Poster Session

Below are the abstracts for posters presented at the 2016 UMass Center for Clinical and Translational Science Research Retreat.

View the Poster Session Program

2016
Friday, May 20th
12:30 PM

5-Hyroxymethylcytosine Immunohistochemical Staining Correlates with Overall Survival in Patients with Chronic Myelomonocytic Leukemia

William Selove, University of Massachusetts Medical School
Karen A. Dresser, University of Massachusetts Medical School
Benjamin Chen, University of Massachusetts Medical School

12:30 PM

Introduction Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm that has been associated with a number of genetic mutations, most commonly TET2 mutations in up to 50-60% of cases. Mutations in epigenetic genes such as TET2 are known to disrupt the conversion of 5-methycytosine to 5-hydroxymethylcytosine (5hmC), contributing to oncogenesis. We hypothesized that CMML cases would exhibit decreased 5hmC expression, reflecting the propensity for TET2 mutations in CMML. We also sought to determine whether 5hmC IHC status reflected disease severity in terms of progression to AML and overall patient survival.

Methods Thirty-five cases of CMML from between 1/2006 and 12/2014 were identified from the pathology archives at UMass, under an IRB-approved protocol. IHC was performed on FFPE bone marrow biopsy specimens with an anti-5hmC antibody. Staining was scored based on intensity of nuclear staining: 0 (neg) to 3+ (strong); and proportion of cells staining: 0 ( < 1%), 1 (1-25%), 2 (26-50%), 3 (51-75%), 4 ( > 76%). A combined product score was calculated yielding scores of 0-12. Correlation to clinical parameters (age, blast count, progression to AML, and overall patient survival) was investigated.

Results 60% (21/35) of CMML cases showed low expression of 5hmc (combined score < =4). This loss of 5hmC expression correlated significantly with poorer overall survival in Kaplan-Meier curves (p=0.0287). There was no significant correlation between 5hmC score and patient age, blast count, or AML progression.

Conclusion IHC detection of 5hmC in CMML is significantly correlated with patient overall survival and could potentially be utilized as a prognostic biomarker. Loss of 5hmC expression likely reflects mutations to epigenetic pathways and could be useful in guiding treatment with hypomethylating agents.

6-Month Change in Pain and Function by Pre-Operative Pain and Function among Patients Selected for Total Knee Replacement in the United States

Uyen-Sa D.T. Nguyen, University of Massachusettts Medical School
David Ayers, University of Massachusetts Medical School
Wenjun Li, University of Massachusetts Medical School
Leslie R. Harrold, University of Massachusetts Medical School
Patricia D. Franklin, University of Massachusetts Medical School

12:30 PM

Background/Purpose: The increase in total knee replacements (TKRs) between 1979 and 2006 is staggering. Debate is growing regarding the appropriate utilization of TKRs. We examined pain, function, quality of life (QOL), and satisfaction at 6-month post-surgery by pain and function at time of surgery.

Methods: Data came from the nationally representative FORCE-TJR cohort of patients from 150 surgeons. Participants had primary, unilateral TKRs due to osteoarthritis between 2011 and 2014. Their knee pain (KOOS), physical functions (SF36), and QOL were measured at pre- and 6 months post-surgery. We classified patients as having high or low pre-operative pain (KOOS Pain < 70 vs. ≥70), low or high pre-operative physical function (SF-36 PCS < 40 vs. ≥40), and grouped as: 1) Low pain-High function (LP-HF), 2) Low pain-Low function (LP-LF), 3) High pain-High function (HP-HF), and 4) High pain-Low function (HP-LF). We compared pre- and post-operative changes in pain and function scores among the four groups.

Results: Of 4,563 participants, 5% had pre-operative LP-HF and 75% HP-LF. By 6-month post-surgery, 85% of LP-HF patients reported no change and 4% reported worse symptoms; the HP-LF group had 18% no change and 52% with large improvement. For function in the LP-HF group, mean 6-month change (SD) was 2.6 (7.8), with post-operative mean of 50.0 (7.4). Mean change for the HP-LF group was 11.9 (9.0), with post-operative mean of 42.0 (9.5). For pain score in the LP-HF group, mean 6-month change was 8.3 (14.6), with post-operative mean (SD) of 88.9 (13.0). The HP-LF group had average improvement of 37.2 (19.7), and post-operative mean of 79.9 (17.3). QOL was better among the LP-HF than HP-LF groups; satisfaction was similar.

Conclusion: The majority of patients had appropriate TKR utilization and achieved large improvement in pain and function. Patients with pre-operative LP-HF achieved the smaller mean change, but better absolute outcomes.

A Non-Restrictive Weight Loss Diet Focused on Increasing Fiber and Lean Protein: Results of a Pilot Trial

Lijuan Zhang, University of Massachusetts Medical School
Sherry L. Pagoto, University of Massachusetts Medical School
Barbara C. Olendzki, University of Massachusetts Medical School
Gioia Persuitte, University of Massachusetts Medical School
Linda C. Churchill, University of Massachusetts Medical School
Jessica Oleski, University of Massachusetts Medical School
Yunsheng Ma, University of Massachusetts Medical School

12:30 PM

Objective. The vast majority of diets are not only multicomponent but also restrictive. Dietary fiber or protein can reduce hunger and enhance satiety; they also exert clinical benefits. We examined feasibility and acceptability of a non-restrictive diet combining the two for weight loss.

Population and Methods. Fifteen patients were enrolled in the trial (2 men, 13 women, mean age=48 y and mean BMI = 36 kg/m2) to attend 6 bi-weekly individual counselling sessions for the diet during the 12-week study period. The goals of the intervention were to attain a daily goal of higher fiber (>35g)/ and lean protein (120g). 24-hour diet recalls and body weight were collected at baseline, 6- and 12-week assessments.

Results. All participants completed 6-week assessment, one participant dropped from the study before 12-week assessment. At 12 weeks, 93% of participants liked the diet much/very much, 92% were very/extremely confident in adhering to the diet and 85% did not feel hungry on the diet. Mean fiber intake increased by 9.4 g/day (95% CI: 5.9, 12.8) at 6 weeks, and by 6.9 g/day (CI: 3.3, 10.5) at 12 weeks. Protein intake increased by a mean of 13.7 g/day (CI: 4.8, 22.6) at 6 weeks, and by 6.0 g/day (CI: -3.3, 15.3) at 12 weeks. % of calories from saturated fat decreased by 2.0% (CI: 0.5, 3.4) at 6 weeks and by 2.7% (CI: 0.5, 3.4) at 12 weeks. Alternative Healthy Eating Index score increased by 9.7 (CI: 5.3, 14.0) at 6 weeks and by 6.1 (CI: 1.5, 10.7) at 12 weeks. Mean weight loss was -2.7 lbs (CI: -4.9, 0.6) at 6 weeks and -4.7 lbs (CI: -8.0, -1.4) at 12 weeks.

Conclusion. Participants liked the diet prescribed, and significantly increased their fiber and lean protein intake, resulting in significant weight loss with improvement to dietary quality.

A Novel Population Of Natural Killer Cells Pplays A Critical Role in the Depletion of Splenic B2 B Cells During Experimental Africian Trypanosomiasis

Deborah Frenkel, University of Massachusetts Amherst
Samuel J. Black, University of Massachusetts Amherst

12:30 PM

Mice infected with Trypanosoma brucei, the causative agent of human sleeping sickness and a contributor to nagana in cattle, rapidly lose the capacity to mount VSG-specific antibody responses, and die with uncontrolled parasitemia. We have shown (Bockstal et al., 2011, PLOS Pathogens) that the loss of humoral immune competence in the infected mice results from depletion of developing and mature splenic B cells. We now report that T. brucei-induced splenic B cell depletion is dependent upon the presence of the pore forming molecule perforin which is present in the cytotoxic granules of cytotoxic T lymphocytes, natural killer T cells and natural killer cells, occurs in the absence of T cells (and natural killer T cells), i.e., in T cell receptor (αβγδ)-/- mice, but does not occur in intact mice that are depleted of natural killer (NK) cells by treatment with monoclonal antibody specific for the NK1.1 differentiation antigen. In the intact mice, B cells are deleted after remission of the first T. brucei parasitemic wave. At this time natural killer cells are expressing the cytotoxic granule marker CD107a, indicating that they have degranulated, executing their effector function. Moreover, in vitro assays show that B cells from T. brucei infected mice are killed by natural killer cells from uninfected C57BL/6 mice but not efficiently killed by CD107a positive natural killer cells isolated from infected mice, which may be functionally exhausted.

A Pilot Randomized Controlled Trial of a Videoconferencing Smoking Cessation Intervention for Korean American Women: Preliminary Findings

Sun S. Kim, University of Massachusetts Boston
Somporn Sitthisongkram, University of Massachusetts Boston
Kunsook Bernstein, CUNY Hunter College
Hua (Julia) Fang, University of Massachusetts Medical School
Won S. Choi, University of Kansas
Douglas M. Ziedonis, University of Massachusetts Medical School

12:30 PM

Introduction: Korean American women prefer online or telephone smoking cessation interventions that can be remotely accessed from home. However, these interventions have been found ineffective for the group.

Methods: This study is a pilot clinical trial testing the feasibility and acceptability of a videoconferencing smoking cessation intervention for Korean American women and compared its preliminary efficacy with a telephone-based smoking cessation intervention. Korean women in the United States were recruited nationwide and randomly assigned at a ratio of 1:1 to either a video arm or a telephone arm. Participants in both arms received eight 30-minute weekly individualized counseling sessions of a culturally adapted smoking cessation intervention and nicotine patches for 8 weeks. They were followed up at post-quit 1, 2, and 3 months.

Results: A total of 168 Korean Americans were assessed for eligibility, 77 were determined to eligible and 49 participated in the study. The videoconferencing intervention was acceptable and feasible for women under 50 years, whereas it was not for older women. The videoconferencing intervention produced abstinence rates of 67% at post-quit 1 month and 42% at post-quit 3 months based on self-report. The rate at post-quit 3 months dropped to 33% when those women whose abstinence could not be validated with salivary cotinine tests were treated as smoking. Abstinence rates in the telephone arm did not differ from those in the video arm.

Conclusion: Findings suggest that videoconferencing smoking cessation intervention may be feasible and acceptable for Korean American women under 50 years. However, for older Korean American women, the intervention may not be feasible and telephone-based intervention seems to be just as effective if smoking cessation intervention components are adapted at a deep structural level of Korean culture by integrating its core cultural values and addressing psychosocial, social and environmental forces affecting the behavior.

A Pilot Study to Assess the Feasibility, Safety and Acceptability of Soy-based Diet for Pregnant Women at High Risk for Gestational Diabetes Mellitus

Ling Shi, University of Massachusetts Boston
Vidya Iyer, Tufts Medical Center
Emily Jones, University of Massachusetts Boston
Tiffany A. Moore Simas, University of Massachusetts Medical School
Alice H. Lichtenstein, Tufts University
Laura L. Hayman, University of Massachusetts Boston

12:30 PM

Background: Diet plays an important role in the prevention and management of gestational diabetes mellitus (GDM). Previous studies suggest that soy protein and isoflavones may have beneficial effects on lipid and glucose metabolism. Little is known regarding the cardiometabolic effects of soy intake during pregnancy. This pilot study assessed the feasibility, safety and acceptability of daily consumption of soy foods during pregnancy in women at high risk for GDM, and participant adherence to their assigned treatment.

Methods: A randomized controlled trial (RCT) was conducted among pregnant women at high risk for GDM. The Soy group were counseled to consume a combination of foods designed to contain ~25 grams of soy protein and 60-75 mg of isoflavones daily from 14 weeks until birth. They were provided with recipes and contents of different soy foods. The Control group maintained their regular diet while minimizing intake of soy containing foods. Assessments, conducted at 14 and 28 weeks of pregnancy, and 6 week postpartum, included physical measurement, questionnaire, and fasting blood samples for lipid, glucose and isoflavone metabolism biomarkers. Monthly follow-up calls were conducted to assess safety and encourage adherence.

Results: Twenty-nine subjects were recruited over a 10 month period. Both Soy and Control groups demonstrated high adherence (80-90%), defined as ≥ 15 days consuming soy foods in the past four weeks for soy group and ≤ 5 days for controls. Only five adverse events were reported possibly associated with soy intake, including nausea, vomiting, diarrhea, and itchy mouth. They were all transient and resolved without sequelae.

Conclusion: Although adherence can be challenging in such a trial, this study used a variety of approaches such as recommended recipes, dietician consultation, and monthly follow-up calls to enhance feasibility and compliance. Results indicated feasibility and adherence to treatment assignment, including the soy-based diet intervention.

A Reduced Order Model For Efficient Physiological Flow Analysis In Aneurysms by Proper Orthogonal Decomposition

Gary Han Chang, University of Massachusetts Amherst
Yahya Modarres-Sadeghi, University of Massachusetts Amherst

12:30 PM

Simulating physiological flows using computational fluid dynamics (CFD) remains to be computationally expensive and difficult for clinical usage because of the physiological flow and geometrical complexity involved in patient specific situations. We use the reduced order modeling (ROM) of such systems with high nonlinearity and geometrical non-uniformity to replace the full, nonlinear model with a low-degrees of freedom ROM model. We construct ROM models by the proper orthogonal decomposition (POD) method to estimate the flow-induced wall shear stress (WSS) and pressure loading of a simplified abdominal aortic aneurysm and a bifurcation cerebral aneurysm. This method allows us to investigate a wide range of different physiological flow parameters without conducting the computationally expensive CFD simulations repetitively, which is promising for clinical usage.

We obtain a set of snapshots from a set of flow simulations with multiple variable parameters, called the training set. The training set should be simulated in a parameter space that contains all the physiological parameters of interest. We show that both the velocity and pressure distributions are well reconstructed when compared with the exact values with a small number of modes. A mesh-less shell model is used to estimate the aneurysm sidewall’s in-plane stresses. Sidewalls with non-uniform thickness are considered to study the influence of local weakness on the aneurysm’s risk of failure. We found that the sensitivity of the material’s strength to the local weakness depends on the aneurysms sidewall’s Gaussian curvatures, the curvature to thickness ratio and the distribution of the flow loading. It is therefore critical to describe the distribution of curvature and thickness accurately when estimating the in-plane stress of aneurysms.

Advanced MRI Center: a 3 Tesla Magnetic Resonance system for preclinical, translational and clinical imaging studies

Letterio S. Politi, University of Massachusetts Medical School
Shaokuan Zheng, University of Massachusetts Medical School
Matthew J. Gounis, University of Massachusetts Medical School

12:30 PM

The Advanced MRI Center, located in the UMass Medical School building, is a research core facility providing the latest magnetic resonance imaging and spectroscopy capabilities to UMass scientists. It is equipped with a Philips Achieva 3.0T X-series whole-body scanner and radiofrequency coils for studying all organs of the human body, and small and large animals, such as mice, rats, rabbits, dogs, sheep and non-human primates. The center also includes a radiofrequency coil lab, a nurses’ station, two patient holding rooms and two patient changing rooms.

The Center’s specialized techniques are able to elucidate functional, physiological and biochemical information from all organs of the body.

The 3.0 Tesla system features the Quasar Dual gradient system with industry leading performance specifications, that allow high-level diffusion tensor imaging and functional MRI (fMRI) applications in humans, and high resolution imaging studies in small animal studies. A fMRI stimulus delivery system, a MRI compatible goggle set with eye tracking system, microphone and earphones are available for facilitating fMRI studies.

Small animal monitoring and gating system and an MR compatible Anesthesia system with heater and ventilator option are also available.

The 3.0T MR system is also equipped with a Multi-nuclear spectroscopy system, which provide the ability to perform 13C, 31P, 7Li, 23Na and other nuclei spectroscopy and imaging. Technical and clinical expertise for collaborative research is also provided.

Advancing Medical Device and Biotech Innovations

Nathaniel Hafer, University of Massachusetts Medical School
Margaret Koziel, University of Massachusetts Medical School
Stephen McCarthy, University of Massachusetts Lowell
Steven Tello, University of Massachusetts Lowell

12:30 PM

M2D2 is a UMass Lowell – UMass Medical School Worcester initiative that helps entrepreneurs move new medical device and biotech ideas from patent to production and offers early-stage inventors and established companies easy, affordable and coordinated access to world-class researchers and resources at both the Lowell and Worcester campuses.

UMass Lowell and UMass Worcester extend use of engineering and scientific resources to M2D2 companies. These core resources are available to researchers by using the research services agreement. The use of UMass Lowell and UMass Worcester interns and faculty is an enormous benefit to an emerging medical device or biotech company.

UMass Worcester’s campus offers access to core research supports and highly trained personnel to efficiently conduct animal or clinical studies across the life cycle of projects.

UMass Lowell has two M2D2 facilities with private and shared wet lab space, equipment, office space and conference rooms. It offers business and medical feasibility assessments, product development, medical and clinical pathway assistance, SBIR and STTR research partnerships and access to capital.

M2D2 was established with seed funding from the UMass President’s Office, the Mass Life Sciences Center and the Commonwealth of Massachusetts.

Airway smooth muscle pathology in Pompe Disease

Lang Xiong, University of Massachusetts Medical School
Allison M. Keeler, University of Massachusetts Medical School
Donghai Lui, University of Massachusetts Medical School
Kaitlyn Desrochers, University of Massachusetts Medical School
Ronghua Zhuge, University of Massachusetts Medical School
Mai K. Elmallah, University of Massachusetts Medical School

12:30 PM

Pompe disease is a rare autosomal recessive disease which results from a deficiency of acid α-glucosidase (GAA) - an enzyme that degrades lysosomal glycogen. Patients with Pompe disease develop intra-lysosomal accumulation of glycogen in multiple tissues including skeletal muscle, CNS and smooth muscle.

Pulmonary dysfunction is a hallmark of Pompe disease and has classically been attributed to muscle weakness and CNS neuropathology. However, the potential role of respiratory smooth muscles in the respiratory pathology is unknown. Therefore we postulated that GAA deficiency results in airway smooth muscle glycogen accumulation that leads to airway smooth muscle dysfunction.

Using the Pompe mouse model, the Gaa-/- mouse, we examined the airway smooth muscle structure and function. We used in vivo forced oscillometry measurements (N=7WT, N=7 Gaa-/-) to examine pulmonary physiology and administered methacholine challenges to assess in vivo airway resistance. Also, we used ex-vivo contraction testing (N=6WT, N=5 Gaa-/-) to determine bronchi contractility. In response to the highest dose methacholine challenge (100mg/ml), there was a significant decrease in conducting airway resistance in Gaa-/- versus WT mice (p=0.007). Also, ex vivo bronchi contraction testing demonstrated a significantly weaker response to potassium chloride (p=0.008) and methacholine (2-way ANOVA p=0.005) in Pompe mice compared to WT mice, suggesting impaired smooth muscle contraction. Furtherly, we performed PAS staining on fresh-frozen tissue to examine the degree of glycogen accumulation as a result of GAA deficiency. PAS staining revealed robust glycogen accumulation in the trachea and bronchi of Pompe mice and a disruption of the airway smooth muscle architecture.

In conclusion, GAA deficiency results in glycogen accumulation and a disruption of the architecture in the airway smooth muscles of Gaa-/- mice. Furthermore, both in vivo and ex vivo tests reveal that Gaa-/- murine airways have impaired function as evidenced by decreased contractility and a decreased response to methacholine.

Analysis of A Novel Nonsense Mutation of Androgen Receptor Gene in Castration-Resistant Prostate Cancer

Dong Han, University of Massachusetts Boston
Kevin Valencia, University of Massachusetts Boston
Shuai Gao, University of Massachusetts Boston
Changmeng Cai, University of Massachusetts Boston

12:30 PM

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer mortality in American men. The standard treatment for PCa is androgen deprivation therapy (ADT) that blocks transcriptional activity of androgen receptor, but ADT invariably leads to the development of castration-resistant form of PCa (CRPC) with restored activity of AR. CRPC can be further treated with more intensive ADTs, including CYP17-inhibitors to block intratumoral androgen synthesis and more potent AR antagonist (enzalutamide). Most CRPC patients still relapse after a year of treatment and AR activity appears to be restored again. By analyzing the tumor mRNA from a CRPC patient biopsy who had developed resistance to CYP17-inhibitor treatment, we identified a novel nonsense AR mutation on ligand binding domain (Q784sc), which presumably produces a C-terminal truncated form of AR protein that lacks ligand binding domain (LBD) and may mimic certain AR splice variants that also lack LBD. We thus hypothesized that AR-Q784sc mutant may gain the androgen-independent activity or may enhance the transcriptional activity of full-length AR under low androgen environment through dimerization with full-length AR.

METHOD: We utilized luciferase reporter assays to assess the activity of AR-Q784sc in absence or presence of androgens, and with/out full-length AR. We also examined the protein stability and cellular localization of AR-Q784sc using immunoblotting and immunofluorescence. Moreover, stable cell lines that overexpress AR and/or AR-Q784sc were generated to assess the transcription activity on endogenous target genes and on PCa cell growth.

CONCLUSION: AR-Q784sc mutant produces a LBD truncated AR protein that does not have any transcriptional activity by it alone. However, AR-Q784sc can significantly enhance transcriptional activity of full-length AR though dimerization, indicating that the more intensive ADTs may allow CRPC cells to select for LBD truncated form of AR to further enhance the full-length AR activity under low androgen environment.

Angina Characteristics as Predictors of Trajectories of Quality of Life Following Acute Coronary Syndrome in the Transitions, Risks and Actions in Coronary Events-Center for Outcomes Research and Education cohort (TRACE-CORE)

Lisa Nobel, University of Massachusettts Medical School
Jennifer Tjia, University of Massachusetts Medical School
Jane S. Saczynski, University of Massachusetts Medical School
Molly E. Waring, University of Massachusetts Medical School
Milena D. Anatchkova, University of Massachusetts Medical School
Arlene Ash, University of Massachusetts Medical School
Catarina I. Kiefe, University of Massachusetts Medical School
Jeroan Allison, University of Massachusetts Medical School

12:30 PM

BACKGROUND: To describe longitudinal trajectories of health-related quality of life (HRQoL) after hospitalization with an acute coronary syndrome (ACS), their associations with baseline angina characteristics, and associations with anxiety, depression, and cognitive impairment.

METHODS: TRACE-CORE participants (N=1,613) completed the SF-36 during hospitalization for ACS and 1, 3, & 6 months post-discharge. Latent growth curves identified trajectories of physical and mental components of HRQOL (MCS and PCS) and sequential multiple logistic regression estimated associations between trajectories and angina characteristics.

RESULTS: Participants (N=1613) had mean age 63.3 (SD 11.4) years, 33.0% female, and 78.2% non-Hispanic white. We identified 2 MCS trajectories: AVERAGE and IMPAIRED HRQoL. The majority of participants (81.0%) had AVERAGE MCS at baseline (mean MCS 53.6) and slight improvement in scores over time. A minority (19.0%) had IMPAIRED HRQoL at baseline (mean MCS 36.7) and slight improvement in scores over time. We identified 2 similar PCS trajectories with similar patterns of scores over time: AVERAGE (71.1%) and IMPAIRED (28.9%) HRQoL at baseline. Adjusting for demographics & comorbidities, patients with less severe baseline angina were more likely to have AVERAGE MCS (odds ratio [OR]/10 unit change in severity 1.1) and PCS (OR 1.1) trajectories, and similarly for less frequent angina (MCS OR 1.2; PCS OR 1.3). The associations of MCS trajectory with severity and frequency lost significance after adjusting for psychosocial factors, whereas the PCS associations remained significant [All p < 0.05 unless noted].

