Special issue: Innovations in farming systems approaches: Introduction

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Effects of organically and conventionally produced feed on biomarkers of health in a chicken model

Consumers expect organic products to be healthier. However, limited research has been performed to study the effect of organic food on health. The present study aimed to identify biomarkers of health to enable future studies in human subjects. A feeding experiment was performed in two generations of three groups of chickens differing in immune responsiveness, which were fed identically composed feeds from either organic or conventional produce. The animals of the second generation were exposed to an immune challenge and sacrificed at 13 weeks of age. Feed and ingredients were analysed on macro- and micronutrients, i.e. vitamins, minerals, trace elements, heavy metals and microbes. The chickens were studied by general health and immune parameters, metabolomics, genomics and post-mortem evaluation. The organic and conventional feeds were comparable with respect to metabolisable energy. On average, the conventionally produced feeds had a 10 % higher protein content and some differences in micronutrients were observed. Although animals on both feeds were healthy, differences between the groups were found. The random control group of chickens fed conventional feed showed overall a higher weight gain during life span than the group on organic feed, although feed intake was mostly comparable. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge as well as a slightly stronger ‘catch-up growth’ after the challenge. Biomarkers for future research were identified in the parameters feed intake, body weight and growth rate, and in immunological, physiological and metabolic parameters, several of these differing most pronounced after the challeng

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia

BACKGROUND: Sensitization of leukemic cells with hematopoietic growth factors may enhance the cytotoxicity of chemotherapy in acute myeloid leukemia (AML). METHODS: In a multicenter randomized trial, we assigned patients (age range, 18 to 60 years) with newly diagnosed AML to receive cytarabine plus idarubicin (cycle 1) and cytarabine plus amsacrin (cycle 2) with granulocyte colony-stimulating factor (G-CSF) (321 patients) or without G-CSF (319). G-CSF was given concurrently with chemotherapy only. Idarubicin and amsacrin were given at the end of a cycle to allow the cell-cycle-dependent cytotoxicity of cytarabine in the context of G-CSF to have a greater effect. The effect of G-CSF on disease-free survival was assessed in all patients and in cytogenetically distinct prognostic subgroups. RESULTS: After induction chemotherapy, the rates of response were not significantly different in the two groups. After a median follow-up of 55 months, patients in complete remission after induction chemotherapy plus G-CSF had a higher rate of disease-free survival than patients who did not receive G-CSF (42 percent vs. 33 percent at four years, P=0.02), owing to a reduced probability of relapse (relative risk, 0.77; 95 percent confidence interval, 0.61 to 0.99; P=0.04). G-CSF did not significantly improve overall survival (P=0.16). Although G-CSF did not improve the outcome in the subgroup with an unfavorable prognosis, the 72 percent of patients with standard-risk AML benefited from G-CSF therapy (overall survival at four years, 45 percent, as compared with 35 percent in the group that did not receive G-CSF [relative risk of death, 0.75; 95 percent confidence interval, 0.59 to 0.95; P=0.02]; disease-free survival, 45 percent vs. 33 percent [relative risk, 0.70]; 95 percent confidence interval, 0.55 to 0.90; P=0.006). CONCLUSIONS: Sensitization of leukemic cells with growth factors is a clinically applicable means of enhancing the efficacy of chemotherapy in patients with AML

The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt

Alternative Magnesium Sulfate Dosing Regimens for Women With Preeclampsia: A Population Pharmacokinetic Exposure-Response Modeling and Simulation Study

Magnesium sulfate is the anticonvulsant of choice for eclampsia prophylaxis and treatment; however, the recommended dosing regimens are costly and cumbersome and can be administered only by skilled health professionals. The objectives of this study were to develop a robust exposure-response model for the relationship between serum magnesium exposure and eclampsia using data from large studies of women with preeclampsia who received magnesium sulfate, and to predict eclampsia probabilities for standard and alternative (shorter treatment duration and/or fewer intramuscular injections) regimens. Exposure-response modeling and simulation were applied to existing data. A total of 10 280 women with preeclampsia who received magnesium sulfate or placebo were evaluated. An existing population pharmacokinetic model was used to estimate individual serum magnesium exposure. Logistic regression was applied to quantify the serum magnesium area under the curve-eclampsia rate relationship. Our exposure-response model-estimated eclampsia rates were comparable to observed rates. Several alternative regimens predicted magnesium peak concentration < 3.5 mmol/L (empiric safety threshold) and eclampsia rate ≤ 0.7% (observed response threshold), including 4 g intravenously plus 10 g intramuscularly followed by either 8 g intramuscularly every 6 hours × 3 doses or 10 g intramuscularly every 8 hours × 2 doses and 10 g intramuscularly every 8 hours × 3 doses. Several alternative magnesium sulfate regimens with comparable model-predicted efficacy and safety were identified that merit evaluation in confirmatory clinical trials

Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity.Robert J. Norman, Fernando Zegers-Hochschild, Bruno S. Salle, Jolanda Elbers, Esther Heijnen, Maya Marintcheva-Petrova, and Bernadette Mannaerts for the Trust Investigator

Improving the quality of pork and pork products for the consumer : development of innovative, integrated, and sustainable food production chains of high quality pork products matching consumer demands

Improving the quality of pork and pork products for the consumer: development of innovative, integrated, and sustainable food production chains of high quality pork products matching consumer demands