The impact of Lacticaseibacillus paracasei GMNL-143 toothpaste on gingivitis and oral microbiota in adults: a randomized, double-blind, crossover, placebo-controlled trial.

BACKGROUND: This study examines the oral health benefits of heat-killed Lacticaseibacillus paracasei GMNL-143, particularly its potential in oral microbiota alterations and gingivitis improvement. METHODS: We assessed GMNL-143's in vitro interactions with oral pathogens and its ability to prevent pathogen adherence to gingival cells. A randomized, double-blind, crossover clinical trial was performed on gingivitis patients using GMNL-143 toothpaste or placebo for four weeks, followed by a crossover after a washout. RESULTS: GMNL-143 showed coaggregation with oral pathogens in vitro, linked to its surface layer protein. In patients, GMNL-143 toothpaste lowered the gingival index and reduced Streptococcus mutans in crevicular fluid. A positive relationship was found between Aggregatibacter actinomycetemcomitans and gingival index changes, and a negative one between Campylobacter and gingival index changes in plaque. CONCLUSION: GMNL-143 toothpaste may shift oral bacterial composition towards a healthier state, suggesting its potential in managing mild to moderate gingivitis. TRIAL REGISTRATION: ID NCT04190485 ( https://clinicaltrials.gov/ ); 09/12/2019, retrospective registration.

BacMam Expressing Highly Glycosylated Porcine Interferon Alpha Induces Robust Antiviral and Adjuvant Effects against Foot-and-Mouth Disease Virus in Pigs.

Foot-and-mouth disease (FMD) is an acute contagious disease that affects cloven-hoofed animals and has severe global economic consequences. FMD is most commonly controlled by vaccination. Currently available commercial FMD vaccines contain chemically inactivated whole viruses, which are thought to be slow acting as they are effective only 4 to 7 days following vaccination. Hence, the development of a novel rapid vaccine or alternative measures, such as antiviral agents or the combination of vaccines and antiviral agents for prompt FMD virus (FMDV) outbreak containment, is desirable. Here, we constructed a recombinant baculovirus (BacMam) expressing consensus porcine interferon alpha (IFN-α) that has three additional N-glycosylation sites driven by a cytomegalovirus immediate early (CMV-IE) promoter (Bac-Con3N IFN-α) for protein expression in mammalian cells. Bac-Con3N IFN-α expressing highly glycosylated porcine IFN-α protein increased the duration of antiviral effects. We evaluated the antiviral effects of Bac-Con3N IFN-α in swine cells and mice and observed sustained antiviral effects in pig serum; additionally, Bac-Con3N IFN-α exhibited sustained antiviral effects in vivo as well as adjuvant effects in combination with an inactivated FMD vaccine. Pigs injected with a combination of Bac-Con3N IFN-α and the inactivated FMD vaccine were protected against FMDV at 1, 3, and 7 days postvaccination. Furthermore, we observed that in combination with the inactivated FMD vaccine, Bac-Con3N IFN-α increased neutralizing antibody levels in mice and pigs. Therefore, we suggest that Bac-Con3N IFN-α is a strong potential antiviral and adjuvant candidate for use in combination with inactivated FMD vaccines to protect pigs against FMDV. IMPORTANCE Early inhibition of foot-and-mouth disease (FMD) virus (FMDV) replication in pigs is highly desirable as FMDV transmission and shedding rates are higher in pigs than in cattle. However, commercial FMD vaccines require at least 4 to 7 days postvaccination (dpv) for protection, and animals are vulnerable to heterologous viruses before acquiring high antibody levels after the second vaccination. Therefore, the development of antiviral agents for use in combination with FMD vaccines is essential. We developed a novel antiviral and immunostimulant, Bac-Con3N IFN-α, which is a modified porcine IFN-α-expressing recombinant baculovirus, to improve IFN stability and allow its direct delivery to animals. We present a promising candidate for use in combination with inactivated FMD vaccines as pigs applied to the strategy had early protection against FMDV at 1 to 7 dpv, and their neutralizing antibody levels were higher than those in pigs administered the vaccine only.

