Areas Of Inflammation Research Articles

Non-Surgical Periodontal Therapy's Influence on Alpha-Synuclein and Inflammatory Marker Levels: A Pilot Study.

Background: Microbial dysbiosis may contribute to alpha-synuclein (α-Syn) homeostasis disruption, yet the burden of inflammatory periodontal infection and its treatment have never been studied in this regard. We aimed to compare the cytokine and α-Syn levels in the saliva and blood of patients with periodontitis who underwent non-surgical periodontal therapy (NSPT) and those of their healthy counterparts. Methods: Periodontal examination and saliva and blood sample collection were carried out in incoming patients at a university clinic. The periodontitis group (PG) received NSPT. The sample collection and periodontal observation were repeated 30 days after. IL-6, IL1-β and total α-Syn were quantified using immunoassay methods. The periodontal inflamed surface area (PISA) was calculated as a proxy for periodontal inflammation. Results: Eleven participants formed the PG, and there were fifteen healthy controls (HC). At baseline, no correlation between salivary and plasma α-Syn was found. The salivary α-Syn levels revealed a tendency to decrease 30 days after, particularly in the PD cases. The variation in PISA and α-Syn showed significant correlation. Salivary α-Syn correlated negatively with salivary IL-6 levels at both timepoints in the total sample (rho = -0.394 and rho = -0.451) and in the HC (rho = -0.632 and rho = -0.561). Variations in plasma IL-6 and α-Syn were negatively correlated (rho = -0.518) in the healthy participants. Baseline plasma IL1-β negatively correlated with plasmatic α-Syn at 30 days in the HC (rho = -0.581). Conclusions: Salivary and plasma α-Syn bioavailability operate independently, and periodontal diagnosis was not a confounding factor. Salivary α-Syn levels were significantly affected by NSPT, contrary to plasma levels. These results should be confirmed in future larger and prospective studies.

A prospective study on maternal periodontal diseases and neonatal adverse outcomes.

It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. A total of 193 generally healthy females in their third trimester (34-36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA. Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Periodontal Disease in Patients with Ischemic Stroke - an Exploratory Study.

The aim of this study was to assess the periodontal disease parameters in patients with ischemic stroke. The study included 21 patients with ischemic brain stroke and a control group that was matched in number, age, and gender. All participants underwent a standard periodontal examination. The inclusion criterion of this study was the presence of at least 15 teeth. Periodontal epithelial surface area, periodontal inflamed surface area (PISA), and periodontal disease stage were determined. All participants were given a questionnaire to determine oral health-related quality of life (OHQL). Stroke risk factors were assessed. Stroke patients had a significantly higher OHQL score than the control group (20.81 vs. 12.57) and a full-mouth plaque score (FMPS, 27.57 vs. 16.83), while full-mouth bleeding score (FMBS) was significantly higher in the control group than in the hospital group (10.17 vs. 6.42). For PISA, statistically significant negative correlations were found for smoking, cholesterol levels, and LDL levels, while significant positive correlations were found for FMBS, clinical attachment level and probing depth. Although PISA does represent the amount of periodontal tissue that is inflamed, tooth loss due to advanced periodontal disease combined with oral hygiene limitations imposed by the hospital setting and the stroke recovery process remain the most significant obstacles for a more meaningful understanding of the data represented by specific clinical, laboratory and various demographic parameters that characterize the two diseases.

Assessing the Correlation of Periodontal Inflamed Surface Area (PISA) With Systemic Inflammatory Markers.

