Browsing by Author "Srinivasan, Mythily"
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Item Are Adults Over 18 Years of Age with Anaemia More Likely to Develop Chronic Periodontitis Than Adults Without Anaemia? - A Systematic Review and Meta-Analysis(Wolters Kluwer, 2023-08-30) Roberts, Madison; Jimson, Sudha; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryAims and objectives: Periodontitis is a chronic disease affecting the supporting tissues of the teeth and exhibits bidirectional relation with systemic diseases. This study aims to determine the association between chronic periodontitis and erythrocyte functional measures: total red blood cells (RBCs), hemoglobin (Hb) concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC) by systematic review and meta-analysis. Materials and methods: A systematic search of the electronic databases PUBMED, OVID, Embase, Web on Science, and Google Scholar was undertaken from inception to July 2022. English language studies that evaluated the erythrocyte functional measures in periodontitis and health were selected. Other review reports, letters/opinion articles, studies without a definition of periodontitis, and the concomitant presence of systemic conditions (diabetes, kidney disease, cancer) were excluded. Two reviewers determined full-text eligibility in a blinded process. Meta-Essentials software was used to generate forest plots and to determine heterogeneity and publication bias. Results: Twenty-six studies involving 1082 patients with chronic periodontitis and 980 healthy controls were analyzed. Pooled results showed lower Hb concentration (Hedges' g = -1.16; 95% confidence intervals [CI], -1.7 to -0.62), RBC counts (Hedges' g = -0.85; 95% CI, -1.31 to -0.38) and packed cell volume (-0.56; 95% CI, -1.02 to -0.11) in patients with chronic periodontitis. Conclusion: This meta-analysis showed a decreasing trend in the hematological parameters, including hemoglobin concentration, number of erythrocytes, and hematocrit in patients with chronic periodontitis compared to healthy controls.Item Assessment of Salivary Adipokines Resistin, Visfatin, and Ghrelin as Type 2 Diabetes Mellitus Biomarkers(Hindawi Publishing Corporation, 2018-02-01) Srinivasan, Mythily; Meadows, Melinda L.; Maxwell, Lisa; Oral Pathology, Medicine and Radiology, School of DentistryType 2 diabetes mellitus (T2DM) is emerging as a metabolic epidemic worldwide. Pathologically, dysregulation of many biological pathways precedes hyperglycemia and the clinical diagnosis of T2DM. Changing trajectories along the process of T2DM development necessitates frequent measurement of biomarkers for early identification of at-risk individuals and successful prevention. Increase in circulating inflammatory adipokines has been suggested as predictive of T2DM. Human saliva is an easily accessible biospecimen amenable for painless frequent collection and possesses nearly 50% of serum proteome. In this study, we measured the adipokines resistin, visfatin, TNF-α, and ghrelin as markers for T2DM in unstimulated whole saliva (UWS) using specific assay kits. Resistin and visfatin concentrations were significantly higher in T2DM saliva. Although the concentration of acylated or unacylated ghrelin was lower in diabetic saliva, the decrease was not significant. Since resistin and visfatin are biomarkers integral to T2DM pathology, their salivary assessments may receive clinical acceptance.Item Can Salivary Innate Immune Molecules Provide Clue on Taste Dysfunction in COVID-19?(Frontiers, 2021-10) Ermel, Aaron; Thyvalikakath, Thankam Paul; Foroud, Tatiana; Khan, Babar; Srinivasan, Mythily; Medicine, School of MedicineEmerging concerns following the severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) pandemic are the long-term effects of coronavirus disease (COVID)-19. Dysgeusia in COVID-19 is supported by the abundant expression of the entry receptor, angiotensin-converting enzyme-2 (ACE2), in the oral mucosa. The invading virus perturbs the commensal biofilm and regulates the host responses that permit or suppress viral infection. We correlated the microbial recognition receptors and soluble ACE2 (sACE2) with the SARS-CoV2 measures in the saliva of COVID-19 patients. Data indicate that the toll-like receptor-4, peptidoglycan recognition protein, and sACE2 are elevated in COVID-19 saliva and correlate moderately with the viral load.Item Characteristics of Chemosensory Perception