Microrobotics in endodontics: A perspective.

Microorganisms are the primary aetiological factor of apical periodontitis. The goal of endodontic treatment is to prevent and eliminate the infection by removing the microorganisms. However, microbial biofilms and the complex root canal anatomy impair the disinfection process. Effective and precise endodontic therapy could potentially be achieved using advanced multifunctional technologies that have the ability to access hard-to-reach surfaces and perform simultaneous biofilm killing, removal, and detection of microorganisms. Advances in microrobotics are providing novel therapeutic and diagnostic opportunities with high precision and efficacy to address current biofilm-related challenges in biomedicine. Concurrently, multifunctional magnetic microrobots have been developed to overcome the disinfection challenges of current approaches to disrupt, kill, and retrieve biofilms with the goal of enhancing the efficacy and precision of endodontic therapy. This article reviews the recent advances of microrobotics in healthcare and particularly advances to overcome disinfection challenges in endodontics, and provides perspectives for future research in the field.

Luteolin 4'-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo.

Multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for the development of new potential antimicrobials. This research investigated whether luteolin 4'-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, fosA-positive shiga toxin producing the Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti-K. pneumoniae (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of B. cereus, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), and immunoglobulin (IgM). Additionally, the renal and pulmonary lesions were remarkably enhanced, with a significant decrease in the bacterial loads in the tissues. Finally, this study presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti-K. pneumoniae potential, a finding which is reported here for the first time.

Isochlorogenic Acid Glucosides from the Arabian Medicinal Plant Artemisia sieberi and Their Antimicrobial Activities.

A phytochemical investigation of the stems of the Arabian plant Artemisia sieberi afforded three new isochlorogenic acid derivatives, namely isochlorogenic acid A-3'-O-ß-glucopyranoside (1), isochlorogenic acid A-3'-O-ß-glucopyranoside methyl ester (2), and isochlorogenic acid C-3'-O-ß-glucopyranoside (3), obtained along with thirteen known secondary metabolites belonging to distinct structural classes. The structures of the new metabolites were elucidated by modern spectroscopic techniues based on high-resolution mass spectrometry (HR-ESIMS) and 1D/2D nuclear magnetic resonance (NMR). All isolated compounds were tested for their potential antimicrobial activity against four different bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), in addition to a fungal strain (Candida tropicalis), The results were expressed as the diameter of the clear zone (in millimetres) around each well. Compounds 1 and 3 (isochlorogenic acid A-3'-O-ß-glucopyranoside and isochlorogenic acid C-3'-O-ß-glucopyranoside, respectively) displayed remarkable antifungal effect and potent antibacterial activities against B. subtilis and S. aureus, respectively. 3α,4α-10ß-trihydroxy-8α-acetyloxyguaian-12,6α-olide (6) and angelicoidenol 2-O-ß-d-glucopyranoside (9) emerged as interesting dual antibacterial (selective on P. aeruginosa)/antifungal agents.

Proposed Mechanism for Emodin as Agent for Methicillin Resistant Staphylococcus Aureus: In Vitro Testing and In Silico Study.

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge of the drug target, α-hemolysin of Staphylococcus aureus was used in this study because it has an essential role in Staphylococcus infections and because emodin shares structural features with compounds that target this enzyme. In order to explore emodin's interactions with α-hemolysin, all possible ligand binding pockets were identified and investigated. Two ligand pockets were detected based on bound ligands and other reports. The third pocket was identified as a cryptic site after molecular dynamics (MD) simulations. MD simulations were conducted for emodin in each pocket to identify the most plausible ligand site and to aid in the design of potent anti-MRSA agents. Binding of emodin to site 1 was most stable (RMSD changes within 1 Å), while in site 2, the binding pose of emodin fluctuated, and it left after 20 ns. In site 3, it was stable during the first 50 ns, and then it started to move out of the binding site. Site 1 is a possible ligand binding pocket, and this study sheds more light on interaction types, binding mode, and key amino acids involved in ligand binding essential for better lead design. Emodin showed an IC50 value of 6.3 µg/mL, while 1, 6, and 8 triacetyl emodin showed no activity against MRSA. A molecular modeling study was pursued to better understand effective binding requirements for a lead.

Milk-Compositional Study of Metabolites and Pathogens in the Milk of Bovine Animals Affected with Subclinical Mastitis.