Background Periodontitis has a vital role in eliciting a cross-reactivity or systemic inflammatory response, making periodontal inflamed surface area (PISA)a primary contributor to the inflammatory burden posed by periodontitis. PISA helps in the quantification of the amount of inflamed periodontal tissue. However, the existing literature data concerning PISA as an indicator of inflammatory burden are scarce, with limited research on the relationship between systemic inflammatory markers and PISA. Aim The present clinic-hematological cross-sectional study aimed to correlate PISA with systemic inflammatory markers. The studyalso aimed to assess serum concentrations of inflammatory markers such as erythrocyte sedimentation rates (ESR), C-reactive protein (CRP), and peripheral blood markers such as neutrophils and monocytes and to correlate these markers with PISA. Methods The study assessed 62 subjects, who were divided into two groups of 31 subjects, each followingbleeding on probing (BOP) criteria. Group I consisted of subjects with generalized chronic gingivitis, and Group II included subjects with generalized chronic periodontitis. In two groups, BOP, probing pocket depth, clinical attachment level, and gingival recession were assessed along with PISA by a custom-made R function derived from a pre-existing, freely available MS Excel spreadsheet(Microsoft Corporation, Redmond, Washington). The results of the assessment were then compared. Results A statistically highly significant positive correlation was seen in PISA and CRP with a correlation coefficient of 0.4875 and p-value of 0.000059. A similar statistically significant positive correlation was seen in ESR and PISA with a correlation coefficient of 0.4089 and p-value of 0.000968. A statistically non-significant correlation was seen in neutrophils and PISA with p=0.576018. However, a moderate and positive statistically significant association was seen in monocyte and PISA with a correlation coefficient of 0.3258 and p-value of 0.009956. Conclusions The present study concludes that most of the common systemic inflammatory markers have a positive correlation with PISA. However, more studies are required to establish this correlation.

Immune phenotype profiling based on anatomic origin of melanoma and impact on clinical outcomes of immune checkpoint inhibitor treatment.

9569 Background: The inflamed immune phenotype is associated with a favorable response to immunotherapy in metastatic malignant melanoma. Although variations in molecular features across melanoma subtypes and differing ethnic distributions have been well reported, studies investigating immune phenotypes across multiple institutions within the context of different melanoma subtypes are scarce. We examined the association of immune phenotypes with outcomes after immunotherapy, based on subtypes of malignant melanoma. Methods: Two institutional advanced melanoma cohortsrepresenting Asian and Western populations (YUHS, n = 123; Stanford University, n = 102) were included. H&amp;E-stained tumor slides were assessed using Lunit SCOPE IO, an AI-powered whole slide image analyzer, to define the inflamed score (IS, % of inflamed area) and the inflamed phenotype (&gt;33.3% IS). Clinical outcomes after immune checkpoint inhibitor (anti-PD-1/PD-L1) treatment, including progression-free survival (PFS) and overall-survival (OS), were assessed. Results: In the overall cohort (n = 225), the inflamed phenotype was associated with prolonged PFS (HR = 0.634, 95% CI: 0.453 – 0.887, p = 0.007) and OS (HR = 0.655, 95% CI: 0.432 – 0.992, p = 0.044). On analysis of melanoma subtypes, we identified non-acral cutaneous melanomas (CM, n = 94), acral melanomas (AM, n = 52), mucosal melanomas (n = 43), uveal melanomas (n = 16), and melanomas of unknown primary site (n = 20), with a disproportionate enrichment of AM (37.4%) and mucosal (29.3%) melanoma cases in the YUHS cohort and CM cases (68.6%) in the Stanford cohort. The IS varied across different melanoma subtypes, with the highest IS observed in CM (median, [IQR]; 34.0, [5.8–52.2]), and significantly lower scores in AM (22.3, [7.7–36.9]), mucosal (13.6, [0–31.4]), and uveal melanoma (5.5, [0–13.6]). Among CM patients, the inflamed phenotype was significantly associated with better post-immunotherapy PFS (HR = 0.476, 95% CI: 0.274 – 0.826, p = 0.007). In contrast, the inflamed phenotype did not correlate with survival in AM patients (p = 0.58), who exhibited universally poorer PFS compared to non-AM patients (HR = 2.124, 95% CI: 1.486 - 3.005). Conclusions: AI-powered immune phenotype assessment highlights a heterogeneity of immune phenotypes across specific melanoma subtypes, as well as differential association with outcomes after immune checkpoint inhibitor treatment. While CM patients were well-stratified by immune phenotype, the predictive value of immune phenotyping was less pronounced in acral melanomas, which demonstrated poorer outcomes following immunotherapy.

Anti-Inflammatory Potential of Beclometasone-Loaded Filomicelles on Activated Human Monocytes.

