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Agenda: 2017 Community Engagement and Research Symposium

Fri, 03/03/2017 - 11:00am

Agenda for the 6th annual Community Engagement and Research Symposium, held Friday, March 3, 2017 at the University of Massachusetts Medical School, Worcester, MA.

Evaluating Factors Affecting Clinicians’ Knowledge on Contrast Media: Kenyan Experience

Fri, 02/17/2017 - 8:35am

Purpose: Our study aimed to establish exposure to and level of knowledge about contrast media among non-radiological clinicians and evaluate the contributory factors to the status.

Methods and Materials: A cross-sectional study was conducted between April and December 2015 through interviews using structured questionnaires. We recruited 197 non-radiological clinicians with experience in use of contrast media in their routine practice. They were of different cadres and years of experience, all working in a large referral hospital in Kenya. Levels of basic knowledge on contrast media were evaluated through a scoring system after each clinician responded to the questions provided. We also sought for training on contrast media among these clinicians and where applicable the source of the same recorded. Descriptive and inferential statistical methods were applied across the different clinicians’ subsets.

Results: Thirty-seven respondents representing 18.8% of the study sample had received formal training on contrast media. Mean knowledge score for all clinicians in this study was 14.6 translating to 14.1% of a set maximal theoretical score of 103 points. The standard deviation was 5.5. Analysis of variance (ANOVA) test for knowledge mean score among different cadres gave a P value 0.079. Unpaired t-test gave a two- tailed P value 0.2410 for mean score when trained and untrained clinicians were compared. The level of knowledge (mean score) when analysed against years of experience for the clinicians produced statistically significant results with P value 0.001084.

Conclusion: Training and knowledge on contrast media can be profoundly low for clinicians. However, there is a possibility of knowledge improving from experience in practice due to multidisciplinary interaction and the implied advantage of encapsulated knowledge.

Objectively Measured Physical Activity and Symptoms Change in Knee Osteoarthritis

Thu, 02/16/2017 - 3:05pm

OBJECTIVE: The study objective was to quantify the association between daily physical activity measured by accelerometer and 1-year changes in symptoms among people with knee osteoarthritis.

METHODS: Participants from the Osteoarthritis Initiative had knee radiographs and physical activity assessed using GT1M ActiGraph (Pensacola, FL) uniaxial accelerometers at the 48-month visit. Physical activity was calculated and categorized as tertiles of average daily minutes in light and moderate-to-vigorous activity. Outcomes were 1-year change in symptoms measured by Western Ontario and McMaster Universities scales, including pain, stiffness, and physical function. Adjusted multivariable linear models estimated the relationship between tertiles of light or moderate-to-vigorous physical activity and changes in knee symptoms.

RESULTS: Among 1059 participants (55% were women; mean age, 66 +/- 9 years), greater time in light activity was associated with a trend toward declined physical function (P = .01). Greater time in daily moderate-to-vigorous activity also was associated with declined physical function (P = .01) and increased pain (P = .08). None of these average changes in symptoms reached minimally important clinical differences. However, greater daily time in both activities was associated with a higher probability of worsening symptoms among persons with Kellgren-Lawrence grade 4 osteoarthritis.

CONCLUSIONS: Objectively measured daily activity was not associated with 1-year symptom improvements among community-dwelling adults with knee osteoarthritis. In those with advanced disease (Kellgren-Lawrence grade 4), greater daily minutes in physical activity were associated with worsening symptoms. How best to implement exercise regimens in persons with advanced knee osteoarthritis to reduce the deleterious impact on symptoms needs to be explored.

Speak Up! Addressing the Paradox Plaguing Patient-Centered Care

Thu, 02/16/2017 - 3:05pm

Beneath the patient-centered rhetoric that dominates health care lurks a major paradox: The language of patient-centered care is omnipresent, but the reality is falling short. Patients are bombarded with surveys, post-discharge calls, opportunities to share “compliments and concerns,” and requests to “speak up.” In actuality, patients' perceptions of care are often ignored and rarely translate into improvements. Two flaws underlie this paradox.

