Development of fucoidan/polyethyleneimine based sorafenib-loaded self-assembled nanoparticles with machine learning and DoE-ANN implementation: Optimization, characterization, and in-vitro assessment for the anticancer drug delivery.

This study aims to develop sorafenib-loaded self-assembled nanoparticles (SFB-SANPs) using the combined approach of artificial neural network and design of experiments (ANN-DoE) and to compare it with other machine learning (ML) models. The central composite design (CCD) and ML algorithms were used to screen the effects of concentrations of both the polymers (polyethyleneimine and fucoidan) on the outcome responses, i.e., particle size and entrapment efficiency with defined constraints. The prediction from different ML models (bootstrap forest, K-nearest neighbors, artificial neural network, generalized regression-lasso and support vector machines) were compared with ANN-DoE model. The ANN-DoE model showed better accuracy and predictability and outperformed all the other models. This depicted that the concept of using ANN and DoE combination approach provided the best, uncomplicated and cost-effective way to optimized the nanoformulations. The optimized formulation generated from the ANN-DoE combined model was further evaluated for characterization and anticancer activity. The optimized SFB-SANPs were prepared using the polyelectrolyte complexation method with Polyethyleneimine (PEI) as a cationic polymer and fucoidan (FCD) as an anionic. The SFB-SANPs were nanometric in size (280.4 ± 0.089 nm) and slightly anionic in nature (zeta potential = -6.03 ± 0.92 mV) with an encapsulation efficiency of 95.56 ± 0.30 %. The drug release from SFB-SANPs was controlled and sustained in the cancer microenvironment (pH 5.0). The SFB-SANPs were compatible with red blood cells (RBCs), and the % hemolysis was found to be <5.0 %. The anticancer activity of the SFB-SANPs exhibited an IC50 at 2.017 ± 0.516 µM against MDMB-231 cells, showing a significantly high inhibitory effect on breast cancer cell lines. Therefore, the nanocarriers developed using various ML tools inherit a huge promise in anticancer drug delivery.

The role of community health and nutrition volunteers in improving the health and nutrition status of infant and young children in remote areas, Hajjah, Yemen.

BACKGROUND: In Yemen, morbidity and malnutrition are major public health problems. The Community Health and Nutrition Volunteers (CHNVs) program was launched to tackle these problems through providing services to mothers and their children residing in remote villages. Since establishment of the CHNVs program in Yemen, its outcome has never been evaluated. Therefore, the aim of this study was to assess the role of CHNVs in improving the immunization, morbidity and nutritional status of infant and young children (IYC). METHODS: A comparative cross-sectional study design was conducted in Al-Maghrabah and Bani-Qais districts, Hajjah governorate. It was carried out between January and April 2023. A three-stage cluster sampling method was used. A total of 926 IYC with their mothers were interviewed using a pre-tested questionnaire. SPSS 26 was used for data analysis. The multinomial logistic regression and chi-square or fisher exact tests were used to compare the vaccination, morbidity and nutritional status of IYC between the volunteer and non-volunteer villages. Odds Ratio (OR) with 95% Confidence Interval (CI) were calculated. A p value < 0.05 was considered statistically significant. RESULTS: The IYC in volunteer villages were more likely to be fully or partially vaccinated compared to those in non-volunteer villages [OR = 2.3, 95% CI: 1.5-3.7, p < 0.0001, and OR = 1.9, 95% CI: 1.3-2.8, p = 0.001, respectively]. The specific coverage rates for BCG, and the 1st and 2nd doses of OPV/Pentavalent/Pneumo/Rota vaccines were significantly higher in the volunteer compared to non-volunteer villages [(OR = 1.8, 95% CI: 1.3-2.5, p < 0.0001), (OR = 1.5, 95% CI: 1.2-2.1, p = 0.003), and (OR = 1.5, 95% CI: 1.2-2.0, p = 0.002), respectively]. Moreover, the prevalence of diarrhea and fever among IYC was significantly lower in the volunteer compared to non-volunteer villages [(OR = 0.7, 95% CI: 0.5-0.9, p = 0.004) and (OR = 0.7 95% CI: 0.5-0.9, p = 0.045), respectively]. CONCLUSIONS: The study found that CHNVs play a significant role in improving vaccination status and the coverage rate for BCG, and 1st and 2nd doses of OPV/Pentavalent/Pneumo/Rota vaccines, and reducing the prevalence of diarrhea and fever among IYC in their villages compared to non-volunteer villages, in Hajjah governorate. Future follow-up study and expansion to other settings in different governorates is recommended.

