Review: Feed residues of glyphosate - potential consequences for livestock health and productivity.

Glyphosate is the active ingredient in a wide range of herbicides used for weed control, including weed control in genetically modified, glyphosate-insensitive crops. In addition, glyphosate herbicides are used for pre-harvest desiccation of glyphosate-sensitive crops. Together, the use of glyphosate leads to residues in livestock feed. In addition to its herbicidal property, glyphosate has documented antimicrobial and mineral-chelating properties. The aim of the present paper is to address, based on the published literature and own observations, whether dietary glyphosate residues may affect livestock gut microbiota and/or mineral status potentially with derived unfavourable effects on animal health and productivity. However, and as reported, literature on the potential effects of glyphosate on livestock is very scarce and mainly reporting in vitro studies; hence, a solid basis of in vivo studies with livestock in physiological and productive phases, particularly sensitive to disorders in mineral status and in the gut microbiota, is needed for drawing final conclusions.

Influence of volumetric modulated arc therapy and FET-PET scanning on treatment outcomes for glioblastoma patients.

BACKGROUND: We sought to assess the influence of the clinical introduction of new radiotherapy technologies on glioblastoma patients' outcomes. METHODS: Newly diagnosed glioblastoma patients treated with 60 Gy and temozolomide (2005-2014) were analyzed. The patients' GTV and CTV were defined based on MR (n = 521) or FET-PET/MR (n = 190), and were treated using conformal radiotherapy (CRT, n = 159) or image-guided volumetric modulated arc therapy with hippocampal sparing (IG-VMAT, n = 362). Progression-free survival (PFS) was assessed using the McDonald criteria. Associations between clinical data, dosimetry data, treatment technology, for PFS and overall survival (OS) were explored. RESULTS: The PFS (7 months) and OS (15 months) were unaffected by CRT, IG-VMAT and FET-PET technology. Mean brain dose was correlated with tumor volume, and was lower for IG-VMAT vs. CRT (p < 0.001). Larger mean brain dose was associated with inferior PFS (univariate/multivariate Cox models, p < 0.001) and OS (univariate, p < 0.001). Multivariate Cox models revealed association of larger mean brainstem dose (p < 0.001), BTV (p = 0.045), steroid use at baseline (p = 0.003), age (p = 0.019) and MGMT status (p = 0.022) with lower OS. CONCLUSIONS: Introduction of hippocampal-sparing IG-VMAT technology appeared to be safe, and may have reduced toxicity and cognitive impairment. Larger mean brain dose was strongly associated with inferior PFS and OS.

A multisystem composite biomarker as a preliminary diagnostic test in bipolar disorder.

OBJECTIVE: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available laboratory tests. We aimed to combine data from different molecular levels and tissues into a composite diagnostic and state biomarker. METHODS: Expression levels of 19 candidate genes in peripheral blood, plasma levels of BDNF, NT-3, IL-6 and IL-18, leukocyte counts, and urinary markers of oxidative damage to DNA and RNA were measured in 37 adult rapid-cycling patients with BD in different affective states during a 6- to 12-month period and in 40 age- and gender-matched healthy individuals in a longitudinal, repeated measures design comprising a total of 211 samples. A composite biomarker was constructed using data-driven variable selection. RESULTS: The composite biomarker discriminated between patients with BD and healthy control individuals with an area under the receiver operating characteristic curve (AUC) of 0.83 and a sensitivity of 73% and specificity of 71% corresponding with a moderately accurate test. Discrimination between manic and depressive states had a moderate accuracy, with an AUC of 0.82 and a sensitivity of 92% and a specificity of 40%. CONCLUSION: Combining individual biomarkers across tissues and molecular systems could be a promising avenue for research in biomarker models in BD.

Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients.

The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5% grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations of the study lom-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision in recurrent GBM therapy as efficacy is equal and no predictive factors for efficacy exist.

Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis.

