Impact of N-terminal pro-B-type natriuretic peptide and related inflammatory biomarkers on periodontal treatment outcomes in patients with periodontitis: An explorative human randomized-controlled clinical trial.

BACKGROUND: N-terminal portion of the B-type natriuretic propeptide (NT-proBNP) has potentially been shown to play an important role in the development of periodontitis and cardiovascular disease (CVD). This study evaluated the efficacy of periodontal treatment on NT-proBNP and related CVD biomarkers and explored whether subjects harboring high NT-proBNP at baseline showed increased clinical benefits with the non-surgical periodontal treatment performed with full-mouth scaling and root planing (FM-SRP) at 6-month follow-up. METHODS: Forty-eight patients with stage III periodontitis were randomized to receive minimal standard oral care (SOC) (n = 24) or FM-SRP (n = 24) protocol. Clinical periodontal parameters (probing depth, clinical attachment loss, bleeding on probing), serum NT-proBNP, α1-antitrypsin, C-reactive protein (hs-CRP), endothelial cell-specific molecule-1 (ECM-1), and neutrophil gelatinase-associated lipocalin (NGAL) concentrations were assessed at baseline and at 1-, 3-, and 6- month follow-up. RESULTS: At 6 months, FM-SRP was more effective than SOC in reducing periodontal parameters and mean proportions of NT-proBNP (p = 0.004), hs-CRP (p = 0.003), α1-antitrypsin (p = 0.012), ECM-1 (p = 0.014), and NGAL (p = 0.045). At 6-month follow-up, the reduced NT-proBNP, α1-antitrypsin, hs-CRP, ECM-1, and NGAL levels were significantly correlated with the extent of periodontitis (p < 0.05). Furthermore, the analysis of variance analysis evidenced that, at 6-month follow-up, FM-SRP significantly impacted the reduction of NT-proBNP, hs-CRP, ECM-1, and NGAL. Moreover, high levels of NT-proBNP, hs-CRP, ECM-1, and NGAL at baseline significantly influenced the efficacy of periodontal treatment positively. CONCLUSION: In this study, FM-SRP was more effective than SOC in reducing clinical variables and NT-proBNP levels, although subjects who harbored high NT-proBNP concentrations at baseline showed greater clinical benefits of periodontal treatment at 6-month follow-up.

The Harvard Macy Institute Art Museum-based Health Professions Education Fellowship: Transformational faculty development through the arts.

Museum-based education for health professionals can lead to a variety of important learning outcomes within the domain of skills development, personal insight, perspective-taking and social advocacy. The Harvard Macy Institute's Art Museum-based Health Professions Education Fellowship was designed to develop faculty expertise in art museum-based practices, encourage scholarship, and cultivate a cohesive and supportive community of educators. The Fellowship was piloted from January to May 2019 with twelve interprofessional Fellows. Two in-person experiential sessions were held at Boston-area museums with intervening virtual learning. Fellows were introduced to a variety of approaches used in art museum-based education and developed a project for implementation at their home institution. A qualitative formative evaluation assessed immediate and 6-month post-Fellowship outcomes. Outcomes are reported in four categories: (1) Fellows' personal and professional development; (2) Institutional projects and curriculum development; (3) Community of practice and scholarly advancement of the field; and (4) Development of Fellowship model. A follow-up survey was performed four years after the conclusion of the pilot year, documenting Fellows' significant accomplishments in museum-based education, reflections on the Fellowship and thoughts on the future of the field.

Periodontitis activates the NLRP3 inflammasome in serum and saliva.

