS were created utilizing an extreme verices mixture design, and varying concentrations of ThO (10% and 25%), labrasol (40% and 70%), and transcutol (20% and 40%) were used. The ItZ-ThO-SNEDDS had droplet sizes of less than 250 nm, a drug-loading efficiency of up to 64%, and a fungal growth inhibition zone of up to 20 mm. The accepted design was used to obtain the ideal formulation, which contained ThO in the amount of 0.18 g/ml, labrasol 0.62 g/ml, and transcutol 0.2 g/ml. The best ItZ-ThO-SNEDDS formulation was incorporated into a honey-based gel, which demonstrated improved release of ItZ in vitro and improved transbuccal permeation ex vivo. In addition, when compared with various formulations tested in rats, the optimized loaded emulgel decreased the ulcer index. This study therefore demonstrated that the ItZ-ThO-SNEDDS could offer an effective defense against oral diseases caused by microbial infections.

A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses.

All the previously reported phenylpyrazoles as carbonic anhydrase inhibitors (CAIs) were found to have small sizes and high levels of flexibility, and hence showed low selectivity profiles toward a particular isoform of CA. Herein, we report the development of a more rigid ring system bearing a sulfonamide hydrophilic head and a lipophilic tail to develop novel molecules that are suggested to have a better selectivity toward a special CA isoform. Accordingly, three novel sets of pyrano[2,3-c]pyrazoles attached with sulfonamide head and aryl hydrophobic tail were synthesized to enhance the selectivity toward a specific isoform of human carbonic anhydrases (hCAs). The impact of both attachments on the potency and selectivity has been extensively discussed in terms of in vitro cytotoxicity evaluation under hypoxic conditions, structure-activity relationship and carbonic anhydrase enzyme assay. All of the new candidates displayed good cytotoxic activities against breast and colorectal carcinomas. Results of the carbonic anhydrase enzyme assay demonstrated the preferential of compounds 22, 24 and 27 to inhibit the isoform IX of hCAs selectively. Wound-healing assay has also been performed and revealed the potential of 27 to decrease the wound closure percentage in MCF-7 cells. Molecular docking and molecular orbital analysis have finally been conducted. Results indicate the potential binding interactions of 24 and 27 with several crucial amino acids of the hCA IX.Communicated by Ramaswamy H. Sarma.

Clustering algorithm with strength of connectedness for m-polar fuzzy network models.

In this research study, we first define the strong degree of a vertex in an m-polar fuzzy graph. Then we present various useful properties and prove some results concerning this new concept, in the case of complete m-polar fuzzy graphs. Further, we introduce the concept of m-polar fuzzy strength sequence of vertices, and we also investigate it in the particular instance of complete m-polar fuzzy graphs. We discuss connectivity parameters in m-polar fuzzy graphs with precise examples, and we investigate the m-polar fuzzy analogue of Whitney's theorem. Furthermore, we present a clustering method for vertices in an m-polar fuzzy graph based on the strength of connectedness between pairs of vertices. In order to formulate this method, we introduce terminologies such as ϵA-reachable vertices in m-polar fuzzy graphs, ϵA-connected m-polar fuzzy graphs, or ϵA-connected m-polar fuzzy subgraphs (in case the m-polar fuzzy graph itself is not ϵA-connected). Moreover, we discuss an application for clustering different companies in consideration of their multi-polar uncertain information. We then provide an algorithm to clearly understand the clustering methodology that we use in our application. Finally, we present a comparative analysis of our research work with existing techniques to prove its applicability and effectiveness.

Secondary Psychosis Following Neoadjuvant AC-T Chemotherapy for Triple-Negative Breast Cancer: Case Report and Literature Review of Psychosis Postchemotherapy.

Triple-negative breast cancer is a unique subtype among breast cancers. Management includes a neoadjuvant chemotherapy regimen. Psychiatric complications of the regimen have not been reported before. We present a case of acute psychosis after the second cycle of chemotherapy in a 42-year-old woman with triple-negative breast cancer. The patient presented with sudden irritability, agitation, disorganization in speech and behavior, and paranoia involving her coworkers conspiring against her and causing her trouble with the law for 4 days. She was in her usual state of health until after her second cycle of chemotherapy. This was the first presentation of psychotic symptoms in her life. She was conscious and oriented. There were no neurologic deficits. She denied any change in her mood and any features of hallucinations. She was uncooperative, restless, had flight of ideas, and persecutory delusions. The remainder of the examination was normal. An autoimmune process, nervous system infection, or psychosis secondary to the chemotherapy were suspected. Serum electrolytes and other biochemical parameters were normal. Imaging of the brain showed no signs of acute brain insults or intracranial metastasis. Cerebrospinal fluid analysis and culture showed no abnormality or growth. The work-up revealed that neurologic, infectious, or autoimmune causes of her psychotic symptoms were less likely. Thus, a diagnosis of psychosis secondary to chemotherapy was considered. Treatment was with paliperidone, risperidone, clonazepam, and sertraline. Over the course of treatment, she showed substantial improvement and completed all of the chemotherapy sessions without adverse effects. In summary, we report a case of a patient whose initial chemotherapy course was complicated by psychosis. Since the neurotoxic and psychiatric effects of chemotherapeutics are not yet sufficiently elucidated, our case emphasizes that early signs of behavioral changes in patients receiving chemotherapy should trigger comprehensive psychiatric evaluation and monitoring of the patient's mental state.