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Objective This study examined the feasibility of eliciting dietary changes in subjects recruited from a diverse primary care setting in Michigan using a written, one-page plan, either alone or with telephone counseling. Methods A total of 96 subjects were enrolled from 9/28/06 to 5/7/07 (49% minorities). Subjects were randomized into three groups. Group 1 received written materials. Group 2 received written materials plus a one-page form that asked them to make a specific daily plan for substituting one less nutritious food with two servings of fruits and vegetables. Group 3 received the written materials, the one-page form and telephone counseling from a dietitian. Results Subject retention was 76% for the 12-week study. Subjects in Groups 1, 2 and 3 changed their mean intakes of fruit and vegetables by 0.4, −0.7 and 1.4 servings/day, respectively. Participants in Group 3 lost an average of 0.73 kg, increased their perception of the importance of eating fruits and vegetables, and 63% increased their serum levels of carotenoids by 20% or more. Conclusion Recruitment through a primary care clinic was effective. Formulation of a written plan combined with telephone counseling appears to be promising for improving fruit and vegetable intakes and warrants more definitive study.

Background: Women with chronic medical conditions, such as diabetes and hypertension, have a higher risk of pregnancy-related complications compared with women without medical conditions and should be offered contraception if desired. Although evidence based guidelines for contraceptive selection in the presence of medical conditions are available via the United States Medical Eligibility Criteria (US MEC), these guidelines are underutilized. Research also supports the use of decision tools to promote shared decision making between patients and providers during contraceptive counseling. Objective: The overall goal of the MiHealth, MiChoice project is to design and implement a theory-driven, Web-based tool that incorporates the US MEC (provider-level intervention) within the vehicle of a contraceptive decision tool for women with chronic medical conditions (patient-level intervention) in community-based primary care settings (practice-level intervention). This will be a 3-phase study that includes a predesign phase, a design phase, and a testing phase in a randomized controlled trial. This study protocol describes phase 1 and aim 1, which is to determine patient-, provider-, and practice-level factors that are relevant to the design and implementation of the contraceptive decision tool. Methods: This is a mixed methods implementation study. To customize the delivery of the US MEC in the decision tool, we selected high-priority constructs from the Consolidated Framework for Implementation Research and the Theoretical Domains Framework to drive data collection and analysis at the practice and provider level, respectively. A conceptual model that incorporates constructs from the transtheoretical model and the health beliefs model undergirds patient-level data collection and analysis and will inform customization of the decision tool for this population. We will recruit 6 community-based primary care practices and conduct quantitative surveys and semistructured qualitative interviews with women who have chronic medical conditions, their primary care providers (PCPs), and clinic staff, as well as field observations of practice activities. Quantitative survey data will be summarized with simple descriptive statistics and relationships between participant characteristics and contraceptive recommendations (for PCPs), and current contraceptive use (for patients) will be examined using Fisher exact test. We will conduct thematic analysis of qualitative data from interviews and field observations. The integration of data will occur by comparing, contrasting, and synthesizing qualitative and quantitative findings to inform the future development and implementation of the intervention. Results: We are currently enrolling practices and anticipate study completion in 15 months. Conclusions: This protocol describes the first phase of a multiphase mixed methods study to develop and implement a Web-based decision tool that is customized to meet the needs of women with chronic medical conditions in primary care settings. Study findings will promote contraceptive counseling via shared decision making and reflect evidence-based guidelines for contraceptive selection. Trial Registration: ClinicalTrials.gov NCT03153644; https://clinicaltrials.gov/ct2/show/NCT03153644 (Archived by WebCite at http://www.webcitation.org/6yUkA5lK8)

Purpose: To determine whether family medical history as a risk factor for six common diseases is related to patients' perceptions of risk, worry, and control over getting these diseases. Methods: We used data from the cluster-randomized, controlled Family Healthware™ Impact Trial (FHITr). At baseline, healthy primary care patients reported their perceptions about coronary heart disease, stroke, diabetes, and breast, ovarian, and colon cancers. Immediately afterward, intervention group participants used Family Healthware™ to record family medical history; this web-based tool stratified familial disease risks. Multivariate and multilevel regression analyses measured the association between familial risk and patient perceptions for each disease, controlling for personal health and demographics. Results: For the 2330 participants who used Family Healthware™ immediately after providing baseline data, perceived risk and worry for each disease were strongly associated with family history risk, adjusting for personal risk factors. The magnitude of the effect of family history on perceived risk ranged from 0.35 standard deviation for ovarian cancer to 1.12 standard deviations for colon cancer. Family history was not related to perceived control over developing diseases. Risk perceptions seemed optimistically biased, with 48–79% of participants with increased familial risk for diseases reporting that they were at average risk or below. Conclusions: Participants' ratings of their risk for developing common diseases, before feedback on familial risk, parallels but is often lower than their calculated risk based on family history. Having a family history of a disease increases its salience and does not change one's perceived ability to prevent the disease.

Objective We describe factors, in the context of the Social Determinants of Health model, associated with receiving Pap smears within risk-appropriate guidelines (i.e., guidelines that specify screening intervals based upon a woman's individual risk of developing cervical cancer). Methods Completed in June 2006, we conducted a cross-sectional survey of women from 14 health clinics in Ohio Appalachia pertaining to psychosocial, demographic, biological, and health-related factors. A logistic regression model was constructed to predict whether or not a woman was within risk-appropriate cervical cancer screening guidelines. Results Of 562 women with a date of last Pap smear, 380 (68%) were within risk-appropriate guidelines. Logistic regression showed that, compared to women with low-level SES, women with middle- and high-level SES had 3.39 [1.85, 6.21] and 3.86 [2.03, 7.34] times the odds, respectively, of being within risk-appropriate guidelines. Odds of being within guidelines increased 1.09 [1.04, 1.15] fold for each decrease of one major life event. Additionally, women that were financially better off or financially worse off than their parents at the same age had lower odds (0.41 [0.23, 0.73] and 0.49 [0.24, 0.98], respectively) of being within guidelines than women who reported their finances were the same as their parents. Results also showed an interaction between marital status and age at first intercourse ( p = 0.001). Conclusion The results suggest an impact of psychosocial factors on Pap smear testing behaviors, and illustrate the need to examine risk-appropriate interventions to improve screening.

