Health Literacy and Medication Practices in Senior Housing Residents

Objective: To conduct a descriptive analysis of health literacy, knowledge of prescribed medications, and methods of administering medications in a cohort of senior housing residents.https://scholarworks.uvm.edu/comphp_gallery/1027/thumbnail.jp

Examination of the Efficacy of Proximity Warning Devices for Young and Older Drivers

OBJECTIVESThe study was conducted to examine the efficacy of uni- and multi-modal proximity warningdevices for forward object collision and side-object detection for young and older adult drivers.METHODSTwo experiments were conducted, each with 20 young (18 to 30 years of age) and 20 older (61to 80 years of age) healthy and high functioning drivers. In each, participants drove a series ofbrief (~ 4 minute) highway scenarios with temporally unpredictable forward and side collisionevents (i.e., other vehicles). The experiments were conducted in a fixed-base Drive Safetysimulator with a 135-degree wrap-around forward field and a 135-degree rear field. Light crosswindswere included in Experiment 1, while heavier crosswinds were introduced in the secondexperiment. A secondary visual read-out task from an in-vehicle LCD display was also includedin the second experiment.In Experiment 1, potential collision events were signaled 2.2 seconds before impact by visual,auditory, auditory+visual or tactile+visual warnings that were spatially mapped to the location ofthe obstacle (left, right or center). A control condition in which subjects drove without anyproximity warning device was also included in the experiment. Experiment 2 included thecontrol, auditory+visual and visual warnings from Experiment 1.A number of dependent measures were collected, including velocity, lane position, steeringwheel movement, brake and accelerator position. However, we will focus on the response time(as measured by steering wheel deflections or removal of the foot from the accelerator) topotential collision events as well as the number of collisions in different experimental conditions.RESULTSIn both Experiments 1 and 2, the auditory+visual warning device produced the most rapidresponse and also resulted in the fewest collisions. The reduction in response time and collisions,relative to the no-warning control condition was larger in Experiment 2 than in Experiment 1, likely as a result to the more challenging driving scenarios (with the higher and unpredictablewinds and introduction of the secondary task) in this experiment.Older adults responded just as quickly as younger adults to the potential collision events in bothof the experiments. This is a very surprising finding given a voluminous laboratory literature,which suggests that older adults display slower responses than younger adults on almost any taskthat has been examined in the laboratory.In an effort to understand the age-equivalent response times to collision events, we asked youngand older participants from the first experiment to take part in an additional experimental sessionin which they made simple and choice responses to visual and auditory events in a soundattenuated subject booth. Older adults were substantially (~ 35%) slower in each of these simpleand choice tasks performed in the laboratory.Older adults displayed the same performance benefits (in terms of speeded response time andreductions in collisions) from the proximity warning devices, and particularly theauditory+visual device, in both of the experiments as younger adults. However, in Experiment 2,older adults displayed these benefits by neglecting the number read-out secondary task.CONCLUSIONSThere are several important conclusions from the present study. First, proximity warningdevices, and particularly auditory+visual devices, can substantially speed response time andreduce potential collisions in simulated driving. This is an important observation that has thepotential to reduce automobile accidents. Second, both younger and older adults benefit from theproximity warning devices. Such a finding suggests, that at least for individuals with normalvision and hearing, these devices might have substantial utility across a wide variety of drivers.Third, quite to our surprise, older adult drivers responded just as quickly, with and without theproximity warning devices, to potential collision events as younger drivers. Interestingly, ageequivalencein response time to potential collisions was not observed in simple and choiceauditory and visual laboratory response time tasks. Such data tentatively suggests that experienceand expertise in driving may act as a moderator of age-related decline in general slowing.Given the unpredictable nature of the potential collision events in our study, older drivers may becapitalizing on high levels of vigilance and attentional focus on driving relevant tasks to maintaintheir ability to rapidly respond to collision events. This hypothesis is supported, in part, by thedecrements in secondary task performed observed for the older but not for the younger adults inExperiment 2.The results from the present study are encouraging both with respect to the utility of proximitywarning devices as a means to enhance driver safety as well as for their potential application todrivers of different ages and experience levels. However, clearly additional research will beneeded to verify these results in more challenging simulator and on the road driving situations