CONCLUSIONS: About 1/3 of patients exhibited impaired 6-month HRQoL trajectories, which can be predicted by angina characteristics. Psychosocial factors may explain the prediction of mental, not physical, trajectories. Interventions to improve HRQoL after ACS should consider psychosocial factors and angina.

Anthelminthic Screening for Parasitic Nematodes

Elfawal A. Mostafa, University of Massachusetts Medical School
Dan Lawler, Worcester Polytechnic Institute
Dirk Albrecht, Worcester Polytechnic Institute
Raffi V. Aroian, University of Massachusetts Medical School

12:30 PM

For many parasitic diseases, high-throughput phenotypic screening is an important tool in finding new drugs. Some of the most important parasitic diseases are caused by nematodes. However, these parasitic nematodes are not typically amenable to high throughput screening. Due to the ease of its maintenance and suitability for high throughput assay, the nematode Caenorhabditis elegans is instead used. To address whether C. elegans is a good model for nematode drug discovery, we compared the drug susceptibility of C. elegans relative to the human hookworm nematode parasite Ancylostoma ceylanicum at several developmental stages using a library of FDA approved drugs. I will present results of these studies that point to how well C. elegans efficacy correlates with hookworm efficacy and how early larval stages (easier to get) correlated with adult stages (more representative of what stage is targeted in human therapy). In addition, we are working on moderate-high throughput system for screening adult parasites. Murine Holigmosomoides polygyrus is a good model for human parasitic nematodes. Using Union Biometrica, Copas, worm sorter we were able to sort H. polygyrus into 384 well format. Here I will discuss the capabilities of this system as well as how we are building de novo, in collaboration with the Albrecht laboratory at WPI, an imaging and image analysis platform for screening adult stages of this parasite against large drug libraries.

Association between First Trimester Pregnancy Associated Plasma Protein–A and the Development of Gestational Diabetes Mellitus

Aylin Sert, University of Massachusetts Medical School
Katherine Leung, University of Massachusetts Medical School
Molly E. Waring, University of Massachusetts Medical School
Raziel Rojas-Rodriguez, University of Massachusetts Medical School
Silvia Corvera, University of Massachusetts Medical School
Tiffany A. Moore Simas, University of Massachusetts Medical School

12:30 PM

Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism.

Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk.

Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM.

Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile.

Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis.

Bioavailability of the Antimalarial Drug Artemisinin Delivered Orally as Dried Leaves of Artemisia annua: the Role of Solubility and Protein.

Matthew Desrosiers, Worcester Polytechnic Institute
Pamela Weathers, Worcester Polytechnic Institute

12:30 PM

Malaria treatment using orally consumed dried leaves of the artemisinin producing GRAS plant Artemisia annua has recently shown promise. Previously we showed, oral consumption of A. annua dried leaves (DLA) yielded >40 times more artemisinin in the blood of mice than treatment with pure artemisinin. Using the Caco-2 cell culture model of the human intestinal epithelium, we also showed that compared to pure artemisinin, digested DLA doubled the permeability (Papp). Here, using simulated human digestion, we show that artemisinin solubility is about seven times higher in digestates of DLA than in digestates of pure artemisinin, likely contributing to its enhanced bioavailability. Digestion with pure artemisinin combined with levels of essential oils comparable to that in DLA increased the solubility of artemisinin 2.5 times indicating essential oils play a role in increasing artemisinin solubility. Interestingly, increasing the starting concentration of artemisinin in Caco-2 transport studies did not alter Papp. Considering malaria affects mostly young children and about 60% of the population experiences DLA as unpleasant tasting, we also tested several protein rich foods as potential flavor-masking agents for their effects on bioavailability. We showed that while taste was masked, peanuts and a peanut-based paste used to treat malnutrition, PlumpyNut, reduced artemisinin and flavonoid levels in simulated digestates, respectively, likely decreasing their bioavailability. Experiments to further investigate the role of several compounds such as camphor, a principle component of the essential oil fraction, and flavonoids on artemisinin solubility and bioavailability are ongoing. The results of these experiments are helping to explain the increased bioavailability afforded by DLA seen in mice.

Burden of Adverse Metabolic Factors Is Associated With Increased Left Ventricular Concentricity in Adults With Normal-Range Body Mass Index: The Framingham Heart Study

Philimon Gona, University of Massachusetts Boston
Jane Lee, Framingham Heart Study
Carol J. Salton, Beth Israel Deaconess Medical Center
Christopher J. O'Donnell, Harvard Medical School
Warren J. Manning, Beth Israel Deaconess Medical Center
Michael L. Chuang, Beth Israel Deaconess Medical Center

12:30 PM

Introduction: Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI. Methods: From the 1794 Framingham Heart Study Offspring cohort adults who underwent cardiac magnetic resonance imaging (CMRI) , we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI<25.0 kg/m2 and complete covariates. We calculated a metabolic score (MS) where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥140 or DBP≥90 mmHg or antihypertensive treatment; c) TG≥150 or HDL_C <40(M)/<50(W) mg/dL or lipid treatment; d) HOMA-IR≥2.5; e) waist circumference ≥102/88cm for M/W. Participants were classified as MS0 (no points), MS1 (exactly 1 point), or MS2+ (≥2 points). LV mass (LVM), end-diastolic volume (EDV), ejection fraction (EF), and concentricity (LVM/EDV) were measured from breathhold cine SSFP CMR scans; we calculated LVM/BSA. Analysis of covariance (ANCOVA) was used to compare MS1 and MS2+ groups to the MS0 group. CMRI variables were adjusted for sex, age, heart rate (HR) and body size (BSA); LVM/BSA was adjusted for sex, age, HR only. We also tested for linear trend across metabolic groups. Results: LV concentricity increased with worsening metabolic status. This was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups. Conclusions: In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity.

Can Physician Champions Improve Kangaroo Care? Trends over 5 Years in Rural Western India

Apurv Soni, University of Massachusetts Medical School
Amee Amin, Pramukhswami Medical College
Dipen V. Patel, Pramukhswami Medical College
Nisha Fahey, Des Moines University
Ajay G. Phatak, Pramukhswami Medical College
Jeroan Allison, University of Massachusetts Medical School
Somashekhar M. Nimbalkar, Pramukhswami Medical College

12:30 PM

Introduction: In 2013, approximately 2.8 million children worldwide died within the neonatal period. India is at the epicenter of this tragedy, accounting for one-third of all neonatal mortalities. Prematurity and/or with low birth weight are the leading cause of neonatal mortality and India has the highest number of neonates born preterm and weighing less than 2,500 grams worldwide. It is estimated that Kangaroo Care can avert up to 48% of all neonatal deaths among premature babies by 2025. However, the promise of Kangaroo Care as a low-cost, safe, and efficacious intervention to reduce neonatal mortality in India has not been realized due to suboptimal implementation. Physician champions can improve Kangaroo Care implementation, but the magnitude of their impact is unknown.

Methods: A retrospective cohort study of 648 infants identified using clinical data from a NICU located in rural western India. Physicians who led Kangaroo Care training sessions with neonates and coached peer healthcare professionals were considered champions. Two Kangaroo Care champions were on staff full-time from January 2010 through June 2011, part-time from July 2011 through June 2012, and absent thereafter. We examined the effect of the withdrawal of physician champions on overall use using logistic regression, time to initiation using competing risk cox regression, and intensity using linear regression models of the two main components of Kangaroo Care, skin-to-skin care and breastfeeding, separately.

Findings: In comparison to when Kangaroo Care champions were present, their absence was associated with a 45% decrease in the odds of receiving skin-to-skin care (95% CI): 64% to 17%), 38% decrease in the rate of initiation of skin-to-skin care (95% CI: 53% to 82%), and on average, 1.47 less hours of skin-to-skin care (95% CI: -2.07 to -0.86). Breastfeeding practices were similar across different champion environments.

Interpretation: Withdrawal of Kangaroo Care champions from neonatal intensive care unit in rural western India is associated with diminished administration, delayed initiation, and shorter duration of skin-to-skin care, but did not impact breastfeeding practices. Training healthcare workers and community stakeholders to become champions could help in scaling up and maintaining Kangaroo Care practices.

Funding: This research was supported by TL1-TR001454 (to A.S.) from National Center for Advancing Translational Sciences, and P60-MD006912-05 (to J.A.) from National Institute on Minority Health and Disparities. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Change in Anti- gp120 Human Monoclonal Antibody Isotype Significantly Improves HIV-1 Neutralization

Mark Duval, University of Massachusetts Medical School
Melissa Gawron, University of Massachusetts Medical School
Lisa Cavacini, University of Massachusetts Medical School

12:30 PM

HIV vaccine efforts tend to focus on the induction of IgG neutralizing antibodies. In part, this may stem from the observations that most HIV infected individuals fail to produce significant mucosal IgA. However, this is unlike most other infections and in turn it can be argued that mucosal IgA with appropriate function and specificity may contribute significantly to the prevention of HIV transmission. To explore this, we previously isotype switched F425A1g8, an anti-HIV CD4i human monoclonal antibody that binds to epitopes exposed upon CD4 binding (CD4i) The VH and VL chains were amplified from the IgG hybridoma and inserted into IgA1 or IgA2 and IgKappa vectors respectively. Stable cells lines were produced and antibody was collected and purified. Initial results showed that the IgA1 variant neutralized a number of HIV-1 isolates better than its parental form IgG1. We believe the increased neutralization of HIV is mainly due to the structural differences between IgG1 and IgA1. We hypothesize that the extended hinge of IgA1 may increase segmental flexibility and change the interaction of antibody with CD4i epitopes of the HIV, resulting in greater avidity. To look at this further, we have generated monomeric and dimeric IgA1 and IgA2 variants of three different CD4i antibodies: F425A1g8, 17b and E51. All antibody variants will be tested for immumoreactivity, HIV neutralization, prevention of transmission and ADCVI activity. Consistent with our previous results, there are significant differences in functional activity of the other CD4i antibodies with IgA1 more effective than the IgA2 variants. Additional activities will contribute to the hypothesis that the extended hinge region of the IgA1 antibody increases the antibodies ability to access the CD4i epitopes upon HIV-1 binding to CD4. These studies should impact on the design of active and passive immunotherapy and the prevention of HIV transmission.

Characterization of neutrophils and macrophages from ex vivo cultured murine bone marrow for morphologic maturation and functional responses by imaging flow cytometry

Klaudia Szymczak, University of Massachusetts Lowell
Margery G.H. Pelletier, University of Massachusetts Lowell
Anna M. Barbeau, University of Massachusetts Lowell
Kevin O'Fallon, US Army Natick Soldier RDE Center
Peter Gaines, University of Massachusetts at Lowell

12:30 PM

Neutrophils and macrophages differentiate from common myeloid progenitors in the bone marrow, where they undergo unique nuclear morphologic changes as they mature into fully functional phagocytes. These changes include condensation of chromatin, the most pronounced exhibited by mature neutrophils. Both myeloid cells acquire multiple functions critical to their ability to kill pathogens, including phagocytosis, the production of proteolytic enzymes and reactive oxygen species (ROS), and in the case of neutrophils, release of nuclear material known as nuclear extracellular traps (NETs). Studies on these functions often rely on the use of cells acquired from mature mouse tissues, but these tend to produce limited numbers of cells. Strategies to analyze the morphologic features and functional responses of these cells include the use of conventional brightfield or fluorescence microscopy to examine changes in nuclear structure, internalization of fluorescein-labeled bacterial or yeast particles, or release of nuclear material. Flow cytometry also is often used, especially for identifying changes in the expression of lineage-specific cell surface markers and ROS production. However, each of these techniques presents certain limitations. Here we describe methods to generate abundant populations highly enriched for neutrophils or macrophages from previously frozen, ex vivo cultured mouse bone marrow. We then apply state-of-the-art imaging flow cytometry, which combines the resolution of microscopy with the speed of flow cytometry, to analyze each lineage for changes in nuclear structure and expression of key cell surface markers. Different gating and masking strategies are applied to characterize phagocytosis of pH-dependent fluorescein-labeled E. coli, ROS production, and NET release by neutrophils. We also demonstrate that neutrophils engulfing E. coli bioparticles produce NETs in a process we term PhagoNETosis. Together these assays reveal the power of imaging flow cytometry for simultaneously assessing the maturation features and functional responses of these critical mediators of innate immunity.

Characterization of Respiratory Phenotype in Very Long-chain Acyl-CoA Dehydrogenase Deficient Mice.

Allison M. Keeler, University of Massachusetts Medical School
Kaitlyn Desrochers, University of Massachusetts Medical School
Mai K. Elmallah, University of Massachusetts Medical School

12:30 PM

Rationale: Very Long-chain Acyl-CoA dehydrogenase (VLCAD) deficiency the most common inherited long-chain fatty acid disorder. The VLCAD enzyme catalyzes the first step of mitochondrial fatty acid oxidation and loss of the enzyme results in energy deficiency as well as accumulation of long chain fatty acids. Recently, a related enzyme, Long-chain Acyl-CoA dehydrogensase (LCAD), which unlike VLCAD is not highly expressed in metabolic tissues like liver, heart and skeletal muscle, was found to be expressed in the lung and surfactant and lung dysfunction were observed in LCAD deficient mice. Respiratory distress syndrome has been described in other fatty acid oxidation disorders. VLCAD is expressed in lung, and likely plays an important role in lung compliance.

Methods: VLCAD deficient mice and litter-mate controls were fasted for 18 hours, then exercised on a treadmill for 2 hours. Breathing was immediately assessed using whole body plethysmography in unanaesthetized spontaneously breathing mice. After a stable baseline was achieved, mice were given a “respiratory” challenge with 7% hypercapnia. In a subgroup of animals, pulmonary mechanics were assessed using Flexivent (Scireq).

Results: Following exercise, VLCAD deficient mice had a decreased tidal volume and minute ventilation compared to their wild type controls. However, post-exercise VLCAD deficient mice were able to stabilize to similar levels as wild-type during baseline. The VLCAD deficient mice had a decreased response to a respiratory challenge with 7% hypercapnia. Early preliminary results suggest that VLCAD deficient animals have lower airway resistance.

Conclusions: Respiratory insufficiency was demonstrated in a fasted and exercise challenged VLCAD deficient mice.

Collecting Histories of Education and Employment Activities from Young Adults with Serious Mental Health Conditions

Kathryn Sabella, University of Massachusetts Medical School
Peter Bui, University of Massachusetts Medical School
Laura Golden, University of Massachusetts Medical School
Kathleen Biebel, University of Massachusetts Medical School

12:30 PM

Young adulthood is a critical time for establishing the foundation of an adult working life. As adolescents mature and explore career interests, they also begin to focus in on particular career pathways. However, lower levels of employment and educational attainment, as well as the demands of parenting, prevent and delay Youth and Young adults (Y&YAs) with serious mental health conditions (SMHCs) from participating in settings where career development and exploration activities typically occur. Of Y&YA parents who do work, the majority will work part-time, at low-level service jobs, and at low salaries (Osgood, et al., 2005). Y&YA parents with SMHCs are particularly vulnerable as they are more likely than their normative peers to experience unemployment, poverty, and dependence on government assistance (Luciano, et al., 2013). Through a one-time, semi-structured interview, this study seeks to describe the education and employment activities of Y&YAs between the ages of 25-30 with SMHCs, explore barriers and facilitators to these activities, and understand how parenting affects these experiences. Preliminary findings will be presented as they relate to themes of career exploration/development, the barriers and facilitators to education and employment activities this population encounters, including the impact that parenthood can have on these activities in young adulthood. We will also describe the education and employment activities and trajectories that were obtained as part of these interviews.

Community-based Participatory Research to Promote Healthy Diet and Nutrition and Prevent and Control Obesity among African Americans: A Literature Review

Steven Coughlin, University of Massachusetts Lowell
Selina Smith, Augusta University

12:30 PM

The literature on community-based participatory research (CBPR) approaches for promoting healthy diet, nutrition, and preventing and controlling obesity in African American communities was systematically reviewed.

CBPR studies of diet, nutrition, and weight management among African Americans were identified from 1989 through October 31, 2015 using PubMed and CINAHL databases and MeSH term and keyword searches.

A total of 16 CBPR studies on healthy diet, nutrition, and weight management among African Americans were identified; outcome evaluation results were available for all but two. Of the remaining 14 studies, 11 focused on adults, 1 on children, and 2 on both children and adults. Eight studies employed CBPR methods to address diet, nutrition, and weight management in church settings. Four had a cluster randomized controlled design. Others had a pre-post test, quasi-experimental, or uncontrolled design. Only one study addressed four levels of the socioecological model; none addressed all five levels of the model. The identified studies indicate that CBPR approaches can be effective for promoting healthy diet, nutrition, and weight management among African American adults but there is a need for additional studies with rigorous study designs that overcome methodologic limitations of many existing studies. There is only limited evidence for the effectiveness of CBPR approaches for promoting healthy eating and weight control among African American children and adolescents

To address health disparities, additional CBPR studies are needed to promote healthy diet, nutrition, and weight management in African American communities. Of particular interest are multilevel CBPR studies that include interventions aimed at multiple levels of the socioecological model.

Comparison of Diabetic Remission Rates following Roux en-Y Gastric Bypass and Longitudinal Sleeve Gastrectomy

Zachary Weitzner, University of Massachusetts Medical School
Julie Flahive, University of Massachusetts Medical School
Gordon Fitzgerald, University of Massachusetts Medical School
Donald Czerniach, University of Massachusetts Medical School
Philip Cohen, University of Massachusetts Medical School
John Kelly, University of Massachusetts Medical School
Richard A. Perugini, University of Massachusetts Medical School

12:30 PM

Introduction: Bariatric surgery is being increasingly investigated as treatment for Type II Diabetes Mellitus (T2DM). As Sleeve Gastrectomy (SG) surpasses Roux-en-Y Gastric Bypass (RYGB) as the new standard in bariatric surgery, it is still unknown if its efficacy in achieving remission is comparable to RYGB. This study compared diabetic remission rates between SG and RYGB in order to identify the predictive factors for remission and the mechanisms of achieving remission.

Methods: This was a retrospective cohort study comparing all diabetic patients undergoing RYGB and SG at an academic medical center from 1/1/11-7/1/15. Patients were followed preoperatively and at 6 week, 6 month, and 1, 2, and 3 year intervals. We defined diabetic remission as HbA1c under 7 without insulin or hypoglycemic use and excess body weight (EBW) as percent over ideal body weight. Data were analyzed using Cox analysis, Fisher’s Exact Tests, and Student T Tests.

Results: During the study, 96 patients underwent RYGB and 89 underwent SG. Preoperatively, patients from both groups had similar age, weight, gender, preoperative weight loss, HbA1c at onset and at surgery, oral hypoglycemic use, insulin use, and HOMA2 parameters. At one year postoperatively, patients who underwent RYGB showed a statistically greater postoperative EBW loss (62% vs. 36% p < 0.0001). Kaplan Meier analysis showed a significantly higher rate of remission, (83% vs. 66%) in patients who underwent SG (p=0.02). After using Cox analysis to account for differences in delta BMI (p=0.04), EBW loss (p=0.04), preoperative HOMA2 parameters (p=0.008-0.011), and preoperative factors such as HbA1c and insulin use (p=0.001 for both), there was no change in RYGB’s impact on diabetic remission compared to SG.

Conclusion: Our results confirm that RYGB achieves a significantly greater rate of diabetic remission and a significantly higher weight loss than SG. Additionally, the difference in rate of diabetic remission is not explained by weight loss or preoperative predictors of less reversible diabetes (HOMA2 parameters, use of insulin). Identification of the factor(s) responsible for this differential effect on diabetes may afford opportunity for therapeutic intervention.

Contemporary Analysis of Malignancies in Women of Child-Bearing Age: An NSQIP Analysis

Eva Rouanet, University of Massachusetts Medical School
Ann-Kristin U. Friedrich, University of Massachusetts Medical School
Kate Dinh, University of Massachusetts Medical School
Kevin P. Baratta, University of Massachusetts Medical Shool
Giles F. Whalen, University of Massachusetts Medical School
Heena Santry, University of Massachusetts Medical School
Jennifer LaFemina, University of Massachusetts Medical School

12:30 PM

Background: Recent evidence suggests that cancer incidence among pregnant women is increasing. The pattern of malignancies in pregnant women and how these compare to their nonpregnant counterparts has not been explored. Here we describe the differences in the proportion of resected malignancies in this population. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify women aged 18-49 who underwent an operation for malignancy from 2007-2012. Age-adjusted distribution of specific surgical interventions for malignancy based on ICD-9 codes were compared among pregnant and non-pregnant women using logistic regression analysis. Results: 42,732 subjects with malignancies surgically treated during child-bearing age were identified. 0.33% (n=143) were pregnant. The most common tumors requiring resection were breast (51%), thyroid (17%), and colorectal (9%). The distribution for most cancers was similar between groups. The age-adjusted proportion was significantly increased in breast, major salivary gland and oropharyngeal malignancies (p<0.05). The proportion of resected colorectal cancers was significantly lower in pregnant women (p<0.05; Table 1). Conclusion: This study serves as the first comprehensive and contemporary overview of malignancies resected in women of childbearing age. This study demonstrates that the proportion of resections among pregnant women was significantly greater in breast, major salivary gland and oropharyngeal cancers and lower for colorectal cancers. While these data might represent true differences in cancer incidence, further work is necessary to demonstrate if these are true differences in incidence versus differences in detection and treatment of the pregnant patient.

Correlates of hyaluronic acid and corticosteroid injections among patients with radiographically confirmed osteoarthritis

Shao-Hsien Liu, University of Massachusettts Medical School
Catherine E. Dube, University of Massachusetts Medical School
Jeffrey B. Driban, Tufts Medical Center
Timothy E. McAlindon, Tufts Medical Center
Charles Eaton, Brown University
Kate L. Lapane, University of Massachusetts Medical School

12:30 PM

Objective: Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving them is scarce. We described use of injections among adults with radiographically confirmed knee OA and identified correlates of injection use.

Methods: We used publicly available data from Osteoarthritis Initiative and included participants with ≥ one radiographically confirmed knee OA (Kellgren-Lawrence grade (K-L) > 2) at baseline. We matched 415 participants reporting HA and/or CO during the 6 month before one of the first 7 annual follow-up assessments to 1,841 non-injection users by randomly selecting a study visit to match the distribution observed in the injection users. Multinomial logistic regression models identified correlates of injection use including sociodemographics and clinical/functional factors.

Results: Injections were common (16.9% -year 1, 13.7% -year 2, 16.6 % -year 3, 13.5% - year 4, 15.9% -year 5, 13.5 % -year 6 and 9.9% -year 7) with corticosteroid injections most common (68.4%). HA and CO were more commonly reported by those with higher income (e.g. adjusted Odds Ratio (aOR) HA > $50k versus < $25k: 3.63; (95% CI: 1.20-10.99)) and less common among blacks (aOR HA: 0.19; 95% CI: 0.06-0.55). Greater K-L grade (grade 4 versus 2) was associated with increased odds of HA (aOR: 4.79; 95% CI: 2.47-9.30), CO (aOR: 1.56; 95% CI: 1.04-2.34), or both (aOR: 4.94; 95% CI: 1.99-12.27).

Conclusion: Hyaluronic acid or corticosteroid injections are associated with higher socioeconomic positioning and indicators of greater disease severity.

