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Background: In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac-dental centers.Methods: Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity C-reactive protein (hs-CRP).Results: After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l) at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95% confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender.Conclusion: This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Population-based clinical and laboratory studies have reported findings providing support for a possible relationship between periodontal disease and cardiovascular disease. The Periodontitis and Vascular Events (PAVE) pilot study was conducted to investigate the feasibility of a randomized secondary prevention trial to test whether treatment of periodontal disease reduces the risk for cardiovascular disease. Methods: Five clinical centers recruited participants who had documented coronary heart disease and met study criteria for periodontal disease. Eligible participants were randomized to receive periodontal therapy provided by the study or community dental care. Follow up telephone calls and clinic visits were planned to alternate at 3 month intervals after randomization, with all participants followed until at least the 6 month clinic visit. Participants were followed for adverse events and periodontal and cardiovascular out-comes. Results: A total of 303 participants were randomized Recruitment that involved active participation of a cardiologist with responsibility for the patients worked best among the strategies used. Of those who had not withdrawn, 93% completed the 6 month contact. During follow up, 11% of the 152 subjects in the community dental care group reported receiving periodontal therapy outside of the study. Conclusions: If appropriate recruitment strategies are used, this pilot study demonstrated that it is feasible to conduct a secondary prevention trial of periodontal therapy in patients who have had coronary heart disease. If a community dental care group is used, sample size estimation needs to take into account that a non trivial proportion of participants in this group may receive periodontal therapy outside of the study. [ABSTRACT FROM AUTHOR]

Background: The control of dental biofilm regrowth after nonsurgical periodontal therapy is associated with better clinical outcomes. However, many patients have difficulty achieving optimal plaque control. Subjects with diabetes, in which immune and wound-healing responses are typically impaired, may benefit from intensive antiplaque control regimens after scaling and root planing (SRP)., Objectives: This study aimed to evaluate the effects of an intensive, at-home, chemical, and mechanical antiplaque regimen as an adjunct to SRP for the treatment of moderate to severe periodontitis. A secondary objective was to compare responses in subjects with type 2 diabetes and nondiabetics., Methods: This was a 6-mo, single-center, parallel-group, randomized trial. The test group received SRP and oral hygiene instructions, and subjects were instructed to use a 0.12% chlorhexidine gluconate mouthrinse twice a day for 3 mo and utilize rubber interproximal bristle cleaners twice a day for 6 mo. The control group received SRP and oral hygiene instructions. The main outcome was change in mean probing depth (PD) from baseline to 6 mo. Secondary outcomes included change in sites with deep PDs, mean clinical attachment level, bleeding on probing, plaque index, hemoglobin A1C, fasting blood glucose, C-reactive protein, and taste assessment. This study was registered at ClinicalTrials.gov as NCT04830969., Results: In total, 114 subjects were randomized to either treatment. Eighty-six subjects completed the trial with no missing visits. Neither an intention-to-treat nor a per-protocol analysis showed statistically significant differences between treatment groups in mean PD at 6 mo. In a subgroup analysis, subjects with diabetes in the test group showed a statistically significant greater reduction in mean PD at 6 mo when compared to subjects with diabetes receiving the control treatment (Δ = 0.15, P = 0.04), while there were no differences within nondiabetics (Δ = 0.02, P = 0.75)., Conclusion: Outcomes in subjects with diabetes may be improved by chemo-mechanical antiplaque measures after nonsurgical periodontal therapy., Knowledge Transfer Statement: This study suggests diabetic subjects may benefit from an intensive, at-home, chemical, and mechanical antiplaque regimen to improve nonsurgical periodontal therapy outcomes., Competing Interests: Declaration of Conflicting InterestsThis study was funded by Sunstar, Inc. who manufactures Paroex and Soft-Picks. Sunstar employees who are coauthors in this manuscript participated in the study design but did not participate in data analysis or manuscript writing.

