Studies of red cell and other membrane extracts in relation to glucose permeability

Two possible mechanisms involved in the facilitated transfer of glucose through red cell and other membranes have been investigated. In the first section, the hypothesis that glucose transfer involves phosphorylation was tested by estimating phosphatase activities in human red cells, adult and foetal guinea-pig red cells and kidney homogenates, and the effects upon them of known inhibitors of glucose transfer. No correlation between phosphatase activity and glucose transfer in the red cell could be found. Histochemical studies are presented to show the distribution of acid and alkaline phosphatases in the adult and foetal guinea-pig kidney, and the placenta. In the second section, the possibility is explored that glucose forms a reversible complex with a phospholipid component of the cell membrane. Methods were developed to extract phospholipids from sheep placental tissue and human and sheep red cells, to separate them chromatographically and to isolate the glucose-lipid complex. Uptake of the irreversible inhibitor 2,4-dinitrofluorobenzene (DNFB) labelled with was measured, and calculated to be 400 million molecules per red cell to give full inhibition of glucose transfer. The lipids extracted from the DNFB inhibited red cells contained radioactivity equivalent to 10-20 million molecules DNFB per red cell, which considerably exceeds the number of carrier sites thought to be involved in glucose transfer. A large proportion of the radioactivity was found in the cephalin fractions, and the possibility is discussed that phosphatidyl ethanolamine is the membrane carrier component. The technique of monolayers was used to study the surface behaviour of certain phospholipids in the presence of glucose, and the preliminary results obtained were discussed.<p

Effectiveness of Digital Interventions for Reducing Behavioral Risks of Cardiovascular Disease in Nonclinical Adult Populations: Systematic Review of Reviews

Background: Digital health interventions are increasingly being used as a supplement or replacement for face-to-face services as a part of predictive prevention. They may be offered to those who are at high risk of cardiovascular disease and need to improve their diet, increase physical activity, stop smoking, or reduce alcohol consumption. Despite the popularity of these interventions, there is no overall summary and comparison of the effectiveness of different modes of delivery of a digital intervention to inform policy. Objective: This review aims to summarize the effectiveness of digital interventions in improving behavioral and health outcomes related to physical activity, smoking, alcohol consumption, or diet in nonclinical adult populations and to identify the effectiveness of different modes of delivery of digital interventions. Methods: We reviewed articles published in the English language between January 1, 2009, and February 25, 2019, that presented a systematic review with a narrative synthesis or meta-analysis of any study design examining digital intervention effectiveness; data related to adults (≥18 years) in high-income countries; and data on behavioral or health outcomes related to diet, physical activity, smoking, or alcohol, alone or in any combination. Any time frame or comparator was considered eligible. We searched MEDLINE, Embase, PsycINFO, Cochrane Reviews, and gray literature. The AMSTAR-2 tool was used to assess review confidence ratings. Results: We found 92 reviews from the academic literature (47 with meta-analyses) and 2 gray literature items (1 with a meta-analysis). Digital interventions were typically more effective than no intervention, but the effect sizes were small. Evidence on the effectiveness of digital interventions compared with face-to-face interventions was mixed. Most trials reported that intent-to-treat analysis and attrition rates were often high. Studies with long follow-up periods were scarce. However, we found that digital interventions may be effective for up to 6 months after the end of the intervention but that the effects dissipated by 12 months. There were small positive effects of digital interventions on smoking cessation and alcohol reduction; possible effectiveness in combined diet and physical activity interventions; no effectiveness for interventions targeting physical activity alone, except for when interventions were delivered by mobile phone, which had medium-sized effects; and no effectiveness observed for interventions targeting diet alone. Mobile interventions were particularly effective. Internet-based interventions were generally effective. Conclusions: Digital interventions have small positive effects on smoking, alcohol consumption, and in interventions that target a combination of diet and physical activity. Small effects may have been due to the low efficacy of treatment or due to nonadherence. In addition, our ability to make inferences from the literature we reviewed was limited as those interventions were heterogeneous, many reviews had critically low AMSTAR-2 ratings, analysis was typically intent-to-treat, and follow-up times were relatively short

Determining the Minimum Inhibitory Concentration of Medium Chain Fatty Acids for Generic Escherichia coli, Enterotoxigenic Escherichia coli, Salmonella Typhimurium, and Campylobacter coli

