Evaluation of postoperative pain in endodontic retreatment with apical periodontitis using ozonated 2% chlorhexidine and 0.1% octenidine application: A randomized clinical trial.

Introduction: This study aimed to evaluate and compare postoperative pain (PP) in single-visit nonsurgical endodontic retreatment (SV NSER) with 2% chlorhexidine (CHX), 0.1% octenidine (OCT) with or without ozone, and 5.25% sodium hypochlorite (NaOCl). Materials and Methods: In this randomized, parallel, prospective, double-blind, clinical trial, 132 single-rooted, root-filled teeth with symptomatic apical periodontitis (AP) requiring NSER were allocated into six groups randomly (n = 22/group): 2% CHX with NaOCl (CHXH), 2% Ozonated CHX without NaOCl (OCHX), 2% Ozonated CHX with NaOCl (OCHXH), 0.1% OCT with NaOCl (OCTH), 0.1% Ozonated OCT without NaOCl (OOCT), and 0.1% Ozonated OCT with NaOCl (OOCTH). Standard NSER protocol was followed groups were irrigated with 15 ml of ozonated or nonozonated irrigant (CHX/OCT) for 3-5 min with ultrasonic agitation. PP at baseline, after 6, 12, 24, 48 h, and 7 days was recorded using the Visual Analog Scale (VAS). Logistic regression of predictor variables was compared using the Chi-square test. For group-wise and time-wise comparisons, a two-way analysis of variance followed by the post hoc Bonferroni test was carried out. Results: None of the patient-related variables in logistic regression obtained a statistically significant (P > 0.05) role in PP. The VAS score after 6 h was OCHX (4.72) > OOCT (4.42) > CHXH (4.23) > OCTH (3.95) > OCHXH (3.42) > OOCTH (3.21). OOCTH and OCHXH groups demonstrated statistically significant reductions in VAS scores at various time intervals (P < 0.05). Conclusion: SV NSER with ozonated OCT, CHX irrigation, and NaOCl resulted in lesser PP at all time intervals, i.e., 6, 12, 24, 48 h, and 7 days in patients with symptomatic AP.

Saliva as a propitious diagnostic biofluid, biomarker, and bodies first line of defense against COVID-19: A review.

This review aims to recognize the role of saliva not just as a transmitting agent of COVID 19, but also comprehend its role in the diagnosis, and as a biomarker. A systematic literature search was performed in the PubMed database and eligible studies were included if they addressed the key issues i.e saliva as a diagnostic aid. As of January 10, 2021, a total of 309 articles across the PubMed database were identified of which 28 studies met the inclusion criteria. They were carefully examined for the type of study, sample size, parameters used, sample collection technique, and conclusions drawn. Diagnostic properties of saliva, the role of ACE 2 receptors, antibody formation ability, and antiviral characteristics were also explored. Comparisons among methods of sample collection like nasopharyngeal swabs and oropharyngeal swabs to saliva were also investigated. The observations and important deductions among the different studies were compared. Results indicated that saliva could be a reliable and financially viable option in both testing viral titers as well as marking for bio analytes due to its propitious specificity and sensitivity results reported in most of the studies. However, the inferences drawn from many of these studies should be interpreted with caution due to small sample sizes, inadequate detailing on the sample handling, laboratory processing, and rush in Corona-related publication. Scientific research with larger sample sizes, in diverse populations and age groups, at different phases of disease progression of COVID-19 are essential to reach any conclusion regarding its multi-facet use in the future.

Imiquimod-gemcitabine nanoparticles harness immune cells to suppress breast cancer.

