Alterations of Whole-Body Glucose Metabolism in a Feline SARS-CoV-2 Infection Model.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been especially devastating to patients with comorbidities, including metabolic and cardiovascular diseases. Elevated blood glucose during SARS-CoV-2 infection increased mortality of COVID-19 patients, although the mechanisms are not well understood. It has been previously demonstrated that glucose transport and utilization is a crucial pathway for other highly infectious RNA viruses. Thus, we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Specific pathogen free domestic cats were intratracheally inoculated with USA-WA1/2020 (Wild-type) SARS-CoV-2 or vehicle-inoculated, then sacrificed at 4- and 8-days post-inoculation (dpi). Blood glucose and cortisol concentrations were elevated at 4 and 8 dpi. Blood ketones, insulin, and angiotensin 2 concentrations remained unchanged throughout the experimental timeline. SARS-CoV-2 RNA was detected in the lung and heart, without changes in angiotensin converting enzyme 2 (ACE2) RNA expression. In the lung, SARS-CoV-2 infection increased glucose transporter 1 (GLUT1) protein level at 4 and 8 dpi., while GLUT4 level was only upregulated at 8 dpi. In the heart, GLUT-1 and -4 protein levels remained unchanged. Furthermore, GLUT1 level was upregulated in the skeletal muscle at 8 dpi, and AMPK was activated in the heart of infected cats. SARS-CoV-2 infection increased blood glucose concentration and pulmonary GLUT protein levels. These findings suggest that SARS-CoV-2 infection induces metabolic reprogramming primarily in the lung to support viral replication. Furthermore, this translational feline model mimicked human COVID-19 and could be used to explore novel therapeutic targets to treat metabolic disease during SARS-CoV-2 infection.

Alternatives to dental opioid prescribing after tooth extraction (ADOPT): protocol for a stepped wedge cluster randomized trial.

BACKGROUND: Dentists and oral surgeons are leading prescribers of opioids to adolescents and young adults (AYA), who are at high risk for developing problematic opioid use after an initial exposure. Most opioids are prescribed after tooth extraction, but non-opioid analgesics provide similar analgesia and are recommended by multiple professional organizations. METHODS: This multi-site stepped wedge cluster-randomized trial will assess whether a multicomponent behavioral intervention can influence opioid prescribing behavior among dentists and oral surgeons compared to usual practice. Across up to 12 clinical practices (clusters), up to 33 dentists/oral surgeons (provider participants) who perform tooth extractions for individuals 12-25 years old will be enrolled. After enrollment, all provider participants will receive the intervention at a time based on the sequence to which their cluster is randomized. The intervention consists of prescriber education via academic detailing plus provision of standardized patient post-extraction instructions and blister packs of acetaminophen and ibuprofen. Provider participants will dispense the blister packs and distribute the patient instructions at their discretion to AYA undergoing tooth extraction, with or without additional analgesics. The primary outcome is a binary, patient-level indicator of electronic post-extraction opioid prescription. Data for the primary outcome will be collected from the provider participant's electronic health records quarterly throughout the study. Provider participants will complete a survey before and approximately 3 months after transitioning into the intervention condition to assess implementation outcomes. AYA patients undergoing tooth extraction will be offered a survey to assess pain control and satisfaction with pain management in the week after their extraction. Primary analyses will use generalized estimating equations to compare the binary patient-level indicator of being prescribed a post-extraction opioid in the intervention condition compared to usual practice. Secondary analyses will assess provider participants' perceptions of feasibility and appropriateness of the intervention, and patient-reported pain control and satisfaction with pain management. Analyses will adjust for patient-level factors (e.g., sex, number of teeth extracted, etc.). DISCUSSION: This real-world study will address an important need, providing information on the effectiveness of a multicomponent intervention at modifying dental prescribing behavior and reducing opioid prescriptions to AYA. CLINICALTRIALS: GOV: NCT06275191.

Whole unstimulated salivary flow rate decreases during acute stressful condition.

