University of North Carolina System

This review examines the current knowledge of water intake as it pertains to human health, including overall patterns of intake and some factors linked with intake, the complex mechanisms behind water homeostasis, and the effects of variation in water intake on health and energy intake, weight, and human performance and functioning. Water represents a critical nutrient, the absence of which will be lethal within days. Water's importance for the prevention of nutrition-related noncommunicable diseases has received more attention recently because of the shift toward consumption of large proportions of fluids as caloric beverages. Despite this focus, there are major gaps in knowledge related to the measurement of total fluid intake and hydration status at the population level; there are also few longer-term systematic interventions and no published randomized, controlled longer-term trials. This review provides suggestions for ways to examine water requirements and encourages more dialogue on this important topic.

In this article we use a single unifying framework to analyze the sources of profits to a wide spectrum of return-based trading strategies implemented in the literature. We show that less than 50% of the 120 strategies implemented in the article yield statistically significant profits and, unconditionally, momentum and contrarian strategies are equally likely to be successful. However, when we condition on the return horizon (short, medium, or long) of the strategy, or the time period during which it is implemented, two patterns emerge. A momentum strategy is usually profitable at the medium (3- to 12-months) horizon, while a contrarian strategy nets statistically significant profits at long horizons, but only during the 1926–1947 subperiod. More importantly, our results show that the cross-sectional variation in the mean returns of individual securities included in these strategies play an important role in their profitability. The cross-sectional variation can potentially account for the profitability of momentum strategies and it is also responsible for attenuating the profits from price reversals to long-horizon contrarian strategies.

BACKGROUND: Opioid misuse can complicate chronic pain management, and the non-medical use of opioids is a growing public health problem. The incidence and risk factors for opioid misuse in patients with chronic pain, however, have not been well characterized. We conducted a prospective cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice. METHODS: One-hundred and ninety-six opioid-treated patients with chronic, non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals. Opioid misuse was defined as: 1. Negative urine toxicological screen (UTS) for prescribed opioids; 2. UTS positive for opioids or controlled substances not prescribed by our practice; 3. Evidence of procurement of opioids from multiple providers; 4. Diversion of opioids; 5. Prescription forgery; or 6. Stimulants (cocaine or amphetamines) on UTS. RESULTS: The mean patient age was 52 years, 55% were male, and 75% were white. Sixty-two of 196 (32%) patients committed opioid misuse. Detection of cocaine or amphetamines on UTS was the most common form of misuse (40.3% of misusers). In bivariate analysis, misusers were more likely than non-misusers to be younger (48 years vs 54 years, p < 0.001), male (59.6% vs. 38%; p = 0.023), have past alcohol abuse (44% vs 23%; p = 0.004), past cocaine abuse (68% vs 21%; p < 0.001), or have a previous drug or DUI conviction (40% vs 11%; p < 0.001%). In multivariate analyses, age, past cocaine abuse (OR, 4.3), drug or DUI conviction (OR, 2.6), and a past alcohol abuse (OR, 2.6) persisted as predictors of misuse. Race, income, education, depression score, disability score, pain score, and literacy were not associated with misuse. No relationship between pain scores and misuse emerged. CONCLUSION: Opioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice. Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed. Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

UNLABELLED: Whether dietary fiber protects against colorectal cancer is controversial because of conflicting results from human epidemiologic studies. However, these studies and mouse models of colorectal cancer have not controlled the composition of gut microbiota, which ferment fiber into short-chain fatty acids such as butyrate. Butyrate is noteworthy because it has energetic and epigenetic functions in colonocytes and tumor-suppressive properties in colorectal cancer cell lines. We used gnotobiotic mouse models colonized with wild-type or mutant strains of a butyrate-producing bacterium to demonstrate that fiber does have a potent tumor-suppressive effect but in a microbiota- and butyrate-dependent manner. Furthermore, due to the Warburg effect, butyrate was metabolized less in tumors where it accumulated and functioned as a histone deacetylase (HDAC) inhibitor to stimulate histone acetylation and affect apoptosis and cell proliferation. To support the relevance of this mechanism in human cancer, we demonstrate that butyrate and histone-acetylation levels are elevated in colorectal adenocarcinomas compared with normal colonic tissues. SIGNIFICANCE: These results, which link diet and microbiota to a tumor-suppressive metabolite, provide insight into conflicting epidemiologic findings and suggest that probiotic/prebiotic strategies can modulate an endogenous HDAC inhibitor for anticancer chemoprevention without the adverse effects associated with synthetic HDAC inhibitors used in chemotherapy.

