Pain, Fear, Anxiety, and Stress: Relations to the Endogenous Opioid System.

Pain, fear, stress, and anxiety are separate yet interrelated phenomena. Each of these concepts has an extensive individual body of research, with some more recent work focusing on points of conceptual overlap. The role of the endogenous opioid system in each of these phenomena is only beginning to be examined and understood. Research examining the ways in which endogenous opioids (e.g., beta-endorphin; ßE) may mediate the relations among pain, fear, stress, and anxiety is even more nascent. This chapter explores the extant evidence for endogenous opioid activity as an underpinning mechanism of these related constructs, with an emphasis on research examining ßE.

THE 3P MODEL AND ORAL HEALTH IMPACT: DEMONSTRATING THE IMPORTANCE OF BEHAVIORAL AND SOCIAL SCIENCES IN THE FUTURE OF EVIDENCE-BASED DENTISTRY.

Oral health impact or oral health related quality of life is an increasingly important and well-known metric in dental care and research. There have been recent calls for greater integration of the behavioral and social sciences into oral health research and practice, including the need for frameworks and theories to guide this work. One such framework for understanding the role of predisposing, precipitating, and perpetuating biopsychosocial mechanisms in health and disease is the "3P" model. Here, the 3P model is described and applied to case examples to help understand the development and maintenance of oral health impact. Additionally, this paper outlines how this conceptualization using the 3P model and oral health impact makes way for greater integration of behavioral interventions to prevent, mitigate, or treat the negative impact that oral, craniofacial, or dental disease may have on individuals. Doing this allows for a broadening of what evidence-based dentistry means for the future and provides a roadmap going forward.

Exploring and describing current behavioral and social sciences curricula in predoctoral dental programs.

PURPOSE: To maintain accreditation status, predoctoral dental programs in the United States and Canada are required to train future dentists in the fundamentals of behavioral sciences. Each program independently determines how to fulfill this task, and little information exists on the consistency of training across programs. The purpose of this study was to identify the range of topics currently taught in predoctoral dental programs in the United States and Canada, who teaches them, and the modes of instruction and assessment. METHODS: Invitations to complete an online survey were emailed to faculty responsible for, or familiar with, the behavioral sciences curricula at 75 predoctoral dental programs in the United States and Canada. Questions elicited information on behavioral sciences education at each program, including instructor background, topics taught, instructional and assessment methods, and sources of content. RESULTS: Of those invited, 27 (36%) completed surveys. Per the responses, prototypical behavioral sciences programs usually consist of didactic/lecture format teaching, mostly during the first 2 years of the predoctoral program, by a dentist who assesses students using multiple-choice or true/false exams. The results indicated, however, substantial variation in what is taught, how it is taught, who teaches it, and how it is assessed. CONCLUSIONS: While being a requirement for accreditation, this study demonstrated how behavioral and social sciences topics, teaching strategies, and assessments, along with the individuals teaching those topics varied across predoctoral programs. Consistency, coordination, and clinical integration are possible ways of enhancing behavioral science instruction.

Gastrointestinal distress as a potential mediator between stress and periodontal inflammation.

OBJECTIVES: Periodontal disease is multifactorial in its aetiology, which encompasses biopsychosocial contributors, including psychological stress. Gastrointestinal distress and dysbiosis have been associated with several chronic inflammatory diseases yet have rarely been investigated with respect to oral inflammation. Given the implications of gastrointestinal distress on extraintestinal inflammation, this study aimed to evaluate the potential role of such distress as a mediator between psychological stress and periodontal disease. METHODS: Utilizing a cross-sectional, nationwide sample of 828 adults in the USA generated via Amazon Mechanical Turk, we evaluated data collected from a series of validated self-report psychosocial questionnaires on stress, gut-specific anxiety around current gastrointestinal distress and periodontal disease, including periodontal disease subscales targeted at physiological and functional factors. Structural equation modelling was used to determine total, direct and indirect effects, while controlling for covariates. RESULTS: Psychological stress was associated with gastrointestinal distress (ß = .34) and self-reported periodontal disease (ß = .43). Gastrointestinal distress also was associated with self-reported periodontal disease (ß = .10). Gastrointestinal distress likewise mediated the relation between psychological stress and periodontal disease (ß = .03, p = .015). Given the multifactorial nature of periodontal disease(s), similar results were demonstrated using the subscales of the periodontal self-report measure. CONCLUSIONS: Associations exist between psychological stress and overall reports of periodontal disease as well as more specific physiological and functional components. Additionally, this study provided preliminary data supporting the potential mechanistic role that gastrointestinal distress plays in connecting the gut-brain and the gut-gum pathways.