Polymeric micelles with a hydrophobic core represent versatile nanostructures for encapsulation and delivery of water-insoluble drugs. Here, water-insoluble beclometasone dipropionate (BDP) which is a potent anti-inflammatory therapeutic agent but limited to topical applications so far, is encapsulated. Therefore, this work used an amphiphilic block copolymer self-assembling into flexible polymeric filomicelles, which have recently proven to selectively target inflamed areas in patients with inflammatory bowel disease (IBD). The small diameter and flexibility of these filomicelles is considered beneficial for transepithelial passages, while their length minimizes the unspecific uptake into nontargeted cells. This work successfully establishes a protocol to load the water-insoluble BDP into the core of the filomicelles, while maintaining the particle stability to prevent any premature drug release. The anti-inflammatory efficacy of BDP-loaded filomicelles is further investigated on lipopolysaccharide (LPS) stimulated human monocytes. In these ex vivo assays, the BDP-loaded filomicelles significantly reduce TNF-α, IL-6, IL-1ß, IL-12p70, IL-17a, and IL-23 release after 24 h. Additional time course study of drug-loaded filomicelles and their comparison with a common water-soluble and unspecific corticosteroid demonstratepromising results with significant immune response suppression in stimulated monocytes after 2 and 6 h. These findings demonstrate the potential of polymeric filomicelles as a vehicle for potent water-insoluble corticosteroids.

Evaluation of inflammasomes as biomarker following non-surgical periodontal treatment

ObjectiveThe purpose of this study was to investigate interleukin (IL)-1β, IL-18, nod-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-related speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 levels in saliva and serum in different periodontal diseases and to evaluate the changes after non-surgical periodontal treatment (NSPT). DesignA total of 45 participants, 15 healthy, 15 gingivitis, and 15 stage III grade C (SIIIGC) periodontitis patients, were included in the study. Periodontal parameters were assessed, and salivary and serum samples were collected at baseline in all groups and one and three months after NSPT in gingivitis and periodontitis groups. An enzyme-linked immunosorbent assay was used to analyse IL-1β, IL-18, NLRP3, ASC, and caspase-1 levels. ResultsAfter NSPT, improvement was observed in all clinical parameters, along with periodontal inflamed surface area (PISA) in gingivitis and periodontitis groups. PISA scores were positively correlated with IL-1β, NLRP3, and caspase-1 at baseline (p < 0.05). Salivary and serum IL-1β, NLRP3 levels were higher in periodontitis compared to healthy controls at baseline and reduced after treatment (p < 0.05). Receiver operating characteristic analysis revealed that salivary IL-1β, NLRP3, and caspase-1 had the ability to discriminate SIIIGC periodontitis patients from healthy subjects (p < 0.05). ConclusionIn conclusion, salivary IL-1β, NLRP3, and caspase-1 are at aberrantly high levels in SIIIGC periodontitis and are remarkably decreased following NSPT; these inflammasome biomarkers may show potential utility in diagnosing and monitoring periodontitis.

Multi-nutrients and periodontal disease - a new adjunct to improving treatment outcomes? A randomised placebo-control clinical trial.

