Serotonin (5-HT) is an important neurotransmitter involved in the brain–gut axis. It is possible to lower the 5-HT level in the body by means of a nutritional intervention using an amino acid ...mixture; the acute tryptophan depletion (ATD) method. We studied the effect of ATD on gastric emptying in healthy females, who received both ATD and placebo in a random order. Gastric emptying was measured using the 13Coctanoic acid breath test. The present data demonstrate significant differences in both gastric emptying and lag phase (Tlag) between the ATD and placebo experiment. Eight out of ten subjects showed a delayed gastric emptying in the ATD experiment. Both the gastric half-emptying time (T1/2) and the Tlag were significantly higher in the ATD experiment. T1/2 in the ATD experiment was 137·2 (range 76·2–634·8) min; T1/2 for the placebo experiment was 98·5 (range 63·7–168·8) min (P=0·028). Tlag in the ATD experiment was 83·7 (range 45·1–356·2) min; Tlag for the placebo experiment was 56·9 (range 23·2–101·2) min (P=0·007). We conclude that lowering the 5-HT level in the body using the ATD method leads to a significantly delayed gastric emptying of a solid meal. Nutritional manipulation of the serotonergic system in healthy volunteers may lead to alterations in gastrointestinal motility.
Malnutrition is observed frequently in patients with inflammatory bowel disease (IBD). Knowledge of the nutritional status in patients with recently diagnosed IBD is limited. The aim of this study ...was to establish a comprehensive picture of the nutritional status in recently diagnosed IBD patients.
Sixty-nine IBD patients (23 Crohn's disease (CD) and 46 with ulcerative colitis (UC)) within 6 months of diagnosis and 69 age- and sex-matched population controls were included in the study.
The nutritional status was assessed by: (1) body composition (anthropometry and dual-energy X-ray absorptiometry); (2) dietary intake (dietary history); (3) biochemical indexes of nutrition; and (4) muscle strength (isokinetic dynamometer).
Body weight and body mass index were significantly lower in UC patients compared with controls. The mean daily intake of carbohydrates was significantly higher in CD patients and the intakes of protein, calcium, phosphorus, and riboflavin were significantly lower in UC patients compared with controls, respectively. Serum concentrations of several nutrients (beta-carotene, magnesium, selenium and zinc) were significantly lower in UC patients compared with controls. Serum vitamin B12 concentration was significantly lower in CD patients. Muscle strength did not significantly differ between IBD patients and controls.
This study showed that the nutritional status of IBD patients was already affected negatively at time of diagnosis. It needs to be elucidated whether nutritional supplementation in recently diagnosed IBD patients may improve the clinical course of the disease.
Pacific Ocean sea surface temperatures (SST) influence rainfall variability on multidecadal and interdecadal timescales in concert with the Pacific Decadal Oscillation (PDO) and Interdecadal Pacific ...Oscillation (IPO). Rainfall variations in locations such as Australia and North America are therefore linked to phase changes in the PDO. Furthermore, studies have suggested teleconnections exist between the western Indian Ocean and Pacific Decadal Variability (PDV), similar to those observed on interannual timescales related to the El Niño Southern Oscillation (ENSO). However, as instrumental records of rainfall are too short and sparse to confidently assess multidecadal climatic teleconnections, here we present four coral climate archives from Madagascar spanning up to the past 300 yr (1708-2008) to assess such decadal variability. Using spectral luminescence scanning to reconstruct past changes in river runoff, we identify significant multidecadal and interdecadal frequencies in the coral records, which before 1900 are coherent with Asian-based PDO reconstructions. This multidecadal relationship with the Asian-based PDO reconstructions points to an unidentified teleconnection mechanism that affects Madagascar rainfall/runoff, most likely triggered by multidecadal changes in North Pacific SST, influencing the Asian Monsoon circulation. In the 20th century we decouple human deforestation effects from rainfall-induced soil erosion by pairing luminescence with coral geochemistry. Positive PDO phases are associated with increased Indian Ocean temperatures and runoff/rainfall in eastern Madagascar, while precipitation in southern Africa and eastern Australia declines. Consequently, the negative PDO phase that started in 1998 may contribute to reduced rainfall over eastern Madagascar and increased precipitation in southern Africa and eastern Australia. We conclude that multidecadal rainfall variability in Madagascar and the western Indian Ocean needs to be taken into account when considering water resource management under a future warming climate.