Comparison of Novice and Experienced Drivers Using the SEEV Model to Predict Attention Allocation at Intersections During Simulated Driving

We compared the eye movements of novice drivers and experienced drivers while they drove a simulated driving scenario that included a number of intersections interspersed with stretches of straight road. The intersections included non-hazard events. Cassavaugh, Bos, McDonald, Gunaratne, & Backs (2013) attempted to model attention allocation of experienced drivers using the SEEV model. Here we compared two SEEV model fits between those experienced drivers and a sample of novice drivers. The first was a simplified model and the second was a more complex intersection model. The observed eye movement data was found to be a good fit to the simplified model for both experienced (R2 = 0.88) and novice drivers (R2 = 0.30). Like the previous results of the intersection model for the experienced drivers, the fit of the observed eye movement data to the intersection model for novice drivers was poor, and was no better than fitting the data to a randomized SEEV model. We concluded based on the simplified SEEV model, fixation count and fixation variance that experienced drivers were found to be more efficient at distributing their visual search compared to novice drivers

Comparison of Novice and Experienced Drivers Using the SEEV Model to Predict Attention Allocation at Intersections During Simulated Driving

We compared the eye movements of novice drivers and experienced drivers while they drove a simulated driving scenario that included a number of intersections interspersed with stretches of straight road. The intersections included non-hazard events. Cassavaugh, Bos, McDonald, Gunaratne, & Backs (2013) attempted to model attention allocation of experienced drivers using the SEEV model. Here we compared two SEEV model fits between those experienced drivers and a sample of novice drivers. The first was a simplified model and the second was a more complex intersection model. The observed eye movement data was found to be a good fit to the simplified model for both experienced (R2 = 0.88) and novice drivers (R2 = 0.30). Like the previous results of the intersection model for the experienced drivers, the fit of the observed eye movement data to the intersection model for novice drivers was poor, and was no better than fitting the data to a randomized SEEV model. We concluded based on the simplified SEEV model, fixation count and fixation variance that experienced drivers were found to be more efficient at distributing their visual search compared to novice drivers

Bicalutamide-induced hypoxia potentiates RUNX2-mediated Bcl-2 expression resulting in apoptosis resistance.

BACKGROUND: We have previously shown that hypoxia selects for more invasive, apoptosis-resistant LNCaP prostate cancer cells, with upregulation of the osteogenic transcription factor RUNX2 and the anti-apoptotic factor Bcl-2 detected in the hypoxia-selected cells. Following this observation, we questioned through what biological mechanism this occurs. METHODS: We examined the effect of hypoxia on RUNX2 expression and the role of RUNX2 in the regulation of Bcl-2 and apoptosis resistance in prostate cancer. RESULTS: Hypoxia increased RUNX2 expression in vitro, and bicalutamide-treated LNCaP tumours in mice (previously shown to have increased tumour hypoxia) exhibited increased RUNX2 expression. In addition, RUNX2-overexpressing LNCaP cells showed increased cell viability, following bicalutamide and docetaxel treatment, which was inhibited by RUNX2 siRNA; a range of assays demonstrated that this was due to resistance to apoptosis. RUNX2 expression was associated with increased Bcl-2 levels, and regulation of Bcl-2 by RUNX2 was confirmed through chromatin immunoprecipitation (ChIP) binding and reporter assays. Moreover, a Q-PCR array identified other apoptosis-associated genes upregulated in the RUNX2-overexpressing LNCaP cells. CONCLUSION: This study establishes a contributing mechanism for progression of prostate cancer cells to a more apoptosis-resistant and thus malignant phenotype, whereby increased expression of RUNX2 modulates the expression of apoptosis-associated factors, specifically Bcl-2

KAI1 suppresses HIF-1α and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer

