From Global to Nano: A Geographical Perspective of .

The periodontal disease pathobiont () may exert a range of detrimental effects on periodontal diseases in general and, more specifically, with the initiation and progression of Localized Stage III Grade C periodontitis (molar-incisor pattern). In this review of the biogeography of this pathobiont, the full range of geographical scales for , from global origins and transmission to local geographical regions, to more locally exposed probands and families, to the individual host, down to the oral cavity, and finally, to spatial interactions with other commensals and pathobionts within the plaque biofilms at the micron/nanoscale, are reviewed. Using the newest technologies in genetics, imaging, in vitro cultures, and other research disciplines, investigators may be able to gain new insights to the role of this pathobiont in the unique initial destructive patterns of Localized Stage III Grade C periodontitis.

Functional Adaptation of LPS-affected Dentoalveolar Fibrous Joints in Rats.

Introduction: The functional interplay between cementum of the root and alveolar bone of the socket is tuned by a uniquely positioned 70-80 µm wide fibrous and lubricious ligament in a dentoalveolar joint (DAJ). In this study, structural and biomechanical properties of the DAJ, periodontal ligament space (PDL-space also known as the joint space), alveolar bone of the socket, and cementum of the tooth root that govern the biomechanics of a lipopolysaccharide (LPS)-affected DAJ were mapped both in space and time.

Methods: The hemi-maxillae from 20 rats (4 control at 6 weeks of age, 4 control and 4 LPS-affected at 12 weeks of age, 4 control and 4 LPS-affected at 16 weeks of age) were investigated using a hybrid technique; micro-X-ray computed tomography (5 µm resolution) in combination with biomechanical testing in situ.

Alzheimer disease and the periodontal patient: New insights, connections, and therapies.

Loss of cognitive function in the aging population, particular those with Alzheimer disease, presents unique challenges to health practitioners. For the dental practitioner these include management of periodontal diseases, caries, and other dental conditions in this special population. It is well established in the cognitively impaired patient that a lack of adherence to dental hygiene routines and professional care leads to increases in the prevalence and severity of these dental conditions, leading to increased loss of teeth.

Porphyromonas gingivalis and Alzheimer disease: Recent findings and potential therapies.

Epidemiological studies have identified an association between periodontitis and Alzheimer disease (AD); however, the nature of this association has been unclear. Recent work suggests that brain colonization by the periodontal pathogen Porphyromonas gingivalis may link these two inflammatory and degenerative conditions. Evidence of P.

Treatment of Porphyromonas gulae infection and downstream pathology in the aged dog by lysine-gingipain inhibitor COR388.

COR388, a small-molecule lysine-gingipain inhibitor, is currently being investigated in a Phase 2/3 clinical trial for Alzheimer's disease (AD) with exploratory endpoints in periodontal disease. Gingipains are produced by two species of bacteria, Porphyromonas gingivalis and Porphyromonas gulae, typically associated with periodontal disease and systemic infections in humans and dogs, respectively. P.

Microbial biogeography and ecology of the mouth and implications for periodontal diseases.

In humans, the composition of microbial communities differs among body sites and between habitats within a single site. Patterns of variation in the distribution of organisms across time and space are referred to as "biogeography." The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease.

Periodontics in the USA: An introduction.

The United States continues to be an incubator for new concepts and approaches to the diagnosis, treatment, and prevention of periodontal diseases. This volume of Periodontology 2000 presents some of these newer areas of research and paradigms that have emerged in the United States from both long-established and new investigators. These areas include: (1) more comprehensive approaches to assessing the total periodontal microbiome, including bacteria, viruses, and fungi, and their interactions with both the local and systemic inflammatory and immune responses, as well as with other oral and systemic conditions and diseases; (2) new developments for a more comprehensive characterization of the patient genome, transcriptome, and proteome profiles and the role of these profiles in periodontal disease pathogenesis; (3) new developments in nonsurgical approaches to periodontal diseases, including broad-based lines of attack using natural antimicrobials and host-modulation therapies and more focused approaches that target specific interactions in the host response; and (4) new big data analysis, machine learning, and imaging approaches, both for understanding the pathogenesis of periodontal diseases and for developing improved risk-assessment tools and better treatment outcomes.