Microbiological and Salivary Biomarkers Successfully Predict Site-Specific and Whole-Mouth Outcomes of Nonsurgical Periodontal Treatment.

Background/Objectives: Nonsurgical periodontal treatment (NSPT) is the gold-standard technique for treating periodontitis. However, an individual's susceptibility or the inadequate removal of subgingival biofilms could lead to unfavorable responses to NSPT. This study aimed to assess the potential of salivary and microbiological biomarkers in predicting the site-specific and whole-mouth outcomes of NSPT. Methods: A total of 68 periodontitis patients exhibiting 1111 periodontal pockets 4 to 6 mm in depth completed the active phase of periodontal treatment. Clinical periodontal parameters, saliva, and subgingival biofilm samples were collected from each patient at baseline and three months after NSPT. A quantitative PCR assay was used to detect the presence of Fusobaterium nucleatum and Porphyromonas gingivalis in the biofilm samples. Salivary biomarkers including matrix metalloproteinase (MMP)-9, glutathione S-transferase (GST), and Annexin-1 were assayed both qualitatively (Western blot analysis) and quantitively (ELISA). Results: NSPT yielded significant improvements in all clinical parameters, including a reduction in bacterial load and decreased levels of MMP-9 together with increased concentrations of GST and Annexin-1. The binary logistic regression suggested that the overall accuracy of P. gingivalis identification, probing pocket depth, and interproximal sites was 71.1% in predicting successful site-specific outcomes. The salivary biomarker model yielded an overall accuracy of 79.4% in predicting whole-mouth outcomes following NSPT. Conclusions: At baseline, the presence of shallow periodontal pockets at interdental locations with a lower abundance of P. gingivalis is predictive of a favorable response to NSPT at the site level. Decreased salivary MMP-9 associated with increased GST and Annexin-1 levels can predict successful whole-mouth outcomes following NSPT.

Impact of Nonsurgical Periodontal Treatment of Periodontitis Stages 2 and 3 on Oral Health-Related Quality of Life.

This study investigates the impact of nonsurgical periodontal treatment (NSPT) on oral health-related quality of life (OHRQoL) in patients with periodontitis stages (S)2 and S3, and the factors associated with the prediction of patient-reported outcomes. Periodontitis patients (n = 68) with moderately deep periodontal pockets were recruited. Responses to the Oral Health Impact Profile (OHIP)-14 questionnaire and clinical parameters including plaque index, bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded. All patients received supra- and subgingival professional mechanical plaque removal. All clinical parameters and questionnaire responses were recorded again 3 months after NSPT. Clinical parameters and OHIP-14 scores for both stages of periodontitis were significantly improved 3 months after treatment. However, participants with periodontitis S3 had significantly higher total OHIP-14, physical pain, and functional limitation domains scores than periodontitis S2 cases. Baseline CAL, BOP, and the presence of PPD in anterior teeth were positively associated with increased OHIP-14 scores after NSPT. NSPT improved OHRQoL in participants with periodontitis S2 and S3. This was more pronounced in participants having periodontitis S3 than S2. Poorer OHRQoL could be anticipated in people having severe CAL, high BOP, and presence of pockets in the anterior teeth.

Lipid-based microemulsion gel for the topical delivery of methotrexate: an optimized, rheologically acceptable formulation with conducive dermatokinetics.

In the present study, we have formulated a methotrexate (MTX)-loaded microemulsion topical gel employing quality-by-design optimization. The optimized lipid-based microemulsion was incorporated into a 2% carbopol gel. The prepared formulation was characterized for micromeritics, surface charge, surface morphology, conductivity studies, rheology studies, texture analysis/spreadability, drug entrapment, and drug loading studies. The formulation was further evaluated for drug release and release kinetics, cytotoxicity assays, drug permeation and drug retention studies, and dermatokinetics. The developed nanosystem was not only rheologically acceptable but also offered substantial drug entrapment and loading. From drug release studies, it was observed that the nanogel showed higher drug release at pH 5.0 compared to plain MTX, plain gel, and plain microemulsion. The developed system with improved dermatokinetics, nanometric size, higher drug loading, and enhanced efficacy towards A314 squamous epithelial cells offers a huge promise in the topical delivery of methotrexate.

