Verkennende studie naar hittestress bij melkvee tijdens weidegang in gematigde klimaatstreken

An exploratory study has been conducted to gain insight into the effects of heat stress during grazing on milk production, health and welfare of dairy cows, and the economic consequences of this under Dutch climate conditions. Furthermore an exploration was carried out into options to reduce the effects of heat stress during grazing. The results of this study are described in this report

Werken aan meerwaarde van regionale landbouw en biodiversiteit : de oogst van vier jaar Echt Overijssel!

"Werken aan" heeft in Echt Overijssel! vele betekenissen. Livestock Research, CLM, Natuurmonumenten, Louis Bolk Instituut hebben gewerkt aan de ontwikkeling van duurzaamheid via de drie thema’s: (agro)biodiversiteit, regionale landbouw en markt. De werkvorm was er een met agrarische ondernemers, met kennisinstellingen, met terreinbeheerders, en vele andere partners in het keten- en kennisnetwerk. Kosten en opbrengsten voor biologische bedrijfsvoering zijn berekend voor verschillende bedrijfsvormen. Gebruikmakend van diverse teelten, die alternatief veevoer leveren. Vanuit teelt en beheerperspectief is het zoeken naar de balans tussen gewasopbrengst (productwaarde) en biodiversiteit (natuurwaarde)

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change

Validity of the self-administered comorbidity questionnaire in patients with inflammatory bowel disease

Background: The International Consortium for Health Outcomes Measurement has selected the self-administered comorbidity questionnaire (SCQ) to adjust case-mix when comparing outcomes of inflammatory bowel disease (IBD) treatment between healthcare providers. However, the SCQ has not been validated for use in IBD patients. Objectives: We assessed the validity of the SCQ for measuring comorbidities in IBD patients. Design: Cohort study. Methods: We assessed the criterion validity of the SCQ for IBD patients by comparing patient-reported and clinician-reported comorbidities (as noted in the electronic health record) of the 13 diseases of the SCQ using Cohen’s kappa. Construct validity was assessed using the Spearman correlation coefficient between the SCQ and the Charlson Comorbidity Index (CCI), clinician-reported SCQ, quality of life, IBD-related healthcare and productivity costs, prevalence of disability, and IBD disease activity. We assessed responsiveness by correlating changes in the SCQ with changes in healthcare costs, productivity costs, quality of life, and disease activity after 15 months. Results: We included 613 patients. At least fair agreement (κ &gt; 0.20) was found for most comorbidities, but the agreement was slight (κ &lt; 0.20) for stomach disease [κ = 0.19, 95% CI (−0.03; 0.41)], blood disease [κ = 0.02, 95% CI (−0.06; 0.11)], and back pain [κ = 0.18, 95% CI (0.11; 0.25)]. Correlations were found between the SCQ and the clinician-reported SCQ [ρ = 0.60, 95% CI (0.55; 0.66)], CCI [ρ = 0.39, 95% CI (0.31; 0.45)], the prevalence of disability [ρ = 0.23, 95% CI (0.15; 0.32)], and quality of life [ρ = −0.30, 95% CI (−0.37; −0.22)], but not between the SCQ and healthcare or productivity costs or disease activity (|ρ| ⩽ 0.2). A change in the SCQ after 15 months was not correlated with a change in any of the outcomes.Conclusion: The SCQ is a valid tool for measuring comorbidity in IBD patients, but face and content validity should be improved before being used to correct case-mix differences.</p

Update on the Endoscopic Management of Peptic Ulcer Bleeding

Upper gastrointestinal bleeding is the most common gastrointestinal emergency, with peptic ulcer as the most common cause. Appropriate resuscitation followed by early endoscopy for diagnosis and treatment are of major importance in these patients. Endoscopy is recommended within 24 h of presentation. Endoscopic therapy is indicated for patients with high-risk stigmata, in particular those with active bleeding and visible vessels. The role of endoscopic therapy for ulcers with adherent clots remains to be elucidated. Ablative or mechanical therapies are superior to epinephrine injection alone in terms of prevention of rebleeding. The application of an ulcer-covering hemospray is a new promising tool. High dose proton pump inhibitors should be administered intravenously for 72 h after endoscopy in high-risk patients. Helicobacter pylori should be tested for in all patients with peptic ulcer bleeding and eradicated if positive. These recommendations have been captured in a recent international guideline

