An Ultra-Thin Polymer Coating for the Tethering of Adenoviral Vector to the Surface of Coronary Stents

Our group has previously demonstrated stent-based gene delivery with either viral or plasmid vectors. However, these previous studies utilized bulky PLGA or collagen stent coatings, known to cause inflammatory reactions in stented arteries. In the present experiments we successfully attached adenoviruses either directly, or via anti-adenovirus antibodies to the steel surface of stents using chemical coordination with biphosphonates

Biphosphonate-Mediated Gene Vector Delivery from the Metal Surfaces of Stents

The clinical use of metallic expandable intravascular stents has resulted in imporved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat in-stent restenosis by using gene vector delivery from the metallic stent surfaces has never been demonstrated. The present studies investigated the hypothesis that metal-biphosphonate binding can enable site-specific gene vector delivery from metal surfaces. Polyallylamine biphosphonate (PAA-BP) was synthesized by using Michael addition methodology. Exposure to aqueous solutions of PAA-BP resulted in the formation of a monomolecular biphosphonate later on metal alloy surfaces (steel, nitinol, and cobalt-chromium), as demonstrated by x-ray photoelectron spectroscopy. Surface-bound PAA-BP enabled adenoviral (Ad) tethering due to covalent thiol-binding of either anti-Ad antibody or a recombinant Ad-receptor protein, D1. In arterial smooth muscle cell cultures, alloy samples configured with surface-tethered Ad were demonstrated to achieve site-specific transduction with a reporter gene, (GFP). Rat carotid stent angioplasties using metal stents exposed to aqueous PAA-BP and derivatized with anti-knob antibody or D1 resulted in extensive localized Ad-GFP expression in the arterial wall. In a separate study with a model therapeutic vector, Ad-inducible nitric oxide synthase (iNOS) attached to the biphosphonate-treated metal stent surface via D1, significant inhibition of restenosis was demonstrated (neointimal/media ration 1.68 ± 0.27 and 3.4 ± 0.35; Ad-iNOS vs. control, P \u3c 0.01). Is is concluded that effective gene vector delivery from metallic stent surfaces can be achieved using this approach

Blood transcriptomic comparison of individuals with and without autism spectrum disorder: A combined‐samples mega‐analysis

Blood-based microarray studies comparing individuals affected with autism spectrum disorder (ASD) and typically developing individuals help characterize differences in circulating immune cell functions and offer potential biomarker signal. We sought to combine the subject-level data from previously published studies by mega-analysis to increase the statistical power. We identified studies that compared ex vivo blood or lymphocytes from ASD-affected individuals and unrelated comparison subjects using Affymetrix or Illumina array platforms. Raw microarray data and clinical meta-data were obtained from seven studies, totaling 626 affected and 447 comparison subjects. Microarray data were processed using uniform methods. Covariate-controlled mixed-effect linear models were used to identify gene transcripts and co-expression network modules that were significantly associated with diagnostic status. Permutation-based gene-set analysis was used to identify functionally related sets of genes that were over- and under-expressed among ASD samples. Our results were consistent with diminished interferon-, EGF-, PDGF-, PI3K-AKT-mTOR-, and RAS-MAPK-signaling cascades, and increased ribosomal translation and NK-cell related activity in ASD. We explored evidence for sex-differences in the ASD-related transcriptomic signature. We also demonstrated that machine-learning classifiers using blood transcriptome data perform with moderate accuracy when data are combined across studies. Comparing our results with those from blood-based studies of protein biomarkers (e.g., cytokines and trophic factors), we propose that ASD may feature decoupling between certain circulating signaling proteins (higher in ASD samples) and the transcriptional cascades which they typically elicit within circulating immune cells (lower in ASD samples). These findings provide insight into ASD-related transcriptional differences in circulating immune cells. © 2016 Wiley Periodicals, Inc

The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine

Background: Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care. Methods/Design This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients’ genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes, behaviors and outcomes of physician and patient participants at multiple time points before and after the disclosure of these results. Discussion The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine will evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies. Trial registration ClinicalTrials.gov identifier NCT0173656

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.

