Building Health Equity One Institution at a Time: The Research Infrastructure in Minority Institutions Project

Developing a well-trained workforce interested in, and prepared for, conducting health equity research is an important national priority. Scientists from Minority-Serving Institutions (MSIs) bring unique perspectives and experiences with racial, ethnic and social inequities in health and health status but often lack access to training and mentoring opportunities, which is crucial for increasing the diverse pool of investigators who are adequately prepared to conduct health disparities research and to compete for National Institutes of Health research funding. The focus of the California State University, Long Beach (CSULB) Research Infrastructure in Minority Institutions (RIMI) Project was to: (a) enhance CSULB’s infrastructure and research capacity, (b) conduct applied community health research on health conditions disproportionately affecting disadvantaged populations, and (c) support faculty to embark on careers in reducing health disparities. Faculty received training, mentorship, and release time support to participate in research-related activities. Select faculty also received funding to conduct a two-year health disparities research project. Within a relatively short period of time, the RIMI Project made important strides toward strengthening the research infrastructure at CSULB by enhancing faculty capacity, improving research utilization to address health disparities, and strengthening campus and community collaborations. MSIs are encouraged to apply for opportunities to build their institution’s research capacity. The lessons learned from this project may be used as a guide for other teaching institutions that have the goal to develop minority faculty researchers

Using Spectral and Cross-Spectral Analysis to Identify Patterns and Synchrony in Couples\u27 Sexual Desire

Sexual desire discrepancy is one of the most frequently reported sexual concerns for individuals and couples and has been shown to be negatively associated with sexual and relationship satisfaction. Sexual desire has increasingly been examined as a state-like construct that ebbs and flows, but little is known about whether there are patterns in the fluctuation of sexual desire. Utilizing spectral and cross-spectral analysis, we transformed 30 days of dyadic daily diary data for perceived levels of sexual desire for a non-clinical sample of 133 couples (266 individuals) into the frequency domain to identify shared periodic state fluctuations in sexual desire. Spectral analysis is a technique commonly used in physics and engineering that allows time series data to be analyzed for the presence of regular cycles of fluctuation. Cross-spectral analysis allows for dyadic data to be analyzed for shared rates of fluctuation between partners as well as the degree of (a)synchrony (or phase shift) between these fluctuations. Men and women were found to exhibit fluctuations in sexual desire at various frequencies including rates of once and twice per month, and to have sexual desire that was unlikely to fluctuate over periods of three days or less and therefore exhibited persistence. Similar patterns of fluctuation were exhibited within couples and these patterns were found to be largely synchronous. While instances of desire discrepancy may arise due to differences in rates of sexual desire fluctuation and random fluctuations, such instances may be normal for romantic relationships. The results have important implications for researchers, clinicians, and educators in that they corroborate the supposition that sexual desire ebbs and flows and suggest that it does so with predictable regularity

Amyloid beta and diabetic pathology cooperatively stimulate cytokine expression in an Alzheimer's mouse model

Background Diabetes is a risk factor for developing Alzheimer's disease (AD); however, the mechanism by which diabetes can promote AD pathology remains unknown. Diabetes results in diverse molecular changes in the brain, including dysregulation of glucose metabolism and loss of cerebrovascular homeostasis. Although these changes have been associated with increased A beta pathology and increased expression of glial activation markers in APPswe/PS1dE9 (APP/PS1) mice, there has been limited characterization, to date, of the neuroinflammatory changes associated with diabetic conditions. Methods To more fully elucidate neuroinflammatory changes associated with diabetes that may drive AD pathology, we combined the APP/PS1 mouse model with either high-fat diet (HFD, a model of pre-diabetes), the genetic db/db model of type 2 diabetes, or the streptozotocin (STZ) model of type 1 diabetes. We then used a multiplexed immunoassay to quantify cortical changes in cytokine proteins. Results Our analysis revealed that pathology associated with either db/db, HFD, or STZ models yielded upregulation of a broad profile of cytokines, including chemokines (e.g., MIP-1 alpha, MIP-1 beta, and MCP-1) and pro-inflammatory cytokines, including IL-1 alpha, IFN-gamma, and IL-3. Moreover, multivariate partial least squares regression analysis showed that combined diabetic-APP/PS1 models yielded cooperatively enhanced expression of the cytokine profile associated with each diabetic model alone. Finally, in APP/PS1xdb/db mice, we found that circulating levels of A beta 1-40, A beta 1-42, glucose, and insulin all correlated with cytokine expression in the brain, suggesting a strong relationship between peripheral changes and brain pathology. Conclusions Altogether, our multiplexed analysis of cytokines shows that Alzheimer's and diabetic pathologies cooperate to enhance profiles of cytokines reported to be involved in both diseases. Moreover, since many of the identified cytokines promote neuronal injury, A beta and tau pathology, and breakdown of the blood-brain barrier, our data suggest that neuroinflammation may mediate the effects of diabetes on AD pathogenesis. Therefore, strategies targeting neuroinflammatory signaling, as well as metabolic control, may provide a promising strategy for intervening in the development of diabetes-associated AD

Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and elicits orthostatic issues present post-spaceflight (contributing to instability); however, it does not sufficiently address the vestibular dysfunction which occurs post-spaceflight

Finely tuned temporal and spatial delivery of GDNF promotes enhanced nerve regeneration in a long nerve defect model

The use of growth factors, such as glial cell line-derived neurotrophic factor (GDNF), for the treatment of peripheral nerve injury has been useful in promoting axon survival and regeneration. Unfortunately, finding a method that delivers the appropriate spatial and temporal release profile to promote functional recovery has proven difficult. Some release methods result in burst release profiles too short to remain effective over the regeneration period; however, prolonged exposure to GDNF can result in axonal entrapment at the site of release. Thus, GDNF was delivered in both a spatially and temporally controlled manner using a two-phase system comprised of an affinity-based release system and conditional lentiviral GDNF overexpression from Schwann cells (SCs). Briefly, SCs were transduced with a tetracycline-inducible (Tet-On) GDNF overexpressing lentivirus before transplantation. Three-centimeter acellular nerve allografts (ANAs) were modified by injection of a GDNF-releasing fibrin scaffold under the epineurium and then used to bridge a 3 cm sciatic nerve defect. To encourage growth past the ANA, GDNF-SCs were transplanted into the distal nerve and doxycycline was administered for 4, 6, or 8 weeks to determine the optimal duration of GDNF expression in the distal nerve. Live imaging and histomorphometric analysis determined that 6 weeks of doxycycline treatment resulted in enhanced regeneration compared to 4 or 8 weeks. This enhanced regeneration resulted in increased gastrocnemius and tibialis anterior muscle mass for animals receiving doxycycline for 6 weeks. The results of this study demonstrate that strategies providing spatial and temporal control of delivery can improve axonal regeneration and functional muscle reinnervation

Ensuring the Health Care Needs of Women: A Checklist for Health Exchanges

To inform the development of the state health insurance Exchanges under the Affordable Care Act, this checklist identifies key coverage, affordability and access issues that are important for women. Based on lessons learned from women’s health research and the Massachusetts experience, the checklist considers essential health benefits, implementation of no-cost preventive services including contraception, provider networks and affordability, outreach and enrollment efforts, and the importance of including gender and other demographic characteristics in data collection and reporting standards. It was jointly authored by policy experts at the Kaiser Family Foundation, The Connors Center for Women’s Health and Gender Biology at the Brigham and Women’s Hospital and the Jacobs Institute of Women’s Health at The George Washington University

Multifaceted Role for p53 in Pancreatic Cancer Suppression

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53\u27s critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC. However, the cellular basis for p53 action during PDAC development has not been explored in detail. Here, we leverage a hyperactive p53 variant-p5353,54-which we previously showed is a more robust PDAC suppressor than wild-type p53, to elucidate how p53 acts at the cellular level to dampen PDAC development. Using both inflammation-induced and KRASG12D-driven PDAC models, we find that p5353,54 both limits ADM accumulation and suppresses PanIN cell proliferation and does so more effectively than wild-type p53. Moreover, p5353,54 suppresses KRAS signaling in PanINs and limits effects on the extracellular matrix (ECM) remodeling. While p5353,54 has highlighted these functions, we find that pancreata in wild-type p53 mice similarly show less ADM, as well as reduced PanIN cell proliferation, KRAS signaling, and ECM remodeling relative to Trp53-null mice. We find further that p53 enhances chromatin accessibility at sites controlled by acinar cell identity transcription factors. These findings reveal that p53 acts at multiple stages to suppress PDAC, both by limiting metaplastic transformation of acini and by dampening KRAS signaling in PanINs, thus providing key new understanding of p53 function in PDAC

A person-centered approach to understanding negative reinforcement drinking among first year college students [post-print]

