Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial.

This study evaluated changes in fatty acids from sera, red blood cells, and colonic biopsies from a phase Ib clinical trial of personalized ω-3 fatty acid dosing in 47 healthy volunteers. The trial aimed to reduce colonic prostaglandin E2 (PGE2), a pro-inflammatory product of arachidonic acid (AA) oxidation. The personalized doses ranged 2-10 grams/day (54% eicosapentaenoic acid, EPA, 24% other ω-3 fatty acids). In colon, increases in ω-3 highly unsaturated fatty acids (HUFA) and EPA:AA ratios each were correlated with decreases in PGE2. Changes in either colonic EPA:AA ratios or ω-3 HUFA were significantly correlated with changes in the same fatty acid measures in red blood cells or serum. The only blood-based measure significantly correlated with changes in colonic PGE2 was change in red blood cell ω-3 HUFA (ρ = -0.39), and the increase in red blood cell ω-3 HUFA was significantly greater in participants who had at least a median reduction in colonic PGE2 vs. those who did not. In summary, fatty acid changes in blood did reflect fatty acid changes in the colon, but additional factors will be needed for optimizing dosing models that seek to predict the anti-inflammatory effects of ω-3 fatty acids on the colon.

Disparities in Cancer Screening: The Role of County-Level Metropolitan Status and Racial Residential Segregation.

Mortality from cervical and colorectal cancers can be reduced through routine screening, which can often be accessed through primary care. However, uptake of screening in the US remains suboptimal, with disparities observed across geographic characteristics, such as metropolitan status or level of racial residential segregation. Little is known about the interaction of metropolitan status and segregation in their relationship with cancer screening. We conducted a quantitative survey of 474 women aged 45-65 in central Pennsylvania. The survey collected county-level characteristics and participant-level demographics, beliefs, cancer screening barriers, and cervical and colorectal cancer screening. We used bivariate and multivariable logistic regression to analyze relationships between metropolitan status and segregation with screening. For cervical cancer screening, 82.8% of participants were up-to-date, which did not differ by county type in the final analysis. Higher healthcare trust, higher cancer fatalism, and reporting cost as a barrier were associated with cervical cancer screening. For colorectal cancer screening, 55.4% of participants were up-to-date, which differed by county type. In metropolitan counties, segregation was not associated with colorectal cancer screening, but in non-metropolitan counties, segregation was associated with greater colorectal cancer screening. The relationship between metropolitan status and being up-to-date with colorectal, but not cervical, cancer screening varied by segregation. Other important beliefs and barriers to screening varied by county type. This research can guide future cancer screening interventions in primary care settings in underserved communities.

Multilevel Associations with Cancer Screening Among Women in Rural, Segregated Communities Within the Northeastern USA: a Mixed-Methods Study.

We recruited women (primarily non-Hispanic White) from 14 rural, segregated counties in a Northeastern US state for an explanatory sequential study: 100 women (ages 50-65 years) completed a survey, and 16 women participated in focus groups. We sought to identify personal (e.g., healthcare mistrust) and environmental (e.g., travel time to healthcare providers) factors related to colorectal and cervical cancer screening. Quantitatively, 89% of participants were up-to-date for cervical screening, and 65% for colorectal screening. Factors interacted such that compounding barriers were associated with lower odds of screening (e.g., insurance status and healthcare mistrust: interaction p = .02 for cervical; interaction p = .05 for colorectal). Qualitatively, three themes emerged regarding barriers to screening: privacy concerns, logistical barriers, and lack of trust in adequacy of healthcare services. While cancer screening was common in rural, segregated counties, women who reported both environmental and personal barriers to screening had lower uptake. Future interventions to promote screening can target these barriers.

Predictors of Human Papillomavirus Seropositivity in Appalachian Women Aged 18 to 26 Years.

BACKGROUND: Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. METHOD: Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. RESULTS: Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti-HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. CONCLUSIONS: Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

Knowledge, Perceptions, and Preferred Information Sources Related to COVID-19 Among Central Pennsylvania Adults Early in the Pandemic: A Mixed Methods Cross-Sectional Survey.

