Vascular endothelial growth factor B (VEGF-B) is up-regulated and exogenous VEGF-B is neuroprotective in a culture model of Parkinson's disease

Parkinson's disease (PD) results from the degeneration of dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine released in the striatum. Current oral dopamine replacement or surgical therapies do not address the underlying issue of neurodegeneration, they neither slow nor halt disease. Neurotrophic factors have shown preclinical promise, but the choice of an appropriate growth factor as well as the delivery has proven difficult. In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1) We challenged rat midbrain cultures with rotenone (20 nM), a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B) was evident, while vascular endothelial growth factor A (VEGF-A) levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using β-actin as the internal standard. (2) We have also found evidence that exogenously applied VEGF-B performed as a neuroprotective agent facilitating neuron survival in an even more severe rotenone culture model of PD (40 nM rotenone). VEGF-B has very recently been added to the list of trophic factors that reduce effects of neurodegeneration, as was shown in an in vivo model of motor neuron degeneration, while lacking potential adverse angiogenic activity. The data of an in vivo protective effect on motor neurons taken together with the presented results demonstrate that VEGF-B is a new candidate trophic factor distinct from the GDNF family of trophic factors. VEGF-B is activated by neurodegenerative challenges to the midbrain, and exogenous application of VEGF-B has a neuroprotective effect in a culture model of PD. Strengthening this natural protective response by either adding exogenous VEGF-B or up-regulating the endogenous VEGF-B levels may have the potential to be a disease modifying therapy for PD. We conclude that the growth factor VEGF-B can improve neuronal survival in a culture model of PD

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

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

Demographic trends among older cannabis users in the United States, 2006–13

Background and Aims: The ageing US population is providing an unprecedented population of older adults who use recreational drugs. We aimed to estimate the trends in the prevalence of past-year use of cannabis, describe the patterns and attitudes and determine correlates of cannabis use by adults age 50 years and older. Design: Secondary analysis of the National Survey on Drug Use and Health survey from 2006 to 2013, a cross-sectional survey given to a nationally representative probability sample of populations living in US households. Setting: USA. Participants: A total of 47 140 survey respondents aged ≥ 50 years. Measures: Estimates and trends of past-year use of cannabis. Findings: The prevalence of past-year cannabis use among adults aged ≥ 50 increased significantly from 2006/07 to 2012/13, with a 57.8% relative increase for adults aged 50–64 (linear trend P < 0.001) and a 250% relative increase for those aged ≥ 65 (linear trend P = 0.002). When combining data from 2006 to 2013, 6.9% of older cannabis users met criteria for cannabis abuse or dependence, and the majority of the sample reported perceiving no risk or slight risk associated with monthly cannabis use (85.3%) or weekly use (79%). Past-year users were more likely to be younger, male, non-Hispanic, not have multiple chronic conditions and use tobacco, alcohol or other drugs compared with non-past-year cannabis users. Conclusions: The prevalence of cannabis use has increased significantly in recent years among US adults aged ≥ 50 years

PEDF and VEGF-A Output from Human Retinal Pigment Epithelial Cells Grown on Novel Microcarriers

Human retinal pigment epithelial (hRPE) cells have been tested as a cell-based therapy for Parkinson's disease but will require additional study before further clinical trials can be planned. We now show that the long-term survival and neurotrophic potential of hRPE cells can be enhanced by the use of FDA-approved plastic-based microcarriers compared to a gelatin-based microcarrier as used in failed clinical trials. The hRPE cells grown on these plastic-based microcarriers display several important characteristics of hRPE found in vivo: (1) characteristic morphological features, (2) accumulation of melanin pigment, and (3) high levels of production of the neurotrophic factors pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A). Growth of hRPE cells on plastic-based microcarriers led to sustained levels (>1 ng/ml) of PEDF and VEGF-A in conditioned media for two months. We also show that the expression of VEGF-A and PEDF is reciprocally regulated by activation of the GPR143 pathway. GPR143 is activated by L-DOPA (1 μM) which decreased VEGF-A secretion as opposed to the previously reported increase in PEDF secretion. The hRPE microcarriers are therefore novel candidate delivery systems for achieving long-term delivery of the neuroprotective factors PEDF and VEGF-A, which could have a value in neurodegenerative conditions such as Parkinson's disease

Measuring Practicing Clinicians’ Information Literacy: An Exploratory Analysis in the Context of Panel Management

BACKGROUND: As healthcare moves towards technology-driven population health management, clinicians must adopt complex digital platforms to access health information and document care. OBJECTIVES: This study explored information literacy, a set of skills required to effectively navigate population health information systems, among primary care providers in one Veterans' Affairs (VA) medical center. METHODS: Information literacy was assessed during an 8-month randomized trial that tested a population health (panel) management intervention. Providers were asked about their use and comfort with two VA digital tools for panel management at baseline, 16 weeks, and post-intervention. An 8-item scale (range 0-40) was used to measure information literacy (Cronbach's α=0.84). Scores between study arms and provider types were compared using paired t-tests and ANOVAs. Associations between self-reported digital tool use and information literacy were measured via Pearson's correlations. RESULTS: Providers showed moderate levels of information literacy (M= 27.4, SD 6.5). There were no significant differences in mean information literacy between physicians (M=26.4, SD 6.7) and nurses (M=30.5, SD 5.2, p=0.57 for difference), or between intervention (M=28.4, SD 6.5) and control groups (M=25.1, SD 6.2, p=0.12 for difference). Information literacy was correlated with higher rates of self-reported information system usage (r=0.547, p=0.001). Clinicians identified data access, accuracy, and interpretability as potential information literacy barriers. CONCLUSIONS: While exploratory in nature, cautioning generalizability, the study suggests that measuring and improving clinicians' information literacy may play a significant role in the implementation and use of digital information tools, as these tools are rapidly being deployed to enhance communication among care teams, improve health care outcomes, and reduce overall costs