Vaccination intention and uptake within the Black community in Appalachia.

OBJECTIVE: Black communities have disproportionately experienced adverse health effects from the COVID-19 pandemic while simultaneously having less vaccination access and decreased vaccine utilization. As such, predictors of vaccination uptake within Black communities are a public health imperative. Black Americans from socio-geographic regions associated with health inequities (e.g., Appalachia), including vaccination disparities, represent an intersection of racial, economic, and ethnic social identities. To better understand the preventive health needs of Black communities in Appalachia and elsewhere, this study examined psychosocial predictors of vaccination intention or behavior. METHOD: Adults (n = 336) identifying as Black or African American from West Virginia indicated demographics, reported COVID-19 vaccination intention, flu vaccination uptake, and human papillomavirus (HPV) vaccination uptake, and completed assessments of vaccine hesitancy, medical mistrust, and racial discrimination. Hierarchical logistic regression modeling examined potential associations between psychosocial predictors and each vaccine type. RESULTS: Results showed variation in significant predictors across the vaccines of focus. Racial discrimination (OR = 0.64) and medical mistrust (OR = 0.93) were negatively associated with COVID-19 vaccination intention. Vaccine confidence was positively associated with COVID-19 vaccination intention (OR = 2.17) and HPV vaccination uptake (OR = 1.77). Total household income was the only predictor associated with flu vaccination uptake (OR = 1.12). CONCLUSIONS: These findings suggest that social interventions targeting racial discrimination in healthcare may significantly help address vaccination disparities in rural Black communities. Moreover, results emphasize unique aspects of vaccination behavior in the Black community within Appalachia that may generalize to other Black communities living in rural regions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Food insecurity and consumption of cariogenic foods in mothers and their two-year-old children in Appalachia.

OBJECTIVES: To describe the association between household food insecurity and intake of cariogenic foods that increase risk of dental caries. METHODS: Cross-sectional analysis of 842 mothers in Appalachia and their children participating in the Center for Oral Health Research Cohort 2 between 2011 and 2017 when their children were ~ 24 months of age. Mothers completed a telephone interview regarding cariogenic food consumption and food insecurity. Associations between food insecurity and daily food intake were adjusted for education, income, state residence, and daily snacking. RESULTS: After adjustment for household income, state residence, daily snacking, and maternal education, mothers from moderately/severely food insecure households drank on average ½ more sugar-sweetened beverage servings per day (p = 0.005) and children drank almost 1/3 servings more (p = 0.006). Further, mothers and children from moderately/severely food insecure households had lower, but not statistically significant, daily average consumption of vegetables (mothers: 1/5 less of a vegetable serving per day, children: ~1/10 less) and fruits (mothers: 1/5 less of a fruit serving per day, children: ~ 1/10 les) and elevated consumption of sweets (mothers: ~ 1/25 more sweet servings per day, children: ~ 2/25 more); differences based on state residence were noted. CONCLUSIONS: Food insecurity is associated with higher consumption of foods that increase risk of dental caries, but this association is modified by maternal education, income, and state residence. Food insecurity, and its socioeconomic determinants, should be considered when designing and implementing interventions to prevent dental caries.

Twitter Trends for Celiac Disease and the Gluten-Free Diet: Cross-sectional Descriptive Analysis.