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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent epidemiological studies have shown that inflammatory bowel disease is associated with periodontal disease. The oral-gut microbiota axis is a potential mechanism intersecting the two diseases. Porphyromonas gingivalis is currently considered a keystone oral pathogen involved in periodontal disease pathogenesis and disease progression. Recent studies have shown that oral ingestion of P. gingivalis leads to intestinal inflammation. However, the molecular underpinnings of P. gingivalis-mediated gut inflammation have remained elusive. In this study, we show that the oral administration of P. gingivalis indeed leads to ileal inflammation and alteration in gut microbiota with significant reduction in bacterial alpha diversity despite the absence of P. gingivalis in the lower gastrointestinal tract. Utilizing an antibiotic-conditioned mouse model, cecal microbiota transfer experiments were performed to demonstrate that P. gingivalis-induced dysbiotic gut microbiota is sufficient to reproduce gut pathology. Furthermore, we observed a significant expansion in small intestinal lamina propria IL9 + CD4 + T cells, which was negatively correlated with both bacterial and fungal alpha diversity, signifying that P. gingivalis-mediated intestinal inflammation may be due to the subsequent loss of gut microbial diversity. Finally, we detected changes in gene expression related to gut epithelial barrier function, showing the potential downstream effect of intestinal IL9 + CD4 + T-cell induction. This study for the first time showed the mechanism behind P. gingivalis-mediated intestinal inflammation where P. gingivalis indirectly induces intestinal IL9 + CD4 + T cells and inflammation by altering the gut microbiota. Understanding the mechanism of P. gingivalis-mediated intestinal inflammation may lead to the development of novel therapeutic approaches to alleviate the morbidity from inflammatory bowel disease patients with periodontal disease., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aging invokes physiological changes, such as immunosenescence and inflammation, that could increase host susceptibility to oral microbiome shifts that enable periodontitis progression in later life. At present, there is a dearth of studies specifically evaluating the oral microbiome and periodontitis in older adults. We used high-throughput untargeted sequencing methods and functional metagenomic analyses to assess and compare the subgingival biofilm of postmenopausal women (mean age 71 years) according to periodontitis status. Subgingival plaque samples were obtained from 15 postmenopausal women with no periodontitis, and from 15 women with severe periodontitis, determined by probing measures. The 16S rRNA gene (V1⁻V3 region) was sequenced on the 454 FLX platform. The PICRUSt technique was used to provide information on what the potential functional characteristics of microbiota might be in healthy, compared with diseased, periodontium. The subgingival microbiome associated with periodontitis showed clear differences to that associated with health. Of the 464 species identified, 22.8% had elevated abundance in disease, while only 6.3% had elevated abundance in health. Among the 12 most prevalent organisms in periodontitis, one-half have previously been recognized as periodontal pathogens by other investigators. The subgingival microbiome in periodontitis contained genes that could code for specific activities, including microbial mobility, synthesis of endotoxin, and proteolytic degradation. The healthy microbiome included genes that could code for sustaining microbial life, including encoding for transporters, glycolysis, gluconeogenesis, the Krebs cycle, and protein kinases. In the present study on postmenopausal women, aged 60 and older, the subgingival microbiome differed in composition and potential function between those with and without periodontitis. Studies of functional gene expression, such as transcriptomics, are needed to definitively identify the molecules carrying out functions associated with pathogenic subgingival complexes. This, in turn, could lead to identification of targets for enhanced management of periodontitis and, possibly, other diseases, in later life.

Aim: The goal of the present longitudinal cohort study was to examine patterns of periodontal disease progression at progressing sites and subjects defined based on linear mixed models (LMM) of clinical attachment loss (CAL)., Materials and Methods: A total of 113 periodontally healthy and 302 periodontitis subjects had their CAL calculated bimonthly for 12 months. LMMs were fitted for each site and the predicted CAL levels used to categorize their progression state. Participants were grouped based on the number of progressing sites into unchanged, transitional and active subjects. Patterns of periodontal disease progression were explored using descriptive statistics., Results: Progression occurred primarily at molars (50% of progressing sites) and inter-proximal sites (72%), affected a higher proportion of deep than shallow sites (2.7% versus 0.7%), and pocketing was the main mode of progression (49%). We found a low level of agreement (47%) between the LMM and traditional approaches to determine progression such as change in CAL ≥3 mm. Fourteen per cent of subjects were classified as active and among those 93% had periodontitis. The annual mean rate of progression for the active subjects was 0.35 mm/year., Conclusion: Progressing sites and subjects defined based on LMMs presented patterns of disease progression similar to those previously reported in the literature., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The goal of this study was to identify progressing periodontal sites by applying linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL)., Methods: Ninety-three periodontally healthy and 236 periodontitis subjects had their CAL measured bi-monthly for 12 months. The proportions of sites demonstrating increases in CAL from baseline above specified thresholds were calculated for each visit. The proportions of sites reversing from the progressing state were also computed. LMM were fitted for each tooth site and the predicted CAL levels used to categorize sites regarding progression or regression. The threshold for progression was established based on the model-estimated error in predictions., Results: Over 12 months, 21.2%, 2.8% and 0.3% of sites progressed, according to thresholds of 1, 2 and 3 mm of CAL increase. However, on average, 42.0%, 64.4% and 77.7% of progressing sites for the different thresholds reversed in subsequent visits. Conversely, 97.1%, 76.9% and 23.1% of sites classified as progressing using LMM had observed CAL increases above 1, 2 and 3 mm after 12 months, whereas mean rates of reversal were 10.6%, 30.2% and 53.0% respectively., Conclusion: LMM accounted for several sources of error in longitudinal CAL measurement, providing an improved method for classifying progressing sites., (© 2016 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.)

