An Evaluability Assessment of the West Virginia Physical Activity Plan, 2015: Lessons Learned for Other State Physical Activity Plans

Background The US National Physical Activity Plan (NPAP) was released in 2009 as a national strategic plan to increase physical activity (PA). The NPAP emphasized implementing state and local PA pro- grams. Dissemination of information about NPAP has been lim- ited, however. Community Context West Virginia is a predominantly rural state with high rates of chronic diseases associated with physical inactivity. In 2015 an evaluability assessment (EA) of the West Virginia Physical Activ- ity Plan (WVPAP) was conducted, and community stakeholders were invited to participate in updating the plan. Methods A good EA seeks stakeholder input, assists in identifying program areas that need improvement, and ensures that a full evaluation will produce useful information. Data for this EA were collected via national stakeholder interviews, document reviews, discussions among workgroups consisting of state and local stakehold- ers, and surveys to determine how well the WVPAP had been im- plemented. Outcome The EA highlighted the need for WVPAP leaders to 1) establish a specific entity to implement local PA plans, 2) create sector-spe- cific logic models to simplify the WVPAP for local stakeholders, 3) evaluate the PA plan’s implementation frequently from the out- set, 4) use quick and efficient engagement techniques with stake- holders when working with them to select strategies, tactics, and measurable outcomes, and 5) understand the elements necessary to implement, manage, and evaluate a good PA plan. Interpretation An EA process is recommended for other leaders of PA plans. Our project highlights the stakeholders’ desire to simplify the WVPAP so that it can be set up as a locally driven process that engages communities in implementation

Direct activation of NADPH oxidase 2 by 2-deoxyribose-1-phosphate triggers nuclear factor kappa B-dependent angiogenesis.

AbstractAims: Deoxyribose-1-phosphate (dRP) is a proangiogenic paracrine stimulus released by cancer cells, platelets, and macrophages and acting on endothelial cells. The objective of this study was to clarify how dRP stimulates angiogenic responses in human endothelial cells.Results: Live cell imaging, electron paramagnetic resonance, pull-down of dRP-interacting proteins, followed by immunoblotting, gene silencing of different NADPH oxidases (NOXs), and their regulatory cosubunits by small interfering RNA (siRNA) transfection, and experiments with inhibitors of the sugar transporter glucose transporter 1 (GLUT1) were utilized to demonstrate that dRP acts intracellularly by directly activating the endothelial NOX2 complex, but not NOX4. Increased reactive oxygen species generation in response to NOX2 activity leads to redox-dependent activation of the transcription factor nuclear factor kappa B (NF-κB), which, in turn, induces vascular endothelial growth factor receptor 2 (VEGFR2) upregulation. Using endothelial tube formation assays, gene silencing by siRNA, and antibody-based receptor inhibition, we demonstrate that the activation of NF-κB and VEGFR2 is necessary for the angiogenic responses elicited by dRP. The upregulation of VEGFR2 and NOX2-dependent stimulation of angiogenesis by dRP were confirmed in excisional wound and Matrigel plug vascularization assays in vivo using NOX2−/− mice.Innovation: For the first time, we demonstrate that dRP acts intracellularly and stimulates superoxide anion generation by direct binding and activation of the NOX2 enzymatic complex.Conclusions: This study describes a novel molecular mechanism underlying the proangiogenic activity of dRP, which involves the sequential activation of NOX2 and NF-κB and upregulation of VEGFR2. Antioxid. Redox Signal. 28, 110–130

Volatile profiling reveals intracellular metabolic changes in Aspergillus parasticus: veA regulates branched chain amino acid and ethanol metabolism

Background: Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results: Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions: 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary metabolites with catabolism of branched chain amino acids, alcohol biosynthesis, and b-oxidation of fatty acids. 3) Intracellular chemical development in A. parasiticus is linked to morphological development. 4) Understanding carbon flow through secondary metabolic pathways and catabolism of branched chain amino acids is essential for controlling and customizing production of natural products

Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

<p>Abstract</p> <p>Background</p> <p>Filamentous fungi in the genus <it>Aspergillus </it>produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by <it>Aspergillus parasiticus </it>in an attempt to define the association of secondary metabolism with other metabolic and cellular processes.</p> <p>Results</p> <p>Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain <it>Aspergillus parasiticus </it>SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator <it>veA </it>affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a <it>veA </it>disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation.</p> <p>Conclusions</p> <p>1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary metabolites with catabolism of branched chain amino acids, alcohol biosynthesis, and β-oxidation of fatty acids. 3) Intracellular chemical development in <it>A. parasiticus </it>is linked to morphological development. 4) Understanding carbon flow through secondary metabolic pathways and catabolism of branched chain amino acids is essential for controlling and customizing production of natural products.</p

Community Readiness for Adopting a Physical Activity Program for People With Arthritis in West Virginia

Introduction: The health benefits of physical activity are well established in older adults with arthritis. Despite these benefits, many older adults with arthritis are not active enough to maintain health; therefore, increasing physical activity in adults with arthritis is a public health priority. The purpose of this study was to use the Community Readiness Model to assess readiness for adopting a physical activity program for people with arthritis in 8 counties in West Virginia. Methods: During 2007 and 2008, we conducted a telephone survey among 94 key informants who could provide insight into their community's efforts to promote physical activity among older adults with arthritis. We matched survey scores with 1 of 9 stages of readiness, ranging from 1 (no awareness) to 9 (high level of community ownership). Results: The survey placed the counties in stage 3 (vague awareness), indicating recognition of the need for more physical activity programming; community efforts were not focused and leadership was minimal. The interviews suggested that culturally sensitive, well-promoted free or low-cost programs conducted by community volunteers may be keys to success in West Virginia. Conclusion: Information derived from our survey can be used to match intervention strategies for promoting physical activity among people with arthritis to communities in West Virginia according to their level of readiness.This is the publisher’s final pdf. The article is published by the Centers for Disease Control and Prevention and can be found at: http://www.cdc.gov/pcd/index.ht

