Public Response to Park and Recreation Funding and Cost-saving Strategies: The Role of Organizational Trust and Committment

Historically, public park and recreation services have been funded through general funds and appropriations, with minimal amounts derived from non-tax revenue sources. The fiscal conservative movement, however, has spawned an expansion of nontax revenues and cost saving strategies. Th is study examines the level of citizen support for a variety of funding and cost-saving strategies for park and recreation agencies in a metropolitan region, and the factors related to citizens’ opinions about such strategies. Data were collected through a mail survey of adult residents of the Harrisburg, Pennsylvania region. A total of 578 questionnaires were completed. Results showed that funding strategies involving external contributions such as donations and corporate sponsorships were most strongly supported by the local citizenry. Respondents were least supportive of park services privatization and the use of park entrance fees. Regression analysis was used to test the relationships between citizen socio-demographic characteristics, park use patterns, organizational trust and commitment, and level of support for the various strategies. Organizational trust, commitment, and citizen characteristics were signifi cantly related to a number of funding strategies. While prior research has examined the role of trust and commitment in the implementation of enterprise funding strategies (e.g. user fees), our data indicates that trust and commitment were more salient for general tax support than for other, more transactional funding strategies, such as user fees and corporate sponsorships. Respondents who perceived that their local park agencies were socially competent and who were more committed to the agency were also more likely to support taxes and less likely to support park privatization. These results affirm that a trusting and committed citizenry is a key ingredient in preventing the erosion of tax-based support and the subsequent privatization of park and recreation services. Park and recreation administrators who wish to expand their funding beyond existing tax support should take actions to foster trust and commitment across their multiple constituent groups. Agencies that currently enjoy a high level of constituent trust and commitment should be cautious when privatizing park services, lest they compromise existing levels of trust and commitment

S-Adenosyl-Methionine and Betaine Improve Early Virological Response in Chronic Hepatitis C Patients with Previous Nonresponse

Treatment of chronic hepatitis C (CHC) with pegylated interferon (pegIFN ) and ribavirin results in a sustained response in approximately half of patients. Viral interference with IFN signal transduction through the Jak-STAT pathway might be an important factor underlying treatment failure. S-adenosyl-L-methionine (SAMe) and betaine potentiate IFN signaling in cultured cells that express hepatitis C virus (HCV) proteins, and enhance the inhibitory effect of IFN on HCV replicons. We have performed a clinical study with the aim to evaluate efficacy and safety of the addition of SAMe and betaine to treatment of CHC with pegIFN /ribavirin

Effective risk relievers for dimensional perceived risks on mail-order purchase: a case study on speciality foods in the UK

This article examines the effective risk relievers for different dimensions of perceived risk on mail-order purchase of food products. The sample comprised 1,600 active and inactive mail-order specialty food shoppers in the UK. The analysis focused on the correlation coefficients between consumers' levels of perceived risk and their weight on the importance of the risk relievers. Amongst 15 risk relievers, the results implied that there are certain risk relievers attached to higher levels of importance by consumers, who perceive higher levels of risks in certain aspects of mail-order purchase. Therefore, mail-order companies should promote the effective risk relievers to reduce specific dimensions of perceived risks

Myeloid-Specific Deletion of Peptidylarginine Deiminase 4 Mitigates Atherosclerosis

Increasing evidence suggests that neutrophil extracellular traps (NETs) may play a role in promoting atherosclerotic plaque lesions in humans and in murine models. The exact pathways involved in NET-driven atherogenesis remain to be systematically characterized. To assess the extent to which myeloid-specific peptidylarginine deiminase 4 (PAD4) and PAD4-dependent NET formation contribute to atherosclerosis, mice with myeloid-specific deletion of PAD4 were generated and backcrossed to Apoe−/− mice. The kinetics of atherosclerosis development were determined. NETs, but not macrophage extracellular traps, were present in atherosclerotic lesions as early as 3 weeks after initiating high-fat chow. The presence of NETs was associated with the development of atherosclerosis and with inflammatory responses in the aorta. Specific deletion of PAD4 in the myeloid lineage significantly reduced atherosclerosis burden in association with diminished NET formation and reduced inflammatory responses in the aorta. NETs stimulated macrophages to synthesize inflammatory mediators, including IL-1β, CCL2, CXCL1, and CXCL2. Our data support the notion that NETs promote atherosclerosis and that the use of specific PAD4 inhibitors may have therapeutic benefits in this potentially devastating condition