Purpose The objective of this study was to compare the reasons why mothers do or do not have their adolescent daughters vaccinated against HPV. Methods Mothers of vaccinated and unvaccinated 11- to 17-year-old girls seen during preventive care visits in outpatient family medicine or pediatric clinics underwent an audiotaped structured telephone interview that used open-ended questions to assess the reasons underlying maternal decisions about HPV vaccination. Qualitative methods categorized maternal responses into themes. Results Interviews of 52 mothers (19 declining vaccination, 33 accepting) identified several distinct factors underlying their decisions about HPV vaccination. Lack of knowledge about HPV, age-related concerns, and low perceived risk of infection were commonly cited reasons for declining vaccination. Desire to prevent illness, physician recommendation, and a high perceived risk of infection were commonly identified motivating factors. Both groups of mothers had significant concerns about vaccine safety. Locus of control (e.g., mother or daughter) of health-related decisions arose as a novel factor influencing this decision that had not been previously described in the context of HPV vaccination. Conclusions Addressing safety concerns, educating parents about the age-specific risk of HPV infection, and promoting strong physician recommendation for vaccination may be the most useful targets for future interventions to increase HPV vaccine utilization.

Context Family history is a risk factor for many common chronic diseases, yet it remains underutilized in primary care practice. Background Family Healthware™ is a self-administered, web-based tool that assesses familial risk for CHD; stroke; diabetes; and colorectal, breast, and ovarian cancer, and provides a personalized prevention plan based on familial risk. The Family Healthware Impact Trial evaluated the tool. Design In this cluster RCT, participants completed baseline and 6-month follow-up surveys. The intervention group used Family Healthware directly after the baseline survey. Controls used the tool after completing the follow-up survey. Setting/participants Patients aged 35–65 years with no known diagnosis of these six diseases were enrolled from 41 primary care practices. Main outcome measures The prevalence of family-history–based risk for coronary heart disease (CHD); stroke; diabetes; and colorectal, breast, and ovarian cancer was determined in a primary care population. Results From 2005 to 2007, 3786 participants enrolled. Data analysis was undertaken from September 2007 to March 2008. Participants had a mean age of 50.6 years and were primarily white (91%) women (70%). Of the 3585 participants who completed the risk assessment tool, 82% had a strong or moderate familial risk for at least one of the diseases: CHD (strong=33%, moderate=26%); stroke (strong=15%, moderate=34%); diabetes (strong=11%, moderate=26%); colorectal cancer (strong=3%, moderate=11%); breast cancer (strong=10%, moderate=12%); and ovarian cancer (strong=4%, moderate=6%). Women had a significantly ( p p ≤0.02) more likely to have a strong family history for CHD, stroke, and diabetes. Older participants were significantly ( p ≤0.02) more likely to report a strong family history for CHD and stroke as well as colorectal and breast cancer. Conclusions This self-administered, online tool delineated a substantial burden of family-history–based risk for these chronic diseases in an adult, primary care population. Trial registration NCT00164658.

To assess HPV vaccine acceptability, focus groups of women (18–26 years), parents, community leaders, and healthcare providers were conducted throughout Ohio Appalachia. Themes that emerged among the 23 focus groups (n=114) about the HPV vaccine were: barriers (general health and vaccine specific), lack of knowledge (cervical cancer and HPV), cultural attitudes, and suggestions for educational materials and programs. Important Appalachian attitudes included strong family ties, privacy, conservative views, and lack of trust of outsiders to the region. There are differences in HPV vaccine acceptability among different types of community members highlighting the need for a range of HPV vaccine educational materials/programs to be developed that are inclusive of the Appalachian culture.

Pancreatic cancer is a formidable disease and early detection biomarkers are needed to make inroads into improving the outcomes in these patients. In this work, lectin antibody microarrays were utilized to detect unique glycosylation patterns of proteins from serum. Antibodies to four potential glycoprotein markers that were found in previous studies were printed on nitrocellulose coated glass slides and these microarrays were hybridized against patient serum to extract the target glycoproteins. Lectins were then used to detect different glycan structural units on the captured glycoproteins in a sandwich assay format. The biotinylated lectins used to assess differential glycosylation patterns were Aleuria aurentia lectin (AAL), Sambucus nigra bark lectin (SNA), Maackia amurensis lectin II (MAL), Lens culinaris agglutinin (LCA), and Concanavalin A (ConA). Captured glycoproteins were evaluated on the microarray in situ by on-plate digestion and direct analysis using MALDI QIT-TOF mass spectroscopy. Analysis was performed using serum from 89 normal controls, 35 chronic pancreatitis samples, 37 diabetic samples and 22 pancreatic cancer samples. We found that this method had excellent reproducibility as measured by the signal deviation of control blocks as on-slide standard and 41 pairs of pure technical replicates. It was possible to discriminate cancer from the other disease groups and normal samples with high sensitivity and specificity where the response of Alpha-1-beta glycoprotein to lectin SNA increased by 69% in the cancer sample compared to the other noncancer groups (95% confidence interval 53-86%). These data suggest that differential glycosylation patterns detected on high-throughput lectin glyco-antibody microarrays are a promising biomarker approach for the early detection of pancreatic cancer.

