Investigating the Interplay: Periodontal Disease and Type 1 Diabetes Mellitus-A Comprehensive Review of Clinical Studies.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived from the interplay between oral microbiota and the host immune response. A comprehensive search of studies published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

JAK/STAT as a Potential Therapeutic Target for Osteolytic Diseases.

Several cytokines with major biological functions in inflammatory diseases exert their functions through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signal transduction pathway. JAKs phosphorylate the cytoplasmic domain of the receptor, inducing the activation of its substrates, mainly the proteins known as STATs. STATs bind to these phosphorylated tyrosine residues and translocate from the cytoplasm to the nucleus, further regulating the transcription of several genes that regulate the inflammatory response. The JAK/STAT signaling pathway plays a critical role in the pathogenesis of inflammatory diseases. There is also increasing evidence indicating that the persistent activation of the JAK/STAT signaling pathway is related to several inflammatory bone (osteolytic) diseases. However, the specific mechanism remains to be clarified. JAK/STAT signaling pathway inhibitors have gained major scientific interest to explore their potential in the prevention of the destruction of mineralized tissues in osteolytic diseases. Here, our review highlights the importance of the JAK/STAT signaling pathway in inflammation-induced bone resorption and presents the results of clinical studies and experimental models of JAK inhibitors in osteolytic diseases.

IL-1B(3954) polymorphism and red complex bacteria increase IL-1ß (GCF) levels in periodontitis.

OBJECTIVE: The aim of this study was to compare IL-1ß levels in gingival crevicular fluid (GCF) from healthy and periodontitis sites of IL-1B(3954)-Single Nucleotide Polymorphism (SNP) positive and IL-1B(3954)-SNP negative periodontitis subjects in association with their bacterial profiles. BACKGROUND: Susceptibility to periodontitis has been associated with several risk factors, including allelic variants at multiple gene loci. Variations in the IL-1 gene cluster have been linked with increased risk for periodontitis. IL-1B(3954)-SNP has been previously associated with increased levels of IL-1ß in GCF or periodontal tissues in chronic periodontitis patients, as well as higher levels of specific periodontal pathogens. There is insufficient evidence to conclude if IL-1B gene polymorphisms affect the susceptibility to periodontitis by ultimately modulating the levels of IL-1ß in GCF, the subgingival microbial profile or both. MATERIALS AND METHODS: GCF, subgingival plaque, and buccal epithelial cells were collected from 32 individuals with periodontitis. GCF IL-1ß levels were measured by an enzyme-linked immunosorbent assay (ELISA). Bacterial plaque samples were analyzed for 11 periodontal pathogens using polymerase chain reaction (PCR) analysis with specific primers for the 16SrRNA gene of each bacterium. IL-1B(3954)-SNP status was determined by identifying the carriers of the polymorphic T allele. RESULTS: A significant association was shown between IL-1B(3954)-SNP and IL-1ß GCF levels (amount and concentration). The concomitant presence of two or three red complex bacterial species was associated with increased IL-1ß GCF levels in periodontitis sites (site-level analysis). The concurrent presence of all three red complex periodontal pathogens and IL-1B(3954)-SNP was associated with the highest IL-1ß GCF levels in periodontitis sites. CONCLUSIONS: Our results indicate an independent association of both IL-1B(3954)-SNP and red complex bacterial species with increased IL-1ß levels in GCF of periodontitis sites. A better understanding of the interaction between genetics, bacteria, and inflammation is essential to develop more effective diagnostic, prognostic, and therapeutic tools for periodontitis.

Presentation, Management, and Outcomes of Pathologic Scars Within a Pediatric Otolaryngology Practice.