AIMS: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status. METHODS: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population-based Region of Southern Denmark (RSD)-cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM-patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules. RESULTS: When divided at the median, patients with low expression of MGMT protein (AF-low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS-cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF-low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF-low had the best outcome; median OS 23.1 and 20.0 months, respectively. CONCLUSION: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour-specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.

Transport of valine across the small intestinal epithelium in pigs fed different valine levels and Bacillus subtilis.

Mutants of Bacillus subtilis overproducing valine (B. subtilis VAL) could be an approach to supply pigs dietary valine (Val). In the study, 18 gilts were fed: (i) negative diet with a standardized ileal digestible (SID) Val:Lys of 0.63:1 (Neg); (ii) Neg added B. subtilis VAL (1.28 × 1011  cfu/kg as-fed) or; (iii) Neg added L-Val to a Val:Lys of 0.69:1. Using the Ussing chamber method, the study aimed to investigate whether (i) the diets affect intestinal transport of additions of 0, 5, 10 or 20 mmol Val/L from the mucosal to the serosal side and (ii) the B. subtilis VAL contributes to a net transport of Val produced in situ. The results showed that the Isc (ΔIscVal ) and release of Val to the serosal side solution (Srel ; µmol cm-2  min-1 ) increased with Val addition (linear and quadratic, p < .0001) but was similar for 5, 10 or 20 mmol Val/L and not affected by diet. No net transport of in situ produced Val by B. subtilis VAL was detected. In conclusion, feeding a Val-deficient diet with or without B. subtilis VAL or a Val sufficient diet did not affect the Val transport across intestinal epithelia. No in situ Val production by B. subtilis VAL was observed in the Ussing chambers.

Associations among gait score, production data, abattoir registrations, and postmortem tibia measurements in broiler chickens.

Lameness and impaired walking ability in rapidly growing meat-type broiler chickens are major welfare issues that cause economic losses. This study analyzed the prevalence of impaired walking and its associations with production data, abattoir registrations, and postmortem tibia measurements in Norwegian broiler chickens. Gait score (GS) was used to assess walking ability in 59 different commercial broiler flocks (Ross 308) close to the slaughter d, 5,900 broilers in total, in 3 different geographical regions. In each flock, 100 arbitrary broilers were gait scored and 10 random broilers were culled to harvest tibias. Abattoir registrations on flock level were collected after slaughter. A total of 24.6% of the broilers had moderate to severe gait impairment. The broilers were sampled in 2 stages, first slaughterhouse/region, and then owner/flock. The final models showed that impaired gait is associated with first-week mortality (P < 0.05), region (P < 0.001), height of tibias mid-shaft (P < 0.05), and calcium content in the tibia ash (P < 0.05), and negatively associated with DOA (P < 0.05). The prevalence of impaired gait indicates that this is a common problem in the broiler industry in Norway, although the mean slaughter age is only 31 d and the maximum allowed animal density is relatively low. Impaired walking ability could not be predicted by the welfare indicators footpad lesion score, total on-farm mortality, and decreasing DOA prevalence. Further studies are needed to explore the relationship between first-week mortality and gait score.

Increased DNA and RNA damage by oxidation in patients with bipolar I disorder.

The mechanisms underlying bipolar disorder (BD) and the associated medical burden are unclear. Damage generated by oxidation of nucleosides may be implicated in BD pathophysiology; however, evidence from in vivo studies is limited and the extent of state-related alterations is unclear. This prospective study investigated for we believe the first time the damage generated by oxidation of DNA and RNA strictly in patients with type I BD in a manic or mixed state and subsequent episodes and remission compared with healthy control subjects. Urinary excretion of 8-oxo-deoxyguanosine (8-oxodG) and 8-oxo-guanosine (8-oxoGuo), valid markers of whole-body DNA and RNA damage by oxidation, respectively, was measured in 54 patients with BD I and in 35 healthy control subjects using a modified ultraperformance liquid chromatography and mass spectrometry assay. Repeated measurements were evaluated in various affective phases during a 6- to 12-month period and compared with repeated measurements in healthy control subjects. Independent of lifestyle and demographic variables, a 34% (P<0.0001) increase in RNA damage by oxidation across all affective states, including euthymia, was found in patients with BD I compared with healthy control subjects. Increases in DNA and RNA oxidation of 18% (P<0.0001) and 8% (P=0.02), respectively, were found in manic/hypomanic states compared with euthymia, and levels of 8-oxodG decreased 15% (P<0.0001) from a manic or mixed episode to remission. The results indicate a role for DNA and RNA damage by oxidation in BD pathophysiology and a potential for urinary 8-oxodG and 8-oxoGuo to function as biological markers of diagnosis, state and treatment response in BD.