Epigenetic Regulation of NGF-Mediated Osteogenic Differentiation in Human Dental Mesenchymal Stem Cells.

Nerve growth factor (NGF) is the best-characterized neurotrophin and is primarily recognized for its key role in the embryonic development of the nervous system and neuronal cell survival/differentiation. Recently, unexpected actions of NGF in bone regeneration have emerged as NGF is able to enhance the osteogenic differentiation of mesenchymal stem cells. However, little is known regarding how NGF signaling regulates osteogenic differentiation through epigenetic mechanisms. In this study, using human dental mesenchymal stem cells (DMSCs), we demonstrated that NGF mediates osteogenic differentiation through p75NTR, a low-affinity NGF receptor. P75NTR-mediated NGF signaling activates the JNK cascade and the expression of KDM4B, an activating histone demethylase, by removing repressive H3K9me3 epigenetic marks. Mechanistically, NGF-activated c-Jun binds to the KDM4B promoter region and directly upregulates KDM4B expression. Subsequently, KDM4B directly and epigenetically activates DLX5, a master osteogenic gene, by demethylating H3K9me3 marks. Furthermore, we revealed that KDM4B and c-Jun from the JNK signaling pathway work in concert to regulate NGF-mediated osteogenic differentiation through simultaneous recruitment to the promoter region of DLX5. We identified KDM4B as a key epigenetic regulator during the NGF-mediated osteogenesis both in vitro and in vivo using the calvarial defect regeneration mouse model. In conclusion, our study thoroughly elucidated the molecular and epigenetic mechanisms during NGF-mediated osteogenesis.

Prolonged patency of fully covered self-expandable metal stents with an externally anchored plastic stent in distal malignant biliary obstruction.

BACKGROUND : Fully covered self-expandable metal stents (FCSEMSs) are widely used for endoscopic treatment of distal malignant biliary obstruction (dMBO). We aimed to assess the efficacy of anchoring an external plastic stent to an FCSEMS in dMBO. METHODS : A multicenter retrospective cohort study was performed in patients with dMBO to compare stent patency between FCSEMSs and FCSEMSs with an externally anchored plastic stent (EPS). For external anchoring, a 7-Fr double-pigtail plastic stent (DPPS) was placed first in the bile duct, then an FCSEMS was deployed side-by-side. RESULTS : Among a total of 185 patients, 65 had an FCSEMS alone and 120 had an FCSEMS with an EPS. The median stent patency was significantly longer in the FCSEMS with an EPS group than in the FCSEMS only group (342 vs. 240 days; P = 0.04). The rate of stent migration was significantly lower in the FCSEMS with an EPS group than in the FCSEMS only group (10.8 % vs. 27.7 %; P = 0.01). There were no significant differences in the rates of stent occlusion and adverse events between the two groups. CONCLUSIONS : A novel and simple technique of anchoring an external plastic stent may decrease the risk of FCSEMS migration and prolong stent patency, without significantly increasing the adverse events rate in dMBO.

Photoswitchable and Solvent-Controlled Directional Actuators: Supramolecular Assembly and Crosslinked Polymers.

Untethered small actuators have drawn tremendous interest owing to their reversibility, flexibility, and widespread applications in various fields. For polymer actuators, however, it is still challenging to achieve programmable structural changes under different stimuli caused by the intractability and single-stimulus responses of most polymer materials. Herein, multi-stimuli-responsive polymer actuators that can respond to light and solvent via structural changes are developed. The actuators are based on bilayer films of polydimethylsiloxane (PDMS) and azobenzene chromophore (AAZO)-crosslinked poly(diallyldimethylammonium chloride) (PDAC). Upon UV light irradiation, the AAZO undergoes trans-cis-trans photoisomerization, causing the bending of the bilayer films. When the UV light is off, a shape recovery toward an opposite direction occurs spontaneously. The reversible deformation can be repeated at least 20 cycles. Upon solvent vapor annealing, one of the bilayer films can be selectively swollen, causing the bending of the bilayer films with the directions controlled by the solvent vapors. The effects of different parameters, such as the weight ratios of AAZO and film thicknesses, on the bending angles and curvatures of the polymer films are also analyzed. The results demonstrate that multi-stimuli-responsive actuators with fast responses and high reproducibility can be fulfilled.