PURPOSE: To explore public knowledge, understanding of public health recommendations, perceptions, and trust in information sources related to COVID-19. METHODS: A cross-sectional survey of central Pennsylvanian adults evaluated self-reported knowledge, and a convergent, mixed methods design was used to assess beliefs about recommendations, intended behaviors, perceptions, and concerns related to infectious disease risk, and trust of information sources. RESULTS: The survey was completed by 5,948 adults. The estimated probability of correct response for the basic knowledge score, weighted with confidence, was 0.79 (95% CI, 0.79-0.80). Knowledge was significantly higher in patients with higher education and nonminority race. While the majority of respondents reported that they believed following CDC recommendations would decrease the spread of COVID-19 in their community and intended to adhere to them, only 65.2% rated social isolation with the highest level of belief and adherence. The most trusted information source was federal public health websites (42.8%). Qualitative responses aligned with quantitative data and described concerns about illness, epidemiologic issues, economic and societal disruptions, and distrust of the executive branch's messaging. The survey was limited by a lack of minority representation, potential selection bias, and evolving COVID-19 information that may impact generalizability and interpretability. CONCLUSIONS: Knowledge about COVID-19 and intended adherence to behavioral recommendations were high. There was substantial distrust of the executive branch of the federal government, however, and concern about mixed messaging and information overload. These findings highlight the importance of consistent messaging from trusted sources that reaches diverse groups.

What is lacking in current decision aids on cancer screening?

Recent guidelines on cancer screening have provided not only more screening options but also conflicting recommendations. Thus, patients, with their clinicians' support, must decide whether to get screened, which modality to use, and how often to undergo screening. Decision aids could potentially lead to better shared decision-making regarding screening between the patient and the clinician. A total of 73 decision aids concerning screening for breast, cervical, colorectal, and prostate cancers were reviewed. The goal of this review was to assess the effectiveness of such decision aids, examine areas in need of more research, and determine how the decision aids can be currently applied in the real-world setting. Most studies used sound study designs. Significant variation existed in the setting, theoretical framework, and measured outcomes. Just over one-third of the decision aids included an explicit values clarification. Other than knowledge, little consistency was noted with regard to which patient attributes were measured as outcomes. Few studies actually measured shared decision-making. Little information was available regarding the feasibility and outcomes of integrating decision aids into practice. In this review, the implications for future research, as well as what clinicians can do now to incorporate decision aids into their practice, are discussed.

Inherited alterations of TGF beta signaling components in Appalachian cervical cancers.

PURPOSE: This study examined targeted genomic variants of transforming growth factor beta (TGFB) signaling in Appalachian women. Appalachian women with cervical cancer were compared to healthy Appalachian counterparts to determine whether these polymorphic alleles were over-represented within this high-risk cancer population, and whether lifestyle or environmental factors modified the aggregate genetic risk in these Appalachian women. METHODS: Appalachian women's survey data and blood samples from the Community Awareness, Resources, and Education (CARE) CARE I and CARE II studies (n = 163 invasive cervical cancer cases, 842 controls) were used to assess gene-environment interactions and cancer risk. Polymorphic allele frequencies and socio-behavioral demographic measurements were compared using t tests and χ2 tests. Multivariable logistic regression was used to evaluate interaction effects between genomic variance and demographic, behavioral, and environmental characteristics. RESULTS: Several alleles demonstrated significant interaction with smoking (TP53 rs1042522, TGFB1 rs1800469), alcohol consumption (NQO1 rs1800566), and sexual intercourse before the age of 18 (TGFBR1 rs11466445, TGFBR1 rs7034462, TGFBR1 rs11568785). Interestingly, we noted a significant interaction between "Appalachian self-identity" variables and NQO1 rs1800566. Multivariable logistic regression of cancer status in an over-dominant TGFB1 rs1800469/TGFBR1 rs11568785 model demonstrated a 3.03-fold reduction in cervical cancer odds. Similar decreased odds (2.78-fold) were observed in an over-dominant TGFB1 rs1800469/TGFBR1 rs7034462 model in subjects who had no sexual intercourse before age 18. CONCLUSIONS: This study reports novel associations between common low-penetrance alleles in the TGFB signaling cascade and modified risk of cervical cancer in Appalachian women. Furthermore, our unexpected findings associating Appalachian identity and NQO1 rs1800566 suggests that the complex environmental exposures that contribute to Appalachian self-identity in Appalachian cervical cancer patients represent an emerging avenue of scientific exploration.

