Twenty-five-Year Follow-up of Short-term Cancer Research Trainees at the University of Alabama at Birmingham: a Brief Report.

Long-term follow-up is needed to evaluate the impact of short-term cancer research programs on the career trajectories of medical and graduate students. Participation in these programs may be crucial in fostering the next generation of cancer research scientists. This report presents the career outcomes and research productivity of 77 medical and public health students with 25 years of tracking data following their participation in a summer cancer research training program at the University of Alabama at Birmingham (UAB) in 1990-1998. Of 64 summer trainees with contact information, complete survey responses were received from 55 (86.0%) individuals. Over half reported clinical care of cancer patients and 18.2% stated that they were engaged in cancer research. Literature searches confirmed that 23.4% (18/77) of trainees have published cancer research papers. Future studies should explore the optimal timing of short-term post-baccalaureate academic cancer training experiences to identify participant characteristics and institutional factors that influence career choices and determine research productivity.

Automated Literature Searches for Longitudinal Tracking of Cancer Research Training Program Graduates.

A key outcome measure of cancer research training programs is the number of cancer-related peer-reviewed publications after training. Because program graduates do not routinely report their publications, staff must periodically conduct electronic literature searches on each graduate. The purpose of this study is to compare findings of an innovative computer-based automated search program versus repeated manual literature searches to identify post-training peer-reviewed publications. In late 2014, manual searches for publications by former R25 students identified 232 cancer-related articles published by 112 of 543 program graduates. In 2016, a research assistant was instructed in performing Scopus literature searches for comparison with individual PubMed searches on our 543 program graduates. Through 2014, Scopus found 304 cancer publications, 220 of that had been retrieved manually plus an additional 84 papers. However, Scopus missed 12 publications found manually. Together, both methods found 316 publications. The automated method found 96.2 % of the 316 publications while individual searches found only 73.4 %. An automated search method such as using the Scopus database is a key tool for conducting comprehensive literature searches, but it must be supplemented with periodic manual searches to find the initial publications of program graduates. A time-saving feature of Scopus is the periodic automatic alerts of new publications. Although a training period is needed and initial costs can be high, an automated search method is worthwhile due to its high sensitivity and efficiency in the long term.

Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer.

BACKGROUND: Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight and obese men with prostate cancer. METHODS: This single-blinded, two-arm randomised controlled trial explored outcomes of a presurgical weight loss intervention (WLI) that promoted ∼1 kg per week loss via caloric restriction and increased physical activity (PA). Forty overweight/obese men with clinically confirmed prostate cancer were randomised to the WLI presurgery or to a control arm; changes in weight, body composition, quality-of-life, circulating biomarkers, gene expression, and immunohistochemical markers in tumour and benign prostatic tissue were evaluated. RESULTS: The study period averaged 50 days. Mean (s.d.) change scores for the WLI vs control arms were as follows: weight: -4.7 (3.1) kg vs -2.2 (4.4) kg (P=0.0508); caloric intake: -500 (636) vs -159 (600) kcal per day (P=0.0034); PA: +0.9 (3.1) vs +1.7 (4.6) MET-hours per day (NS); vitality: +5.3 (7.l4) vs -1.8 (8.1) (P=0.0491); testosterone: +55.1 (86.0) vs -48.3 (203.7) ng dl-1 (P=0.0418); sex hormone-binding globulin: +14.0 (14.6) vs +1.8 (7.6) nmol l-1 (P=0.0023); and leptin: -2.16 (2.6) vs -0.03 (3.75) (P=0.0355). Follow-up Ki67 was significantly higher in WLI vs control arms; median (interquartile range): 5.0 (2.5,10.0) vs 0.0 (0.0,2.5) (P=0.0061) and several genes were upregulated, for example, CTSL, GSK3B, MED12, and LAMC2. CONCLUSIONS: Intentional weight loss shows mixed effects on circulating biomarkers, tumour gene expression, and proliferative markers. More study is needed before recommending weight loss, in particular rapid weight loss, among men with prostate cancer.

Disparities in Cancer Survivorship Indicators in the Deep South Based on BRFSS Data: Recommendations for Survivorship Care Plans.