Periodontitis is associated with the development of fungal sinusitis: A nationwide 12-year follow-up study.

AIM: The incidence of fungal sinusitis is increasing; however, its pathophysiology has not been investigated previously. We investigate the effect of periodontitis on the incidence of fungal sinusitis over a 12-year follow-up period using nationwide population-based data. MATERIALS AND METHODS: The periodontitis group was randomly selected from the National Health Insurance Service database. The non-periodontitis group was obtained by propensity score matching considering several variables. The primary end point was the diagnosis of sinonasal fungal balls (SFBs) and invasive fungal sinusitis (IFS). RESULTS: The periodontitis and non-periodontitis groups included 12,442 and 12,442 individuals, respectively. The overall adjusted hazard ratio (aHR) for SFBs in the periodontitis group was 1.46 (p = .002). In subgroup analysis, the aHR for SFBs was 1.59 (p = 0.008) for those with underlying chronic kidney disease (CKD), 1.58 (p = .022) for those with underlying atopic dermatitis, 1.48 (p = .019) for those with chronic obstructive pulmonary disease (COPD), and 1.36 (p = .030) for those with diabetes mellitus (DM), but these values are applicable only when considering the relationship between periodontitis and SFB. The aHR for IFS in the periodontitis group was higher than in the non-periodontitis group (2.80; p = .004). CONCLUSIONS: The risk of SFBs and IFS increased after diagnosis of periodontitis. This trend is often more severe in patients with DM, COPD, or CKD, but this association with underlying diseases is applicable only when considering the association between periodontitis and fungal sinusitis.

Poly(butylene adipate-co-terephthalate) biodegradation by Purpureocillium lilacinum strain BA1S.

Poly(butylene adipate-co-terephthalate) (PBAT), a promising biodegradable aliphatic-aromatic copolyester material, can be applied as an alternative material to reduce the adverse effects of conventional plastics. However, the degradation of PBAT plastics in soil is time-consuming, and effective PBAT-degrading microorganisms have rarely been reported. In this study, the biodegradation properties of PBAT by an elite fungal strain and related mechanisms were elucidated. Four PBAT-degrading fungal strains were isolated from farmland soils, and Purpureocillium lilacinum strain BA1S showed a prominent degradation rate. It decomposed approximately 15 wt.% of the PBAT films 30 days after inoculation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and Liquid chromatography mass spectrometry (LC‒MS) were conducted to analyze the physicochemical properties and composition of the byproducts after biodegradation. In the presence of PBAT, the lipolytic enzyme activities of BA1S were remarkably induced, and its cutinase gene was also significantly upregulated. Of note, the utilization of PBAT in BA1S cells was closely correlated with intracellular cytochrome P450 (CYP) monooxygenase. Furthermore, CreA-mediated carbon catabolite repression was confirmed to be involved in regulating PBAT-degrading hydrolases and affected the degradation efficiency. This study provides new insight into the degradation of PBAT by elite fungal strains and increases knowledge on the mechanism, which can be applied to control the biodegradability of PBAT films in the future. KEY POINTS: • Purpureocillium lilacinum strain BA1S was isolated from farmland soils and degraded PBAT plastic films at a prominent rate. • The lipolytic enzyme activities of strain BA1S were induced during coculture with PBAT, and the cutinase gene was significantly upregulated during PBAT degradation. • CreA-mediated carbon catabolite repression of BA1S plays an essential role in regulating the expression of PBAT-degrading hydrolases.

Blockchain technology and federated machine learning for collaborative initiatives in orthodontics and craniofacial health.