Crystal protein Cry5B as a novel and powerful anthelmintic

David Koch, University of Massachusetts Medical School
Zeynep Mirza, University of Massachusetts Medical School
Yan Hu, University of Massachusetts Medical School
Thanh-thanh Nguyen, University of Massachusetts Medical School
Gary R. Ostroff, University of Massachusetts Medical School
Raffi V. Aroian, University of Massachusetts Medical School

12:30 PM

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH infections in rodents (Heligomasmidoes polygyrus and Ancylostoma ceylanicum) and in pigs (Ascaris suum).

An enormous challenge for STHs, very different from most diseases worked on in the developing world, is the requirement that therapies be very cheap (the people infected are very poor and current drugs costs pennies a dose), massively scalable (over 4 billion people are at risk from infection), and have a long shelf life in harsh environments, that have high temperature and humidity and no cold chain.

We will update our progress in several key areas. We will present new data on the in vivo activity of Cry5B against a major human parasite in humans. We will also present data on the whether or not the immune system is required for Cry5B action in vivo. We will also present on our development efforts to produce a deployable version of Cry5B that is cheap, safe, scalable, and stable. These efforts are currently focused on bacterial engineering, expression, and formulation.

Developing anti-GDF6 therapeutics for treatment of advanced melanoma

Alec Gramann, University of Massachusetts Medical School
Arvind Venkatesan, University of Massachusetts Medical School
Ejemel Monir, University of Massachusetts Medical School
Danielle Wisheart, University of Massachusetts Medical School
Yan Wang, University of Massachusetts Medical School
Craig J. Ceol, University of Massachusetts Medical School

12:30 PM

Melanoma, the leading cause of skin cancer death in the U.S., is increasing in incidence. Targeted therapies have been approved for treatment of advanced melanoma, but few patients experience extended survival benefit. In order to combat poor outcomes, new therapeutic targets are needed. Using cross-species oncogenomic analyses, our lab has identified a novel melanoma driver, Growth differentiation factor 6 (GDF6), a secreted bone morphogenetic protein (BMP) ligand that is amplified and overexpressed in human melanomas. Functional analyses show GDF6 acts via the BMP-SMAD1 pathway as a pro-survival factor in melanomas. Inhibiting GDF6 or the BMP pathway using shRNAs or the small molecule inhibitor, DMH1, induces melanoma cell death thereby abrogating melanoma growth in mouse xenografts. These results suggest GDF6 is an optimal target melanoma therapy. In order to better understand the dynamics of GDF6 signaling in melanoma cells, we are currently investigating the effect of exogenous GDF6 on cells with inhibited GDF6 expression to determine the required concentration to activate SMAD1 signaling and rescue viability. As GDF6 is a secreted ligand, we proposed developing antibodies to block the GDF6 interaction at its receptor, thereby inhibiting signaling. In collaboration with MassBiologics, we have generated a panel of monoclonal antibodies targeting GDF6. To identify antibodies capable of blocking GDF6 activity, we have devised a series of assays to eliminate antibodies from the panel. First, candidates are screened for affinity to GDF6. Second, candidates are screened for ability to block interaction between GDF6 and its receptor. Third, candidates are evaluated for ability to inhibit downstream signaling via SMAD1 pathway. After selection of final candidates, we will use a xenograft model to determine ability to inhibit melanoma growth in vivo. Currently, we have identified antibodies that are able to recognize GDF6 via western blot, and are proceeding to screen these antibodies for anti-GDF6 activity.

Differences in Complication Rates Between Roux-en-Y Gastric Bypass and Longitudinal Sleeve Gastrectomy

Zachary Weitzner, University of Massachusetts Medical School
Julie Flahive, University of Massachusetts Medical School
Gordon Fitzgerald, University of Massachusetts Medical School
Donald Czerniach, University of Massachusetts Medical School
Philip Cohen, University of Massachusetts Medical School
John Kelly, University of Massachusetts Medical School
Richard A. Perugini, University of Massachusetts Medical School

12:30 PM

Introduction: Sleeve Gastrectomy (SG) has surpassed Roux-en-Y Gastric Bypass (RYGB) as the most commonly performed bariatric operation. Though the beneficial effect of SG on Type 2 Diabetes Mellitus is less than that of RYGB, it is perceived to have a lower complication rate. The purpose of this study was to quantify the complication rates between of SG and RYGB in a severely obese diabetic population.

Methods: This was a retrospective cohort study that included all diabetic patients undergoing RYGB and SG at an academic medical center from January 1, 2011 to July 1, 2015. Patients were followed at 6 week, 6 month, 1 year, 2 year, and 3 year postoperatively. Outpatient and emergency visits were identified in the EMR system. Continuous data was analyzed using Student T tests and discrete data was analyzed using Fisher’s Exact Test. We defined early complications as those occurring within 30 days postoperatively, and late complications as those after 30 days.

Results: A total of 96 patients underwent RYGB and 89 underwent SG. The groups were concurrent and similar with regards to preoperative demographic factors such as age, gender, Hgb-A1c, HOMA2 parameters, excess body weight, BMI, and diabetic medication use. In terms of early complications, the rate of hemorrhage requiring transfusion was higher in the SG group compared to RYGB (10.1% vs. 3.1%, p=0.073). Postoperative length of stay was lower in the SG group (m=1.7 d vs. m=2 d, p=0.02), but the early readmission rate was also higher in the SG group (7.9% vs. 2.1%, p=0.09). For late postoperative complications, there were 4 anastomotic ulcer perforations and one case of internal hernia in the RYGB group. There were 6 late postoperative reoperations in the RYGB group (6% vs. 0%, p=0.03). In addition, 13 patients underwent 16 total upper endoscopies in the RYGB group (13.5% vs. 0%, p=0.0002). The cumulative rate of early and late interventions was higher in the RYGB group (20% vs. 3.4%, p=0.0005).

Conclusions: While the rate of early postoperative complication is similar between SG and RYGB, the need for late intervention is higher after RYGB. The cumulative need for reintervention (early and late) is higher after RYGB. This may explain the shift from Roux-en-Y Gastric Bypass to Sleeve Gastrectomy as the most commonly performed bariatric intervention.

Discovery and Development of Human Monoclonal Antibodies to Block RhD Alloimmunization During Pregnancy

Tushar Gupta, University of Massachusetts Medical School
Melissa Gawron, University of Massachusetts Medical School
Colby A. Souders, University of Massachusetts Medical School
Michael A. Brehm, University of Massachusetts Medical School
Dale Greiner, University of Massachusetts Medical School
Leonard D. Shultz, The Jackson Laboratory
Smita Jaiswal, University of Massachusetts Medical School
Sean McCauley, University of Massachusetts Medical School
Ann Dauphin, University of Massachusetts Medical School
Jeremy Luban, University of Massachusetts Medical School
Lisa Cavacini, University of Massachusetts Medical School

12:30 PM

Exposure of an Rh negative mother to red blood cells (RBCs) of an Rh positive fetus results in alloimmunization and development of anti-RhD antibodies. The anti-RhD antibodies cause hemolytic disease of the new born babies during subsequent pregnancies. Current prophylactic treatment involves polyclonal anti-RhD IgG purified from plasma of humans and is administered in approximately 20% of pregnancies. While the current prophylaxis is effective, it involves the use of human plasma and non-RhD specific antibodies, thus posing a risk of transmitting infections and undesired antibody reactions. Moreover, there is a serious scarcity of plasma donors to meet the requirement of anti-RhD antibodies. In this study we propose to discover and develop anti-RhD monoclonal human antibodies to replace the current polyclonal prophylaxis. We are using humanized BLT mice (fetal CD34+ stem cells, liver and thymus) reconstituted with RhD negative donor material and were immunized by using adenovirus containing RhD transgene. Serum samples were collected after 4-6 weeks of immunization. Our results show that the RhD immunized mice had considerably higher titer of IgG and IgA antibodies in the serum compared to the control, suggesting an immune response developed upon immunization. Splenocytes from antibody producing mice will be fused with a human fusion partner for the isolation of hybridomas producing human monoclonal antibodies. The immunoreactivity and functional activity of these antibodies will be discussed.

Does the Indication for Breast Surgery Impact Surgical Outcomes? A Contemporary Analysis of the ACS-NSQIP Database

Connie Lee, University of Massachusetts Medical School
Ann-Kristin U. Friedrich, University of Massachusetts Medical School
Anne C. Larkin, University of Massachusetts Medical School
B. Marie Ward, University of Massachusetts Medical School
Ashling O'Connor, University of Massachusetts Medical School
Robert M. Quinlan, University of Massachusetts Medical School
Giles F. Whalen, University of Massachusetts Medical School
Jennifer LaFemina, University of Massachusetts Medical School

12:30 PM

Background. There is limited data about whether perioperative outcomes differ based on the indication for breast surgery. Herein we aim to assess if breast surgery for prophylaxis, compared to that for malignancy, impacts surgical outcomes.

Methods. All women who underwent simple or subcutaneous mastectomy were identified from the 2007-2012 ACS-NSQIP database. Patients were identified by their ICD-9 codes and categorized into two groups. Group 1 consisted of patients diagnosed with breast cancer or carcinoma in situ; group 2 consisted of patients diagnosed with a genetic predisposition to malignant neoplasm of the breast (i.e., BRCA mutation). Demographic and preoperative variables were compared between groups and outcome variables. Outcome variables were analyzed using age- and operative time-adjusted logistic regression models.

Results. 30,803 patients were identified. Group 1 consisted of 30,644 (99.5%) patients diagnosed with malignancy; group 2 consisted of 159 (0.5%) who underwent prophylactic surgery. In univariate analyses, those undergoing prophylactic surgery were significantly younger (p < 0.01). There were no other preoperative differences between groups. When adjusted, the prophylactic group demonstrated a greater risk of DVT (p = 0.03). There were no differences in mortality, superficial/deep/organ space infections, UTI, wound dehiscence, or MI.

Conclusion. In this analysis of a national cohort of breast surgery patients, those undergoing prophylactic surgery due to a genetic predisposition had a greater risk of perioperative DVT, compared to those who underwent surgery for a diagnosis of malignancy. This data may allow for improved perioperative management of patients to prevent DVT development and their devastating consequences.

Effect of Left Atrial Function Index on Late Atrial Fibrillation Recurrence after Pulmonary Vein Isolation

Mayank Sardana, University of Massachusetts Medical School
Owusu Asamoah, University of Massachusetts Medical School
Glenn Stokken, University of Massachusetts Medical School
Matthew Spring, University of Massachusetts Medical School
Amir Y. Shaikh, University of Massachusetts Medical School
Adedotun Ogunsua, University of Massachusetts Medical School
Barinder Hansra, University of Massachusetts Medical School
Deego Mohamud, University of Massachusetts Medical School
Michael Gagnier, University of Massachusetts Medical School
Summer Aldrugh, University of Massachusetts Medical School
Nada Esa, University of Massachusetts Medical School
Kevin C. Floyd, University of Massachusetts Medical School
Clifford Browning, University of Massachusetts Medical School Worcester
Cynthia Ennis, University of Massachusetts Medical School
Kevin Donahue, University of Massachusetts Medical School
Lawrence S. Rosenthal, University of Massachusetts Medical School
Gerard P. Aurigemma, University of Massachusetts Medical School
David D. McManus, University of Massachusetts Medical School

12:30 PM

Background: Although the rates of catheter ablation (CA) for atrial fibrillation (AF) are rapidly increasing, there are few predictors of outcome to help inform appropriate patient selection for this procedure. Traditional echocardiographic measures of atrial structure do not significantly reclassify risk of AF recurrence over and above the clinical risk factors. Left Atrial Function Index (LAFI) is a rhythm-independent measure of atrial function. We hypothesized that baseline LAFI would relate to AF recurrence after CA.

Methods: Pre-procedural echocardiograms from 170 participants, who underwent CA for AF and were enrolled in the UMMC AF Treatment Registry, were analyzed. LAFI was calculated by a previously validated formula. Primary outcome was late or clinically significant AF recurrence 3-12 months after CA. Baseline clinical, laboratory and echocardiographic variables were compared between the recurrence and non-recurrence groups.

Results: Study participants were middle aged (60+/10 years) and had a moderate-to-severe burden of cardiovascular comorbidities. 78 participants (46%) experienced late AF recurrence. Mean LAFI was 0.26+/-0.18. In multivariate analysis, lower LAFI was independently associated with the risk of recurrence (0.23 in recurrence group vs 0.29 in non-recurrence group, p < 0.01). Predictive value of LAFI for AF recurrence was similar to CHADS2 score (c-statistic 0.60 vs 0.58, p 0.76). In subgroup of patients with persistent AF, LAFI predicted AF recurrence more strongly than CHADS2 score (c-statistic: 0.79 vs 0.58, p 0.02).

Conclusions: In our cohort of 170 participants with AF undergoing index CA ablation, we observed that LAFI related to late AF recurrence after CA, independent of the traditional risk factors. Since LAFI can be calculated from almost any traditional echocardiographic recording, our findings suggest that LAFI may help guide therapeutic decision-making regarding application of CA, particularly among challenging patients with symptomatic persistent AF.

Effective Pain Information Pre-operatively is Associated with Improved Functional Gain after Total Joint Replacement

Celeste A. Lemay, University of Massachusetts Medical School
David Ayers, University of Massachusetts Medical School
Patricia D. Franklin, University of Massachusetts Medical School

12:30 PM

Objective: We evaluated receipt of pre-operative pain management education in a national prospective cohort on post-operative pain and function.

Methods: Preoperative, 2 week and 6 month postoperative data from a nationally representative cohort of 1404 primary unilateral TJR patients with a date of surgery between May 2011 and December 2014. Data included demographics, comorbid conditions, operative joint pain severity (HOOS/KOOS), musculoskeletal disease burden, physical function (SF36 PCS), and mental health (SF36 MCS). At 2 weeks post-op, patients were asked if they had received information prior to surgery about pain management options and if so, how helpful the information was. Additionally, patients were asked about use of non-medication methods to relieve operative joint pain. Descriptive statistics were performed.

Results: One third reported not receiving information about pain management; an additional 11% did not find it helpful. There were no differences pre-operatively in demographics, comorbid conditions, operative joint pain severity, musculoskeletal disease burden, SF36 PCS and MCS between those who received information and those who did not. Patients who received information about pain management options were more likely to use non-medication methods to relieve operative joint pain (p< 0.000). They reported less current pain (p = 0.02) and maximum pain (p = 0.03) in their operative joint at 2 weeks post-op. At 6 months post-op, patients who reported not receiving information about pain management had statistically lower physical function scores that those receiving information (p = 0.04). There was no difference in HOOS/KOOS pain scores 6 months post-op.

Conclusion: More than 40% of TJR patients in this study reported that they did not receive or received unhelpful information regarding post-op pain management options, highlighting a need for more consistent patient education. In this study, the lack of pain management information appears to negatively impact 6 month post-operative function.

Emergency Medicine Providers Systematically Underestimate Their Opioid Prescribing Practices

Sean S. Michael, University of Massachusettts Medical School
Kavita Babu, University of Massachusetts Medical School
Christopher Androskl Jr., University of Massachusetts Medical School
Martin A. Reznek, University of Massachusetts Medical School

12:30 PM

Background: Opioid misuse is a known public health problem, nationwide and in Massachusetts. The Massachusetts Hospital Association (MHA) developed recommendations to address opioid prescribing in the ED setting, and UMassMemorial Health Care recently implemented a system-wide opioid practice guideline mirroring the MHA policy. Little is known about methods to influence behavior change among ED providers related to opioid prescribing practices. Guideline implementation provided a unique opportunity for a natural experiment related to prescribing patterns, and we hypothesized that a simultaneous experimental intervention to provide clinicians with their individual prescribing data would alter their practices beyond any effect achieved solely by being subject to the new guidelines.

Methods: As part of an ongoing, prospective, randomized trial of an intervention hypothesized to influence providers’ opioid prescribing, we developed a survey instrument consisting of graphical depictions of the distributions of three measures of opioid prescribing among all ED providers at four UMass-affiliated EDs (attending and resident physicians and advanced practice providers). Clinicians randomized to the intervention arm were asked to identify his/her perceived position on each distribution. We compared each provider’s self-perception to their actual decile.

Results: Fifty-one providers were randomized to the intervention arm. Forty-eight completed the survey (94%). Providers underestimated their decile of opioid prescriptions per hundred total prescriptions by a median of one decile (p=0.0399 for difference from zero). Attendings underestimated their decile of percentage of patients dispositioned with an opioid prescription by a median of two deciles (p=0.0292), while residents did not exhibit a significant difference. Providers showed systematic disagreement with their raw number of prescriptions for extended-release opioid formulations (kappa -0.18), underestimating by a median of one.

Conclusions: Based upon three measures of ED opioid prescribing, providers’ self-perceptions of their practices systematically underestimated their actual prescribing, which likely has implications related to efforts to influence clinician behavior change.

ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer

Shuai Gao, University of Massachusetts Boston
Huihui Ye, Beth Israel Deaconess Medical Center
Sean Gerrin, Beth Israel Deaconess Medical Center
Hongyun Wang, Beth Israel Deaconess Medical Center
Ankur Sharma, Thomas Jefferson University
Sen Chen, Beth Israel Deaconess Medical Center
Akash Patnaik, University of Chicago
Adam Sowalsky, National Cancer Institute
Olga Voznesensky, Beth Israel Deaconess Medical Center
Wanting Han, University of Massachusetts Boston
Ziyang Yu, Beth Israel Deaconess Medical Center
Elahe Mostaghel, Fred Hutchinson Cancer Research Center
Peter S. Nelson, Fred Hutchinson Cancer Research Center
Mary-Ellen Taplin, Dana-Farber Cancer Institute
Steven P. Balk, Beth Israel Deaconess Medical Center
Changmeng Cai, University of Massachusetts Boston

12:30 PM

Purpose: ErbB2 signaling appears to be increased and may enhance AR activity in a subset of CRPC, but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer (PCa), and determine whether it may contribute to androgen receptor (AR) signaling in these tumors.

Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone, and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model.

Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients, and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors, while ERBB2 message level was not changed. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Inhibitors targeting ErbB2/PI3K/AKT pathway disrupt AR transcriptional activity. Furthermore, concomitantly treating CRPC xenograft with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression.

Conclusions: ErbB2 signaling is elevated in a subset of abiraterone-resistant prostate cancer patients and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity.

Estimated and self-reported workloads and lower extremity symptoms for nurses and nursing assistants

Alicia Kurowski, University of Massachusetts Lowell
Laura Punnett, University of Massachusetts Lowell

12:30 PM

Objectives and Significance: In US nursing homes, nursing assistants (NAs) are responsible for direct care and resident handling, while nurses’ roles consist primarily of medication distribution and administrative duties. This study examines differences in observed physical exposures and self-reported knee and ankle symptoms of nurses and NAs.

Methods: Observations of clinical staff’s postures and handling were made at fixed time intervals using the PATH Method. An additive physical workload index (PWI) was computed to compare LE workload of NAs and nurses. The PWI combined observed frequencies of postures and handling with their associated forces on the knee and ankle derived from the University of Michigan’s 3D Static Strength Prediction Program. Additionally, surveys on health and working conditions were distributed to employees at 24 nursing homes. Knee and ankle symptoms in the past three months and physical demands were examined by clinical job.

Results: Frequencies of postures and handling input into the PWI were based on observations of 275 NAs and 40 nurses. The analysis of PWI for the LE demonstrated higher physical exposures on both the knee and ankle for NAs compared to nurses, especially while NAs were performing resident handling. Among survey participants (n = 1467), NAs reported higher mean physical exertion scores than nurses and also higher frequencies of knee and ankle symptoms (p=0.0076) in the previous three months.

Conclusions: In this study, both estimated and self-reported physical workloads were higher among NAs compared to nurses. LE symptoms were also more common among NAs. Safe handling equipment helps reduce some LE exposures for NAs, but interventions for other strenuous tasks should be considered to reduce LE pain symptoms, such as introducing lighter food carts often pushed by NAs and limiting the number of dirty linens bagged before transporting to the soiled linen drop-off.

Geometric Control of YAP-dependent Mechanotransduction: A Proposed Model

Ngozi A. Eze, Worcester Polytechnic Institute
Heather A. Cirka, Worcester Polytechnic Institute
Kristen L. Billiar, Worcester Polytechnic Institute

12:30 PM

The Billiar lab is interested in the interplay between mechanical tension and programmed cell death (namely, apoptosis) in cells growing on micro-contact printed aggregates. The Billiar lab uses a bioinspired hydrogel to develop an in vitro model for mechanosensitive signaling in mammalian cells. The micro-contact printed cell aggregates experience a loss of tensional homeostasis at the center of the aggregates, which results in selective cell death at the center, but not periphery of the aggregates, followed by calcification, similar to excised diseased aortic valves. However, the subcellular mechanisms responsible for transducing the mechanical cues from the loss of tensional homeostasis to pro-apoptotic signaling have yet to be elucidated; the Billiar lab is interested in finding this link.

Mechanotransduction is the functional link between mechanical cues and the consequent subcellular biochemical response.1 Cells sense and respond to their physical surroundings via cell-cell junctions, cell-matrix adhesions, and intracellular actin networks.1 For example, in epithelial cells, restriction of cell growth to spatially patterned circular arrays leads to (1) increased proliferation and (2) higher tractional stresses at the periphery than at the center.2-3 Proliferation at the periphery of these circular cell aggregates is YAP-dependent, with nuclear localization of YAP at the periphery.4 Transcriptional co-activator YAP is (1) a nuclear relay of mechanical signals,5 (2) the main transcriptional effector of the Hippo pathway,6 and (3) involved in both proliferation (via TEAD promoter) and apoptosis (via p73 promoter).7 Cell competition is an apoptosis-dependent cell communication phenomenon based on cell fitness comparisons, and which creates “loser” cells that die via apoptosis and “winner” cells that survive.8-9 For example, co-culture of TEAD-activity-manipulated fibroblasts with WT induces cell competition, in which cells with higher TEAD activity “won,” and cells with lower TEAD activity “lost” (underwent apoptosis).10

Hypothesis: Culture of fibroblasts in geometrically constrained, circular cell aggregates induces cell competition via the formation of “winner” and “loser” cell populations due to differences in tensional homeostasis experienced at the periphery vs. center of the aggregates.

Health Applications of Social Network Analysis and Computational Social Science

James Kitts, University of Massachusetts Amherst

12:30 PM

Social network analysis has proliferated across the social and behavioral sciences, shifting our analytical focus from individuals to the patterns of social ties that connect them. This perspective has enriched our understanding of a great variety of health-related phenomena, including the spread of STDs on contact networks, the spread of health care practices on physicians’ professional networks, the dynamics of patient transfers on networks of clinics, and the spread of weight-related behaviors among adolescents at risk for obesity. The advent of the era of computational social science has augmented the contributions of this perspective, by moving beyond expensive and laborious methods of questionnaires and direct observation to incorporate new techniques of data collection and analysis. For example, these include analysis of electronic health records or other time-stamped communication traces among healthcare practitioners; streams of behavioral data from wearable sensors, location-aware devices, or electronic calendars; automated analysis of text in documents; and mapping networks of interaction by citations and collaboration in clinical research literatures. Whereas much of computational social science has offered new ways of monitoring health behavior and healthcare behavior, or for analyzing those data, a further contribution has been to directly analyze these social processes in system dynamics models, microsimulation, and agent-based models. These approaches allow for computational experiments that assist in predicting and interpreting outcomes from health interventions. This poster will highlight some of my recent and pending work in this domain, aiming to identify potential collaborators in UMCCTS for projects that involve social networks or computational social science.