Efficacy of Non-Surgical Periodontal Therapy with Adjunctive Methylene Blue and Toluidine Blue O Mediated Photodynamic in Treatment of Periodontitis: A Randomized Clinical Trial.

BACKGROUND: This study aimed to examine the efficacy of methylene blue (MB) and toluidine blue O (TBO) photodynamic therapy (PDT) as adjuncts to root surface debridement (RSD). METHODS: This split-mouth, randomized, controlled clinical trial included eighteen patients, and a total of 332 sites (control = 102, MB = 124 and TBO = 106) were examined. Two sessions of PDT were completed at baseline and two weeks after RSD. Clinical parameters of bleeding on probing (BOP), plaque index (PI), probing pocket depth (PPD), and clinical attachment level (CAL) were measured pre- and post-treatment. RESULTS: PPD and BOP reductions in sites treated by RSD with adjunctive photosensitizers (MB and TBO) were significantly higher than in control sites. RSD with MB showed higher efficacy in improving moderately deep pockets (OR 3.350), while adjunctive TBO showed better results in treating deeper pockets (OR 4.643). CONCLUSIONS: Results suggested that adjunctive use of MB and TBO to RSD could significantly improve periodontal pocket closure and reduce signs of inflammation. In addition, TBO seems to be more efficient in treating deep periodontal pockets than MB, which is more effective in resolving shallower pockets.

Applications of artificial intelligence in the utilisation of imaging modalities in dentistry: A systematic review and meta-analysis of in-vitro studies.

Background: In the past, dentistry heavily relied on manual image analysis and diagnostic procedures, which could be time-consuming and prone to human error. The advent of artificial intelligence (AI) has brought transformative potential to the field, promising enhanced accuracy and efficiency in various dental imaging tasks. This systematic review and meta-analysis aimed to comprehensively evaluate the applications of AI in dental imaging modalities, focusing on in-vitro studies. Methods: A systematic literature search was conducted, in accordance with the PRISMA guidelines. The following databases were systematically searched: PubMed/MEDLINE, Embase, Web of Science, Scopus, IEEE Xplore, Cochrane Library, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Google Scholar. The meta-analysis employed fixed-effects models to assess AI accuracy, calculating odds ratios (OR) for true positive rate (TPR), true negative rate (TNR), positive predictive value (PPV), and negative predictive value (NPV) with 95 % confidence intervals (CI). Heterogeneity and overall effect tests were applied to ensure the reliability of the findings. Results: 9 studies were selected that encompassed various objectives, such as tooth segmentation and classification, caries detection, maxillofacial bone segmentation, and 3D surface model creation. AI techniques included convolutional neural networks (CNNs), deep learning algorithms, and AI-driven tools. Imaging parameters assessed in these studies were specific to the respective dental tasks. The analysis of combined ORs indicated higher odds of accurate dental image assessments, highlighting the potential for AI to improve TPR, TNR, PPV, and NPV. The studies collectively revealed a statistically significant overall effect in favor of AI in dental imaging applications. Conclusion: In summary, this systematic review and meta-analysis underscore the transformative impact of AI on dental imaging. AI has the potential to revolutionize the field by enhancing accuracy, efficiency, and time savings in various dental tasks. While further research in clinical settings is needed to validate these findings and address study limitations, the future implications of integrating AI into dental practice hold great promise for advancing patient care and the field of dentistry.

Nanoparticles of Thiolated Xanthan Gum for the Oral Delivery of Miconazole Nitrate: In Vitro and In Vivo Evaluation.