Background: Few studies have systematically analyzed information regarding chronic medical conditions and available treatments on social media. Celiac disease (CD) is an exemplar of the need to investigate web-based educational sources. CD is an autoimmune condition wherein the ingestion of gluten causes intestinal damage and, if left untreated by a strict gluten-free diet (GFD), can result in significant nutritional deficiencies leading to cancer, bone disease, and death. Adherence to the GFD can be difficult owing to cost and negative stigma, including misinformation about what gluten is and who should avoid it. Given the significant impact that negative stigma and common misunderstandings have on the treatment of CD, this condition was chosen to systematically investigate the scope and nature of sources and information distributed through social media. Objective: To address concerns related to educational social media sources, this study explored trends on the social media platform Twitter about CD and the GFD to identify primary influencers and the type of information disseminated by these influencers. Methods: This cross-sectional study used data mining to collect tweets and users who used the hashtags #celiac and #glutenfree from an 8-month time frame. Tweets were then analyzed to describe who is disseminating information via this platform and the content, source, and frequency of such information. Results: More content was posted for #glutenfree (1501.8 tweets per day) than for #celiac (69 tweets per day). A substantial proportion of the content was produced by a small percentage of contributors (ie, "Superuser"), who could be categorized as self-promotors (eg, bloggers, writers, authors; 13.9% of #glutenfree tweets and 22.7% of #celiac tweets), self-identified female family members (eg, mother; 4.3% of #glutenfree tweets and 8% of #celiac tweets), or commercial entities (eg, restaurants and bakeries). On the other hand, relatively few self-identified scientific, nonprofit, and medical provider users made substantial contributions on Twitter related to the GFD or CD (1% of #glutenfree tweets and 3.1% of #celiac tweets, respectively). Conclusions: Most material on Twitter was provided by self-promoters, commercial entities, or self-identified female family members, which may not have been supported by current medical and scientific practices. Researchers and medical providers could potentially benefit from contributing more to this space to enhance the web-based resources for patients and families.

Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload.

AIMS: Free fatty acid receptor 4 (Ffar4) is a G-protein-coupled receptor for endogenous medium-/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. METHODS AND RESULTS: In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high-density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. CONCLUSION: Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.

Predictors of use of dental care by children in north-central Appalachia in the USA.

Use of dental services in childhood, especially preventive care, is associated with many important oral health outcomes throughout life. The Andersen behavioral model of healthcare utilization posits that predisposing characteristics, enabling resources, and need factors predict utilization in oral and other healthcare domains. Inequities that produce lower utilization of dental services in north-central Appalachia have been documented in comparison to the USA generally. Additionally, within Appalachia, there are disparities, such as those across different states related to varying public policies and resources supporting healthcare. Predictors of dental utilization in Appalachia have been a focus in adults, but less so in children. The aim of the current study was to understand predictors of dental utilization in children in north-central Appalachia in order to inform future research about how to intervene to address these disparities. In this study, there were 1,178 children, ages 1 through 10 years, from selected representative counties in West Virginia and Pennsylvania, along with a parent/caregiver, who were part of the Center for Oral Health Research in Appalachia (COHRA1) cohort. Use of dental services by their child was indicated by parents/caregivers, who also reported on sociodemographic, dental care-related anxiety and fear, and values and attitudes associated with oral healthcare. Results indicated that use of professional dental services by children was related to child age, dental anxiety and fear, and parental oral health values and attitudes. Older children in this age group, those who evidenced more dental care-related anxiety and fear, and whose parent/caregiver placed higher value on oral health and healthcare for themselves, were more likely to have had a dental visit in the past year.

Development and validation of a latent, multidimensional, self-report periodontal disease measure.

BACKGROUND: Self-report measures of periodontal disease have utility for screening, but have not capitalized on a latent variable approach based on psychometric theory to validate such measures. This study aimed to develop a psychometrically valid self-report measure of periodontal disease using latent variable factor analysis and other evidence-based psychometric analyses. METHODS: Likert-type items reflecting periodontal disease were administered to a sample of adults (n = 828) in the United States via an online survey. Items were adapted from prior self-report measures or were newly developed based on psychometric item development theory and theoretical knowledge of periodontal disease. Psychometric analyses included exploratory and confirmatory factor analysis, parallel analysis, and a calculation of internal consistency. RESULTS: Exploratory factor analysis (EFA) was indicative of the goodness-of-fit with two factors (root mean square error of approximation (RMSEA) = 0.08; comparative fit index (CFI) = 0.97; Tucker Lewis index (TLI) = 0.96; standardized root mean squared residual = 0.06); five of the 22 original survey questions were eliminated based on the results of this EFA. Parallel analysis supported a two-factor model to represent the similarities across items-one factor reflecting physiologic components and another reflecting functional components of periodontal disease. Confirmatory Factor Analysis also indicated adequate model fit (RMSEA = 0.07; CFI = 0.98; TLI = 0.98; and weighted root mean square residual = 1.20). CONCLUSIONS: Psychometric analyses of a new 17-item periodontal disease self-report measure provided initial evidence of construct/factor validity. This approach to developing self-report periodontal disease measures may facilitate useful and cost-effective estimates of periodontal disease and provide a testable scale. Future work should include clinical validation.

Development and validation of the Brief Assessment of Distress about Pain.