Results of a Pilot Study of a Mail-Based Human Papillomavirus Self-Testing Program for Underscreened Women From Appalachian Ohio.

BACKGROUND: Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet few mail-based HPV self-testing programs have been implemented in the United States. We report the results of a pilot study of a mail-based program, the Health Outcomes through Motivation and Education Project. METHODS: In 2015 to 2016, we recruited 103 women from Appalachian Ohio who were aged 30 to 65 years and had not received a Papanicolaou (Pap) test in at least 3 years. Women were mailed an HPV self-test and randomized to receive either (a) self-test instructions developed by the device manufacturer and a standard information brochure about cervical cancer (control group) or (b) self-test instructions developed by the Health Outcomes through Motivation and Education Project and a photo story information brochure about cervical cancer (intervention group). Logistic regression compared study arms on HPV self-test return and receipt of a Pap test. RESULTS: Overall, 80 (78%) women returned their HPV self-test. Return was similar among the intervention and control groups (78% vs. 77%; odds ratio, 1.09; 95% confidence interval, 0.43-2.76). Among returners, 26% had an oncogenic HPV type detected in their sample. Women who returned their self-test reported high levels of satisfaction and positive experiences with the self-testing process. Few women overall received a Pap test (11%), and Pap testing was similar among the intervention and control groups (14% vs. 8%; odds ratio, 1.91; 95% confidence interval, 0.52-6.97). CONCLUSIONS: Mail-based HPV self-testing programs are a potentially promising strategy for reaching underscreened women in Appalachia. Efforts are needed to better understand how to optimize the success of such programs.

Increases in Colonic Bacterial Diversity after ω-3 Fatty Acid Supplementation Predict Decreased Colonic Prostaglandin E2 Concentrations in Healthy Adults.

BACKGROUND: The intestinal microbiome is an important determinant of inflammatory balance in the colon that may affect response to dietary agents. OBJECTIVE: This is a secondary analysis of a clinical trial, the Fish Oil Study, to determine whether interindividual differences in colonic bacteria are associated with variability in the reduction of colonic prostaglandin E2 (PGE2) concentrations after personalized supplementation with ω-3 (n-3) fatty acids. METHODS: Forty-seven healthy adults (17 men, 30 women, ages 26-75 y) provided biopsy samples of colonic mucosa and luminal stool brushings before and after personalized ω-3 fatty acid supplementation that was based on blood fatty acid responses. Samples were analyzed using 16S ribosomal RNA sequencing. The data analyses focused on changes in bacterial community diversity. Linear regression was used to evaluate factors that predict a reduction in colonic PGE2. RESULTS: At baseline, increased bacterial diversity, as measured by the Shannon and Inverse Simpson indexes in both biopsy and luminal brushing samples, was positively correlated with dietary fiber intakes and negatively correlated with fat intakes. Dietary supplementation with ω-3 fatty acids increased the Yue and Clayton community dis-similarity index between the microbiome in luminal brushings and colon biopsy samples post-supplementation (P = 0.015). In addition, there was a small group of individuals with relatively high Prevotella abundance who were resistant to the anti-inflammatory effects of ω-3 fatty acid supplementation. In linear regression analyses, increases in diversity of the bacteria in the luminal brushing samples, but not in the biopsy samples, were significant predictors of lower colonic PGE2 concentrations post-supplementation in models that included baseline PGE2, baseline body mass index, and changes in colonic eicosapentaenoic acid-to-arachidonic acid ratios. The changes in bacterial diversity contributed to 6-8% of the interindividual variance in change in colonic PGE2 (P = 0.001). CONCLUSIONS: Dietary supplementation with ω-3 fatty acids had little effect on intestinal bacteria in healthy humans; however, an increase in diversity in the luminal brushings significantly predicted reductions in colonic PGE2. This trial was registered at www.clinicaltrials.gov as NCT01860352.