The objective of this research was to develop a mucoadhesive delivery system that improves permeation for the administration of poorly absorbed oral medications. Thiolation of xanthan gum (XGM) was carried out by esterification with mercaptobutyric acid. Fourier-transformed infrared spectroscopy was used to confirm thiol-derivatization. Using Ellman's technique, it was revealed that the xanthan-mercaptobutyric acid conjugate had 4.7 mM of thiol groups in 2 mg/mL of polymeric solution. Using mucosa of sheep intestine, the mucoadhesive properties of XGM and thiolated xanthan gum (TXGM) nanoparticles were investigated and we found that TXGM had a longer bioadhesion time than XGM. The disulfide link that forms between mucus and thiolated XGM explains why it has better mucoadhesive properties than XGM. A study on in vitro miconazole (MCZ) release using phosphate buffer (pH 6.8) found that TXGM nanoparticles released MCZ more steadily than MCZ dispersion did. A 1-fold increase in the permeation of MCZ was observed from nanoparticles using albino rat intestine compared to MCZ. Albino rats were used to test the pharmacokinetics of MCZ, and the results showed a 4.5-fold increase in bioavailability. In conclusion, the thiolation of XGM enhances its bioavailability, controlled release of MCZ for a long period of time, and mucoadhesive activity.

E-cadherin and TAC in GCF accurately discriminate periodontal health and disease.

OBJECTIVE: To investigate the accuracy of gingival crevicular fluid (GCF) E-cadherin and total antioxidant capacity (TAC) to discriminate periodontal health from disease. SUBJECTS AND METHODS: GCF samples were collected from participants with periodontal health (control), gingivitis, and periodontitis (n = 25 each group). The latter group was further subdivided according to stage (S) and grade. Periodontal parameters were recorded then levels of biomarkers were assayed using ELISA and antioxidant status by use of the Total Antioxidant Capacity Assay for E-cadherin and TAC, respectively. RESULTS: All periodontal parameters were significantly higher in periodontally diseased groups than controls. The GCF E-cadherin significantly increased in gingivitis and periodontitis (S2 to S4) cases as compared to controls. Level of this protein in GCF samples from periodontitis S3 was significantly higher than in gingivitis and S2 groups. The GCF-TAC level was significantly higher in controls than in periodontally diseased groups. No significant differences were observed in the levels of these proteins between grade B and C periodontitis. Both molecules could discriminate periodontal health from gingivitis and periodontitis stages and differentiating periodontitis S3 from gingivitis and other periodontitis stages. CONCLUSIONS: Levels of TAC and unbounded E-cadherin in GCF samples exhibited promising diagnostic abilities to differentiate periodontal health and disease.

Ability of gingival crevicular fluid volume, E-cadherin, and total antioxidant capacity levels for predicting outcomes of nonsurgical periodontal therapy for periodontitis patients.

OBJECTIVES: To determine the potential of gingival crevicular fluid (GCF) volume, E-cadherin and total antioxidant capacity (TAC) levels to predict the outcomes of nonsurgical periodontal therapy (NSPT) for periodontitis patients. BACKGROUND: NSPT is the gold-standard treatment for periodontal pockets < 6 mm in depth, however, successful outcomes are not always guaranteed due to several factors. Periodontitis-associated tissue destruction is evidenced by the increased level of soluble E-cadherin and reduced antioxidants in oral fluids which could be used as predictors for success/failure of NSPT. MATERIALS AND METHODS: Patients with periodontitis (n = 24) were included in this clinical trial and full-mouth periodontal charting was recorded for each patient. GCF samples from periodontal pockets with probing pocket depth (PPD) 4-6 mm from the interproximal surfaces of anterior and premolar teeth were obtained. These sites subsequently received NSPT and were clinically re-evaluated after 1 and 3 months. Levels of GCF E-cadherin and TAC levels were assayed using ELISA. RESULTS: All clinical periodontal parameters were significantly improved 3 months after completion of NSPT. These outcomes were associated with a significant decrease in E-cadherin levels and GCF volume, while TAC levels were significantly increased in samples obtained in follow-up appointments. Binary regression model analysis showed that PPD, GCF volume, E-cadherin, and TAC levels could significantly (p < .05) predict the outcomes of NSPT. The cut-off points for PPD, GCF volume, E-cadherin and TAC were 5 mm, 4 × 10-3, 1267.97 pg/mL and 0.09 µmol/g, respectively. CONCLUSION: NSPT improved clinical parameters along with increased antioxidants capacity and epithelial pocket lining integrity. Discrimination of favorable/unfavorable responsiveness of periodontally diseased sites to NSPT could be possible by using GCF volume, PPD, E-cadherin and TAC level assessments.

Socio-behavioural determinants associated with the first dental visit in Saudi children: A cross-sectional study.