Hepatic STAT1-Nuclear Translocation and Interleukin 28B Polymorphisms Predict Treatment Outcomes in Hepatitis C Virus Genotype 1-Infected Patients

We investigated associations between signal transducer and activator of transcription (STAT) 1 in pretreated liver tissues, interleukin (IL) 28B polymorphism and treatment response in hepatitis C virus (HCV)-infected patients treated with peginterferon and ribavirin.We performed immunostaining analysis of STAT1 in liver tissues and determined IL28B polymorphism at rs8099917. We then compared the results with treatment outcomes in HCV genotype 1 patients with high viral load who were receiving peginterferon plus ribavirin. In univariate analysis, younger age, white blood cell counts, virological responder, early virological responder (EVR), mild activity (A1) of liver inflammation grading, and lower STAT1 nuclear-stain of hepatocytes in zone 1, zone 2 and total zones of liver were associated with sustained virological responder (SVR). Multivariate analysis showed that EVR, age and hepatic STAT1 nuclear-stain in zone 2 of liver were independent predictors of SVR. It was also revealed that IL28B and STAT1-nuclear translocation in hepatocytes are independent predictors of response to treatment with peginterferon and ribavirin in chronic hepatitis C patients.Concomitant assessment of lower STAT1 nuclear-stain of hepatocytes and IL28B polymorphism is useful for prediction of SVR in HCV genotype 1 patients

Methylthioadenosine reprograms macrophage activation through adenosine receptor stimulation

Regulation of inflammation is necessary to balance sufficient pathogen clearance with excessive tissue damage. Central to regulating inflammation is the switch from a pro-inflammatory pathway to an anti-inflammatory pathway. Macrophages are well-positioned to initiate this switch, and as such are the target of multiple therapeutics. One such potential therapeutic is methylthioadenosine (MTA), which inhibits TNFα production following LPS stimulation. We found that MTA could block TNFα production by multiple TLR ligands. Further, it prevented surface expression of CD69 and CD86 and reduced NF-KB signaling. We then determined that the mechanism of this action by MTA is signaling through adenosine A2 receptors. A2 receptors and TLR receptors synergized to promote an anti-inflammatory phenotype, as MTA enhanced LPS tolerance. In contrast, IL-1β production and processing was not affected by MTA exposure. Taken together, these data demonstrate that MTA reprograms TLR activation pathways via adenosine receptors to promote resolution of inflammation. © 2014 Keyel et al

Identification of a Shared Genetic Susceptibility Locus for Coronary Heart Disease and Periodontitis

Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33–2.94; P = 6.9×10−4) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6×10−2) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases

A preliminary investigation of materialism and impulsiveness as predictors of technological addictions among young adults

Background and aims: The primary objective of the present research is to investigate the drivers of technological addiction in college students — heavy users of Information and Communication Technology (ICT). The study places cell phone and instant messaging addiction in the broader context of consumption pathologies, investigating the influence of materialism and impulsiveness on these two technologies. Clearly, cell phones serve more than just a utilitarian purpose. Cell phones are used in public and play a vital role in the lives of young adults. The accessibility of new technologies, like cell phones, which have the advantages of portability and an ever increasing array of functions, makes their over-use increasingly likely. Methods: College undergraduates (N = 191) from two U.S. universities completed a paper and pencil survey instrument during class. The questionnaire took approximately 15–20 minutes to complete and contained scales that measured materialism, impulsiveness, and mobile phone and instant messaging addiction. Results: Factor analysis supported the discriminant validity of Ehrenberg, Juckes, White and Walsh's (2008) Mobile Phone and Instant Messaging Addictive Tendencies Scale. The path model indicates that both materialism and impulsiveness impact the two addictive tendencies, and that materialism's direct impact on these addictions has a noticeably larger effect on cell phone use than instant messaging. Conclusions: The present study finds that materialism and impulsiveness drive both a dependence on cell phones and instant messaging. As Griffiths (2012) rightly warns, however, researchers must be aware that one's addiction may not simply be to the cell phone, but to a particular activity or function of the cell phone. The emergence of multi-function smart phones requires that research must dig beneath the technology being used to the activities that draw the user to the particular technology

Citrullination regulates pluripotency and histone H1 binding to chromatin.

Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.Cancer Research UKThis is the author accepted manuscript. The final version is available from the Nature Publishing Group via http://dx.doi.org/10.1038/nature1294