This study by Laky et al. is a single-centre, double-blinded randomised placebo-controlled clinical trial, examining the effects of micronutrient supplementation in combination with non-surgical hygiene phase therapy (nsHPT)for Stage III and IV periodontal disease. The study was carried out at the Medical University of Vienna (Austria), School of Dentistry. The patients enrolled in the study were randomised to receive a commercially available multi-nutrient supplement (containing: vitamin C, vitamin E, zinc, selenium, alpha-lipoic-acid, cranberry extract, grapeseed extract, and coenzyme Q10) or a cellulose placebo to take for 2 months, alongside a course of non-surgical hygiene phase therapy. At baseline, the patients had a periodontal index screening (PSI) performed. Patients scoring >3 and meeting the inclusion criteria were enrolled in the trial. Oral hygiene instruction and patient education was performed, followed by 1 or more sessions of nsHPT depending on the clinical assessment of each patient, and a full periodontal probing depth (PPD) chart was recorded. The patients were then randomised to receive either the multi-nutrient supplement or the placebo to take twice daily for 8 weeks. Following this 8-week period the PPD as well as bleeding on probing (BOP), gingival recession (GR) and clinical attachment loss (CAL) were measured. The randomisation was carried out by a study-independent member of staff at the centre using a computer programme. A total of 149 patients were assessed for eligibility for this trial. Out of these patients, 83 were deemed to be unsuitable for the trial as they failed to meet the inclusion criteria, and 24 declined to participate. A total of 42 patients were then randomised to each arm of the study. The inclusion criteria included patients with Stage III and IV periodontal disease. Patients were deemed eligible if they met the following criteria: presence of 18 or more scorable teeth (excluding 3rd molars); >4 teeth with PPD of >6 mm; CAL > 5 mm, and no previous periodontal treatment in the past. Percentage bone loss at the most severe site, smoking status, and presence of diabetes and diabetic control were all taken into consideration. Patients were deemed ineligible for the trial if they were pregnant or under 18 years old. Exclusion criteria also included: recent periodontal abscess; a past or current co-morbidity which may confound the results of the study or endanger patients partaking in the study (i.e. malignancy, rheumatoid arthritis, and other severe systemic conditions); and obesity. PPD was used as the primary variable in this study. Other measured outcomes such as GR, CAL, BOP and other measurements taken, such as papillary bleeding index (PBI) and papillary inflamed surface area (PISA), were considered as secondary outcome variables. A variety of tests were used in order to assess the collected data. The Kolmogorov‒Smirnov test and Levene test were used for the equality of variances, and ICC and 95% CI were used when comparing periodontal chartings for PPD (in mm). Chi-square or Fisher tests were used for categorical data between intervention and placebo. The baseline and reevaluation data was compared using the McNemar test. All data was analysed using statistical software. Significant data is indicated by a p value < 0.05. The number of patients included for analysis was reduced to n = 20 for the intervention group and n = 19 for the placebo group. Patients were lost due to a variety of reasons including need for antibiotics and lost to follow-up. The authors concluded that in each arm of the trial, periodontal and hygiene parameters improved overall. The results show that the intervention group had a significantly higher reduction in PPD; however, following data analysis, these findings were found to be statistically insignificant. The authors conclude that the addition of a multi-nutrient supplement, alongside nsHPT for patients undergoing treatment for Stage III and IV periodontal disease, showed a reduction in PPD and BOP when compared with a placebo and nsHPT.

Prevalence of oral Capnocytophaga species and their association with dental plaque accumulation and periodontal inflammation in middle‑aged and older people.

Capnocytophaga species are commonly found in human oral microbiome. The aim of the present study was to understand the association of the prevalence of oral Capnocytophaga species with oral hygiene and periodontal inflammation. A total of 136 patients (median age 72 years) who visited the Hiroshima University Hospital (Hiroshima, Japan) between April 2021 and June 2023 were enrolled. Swab samples were obtained from the tongue surface. DNA from Capnocytophaga species (C. ochracea and C. sputigena) was detected by real-time PCR analysis. Dental plaque accumulation was observed to assess the oral hygiene condition of participants. Additionally, clinical periodontal inflammation was assessed with periodontal inflamed surface area (PISA) scores. Clinical confounding factors such as age, sex, lifestyle-related disease, remaining teeth and denture wearing between Capnocytophaga species-positive and -negative groups were adjusted with a propensity score matching method. Mann-Whitney U and χ2 or Fisher's exact test were employed for statistical analysis. The prevalence rate was 67.6% for oral C. ochracea and 83.1% for C. sputigena. C. ochracea-positive participants showed significantly higher plaque control record scores (an indicator of dental plaque accumulation) than C. ochracea-negative participants (P=0.03). Additionally, C. ochracea/C. sputigena dual-positive participants exhibited significantly higher plaque control record and PISA scores than non-dual-positive participants (P=0.01 and P=0.04, respectively). Propensity score matching was conducted in the C. ochracea/C. sputigena dual-positive group and the non-dual-positive group for adjustment of clinical factors, resulting in 51 matched patient pairs. C. ochracea/C. sputigena dual-positive participants had significantly higher plaque control record scores than non-dual-positive participants (P=0.02). The present results suggest that the prevalence of both oral C. ochracea and C. sputigena is associated with poor oral hygiene in middle-aged and older people.

Leucine-rich alpha-2-glycoprotein 1 affects bone destruction via IL-6 in mouse periodontitis model.