Bovine milk is an important food component in the human diet due to its nutrient-rich metabolites. However, bovine subclinical mastitis alters the composition and quality of milk. In present study, California mastitis testing, somatic cell count, pH, and electrical conductivity were used as confirmatory tests to detect subclinical mastitis. The primary goal was to study metabolome and identify major pathogens in cows with subclinical mastitis. In this study, 29 metabolites were detected in milk using gas chromatography−mass spectrometry. Volatile acidic compounds, such as hexanoic acid, hexadecanoic acid, lauric acid, octanoic acid, n-decanoic acid, tricosanoic acid, tetradecanoic acid, and hypogeic acid were found in milk samples, and these impart good flavor to the milk. Metaboanalyst tool was used for metabolic pathway analysis and principal component estimation. In this study, EC and pH values in milk were significantly increased (p < 0.0001), whereas fat (p < 0.04) and protein (p < 0.0002) significantly decreased in animals with subclinical mastitis in comparison to healthy animals. Staphylococcus aureus was the predominant pathogen found (n = 54), followed by Escherichia coli (n = 30). Furthermore, antibiotic sensitivity revealed that Staphylococcus aureus was more sensitive to gentamicin (79.6%), whereas Escherichia coli showed more sensitivity to doxycycline hydrochloride (80%).

Design, Synthesis, and Antimicrobial Activity of Certain New Indole-1,2,4 Triazole Conjugates.

The increasing prevalence of microbial infections and the emergence of resistance to the currently available antimicrobial drugs urged the development of potent new chemical entities with eminent pharmacokinetic and/or pharmacodynamic profiles. Thus, a series of new indole-triazole conjugates 6a-u was designed and synthesized to be assessed as new antimicrobial candidates using the diameter of the inhibition zone and minimum inhibitory concentration assays against certain microbial strains. Their in vitro antibacterial evaluation revealed good to moderate activity against most of the tested Gram-negative strains with diameter of the inhibition zone (DIZ) values in the range of 11-15 mm and minimum inhibition concentration (MIC) values around 250 µg/mL. Meanwhile, their in vitro antifungal evaluation demonstrated a potent activity against Candida tropicalis with MIC value as low as 2 µg/mL for most of the tested compounds. Moreover, compound 6f is the most potent congener with an MIC value of 2 µg/mL against Candida albicans.

Experimental Solubility, Thermodynamic/Computational Validations, and GastroPlus-Based In Silico Prediction for Subcutaneous Delivery of Rifampicin.

We focused to explore a suitable solvent for rifampicin (RIF) recommended for subcutaneous (sub-Q) delivery [ethylene glycol (EG), propylene glycol (PG), tween 20, polyethylene glycol-400 (PEG400), oleic acid (OA), N-methyl-2-pyrrolidone (NMP), cremophor-EL (CEL), ethyl oleate (EO), methanol, and glycerol] followed by computational validations and in-silico prediction using GastroPlus. The experimental solubility was conducted over temperature ranges T = 298.2-318.2 K) and fixed pressure (p = 0.1 MPa) followed by validation employing computational models (Apelblat, and van't Hoff). Moreover, the HSPiP solubility software provided the Hansen solubility parameters. At T = 318.2K, the estimated maximum solubility (in term of mole fraction) values of the drug were in order of NMP (11.9 × 10-2) ˃ methanol (6.8 × 10-2) ˃ PEG400 (4.8 × 10-2) ˃ tween 20 (3.4 × 10-2). The drug dissolution was endothermic process and entropy driven as evident from "apparent thermodynamic analysis". The activity coefficients confirmed facilitated RIF-NMP interactions for increased solubility among them. Eventually, GastroPlus predicted the impact of critical input parameters on major pharmacokinetics responses after sub-Q delivery as compared to oral delivery. Thus, NMP may be the best solvent for sub-Q delivery of RIF to treat skin tuberculosis (local and systemic) and cutaneous related disease at explored concentration.

Pluronic-Coated Biogenic Gold Nanoparticles for Colon Delivery of 5-Fluorouracil: In vitro and Ex vivo Studies.

The aim of the study was to prepare 5-fluorouracil (5-FU)-loaded biogenic gold nanoparticles with pluronic-based coating (PFGNPs), their optimization (full factorial predicted OBPN-1) and in vitro-ex vivo evaluation. Several formulations were prepared, selected for optimization using Design Expert®, and compared for morphology, 5-FU release kinetics, compatibility, cell line toxicity, in vitro hemocompatibility, and ex vivo intestinal permeation across the rat duodenum, jejunum, and ileum. The pluronic-coated 5-FU-carrying GNPs were spherical, 29.11-178.21 nm in diameter, with a polydispersity index (PDI) range of 0.191-292, and a zeta potential (ZP) range of 11.19-29.21 (-mV). The optimized OBPN-1 (desirability = 0.95) demonstrated optimum size (175.1 nm), %DL as 73.8%, ZP as 21.7 mV, % drug release (DR) as 75.7%, and greater cytotoxicity (viability ~ 8.9%) against the colon cancer cell lines than 5-FU solution (~ 24.91%), and less hemocompatibility. Moreover, OBPN-1 exhibited 4.5-fold permeation across the rat jejunum compared with 5-FU solution. Thus, the PFGNPs exhibit high DL capacity, sustained delivery, hemocompatibility, improved efficacy, and enhanced permeation profiles compared with 5-FU solution and several other NPs preparations suggesting it is a promising formulation for effective colon cancer control with reduced side effects.