BACKGROUND: Nod-like receptor family pyrin domain-containing protein-3 (NLRP3) complex inflammasome has potentially been shown to play an important role in the development of periodontitis and diabetes. The objective of this study was to analyze the association between serum and salivary NLRP3 concentrations in patients with periodontitis and type-II diabetes mellitus (DM) and to evaluate whether this association was influenced by potential confounders. METHODS: For the present study, a cohort of healthy controls (n = 32), and patients with periodontitis (n = 34), type-II DM (n = 33), and a combination of periodontitis + type-II DM (n = 34) were enrolled. Patients were characterized on the basis of their periodontal status and analyzed for demographic characteristics, serum mediators, and for serum and salivary concentrations of NLRP3. A uni- and multivariate model was established to analyze whether periodontitis, type-II DM, and CRP influenced serum and salivary NLRP3 concentrations. RESULTS: In comparison to type-II DM patients and healthy controls, patients with periodontitis (serum, P = 0.003; saliva P = 0.012) and periodontitis + type-II DM (serum, P = 0.028; saliva, P = 0.003) had elevated serum and salivary NLRP3 concentrations. The multivariate regression model showed that periodontitis (P = 0.029) and HDL-cholesterol (P = 0.012) were significant predictors of serum NLRP3 concentrations whereas periodontitis (P = 0.036) and CRP (P = 0.012) were significant predictors of salivary NLRP3. CONCLUSION: The results of the present study showed that periodontitis and periodontitis + type-II DM patients had higher serum and salivary NLRP3 concentrations in comparison to healthy controls and patients with type-II DM. Periodontitis was demonstrated to be a significant predictor of both serum and salivary NLRP3 concentrations.

Analysis of galectin-3 levels as a source of coronary heart disease risk during periodontitis.

BACKGROUND AND OBJECTIVE: Different evidence has shown that Galectins have a key role as modulators of cell surface functions and signaling in a wide range of inflammatory diseases during their preclinical stages. The aim of this study was to analyze the association and impact of periodontitis and coronary heart disease (CHD) on salivary and serum Galectin-3 in patients with periodontitis and CHD. MATERIALS AND METHODS: For the present study, healthy controls (n = 38), periodontitis (n = 40), CHD (n = 39), and a combination of periodontitis +CHD (n = 38) patients were enrolled and analyzed. In each patient, demographic characteristics and a full-mouth clinical periodontal examination were achieved. Moreover, serum and salivary samples were collected to assess Galectin-3 and Endothelin-1 (ET-1) levels. The Jonckheere-Terpstra p-trend and Spearman's correlation tests as well as uni- and linear regression analyses were used to analyze the study data. RESULTS: Patients with periodontitis (serum, p = .003; saliva, p < .001) and periodontitis + CHD groups (serum p = .004; saliva, p < .001) had higher median serum and salivary concentrations of Galectin-3 in comparison with CHD and healthy controls. Serum (p = .006) and salivary (p = .009) Galectin-3 levels were significantly correlated with serum ET-1. The multivariate regression analysis highlighted that periodontitis (p = .047) was the significant predictor of serum Galectin-3 levels while ET-1 (p = .028) was the significant predictor of salivary Galectin-3 levels. CONCLUSION: The results showed that patients with periodontitis and periodontitis + CHD presented significant higher serum and salivary Galectin-3 levels in comparison with CHD patients and healthy subjects. Periodontitis and ET-1 were the significant predictors of serum and salivary Galectin-3 levels, respectively.

Independent impact of periodontitis and cardiovascular disease on elevated soluble urokinase-type plasminogen activator receptor (suPAR) levels.

BACKGROUND: Previous studies have demonstrated that a soluble urokinase-type plasminogen activator receptor (suPAR) plays an essential function in leukocytes and endothelial homeostasis and, therefore, in the development of coronary heart disease (CHD) and periodontitis. The aim of this study was to analyze the impact of gingival health, periodontitis, and CHD on suPAR levels in plasma and saliva and to evaluate suPAR as a biomarker of periodontitis and CHD. METHODS: Healthy controls (n = 33), patients with periodontitis (n = 31), CHD (n = 29), and a combination of periodontitis + CHD (n = 29) were enrolled in the present study. All patients were clinically and periodontally evaluated and regularly assessed for socioeconomic status, serum lipids, high-sensitivity C-reactive protein (hs-CRP), and for plasma and salivary suPAR levels. RESULTS: Patients with periodontitis (P <.001) and with periodontitis + CHD (P <.001) presented higher median plasma and salivary suPAR levels compared with CHD and healthy controls. Moreover, univariate regression analysis demonstrated that hs-CRP (P <.001) and periodontitis (P <.001) had a significant negative direct effect on both plasma and salivary suPAR levels. The multivariate regression analysis showed that periodontitis was the only significant predictor of plasma suPAR (P = .035) while hs-CRP was the only significant predictor of salivary suPAR (P <.001). CONCLUSIONS: The results of the present study demonstrated that patients with periodontitis and periodontitis + CHD presented higher suPAR levels in both plasma and saliva in comparison with healthy controls and CHD. Moreover, periodontitis and hs-CRP were the only significant predictors of the augmented suPAR levels in plasma and saliva, respectively.