Validation of a Novel Immunoline Assay for Patient Stratification according to Virulence of the Infecting Helicobacter pylori Strain and Eradication Status

Helicobacter pylori infection shows a worldwide prevalence of around 50%. However, only a minority of infected individuals develop clinical symptoms or diseases. The presence of H. pylori virulence factors, such as CagA and VacA, has been associated with disease development, but assessment of virulence factor presence requires gastric biopsies. Here, we evaluate the H. pylori recomLine test for risk stratification of infected patients by comparing the test score and immune recognition of type I or type II strains defined by the virulence factors CagA, VacA, GroEL, UreA, HcpC, and gGT with patient's disease status according to histology. Moreover, the immune responses of eradicated individuals from two different populations were analysed. Their immune response frequencies and intensities against all antigens except CagA declined below the detection limit. CagA was particularly long lasting in both independent populations. An isolated CagA band often represents past eradication with a likelihood of 88.7%. In addition, a high recomLine score was significantly associated with high-grade gastritis, atrophy, intestinal metaplasia, and gastric cancer. Thus, the recomLine is a sensitive and specific noninvasive test for detecting serum responses against H. pylori in actively infected and eradicated individuals. Moreover, it allows stratifying patients according to their disease state

Systematic Review of Medicine-Related Problems in Adult Patients with Atrial Fibrillation on Direct Oral Anticoagulants

New oral anticoagulant agents continue to emerge on the market and their safety requires assessment to provide evidence of their suitability for clinical use. There-fore, we searched standard databases to summarize the English language literature on medicine-related problems (MRPs) of direct oral anticoagulants DOACs (dabigtran, rivaroxban, apixban, and edoxban) in the treatment of adults with atri-al fibrillation. Electronic databases including Medline, Embase, International Pharmaceutical Abstract (IPA), Scopus, CINAHL, the Web of Science and Cochrane were searched from 2008 through 2016 for original articles. Studies pub-lished in English reporting MRPs of DOACs in adult patients with AF were in-cluded. Seventeen studies were identified using standardized protocols, and two reviewers serially abstracted data from each article. Most articles were inconclusive on major safety end points including major bleeding. Data on major safety end points were combined with efficacy. Most studies inconsistently reported adverse drug reactions and not adverse events or medication error, and no definitions were consistent across studies. Some harmful drug effects were not assessed in studies and may have been overlooked. Little evidence is provided on MRPs of DOACs in patients with AF and, therefore, further studies are needed to establish the safety of DOACs in real-life clinical practice

Systematic evaluation of variability in ChIP-chip experiments using predefined DNA targets

The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of tiling array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures of human genomic DNA and “spike-ins” comprised of nearly 100 human sequences at various concentrations were hybridized to four tiling array platforms by eight independent groups. Blind to the number of spike-ins, their locations, and the range of concentrations, each group made predictions of the spike-in locations. We found that microarray platform choice is not the primary determinant of overall performance. In fact, variation in performance between labs, protocols, and algorithms within the same array platform was greater than the variation in performance between array platforms. However, each array platform had unique performance characteristics that varied with tiling resolution and the number of replicates, which have implications for cost versus detection power. Long oligonucleotide arrays were slightly more sensitive at detecting very low enrichment. On all platforms, simple sequence repeats and genome redundancy tended to result in false positives. LM-PCR and WGA, the most popular sample amplification techniques, reproduced relative enrichment levels with high fidelity. Performance among signal detection algorithms was heavily dependent on array platform. The spike-in DNA samples and the data presented here provide a stable benchmark against which future ChIP platforms, protocol improvements, and analysis methods can be evaluated

Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project

We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome

Verkennende studie naar hittestress bij melkvee tijdens weidegang in gematigde klimaatstreken

An exploratory study has been conducted to gain insight into the effects of heat stress during grazing on milk production, health and welfare of dairy cows, and the economic consequences of this under Dutch climate conditions. Furthermore an exploration was carried out into options to reduce the effects of heat stress during grazing. The results of this study are described in this report