Unsynchronised, dry-running screw machines have advantages compared to conventional oil-injected and synchronised, dry-running screw machines. Because of the absence of an additional timing gear and ...no injected lubricant, the effort for manufacturing and assembly can be reduced and lubricant residues in the process gas are avoided. In this design the female rotor torque resulting from the gas pressure is transferred directly to the male rotor by the contacting rotor surfaces. To investigate this contact, a two-dimensional boundary element method contact algorithm is developed to calculate the loads in terms of contact tractions and sliding velocities. The contact kinematics of the screw rotors and the non-constant curvature of the rotor surfaces are considered. The movement between the screw rotors is transformed into a relative coordinate system fixed on the male rotor. Furthermore, the influence of manufacturing tolerances to the occurring contact loads are investigated.
An innate immune memory response can manifest in two ways: immune training and immune tolerance, which refers to an enhanced or suppressed immune response to a second challenge, respectively. ...Exposing monocytes to moderate-to-high amounts of bacterial lipopolysaccharide (LPS) induces immune tolerance, whereas fungal β-glucan (BG) induces immune training. In microglia, it has been shown that different LPS inocula in vivo can induce either immune training or tolerance. Few studies focused on impact of BG on microglia and were only performed in vitro. The aim of the current study was to determine whether BG activates and induces immune memory in microglia upon peripheral administration in vivo.
Two experimental designs were used. In the acute design, mice received an intraperitoneal (i.p.) injection with PBS, 1 mg/kg LPS or 20 mg/kg BG and were terminated after 3 h, 1 or 2 days. In the preconditioning design, animals were first challenged i.p. with PBS, 1 mg/kg LPS or 20 mg/kg BG. After 2, 7 or 14 days, mice received a second injection with PBS or 1 mg/kg LPS and were sacrificed 3 h later. Microglia were isolated by fluorescence-activated cell sorting, and cytokine gene expression levels were determined. In addition, a self-developed program was used to analyze microglia morphological changes. Cytokine concentrations in serum were determined by a cytokine array.
Microglia exhibited a classical inflammatory response to LPS, showing significant upregulation of Tnf, Il6, Il1β, Ccl2, Ccl3 and Csf1 expression, three h after injection, and obvious morphological changes 1 and 2 days after injection. With an interval of 2 days between two challenges, both BG and LPS induced immune training in microglia. The training effect of LPS changed into immune tolerance after a 7-day interval between 2 LPS challenges. Preconditioning with BG and LPS resulted in increased morphological changes in microglia in response to a systemic LPS challenge compared to naïve microglia.
Our results demonstrate that preconditioning with BG and LPS both induced immune training of microglia at two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning resulted in immune tolerance in microglia.
This paper examines the $^{18}$Ne($\alpha, p_{0}$)$^{21}$Na cross-section
relevant in X-ray bursts. The study was performed with the K600 magnetic
spectrometer in coincidence with the CAKE, a silicon ...detector array, at iThemba
LABS in Cape Town, South Africa. A 100-MeV proton beam was impinged on a
$^{24}$Mg target to study the $^{24}$Mg($p,t$)$^{22}$Mg reaction. The triton
ejectiles were momentum-analysed with the magnetic spectrometer and proton
decays from the $^{22}$Mg recoil nucleus to the ground state of $^{21}$Na and
various excited states thereof were detected with the CAKE. In doing so, we
were able to compare our results to previous direct and indirect measurements
of the $^{18}$Ne($\alpha, p$)$^{21}$Na reaction.
Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of a patient with the aim to restore a disturbed gut microbiota. In this study, it was ...investigated whether FMT has an effect on faecal microbial composition, its functional capacity, faecal metabolite profiles and their interactions in 16 irritable bowel syndrome (IBS) patients. Faecal samples from eight different time points before and until six months after allogenic FMT (faecal material from a healthy donor) as well as autologous FMT (own faecal material) were analysed by 16S RNA gene amplicon sequencing and gas chromatography coupled to mass spectrometry (GS-MS). The results showed that the allogenic FMT resulted in alterations in the microbial composition that were detectable up to six months, whereas after autologous FMT this was not the case. Similar results were found for the functional profiles, which were predicted from the phylogenetic sequencing data. While both allogenic FMT as well as autologous FMT did not have an effect on the faecal metabolites measured in this study, correlations between the microbial composition and the metabolites showed that the microbe-metabolite interactions seemed to be disrupted after allogenic FMT compared to autologous FMT. This shows that FMT can lead to altered interactions between the gut microbiota and its metabolites in IBS patients. Further research should investigate if and how this affects efficacy of FMT treatments.
Summary Background & Aims Butyrate, produced by colonic fermentation of dietary fibers is often hypothesized to beneficially affect colonic health. This study aims to assess the effects of butyrate ...on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress. Methods Thirty-five patients with ulcerative colitis in clinical remission daily administered 60 ml rectal enemas containing 100 mM sodium butyrate ( n = 17) or saline ( n = 18) during 20 days (NCT00696098). Before and after the intervention feces, blood and colonic mucosal biopsies were obtained. Parameters of antioxidant defense and oxidative damage, myeloperoxidase, several cytokines, fecal calprotectin and CRP were determined. Results Butyrate enemas induced minor effects on colonic inflammation and oxidative stress. Only a significant increase of the colonic IL-10/IL-12 ratio was found within butyrate-treated patients ( p = 0.02), and colonic concentrations of CCL5 were increased after butyrate compared to placebo treatment ( p = 0.03). Although in general butyrate did not affect colonic glutathione levels, the effects of butyrate enemas on total colonic glutathione appeared to be dependent on the level of inflammation. Conclusion Although UC patients in remission were characterized by low-grade oxidative stress and inflammation, rectal butyrate enemas showed only minor effects on inflammatory and oxidative stress parameters.
Microglia are the resident macrophages of the central nervous system (CNS) and play a pivotal role in immune surveillance and CNS homeostasis. Morphological transitions in microglia are indicative ...for local changes in the CNS microenvironment and serve as a proxy for the detection of alterations in the CNS, both in health and disease. Current strategies to ‘measure’ microglia combine advanced morphometrics with clustering approaches to identify and categorize microglia morphologies. However, these studies are labor intensive and clustering approaches are often subject to relevant feature selection bias. Here, we provide a morphometrics pipeline with user‐friendly computational tools for image segmentation, automated feature extraction and morphological categorization of microglia by means of hierarchical clustering on principal components (HCPC) without the need for feature inclusion criteria. With this pipeline we provide new and detailed insights in the distribution of microglia morphotypes across sixteen CNS regions along the rostro‐caudal axis of the adult C57BL/6J mouse CNS. Although regional variations in microglia morphologies were evident, we found no evidence for male–female dimorphism at any CNS region investigated, indicating that ‐ by and large ‐ microglia in adult male and female mice are morphometrically indistinguishable. Taken together, our newly developed pipeline provides valuable tools for objective and unbiased identification and categorization of microglia morphotypes and can be applied to any CNS (disease) model.
Main Points
User‐friendly computational tools for morphological categorization of microglia.
Detailed insights in the distribution of microglia morphotypes across 16 CNS regions in the adult mouse.
No evidence for male–female microglial dimorphism.
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