To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. Invivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated. A positive correlation existed between the periodontal inflamed surface area and serum LRG1 levels (Spearman's rank correlation coefficient: 0.60). LRG1 mRNA expression in human gingival epithelial cells and fibroblasts was upregulated by Porphyromonas gingivalis stimulation or tumor necrosis factor-α stimulation. Interleukin-6 in human gingival epithelial cells and fibroblasts induced the production of LRG1 and transforming growth factor-β. LRG1 levels in the periodontal tissue and serum in the periodontitis model were higher than those in control mice. LRG1 local administration resulted in alveolar bone resorption, whereas the administration of interleukin-6R antibody inhibited bone resorption. LRG1 levels in serum and periodontal tissue are upregulated in periodontitis and are implicated in periodontal tissue destruction through interleukin-6 production.

Correlation of periodontal inflamed surface area with glycated hemoglobin, interleukin-6 and lipoprotein(a) in type 2 diabetes with retinopathy.

The two-way relationship between periodontitis and type 2 diabetes mellitus (T2DM) is well established. Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis, accentuating diabetic complications. An inflammatory link exists between diabetic retinopathy (DR) and periodontitis, but the studies regarding this association and the role of lipoprotein(a) [Lp(a)] and interleukin-6 (IL-6) in these conditions are scarce in the literature. To determine the correlation of periodontal inflamed surface area (PISA) with glycated Hb (HbA1c), serum IL-6 and Lp(a) in T2DM subjects with retinopathy. This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR. All subjects were assessed for periodontal parameters [bleeding on probing (BOP), probing pocket depth, clinical attachment loss (CAL), oral hygiene index-simplified, plaque index (PI) and PISA], and systemic parameters [HbA1c, fasting plasma glucose and postprandial plasma glucose, fasting lipid profile, serum IL-6 and serum Lp(a)]. The proportion of periodontitis in T2DM with and without DR was 47.5% and 27.5% respectively. Severity of periodontitis, CAL, PISA, IL-6 and Lp(a) were higher in T2DM with DR group compared to T2DM without DR group. Sig-nificant difference was observed in the mean percentage of sites with BOP between T2DM with DR (69%) and T2DM without DR (41%), but there was no significant difference in PI (P > 0.05). HbA1c was positively correlated with CAL (r = 0.351, P = 0.001), and PISA (r = 0.393, P ≤ 0.001) in study subjects. A positive correlation was found between PISA and IL-6 (r = 0.651, P < 0.0001); PISA and Lp(a) (r = 0.59, P < 0.001); CAL and IL-6 (r = 0.527, P < 0.0001) and CAL and Lp(a) (r = 0.631, P < 0.001) among study subjects. Despite both groups having poor glycemic control and comparable plaque scores, the periodontal parameters were higher in DR as compared to T2DM without DR. Since a bidirectional link exists between periodontitis and DM, the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Periodontal Treatment During the Blanking Period Improves the Outcome of Atrial Fibrillation Ablation.

Periodontitis has not been recognized as a modifiable risk factor for atrial fibrillation (AF). This prospective nonrandomized study investigated whether periodontal treatment improves the AF ablation outcome. We prospectively enrolled 288 AF patients scheduled to undergo initial radiofrequency catheter ablation. Each patient underwent periodontal inflamed surface area (PISA; a quantitative index of periodontal inflammation) measurement. All eligible patients were recommended to receive periodontal treatment within the blanking period, and 97 consented. During the mean follow-up period of 507±256 days, 70 (24%) AF recurrences were documented. Patients who exhibited AF recurrences had a higher PISA than those who did not (456.8±403.5 versus 277.7±259.0 mm2, P=0.001). These patients were categorized into high-PISA (>615 mm2) and low-PISA (<615 mm2) groups according to the receiver operating characteristic analysis for AF recurrence (area under the curve, 0.611; sensitivity, 39%; specificity, 89%). A high PISA, as well as female sex, AF duration, and left atrial volume, were the statistically significant predicter for AF recurrence (hazard ratio [HR], 2.308 [95% CI, 1.234-4.315]; P=0.009). In patients with a high PISA, those who underwent periodontal treatment showed significantly fewer AF recurrences (P=0.01, log-rank test). The adjusted HR of periodontal treatment for AF recurrence was 0.393 (95% CI, 0.215-0.719; P=0.002). Periodontitis may serve as a modifiable risk factor for AF. PISA is a hallmark of AF recurrence, and periodontal treatment improves the AF ablation outcome, especially for those with poor periodontal condition.

The Impact of Periodontal Inflammation on the Severity of Coronary Atherosclerosis.