Herpes Zoster and Cardiovascular Events in Adults: A Systematic Review

Nathaniel A. Erskine, University of Massachusetts Medical School
Hoang Tran, University of Massachusetts Medical School
Len L. Levin, University of Massachusetts Medical School
Christine M. Ulbricht, University of Massachusetts Medical School
Joyce D. Fingeroth, University of Massachusetts Medical School
Catarina I. Kiefe, University of Massachusetts Medical School
Robert J. Goldberg, University of Massachusetts Medical School

12:30 PM

Background: Stroke and myocardial infarction have been reported to occur after the development of herpes zoster (shingles), a common and preventable disease.

Purpose: To evaluate literature describing the association between herpes zoster and its subtypes with the occurrence of cardiovascular events.

Data Sources: PubMed, SCOPUS (Embase), OAIster, Google Scholar (searched in January 2016)

Study Selection: Studies published up to January 2016 examining the association between herpes zoster or subtype of herpes zoster with the occurrence of cardiovascular events, including stroke, transient ischemic attack, or an acute coronary event, were selected. Case reports, case studies, and studies of non-general adult populations were excluded.

Data Extraction: Data from studies meeting criteria were abstracted on a standardized form, and evaluated following modified set of standard guidelines.

Data Synthesis: Nine published articles, with study populations ranging from 2,632 to 4,620,980 patients, met our pre-defined eligibility criteria. Eight studies found at least one positive association between herpes zoster type unspecified and subsequent stroke, transient ischemic attack, or an acute coronary event. Five studies found positive associations between herpes zoster ophthalmicus and stroke or myocardial infarction. Subgroup analyses from three studies were inconsistent regarding the association of cardiovascular events with receipt of antiviral therapy for herpes zoster.

Limitations: Excludes non-English publications and non-published evidence.

Conclusions: A small number of studies showed greater risks of stroke, transient ischemic attack, and acute cardiac events following the development of herpes zoster and herpes zoster ophthalmicus. Further prospective studies should develop strategies to reduce the risk of cardiovascular disease among patients with herpes zoster.

Hospice and pain management in nursing home residents with cancer

Jacob N. Hunnicutt, University of Massachusetts Medical School
Jennifer Tjia, University of Massachusetts Medical School
Kate L. Lapane, University of Massachusetts Medical School

12:30 PM

Background: The prevalence of untreated pain in nursing home residents with cancer is unacceptably high. Hospice may increase the likelihood of receiving pain management at the end of life.

Objectives: To estimate whether receipt of hospice in nursing homes increases the receipt of pain management for nursing home residents with cancer at the end of life.

Methods: We conducted a cross-sectional study on a national sample of Medicare decedents who had cancer and were nursing home residents during the last 90 days of life in 2011–2012. We used the last Minimum Data Set (MDS) 3.0 assessment before death and the Medicare Beneficiary Summary File to measure hospice use, pain, and pain management at the last MDS assessment. We matched residents with cancer and in pain who received hospice care to residents in pain not receiving hospice care on nursing home facility and time from last MDS assessment to death. The primary outcomes were receipt of pharmacologic pain management including scheduled and PRN analgesics and non-pharmacologic pain management. Conditional logistic models were used to estimate the association between hospice use and pain management.

Results: In matched analyses, untreated pain was uncommon (2.9% in hospice users and 5.6 in non-hospice users), though there was an absolute difference of 15.4% in scheduled analgesics use between hospice and non-hospice users (71.5% vs. 56.1%, respectively). Hospice use was associated with receipt of scheduled analgesics (adjusted Odds Ratio(aOR): 1.85, 95% Confidence Interval(CI):1.73–1.97), PRN medication (aOR: 1.31, 95% CI:1.20–1.43), and non-pharmacologic pain management (aOR: 1.18, 95% CI:1.11–1.26).

Conclusions: Untreated pain at the end of life among nursing home residents with cancer was unusual. Hospice use was associated with increased pain management in nursing home residents with documented pain. Further work to examine the type and effectiveness of pain management strategies used is warranted.

Human monoclonal antibodies to Plasmodium falciparum circumsporozoite protein for transient passive protection of malaria travelers to endemic areas

Stuart Nelson, University of Massachusettts Medical School
Douglas Golenbock, University of Massachusetts Medical School
Ann M. Moormann, University of Massachusetts Medical School
Colby A. Souders, University of Massachusetts Medical School
Lisa Cavacini, University of Massachusetts Medical School

12:30 PM

Plasmodium falciparum, is a protozoa that causes over 214 million cases of Malaria worldwide and the World Health Organization reported an estimated 438,000 deaths attributed to malaria in 2015. Current prevention strategies have reduced malaria cases but they are either costly, have poor efficacy or resistance has begun to develop. There is a global need for an effective pre-exposure prophylaxis treatment.

The leading Malaria vaccine candidate is RTS,S which contains a monovalent Plasmodium falciparum circumsporozoite protein (CSP). The goal of this vaccine is to induce anti-CSP antibodies that would block sporozoite invasion of hepatocytes and thereby hinder parasite development into a blood-stage infection that causes malaria morbidity and mortality. Antibodies isolated from individuals who have received the RTS,S vaccine have been shown to prevent infection of hepatocytes, suggesting that CSP antibodies could be used prophylactically. However, phase III trial results of the vaccine have shown underwhelming efficacy in children.

Growing resistance to transient protection strategies for travelers and low efficacy in vaccine trials suggest there is a need for a new treatment strategy. The generation of CSP specific human monoclonal antibodies (mAbs) would be useful as prevention especially for individuals that are temporarily exposed to Malaria in endemic regions such as travelers or military personnel.

Isolation and production of therapeutic mAbs traditionally utilizes a handful of techniques including antibody engineering, phage display or hybridoma generation from transgenic mice. We have sorted antigen-specific memory B-cells from the peripheral blood of children naturally infected with malaria to isolate CSP-specific memory B-cells. These cells were individually sorted and PCR was performed to amplify antibody variable regions of the B-cell’s antibody mRNA. Samples that produced heavy and light chain antibody sequence were cloned and transiently expressed. We plan to characterize these mAbs for binding and neutralization of CSP to identify functional therapeutic mAbs.

Humanized Mice for the Generation of HIV-1 Human Monoclonal Antibodies

Melissa Gawron, University of Massachusetts Medical School
Mark Duval, University of Massachusetts Medical School
Michael A. Brehm, University of Massachusetts Medical School
Dale Greiner, University of Massachusetts Medical School
Leonard D. Shultz, The Jackson Laboratory
Smita Jaiswal, University of Massachusetts Medical School
Sean M. McCauley, University of Massachusetts Medical School
Ann Dauphin, University of Massachusetts Medical School
Jeremy Luban, University of Massachusetts Medical School
Lisa Cavacini, University of Massachusetts Medical School

12:30 PM

Background: Despite the length of time HIV has been wreaking havoc on its victims, improvements in the prevention and treatment of HIV are needed. Anti-retroviral therapy can be effective but is expensive and not entirely accessible for people infected in third world countries. Several promising broadly neutralizing antibodies have been isolated from infected individuals; we propose that generating antigen specific human monoclonal antibodies using humanized mice further represents a promising approach to engineer prophylactic antibodies to reduce spread and infection of HIV.

Methods: Immunodeficient mice were engrafted with fetal liver and thymus (BLT) prior to infection with different HIV isolates. HIV infection of the mice was monitored by viral load and antibody response followed by ELISA using gp120, gp41 or gp120/CD4 complex as antigens. Approximately 8-12 weeks post infection, spleens were harvested and splenocytes fused with human fusion partner HMMA 2.5 to isolate antibody-expressing hybridomas. Lead clones were scaled and purified for testing in functional assays such as TZM-bl neutralization assays as well as ADCVI to determine neutralizing and cytotoxic ability of the antibodies. Antibody sequences were also determined for analysis.

Results: A robust, specific antibody response, of both IgG and IgA isotypes, was generated in response to HIV infection. Over 60 hybridomas were created that were not only immunoreactive with env antigens, but also had neutralization activity. Moreover, variable family usage was not limited and somatic mutation was clearly evident.

Conclusions: These findings suggest that humanized BLT mice are a novel source for well-characterized, stable human monoclonal antibodies to HIV.

Identification of fully human monoclonal antibodies against the adhesin domain of colonizing factor antigen I of Escherichia coli

Maja Sedic, University of Massachusetts Medical School
Danielle Wisheart, University of Massachusetts Medical School
Monir Ejemel, University of Massachusetts Medical School
Matteo Stoppato, University of Massachusetts Medical School
Serena Giuntini, University of Massachusetts Medical School
Eileen Barry, University of Maryland
William D. Thomas, University of Massachusetts Medical School
Mark S. Klempner, University of Massachusetts Medical School
Yan Wang, University of Massachusetts Medical School

12:30 PM

Enterotoxigenic Escherichia coli (ETEC) causes significant diarrheal illness in infants in the developing world and travelers to endemic countries including military personnel. Infection of the host involves bacterial colonization of the small intestinal epithelium and toxin secretion leading to watery diarrhea. CFA/I is the most common colonizing factor antigens expressed on the surface of ETEC isolates. The CFA/I adhesin, CfaE, appears to be required for ETEC binding to human intestinal cells for colonization. Human antibodies against the binding domain of CfaE have potential to block colonization of ETEC and serve as a potent immunoprophylactic therapeutic for ETEC-related diarrhea.

In the current study, we generated a panel of fully human monoclonal antibodies (HuMabs) against the adhesin domain of CfaE using mice transgenic for human immunoglobulin genes and identified lead antibodies utilizing a series of in vitro assays. Mice were immunized with the N-terminal binding domain of CfaE fused to maltose binding protein. Over thirty unique IgG1 HuMabs were identified with binding activity to recombinant CfaE. These antibodies were tested for inhibition of hemagglutination of type A human erythrocytes by ETEC. Two lead HuMabs, 837-6 and 840-53, inhibited hemagglutination at low concentrations (< 1 nM). Both antibodies also blocked the binding of ETEC with intestinal epithelial cells. Biacore analysis revealed an affinity of less than 2 nM with distinct epitopes of CfaE. Our analysis suggests that CfaE specific HuMabs 837-6 and 840-53, as the first isolated fully human monoclonal antibodies against CfaE adhesion domain, could potentially be used in combination with heat labile toxin neutralizing antibodies to prevent traveler’s diarrhea.

Identification of GDF-6 blocking antibodies as anti-melanoma therapeutics

Ejemel Monir, University of Massachusetts Medical School
Danielle Wisheart, University of Massachusetts Medical School
Alec Gramann, University of Massachusetts Medical School
Arvind Venkatesan, University of Massachusetts Medical School
Mark S. Klempner, University of Massachusetts Medical School
Craig J. Ceol, University of Massachusetts Medical School
Yang Wang, University of Massachusetts Medical School

12:30 PM

Through comparative oncogenomic studies and functional analyses, we have identified the bone morphogenetic protein (BMP) factor GDF6 as a new melanoma oncogene. The secreted, carboxy-terminal portion of GDF6 is the active form that binds to cell-surface receptors to initiate BMP signaling. Targeted antibodies directed against secreted proteins are a proven therapeutic modality in several diseases.

To develop therapeutic antibodies against the active form of GDF6, we generated a panel of monoclonal antibodies. Due to the high similarity of human and mouse GDF6 proteins, the C-terminal GDF6 protein was expressed as bacterial recombinant protein with fusion tags to enhance immunogenicity. The Expresso Screening System (Lucigen) was used to select fusion tags, and MBP and SlyD were chosen for optimal protein solubility and purification recovery. Ten CD1 mice were immunized with GDF6-MBP fusion protein and robust immune responses were observed in all animals after 5 immunizations. Animals were sacrificed for hybridoma fusion, and hybridoma clones were screened by ELISA using GDF6-SlyD fusion protein to select clones with specific binding activity to GDF6. Over 70 monoclonal antibodies were identified with strong reactivity to GDF6, and a subset has been shown to recognize the endogenous, secreted form of GDF6 via western blot. These antibodies will be screened for their activity to block GDF6 binding to melanoma cells and ability to inhibit downstream signaling using both in vitro assays and in vivo xenograft models.

Immune features that afford protection from clinical disease versus sterilizing immunity to Bordetella pertussis infection in a nonhuman primate model of whooping cough

Keith A. Reimann, University of Massachusetts Medical School
Aaron J. Belli, University of Massachusetts Medical School
Sarah Fulco, University of Massachusetts Medical School
Jason M. Warfel, Food and Drug Administration
Rijian Wang, University of Massachusetts Medical School
Lisa Cavacini, University of Massachusetts Medical School
James F. Papin, University of Oklahoma Health Sciences Center
Steven F. Merkel, Temple University School of Medicine
Tod J. Merkel, Food and Drug Administration
Mark S. Klempner, University of Massachusetts Medical School

12:30 PM

The respiratory bacterial infection caused by Bordetella pertussis (whooping cough) is the only vaccine-preventable disease whose incidence has been increasing over the last 3 decades. To better understand the resurgence of this infection, a baboon animal model of pertussis infection has been developed. Naïve baboons that recover from experimental pertussis infection are resistant both to clinical disease and to airway colonization when re-challenged. In contrast, animals vaccinated with acellular pertussis vaccine and experimentally challenged do not develop disease, but airways remain colonized for 4-6 weeks. We explored the possibility that the IgG antibody response to pertussis infection is qualitatively different from antibodies induced by acellular pertussis vaccination.

IgG was purified from pertussis-convalescent baboons shown to be resistant to pertussis disease and airway colonization. Purified IgG contained high titers to pertussis toxin, pertactin, and filamentous hemagglutinin. This pertussis-immune IgG or control IgG was passively transferred to naïve, juvenile baboons before experimental airway pertussis inoculation. The control animal that received normal IgG developed a typical symptomatic infection including leukocytosis, cough and airway colonization for 4 weeks. In contrast, baboons that received convalescent IgG maintained normal WBC counts and were asymptomatic. However, despite remaining asymptomatic, their airways were colonized for 4-6 weeks with B. pertussis. All animals developed IgG and IgA anti-pertussis antibody responses. Interestingly, the clearance of B. pertussis from airways coincided with the emergence of a serum anti-pertussis IgA response.

These studies demonstrate that passive administration of pertussis-specific IgG from previously infected animals can prevent clinical disease but does not affect prolonged airway colonization with B. pertussis. This outcome is similar to that observed following acellular pertussis vaccination. Understanding immune mechanisms—other than IgG—that are capable of preventing airway colonization with B. pertussis will be critical for developing more effective vaccines to prevent whooping cough.

Impact of multimorbidity on clinical outcomes in older adults with cardiovascular disease

Mayra Tisminetsky, University of Massachusetts Medical School
Robert J. Goldberg, University of Massachusetts Medical School
Jerry H. Gurwitz, University of Massachusetts Medical School

12:30 PM

Objective: To synthesize the current literature on the magnitude and impact of multiple chronic conditions on clinical outcomes, including total in-hospital and post discharge mortality and hospitalizations, in older patients with cardiovascular disease (CVD).

Methods: A systematic review was conducted. Four electronic databases and article bibliographies were searched for publications from 2005 to 2015 which assessed the impact of multimorbidity on clinical outcomes in the elderly with CVD. Identified studies were screened using pre-defined criteria for eligibility.

Results: Fifteen studies met our inclusion criteria. Multimorbidity was assessed by simple counting of morbidities and by the Charlson and Elixhauser indices. Case-fatality rates ranged from between 13% and 21% for patients with a myocardial infarction. Long-term mortality ranged from 28% to 73% among patients with heart failure, and 24% of patients with heart failure and presenting multimorbidities had at least one readmission during a follow-up period of 17 months. Most of the studies reported a significant association between number of multimorbidities or particular morbidities and the risk of dying, the most frequent morbidities examined were diabetes, chronic kidney disease, anemia, chronic pulmonary disease and dementia/cognitive impairment

Conclusions: There are limited data on the magnitude and impact of multimorbidities on clinical outcomes, and even less data on patient centered outcomes among elderly patients with CVD. There are also inconsistencies in the manner by which multimorbidities are assessed; very few studies have approached the “real” complexity of patients with CVD and multimorbidities and how best to manage these high risk patients.

Implantable Microenvironments to Capture Stable-to- Aggressive Tumor Transition

Ryan Carpenter, University of Massachusetts Amherst
Jungwoo Lee, University of Massachusetts Amherst

12:30 PM

Clinical stability occurs when cancers reach a state where the disease neither advances nor regresses. Tumors can remain in this state for multiple years before progressing to more aggressive phenotypes. The mechanisms for maintaining a stable state and the factors that contribute to tumor activation are poorly understood. We hypothesized that an implantable biomaterial scaffold would be able to isolate a population of stable tumor cells that could then be used to study the transition to an aggressive phenotype. In this work we developed a tunable and highly controlled, porous acrylamide scaffold and subcutaneously implanted them in immunodeficient (NSG) mice. Prior to implantation scaffolds were seeded with a variety of different cell types. Specifically, human bone marrow stromal cells were supplemented with mouse stromal cells genetically engineered to express human cytokines to promote the generation of different tissue microenvironments in the scaffolds. After implantation the mice received an orthotopic injection of either human breast or prostate cancer cells. The tumors were allowed to generate metastases to the scaffolds and other tissues. Scaffolds were transplanted to non-tumor bearing mice once the tumor burden became exhaustive to the host to allow for further study of the microenvironment. The role of immune cells on the tumor microenvironment was also explored. Human peripheral blood mononuclear cells were isolated from donors and injected intravenously prior to transplantation. Bioluminescent imaging was used to capture tumor growth in vivo over a ten week period. The scaffolds were analyzed via immunohistochemical staining on thinly sectioned tissue and intact tissue cleared samples to characterize the tissue microenvironment and its effect on tumor progression. Our work has demonstrated the application of implantable tissue engineered microenvironments to study the phenomena of tumor stability in vivo and has uncovered some potentially important factors that drive the transition from stable to aggressive tumors.

Implementation and Utilization of Mobile Technology In Adolescent Bariatric Surgery Patients

Jonathan Green, University of Massachusetts Medical School
Jeremy T. Aidlen, University of Massachusetts Medical School
Sherry L. Pagoto, University of Massachusetts Medical School
Jennifer Bram, University of Massachusetts Medical School

12:30 PM

Obesity is the most prevalent chronic disease of childhood. Obese adolescents are likely to become obese adults with significant associated co-morbidities and early mortality. In Massachusetts, 30% of children ages 10-17 are overweight or obese. It is projected that 48% of Massachusetts’ adults will be obese by 2030. In March of 2015, the Good Fit Adolescent Weight and Wellness Center opened, with a goal of addressing this issue with a proven multidisciplinary approach.

Mobile technology continues to develop at a rapid pace. Adolescent access to mobile technology on smart phones and tablets continues to increase. Mobile fitness tracker applications are numerous and easy to use for today’s tech savvy teens. Successful weight loss and health maintenance is variable and has been difficult to validate with this technology so far.

The purpose of this study is to evaluate existing mobile applications to be used by adolescent patients in the Good Fit Center. Our aim is to determine whether adolescent patients will be compliant with diet and exercise challenges sent through a mobile application and social media platform. We will work closely with dietitians, physicians and surgeons to evaluate feasibility and compliance within the first year of this project. In the second year, we will then test the functionality of this mobile application as it relates to patient success in the Good Fit program.

The proposed research is a novel multimodal study combining behavioral sciences research, clinical outcomes research, and mobile technology to help to better understand the fitness management of adolescents struggling with morbid obesity. The findings of our research may have a number of important implications. These include the refinement of existing fitness strategies, as well as the development of a new useful piece of technology to combat obesity and improve the health and clinical outcomes of our nation’s children.

Interrogating Plant Cell Culture Library for Novel Antimicrobial Agents

John Solitro, University of Massachusetts Amherst
Yong Zhang, University of Massachusetts Amherst
Vanessa Bartolo, University of Massachusetts Amherst
Alexander Popchuk, University of Massachusetts Amherst
Sergey Savinov, University of Massachusetts Amherst
Lin-Jun Ma, University of Massachusetts Amherst
Jennifer Normanly, University of Massachusetts Amherst
Tristram Seidler, University of Massachusetts Amherst
Elizabeth Vierling, University of Massachusetts Amherst

12:30 PM

The Plant Cell Culture Library (PCCL) at UMass Amherst contains more than 2,200 live plant cell cultures, representing diverse plant species from around the world. The availability of this collection offers a rich resource for us to discover bioactive phytochemicals and uncover their mechanisms of action. Using data-mining surveys of bioactive plant extracts, I have organized subsets of PCCL cell lines that are likely to possess antifungal, antibacterial, antiviral, anthelmintic, anti-trypanosomal, or anticancer properties, which prove to be useful when deciding which species to screen first against a specific pathogen. Another distinct advantage of using the live plant cells in this research is the ability to stimulate the biosynthesis of pathogen-specific phytochemicals upon simulation of an attack (elicitation) by the microorganism in question. This could be accomplished by pathogen homogenates or plant hormones responsible for mounting defenses to infection.

Over the past six months, I have been working to optimize elicitation, lysis, and extraction conditions for obtaining high-throughput screening materials to be used against variable pathogens. Equipped with crude extracts from appropriately elicited cells, I am collaborating with a multidisciplinary team of UMass scientists to develop and implement high-throughput screening protocols for profiling a large number of plant-derived materials against various pathogens. Recently, I have screened a small pool (40) of extracts derived from cell lines with predicted anti-fungal properties against the highly resistant strain of fungus Fusarium oxysporum, one of the causal agents of an opportunistic infection often seen in immunocompromised patients known as fusariosis. Gratifyingly, I have found several plant species that produced specialized metabolites with better antifungal activity than the leading antibiotic against F. oxysporum, Amphotericin B, validating this line of antimicrobial research. We are also actively reaching out to other academic labs partners to form partnerships in diverse antimicrobial research venues.

Lipoaspirate and Adipose Stem Cells as Potential Therapeutics for Chronic Scars

Dylan Perry, University of Massachusetts Medical School
Jorge Lujan-Hernandez, University of Massachusetts Medical School
Michael S. Chin, University of Massachusetts Medical School
So-Yun Min, University of Massachusetts Medical School
Ava Chappell, University of Massachusetts Medical School
Raziel Rojas-Rodriguez, University of Massachusetts Medical School
Raghu Appasani, University of Massachusetts Medical School
Patrick Teebagy, University of Massachusetts Medical School
Silvia Corvera, University of Massachusetts Medical School
Janice F. Lalikos, University of Massachusetts Medical School

12:30 PM

Introduction: Burn injuries can lead to hypertrophic or keloid scars, causing pain and long lasting mobility issues. Current therapies are often unsatisfactory, costly, or morbid. Prior studies suggest adipose derived stem cells (ADSCs) and lipoaspirate can improve scar outcomes of acute thermal wounds. Clinical reports suggest lipoaspirate and ADSCs can improve chronic burn scar remodeling. However, this has not been extensively studied in animal models. We sought to determine if adipose tissue can improve chronic scar remodeling and to compare the effects of ADSCs and processed lipoaspirate.

Methods: 50 CD1 nu/nu athymic mice received a standardized deep partial-thickness thermal burn. Scars matured for 6 weeks. Photographs and perfusion measurements by hyperspectral imaging (HSI) were taken over the entire study. Lipoaspirate and ADSCs (SVF and ex-vivo culture with flow cytometry confirmation) were obtained from a discarded human pannus specimen. After 6 weeks, animals received a 0.6cc subcutaneous graft beneath the scar of either: human lipoaspirate processed with the Coleman technique, high-dose (106) hADSCs in Matrigel, low-dose (104) hADSCs in Matrigel, Matrigel only, or not injected (n=10 per group). At 10 weeks, animals were sacrificed and scar tissue was harvested for histological and molecular analysis.

