Growing Pains or Opportunities? A Customer Survey of Three Farmers\u27 Markets in One Rural Community

The continued growth of farmers\u27 markets is presenting new challenges to Extension. As the number of markets expands, how can Extension help those in the same community work together for mutual benefit? The study reported here examined similarities and differences among customers attending three different farmers\u27 markets within a single locality in Gettysburg, Pennsylvania. Based on 370 customer surveys, study results underscore the diversity of markets operating within the same community and provide insights into ways Extension might assist markets to work together to expand their shared customer base, increase revenues, and better serve local residents

Integrative multiomics analysis highlights immune-cell regulatory mechanisms and shared genetic architecture for 14 immune-associated diseases and cancer outcomes

Developing functional insight into the causal molecular drivers of immunological disease is a critical challenge in genomic medicine. Here, we systematically apply Mendelian randomization (MR), genetic colocalization, immune-cell-type enrichment, and phenome-wide association methods to investigate the effects of genetically predicted gene expression on ten immune-associated diseases and four cancer outcomes. Using whole blood-derived estimates for regulatory variants from the eQTLGen consortium (n = 31,684), we constructed genetic risk scores for 10,104 genes. Applying the inverse-variance-weighted MR method transcriptome wide while accounting for linkage disequilibrium structure identified 664 unique genes with evidence of a genetically predicted effect on at least one disease outcome (p < 4.81 × 10(−5)). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci by using gene expression data derived from 18 types of immune cells. This highlighted many cell-type-dependent effects, such as PRKCQ expression and asthma risk (posterior probability = 0.998), which was T cell specific. Phenome-wide analyses on 311 complex traits and endpoints allowed us to explore shared genetic architecture and prioritize key drivers of disease risk, such as CASP10, which provided evidence of an effect on seven cancer-related outcomes. Our atlas of results can be used to characterize known and novel loci in immune-associated disease and cancer susceptibility, both in terms of elucidating cell-type-dependent effects as well as dissecting shared disease pathways and pervasive pleiotropy. As an exemplar, we have highlighted several key findings in this study, although similar evaluations can be conducted via our interactive web platform

Liquid phase catalytic hydrogenation of carbon dioxide

Concerns of global warming and climate change have dominantly been the consequence of rising anthropogenic carbon dioxide (CO2) atmospheric concentration. One method of reducing CO2 emissions is unlocking the potential of CO2 as a chemical C-1 feedstock, converting this current waste compound into high value chemicals and fuels. The research presented in this thesis addresses the utilisation of CO2 using catalysis to form formate. This work can be divided into three catalytic materials, hence, 3 results chapters. First, a series of Pd/Mo2C catalysts were synthesised, optimised and evaluated for CO2 hydrogenation, achieving TON of 109. The role of base and the pH of the reaction medium is importantly identified, having an impact on the intermediates essential for the reaction process. A key message conveyed is the crucial role of adding Ru to Pd in enhancing catalytic stability. The two next chapters of research were inspired by the origin of life theory. First investigated is the iron sulphide pyrrhotite, (Fe1-xS), and its ability as a catalyst towards the hydrogenation of CO2. Controlled oxidation of the material was found to increase the surface oxygen content, creating new oxygen containing Fe and S species, having a positive effect on the catalytic activity increasing formate productivity from 0.3 μmol to 1.0 μmol. The material was characterised, and catalyst preparation optimised for catalytic activity. In the next chapter, iron nickel sulphide was then investigated under the same study. Violarite (Fe,Ni)3S4 was synthesised, characterised, and the synthesis procedure was optimised. Again, calcination is required for the optimal catalytic activity, creating vital oxygen containing species. Violarite achieved a superior catalytic performance than pyrrhotite, producing 4.9 μmol of formate. Overall, this work was intended to investigate novel materials for the catalytic hydrogenation of CO2. Catalyst characterisation has been crucial for understanding the catalytic properties of such materials, and this work hopes to convey their importance within this globally significant reaction process

Concentration of Heavy Metals in Three Distinct Algae Families from Humboldt County, California

Anthropogenic impacts on marine environments can impact metal fluxes and concentrations available to marine species. Monitoring these impacts is necessary to better understand the interactions between the biotic and abiotic components of these ecosystems and mitigate the risk posed by harmful toxins introduced by human activities. Biomoniters, like macroscopic algae, are useful indicators that illuminate the bioaccumulation of toxins commonly introduced from anthropogenic activity. With this in mind, the concentrations of heavy metals zinc (Zn), nickel (Ni), and copper (Cu) were analyzed via the assessment of algae (Representatives from Ulva, Mastocarpus, Fucus) in two sites in Humboldt County: Samoa (urbanized) and Petrolia (rural). Flame atomic absorption spectroscopy (FAAS) was used to quantify the concentration of metals in both algae and sedimental substrate, providing both algal metal content and a biota-sediment accumulation factor (BSAF). It was determined that the order of metal concentration followed Zn \u3e Ni ≥ Cu within algae at both locations for all three algae families. This data is consistent with previous studies of algae species as bioindicators of heavy metal contamination (Kangas et al. 1984)

