Upconversion Nanoparticles as Imaging Agents for Dental Caries.

Dental caries (cavities) is the most prevalent disease worldwide; however, current detection methods suffer from issues associated with sensitivity, subjective interpretations, and false positive identification of carious lesions. Therefore, there is a great need for the development of more sensitive, noninvasive imaging methods. The 30 nm core@shell NaYF4; Yb20%, Er2%@NaYF4 upconversion nanoparticles (UCNPs), exhibiting strong upconversion emission from erbium upon excitation at 975 nm, were used in the imaging of locations of demineralized enamel and oral biofilm formation for the detection of dental caries. UCNPs were modified with poly(acrylic acid) (PAA) or poly-d-lysine (PDL), and targeting peptides were conjugated to their surface with affinity for either hydroxyapatite (HA), the material dentin is composed of, or the caries causing bacteria Streptococcus mutans. A statistical difference in the binding of targeted vs nontargeted UCNPs to HA was observed after 15 min, using both upconversion fluorescence of UCNP (p < 0.001) and elemental analysis (p = 0.0091). Additionally, using the HA targeted UCNPs, holes drilled in the enamel of bovine teeth with diameters of 1.0 and 0.5 mm were visible by the green emission after a 20 min incubation with no observable nonspecific binding. A statistical difference was also observed in the binding of targeted versus nontargeted UCNPs to S. mutans biofilms. This difference was observed after 15 min, using the fluorescence measurements (p = 0.0125), and only 10 min (p < 0.001) using elemental analysis via ICP-OES measurements of Y3+ concentration present in the biofilms. These results highlight the potential of these UCNPs for use in noninvasive imaging diagnosis of oral disease.

Periodontal disease is associated with increased gut colonization of pathogenic Haemophilus parainfluenzae in patients with Crohn's disease.

Intestinal colonization of the oral bacterium Haemophilus parainfluenzae has been associated with Crohn's disease (CD) severity and progression. This study examines the role of periodontal disease (PD) as a modifier for colonization of H. parainfluenzae in patients with CD and explores the mechanisms behind H. parainfluenzae-mediated intestinal inflammation. Fifty subjects with and without CD were evaluated for the presence of PD, and their oral and fecal microbiomes were characterized. PD is associated with increased levels of H. parainfluenzae strains in subjects with CD. Oral inoculation of H. parainfluenzae elicits strain-dependent intestinal inflammation in murine models of inflammatory bowel disease, which is associated with increased intestinal interferon-γ (IFN-γ)+ CD4+ T cells and disruption of the host hypusination pathway. In summary, this study establishes a strain-specific pathogenic role of H. parainfluenzae in intestinal inflammation and highlights the potential effect of PD on intestinal colonization by pathogenic H. parainfluenzae strains in patients with CD.

Computational approach to modeling microbiome landscapes associated with chronic human disease progression.

A microbial community is a dynamic system undergoing constant change in response to internal and external stimuli. These changes can have significant implications for human health. However, due to the difficulty in obtaining longitudinal samples, the study of the dynamic relationship between the microbiome and human health remains a challenge. Here, we introduce a novel computational strategy that uses massive cross-sectional sample data to model microbiome landscapes associated with chronic disease development. The strategy is based on the rationale that each static sample provides a snapshot of the disease process, and if the number of samples is sufficiently large, the footprints of individual samples populate progression trajectories, which enables us to recover disease progression paths along a microbiome landscape by using computational approaches. To demonstrate the validity of the proposed strategy, we developed a bioinformatics pipeline and applied it to a gut microbiome dataset available from a Crohn's disease study. Our analysis resulted in one of the first working models of microbial progression for Crohn's disease. We performed a series of interrogations to validate the constructed model. Our analysis suggested that the model recapitulated the longitudinal progression of microbial dysbiosis during the known clinical trajectory of Crohn's disease. By overcoming restrictions associated with complex longitudinal sampling, the proposed strategy can provide valuable insights into the role of the microbiome in the pathogenesis of chronic disease and facilitate the shift of the field from descriptive research to mechanistic studies.

The association between serum inflammatory biomarkers and incident hypertension among postmenopausal women in the Buffalo OsteoPerio Study.