in Long COVID and COVID Reinfection(MDPI, 2023-05-22) Jaramillo, Mikki; Thyvalikakath, Thankam P.; Eckert, George; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryEmerging data suggest an increasing prevalence of persistent symptoms in individuals affected by coronavirus disease-19 (COVID-19). The objective of this study was to determine the relative frequency of altered taste and smell in COVID reinfection (multiple COVID positive tests) and long COVID (one COVID positive test). We sent an electronic survey to patients in the Indiana University Health COVID registry with positive COVID test results, querying if they were experiencing symptoms consistent with long COVID including altered chemosensory perceptions. Among the 225 respondents, a greater long COVID burden and COVID reinfection was observed in women. Joint pain was reported as the most common symptom experienced by 18% of individuals in the long COVID cohort. In the COVID reinfection cohort >20% of individuals reported headache, joint pain, and cough. Taste perception worse than pre-COVID was reported by 29% and 42% of individuals in the long COVID and COVID reinfection cohorts, respectively. Smell perception worse than pre-COVID was reported by 37% and 46% of individuals in long COVID and COVID reinfection cohorts, respectively. Further, Chi-square test suggested significant association between pre-COVID severity of taste/smell perception and headache in both cohorts. Our findings highlight the prevalence of persistent chemosensory dysfunction for two years and longer in long COVID and COVID reinfection.Item Characterizing clinical findings of Sjögren's Disease patients in community practices using matched electronic dental-health record data(Public Library of Science, 2023-07-31) Felix Gomez, Grace Gomez; Hugenberg, Steven T.; Zunt, Susan; Patel, Jay S.; Wang, Mei; Rajapuri, Anushri Singh; Lembcke, Lauren R.; Rajendran, Divya; Smith, Jonas C.; Cheriyan, Biju; Boyd, LaKeisha J.; Eckert, George J.; Grannis, Shaun J.; Srinivasan, Mythily; Zero, Domenick T.; Thyvalikakath, Thankam P.; Cariology, Operative Dentistry and Dental Public Health, School of DentistryEstablished classifications exist to confirm Sjögren's Disease (SD) (previously referred as Sjögren's Syndrome) and recruit patients for research. However, no established classification exists for diagnosis in clinical settings causing delayed diagnosis. SD patients experience a huge dental disease burden impairing their quality of life. This study established criteria to characterize Indiana University School of Dentistry (IUSD) patients' SD based on symptoms and signs in the electronic health record (EHR) data available through the state-wide Indiana health information exchange (IHIE). Association between SD diagnosis, and comorbidities including other autoimmune conditions, and documentation of SD diagnosis in electronic dental record (EDR) were also determined. The IUSD patients' EDR were linked with their EHR data in the IHIE and queried for SD diagnostic ICD9/10 codes. The resulting cohorts' EHR clinical findings were characterized and classified using diagnostic criteria based on clinical experts' recommendations. Descriptive statistics were performed, and Chi-square tests determined the association between the different SD presentations and comorbidities including other autoimmune conditions. Eighty-three percent of IUSD patients had an EHR of which 377 patients had a SD diagnosis. They were characterized as positive (24%), uncertain (20%) and negative (56%) based on EHR clinical findings. Dry eyes and mouth were reported for 51% and positive Anti-Ro/SSA antibodies and anti-nuclear antibody (ANA) for 17% of this study cohort. One comorbidity was present in 98% and other autoimmune condition/s were present in 53% respectively. Significant differences were observed between the three SD clinical characteristics/classifications and certain medical and autoimmune conditions (p<0.05). Sixty-nine percent of patients' EDR did not mention SD, highlighting the huge gap in reporting SD during dental care. This study of SD patients diagnosed in community practices characterized three different SD clinical presentations, which can be used to generate SD study cohorts for longitudinal studies using EHR data. The results emphasize the heterogenous SD clinical presentations and the need for further research to diagnose SD early in community practice settings where most