Twelve Tips for Starting a Collaboration with an Art Museum.

In recent years, collaboration between medical educators and art museum educators has emerged as an important trend. The museum environment can support a kind of professional reflection and conversation that is difficult to develop in a medical setting. Skills such as close looking, empathic communication, resilience, and cultural awareness may also be developed in the art museum when plans for the visit are developed with attention to their relevance to health professions. Working across disciplines requires identifying and cultivating a strong partner as well as clear communication about goals and possibilities. The following tips were developed by museum educators based on their extensive experience working with medical students, interns, residents and faculty at Harvard Medical School and the University of Texas at Austin's Dell Medical School over the past twelve years.

Association of vitamin D in patients with periodontitis: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Vitamin D has been considered to possess anti-inflammatory and antimicrobial activity, which may be a link for the known interaction of periodontitis (CP) and coronary heart disease (CHD). This study investigated the association between serum vitamin D levels and periodontitis in patients with CP and with CHD. Furthermore, the objective was to determine whether periodontitis and CHD had an impact on serum vitamin D levels. MATERIAL AND METHODS: Using a cross-sectional design, a total of 46 patients with CP, 45 patients with CHD, 45 patients with both CP and CHD, and 43 healthy patients were enrolled in the present study. RESULTS: Patients in the CP (17.4 ± 5.2 ng/mL) and in the CP + CHD (16.5 ± 5.6 ng/mL) group presented a significantly lower mean serum level of 25(OH)vitamin D compared to patients in the CHD (24.6 ± 3.7 ng/mL) and healthy control groups (29.9 ± 5.4 ng/mL) (P < .001). 25(OH)vitamin D levels were positively correlated with the number of teeth and negatively with C-reactive protein (CRP) and all periodontal parameters (P < .001). In all patients, there was a proportional increase of 25(OH)vitamin D levels with a progressive increase in number of teeth (P-trend <.001) while there were a proportional decrease in 25(OH)vitamin D levels with a progressive increase in clinical attachment level (CAL, P-trend = .001), probing depth (PD, P-trend = .006), and bleeding sites (BOP, P-trend <.001) levels. CONCLUSION: Patients with CP and CP + CHD presented significantly lower serum levels of vitamin D compared to CHD and healthy controls. Moreover, the presence of CP negatively influenced serum vitamin D levels.

Distribution of the Specialist Aphid Uroleucon nigrotuberculatum (Homoptera: Aphididae) in Response to Host Plant Semiochemical Induction by the Gall Fly Eurosta solidaginis (Diptera: Tephritidae).

Many plants use terpenoids and other volatile compounds as semiochemicals. Reception of plant volatiles by conspecifics may trigger a defensive phytochemical response. These same compounds can also function as host recognition signals for phytophagous insects. In this experiment, we find that when the specialist gall-forming fly Eurosta solidaginis (Fitch; Diptera: Tephritidae) attacks its tall goldenrod (Solidago altissima (L.; Asterales: Asteraceae)) host plant, the fly indirectly induces a phytochemical response in nearby tall goldenrod plants. This phytochemical response may, in turn, act as a positive signal attracting the goldenrod specialist aphid Uroleucon nigrotuberculatum (Olive; Hemiptera: Aphididae). Laboratory-based experiments exposing ungalled tall goldenrod plants to the volatiles released by E. solidaginis galls demonstrated a consistent increase in foliar terpenoid concentrations in ungalled plants. Analysis of tall goldenrod stem and gall tissue chemistry revealed induction of terpenoids in gall tissue, with a simultaneous decrease in green leaf volatile concentrations. Field experiments demonstrated a consistent spatial relationship in tall goldenrod foliar terpenoid concentrations with distance from an E. solidaginis gall. Both laboratory and field experiments establish consistent induction of the terpene ß-farnesene, and that this compound is a strong positive predictor of U. nigrotuberculatum aphid presence on goldenrod plants along with plant biomass and several other foliar terpenoids. These findings suggest E. solidaginis induced phytochemistry, especially ß-farnesene, may be acting as a kairomone, driving aphid distribution in the field.

Histologic Evaluation of Soft and Hard Tissue Healing Following Alveolar Ridge Preservation with Deproteinized Bovine Bone Mineral Covered with Xenogenic Collagen Matrix.