There is a paucity of largescale collaborative initiatives in orthodontics and craniofacial health. Such nationally representative projects would yield findings that are generalizable. The lack of large-scale collaborative initiatives in the field of orthodontics creates a deficiency in study outcomes that can be applied to the population at large. The objective of this study is to provide a narrative review of potential applications of blockchain technology and federated machine learning to improve collaborative care. We conducted a narrative review of articles published from 2018 to 2023 to provide a high level overview of blockchain technology, federated machine learning, remote monitoring, and genomics and how they can be leveraged together to establish a patient centered model of care. To strengthen the empirical framework for clinical decision making in healthcare, we suggest use of blockchain technology and integrating it with federated machine learning. There are several challenges to adoption of these technologies in the current healthcare ecosystem. Nevertheless, this may be an ideal time to explore how best we can integrate these technologies to deliver high quality personalized care. This article provides an overview of blockchain technology and federated machine learning and how they can be leveraged to initiate collaborative projects that will have the patient at the center of care.

Call for algorithmic fairness to mitigate amplification of racial biases in artificial intelligence models used in orthodontics and craniofacial health.

Machine Learning (ML), a subfield of Artificial Intelligence (AI), is being increasingly used in Orthodontics and craniofacial health for predicting clinical outcomes. Current ML/AI models are prone to accentuate racial disparities. The objective of this narrative review is to provide an overview of how AI/ML models perpetuate racial biases and how we can mitigate this situation. A narrative review of articles published in the medical literature on racial biases and the use of AI/ML models was undertaken. Current AI/ML models are built on homogenous clinical datasets that have a gross underrepresentation of historically disadvantages demographic groups, especially the ethno-racial minorities. The consequence of such AI/ML models is that they perform poorly when deployed on ethno-racial minorities thus further amplifying racial biases. Healthcare providers, policymakers, AI developers and all stakeholders should pay close attention to various steps in the pipeline of building AI/ML models and every effort must be made to establish algorithmic fairness to redress inequities.

Rutin alleviates bisphenol A-glycidyl methacrylate-induced generation of proinflammatory mediators through the MAPK and NF-κB pathways in macrophages.

Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 µM for 30 min before being incubated with BisGMA at 0 or 3 µM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.

Development of Gelatin Methacryloyl/Sodium Alginate Interpenetrating Polymer Network Hydrogels for Bone Regeneration by Activating the Wnt/ß-Catenin Signaling Pathway via Lithium Release.

Hydrogels have gained significant attention as biomaterials due to their remarkable properties resembling those of the extracellular matrix (ECM). In the present investigation, we successfully synthesized interpenetrating polymer network (IPN) hydrogels using gelatin methacryloyl (GelMA) and sodium alginate (SA), incorporating various concentrations of lithium chloride (LiCl; 0, 5, and 10 mM), aiming to develop a hydrogel scaffold for bone regeneration. Notably, the compressive modulus of the IPN hydrogels remained largely unaffected upon the inclusion of LiCl. However, the hydrogel with the high concentration of LiCl exhibited reduced fragmentation after compression testing. Intriguingly, we observed a significant improvement in cellular biocompatibility, primarily attributed to activation of the Wnt/ß-catenin signaling pathway induced by LiCl. Subsequently, we evaluated the efficacy of the newly developed IPN-Li hydrogels in a rat cranial defect model and found that they substantially enhanced bone regeneration. Nevertheless, it is important to note that the introduction of high concentrations of LiCl did not significantly promote osteogenesis. This outcome can be attributed to the excessive release of Li+ ions into the extracellular matrix, hindering the desired effect. Overall, the IPN-Li hydrogel developed in this study holds great promise as a biodegradable material for bone regeneration applications.

Harnessing the power of collective intelligence in dentistry: a pilot study in Victoria, Australia.