An in vitro investigation comparing methods of minimizing excess luting agent for cement-retained implant-supported fixed partial dentures.

STATEMENT OF PROBLEM: The use of cement-retained implant-supported prostheses is a well-established treatment option. Techniques have been proposed to reduce the amount of residual excess cement (REC) around cement-retained single-implant restorations. However, studies evaluating the effectiveness of such techniques related to cement-retained implant-supported fixed partial dentures (CRISFPDs) are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effectiveness of various cement application techniques for CRISFPDs. MATERIAL AND METHODS: Two implant analogs were placed in the lateral incisor sites in a maxillary, 3D printed cast with 4 missing incisors. Twenty standardized, removable, printed soft-tissue replicas, 40 milled titanium custom abutments, and 20 milled zirconia CRISFPDs were fabricated. Two cement application techniques, the brush on technique (BOT), and the polyvinyl siloxane index (PI) technique were compared. Two cementation techniques, without bib (control) (n=10) and with a polytetrafluoroethylene (PTFE) bib (test) (n=10), were used. A premeasured amount of interim cement was used to cement the CRISFPDs. The CRISFPDs were retrieved after cementation, and standardized photographs of 4 quadrants of each abutment-CRISFPD assembly were made by using a software program that is used to calculate the ratio between the area covered with REC and the total specimen area. The extension of the REC on both the abutment and soft-tissue replica was measured at sites before and after cleaning the REC. A generalized linear mixed-model procedure was used for statistical analysis (α=.05). RESULTS: For cement application, the polyvinyl siloxane (PVS) index technique had significantly less REC than the brush on technique (P<.05). The use of a PTFE bib led to significantly less REC than when no bib was used (P<.05). CONCLUSIONS: The use of the PVS index technique along with a PTFE bib was effective in reducing REC for CRISFPDs.

Association of OprF mutant and disturbance of biofilm and pyocyanin virulence in pseudomonas aeruginosa.

Outer membrane porin F (OprF) is a major structural membrane protein of Pseudomonas aeruginosa, a recognised human opportunistic pathogen which is correlated with severe hospital-acquired infections. This study investigating a multiphenotypic approach, based on the comparative study of a wild type strain of P. aeruginosa, its isogenic OprF mutant. Both P. aeruginosa PAO1 and OprF mutant strains were grown in same condition and cultures were subjected to further analysis by SDS PAGE, pyocyanin production and biofilm formation that was analyse using scanning electron microscopy. Based on biofilm formation essay and pyocyanin production, the study showed that OprF plays a dynamic role in P. aeruginosa virulence. The absence of OprF results in slow growth rate corresponded to elongated lag phase and reduced biofilm production also a significance reduction in the production of the quorum-sensing-dependent virulence factors pyocyanin. Accordingly, in the OprF mutant scanning electron microscope "SEM" images showed impaired cellular niche and detached cells when compared to regular attached P. aeruginosa wild type cells in the niche. Taken together, this study shows the contribution of OprF in P. aeruginosa virulence, at least partly through impairment of biofilm, cell to cell attachment in niche and pyocyanin production. This study show a vital link between OprF and virulence factor production, providing novel insights for its role in pathogenicity and future could provide the basis for the development of novel drug targets for antibiotics and vaccines.

Coronavirus nCOVID-19: A pandemic disease and the Saudi precautions.

Now nCOVID-19 has a foothold in many countries, and the threat of a pandemic situation has risen. Recently a novel coronavirus (nCOVID-19) has first emerged in China, causing multiple symptoms in humans and closely related to those caused by SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The nCOVID-19 has reported in Wuhan city of China has recently infected over six million people and at least 0.4 million confirmed deaths all over the world, while 2.8 million people has recovered from this deadly virus. Many instances of this respiratory syndrome coronavirus infection have already reported in more than 216 countries and territories. In contrast, the majority of cases reported in the USA, Brazil, Russia, Spain, UK, Italy, France and many more countries. In today's context, the coronavirus is one of the significant issues faced by the world with plenty of cases. In these circumstances, rapid reviews which recommended by WHO (World Health Organization), and these recommendations are very significant, helpful and cover current data with different preventive measures developed by the Saudi CDC (Saudi Centre for Disease Prevention and Control). This review article describes the possible modes of transmission so that proper preventive actions should be taking. Importantly, this work mentioned the animal reservoir through which may infect humans, and it must be identified to break the transmission chain. In additions, this review paper briefly discussed the spread of the coronavirus in the Arabian Peninsula and what precaution measures are in place by each country to limit the spreading of this virus. Finally, since the number of infected people specifically those with close contact with nCOVID-19 patients is increasing daily and appears unstoppable, we used the preventive measures by pharmacists as part of health care professions.