Effects of an Education Intervention about HPV Self-Testing for Healthcare Providers and Staff.

Human papillomavirus (HPV) self-testing is an emerging cervical cancer screening strategy, yet efforts to educate healthcare providers and staff about HPV self-testing are lacking. We report the findings of a brief education intervention about HPV self-testing for healthcare providers and staff. We conducted education sessions during 2015 with healthcare providers and staff (n = 33) from five federally qualified health centers located in Appalachian Ohio. Participants attended a one-time session and completed pre- and post-intervention surveys. Analyses for paired data assessed changes in knowledge and beliefs about HPV, HPV-related disease, and HPV self-testing. The intervention increased participants' knowledge and affected many of the beliefs examined. Participants answered an average of 4.67 of six knowledge items correctly on pre-intervention surveys and 5.82 items correctly on post-intervention surveys (p < 0.001). The proportion of participants who answered all six knowledge items correctly increased substantially (pre-intervention =9% vs. post-intervention =82%, p < 0.001). Compared to pre-intervention surveys, participants more strongly believed on post-intervention surveys that it is important to examine HPV self-testing as a potential cervical cancer screening strategy, that their female patients would be willing to use an HPV self-test at home by themselves, and that they have the knowledge to talk with their patients about HPV self-testing (all p < 0.05). A brief education intervention can be a viable approach for increasing knowledge and affecting beliefs about HPV self-testing among healthcare providers and staff. Findings will be valuable for planning and developing future HPV self-test interventions that include an education component for healthcare providers and staff.

The Effect of Perceived Stress on Epstein-Barr Virus Antibody Titers in Appalachian Ohio Women.

OBJECTIVE: The Appalachian population suffers a disparate burden of chronic stress leading to high perceived stress. The study aim was to determine the association between perceived stress and Epstein-Barr virus (EBV) antibody titers, along with the impact of perceived social support, Appalachian self-identify, and health behaviors. METHODS: Serum EBV VCA-IgG antibody titer levels from 169 female Appalachian residents (aged 18-26 years) were examined. Perceived stress, perceived social support, Appalachian self-identity, and health behaviors were assessed via self-administered questionnaires. RESULTS: There were 169 of 185 women positive for EBV. Among these women, the median EBV antibody titer level was 404 U/mL (range 101-6,464), and the overall geometric mean was 563.2 (95% CI 486.6-651.9). For a 1-point increase in perceived stress, the EBV antibody titer increased by 1.92% (95% CI 0.04-3.76%). For every point increase in perceived social support, the EBV antibody titer decreased by 1.00% (95% CI 0.06-1.98%). Perceived stress was significantly associated with sleep quality, BMI, and current smoking status, but not with binge-drinking, drug use, or Appalachian self-identity. No mediating effects of sleep quality, BMI, binge-drinking, current drug use, or >4 sexual partners were observed in the relationship between perceived stress and EBV titer level. CONCLUSION: Young Appalachian women reported high levels of perceived stress that were significantly associated with higher EBV titers. Higher perceived social support was associated with lower EBV titers. Health behaviors and Appalachian self-identity did not impact the relationship between perceived stress and EBV titers.

Consumer Perceptions of Interactions With Primary Care Providers After Direct-to-Consumer Personal Genomic Testing.