BACKGROUD: Oral health is an integral component of overall well-being, understanding the age at which children have their first dental visit (FDV) and the socio-behavioural factors influencing these visits is essential for improving oral health outcomes in children. AIM: This study aimed to determine the age at which Saudi children had their FDV and the socio-behavioural predictors associated with these visits in Al Jouf Province, Kingdom of Saudi Arabia. DESIGN: This cross-sectional study used a multistage stratified random sampling technique to invite 566 parents/guardians of schoolchildren aged 12 years or younger. Multinomial logistic regression analysis was used to identify socio-behavioural variables that predict children's FDV. p < 0.05 was considered statistically significant. RESULTS: Most FDVs in children occurred between the ages of 6 and 10 years. More than half of the participants stated that FDVs occurred primarily because of dental pain. Furthermore, educated mothers reported a higher frequency of dental visits for their children. Children with a low family income were 63% (95% confidence interval 0.16-0.83; p = .015) less likely to visit a dentist between the ages of 1 and 5 years. CONCLUSION: First dental visits in children in Al Jouf Province typically occurred between the ages of 6 and 10 years, with dental pain being the main reason. Parents' or caregiver's relationships with children, parental age and familial income were identified as predictors of the FDV.

Machine learning in the detection of dental cyst, tumor, and abscess lesions.

BACKGROUND AND OBJECTIVE: Dental panoramic radiographs are utilized in computer-aided image analysis, which detects abnormal tissue masses by analyzing the produced image capacity to recognize patterns of intensity fluctuations. This is done to reduce the need for invasive biopsies for arriving to a diagnosis. The aim of the current study was to examine and compare the accuracy of several texture analysis techniques, such as Grey Level Run Length Matrix (GLRLM), Grey Level Co-occurrence Matrix (GLCM), and wavelet analysis in recognizing dental cyst, tumor, and abscess lesions. MATERIALS & METHODS: The current retrospective study retrieved a total of 172 dental panoramic radiographs with lesion including dental cysts, tumors, or abscess. Radiographs that failed to meet technical criteria for diagnostic quality (such as significant overlap of teeth, a diffuse image, or distortion) were excluded from the sample. The methodology adopted in the study comprised of five stages. At first, the radiographs are improved, and the area of interest was segmented manually. A variety of feature extraction techniques, such GLCM, GLRLM, and the wavelet analysis were used to gather information from the area of interest. Later, the lesions were classified as a cyst, tumor, abscess, or using a support vector machine (SVM) classifier. Eventually, the data was transferred into a Microsoft Excel spreadsheet and statistical package for social sciences (SPSS) (version 21) was used to conduct the statistical analysis. Initially descriptive statistics were computed. For inferential analysis, statistical significance was determined by a p value < 0.05. The sensitivity, specificity, and accuracy were used to find the significant difference between assessed and actual diagnosis. RESULTS: The findings demonstrate that 98% accuracy was achieved using GLCM, 91% accuracy using Wavelet analysis & 95% accuracy using GLRLM in distinguishing between dental cyst, tumor, and abscess lesions. The area under curve (AUC) number indicates that GLCM achieves a high degree of accuracy. The results achieved excellent accuracy (98%) using GLCM. CONCLUSION: The GLCM features can be used for further research. After improving the performance and training, it can support routine histological diagnosis and can assist the clinicians in arriving at accurate and spontaneous treatment plans.

Impact of Solidago virgaurea Extract on Biofilm Formation for ESBL-Pseudomonas aeruginosa: An In Vitro Model Study.