OBJECTIVE: To examine the influence of acute stress on salivary flow using a validated stressor paradigm. STUDY DESIGN: This uniform crossover study consisted of 40 healthy adults who underwent the Trier Social Stress Test, consisting of a 5-minute mental arithmetic task (MAT), and a nonstressful task (NST), consisting of a 5-minute free speech task. The order of the tasks was counterbalanced and unstimulated whole saliva (UWS) was measured in 2 groups of 20 participants during each 5-minute task condition, with a 10-minute washout period between tasks. At baseline, mathematical ability was self-reported and psychological distress was measured using the Symptom Checklist-90-Revised. Heart rate (HR) and breathing rate (BR) were recorded during each task. RESULTS: Age, sex, HR, BR, and psychological distress were similar between groups at baseline (P > .05). During the MAT, HR increased significantly and mean UWS flow rate decreased significantly compared with the NST (P < .001). CONCLUSIONS: An acute psychobiological stressor task was associated with a rapid decrease in salivary flow in adults. Thus, stress can contribute to reduced salivary flow and should be considered as a factor during the diagnostic workup of patients who complain of a dry mouth.

A review of animal models for burning mouth syndrome: Mechanistic insights and knowledge gaps.

OBJECTIVES: The underlying mechanisms of burning mouth syndrome (BMS) remain unclear leading to challenges and unsatisfactory management. Current treatments focus primarily on symptom relief, with few consistently achieving a 50% reduction in pain. This review aims to explore animal models of BMS to gain a better understanding of the underlying mechanisms and to discuss potential and existing knowledge gaps. METHODS: A comprehensive review of PubMed® , Google Scholar, and Scopus was performed to assess advances and significant gaps of existing rodent models that mimic BMS-related symptoms. RESULTS: Rodent models of BMS involve reproduction of dry-tongue, chorda tympani transection, or overexpression of artemin protein. Existing preclinical models tend to highlight one specific etiopathogenesis and often overlook sex- and hormone-specific factors. CONCLUSION: Combining aspects from various BMS models could prove beneficial in developing comprehensive experimental designs and outcomes encompassing the multifaceted nature of BMS.

Impact of Delta SARS-CoV-2 Infection on Glucose Metabolism: Insights on Host Metabolism and Virus Crosstalk in a Feline Model.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes enhanced mortality in people with metabolic and cardiovascular diseases. Other highly infectious RNA viruses have demonstrated dependence on glucose transport and utilization, so we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Twenty-four healthy domestic cats were intratracheally inoculated with B.1.617.2 (delta) SARS-CoV-2 and samples were collected at 4- and 12-days post-inoculation (dpi). Blood glucose and circulating cortisol concentrations were elevated at 4 and 12 dpi. Serum insulin concentration was statistically significantly decreased, while angiotensin 2 concentration was elevated at 12 dpi. SARS-CoV-2 RNA was detected in the pancreas and skeletal muscle at low levels; however, no change in the number of insulin-producing cells or proinflammatory cytokines was observed in the pancreas of infected cats through 12 dpi. SARS-CoV-2 infection statistically significantly increased GLUT protein expression in both the heart and lungs, correlating with increased AMPK expression. In brief, SARS-CoV-2 increased blood glucose concentration and cardio-pulmonary GLUT expression through an AMPK-dependent mechanism, without affecting the pancreas, suggesting that SARS-CoV-2 induces the reprogramming of host glucose metabolism. A better understanding of host cell metabolism and virus crosstalk could lead to the discovery of novel metabolic therapeutic targets for patients affected by COVID-19.

Effects of diet on the bacterial and eukaryotic microbiota across the gastrointestinal tract of healthy rabbits (Oryctolagus cuniculus).