OBJECTIVES: The purpose of this investigation was to describe cancer survivorship based on the Behavioral Risk Factor Surveillance System (BRFSS) cancer survivorship modules in Alabama, Georgia, and Mississippi, conducted in 2012 and 2014, and to investigate disparities across the US Deep South region. METHODS: The optional BRFSS cancer survivorship module was introduced in 2009. Data from Alabama (2012), Georgia (2012), and Mississippi (2014) were assessed. Demographic factors were analyzed through weighted regression for risk of receiving cancer treatment summary information and follow-up care. RESULTS: Excluding nonmelanoma skin cancer cases, a total of 1105 adults in the Alabama 2012 survey, 571 adults in the Georgia 2012 survey, and 442 adults in the 2014 Mississippi survey reported ever having cancer and were available for analysis. Among Alabamians, those with a higher level of education (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.7) and higher income (OR 1.3, 95% CI 1.1-1.6) were more likely to receive a written summary of their cancer treatments. Adults older than age 65 were only half as likely to receive a written summary of cancer treatments compared with adults 65 years or younger (OR 0.5, 95% CI 0.3-0.8). We found no significant differences in receipt of treatment summary by race or sex. Among those who reported receiving instructions from a doctor for follow-up care, these survivors tended to have a higher level of education, higher income, and were younger (younger than 65 years). Receipt of written or printed follow-up care was positively associated with higher income (OR 1.4, 95% CI 1.1-1.8) and inversely associated with age older than 65 years (OR 0.9, 95% CI 0.1-0.6) in Georgia. CONCLUSIONS: Addressing the gap identified between survivorship care plan development by the health team and the delivery of it to survivors is important given the evidence of disparities in the receipt of survivorship care plans across survivor age and socioeconomic status in the Deep South.

Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.

BACKGROUND: Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS: We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFß, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFß, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS: The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS: Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION: NCT01886677.

An Evaluation Methodology for Longitudinal Studies of Short-Term Cancer Research Training Programs.

The need to familiarize medical students and graduate health professional students with research training opportunities that cultivate the appeal of research careers is vital to the future of research. Comprehensive evaluation of a cancer research training program can be achieved through longitudinal tracking of program alumni to assess the program's impact on each participant's career path and professional achievements. With advances in technology and smarter means of communication, effective ways to track alumni have changed. In order to collect data on the career outcomes and achievements of nearly 500 short-term cancer research training program alumni from 1999-2013, we sought to contact each alumnus to request completion of a survey instrument online, or by means of a telephone interview. The effectiveness of each contact method that we used was quantified according to ease of use and time required. The most reliable source of contact information for tracking alumni from the early years of the program was previous tracking results, and for alumni from the later years, the most important source of contact information was university alumni records that provided email addresses and telephone numbers. Personal contacts with former preceptors were sometimes helpful, as were generic search engines and people search engines. Social networking was of little value for most searches. Using information from two or more sources in combination was most effective in tracking alumni. These results provide insights and tools for other research training programs that wish to track their alumni for long-term program evaluation.

Career Outcomes of Graduates of R25E Short-Term Cancer Research Training Programs.

The efficacy of short-term cancer research educational programs in meeting its immediate goals and long-term cancer research career objectives has not been well studied. The purpose of this report is to describe the immediate impact on, and the long-term career outcomes of, 499 medical students and graduate students who completed the Cancer Research Experiences for Students (CaRES) program at the University of Alabama at Birmingham (UAB) from 1999 to 2013. In summer 2014, all 499 program alumni were located and 96.4 % (481 of 499) agreed to complete a longitudinal tracking survey. About 23 % of CaRES alumni (110 of 499) have published at least one cancer-related paper. Overall 238 cancer-related papers have been published by CaRES alumni, one third of this number being first-authored publications. Nearly 15 % (71 of 481 respondents) reported that their current professional activities include cancer research, primarily clinical research and outcomes research. Of these 71 individuals, 27 (38 %) have completed their training and 44 (62 %) remain in training. Of all respondents, 58 % reported that they administered care to cancer patients and 30 % reported other cancer-related professional responsibilities such as working with a health department or community group on cancer control activities. Of the 410 respondents not currently engaged in cancer research, 118 (29 %) stated intentions to conduct cancer research in the next few years. Nearly all respondents (99.6 %) recommended CaRES to today's students. Challenging short-term educational cancer research programs for medical students and graduate health professional students can help them refine and solidify their career plans, with many program alumni choosing cancer research careers.

Sustainability in a state comprehensive cancer control coalition: lessons learned.