Several serum inflammatory biomarkers have been associated with blood pressure and hypertension prevalence in cross-sectional studies. Few of these associations have been evaluated prospectively. We examined associations for 10 serum inflammatory biomarkers with incident hypertension among 471 postmenopausal women (mean age = 65) in the Buffalo OsteoPerio Study. Concentrations of C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, adiponectin, and leptin were measured using multiplexed sandwich immunoassays on fasting serum samples collected at baseline (1997-2001). Incident hypertension (195 cases) was defined as physician-diagnosed hypertension and treatment with medication identified on annual mailed health surveys during follow-up (mean 10 years). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between log-transformed biomarkers (per 1-SD) and hypertension. When adjusted for age, leptin was significantly associated with hypertension risk (HR = 1.55, 95% CI: 1.04, 2.29), however, the association was attenuated and not significant after adjustment for demographic and lifestyle factors, including BMI. Significant (P < 0.10) interactions were observed for smoking (never, ever) with CRP (HR: never, 1.31; ever, 0.91; P = 0.06) and MCP-1 (HR: never, 0.59; ever, 5.11; P = 0.004); for BMI (<25, ≥25) with MCP-1(HR: <25, 3.45; ≥25, 0.95; P = 0.07); for systolic BP with IL-10 (HR: <120, 0.85; 120-139, 1.11; P = 0.07); and for diastolic BP with MCP-1 (HR: <80, 1.29; 80-89, 0.84; P = 0.03) and with adiponectin (HR: <80, 0.86; 80-89, 1.50; P = 0.03). This study adds needed understanding on prospective associations between several serum inflammatory biomarkers and hypertension risk in older postmenopausal women, among whom hypertension burden is substantial.

Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study.

The aim of this study was to examine the effect of adjunct local minocycline administration on the microbiological parameters of subgingival plaque samples in the residual periodontal pockets. Ten chronic periodontitis patients under a supportive periodontal therapy regimen were recruited. After subgingival debridement, either 2% minocycline gel, Periocline™, (Test Group) or a placebo (Control Group) was administered to the selected sites once a week for three weeks. Subgingival plaque was collected at baseline, and at four weeks and eight weeks. The microbiological composition was analyzed by 16S ribosomal RNA sequencing. In the Test Group, α-diversity (evenness) decreased compared to the baseline (p = 0.005) and was lower compared to the control group at four weeks (p = 0.003). The microbial community composition between the two groups was significantly different at four weeks (p = 0.029). These changes were attributable to a decrease in the bacteria associated with periodontitis and an increase in the bacteria associated with periodontal health. Additionally, the improvement in bleeding on probing continued at eight weeks; however, there were little microbial effects of 2% minocycline gel observed at eight weeks. The control group demonstrated no change throughout the eight-week experimental period. Thus, local minocycline administration can change the subgingival microbial community of residual periodontal pockets.

Effects of periodontal disease on glycemic control, complications, and incidence of diabetes mellitus.

Diabetes mellitus is a group of metabolic disorders with high mortality and morbidity associated with complications such as cardiovascular disease, kidney disease, and stroke. The prevalence of diabetes is 9.4% in US adults, and prevalence increases markedly with age, with 1 in 4 adults aged ≥65 years affected by diabetes. The estimated number of adults with type 2 diabetes globally almost tripled between 2002 and 2017, reflecting increases seen in the USA and elsewhere. This increase raises concerns about the increased morbidity and mortality associated with the complications of diabetes, including periodontal disease and tooth loss. There is a reciprocal adverse relationship between diabetes and periodontal disease, with diabetes as a major risk factor for periodontal disease, and in those patients with diabetes who also have periodontal disease then there are adverse effects on glycemic control and complications such as cardiovascular disease and end stage renal disease. In this review, those studies detailing the adverse effects of periodontal disease and diabetes will be discussed. Also, evidence is accumulating that periodontitis may play a role in increasing the incidence of new cases of type 2 diabetes, and possibly gestational diabetes. Of course, these studies need to be expanded to better understand the effects of periodontitis on diabetes glycemic control, complications, prediabetes, and the incidence of new cases. However, given the tremendous burden of diabetes on society, the dental profession should be proactive in preventing and treating periodontal disease, not only to preserve the dentition, but also to minimize the adverse effects of periodontitis on diabetes and its complications.

Clinical and public health implications of periodontal and systemic diseases: An overview.