OBJECTIVE: This study aimed to characterize the bacterial and eukaryotic microbiota of the gastrointestinal (GI) tract in domestic rabbits and to evaluate the effect of different diet characteristics, such as pelleting, extrusion, and hay supplementation. ANIMALS: 30 New Zealand White rabbits (15 male and 15 female; 6 to 7 months old) were fed 1 of 6 diets (5 rabbits per diet) for 30 days after an initial acclimation period. At the end of the trial, samples were collected from the stomach, small intestine, cecum, large intestine, and hard feces. METHODS: The samples were analyzed using 16S rRNA and internal transcribed spacer 1 region-targeted amplicon sequencing. RESULTS: The bacterial microbiota was distinct between the foregut and hindgut. The most abundant bacterial genera included an unclassified genus in the Bacteroidales order and Alistipes. Candida was the most abundant genus in the eukaryotic dataset. In the bacterial dataset, diet No Hay/Pellet E was shown to have lower diversity (Shannon diversity, P < .05) compared to all diet groups except for No Hay/Pellet M. Few significant differences in alpha-diversity indexes between diet groups were detected in the eukaryotic dataset. CLINICAL RELEVANCE: Our findings demonstrated that feeding hay had a significant effect on the beta diversity of the bacterial microbiota. Given the prevalence of gastrointestinal disease in the domestic rabbit population, furthering our understanding of what constitutes a healthy rabbit microbiota and the effects of different diets on the microbial community can help veterinarians implement better intervention strategies and allow pet owners to provide the best level of care.

Imaging Evaluation of the Temporomandibular Joint.

This article describes the anatomy and function of the temporomandibular joint (TMJ), provides an overview of the various imaging modalities available for evaluating the TMJ, and discusses a variety of miscellaneous diseases that affect the TMJ.

Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].

Spatial Modeling of Sociodemographic Risk for COVID-19 Mortality.

In early 2020, the Coronavirus Disease 19 (COVID-19) rapidly spread across the United States (US), exhibiting significant geographic variability. While several studies have examined the predictive relationships of differing factors on COVID-19 deaths, few have looked at spatiotemporal variation at refined geographic scales. The objective of this analysis is to examine this spatiotemporal variation in COVID-19 deaths with respect to association with socioeconomic, health, demographic, and political factors. We use multivariate regression applied to Health and Human Services (HHS) regions as well as nationwide county-level geographically weighted random forest (GWRF) models. Analyses were performed on data from three separate time frames which correspond to the spread of distinct viral variants in the US: pandemic onset until May 2021, May 2021 through November 2021, and December 2021 until April 2022. Multivariate regression results for all regions across three time windows suggest that existing measures of social vulnerability for disaster preparedness (SVI) are predictive of a higher degree of mortality from COVID-19. In comparison, GWRF models provide a more robust evaluation of feature importance and prediction, exposing the value of local features for prediction, such as obesity, which is obscured by coarse-grained analysis. Overall, GWRF results indicate that this more nuanced modeling strategy is useful for determining the spatial variation in the importance of sociodemographic risk factors for predicting COVID-19 mortality.

Modulation of tooth regeneration through opposing responses to Wnt and BMP signals in teleosts.

Most vertebrate species undergo tooth replacement throughout adult life. This process is marked by the shedding of existing teeth and the regeneration of tooth organs. However, little is known about the genetic circuitry regulating tooth replacement. Here, we tested whether fish orthologs of genes known to regulate mammalian hair regeneration have effects on tooth replacement. Using two fish species that demonstrate distinct modes of tooth regeneration, threespine stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio), we found that transgenic overexpression of four different genes changed tooth replacement rates in the direction predicted by a hair regeneration model: Wnt10a and Grem2a increased tooth replacement rate, whereas Bmp6 and Dkk2 strongly inhibited tooth formation. Thus, similar to known roles in hair regeneration, Wnt and BMP signals promote and inhibit regeneration, respectively. Regulation of total tooth number was separable from regulation of replacement rates. RNA sequencing of stickleback dental tissue showed that Bmp6 overexpression resulted in an upregulation of Wnt inhibitors. Together, these data support a model in which different epithelial organs, such as teeth and hair, share genetic circuitry driving organ regeneration.

The magmatic system under Hunga volcano before and after the 15 January 2022 eruption.