Inflammasome Complexes: Emerging Mechanisms and Effector Functions

Thu, 02/16/2017 - 3:05pm

Canonical activation of the inflammasome is critical to promote caspase-1-dependent maturation of the proinflammatory cytokines IL-1beta and IL-18, as well as to induce pyroptotic cell death in response to pathogens and endogenous danger signals. Recent discoveries, however, are beginning to unveil new components of the inflammasome machinery as well as the full spectrum of inflammasome functions, extending their influence beyond canonical functions to regulation of eicosanoid storm, autophagy, and metabolism. In addition, the receptor components of the inflammasome can also regulate diverse biological processes, such as cellular proliferation, gene transcription, and tumorigenesis, all of which are independent of their inflammasome complex-forming capabilities. Here, we review these recent advances that are shaping our understanding of the complex biology of the inflammasome and its constituents.

Improving Rates of Influenza Vaccination Through Electronic Health Record Portal Messages, Interactive Voice Recognition Calls and Patient-Enabled Electronic Health Record Updates: Protocol for a Randomized Controlled Trial

Thu, 02/16/2017 - 3:04pm

BACKGROUND: Clinical decision support (CDS), including computerized reminders for providers and patients, can improve health outcomes. CDS promoting influenza vaccination, delivered directly to patients via an electronic health record (EHR) patient portal and interactive voice recognition (IVR) calls, offers an innovative approach to improving patient care.

OBJECTIVE: To test the effectiveness of an EHR patient portal and IVR outreach to improve rates of influenza vaccination in a large multispecialty group practice in central Massachusetts.

METHODS: We describe a nonblinded, randomized controlled trial of EHR patient portal messages and IVR calls designed to promote influenza vaccination. In our preparatory phase, we conducted qualitative interviews with patients, providers, and staff to inform development of EHR portal messages with embedded questionnaires and IVR call scripts. We also provided practice-wide education on influenza vaccines to all physicians and staff members, including information on existing vaccine-specific EHR CDS. Outreach will target adult patients who remain unvaccinated for more than 2 months after the start of the influenza season. Using computer-generated randomization and a factorial design, we will assign 20,000 patients who are active users of electronic patient portals to one of the 4 study arms: (1) receipt of a portal message promoting influenza vaccines and offering online appointment scheduling; (2) receipt of an IVR call with similar content but without appointment facilitation; (3) both (1) and (2); or (4) neither (1) nor (2) (usual care). We will randomize patients without electronic portals (10,000 patients) to (1) receipt of IVR call or (2) usual care. Both portal messages and IVR calls promote influenza vaccine completion. Our primary outcome is percentage of eligible patients with influenza vaccines administered at our group practice during the 2014-15 influenza season. Both outreach methods also solicit patient self-report on influenza vaccinations completed outside the clinic or on barriers to influenza vaccination. Self-reported data from both outreach modes will be uploaded into the EHR to increase accuracy of existing provider-directed EHR CDS (vaccine alerts).

RESULTS: With our proposed sample size and using a factorial design, power calculations using baseline vaccination rate estimates indicated that 4286 participants per arm would give 80% power to detect a 3% improvement in influenza vaccination rates between groups (alpha=.05; 2-sided). Intention-to-treat unadjusted chi-square analyses will be performed to assess the impact of portal messages, either alone or in combination with the IVR call, on influenza vaccination rates. The project was funded in January 2014. Patient enrollment for the project described here completed in December 2014. Data analysis is currently under way and first results are expected to be submitted for publication in 2016.

CONCLUSIONS: If successful, this study's intervention may be adapted by other large health care organizations to increase vaccination rates among their eligible patients.

CLINICALTRIAL: ClinicalTrials.gov NCT02266277; https://clinicaltrials.gov/ct2/show/NCT02266277 (Archived by WebCite at http://www.webcitation.org/6fbLviHLH).

Association between body composition and hip fractures in older women with physical frailty

Thu, 02/16/2017 - 3:04pm

AIM: We sought to determine the extent to which higher lean and fat mass as measured by dual X-ray absorptiometry in older adults with frailty are related to total hip bone mass density (BMD) index and the rate of hip fractures.

METHODS: The data are from the Women's Health Initiative Observational Study. We identified 872 participants aged > /=65 years with body composition measures and positive frailty. Frailty was determined using modified Fried's criteria. Linear and Cox regressions were used to model study outcomes.