Synthesis and Antimicrobial Activity of a New Series of Thiazolidine-2,4-diones Carboxamide and Amino Acid Derivatives.

Novel thiazolidine-2,4-dione carboxamide and amino acid derivatives were synthesized in excellent yield using OxymaPure/N,N'-diisopropylcarbodimide coupling methodology and were characterized by chromatographic and spectrometric methods, and elemental analysis. The antimicrobial and antifungal activity of these derivatives was evaluated against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), two-Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and one fungal isolate (Candida albicans). Interestingly, several samples demonstrated weak to moderate antibacterial activity against Gram-negative bacteria, as well as antifungal activity. However, only one compound namely, 2-(5-(3-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid, showed antibacterial activity against Gram-positive bacteria, particularly S. aureus.

Use of Implant-Supported Custom Milled Impression Copings to Capture Soft-Tissue Contours and Incisal Guidance.

A technique is presented where a custom milled impression coping is used to replicate the clinically established anterior incisal guidance to the definitive prosthesis when multiple implants are restored in the esthetic zone. A conventional impression is initially made, then the stone cast is scanned, and a digitally designed custom screw-retained, implant-supported interim prosthesis is milled from a polymethylmethacrylate (PMMA) billet. This is aimed to digitally design the pontic areas, contour the gingival soft tissue, and establish an anterior incisal guidance. A custom milled impression coping (CMIC) is then fabricated. The CMIC has contours similar to the contours of the interim prosthesis and is fabricated from a PMMA billet. Titanium inserts are placed in the interim prosthesis and the CMIC. The CMIC is inserted intraorally and used for the final impression by using a custom tray and by following the open tray impression protocol. With the proposed technique, the exact contours of the digitally designed and clinically verified interim prosthesis are used to fabricate the definitive restoration.

Predictable prosthetic space maintenance during staged complete-mouth rehabilitation.

Staged complete-mouth rehabilitation to accommodate a patient's financial constraints during the course of treatment is presented. Clear acrylic resin added to the anterior cameo surface of the maxillary fixed complete denture (FCD) served as a space maintainer. The restoration of the maxillary FCD addressed the patient's chief complaint. By adding the space maintainer, supraeruption of mandibular anterior teeth and encroachment of the prosthetic space, which could have resulted in additional treatment, was avoided. During the second stage of the complete-mouth rehabilitation, zirconia restorations were used to restore the mandibular arch to the maxillary FCD after straightforward removal of the space maintainer. This allowed a smooth transition after a delay in treatment without having to modify the previous treatment.

Three-dimensional printing in contemporary fixed prosthodontics: A technique article.

Digital dentistry has gained in popularity among clinicians and laboratory technicians because of its versatile applications. Three-dimensional (3D) printing has been applied in many areas of dentistry as it offers efficiency, affordability, accessibility, reproducibility, speed, and accuracy. This article describes a technique where 3D printing is used to fabricate a die-trimmed cast and to replicate gingival tissue and implant analogs. The digital workflow that replaces the conventional laboratory procedure is outlined.

Use of Patient's Own Natural Teeth as Part of the Interim Prosthesis on Immediately Placed Single Implants in a Staged Surgical Approach: A Clinical Report.

A technique is described where the tooth's natural crown is used as part of the interim implant supported prosthesis in clinical situations where a tooth with poor prognosis is extracted and an implant is placed immediately after tooth extraction. A preliminary impression is made before tooth extraction, and the exact tooth positioning is assessed in the laboratory as part of the treatment plan. An acrylic resin repositioning jig is fabricated that will guide the clinician in seating and orienting the crown intraorally after implant placement is completed. After the natural tooth is extracted and an implant is immediately placed via guided approach, the extracted natural crown is hollowed and placed on top of an interim abutment. The natural crown is positioned intraorally by using the acrylic resin repositioning jig. The crown is then internally relined and placed as part of the interim implant supported prosthesis. After osseointegration has been confirmed, a definitive prosthesis is placed.