The increasing disparity between antimicrobial resistance (AMR) and the development of new antimicrobials continues to pose a significant global health concern. However, plant extracts have shown promise in combating this issue either through their inherent antimicrobial activity or by serving as potential reservoirs of effective antimicrobial compounds. These compounds have the ability to target pathogenic biofilms and inhibit the production of extended-spectrum ß -lactamases (ESBLs). However, there is limited research available on the antibacterial properties of goldenrod extract. Thus, the objective of this study was to investigate the impact of S. virgaurea (SV) extract on the viability and ability to form biofilms of ESBL-Pseudomonas aeruginosa (P. aeruginosa). A cross-sectional study was conducted from August 2022 to March 2023. The broth microdilution method was employed to determine the minimum inhibitory concentration (MIC) of the (SV) extract. Subsequently, the minimum bactericidal concentration (MBC) was determined based on the MIC values obtained. The antibiotic susceptibility of bacteria was evaluated using the Kirby disk diffusion assay and an Antimicrobial Susceptibility Testing (AST) card in conjunction with the Vitek-2 compact system. Biofilm formation was evaluated using Congo red and a 96-well Elisa plate, while the presence of extended-spectrum ß-lactamases (ESBLs) was estimated by measuring the reduction of nitrocefin at a wavelength of 390 nm. In addition, treatment of biofilm and ESBL activity with SV extract using 96-well Elisa plate and nitrocefin hydrolyzing, respectively. The resistance rates of P. aeruginosa isolates to the tested antibiotics were as follows: Levofloxacin 33%, Ciprofloxacin 40%, Amikacin 49%, Meropenem 50%, Cefepime 70%, Ceftazidime 75%, Cefotaxime 85%, Piperacillin-Tazobactam 90%, Amoxiclav 97%, Ampicillin 99%, Ceftriaxone 100%. The prevalence of MDR-P. aeruginosa, XDR-P. aeruginosa, PDR-P. aeruginosa and non-MDR-PA were 40% (n = 40), 7% (n = 7), 3% (n = 3) and 50% (n = 50), respectively. From the GC-MS results, it was observed that the presence of Octadecane, Clioquinol, Glycerol tricaprylate, hexadecanoic acid, cis-13-octadecenoic acid, oleic acid and Propanamide were the major components in the Solidago extract. In the determination of plant crude extracts, the values ranged between 0.25 and 64 mg/mL against bacteria. The resulting activity of the extract showed a significant statistical relationship at a p-value ≤ 0.01 against ESBL production and biofilm formation in P. aeruginosa. The S. virgaurea extract exhibited effectiveness in inhibiting biofilm formation and combating P. aeruginosa strains that produce extended-spectrum ß-lactamases (ESBLs).

CRISPR-Cas-Based Adaptive Immunity Mediates Phage Resistance in Periodontal Red Complex Pathogens.

Periodontal diseases are polymicrobial immune-inflammatory diseases that can severely destroy tooth-supporting structures. The critical bacteria responsible for this destruction include red complex bacteria such as Porphoromonas gingivalis, Tanerella forsythia and Treponema denticola. These organisms have developed adaptive immune mechanisms against bacteriophages/viruses, plasmids and transposons through clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas). The CRISPR-Cas system contributes to adaptive immunity, and this acquired genetic immune system of bacteria may contribute to moderating the microbiome of chronic periodontitis. The current research examined the role of the CRISPR-Cas system of red complex bacteria in the dysbiosis of oral bacteriophages in periodontitis. Whole-genome sequences of red complex bacteria were obtained and investigated for CRISPR using the CRISPR identification tool. Repeated spacer sequences were analyzed for homologous sequences in the bacteriophage genome and viromes using BLAST algorithms. The results of the BLAST spacer analysis for T. denticola spacers had a 100% score (e value with a bacillus phage), and the results for T. forsthyia and P. gingivalis had a 56% score with a pectophage and cellulophage (e value: 0.21), respectively. The machine learning model of the identified red complex CRISPR sequences predicts with area an under the curve (AUC) accuracy of 100 percent, indicating phage inhibition. These results infer that red complex bacteria could significantly inhibit viruses and phages with CRISPR immune sequences. Therefore, the role of viruses and bacteriophages in modulating sub-gingival bacterial growth in periodontitis is limited or questionable.

Assessing cardiovascular changes in Iraqi women with hypothyroidism.

This study aimed to investigate the cardiovascular changes associated with hypothyroidism, a topic that has received significant research attention. Although only a limited number of studies have been conducted in Iraq to evaluate cardiac parameters in patients with hypothyroidism, it is widely recognized that hypothyroidism can lead to reversible cardiac dysfunction in humans. The study enrolled 100 subjects, of which 50 were diagnosed with hypothyroidism and 50 without hypothyroidism. Medical history and body mass index (BMI) were recorded for each patient, and lipid profile, thyroid function tests, ECG, and echocardiogram results were obtained. The results revealed significant differences in the thyroid functions of hypothyroid patients compared to healthy controls, except for HDL-C, which did not show any significant difference. Hypothyroid patients had higher triglyceride and total cholesterol levels and lower HDL-C, while LDL, LDL-C, VLDL, and VLDL-C were within normal range. Patients with hypothyroidism showed a higher prevalence of ECG and echocardiogram abnormalities, including diastolic dysfunction and pericardial effusion, compared to the control subjects. Our findings suggest that hypothyroidism can affect the cardiovascular system, with the degree of impact depending on TSH elevation.

