Bismuth-based drugs sensitize Pseudomonas aeruginosa to multiple antibiotics by disrupting iron homeostasis.

Pseudomonas aeruginosa infections are difficult to treat due to rapid development of antibiotic drug resistance. The synergistic combination of already-in-use drugs is an alternative to developing new antibiotics to combat antibiotic-resistant bacteria. Here we demonstrate that bismuth-based drugs (bismuth subsalicylate, colloidal bismuth subcitrate) in combination with different classes of antibiotics (tetracyclines, macrolides, quinolones, rifamycins and so on) can eliminate multidrug-resistant P. aeruginosa and do not induce development of antibiotic resistance. Bismuth disrupts iron homeostasis by binding to P. aeruginosa siderophores. Inside cells, bismuth inhibits the electron transport chain, dissipates the proton motive force and impairs efflux pump activity by disrupting iron-sulfur cluster-containing enzymes, including respiration complexes. As a result, bismuth facilitates antibiotic accumulation inside bacteria, enhancing their efficacy. The combination therapy shows potent antibacterial efficacy and low toxicity in an ex vivo bacteraemia model and increases the survival rate of mice in in vivo mouse lung-infection models. Our findings highlight the potential of bismuth-based drugs to be repurposed to combat P. aeruginosa infections in combination with clinically used antibiotics.

Survival rate of teeth adjacent and nonadjacent to dental implants: A retrospective cohort study.

BACKGROUND: The aim of this retrospective study was to investigate the risk of tooth loss for teeth adjacent and nonadjacent to dental implants. METHODS: A total of 787 patients with an average follow-up of 57.1 months were examined to define the tooth loss, cumulative survival rate, and odds ratio (OR) for teeth adjacent versus nonadjacent to implants. A multivariate logistic regression was employed to assess the association between dental history and various recorded etiologies of tooth loss among teeth adjacent to implants. RESULTS: The incidence of tooth loss for teeth adjacent to implants was 8.1% at the tooth level and 15.1% at the patient level, while 0.7% and 9.5% at the tooth and patientlevel for teeth nonadjacent to implants. The 10-year cumulative survival rate for teeth adjacent to implants was 89.2%, and the primary etiology of tooth loss was root fracture (45.2%). The risk of tooth loss among teeth adjacent versus nonadjacent to implants was significantly higher (OR 13.15). Among teeth adjacent to implants, root canal-treated teeth had a significantly higher risk of tooth loss due to root fracture (OR 7.72), a history of existing restoration significantly increased the risk of tooth loss due to caries (OR 3.05), and a history of periodontitis significantly increased the risk of tooth loss due to periodontitis (OR 38.24). CONCLUSION: The present study demonstrated that after patients received dental implant treatment, teeth adjacent to implants showed a 13.2-fold higher risk of tooth loss compared to teeth nonadjacent to implants, with the primary etiology being root fracture.

Dual-action gallium-flavonoid compounds for combating Pseudomonas aeruginosa infection.

The opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa) causes infections that are difficult to treat, which is due to the bacterial natural resistance to antibiotics. The bacterium is also able to form a biofilm that protects the bacterium from clearance by the human immune system and leads to chronic infection. Herein, we synthesized and characterized a novel gallium compound that interferes with both the iron metabolism and quorum sensing system of P. aeruginosa to achieve a significant bactericidal activity. The compound could substantially reduce the secretion of bacterial virulence factors as well as eliminate biofilm formation. Integrative omics analysis indicates that this compound can significantly disturb the gene transcription and metabolism of P. aeruginosa. The effectiveness of the gallium compound was further validated in mammalian cell and murine skin infection models. Our study offers a new strategy to design new gallium-based antimicrobials to combat P. aeruginosa infection.

The Effect of Bone Morphogenetic Protein-2 (BMP-2) on Volumetric and Histometric Outcomes for Peri-Implant Defects in the Animal Model: A Systematic Review and Meta-Analysis.