One of the largest explosive eruptions instrumentally recorded occurred at Hunga volcano on 15 January 2022. The magma plumbing system under this volcano is unexplored because of inherent difficulties caused by its submarine setting. We use marine gravity data derived from satellite altimetry combined with multibeam bathymetry to model the architecture and dynamics of the magmatic system before and after the January 2022 eruption. We provide geophysical evidence for substantial high-melt content magma accumulation in three reservoirs at shallow depths (2 to 10 kilometers) under the volcano. We estimate that less than ~30% of the existing magma was evacuated by the main eruptive phases, enough to trigger caldera collapse. The eruption and caldera collapse reorganized magma storage, resulting in an increased connectivity between the two spatially distinct reservoirs. Modeling global satellite altimetry-derived gravity data at undersea volcanoes offer a promising reconnaissance tool to probe the subsurface for eruptible magma.

Statistical modeling to quantify the uncertainty of FoldX-predicted protein folding and binding stability.

BACKGROUND: Computational methods of predicting protein stability changes upon missense mutations are invaluable tools in high-throughput studies involving a large number of protein variants. However, they are limited by a wide variation in accuracy and difficulty of assessing prediction uncertainty. Using a popular computational tool, FoldX, we develop a statistical framework that quantifies the uncertainty of predicted changes in protein stability. RESULTS: We show that multiple linear regression models can be used to quantify the uncertainty associated with FoldX prediction for individual mutations. Comparing the performance among models with varying degrees of complexity, we find that the model precision improves significantly when we utilize molecular dynamics simulation as part of the FoldX workflow. Based on the model that incorporates information from molecular dynamics, biochemical properties, as well as FoldX energy terms, we can generally expect upper bounds on the uncertainty of folding stability predictions of ± 2.9 kcal/mol and ± 3.5 kcal/mol for binding stability predictions. The uncertainty for individual mutations varies; our model estimates it using FoldX energy terms, biochemical properties of the mutated residue, as well as the variability among snapshots from molecular dynamics simulation. CONCLUSIONS: Using a linear regression framework, we construct models to predict the uncertainty associated with FoldX prediction of stability changes upon mutation. This technique is straightforward and can be extended to other computational methods as well.

Jaw size variation is associated with a novel craniofacial function for galanin receptor 2 in an adaptive radiation of pupfishes.

Understanding the genetic basis of novel adaptations in new species is a fundamental question in biology. Here we demonstrate a new role for galr2 in vertebrate craniofacial development using an adaptive radiation of trophic specialist pupfishes endemic to San Salvador Island, Bahamas. We confirmed the loss of a putative Sry transcription factor binding site upstream of galr2 in scale-eating pupfish and found significant spatial differences in galr2 expression among pupfish species in Meckel's cartilage using in situ hybridization chain reaction (HCR). We then experimentally demonstrated a novel role for Galr2 in craniofacial development by exposing embryos to Garl2-inhibiting drugs. Galr2-inhibition reduced Meckel's cartilage length and increased chondrocyte density in both trophic specialists but not in the generalist genetic background. We propose a mechanism for jaw elongation in scale-eaters based on the reduced expression of galr2 due to the loss of a putative Sry binding site. Fewer Galr2 receptors in the scale-eater Meckel's cartilage may result in their enlarged jaw lengths as adults by limiting opportunities for a circulating Galr2 agonist to bind to these receptors during development. Our findings illustrate the growing utility of linking candidate adaptive SNPs in non-model systems with highly divergent phenotypes to novel vertebrate gene functions.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

RIG-I agonist SLR10 promotes macrophage M1 polarization during influenza virus infection.