Current trends and new developments in HIV research and periodontal diseases.

With the advent of combined antiretroviral therapies, the face of HIV infection has changed dramatically from a disease with almost certain mortality from serious comorbidities, to a manageable chronic condition with an extended lifespan. In this paper we present the more recent investigations into the epidemiology, microbiology, and pathogenesis of periodontal diseases in patients with HIV, and the effects of combined antiretroviral therapies on the incidence and progression of these diseases both in adults and perinatally infected children. In addition, comparisons and potential interactions between the HIV-associated microbiome, host responses, and pathogenesis in the oral cavity with the gastrointestinal tract and other areas of the body are presented.

Biomarkers of oral inflammation in perinatally HIV-infected and perinatally HIV-exposed, uninfected youth.

Aim: To examine oral biomarkers that have been associated with periodontal disease progression in HIV-infected adults in perinatally HIV-infected and HIV-exposed but uninfected youth.

Material And Methods: This was a cross-sectional, multicentre substudy of youth participating in the Oral Health Pediatric HIV/AIDS Cohort study. Gingival crevicular fluid repository samples from participants with and without periodontal disease (using Gingival Index [GI] and Bleeding on Probing [BOP] parameters on dental examination) were tested for concentration levels of inflammatory biomarkers.

in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.

, the keystone pathogen in chronic periodontitis, was identified in the brain of Alzheimer's disease patients. Toxic proteases from the bacterium called gingipains were also identified in the brain of Alzheimer's patients, and levels correlated with tau and ubiquitin pathology. Oral infection in mice resulted in brain colonization and increased production of Aβ, a component of amyloid plaques.

Personalized periodontal treatment for the tobacco- and alcohol-using patient.

The use of various forms of tobacco is one of the most important preventable risk factors for the incidence and progression of periodontal disease. Tobacco use negatively affects treatment outcomes for both periodontal diseases and conditions, and for dental implants. Tobacco-cessation programs can mitigate these adverse dental treatment outcomes and may be the most effective component of a personalized periodontal treatment approach.

The association between oral disease and type of antiretroviral therapy among perinatally HIV-infected youth.

Objectives: This study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth.

Methods: We conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination.

Oral microbiota in youth with perinatally acquired HIV infection.

Background: Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth.

A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow.

Spatial and temporal patterns in microbial communities provide insights into the forces that shape them, their functions and roles in health and disease. Here, we used spatial and ecological statistics to analyze the role that saliva plays in structuring bacterial communities of the human mouth using >9000 dental and mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa, keratinized gingiva, or buccal mucosa), surface-associated bacterial communities vary along an ecological gradient from the front to the back of the mouth, and that on exposed tooth surfaces, the gradient is pronounced on lingual compared to buccal surfaces.

Prevalence of periodontal diseases in a multicenter cohort of perinatally HIV-infected and HIV-exposed and uninfected youth.

Aims: To compare the prevalence and severity of periodontal diseases between 180 perinatally HIV-infected (PHIV) and 118 perinatally HIV-exposed and uninfected (PHEU) youth in a cross-sectional study conducted at 11 clinical sites in the United States and Puerto Rico from the Adolescent Master Protocol study of the Pediatric HIV/AIDS cohort study (PHACS) network.

Methods: Several analyses were conducted, employing the current CDC/AAP classification for periodontitis and incorporating a definition of gingivitis based on a bleeding on probing (BOP) threshold, and analyses based on more detailed whole-mouth, intra-oral regionally, site-based and tooth-based criteria of BOP, plaque levels, pockets depths and clinical attachment levels.

Results: After adjusting for plaque control habits and behavioural and sociodemographic factors, there were no significant differences in periodontal diseases between the PHIV and PHEU youth using any of these criteria.

Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study.

In contrast to high rates of oral human papillomavirus (HPV) found in human immunodeficiency virus (HIV)-infected adults, only 2% of 209 perinatally HIV-infected youth had oral HPV. This rate was similar in HIV-exposed but uninfected youth. No association was found with sexual activity; however, low CD4 counts were associated with oral HPV.

The Burden of Oral Disease among Perinatally HIV-Infected and HIV-Exposed Uninfected Youth.