Purpose: To study the effect of BMP-2 on the volumetric and histometric changes in peri-implant defect treatments in animal models. Materials and Methods: An electronic search of four databases and a manual search of peer-reviewed journals for relevant articles were performed. Animal studies with data that compared the volumetric and/or histometric outcomes of peri-implant defect treatment with and without the use of BMP-2 were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. Results: After completing the search process, 21 randomized controlled trials were included. The results of the meta-analyses showed that the WMD of bone-to-implant contact (%BIC) with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.50% (95% CI = 3.28% to 27.72%, P = .01) and 16.17% (95% CI = 11.17% to 21.16%, P < .00001), respectively, favoring the BMP-2 group. The WMD for the percentage of defect fill with 4 to 8 weeks and 12 to 24 weeks of follow-up was 15.88% (95% CI = 3.90% to 27.86%, P = .009) and 10.48% (95% CI = 0.95% to 20.02%, P = .03), respectively, favoring the BMP-2 group. The WMD for the vertical bone gain with 8 to 16 weeks of follow-up was 1.63 mm (95% CI = 0.58 to 2.67 mm, P = .002), also favoring the BMP-2 group. Conclusion: This review demonstrated that the use of BMP-2 in treating peri-implant defects showed better clinical and histometric outcomes than defects not treated with BMP-2 in animal models.

Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance.

The rapid emergence of antimicrobial resistance (AMR) pathogens highlights the urgent need to approach this global burden with alternative strategies. Cefiderocol (Fetroja®) is a clinically-used sideromycin, that is utilized for the treatment of severe drug-resistant infections, caused by Gram-negative bacteria; there is evidence of cefiderocol-resistance occurring in bacterial strains however. To increase the efficacy and extend the life-span of sideromycins, we demonstrate strong synergisms between cefiderocol and metallodrugs (e.g., colloidal bismuth citrate (CBS)), against Pseudomonas aeruginosa and Burkholderia cepacia. Moreover, CBS enhances cefiderocol efficacy against biofilm formation, suppresses the resistance development in P. aeruginosa and resensitizes clinically isolated resistant P. aeruginosa to cefiderocol. Notably, the co-therapy of CBS and cefiderocol significantly increases the survival rate of mice and decreases bacterial loads in the lung in a murine acute pneumonia model. The observed phenomena are partially attributable to the competitive binding of Bi3+ to cefiderocol with Fe3+, leading to enhanced uptake of Bi3+ and reduced levels of Fe3+ in cells. Our studies provide insight into the antimicrobial potential of metallo-sideromycins.

SaeR as a novel target for antivirulence therapy against Staphylococcus aureus.

Staphylococcus aureus is a major human pathogen responsible for a wide range of clinical infections. SaeRS is one of the two-component systems in S. aureus that modulate multiple virulence factors. Although SaeR is required for S. aureus to develop an infection, inhibitors have not been reported. Using an in vivo knockdown method, we demonstrated that SaeR is targetable for the discovery of antivirulence agent. HR3744 was discovered through a high-throughput screening utilizing a GFP-Lux dual reporter system driven by saeP1 promoter. The antivirulence efficacy of HR3744 was tested using Western blot, Quantitative Polymerase Chain Reaction, leucotoxicity, and haemolysis tests. In electrophoresis mobility shift assay, HR3744 inhibited SaeR-DNA probe binding. WaterLOGSY-NMR test showed HR3744 directly interacted with SaeR's DNA-binding domain. When SaeR was deleted, HR3744 lost its antivirulence property, validating the target specificity. Virtual docking and mutagenesis were used to confirm the target's specificity. When Glu159 was changed to Asn, the bacteria developed resistance to HR3744. A structure-activity relationship study revealed that a molecule with a slight modification did not inhibit SaeR, indicating the selectivity of HR3744. Interestingly, we found that SAV13, an analogue of HR3744, was four times more potent than HR3744 and demonstrated identical antivirulence properties and target specificity. In a mouse bacteraemia model, both HR3744 and SAV13 exhibited in vivo effectiveness. Collectively, we identified the first SaeR inhibitor, which exhibited in vitro and in vivo antivirulence properties, and proved that SaeR could be a novel target for developing antivirulence drugs against S. aureus infections.

