Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Interferon-α/β and Anti-Fibroblast Growth Factor Receptor 1 Monoclonal Antibody Suppress Hepatic Cancer Cells In Vitro and In Vivo

Hepatocellular carcinoma (HCC) is the most commonly occurring primary liver cancer and ranks as the fifth most frequently occurring cancer, overall, and the third leading cause of cancer deaths, worldwide. At present, effective therapeutic options available for HCC are limited; consequently, the prognosis for these patients is poor. Our aim in the present study was to identify a novel target for antibody therapy against HCC..Our results suggest that the combined use of an anti-FGFR1 antibody and interferon-α/β is a promising approach to the treatment of HCC

Active-site structure, binding and redox activity of the heme–thiolate enzyme CYP2D6 immobilized on coated Ag electrodes: a surface-enhanced resonance Raman scattering study

Surface-enhance resonance Raman scattering spectra of the heme–thiolate enzyme cytochrome P450 2D6 (CYP2D6) adsorbed on Ag electrodes coated with 11-mercaptoundecanoic acid (MUA) were obtained in various experimental conditions. An analysis of these spectra, and a comparison between them and the RR spectra of CYP2D6 in solution, indicated that the enzyme’s active site retained its nature of six-coordinated low-spin heme upon immobilization. Moreover, the spectral changes detected in the presence of dextromethorphan (a CYP2D6 substrate) and imidazole (an exogenous heme axial ligand) indicated that the immobilized enzyme also preserved its ability to reversibly bind a substrate and form a heme–imidazole complex. The reversibility of these processes could be easily verified by flowing alternately solutions of the various compounds and the buffer through a home-built spectroelectrochemical flow cell which contained a sample of immobilized protein, without the need to disassemble the cell between consecutive spectral data acquisitions. Despite immobilized CYP2D6 being effectively reduced by a sodium dithionite solution, electrochemical reduction via the Ag electrode was not able to completely reduce the enzyme, and led to its extensive inactivation. This behavior indicated that although the enzyme’s ability to exchange electrons is not altered by immobilization per se, MUA-coated electrodes are not suited to perform direct electrochemistry of CYP2D6

Design of the DIRECT-project: interventions to increase job resources and recovery opportunities to improve job-related health, well-being, and performance outcomes in nursing homes

Background Because of high demands at work, nurses are at high risk for occupational burnout and physical complaints. The presence of job resources (such as job autonomy or social support) and recovery opportunities could counteract the adverse effect of high job demands. However, it is still unclear how job resources and recovery opportunities can be translated into effective workplace interventions aiming to improve employee health, well-being, and performance-related outcomes. The aim of the current research project is developing and implementing interventions to optimize job resources and recovery opportunities, which may lead to improved health, well-being and performance of nurses. Methods/design The DIRECT-project (DIsc Risk Evaluating Controlled Trial) is a longitudinal, quasi-experimental field study. Nursing home staff of 4 intervention wards and 4 comparison wards will be involved. Based on the results of a base-line survey, interventions will be implemented to optimize job resources and recovery opportunities. After 12 and 24 month the effect of the interventions will be investigated with follow-up surveys. Additionally, a process evaluation will be conducted to map factors that either stimulated or hindered successful implementation as well as the effectiveness of the interventions. Discussion The DIRECT-project fulfils a strong need for intervention research in the field of work, stress, performance, and health. The results could reveal (1) how interventions can be tailored to optimize job resources and recovery opportunities, in order to counteract job demands, and (2) what the effects of these interventions will be on health, well-being, and performance of nursing staff

Optical imaging of the peri-tumoral inflammatory response in breast cancer

<p>Abstract</p> <p>Purpose</p> <p>Peri-tumoral inflammation is a common tumor response that plays a central role in tumor invasion and metastasis, and inflammatory cell recruitment is essential to this process. The purpose of this study was to determine whether injected fluorescently-labeled monocytes accumulate within murine breast tumors and are visible with optical imaging.</p> <p>Materials and methods</p> <p>Murine monocytes were labeled with the fluorescent dye DiD and subsequently injected intravenously into 6 transgenic MMTV-PymT tumor-bearing mice and 6 FVB/n control mice without tumors. Optical imaging (OI) was performed before and after cell injection. Ratios of post-injection to pre-injection fluorescent signal intensity of the tumors (MMTV-PymT mice) and mammary tissue (FVB/n controls) were calculated and statistically compared.</p> <p>Results</p> <p>MMTV-PymT breast tumors had an average post/pre signal intensity ratio of 1.8+/- 0.2 (range 1.1-2.7). Control mammary tissue had an average post/pre signal intensity ratio of 1.1 +/- 0.1 (range, 0.4 to 1.4). The p-value for the difference between the ratios was less than 0.05. Confocal fluorescence microscopy confirmed the presence of DiD-labeled cells within the breast tumors.</p> <p>Conclusion</p> <p>Murine monocytes accumulate at the site of breast cancer development in this transgenic model, providing evidence that peri-tumoral inflammatory cell recruitment can be evaluated non-invasively using optical imaging.</p