Objective: To compare oral health parameters in perinatally HIV-infected (PHIV) and perinatally HIV-exposed but uninfected youth (PHEU).

Methods: In a cross-sectional substudy within the Pediatric HIV/AIDS Cohort Study, participants were examined for number of decayed teeth (DT), Decayed, Missing, and Filled Teeth (DMFT), oral mucosal disease, and periodontal disease (PD). Covariates for oral health parameters were examined using zero-inflated negative binomial regression and ordinal logistic regression models.

The tobacco-using periodontal patient: role of the dental practitioner in tobacco cessation and periodontal disease management.

Although the prevalence of tobacco use has declined in some parts of the world, tobacco use remains a persistent and, in some cases, growing problem that will continue to be a fundamental challenge facing dental practitioners in the decades ahead. Dental practitioners have a unique opportunity and professional obligation to be a positive influence in reducing the economic and social burden inflicted by tobacco use on dental and general health. In this article, the current noninvasive, evidence-based approaches are presented for dental practitioners to help patients avoid initiating tobacco use, to encourage and assist patients in ceasing tobacco use and to address tobacco-induced damage to periodontal supporting tissues.

Minimally invasive periodontal therapy for general practitioners.

There remains a high prevalence of mild-to-moderate forms of periodontal diseases in both developed and developing countries. Although many periodontal specialty practices currently place strong emphasis on implant surgery, periodontal plastic surgery and esthetics, general dentists and hygienists have often assumed more responsibility than periodontal specialty practices for the diagnosis, treatment, assessment and maintenance, and possible referral, of their patients. To address these current trends and challenges, this volume of Periodontology 2000 presents a series of topics on the basic biological principles of periodontal disease, as well as on approaches to diagnosis, treatment planning and treatment, in what is called 'conservative' or 'noninvasive' periodontal therapy.

Adaptive properties of human cementum and cementum dentin junction with age.

Objectives: The objective of this study was to evaluate age related changes in physical (structure/mechanical properties) and chemical (elemental/inorganic mineral content) properties of cementum layers interfacing dentin.

Methods: Human mandibular molars (N=43) were collected and sorted by age (younger=19-39, middle=40-60, older=61-81 years). The structures of primary and secondary cementum (PC, SC) types were evaluated using light and atomic force microscopy (AFM) techniques.

Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota.

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders.

Proteomic analysis of saliva in HIV-positive heroin addicts reveals proteins correlated with cognition.

The prevalence of HIV-associated neurocognitive disorders (HAND) remains high despite effective antiretroviral therapies. Multiple etiologies have been proposed over the last several years to account for this phenomenon, including the neurotoxic effects of antiretrovirals and co-morbid substance abuse; however, no underlying molecular mechanism has been identified. Emerging evidence in several fields has linked the gut to brain diseases, but the effect of the gut on the brain during HIV infection has not been explored.

The plastic nature of the human bone-periodontal ligament-tooth fibrous joint.

This study investigates bony protrusions within a narrowed periodontal ligament space (PDL-space) of a human bone-PDL-tooth fibrous joint by mapping structural, biochemical, and mechanical heterogeneity. Higher resolution structural characterization was achieved via complementary atomic force microscopy (AFM), nano-transmission X-ray microscopy (nano-TXM), and microtomography (MicroXCT™). Structural heterogeneity was correlated to biochemical and elemental composition, illustrated via histochemistry and microprobe X-ray fluorescence analysis (μ-XRF), and mechanical heterogeneity evaluated by AFM-based nanoindentation.

The adaptive nature of the bone-periodontal ligament-cementum complex in a ligature-induced periodontitis rat model.

The novel aspect of this study involves illustrating significant adaptation of a functionally loaded bone-PDL-cementum complex in a ligature-induced periodontitis rat model. Following 4, 8, and 15 days of ligation, proinflammatory cytokines (TNF- α and RANKL), a mineral resorption indicator (TRAP), and a cell migration and adhesion molecule for tissue regeneration (fibronectin) within the complex were localized and correlated with changes in PDL-space (functional space). At 4 days of ligation, the functional space of the distal complex was widened compared to controls and was positively correlated with an increased expression of TNF- α.