Monotherapy with a single chemotherapeutic regimen has met with significant hurdles in terms of clinical efficacy. The complexity of cancer accentuates the need for an alternative approach with a combination of two or more therapeutic regimens to win the battle. However, it is still a challenge to develop a successful combination of drugs with high efficiency and low toxicity to control cancer growth. While gemcitabine monotherapy remains a choice of standard treatment for advanced breast cancer, the approach has not prolonged the median survival time of metastatic breast cancer patients. Here, we report a hyaluronic acid (HA)-based drug combination of gemcitabine (GEM) with imiquimod (IMQ) to stimulate immune cells for anticancer activity. Treatment of the drug combination (IMQ-HA-GEM) showed enhanced anticancer activity against 4T1 breast tumor cells in vitro. Our study with a microfluidics-based 3D, compartmentalized cancer model showed that infiltration of THP-1 monocytes occurred particularly at the site of cancer cells treated with IMQ-HA-GEM. Moreover, IMQ-HA-GEM significantly suppressed the volume of 4T1 breast tumor of mice in vivo. Flow cytometry study displayed a significantly higher activation of CD11b+ immune cells in the blood of mice treated with IMQ-HA-GEM, whereas immunohistochemistry study revealed greater prevalence of CD68+ tumor-associated macrophages in the tumor. Histological examination of isolated tumors of mice treated with IMQ-HA-GEM further confirmed the efficacy of drug combination on cancer cells. This study supports the conclusion that imiquimod potentiates the effect of gemcitabine by activating immune cells to suppress tumors in the form of combination nanoparticles.

Evaluation of Ozone Therapy in Endodontic Treatment of Teeth with Necrotic Pulp and Apical Periodontitis: A Randomized Clinical Trial.

INTRODUCTION: The aim of this study was to compare the effect of different application techniques of ozone on the prevalence of postendodontic pain in patients undergoing single-visit root canal treatment. METHODS: hundred eight patients with necrotic pulp in single-rooted teeth and apical periodontitis participated in the trial. A standard single-visit endodontics protocol was followed with 5.25% sodium hypochlorite and rotary nickel-titanium files. After shaping and cleaning, patients were randomly allocated into the following groups: group 1 (n = 21), ozone treatment with no activation (NA); group 2 (n = 22), ozone treatment with manual dynamic activation (MDA); group 3, (n = 21), ozone treatment with passive ultrasonic activation (PUA); group 4 (n = 23), ozone treatment with sonic activation (SA); and group 5 (n = 21), no ozone treatment (the control group). Patient levels of discomfort were recorded at 6 different time intervals using the visual analog scale (VAS). Comparison of the mean difference between the groups and time intervals was performed using 2-way analysis of variance followed by a post hoc Bonferroni test. The level of significance was set at 5%. RESULTS: VAS scores were highest for the control > NA > MDA > SA > PUA groups. A statistically significant reduction in VAS scores was observed in the PUA and SA groups in comparison with the NA, control, and MDA groups. Timewise comparison showed a highly significant decline in VAS scores at all time intervals (P < .001). CONCLUSIONS: Ultrasonic and sonic activation of ozone resulted in less pain in patients undergoing single-visit endodontics compared with no ozone treatment.

A prospective case-control study to evaluate oral health status before and after intervention using different dental aids in children with visual impairment.

BACKGROUND: A major dental concern in children with special health-care needs is poor oral hygiene, which results in increased incidences of dental caries, gingivitis, and periodontal disease. AIMS: The study intended to determine if there was a difference in the oral health status of children with visual impairment and normal children and to evaluate the efficacy of the frequently used dental aids. SETTINGS AND DESIGN: The study population included 90 children, 45 children with visual impairment (study group) with age- and sex-matched 45 normal children (control group). Both the groups were further divided into three intervention subgroups. Subgroup A: manual toothbrushes, Subgroup B: manual toothbrush with medicated mouthwashes, and Subgroup C: powered toothbrushes. MATERIALS AND METHODS: For each subject, oral hygiene index simplified (OHIS), Turesky-Gilmore-Glickman modification of the Quigley-Hein Plaque Index (TQPHI), and decayed missing filled teeth (DMFT) indices were recorded at baseline, i.e., before any intervention. This was followed by oral prophylaxis by ultrasonic scaling. The three indices were recorded in 0 (baseline), 30 days (1 month), 90 days (3 months), and 180 days (6 months), respectively. STATISTICAL ANALYSIS USED: ANOVA test, Chi-square test, and student paired test were used for statistical analysis. RESULTS: The mean TQHPI and OHIS values of mouthwashes at the end of 6 months were 1.01 and 1.60, respectively, which were lower than manual and power brushes. No statistically significant reduction in the DMFT scores with the use of any of the adjuncts was noted. CONCLUSIONS: Among the dental aids used in the study, mouthwash showed a significant reduction in plaque and oral hygiene scores as compared to powered toothbrushes and manual brushes alone.

Sustained, local delivery of the PARP inhibitor talazoparib prevents the development of mammary gland hyperplasia in Brca1-deficient mice.