Despite high levels of awareness among primary care physicians of the recommendations for colorectal cancer (CRC) screening, rates of screening remain low nationally.1 One solution that has been proposed and studied to remedy this problem is computerized reminders. Studies that have examined the use of computerized reminders to increase cancer screening rates have generally shown favorable results. Unfortunately, the potential for gains has been outweighed in the past by the fact that computerized systems are frequently designed around specific practices’ computer infrastructure.2–4 Therefore, these systems have largely not been generalizable or sustainable. In addition, few of the reminder system studies have been performed in community-based practices, most likely because of technology barriers. Another theme in the primary care preventive services literature explores the role of practice organization. One group has conceptualized this in terms of “tools, teamwork and tenacity.”5 In this model, technology is a tool that operates within the context of a complex, adaptive system. The specific role that the system plays is just now being explored, especially with respect to the implementation of electronic health records (EHR).6 It is clear based on this work that unless attention is devoted to the organizational context, efforts to introduce new technology into a practice are not likely to produce consistent results and may produce negative results.7 Prompting and reminding at encounters for prevention (PREP) was undertaken to examine the feasibility of integrating a computerized reminder system (CRS) into a wide variety of practice infrastructures and to examine potential differential effects of directing encounter-based reminders toward clinicians, patients, or both. The study was designed to recruit practices from nonacademic, community settings to maximize the generalizability of its findings. In addition to examining whether a generalizable reminder system could produce increased CRC screening rates, we also sought to understand the impact of practices’ organizational contexts.

Transformative growth in the capacity of family medicine and primary care research and scholarship in the United States and Canada is crucial.1 Far greater capacity is needed to: generate the necessary knowledge; design, evaluate, and disseminate the innovations; and inform the implementation of sustainable systems change that will move us closer to better health, better health care, and affordable cost (The Triple Aim).1 Family medicine research encompasses clinical, health services, prevention, population health, health policy, community-based participatory research, educational innovation and evaluation, synthesis and dissemination of evidence, and the science of implementation. Each of these domains is necessary for the efficient and effective translation of biological discovery and new technology development into ethically sound practice and policy.

The initiation and timely completion of the human papillomavirus (HPV) vaccine in young women is critical. We compared the initiation and completion of the HPV vaccine among women in 2 community-based networks with electronic health records: 1 with a prompt and reminder system (prompted cohort) and 1 without (unprompted cohort).Female patients aged 9 to 26 years seen between March 1, 2007, and January 25, 2010, were used as the retrospective cohort. Patient demographics and vaccination dates were extracted from the electronic health records.Patients eligible for the vaccine included 6019 from the prompted cohort and 9096 from the unprompted cohort. Mean age at initiation was 17.3 years in the prompted cohort and 18.1 years in the unprompted cohort. Significantly more (P.001) patients initiated the vaccine in the prompted cohort (34.9%) compared with the unprompted cohort (21.5%). African Americans aged 9 to 18 years with ≥3 visits during the observation period were significantly more likely to initiate in the prompted cohort (P.001). The prompted cohort was significantly more likely (P.001) to complete the vaccine series in a timely manner compared with the unprompted cohort.More patients aged 9 to 26 years initiated and achieved timely completion of the HPV vaccine series in clinics using an electronic health record system with prompts compared with clinics without prompts.

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 six months 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 pro-inflammatory 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 pro-inflammatory and proliferative pathways. Hence, biomarkers from cancer models might not be relevant in a true prevention setting.

PGE2 is a well-known biomarker for colon cancer risk. PGE2 is formed from arachidonic acid (AA) via cyclooxygenases (COX-1 and 2) and prostaglandin E synthases (PGES), whereas it is catabolized by1...

While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20–7.76), smoking (OR = 3.0, 95% CI 1.19–7.56), high viral load (OR = 5.27, 95% CI 2.05–13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1–47.58) and high transcript copies (OR = 5.56, 95% CI 2.05–13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening. © 2005 Wiley-Liss, Inc.

Objective: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III. Methods: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks. Results: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities. Conclusion: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

This review contrasts the planned and actual recruitment and retention efforts for a cervical cancer prevention study within a predominantly underserved population. Recruitment was a primary obstacle to trial progression and multiple strategies to improve recruitment were implemented to meet objectives. The actual recruitment strategies were expansion to five geographically distinct clinical sites, use of nurse practitioners focused primarily on patient issues, extremely flexible study hours and location, honorariums, support for transportation and child care, and creativity in maintaining contact with study participants. With these strategies, 90% of eligible patients consented to participate in the study.

Epidemiological, experimental, and clinical observations provide support for a colorectal cancer chemopreventive role for aspirin. We have evaluated the effects of aspirin on proliferation biomarkers in normal-risk and high-risk human subjects for colorectal cancer. Colorectal biopsies were obtained at baseline and at 24h after 28 daily doses of 81mg of aspirin from 13 high-risk and 15 normal-risk subjects for colorectal cancer. We evaluated aspirin's effects on proliferating cell nuclear antigen (PCNA) immunohistochemistry and epithelial mucin histochemistry using the lectin, Amaranthus caudatus agglutinin (ACA) in crypt sections from rectal biopsies. The baseline whole crypt PCNA LIs differed significantly between normal-risk and high-risk subjects. PCNA LIs are not affected by 28 days of aspirin at 81mg daily. ACA LIs are decreased by 28 days of aspirin at 81mg daily in both normal-risk and high-risk subjects. Aspirin's effects on ACA LIs may have mechanistic and biological implications that deserve further attention. PCNA and ACA LIs are not useful as proliferation biomarkers for aspirin's chemopreventive activity in morphologically normal human colorectal mucosa.