Results: HSI oxygenated hemoglobin values in lipoaspirate treated scars increased significantly more compared to 6-week pre-treatment baseline than all other groups (p < 0.05). Planimetry analysis showed reduction in wound area in lipoaspirate treated mice compared to control groups (p < 0.01). Blood vessel density quantification on Masson’s trichrome stains suggests increased density in lipoaspirate treated scars versus controls (p < 0.01).

Conclusion: HSI, blood vessel density, and scar analysis suggest improvement in lipoaspirate treated scars compared to controls. Preliminary molecular data offers some insight to this trend. No effect was seen with ADSCs at either concentration at the analyzed timepoints. Molecular analyses are ongoing to investigate cellular mechanisms in regulating scar remodeling.

Long-lasting Effects of Perinatal Exposure to Brominated Flame Retardant on Male Reproductive Outcomes in Rat Model

Ahmed Khalil, University of Massachusetts Amherst
Daneal Portman, University of Massachusetts Amherst
Jake Jensen, University of Massachusetts Amherst
Michael Panchenko, University of Massachusetts Amherst
Alexander Suvorov, University of Massachusetts Amherst

12:30 PM

Meta-analysis of 101 studies published between 1934 and 1996 indicates that mean sperm concentration decreased around 50% during this period. More recent studies have found alarmingly poor semen quality in the general population of Northern Europe. Additional adverse trends include increased incidence of testicular cancer, and congenital malformations such as cryptorchidism and hypospadias. Testicular germ cell cancers increased by about 400% over the period of 50 years in industrialized countries. Decreased quality of male reproductive health has been linked to environmental endocrine disruptors exposure. However, the ability of xenobiotics to produce long-lasting effects and mechanisms of perturbation of the male reproductive system following developmental exposures are not well understood. Both animal experiments and human studies show male reproductive toxicity to polybrominated diphenyl ethers (PBDE), a group of ubiquitous, persistent, and bioaccumulative environmental xenobiotics. Here we report the result of experiment in which pregnant Wistar rats were fed 0.2 mg/kg body weight BDE-47 (the most ubiquitous PBDE congener) daily starting from the eighth day of pregnancy until weaning. Multiple endpoints of male reproductive health were assessed in offspring on postnatal week 20: testis size, sperm production, morphology, motility, circulating testosterone, select gene expression in prostate (qRT-PCR) and all-genome gene expression in testis (RNA-seq). Seventeen weeks after exposure was abolished testis size was significantly smaller in adult rats and genes of inflammatory response were significantly upregulated in testis tissue among other results. Our findings confirm male-reproductive toxicity of PBDE and identify inflammatory response as a long lasting mechanism of repro-toxicity triggered by perinatal exposure.

Microengineering Approaches for Regenerative Medicine

Yubing Sun, University of Massachusetts Amherst

12:30 PM

Stem cells, especially human pluripotent stem cells (hPSCs), hold significant promise for modeling developmental and disease processes, drug and toxicology screening, and cell-based regenerative medicine. Most hPSC studies have so far focused on identifying extrinsic soluble factors, intracellular signaling pathways, and transcriptional regulatory networks involved in regulating hPSC behaviors. We focus on the development and applications of some novel synthetic micromechanical systems to understand the mechano-sensitive and -responsive properties of hPSCs and their functional regulation of self-renewal, directed differentiation, and survival of hPSCs. First, we have demonstrated that rigid PDMS micropost arrays (PMAs) support the maintenance of pluripotency of hPSCs. Blocking cytoskeleton contractility by blebbistatin and inhibiting E-cadherin functions by DECMA-1 antibody both impair mechanoresponsive self-renewal of hPSCs on rigid substrates. We have further achieved efficient neuroepithelial induction, caudalization, and motor neuron differentiation from hPSCs combining soft PMAs (Eeff < 5kPa) with dual Smad inhibition. The purity and yield of functional motor neurons derived from hPSCs within 23 days of culture using soft PMAs were improved four- and twelve-fold, respectively, compared to coverslips or rigid PMAs. Our mechanistic work has helped reveal for the first time that biomechanical cues, including intracellular contractile forces and cell shape, converge and reinforce signal integration of TGF-β, Wnt, Hippo/YAP, Rho GTPase, and the actomyosin cytoskeleton to regulate the neural plate specification. We also developed a novel acoustic tweezing cytometry (ATC) utilizing ultrasound pulses to actuate functionalized lipid-encapsulated microbubbles (MBs) targeted to cell surface integrin receptors to exert subcellular mechanical forces in the pN - nN range. ATC can robustly induce cell traction force changes through acoustic radiation forces and bubble cavitation induced shear stresses. Importantly, ATC stimulations increased the survival rate and cloning efficiency of hESCs by 3-fold, suggesting its potential application in large-scale expansion of hPSCs.

Microfluidic platforms to study host-microbiome interactions

Abhinav Sharma, University of Massachusetts Amherst
Neil Forbes, University of Massachusetts Amherst
Jungwoo Lee, University of Massachusetts Amherst

12:30 PM

About three-quarters of human body surface is exposed to dense microbial population along the gastro-intestinal tract (GIT) that accommodates around 80% of immune cells. The GIT is one of the most critical sites for metabolic and immunologic homeostasis in the body. While large-scale genomic analysis and germ-free mice have been widely used, they are limited to capture the dynamic functional interaction between host-microbiome in a humanized setting. in-vitro recapitulation of GIT physiology can be a powerful alternative for hypothesis testing in diseases like IBD and cancer.

As a first step, we developed a simple transwell assembly to closely emulate GIT anatomy and the barrier function in a quantitative and analytical manner. The system enables us to sequentially house bacterial cells, a mucus layer, human intestinal epithelial cells and human peripheral blood mononuclear cells (hPBMCs) in a single co-culture platform. Porcine intestine-derived mucin formed a biophysically relevant barrier and also provided in-vivo like biochemical milieu to bacterial cells. Addition of human epithelial cell monolayer on a collagen coated semi-permeable membrane added another level of cellular and biophysical complexity. Finally, by introducing human peripheral blood mononuclear cells (hPBMCs), we simulated host-microbiome interactions and successfully captured responses relevant to gut inflammation. Initial data indicate that bacterial products successfully stimulate hPBMCs. Whereas, mucus and epithelial barriers demonstrated strong immunomodulatory functions. Further investigations are being carried out in order to create models that will incorporate differentiated epithelial cells (villi), physiologically relevant flow and stress conditions along with co-culture of aerobic (mucosal) and anaerobic (luminal) components of the human GIT. Hopefully, these models will enable us to study mechanistic interactions of the microbiome with the host and reveal novel therapeutic targets for diseases associated with the dysregulation of host-microbiome homeostasis in human GIT.

Multiple Chronic Conditions and Psychosocial Limitations in a Contemporary Cohort of Patients Hospitalized with an Acute Coronary Syndrome

Mayra Tisminetsky, University of Massachusetts Medical School
Jerry H. Gurwitz, University of Massachusetts Medical School
David D. McManus, University of Massachusetts Medical School
Jane S. Saczynski, University of Massachusetts Medical School
Molly E. Waring, University of Massachusetts Medical School
Nathaniel Erskine, University of Massachusetts Medical School
Milena D. Anatchkova, University of Massachusetts Medical School
David C. Parish, Mercer University
Darleen M. Lessard, University of Massachusetts Medical School
Catarina I. Kiefe, University of Massachusetts Medical School
Robert J. Goldberg, University of Massachusetts Medical School

12:30 PM

Background: As adults live longer, multiple chronic conditions have become more prevalent over the past several decades. We describe the prevalence of, and patient characteristics associated with, cardiac and non-cardiac-related multimorbidities in patients discharged from the hospital after an acute coronary syndrome (ACS).

Methods: We studied 2,174 patients discharged from the hospital after an ACS at 6 medical centers in Massachusetts and Georgia between April, 2011 and May, 2013. Hospital medical records yielded clinical information including presence of 8 cardiac-related and 8 non-cardiac-related morbidities on admission. We assessed multiple psychosocial characteristics during the index hospitalization using standardized in-person instruments.

Results: The mean age of the study sample was 61 years, 67% were men, and 81% were non-Hispanic whites. The most common cardiac-related morbidities were hypertension, hyperlipidemia, and diabetes (76%, 69%, and 31%, respectively). Arthritis, chronic pulmonary disease, and depression (20%, 18%, and 13%, respectively) were the most common non-cardiac morbidities. Patients with ≥4 morbidities (37% of the population) were slightly older and more frequently female than those with 0-1 morbidity; they were also heavier and more likely to be cognitively impaired (26% vs. 12%), have symptoms of moderate/severe depression (31% vs. 15%), high perceived stress (48% vs. 32%), a limited social network (22% vs. 15%), low health literacy (42% vs. 31%), and low health numeracy (54% vs. 42%).

Conclusions: Multimorbidity, highly prevalent in patients hospitalized with an ACS, is strongly associated with indices of psychosocial deprivation. This emphasizes the challenge of caring for these patients, which extends well beyond ACS management.

Neighborhood Differences in the Availability of Healthy Foods in the City of Worcester

Kevin Kane, University of Massachusetts Medical School
Maximilian Hoffman, University of Massachusetts Medical School
Jie Cheng, University of Massachusetts Medical School
Barbara C. Olendzki, University of Massachusetts Medical School
Wenjun Li, University of Massachusetts Medical School

12:30 PM

INTRODUCTION. Neighborhood food environment is important to healthy eating. The availability and proximity of healthy foods has been shown to affect dietary quality, obesity, and overall health. We surveyed food stores throughout City of Worcester to assess the variability of food availability in neighborhoods and inequalities in access to fresh produce, unprocessed foods, and other healthy food options by neighborhood socioeconomic status (N-SES).

METHODS. Where permitted by the store manager, the Community Nutrition Environment Evaluation Data Systems (C-NEEDS) survey was completed inside the store by trained staff. Healthy Food Availability Index (HFAI; range 0-56) and Unhealthy Food Availability Index (UFAI; range 0-39) were calculated for each store. Higher HFAI indicates higher availability of healthy food items, and higher UFAI indicates high availability of unhealthy foods. Median household income and car ownership data were derived at the census tract level as measures of N-SES using the 2013 US Census American Community Surveys 5-Year estimates.

RESULTS. Convenience stores (mean HFAI 7.9, UFAI 21.1) had lower availability of both healthy and unhealthy foods than grocery stores (HFAI 32.4, UFAI 29.8). However, convenience stores had a higher proportion of unhealthy foods to healthy foods. Neighborhoods with lower median income and car ownership had a greater density of convenience stores. Neighborhoods with higher SES and car ownership had less access to convenience stores. Grocery stores in higher SES neighborhoods had more healthy food options.

DISCUSSION. These results demonstrate that residents in lower SES neighborhoods may be disadvantaged when it comes to availability of healthy foods. These neighborhoods have higher density of convenience stores that may promote an unhealthy eating environment. Residents in these neighborhoods may wish to make healthy choices, but without access to a car may be unable or unwilling to walk to the nearest store where healthy alternatives are available.

Older women’s muscle and gait response to a bout of exercise differs by physical activity level

Jocelyn F. Hafer, University of Massachusetts Amherst
Katherine A. Boyer, University of Massachusetts Amherst

12:30 PM

Changes in gait are a consequence of aging and likely contribute to knee osteoarthritis (OA) incidence. Decrements in muscle function with age, including muscle power and fatigue resistance, may contribute to changes in gait and, subsequently, knee OA. Examining the impact of habitual physical activity (PA) on gait mechanics and muscle function may provide insight for interventions to modify knee OA risk. As knee OA affects women at greater rates than men, the current study focused on older women. The aim of this study was to determine if older women with different levels of habitual PA experienced the same effect, in terms of muscle function and gait biomechanics, in response to 30 minutes of treadmill walking (30MTW). We hypothesized that sedentary women (SED) would display greater decreases in knee extensor strength and power and larger changes in gait biomechanics compared to highly active women (ACT). Twelve women (6 SED, 6 ACT) aged 61.3±3.9 years with BMI 22.3±2.2 participated in this study. Gait mechanics and knee extensor strength and power were collected pre- and post-30MTW. Unpaired t-tests were used to compare changes in knee extensor function and gait mechanics between SED and ACT with significance set at p<0.1. In response to the 30MTW, there was a larger decrease in high-velocity knee extensor power for SED vs. ACT (-26.3±12.2 vs. -12.9±13.7%). In addition, SED compared to ACT had a larger increase in sagittal hip range of motion during stance (+1.9±2.5 vs. +0.3±0.7°), a larger increase in dorsiflexion at heel strike (+2.2±1.7 vs. +0.3±2.3°), a larger decrease in plantarflexion at toe-off (-1.6±2.5 vs. +0.9±1.9°), and a larger decrease in anterior position of the femur relative to the tibia during loading response (-2.6±4.0 vs. +0.5±2.9 mm). These findings suggest PA level may affect biomechanical health in older women, especially with regard to exercise-induced fatigue.

Optimization of the Design of an Amphiphilic Biodegradable Polymer for Tissue-engineering Application

Ben Zhang, University of Massachusetts Medical School
Tera M. Filion, University of Massachusetts Medical School
Jie Song, University of Massachusetts Medical School

12:30 PM

Biodegradable polymers have been widely utilized as drug delivery vehicles and tissue engineering scaffolds. We previously designed amphiphilic triblock copolymer poly(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid) (PELA) and its hydroxyapatite (HA) composites for bone tissue engineering applications. The hydrophilic electrospun PELA-HA composite exhibited aqueous stability and elastic handling characteristics, and was able to template the proliferation and osteogenesis of bone marrow stromal cells (BMSCs) in vitro and in vivo when spiral-wrapped into cylinders and press-fit into critical size femoral segmental defects in rats. However, the slow degradation of PELA has prevented timely disappearance of the scaffold and impeded more effective restoration of biomechanical integrity of the defect. To accelerate degradation, in this work we designed poly(lactic/glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic/glycolic acid) (PELGA) with varying ratios of glycolide and lactide and confirmed their more accelerated degradations as compared to PELA. Processing conditions (e.g. solvent-casting vs. electrospinning, with or without hydration) significantly impacted the structural characteristics of PELGA and their HA composites. The PEG crystallization in PELGA was not as strong as in PEG homopolymers, giving rise to a lower Tm. HA could be well dispersed in PELGA and electrospun to give a uniform composite where the crystallization of PEG was promoted by water resulting in enhanced mechanical strength upon hydration. These HA-contained electrospun meshes exhibited excellent cytocompatibility and efficacy in templating osteogenesis of rat BMSCs in vitro.

Physiological and Social Stress on Cognitive Performance

Doreet Nagatti, Worcester Polytechnic Institute
Daniele Anina, Worcester Polytechnic Institute
Maria Daigle, Worcester Polytechnic Institute
Kymberlee M. O'Brien, Worcester Polytechnic Institute

12:30 PM

Humans are highly social creatures and this provides us with a number of benefits, such as protection and support, but it also brings new avenues for stress from social sources. Basic and translational neuroendocrine research has yielded a rich set of findings and a general understanding of how acute and chronic stress can result in reduced health, earlier aging, and earlier death. Although stress can be indexed by level of cortisol, the major stress hormone in humans, many interrelated physiological systems are involved in a stress response, including the cardio and vascular systems. Research toward greater understanding of stress buffering mechanisms holds value for improved human health in the face of entrenched social stressors.

In particular, acute and chronic stress have consistently been found to impair cognitive performance, Many adults in high stress environments also face a changing social landscape during college years: changes in living partners, less control over noise, sleep, exercise, and nutrition. In this pilot investigation, we are interested in measuring the influences of acute stress on cognitive performance and whether social support, a factor that is modifiable, would be protective on the multi-systems relationships between stress and cognition.

Broadly, we found (1) that higher levels of cortisol measured in saliva was associated with a faster return to resting levels of salivary cortisol (a measure of flexible, adaptive functioning of the central HPA stress system) after the stressor is removed and may also be associated with lower cortisol in the initial response to the stressor. In parallel, we found (2) that higher levels of cortisol were associated with impaired cognitive performance after the stress task, (3) finally, we found that those reporting high social support showed faster recovery to baseline in the cardiovascular systems and greater social support produced some buffering of stress response on their post-stress cognitive performance.

Piloting Signs of Safety: A Deaf-Accessible Toolkit for Trauma and Addiction

Melissa L. Anderson, University of Massachusetts Medical School
Kelly S. Wolf Craig, Department of Developmental Services, East Hartford, CT
Amanda Sortwell, Deaf Community Behavioral Health Services, San Diego, CA
Douglas M. Ziedonis, University of Massachusetts Medical School

12:30 PM

The Deaf community - a minority group of 500,000 Americans who use American Sign Language (ASL) - experiences trauma and addiction at rates double to the general population. Yet, there are no evidence-based treatments that have been evaluated to treat trauma, addiction, or other behavioral health conditions among Deaf people.

Current evidence-based treatments fail to meet the needs of Deaf clients. One example is Seeking Safety, a well-validated therapy for people recovering from trauma and addiction. Seeking Safety includes a therapist guide and client handouts for 25 therapy sessions, each teaching clients a safe coping skill. When Seeking Safety was used with Deaf clients, unique barriers were revealed with regard to the client materials: they were presented in complex English instead of ASL, nor sensitive to Deaf people’s culture, social norms, and history of oppression.

To address these barriers, Dr. Anderson assembled a team of Deaf and hearing researchers, clinicians, filmmakers, actors, artists, and Deaf people in recovery to develop Signs of Safety, a Deaf-accessible toolkit to be used with Seeking Safety. Signs of Safety is comprised of a therapist companion guide and population-specific client materials, including visual handouts and ASL teaching stories on digital video, which present key learning points via an “educational soap opera.”

Dr. Anderson is currently leading a pilot study of Signs of Safety. Preliminary results show that participants are reporting symptom reduction from baseline to follow-up and high levels of satisfaction with the model, giving us the confidence to further pursue this line of research.

Plasma PLP Concentration and Depressive Symptomatology, over time, in older Latino Adults

Sandra P. Arévalo, University of Massachusetts at Lowell
Tammy Scott, Tufts University
Luis M. Falcón, University of Massachusetts at Lowell
Katherine L. Tucker, University of Massachusetts Lowell

12:30 PM

Background: Low vitamin B-6 status has been linked to depressive symptomatology. However, most studies have been cross-sectional and may not have controlled for relevant confounders. Few studies have examined this association in Latino populations at high risk for major depression.

Design: We used two-level hierarchical linear regression models (HLM) for continuous outcomes. Level-1 data included three measures of participant’s depressive symptomatology collected at baseline, 2y follow-up and 5y follow-up. Participants constituted level-2 data. Vitamin B-6 was associated with depressive symptomatology across these time points.

Objective: We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3 time points over ~ 5-7 y in a cohort of older Puerto Rican adults, a population previously identified to be at high risk for depressive symptomatology and clinical depression.

Results: Plasma pyridoxyl-5’-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (22±14, vs. 20±13); this differential remained constant over time and persisted after controlling for age, sex, education, BMI, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events and allostatic load; and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time.

Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Puerto Rican adults and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive and intervention approach in this population.

Pre-exposure prophylaxis with OspA-specific human monoclonal antibodies protects mice against tick transmission of Lyme disease spirochetes

Yang Wang, University of Massachusetts Medical School
Aurélie Kern, Tufts University
Naomi Boatright, University of Massachusetts Medical School
Zachary Schiller, University of Massachusetts Medical School
Andrew Sadowski, University of Massachusetts Medical School
Monir Ejemel, University of Massachusetts Medical School
Colby A. Souders, University of Massachusetts Medical School
Keith A. Reimann, University of Massachusetts Medical School
Linden Hu, Tufts University
William D. Thomas, University of Massachusetts Medical School

12:30 PM

Background. Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States.

Methods. Mice transgenic for human immunoglobulin genes were immunized with OspA protein of B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays.

Results. Nearly 100 unique OspA specific HuMabs were generated and four HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates based on borreliacidal activity. HuMab 319-44, 857-2 and 212-55 were borreliacidal against one or two Borrelia genospecies, whereas 221-7 was borreliacidal (IC50 < 1nM) against B. burgdorferi, B. afzelii and B. garinii, the three main genospecies endemic in the US, Europe and Asia. All four HuMabs completely protected mice from infection at 10 mg/kg in a murine model of tick-mediated transmission of B. burgdorferi.

Conclusions. Our study indicates that OspA-specific HuMabs can prevent the transmission of Borrelia and administration of these antibodies could be employed as pre-exposure prophylaxis for Lyme disease.

Predicting Early Failure in Total Knee Arthroplasty: A Critical Review of Oxinium Femoral Components

Steven DiSegna, University of Massachusetts Medical School
Wenyun Yang, University of Massachusetts Medical School
Patricia D. Franklin, University of Massachusetts Medical School

12:30 PM

Introduction: Retrospectively, it has been shown that significant patient-reported pain 6 months following total knee arthroplasty (TKA) is associated with a 7 times greater revision rate at 5 years. Our goal is to use the FORCE-TJR registry to prospectively evaluate if postoperative pain and function scores can predict increased revision rate 5 years following TKA. Our preliminary analyses have focused on one implant reported by Australia to have a significantly high 5-year revision rate: Oxinium femoral components. Materials and Methods: FORCE-TJR matched implant catalog numbers to the international implant library to define TKA patients who received oxinium femoral components and all other implants. We defined 12-month KOOS pain and function (SF PCS) for patients with the study implant and all others (n=9187). Age, BMI, sex, pre-TKA pain, function, low back pain severity, and Charlson comorbidity index were compared for patients with moderate pain (KOOS pain<75) vs. minimal pain (KOOS pain>75) at 12 months postoperatively. Results: We observed that 27% of oxinium patients reported moderate pain vs. 21% of patients receiving all implants at 12 months postoperatively. Compared to patients with minimal pain, moderate pain patients had greater pre-op pain (KOOS=37 vs. 50; p< 0.0002), poorer pre-op function (PCS=30 vs. 33; p<0.04), and more moderate to severe low back pain (52% vs. 24%; p<0.027). In addition, high 12-month pain patients had poorer 12-month function (PCS=37 vs. 45; p<0.0000). Conclusion: These preliminary results indicate that moderate pain at 12-months post operatively is associated with poorer functional gain following TKA. Surgeons should recognize and potentially intervene on this group if improvement in their ultimate functional gain is desired. By continuing to follow this group of oxinium patients we will be able to determine if early pain and decreased function following TKA is associated with an increased revision rate.

Predisposed Health Conditions of Children Exposed to Methamphetamine In Utero

Seth Peters, University of Massachusetts Medical School

12:30 PM

Methamphetamine (MA) use and abuse is a growing problem worldwide [United Nations World Drug Report]. It is common knowledge that MA use affects not only the user, but also friends, family, and the communities close to them [NIDA]. One area of impact that is lacking sufficient study is the effects of MA use by expectant mothers on her child later in life. That is to say, a child who was exposed to MA in utero may be more likely than an unexposed fetus to have predispositions to a variety of health conditions. After an extensive PubMed database search, it is apparent that research is limited on the childhood illnesses and health conditions related to fetal exposure to MA. Some research, suggests a potential link between a fetus exposed to MA and the development of attention deficit hyperactivity disorder (ADHD) later in childhood. [Kiblawi, et. al.; Legasse, et. al.] The lack of available research warrants an exhaustive database search and a retrospective epidemiological study to better understand the health risk of children exposed to MA. The knowledge gained from this work can inform healthcare providers and public health officials when intervening to reduce MA use and addiction.