Research has demonstrated that medium chain fatty acids (MCFA) can serve as reduction strategies for bacterial and viral pathogens in animal feed and ingredients. However, it is unknown how the type or level of MCFA impact bacteria growth. This can be tested through a minimum inhibitory concentration (MIC) benchtop assay, which identifies the lowest concentration of a chemical that prevents visible growth of a bacterium. The objective of this study was to 1) determine the MCFA MIC of C6:0, C8:0, C10:0, and C12:0 for generic Escherichia coli, Enterotoxigenic Escherichia coli, Salmonella Typhimurium, Campylobacter coli, and Clostridium perfringens; 2) determine the MIC of commercial based MCFA products against the same bacteria; and 3) determine the effect of 2 commercial based MCFA products on the quantification of Enterotoxigenic Escherichia coli. For Exp. 1 and 2, MIC were determined by modified microbroth dilution method using a 96 well microtiter plate with a concentration of 105 CFU/mL for each bacterial strain. For Exp. 3, the two products selected for quantification were mixed with a complete swine diet and inoculated with two concentrations (106 or 102 CFU/g of feed) of a NalR strain of Enterotoxigenic Escherichia coli (ETEC) for bacterial enumeration. From Exp. 1, the MIC of MCFA varied among bacteria species. The lowest MIC of the MCFA was 0.43% of a 1:1:1 blend of C6:0, C8:0, and C10:0 for Campylobacter coli, 0.25% C12:0 for Clostridium perfringens, 0.60% 1:1:1 blend for generic Escherichia coli, 0.53% C6:0 for ETEC, and 0.40% C6:0 for Salmonella Typhimurium. In Exp. 2, products containing high concentrations of C6:0 or C8:0 had lower MIC in gram negative bacteria. In Exp. 3, feed containing either of the commercial based MCFA products reduced (linear, P \u3c 0.05) quantifiable ETEC. Overall, the inhibitory efficacy of MCFA varies among bacteria species. This suggests that MCFA mixtures may provide a wider spectrum of bacterial control. As commercial products containing MCFA become available for livestock, it is important to consider the interaction between MCFA chain length and concentration on the potential to effectively mitigate various feed-based bacteria

Effects of Tylosin Administration Routes on the Development of Antimicrobial Resistance in Fecal Enterococci of Finishing Swine

Antibiotics can be administered via various routes in pigs, which may influence antimicrobial resistance development. A total of 40 barrows and 40 gilts (Line 600 × 241; DNA, Columbus, NE; initially 207 ± 7.9 lb) were used in a 35-d trial to determine the effects of tylosin administration route on pig growth performance and development of antimicrobial resistance in fecal Enterococcus spp. isolates. Pens of pigs (1 pig/ pen, 20 pigs/treatment) were blocked by initial body weight (BW) and gender. Within blocks, pens were randomly allotted to 1 of 4 treatments. The antibiotic treatments followed US label directions and were: 1) no antibiotic (Control); 2) 110 mg tylosin per kg of feed for 21 d (Feed); 3) 8.82 mg tylosin per kg of BW through intramuscular injection twice daily for the first 3 d of each wk during the 3-wk treatment period (Injection); and 4) 66 mg of tylosin per liter of drinking water for the first 3 d of each wk during treatment period (Water). Treatments were offered during d 0 to 21, after which all pigs were fed a common diet with no antibiotic until d 35. Fecal samples were collected on d 0, 21, and 35. No evidence for route × gender interactions (P \u3e 0.55) were observed for any growth responses. From d 0 to 21, control pigs and pigs fed medicated feed had greater (P \u3c 0.05) average daily gain (ADG) than those that received injected tylosin, with the ADG of pigs receiving tylosin through the water intermediate. There was no evidence for different average daily feed intake (ADFI) among treatment groups. Pigs that received tylosin through injection or water had poorer (P \u3c 0.05) feed efficiency (F/G) compared with control pigs, but there was no evidence for difference from pigs receiving tylosin through feed. Among the medicated pigs, total tylosin dose administered was the greatest through injection, second highest through feed, with the water medication route the lowest. No evidence for route × day interactions (P \u3e 0.23) were observed for the development of bacterial resistance to any antibiotics. Enterococcal isolates collected from pigs receiving tylosin via feed or injection were more resistant (P \u3c 0.05) to erythromycin and tylosin compared with control pigs and those that received tylosin through water. The estimated probability of antimicrobial resistance to these 2 antibiotics was greater on d 21 and 35 than d 0. In summary, tylosin injection resulted in poorer ADG and F/G of finishing pigs, likely due to stress associated with handling and injection. Tylosin administration through injection and feed resulted in greater probability of enterococcal resistance to erythromycin and tylosin compared with in-water treatment, which is likely a combined effect of administration route and dosage

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01-1.55), NO2 (1.13; 0.95-1.34 per 10 µg/m3), and BC (1.12; 0.94-1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58-0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. CONCLUSION: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality

Long-term air pollution exposure and Parkinson's disease mortality in a large pooled European cohort: An ELAPSE study

BACKGROUND: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. METHODS: Within the project 'Effects of Low-Level Air Pollution: A Study in Europe' (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM 2.5), nitrogen dioxide (NO 2), black carbon (BC), and ozone (O 3), as well as 8 PM 2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. RESULTS: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM 2.5 (hazard ratio per 5 µg/m 3: 1.25; 95% confidence interval: 1.01-1.55), NO 2 (1.13; 0.95-1.34 per 10 µg/m 3), and BC (1.12; 0.94-1.34 per 0.5 × 10 -5m -1), and a negative association with O 3 (0.74; 0.58-0.94 per 10 µg/m 3). Associations of PM 2.5, NO 2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM 2.5 remained robust when adjusted for NO 2 (1.24; 0.95-1.62) or BC (1.28; 0.96-1.71), whereas associations with NO 2 or BC attenuated to null. O 3 associations remained negative, but no longer statistically significant in models with PM 2.5. We detected suggestive positive associations with the potassium component of PM 2.5. CONCLUSION: Long-term exposure to PM 2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality