Fats and oils in cookery. Cooking temperatures, 14:47

At head of title: ... Department of Household Science

Galphas-coupled receptor signaling actively down-regulates α4β1-integrin affinity: A possible mechanism for cell de-adhesion

<p>Abstract</p> <p>Background</p> <p>Activation of integrins in response to inside-out signaling serves as a basis for leukocyte arrest on endothelium, and migration of immune cells. Integrin-dependent adhesion is controlled by the conformational state of the molecule (i.e. change in the affinity for the ligand and molecular unbending (extension)), which is regulated by seven-transmembrane Guanine nucleotide binding Protein-Coupled Receptors (GPCRs). α₄β₁-integrin (CD49d/CD29, Very Late Antigen-4, VLA-4) is expressed on leukocytes, hematopoietic stem cells, hematopoietic cancer cells, and others. Affinity and extension of VLA-4 are both rapidly up-regulated by inside-out signaling through several Gα_i-coupled GPCRs. The goal of the current report was to study the effect of Gα_s-coupled GPCRs upon integrin activation.</p> <p>Results</p> <p>Using real-time fluorescent ligand binding to assess affinity and a FRET based assay to probe α₄β₁-integrin unbending, we show that two Gα_s-coupled GPCRs (H2-histamine receptor and β2-adrenergic receptor) as well as several cAMP agonists can rapidly down modulate the affinity of VLA-4 activated through two Gα_i-coupled receptors (CXCR4 and FPR) in U937 cells and primary human peripheral blood monocytes. This down-modulation can be blocked by receptor-specific antagonists. The Gα_s-induced responses were not associated with changes in the expression level of the Gα_i-coupled receptors. In contrast, the molecular unbending of VLA-4 was not significantly affected by Gα_s-coupled GPCR signaling. In a VLA-4/VCAM-1-specific myeloid cell adhesion system, inhibition of the VLA-4 affinity change by Gα_s-coupled GPCR had a statistically significant effect upon cell aggregation.</p> <p>Conclusion</p> <p>We conclude that Gα_s-coupled GPCRs can rapidly down modulate the affinity state of VLA-4 binding pocket through a cAMP dependent pathway. This plays an essential role in the regulation of cell adhesion. We discuss several possible implications of this described phenomenon.</p

Impact of Extreme Heat Events on Emergency Department Visits in North Carolina (2007–2011)

Extreme heat is the leading cause of w eather-related mortality in the U.S. Extreme heat also affects human health through heat stress and can exacerbate underlying medical conditions that lead to increased morbidity and mortality. In this study, data on emergency department (ED) visits for heat-related illness (HRI) and other selected diseases were analyzed during three heat events across North Carolina from 2007 to 2011. These heat events were identified based on the issuance and verification of heat products from local National Weather Service forecast offices (i.e. Heat Advisory, Heat Watch, and Excessive Heat Warning). The observed number of ED visits during these events were compared to the expected number of ED visits during several control periods to determine excess morbidity resulting from extreme heat. All recorded diagnoses were analyzed for each ED visit, thereby providing insight into the specific pathophysiological mechanisms and underlying health conditions associated with exposure to extreme heat. The most common form of HRI was heat exhaustion, while the percentage of visits with heat stroke was relatively low (65 years of age) were at greatest risk for HRI during the early summer heat event (8.9 visits per 100,000), while young and middle age adults (18–44 years of age) were at greatest risk during the mid-summer event (6.3 visits per 100,000). Many of these visits were likely due to work-related exposure. The most vulnerable demographic during the late summer heat event was adolescents (15–17 years of age), which may relate to the timing of organized sports. This demographic also exhibited the highest visit rate for HRI among all three heat events (10.5 visits per 100,000). Significant increases (p < 0.05) in visits with cardiovascular and cerebrovascular diseases were noted during the three heat events (3–8 %). The greatest increases were found in visits with hypotension during the late summer event (23 %) and sequelae during the early summer event (30 %), while decreases were noted for visits with hemorrhagic stroke during the middle and late summer events (13–24 %) and for visits with aneurysm during the early summer event (15 %). Significant increases were also noted in visits with respiratory diseases (5–7 %). The greatest increases in this category were found in visits with pneumonia and influenza (16 %), bronchitis and emphysema (12 %), and COPD (14 %) during the early summer event. Significant increases in visits with nervous system disorders were also found during the early summer event (16 %), while increases in visits with diabetes were noted during the mid-summer event (10 %)

Farming practices in Sweden related to feeding milk and colostrum from cows treated with antimicrobials to dairy calves