Severe periodontitis is defined by extensive loss of the tooth attachment apparatus. It is the sixth most common human disease and is estimated to affect 11.2% of the global adult population, hence representing a significant healthcare, social, and economic burden. Since the 1990s, multiple epidemiologic, experimental, and interventional studies have evidenced how periodontitis may also impact systemic health and it has been independently associated with the majority of chronic noncommunicable diseases. The evidence supporting these associations, mainly focusing on diabetes, pregnancy complications, and cardiovascular disease, was thoroughly reviewed in 2012 by an international consensus workshop. In the last 5 years, however, important advances have been made, not only in our understanding of the etiopathogenesis of periodontitis, or concerning the mounting evidence regarding the independent associations between periodontitis, diabetes, and cardiovascular disease, but also with many other systemic diseases including metabolic disease and obesity, rheumatoid arthritis, certain cancers, respiratory diseases, and cognitive disorders including Alzheimer's disease. This review describes these scientific advances by gathering together the existing evidence on the importance and relevance of the associations between periodontitis and many systemic diseases.

Mechanisms underlying the association between periodontitis and atherosclerotic disease.

Atherosclerosis is central to the pathology of cardiovascular diseases, a group of diseases in which arteries become occluded with atheromas that may rupture, leading to different cardiovascular events, such as myocardial infarction or ischemic stroke. There is a large body of epidemiologic and animal model evidence associating periodontitis with atherosclerotic disease, and many potential mechanisms linking these diseases have been elucidated. This chapter will update knowledge on these mechanisms, which generally fall into 2 categories: microbial invasion and infection of atheromas; and inflammatory and immunologic. With respect to the invasion and infection of atheromas, it is well established that organisms from the subgingival biofilm can enter the circulation and lodge in most distant tissues. Bacteremias resulting from oral interventions, and even oral hygiene activities, are well documented. More recently, indirect routes of entry of oral organisms (via phagocytes or dendritic cells) have been described for many oral organisms, into many tissues. Such organisms include the periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Tannerella forsythia, and Fusobacterium nucleatum. Intracellular survival of these organisms with dissemination to distant sites (The Trojan Horse approach) has been described. Their relative contribution to atheroma formation and progression has been studied mainly in experimental research, with results demonstrating that these organisms can invade endothelial cells and phagocytic cells within the atheroma, leading to pathogenic changes and progression of the atheroma lesion. The second category of mechanisms potentially linking periodontitis to atherosclerosis includes the dumping of inflammatory mediators originating from periodontal lesions into the systemic circulation. These inflammatory mediators, such as C-reactive protein, matrix metalloproteinases, fibrinogen, and other hemostatic factors, would further accelerate atheroma formation and progression, mainly through oxidative stress and inflammatory dysfunction. Moreover, direct effects on lipid oxidation have also been described. In summary, the evidence supports the concept that periodontitis enhances the levels of systemic mediators of inflammation that are risk factors for atherosclerotic diseases.

Diabetes as a potential risk for periodontitis: association studies.

Diabetes affects one in 10 adults and periodontal disease affects four in 10 adults in the USA, and they are linked. Individuals with diabetes are more likely to suffer from periodontal disease and periodontal disease affects glycemic control and complications of diabetes. The role of diabetes as a risk factor for periodontal disease and other oral conditions will be discussed in this review. The fact that type 2 diabetes, especially uncontrolled, is a risk factor for periodontal disease has long been recognized. However, the role of type 1 diabetes and gestational diabetes in periodontal risk has recently been described. Also, diabetes as a risk factor for tooth loss has more recently been described and the deleterious effects of tooth loss, especially edentulism, in comparing the diets of patients with diabetes is now fully appreciated. From longitudinal studies it is clear that diabetes often precedes periodontitis and, hence, may contribute to the causal pathway of periodontitis. Other oral manifestations of diabetes include increased risk of oral and nonoral (vaginal) fungal infections. In patients with diabetes there is often reduced salivary flow associated with diabetes medications and neuropathy affecting the salivary glands. This may lead to increased caries. Burning mouth, resulting from diabetes neuropathy, and taste impairment may also be seen. It has long been known that there is delayed wound healing in patients with diabetes, especially if uncontrolled. Hence, it is critical to achieve good glycemic control before carrying out surgical procedures or dental implant placement in patients with diabetes.

Periodontal disease and cancer: Epidemiologic studies and possible mechanisms.