Identification of a Small Molecule Compound Active against Antibiotic-Tolerant Staphylococcus aureus by Boosting ATP Synthesis.

Antibiotic tolerance poses a threat to current antimicrobial armamentarium. Bacteria at a tolerant state survive in the presence of antibiotic treatment and account for persistence, relapse and recalcitrance of infections. Antibiotic treatment failure may occur due to antibiotic tolerance. Persistent infections are difficult to treat and are often associated with poor prognosis, imposing an enormous burden on the healthcare system. Effective strategies targeting antibiotic-tolerant bacteria are therefore highly warranted. In this study, small molecule compound SA-558 was identified to be effective against Staphylococcus aureus that are tolerant to being killed by conventional antibiotics. SA-558 mediated electroneutral transport across the membrane and led to increased ATP and ROS generation, resulting in a reduction of the population of antibiotic-tolerant bacteria. In a murine chronic infection model, of which vancomycin treatment failed, we demonstrated that SA-558 alone and in combination with vancomycin caused significant reduction of MRSA abundance. Our results indicate that SA-558 monotherapy or combinatorial therapy with vancomycin is an option for managing persistent S. aureus bacteremia infection and corroborate that bacterial metabolism is an important target for counteracting antibiotic tolerance.

The significance of vertical platform discrepancies and splinting on marginal bone levels for adjacent dental implants.

OBJECTIVE: The aim of this retrospective study was to investigate the influence of vertical platform discrepancies for splinted and non-splinted adjacent implants on radiographic marginal bone loss (RMBL). METHODS: Data from January 2000 to February 2021 were collected from the electronic charts of 156 patients with 337 implants at the UCSF School of Dentistry. Five different implant restoration categories were evaluated for radiographic evidence of proximal RMBL. Patients with (1) two adjacent single crowns, (2) two adjacent splinted crowns, (3) three-unit bridges supported by two implants, (4) three adjacent single crowns, and (5) three adjacent splinted crowns. Inclusion required baseline radiograph taken at the time of prosthesis delivery or final impression, and follow-up radiographs at least 12 months after restorations have been in function. Measurements assessed included vertical distance between adjacent implant platforms and proximal RMBL around implants. Odds ratios (ORs) and 95% confidence interval (95% CI) of implants with ≥1 mm RMBL between different type of restorations were calculated. RESULTS: In general, prostheses supported by splinted adjacent implants demonstrated a significant association with the presence of ≥1 mm RMBL (OR = 2.55, 95% CI = 1.17-5.17, p = 0.018) when compared to prostheses supported by non-splinted adjacent implants. In addition, prostheses with a vertical platform discrepancy ≥0.5 mm demonstrated a significant association with the presence of ≥1 mm RMBL (OR = 4.30, 95% CI = 1.85 to 10.01, p = 0.007) when compared to prostheses with a vertical platform discrepancy <0.5 mm. When adjacent implants had ≥0.5 mm vertical platform discrepancy, the majority (66.67%) of three splinted adjacent crowns had at least one implant with ≥1 mm RMBL. This was followed by two splinted adjacent crowns (58.97%), three-unit bridge (25.93%), two single adjacent crowns (24.24%), and three single adjacent crowns (18.18%). When adjacent implants had ≥1 mm vertical platform discrepancy, there was an increased percentage of implants with ≥1 mm RMBL. The restorative design associated with the highest percent of implants with bone loss was three splinted adjacent crowns (70%), two splinted adjacent crowns (61.11%), three single adjacent crowns (40%), and three-unit bridge and two single adjacent implants (21.05%). Three splinted adjacent crowns were significantly associated with ≥1 mm RMBL when compared to three-unit bridge (OR 6.56, 95% CI 1.59-27.07). Similarly, two splinted crowns were significantly associated with ≥1 mm RMBL when compared to two single crowns (OR = 2.50, 95% CI = 1.08-5.79). CONCLUSION: Two or three adjacent implants placed with a vertical platform discrepancy, when splinted together, are associated with higherincidence of ≥1 mm RMBL than non-splinted restorations.