OBJECTIVES: This study aims to review the spectrum of scarring that may present to an urban, pediatric otolaryngology practice and determine if associations exist between race, scar location, treatment modality, and outcomes following interventions for scarring. METHODS: Retrospective cohort study among 115 pediatric patients with 138 unique keloids or hypertrophic scars (HTS), and 141 children presenting for tonsillectomy at Tufts Medical Center. Age at presentation and sex assigned at birth were collected for both populations. For those presenting for pathologic scars, income quintile, self-identified race/ethnicity, anatomical location, treatment number and type, and clinical outcome were also analyzed. Multivariate analyses calculated adjusted odds ratios (aORs) and 95% confidence intervals to assess associations between scar subsite, intervention type, and persistence after treatment. RESULTS: Compared to individuals presenting for tonsillectomy, a disproportionate percentage of patients presenting for scarring identified as Black (26.6% vs. 13.5%) or Asian (17.4% vs. 7.1%, p = 0.016) or were male (61.7% vs. 49.7%, p = 0.053). Individuals identifying as Black or Asian were more likely to present with ear lobe and neck scars, respectively (50.0% vs. 45.5%, p = <0.001). Ear scars were significantly more likely to receive excision at initial treatment (aOR = 5.86 [1.43-23.96]) compared to other subsites, and were more likely to require >1 treatment (aOR = 5.91 [1.53-22.75]). CONCLUSION: Among pediatric patients presenting with keloids or HTS, children who identified as Black or Asian were more likely to present with ear and neck scars, respectively. Ear scars were frequently treated with excision and appear more likely to require adjuvant treatments and multiple interventions. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3127-3135, 2024.

Anti-Inflammatory Benefits of Food Ingredients in Periodontal Diseases.

Periodontitis is a multi-faceted inflammatory disease that impacts the gingiva and the structures that support our teeth, and may eventually increase tooth mobility and the risk of tooth loss. Inflammation is a viable therapeutic target of periodontitis for both biologic (dietary) and host modulatory agents/drugs. Conventional therapeutic approaches for periodontitis, including nonsurgical or surgical periodontal therapy as well as occasional adjunctive antimicrobial therapy, have been only marginally effective. Malnutrition, or at least poor dietary habits, can be highly prevalent among patients with periodontal diseases. As several food nutrients can aid in periodontal healing and regeneration, there is a critical need to evaluate natural dietary sources and supplement ingredients that can counterbalance the inflammatory processes and improve the periodontal status of our patients. Here, we reviewed the current state of knowledge (search period: 2010 to 2022; PubMed and Web of Science) on the anti-inflammatory actions of food ingredients and supplements in clinical studies of patients with periodontal diseases. A diet that includes fruits and vegetables, omega-3 polyunsaturated fatty acids, and supplements of vitamins and plant-derived compounds seems to counteract gingival inflammation and has a promising therapeutic impact in patients with periodontal diseases. Despite the positive indications that several nutrients can be used as an adjunct to periodontal therapy, additional studies with bigger sample sizes and longer follow-up periods are needed to elucidate their therapeutic benefits and the most effective doses and administration.

Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair.

Objective: Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A4 (LXA4-ME) on scarring in a novel rabbit model of cleft lip repair. Methods: A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars. Rabbits were randomly assigned to topical application of PBS (control) or 1 ug of LXA4-ME (treatment). 42 days post surgery all animals were euthanized. Photographs of the cleft lip area defect and histologic specimens were evaluated. Multiple scar assessment scales were used to compare scarring. Results: Animals treated with LXA4-ME exhibited lower Visual Scar Assessment scores compared to animals treated with PBS. Treatment with LXA4-ME resulted in a significant reduction of inflammatory cell infiltrate and density of collagen fibers. Control animals showed reduced 2D directional variance (orientation) of collagen fibers compared to animals treated with LXA4-ME demonstrating thicker and more parallel collagen fibers, consistent with scar tissue. Conclusions: These data suggest that LXA4-ME limits scarring after cleft lip repair and improves wound healing outcomes in rabbits favoring the resolution of inflammation. Further studies are needed to explore the mechanisms that underlie the positive therapeutic impact of LXA4-ME on scarring to set the stage for future human clinical trials of LXA4-ME for scar prevention or treatment after cleft lip repair.