Integrin-mediated migration of neutrophils to infected tissue sites is vital for pathogen clearance and therefore host survival. Although β2 integrins have been shown to mediate neutrophil transendothelial migration during systemic and local inflammation, relatively little information is available regarding neutrophil migration in sepsis beyond the endothelial cell layer. In this study, we report that integrin α3β1 (VLA-3; CD49c/CD29) is dramatically upregulated on neutrophils isolated from both human septic patients and in mouse models of sepsis. Compared with the α3β1 (low) granulocytes, α3β1 (high) cells from septic animals displayed hyperinflammatory phenotypes. Administration of a α3β1 blocking peptide and conditional deletion of α3 in granulocytes significantly reduced the number of extravasating neutrophils and improved survival in septic mice. In addition, expression of α3β1 on neutrophils was associated with Toll-like receptor-induced inflammatory responses and cytokine productions. Thus, our results show that α3β1 is a novel marker of tissue homing and hyperresponsive neutrophil subtypes in sepsis, and blocking of α3β1 may represent a new therapeutic approach in sepsis treatment., (© 2014 by The American Society of Hematology.)

Background: In this field trial, the authors assess the feasibility of screening for diabetes and prediabetes in dental practices and in a community health center., Methods: Dental patients 45 years and older who were not aware of their diabetic status underwent evaluation for diabetes risk with an American Diabetes Association Diabetes Risk Test and with hemoglobin (Hb) A1c measurement. Participants with an HbA1c level of 5.7 percent or greater were referred to their physicians for diagnosis., Results: Of the 1,022 patients screened, 416 (40.7 percent) had an HbA1c blood level of 5.7 percent or greater and were referred for diagnosis. The HbA1c and the American Diabetes Association Diabetes Risk Test were correlated (P < .001). Of the 416 participants who were referred, 35.1 percent received a diagnosis from their physicians within one year; 78.8 percent of these patients were seen in the community health center and 21.4 percent were seen in private dental offices. The diagnoses were diabetes (12.3 percent of patients), high risk of developing diabetes (that is, prediabetes) (23.3 percent) and no diabetes (64.4 percent)., Conclusions: The study results show that screening for prediabetes and diabetes is feasible in a dental office, with acceptance by the dentist and dental office staff members, patients' physicians and patients. Patients from the community health center demonstrated good compliance with referrals to physicians; however, compliance was poor among those in the private dental offices., Practical Implications: Screening for diabetes and prediabetes in the dental office may provide an important benefit to patients and encourage interprofessional collaboration to achieve a chronic care model in which health care professionals work together to care for a panel of patients.