Evaluation of in situ valine production by Bacillus subtilis in young pigs.

Mutants of Bacillus subtilis can be developed to overproduce Val in vitro. It was hypothesized that addition of Bacillus subtilis mutants to pig diets can be a strategy to supply the animal with Val. The objective was to investigate the effect of Bacillus subtilis mutants on growth performance and blood amino acid (AA) concentrations when fed to piglets. Experiment 1 included 18 pigs (15.0±1.1 kg) fed one of three diets containing either 0.63 or 0.69 standardized ileal digestible (SID) Val : Lys, or 0.63 SID Val : Lys supplemented with a Bacillus subtilis mutant (mutant 1). Blood samples were obtained 0.5 h before feeding and at 1, 2, 3, 4, 5 and 6 h after feeding and analyzed for AAs. In Experiment 2, 80 piglets (9.1±1.1 kg) were fed one of four diets containing 0.63 or 0.67 SID Val : Lys, or 0.63 SID Val : Lys supplemented with another Bacillus subtilis mutant (mutant 2) or its parent wild type. Average daily feed intake, daily weight gain and feed conversion ratio were measured on days 7, 14 and 21. On day 17, blood samples were taken and analyzed for AAs. On days 24 to 26, six pigs from each dietary treatment were fitted with a permanent jugular vein catheter, and blood samples were taken for AA analysis 0.5 h before feeding and at 1, 2, 3, 4, 5 and 6 h after feeding. In experiment 1, Bacillus subtilis mutant 1 tended (P<0.10) to increase the plasma levels of Val at 2 and 3 h post-feeding, but this was not confirmed in Experiment 2. In Experiment 2, Bacillus subtilis mutant 2 and the wild type did not result in a growth performance different from the negative and positive controls. In conclusion, results obtained with the mutant strains of Bacillus subtilis were not better than results obtained with the wild-type strain, and for both strains, the results were not different than the negative control.

A comprehensive profile of recurrent glioblastoma.

In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkably, however, fundamental knowledge on the biology of recurrent glioblastoma is just slowly emerging. Here, we review current knowledge on recurrent glioblastoma and ask whether and how therapies change intra-tumor heterogeneity, molecular traits and growth pattern of glioblastoma, and to which extent this information can be exploited for therapeutic decision-making. We conclude that the ability to characterize and predict therapy-induced changes in recurrent glioblastoma will determine, whether, one day, glioblastoma can be contained in a state of chronic disease.

Requirement of standardized ileal digestible valine to lysine ratio for 8- to 14-kg pigs.