BACKGROUND: Direct-to-consumer (DTC) personal genomic testing (PGT) allows individuals to learn about their genetic makeup without going through a physician, but some consumers share their results with their primary care provider (PCP). OBJECTIVE: To describe the characteristics and perceptions of DTC PGT consumers who discuss their results with their PCP. DESIGN: Longitudinal, prospective cohort study. SETTING: Online survey before and 6 months after results. PARTICIPANTS: DTC PGT consumers. MEASUREMENTS: Consumer satisfaction with the DTC PGT experience; whether and, if so, how many results could be used to improve health; how many results were not understood; and beliefs about the PCP's understanding of genetics. Participants were asked with whom they had discussed their results. Genetic reports were linked to survey responses. RESULTS: Among 1026 respondents, 63% planned to share their results with a PCP. At 6-month follow-up, 27% reported having done so, and 8% reported sharing with another health care provider only. Common reasons for not sharing results with a health care provider were that the results were not important enough (40%) or that the participant did not have time to do so (37%). Among participants who discussed results with their PCP, 35% were very satisfied with the encounter, and 18% were not at all satisfied. Frequently identified themes in participant descriptions of these encounters were actionability of the results or use in care (32%), PCP engagement or interest (25%), and lack of PCP engagement or interest (22%). LIMITATION: Participants may not be representative of all DTC PGT consumers. CONCLUSION: A comprehensive picture of DTC PGT consumers who shared their results with a health care provider is presented. The proportion that shares results is expected to increase with time after testing as consumers find opportunities for discussion at later appointments or if results become relevant as medical needs evolve. PRIMARY FUNDING SOURCE: National Institutes of Health.

Colonic Saturated Fatty Acid Concentrations and Expression of COX-1, but not Diet, Predict Prostaglandin E2 in Normal Human Colon Tissue.

Prostaglandin E2 (PGE2) in the colon is a pro-inflammatory mediator that is associated with increased risk of colon cancer. In this study, expression of genes in the PGE2 pathway were quantified in colon biopsies from a trial of a Mediterranean versus a Healthy Eating diet in 113 individuals at high risk for colon cancer. Colon biopsies were obtained before and after 6 months of intervention. Quantitative, real-time PCR was used to measure mRNA expression of prostaglandin H synthases (PTGS1 and 2), prostaglandin E synthases (PTGES1 and 3), prostaglandin dehydrogenase (HPGD), and PGE2 receptors (PTGER2, PTGER4). The most highly expressed genes were HPGD and PTGS1. In multivariate linear regression models of baseline data, both colon saturated fatty acid concentrations and PTGS1 expression were significant, positive predictors of colon PGE2 concentrations after controlling for nonsteroidal anti-inflammatory drug use, gender, age, and smoking status. The effects of dietary intervention on gene expression were minimal with small increases in expression noted for PTGES3 in both arms and in PTGER4 in the Mediterranean arm. These results indicate that short-term dietary change had little effect on enzymes in the prostaglandin pathway in the colon and other factors, such as differences in fatty acid metabolism, might be more influential.

Markers of systemic exposures to products of intestinal bacteria in a dietary intervention study.

PURPOSE: Systemic exposures to intestinal bacteria may play a role in the etiology of the chronic, low-grade inflammation that is associated with western diets. Production of lipopolysaccharide-binding protein (LBP) is one biomarker of increased exposures to intestinal bacteria. This study evaluated whether changes in diet quality could affect serum LBP. METHODS: This was a randomized, controlled trial of Mediterranean and Healthy Eating diets over 6 months in 120 healthy subjects at increased risk of colon cancer. Blood samples obtained before and after intervention were analyzed for LBP, branched-chain fatty acids characteristic of intestinal bacteria, micronutrients and cytokines. Data were analyzed for changes in LBP over time and for predictors of LBP. RESULTS: Serum concentrations of branched-chain bacterial fatty acids declined significantly in both diet groups. However, there was no significant change in mean serum LBP concentrations with either diet intervention. In serum, LBP was positively associated with CRP and negatively associated with carotenoids both before and after intervention. After intervention, LBP was predicted positively by both CRP and bacterial fatty acid concentrations in serum, and negatively by serum carotenoids and the ω3/ω6 fatty acid ratio. This model accounted for 30 % of the inter-individual variation in serum LBP after intervention. CONCLUSIONS: These results indicate that dietary intervention over 6 months was insufficient to alter serum LBP. The relationships with inflammation-related markers, however, indicate that anti-inflammatory strategies other than changes in diet quality, such as weight loss or improved fitness, may have more potential for reducing systemic markers of LPS exposures in well-nourished populations.

Large-scale identification of core-fucosylated glycopeptide sites in pancreatic cancer serum using mass spectrometry.