Multiplexing arrays increase the throughput and decrease sample requirements for studies employing multiple biomarkers. The goal of this project was to examine the performance of Multiplex arrays for measuring multiple protein biomarkers in saliva and serum. Specimens from the OsteoPerio ancillary study of the Women's Health Initiative Observational Study were used. Participants required the presence of at least 6 teeth and were excluded based on active cancer and certain bone issues but were not selected on any specific condition. Quality control (QC) samples were created from pooled serum and saliva. Twenty protein markers were measured on five multiplexing array panels. Sample pretreatment conditions were optimized for each panel. Recovery, lower limit of quantification (LLOQ) and imprecision were determined for each analyte. Statistical adjustment at the plate level was used to reduce imprecision estimates and increase the number of usable observations. Sample pre-treatment improved recovery estimates for many analytes. The LLOQ for each analyte agreed with manufacturer specifications except for MMP-1 and MMP-2 which were significantly higher than reported. Following batch adjustment, 17 of 20 biomarkers in serum and 9 of 20 biomarkers in saliva demonstrated acceptable precision, defined as <20% coefficient of variation (<25% at LLOQ). The percentage of cohort samples having levels within the reportable range for each analyte varied from 10% to 100%. The ratio of levels in saliva to serum varied from 1∶100 to 28∶1. Correlations between saliva and serum were of moderate positive magnitude and significant for CRP, MMP-2, insulin, adiponectin, GM-CSF and IL-5. Multiplex arrays exhibit high levels of analytical imprecision, particularly at the batch level. Careful sample pre-treatment can enhance recovery and reduce imprecision. Following statistical adjustments to reduce batch effects, we identified biomarkers that are of acceptable quality in serum and to a lesser degree in saliva using Multiplex arrays.

Background: After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied., Purpose: We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials., Methods: We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees., Results: The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76)., Limitations: We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols., Conclusions: Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.

Background: Periodontal disease and cardiovascular disease (CVD) have been the focus of much research, but little is known about their roles in the recurrent event risk in patients with CVD. This study investigates whether periodontal disease is related to recurrent CVD events and mortality in survivors of incident myocardial infarction (MI)., Methods: Participants (668 males and 216 females; mean age: 54 + or - 8.5 years) were recruited (1997 through 2004) from two western New York county hospitals and completed an interviewer-administered questionnaire regarding lifestyle habits, clinical measurements, and a comprehensive dental examination. The periodontal disease status was measured by the mean clinical attachment loss (AL). Follow-up surveys assessed hospitalizations or medical procedures; cardiovascular events were validated by medical records. A National Death Index (NDI) Plus search was conducted. The outcome was recurrent fatal and non-fatal cardiovascular events (International Classification of Diseases codes 390 to 450)., Results: After an average follow-up of 2.9 years, 154 events were reported. Among never-smokers, the adjusted hazard ratio (95% confidence interval) for the mean clinical AL (millimeters) was 1.43 (1.09 to 1.89). No associations were found in ever-smokers (clinical AL by smoking interaction: P <0.05)., Conclusion: These findings indicate that periodontal disease may be an important factor in determining recurrent cardiovascular events in MI patients and not merely a marker for the effects of cigarette smoking.

Background: During the last 15 years, a substantial number of population-based, clinical, laboratory, and animal studies have been published that reported findings on the relationship between periodontal disease and cardiovascular disease. The Periodontitis and Vascular Events (PAVE) pilot study was conducted to investigate the feasibility of a randomized secondary prevention trial to test whether treatment of periodontal disease reduces the risk for cardiovascular disease. This article describes the occurrence of adverse events during the pilot study., Methods: The PAVE pilot study was a multicenter, randomized trial comparing periodontal therapy to community dental care. Baseline and follow-up clinic visits included a periodontal examination; blood, subgingival plaque, and crevicular fluid specimen collection; and medical and dental histories. Telephone follow-up contacts were scheduled to occur 3 months after randomization and every 6 months thereafter to assess adverse events or endpoints., Results: Cardiovascular adverse events occurred with similar frequency (23 versus 24 [P = 0.85] in the community control and the treatment groups, respectively). There were 15 serious adverse events (SAEs) with a non-significantly higher percentage occurring in the community care group (6.6% versus 3.3%; P = 0.19). A time-to-event analysis of patterns of SAEs indicated that subjects in the periodontal therapy group tended to be less likely to experience an SAE over the entire 25 months of the study., Conclusion: For those individuals who remained in the study, it appears that provision of periodontal scaling and root planing treatment to individuals with heart disease resulted in a similar pattern of adverse events as seen in the community care group, which also received some treatment.