The Alabama Comprehensive Cancer Control Coalition (ACCCC) has developed an integrated and coordinated approach to reducing cancer incidence, morbidity, and mortality, and to improving the quality of life for cancer survivors, their families, and their caregivers. The ACCCC is currently in a maintenance phase and a formal plan for sustainability of the coalition was needed to keep the members engaged and productive. A training session in coalition sustainability conducted in 2013 identified the following elements as essential to success: (1) increased marketing of the coalition by simplifying its mission; (2) improved networking including flexibility in coalition meeting location and attendance; (3) increased membership satisfaction through transformational leadership; (4) revision of the working structure of committees and improved accountability; and (5) enhancement of partner satisfaction with coalition activities designed to recruit and retain new partners. A self-administered membership satisfaction survey was given to assess coalition mission, meeting logistics, organization, capacity building, and coalition goals. Results indicated that the subcategories of communication, mission, and meeting logistics were rated satisfied to very satisfied on a five-point scale. Although the ACCCC had clearly written goals, improvement could be made in leadership participation and new member orientation could be improved. Most members rated their parent organization as highly involved with the ACCCC and many offered suggestions on capacity building. Results of the sustainability training have clarified the ACCCC's plans to ensure coalition viability and improve strategies to inform stakeholders of the benefits of participation in the coalition.

Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS.

OBJECTIVE: Diet-induced reduction in circulating insulin may be an attractive nonpharmacological treatment for women with polycystic ovary syndrome (PCOS) among whom elevated insulin may exacerbate symptoms by stimulating testosterone synthesis. This study was designed to determine whether a modest reduction in dietary carbohydrate (CHO) content affects ß-cell responsiveness, serum testosterone concentration and insulin sensitivity in women with PCOS. DESIGN: In a crossover design, two diets ('Standard,' STD, 55:18:27% energy from carbohydrate/protein/fat; lower-carbohydrate, 41:19:40) were provided for 8 weeks in random order with a 4-week washout between. PATIENTS: Thirty women with PCOS. MEASUREMENTS: ß-cell responsiveness assessed as the C-peptide response to glucose during a liquid meal test; insulin sensitivity from insulin and glucose values throughout the test; insulin resistance (HOMA-IR); and total testosterone by immunoassay. RESULTS: Paired t-test indicated that the lower-CHO diet induced significant decreases in basal ß-cell response (PhiB), fasting insulin, fasting glucose, HOMA-IR, total testosterone and all cholesterol measures, and significant increases in insulin sensitivity and dynamic ('first-phase') ß-cell response. The STD diet induced a decrease in HDL-C and an increase in the total cholesterol-to-HDL-C ratio. Across all data combined, the change in testosterone was positively associated with the changes in fasting insulin, PhiB and insulin AUC (P < 0·05). CONCLUSIONS: In women with PCOS, modest reduction in dietary CHO in the context of a weight-maintaining diet has numerous beneficial effects on the metabolic profile that may lead to a decrease in circulating testosterone.

Harvest for health gardening intervention feasibility study in cancer survivors.

BACKGROUND: Cancer survivors are at increased risk for second malignancies, cardiovascular disease, diabetes, and functional decline. Evidence suggests that a healthful diet and physical activity may reduce the risk of chronic disease and improve health in this population. METHODS: We conducted a feasibility study to evaluate a vegetable gardening intervention that paired 12 adult and child cancer survivors with Master Gardeners to explore effects on fruit and vegetable intake, physical activity, quality-of-life, and physical function. Throughout the year-long study period, the survivor-Master Gardener dyads worked together to plan/plant three gardens, harvest/rotate plantings, and troubleshoot/correct problems. Data on diet, physical activity, and quality-of-life were collected via surveys; anthropometrics and physical function were objectively measured. Acceptability of the intervention was assessed with a structured debriefing survey. RESULTS: The gardening intervention was feasible (robust enrollment; minimal attrition) and well-received by cancer survivors and Master Gardeners. Improvement in three of four objective measures of strength, agility, and endurance was observed in 90% of survivors, with the following change scores [median (interquartile range)] noted between baseline and one-year follow-up: hand grip test [+ 4.8 (3.0, 6.7) kg], 2.44 meter Get-Up-and-Go [+ 1.0 (+ 1.8, + 0.2) seconds], 30-second chair stand [+ 3.0 (+ 1.0, 5.0) stands], and six-minute walk [+ 11.6 (6.1, 48.8) meters]. Increases of ≥ 1 fruit and vegetable serving/day and ≥ 30 minutes/week of physical activity were observed in 40% and 60%, respectively. CONCLUSION: These preliminary results support the feasibility and acceptability of a mentored gardening intervention and suggest that it may offer a novel and promising strategy to improve fruit and vegetable consumption, physical activity, and physical function in cancer survivors. A larger randomized controlled trial is needed to confirm our results.