RESULTS: During the follow-up period, 5.6% patients (n = 49) had sustained a hip fracture. Body composition indexes were associated with total hip BMD (P < 0.001 for all). In models adjusted for age, ethnicity, smoking, history of fractures, recurrent falls, number of frailty criteria and corresponding lean mass, the hazard ratio for hip fracture per 1 kg/m2 increase in fat mass was 0.73 (95% confidence interval 0.60-0.88) for appendicular compartment, 0.76 (95% confidence interval 0.65-0.89) for trunk and 0.84 (95% confidence interval 0.77-0.93) for whole-body fat mass. The hazard ratio for hip fracture per 1 kg/m2 increase in appendicular lean mass was 0.63 (95% confidence interval 0.46-0.88). However, after final adjustment for total hip BMD, the only index that remained statistically significant was whole-body fat mass (P for trend = 0.04).

CONCLUSIONS: We showed that in frail older women, higher fat and lean mass was associated with reduced hip-fracture rates. Higher whole-body adiposity, however, was also associated with lower hip-fracture rate independent of total hip BMD. The present results confirm the importance of weight maintenance in frail populations.

Predictors of the Onset of Cigarette Smoking: A Systematic Review of Longitudinal Population-Based Studies in Youth

Thu, 02/16/2017 - 3:04pm

CONTEXT: The onset of cigarette smoking typically occurs during childhood or early adolescence. Nicotine dependence symptoms can manifest soon after onset, contributing to sustained, long-term smoking. Previous reviews have not clarified the determinants of onset.

EVIDENCE ACQUISITION: In 2015, a systematic review of the literature in PubMed and EMBASE was undertaken to identify peer-reviewed prospective longitudinal studies published between January 1984 and August 2015 that investigated predictors of cigarette smoking onset among youth aged < 18 years who had never smoked.

EVIDENCE SYNTHESIS: Ninety-eight conceptually different potential predictors were identified in 53 studies. An increased risk of smoking onset was consistently (i.e., in four or more studies) associated with increased age/grade, lower SES, poor academic performance, sensation seeking or rebelliousness, intention to smoke in the future, receptivity to tobacco promotion efforts, susceptibility to smoking, family members' smoking, having friends who smoke, and exposure to films, whereas higher self-esteem and high parental monitoring/supervision of the child appeared to protect against smoking onset. Methodologic weaknesses were identified in numerous studies, including failure to account for attrition or for clustering in samples, and misidentification of potential confounders, which may have led to biased estimates of associations.

CONCLUSIONS: Predictors of smoking onset for which there is robust evidence should be considered in the design of interventions to prevent first puff in order to optimize their effectiveness. Future research should seek to define onset clearly as the transition from never use to first use (e.g., first few puffs).

Use of selective serotonin reuptake inhibitors (SSRIs) in women delivering liveborn infants and other women of child-bearing age within the U.S. Food and Drug Administration's Mini-Sentinel program

Thu, 02/16/2017 - 3:04pm

This study was conducted in order to assess the prevalence of use of selective serotonin reuptake inhibitors (SSRIs) among pregnant women delivering a liveborn infant in the USA. A retrospective study was conducted using the automated databases of 15 health-care systems participating in the Mini-Sentinel program. Diagnosis and procedure codes were used to identify women ages 10 to 54 years delivering a liveborn infant between April 2001 and December 2013. A comparison group of age- and date-matched women without live births was identified. The frequency of use of SSRIs was identified from outpatient dispensing data. Among the 1,895,519 liveborn deliveries, 113,689 women (6.0 %) were exposed to an SSRI during pregnancy during the period 2001-2013; 5.4 % were exposed to an SSRI during 2013. During the corresponding time period, 10.5 % of the age- and date-matched cohort of women without live births was exposed to an SSRI, with 10.1 % exposed to an SSRI during 2013. The most common agents dispensed during pregnancy were sertraline (n = 48,678), fluoxetine (n = 28,983), and citalopram (n = 20,591). Among those women exposed to an SSRI during pregnancy, 53.8 % had a diagnosis of depression and 37.3 % had a diagnosis of an anxiety disorder during pregnancy or within 180 days prior to pregnancy. Our finding that 6 % of women with live births were prescribed SSRIs during pregnancy highlights the importance of understanding the differential effects of these medications and other therapeutic options on the developing fetus and on the pregnant women.