Background: Public health and other population-based studies often depend on participants' self-reported disease status to assess prevalence, incidence, and disease trends. We sought to assess the feasibility of self-reported periodontal disease measures using dental history questions combined with demographic and medical history to predict periodontal disease., Methods: We evaluated results from two separate population-based studies carried out at the University at Buffalo, Buffalo, New York, i.e., the "Periodontal Infection and Risk for Myocardial Infarction Study," a study of 1,578 adults assessing the association between periodontal disease and myocardial infarction and the "Periodontal Disease Research Center" (the Erie County Study), an epidemiologic risk assessment study of 1,438 adults. In each study, an extensive list of oral health questions was asked, and a comprehensive medical history, blood analysis using chemistry and hematology tests, and demographic data were collected., Results: Using a predefined measure of severity of periodontal disease, we compared patients with severe disease to all others (i.e., those with moderate and no or mild disease). We examined areas under the curve (AUC) of the receiver operating curve to determine the best models, adding one, two, or three dental variables in all possible combinations. The AUC maximized at 0.76, and the combined sensitivity and specificity maximized at 142 and were comparable in both studies., Conclusions: Self-reported measures of periodontal disease are moderately predictive of clinical attachment loss. The demographic variables of age, race, smoking, gender, and diabetes mellitus accounted for much of the predictive power for self-reported periodontal disease; however, increases in sensitivity and specificity in the C statistics occurred when questions, including "Gum surgery in the past?," "Sore gums in the past?," "Scaling in the past?," "Bleeding gums now?," "Periodontal surgery in the past 2 years?," and "Chewing satisfaction?," were added to the model.

Background: Studies examining the association between periodontal disease and coronary heart disease have shown a consistent but weak to moderate relationship. Limited data have been reported in women and the role of smoking has not been fully clarified., Methods/results: A population-based case-control study examining the association between periodontal disease (PD) and acute non-fatal myocardial infarction (MI) was conducted in Erie and Niagara counties in Western New York State. Cases (574) were discharged alive from local hospitals with MI diagnosis. Controls (887) were county residents randomly selected from the NY State Department of Motor Vehicles rolls and Health Care Financing Administration files. Periodontal disease was assessed using clinical attachment loss (CAL). Among men (415 cases), the odds ratio (OR) of the association between mean CAL (mm) and MI, adjusting for the effects of age, body mass index (BMI), physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking was 1.34 (1.15-1.57). In women (120 cases), the corresponding OR was 2.08 (1.47-2.94). The estimate of this association among non-smokers, also adjusting for age, gender, BMI, physical activity, hypertension, cholesterol, diabetes, and total pack-years of cigarette smoking, was 1.40 (1.06-1.86), while it was 1.49 (1.26-1.77) among smokers., Conclusions: This study provides evidence of an association between PD and incident MI in both genders. This association appears to be independent from the possible confounding effect of smoking.

Background: The role of periodontal disease as an independent risk factor for cardiovascular disease (CVD) has been under debate because of the inconsistency of findings across studies. One of the major issues is the method used to assess or define periodontal disease. The present study assesses if the observed association between periodontal disease and incident myocardial infarction (MI) depends on the measurements and/or criteria used to define periodontal disease., Methods: A population-based case-control study to evaluate the association between PD and risk of MI was conducted between 1997 and 2001 in Western New York with 537 cases and 800 controls, aged 35 to 69 years. Cases were survivors of incident MI from local hospitals in Erie and Niagara counties. Controls were randomly selected from residents of the same counties. Periodontal disease was assessed using interproximal clinical attachment loss (CAL), probing depth (PD), alveolar crest height (ACH), and number of missing teeth. From these measurements, four different case definitions of periodontal disease were created., Results: Using the continuous forms of periodontal measurements, the odds ratios (ORs) (95% confidence interval) of the association with incident MI were 1.46 (1.26 to 1.69), 2.19 (1.66 to 2.89), 1.30 (1.14 to 1.49), and 1.04 (1.02 to 1.07) for mean CAL, PD, ACH, and number of missing teeth, respectively. Regardless of the case definition of periodontal disease, the estimates of the association with incident MI were statistically significant., Conclusions: The observed association between periodontal disease and incident MI was consistent across different measurements and/or case definitions of periodontal disease used. The magnitude of the association varies depending on the measurements or the criteria used to define periodontal disease.

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35-134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer.