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19.

The recent outbreak of SARS-CoV2 has emerged as one of the biggest pandemics of our century, with outrageous health, social and economic consequences globally. Macrophages may lay in the center of COVID-19 pathogenesis and lethality and treatment of the macrophage-induced cytokine storm has emerged as essential. Specialized pro-resolving mediators (SPMs) hold strong therapeutic potentials in the management of COVID-19 as they can regulate macrophage infiltration and cytokine production but also promote a pro-resolving macrophage phenotype. In this review, we discuss the homeostatic functions of SPMs acting directly on macrophages on various levels, towards the resolution of inflammation. Moreover, we address the molecular events that link the lipid mediators with COVID-19 severity and discuss the clinical potentials of SPMs in COVID-19 immunotherapeutics.

Repeated delivery of chlorhexidine chips for the treatment of peri-implantitis: A multicenter, randomized, comparative clinical trial.

BACKGROUND: Peri-implantitis is a challenging condition to manage and is frequently treated using non-surgical debridement. The local delivery of antimicrobial agents has demonstrated benefit in mild to moderate cases of peri-implantitis. This study compared the safety and efficacy of chlorhexidine gluconate 2.5 mg chip (CHX chips) as an adjunctive treatment to subgingival debridement in patients afflicted with peri-implantitis. METHODS: A multicenter, randomized, single-blind, two-arm, parallel Phase-3 study was conducted. Peri-implantitis patients with implant pocket depths (IPD) of 5-8 mm underwent subgingival implant surface debridement followed by repeated bi-weekly supragingival plaque removal and chlorhexidine chips application (ChxC group) for 12 weeks, or similar therapy but without application of ChxC (control group). All patients were followed for 24 weeks. Plaque and gingival indices were measured at every visit whereas IPD, recession, and bleeding on probing were assessed at 8, 12, 16, 24 week. RESULTS: A total of 290 patients were included: 146 in the ChxC group and 144 in the control. At 24 weeks, a significant reduction in IPD (P = 0.01) was measured in the ChxC group (1.76 ± 1.13 mm) compared with the control group (1.54 ± 1.13 mm). IPD reduction of ≥2 mm was found in 59% and 47.2% of the implants in the ChxC and control groups, respectively (P = 0.03). Changes in gingival recession (0.29 ± 0.68 mm versus 0.15 ± 0.55 mm, P = 0.015) and relative attachment gain (1.47 ± 1.32 mm and 1.39 ± 1.27 mm, P = 0.0017) were significantly larger in the ChxC group. Patients in the ChxC group that were < 65 years exhibited significantly better responses (P < 0.02); likewise, non-smokers had similarly better response (P < 0.02). Both protocols were well tolerated, and no severe treatment-related adverse events were recorded throughout the study. CONCLUSIONS: Patients with peri-implantitis that were treated with an intensive treatment protocol of bi-weekly supragingival plaque removal and local application of chlorhexidine chips had greater mean IPD reduction and greater percentile of sites with IPD reduction of ≥2 mm as compared with bi-weekly supra-gingival plaque removal.

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity.

OBJECTIVES: To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment. MATERIALS AND METHODS: This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age. RESULTS: Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II (P < .001) and between CVMS I and CVMS V (P = .004). A significant positive correlation between age and CVMS was found (rs = 0.763, P < .001). The models' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age. CONCLUSIONS: The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.

Prevalence, Etiology and Treatment of Peri-Implant Mucositis and Peri-Implantitis: A Survey of Periodontists in the United States.