BACKGROUND: In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS: ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS: ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION: The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

This paper reviews studies on the prevalence of overweight, obesity and related nutrition-related non-communicable diseases in Bahrain, Kuwait, Qatar, Oman, Saudi Arabia and the UAE. Obesity is common among women; while men have an equal or higher overweight prevalence. Among adults, overweight plus obesity rates are especially high in Kuwait, Qatar and Saudi Arabia, and especially among 30-60 year olds (70-85% among men; 75-88% among women), with lower levels among younger and elderly adults. The rate of increase in obesity was pronounced in Saudi Arabia and Kuwait. Prevalence of obesity is high among Kuwaiti and Saudi pre-schoolers (8-9%), while adolescent overweight and obesity are among the highest in the world, with Kuwait having the worst estimates (40-46%); however, comparison of child data is difficult because of differing standards. Among nutrition-related non-communicable diseases, hypertension and diabetes levels are very high and increase with age, with the UAE performing the worst because of a rapid rate of increase between 1995 and 2000. Additional monitoring of the prevalence of metabolic syndrome and cancers is necessary. Nationally representative longitudinal surveys with individual, household and community-level information are needed to determine the importance of various factors that contribute to these troubling trends.

All invasive procedures involve contact between a medical device or surgical instrument and a patient's sterile tissue or mucous membranes. A major risk of all such procedures is the introduction of pathogenic microbes that could lead to infection. Failure to properly disinfect or sterilize reusable medical equipment carries a risk associated with breach of the host barriers. The level of disinfection or sterilization is dependent on the intended use of the object: critical items (such as surgical instruments, which contact sterile tissue), semicritical items (such as endoscopes, which contact mucous membranes), and noncritical items (such as stethoscopes, which contact only intact skin) require sterilization, high-level disinfection, and low-level disinfection, respectively. Cleaning must always precede high-level disinfection and sterilization. Users must consider the advantages and disadvantages of specific methods when choosing a disinfection or sterilization process. Adherence to these recommendations should improve disinfection and sterilization practices in health care facilities, thereby reducing infections associated with contaminated patient-care items.

OBJECTIVE: The goal was to estimate whether maternal periodontal disease was predictive of preterm (less than 37 weeks) or very preterm (less than 32 weeks) births. METHODS: A prospective study of obstetric outcomes, entitled Oral Conditions and Pregnancy (OCAP), was conducted with 1,020 pregnant women who received both an antepartum and postpartum periodontal examination. Predictive models were developed to estimate whether maternal exposure to either periodontal disease at enrollment (less than 26 weeks) and/or periodontal disease progression during pregnancy, as determined by comparing postpartum with antepartum status, were predictive of preterm or very preterm births, adjusting for risk factors including previous preterm delivery, race, smoking, social domain variables, and other infections. RESULTS: Incidence of preterm birth was 11.2% among periodontally healthy women, compared with 28.6% in women with moderate-severe periodontal disease (adjusted risk ratio [RR] 1.6, 95% confidence interval [CI] 1.1-2.3). Antepartum moderate-severe periodontal disease was associated with an increased incidence of spontaneous preterm births (15.2% versus 24.9%, adjusted RR 2.0, 95% CI 1.2-3.2). Similarly, the unadjusted rate of very preterm delivery was 6.4% among women with periodontal disease progression, significantly higher than the 1.8% rate among women without disease progression (adjusted RR 2.4, 95% CI 1.1-5.2). CONCLUSION: The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, periodontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors. LEVEL OF EVIDENCE: II-2.