Background: While prior studies of thyroid cancer incidence within Belarus have increased since the 1986 Chernobyl reactor accident, the magnitude of increase is not well quantified., Methods: Using Belarussian national cancer registry data, trends in average annual age-adjusted thyroid cancer incidence rates were examined by calendar year and gender. Incidence rates were also examined across specified time intervals, for specific age groups at diagnosis, and in 'higher exposure' regions compared with 'lower exposure' areas., Results: Age-adjusted thyroid cancer incidence rates (adjusted to the WHO 2000 world population) have increased between 1970 and 2001 from 0.4 per 100 000 to 3.5 per 100 000 among males (+775%) and from 0.8 per 100 000 to 16.2 per 100 000 among females (+1925%). The relative increase among males (+1020%) and females (+3286%) in 'high exposure' areas exceeded increases among males (+571%) and females (+250%) in 'lower exposure' areas of Belarus. Dramatic increases in thyroid cancer incidence rate ratios were noted among both males and females and in all age groups. The highest incidence rate ratios were observed among people from 'higher exposure' areas ages 0-14 yr at time of diagnosis., Conclusions: Marked increases in the incidence of thyroid cancer have occurred over a relatively limited period of observation in all areas of the Republic of Belarus and among all age categories. The greatest increases have occurred among children, suggesting that a high prevalence of pre-existing iodine deficiency in combination with unique susceptibility among younger people might have contributed to potential carcinogenic exposures to the thyroid.

Background: Although a large number of epidemiological studies have examined the role of aspirin in the chemoprevention of colon cancer and other solid tumors, there is a limited body of research focusing on the association between aspirin and lung cancer risk., Methods: We conducted a hospital-based case-control study to evaluate the role of regular aspirin use in lung cancer etiology. Study participants included 868 cases with primary, incident lung cancer and 935 hospital controls with non-neoplastic conditions who completed a comprehensive epidemiological questionnaire. Participants were classified as regular aspirin users if they had taken the drug at least once a week for at least one year., Results: Results indicated that lung cancer risk was significantly lower for aspirin users compared to non-users (adjusted OR = 0.57; 95% CI 0.41-0.78). Although there was no clear evidence of a dose-response relationship, we observed risk reductions associated with greater frequency of use. Similarly, prolonged duration of use and increasing tablet years (tablets per day x years of use) was associated with reduced lung cancer risk. Risk reductions were observed in both sexes, but significant dose response relationships were only seen among male participants. When the analyses were restricted to former and current smokers, participants with the lowest cigarette exposure tended to benefit most from the potential chemopreventive effect of aspirin. After stratification by histology, regular aspirin use was significantly associated with reduced risk of small cell lung cancer and non-small cell lung cancer., Conclusions: Overall, results from this hospital-based case-control study suggest that regular aspirin use may be associated with reduced risk of lung cancer.

Breast cancer is a major public health problem in the United States and in most industrialized countries. Although epidemiologic studies have identified a number of established risk factors for this disease, these factors explain only a small proportion of breast cancer incidence. Environmental exposure has been implicated in breast cancer etiology because of the vast geographic variation in breast cancer incidence rates across countries and regions within countries. Further, the steady increase in breast cancer rates over the past decades points to a potential role of environmental exposure in its development. One suspected environmental factor is the polychlorinated biphenyls (PCBs), which were manufactured commercially for a variety of industrial applications from the 1930s until the 1970s. PCBs have been associated with estrogenic, tumor promoting, and immunosuppressive activities, all of which are relevant in the development of breast cancer. The purpose of this review is to summarize the growing body of epidemiological evidence on the association between environmental PCB exposure and breast cancer risk. Three major types of study design have been used to investigate such a relation: clinic-based case-control studies, retrospective case-control studies, and nested case-control studies. Although findings from clinic-based case-control studies tend to point to an adverse effect of high PCB body burden on risk, the results from the more methodologically sound retrospective and nested studies do not provide strong support for a role of PCBs in breast cancer development. The association between PCB exposure and risk among racially and genetically susceptible subgroups may warrant further investigation. Methodological challenges in the design and analysis of epidemiologic studies on PCBs and breast cancer risk are discussed.