This study identifies the risks, benefits, and social influences affecting the decision to participate in a chemoprevention trial for cervical dysplasia. Women from three clinical sites in southeastern Michigan were invited to participate in a semi-structured interview. In previous studies, minority women have significant barriers to participation in clinical trials. However, in this study, women (63% black, 26% white, and 9% other ethnicity), were interested in participating and reported only moderate barriers. These barriers could easily be addressed with resources available to investigators. Copyright 2003, Elsevier Science (USA). All rights reserved.

Aim: To assess customer comprehension of health-related personal genomic testing (PGT) results. Methods: We presented sample reports of genetic results and examined responses to comprehension questions in 1,030 PGT customers (mean age: 46.7 years; 59.9% female; 79.0% college graduates; 14.9% non-White; 4.7% of Hispanic/Latino ethnicity). Sample reports presented a genetic risk for Alzheimer's disease and type 2 diabetes, carrier screening summary results for >30 conditions, results for phenylketonuria and cystic fibrosis, and drug response results for a statin drug. Logistic regression was used to identify correlates of participant comprehension. Results: Participants exhibited high overall comprehension (mean score: 79.1% correct). The highest comprehension (range: 81.1-97.4% correct) was observed in the statin drug response and carrier screening summary results, and lower comprehension (range: 63.6-74.8% correct) on specific carrier screening results. Higher levels of numeracy, genetic knowledge, and education were significantly associated with greater comprehension. Older age (≥60 years) was associated with lower comprehension scores. Conclusions: Most customers accurately interpreted the health implications of PGT results; however, comprehension varied by demographic characteristics, numeracy and genetic knowledge, and types and format of the genetic information presented. Results suggest a need to tailor the presentation of PGT results by test type and customer characteristics.

OBJECTIVE: To describe how Ohio Appalachian women are over- or under-estimating risk for cervical cancer by comparing an objective measure of cervical cancer risk to subjective interpretations of risk. METHODS: A cervical cancer risk index was computed for 530 female participants recruited from clinics in Ohio Appalachia (2006–2008). Risk factors for cervical cancer, including human papillomavirus infection, number of sexual partners, parity, age at first intercourse, age at first pregnancy, oral contraceptive use and cigarette smoking were used to create a cervical cancer risk index. This index was used to categorize participants into low, average or high risk for cervical cancer. Subjective risk was assessed by asking women to indicate whether they believe their risk of cervical cancer to be below, about average, or higher than other women. Objective risk categories were compared to subjective risk to determine if women were accurately perceiving risk, or over- or under-estimating risk. A multinomial logistic regression model was used to determine correlates of risk perception accuracy. The outcome was a categorical variable consisting of over-estimating risk, underestimating risk and accurate risk perception, with accurate risk perception serving as the reference level in the model. RESULTS: Out of 530 women, 33.6% (n = 178) over-estimated risk and 24.9% (n = 132) under-estimated risk. Women with household incomes of

Persistent infection with high-risk human papillomavirus (HPV) types is necessary for the development of high-grade cervical dysplasia and cervical carcinoma. The presence of HPV DNA in the blood of cervical cancer patients has been reported; however, whether HPV DNA is detectable in the blood of patients with pre-invasive cervical disease is unclear.The objectives of this study were to determine if HPV 16 and HPV 18 DNA could be detected in the serum of colposcopy clinic patients, and if serum HPV detection was associated with grade of cervical disease and HPV cofactors.Samples were selected from a biorepository collected from non-pregnant, HIV-negative women ages 18-69 attending colposcopy clinics at two urban public hospitals. Cervical disease status was based on review of colposcopy, biopsy and cytology findings. Serum HPV DNA detection was conducted using a novel PCR and mass spectroscopy-based assay.Of the 116 adequate serum samples, all (100%) were negative for HPV 16 and HPV 18. Over half (51.7%) of participants had cervical HPV 16 and/or HPV 18 infection. Nearly one-third (31.1%) had high grade, 10.3% had low grade, and 50.9% had no cervical disease. Nearly one-third (28.5%) had ever regularly smoked cigarettes, 70.7% had early onset of sexual intercourse, and 75% had ever used oral contraceptives.In this colposcopy clinic population with a range of clinical characteristics and established HPV cofactors, HPV DNA was undetectable in their serum. Our findings suggest that serum HPV DNA detection is not a cervical cancer screening tool.

In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman’s Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo.

Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information. Cancer Prev Res; 7(11); 1112–21. ©2014 AACR.

Human papillomavirus (HPV) vaccination rates do not meet the Healthy People 2020 objective of 80 % coverage among adolescent females. We describe the development and initial feedback about an HPV vaccine comic book for young adolescents. The comic book is one component of a multilevel intervention to improve HPV vaccination rates among adolescents. Parents suggested and provided input into the development of a HPV vaccine comic book. Following the development of the comic book, we conducted a pilot study to obtain initial feedback about the comic book among parents (n = 20) and their adolescents ages 9 to 14 (n = 17) recruited from a community-based organization. Parents completed a pre-post test including items addressing HPV knowledge, HPV vaccine attitudes, and about the content of the comic book. Adolescents completed a brief interview after reading the comic book. After reading the comic book, HPV knowledge improved (2.7 to 4.6 correct answers on a 0–5 scale; p < 0.01) and more positive attitudes toward HPV vaccination (p < 0.05) were reported among parents. Parents confirmed that the comic book’s content was acceptable and adolescents liked the story, found it easy to read, and thought the comic book was a good way to learn about being healthy. Parents provided valuable information in the development of a theoretically-based comic book and the comic book appears to be an acceptable format for providing HPV vaccine information to adolescents. Future research will include the comic book in an intervention study to improve HPV vaccination rates.