Identification and Characteristics of Low-Risk Survivors of an Acute Myocardial Infarction

Thu, 02/16/2017 - 3:04pm

There are limited contemporary data available describing the characteristics of patients who neither died nor were readmitted to the hospital during the first year after hospital discharge for an acute myocardial infarction (AMI) in comparison with those who died and/or were readmitted to the hospital during this high-risk period. Residents of the Worcester, Massachusetts, metropolitan area discharged after an AMI from 3 central Massachusetts hospitals on a biennial basis from 2001 to 2011 comprised the study population. The average age of this population (n = 4,268) was 69 years, 62% were men, and 92% were white. From 2001 to 2011, 43.5% of patients were classified as low-risk survivors of an AMI, 12.3% died, and 44.2% did not die but had at least 1 rehospitalization during the subsequent year. The proportion of low-risk survivors increased from 42.6% to 46.4%, whereas the proportion of those who died within a year after hospital discharge decreased from 14.3% to 10.5%, respectively, during the years under study. After adjusting for several patient characteristics, younger ( < /=65 years) persons, men, those who were married, those who did not present with multimorbidities, and patients who did not develop in-hospital clinical complications were more likely to be classified as a low-risk AMI survivor. Identifying low-risk survivors of an AMI may help health care providers to focus more intensive efforts and interventions on those at higher risk for dying and/or being readmitted to the hospital during the postdischarge transition period after an AMI.

Neighborhood Walkability and Adiposity in the Women's Health Initiative Cohort

Thu, 02/16/2017 - 3:04pm

INTRODUCTION: Neighborhood environments may play a role in the rising prevalence of obesity among older adults. However, research on built environmental correlates of obesity in this age group is limited. The current study aimed to explore associations of Walk Score, a validated measure of neighborhood walkability, with BMI and waist circumference in a large, diverse sample of older women.

METHODS: This study linked cross-sectional data on 6,526 older postmenopausal women from the Women's Health Initiative Long Life Study (2012-2013) to Walk Scores for each participant's address (collected in 2012). Linear and logistic regression models were used to estimate associations of BMI and waist circumference with continuous and categorical Walk Score measures. Secondary analyses examined whether these relationships could be explained by walking expenditure or total physical activity. All analyses were conducted in 2015.

RESULTS: Higher Walk Score was not associated with BMI or overall obesity after adjustment for sociodemographic, medical, and lifestyle factors. However, participants in highly walkable areas had significantly lower odds of abdominal obesity (waist circumference >88 cm) as compared with those in less walkable locations. Observed associations between walkability and adiposity were partly explained by walking expenditure.

CONCLUSIONS: Findings suggest that neighborhood walkability is linked to abdominal adiposity, as measured by waist circumference, among older women and provide support for future longitudinal research on associations between Walk Score and adiposity in this population.

Effects of Obstetric Complications on Adolescent Postpartum Contraception and Rapid Repeat Pregnancy

Thu, 02/16/2017 - 3:04pm

STUDY OBJECTIVE: To determine whether complications during pregnancy or at delivery influence postpartum contraception choices and rapid repeat pregnancy rates in adolescent women.

DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This retrospective cohort study included 321 adolescents delivering at UMASS Memorial Healthcare. Complications during pregnancy and delivery along with subsequent contraception use were investigated. Postpartum contraception choice (long-acting reversible contraception [LARC] vs non-LARC) at either delivery, hospitalization discharge, or at postpartum outpatient appointment, and rapid repeat pregnancy rate (pregnancy confirmed within 12 months of index delivery), were analyzed according to pregnancy complications. Comparisons were made with chi2 and Fisher exact tests for categorical variables, and with Wilcoxon rank sum test for continuous variables.

RESULTS: Of the study population, 27.7% (n = 89/321) used LARC in the postpartum period. The LARC and non-LARC patient populations differed significantly regarding history of abortion (P = .029), with no differences in obstetric complications between the groups. Of the population, 16.6% (n = 53/320) became pregnant again within 1 year of their index delivery. Those with a rapid repeat pregnancy had significantly increased gravidity (P = .002), parity (P = .003), number of previous spontaneous or therapeutic abortions (P = .026); they were also more like to have nonlive birth as a complication (P = .028), compared with those without repeat pregnancy. No other obstetrical complications were statistically significantly different between the compared groups.

CONCLUSION: Obstetrical complications seem to have little effect on postpartum contraception choice or repeat pregnancy rate with the notable exception of nonlive birth being associated with rapid repeat pregnancy.