Any account of the social and economic conditions of democracy must come to terms with the central finding of the cross-national statistical research: a sturdy (though not perfect) association between economic development and democracy. To tackle these questions of causation, we adopted a strategy of analytic induction based on comparative historical research. Our program of comparative historical research confirmed the conclusion of the cross-national statistical analyses of the correlates of political democracy: the level of economic development is causally related to the development of political democracy. However, the underlying reason for the connection, in our view, is that capitalist development transforms the class structure, enlarging the working and middle classes and facilitating their self-organization, thus making it more difficult for elites to exclude them politically. Simultaneously, development weakens the landed upper class, democracy's most consistent opponent.

This research investigates how movie ratings from professional critics, amateur communities, and viewers themselves influence key movie performance measures (i.e., movie revenues and new movie ratings). Using movie-level data, the authors find that high early movie revenues enhance subsequent movie ratings. They also find that high advertising spending on movies supported by high ratings maximizes the movie's revenues. Furthermore, they empirically show that sequel movies tend to reap more revenues but receive lower ratings than originals. Using individual viewer–level data, this research highlights how viewers’ own viewing and rating histories and movie communities’ collective opinions explain viewer satisfaction. The authors find that various aspects of these ratings explain viewers’ new movie ratings as a measure of viewer satisfaction, after controlling for movie characteristics. Furthermore, they find that viewers’ movie experiences can cause them to become more critical in ratings over time. Finally, they find a U-shaped relationship between viewers’ genre preferences and genre-specific movie ratings for heavy viewers.

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. Recommendation 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). Recommendation 2: ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). Recommendation 4: ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

BACKGROUND: In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) was identified as the etiological agent of severe acute respiratory syndrome, a disease characterized by severe pneumonia that sometimes results in death. SARS-CoV is a zoonotic virus that crossed the species barrier, most likely originating from bats or from other species including civets, raccoon dogs, domestic cats, swine, and rodents. A SARS-CoV vaccine should confer long-term protection, especially in vulnerable senescent populations, against both the 2003 epidemic strains and zoonotic strains that may yet emerge from animal reservoirs. We report the comprehensive investigation of SARS vaccine efficacy in young and senescent mice following homologous and heterologous challenge. METHODS AND FINDINGS: Using Venezuelan equine encephalitis virus replicon particles (VRP) expressing the 2003 epidemic Urbani SARS-CoV strain spike (S) glycoprotein (VRP-S) or the nucleocapsid (N) protein from the same strain (VRP-N), we demonstrate that VRP-S, but not VRP-N vaccines provide complete short- and long-term protection against homologous strain challenge in young and senescent mice. To test VRP vaccine efficacy against a heterologous SARS-CoV, we used phylogenetic analyses, synthetic biology, and reverse genetics to construct a chimeric virus (icGDO3-S) encoding a synthetic S glycoprotein gene of the most genetically divergent human strain, GDO3, which clusters among the zoonotic SARS-CoV. icGD03-S replicated efficiently in human airway epithelial cells and in the lungs of young and senescent mice, and was highly resistant to neutralization with antisera directed against the Urbani strain. Although VRP-S vaccines provided complete short-term protection against heterologous icGD03-S challenge in young mice, only limited protection was seen in vaccinated senescent animals. VRP-N vaccines not only failed to protect from homologous or heterologous challenge, but resulted in enhanced immunopathology with eosinophilic infiltrates within the lungs of SARS-CoV-challenged mice. VRP-N-induced pathology presented at day 4, peaked around day 7, and persisted through day 14, and was likely mediated by cellular immune responses. CONCLUSIONS: This study identifies gaps and challenges in vaccine design for controlling future SARS-CoV zoonosis, especially in vulnerable elderly populations. The availability of a SARS-CoV virus bearing heterologous S glycoproteins provides a robust challenge inoculum for evaluating vaccine efficacy against zoonotic strains, the most likely source of future outbreaks.