Glycosylation has significant effects on protein function and cell metastasis, which are important in cancer progression. It is of great interest to identify site-specific glycosylation in search of potential cancer biomarkers. However, the abundance of glycopeptides is low compared to that of nonglycopeptides after trypsin digestion of serum samples, and the mass spectrometric signals of glycopeptides are often masked by coeluting nonglycopeptides due to low ionization efficiency. Selective enrichment of glycopeptides from complex serum samples is essential for mass spectrometry (MS)-based analysis. Herein, a strategy has been optimized using LCA enrichment to improve the identification of core-fucosylation (CF) sites in serum of pancreatic cancer patients. The optimized strategy was then applied to analyze CF glycopeptide sites in 13 sets of serum samples from pancreatic cancer, chronic pancreatitis, healthy controls, and a standard reference. In total, 630 core-fucosylation sites were identified from 322 CF proteins in pancreatic cancer patient serum using an Orbitrap Elite mass spectrometer. Further data analysis revealed that 8 CF peptides exhibited a significant difference between pancreatic cancer and other controls, which may be potential diagnostic biomarkers for pancreatic cancer.

Pilot clinical study of the effects of ginger root extract on eicosanoids in colonic mucosa of subjects at increased risk for colorectal cancer.

Colorectal cancer (CRC) remains a significant cause of mortality. Inhibitors of cyclooxygenase (COX) and thus prostaglandin E2, are promising CRC preventives, but have significant toxicities. Ginger has been shown to inhibit COX, to decrease the incidence and multiplicity of adenomas, and decrease PGE2 concentrations in subjects at normal risk for CRC. This study was conducted to determine the effects of 2.0 g/d of ginger given orally on the levels of PGE2, leukotriene B4 (LTB4), 13-hydroxy-octadecadienoic acids, and 5-, 12-, & 15-hydroxyeicosatetraenoic acid, in the colonic mucosa of subjects at increased risk for CRC. We randomized 20 subjects to 2.0 g/d ginger or placebo for 28 d. At baseline and Day 28, a flexible sigmoidoscopy was used to obtain colon biopsies. A liquid chromatography mass spectrometry method was used to determine eicosanoid levels in the biopsies, and levels were expressed per amount of protein or free arachidonic acid (AA). There was a significant decrease in AA between baseline and Day 28 (P = 0.05) and significant increase in LTB4 (P = 0.04) when normalized to protein, in subjects treated with ginger versus placebo. No other changes in eicosanoids were observed. There was no difference between the groups in total adverse events (AE; P = 0.06). Ginger lacks the ability to decrease eicosanoid levels in people at increased risk for CRC. Ginger did appear to be both tolerable and safe; and could have chemopreventive effects through other mechanisms. Further investigation should focus on other markers of CRC risk in those at increased CRC risk.

Effects of vitamin E from supplements and diet on colonic α- and γ-tocopherol concentrations in persons at increased colon cancer risk.

The available evidence indicates that γ-tocopherol has more potential for colon cancer prevention than α-tocopherol, but little is known about the effects of foods and supplements on tocopherol levels in human colon. This study randomized 120 subjects at increased colon cancer risk to either a Mediterranean or a Healthy Eating diet for 6 mo. Supplement use was reported by 39% of the subjects, and vitamin E intake from supplements was twofold higher than that from foods. Serum α-tocopherol at baseline was positively predicted by dietary intakes of synthetic vitamin E in foods and supplements but not by natural α-tocopherol from foods. For serum γ-tocopherol, dietary γ-tocopherol was not a predictor, but dietary α-tocopherol was a negative predictor. Unlike with serum, the data supported a role for metabolic factors, and not a direct effect of diet, in governing concentrations of both α- and γ-tocopherol in colon. The Mediterranean intervention increased intakes of natural α-tocopherol, which is high in nuts, and decreased intakes of γ-tocopherol, which is low in olive oil. These dietary changes had no significant effects on colon tocopherols. The impact of diet on colon tocopherols therefore appears to be limited.

Effects of a Mediterranean Diet Intervention on Anti- and Pro-Inflammatory Eicosanoids, Epithelial Proliferation, and Nuclear Morphology in Biopsies of Normal Colon Tissue.