BACKGROUND: In many dental settings, diagnosis and treatment planning is the responsibility of a single clinician, and this process is inevitably influenced by the clinician's own heuristics and biases. Our aim was to test whether collective intelligence increases the accuracy of individual diagnoses and treatment plans, and whether such systems have potential to improve patient outcomes in a dental setting. METHODS: This pilot project was carried out to assess the feasibility of the protocol and appropriateness of the study design. We used a questionnaire survey and pre-post study design in which dental practitioners were involved in the diagnosis and treatment planning of two simulated cases. Participants were provided the opportunity to amend their original diagnosis/treatment decisions after viewing a consensus report made to simulate a collaborative setting. RESULTS: Around half (55%, n = 17) of the respondents worked in group private practices, however most practitioners (74%, n = 23) did not collaborate when planning treatment. Overall, the average practitioners' self-confidence score in managing different dental disciplines was 7.22 (s.d. 2.20) on a 1-10 scale. Practitioners tended to change their mind after viewing the consensus response, particularly for the complex case compared to the simple case (61.5% vs 38.5%, respectively). Practitioners' confidence ratings were also significantly higher (p < 0.05) after viewing the consensus for complex case. CONCLUSION: Our pilot study shows that collective intelligence in the form of peers' opinion can lead to modifications in diagnosis and treatment planning by dentists. Our results lay the foundations for larger scale investigations on whether peer collaboration can improve diagnostic accuracy, treatment planning and, ultimately, oral health outcomes.

Conformationally Flexible Dimeric-Serotonin-Based Sensitive and Selective Electrochemical Biosensing Strategy for Serotonin Recognition.

A novel electrochemical sensor was constructed based on an enzyme-mediated physiological reaction between neurotransmitter serotonin per-oxidation to reconstruct dual-molecule 4,4'-dimeric-serotonin self-assembled derivative, and the potential biomedical application of the multi-functional nano-platform was explored. Serotonin accelerated the catalytic activity to form a dual molecule at the C4 position and created phenolic radical-radical coupling intermediates in a peroxidase reaction system. Here, 4,4' dimeric-serotonin possessed the capability to recognize intermolecular interactions between amine groups. The excellent quenching effects on top of the gold surface electrode system archive logically inexpensive and straightforward analytical demands. In biochemical sensing analysis, the serotonin dimerization concept demonstrated a robust, low-cost, and highly sensitive immunosensor, presenting the potential of quantifying serotonin at point-of-care (POC) testing. The high-specificity serotonin electrochemical sensor had a limit of detection (LOD) of 0.9 nM in phosphate buffer and 1.4 nM in human serum samples and a linear range of 10 to 400 with a sensitivity of 2.0 × 10-2 nM. The bivalent 4,4'-dimer-serotonin interaction strategy provides a promising platform for serotonin biosensing with high specificity, sensitivity, selectivity, stability, and reproducibility. The self-assembling gold surface electrochemical system presents a new analytical method for explicitly detecting tiny neurotransmitter-responsive serotonin neuromolecules.

Polypyrrole-palladium nanocomposite as a high-efficiency transducer for thrombin detection with liposomes as a label.

Sensitive and selective determination of protein biomarkers with high accuracy often remains a great challenge due to their existence in the human body at an exceptionally low concentration level. Therefore, sensing mechanisms that are easy to use, simple, and capable of accurate quantification of analyte are still in development to detect biomarkers at a low concentration level. To meet this end, we demonstrated a methodology to detect thrombin in serum at low concentration levels using polypyrrole (PPy)-palladium (Pd)nanoparticle-based hybrid transducers using liposomes encapsulated redox marker as a label. The morphology of Ppy-Pd composites was characterized by scanning electron microscopy, and the hybrid structure provided excellent binding and detection platform for thrombin detection in both buffer and serum solutions. For quantitative measurement of thrombin in PBS and serum, the change in current was monitored using differential pulse voltammetry, and the calculated limit of quantification (LOQ) and limit of detection (LOD) for the linear segment (0.1-1000 nM of thrombin) were 1.1 pM and 0.3 pM, in serum, respectively. The sensors also exhibited good stability and excellent selectivity towards the detection of thrombin, and thus make it a strong candidate for adopting its sensing applications in biomarker detection technologies.