Auricular Composite Graft Survival in Rhinoplasty.

Auricular composite grafts can be used in rhinoplasty to correct defects of the internal nasal valve, ala, vestibule, sill, and external nose. The objective of this study was to measure the auricular composite graft (ACG) survival rate and patient-reported outcome with Nasal Obstruction Symptom Evaluation (NOSE) score among patients undergoing rhinoplasty. A retrospective chart review was performed of all patients who underwent rhinoplasty with ACGs from 2002 to 2019 by the senior author. Median patient age was 42 years (range 14-79) with 80.3% being female. In total, 234 rhinoplasty procedures were performed utilizing 367 auricular composite grafts. Secondary rhinoplasty (n = 160, 68.4%) was the most common. And 93.7% of ACGs had full take. There were 23 partial or total graft failures, producing graft failure rate of 6.3%. Mean preoperative NOSE score was 24.08, and mean postoperative NOSE score was 21.84, with a p-value of 0.63. Auricular composite grafts can be used to repair a wide range of defects of the internal nasal valve, nasal sill-ala junction, nasal vestibule, and external nose.

The Pattern of Tooth Loss for Periodontally Favorable Teeth: A Retrospective Study.

To retrospectively analyze local and systemic factors that resulted in the short-term tooth loss of teeth that were previously assigned a favorable prognosis in patients who were seen and treated over an observational five-year period. This retrospective study included the records of patients who had a minimum of two dental exams at least twelve months apart over a 5-year period. This study investigated extracted teeth with an initially favorable periodontal prognosis that were then divided into one of four categories based on the reason for extraction: caries, periodontal disease, endodontic reasons, or fracture. Patient- and tooth-related factors associated with the extracted teeth were recorded: crown-to-root ratio, initial pocket depth, initial periodontal diagnosis, maintenance interval, presence of existing restoration, furcation involvement, and systemic conditions. Data analysis was performed using a linear mixed model. A total of 50 patients with 111 teeth met the inclusion criteria for this study. A higher odds ratio (OR) for tooth loss due to caries, endodontic reasons, and fracture were found in teeth with a history of root canal treatment with an OR of 3.61, 3.86, and 2.52, respectively. For tooth loss due to periodontal disease, higher ORs were found in patients who were on anti-depressants (OR = 4.28) and patients who had an initial diagnosis of Stage III/IV periodontitis (OR = 2.66). In addition, teeth with initial probing depths ≥5 mm (OR = 4.32) and with furcation involvement (OR = 1.93) showed a higher OR for tooth loss due to periodontal disease. Within the limitations of this study, previously root-canal-treated teeth present a higher OR for early loss due to caries, recurrent endodontic lesions, or fracture. In addition, patients with anti-depressant medication use, sporadic maintenance, initial probing depths ≥5 mm, and furcation involvement represent a significantly higher OR of tooth loss due to periodontal disease even for initially favorable teeth.

Linoleic acid metabolism activation in macrophages promotes the clearing of intracellular Staphylococcus aureus.