Mutations in BRCA genes are the leading cause of hereditary breast cancer. Current options to prevent cancer in these high-risk patients, such as anti-estrogen drugs and radical mastectomy, are limited by lack of efficacy, undesirable toxicities, or physical and emotional challenges. We have previously shown that PARP inhibitors can significantly delay tumor development in BRCA1-deficient mice. Here, we fabricated the PARP inhibitor talazoparib (TLZ) into spacer implants (InCeT-TLZ) for localized and sustained delivery. We hypothesized that this novel formulation will provide an effective chemopreventive strategy with minimal toxicity. TLZ was released gradually over 30 days as implants degraded. InCeT-TLZ significantly decreased proliferation and increased DNA damage in the mammary glands of BRCA1-deficient mice. Notably, the number of mice that developed hyperplasia in the mammary glands was significantly lower with InCeT-TLZ treatment compared to the control group. Meanwhile, InCeT-TLZ was also better tolerated than oral TLZ, without loss of body weight or anemia. This study provides proof of concept for a novel and safe chemopreventive strategy using localized delivery of a PARP inhibitor for high-risk individuals. Future studies will directly evaluate the effects of InCeT-TLZ for preventing tumor development.

Nanoparticle Formulations of Poly (ADP-ribose) Polymerase Inhibitors for Cancer Therapy.

A number of poly(ADP-ribose) polymerase (PARP) inhibitors have been recently approved for clinical use in BRCA mutated and other cancers. However, off-target toxicity of PARP inhibitors and the emergence of drug resistance following prolonged administration of these inhibitors indicate the need for improved methods of drug delivery to the tumors. Nanomedicines based upon nanoparticle formulations of conventional small molecule drugs and inhibitors offer many advantages, such as increased solubility and bioavailability of drugs, reduced toxicity and drug resistance, and improved tissue selectivity and therapeutic efficacy. This review highlights the current trends in formulations of PARP inhibitors developed by nanotechnology approaches and provides an insight into the applications and limitations of these PARP inhibitor nanomedicines for cancer therapies.

Author Correction: Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Roadmap for metal nanoparticles in radiation therapy: current status, translational challenges, and future directions.

This roadmap outlines the potential roles of metallic nanoparticles (MNPs) in the field of radiation therapy. MNPs made up of a wide range of materials (from Titanium, Z = 22, to Bismuth, Z = 83) and a similarly wide spectrum of potential clinical applications, including diagnostic, therapeutic (radiation dose enhancers, hyperthermia inducers, drug delivery vehicles, vaccine adjuvants, photosensitizers, enhancers of immunotherapy) and theranostic (combining both diagnostic and therapeutic), are being fabricated and evaluated. This roadmap covers contributions from experts in these topics summarizing their view of the current status and challenges, as well as expected advancements in technology to address these challenges.

Harnessing cells to deliver nanoparticle drugs to treat cancer.

Clinical translation of nanoparticle drug (nanodrug) delivery systems for cancer therapy is primarily hindered by short half-life of nanodrugs in blood circulation and their poor ability of tumor targeting and penetration in vivo. Circulatory cells have garnered much attention in cancer therapy as drug delivery vehicles due to their biocompatibility, high mobility, biodegradability, tissue targeting capability, high drug loading capacity, ability to cross biological barriers and inherent ability to remain in blood circulation long enough to accumulate within the tumors. Here, we review the progress and potential of circulatory cells as nanodrug delivery vehicles, especially for cancer therapy.

Selective Priming of Tumor Blood Vessels by Radiation Therapy Enhances Nanodrug Delivery.