Streams, as low-lying points in the landscape, are strongly influenced by the stormwaters, pollutants, and warming that characterize catchment urbanization. River restoration projects are an increasingly popular method for mitigating urban insults. Despite the growing frequency and high expense of urban stream restoration projects, very few projects have been evaluated to determine whether they can successfully enhance habitat structure or support the stream biota characteristic of reference sites. We compared the physical and biological structure of four urban degraded, four urban restored, and four forested streams in the Piedmont region of North Carolina to quantify the ability of reach-scale stream restoration to restore physical and biological structure to urban streams and to examine the assumption that providing habitat is sufficient for biological recovery. To be successful at mitigating urban impacts, the habitat structure and biological communities found in restored streams should be more similar to forested reference sites than to their urban degraded counterparts. For every measured reach- and patch-scale attribute, we found that restored streams were indistinguishable from their degraded urban stream counterparts. Forested streams were shallower, had greater habitat complexity and median sediment size, and contained less-tolerant communities with higher sensitive taxa richness than streams in either urban category. Because heavy machinery is used to regrade and reconfigure restored channels, restored streams had less canopy cover than either forested or urban streams. Channel habitat complexity and watershed impervious surface cover (ISC) were the best predictors of sensitive taxa richness and biotic index at the reach and catchment scale, respectively. Macroinvertebrate communities in restored channels were compositionally similar to the communities in urban degraded channels, and both were dissimilar to communities in forested streams. The macroinvertebrate communities of both restored and urban degraded streams were correlated with environmental variables characteristic of degraded urban systems. Our study suggests that reach-scale restoration is not successfully mitigating for the factors causing physical and biological degradation.

Abstract The California Research at the Nexus of Air Quality and Climate Change (CalNex) field study was conducted throughout California in May, June, and July of 2010. The study was organized to address issues simultaneously relevant to atmospheric pollution and climate change, including (1) emission inventory assessment, (2) atmospheric transport and dispersion, (3) atmospheric chemical processing, and (4) cloud‐aerosol interactions and aerosol radiative effects. Measurements from networks of ground sites, a research ship, tall towers, balloon‐borne ozonesondes, multiple aircraft, and satellites provided in situ and remotely sensed data on trace pollutant and greenhouse gas concentrations, aerosol chemical composition and microphysical properties, cloud microphysics, and meteorological parameters. This overview report provides operational information for the variety of sites, platforms, and measurements, their joint deployment strategy, and summarizes findings that have resulted from the collaborative analyses of the CalNex field study. Climate‐relevant findings from CalNex include that leakage from natural gas infrastructure may account for the excess of observed methane over emission estimates in Los Angeles. Air‐quality relevant findings include the following: mobile fleet VOC significantly declines, and NO x emissions continue to have an impact on ozone in the Los Angeles basin; the relative contributions of diesel and gasoline emission to secondary organic aerosol are not fully understood; and nighttime NO 3 chemistry contributes significantly to secondary organic aerosol mass in the San Joaquin Valley. Findings simultaneously relevant to climate and air quality include the following: marine vessel emissions changes due to fuel sulfur and speed controls result in a net warming effect but have substantial positive impacts on local air quality.

Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

Coronary heart disease is responsible for one of every five deaths in the United States. Recent epidemiological studies have shown an association between periodontal disease and coronary heart disease. The purpose of this cross-sectional study was to verify this association using data from the third National Health and Nutrition Examination Survey (NHANES III). Data for 5564 people 40 years of age and older who had complete periodontal assessments and information on heart attack were evaluated. The outcome was the self-reported history of heart attack (yes vs. no). The main independent variable was the percent of periodontal sites per person with attachment loss of 3 mm or greater (categorized as 0%, > 0-33%, > 33-67%, and > 67%). Periodontal attachment loss was measured at two sites per tooth in randomly assigned half-mouths, one upper and one lower quadrant. The covariables included sociodemographic variables and established risk factors for cardiovascular disease. Relative to the 0% category, the unadjusted odds of heart attack increased with each higher category of attachment loss-2.2 (95% confidence interval = 1.3-3.8), 5.5 (3.4-9.1), and 9.8 (4.5-21.0), respectively. Adjustment for age, sex, race, poverty, smoking, diabetes, high blood pressure, body mass index, and serum cholesterol decreased these odds to 1.4 (0.8-2.5), 2.3 (1.2-4.4), and 3.8 (1.5-9.7), respectively. This study supports findings from previous studies of an association between periodontal disease and coronary heart disease.