Salivary interleukin-1ß as a biomarker to differentiate between periodontal health, gingivitis, and periodontitis.

BACKGROUND: Periodontal diagnosis is based on recording clinical parameters including bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment loss (CAL). These techniques may be prone to errors due to different factors. Available biomarkers in the oral biofluid such as interleukin (IL)-1ß could provide solutions for these issues. The study aimed to determine the potential of salivary IL-1ß to differentiate periodontal health from disease and between gingivitis and periodontitis. METHODS: Patients with gingivitis (N.=25), periodontitis (N.=50), and healthy periodontium (N.=25) were recruited for this study. For each patient, whole unstimulated saliva was collected followed by recording periodontal parameters namely; Plaque Index (PI), BOP, PPD, CAL. Level of salivary IL-1ß was assayed by using enzyme-linked immunosorbent assays. Sensitivity and specificity of IL-1ß, to differentiate any given condition, was determined by Receiver operating characteristic curve and area under the curve (AUC). RESULTS: Both BOP and PI were significantly higher in association with gingivitis and periodontitis groups as compared to controls. Concentration of salivary IL-1ß in periodontal health was significantly lower than gingivitis and periodontitis groups. The biochemical analyses showed that salivary IL-1ß differentiated periodontal health from gingivitis (AUC 0.949) and periodontitis (AUC 0.852) but could not discriminate gingivitis from periodontitis (AUC 0.532). The proposed cut-off points to differentiate periodontal health from gingivitis was 103.8 pg/mL, while the value of the biomarker to differentiate periodontal health from periodontitis was 102.0 pg/mL. CONCLUSIONS: Salivary IL-1ß could be a reliable biomarker with a good level of accuracy to differentiate periodontal health from disease but not to discriminate gingivitis from periodontitis.

Salivary E-cadherin as a biomarker for diagnosis and predicting grade of periodontitis.

OBJECTIVES: To determine the abilities of salivary E-cadherin to differentiate between periodontal health and periodontitis and to discriminate grades of periodontitis. BACKGROUND: E-cadherin is the main protein responsible for maintaining the integrity of epithelial-barrier function. Disintegration of this protein is one of the events associated with the destructive forms of periodontal disease leading to increase concentration of E-cadherin in the oral biofluids. MATERIALS AND METHODS: A total of 63 patients with periodontitis (case) and 35 periodontally healthy subjects (control) were included. For each patient, periodontal parameters including bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded. Concentration of salivary E-cadherin was determined by ELISA. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to determine the diagnostic potentials of E-cadherin. RESULTS: Level of salivary E-cadherin was significantly higher in periodontitis cases than controls. The ROC analysis showed that salivary E-cadherin exhibits excellent sensitivity and specificity (AUC 1.000) to differentiate periodontal health from periodontitis with a cutoff concentration equal to 1.325 ng/mL. The AUCs of E-cadherin to differentiate grade A from grade B and C periodontitis were 0.731 (cutoff point = 1.754 ng/mL) and 0.746 (cutoff point = 1.722 ng/mL), respectively. However, the AUC of salivary E-cadherin to differentiate grade B from grade C periodontitis was lower (0.541). Additionally, BOP and PPD were significantly and positively correlated with the concentration of salivary E-cadherin. CONCLUSION: Salivary E-cadherin exhibited excellent sensitivity and specificity to differentiate periodontitis from a healthy periodontium. The level of accuracy of E-cadherin was also sufficient to recognize grade A periodontitis from grade B and C periodontitis.

Detection of orthodontically induced inflammatory root resorption-associated biomarkers from the gingival crevicular fluid by proteomics analysis: a randomized-controlled clinical trial.