Rationale: A family of short synthetic, triphosphorylated stem-loop RNAs (SLRs) have been designed to activate the retinoic-acid-inducible gene I (RIG-I) pathway and induce a potent interferon (IFN) response, which may have therapeutic potential. We investigated immune response modulation by SLR10. We addressed whether RIG-I pathway activation with SLR10 leads to protection of nonsmoking (NS) and cigarette smoke (CS)-exposed mice after influenza A virus (IAV) infection. Methods: Mice were given 25 µg of SLR10 1 day before IAV infection. We compared the survival rates and host immune responses of NS and CS-exposed mice following challenge with IAV. Results: SLR10 significantly decreased weight loss and increased survival rates in both NS and CS-exposed mice during IAV infection. SLR10 administration repaired the impaired proinflammatory response in CS-exposed mice without causing more lung injury in NS mice as assessed by physiologic measurements. Although histopathologic study revealed that SLR10 administration was likely to result in higher pathological scores than untreated groups in both NS and CS mice, this change was not enough to increase lung injury evaluated by lung-to-body weight ratio. Both qRT-PCR on lung tissues and multiplex immunoassay on bronchoalveolar lavage fluids (BALFs) showed that most IFNs and proinflammatory cytokines were expressed at lower levels in SLR10-treated NS mice than control-treaded NS mice at day 5 post infection (p.i.). Remarkably, proinflammatory cytokines IL-6, IL-12, and GM-CSF were increased in CS-exposed mice by SLR10 at day 5 p.i. Significantly, SLR10 elevated the ratio of the two chemokines (CXCL9 and CCL17) in BALFs, suggesting macrophages were polarized to classically activated (M1) status. In vitro testing also found that SLR10 not only stimulated human alveolar macrophage polarization to an M1 phenotype, but also reversed cigarette smoke extract (CSE)-induced M2 to M1 polarization. Conclusions: Our data show that SLR10 administration in mice is protective for both NS and CS-exposed IAV-infected mice. Mechanistically, SLR10 treatment promoted M1 macrophage polarization in the lung during influenza infection. The protective effects by SLR10 may be a promising intervention for therapy for infections with viruses, particularly those with CS-enhanced susceptibility to adverse outcomes.

Jaw size variation is associated with a novel craniofacial function for galanin receptor 2 in an adaptive radiation of pupfishes.

Understanding the genetic basis of novel adaptations in new species is a fundamental question in biology that also provides an opportunity to uncover new genes and regulatory networks with potential clinical relevance. Here we demonstrate a new role for galr2 in vertebrate craniofacial development using an adaptive radiation of trophic specialist pupfishes endemic to San Salvador Island in the Bahamas. We confirmed the loss of a putative Sry transcription factor binding site in the upstream region of galr2 in scale-eating pupfish and found significant spatial differences in galr2 expression among pupfish species in Meckel's cartilage and premaxilla using in situ hybridization chain reaction (HCR). We then experimentally demonstrated a novel function for Galr2 in craniofacial development and jaw elongation by exposing embryos to drugs that inhibit Galr2 activity. Galr2-inhibition reduced Meckel's cartilage length and increased chondrocyte density in both trophic specialists but not in the generalist genetic background. We propose a mechanism for jaw elongation in scale-eaters based on the reduced expression of galr2 due to the loss of a putative Sry binding site. Fewer Galr2 receptors in the scale-eater Meckel's cartilage may result in their enlarged jaw lengths as adults by limiting opportunities for a postulated Galr2 agonist to bind to these receptors during development. Our findings illustrate the growing utility of linking candidate adaptive SNPs in non-model systems with highly divergent phenotypes to novel vertebrate gene functions.

Xerostomia, reduced salivary flow, and oral burning: Associations from a cross-sectional study.

OBJECTIVE: Determine the association between xerostomia, salivary flow, and oral burning. STUDY DESIGN: A cross-sectional retrospective study involving consecutive patients with an oral burning complaint during a 6-year period. Treatments including a dry mouth management protocol (DMP) along with other therapies were implemented. Study variables included xerostomia, unstimulated whole salivary flow rate (UWSFR), pain intensity, and medication use. Statistical analyses included Pearson correlations, linear regression, and Analysis of Variance. RESULTS: Among the 124 patients meeting the inclusion criteria, 99 were female, with a mean age of 63.1 (range 26-86) years. The baseline UWSFR was low (0.24 ± 0.29 mL/min) and 46% experienced hyposalivation (<0.1 mL/min). Xerostomia was reported by 77.7%, and 82.8% had coexistence of xerostomia and hyposalivation. DMP resulted in significant pain reduction between visits (P < .001). CONCLUSIONS: Hyposalivation and xerostomia were highly prevalent in patients with oral burning. A DMP proved beneficial to these patients.