Prenylated retinal ciliopathy protein RPGR regulates ciliary localization of Joubert Syndrome-associated protein INPP5E in cooperation with PDE6

Wei Zhang, University of Massachusetts Medical School
Kollu N. Rao, University of Massachusetts Medical School
Linjing Li, University of Massachusetts Medical School
Manisha Anand, University of Massachusetts Medical School
Hemant Khanna, University of Massachusetts Medical School

12:30 PM

Ciliary dysfunction is an underlying cause of severe human disorders (collectively called ciliopathies), such as retinitis pigmentosa (RP), Joubert Syndrome (JBTS), and Bardet-Biedl Syndrome. Ciliary proteins form distinct functional networks for localization to cilia as well as regulation of ciliary function. However, not much is known about the mechanism of ciliary localization and function of RPGR (retinitis pigmentosa GTPase regulator), a ciliary protein frequently associated with RP worldwide. Using tandem mass spectrometry analysis, we show that RPGR interacts with two JBTS-associated proteins: PDE6Π (delta subunit of Phosphodiesterase; a prenyl-binding protein) and INPP5E (inositol polyphosphate-5-phosphatase 5E; a ciliary cargo). Whereas PDE6Π binds in a prenylation-dependent manner to the C-terminus of RPGR, INPP5E associates with the N-terminus of RPGR. Prenylation and interaction of RPGR with PDE6Π are critical for its localization to cilia. We further show that loss of RPGR results in reduced amount of INPP5E in cilia of fibroblasts and in photoreceptor outer segment, a modified sensory cilium. Overall, our results suggest that RPGR, in complex with PDE6D, regulates the trafficking of ciliary cargo INPP5E and implicate reduction in ciliary INPP5E in the pathogenesis of RPGR-ciliopathy.

Prospective Relations between Red Blood Cell ω-6 and ω-3 Fatty Acid Composition and Cognitive Function among Older Puerto Rican Adults

Sherman J. Bigornia, University of Massachusetts Lowell
Tammy Scott, Tufts University
William S. Harris, University of South Dakota
Katherine L. Tucker, University of Massachusetts Lowell

12:30 PM

Objectives: To examine the association between red blood cell (RBC) ω-6 and ω-3 fatty acid (FA) composition and cognitive function over 2-y follow-up among older U.S. mainland Puerto Ricans.

Methods: Data are from the Boston Puerto Rican Health Study (74% female; 57±8 y). RBC membrane FA status was ascertained at baseline. Individual FA were expressed as a percentage of total FA identified. Cognitive function was measured at baseline and at 2-y using the Mini-Mental State Exam (MMSE), where a higher score ranging from 0-30 indicates better function. Cognitive impairment was defined as MMSE scores ≤21, ≤23, and ≤24 for those with less than a 9th grade education, a 9th to 12th grade education, and some college education or higher, respectively. Relations between FA and MMSE scores were examined in 946 participants and incidence of cognitive impairment among those considered to be cognitively normal at baseline (n=639).

Results: In multivariate models additionally adjusted for baseline MMSE, total ω-6 FA (quartiles) were associated with lower MMSE score at 2-y (P-trend=0.003). Total ω-3 FA were positively (P-trend=0.04) and the ω-6:ω-3 ratio inversely (P-trend=0.007) related to 2-y MMSE, but these relationships attenuated with adjustment for baseline score. The incidence of cognitive impairment at follow-up was 22%. In multivariate models, a 1% increase in total ω-6 FA related to a 9% greater incidence of cognitive impairment [RR=1.09 (95% CI: 1.00, 1.18), P=0.04]. Total ω-3 FA were inversely related to incident cognitive impairment [RR=0.92 (0.81 to 1.05), P=0.21], whereas the ω-6:ω-3 ratio was positively associated [RR=1.12 (95% CI: 0.98, 1.26), P=0.08].

Conclusions: An objective biomarker of ω-6 FA consumption was associated with poorer cognitive function and incidence of cognitive impairment over 2-y follow-up, suggesting that greater intakes of food sources of ω-6 FA may play a role in cognitive decline among older U.S. mainland Puerto Ricans.

Race/Sex Group Modification of the Association between Allostatic Load and Depression: Findings from the National Health and Nutrition Examination Survey, 2005-2010

Ganga Bey, University of Massachusetts Medical School
Sharina D. Person, University of Massachusetts Medical School

12:30 PM

Objective: We assessed whether the relationship between depression and chronic stress as measured in allostatic load (AL) differs by race and sex among US black and white adults.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, we examined race/sex modification of the relationship between AL and depression in black and white women and men aged 18-64 years (n=6431). AL scores, ranging from 0-9, were calculated using 9 cardiovascular, metabolic, and immunologic biomarkers; scores ≥ 4 were considered “high-risk”. Depression was assessed using the PHQ-9; scores ≥ 10 indicate clinical depression. Logistic regression models estimated odds of elevated depressive symptoms as a function of AL for each race/sex group; age and socioeconomic status were included as covariates in each model. All analyses were weighted to represent U.S. adults.

Results: The association between AL and depression was strongest among white women (OR=2.1, 95% CI: 1.5, 3.0), followed by black men (OR=1.7 95% CI: 1.0, 2.9), and not statistically significant among black women (OR=1.1 95% CI: .60, 2.0) or white men (OR=1.4 95% CI: .82, 2.5).

Conclusions: Our findings that the association between AL and depression was strongest and statistically significant only among white women and black men despite black women having the highest mean AL and depression scores suggests a measure of psychological resistance to chronic stress among those coping with intersecting pressures of systemic race and gender-based discrimination. These results also suggest that social inequality may shape the manner in which chronic stress is expressed. Further research should explore other potential racialized and gendered manifestations of chronic stress in order to better understand social factors influencing health inequity.

Racial/Ethnic Disparities in Meeting 5-2-1-0 Recommendations among Adolescents in the United States

Christina Haughton, University of Massachusetts Medical School
Stephenie C. Lemon, University of Massachusetts Medical School

12:30 PM

BACKGROUND: Obesity prevention has become a major focus of public health efforts in the United States. The Federal Government set forth national nutrition and physical activity recommendations to prevent obesity and promote well-being among children. A succinct message developed through a program in Maine “Let’s Go! 5-2-1-0” summarizes these obesity prevention behaviors including ≥5 fruit and vegetables, ≤2 hours of screen time, ≥1 hour of physical activity, and 0 sugar sweetened beverages daily. The study evaluates racial/ethnic disparities among adolescents meeting the 5-2-1-0 targets in a nationally representative sample.

METHODS: The 2011-2012 NHANES dataset was used to conduct a cross sectional analysis of Hispanic (n=287), non-Hispanic Black (n=321), Asian (n=145) and non-Hispanic White (n=234) adolescents 12-19 years old. The 5-2-1-0 targets were evaluated using dietary recalls, Global Physical Activity Questionnaire, and questions about sedentary activities. Differences in the proportion of racial/ethnic groups meeting the 5-2-1-0 targets were compared using chi-square tests. Logistic models accounting for the complex sampling design were used to evaluate racial/ethnic disparities in meeting the 5-2-1-0 targets.

RESULTS: There were no adolescents that met all four 5-2-1-0 targets. Meeting individual targets and meeting none of the targets differed by racial/ethnic group. The study found 28% of White, 39% of Hispanic, 44% of Black and 35% of Asian adolescents met zero 5-2-1-0 targets. Adolescents from different racial/ethnic groups had increased odds of meeting no 5-2-1-0 targets compared to their White peers (adjusted odds ratio [95% Confidence Interval] – Hispanic: 1.76 [1.04-2.98], Black: 1.82[1.04-3.17], Asian: 1.48[1.08-2.04]).

CONCLUSION: Understanding the uptake of national nutrition and physical activity recommendations is necessary to reduce future obesity and health consequences in adulthood. Despite national initiatives, adolescents in the United States are far from meeting the 5-2-1-0 targets and there are racial/ethnic disparities in meeting the recommendations.

Rapid Diagnostics for Infectious Disease using Noble Metal Nanoparticles

Chun-Wan Yen, Massachusetts Institute of Technology
Helena de Puig, Massachusetts Institute of Technology
Justina Tam, Winchester Engineering Analytical Center
José Gómez-Márquez, Massachusetts Institute of Technology
Irene Bosch, Massachusetts Institute of Technology
Lee Gehrke, Harvard Medical School
Kimberly Hamad-Schifferli, University of Massachusetts Boston

12:30 PM

Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses such as dengue, Ebola, chikungunya, and others. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. We present a platform for multiplexed pathogen detection which uses gold or silver nanoparticles conjugated to antibodies to sense the presence of biomarkers for different infectious diseases. We exploit the size-dependent optical properties of Ag NPs to construct a multiplexed paperfluidic lateral flow POC sensor. AgNPs of different sizes were conjugated to antibodies that bind to specific biomarkers. Red AgNPs were conjugated to antibodies that could recognize the glycoprotein for Ebola virus, green AgNPs to those that could recognize nonstructural protein 1 for dengue virus, and orange AgNPs for non structural protein 1 for yellow fever virus. Presence of each of the biomarkers resulted in a different colored band on the test line in the lateral flow test. Thus, we were able to use NP color to distinguish among three pathogens that cause a febrile illness. Because positive test lines can be imaged by eye or a mobile phone camera, the approach is adaptable to low-resource, widely deployable settings. This design requires no external excitation source and permits multiplexed analysis in a single channel, facilitating integration and manufacturing. We will also discuss engineering the nanoparticle physical properties and surface chemistry for improving detection and also optimizing device properties, and expansion of the device to detect other diseases.

Rational Design of an Epitope-Based Hepatitis C Virus Vaccine

Brian G. Pierce, University of Maryland
Elisabeth N. Boucher, University of Massachusetts Medical School
Ejemel Monir, University of Massachusetts Medical School
William D. Thomas, University of Massachusetts Medical School
Zhiping Weng, University of Massachusetts Medical School
Yan Wang, University of Massachusetts Medical School

12:30 PM

Despite improving treatment methods and therapeutic options, hepatitis C virus (HCV) remains a major global disease burden, and a vaccine would help greatly in reducing its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response, thus a vaccine must elicit an immune response toward conserved, functionally important epitopes.

Using structural data of the broadly neutralizing antibody HCV1 in complex with a conserved linear epitope from the HCV E2 protein (aa 412-423, referred to as epitope I or domain E), we performed structure-based design to generate vaccine immunogens to induce antibody responses to this epitope. Designs selected for immunological characterization included a stabilized minimal epitope structure based on a defensin protein, as well as a bivalent vaccine featuring two copies of epitope I on the E2 surface. In vivo studies confirmed that these designs successfully generated robust antibody responses to this epitope, and sera from vaccinated mice neutralized HCV. In addition to presenting several effective HCV vaccine immunogens, this study demonstrates that induction of neutralizing anti-HCV antibodies is possible using an epitope-based vaccine, providing the basis for further efforts in structure-based vaccine design to target this and other critical epitopes of HCV.

Reducing Phlebotomy-­Induced Blood Loss in the PICU: A Quality Improvement Study

Amanda Johnson, University of Massachusetts Medical School
Ariel Hoch, University of Massachusetts Medical School
Scot T. Bateman, University of Massachusetts Medical School
Stacey L. Valentine, University of Massachusetts Medical School

12:30 PM

Introduction: Phlebotomy­induced blood loss contributes to development of anemia in critically ill children. Major factors contributing to this include blood overdraw from indwelling catheters and utilization of larger volume containers. We targeted these causes of excessive blood draws to decrease volumes of both the discarded blood and sample sent to the laboratory for standard tests. Methods: Pre and post quality improvement study in a 10­bed pediatric intensive care unit 2014­2015. All patients admitted to PICU during each 2­month study period were eligible for enrollment. Pre-intervention, nurses used standard pediatric tubes (3­3.5mL). A wash­out period followed. For intervention, email survey and nursing/resident education sessions were used to standardize discard volumes and introduce microtainers (500µL) for standard hematology, chemistry, and coagulation tests. All blood draws were recorded. Incomplete tests due to lack of volume or clotting were recorded. Results: 45 patients (138 blood draws) in pre­intervention phase and 32 patients (142 draws) in intervention phase were enrolled. Pre­intervention, mean total blood volume sent to the lab was 2.25 ±1.87mL and mean discard volume was 1.64 ±1.67mL. Post­intervention, mean total volume of blood sent and mean discard volume were significantly reduced, 1.52 ±1.50mL, p<0.05, and 0.89 ±0.61mL, p<0.05, demonstrating 32.4% and 45.7% reductions in blood volume respectively. There was no change in test failures due to low volume or clotting. Samples from peripheral intravenous catheters comprised the majority of the cohort. Pre­intervention, mean total blood volume from PIVs (n=116) was 2.06 ±1.51mL, and mean discard volume was 1.74 ±1.33mL. Post­ intervention (n=72), mean total volumes significantly decreased to 1.39 ±1.49mL and 1.15 ±0.53mL respectively (p<0.05). Conclusions: We demonstrated a significant reduction in phlebotomy­induced blood loss by standardizing discard volumes and using microtainers to avoid sending unnecessary blood volumes to the lab.

Remotely Triggered Polymeric Nanoparticles for the Treatment of Triple Negative Breast Cancer

Rahul Jadia, University of Massachusetts Lowell
Brandon Piel, University of Massachusetts Lowell
Michael Tilton, University of Massachusetts Lowell
Prakash Rai, University of Massachusetts Lowell

12:30 PM

Triple Negative Breast Cancer (TNBC) has the worst prognosis among all the sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC management. While TNBC does not overexpress hormone receptors, it has been found to over express certain receptors like transferrin (TfR) or folate receptors. The aim of this research is to synthesize targeted polymeric nanoparticles for TNBC. MDA-MB-231 cells are used as a representative TNBC cell line in this study. Active targeting of TNBC is achieved by conjugating the nanoparticles to a peptide (Tr) that binds to the TfR. Photodynamic Therapy (PDT) using polymeric nanoparticles was explored for TNBC treatment. PDT utilizes a secondary form of targeting by remotely triggering benzoporphyrin derivative monoacid (BPD) using near infrared light. When irradiated at 690nm, BPD induces cytotoxicity via generation of reactive oxygen species. The polymeric nanoparticles were characterized for size, zeta potential, and drug release at 37°C. The morphology of the nanoparticles was confirmed using electron microscopy and cell uptake was monitored in vitro using fluorescent microscopy. PDT was carried out at 500nM BPD concentration using a 690nm laser. Cytotoxicity of these targeted polymeric nanoparticles was assessed using a standard colorimetric viability assay (MTT). The nanoparticles synthesized were fairly monodisperse and the release studies demonstrated sustained BPD release from the nanoparticles. Receptor mediated endocytosis of the active nanoparticles was studied by using FITC conjugated peptide and the FITC signal was observed using fluorescent microscopy. Stronger BPD fluorescent signal for the active targeting nanoparticles (PLGA-PEG-Tr) compared to the passive (PLGA-PEG) nanoparticles. Significant cell death following PDT was observed in all the treatment groups, which was also confirmed by imaging the cells post-treatment using standard live-dead stain. PDT is a fairly versatile and non-invasive form of treatment and using targeted nanoparticles it can be adapted for other drugs and diseases.

Reprogramming of mTOR Signaling by Perinatal Exposure to Brominated Flame Retardant

Cassandra Thorburn, University of Massachusetts Amherst
Benjamin Kim, University of Massachusetts Amherst
Michael Panchenko, University of Massachusetts Amherst
Aser Abrha, University of Massachusetts Amherst
Ahmed Khalil, University of Massachusetts Amherst
Alexander Suvorov, University of Massachusetts Amherst

12:30 PM

Mammalian target of rapamycin (mTOR), also known as mechanistic target of rapamycin, is a known metabolic master-switch. In conditions of starvation, mTOR suppresses biosynthetic programs and increases the recycling of proteins and organelles. Upon stimulation by nutrients and growth factors, however, mTOR causes activation of biosynthesis and suppression of autophagy. The mTOR-centered molecular pathway is a major pathway of growth regulation and metabolism, linked to aging and the development of cancer, obesity, type 2 diabetes, neurodevelopmental and neurodegenerative diseases. Currently, the role of environmental factors in the modulation of the mTOR pathway remains largely unknown. The present study suggests that perinatal exposure to environmentally-relevant doses of polybrominated diphenyl ethers (PBDEs), a group of ubiquitous flame-retardants, results in long-lasting reprogramming of the mTOR pathway in mouse liver. This reprogramming includes suppression of mTORC1 and mTORC2 activity, accompanied by coordinated up-regulation of protein synthesis machinery and increased concentrations of circulating IGF-1. Further, experiments with MCF-7 breast cancer cells demonstrate that exposure to PBDEs results in fast induction of the REDD1/DDIT4 gene – a potent suppressor of mTORC1. This data indicates that the response of liver tissue to PBDE exposure during this critical developmental window is a dynamic process, and is likely triggered via a REDD1-dependent mechanism, ultimately resulting in long-lasting changes in the metabolic profile of the tissue. This study suggests that environmental exposures to brominated flame retardants may have profound and long-term effects on the central regulation hub of metabolic health, and may be implicated in the pathogenesis of the most relevant diseases of modern society.

Role of TSH and excess Heart Age in Predicting Atrial Fibrillation Recurrence Post-Ablation

Aditya Vaze, University of Massachusetts Medical School
Adedotun Ogunsua, University of Massachusetts Medical School
Jakub Pach, University of Massachusetts Medical School
David D. McManus, University of Massachusetts Medical School

12:30 PM

Background: The association between atrial fibrillation (AF) and thyroid disease as defined by thyroid stimulating hormone (TSH) is established in literature. However, the relationship between TSH and recurrence of AF post ablation has not been established.

Methods: We studied 207 patients (60.54±9.39yrs, 35.7% female) with persistent or paroxysmal AF who underwent either Cryo or RFA ablation between April 2011 and Jan 2015 at our center. Patients were stratified into hypothyroid (TSH > >4.5 U/mL), euthyroid (TSH 0.5-4.5 U/mL) and hyperthyroid (TSH < 0.5 U/mL) based on pre procedure testing. Heart age was computed based on Framingham risk factors. Excess heart age was defined as the difference between actual age and heart age. Logistic regression and cox-proportional hazards model were implemented using R statistical software (v3.2.0).

Results: There was a statistically significant lower rate of AF recurrence among male patients (OR 2.92, p=0.003). In univariate analysis, there was no statistically significant relationship between TSH and incidence of AF recurrence (OR 1.05, p=0.74). Cox proportional hazards models did not show an association between recurrence and TSH states (HR 0.85, p=0.74 for hypothyroid and HR 0.75, p=0.56 for hyperthyroid).

Conclusions: This exploratory showed that TSH may not play a role in AF recurrence. While there is a tendency towards an association between TSH and AF recurrence, this was not statistically significant. We hypothesize that overt hyperthyroidism prior to ablation will not increase chance of recurrence. This was true after adjustment for Framingham risk factors. The limitation of this study was the small sample size of the patients with TSH in the hyperthyroid range. Further analysis using larger dataset is indicated.

Sedentary Behavior and Cardiovascular Disease Risk Factors among Latino Adults

Valerie J. Silfee, University of Massachusetts Medical School
Stephenie C. Lemon, University of Massachusetts Medical School
Vilma Lora, YWCA of Greater Lawrence
Milagros C. Rosal, University of Massachusetts Medical School

12:30 PM

Background: Compared to other racial/ethnic subgroups in the U.S., Latinos experience increased rates of cardiovascular disease (CVD) and CVD risk factors such as hypertension, inactivity, and diabetes. Sedentary behavior has also been defined as an additional risk factor for CVD, independent of physical activity participation. However, while sedentary behavior has been associated with increased risk for CVD among primarily White samples, previous studies in Latinos have shown mixed results.

Purpose: To explore the relationships between sedentary behavior and CVD risk factors, including BMI, waist circumference, blood pressure, physical activity, dyslipidemia, and diabetes, among a sample of Latino adults.

Methods: Cross-sectional secondary analysis of the Latino Health and Well-Being Study. Latino adults were recruited from the Greater Lawrence Family Health Center (N= 602). Surveys of sedentary behavior and physical activity were verbally administered. Anthropometric measurements included weight, height, waist circumference and blood pressure. Medical record data for diabetes and dyslipidemia were obtained.

Results: This study showed that individuals in older age strata, females, and individuals with a less than high school education were more sedentary than their younger, male, and more educated counter parts. Sedentary behavior was positively associated with BMI (β = .164, p < .001) and waist circumference (β = .162, p < .001). There were no associations between sedentary behavior and blood pressure, high cholesterol, diabetes, or physical activity.

Conclusions: There is growing evidence that sedentary behavior may have its own unique set of metabolic consequences. However, the consequences of sedentary behavior may not be uniform across subgroups. Evaluating the relationship between sedentary behavior and CVD risk is critical in identifying behaviors, like sedentariness, that contribute to the development of CVD.

Serum Levels of Alpha-1 Antitrypsin following Vascular Limb or Intra-Muscular Delivery of AAV1 or AAV8 Gene Therapy Vectors in Rhesus Macaques

Alisha M. Gruntman, University of Massachusetts Medical School
Gwladys Gernoux, University of Massachusetts Medical School
Gensheng Wang, Lovelace Biomedical and Environmental Research Institute
Janet M. Benson, Lovelace Biomedical and Environmental Research Institute
Jeffrey D. Chulay, Applied Genetic Technologies Corporation
David R. Knop, Applied Genetic Technologies Corporation
Christian Mueller, University of Massachusetts Medical School
Terence R. Flotte, University of Massachusetts Medical School

12:30 PM

Alpha-one antitrypsin (AAT) deficiency is a genetic disease that results in both lung disease and potentially liver failure in affected patients. In un-affected people AAT is produced in the liver and secreted to act as an anti-protease (primarily counteracting the effects of neutrophil elastase) in the lung. On-going human clinical trials have focused on intra-muscular delivery of adeno-associated virus (AAV1) to patients. The goal of delivery to the muscle is to have the myocytes serve as bio-factories to produce normal AAT protein and secrete it into the blood where it can exert its normal function in the lung. In the last Phase II trial patients in the highest dose cohort were given 100 intra-muscular (IM) injections with serum AAT levels still below therapeutic thresholds.

Previous work has shown that delivering AAV vector to the musculature of the limb via the vasculature, while blood flow is obstructed using a tourniquet, leads to wide-spread gene expression in myocytes. We hypothesize that local delivery via IM injection results in saturated AAT expression within the myocytes surrounding the injection sight and that a more widespread delivery would result in an overall increase in serum AAT levels with the same dose of AAV gene therapy vector due to production by a larger overall number of myocytes. We have been able to show that we can attain similar or slightly higher (573.0 ng/ml versus 562.5 ng/nl) serum AAT levels using a vascular delivery method in rhesus macaques when compared to IM delivery. These results have been obtained using AAV1. Animals receiving either AAV1 or AAV8 show a decrease in muscle immune cell infiltrates following intra-vascular delivery versus IM delivery, which may improve long-term expression. Serum AAT data from animals dosed using AAV8, a serotype shown to better target muscle following vascular delivery, are currently being processed.