CD147 expression in advanced cutaneous squamous cell carcinoma.

BACKGROUND: CD147 is upregulated in multiple cancer types, but its expression in advanced cutaneous squamous cell carcinoma (SCC) is unknown. Our purpose was to evaluate the expression patterns of CD147 and related monocarboxylate transporters (MCT1, MCT4) to determine their correlation with survival. METHODS: This is a retrospective cohort study of patients with advanced stage cutaneous SCC of the head and neck who presented to a tertiary care center between 1998 and 2006 (n=50). CD147, MCT1 and MCT4 expression levels were assessed using immunofluorescence analysis of archived tumor samples and correlated with survival and clinicopathologic characteristics. RESULTS: The majority of patients (92%, n = 46) were diagnosed with stage III disease, with 46% (n = 23) having positive regional lymph node metastasis and 8% (n = 4) with distant metastasis. Primary malignancies had an overexpression of CD147 (78%; n = 35), MCT1 (23%; n = 10) and MCT4 (47%; n = 20). In addition, there was a significant relationship between the overexpression of CD147 and node positive disease (p = 0.048). Two- and five-year survival rates were 69 and 61%, respectively. There was a trend toward decreased survival in patients with overexpression of CD147 (p = 0.17), MCT1 (p = 0.11) and MCT4 (p = 0.15). CONCLUSION: CD147 may represent a biomarker or potential therapeutic target in advanced cutaneous SCC.

An achievement of professional, public, and patient education: the design and evaluation of a comprehensive cancer control plan for Alabama.

This Alabama statewide cancer control plan for 2011-2015 seeks to build on the successes of two previous 5-year plans while developing new objectives that address cancer disparities and cancer prevention over the entire lifespan. The approach to defining objectives for this Plan was systematic and sought input from all members of the Alabama Comprehensive Cancer Control Coalition (ACCCC). The Plan that was fashioned is based on input from academic medical centers, private physicians, government agencies, regulatory agencies, health societies, private citizens, and cancer survivors, all of whom are active Coalition members who exchange information, opinions, and knowledge from their respective points of view. The Plan could not have taken shape without the full input of health professionals, statisticians, graduate students, former patients, and concerned citizens; it is truly an example of the synergy of professional, public, and patient education.

Prevention of carcinogenesis and inhibition of breast cancer tumor burden by dietary stearate.

Previous studies have shown that stearate (C18:0), a dietary long-chain saturated fatty acid, inhibits breast cancer cell neoplastic progression; however, little is known about the mechanism modulating these processes. We demonstrate that stearate, at physiological concentrations, inhibits cell cycle progression in human breast cancer cells at both the G(1) and G(2) phases. Stearate also increases cell cycle inhibitor p21(CIP1/WAF1) and p27(KIP1) levels and concomitantly decreases cyclin-dependent kinase 2 (Cdk2) phosphorylation. Our data also show that stearate induces Ras- guanosine triphosphate formation and causes increased phosphorylation of extracellular signal-regulated kinase (pERK). The MEK1 inhibitor, PD98059, reversed stearate-induced p21(CIP1/WAF1) upregulation, but only partially restored stearate-induced dephosphorylation of Cdk2. The Ras/mitogen-activated protein kinase/ERK pathway has been linked to cell cycle regulation but generally in a positive way. Interestingly, we found that stearate inhibits both Rho activation and expression in vitro. In addition, constitutively active RhoC reversed stearate-induced upregulation of p27(KIP1), providing further evidence of Rho involvement. To test the effect of stearate in vivo, we used the N-Nitroso-N-methylurea rat breast cancer carcinogen model. We found that dietary stearate reduces the incidence of carcinogen-induced mammary cancer and reduces tumor burden. Importantly, mammary tumor cells from rats on a stearate diet had reduced expression of RhoA and B as well as total Rho compared with a low-fat diet. Overall, these data indicate that stearate inhibits breast cancer cell proliferation by inhibiting key check points in the cell cycle as well as Rho expression in vitro and in vivo and inhibits tumor burden and carcinogen-induced mammary cancer in vivo.

Tinidazole vs metronidazole for the treatment of bacterial vaginosis.