BACKGROUND: Currently, information available on the exact prevalence and standard therapeutic protocol of peri-implant diseases is insufficient. The aim of this survey was to investigate the perceived prevalence, etiology, and management of peri-implant mucositis and peri-implantitis by periodontists in the United States. METHODS: A twenty-question survey was developed. Periodontists currently practicing in the United States were contacted by an e-mail that contained a link to access the survey. RESULTS: Two hundred eighty periodontists (79.3% males; 62.9% with >10 years in practice, 75.7% in private practice) completed the survey. Most (96.1%) of the participants were placing implants (58.3% for >10 years and 32.4% >150 implants/year). The majority reported that the prevalence of peri-implant mucositis and peri-implantitis in their practices is up to 25% but is higher in the general US population and that up to 10% of implants must be removed due to peri-implantitis. There was agreement among contributing etiologic factors such as: 1) plaque; 2) smoking; 3) adverse loading; 4) oral hygiene; 5) use of antimicrobial gel/mouthrinse; 6) non-surgical debridement; 7) use of systemic antibiotics; and 8) 3-month supportive care for treatment of peri-implantitis. Significant heterogeneity was recorded in relation to the instruments used for debridement, use and type of surgical treatment, and materials used for regeneration. Only 5.1% believed that treatment is very effective. CONCLUSIONS: This survey indicates that peri-implant diseases are a frequently encountered problem in periodontal practices and that the absence of a standard therapeutic protocol results in significant empirical use of therapeutic modalities and a moderately effective treatment outcome.

Use of polyphenols in periodontal inflammation.

Periodontitis is an oral inflammatory disease of polymicrobial origin that causes the destruction of gingival connective tissue and the alveolar bone supporting the teeth. Host immune and inflammatory responses due to specific periodontopathogens and their metabolic products mediate local tissue destruction. Periodontal disease affects as many as 30% of adults and it is one of the most common chronic human diseases. However, traditional therapeutic modalities for periodontitis, including non-surgical or surgical periodontal therapy and occasional adjunctive antimicrobial therapy, have been only partially successful. Moreover, the widespread development of antibiotic resistance in pathogenic bacteria and unwanted effects on the gut flora necessitates new strategies to better control periodontal inflammation. Recently, natural compounds capable of modulating the host inflammatory response have received considerable attention. Here we review (Pubmed 1997 to 2013) the orally-related anti-bacterial and anti-inflammatory actions of polyphenols, naturally occurring molecules, capable of modulating the host inflammatory response. Of these, certain flavonoids appear to stand out because of their beneficial profile and clinical evidence. Unique formulations of novel flavonoids may be useful for further development as possible therapeutic agents for periodontal inflammation.

Assessment of the impact of heavy metal pollution from a ferro-nickel smelting plant using biomarkers.

A set of biomarkers was used to assess the impact of heavy metal pollution by a ferro-nickel smelting plant in Larymna bay (North Evoikos Gulf, Greece). These included a biomarker reflecting health status of an organism (scope for growth, SFG), a cellular biomarker of heavy metal exposure (composition of metal-containing granules), and two biochemical biomarkers reflecting oxidative stress (glutathione peroxidase, GPX) and neurotoxicity (acetylcholinesterase, AChE) measured in mussels (Mytilus galloprovincialis) both native and transplanted for 1 and 6 months at the coastal area of Larymna. All biomarkers in mussels at Larymna revealed differences from mussels at a reference site, signaling effects of the increased heavy metal levels on the biota. While effects on SFG and GPX in Larymna mussels were obvious on short-term exposure and persistent during chronic exposure, only chronic exposure induced a possibly cumulative effect on AChE. To validate the causal relationship between heavy metal exposure and effects observed in Larymna, SFG, GPX, and ACHE were examined in mussels exposed to a mixture of heavy metals (Ni, Cr, and Fe) under controlled laboratory conditions. The laboratory experiment verified the causal relationship between SFG and GPX responses and heavy metals but this was not demonstrated for AChE. Results from field-collected and laboratory-exposed mussels indicated a potential of GPX as predictive biomarker of population-level effects of heavy metal exposure.