BACKGROUND: Milk produced by cows in receipt of antimicrobial therapy may contain antimicrobial residues. Such antimicrobial-containing waste milk must be withdrawn from human consumption and is therefore sometimes used as calf feed. Unfortunately, this approach might promote selection of antimicrobial resistant bacteria in the calves’ intestinal microbiota. The objectives of this study were therefore to obtain an overview of waste milk feeding practices on Swedish dairy farms and to investigate if these practices were associated with certain farm characteristics. A representative group of 457 Swedish dairy farmers participated in a web-based survey with questions about the use of colostrum and milk from cows treated with antimicrobials at dry off or during lactation, respectively, as calf feed. RESULTS: Colostrum (milk from the first milking after calving) and transition milk (milk from the second milking to the fourth day after calving) from cows treated with antimicrobials at dry off was fed to calves on 89% and 85% of the farms in the study, respectively. When antimicrobial therapy was given to cows during lactation, 56% of the farms fed milk that was produced during the course of treatment to calves, whereas milk that was produced during the subsequent withdrawal period was fed to calves on 79% of the farms. Surveyed farmers were less prone to feed such milk if the antimicrobial therapy was due to mastitis than other infections. In Sweden, a majority of antimicrobial treatments during lactation are systemic administration of benzylpenicillin and thus, the bulk of waste milk in Sweden is likely to contain residues of this drug. Feeding waste milk to calves was more common on non-organic farms, and on farms located in Southern Sweden, and was less common on farms with cows housed in cold free stalls barns. CONCLUSIONS: Waste milk that may contain antimicrobial residues is, at least occasionally, used as feed for calves on a majority of surveyed Swedish dairy farms. Future work should focus on the effect of waste milk feeding on the occurrence of antimicrobial resistant bacteria in the calves’ intestinal microbiota

We Can Have It All: Improved Surveillance Outcomes and Decreased Personnel Costs Associated With Electronic Reportable Disease Surveillance, North Carolina, 2010

Objectives. We assessed the timeliness, accuracy, and cost of a new electronic disease surveillance system at the local health department level. We describe practices associated with lower cost and better surveillance timeliness and accuracy. Methods. Interviews conducted May through August 2010 with local health department (LHD) staff at a simple random sample of 30 of 100 North Carolina counties provided information on surveillance practices and costs; we used surveillance system data to calculate timeliness and accuracy. We identified LHDs with best timeliness and accuracy and used these categories to compare surveillance practices and costs. Results. Local health departments in the top tertiles for surveillance timeliness and accuracy had a lower cost per case reported than LHDs with lower timeliness and accuracy ($71 and$124 per case reported, respectively; P = .03). Best surveillance practices fell into 2 domains: efficient use of the electronic surveillance system and use of surveillance data for local evaluation and program management. Conclusions. Timely and accurate surveillance can be achieved in the setting of restricted funding experienced by many LHDs. Adopting best surveillance practices may improve both efficiency and public health outcomes

Effects of reduced-risk nicotine-delivery products on smoking prevalence and cigarette sales: an observational study

BACKGROUND: It is not currently clear what impact alternative nicotine-delivery products (electronic cigarettes, heated tobacco products and snus) have on smoking rates and cigarette sales. OBJECTIVE: To assess whether access to these products promotes smoking in the population. DESIGN AND DATA SOURCES: We examined associations of alternative nicotine product use and sales with smoking rates and cigarette sales overall, and in different age and socioeconomic groups, and compared smoking prevalence over time in countries with contrasting regulations of these products. For electronic cigarettes, we examined data from countries with historically similar smoking trajectories but differing current electronic cigarette regulations (United Kingdom and United States of America vs. Australia, where sales of nicotine-containing electronic cigarettes are banned); for heated tobacco, we used data from countries with state tobacco monopolies, where cigarette and heated tobacco sales data are available (Japan, South Korea), and for snus we used data from Sweden. ANALYSIS METHODS: We pre-specified dynamic time series analyses to explore associations between use and sales of alternative nicotine-delivery products and smoking prevalence and cigarette sales, and time series analyses to compare trends of smoking prevalence in countries with different nicotine product policies. RESULTS: Because of data and analysis limitations (see below), results are only tentative and need to be interpreted with caution. Only a few findings reached statistical significance and for most results the Bayes factor indicated inconclusive evidence. We did not find an association between rates of smoking and rates of the use of alternative nicotine products. The increase in heated tobacco product sales in Japan was accompanied by a decrease in cigarette sales. The decline in smoking prevalence seems to have been slower in Australia than in the United Kingdom overall, and slower than in both the United Kingdom and the United States of America among young people and also in lower socioeconomic groups. The decline in cigarette sales has also accelerated faster in the United Kingdom than in Australia. LIMITATIONS: Most of the available data had insufficient data points for robust time series analyses. The assumption of our statistical approach that causal interactions are more likely to be detected when longer-term changes are screened out may not apply for short time series and in product interaction scenarios, where short-term fluctuations can be caused by, for example, fluctuations in prosperity or product supplies. In addition, due to dual use, prevalence figures for smoking and alternative product use overlap. The ecological study design limits the causal inferences that can be made. Longer time periods are needed for any effects of exclusive use of the new products on smoking prevalence to emerge. CONCLUSIONS: We detected some indications that alternative nicotine products are competing with cigarettes rather than promoting smoking and that regulations that allow their sales are associated with a reduction rather than an increase of smoking, but the findings are inconclusive because of insufficient data points and issues with the assumptions of the pre-specified statistical analyses. FUTURE WORK: As further prevalence and sales data emerge the analyses will become more informative. Accessing sales figures in particular is the current research priority. STUDY REGISTRATION: The project is registered on Open Science Framework https://osf.io/bd3ah. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR129968) and will be published in full in Public Health Research; Vol. 11, No. 7. See the NIHR Journals Library website for further project information