BACKGROUND: The experience of pain is a complex interaction of somatic, behavioural, affective and cognitive components. Negative psychological states (e.g., anxiety, fear and depression) are intertwined with pain and contribute to poorer outcomes for individuals suffering from chronic and acute pain by exacerbating the overall experience of pain and leading to increased dysfunction, disability, and distress. A need exists for efficient assessment of aversive emotional states that are associated with pain. METHODS: A multistage developmental process included expert judges, two undergraduate samples, and a chronic pain patient sample. The 4-item Brief Assessment of Distress about Pain (BADP) scale was developed to assess anxiety, fear, and depression related to pain, as well as an overall evaluation of distress about pain. RESULTS: Principal components analyses indicated that the BADP consisted of one factor. Inter-scale correlation coefficients revealed that the BADP was highly related to other measures that assess similar constructs, suggesting evidence for convergent validity. Intra-scale correlation coefficients indicated that the items of the BADP were only moderately associated with each other. Findings also supported evidence for discriminative validity, test-retest reliability, and internal consistency of the BADP. CONCLUSIONS: The BADP has good psychometric properties as a measure of negative affectivity related to pain. The scale's single negative affectivity item may be useful for screening. The BADP helps address a gap in the literature with regard to a brief measure assessing fear, anxiety, depression, and negative affect in relation to pain. Demonstrated utility in a patient sample indicates the measure is suitable for further clinical study. SIGNIFICANCE: The BADP provides an efficient, psychometrically-supported means to assess affective distress (i.e., anxiety, fear, depression, and negative affect) associated with pain.

Fear of Pain Across the Adult Life Span.

BACKGROUND: Pain continues to be an important public health concern, especially given the opioid crisis in industrialized countries. It is important to understand the association between emotions such as fear and anxiety and the experience of pain as both a physiological and affective experience. Fear or anxiety about pain is in fact a well-known predictor of and close associate of pain. Nociception and pain history differ depending on age, yet little empirical evidence exists on how fear of pain varies over the life span. The purpose of this study was to provide a cross-sectional examination of the relations between age and fear of pain across the adult life span. METHODS: Using cross-sectional data from 4,122 participants who completed the Fear of Pain Questionnaire-9, structural equation modeling and regression techniques were used to examine the association between fear of pain and age. RESULTS: A positive linear association was discovered between age and fear of severe or minor pain, and a negative association was discovered between age and fear of medical or dental pain. Quadratic and cubic relations were also significant for fear of severe pain, fear of medical and dental pain, and overall fear of pain, but not for fear of minor pain. CONCLUSIONS: Unique trajectories for different components of pain-related fear exist across the adult life span and may be affected by increased exposure to medical and dental experiences over time and by the awareness of a greater likelihood of experiencing pain later in the life span.

Oral health and related risk indicators in north-central Appalachia differ by rurality.

OBJECTIVES: This cross-sectional study assessed differences in oral health and related behaviours and risk indicators by rurality in a north-central Appalachian population using the Andersen behavioural model as a conceptual framework. METHODS: Participants were residents aged 18-59 years (n = 1311) from the Center for Oral Health Research in Appalachia, selected according to a household-based sampling strategy. Rural-Urban Continuum codes (RUC) corresponding to the participants' residences were used to classify participants as rural or urban. Mixed models were used to test rural-urban differences in measures of oral health, related behaviours, and need, enabling, and predisposing risk indicators. Models were adjusted for sociodemographic variables: age, sex, race, income, perceived socioeconomic status, educational attainment and dental insurance. RESULTS: Rural residents had poorer oral health overall, with fewer sound teeth (ß = -1.79), more dental caries (ß = 0.27) and higher rates of edentulism (5.2% vs 2.8%). Differences also were observed for dental care utilization and perceived barriers to care. Rural residents were less likely to attend dental visits as often as needed (26.9% vs 42.8%) and were more prone to seek care only after experiencing a dental problem (64.3% vs 43.9%). Rural residents also were more likely to report high costs (89% vs 62.6%) as a major reason for not having dental visits. Rural-urban differences for some oral health characteristics and behaviours could be explained by sociodemographic characteristics, whereas others could not. CONCLUSIONS: This study revealed rural-urban differences in risk indicators and oral health outcomes in north-central Appalachia. Many of these differences were explained, completely or partly, by sociodemographic factors.