Epidemiologic and cancer control studies on the association of periodontal disease and cancer risk mostly suggest a positive association with overall cancer risk and certain specific types of cancer. These findings are generally consistent among cross-sectional and longitudinal studies. In this paper, we review epidemiologic studies and current knowledge on periodontal disease and cancer, with a focus on those studies conducted in the years following the Joint European Federation of Periodontology/American Academy of Periodontology Workshop on "Periodontitis and Systemic Diseases" in November 2012. This review also explores the role of chronic inflammation as a biologically plausible mechanistic link between periodontal disease and risk of cancer. Furthermore, it highlights studies that have examined the potential importance of certain periodontal pathogens in this association.

Recent epidemiologic trends in periodontitis in the USA.

The most important development in the epidemiology of periodontitis in the USA during the last decade is the result of improvements in survey methodologies and statistical modeling of periodontitis in adults. Most of these advancements have occurred as the direct outcome of work by the joint initiative known as the Periodontal Disease Surveillance Project by the Centers for Disease Control and Prevention and the American Academy of Periodontology that was established in 2006. This report summarizes some of the key findings of this important initiative and its impact on our knowledge of the epidemiology of periodontitis in US adults. This initiative first suggested new periodontitis case definitions for surveillance in 2007 and revised them slightly in 2012. This classification is now regarded as the global standard for periodontitis surveillance and is used worldwide. First, application of such a standard in reporting finally enables results from different researchers in different countries to be meaningfully compared. Second, this initiative tackled the concern that prior national surveys, which used partial-mouth periodontal examination protocols, grossly underestimated the prevalence of periodontitis of potentially more than 50%. Consequently, because previous national surveys significantly underestimated the true prevalence of periodontitis, it is not possible to extrapolate any trend in periodontitis prevalence in the USA over time. Any difference calculated may not represent any actual change in periodontitis prevalence, but rather is a consequence of using different periodontal examination protocols. Finally, the initiative addressed the gap in the need for state and local data on periodontitis prevalence. Through the direct efforts of the Centers for Disease Control and Prevention and the American Academy of Periodontology initiative, full-mouth periodontal probing at six sites around all nonthird molar teeth was included in the 6 years of National Health and Nutrition Examination Surveys from 2009-2014, yielding complete data for 10 683 dentate community-dwelling US adults aged 30 to 79 years. Applying the 2012 periodontitis case definitions to the 2009-2014 National Health and Nutrition Examination Surveys data, the periodontitis prevalence turned out to be much greater than previously estimated, namely affecting 42.2% of the population with 7.8% of people experiencing severe periodontitis. It was also discovered that only the moderate type of periodontitis is driving the increase in periodontitis prevalence with age, not the mild or the severe types whose prevalence do not increase consistently with age, but remain ~ 10%-15% in all age groups of 40 years and older. The greatest risk for having periodontitis of any type was seen in older people, in males, in minority race/ethnic groups, in poorer and less educated groups, and especially in cigarette smokers. The Centers for Disease Control and Prevention and the American Academy of Periodontology initiative reported, for the first time, the periodontitis prevalence estimated at both local and state levels, in addition to the national level. Also, this initiative developed and validated in field studies a set of eight items for self-reported periodontitis for use in direct survey estimates of periodontitis prevalence in existing state-based surveys. These items were also included in the 2009-2014 National Health and Nutrition Examination Surveys for validation against clinically determined cases of periodontitis. Another novel result of this initiative is that, for the first time, the geographic distribution of practicing periodontists in relation to the geographic distribution of people with severe periodontitis is illustrated. In summary, the precise periodontitis prevalence and distribution among subgroups in the dentate US noninstitutionalized population aged 30-79 years is better understood because of application of valid periodontitis case definitions to full-mouth periodontal examination, in combination with reliable information on demographic and health-related measures. We now can monitor the trend of periodontitis prevalence over time as well as guide public health preventive and intervention initiatives for the betterment of the health of the adult US population.

Validation of self-reported measures of periodontitis in a Spanish Population.