The current study used a person-centered approach (i.e. latent profile analysis) to identify distinct types of college student drinkers based on the predictions of motivational, social learning, and stress and coping theories of maladaptive drinking. A large sample (N = 844; 53% female) of first-year undergraduates from two institutions, public and private, who reported consuming one or more drinks in the last three months completed measures of depressive and anxiety symptoms, positive alcohol-outcome expectancies, negative life events, social support, drinking motives, drinking level and drinking-related problems. Latent profile analysis revealed a small subgroup of individuals (n = 81, 9%) who conformed to the anticipated high-risk profile; specifically, this group demonstrated high levels of negative affect, coping motives, drinks per week, and drinking-related problems. However, additional groups emerged that showed patterns inconsistent with the proposed vulnerability profile (e.g., high negative affect, positive expectancies, and negative life events, but relatively low drinking levels). Findings from our person-centered approach showing the presence of groups both consistent and inconsistent with the predictions of motivational, social learning, and stress and coping theories highlight the need to identify and target certain college students for prevention and intervention of negative affect-related drinking

Waldo Lake Research in 2004

The Willamette National Forest has worked with Portland State University, Center for Lakes and Reservoirs (PSU) and the University of Oregon (UO) to investigate ecosystem changes, provide guidance on long-term monitoring methods, assess monitoring data, develop predictive water quality models, and conduct research that will lead to better protection and understanding of the Waldo Lake ecosystem. This report summarizes the second year of collaborative PSU-UO research at Waldo Lake. Research has focused on understanding physical, chemical and biological characteristics of Waldo Lake across a range of spatial and temporal scales. Research tasks that continued from 2003 into 2004 included temperature monitoring, hydrodynamic and water quality model development, climate and hydrological forcing scenario investigation, bathymetric map refinement, and analysis of phytoplankton and zooplankton community changes. Research tasks initiated in 2004 included evaluation of wavelength-specific light attenuation, diel phytoplankton and zooplankton vertical distribution patterns, phytoplankton photoinhibition and photoprotection, and the role of mixotrophy in the pelagic microbial food web. Preliminary efforts were made to characterize Waldo Lake benthos through assessment of algal species diversity and chemical composition of the benthic community, as very little is currently known about the Waldo Lake benthic ecosystem. In addition, an attempt was made to map benthic substrate types through reinterpretation of data collected during the 2003 bathymetric survey

A screen for Plasmodium falciparum sporozoite surface protein binding to human hepatocyte surface receptors identifies novel host–pathogen interactions

Background: Sporozoite invasion of hepatocytes is an essential step in the Plasmodium life-cycle and has similarities, at the cellular level, to merozoite invasion of erythrocytes. In the case of the Plasmodium blood-stage, efforts to identify host–pathogen protein–protein interactions have yielded important insights including vaccine candidates. In the case of sporozoite-hepatocyte invasion, the host–pathogen protein–protein interactions involved are poorly understood. Methods: To gain a better understanding of the protein–protein interaction between the sporozoite ligands and host receptors, a systematic screen was performed. The previous Plasmodium falciparum and human surface protein ectodomain libraries were substantially extended, resulting in the creation of new libraries comprising 88 P. falciparum sporozoite protein coding sequences and 182 sequences encoding human hepatocyte surface proteins. Having expressed recombinant proteins from these sequences, a plate-based assay was used, capable of detecting low affinity interactions between recombinant proteins, modified for enhanced throughput, to screen the proteins for interactions. The novel interactions identified in the screen were characterized biochemically, and their essential role in parasite invasion was further elucidated using antibodies and genetically manipulated Plasmodium parasites. Results: A total of 7540 sporozoite-hepatocyte protein pairs were tested under conditions capable of detecting interactions of at least 1.2 µM KD. An interaction between the human fibroblast growth factor receptor 4 (FGFR4) and the P. falciparum protein Pf34 is identified and reported here, characterizing its affinity and demonstrating the blockade of the interaction by reagents, including a monoclonal antibody. Furthermore, further interactions between Pf34 and a second P. falciparum rhoptry neck protein, PfRON6, and between human low-density lipoprotein receptor (LDLR) and the P. falciparum protein PIESP15 are identified. Conditional genetic deletion confirmed the essentiality of PfRON6 in the blood-stage, consistent with the important role of this protein in parasite lifecycle. Pf34 was refractory to attempted genetic modification. Antibodies to Pf34 abrogated the interaction and had a modest effect upon sporozoite invasion into primary human hepatocytes. Conclusion: Pf34 and PfRON6 may be members of a functionally important invasion complex which could be a target for future interventions. The modified interaction screening assay, protein expression libraries and P. falciparum mutant parasites reported here may be a useful tool for protein interaction discovery and antigen candidate screening which could be of wider value to the scientific community