people seek care.Item Circadian Clock, Glucocorticoids and NF-κB Signaling in Neuroinflammation- Implicating Glucocorticoid Induced Leucine Zipper as a Molecular Link(Sage, 2022) Srinivasan, Mythily; Walker, Chandler; Biomedical Sciences and Comprehensive Care, School of DentistryInflammation including neuroinflammation is considered a protective response and is directed to repair, regenerate, and restore damaged tissues in the central nervous system. Persistent inflammation due to chronic stress, age related accrual of free radicals, subclinical infections or other factors lead to reduced survival and increased neuronal death. Circadian abnormalities secondary to altered sleep/wake cycles is one of the earliest signs of neurodegenerative diseases. Brain specific or global deficiency of core circadian trans-activator brain and muscle ARNT (Arylhydrocarbon Receptor Nuclear Translocator)-like protein 1 (BMAL1) or that of the transrepressor REV-ERBα, impaired neural function and cognitive performance in rodents. Consistently, transcripts of inflammatory cytokines and host immune responses have been shown to exhibit diurnal variation, in parallel with the disruption of the circadian rhythm. Glucocorticoids that exhibit both a circadian rhythm similar to that of the core clock transactivator BMAL1 and tissue specific ultradian rhythm are critical in the control of neuroinflammation and re-establishment of homeostasis. It is widely accepted that the glucocorticoids suppress nuclear factor-kappa B (NF-κB) mediated transactivation and suppress inflammation. Recent mechanistic elucidations suggest that the core clock components also modulate NF-κB mediated transactivation in the brain and peripheral tissues. In this review we discuss evidence for interactions between the circadian clock components, glucocorticoids and NF-κB signaling responses in the brain and propose glucocorticoid induced leucine zipper (GILZ) encoded by Tsc22d3, as a molecular link that connect all three pathways in the maintenance of CNS homeostasis as well as in the pathogenesis of neuroinflammation-neurodegeneration.Item COVID-19 and saliva: A primer for dental health care professionals(Wiley, 2020-08-23) Srinivasan, Mythily; Thyvalikakath, Thankam P.; Cook, Blaine N.; Zero, Domenick T.; Oral Pathology, Medicine and Radiology, School of DentistryTo contain the COVID‐19 pandemic, it is essential to find methods that can be used by a wide range of health care professionals to identify the virus. The less potential contagious nature of the collection process, the ease of collection and the convenience of frequent collection for real‐time monitoring makes saliva an excellent specimen for home‐based collection for epidemiological investigations. With respect to COVID‐19, the use of saliva offers the added advantages of greater sensitivity and potential for detection at an early stage of infection. However, the advantages from a diagnostic perspective also reflect the potential risk to dental professionals from saliva from infected patients. Although not validated in COVID‐19 patients, but by extension from studies of SARS‐CoV‐1 studies, it is suggested that using antimicrobial mouthrinses such as chlorhexidine, hydrogen peroxide or sodium hypochlorite solutions could reduce the viral load in saliva droplets and reduce the risk of direct transmission. Because large saliva droplets could deposit on inanimate surfaces, changing the personal protective equipment including the clinical gown, gloves, masks, protective eye wear and face shield between patients, as well as decontamination of the work surfaces in the clinic, could reduce the risk of indirect contact transmission.Item Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis(PLOS, 2018-12-20) AlQallaf, Hawra; Hamada, Yusuke; Blanchard, Steven; Shin, Daniel; Gregory, Richard; Srinivasan, Mythily; Periodontology, School of DentistryChronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.Item Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis(PLOS, 2018-12-20) AlQallaf, Hawra; Hamada, Yusuke; Blanchard, Steven; Shin, Daniel; Gregory, Richard; Srinivasan, Mythily; Periodontology, School of DentistryChronic periodontitis is a common inflammatory disease initiated by a complex microbial biofilm and mediated by the host response causing destruction of the supporting tissues of the teeth. Host recognition of pathogens is mediated by toll-like receptors (TLRs) that