Multidrug-resistant bacterial pathogens pose an increasing threat to human health. Certain bacteria, such as Staphylococcus aureus, are able to survive within professional phagocytes to escape the bactericidal effects of antibiotics and evade killing by immune cells, potentially leading to chronic or persistent infections. By investigating the macrophage response to S. aureus infection, we may devise a strategy to prime the innate immune system to eliminate the infected bacteria. Here we applied untargeted tandem mass spectrometry to characterize the lipidome alteration in S. aureus infected J774A.1 macrophage cells at multiple time points. Linoleic acid (LA) metabolism and sphingolipid metabolism pathways were found to be two major perturbed pathways upon S. aureus infection. The subsequent validation has shown that sphingolipid metabolism suppression impaired macrophage phagocytosis and enhanced intracellular bacteria survival. Meanwhile LA metabolism activation significantly reduced intracellular S. aureus survival without affecting the phagocytic capacity of the macrophage. Furthermore, exogenous LA treatment also exhibited significant bacterial load reduction in multiple organs in a mouse bacteremia model. Two mechanisms are proposed to be involved in this progress: exogenous LA supplement increases downstream metabolites that partially contribute to LA's capacity of intracellular bacteria-killing and LA induces intracellular reactive oxygen species (ROS) generation through an electron transport chain pathway in multiple immune cell lines, which further increases the capacity of killing intracellular bacteria. Collectively, our findings not only have characterized specific lipid pathways associated with the function of macrophages but also demonstrated that exogenous LA addition may activate lipid modulator-mediated innate immunity as a potential therapy for bacterial infections.

Phosphatidic acid phosphatase 1 impairs SARS-CoV-2 replication by affecting the glycerophospholipid metabolism pathway.

Viruses exploit the host lipid metabolism machinery to achieve efficient replication. We herein characterize the lipids profile reprogramming in vitro and in vivo using liquid chromatography-mass spectrometry-based untargeted lipidomics. The lipidome of SARS-CoV-2-infected Caco-2 cells was markedly different from that of mock-infected samples, with most of the changes involving downregulation of ceramides. In COVID-19 patients' plasma samples, a total of 54 lipids belonging to 12 lipid classes that were significantly perturbed compared to non-infected control subjects' plasma samples were identified. Among these 12 lipid classes, ether-linked phosphatidylcholines, ether-linked phosphatidylethanolamines, phosphatidylcholines, and ceramides were the four most perturbed. Pathway analysis revealed that the glycerophospholipid, sphingolipid, and ether lipid metabolisms pathway were the most significantly perturbed host pathways. Phosphatidic acid phosphatases (PAP) were involved in all three pathways and PAP-1 deficiency significantly suppressed SARS-CoV-2 replication. siRNA knockdown of LPIN2 and LPIN3 resulted in significant reduction of SARS-CoV-2 load. In summary, these findings characterized the host lipidomic changes upon SARS-CoV-2 infection and identified PAP-1 as a potential target for intervention for COVID-19.

Antivirulence Agent as an Adjuvant of ß-Lactam Antibiotics in Treating Staphylococcal Infections.

Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for ß-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of antivirulence agents and antibiotics may be a novel approach to controlling antibiotic-induced S. aureus pathogenicity. We have illustrated that under in vitro conditions, antivirulence agent M21, when administered concurrently with ampicillin, suppressed the expression and production of virulence factors induced by ampicillin. In a mouse peritonitis model, M21 reduced bacterial load irrespective of administration of ampicillin. In a bacteremia model, combinatorial treatment consisting of ampicillin or ceftazidime and M21 increased the survival rate of mice and reduced cytokine abundance, suggesting the suppression of antibiotic-induced virulence by M21. Different from traditional antibiotic adjuvants, an antivirulence agent may not synergistically inhibit bacterial growth in vitro, but effectively benefit the host in vivo. Collectively, our findings from this study demonstrated the benefits of antivirulence-antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants.

Subinhibitory Concentrations of Antibiotics Exacerbate Staphylococcal Infection by Inducing Bacterial Virulence.