BACKGROUND AND OBJECTIVE: Use of self-reported questionnaires in Dentistry may be useful to estimate the prevalence of periodontitis in epidemiological studies. This study aims to assess the accuracy of self-reporting for predicting the prevalence of periodontitis in a Spanish population participating in a diabetes incidence study. MATERIALS AND METHODS: Data were collected from 231 patients participating in the Di@bet.es study. Eight questions about periodontal health were included in a health patient-reported questionnaire. The outcomes from self-reporting were validated against a full-mouth periodontal examination. Multivariable logistic regression predictive modeling was used to determine the sensitivity, specificity, and area under the receiver operator characteristic curve (AUROCC). RESULTS: Self-reported gum health, loose teeth, tooth appearance, and use of dental floss were associated with different definitions of severe periodontitis. Correlations between responses to the questions were weak. The question "Do you think you might have gum disease?" combined with demographic and well-established risk factors resulted in an AUC value of 0.75, sensitivity of 75.2%, and specificity of 60.6% for severe periodontitis. The answer to 4 questions combined with age, educational level, smoking status, and tooth loss was 76.4% sensitive and 63.5% specific, with an AUC of 0.75 in predicting prevalence of ≥25% of teeth with probing pocket depth (PPD) ≥6 mm. CONCLUSION: Predictive models, combining self-reporting on oral health status with demographic and risk factors, were useful for estimating the prevalence of severe periodontitis in the Spanish population.

Composition and diversity of the subgingival microbiome and its relationship with age in postmenopausal women: an epidemiologic investigation.

BACKGROUND: The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood. METHODS: The 16S rRNA gene of subgingival plaque in 1219 women, aged 53-81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method. RESULTS: Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = - 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50-59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older. CONCLUSIONS: We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.

Unique etiologic, demographic, and pathologic characteristics of localized aggressive periodontitis support classification as a distinct subcategory of periodontitis.

BACKGROUND: Localized aggressive periodontitis (LAgP) occurs in 2% of African-American adolescents but only 0.15% of white adolescents. First molars and incisors are affected by rapid onset and progression. METHODS: This nonsystematic critical review evaluated published data for LAgP and chronic periodontitis (CP), focusing on potential differences in epidemiology, microbiology, immunology, genetics, and response to therapy. RESULTS: LAgP differs from CP by localization to incisors and first molars, early onset and rapid progression in adolescents and young adults, and a 10-fold higher prevalence in populations of African or Middle Eastern origin, often with strong familial aggregation. The bacterium Aggregatibacter actinomycetemcomitans and hyperresponsive neutrophils are frequently observed. Antibiotic and nonsurgical therapies are highly effective. CONCLUSIONS: LAgP differs in many ways from the far more common CP that affects older adults. The substantial evidence of dissimilarities summarized in this review strongly supports the classification of LAgP as a distinct form of periodontitis. PRACTICAL IMPLICATIONS: Classifying LAgP as a distinct subcategory of periodontitis will encourage future research and does not conflict with the newly proposed "staging and grading" system. The silent onset and rapid progression of LAgP make early diagnosis and frequent follow-up with patients essential for effective treatment.

Is the Oral Microbiome Associated with Blood Pressure in Older Women?

INTRODUCTION: A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control. AIM: This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53-82 years. METHODS: Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic < 120 and diastolic < 80; N = 179), elevated BP/Stage I hypertension (systolic 120-139 or diastolic 80-90; N = 106), Stage II hypertension (systolic > 140 or diastolic > 90; N = 42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N = 119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal-Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups. RESULTS: Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P < 0.05). CONCLUSIONS: These data provide novel description of oral subgingival bacteria grouped according to BP status. Additional larger studies including functional analysis and prospective designs will help further assess the potential role of the oral microbiome in BP regulation and hypertension.

Characterization of periodontitis in people with type 1 diabetes of 50 years or longer duration.

BACKGROUND: Periodontitis is more common and severe in people with diabetes than the general population. We have reported in the Joslin Medalist Study that people with type 1 diabetes of ≥50 years (Medalists) may have endogenous protective factors against diabetic nephropathy and retinopathy. METHODS: In this cross-sectional study, the prevalence of periodontitis according to the Centers for Disease Control/American Academy of Periodontology classification in a subset (n = 170, mean age = 64.6 ± 6.9 years) of the Medalist cohort, and its associations to various criteria of periodontitis and diabetic complications were assessed. RESULTS: The prevalence of severe periodontitis in Medalists was only 13.5% which was lower than reported levels in diabetic patients of similar ages. Periodontal parameters, including bleeding on probing, plaque index, gingival index, and demographic traits, including male sex, chronological age, and age at diagnosis were significantly associated with severity of periodontitis, which did not associate with diabetes duration, hemoglobin A1c (HbA1c), body mass index, and lipid profiles. Random serum C-peptide levels inversely associated with severity of periodontitis (P = 0.03), lower probing depth (P = 0.0002), and clinical attachment loss (P = 0.03). Prevalence of cardiovascular diseases (CVD) and systemic inflammatory markers, plasma interleukin-6 (IL-6), and serum immunoglobulin G titer against Porphyromonas gingivalis positively associated with severity of periodontitis (P = 0.002 and 0.02, respectively). Antibody titer to P. gingivalis correlated positively and significantly with CVD, serum IL-6, and high-sensitivity C-reactive protein. CONCLUSIONS: Some Medalists could be protected from severe periodontitis even with hyperglycemia. Endogenous protective factors for periodontitis could possibly be related to residual insulin production and lower levels of chronic inflammation.