The Role of Distress Tolerance as a Potential Mechanism Between Anxiety Sensitivity and Gut-Specific Anxiety.

BACKGROUND: The link between anxiety/fear and gut dysfunction has been robustly documented in both physical and mental health literatures. The current study explored distress tolerance as a potential mechanism in the relation between anxiety sensitivity and gut-specific anxiety. METHOD: A cross-sectional sample of 828 adults completed measures of distress tolerance, gut-specific anxiety, and anxiety sensitivity. Multiple linear regression analyses were conducted to determine variable associations, including potential mediating factors. RESULTS: The results demonstrated a bidirectional relation between anxiety sensitivity and gut-specific anxiety (ß = 0.23, p < 0.001; ß = 0.22, p < 0.001). Findings suggest distress tolerance is a significant mediator that may partially explain the relation between gut-specific anxiety and anxiety sensitivity more broadly (ß = 0.11, CI [0.07-0.14]). Mediation results were consistent when individual subscales of distress tolerance or anxiety sensitivity were incorporated. CONCLUSION: The outcome of the present study merits additional examination of the psychosomatic nature of distress tolerance as a potential clinical target for individuals with both anxiety and gut-related disorders.

A Framework for Understanding the Role of Psychological Processes in Disease Development, Maintenance, and Treatment: The 3P-Disease Model.

Health psychology is multidisciplinary, with researchers, practitioners, and policy makers finding themselves needing at least some level of competency in a variety of areas from psychology to physiology, public health, and others. Given this multidisciplinary ontology, prior attempts have been made to establish a framework for understanding the role of biological, psychological, and socio-environmental constructs in disease development, maintenance, and treatment. Other models, however, do not explain how factors may interact and develop over time. The aim here was to apply and adapt the 3P model, originally developed and used in the treatment of insomnia, to couch the biopsychosocial model in a way that explains how diseases develop, are maintained, and can be treated. This paper outlines the role of predisposing, precipitating, and perpetuating factors in disease states and conditions (the 3Ps) and provides examples of how this model may be adapted and applied to a number of health-related diseases or disorders including chronic pain, gastrointestinal disorders, oral disease, and heart disease. The 3P framework can aid in facilitating a multidisciplinary, theoretical approach and way of conceptualizing the study and treatment of diseases in the future.

Predictors of dental care utilization in north-central Appalachia in the USA.

OBJECTIVES: Dental utilization is an important determinant of oral health and well-being. The aim of this study was to evaluate potential associations between a variety of biopsychosocial factors and dental utilization in north-central Appalachia, USA, a region where oral health disparities are profound. METHODS: This study used household-based data from the Center for Oral Health Research in Appalachia (COHRA1) study in north-central Appalachia, including 449 families with 868 adults. The generalized estimating equation (GEE) approach was used to determine the best-fitting predictor model for dental utilization among adult family members. RESULTS: On average across West Virginia and Pennsylvania, having dental insurance was associated with greater dental utilization over a 3-year time period (OR = 2.20, 95% CI = 1.54, 3.14). When stratified by state, the association held for only West Virginia (OR = 2.41, 95% CI = 1.54, 3.79) and was nonsignificant for Pennsylvania residents (OR = 1.50, 95% CI = 0.80, 2.79). Individuals from Pennsylvania were more likely to utilize dental care and participants from West Virginia less so (2.31, 95% CI = 1.57, 3.40). Females from Pennsylvania were more likely than males to regularly seek dental care (OR = 1.44, 95% CI = 1.00, 2.05), and a higher income was associated with greater frequency of regular dental visits (OR = 1.21, 95% CI = 1.09, 1.34) in West Virginia. Individuals from Pennsylvania who scored higher on the Physiological Arousal subscale of the Dental Fear Survey were more likely to attend routine care visits (OR = 1.18, 95% CI = 1.03, 1.35). Across both states, more fatalistic beliefs related to oral health care also predicted less routine care (OR = 0.87, 95% CI = 0.81, 0.94), and more investment in or more positive attitudes towards one's oral health also was associated with higher utilization (OR = 1.18, 95% CI = 1.13, 1.23). CONCLUSIONS: Overall, the findings of this study suggest state residency, sex, insurance, income, fatalistic beliefs, health values, and aspects of dental care-related anxiety and fear predicted dental care utilization in north-central Appalachia. These findings reinforce the need to address insurance and other economic factors affecting utilization and to consider how individual-level fatalistic beliefs and oral health values may affect utilization of routine oral health care.