The purpose of this study was to histologically evaluate new bone formation and dimensional soft tissue changes of two different healing protocols (16 weeks and 32 weeks) using deproteinized bovine bone mineral (DBBM) covered with collagen matrix (CM) for alveolar ridge preservation in the anterior esthetic zone prior to dental implant placement. Compared to baseline, both treatments yielded statistically significant differences in several clinical parameters and in the microarchitecture of the native bone and in the newly formed bone in the augmented sites. However, the protocol at 32 weeks determined greater new vital bone formation and fewer dimensional tissue changes.

Effects of Intraspecific Genetic Variation and Prior Herbivory in an Old-Field Plant on the Abundance of the Specialist Aphid Uroleucon nigrotuberculatum (Hemiptera: Aphididae).

Intraspecific genetic variation in plants can contribute to the diversity and abundance of associated insects, though many questions remain about why some genotypes support more insects than others. Since plant secondary metabolites, which may be induced after insect attack, may potentially vary among genotypes, these compounds provide a possible explanation for insect abundance variation in plants with substantial genetic variation. In this study, we examined four genotypes of the old-field plant species Solidago altissima (L.; Asterales: Asteraceae) and asked if the abundance of the specialist aphid Uroleucon nigrotuberculatum (Olive; Hemiptera: Aphididae) was affected by genotype and previous foliage damage by a specialist beetle. We hypothesized that different genotypes and prior herbivory would result in different quantities of terpenes produced by S. altissima, and that terpenes would affect aphid abundance. We found evidence of foliar terpene induction in a greenhouse environment, and significant differences in terpene production among genotypes in a field setting, though prior damage had little effect on aphid abundance in the field. There were significant effects of genotypes on aphid abundance, as well as genotype effects on terpenes and foliar nutrients (leaf N and C:N). Noteworthy was a change in the allocation of particular terpenes among genotypes that related to aphid abundance. Our analyses demonstrated that phytochemicals, and especially terpenes, related to aphid abundance. This study adds to a previous finding that variation in leaf terpenes in S. altissima provides a partial explanation for variable abundance among genotypes of a specialist aphid, and suggests that differences in the allocation of compounds is important.

The effects of a desiccant agent in the treatment of chronic periodontitis: a randomized, controlled clinical trial.

OBJECTIVE: Chemotherapeutic agents have been widely used as adjuncts for the treatment of chronic periodontitis (CP). This study investigated and compared a desiccant agent as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of CP. MATERIALS AND METHODS: Thirty-six patients with CP were studied. Using a split-mouth design, the maxillary right and left quadrants were randomly assigned to SRP plus desiccant (Hybenx® EPIEN Medical, Inc. St. Paul, MN, USA) or SRP alone. Patients were examined on a regular basis for clinical, microbiological, and inflammatory mediator changes over a 1-year period. Clinical attachment level (CAL) was the primary outcome variable. In addition, the red complex bacteria and gingival crevicular fluid (GCF) inflammatory mediators were monitored. RESULTS: Compared to baseline, both treatments demonstrated an improvement in periodontal parameters. Compared to SRP alone, SRP plus desiccant yielded a significant improvement in probing depth (PD) (SRP: 2.23 ± 0.31 mm vs. desiccant: 3.25 ± 0.57 mm, p < 0.05), CAL (SRP: 3.16 ± 0.29 mm vs. desiccant: 4.21 ± 0.34 mm, p < 0.05 mm) and bleeding on probing (BOP) (SRP: 4.56 ± 1.5% vs. desiccant: 34.23 ± 4.2%, p < 0.001) at 12 months. Similarly, in the SRP plus desiccant group, the bacteria of the red complex were significantly reduced (p < 0.05); and the level of inflammatory mediators was significantly reduced (p < 0.003) compared to SRP alone. CONCLUSIONS: SRP plus the desiccant resulted in a greater reduction in clinical, microbial and inflammatory mediators compared to SRP alone. CLINICAL RELEVANCE: Desiccant, when combined to SRP, was demonstrated as a significant approach to control the levels of certain periodontal pathogens, inflammatory mediators in patients with CP.

Risk association between scleroderma disease characteristics, periodontitis, and tooth loss.