Sex differences in cognition, emotional reactivity, and motor ability in gonadally-intact middle-aged marmosets (Callithrix jacchus)

Nichole J. Gervais, University of Massachusetts Amherst
Kathryn P. Workman, University of Massachusetts Amherst
Matthew LaClair, University of Massachusetts Amherst
Agnes Lacreuse, University of Massachusetts Amherst

12:30 PM

Sex differences in cognition are well documented. Women outperform men on measures of perceptual speed and verbal abilities, while men outperform women on tests of spatial processing. Robust sex differences also exist in stress responses. However, it is unclear how these sex differences change over time and whether males and females follow different trajectories of age-related cognitive decline. Studies in nonhuman primate models can help resolve this issue. The common marmoset (Callithrix jacchus) is a New World primate with a short lifespan that can perform complex cognitive tasks in computerized settings that are comparable to those used with humans. The present study is part of a longitudinal project aimed at determining whether males and females follow different trajectories of cognitive aging. This report focuses on sex differences at study entry. Thirteen marmosets (7 females), aged 4-6 years were tested on a comprehensive battery of tasks assessing cognitive function, motor skills and emotional reactivity. For cognition, monkeys were initially trained on a simple visual discrimination problem, followed by reversal learning using the Cambridge Neuropsychological Test Automated Battery (CANTAB). They also performed the Hill-and-Valley task as a measure of fine motor skills. To assess emotional reactivity, each marmoset was separated from their colony for 7 hours. Behavioral assessments, which involved recording the occurrence of approximately 25 behaviors, occurred a total of 6 times: immediately before separation, 3 times during separation, immediately after separation, and 24-hr later. No sex difference was found for simple discrimination, but males tended to perform better than females on the reversal learning task. No sex difference was observed in motor skills. During separation from the colony, females were more reactive than males, as indicated by more agitated locomotion, and vocalizations. Together, these findings expand upon previous studies and demonstrate sex differences in reversal learning and emotional reactivity in gonadally-intact middle-aged marmosets. As the study progresses, we should be able to determine the neural correlates of these sex differences and how they may change with aging. Supported by NIH grant AG046266

Show Back: Evaluation of Scoresheet for Identifying Self-Management Medication Problems of Older Adults

Laura Sanford, University of Massachusetts Medical School
Janice B. Foust, University of Massachusetts Boston
Maureen Sarno, VNA Care Network & Hospice
Alok Kapoor, University of Massachusetts Medical School

12:30 PM

Purpose The study purpose was to test the feasibility of a scoresheet to screen for problems older adults may have managing medications after discharge from a hospital or nursing home facility.

Background Adverse drug events (ADE) prevention is an important patient safety priority, with ADEs accounting for an estimated one-third of hospital adverse events and approximately 280,000 hospital admissions annually. Home healthcare nurses work with older adults to avoid ADEs and promote self-management of medications. Few, if any, studies have described older adults’ cognitive and psychomotor abilities to manage their medications after being discharged home.

Methods We enrolled patients if they were aged 65 and older, recently discharged from a hospital, rehabilitation center, or nursing facility, and were prescribed at least one antidiabetic, anticoagulant, or opioid medication. A physician and homecare nurse observed and scored patients’ proficiency managing across five domains: identification, explanation of purpose, organization, administration, and timing. Based on the experiences in the first 20 visits, we created a protocol and a detailed manual for determining proficiency in each domain. Through the subsequent home visits, we determined inter-rater reliability using Cohen’s Kappa (κ).

Results Thirty older adults participated. During the ten visits completed after we developed the protocol and scoring guide, we scored a total of 90 medications with an average of 8 (SD±2.04) medications per patient. The physician and nurse scored the explanation domain most reliably, with an inter-rater reliability Kappa of 0.872 (p < 0.0001), followed by timing (κ=0.707, p < 0.0001), organization (κ=0.624, p < 0.0001), and identification (0.376, p < 0.0001). The physician and nurse scorers were least reliable in scoring the administration domain (κ=0.133, p=0.4454).

Conclusions & Implication: The Show Back scoresheet shows promise to identify domain-specific problems faced by older adults’ managing their medications at home. We plan to hone our protocol and recalculate agreement in subsequent cohort of patients.

Statistical Analysis for Hospital Length-of-Stay and Readmission Rate Study

Hong Yan, Worcester Polytechnic Institute
Shaheryar F. Ansari, Indiana University
Jian Zou, Worcester State College
Robert M. Worth, Indiana University
Nicholas M. Barbaro, Indiana University

12:30 PM

Hospital readmission rate has become a major indicator of quality of care, with penalties given to hospitals that have high rates of readmission. At the same time, insurers are applying increasing pressure to improve efficiency and reduce costs, including decreasing hospital lengths of stay. We analyze these trends to determine if reducing lengths of stay (LOS) may actually worsen readmission rates. All records of patients admitted to the neurosurgical service at one hospital from October 2007 through June 2014 were aggregated and analyzed for several variables, including initial length of stay, readmission occurrence, and length of stay, admitting diagnosis, admission priority and discharge disposition. Any trends over time were also noted. 925 out of 9,409 patient encounters are readmissions. Readmission rate and average length of stay were found significantly negative correlated. Besides linear regression which directly connecting average length of stay and readmission rate, survival analysis methods with Cox proportional hazard ratio model were employed to determine which factors were associated with a higher risk of readmission. There was a clear increase in readmissions over the study period, but LOS remained relatively constant, suggesting that increasing medical complexity confounded efforts to decrease LOS and was responsible for increased readmission rates. This study can help providers avoid readmissions by focusing on effective management of comorbidities.

Structural Activity Relationship Study on Dual PLK1 /BRD4 Inhibitor, BI- 2536

Hailemichael Yosief, University of Massachusetts Boston
Shuai Liu, University of Massachusetts Boston
Dennis L. Buckley, Dana- Farber Cancer Institute
Justin M. Roberts, Dana- Farber Cancer Institute
Alex M. Muthengi, University of Massachusetts Boston
Francesca M. Corsini, University of Massachusetts Boston
James E. Bradner, Dana-Farber Cancer Institute
Wei Zhang, University of Massachusetts Boston

12:30 PM

Polo-like kinase 1 (PLK1) and BRD4 are two different therapeutic targets in cancer drug discovery. Recently it has been reported that PLK1 inhibitor, BI-2536, is also a potent inhibitor of BRD4. The simultaneous inhibition of PLK1 and BRD4 by a single drug molecule is interesting because this could lead to the development of effective therapeutic strategy for different types of disease conditions in which PLK1 and BRD4 are implicated. Structural activity relationship studies has been carried out on BI-2536 to generate analogs with enhanced dual inhibitory activity against BRD4 and PLK1 as well as to render the molecule selective to one target over the other. UMB101 and 160 have been found to exhibit enhanced dual inhibitory activity with selectivity fold of less than 30, UMB160 being the most potent dual-kinase bromodomain inhibitor (BRD4 IC50 = 28 nM, PLK1 IC50 = 40 nM). UMB131 was found to be the most selective PLK1 inhibitor over BRD4.

Structural and Molecular Analysis of a Protective Epitope of Lyme Disease Antigen OspA and Antibody Interactions

Shivender Shandilya, University of Massachusetts Medical School
Nese Kurt Yilmaz, University of Massachusetts Medical School
Ejemel Monir, University of Massachusetts Medical School
Andrew Sadowski, University of Massachusetts Medical School
William D. Thomas, University of Massachusetts Medical School
Mark S. Klempner, University of Massachusetts Medical School
Celia A. Schiffer, University of Massachusetts Medical School
Yan Wang, University of Massachusetts Medical School

12:30 PM

The murine monoclonal antibody LA-2 recognizes a clinically protective epitope on outer surface protein (OspA) of Borrelia burgdorferi, the causative agent of Lyme disease in North America. Human antibody equivalence to LA-2 is the best serologic correlate of protective antibody responses following OspA vaccination. Understanding the structural and functional basis of the LA-2 protective epitope is important for developing OspA-based vaccines and discovering prophylactic antibodies against Lyme disease.

Here, we present a detailed structure-based analysis of the LA-2/OspA interaction interface and identification of residues mediating antibody recognition. Mutations were introduced into both OspA and LA-2 based on computational predictions on the crystal structure of the complex, and experimentally tested for in-vitro binding and borreliacidal activity. We find that Y32 and H49 on the LA-2 light chain, N52 on the LA-2 heavy chain and residues A208, N228 and N251 on OspA were the key constituents of OspA/LA-2 interface. These results reveal specific residues that may be exploited to modulate recognition of the protective epitope of OspA and have implications for design of vaccines against Lyme disease.

Sulforaphane Treatment of Children with Autism Spectrum Disorder

Eileen Diggins, University of Massachusetts Medical School
Andrew Zimmerman, University of Massachusetts Medical School
Kanwaljit Singh, University of Massachusetts Medical School
Susan Connors, University of Massachusetts Medical School

12:30 PM

Abstract This clinical trial in autism spectrum disorder (ASD) tests a nontoxic approach to therapy of ASD.

Background: Direct treatment of underlying mechanisms in ASD is limited. Cellular dysfunction in ASD may involve a number of related metabolic pathways. A clinical clue may be found in the “fever effect” in ASD, in which febrile illness dramatically but temporarily ameliorates disordered behavior. Fever stimulates heat shock proteins (HSP) and cellular stress responses that may ultimately lead to improved synaptic function and increased long-range connectivity. The expression of gene transcription by NFE2L2 (Nrf2), which is reduced in ASD, may also increase during fever. Sulforaphane (SF), an isothiocyanate obtained from 3-day-old broccoli sprouts, induces HSP and Nrf2 as well as “cell-protective” responses. SF has several possible modes of action that may benefit ASD through common cellular mechanisms underlying heterogeneous phenotypes. SF crosses the blood brain barrier and is bioavailable orally.

Preliminary data: In a randomized, double-blind, placebo-controlled pilot trial in 44 male adolescents and adults (13-30 years), results showed SF was well tolerated without significant side effects. On average, participants on SF (particularly those with a history of fever effect) showed significantly more improvements in ASD symptoms than placebo participants. Significant improvements for SF participants included social interaction, aberrant/abnormal behavior, repetitive/stereotypical behavior, and verbal communication.

Current study: Our randomized, double-blind, placebo-controlled phase-2 clinical trial at UMass has three aims: To determine: (1) if orally administered SF has measurable effects in children (ages 3-12 years) with ASD; (2) if treatment with sulforaphane is safe and well tolerated; (3) To elucidate cellular biomarkers that support the mechanisms of action of SF in ASD. We hypothesize that SF will have positive effects, and that these effects will be more marked and lasting in the developing – compared to the mature – brain.

Sustained Expression with Partial Correction of Neutrophil Defects 5 Years After Intramuscular rAAV1 Gene Therapy for Alpha-1 Antitrypsin Deficiency

Terence R. Flotte, University of Massachusetts Medical School
Christian Mueller, University of Massachusetts Medical School
Gwladys Gernoux, University of Massachusetts Medical School
Alisha Gruntman, University of Massachusetts Medical School
Jeffrey D. Chulay, Applied Genetic Technologies Corporation
David R. Knop, Applied Genetic Technologies Corporation
Noel G. McElvaney, Royal College of Surgeons of Ireland
Martha Campbell-Thompson, University of Florida
James M. Wilson, University of Pennsylvania

12:30 PM

Alpha-1 antitrypsin (AAT) deficiency is a common monogenic disorder resulting in emphysema, which is currently treated with weekly infusions of protein replacement. We previously reported achieving plasma wild-type (M) AAT concentrations at 2.5-3.8% of the therapeutic level at 1 year after intramuscular (IM) administration of 6×1012vg/kg of a recombinant adeno-associated virus serotype 1 (rAAV1)-AAT vector in AAT-deficient patients, with an associated regulatory T cell (Treg) response to AAV1 capsid epitopes in the absence of any exogenous immune suppression. Here, we report sustained expression at greater than 2% of the therapeutic level for 5 years after one-time treatment with rAAV1-AAT in an AAT-deficient patient from that study, with partial correction of neutrophil defects previously reported in AAT-deficient patients. There was also evidence of an active Treg response (FoxP3+, Helios+) and an exhausted cytotoxic T cell response (PD-1+, LAG-3+) to AAV1 capsid. These findings suggest that muscle-based AAT gene replacement is toleragenic and that very stable levels of M AAT may exert beneficial effects at lower concentrations than previously anticipated.

Synthetic intestinal mucosal barrier using a hydrogel slab integrated microfluidic chip

Jun-Goo Kwak, University of Massachusetts Amherst
Abhinav Sharma, University of Massachusetts Amherst
Jungwoo Lee, University of Massachusetts Amherst

12:30 PM

The mucosal barrier lining along the intestinal tract plays a key role in metabolic and immunological homeostasis. Repeated disruption of the mucosal barrier integrity has been suggested to be a precursor event that derives inflammatory bowel diseases and colorectal cancer. Multiple in vitro platform technologies have been developed to understand the mucosal barrier function including trans-wells and microfabricated devices, but a static and vertical axis culture settings limits to simulate and observe dynamic complexity of the gut microenvironment. Here, we introduce a biomaterials engineering approach to create a synthetic mucosal barrier in a transverse manner for direct observation of cellular processes. A type I collagen hybridized polyacrylamide hydrogel supporting small molecular transport and epithelial cell adhesion was used as a framework and subsequently anchored covalently to a glass slide via silanization chemistry. Villous microstructures ~250µm in height were manufactured by casting the hydrogel precursor solution in a pre-designed, removable polydimethylsiloxane micropattern mold and polymerizing using UV light. After sealing the device with another glass slide, we increased the cellular and extracellular complexity of this microfluidic chip by sequentially introducing (i) HT-29 colon epithelial cells, (ii) mucin extracts from a pig intestine, (iii) bacteria, and (iv) human peripheral blood-derived mononuclear cells and co-cultured them in a single device. This modular in vitro microphysiological intestinal tissue model may serve as a translational platform to discover the biophysical etiology for disruption of the mucosal barrier and associated inflammatory diseases.

Targeted Combination Treatment for Glioblastoma Multiforme (GBM) Using Polymeric Nanoparticle

Praveena Velpurisiva, University of Massachusetts Lowell
Michael Tilton, University of Massachusetts Lowell
Brandon Piel, University of Massachusetts Lowell
Prakash Rai, University of Massachusetts Lowell

12:30 PM

Glioblastoma Multiforme (GBM) is an aggressive cancer that originates from astrocytes and spreads to spinal cord and other parts of the brain. Increase in replication of glial cells leads to advantageous mutations in the tumor. In 2015 about 15,320 deaths were reported due to GBM. Five-year survival is less than 5% making GBM a dreadful cancer. Current treatment involves complex invasive surgery, followed by chemotherapy and radiation. There is a desperate unmet need for a targeted treatment of GBM with minimum damage to the surrounding normal tissue. Combination treatments are increasingly being used to target multiple hallmarks of cancer. The goal of this study is to develop a combination therapy to treat GBM using Poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with three different drugs namely gefitinib, temozolomide (TMZ) and GSK461364 each with a unique target. Nanoparticles facilitate combination of multiple drugs for simultaneous delivery to cancer cells in a single nano-sized platform. Gefitinib is a Tyrosine Kinase inhibitor, which competes for ATP-binding site of EGFR-TK. TMZ methylates DNA of tumor cells, resulting in apoptosis. GSK461364 is a Polo-like Kinase (PLK-1) inhibitor that blocks the G2/M transition in tumor cell cycle. These three distinct hydrophobic drugs are tested on U-87 MG (human malignant glioma) and MDA-MB-231 (triple negative breast cancer) cell lines. PLGA is attached to Polyethylene glycol (PEG), which is conjugated to transferrin receptor (TfR) binding peptide for targeting TfR overexpression, common in GBM. PEG is known to increase the circulation half-life in vivo and improves colloidal stability of nanoparticles. These transferrin peptides bind to TfR (or CD71) and enable the entry of PLGA across Blood Brain Barrier (BBB). Results of characterization, in vitro drug release profiles, stability at 37C and 4C, cytotoxicity assay, electron micrographs of nanoparticles containing drugs and fluorescent imaging will be presented.

Terpenes as ‘resistance-busting” anthelmintic drug

Zeynep Mirza, University of Massachusettts Medical School
David Koch, University of Massachusetts Medical School
Thanh-thanh Nguyen, University of Massachusetts Medical School
Yan Hu, University of Massachusetts Medical School
Raffi V. Aroian, University of Massachusetts Medical School
Gary R. Ostroff, University of Massachusetts Medical School

12:30 PM

There is an urgent need for new therapies for parasitic helminthic diseases affecting 1.5-2 billion people worldwide due to the threat of wide-spread resistance development to existing treatments and due to problems of incomplete efficacies.

Terpenes are plant secondary metabolites and major essential oil constituents. Historically, the terpene thymol was successfully used to cure hookworm infections in the 1900’s. Although effective, large doses were needed and thymol treatment had significant side effects. Because free terpenes are absorbed in the stomach, less than 10% of oral terpenes entered the site where the parasites live. To overcome these problems we have developed microparticle encapsulated terpenes and enteric coated terpene capsules.

We screened 20 terpenes for anthelmintic activity in vitro against adult stages of the hookworm and whipworm parasitic nematodes Ancylostoma ceylanicum and Trichuris muris. Here we will present results of this work, which shows the promising potential for some terpenes as pan-nematode anthelmintics. This work has allowed us to classify terpenes into at least two groups based on their in vitro killing kinetics. We have also shown that some terpenes are effective against an albendazole-resistant Caenorhabditis elegans strain suggesting that terpenes may play an important role in overcoming helminthic drug resistance. We will also present our work on optimizing lead terpene formulations in vitro and in vivo in animal models of parasitic nematode infection in order to overcome the challenges and realize the potential of “resistance-busting” terpene-based anthelmintic therapies.

Text Mining From Drug Surveillance Report Narratives

Susmitha Wunnava, Worcester Polytechnic Institute
Tabassum Kakar, Worcester Polytechnic Institute
Xiao Qi, Worcester Polytechnic Institute
Elke A. Rudensteiner, Worcester Polytechnic Institute

12:30 PM

Analysis of postmarket drug surveillance reports is imperative to ensure drug safety and effectiveness. FAERS (FDA Adverse Event Reporting System) is a surveillance system that monitors Adverse Events (AEs) from drugs and biologic products. The AEs are reported through MedWatch voluntary reports (initiated from patients and healthcare providers) and mandatory reports (initiated from manufacturers). Much of the information in the voluntary AE reports is narratives or unstructured text. The increasing volume of individual reports, estimated at more than one million per year, poses a challenge for the staff to review large volume of narratives for drug clinical review. We are developing a computational approach using Natural Language Processing and UMLS MetaMap biomedical software to parse the narratives, recognize named-entities in the text and extract consumer/patient and related drug indications and adverse drug reaction information. The goal is to develop a text mining tool that automatically extracts relevant information from the report narratives which can be stored in pre-defined data fields in the FAERS database for efficient searching and querying during clinical review process.

The Effect of Mobile Self-monitoring on Self-care Behaviors in Heart Failure and COPD Patients: A Feasibility Study

Elizabeth Chin, University of Massachusetts Dartmouth
Kristen Sethares, University of Massachusetts Dartmouth
Paul Fortier, University of Massachusetts Dartmouth
Benjamin Viall, University of Massachusetts Dartmouth

12:30 PM

Exacerbations of heart failure (HF) and chronic obstructive lung disease (COPD) are among the most costly illnesses. Patient recognition of changes in symptoms cueing imminent exacerbation is poor. Innovative strategies to improve patient symptom recognition, self-care behaviors and treatment seeking are necessary to improve overall health outcomes.

The aim of this pilot study was to test the feasibility of a wireless health monitoring device and cell phone app in 10 patients (5 with COPD and 5 with HF). This collaborative multidisciplinary study is innovative in its inclusion of the patient as an active partner in the use of technology to monitor changes in physiologic indicators to alert them to baseline status changes and guide self-care decision-making. The nurse-engineer team worked to develop devices that met the data collection needs of the research team, while being mindful of comfort and body image concerns of the patient. Additionally, the engineers provided the nurse researchers essential training on troubleshooting technology problems in the field. Weekly home visits with participants provided ongoing feedback that impacted design decisions and revisions throughout the data collection period.

Data were collected on self-care (SCHFI) at enrollment and post intervention. Participants had a mean age of 67.7 + 11.9 years, EF of 26.5 + 11.8, 60% male, 70% married. Mixed between-within subjects’ analysis of variance was conducted to test the impact of the intervention on the participant’s self-care scores. There was no significant interaction between group and time, Wilk’s Lambda = .97, F (1, 17) = .46, p = .51. There was no significant main effect for time Wilk’s Lambda = .94, F (1, 17) = 1.14, p = .30. Self-care maintenance (31 vs 31.7), management (49.2 vs 63) and confidence (58.2 vs 58.7) scores were inadequate at each time but did increase after intervention.

The Effect of Oral Antibiotics on the Development of Community Acquired Clostridium Difficile Colitis in Medicare Beneficiaries

Charles M. Psoinos, University of Massachusetts Medical School
Courtney E. Collins, University of Massachusetts Medical School
M. Didem Ayturk, University of Massachusetts Medical School
Julie Flahive, University of Massachusetts Medical School
Frederick A. Anderson Jr., University of Massachusetts Medical School
Heena Santry, University of Massachusetts Medical School

12:30 PM

Clostridium difficile infection (CDI) is increasingly prevalent among community dwelling Americans. Older Americans are particularly vulnerable to community-acquired Clostridium difficile (CACD), in part to increasing use of antibiotics. We studied the association between outpatient antibiotics and CACD among Medicare beneficiaries.

Case-control study utilizing a 5% sample of Medicare beneficiaries (2009-2011). Patients with CACD severe enough to warrant hospitalization were identified by a primary diagnosis code for CDI and no exposure to a healthcare environment within 90-days of admission. 1,514 CACD cases were matched to ten controls each on birth year and sex. Potential controls with exposure to healthcare environment were excluded. Outpatient oral antibiotic exposure was classified into three groups: ≤30 days, 31-60 days, or 61-90 days prior to case subject’s index admission. Metronidazole and Vancomycin were excluded because they are used to treat CDI. Multivariable models were utilized to determine the independent effect of antibiotics on the development of CACD while controlling for several patient associated characteristics.

Cases of CACD had more outpatient antibiotic exposure in each time period examined: ≤30 days = 40.0% vs 8.4%; 31-60 = 10.7% vs 5.0%; and 61-90 = 5.5% vs 4.4% (all p-values < 0.05). Subjects exposed to antibiotics ≤30 days prior to admission had a markedly higher risk of being admitted with CACD compared with those not exposed (OR 8.09, 95% CI 7.13, 9.19). Similarly, subjects taking antibiotics 31-60 days and 61-90 days prior to admission had increased risk of CDI admission (OR 3.65, 95% CI 3.02, 4.41) and (OR 2.06, 95% CI 1.61, 2.63) respectively.

Recent exposure to outpatient oral antibiotics increases the risk of CACD among community dwelling elderly with the risk persisting as long as 90 days after exposure. Inappropriate antibiotic usage must be minimized and older Americans who require outpatient antibiotic treatment may warrant close observation for signs of CDI.

The impact of changing guidelines on prostate cancer screening in a population-based setting, 2000-2014

Daniel M. Frendl, University of Massachusetts Medical School
Mara M. Epstein, University of Massachusetts Medical School
Hassan Fouayzi, University of Massachusetts Medical School
Richard Krajenta, Henry Ford Health System
Benjamin A. Rybicki, Henry Ford Health System
Mitchell H. Sokoloff, University of Massachusetts Medical School

12:30 PM

Introduction: This study evaluates the potential impact of the publication of conflicting prostate cancer (PCa) screening trial results in 2009 and changes to the US Preventive Services Task Force (USPSTF) guidelines to recommend against screening in 2012 on temporal trends in PSA testing at two participating sites in the NCI-funded Cancer Research Network.