Pancreatic cancer remains the fourth leading cause of cancer-related deaths in the United States. Risk factors include family history, smoking, chronic pancreatitis, obesity, diabetes mellitus, heavy alcohol use, and possible dietary factors. Because more than two-thirds of adenocarcinomas occur in the head of the pancreas, abdominal pain, jaundice, pruritus, dark urine, and acholic stools may be presenting symptoms. In symptomatic patients, the serum tumor marker cancer antigen 19-9 can be used to confirm the diagnosis and to predict prognosis and recurrence after resection. Pancreas protocol computed tomography is considered standard for the diagnosis and staging of pancreatic cancer. Although surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinomas, less than 20% of surgical candidates survive five years. The decision on resectability requires multidisciplinary consultation. Pancreatic resections should be performed at institutions that complete at least 15 of the surgeries annually. Postoperatively, use of gemcitabine or fluorouracil/leucovorin as adjuvant chemotherapy improves overall survival by several months. However, more than 80% of patients present with disease that is not surgically resectable. For patients with locally advanced or metastatic disease, chemoradiotherapy with gemcitabine or irinotecan provides clinical benefit and modest survival improvement. Palliation should address pain control, biliary and gastric outlet obstruction, malnutrition, thromboembolic disease, and depression.

Commentary on: Ronco G, Dillner J, Elfstrom KM, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;383:524–32.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Over the past 20 years, cervical cancer screening guidelines have evolved from advising performance of cervical cytology on every sexually active woman every year, to advising no screening on women under the age of 21 years and use of cervical cytology every 3 years only in women aged 30–65 years with an intact cervix.1 Many clinicians use human papillomavirus (HPV) testing with cervical cytology to triage abnormal cytology. Others have begun to use HPV alongside normal cytology. The data to support this strategy was based solely on protection from cervical … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.volume%253D383%26rft.spage%253D524%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252813%252962218-7%26rft_id%253Dinfo%253Apmid%252F24192252%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(13)62218-7&link_type=DOI [3]: /lookup/external-ref?access_num=24192252&link_type=MED&atom=%2Febmed%2F19%2F4%2F148.atom [4]: /lookup/external-ref?access_num=000331136400028&link_type=ISI

3. Experimental models for colorectal cancer chemoprevention studies . . . . . . . . . . . . . . . 201 3.1. Animal models of chemical carcinogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 3.2. Aberrant crypt foci (ACF) assay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 3.3. Colon cancer cell lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 3.4. Transfection models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 3.5. Genetic and knock-out models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202

Objective To explore links between genetic responsiveness to the bitter taste of 6-7i-propylthiouracil (PROP) and self-reported preferences for vegetables and fruit of female breast care patients. Methods PROP tasting was defined by detection thresholds and by perceived bitterness and hedonic ratings for PROP solutions. Nontasters, medium tasters, and supertasters were identified by their PROP thresholds and by the ratio of perceived bitterness of PROP to the perceived saltiness of sodium chloride solutions. Subjects rated preferences for vegetables and fruit using 9-point category scales. Subjects/setting A clinical sample of 170 patients with newly diagnosed breast cancer and 156 cancer-free control subjects were recruited from the University of Michigan Breast Care Center. Statistical analyses Principal components factor analysis, one-way analyses of variance, and Pearson correlations and χ 2 tests were used to analyze taste and food preference data. Results Genetic responsiveness to PROP was associated with lower acceptance of cruciferous and selected green and raw vegetables ( P Applications/conclusions Women who are PROP tasters may be less likely to comply with dietary strategies for cancer prevention that emphasize consumption of cruciferous vegetables and bitter salad greens. Alternatively, PROP-sensitive women may seek to reduce bitter taste by adding fat, sugar, or salt. J Am Diet Assoc. 2000; 100:191–197.

Recruitment of subjects is a critical aspect of prevention trials that is often overlooked by investigators. As a consequence, accrual time is often extended, workloads may become heavy, and resource utilization is increased in an effort to complete projects. Recruitment of healthy subjects in cancer prevention and control studies presents unique issues that need to be considered. The barriers to recruitment include participant issues, physician variables, features of the study design, and characteristics of the health care system in the United States. The authors provide their experience in overcoming these difficulties. J. Cell. Biochem. Suppl. 34:80-83, 2000. r 2000 Wiley-Liss, Inc.

Background: As we enter the year 2000, it is worth looking at whether primary care practices are reaching the goals established in Healthy People 2000 for breast, cervical, colorectal, and prostatic cancer screening. The objectives of this study were (1) to determine the current rates of cancer screening; and (2) to determine which factors predict completion of a single screening test, of all tests for each cancer, and of all procedures for age and sex. Methods: Medical records of 200 eligible patients (100 men and 100 women) from each of 24 community-based primary care practices were abstracted for cancer-screening events. Results: We audited 5125 charts. A Papanicolaou smear was documented for 63.8% of women with an intact cervix within 3 years of the audit .. We found that 46.8% of women had documentation of ever having a discussion of breast self-examination. For breast cancer screening, 41.8% of the women had a clinical breast examination within 1 year, 48.2% aged 40 to 49 years had a mammogram within 2 years, and 38.5% aged 50 years and older had a mammogram within 1 year. Only 29% of women aged 40 to 49 years and 17% of women 50 years and older were current for all breast cancer-screening tests. Among patients 50 years and older, 33% of men and 38% of women had a digital rectal examination within 1 year, 26% of men and 28% of women had a fecal occult blood test within 1 year, and 22% of men and 16.8% of women had a Oexible sigmoidoscopy within 5 years. Of all men 28.7% had a prostate-specific antigen test within 1 year. Completion of all tests relevant for age and sex were documented for 8.6% of women aged 40 to 49 years, 3% of women 50 years and older, and 5% of men 50 years and older. The single most Significant predictor of documented cancer screening was a health maintenance visit. Conclusions: This sample of primary care clinicians has not reached the goals set in Healthy People 2000 for cancer screening. Interventions aimed at increasing the percentage of patients who schedule a health maintenance visit could serve to increase cancer screening and help us reach goals set for the year 2010.