(−)‐[ 18 F]Flubatine: evaluation in rhesus monkeys and a report of the first fully automated radiosynthesis validated for clinical use

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101867/1/jlcr3069.pd

The Embryonic Transcriptome Of The Red-Eared Slider Turtle (Trachemys Scripta)

The bony shell of the turtle is an evolutionary novelty not found in any other group of animals, however, research into its formation has suggested that it has evolved through modification of conserved developmental mechanisms. Although these mechanisms have been extensively characterized in model organisms, the tools for characterizing them in non-model organisms such as turtles have been limited by a lack of genomic resources. We have used a next generation sequencing approach to generate and assemble a transcriptome from stage 14 and 17 Trachemys scripta embryos, stages during which important events in shell development are known to take place. The transcriptome consists of 231,876 sequences with an N-50 of 1,166 bp. GO terms and EC codes were assigned to the 61,643 unique predicted proteins identified in the transcriptome sequences. All major GO categories and metabolic pathways are represented in the transcriptome. Transcriptome sequences were used to amplify several cDNA fragments designed for use as RNA in situ probes. One of these, BMP5, was hybridized to a T. scripta embryo and exhibits both conserved and novel expression patterns. The transcriptome sequences should be of broad use for understanding the evolution and development of the turtle shell and for annotating any future T. scripta genome sequences

Telephone care coordination for smokers in VA mental health clinics: protocol for a hybrid type-2 effectiveness-implementation trial

BACKGROUND: This paper describes an innovative protocol for a type-II hybrid effectiveness-implementation trial that is evaluating a smoking cessation telephone care coordination program for Veterans Health Administration (VA) mental-health clinic patients. As a hybrid trial, the protocol combines implementation science and clinical trial methods and outcomes that can inform future cessation studies and the implementation of tobacco cessation programs into routine care. The primary objectives of the trial are (1) to evaluate the process of adapting, implementing, and sustaining a smoking cessation telephone care coordination program in VA mental health clinics, (2) to determine the effectiveness of the program in promoting long-term abstinence from smoking among mental health patients, and (3) to compare the effectiveness of telephone counseling delivered by VA staff with that delivered by state quitlines. METHODS/DESIGN: The care coordination program is being implemented at six VA facilities. VA mental health providers refer patients to the program via an electronic medical record consult. Program staff call referred patients to offer enrollment. All patients who enroll receive a self-help booklet, mailed smoking cessation medications, and proactive multi-call telephone counseling. Participants are randomized to receive this counseling from VA staff or their state\u27s quitline. Four primary implementation strategies are being used to optimize program implementation and sustainability: blended facilitation, provider training, informatics support, and provider feedback. A three-phase formative evaluation is being conducted to identify barriers to, and facilitators for, program implementation and sustainability. A mixed-methods approach is being used to collect quantitative clinical effectiveness data (e.g., self-reported abstinence at six months) and both quantitative and qualitative implementation data (e.g., provider referral rates, coded interviews with providers). Summative data will be analyzed using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. DISCUSSION: This paper describes the rationale and methods of a trial designed to simultaneously study the clinical effectiveness and implementation of a telephone smoking cessation program for smokers using VA mental health clinics. Such hybrid designs are an important methodological design that can shorten the time between the development of an intervention and its translation into routine clinical care

The ‘doing’ and ‘undoing’ of male household decision-making and economic authority in Rwanda and its implications for gender transformative programming

This paper explores two key norms that can underpin intimate partner violence (IPV) in Rwanda: men’s role as economic provider and decision-making authority in the household. It describes the political, legal and socio-economic factors affecting these norms and how they create opportunities and barriers to ‘undoing’ restrictive gender norms. The findings are drawn from an evaluation of Inadshyikirwa, an IPV prevention programme operating in Rwanda. Across 3 intervention sectors, 24 focus groups were conducted with unmarried and married men and women residing in intervention communities. 30 interviews with couples and 9 interviews with opinion leaders were conducted before they completed programme trainings designed to shift gender norms underlying IPV. The data indicates a strong awareness of and accountability to Rwandan laws and policies supporting women’s economic empowerment and decision-making, yet also persisting traditional notions of men as household heads and primary breadwinners. Transgression of these norms could be accommodated in some circumstances, especially those involving economic necessity. The data also identified an increasing recognition of the value of a more equitable partnership model. This paper highlights the importance of carefully assessing cracks in the existing gender order that can be exploited to support gender equality and non-violence