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain.

BACKGROUND: Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. METHODS: A genome-wide association study (GWAS; N = 990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. RESULTS: Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p < 5 × 10-8 for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. CONCLUSIONS: Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain.

Periodontal Status and Quality of Life: Impact of Fear of Pain and Dental Fear.

Background. Oral health-related quality of life (OHRQoL) is impacted by periodontal disease and orofacial pain. There is a limited research examining the impact of avoidance of care or physiological arousal related to the fear of pain response on periodontal-related OHRQoL. Methods. Data are from the Center for Oral Health Research in Appalachia family-based study focusing on 1,339 adults. Measures included a modified Periodontal Screening and Recording Index across sextants of dentition, dental fear survey, Fear of Pain Questionnaire-9, and Oral Health Impact Profile-14. Structural equation modeling was used to estimate the effects of periodontal disease screening indicators on OHRQoL including the mediating role of dental fear while accounting for fear of pain. Results. A significant total effect was found for the mandibular anterior sextant, components of dental anxiety/fear, and indicators of OHRQoL (pain and discomfort, ß = .165, p = .001; psychosocial impact, ß = .199, p < .001). The maxillary anterior region was significantly associated with pain discomfort (ß = .116, p = .017) and functionality (ß = .130, p = .011). Conclusions. Findings provide a granular perspective of periodontal disease indicators and OHRQoL. Dental avoidance/anticipatory fear and physiological arousal mediate OHRQoL in individuals who have indicators of periodontal disease in sextants that may be visible and susceptible to higher pain and psychosocial impact.

Quantification of catecholamine uptake in adult cardiac myocytes.

In adult cardiac myocytes, multiple G protein-coupled receptors (GPCR) localize to and signal at the nucleus. These include endothelin B receptors, angiotensin type 1 and 2 receptors, ß1- and ß3-adrenergic receptors, and α1A- and α1B-adrenergic receptors. Initiation of signaling through nuclear GPCRs requires that ligands be produced within or transported into the cardiac myocytes, yet mechanisms whereby these ligands are produced or transported into cardiac myocytes are largely unclear. To activate nuclear adrenergic receptors in adult cardiac myocytes, uptake of endogenous catecholamines epinephrine and norepinephrine occurs via organic cation transporter 3 (OCT3), a member of the slc22a family of genes. This chapter details a method to detect and quantify catecholamine uptake in intact adult cardiac myocytes using a fluorescent-based catecholamine uptake assay.

Nuclear localization of a1A-adrenergic receptors is required for signaling in cardiac myocytes: an "inside-out" a1-AR signaling pathway.

BACKGROUND: Recent studies indicate that a1-adrenergic receptors (a1-ARs) are cardioprotective by preventing cardiac myocyte death and augmenting contractility in heart failure. Although G-protein-coupled receptors are assumed to localize to and signal at the plasma membrane, we previously demonstrated that endogenous a1-ARs localize to the nuclei in adult cardiac myocytes. However, the functional consequence of this nuclear localization remains unclear. Here, we attempted to reconcile nuclear localization of a1-ARs with their physiologic function by examining a1-AR-induced contractility in adult cardiac myocytes. METHODS AND RESULTS: By measuring shortening in unloaded, cultured adult cardiac myocytes, we found that the a1A-subtype regulated contractility through phosphorylation of cardiac troponin I (cTnI) at the protein kinase C (PKC) site, threonine 144. Reconstitution of an a1A-subtype nuclear localization mutant in cardiac myocytes lacking a1-ARs failed to rescue nuclear a1A-mediated phosphorylation of cTnI and myocyte contractility. Leptomycin B, the nuclear export inhibitor, also blocked a1A-mediated phosphorylation of cTnI. These data indicate that a1-AR signaling originates in the nucleus. Consistent with these observations, we localized the a1A-subtype to the inner nuclear membrane, identified PKCa, d, and e in the nucleus, and found that a1-ARs activate PKCd in nuclei isolated from adult cardiac myocytes. Finally, we found that a PKCd nuclear localization mutant blunted a1-induced phosphorylation of cTnI. CONCLUSIONS: Together, our data identify a novel, "inside-out" nuclear a1A-subtype/PKCd/cTnI-signaling pathway that regulates contractile function in adult cardiac myocytes. Importantly, these data help resolve the discrepancy between nuclear localization of a1-ARs and a1-AR-mediated physiologic function.