The objective was to define the Val requirement for weaned piglets in the context of reducing the dietary protein content. A dose-response experiment was conducted to estimate the standardized ileal digestible (SID) Val to Lys ratio required to support the optimum growth of post-weaned piglets. In this study, 96 pigs weighing 8 kg were allotted to one of six dietary treatments (16 pigs for each dietary treatment) and were housed individually. Diets were formulated to provide 0.58, 0.62, 0.66, 0.70, 0.74 and 0.78 SID Val : Lys by adding graded levels of crystalline l-Val to the 0.58 SID Val : Lys diet. Lysine was sub-limiting and supplied 90% of the recommendation (10.95 g SID Lys/kg equal to 11.8 g/kg total Lys). Average daily feed intake (ADFI), average daily gain (ADG) and gain to feed ratio (G : F) were determined during a 14-day period of ad libitum feeding. Blood and urine samples were taken at the end of each week (day 7 and 14 of the experiment) 3 h after feeding the experimental diets. The maximum ADFI and ADG were obtained in pigs fed the 0.78 SID Val : Lys diet; it was not different from the results of pigs fed 0.70 SID Val : Lys diet. The highest G : F was obtained in pigs fed 0.70 SID Val : Lys. The plasma concentration of Val increased linearly (P<0.001) as the dietary SID Val : Lys increased. The increasing dietary Val : Lys also resulted in a linear increase in Cys (P<0.001) and a quadratic increase in Arg (P=0.003), Lys (P=0.05) and Phe (P=0.009). The plasma Gly showed a quadratic decrease (P=0.05) as the dietary Val : Lys increased. Neither plasma nor urinary urea to creatinine ratio was affected by treatment. The minimum SID Val : Lys required to maximize ADFI, ADG and G : F was estimated at 0.67 SID Val : Lys by a broken-line model, and at 0.71 SID Val : Lys by a curvilinear plateau model. The Val deficiency caused a reduction in ADFI, and Val supplementation above the requirement did not impair animal performance. In conclusion, 0.70 SID Val : Lys is suggested as the Val requirement for 8 to 14 kg individually housed pigs.

The optimum ratio of standardized ileal digestible leucine to lysine for 8 to 12 kg female pigs.

The objective of the study was to estimate Leu requirement for weaned piglets to balance indispensable AA in reduced CP diets. A dose-response experiment was conducted to estimate the standardized ileal digestible (SID) Leu to Lys ratio required for the maximum growth of young pigs after weaning. In this study, 96 female pigs (initial BW of 8 kg) were allotted to 1 of 6 dietary treatments with 16 individually penned pigs per treatment. Graded levels of crystalline L-Leu were added to a basal diet to provide diets containing 0.70, 0.80, 0.90, 1.00, 1.10, and 1.20 SID Leu:Lys. Lysine was limiting and fulfilled 90% of the current recommendations. The ADFI, ADG, and G:F were determined during a 2 wk experimental period. Blood and urine samples were taken at the end of each wk. The ADFI increased linearly (P < 0.001) from 0.70 to 0.80 SID Leu:Lys and then remained constant from 0.90 to 1.20 SID Leu:Lys. The ADG showed a quadratic increase ( P= 0.02), as the SID Leu:Lys level increased from 0.70 to 0.90 SID Leu:Lys and did not change further from 0.90 to 1.20 SID Leu:Lys. The G:F increased quadratically (P < 0.001) with increasing SID Leu:Lys level, and the greatest G:F was achieved with pigs receiving the diet with 0.80 SID Leu:Lys. Increasing the dietary SID Leu:Lys resulted in a linear increase in plasma Leu concentration (P < 0.001) and quadratic increases (P < 0.001) in plasma Cys concentration. The plasma concentration of most of the other AA was lowest in pigs receiving the diets with 0.90 to 1.00 SID Leu:Lys. The plasma urea nitrogen concentration tended (P = 0.08) to be lowest in pigs receiving 1.00 SID Leu:Lys, suggesting a more balanced AA profile at this level. Using a curvilinear-plateau model, the SID Leu:Lys requirement was estimated at 0.93 to maximize growth in female pigs weighing 8 to 12 kg.

Dark-field X-ray microscopy for multiscale structural characterization.

Many physical and mechanical properties of crystalline materials depend strongly on their internal structure, which is typically organized into grains and domains on several length scales. Here we present dark-field X-ray microscopy; a non-destructive microscopy technique for the three-dimensional mapping of orientations and stresses on lengths scales from 100 nm to 1 mm within embedded sampling volumes. The technique, which allows 'zooming' in and out in both direct and angular space, is demonstrated by an annealing study of plastically deformed aluminium. Facilitating the direct study of the interactions between crystalline elements is a key step towards the formulation and validation of multiscale models that account for the entire heterogeneity of a material. Furthermore, dark-field X-ray microscopy is well suited to applied topics, where the structural evolution of internal nanoscale elements (for example, positioned at interfaces) is crucial to the performance and lifetime of macro-scale devices and components thereof.