Antibiotics are widely used for the treatment of bacterial infections. However, injudicious use of antibiotics based on an empirical method may lead to the emergence of resistant strains. Despite appropriate administration of antibiotics, their concentrations may remain subinhibitory in the body, due to individual variations in tissue distribution and metabolism rates. This may promote bacterial virulence and complicate the treatment strategies. To investigate whether the administration of certain classes of antibiotics will induce bacterial virulence and worsen the infection under in vivo conditions. Different classes of antibiotics were tested in vitro for their ability to induce virulence in a methicillin-resistant S. aureus strain Mu3 and clinical isolates. Antibiotic-induced pathogenicity was assessed in vivo using mouse peritonitis and bacteremia models. In vitro, ß-lactam antibiotics and tetracyclines induced the expression of multiple surface-associated virulence factors as well as the secretion of toxins. In peritonitis and bacteremia models, mice infected with MRSA and treated with ampicillin, ceftazidime, or tetracycline showed enhanced bacterial pathogenicity. The release of induced virulence factors in vivo was confirmed in a histological examination. Subinhibitory concentrations of antibiotics belonging to ß-lactam and tetracycline aggravated infection by inducing staphylococcal virulence in vivo. Thus, when antibiotics are required, it is preferable to employ combination therapy and to initiate the appropriate treatment plan, following diagnosis. Our findings emphasize the risks associated with antibiotic-based therapy and underline the need for alternative therapeutic options. IMPORTANCE Antibiotics are widely applied to treat infectious diseases. Empirically treatment with incorrect antibiotics, or even correct antibiotics always falls into subinhibitory concentrations, due to dosing, distribution, or secretion. In this study, we have systematically evaluated in vitro virulence induction effect of antibiotics and in vivo exacerbated infection. The major highlight of this work is to prove the ß-lactam and tetracyclines antibiotics exacerbated disease is due to their induction effect on staphylococcal virulence. This phenomenon is common and suggests that if ß-lactam antibiotics remain the first line of defense during empirical therapy, we either need to increase patient reliability or the treatment approach may improve in the future when paired with anti-virulence drugs.

Screening Repurposed Antiviral Small Molecules as Antimycobacterial Compounds by a Lux-Based phoP Promoter-Reporter Platform.

The emergence of multidrug-resistant strains and hyper-virulent strains of Mycobacterium tuberculosis are big therapeutic challenges for tuberculosis (TB) control. Repurposing bioactive small-molecule compounds has recently become a new therapeutic approach against TB. This study aimed to identify novel anti-TB agents from a library of small-molecule compounds via a rapid screening system. A total of 320 small-molecule compounds were used to screen for their ability to suppress the expression of a key virulence gene, phop, of the M. tuberculosis complex using luminescence (lux)-based promoter-reporter platforms. The minimum inhibitory and bactericidal concentrations on drug-resistant M. tuberculosis and cytotoxicity to human macrophages were determined. RNA sequencing (RNA-seq) was conducted to determine the drug mechanisms of the selected compounds as novel antibiotics or anti-virulent agents against the M. tuberculosis complex. The results showed that six compounds displayed bactericidal activity against M. bovis BCG, of which Ebselen demonstrated the lowest cytotoxicity to macrophages and was considered as a potential antibiotic for TB. Another ten compounds did not inhibit the in vitro growth of the M. tuberculosis complex and six of them downregulated the expression of phoP/R significantly. Of these, ST-193 and ST-193 (hydrochloride) showed low cytotoxicity and were suggested to be potential anti-virulence agents for M. tuberculosis.

Fusion-inhibition peptide broadly inhibits influenza virus and SARS-CoV-2, including Delta and Omicron variants.

Pandemic influenza virus and SARS-CoV-2 vaiants have posed major global threats to public health. Broad-spectrum antivirals blocking viral entry can be an effective strategy for combating these viruses. Here, we demonstrate a frog-defensin-derived basic peptide (FBP), which broadly inhibits the influenza virus by binding to haemagglutinin so as to block low pH-induced HA-mediated fusion and antagonizes endosomal acidification to inhibit the influenza virus. Moreover, FBP can bind to the SARS-CoV-2 spike to block spike-mediated cell-cell fusion in 293T/ACE2 cells endocytosis. Omicron spike shows a weak cell-cell fusion mediated by TMPRSS2 in Calu3 cells, making the Omicron variant sensitive to endosomal inhibitors. In vivo studies show that FBP broadly inhibits the A(H1N1)pdm09 virus in mice and SARS-CoV-2 (HKU001a and Delta)in hamsters. Notably, FBP shows significant inhibition of Omicron variant replication even though it has a high number of mutations in spike. In conclusion, these results suggest that virus-targeting FBP with a high barrier to drug resistance can be an effective entry-fusion inhibitor against influenza virus and SARS-CoV-2 in vivo.