Orthodontically induced inflammatory root resorption (OIIRR) is an undesirable complication of orthodontic treatment (OT) with an ambiguous aetiologic mechanism. This study aimed to identify OIIRR-associated biomarkers in the gingival crevicular fluid (GCF) using proteomic analysis. In this randomized clinical trial, the upper first premolars (UFP) were exposed either to light or heavy force. The GCF was collected at 1 h, 1 day, 7 days, 14 days, 21 days, and 28 days following force application. After extraction of UFP, roots were imaged and resorption premolar, was used to deliver either light forcecraters were measured. Proteomic analysis of GCF was performed using 2D gel electrophoresis with MALDI-TOF/TOF MS/MS. Results were further analyzed by bioinformatics analyses showing the biological functions and predicted pathways. The predicted canonical pathways showed that the expression of immunoglobulin kappa (IGKC), neutrophil gelatinase-associated lipocalin (NGAL), neurolysin mitochondrial (NEUL), keratin, type II cytoskeletal 1 (K2C1), S100-A9, and the extracellular calcium-sensing receptor (CASR) were significantly associated with a range of biological and inflammatory processes. In conclusion, up-regulation of S100A9, CASR, and K2C1 suggested a response to force-related inflammation, chemotactic activities, osteoclastogenesis, and epithelial cell breakdown. Meanwhile, the up-regulation of IGKC, NGAL, and K2C1 indicated a response to the inflammatory process, innate immunity activation, and epithelial cell breakdown. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03572-5.

Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis.

The primary etiological agent for the initiation and progression of periodontal disease is the dental plaque biofilm which is an organized aggregation of microorganisms residing within a complex intercellular matrix. The non-specific plaque hypothesis was the first attempt to explain the role of the dental biofilm in the pathogenesis of periodontal diseases. However, the introduction of sophisticated diagnostic and laboratory assays has led to the realisation that the development of periodontitis requires more than a mere increase in the biomass of dental plaque. Indeed, multispecies biofilms exhibit complex interactions between the bacteria and the host. In addition, not all resident microorganisms within the biofilm are pathogenic, since beneficial bacteria exist that serve to maintain a symbiotic relationship between the plaque microbiome and the host's immune-inflammatory response, preventing the emergence of pathogenic microorganisms and the development of dysbiosis. This review aims to highlight the development and structure of the dental plaque biofilm and to explore current literature on the transition from a healthy (symbiotic) to a diseased (dysbiotic) biofilm in periodontitis and the associated immune-inflammatory responses that drive periodontal tissue destruction and form mechanistic pathways that impact other systemic non-communicable diseases.

Diagnostic potential of salivary interleukin-17, RANKL, and OPG to differentiate between periodontal health and disease and discriminate stable and unstable periodontitis: A case-control study.

Background and Aims: Limitations of the conventional diagnostic techniques urged researchers to seek novel methods to predict, diagnose, and monitor periodontal disease. Use of the biomarkers available in oral fluids could be a revolutionary surrogate for the manual probing/diagnostic radiograph. Several salivary biomarkers have the potential to accurately discriminate periodontal health and disease. This study aimed to determine the diagnostic sensitivity and specificity of salivary interleukin (IL)-17, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), RANKL/OPG for differentiating (1) periodontal health from disease and (2) stable and unstable periodontitis. Methods: Participants with periodontitis (n = 50) and gingivitis (n = 25), both diseases represented the cases, and subjects with healthy periodontium (n = 15) as a control were recruited for this study. Periodontitis cases were further equally subdivided into stable and unstable. Whole unstimulated salivary sample were collected from all participants. Periodontal parameters including bleeding on probing, probing pocket depth, clinical attachment loss, and number of missing teeth were recorded. The protein levels of salivary IL-17, RANKL, and OPG were determined by using enzyme-linked immunosorbent assays technique. Results: Salivary IL-17, OPG, RANKL, and RANKL/OPG showed high sensitivity and specificity to differentiate periodontal health from gingivitis and periodontitis. Similar pattern was observed in discriminating stable and unstable periodontitis. Salivary IL-17 and RANKL showed a good accuracy to differentiate gingivitis from periodontitis. However, OPG and RANKL/OPG did not exhibit enough sensitivity and specificity to differentiate the latter conditions. Conclusion: Salivary IL-17, RANKL, OPG, and RANKL/OPG system are potential candidates for differentiating periodontal health and disease and discriminate stable and unstable periodontitis.