Jammed Microgel-Based Inks for 3D Printing of Complex Structures Transformable via pH/Temperature Variations.

Structure changes mediated by anisotropic volume changes of stimuli-responsive hydrogels are useful for many research fields, yet relatively simple structured objects are mostly used due to limitation in fabrication methods. To fabricate complex 3 dimensional (3D) structures that undergo structure changes in response to external stimuli, jammed microgel-based inks containing precursors of stimuli-responsive hydrogels are developed for extrusion-based 3D printing. Specifically, the jammed microgel-based inks are prepared by absorbing precursors of poly(acrylic acid) or poly(N-isopropylacrylamide) in poly(acrylamide) (PAAm) microgels, and jamming them. The inks exhibit shear-thinning and self-healing properties that allow extrusion of the inks through a nozzle and rapid stabilization after printing. Stimuli-mediated volume changes are observed for the extruded structures when they are post-crosslinked by UV light to form interpenetrating networks of PAAm microgels and stimuli-responsive hydrogels. Using this method, a dumbbell-shaped object that can transform to a biconvex shape, and a gripper that can grasp and lift an object in response to stimuli are 3D-printed. The jammed microgel-based 3D printing strategy is a versatile method useful for variety of applications as diverse types of monomers absorbable in the microgels can be used to fabricate complex 3D objects transformable by external stimuli.

In vivo real-time temperature measurement on the surface of intact and gold-restored teeth during consumption of hot and cold drinks.

This study aimed to measure real-time temperature changes in gold-restored teeth compared with intact teeth during the intake of hot and cold drinks. Sixteen molars, including eight natural intact teeth and eight restored teeth with gold inlays, were selected from the participants. Custom-made thermocouple sensors were attached to the coronal third of the buccal surface of teeth. Participants consecutively consumed hot and cold drinks according to a standardized regimen. Resting, maximum, and minimum temperatures; time to reach peak temperatures; and heating and cooling velocities were obtained. Statistical analysis was performed using independent two-sample t-test. Teeth with gold restorations showed a significantly higher maximum temperature (44.7 °C [SD 2.9]) than did natural teeth (40.5 °C [SD 1.2]) during hot water drinking and showed a lower minimum temperature (25.0 °C [SD 4.9]) than did natural teeth (31.5 °C [SD 3.1]) during cold water drinking. The heating and cooling rates for the teeth with gold restorations were two and three times higher than those of the natural teeth. Gold-restored teeth showed greater temperature change than intact teeth in terms of magnitude and velocity in response to temperature changes induced by hot and cold drinks.

Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model.

OBJECTIVES: This experimental study was carried out to investigate the effects of locally delivered nanoparticles (AMG-487 NP) containing a CXCR3 antagonist in inhibiting the progression of LPS-induced inflammation, osteoclastic activity, and bone resorption on a murine model. MATERIALS AND METHODS: Thirty, 7-week-old C57BL/6 J male mice were used. Inflammatory bone loss was induced by Porphyromonas gingivalis-lipopolysaccharide (P.g.-LPS) injections between the first and second maxillary molars, bilaterally, twice a week for 6 weeks (n = 20). AMG-487 NP were incorporated into a liposome carrier and locally delivered on sites where P.g.-LPS was injected. Control mice (n = 10) were injected with vehicle only. Experimental groups included (1) control, (2) LPS, and (3) LPS + NP. At the end of 1 and 6 weeks, mice were euthanized, maxillae harvested, fixed, and stored for further analysis. RESULTS: Volumetric bone loss analysis revealed, at 1 week, an increase in bone loss in the LPS group (47.9%) compared to control (27.4%) and LPS + NP (27.8%) groups. H&E staining demonstrated reduced inflammatory infiltrate in the LPS + NP group compared to LPS group. At 6 weeks, volumetric bone loss increased in all groups; however, treatment with the CXCR3 antagonist (LPS + NP) significantly reduced bone loss compared to the LPS group. CXCR3 antagonist treatment significantly reduced osteoclast numbers when compared to LPS group at 1 and 6 weeks. CONCLUSIONS: This study showed that local delivery of a CXCR antagonist, via nanoparticles, in a bone resorption model, induced by LPS injection, was effective in reducing inflammation, osteoclast numbers, and bone loss. CLINICAL RELEVANCE: CXCR3 blockade can be regarded as a novel target for therapeutic intervention of bone loss. It can be a safe and convenient method for periodontitis treatment or prevention applicable in clinical practice.