Prior studies suggest that 6-n-propylthiouracil (PROP) taste responsiveness is linked with reduced preferences for sweet and high-fat foods, lower adiposity, and favorable plasma lipid profiles. We hypothesize that women with more severe and persistent cervical intraepithelial neoplasia (CIN) have a greater sensitivity to PROP. To measure this, women with CIN II or III submitted a DNA blood sample and a food frequency questionnaire. Out of the samples tested, thirty- eight (47%) were classified as nontasters (AV) and 36 (44%) were classified as tasters (PA). There were no significant differences (p

Colon cancer is a major public health problem in many developed westernized countries, with an annual incidence in the United States of about 155,000 new cases. 157 Although there has been a trend toward a decrease in incidence and mortality of colon cancer owing to improvements in dietary habits (decreased fat and increased fiber), endoscopic screening, advances in surgical techniques and adjuvant therapies, colon cancer still constitutes about 15% of all types of cancer, with a significant mortality in its advanced stages. Prevention of colon cancer is possible at different levels that include primary (avoidance of harmful environmental carcinogens, that is, chemicals, viruses, radiation exposure), secondary (fecal occult blood testing and annual sigmoidoscopy as recommended by American Cancer Soci ety), and tertiary (dietary intervention and chemoprevention) methods of prevention. Such prevention can collectively reduce the incidence of colon cancer in the general population. This article reviews the current status of colorectal cancer chemoprevention and constructs a model for future chemoprevention strategies based on evidence from epidemiologic and preclinical studies on promising noncytotoxic drugs/micronutrients, molecular genetics of pathways of colon cancer development and the genetics of familial colorectal cancer syndromes, and human clinical trials on effects of chemopreventive drugs. In addition, recent insights into biomarker development and mechanisms of action of some of these putative chemopreventives are also reviewed.

Prevention of cancer is an important objective in health care management, and it is increasingly being recognized and accepted as a method for the eradication of cancer. Several different approaches to cure cancer in the advanced stages have met with limited success. The curative approaches are applicable mostly in the early stages, when tumors are confined to the organ of origin. Many solid tumors present at an advanced, incurable stage when systemic cytotoxic therapy is largely palliative, therefore, resources need to be directed to methods to prevent cancer. Prevention strategies include primary, secondary and tertiary approaches, and require recognition of early lesions, strict screening guidelines, avoidance of well-known carcinogens, and development of better molecular and genetic methods to identify subjects at high risk. Primary care physicians have a vital role in the successful implementation of community-based cancer prevention trials. Cancer is a disease of the human genome, and takes a long time to develop. The genome does not just disintegrate but rather it gets picked at from many stresses. Stresses can be molecular (weak spots in the genome) and environmental (e.g., free radicals and oxygen stress from diet). The role of cancer chemoprevention is to interrupt or slow this process and delay the onset of neoplastic transformation. 35,46,100 This article describes the rationale and scientific principles of cancer chemoprevention using a synthesis of published experimental and clinical studies in animal models and cancer-risk prone human subjects. This should provide primary care physicians with a basic foundation upon which to build and incorporate cancer chemoprevention into their practice as the published literature starts to expand rapidly in this area.

Populations at risk of vitamin A deficiency usually rely on dietary provitamin A carotenoids to meet vitamin A needs, yet bioavailability of these compounds is influenced by several factors as follows: location in the plant source, the presence of other influencing dietary components, and type and extent of processing. The purpose of this study was to examine the plasma beta-carotene response to raw vs. processed carrots and spinach. Subjects were eight healthy females aged 23-36 y who consumed approximately 9.3 mg beta-carotene daily from either raw or thermally processed and pureed vegetables in two 4-wk treatment periods in a crossover study. Plasma concentrations of total, all-trans-, and cis-beta-carotene and alpha-carotene were measured at base line and the end of each treatment period by using HPLC assays. Total and all-trans (but not cis) plasma beta-carotene concentrations were significantly greater than base-line concentrations in the processed feeding period (P < 0. 04) and tended to be greater in the raw feeding period (P = 0.08). Daily consumption of processed carrots and spinach over a 4-wk period produced an increase in plasma beta-carotene concentration that averaged three times that associated with consumption of the same amount of beta-carotene from these vegetables in the raw form (P = 0.09). Increased cis isomers provided in the processed vegetables did not result in significantly greater plasma cis-beta-carotene isomer concentrations. These results suggest that isomerization of beta-carotene by heat treatment does not negate the enhanced beta-carotene uptake associated with consuming commercially processed vegetables compared with raw vegetables.

Although preventive services are a cornerstone of primary care medicine, few currently used screening tests have been demonstrated to be beneficial. Insurance organizations, the media, public advocacy groups, and patient concerns often pressure physicians to provide screening tests of controversial value. Ethical analysis provides the basis for responding to screening requests in a responsible way. Physicians may use an evidence-based medicine strategy to approach controversial screening tests. When physicians educate patients on the relative benefits and harms of controversial screening tests, it is prudent to emphasize that a screening test can assure neither a disease-free nor a risk-free state. Such preventive ethics efforts could discourage against the use of controversial screening tests. Physicians may articulate the boundaries of their own professional integrity in this process, for patients cannot compel physicians to render services that run counter to their best professional and ethical judgment.