<p>Abstract</p> <p>Background</p> <p>KAI1 was initially identified as a metastasis-suppressor gene in prostate cancer. It is a member of the tetraspan transmembrane superfamily (TM4SF) of membrane glycoproteins. As part of a tetraspanin-enriched microdomain (TEM), KAI1 inhibits tumor metastasis by negative regulation of Src. However, the underlying regulatory mechanism has not yet been fully elucidated. CUB-domain-containing protein 1 (CDCP1), which was previously known as tetraspanin-interacting protein in TEM, promoted metastasis via enhancement of Src activity. To better understand how KAI1 is involved in the negative regulation of Src, we here examined the function of KAI1 in CDCP1-mediated Src kinase activation and the consequences of this process, focusing on HIF-1 α and VEGF expression.</p> <p>Methods</p> <p>We used the human prostate cancer cell line PC3 which was devoid of KAI1 expression. Vector-transfected cells (PC3-GFP clone #8) and KAI1-expressing PC3 clones (PC3-KAI1 clone #5 and #6) were picked after stable transfection with KAI1 cDNA and selection in 800 <it>μ</it>g/ml G418. Protein levels were assessed by immunoblotting and VEGF reporter gene activity was measured by assaying luciferase activitiy. We followed tumor growth <it>in vivo </it>and immunohistochemistry was performed for detection of HIF-1, CDCP1, and VHL protein level.</p> <p>Results</p> <p>We demonstrated that Hypoxia-inducible factor 1α (HIF-1α) and VEGF expression were significantly inhibited by restoration of KAI1 in PC3 cells. In response to KAI1 expression, CDCP1-enhanced Src activation was down-regulated and the level of von Hippel-Lindau (VHL) protein was significantly increased. In an <it>in vivo </it>xenograft model, KAI1 inhibited the expression of CDCP1 and HIF-1α.</p> <p>Conclusions</p> <p>These novel observations may indicate that KAI1 exerts profound metastasis-suppressor activity in the tumor malignancy process via inhibition of CDCP1-mediated Src activation, followed by VHL-induced HIF-1α degradation and, ultimately, decreased VEGF expression.</p

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

Abstract 4190: Ezrin plays a key role in the regulation of translation in metastatic osteosarcoma

Abstract Our previous studies have demonstrated the association between Ezrin and the metastatic biology of pediatric sarcomas including osteosarcoma (OS) and rhabdomyosarcoma. Mechanistic studies exploring this association have shown that Ezrin expression enhances the survival of metastatic cells upon their arrival to the secondary metastatic site. In order to better understand this role in metastasis, we undertook two non-candidate analyses of Ezrin function including a microarray subtraction of high and low Ezrin expressing cells and a proteomic approach to identify proteins that bind the N-terminus of Ezrin in tumor lysates. Functional analyses of these data led to a novel and unifying hypothesis that Ezrin contributes to the efficiency of metastasis through regulation of protein translation. In support of this hypothesis we found Ezrin to be part of a ribonucleoprotein complex and to bind with poly A binding protein 1 (PABA1; PABPC1). Using luciferase reporter-based assays, we have shown that OS cells expressing high levels of Ezrin are able to translate mRNAs containing a stem loop 5′ UTR structure, so called “weakly translated mRNAs,” more efficiently than low Ezrin OS cells. This finding suggests that Ezrin's contribution to the metastatic phenotype may be due in part to enhanced translation of specific mRNAs during metastasis that are normally expressed at low levels outside of the metastatic context. Ongoing studies will now assess the ability of Ezrin to enhance the expression of specific mRNAs in 3-dimensional contexts more relevant to cancer cell growth in vivo. We have developed stable high and low Ezrin osteosarcoma cell lines that express a GFP reporter with or without a complex 5′ UTR stem loop structure in the mRNA transcript and with and without protein destabilizing elements. Initial studies have shown that the addition of the 5′ UTR structure and destabilizing elements progressively limits GFP reporter expression. We plan to confirm that this reduction in expression is due to reduced translation and to assess whether 3-D culture conditions or the in vivo environment enhance expression of these tunable reporters of translation in an Ezrin-dependant manner. We expect these results to provide a novel mechanistic basis to consider how Ezrin may contribute to metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4190. doi:1538-7445.AM2012-4190</jats:p