OBJECTIVE: The purpose of this study was to compare the efficacy of 2 different doses of tinidazole with metronidazole for the treatment of bacterial vaginosis and to compare the side effects of the drugs. STUDY DESIGN: Women were assigned randomly to receive metronidazole 500 mg twice daily, tinidazole 500 mg twice daily, or tinidazole 1 g twice, all for 7 days. Follow-up visits were conducted at days 14 and 28. RESULTS: Five hundred ninety-three women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at 1 month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have bacterial vaginosis at the follow-up visit. There were no significant differences in adverse events across treatment arms. CONCLUSION: There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens that were studied. In addition, there were no important differences in the side-effect profiles of metronidazole and tinidazole.

Greater Loss of Central Adiposity from Low-Carbohydrate versus Low-Fat Diet in Middle-Aged Adults with Overweight and Obesity.

The objective of this study is to determine whether middle-aged adults prescribed a low carbohydrate-high fat (LCHF) or low fat (LF) diet would have greater loss of central fat and to determine whether the insulin resistance (IR) affects intervention response. A total of 50 participants (52.3 ± 10.7 years old; 36.6 ± 7.4 kg/m2 BMI; 82% female) were prescribed either a LCHF diet (n = 32, carbohydrate: protein: fat of 5%:30%:65% without calorie restriction), or LF diet (n = 18, 63%:13-23%: 10-25% with calorie restriction of total energy expenditure-500 kcal) for 15 weeks. Central and regional body composition changes from dual-x-ray absorptiometry and serum measures were compared using paired t-tests and ANCOVA with paired contrasts. IR was defined as homeostatic model assessment (HOMA-IR) > 2.6. Compared to the LF group, the LCHF group lost more android (15.6 ± 11.2% vs. 8.3 ± 8.1%, p < 0.01) and visceral fat (18.5 ± 22.2% vs. 5.1 ± 15.8%, p < 0.05). Those with IR lost more android and visceral fat on the LCHF verses LF group (p < 0.05). Therefore, the clinical prescription to a LCHF diet may be an optimal strategy to reduce disease risk in middle-aged adults, particularly those with IR.

Gli1 promotes cell survival and is predictive of a poor outcome in ERalpha-negative breast cancer.

Gli1 is a transcription factor and oncogene with documented roles in the progression of several cancer types, including cancers of the skin and pancreas. The contribution of Gli1 to the progression of breast cancer is less established. In order to investigate the functional impact of Gli1 in breast cancer, expression of Gli1 and its contribution to cell growth was assessed in breast cancer cell lines. These in vitro results were compared to expression of Gli1, determined by immunohistochemistry, in 171 breast cancers. In these cancers, the association of Gli1 with expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR), ErbB2, p53, the rate of proliferation, and clinicopathologic parameters and outcome was assessed. Expression of Gli1 and ERalpha mRNA was strongly correlated in ERalpha-positive cell lines (r = 0.999). Treatment with estrogen increased expression of Gli1 in 2 of 3 ERalpha-positive cell lines; this increase was prevented by treatment with the ERalpha-specific antagonist MPP. Silencing of Gli1 by shRNA markedly reduced the survival of two ERalpha-negative cell lines, but caused only a modest reduction in ERalpha-positive cell lines. In breast cancer tissues, cancers with nuclear localization of Gli1 had a higher ERalpha (P=0.027) and lower p53 expression (P=0.017) than those without nuclear localization of Gli1. However, nuclear localization of Gli1 was predictive of a poorer cancer-specific survival in ERalpha-negative, including triple negative, cancers (P = 0.005), but not ERalpha-positive cancers. In conclusion, we demonstrate a positive association between expression of Gli1 and ERalpha; however, our data indicate a greater functional effect of Gli1 in ERalpha-negative cancers.

A randomized controlled trial of partner notification methods for prevention of trichomoniasis in women.