Effective drug delivery is restricted by pathophysiological barriers in solid tumors. In human pancreatic adenocarcinoma, poorly-permeable blood vessels limit the intratumoral permeation and penetration of chemo or nanotherapeutic drugs. New and clinically viable strategies are urgently sought to breach the neoplastic barriers that prevent effective drug delivery. Here, we present an original idea to boost drug delivery by selectively knocking down the tumor vascular barrier in a human pancreatic cancer model. Clinical radiation activates the tumor endothelial-targeted gold nanoparticles to induce a physical vascular damage due to the high photoelectric interactions. Active modulation of these tumor neovessels lead to distinct changes in tumor vascular permeability. Noninvasive MRI and fluorescence studies, using a short-circulating nanocarrier with MR-sensitive gadolinium and a long-circulating nanocarrier with fluorescence-sensitive nearinfrared dye, demonstrate more than two-fold increase in nanodrug delivery, post tumor vascular modulation. Functional changes in altered tumor blood vessels and its downstream parameters, particularly, changes in Ktrans (permeability), Kep (flux rate), and Ve (extracellular interstitial volume), reflect changes that relate to augmented drug delivery. The proposed dual-targeted therapy effectively invades the tumor vascular barrier and improve nanodrug delivery in a human pancreatic tumor model and it may also be applied to other nonresectable, intransigent tumors that barely respond to standard drug therapies.

Needle-Free Immunization with Chitosan-Based Systems.

Despite successful use, needle-based immunizations have several issues such as the risk of injuries and infections from the reuse of needles and syringes and the low patient compliance due to pain and fear of needles during immunization. In contrast, needle-free immunizations have several advantages including ease of administration, high level of patient compliance and the possibility of mass vaccination. Thus, there is an increasing interest on developing effective needle-free immunizations via cutaneous and mucosal approaches. Here, we discuss several methods of needle-free immunizations and provide insights into promising use of chitosan systems for successful immunization.

Comparative Evaluation of Accuracy of Two Electronic Apex Locators in the Presence of Contemporary Irrigants: An In vitro Study.

AIM: The present study was aimed to compare the accuracy of Root ZX Mini and Propex II in the presence of 0.1% octinidine dohydrochloride (OCT), 2% chlorhexidine gluconate (CHX), and 5% sodium hypochlorite (NaOCl) heated and nonheated before and after preparation. MATERIALS AND METHODS: Eighty extracted single-rooted teeth were selected for the study and decoronated. Teeth were mounted in an alginate model. Actual working length (AL) was measured using a stereomicroscope under ×4 magnification. Electronic working length measurements were recorded using Root ZX Mini and Propex II apex locators in the presence of 0.1% OCT, 2% CHX, and 5% NaOCl (nonheated and heated to 60°C) before and after preparation. Mean and standard deviation differences before and after preparation were calculated and statistically analyzed using analysis of variance and paired t-test. RESULTS: The accuracy of Root ZX Mini before and after preparation within ±0.5 mm of AL was consistently high in the presence of irrigants than Propex II. 5% NaOCl (heated and nonheated) showed more variation than the other irrigants, in the working length determination in both the apex locators. CONCLUSION: Electronic length measurements were shorter with heated and nonheated 5% NaOCl and longer with 0.1% OCT and 2% CHX for both the electronic apex locators.

Digitally Tunable Microfluidic Bioprinting of Multilayered Cannular Tissues.

Despite advances in the bioprinting technology, biofabrication of circumferentially multilayered tubular tissues or organs with cellular heterogeneity, such as blood vessels, trachea, intestine, colon, ureter, and urethra, remains a challenge. Herein, a promising multichannel coaxial extrusion system (MCCES) for microfluidic bioprinting of circumferentially multilayered tubular tissues in a single step, using customized bioinks constituting gelatin methacryloyl, alginate, and eight-arm poly(ethylene glycol) acrylate with a tripentaerythritol core, is presented. These perfusable cannular constructs can be continuously tuned up from monolayer to triple layers at regular intervals across the length of a bioprinted tube. Using customized bioink and MCCES, bioprinting of several tubular tissue constructs using relevant cell types with adequate biofunctionality including cell viability, proliferation, and differentiation is demonstrated. Specifically, cannular urothelial tissue constructs are bioprinted, using human urothelial cells and human bladder smooth muscle cells, as well as vascular tissue constructs, using human umbilical vein endothelial cells and human smooth muscle cells. These bioprinted cannular tissues can be actively perfused with fluids and nutrients to promote growth and proliferation of the embedded cell types. The fabrication of such tunable and perfusable circumferentially multilayered tissues represents a fundamental step toward creating human cannular tissues.

A new way of producing pediocin in Pediococcus acidilactici through intracellular stimulation by internalized inulin nanoparticles.