Integration of a miniaturized DMMB assay with high-throughput screening for identifying regulators of proteoglycan metabolism.

Defective biosynthesis or function of proteoglycans causes pathological conditions in a variety of tissue systems. Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction caused by imbalanced proteoglycan synthesis and degradation. Identifying agents that regulate proteoglycan metabolism may benefit the development of OA-modifying therapeutics. High-throughput screening (HTS) of chemical libraries has paved the way for achieving this goal. However, the implementation and adaptation of HTS assays based on proteoglycan measurement remain underexploited. Using primary porcine chondrocytes as a model, we report a miniaturized dimethyl-methylene blue (DMMB) assay, which is commonly used to quantitatively evaluate sulfated glycosaminoglycan (GAG) content, with an optimized detection range and reproducibility and its integration with HTS. Treatment with TGF-ß1 and IL1-α, known as positive and negative proteoglycan regulators, respectively, supported the assay specificity. A pre-test of chemical screening of 960 compounds identified both stimulators (4.48%) and inhibitors (6.04%) of GAG production. Fluorophore-assisted carbohydrate electrophoresis validated the activity of selected hits on chondroitin sulfate expression in an alginate culture system. Our findings support the implementation of this simple colorimetric assay in HTS to discover modifiers of OA or other diseases related to dysregulated proteoglycan metabolism.

A commentary on strategic extraction.

BACKGROUND: Advancements in strategies to maintain compromised teeth combined with a greater understanding of risks associated with dental implants invite a reassessment of the benefits of strategic extraction of a tooth with a questionable prognosis or of limited strategic value. METHODS: Evidence of the management of compromised teeth and decision making for strategic extraction was reviewed. Additionally, the risks for peri-implantitis were evaluated from the perspective of patient centric, biologic, and biomechanical complications. RESULTS: Recent clinical innovations support a more predictable maintenance of compromised dentition, and the clinical literature provides evidence of the risks associated with dental implants. CONCLUSIONS: Because of the improvements in dental management of compromised dentition, strategic extraction should be deferred, whenever possible, to avoid complications associated with peri-implantitis.

The Significance of Utilizing A Corticotomy on Periodontal and Orthodontic Outcomes: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review compares the clinical and radiographic outcomes for patients who received only a corticotomy or periodontal accelerated osteogenic orthodontics (PAOO) with those who received a conventional orthodontic treatment. METHODS: An electronic search of four databases and a hand search of peer-reviewed journals for relevant articles published in English between January 1980 and June 2021 were performed. Human clinical trials of ≥10 patients treated with a corticotomy or PAOO with radiographic and/or clinical outcomes were included. Meta-analyses were performed to analyze the weighted mean difference (WMD) and confidence interval (CI) for the recorded variables. RESULTS: Twelve articles were included in the quantitative analysis. The meta-analysis revealed a localized corticotomy distal to the canine can significantly increase canine distalization (WMD = 1.15 mm, 95% CI = 0.18-2.12 mm, p = 0.02) compared to a conventional orthodontic treatment. In addition, PAOO also showed a significant gain of buccal bone thickness (WMD = 0.43 mm, 95% CI = 0.09-0.78 mm, p = 0.01) and an improvement of bone density (WMD = 32.86, 95% CI = 11.83-53.89, p = 0.002) compared to the corticotomy group. CONCLUSION: Based on the findings of the meta-analyses, the localized use of a corticotomy can significantly increase the amount of canine distalization during orthodontic treatment. Additionally, the use of a corticotomy as a part of a PAOO procedure significantly increases the rate of orthodontic tooth movement and it is accompanied by an increased buccal bone thickness and bone density compared to patients undergoing a conventional orthodontic treatment.