Methods: Study participants were men aged 40-80 without a history of PCa who sought care at Fallon Health (Worcester, MA) or Henry Ford Health System (Detroit, MI) between 2000-2014. We used health claims and electronic health record data to identify men who underwent PSA testing per calendar year. We also examined trends in PSA testing among high-risk men (African-American, family history of PCa). Testing rates were compared between 2000-2008, 2009-2012, and 2013-2014.

Results: From a population of 279,350 eligible men, 133,038 (48%) had at least one PSA test during the study period. Mean age at PSA test was 57 years, which increased over time at both sites. Overall, PSA testing rates rose between 2000-2008 (27-32% of eligible men per year), but declined between 2009-2012 (25% of eligible men). Testing rates declined further in 2013-2014 (23% of eligible men). We observed similar rates of decline in testing for men aged 55-69 and those aged ≥70. High-risk men were less likely to be screened across all time periods, although data was limited.

Conclusions: This analysis of two population-based electronic health datasets provides evidence of a recent decrease in PSA testing, following an increase in the early 2000s. Although we are unable to determine causality, it is plausible that results of recent screening trials and/or changes to the USPSTF guidelines have impacted PSA testing practices over the past 14 years.

The Therapeutic Effects of per os Artemisinin Delivered as Dried Leaf Artemisia annuavs. Artesunate in Non-small Cell Lung Cancer

Dina Rassias, Worcester Polytechnic Institute
Pamela Weathers, Worcester Polytechnic Institute

12:30 PM

Artemisinin, the active component of Artemisia annua L. used to treat malaria, also has therapeutic efficacy against many types of cancer. Solubility issues led to development of more soluble semi-synthetic derivatives. Artesunate (ART), in particular, is a more soluble derivative of artemisinin and has profound cytotoxicity toward many types of tumor cells, but healthy cells are less sensitive. Artemisinin delivered per os as dried leaves, referred to as dried leaf artemisinin (DLA), was shown in rodent studies to improve bioavailability by more than 40-fold. ART has been widely studied for its anti-cancer properties, but it has yet to be shown if DLA also improves therapeutic efficacy. As A. annua produces a wide array of phytochemicals with anti-cancer activity other than artemisinin, it is reasonable to expect DLA may provide a more potent therapeutic. Using two non-small cell lung cancer cell lines, PC-9 and H1299, artemisinin delivered as DLA effectively reduced viability with 24h IC50 values of 56.3 and 77.5 µM for PC-9 and H1299, respectively, as determined by MTT assay. For PC-9 cells, this was a 2.5-fold improvement in the 24h IC50 value for ART at 142.9 µM. However, for the H1299 cells, ART at 60.6 µM was better than DLA by about 25%. Ongoing studies are comparing the mechanism of action of DLA and ART on these two cell lines and will analyze markers for apoptosis, proliferation and metastatic migration and invasion. Xenograft models also will be used to compare in vivo efficacy of DLA and ART on tumor reduction. These studies will help us further understand the anti-cancer effects of artemisinin when delivered per os as dried plant leaves.

The Use of Complementary and Alternative Medicine (CAM) and Imported Medications by Brazilians in Massachusetts

Adriana Negrini, University of Massachusettts Medical School
Renata Dalla Costa, University of Massachusetts Medical School
Christina Hernon, University of Massachusetts Medical School

12:30 PM

Background: The use of CAM products and imported pharmaceuticals has been rising in the United States. These practices are particularly common in Latino populations. This descriptive study sought to investigate the use of pharmaceuticals imported from Brazil and CAM products by the Brazilian population in Massachusetts.

Methods: A brief anonymous survey was administered online via social media and in paper during visits to Brazilian establishments to a sample of first-generation Brazilian immigrants residing in Massachusetts. The survey questionnaire was administered in Portuguese and explored participants’ use of CAM products and imported pharmaceuticals as well as patient disclosure of use to physician.

Results: 595 surveys responses were collected and a total of 540 surveys were included in the statistical analysis. 59.1% of respondents reported having used imported medications from Brazil during their time of residence in the US. The most commonly used classes of imported medications were analgesics and antibiotics. 31.5% of participants reported use of CAM products; most commonly for cold-like symptoms. CAM products and imported medications were most often obtained through friends or relatives who brought them from Brazil. 63.9% of respondents did not inform their physician about their use of imported medications and/or CAM products. The most common reason for not reporting was because the doctor did not ask.

Conclusions: To improve care of Brazilian immigrants, it is essential that US physicians ask patients about the use of imported medications and CAM products. Familiarity with the most commonly used products is important for patient education regarding efficacy, toxicity, and possible drug interactions.

Theoretical and Experimental Analysis of the Antioxidant and Anti-amyloid Features of Synthetic Resveratrol Mimics

William Horton, University of Massachusetts Boston
Anne Kokel, University of Massachusetts Boston
Fanni Török, University of Massachusetts Boston
Chris Tran, University of Massachusetts Boston
Marianna Török, University of Massachusetts Boston
Bela Török, University of Massachusetts Boston

12:30 PM

Diaryl hydrazones, possessing similar structure to the popular red wine antioxidant resveratrol, have been previously identified as multitarget compounds interfering with several processes associated with the pathogenesis of Alzheimer’s disease (AD). These compounds exhibited particularly strong inhibition of the amyloid beta (A) peptide self-assembly, including blocking the formation of fibrils and oligomers, species that are widely accepted to be neurotoxic. The molecules were also powerful free radical scavengers and thus have a potential to defend against oxidative stress.

In order to learn more about the mode of action of the compounds, theoretical and experimental studies have been carried out. First, the structural, energetic and electronic features of the core structure have been elucidated by density funtional theory (DFT) calculations. The DFT results identified the most likely form of the compounds, which was applied to a broad range of calculations using substituted derivates. Based on the structural information several characteristics such as logP, H-binding energy, HOMO-LUMO energies and band gap and electron densities were calculated. The compounds were subjected to three different antioxidant assays (DPPH, ABTS and ORAC). The % radical scavenging has been analyzed as a function of the above determined structural parameters in order to identify the role of the energetic and electronic features in the antioxidant activity. The analysis of the same parameters as potential markers to the anti-amyloid activity has also been carried out.

Isotope labeling via H-D exchange and in situ hydrazone-radicals as well as hydrazone-A complex formation, applying 1H-NMR and HRMS, have also been used to experimentally observe the potential role of various tautomeric forms and the partially delocalized electron structure of the hydrazones.

Total hip arthroplasty and mental health status

Uyen-Sa D.T. Nguyen, University of Massachusettts Medical School
Thomas Perneger, Geneva University Hospitals
Patricia D. Franklin, University of Massachusetts Medical School
Christophe Barea, Geneva University Hospitals
Pierre Hoffmeyer, Universite of Geneve
Anne Lubbeke, Universite of Geneve

12:30 PM

Purpose. Total hip arthroplasty (THA) effectively restores function and alleviates pain in patients with end-stage hip osteoarthritis. Pain affects mood through its effect on disability and fatigue. Few studies have examined mental health as a consequence of pain or function after THA. We assessed change in mental health 1-year post-surgery, and examined whether change in pain and function predict change in mental health.

Methods. We used data from a prospective THA registry that began in 1996 at a large public Geneva University hospital. We included surgeries performed 2010 and 2012-2014, with demographic information, body mass index (BMI), co-morbidities, baseline and 1-year post-surgery WOMAC pain and function scores, and the SF-12 mental health component score (MCS). The pain, function, and MCS scores were normalized and ranged from 0-100; increasing score indicating better outcome. We calculated descriptive statistics, and used multivariable linear regression to predict 1-year change in MCS.

Results. Of 610 participants, mean (SD) age was 68.5 (11.8) years and BMI of 26.9 (4.9), 53% were women. Mean MCS was 44.7 (11.2) at baseline and 47.5 (10.5) at 1-year post surgery; average 1-year change was 2.8 (95% CI 1.9-3.6). WOMAC pain score was 39.6 (18.3) at baseline and 83.8 (20.4) at 1-year post surgery; 1-year change was 44.2 (95% CI 42.4-46.0). Corresponding WOMAC function was 40.2 (18.8) and 78.3 (22.1); 1-year change was 38.1 (95% CIs 36.2-40.0). On average, a 10-point increase in 1-year change in pain score was associated with a 0.7 point increase in the adjusted 1-year change in MCS (95% CI 0.2-1.1). The change in function was associated with a 0.9 point increase in 1-year change in MCS (95% CI 0.5-1.4).

Conclusion. Mental health significantly improved from baseline to 1-year post-surgery. Patients whose pain and function scores improved the most had also the greatest improvement in mental health.

Towards Pharmacovigilance Using Machine Learning To Identify Unknown Adverse Reactions Triggered By Drug-Drug Interaction

Tabassum Kakar, Worcester Polytechnic Institute
Xiao Qin, Worcester Polytechnic Institute
Susmitha Wunnava, Worcester Polytechnic Institute
Elke A. Rundensteiner, Worcester Polytechnic Institute

12:30 PM

Adverse Drug Reactions (ADRs) are a major cause of morbidity and mortality in world. There is thus a growing need of methods facilitating the automated detection of drugs-related ADR; especially ADRs that were not known from clinical trials but later arise due to drug-drug interactions. In this research our goal is to discover the severe unknown Adverse Drug Reactions caused by a combination of drugs, also known as Drug-Drug-Interaction. We propose to use Association Rule Mining to find the ADRs caused by using a combination of drugs yet not known to be caused if these drugs were taken individually. For evaluation, we will test out the proposed strategies on real-world medical data extracted from the spontaneous adverse drug reaction reporting system called FAERS. The results mined by our tool will be checked both manually by literature review and then verified by domain experts for interestingness and accuracy.

Transferrin Conjugated Polymeric Nanomedicine for Targeting Pancreatic Cancer using Paclitaxel and Gemcitabine

Aniket Gad, University of Massachusetts Lowell
Michael Tilton, University of Massachusetts Amherst
Brandon Piel, University of Massachusetts Lowell
Prakash Rai, University of Massachusetts Lowell

12:30 PM

Pancreatic cancer (PanCa) has a dismal prognosis with five-year survival rates under 5%. PanCa is usally diagnosed at very late stages and even if diagnosed early, surgery is rarely an option. These factors contribute towards the bleak statistics for PanCa Chemo and radiation treatments having deleterious side-effects. There is therefore a clinical, unmet need for novel, targeted treatments with low morbidity in PanCa. Gemzar® (gemcitabine-HCl) is an FDA (Food and Drug Administration) approved chemotherapeutic drug that has been used to treat PanCa. However, intrinsic and acquired chemoresistance to gemcitabine contribute to the poor prognosis of PanCa. A combination of Abraxane® (albumin-stabilized paclitaxel nano-formulation) with gemcitabine has shown survival benefits and has now become the first line treatment for PanCa. Desmoplasia is a fundamental characteristic of PanCa that contributes significantly to its chemoresistance, making drug delivery to PanCa cells difficult. Nanomedicines combining multiple drugs can be designed to overcome this hurdle. This project aims at developing a targeted nanomedicine by using a combination of gemcitabine and paclitaxel encapsulated in polymeric nanoparticles for the treatment of PanCa. Oil/ water emulsion technique was employed for the preparation of poly (lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating gemcitabine and paclitaxel. Synthesis protocols yielded drug-loaded PLGA nanoparticles with an average diameter less than 200 nm, with encapsulation efficiencies ranging from 40-70%. In vitro tests for cell viability studies using the MTT assay demonstrated lower cell viability in AsPC-1 cells when treated with these nano-formulations as compared to their free-drug counterparts. Current studies include conjugating drug-loaded PLGA-polyethylene glycol-Maleimide nanoparticles with transferrin peptide for targeted therapy, which is expected to prove more efficacious when tested for cell viability in vitro than its non-targeted formulations that have been obtained. These results therefore certify this nanotherapeutic approach as a potential therapy for PanCa.

Translating Comparative TJR Outcomes for Performance Improvement to Guide Surgical Quality Improvement

Hua Zheng, University of Massachusetts Medical School
Wenjun Li, University of Massachusetts Medical School
Celeste Lemay, University of Massachusetts Medical School
David Ayers, University of Massachusetts Medical School
Patricia D. Franklin, University of Massachusetts Medical School

12:30 PM

Background/Purpose: With the CMS decision to publicly report hospital-specific post-operative total joint replacement (TJR) complications and readmissions, orthopedic surgeons need new sources of post-operative outcome data to monitor and improve post-hospital care. The AHRQ funded research program, Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR), developed methods to capture longitudinal patient-reported outcomes (PROs) and comprehensive post-TJR medical and surgical events, and established a web reporting system to return comparative outcome reports to participating surgeons and hospitals in order to monitor and improve quality and outcomes.

Methods: This national cohort/registry captures post-TJR measures directly from patients in their homes to assure uniform time, completion, and consistency for data comparisons across hospitals. Quarterly updated web reports deliver hospital- and surgeon-specific TJR outcomes compared with those of their peers and risk-adjusted national benchmarks on PROs as well as on post-operative event rates.

Results: Our national cohort enrolled 25,000 patients from 150 diverse orthopedists in 22 US states with varied hospital and surgeon practices. The secure, HIPAA compliant website was established that presents summary and risk-adjusted comparative statistics for primary TJR for all enrolled patients. The website provides a downloadable and printable report and an Executive Summary of key pre-operative patient risk factors, post-operative events, and post-operative PROs enabling the providers to compare their outcomes to the other participating sites. Individual patient reports are available for surgeons with real-time scores and trended outcome data to facilitate patient and surgeon shared treatment decision making.

Conclusion/Implications: A secure reporting website was established to disseminate comparative outcome reports to all participating hospitals and surgeons. Returning comparative outcome data to hospitals and surgeons encourages their active participation in this national registry and allows them to undstand their relative performance compared to peers while supporting practice-level quality monitoring and improvement efforts in patient care.

Translating dosage compensation to trisomy 21

Jun Jiang, University of Massachusetts Medical School
Yuanchun Jing, University of Massachusetts Medical School
Gregory J. Cost, Sangamo BioSciences
Jen-Chieh Chiang, University of Massachusetts Medical School
Heather J. Kolpa, University of Massachusetts Medical School
Allison M. Cotton, University of British Columbia
Dawn M. Carone, University of Massachusetts Medical School
Benjamin R. Carone, University of Massachusetts Medical School
Meg Byron, University of Massachusetts Medical School
Philip D. Gregory, Sangamo BioSciences
Carolyn J. Brown, University of British Columbia
Fyodor D. Urnov, Sangamo BioSciences
Lisa L. Hall, University of Massachusetts Medical School
Jeanne B. Lawrence, University of Massachusetts Medical School

12:30 PM

Down syndrome is the leading genetic cause of intellectual disabilities, occurring in 1 out of 700 live births. Given that Down syndrome is caused by an extra copy of chromosome 21 that involves over-expression of 400 genes across a whole chromosome, it precludes any possibility of a genetic therapy. Our lab has long studied the natural dosage compensation mechanism for X chromosome inactivation. To “dosage compensate” X-linked genes between females and males, the X-linked XIST gene produces a large non-coding RNA that silences one of the two X chromosomes in female cells. The initial motivation of this study was to translate the natural mechanisms of X chromosome inactivation into chromosome therapy for Down syndrome. Using genome editing with zinc finger nucleases, we have successfully inserted a large XIST transgene into Chromosome 21 in Down syndrome iPS cells, which results in chromosome-wide transcriptional silencing of the extra Chromosome 21. Remarkably, deficits in proliferation and neural growth are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro surmounts the major first step towards potential development of “chromosome therapy” for Down syndrome. The human iPSC-based trisomy correction system we established opens a unique opportunity to identify therapeutic targets and study transplantation therapies for Down syndrome.

Triad of Suffering: Pain, Depression, and Anxiety among Newly Admitted Nursing Homes Residents

Christine M. Ulbricht, University of Massachusetts Medical School
Jacob N. Hunnicutt, University of Massachusetts Medical School
Kate L. Lapane, University of Massachusetts Medical School

12:30 PM

Introduction: Depression and anxiety disorders are prevalent among older adults, as is pain. These conditions are independently associated with reduced functioning and quality of life. Despite the frequent co-occurrence of all three of these disorders, little is known about the epidemiology and treatment of these disorders in nursing homes. The objectives of this study were to: 1) describe the prevalence of depression, anxiety disorders, and pain among newly admitted nursing home residents; and 2) describe the treatment of these disorders.

Methods: We used national Minimum Data Set (MDS) version 3.0 data from 2011-2012. Federally-mandated for all residents living in Medicare/Medicaid-certified nursing facilities, the MDS is a comprehensive clinical assessment including > 400 items on sociodemographics, mood and behavior, symptoms, pain, clinical diagnoses, and treatments. We identified residents with MDS assessments performed at admission between 2011-2012 who were 65 years of age or older; were non-comatose; were not admitted to a swing bed provider; did not have mental retardation or developmental delays; & were able to complete a pain assessment (n = 783,826).

Results: At admission, 36% of residents (n = 283,050) had a documented active diagnosis of depression (other than bipolar disorder), anxiety disorder, or both. Having pain in the last 5 days was reported by 53% of residents. Rates of self-reported pain were similar across psychiatric disorders. 60-62% of residents reporting pain received a combination of pain management interventions. More than a third of residents did not receive any psychiatric treatment.

Conclusions: Many nursing home residents experience pain, depression, and anxiety at admission. Pain management is common. An improved understanding of the relationships between pain, mental health, and analgesic use is necessary since older adults, particularly those in nursing homes, are routinely excluded from clinical trials despite being at high risk for adverse effects of analgesics and other treatments.

Using Interviews to Understand Patients’ Post-operative Pain Management Educational Needs Before and After Elective Total Joint Replacement Surgery

Celeste A. Lemay, University of Massachusetts Medical School
Patricia D. Franklin, University of Massachusetts Medical School

12:30 PM

Objective: To better understand the education needs of patients electing to have TJR in managing their pain in the post-operative period after discharge from the hospital.

Methods: An exploratory, descriptive, qualitative design. Convenience sample of people who reported that they had not received information about pain management prior to TJR surgery were recruited from 9 surgeon practices in 8 states to participate in telephone interviews, utilizing open-ended questions. Questions included: recollection of pre-op class attended and content; experiences with surgical pain after surgery and how it was managed; experiences with pain medicine; experience using non-medicine related pain reduction methods; suggestions for delivery of pain management information. Interviews were recorded and transcribed. Data were categorized using content analysis techniques.

Results: Seventeen patients were interviewed. Although all remembered attending a pre-operative class prior to their joint replacement surgery, none remembered receiving information during that class about managing pain once they were discharged. All had been prescribed an opioid for pain management post-operatively; however no patients reported receiving any information regarding use of the medication other than the information on the pill bottle. Many had concerns regarding the use of opioids to control their pain, including side effects, such as constipation and the risk of addiction. The most common non-medicine method used to manage pain was the use of ice. Participants believed that information about pain management, including both non-medicine approaches and instructions for taking opioids would be helpful and should be delivered at multiple time points, including pre-operatively, at discharge, and within the first few days after discharge.

Conclusion: With trends toward shorter hospital stays, home based pain management is a priority. Understanding the pain management education needs of patients considering elective TJR could inform interventions for this population as well as provide insight into the needs of other patients undergoing surgery.

Utilizing the Green Nursing Project Initiative to Educate Nurses about Health Effects Related to Exposure of Chemicals Contained in Household and Personal Care Products and to Inspire Them to Take Action

Lisa Chan, University of Massachusetts Medical School
Stephanie Chalupka, Worcester State University

12:30 PM

Consumers are exposed to a variety of environmental chemicals including carcinogens, reproductive toxins, and endocrine disrupting chemicals from everyday use of common household and personal care products. Evidence supports concern that exposures to low doses or the combination of low doses of chemicals can pose a health risk for the general population as well as for vulnerable populations. Gaps exist in translating this information to the public and helping people understand the health effects related to chemical exposures and personal actions they could take to reduce exposures.

There are 2.6 million nurses in the U.S. who have direct access to numerous patient populations. Educating and utilizing nurses as a conduit for information-sharing related to environmental health issues could fill the gap, influence health outcomes, and contribute to sustainable communities.

A Speaker’s Bureau was constructed under the Central Mass Health Literacy Project to facilitate community access to health literacy topics. The Green Nursing Project is an initiative to educate hundreds of nurses about Environmental Health Literacy topics and Inspire them to take Personal and Professional Action. The Green Nursing Project includes Hands-on Interactive Workshops to introduce participants to chemicals in consumer products, adverse health effects, and risk reduction strategies.

Which is the primary factor influencing running stride parameters: age or lower limb strength?

Carl Jewell, University of Massachusetts Amherst
Eric Rohr, Brooks Sports, Inc.
J. Hamill, University of Massachusetts Amherst
Katherine A. Boyer, University of Massachusetts Amherst

12:30 PM

Much still remains unknown about the impact of age, and age-related changes in muscle function, on gait parameters. The aim of this study was to examine the impact of strength on running gait parameters across the adult lifespan. We tested the hypothesis that a greater amount of the variance in peak hip, knee and ankle sagittal plane moments would be explained by peak isometric joint torques as compared to age. Twenty-four healthy adults, ages 20-66 years, completed 5 trials on an overground 20-meter runway at a standardized velocity of 3.5 ms-1 (± 5%). Participants performed maximal isometric plantar flexion and knee extension for three contractions lasting three seconds each. Linear regression analysis between strength, age, and moments were performed. At the ankle, age alone explained 14.4% of the variance in the peak ankle joint moment. There was not a significant increase in the variance explained when strength was added to the model. At the knee, neither age nor strength explained a significant portion of the variance in peak knee moments. However, together age and strength explained 27.9% of the variance in the peak knee moment. No significant associations were found between the hip moments and either knee and ankle strength. These results suggest that other age-related physiological changes may drive changes in gait mechanics more so than maximal torque production. A more dynamic measure of muscle function, such as power or isokinetic torque at varying speeds may have greater predictive value for gait performance.

Workplace Predictors of Perceived Quality of Care in Nursing homes

Winnie Chin, University of Massachusetts Lowell
Laura Punnett, University of Massachusetts Lowell
Rebecca Gore, University of Massachusetts Lowell
Laura Kernan, University of Massachusetts Lowell

12:30 PM

Nursing home quality of care (QOC) is a matter of public concern and public policy. Higher nurse-to-patient ratios have been shown to decrease rates of adverse outcomes. Positive nurse-doctor relationships also have a positive effect, which might translate to other clinical staff, such as nursing aides, who perform the majority of direct care tasks in nursing homes. This cross-sectional study examined whether workplace factors in nursing homes were associated with QOC as evaluated by staff members themselves. Surveys were distributed to personnel in 24 nursing home facilities in the Northeast U.S. A total of 1463 respondents provided ratings of QOC and 14 work environment features. Analyses included correlations, Cronbach’s alpha, and principal components analyses (with rotation) to examine psychometric properties of predictor scales and reduce multicollinearity. A multivariable model of QOC was built using all potential workplace factors to determine which factors contribute to self-reported QOC, with removal of those covariates that were not significant (p>0.05), decreased the model fit, or showed a confounding effect (>15% change in other coefficients). The final model showed that perceived commitment and obstacles to safe-lifting programs, respect and support between coworkers and supervisors, adequacy of staffing, physical exertion, safety climate, and psychological demand, were significant contributors to staff-assessed QOC. Nursing homes should consider cultivating these work environment characteristics for the benefit of both direct-care staff and the residents for whom they provide care.