BACKGROUND: Trichomoniasis is associated with adverse pregnancy outcomes and increased risk for human immunodeficiency virus. Males are usually asymptomatic, and thus there is heavy reliance on partner notification for identifying infected male partners. The usual approach is partner referral but it is estimated that only a minority of men seek care. We conducted a randomized trial to compare the effectiveness of 3 methods of partner notification. METHODS: Women were randomized to self-referral of partners (PR), partner-delivered therapy (PDPT), or public health disease intervention (DIS) locating partners and delivering medication in the field, if needed. Test-of-cure visits were conducted at 5 to 9 days after enrollment. Repeat infections at 1 and 3 months of follow-up were the measure of effectiveness. RESULTS: A total of 484 women were randomized. Initial cure rates were 95.3%. At the 1- and 3-month follow-up visits, there was no significant difference in repeat infection rates when PDPT or DIS were compared to the reference of PR. However, when PDPT was compared to DIS or PR/DIS combined, at 1 month the PDPT group had a lower repeat infection rate (5.8 vs. 15% and 5.8 vs. 12.5%, respectively). Of these, 80% of women randomized to PDPT reported delivering medication and 89% thought it likely that partners took the medication. No serious adverse events were reported. CONCLUSIONS: PDPT for trichomoniasis was well accepted and safe in this study. Rates of repeat infection in women in this intervention were lower than those in the DIS arm and DIS/PR arm combined although when compared directly to PR there was no significant difference.

Aflatoxin B1 albumin adducts in plasma and aflatoxin M1 in urine are associated with plasma concentrations of vitamins A and E.

BACKGROUND: Although aflatoxin exposure has been associated with micronutrient deficiency in animals, there are few investigations on the effects of aflatoxin exposure on micronutrient metabolism in humans. OBJECTIVE: To examine the relationship between aflatoxin B1 (AFB1) albumin adducts (AF-ALB) in plasma and the aflatoxin M1 (AFM1) metabolite in urine and plasma concentrations of retinol (vitamin A) and alpha-tocopherol (vitamin E) in Ghanaians. METHODS: A cross-sectional study of 147 adult participants was conducted. Blood and urine samples were tested for aflatoxin and vitamins A and E levels. RESULTS: Multivariable analysis showed that participants with high AF-ALB (>or=0.80 pmol/mg albumin) had increased odds of having vitamin A deficiency compared to those with lower AF-ALB [Odds Ratio (OR)=2.61; CI=1.03-6.58; p=0.04]. Participants with high AF-ALB also showed increased odds of having vitamin E deficiency but this was not statistically significant (OR=2.4; CI=0.96-6.05; p=0.06). Conversely, those with higher AFM1 values had a statistically nonsignificant reduced odds of having vitamin A deficiency (OR=0.31; CI=0.09-1.02; p=0.05) and a statistically significant reduced odds of having vitamin E deficiency (OR=0.31; CI=0.10-0.97; p=0.04). Participants with high AF-ALB or high AFM1 (>or=437.95 pg/dL creatinine) were almost 6 times more likely to be hepatitis B virus surface antigen (HBsAg)-positive (OR=5.88; CI=1.71-20.14; p=0.005) and (OR=5.84; CI=1.15-29.54; p=0.03) respectively. CONCLUSIONS: These data indicate that aflatoxin may modify plasma micronutrient status. Thus, preventing aflatoxin exposure may reduce vitamin A and E deficiencies.

Mre11 inhibition by oncolytic adenovirus associates with autophagy and underlies synergy with ionizing radiation.

New treatment approaches are needed for hormone refractory prostate cancer. Oncolytic adenoviruses are promising anti-cancer agents, and their efficacy can be improved by combining with conventional therapies such as ionizing radiation. The aim of this study was to determine the timing of oncolytic adenovirus treatment with regard to radiation and study the mechanisms of synergy in combination treatment. Prostate cancer cells were infected with oncolytic adenoviruses, irradiated and synergy mechanisms were assessed. In vivo models of combination treatment were tested. Radiation and oncolytic viruses were synergistic when viral infection was scheduled 24 hr after irradiation. Combination of oncolytic adenovirus with radiotherapy significantly increased antitumor efficacy in vivo compared to either agent alone. Microarray analysis showed dysregulated pathways including cell cycle, mTOR and antigen processing pathways. Functional analysis showed that adenoviral infection was accompanied with degradation of proteins involved in DNA break repair. Mre11 was degraded for subsequent inactivation of Chk2-Thr68 in combination treated cells, while gammaH2AX-Ser139 was elevated implicating the persistence of DNA double strand breaks. Increased autophagocytosis was seen in combination treated cells. Combination treatment did not increase apoptosis or virus replication. The results provide evidence of the antitumor efficacy of combining oncolytic adenoviruses with irradiation as a therapeutic strategy for the treatment of prostate cancer. Further, these findings propose a molecular mechanism that may be important in radiation induced cell death, autophagy and viral cytopathic effect.