Plant growth retardation and conserved miRNAs are correlated to hibiscus chlorotic ringspot virus infection

10.1371/journal.pone.0085476PLoS ONE812-POLN

De-excitation of the strongly coupled band in 177Au and implications for core intruder configurations in the light Hg isotopes

Excited states in the proton-unbound nuclide 177Au were populated in the 92Mo(88Sr, p2n) reaction and identified using the Jurogam-II and GREAT spectrometers in conjunction with the RITU gas-filled separator at the University of Jyväskylä Accelerator Laboratory. A strongly coupled band and its decay path to the 11/2− α-decaying isomer have been identified using recoil-decay tagging. Comparisons with cranked HartreeFock-Bogoliubov (HFB) calculations based on Skyrme energy functionals suggest that the band has a prolate deformation and is based upon coupling the odd 1h11/2 proton hole to the excited 0+ 2 configuration in the 178Hg core. Although these configurations might be expected to follow the parabolic trend of core Hg(0+2 ) states as a function of neutron number, the electromagnetic decay paths from the strongly coupled band in 177Au are markedly different from those observed in the heavier isotopes above the midshell. This indicates that a significant change in the structure of the underlying A+1Hg core occurs below the neutron midshell

Prevalence and Risk Factors of Intestinal Parasitism in Rural and Remote West Malaysia

Intestinal parasitic infections (IPIs) are among the most prevalent human afflictions; these infections still have major impact on the socioeconomic and public health of the bottom billion of the world's poorest people. Although Malaysia has a thriving economy, IPIs are still very much prevalent and causing major health problems among the poor and in deprived communities especially in rural and remote areas. A comprehensive study is paramount to determine the current prevalent and factors closely linked to IPIs so that effective control measures can be instituted. In view of this, we conducted this study to provide detailed data of the existing status of IPIs among 716 participants living in rural and remote areas in Peninsular Malaysia. The establishment of such data is beneficial for the public health service to justify and facilitate the reassessment of control strategies and policies in terms of reducing intestinal parasitism. With effective control measures in place, these communities (especially children) will have a greater opportunity for a better future in terms of health and educational achievement and eventually will be at par socially and economically with urban communities in Malaysia

Climate change and climate variability: personal motivation for adaptation and mitigation

BACKGROUND: Global climate change impacts on human and natural systems are predicted to be severe, far reaching, and to affect the most physically and economically vulnerable disproportionately. Society can respond to these threats through two strategies: mitigation and adaptation. Industry, commerce, and government play indispensable roles in these actions but so do individuals, if they are receptive to behavior change. We explored whether the health frame can be used as a context to motivate behavioral reductions of greenhouse gas emissions and adaptation measures. METHODS: In 2008, we conducted a cross-sectional survey in the United States using random digit dialing. Personal relevance of climate change from health threats was explored with the Health Belief Model (HBM) as a conceptual frame and analyzed through logistic regressions and path analysis. RESULTS: Of 771 individuals surveyed, 81% (n = 622) acknowledged that climate change was occurring, and were aware of the associated ecologic and human health risks. Respondents reported reduced energy consumption if they believed climate change could affect their way of life (perceived susceptibility), Odds Ratio (OR) = 2.4 (95% Confidence Interval (CI): 1.4-4.0), endanger their life (perceived severity), OR = 1.9 (95% CI: 1.1-3.1), or saw serious barriers to protecting themselves from climate change, OR = 2.1 (95% CI: 1.2-3.5). Perceived susceptibility had the strongest effect on reduced energy consumption, either directly or indirectly via perceived severity. Those that reported having the necessary information to prepare for climate change impacts were more likely to have an emergency kit OR = 2.1 (95% CI: 1.4-3.1) or plan, OR = 2.2 (95% CI: 1.5-3.2) for their household, but also saw serious barriers to protecting themselves from climate change or climate variability, either by having an emergency kit OR = 1.6 (95% CI: 1.1-2.4) or an emergency plan OR = 1.5 (95%CI: 1.0-2.2). CONCLUSIONS: Motivation for voluntary mitigation is mostly dependent on perceived susceptibility to threats and severity of climate change or climate variability impacts, whereas adaptation is largely dependent on the availability of information relevant to climate change. Thus, the climate change discourse could be framed from a health perspective to motivate behaviour change