Deciphering the Structure and Function of Nuclear Pores Using Single-Molecule Fluorescence Approaches

Thu, 02/16/2017 - 3:04pm

Due to its central role in macromolecular trafficking and nucleocytoplasmic information transfer, the nuclear pore complex (NPC) has been studied in great detail using a wide spectrum of methods. Consequently, many aspects of its architecture, general function, and role in the life cycle of a cell are well understood. Over the last decade, fluorescence microscopy methods have enabled the real-time visualization of single molecules interacting with and transiting through the NPC, allowing novel questions to be examined with nanometer precision. While initial single-molecule studies focused primarily on import pathways using permeabilized cells, it has recently proven feasible to investigate the export of mRNAs in living cells. Single-molecule assays can address questions that are difficult or impossible to answer by other means, yet the complexity of nucleocytoplasmic transport requires that interpretation be based on a firm genetic, biochemical, and structural foundation. Moreover, conceptually simple single-molecule experiments remain technically challenging, particularly with regard to signal intensity, signal-to-noise ratio, and the analysis of noise, stochasticity, and precision. We discuss nuclear transport issues recently addressed by single-molecule microscopy, evaluate the limits of existing assays and data, and identify open questions for future studies. We expect that single-molecule fluorescence approaches will continue to be applied to outstanding nucleocytoplasmic transport questions, and that the approaches developed for NPC studies are extendable to additional complex systems and pathways within cells.

Biochemical and biomechanical drivers of cancer cell metastasis, drug response and nanomedicine

Thu, 02/16/2017 - 3:04pm

Metastasis, drug resistance and recurrence in cancer are regulated by the tumor microenvironment. This review describes recent advances in understanding how cancer cells respond to extracellular environmental cues via integrins, how to build engineered microenvironments to study these interactions in vitro and how nanomaterials can be used to detect and target tumor microenvironments.

Atrial Fibrillation Is Associated With a Worse 90-Day Outcome Than Other Cardioembolic Stroke Subtypes

Thu, 02/16/2017 - 3:04pm

BACKGROUND AND PURPOSE: Patients with a cardioembolic stroke (CES) have worse outcomes than stroke patients with other causes of stroke. Among patients with CES, atrial fibrillation (AF) is a common comorbidity. Mounting data indicate that AF may be related to stroke pathogenesis beyond acute cerebral thromboembolism. We sought to determine whether AF represents an independent risk factor for stroke severity and outcome among patients with CES.

METHODS: We retrospectively analyzed patients with acute hemispheric CES included in an academic medical center's stroke registry. CES was determined using the Causative Classification System of ischemic stroke. Multivariable logistic regression was used to determine whether AF was associated with 90-day outcome functional status.

RESULTS: Our cohort included 140 patients. Of these, 52 had prevalent AF and 28 had incident AF diagnosed during their index hospitalization or within 90 days of hospital discharge. After adjustment for potential confounders or mediators, any AF (odds ratio, 2.51; 95% confidence interval, 1.03-6.33; P=0.049), infarct volume (odds ratio, 1.03; 95% confidence interval, 1.01-1.06; P=0.005), preadmission modified Rankin Scale score (odds ratio, 2.58; 95% confidence interval, 1.66-4.01; P < 0.001), and admission National Institutes of Health Stroke Scale score (odds ratio, 1.17; 95% confidence interval, 1.08-1.28; P < 0.001) remained associated with an unfavorable 90-day outcome (modified Rankin Scale score, 2-6).

CONCLUSIONS: AF is associated with an unfavorable 90-day outcome among patients with a CES independent of established risk factors and initial stroke severity. This suggests that AF-specific mechanisms affect CES severity and functional status after CES. If confirmed in future studies, further investigation into the underlying pathophysiological mechanisms may provide novel avenues to AF detection and treatment.

Multilevel Provider-Based Sampling for Recruitment of Pregnant Women and Mother-Newborn Dyads

Thu, 02/16/2017 - 3:04pm

OBJECTIVE: In 2010, the National Children's Study launched 3 alternative recruitment methods to test possible improvements in efficiency compared with traditional household-based recruitment and participant enrollment. In 2012, a fourth method, provider-based sampling (PBS), tested a probability-based sampling of prenatal provider locations supplemented by a second cohort of neonates born at a convenience sample of maternity hospitals.

METHODS: From a sampling frame of 472 prenatal care provider locations and 59 maternity hospitals, 49 provider and 7 hospital locations within or just outside 3 counties participated in study recruitment. During first prenatal care visits or immediately postdelivery at these locations, face-to-face contact was used to screen and recruit eligible women.