HIGH PREVALENCE OF CYTAUXZOON FELIS IN BOBCATS (LYNX RUFUS) ACROSS OKLAHOMA AND OCCURRENCE IN WEST TEXAS, USA.

Cytauxzoonosis is a fatal tick-borne disease in domestic cats caused by infection with the apicomplexan Cytauxzoon felis. Bobcats are the natural wild-vertebrate reservoirs for C. felis, and infections are typically subclinical and chronic in this species. The present study was done to determine the prevalence and geographic distribution of C. felis infection in wild bobcats from Oklahoma and the occurrence in northwestern Texas. Tongue samples from 360 bobcats were collected from 53 counties in Oklahoma and 13 samples from three counties in Texas. For DNA extracted from each tongue sample, a probe-based droplet digital PCR assay was performed targeting the C. felis mitochondrial gene cytochrome c oxidase subunit III (cox3). Prevalence of C. felis infection was calculated for each county sampled, and data from individual counties were combined according to geographic regions and compared using chi-square tests. Overall prevalence of C. felis in bobcats from Oklahoma was 80.0% (95% confidence interval [CI], 75.6-83.8). The prevalence of infection was >90% for bobcats from central, northeastern, south-central, and southeastern regions of Oklahoma, but <68% for bobcats from northwestern and southwestern regions. Bobcats from central counties in Oklahoma were 25.693 times more likely to be infected with C. felis compared to all other bobcats sampled from the state. Higher prevalence estimates of C. felis in bobcats appeared to be in counties where known tick vectors are most common. Occurrence of C. felis in bobcats from northwestern Texas was 30.8% (95% CI, 12.4%-58.0%) based on 13 samples. Results of this study support the utilization of bobcats as sentinel animals to identify geographic areas with risk of C. felis infection to domestic cats.

Biomarker panel discriminates diabetics with and without periodontitis pre- and post-therapy.

BACKGROUND AND OBJECTIVE: Biological regulators of periodontal inflammation, collagen degradation, and insulin resistance have not been determined in association with severity of periodontitis and response to periodontal treatment in diabetics. Our objective was to determine whether type 2 diabetes (T2DM) patients with periodontal disease present a distinct salivary biomarker profile compared with T2DM patients without periodontal disease and healthy subjects (without diabetes and periodontitis) pre- and post-nonsurgical therapy. METHODS: Clinical parameters of periodontal health and whole unstimulated saliva were collected from 92 participants (31 Not Periodontitis, NP; 32 T2DM without periodontitis, DWoP; and 29 with T2DM with periodontitis, DWP) at baseline. The T2DM groups received scaling and root planning (SRP) and provided saliva at 6-week follow-up. Salivary concentrations of interleukin (IL)-1ß, IL-6, matrix metalloproteinase-8 (MMP-8), and resistin were measured by immunoassay. RESULTS: The DWP group had significantly more disease and higher salivary concentrations at baseline for IL-1ß, MMP-8, and resistin (p's < .01) compared with DWoP and NP. SRP resulted in significant improvement in periodontal parameters for the T2DM groups; however, more disease persisted (p < .001), and IL-1ß, MMP-8, and resistin concentrations remained significantly higher in the DWP than the DWoP group (p < .01) at 6 weeks post-treatment. Principal component analysis demonstrated the DWoP group appeared more biologically similar to the NP group than the DWP group. Concentrations of these salivary biomarkers increased with increasing periodontal disease severity (p < .05) in this study population. CONCLUSION: Salivary concentrations of IL-1ß, MMP-8, and resistin appear to serve as biomarkers of periodontal status pre- and post-treatment, irrespective of diabetes status.