bind conserved molecular patterns shared by large groups of microorganisms. The oral epithelial cells respond to most periodontopathic bacteria via TLR-2 and TLR-4. In addition to the membrane-associated receptors, soluble forms of TLR-2 (sTLR-2) and TLR-4 (sTLR-4) have been identified and are thought to play a regulatory role by binding microbial ligands. sTLR-2 has been shown to arise from ectodomain shedding of the extracellular domain of the membrane receptor and sTLR-4 is thought to be an alternate spliced form. Many studies have previously reported the presence of elevated numbers of viable exfoliated epithelial cells in the saliva of patients with chronic periodontitis. The objective of this study was to investigate the potential value of salivary sTLR-2 and sTLR-4 together with the paired epithelial cell-associated TLR-2/4 mRNA as diagnostic markers for chronic periodontitis. Unstimulated whole saliva was collected after obtaining informed consent from 40 individuals with either periodontitis or gingivitis. The sTLR-2 and sTLR4 in saliva was measured by enzyme-linked immunosorbent assay. The TLR-2 and TLR-4 transcript in the epithelial cells in saliva was measured by real time polymerase chain reaction. While levels of sTLR-2 exhibited an inverse correlation, sTLR-4 positively correlated with clinical parameters in the gingivitis cohort. Interestingly, both correlations were lost in the periodontitis cohort indicating a dysregulated host response. On the other hand, while the sTLR-2 and the paired epithelial cell associated TLR-2 mRNA exhibited a direct correlation (r2 = 0.62), that of sTLR4 and TLR-4 mRNA exhibited an inverse correlation (r2 = 0.53) in the periodontitis cohort. Collectively, assessments of salivary sTLR2 and sTLR4 together with the respective transcripts in the epithelial cells could provide clinically relevant markers of disease progression from gingivitis to periodontitis.Item Distinct Salivary Biomarker Profile in Chronic Periodontitis(Office of the Vice Chancellor for Research, 2012-04-13) Prakasam, S.; Srinivasan, MythilyBackground: Saliva has potential to diagnose chronic periodontitis (CP). Changes in tissue-expression of pattern-recognition-receptors (PRRs), which recognize periodontal-pathogens, correlate with CP. It follows that PRRs-expression in nucleated-cells (NCs) shed in saliva and soluble-PRRs may differentiate CP from health. Additionally, cytokines in gingival cervical fluid (GCF) correlate with worsening CP, which may be reflected in saliva. One significant test for biomarkers is changes in response to treatment. Objectives: Comparison of CP salivary-biomarkers profile with health and to study treatment effects of scaling and root planning (SRP). Methods: Unstimulated whole saliva (UWS) collection and recording of routine clinical periodontal parameters was done for two groups (n=16): healthy (H) (minimal clinical loss of attachment (CAL) and clinical inflammation) and CP (≥30% sites with ≥4mm CAL). UWS was collected at 3 different time points: before, 1-week and 6-weeks after SRP from the CP group. NCs and clarified saliva (CS) were separated from UWS. Messenger RNA was extracted from NCs and TLR-2 expression was quantitated through real-time-PCR. CS depleted of immunoglobulin and amylase to prevent large molecule interferences and diluted to 1 μg/ml of salivary-protein in PBS, normalize for variations in liquid volume, was used to quantify biomarkers through ELISA. Statistical significance between H- and CP-groups biomarkers was determined through Mann-Whitney ‘U' test and one tailed paired ‘t' test. Results: Statistically significant differences were noted for clinical profiles of H- and CP-groups and for changes after SRP within CP-group. Salivary sTLR-2, IL-17 and IL-10, were significantly higher, and sCD14, IL-6, IL-4 and TLR-2 mRNA were significantly lower in H compared to CP. In CP, salivary sTLR-2 and IL10 increased significantly at 1- and 6-weeks after SRP, whilst IL-4 decreased significantly at 6-weeks. Conclusions: Salivary biomarkers profiles are distinct between health and CP as well as before and after SRP treatment. sTLR-2, IL-10 and IL-4 may serve as short-term biomarkers for monitoring response to SRP. sCD14, TLR2-mRNA and other cytokines need exploration as long-term response biomarkers. Depletion of amylase and immunoglobulin, and normalization for total salivary protein may be important in biomarkers quantification.