Obesity inhibits the osteogenic differentiation of human adipose-derived stem cells

Additional file 3: Figure S3. No observable differences in lnASCs and obASCs during early bone regeneration. Critical size calvarial defects were created in the parietal bone of nude mice and assessed after 2 weeks. (A) Representative images of microCT scanning. (B) Quantification of microCT. Scale bar represents 1 mm. Bars, Âą SEM

Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Communicating with providers about racial healthcare disparities: The role of providers’ prior beliefs on their receptivity to different narrative frames

Objective Evaluate narratives aimed at motivating providers with different pre-existing beliefs to address racial healthcare disparities. Methods Survey experiment with 280 providers. Providers were classified as high or low in attributing disparities to providers (HPA versus LPA) and were randomly assigned to a non-narrative control or 1 of 2 narratives: “Provider Success” (provider successfully resolved problem involving Black patient) and “Provider Bias” (Black patient experienced racial bias, which remained unresolved). Participants' reactions to narratives (including identification with narrative) and likelihood of participating in disparities-reduction activities were immediately assessed. Four weeks later, participation in those activities was assessed, including self-reported participation in a disparities-reduction training course (primary outcome). Results Participation in training was higher among providers randomized to the Provider Success narrative compared to Provider Bias or Control. LPA participants had higher identification with Provider Success than Provider Bias narratives, whereas among HPA participants, differences in identification between the narratives were not significant. Conclusions Provider Success narratives led to greater participation in training than Provider Bias narratives, although providers’ pre-existing beliefs influenced the narrative they identified with. Practice implications Provider Success narratives may be more effective at motivating providers to address disparities than Provider Bias narratives, though more research is needed

Age and sex‐related variability in the presentation of generalized anxiety and depression symptoms

Background: Generalized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity. Method: We conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD‐7) and Patient Health Questionnaire (PHQ‐9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16–93 years). We assessed age‐ and sex‐related variability in latent factors and individual symptoms using multiple logistic regression. Results: Four factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker–Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age. Males were more likely to report mood and motor symptoms (p &lt; .001) and females to report somatic symptoms (p &lt; .001). Conclusion: Significant age and sex variability suggest that classic diagnostic criteria reflect the presentation most commonly seen in younger males. This study provides avenues for diagnostic adaptation and factor‐specific interventions

Deglacierization of a marginal basin and implications for outburst floods

This article was submitted to Cryospheric Sciences, a section of the journal Frontiers in Earth ScienceSuicide Basin is a partly glacierized marginal basin of Mendenhall Glacier, Alaska, that has released glacier lake outburst floods (GLOFs) annually since 2011. The floods cause inundation and erosion in the Mendenhall Valley, impacting homes and other infrastructure. Here, we utilize in-situ and remote sensing data to assess the recent evolution and current state of Suicide Basin. We focus on the 2018 and 2019 melt seasons, during which we collected most of our data, partly using unmanned aerial vehicles (UAVs). To provide longer-term context, we analyze DEMs collected since 2006 and model glacier surface mass balance over the 2006–2019 period. During the 2018 and 2019 outburst flood events, Suicide Basin released ∼ 30 Å~ 106 m3 of water within approximately 4–5 days. Since lake drainage was partial in both years, these ∼ 30 Å~ 106 m3 represent only a fraction (∼ 60%) of the basin’s total storage capacity. In contrast to previous years, subglacial drainage was preceded by supraglacial outflow over the ice dam, which lasted ∼ 1 day in 2018 and 6 days in 2019. Two large calving events occurred in 2018 and 2019, with submerged ice breaking off the main glacier during lake filling, thereby increasing the basin’s storage capacity. In 2018, the floating ice in the basin was 36 m thick on average. In 2019, ice thickness was 29 m, suggesting rapid decay of the ice tongue despite increasing ice inflow from Mendenhall Glacier. The ice dam at the basin entrance thinned by more than 5 m a–1 from 2018 to 2019, which is approximately double the rate of the reference period 2006–2018. While ice-dam thinning reduces water storage capacity in the basin, that capacity is increased by declining ice volume in the basin and longitudinal lake expansion, with the latter process challenging to predict. The potential for premature drainage onset (i.e., drainage before the lake’s storage capacity is reached), intermittent drainage decelerations, and early drainage termination further complicates prediction of future GLOF events.This work was funded by the Alaska Climate Adaptation Science Center (AK CASC). UAVs and other surveying equipment were partly funded through the U.S. National Science Foundation (NSF) award EAR-1921598. EH and SH were partially supported by the NSF award OIA-1753748 and the State of Alaska. Streamflow monitoring of the Mendenhall River and real-time imagery of Suicide Basin were funded by the U.S. Geological Survey Groundwater and Streamflow Information Program. Any use of trade, firm, or product names is for descriptive purposes only and does not imply endorsement by the U.S. Government.Ye