Systemic sclerosis (SSc) is a multi-system disorder that can have significant adverse effects on the health of the mouth. The aim of this study was to investigate the associations between the disease characteristics of SSc, periodontal disease (PD), and tooth loss. Fifty-four patients affected by SSc and 55 non-diseased controls were matched for age and gender. SSc was characterized in subtypes and with the mean duration of disease and the Modified Rodnan Skin Score [mRSS]. Patients were surveyed and examined through the evaluation of the periodontal parameters and the number of teeth. A logistic regression analysis showed that patients with SSc presented a higher number of missing teeth (p = 0.001) and a significant median increased odds 2.95 (95% CI 1.26 to 6.84) of PD (defined as clinical attachment loss, CAL) compared to nondiseased controls (6.83, 95% CI 1.94 to 24.36). Moreover, the fewer values of PD was correlated with mRSS in the total SSc group and with the mean duration of disease in patients with limited SSc (p = 0.007), even after adjusting this correlation with the presence of the major organ involvement. This study showed that patients with SSc presented increased odds of PD and tooth loss compared to non-diseased controls. In SSc patients, the magnitude of PD was strongly associated with the mRSS and with the mean duration of the disease. The clinicians should be aware of the potential systemic health problems related to PD.

Gingival crevicular fluid as a source of biomarkers for periodontitis.

In evaluating the pathogenesis of periodontal diseases, the diagnostic potential of gingival crevicular fluid has been extensively explored during the last twenty years, from initially just confirming health and disease states to more recently investigating it as a potential prognostic tool. As host susceptibility is a critical determinant in periodontal disease pathogenesis, the inflammatory mediator levels present in gingival crevicular fluid represent relevant risk indicators for disease activity. Considerable work has been carried out to identify the many different cytokine inflammatory pathways and microbial stimuli that are associated with periodontal disease pathogenesis. Now, 'omics' approaches aim to summarize how these pathways interact and probably converge to create critical inflammatory networks. More recently, gingival crevicular fluid metabolomics appears promising as an additional diagnostic method. Biofilm structure and the host inflammatory response to the microbial challenge may induce specific inflammatory signatures. Host genetics and epigenetics may also modulate microbial colonization, adding to the multiplicity of potential causal pathways. Omics analyses of gingival crevicular fluid, measuring microbial and host interactions in association with the onset and progression of periodontal diseases, still show the potential to expand the landscape for the discovery of diagnostic, prognostic and therapeutic markers.

Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages.

Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-κB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-κB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-α, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-κB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.

Colonization of Solidago altissima by the specialist aphid Uroleucon nigrotuberculatum: effects of genetic identity and leaf chemistry.

In dominant old-field plant species, genotypic variation in traits important for herbivorous insects may explain variation in insect species abundance. While the importance of plant genetic identity on arthropod abundance has been demonstrated, specific factors that drive genotype choice by insects remain largely unknown. Sixteen genotypes of the widely distributed plant species Solidago altissima were used to investigate the possible role of nutrients and terpene secondary metabolites in shaping the abundance of a common specialist aphid, Uroleucon nigrotuberculatum. Ramets were propagated in a greenhouse and then transferred to a natural field setting. After 76 days, aphid abundance was quantified and leaf tissue assayed for nutrients and terpenes. Aphids/g plant biomass significantly differed among genotypes, with a 30-fold difference observed among plant genotypes. Leaf nitrogen, C:N ratio and water did not vary among genotypes. Of eight terpenes quantified, five were influenced by plant genotype. Aphid abundance increased marginally with the concentration of the monoterpene ß-pinene in leaf tissue (P = 0.056). A partial least squares analysis determined that nutritional chemicals did not explain aphid responses, while 49% of the variation in aphid colonization among genotypes was explained by terpenes. This study is one of the first to demonstrate that variation in allelochemicals may be related to differences in the abundance of a key herbivore among genotypes of a plant species that exhibits large intraspecific genetic variation.

Accelerated orthodontic tooth movement: molecular mechanisms.

Accelerating orthodontic tooth movement can significantly reduce treatment duration and risks of side effects. The rate of orthodontic tooth movement is chiefly determined by the remodeling of tissues surrounding the roots; this in turn is under the control of molecular mechanisms regulating cellular behaviors in the alveolar bone and periodontal ligament. This review summarizes the current knowledge on the molecular mechanisms underlying accelerated orthodontic tooth movement, and the clinical and experimental methods that accelerate orthodontic tooth movement with possible molecular mechanisms. The review also shows directions for future studies to develop more clinically applicable methods to accelerate orthodontic tooth movement.