Cardiovascular magnetic resonance:Diagnostic utility and specific considerations in the pediatric population

Cardiovascular magnetic resonance is a non-invasive imaging modality which is emerging as important tool for the investigation and management of pediatric cardiovascular disease. In this review we describe the key technical and practical differences between scanning children and adults, and highlight some important considerations that must be taken into account for this patient population. Using case examples commonly seen in clinical practice, we discuss the important clinical applications of cardiovascular magnetic resonance, and briefly highlight key future developments in this field

Oral Delivery of the P2Y12 Receptor Antagonist Ticagrelor Prevents Loss of Photoreceptors in an ABCA4−/− Mouse Model of Retinal Degeneration

PURPOSE. Accumulation of lysosomal waste is linked to neurodegeneration in multiple diseases, and pharmacologic enhancement of lysosomal activity is hypothesized to reduce pathology. An excessive accumulation of lysosomal-associated lipofuscin waste and an elevated lysosomal pH occur in retinal pigment epithelial cells of the ABCA4 mouse model of Stargardt\u27s retinal degeneration. As treatment with the P2Y12 receptor antagonist ticagrelor was previously shown to lower lysosomal pH and lipofuscin-like autofluorescence in these cells, we asked whether oral delivery of ticagrelor also prevented photoreceptor loss. METHODS. Moderate light exposure was used to accelerate photoreceptor loss in albino ABCA4 mice as compared to BALB/c controls. Ticagrelor (0.1%–0.15%) was added to mouse chow for between 1 and 10 months. Photoreceptor function was determined with electroretinograms, while cell survival was determined using optical coherence tomography and histology. RESULTS. Protection by ticagrelor was demonstrated functionally by using the electroretinogram, as ticagrelor-treated ABCA4 mice had increased a-and b-waves compared to untreated mice. Mice receiving ticagrelor treatment had a thicker outer nuclear layer, as measured with both optical coherence tomography and histologic sections. Ticagrelor decreased expression of LAMP1, implicating enhanced lysosomal function. No signs of retinal bleeding were observed after prolonged treatment with ticagrelor. CONCLUSIONS. Oral treatment with ticagrelor protected photoreceptors in the ABCA4 mouse, which is consistent with enhanced lysosomal function. As mouse ticagrelor exposure levels were clinically relevant, the drug may be of benefit in preventing the loss of photoreceptors in Stargardt’s disease and other neurodegenerations associated with lysosomal dysfunction. © 2019 The Authors. All rights reserved

Medication Exposure Patterns in Primary Care Patients Prescribed Pharmacogenetically Actionable Opioids

Current approaches to assessing medication exposure fail to capture the complexity of the phenomenon and the context in which it occurs. This study’s purpose was to develop a typology of subgroups of patients who share common patterns of medication exposure. To create the typology, we used an exemplar sample of 30 patients in a large public healthcare system who had been prescribed the pharmacogenetically actionable opioids codeine or tramadol. Data related to medication exposure were drawn from large data repositories. Using a person-oriented qualitative approach, eight subgroups of patients who shared common patterns of medication exposure were identified. The subgroups had one of five opioid prescription patterns (i.e., singular, episodic, switching, sustained, multiplex), and one of three types of primary foci of medical care (i.e., pain, comorbidities, both). The findings reveal medication exposure patterns that are dynamic, multidimensional, and complex, and the typology offers an innovative approach to assessing medication exposure

CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids

Purpose When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. Methods We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. Results Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. Conclusion Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol

Polarized Cytokine Release Triggered by P2X7 Receptor from Retinal Pigmented Epithelial Cells Dependent on Calcium Influx

Cytokine release from non-inflammatory cells is a key step in innate immunity, and agonists triggering cytokine release are central in coordinating responses. P2X7 receptor (P2X7R) stimulation by extracellular ATP is best known to active the NLRP3 inflammasome and release IL-1β, but stimulation also leads to release of other cytokines. As cytokine signaling by retinal pigmented epithelial (RPE) cells is implicated in retinal neurodegeneration, the role of P2X7R in release of cytokine IL-6 from RPE cells was investigated. P2X7R stimulation triggered IL-6 release from primary mouse RPE, human iPS-RPE and human ARPE-19 cells. IL-6 release was polarized, with predominant rise across apical membranes. IL-6 release was inhibited by P2X7R antagonists A438079, A839977, and AZ10606120, but not the NRTI lamivudine (3TC), P2X1R antagonist NF279, or P2Y1R antagonist MRS2179. P2X7R-mediated IL-6 release required extracellular Ca2+ and was blocked by Ca2+ chelator BAPTA. IL-6 release and Ca2+ elevation occurred rapidly, consistent with vesicular IL-6 staining in unstimulated cells. P2X7R stimulation did not trigger IL-1β release in these unprimed cells. P2X7R-mediated IL-6 release was enhanced in RPE cells from the ABCA4-/- mouse model of retinal degeneration. In summary, P2X7R stimulation triggers rapid Ca2+-dependent IL-6 release across the apical membrane of RPE cells