Septic shock caused by Slackia exigua in a patient with diabetes.

We report a case of septic shock caused by Slackia exigua, an obligatory anaerobic gram-positive rod, in an 82-year-old woman with diabetes. Dental assessment revealed a palatal lesion and untreated periodontitis. Although a resident species in the oral cavity and associated with localized disorders, S. exigua can cause extra-oral diseases, which can be fatal in individuals with risk factors, such as diabetes. Thus, control of oral lesions caused by S. exigua is important to prevent systemic infection.

Predictors of difficult intubation when using a videolaryngoscope with an intermediate-angled blade during the first attempt: a prospective observational study.

The curvature of a videolaryngoscope blade has been diversified from the standard macintosh-type to the hyperacute-angle-type, resulting in different performances. We aimed to determine the intubation success rate and identify predictors of difficult intubation when using an intermediate-angled videolaryngoscope in the first attempt of intubation under routine anaesthesia settings. We enrolled 808 patients between 19 and 79 years of age, scheduled for elective surgeries under general anaesthesia with orotracheal intubation from July 2017 to November 2018; patients who were candidates for awake intubation were excluded. We obtained patient demographic data and performed airway evaluation before induction of anaesthesia for elective surgeries. We used the UEScope for tracheal intubation with a hockey stick-shaped malleable stylet. The intubation time was defined as the total duration from the entry of the blade into the oropharynx to the detection of first end-tidal carbon dioxide capnogram; this duration was recorded along with the number of intubation attempts. Difficult intubation was defined as either > 60 s duration for tracheal intubation, or > 1 intubation attempt. The use of the UEScope demonstrated a 99.4% success rate for intubation; however, increased difficulties were observed in patients who were male, obese, had a short thyromental distance, limited mouth opening, and high upper-lip-bite test class. Despite the high intubation success rate using an intermediate-angled videolaryngoscope, we recommend preparing backup plans, considering the increased difficulty in patients with certain preoperative features.Clinical trial number and registry URL: Clinical Trials.gov Identifier: NCT03215823 (Date of registration: 12 July).

Development of a Biomaterial Scaffold Integrated with Osteoinductive Oxysterol Liposomes to Enhance Hedgehog Signaling and Bone Repair.

Bone repair requires the tightly regulated control of multiple intrinsic and extrinsic cell types and signaling pathways. One of the positive regulatory signaling pathways in membranous and endochondral bone healing is the Hedgehog (Hh) signaling family. Here, a novel therapeutic liposomal delivery vector was developed by self-assembly of an Hh-activating cholesterol analog with an emulsifier, along with the addition of Smoothened agonist (SAG) as a drug cargo, for the enhancement of Hh signaling in bone regeneration. The drug-loaded nanoparticulate agonists of Hh signaling were immobilized onto trabecular bone-mimetic apatite-coated 3D scaffolds using bioinspired polydopamine adhesives to ensure favorable microenvironments for cell growth and local therapeutic delivery. Results showed that SAG-loaded liposomes induced a significant and dose-dependent increase in Hh-mediated osteogenic differentiation, as evidenced by in vitro analysis of bone marrow stromal cells, and in vivo calvarial bone healing, as evidenced using all radiographic parameters and histomorphometric analyses. Moreover, favorable outcomes were achieved in comparison to standards of care, including collagen sponge-delivered rBMP2 or allograft bone. In summary, this study demonstrates using a nanoparticle packaged Hh small molecule as a widely applicable bone graft substitute for robust bone repair.