RESULTS: Of 1450 screened women, 1270 were eligible. Consent rates at prenatal provider locations (62%-74% by county) were similar to those at birth locations (64%-77% by county). During 6 field months, 3 study centers enrolled a total prenatal cohort of 530 women (the majority in the first trimester) and during 2 months enrolled a birth cohort of an additional 320 mother-newborn dyads. As personnel became experienced in the field, the time required to enroll a woman in the prenatal cohort declined from up to 200 hours to 50 to 100 hours per woman recruited.

CONCLUSIONS: We demonstrated that PBS was feasible and operationally efficient in recruiting a representative cohort of newborns from 3 diverse US counties. Our findings suggest that PBS is a practical approach to recruit large pregnancy and birth cohorts across the United States.

On Edge: the impact of race-related vigilance on obesity status in African-Americans

Thu, 02/16/2017 - 3:04pm

OBJECTIVE: Nearly half of African-Americans are classified as obese. Perceived racism has been associated with obesity, yet the internal experiences of racism have received little attention. African Americans who face racism may "ready themselves" to cope through survival strategies, including race-related vigilance. This study explores the association between race-related vigilance and obesity in African Americans.

DESIGN AND METHODS: The Reactions to Race module of the Behavioral Risk Factor Surveillance Survey (years 2002-2010) was used. Our sample size consisted of 12,214 African-Americans. Race-related vigilance was assessed as: "How often do you think about your race?" and classified as: never, < daily, daily, and > daily. Obesity was dichotomized as body mass index (BMI) > /=30 kg/m2 vs. < 30 kg/m2 using self-reported weight and height. Multivariable logistic models assessed the association between race-related vigilance and obesity.

RESULTS: Seventeen percent of respondents reported thinking about their race > daily; 14% daily; 31% < daily, and 39% reported never thinking about their race. Compared to those who reported never thinking about their race, the adjusted odds of obesity were 0.91, 95% CI: 0.72-1.15 among those thinking about their race < daily, 1.09, 95%CI: 0.81-1.46 among those thinking about their race daily, and 1.37, 95% CI: 1.07-1.76 among those thinking about their race > daily.

CONCLUSIONS: Frequently thinking about one's race was a risk factor for obesity in African-Americans in this study. Internalized impacts of racism captured through race-related vigilance may be particularly detrimental to African-Americans, driving their risk for obesity.

Book(s) Review: The Medical Library Association Guide to Data Management for Librarians and Data Management: A Practical Guide for Librarians

Wed, 02/15/2017 - 9:52am

Book reviews of:

The Medical Library Association Guide to Data Management for Librarians, edited by Lisa Federer, Rowman & Littlefield, Copyright 2016 by Medical Library Association ISBN 978-1-4422-6428-1

Data Management: A Practical Guide for Librarians, by Margaret E. Henderson, Rowman & Littlefield Publishers, 2017 ISBN 978-1-4422-6439-7.

A microRNA/Runx1/Runx2 network regulates prostate tumor progression from onset to adenocarcinoma in TRAMP mice

Wed, 02/15/2017 - 9:44am

While decades of research have identified molecular pathways inducing and promoting stages of prostate cancer malignancy, studies addressing dynamic changes of cancer-related regulatory factors in a prostate tumor progression model are limited. Using the TRAMP mouse model of human prostate cancer, we address mechanisms of deregulation for the cancer-associated transcription factors, Runx1 and Runx2 by identifying microRNAs with reciprocal expression changes at six time points during 33 weeks of tumorigenesis. We molecularly define transition stages from PIN lesions to hyperplasia/neoplasia and progression to adenocarcinoma by temporal changes in expression of human prostate cancer markers, including the androgen receptor and tumor suppressors, Nkx3.1 and PTEN. Concomitant activation of PTEN, AR, and Runx factors occurs at early stages. At late stages, PTEN and AR are downregulated, while Runx1 and Runx2 remain elevated. Loss of Runx-targeting microRNAs, miR-23b-5p, miR-139-5p, miR-205-5p, miR-221-3p, miR-375-3p, miR-382-5p, and miR-384-5p, contribute to aberrant Runx expression in prostate tumors. Our studies reveal a Runx/miRNA interaction axis centered on PTEN-PI3K-AKT signaling. This regulatory network translates to mechanistic understanding of prostate tumorigenesis that can be developed for diagnosis and directed therapy.

Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice

Wed, 02/15/2017 - 9:44am

OBJECTIVE: Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells.

DESIGN: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year.

RESULTS: Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 (p < 0.05 vs control) whereas expression of IFN-gamma and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3.

CONCLUSIONS: Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori-infected mice.