Assessment of physical activity in the distant past, usually by recall, is necessary to evaluate its etiologic effects on chronic disease. Few studies have investigated influences on such long-term recall. The authors investigated the association of gender, age, education, marital status, current physical activity, body weight, body mass index, blood pressure, and pulse with the quality of recall of physical activity in a Buffalo Health Study cohort followed since the early 1960s. Comparisons of original, recalled, and current reports of physical activity were made in 137 survivors of the cohort. The quality of recall (the difference between original and recalled reports) values near zero indicated the best recall; positive values, overestimation; and negative values, underestimation. Overestimators had the highest levels, and good recallers lower levels, of current physical activity. Although the authors found differences by gender, age, and education, the evidence did not support better recall by one group compared with the others. Moreover, no association of marital status, body weight, body mass index, blood pressure, or pulse was found with the quality of recall. The results suggest that individual respondent characteristics have little association with recall of past physical activity; however, current physical activity may be a factor to consider in studies of past physical activity and chronic disease.

Background: Periodontal disease has been found to be a potential risk factor for coronary heart disease. However, its association with cerebrovascular accidents (CVAs) is much less studied., Methods: This study examines the association between periodontal disease and CVA. The study cohort comprises 9962 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey and its follow-up study. Baseline periodontal status was categorized into (1) no periodontal disease, (2) gingivitis, (3) periodontitis, and (4) edentulousness. All CVAs (International Classification of Diseases, Ninth Revision [ICD-9], codes 430-438) were ascertained by hospital records for nonfatal events and death certificates for fatal events. The first CVA, nonfatal or fatal, was used to define incidence. Relative risks were estimated by hazard ratios from the Cox proportional hazard model with adjustment for several demographic variables and well-established cardiovascular risk factors. Weights were used to generate risk estimates., Results: Periodontitis is a significant risk factor for total CVA and, in particular, nonhemorrhagic stroke (ICD-9, 433-434 and 436-438). Compared with no periodontal disease, the relative risks (95% confidence intervals) for incident nonhemorrhagic stroke were 1.24 (0.74-2.08) for gingivitis, 2.11 (1.30-3.42) for periodontitis, and 1.41 (0.96-2.06) for edentulousness. For total CVA, the results were 1.02 (0.70-1.48) for gingivitis, 1.66 (1.15-2.39) for periodontitis, and 1.23 (0.91-1.66) for edentulousness. Increased relative risks for total CVA and nonhemorrhagic stroke associated with periodontitis were also seen in white men, white women, and African Americans. Similar results were found for fatal CVA., Conclusion: Periodontal disease is an important risk factor for total CVA and, in particular, nonhemorrhagic stroke.

The cognitive interview (CI) was modified for use in an epidemiological study in which respondents were asked to recall their daily physical activities from the distant past (35 years ago). In comparison to a traditional epidemiological interview, the CI elicited many more responses and also more precise responses. Several practical costs, however, were incurred by the CI: additional time to train interviewers and to conduct interviews and difficulties in coding the responses. The costs and benefits of conducting the CI are addressed, along with conceptual and methodological challenges. The article ends with an existential question: Is the CI a singular technique if it can be modified so radically for different settings?

Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

Substantial data exist supporting the role of physical activity in the etiology of several chronic diseases. Many chronic diseases begin developing 20-30 years before they become clinically evident. Since researchers often must rely on recall to characterize the long term habits of study participants, the accuracy of recall of physical activity is an important methodological issue in etiologic studies. The purpose of this study was to examine the quality of recall of physical activity in the distant past in a cohort of western New York residents followed since 1960. Paired t tests and intraclass correlation coefficients (ICCs) were used to compare "original" (1960) and "recalled" (1992-1996) reports of weekday (occupational) and free-day (leisure time) physical activity. Results showed that the recalled reports underestimated past weekday activities when overall activity was examined; estimates closer to the originals were found when levels of activity were examined. Recall was best for weekday light (ICC = 0.43) and weekday moderate (ICC = 0.45) activity in both sexes and free-day hard activity in females (ICC = 0.45). Most participants underestimated past free-day activity, but males overestimated free-day hard activity. Correlations for free-day activity were highest for summer sports in females (ICC = 0.29) and winter sports in both sexes (ICC = 0.39) and were low for walking and "other activity." Considering the length of time between the original interviews and the recall interviews, the correlations found here are remarkable and close to those found in other studies where recall intervals were 10 years or less.