One of the most challenging aspects of probiotics as a replacement for antibiotics is to enhance their antimicrobial activity against pathogens. Given that prebiotics stimulate the growth and/or activity of probiotics, we developed phthalyl inulin nanoparticles (PINs) as prebiotics and observed their effects on the cellular and antimicrobial activities of Pediococcus acidilactici (PA). First, we assessed the internalization of PINs into PA. The internalization of PINs was largely regulated by glucose transporters in PA, and the process was energy-dependent. Once internalized, PINs induced PA to produce substantial amounts of antimicrobial peptide (pediocin), which is effective against both Gram-positive (Salmonella Gallinarum) and Gram-negative (Listeria monocytogenes) pathogens. When treated with small-sized PINs, PA witnessed a nine-fold increase in antimicrobial activity. The rise in pediocin activity in PA treated with PINs was accompanied by enhanced expression of stress response genes (groEL, groES, dnaK) and pediocin biosynthesis genes (pedA, pedD). Although the mechanism is not clear, it appears that the internalization of PINs by PA causes mild stress to activate the PA defense system, leading to increased production of pediocin. Overall, we identified a prebiotic in nanoparticle form for intracellular stimulation of probiotics, demonstrating a new avenue for the biological production of antimicrobial peptides.

Self-Assembled, Adjuvant/Antigen-Based Nanovaccine Mediates Anti-Tumor Immune Response against Melanoma Tumor.

Malignant melanoma is a highly aggressive type of cancer that requires radical treatment strategies to inhibit the cancer cell progression and metastasis. In recent years, preclinical research and clinical trials on melanoma treatment have been considerably focused on the adjuvant-based immunotherapy for enhancing the immune response of innate immune cells against cancer cells. However, the clinical outcome of these adjuvant-based treatments is inadequate due to an improper delivery system for these immune activators to reach the target site. Hence, we developed a vaccine formulation containing tumor lysate protein (TL) and poly I:C (PIC) complexed with positively charged poly (sorbitol-co-polyethylenimine (PEI) (PSPEI). The resulting ionic PSPEI-polyplexed antigen/adjuvant (PAA) (PSPEI-PAA) nanocomplexes were stable at the physiological condition, are non-toxic, and have enhanced intracellular uptake of antigen and adjuvant in immature dendritic cells leading to dendritic cell maturation. In the murine B16F10 tumor xenograft model, PSPEI-PAA nanocomplexes significantly suppressed tumor growth and did not exhibit any noticeable sign of toxicity. The level of matured dendritic cells (CD80+/CD86+ cells) in the tumor draining lymph node of PSPEI-PAA treated tumor mice were enhanced and therefore CD8+ T cells infiltration in the tumor were enriched. Additionally, the cytotoxic T lymphocytes (CTLs) assay involving co-culturing of splenocytes isolated from the PSPEI-PAA-treated mice with that of B16F10 cells significantly revealed enhanced cancer killing by the TL-reactivated CTLs compared to untreated control mice bearing tumor. Therefore, we strongly believe that PSPEI-PAA nanocomplexes could be an efficient antigen/adjuvant delivery system and enhance the antitumor immune response against melanoma tumor in the future clinical trials.

Oral Immunization of FMDV Vaccine Using pH-Sensitive and Mucoadhesive Thiolated Cellulose Acetate Phthalate Microparticles.

Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry.

Chitosan-based particulate systems for the delivery of mucosal vaccines against infectious diseases.

Given that most pathogens enter the body at mucosal surfaces for infection and mucosal immune responses act as the first line of defense against the invading pathogens, mucosal vaccination is the most effective method to prevent infectious diseases. However, the development of mucosal vaccines requires an efficient antigen delivery system which should protect the antigens from physical elimination and enzymatic degradation, target mucosal inductive sites, and appropriately stimulate the mucosal and systemic immunity. Accordingly, polymeric particles have garnered much attention because the physicochemical properties of polymers can be adjusted to resolve the issues associated with mucosal vaccine delivery. Particularly, chitosan-based polymeric carriers are the most promising vehicles for mucosal vaccine delivery because chitosan is biodegradable, biocompatible and mucoadhesive in nature. Similarly, chitosan can be modified with chemical and biological molecules to develop delivery carriers for controlled or targeted therapy. Moreover, they can be converted to various formulations, such as solid, liquid and gel, with a wide range of particle sizes. In this review, we highlight and discuss advances in the development of chitosan-based particulate systems, specifically for the delivery of mucosal vaccines against infections.

Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.