This randomized trial evaluated the effects of intervention with either a Healthy Eating or a Mediterranean diet on colon biomarkers in 120 healthy individuals at increased colon cancer risk. The hypothesis was that eicosanoids and markers of proliferation would be favorably affected by the Mediterranean diet. Colon epithelial biopsy tissues and blood samples were obtained at baseline and after 6 mo of intervention. Colonic eicosanoid concentrations were evaluated by HPLC-MS-MS, and measures of epithelial proliferation and nuclear morphology were evaluated by image analysis of biopsy sections. There was little change in proinflammatory eicosanoids and in plasma cytokine concentrations with either dietary intervention. There was, however, a 50% increase in colonic prostaglandin E3 (PGE3), which is formed from eicosapentanoic acid, in the Mediterranean arm. Unlike PGE2, PGE3, was not significantly affected by regular use of non-steroidal anti-inflammatory drugs at baseline, and normal weight subjects had significantly higher colon PGE3 than overweight or obese subjects. Increased proliferation in the colon at baseline, by Ki67 labeling, was associated with morphological features that defined smaller nuclei in the epithelial cells, lower colon leukotriene concentrations and higher plasma cytokine concentrations. Dietary intervention had little effect on measures of epithelial proliferation or of nuclear morphology. The increase in PGE3 with a Mediterranean diet indicates that in normal colon, diet might affect protective pathways to a greater extent than proinflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.

Impact of family history assessment on communication with family members and health care providers: A report from the Family Healthware™ Impact Trial (FHITr).

OBJECTIVE: This study examines the impact of Family Healthware™ on communication behaviors; specifically, communication with family members and health care providers about family health history. METHODS: A total of 3786 participants were enrolled in the Family Healthware™ Impact Trial (FHITr) in the United States from 2005-7. The trial employed a two-arm cluster-randomized design, with primary care practices serving as the unit of randomization. Using generalized estimating equations (GEE), analyses focused on communication behaviors at 6month follow-up, adjusting for age, site and practice clustering. RESULTS: A significant interaction was observed between study arm and baseline communication status for the family communication outcomes (p's<.01), indicating that intervention had effects of different magnitude between those already communicating at baseline and those who were not. Among participants who were not communicating at baseline, intervention participants had higher odds of communicating with family members about family history risk (OR=1.24, p=0.042) and actively collecting family history information at follow-up (OR=2.67, p=0.026). Family Healthware™ did not have a significant effect on family communication among those already communicating at baseline, or on provider communication, regardless of baseline communication status. Greater communication was observed among those at increased familial risk for a greater number of diseases. CONCLUSION: Family Healthware™ prompted more communication about family history with family members, among those who were not previously communicating. Efforts are needed to identify approaches to encourage greater sharing of family history information, particularly with health care providers.

Quantitative analysis of single amino acid variant peptides associated with pancreatic cancer in serum by an isobaric labeling quantitative method.

Single amino acid variations are highly associated with many human diseases. The direct detection of peptides containing single amino acid variants (SAAVs) derived from nonsynonymous single nucleotide polymorphisms (SNPs) in serum can provide unique opportunities for SAAV associated biomarker discovery. In the present study, an isobaric labeling quantitative strategy was applied to identify and quantify variant peptides in serum samples of pancreatic cancer patients and other benign controls. The largest number of SAAV peptides to date in serum including 96 unique variant peptides were quantified in this quantitative analysis, of which five variant peptides showed a statistically significant difference between pancreatic cancer and other controls (p-value < 0.05). Significant differences in the variant peptide SDNCEDTPEAGYFAVAVVK from serotransferrin were detected between pancreatic cancer and controls, which was further validated by selected reaction monitoring (SRM) analysis. The novel biomarker panel obtained by combining α-1-antichymotrypsin (AACT), Thrombospondin-1 (THBS1) and this variant peptide showed an excellent diagnostic performance in discriminating pancreatic cancer from healthy controls (AUC = 0.98) and chronic pancreatitis (AUC = 0.90). These results suggest that large-scale analysis of SAAV peptides in serum may provide a new direction for biomarker discovery research.