Structural diversity of supercoiled DNA

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA min icircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background: Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection. Method: In our prospective cohort study we merged data from three different randomized controlled trials (RCTs) to assess prognostic variables for chronicity of low back pain. Among the outcome and prognostic variables data were missing in the range of 0 and 48.1%. We used four methods to investigate the influence of respectively sampling and imputation variation: MI only, bootstrap only, and two methods that combine MI and bootstrapping. Variables were selected based on the inclusion frequency of each prognostic variable, i.e. the proportion of times that the variable appeared in the model. The discriminative and calibrative abilities of prognostic models developed by the four methods were assessed at different inclusion levels. Results: We found that the effect of imputation variation on the inclusion frequency was larger than the effect of sampling variation. When MI and bootstrapping were combined at the range of 0% (full model) to 90% of variable selection, bootstrap corrected c-index values of 0.70 to 0.71 and slope values of 0.64 to 0.86 were found. Conclusion: We recommend to account for both imputation and sampling variation in sets of missing data. The new procedure of combining MI with bootstrapping for variable selection, results in multivariable prognostic models with good performance and is therefore attractive to apply on data sets with missing values

Expectations, perceptions, and physiotherapy predict prolonged sick leave in subacute low back pain

<p>Abstract</p> <p>Background</p> <p>Brief intervention programs for subacute low back pain (LBP) result in significant reduction of sick leave compared to treatment as usual. Although effective, a substantial proportion of the patients do not return to work. This study investigates predictors of return to work in LBP patients participating in a randomized controlled trial comparing a brief intervention program (BI) with BI and physical exercise.</p> <p>Methods</p> <p>Predictors for not returning to work was examined in 246 patients sick listed 8-12 weeks for low back pain. The patients had participated in a randomized controlled trial, with BI (n = 122) and BI + physical exercise (n = 124). There were no significant differences between the two intervention groups on return to work. The groups were therefore merged in the analyses of predictors. Multiple logistic regression analysis was used to identify predictors for non return to work at 3, 12, and 24 months of follow-up.</p> <p>Results</p> <p>At 3 months of follow-up, the strongest predictors for not returning to work were pain intensity while resting (OR = 5.6; CI = 1.7-19), the perception of constant back strain when working (OR = 4.1; CI = 1.5-12), negative expectations for return to work (OR = 4.2; CI = 1.7-10), and having been to a physiotherapist prior to participation in the trial (OR = 3.3; CI = 1.3-8.3). At 12 months, perceived reduced ability to walk far due to the complaints (OR = 2.6; CI = 1.3-5.4), pain during activities (OR = 2.4; CI = 1.1-5.1), and having been to a physiotherapist prior to participation in the trial (OR = 2.1; CI = 1.1-4.3) were the strongest predictors for non return to work. At 24 months age below 41 years (OR = 2.9; CI = 1.4-6.0) was the only significant predictor for non return to work.</p> <p>Conclusion</p> <p>It appears that return to work is highly dependant on individual and cognitive factors. Patients not returning to work after the interventions were characterized by negative expectations, perceptions about pain and disability, and previous physiotherapy treatment. This is the first study reporting that previous treatment by physiotherapists is a risk factor for long-term sick leave. This has not been reported before and is an interesting finding that deserves more scrutiny.</p

Cost-effectiveness of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Within the working population there is a vulnerable group: workers without an employment contract and workers with a flexible labour market arrangement, e.g. temporary agency workers. In most cases, when sick-listed, these workers have no workplace/employer to return to. Also, for these workers access to occupational health care is limited or even absent in many countries. For this vulnerable working population there is a need for tailor-made occupational health care, including the presence of an actual return-to-work perspective. Therefore, a participatory return-to-work program has been developed based on a successful return-to-work intervention for workers, sick-listed due to low back pain.</p> <p>The objective of this paper is to describe the design of a randomised controlled trial to study the (cost-)effectiveness of this newly developed participatory return-to-work program adapted for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders, compared to usual care.</p> <p>Methods/Design</p> <p>The design of this study is a randomised controlled trial with one year of follow-up. The study population consists of temporary agency workers and unemployed workers sick-listed between 2 and 8 weeks due to musculoskeletal disorders. The new return-to-work program is a stepwise program aimed at making a consensus-based return-to-work implementation plan with the possibility of a (therapeutic) workplace to return-to-work. Outcomes are measured at baseline, 3, 6, 9 and 12 months. The primary outcome measure is duration of the sickness benefit period after the first day of reporting sick. Secondary outcome measures are: time until first return-to-work, total number of days of sickness benefit during follow-up; functional status; intensity of musculoskeletal pain; pain coping; and attitude, social influence and self-efficacy determinants. Cost-benefit is evaluated from an insurer's perspective. A process evaluation is part of this study.</p> <p>Discussion</p> <p>For sick-listed workers without an employment contract there can be gained a lot by improving occupational health care, including return-to-work guidance, and by minimising the 'labour market handicap' by creating a return-to-work perspective. In addition, reduction of sickness absence and work disability, i.e. a reduction of disability claims, may result in substantial benefits for the Dutch Social Security System.</p> <p>Trial registration</p> <p>Trial registration number: NTR1047.</p