Microbial phytase addition resulted in a greater increase in phosphorus digestibility in dry-fed compared with liquid-fed non-heat-treated wheat-barley-maize diets for pigs.

The objective was to evaluate the effect of microbial phytase (1250 FTU/kg diet with 88% dry matter (DM)) on apparent total tract digestibility (ATTD) of phosphorus (P) in pigs fed a dry or soaked diet. Twenty-four pigs (65±3 kg) from six litters were used. Pigs were housed in metabolism crates and fed one of four diets for 12 days; 5 days for adaptation and 7 days for total, but separate collection of feces and urine. The basal diet was composed of wheat, barley, maize, soybean meal and no mineral phosphate. Dietary treatments were: basal dry-fed diet (BDD), BDD with microbial phytase (BDD+phy), BDD soaked for 24 h at 20°C before feeding (BDS) and BDS with microbial phytase (BDS+phy). Supplementation of microbial phytase increased ATTD of DM and crude protein (N×6.25) by 2 and 3 percentage units (P<0.0001; P<0.001), respectively. The ATTD of P was affected by the interaction between microbial phytase and soaking (P=0.02). This was due to a greater increase in ATTD of P by soaking of the diet containing solely plant phytase compared with the diet supplemented with microbial phytase: 35%, 65%, 44% and 68% for BDD, BDD+phy, BSD and BSD+phy, respectively. As such, supplementation of microbial phytase increased ATTD of P in the dry-fed diet, but not in the soaked diet. The higher ATTD of P for BDS compared with BDD resulted from the degradation of 54% of the phytate in BDS by wheat and barley phytases during soaking. On the other hand, soaking of BDS+phy did not increase ATTD of P significantly compared with BDD+phy despite that 76% of the phytate in BDS+phy was degraded before feeding. In conclusion, soaking of BDS containing solely plant phytase provided a great potential for increasing ATTD of P. However, this potential was not present when microbial phytase (1250 FTU/kg diet) was supplemented, most likely because soaking of BDS+phy for 24 h at 20°C did not result in a complete degradation of phytate before feeding.

Antipsychotics and associated risk of out-of-hospital cardiac arrest.

Antipsychotic drugs have been associated with sudden cardiac death, but differences in the risk of out-of-hospital cardiac arrest (OHCA) associated with different antipsychotic drug classes are not clear. We identified all OHCAs in Denmark (2001-2010). The risk of OHCA associated with antipsychotic drug use was evaluated by conditional logistic regression analysis in case-time-control models. In total, 2,205 (7.6%) of 28,947 OHCA patients received treatment with an antipsychotic drug at the time of the event. Overall, treatment with any antipsychotic drug was associated with OHCA (odds ratio (OR) = 1.53, 95% confidence interval (CI): 1.23-1.89), as was use with typical antipsychotics (OR = 1.66, CI: 1.27-2.17). By contrast, overall, atypical antipsychotic drug use was not (OR = 1.29, CI: 0.90-1.85). Two individual typical antipsychotic drugs, haloperidol (OR = 2.43, CI: 1.20-4.93) and levomepromazine (OR = 2.05, CI: 1.18-3.56), were associated with OHCA, as was one atypical antipsychotic drug, quetiapine (OR = 3.64, CI: 1.59-8.30).

Effect of particle size and microbial phytase on phytate degradation in incubated maize and soybean meal.

The objective of the study was to evaluate the effect of screen size (1, 2 and 3 mm) and microbial phytase (0 and 1000 FTU/kg as-fed) on phytate degradation in maize (100% maize), soybean meal (100% SBM) and maize-SBM (75% maize and 25% SBM) incubated in water for 0, 2, 4, 8 and 24 h at 38°C. Samples were analysed for pH, dry matter and phytate phosphorus (P). Particle size distribution (PSD) and average particle size (APS) of samples were measured by the Laser Diffraction and Bygholm method. PSD differed between the two methods, whereas APS was similar. Decreasing screen size from 3 to 1 mm reduced APS by 48% in maize, 30% in SBM and 26% in maize-SBM. No interaction between screen size and microbial phytase on phytate degradation was observed, but the interaction between microbial phytase and incubation time was significant ( P<0.001). This was because microbial phytase reduced phytate P by 88% in maize, 84% in maize-SBM and 75% in SBM after 2 h of incubation ( P<0.05), whereas the reduction of phytate P was limited (<50%) in the feeds, even after 24 h when no microbial phytase was added. The exponential decay model was fitted to the feeds with microbial phytase to analyse the effect of screen size and feed on microbial phytase efficacy on phytate degradation. The interaction between screen size and feed affected the relative phytate degradation rate ( Rd) of microbial phytase as well as the time to decrease 50% of the phytate P ( t1 =2) ( P<0.001). Thus, changing from 3 to 1 mm screen size increased Rd by 22 and 10%/h and shortened t1 =2 by 0.4 and 0.2 h in maize and maize-SBM, respectively ( P<0.05), but not in SBM. Moreover, the screen size effect was more pronounced in maize and maize-SBM compared with SBM as a higher phytate degradation rate constant (Kd) and Rd, and a shorter t1 =2 was observed in maize compared with SBM in all screen sizes ( P<0.05). However, a higher amount of degraded phytate was achieved in SBM than in maize because of the higher initial phytate P content in SBM. In conclusion, reducing screen size from 3 to 1 mm increased Kd and Rd and decreased t1 =2 in maize and maize-SBM with microbial phytase. The positive effect of grinding on improving microbial phytase efficacy, which was expressed as Kd, Rd and t1/2, was greater in maize than in SBM.

Isoleucine requirement of pigs weighing 8 to 18 kg fed blood cell-free diets.

The aim of the present study was to determine the minimum requirement of Ile in young pigs, enabling feeding of balanced low-CP diets. Most previous studies have used experimental diets that included blood cells, which are particularly high in Leu and known to antagonize the use of Ile. One week after weaning at d 28, 100 crossbred female pigs weighing 7.9 ± 0.7 kg were allocated to 1 of 5 dietary treatments. Diets were formulated to contain 1.15 g standardized ileal digestible (SID) Lys/MJ NE and were free of blood cells. The SID Ile was 0.42, 0.47, 0.53, 0.58, and 0.62 relative to Lys. The other indispensable AA were supplied according to requirements. Representative samples from the 5 diets were analyzed in 4 replicates at 3 different laboratories. The pigs were fed ad libitum and individually housed in 7 identical rooms during a 21-d period. At d 0, 7, 14, and 21, the pigs were weighed, and feed intake was determined. At d 15, blood samples were collected from the jugular vein to determine the plasma urea and free AA content. There were differences among the 3 laboratories in the analyzed content of several AA, and also Ile and Lys showed a large variation within the diets, which may cause variation in published requirement estimates. The concentration of Ile in plasma increased linearly (P < 0.01), and Lys in plasma decreased linearly (P = 0.02) with increasing SID Ile:Lys. A tendency for a linear decrease in plasma concentration was found for Thr (P = 0.10). Both ADFI and ADG were reduced when Ile was supplied above the Ile requirement estimate. Quadratic regression curves on ADFI, ADG, and G:F all showed the maximum at 0.52 SID Ile:Lys. Modeling with 2-sloped quadratic broken-line curves showed the maximum at 0.50, 0.53, and 0.54 SID Ile:Lys for ADFI, ADG, and G:F, respectively. In conclusion, the average estimation of requirement in this dose-response study using blood cell-free diets was 0.52 SID Ile:Lys during a 21-d experimental period from 8 kg BW.

Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study.

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.