Background A variety of studies have supported the finding that regular intake of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents can affect colorectal cancer carcinogenesis. These agents inhibit the synthesis of prostaglandins. High levels of prostaglandins are observed in colon cancer tissues. Purpose Experiments were planned to determine the lowest dose of aspirin that can markedly suppress the levels of mucosal prostaglandins E2 and F(2alpha) in colorectal mucosa and to determine whether a relationship exists between these levels and plasma levels of both acetylsalicylic acid and its metabolite, salicylic acid. Methods Healthy men and women aged 18 years or older participated in the study. The participants took a single, daily dose of aspirin (40.5, 81, 162, 324, or 648 mg) or a placebo for 14 days. Colorectal biopsy specimens were taken at baseline, 24 hours after the first dose of aspirin, and 24-30 hours and 72-78 hours after the last, i.e., fourteenth, daily dose of aspirin. The biopsy specimens were assayed for prostaglandins E2 and F(2alpha) by use of a competitive enzyme immunoassay. Plasma concentrations of acetylsalicylic acid and salicylic acid were determined by use of high-performance liquid chromatography. All P values are two-sided. Results A total of 65 subjects (10 receiving placebo, groups of 10 each receiving 40.5, 81, 162, or 324 mg of aspirin, and a group of 15 receiving 648 mg of aspirin) completed the protocol. One subject reported unacceptable drug-induced toxic effects and did not complete the protocol; other subjects reported acceptable side effects. The lowest dose to significantly suppress colorectal mucosal prostaglandin E2 concentrations from baseline at 24 hours after the first dose (by 22.6%; P = .002) and at 24-30 hours after the last dose (by 14.2%; P = .021) was 162 mg. At 72-78 hours after the last dose, there was significant suppression for subjects receiving 81 mg (by 23.7%; P = .008). The lowest dose to significantly suppress colorectal mucosal prostaglandin F(2alpha) concentrations from baseline at 24 hours after the first dose (by 18.3%; P = .032) was 324 mg. The lowest dose causing a marked reduction in the level of prostaglandin F(2alpha) at 24-30 hours (by 15.1%; P = .003) and 72-78 hours (by 23.0%; P = .0002) after the last dose was 40.5 mg. No detectable amounts of acetylsalicylic acid or salicylic acid were present in the plasma at any of the biopsy time points. Conclusions The lowest doses of aspirin taken daily for 14 days to significantly suppress concentrations of colorectal mucosal prostaglandins E2 and F(2alpha) were 81 and 40.5 mg, respectively. The suppression occurred without detectable amounts of aspirin or salicylic acid in the plasma at the time points studied. On the basis of these observations, we recommend a single, daily dose of 81 mg of aspirin in future studies of this drug as a chemopreventive agent for colorectal cancer.

We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE2 and PGF2α and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas > 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation. J. Cell. Biochem. Suppls. 28/29:148–158. Published 1998 Wiley-Liss, Inc.11

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-hydroxy-eicosatetraenoic 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.

We describe a label-free relative quantification LC-MS/MS method for core-fucosylation in alpha-2-macroglobulin (A2MG) immunoprecipitated from human sera. The method utilizes endoglycosidase F partial deglycosylation to reduce glycosylation microheterogeneity, while retaining the innermost N-acetylglucosamine (GlcNAc) and core fucose. Precursor ion peak areas of partially deglycosylated peptides were obtained and site-specific core-fucosylation ratios based on the peak areas of core-fucosylated and nonfucosylated counterparts were calculated and evaluated for assay development. This assay was applied in a preliminary study of sera samples from normal controls and patients with pancreatic diseases, including pancreatic cancer and chronic pancreatitis. A2MG fucosylation levels at sites N396 and N1424 were found to decrease in both chronic pancreatitis and pancreatic cancer compared to normal controls. The two sites were identified by two peptides and their core-fucosylation ratios were found to be internally consistent. This method provides a platform to quantify fucosylation levels and can be used to study site-specific core-fucosylation aberrations in other glycoproteins for other diseases.

Purpose: The purpose of this study was to assess ordering of human papillomavirus (HPV) testing for normal cervical cytology among low-risk women aged 30 to 65 years. Methods: Audits of 833 cytology request forms for low-risk women completing a Papanicolaou smear, from January 2008 to April 2011, from 5 Michigan family medicine clinics determined HPV orders completed by the clinician performing the Papanicolaou smear. Multivariate logistic regression models examined differences in HPV test ordering by patient age at Papanicolaou test, provider status and sex, and clinic across sites. A Poisson regression model analyzed the annual number of HPV test orders over time. Results: Cytology requests were completed by 622 faculty (75%), 169 residents/fellows (20%), and 42 nurse practitioner/physician assistants (NP/PAs) (5%). HPV testing for any cytology result was ordered on 324 request forms (39%) by residents/fellows (48%), faculty (38%), and NP/PAs (10%). Female providers were twice as likely as men to order HPV testing for any cytology result across all clinics and provider statuses (P < .001). There were significant differences in HPV test ordering among clinics. Between 2008 and 2011 annual cytology requests increased 46%, including HPV testing for any cytology result after adjusting for faculty provider sex. Conclusion: HPV test ordering when cytology is collected varied by clinic and provider status and sex. HPV co-testing for any cytology result remains modest, but is increasing over time in these clinics. (J Am Board Fam Med 2013;26:720‐727.)