Formulation of silymarin binary and ternary solid dispersions: Characterization, simulation study and cell viability assessment against lung cancer cell line.

Silymarin (SL) is a water-insoluble flavonoid used in the treatment of different diseases, but its therapeutic activity is limited due to its low solubility. So, in the present study, SL solid dispersions (SDs) were developed using different carriers like Kollidone VA64 (KL), Soluplus (SP), and Poloxamer 188 (PL) by solvent evaporation (SE), microwave irradiation (MI), and freeze-drying (FD) methods. The phase solubility and saturation solubility studies were assessed to estimate the stability constant as well as the carrier effect. The dissolution studies were performed for prepared SL-SDs (binary and ternary) to select the optimum SL-SDs. The selected SL-SDs (F5, F9) were further characterized for infrared spectroscopy (IR), nuclear magnetic resonance (NMR), differential scanning calorimeter (DSC), scanning electron microscope (SEM), and X-ray diffraction (XRD). Finally, the comparative cell viability assay (lung cancer cell line) was performed to evaluate the change in activity after the formulation of SDs. The phase solubility and solubility study results displayed marked enhancements in solubility. The dissolution study findings showed significant enhancement in drug release from ternary solid dispersions (F7-F9) > ternary physical mixture (PM3) > binary solid dispersions (F1-F6) > binary physical mixture (PM1, PM2) in comparison to free SL. A greater release was observed from ternary SDs due to the addition of PL in the formulation, which had a synergistic effect on increasing the solubility. IR and NMR spectra revealed no chemical interaction between SL, KL, and PL. DSC, XRD, and SEM all confirmed the transformation of crystalline SL into amorphous SL. The cell viability assay demonstrated significantly enhanced results from ternary solid dispersion (F9) compared to free SL. Based on the study results, it can be said that SL-SDs are an alternative way to deliver drugs orally that can improve solubility and have anti-cancer activity.

A Novel Inhalable Dry Powder to Trigger Delivery of Voriconazole for Effective Management of Pulmonary Aspergillosis.

Invasive pulmonary aspergillosis (IPA) is a fatal fungal infection with a high mortality rate. Voriconazole (VCZ) is considered a first-line therapy for IPA and shows efficacy in patients for whom other antifungal treatments have been unsuccessful. The objective of this study was to develop a high-potency VCZ-loaded liposomal system in the form of a dry-powder inhaler (DPI) using the spray-drying technique to convert liposomes into a nanocomposite microparticle (NCMP) DPI, formulated using a thin-film hydration technique. The physicochemical properties, including size, morphology, entrapment efficiency, and loading efficiency, of the formulated liposomes were evaluated. The NCMPs were then examined to determine their drug content, production yield, and aerodynamic size. The L3NCMP was formulated using a 1:1 lipid/L-leucine ratio and was selected for in vitro studies of cell viability, antifungal activity, and stability. These formulated inhalable particles offer a promising approach to the effective management of IPA.

Enhancing the Topical Antibacterial Activity of Fusidic Acid via Embedding into Cinnamon Oil Nano-Lipid Carrier.

Presently, antimicrobial resistance is of great risk to remarkable improvements in health conditions and infection management. Resistance to various antibiotics has been considered a great obstacle in their usage, necessitating alternative strategies for enhancing the antibacterial effect. Combination therapy has been recognized as a considerable strategy that could improve the therapeutic influence of antibacterial agents. Therefore, the aim of this study was to combine the antibacterial action of compounds of natural origin like fusidic acid (FA) and cinnamon essential oil (CEO) for synergistic effects. A distinctive nanoemulsion (NE) was developed using cinnamon oil loaded with FA. Applying the Box-Behnken design (BBD) approach, one optimized formula was selected and integrated into a gel base to provide an FA-NE-hydrogel for optimal topical application. The FA-NE-hydrogel was examined physically, studied for in vitro release, and investigated for stability upon storage at different conditions, at room (25 °C) and refrigerator (4 °C) temperatures, for up to 3 months. Ultimately, the NE-hydrogel preparation was inspected for its antibacterial behavior using multidrug-resistant bacteria and checked by scanning electron microscopy. The FA-NE-hydrogel formulation demonstrated a pH (6.32), viscosity (12,680 cP), and spreadability (56.7 mm) that are acceptable for topical application. The in vitro release could be extended for 6 h, providing 52.0%. The formulation was stable under both test conditions for up to 3 months of storage. Finally, the FA-NE-hydrogel was found to inhibit the bacterial growth of not only Gram-positive but also Gram-negative bacteria. The inhibition was further elucidated by a scanning electron micrograph, indicating the efficiency of CEO in enhancing the antibacterial influence of FA when combined in an NE system.