Linking Emergency Medical Services and Emergency Department Data to Improve Overdose Surveillance in North Carolina

Introduction Linking emergency medical services (EMS) data to emergency department (ED) data enables assessing the continuum of care and evaluating patient outcomes. We developed novel methods to enhance linkage performance and analysis of EMS and ED data for opioid overdose surveillance in North Carolina. Methods We identified data on all EMS encounters in North Carolina during January 1–November 30, 2017, with documented naloxone administration and transportation to the ED. We linked these data with ED visit data in the North Carolina Disease Event Tracking and Epidemiologic Collection Tool. We manually reviewed a subset of data from 12 counties to create a gold standard that informed developing iterative linkage methods using demographic, time, and destination variables. We calculated the proportion of suspected opioid overdose EMS cases that received International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes for opioid overdose in the ED. Results We identified 12 088 EMS encounters of patients treated with naloxone and transported to the ED. The 12-county subset included 1781 linkage-eligible EMS encounters, with historical linkage of 65.4% (1165 of 1781) and 1.6% false linkages. Through iterative linkage methods, performance improved to 91.0% (1620 of 1781) with 0.1% false linkages. Among statewide EMS encounters with naloxone administration, the linkage improved from 47.1% to 91.1%. We found diagnosis codes for opioid overdose in the ED among 27.2% of statewide linked records. Practice Implications Through an iterative linkage approach, EMS–ED data linkage performance improved greatly while reducing the number of false linkages. Improved EMS–ED data linkage quality can enhance surveillance activities, inform emergency response practices, and improve quality of care through evaluating initial patient presentations, field interventions, and ultimate diagnoses

Initial ratings of different types of e-cigarettes and relationships between product appeal and nicotine delivery

AIMS: Little is known about features of e-cigarettes (EC) that facilitate or hinder the switch from smoking to vaping. We tested eight brands of EC to determine how nicotine delivery and other product characteristics influence user's initial reactions. METHODS: Fifteen vapers tested each product after overnight abstinence from both smoking and vaping. At each session, participant's vaped ad lib for 5 min. Blood samples were taken at baseline and at 2, 4, 6, 8, 10 and 30 min after starting vaping. Participants rated the products on a range of characteristics. The products tested included six 'cig-a-like' and two refillable products, one with variable voltage. We also tested participants' own EC. RESULTS: All products significantly reduced urges to smoke. Refillable products delivered more nicotine and received generally superior ratings in terms of craving relief, subjective nicotine delivery, throat hit and vapour production but in overall ratings, they were joined by a cig-a-like, Blu. Participants puffed more on low nicotine delivery products. Participants' estimates of nicotine delivery from different EC were closely linked to 'throat hit'. Nicotine delivery was less important in the initial product ratings than draw resistance, mouthpiece comfort and effects on reducing urge to smoke. CONCLUSIONS: All EC products reduced urges to smoke. Refillable products received generally more favourable ratings than 'cig-a-likes' with similar nicotine content. Perception of nicotine delivery was guided by throat sensations. Lower nicotine delivery was associated with more frequent puffing. The first impressions of EC products are guided less by nicotine delivery than by sensory signals