The microbiome and lung cancer.

It has become increasingly clear that we live in a symbiotic relationship with microbes within us. We are just beginning to unravel the nature and strength of this relationship and its impact on both physiology and by extension, pathology. While microorganisms have long been known to have carcinogenic potential, their role may have been underestimated. The knowledge of the role of the microbiome in carcinogenesis is rapidly evolving. This evolution has reached a tipping point with current omics technologies used for cataloguing the microbiome. The lung is an organ constantly exposed to the environment. It is now clear that the lung has a distinct microbiome and that this may influence the development of lung cancer. In addition, evidence suggests that this microbiome originates from the oral microbiome. This review summarizes current knowledge about the role of microbiome, especially the oral and lung microbiome in human lung cancer. The goal of the manuscript is to provide a summary of this rapidly evolving field while providing a context of the general role of the microbiome in carcinogenesis. In addition, a primer of the current technology used in evaluating the microbiome is provided to familiarize the practicing clinician with the experimental methods used to generate the information that will likely impact the field of lung cancer.

A parallel computational framework for ultra-large-scale sequence clustering analysis.

Motivation: The rapid development of sequencing technology has led to an explosive accumulation of genomic data. Clustering is often the first step to be performed in sequence analysis. However, existing methods scale poorly with respect to the unprecedented growth of input data size. As high-performance computing systems are becoming widely accessible, it is highly desired that a clustering method can easily scale to handle large-scale sequence datasets by leveraging the power of parallel computing. Results: In this paper, we introduce SLAD (Separation via Landmark-based Active Divisive clustering), a generic computational framework that can be used to parallelize various de novo operational taxonomic unit (OTU) picking methods and comes with theoretical guarantees on both accuracy and efficiency. The proposed framework was implemented on Apache Spark, which allows for easy and efficient utilization of parallel computing resources. Experiments performed on various datasets demonstrated that SLAD can significantly speed up a number of popular de novo OTU picking methods and meanwhile maintains the same level of accuracy. In particular, the experiment on the Earth Microbiome Project dataset (∼2.2B reads, 437 GB) demonstrated the excellent scalability of the proposed method. Availability and implementation: Open-source software for the proposed method is freely available at https://www.acsu.buffalo.edu/~yijunsun/lab/SLAD.html. Supplementary information: Supplementary data are available at Bioinformatics online.

Association of Periodontal Disease and Edentulism With Hypertension Risk in Postmenopausal Women.

BACKGROUND: Multiple cross-sectional epidemiologic studies have suggested an association between periodontal disease and tooth loss and hypertension, but the temporality of these associations remains unclear. The objective of our study was to evaluate the association of baseline self-reported periodontal disease and edentulism with incident hypertension. METHODS: Study participants were 36,692 postmenopausal women in the Women's Health Initiative-Observational Study who were followed annually from initial periodontal assessment (1998-2003) through 2015 (mean follow-up 8.3 years) for newly diagnosed treated hypertension. Cox proportional hazards regression with adjustment for potential confounders was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Edentulism was significantly associated with incident hypertension in crude (HR (95% CI) = 1.38 (1.28-1.49)) and adjusted (HR (95% CI) = 1.21 (1.11-1.30)) models. This association was stronger among those <60 years compared to ≥60 years (P interaction 0.04) and among those with <120 mm Hg systolic blood pressure, compared to those with ≥120 mm Hg (P interaction 0.004). No association was found between periodontal disease and hypertension. CONCLUSIONS: These findings suggest that edentulous postmenopausal women may represent a group with higher risk of developing future hypertension. As such improved dental hygiene among those at risk for tooth loss as well as preventive measures among the edentulous such as closer blood pressure monitoring, dietary modification, physical activity, and weight loss may be warranted to reduce disease burden of hypertension. Further studies are needed to clarify these results and further elucidate a potential role of periodontal conditions on hypertension risk.