Background There has been little research published on the adaptation of diabetic exchange list diet approaches for the design of intervention diets in health research despite their clinical utility. The exchange list approach can provide clear and precise guidance on multiple dietary changes simultaneously. The present study aimed to develop exchange list diets for Mediterranean and Healthy Eating, and to evaluate adherence, dietary intakes and markers of health risks with each counselling approach in 120 subjects at increased risk for developing colon cancer. Methods A randomised clinical trial was implemented in the USA involving telephone counselling. The Mediterranean diet had 10 dietary goals targeting increases in mono-unsaturated fats, n-3 fats, whole grains and the amount and variety of fruits and vegetables. The Healthy Eating diet had five dietary goals that were based on the US Healthy People 2010 recommendations. Results Dietary compliance was similar in both diet arms, with 82–88% of goals being met at 6 months, although subjects took more time to achieve the Mediterranean goals than the Healthy Eating goals. The relatively modest fruit and vegetable goals in the Healthy Eating arm were exceeded, resulting in fruit and vegetable intakes of approximately eight servings per day in each arm after 6 months. A significant (P

Table 1 was incorrectly a duplicate of Table 3. The correct version of Table 1 is available here

Elevated tissue levels of prostaglandin E2, produced by cyclooxygenase (COX), are an early event in colorectal cancer (CRC). Data suggest the efficacy of nonsteroidal anti-inflammatory drugs, such as cancer preventives, in the inhibition of COX activity; however, side effects of nonsteroidal anti-inflammatory pose unacceptable limitations. Ginger has been reported to have anti-inflammatory activities with significant CRC preventive potential. We investigated whether consumption of 2.0 g ginger daily regulated the level of two key enzymes that control prostaglandin E2 production, COX-1 and NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). Thirty participants at normal and 20 participants at increased risk for CRC were randomized and given 2.0 g/day ginger or placebo for 28 days. Flexible sigmoidoscopy was used to obtain colon biopsies at baseline and the end of the study. Tissue levels of COX-1 and 15-PGDH were assessed using western blotting. After ginger consumption, participants at increased risk for CRC had a significantly reduced colonic COX-1 protein level (23.8±41%) compared with the placebo group (18.9±52%; P=0.03). Protein levels of 15-PGDH in the colon were unchanged. In participants who were at normal risk for CRC, neither protein levels of COX-1 nor 15-PGDH in the colon were altered by ginger consumption. Ginger significantly lowered COX-1 protein expression in participants at increased risk for CRC but not in those at normal risk for CRC. Ginger did not alter 15-PGDH protein expression in either increased or normal-risk participants. Further investigation, in larger studies with a longer ginger intervention, is needed to examine the ability of ginger to impact tissue levels of prostaglandin.

Background: Information is lacking about the capacity of those working in community practice settings to utilize health information technology for colorectal cancer screening. Objective: To address this gap we asked those working in community practice settings to share their perspectives about how the implementation of a Web-based patient-led decision aid might affect patient-clinician conversations about colorectal cancer screening and the day-to-day clinical workflow. Methods: Five focus groups in five community practice settings were conducted with 8 physicians, 1 physician assistant, and 18 clinic staff. Focus groups were organized using a semistructured discussion guide designed to identify factors that mediate and impede the use of a Web-based decision aid intended to clarify patient preferences for colorectal cancer screening and to trigger shared decision making during the clinical encounter. Results: All physicians, the physician assistant, and 8 of the 18 clinic staff were active participants in the focus groups. Clinician and staff participants from each setting reported a belief that the Web-based patient-led decision aid could be an informative and educational tool; in all but one setting participants reported a readiness to recommend the tool to patients. The exception related to clinicians from one clinic who described a preference for patients having fewer screening choices, noting that a colonoscopy was the preferred screening modality for patients in their clinic. Perceived barriers to utilizing the Web-based decision aid included patients’ lack of Internet access or low computer literacy, and potential impediments to the clinics’ daily workflow. Expanding patients’ use of an online decision aid that is both easy to access and understand and that is utilized by patients outside of the office visit was described as a potentially efficient means for soliciting patients’ screening preferences. Participants described that a system to link the online decision aid to a computerized reminder system could promote a better understanding of patients’ screening preferences, though some expressed concern that such a system could be difficult to keep up and running. Conclusions: Community practice clinicians and staff perceived the Web-based decision aid technology as promising but raised questions as to how the technology and resultant information would be integrated into their daily practice workflow. Additional research investigating how to best implement online decision aids should be conducted prior to the widespread adoption of such technology so as to maximize the benefits of the technology while minimizing workflow disruptions. [J Med Internet Res 2013;15(12):e286]

We describe a label-free relative quantification LC-MS/MS method for core-fucosylation in alpha-2-macroglobulin (A2MG) immunoprecipitated from human sera. The method utilizes endoglycosidase F partial deglycosylation to reduce glycosylation microheterogeneity, while retaining the innermost N-acetylglucosamine (GlcNAc) and core fucose. Precursor ion peak areas of partially deglycosylated peptides were obtained and site-specific core-fucosylation ratios based on the peak areas of core-fucosylated and nonfucosylated counterparts were calculated and evaluated for assay development. This assay was applied in a preliminary study of sera samples from normal controls and patients with pancreatic diseases, including pancreatic cancer and chronic pancreatitis. A2MG fucosylation levels at sites N396 and N1424 were found to decrease in both chronic pancreatitis and pancreatic cancer compared to normal controls. The two sites were identified by two peptides and their core-fucosylation ratios were found to be internally consistent. This method provides a platform to quantify fucosylation levels and can be used to study site-specific core-fucosylation aberrations in other glycoproteins for other diseases.