Clinical signs and symptoms, as well as medical and dental history, are all considered in the clinical determination of gingival inflammation and periodontal disease severity. However, the "biologic systems model" highlights that the clinical presentation of periodontal disease is closely tied to the underlying biologic phenotype. We propose that the determination and integration of subject-level factors, microbial composition, systemic immune response, and gingival tissue inflammatory mediator responses will better reflect the biology of the biofilm-gingival interface in a specific patient and may provide insights on clinical management. Disease classifications and multivariable models further refine the biologic basis for the increasing severity of periodontal disease expression. As such, new classifications may better identify disease-susceptible and treatment-non-responsive individuals than current classifications that are heavily influenced by probing and attachment level measurements alone. New data also suggest that the clinical characteristics of some complex diseases, such as periodontal disease, are influenced by the genetic and epigenetic contributions to clinical phenotype. Although the genetic basis for periodontal disease is considered imperative for setting an inflammatory capacity for an individual and, thus, a threshold for severity, there is evidence to suggest an epigenetic component is involved as well. Many factors long associated with periodontitis, including bacterial accumulations, smoking, and diabetes, are known to produce strong epigenetic changes in tissue behavior. We propose that we are now able to rethink periodontal disease in terms of a biologic systems model that may help to establish more homogeneous diagnostic categories and can provide insight into the expected response to treatment.

BACKGROUND: A molecular epidemiologic study provided the opportunity to characterize the biology of the biofilm-gingival interface (BGI) in 6,768 community-dwelling subjects. METHODS: Disease classifications and multivariable models were developed using clinical, microbial, inflammatory, and host-response data. The purpose was to identify new clinical categories that represented distinct biologic phenotypes based upon DNA checkerboard analyses of eight plaque bacteria, serum immunoglobulin G (IgG) titers to 17 bacteria, and the gingival crevicular fluid (GCF) levels of 16 inflammatory mediators. Five BGI clinical conditions were defined using probing depths (PDs) and bleeding on probing (BOP) scores. Subjects with all PDs < or = 3 mm were grouped as BGI-healthy (14.3% of sample) or BGI-gingivitis (BGI-G, 15.1%). Subjects with one or more PDs > or = 4 mm [deep lesion (DL)] were divided into low BOP (18.0%), moderate BOP (BGI-DL/MB, 39.7%), and severe BOP (BGI-DL/SB, 12.9%). RESULTS: Subjects with BGI-G had increased levels of Campylobacter rectus-specific serum IgG levels (P = 0.01), and those with BGI-DL/SB had increased IgG levels to Porphyromonas gingivalis (P < 0.0003) and C. rectus (P < 0.01). BGI-DL/SB subjects had an excessive GCF interleukin (IL)-1beta and prostaglandin E2 response and an enhanced chronic inflammatory response with significant increases in GCF IL-6 and monocyte chemotactic peptide-1. Within BGI-DL/SB subjects, more severe pocketing and BOP were associated with higher levels of GCF IL-1beta, not higher microbial counts or plaque scores. CONCLUSIONS: New BGI classifications create categories with distinct biologic phenotypes. The increased titers of C. rectus IgG among 68.5% of the BGI-G subjects and elevated P. gingivalis titers among BGI-DL/MB and BGI-DL/SB subjects (63.8% and 75.7%, respectively) are strongly supportive of the microbial specificity of pathogenesis for BGI categories.

Mutational profiling (MaP) enables detection of sites of chemical modification in RNA as sequence changes during reverse transcription (RT), subsequently read out by massively parallel sequencing. We introduce ShapeMapper 2, which integrates careful handling of all classes of adduct-induced sequence changes, sequence variant correction, basecall quality filters, and quality-control warnings to now identify RNA adduct sites as accurately as achieved by careful manual analysis of electrophoresis data, the prior highest-accuracy standard. MaP and ShapeMapper 2 provide a robust, experimentally concise, and accurate approach for reading out nucleic acid chemical probing experiments.