Introduction Through plausible biological mechanisms, periodontitis causes systemic inflammatory burden and response, thus resulting in damage far beyond the oral cavity. Studies have demonstrated periodontitis to be a significant risk factor for coronary heart disease (CHD) and stroke. The larger the quantum of periodontal inflamed tissue, the greater the chances of periodontitis eliciting bacteremiaand systemic inflammatory responses. Studies have reported that periodontitis and other common oral infections play an important role in the development of atherosclerosis. Therefore, the quantity of inflamed periodontal tissue assumes significance in determining the severity of atherosclerosis. Hence, this study investigates the impact of periodontal inflamed surface area (PISA) on the severity of coronary atherosclerosis. Materials and methods In this cross-sectional study, a total of 160 patients who presented at the department of periodontics of The British University in Egypt (BUE) from 1 January 2023 to 30 September 2023 were enrolled. Patients were only enrolled if they had undergone coronary angiography within the last six months, were less than 60 years of age, shared their previous medical history and coronary angiographic report, and gave informed written consent. Data on classic coronary risk factors and periodontal inflammatory status and angiographic findings were recorded and subjected to appropriate statistical analysis. Results The results revealed that the periodontal inflamed surface area (p = 0.002) apart from age (p < 0.047) and low-density lipoprotein cholesterol(LDL-C) (p < 0.001) is a significant independent predictor of the severity of coronary atherosclerosis. Conclusions The periodontal inflamed surface area is an independent predictor of the severity of coronary atherosclerosis.

Association of periodontitis with cerebral small vessel disease in hypertensive patients – A pilot study

Objectives: Cerebral small vessel disease is a chronic, progressive disorder of arterioles, capillaries, and small veins supplying the brain’s white matter and deep structures of gray matter. The latest evidence seems to suggest that chronic oral infections such as periodontitis contribute to cerebral small vessel disease progression. This study evaluated the relationship between periodontal disease and brain white matter hyperintensities. Methods: Forty-three hypertensive patients, aged between 38-82, without previous cardiovascular events, of which 42% were female and 50% diabetic, were evaluated. An association between mean probing depth, mean attachment level, bleeding on probing, total periodontal inflamed surface area, and white matter hyperintensities diagnosed by magnetic resonance was studied. A significance level (α) of 0.05 was considered, and Pearson’s chi-square and Mann–Whitney tests were applied. Results: Data analysis revealed an inverse correlation between mean probing depth, bleeding on probing, total periodontal inflamed surface area, and white matter hyperintensities. A positive correlation was found between mean attachment level and white matter hyperintensities. Conclusions: In our study and within our sample, lower values of mean probing depth, bleeding on probing, and total periodontal inflamed surface area were associated with more white matter hyperintensities. Contrarily, mean attachment level was positively associated with white matter hyperintensities.

Predictive factors of periodontal regeneration outcomes using rhFGF-2: A case-control study.

This study aimed to investigate the factors influencing the clinical outcomes of regenerative therapy using recombinant human fibroblast growth factor-2 (rhFGF-2). rhFGF-2 promotes periodontal regeneration, and identifying the factors influencing this regeneration is important for optimizing the effectiveness of rhFGF-2. This study used a hospital information-integrated database to identify patients who underwent periodontal regenerative therapy with rhFGF-2. Factors included age, smoking status, diabetes mellitus (DM), periodontal inflamed surface area (PISA) at the initial visit, whether the most posterior tooth was involved or not, and preoperative radiological bone defect angle. Periodontal regenerative therapy outcomes were defined as good if radiographic bone fill ≥35% or periodontal pocket closure at 9-15 months after surgery. Bone fill rate (%) and periodontal pocket depth (mm) were also used as outcome measures. Factors were evaluated by simple regression analysis, and then the association between factors and the outcomes was determined by multivariate analysis. PISA and age at the first visit did not significantly influence the success or failure of bone fill rate byrhFGF-2. However, DM, radiographic bone defect angle, and the most posterior tooth significantly influenced the regenerative effect (success/failure in bone fill) of rhFGF-2. The most posterior tooth was significantly associated with bone fill rate by rhFGF-2. Examination of the association between pocket closure and factors shows that the most posterior tooth significantly influenced. The most posterior tooth and preoperative PPD were significantly associated with pocket reduction depth. For the most posterior tooth, a significantly higher bone regeneration rate (p < .05) was observed with a combination of autologous bone graft and rhFGF-2 than with rhFGF-2 alone, and the effect was significant in multivariate analysis. The radiographic bone defect angle, the involvement of most posterior teeth, and the presence of DM influenced the effectiveness of rhFGF-2 in periodontal regeneration. However, PISA values and age at the initial visit had no significant effect.

Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn's Disease.

The dynamic assessment of disease activity during the follow-up of patients with Crohn's disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time-intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn's disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn's disease.

Association of Periodontitis with Ambulatory Blood Pressure, Salt Intake, and Neutrophil-Lymphocyte Ratio in High-Risk Hypertensive Patients

&amp;lt;i&amp;gt;Objective&amp;lt;/i&amp;gt;: Periodontitis and cardiovascular disease are prevalent entities that often coexist, with a common pro-inflammatory pathway. The objective of this study was to evaluate the association between periodontitis and cardiovascular pro-inflammatory parameters rarely considered within risk factors. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: Forty-three participants aged between 38-82 years were examined. An association between mean probing depth (MPD), mean attachment loss (MAL), bleeding on probing (BOP), and periodontal inflamed surface area (PISA) was correlated with the following cardiovascular disease factors and inflammatory promoters: neutrophil-to-lymphocyte ratio (NLR), 24h ambulatory blood pressure, global cardiovascular risk, daily salt intake, night-time systolic blood pressure (nSBP), and pulse wave velocity (PWV). A two-way ANOVA and multiple comparison tests were performed using SPSS statistics software. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: A highly significant correlation (p&amp;lt;0.05) was found between BOP, MPD, and MAL with high salt intake, global cardiovascular risk estimation, nSBP, and PISA. Also, significantly statistical correlation (p&amp;lt;0.05) was found between BOP, NLR, and PWV while PISA was only associated with NLR. Logistic regression analysis identified absolute values of nSBP, salt intake and NLR as possible independent contributors to the increase in the &amp;lt;i&amp;gt;log&amp;lt;/i&amp;gt; odds of developing BOP. &amp;lt;i&amp;gt;Conclusions&amp;lt;/i&amp;gt;: Several periodontal disease parameters are linked to cardiovascular risk factors such as hypertension, neutrophil-to-lymphocyte ratio, daily salt intake and night-time systolic blood pressure.

Improvement of periodontal parameters following intensive diabetes care and supragingival dental prophylaxis in patients with type 2 diabetes: A prospective cohort study.

This study aimed to investigate the effects of diabetes care on periodontal inflammation. This prospective cohort study included 51 Japanese patients with type 2 diabetes who underwent intensive diabetes care including educational hospitalization and regular outpatient treatment for 6 months. Dental prophylaxis without subgingival scaling was provided three times during the observational period. Associations between changes in periodontal parameters and glycaemic control levels were evaluated using multiple regression analysis. Overall, 33 participants (mean age: 58.7 ± 12.9) were followed up for 6 months. At baseline examination, 82% were diagnosed with Stage III or IV periodontitis. Haemoglobin A1c (HbA1c) level changed from 9.6 ± 1.8% at baseline to 7.4 ± 1.3% at 6 months. The ratio of probing pocket depth (PPD) ≥4 mm, bleeding on probing (BOP), full-mouth plaque control record (PCR), periodontal epithelial surface area (PESA) and periodontal inflamed surface area (PISA) also significantly improved. The reduction in PPD and PESA was significantly associated with changes in both HbA1c and fasting plasma glucose (FPG) levels, and the reduction in PISA was significantly associated with an improvement in FPG after adjusting for smoking, change in body mass index and full-mouth PCR. This is the first study to report a significant improvement in PPD and BOP after intensive diabetes care and dental prophylaxis without subgingival scaling. UMIN000040218.

Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial.

To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[18F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT). Eighty-five patients with peripheral artery disease and severe periodontitis-randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)-underwent nuclear imaging at baseline and at 3 months. Clinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean 'standardized uptake values' (SUVmax, SUVmean) and 'target-to-background ratios' (TBRmax, TBRmean). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group. 2-[18F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.

Upregulation of TRPC1 in microglia promotes neutrophil infiltration after ischemic stroke

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.