Interactions between multiple helminths and the gut microbiota in wild rodents

The gut microbiota is vital to host health and, as such, it is important to elucidate the mechanisms altering its composition and diversity. Intestinal helminths are host immunomodulators and have evolved both temporally and spatially in close association with the gut microbiota, resulting in potential mechanistic interplay. Host-helminth and host-microbiota interactions are comparatively well-examined, unlike microbiota-helminth relationships, which typically focus on experimental infection with a single helminth species in laboratory animals. Here, in addition to a review of the literature on helminth-microbiota interactions, we examined empirically the association between microbiota diversity and composition and natural infection of multiple helminth species in wild mice (Apodemus flavicollis), using 16S rRNA gene catalogues (metataxonomics). In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host. Within our wild rodent system variation in the composition and abundance of gut microbial taxa associated with helminths was specific to each helminth species and occurred both up- and downstream of a given helminth's niche (gut position). The most pronounced helminth-microbiota association was between the presence of tapeworms in the small intestine and increased S24-7 (Bacteroidetes) family in the stomach. Helminths clearly have the potential to alter gut homeostasis. Free-living rodents with a diverse helminth community offer a useful model system that enables both correlative (this study) and manipulative inference to elucidate helminth-microbiota interactions

Pharmacokinetics of Pamidronate in Patients With Bone Metastases

Background: Pamidronate is a secondgeneration bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. Purpose: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. Methods: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. Results: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (±SD) half-life of the distribution phase was 0.8 hour (±0.3), the mean (±SD) of the area under the curve for drug concentration in plasma × time at 0-24 hours was 22.0 × 8.8 μmol/L × hours, and the mean (±SD) of the maximum plasma concentration was 9.7 μmol/L (±3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. Conclusions: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases. [J Natl Cancer Inst 84: 788-792, 1992

Heterodimers for in Situ Plasmonic Spectroscopy: Cu Nanoparticle Oxidation Kinetics, Kirkendall Effect, and Compensation in the Arrhenius Parameters

The ability to study oxidation, reduction, and other chemical transformations of nanoparticles in real time and under realistic conditions is a nontrivial task due to their small dimensions and the often challenging environment in terms of temperature and pressure. For scrutinizing oxidation of metal nanoparticles, visible light optical spectroscopy based on the plasmonic properties of the metal has been established as a suitable method. However, directly relying on the plasmonic resonance of metal nanoparticles as a built-in probe to track oxidation has a number of drawbacks, including the loss of optical contrast in the late oxidation stages. To address these intrinsic limitations, we present a plasmonic heterodimer-based nanospectroscopy approach, which enables continuous self-referencing by using polarized light to eliminate parasitic signals and provides large optical contrast all the way to complete oxidation. Using Au-Cu heterodimers and combining experiments with finite-difference time-domain simulations, we quantitatively analyze the oxidation kinetics of ca. 30 nm sized Cu nanoparticles up to complete oxidation. Taking the Kirkendall effect into account, we extract the corresponding apparent Arrhenius parameters at various extents of oxidation and find that they exhibit a significant compensation effect, implying that changes in the oxidation mechanism occur as oxidation progresses and the structure of the formed oxide evolves. In a wider perspective, our work promotes the use of model-system-type in situ optical plasmonic spectroscopy experiments in combination with electrodynamics simulations to quantitatively analyze and mechanistically interpret oxidation of metal nanoparticles and the corresponding kinetics in demanding chemical environments, such as in heterogeneous catalysis

Diet-driven mercury contamination is associated with polar bear gut microbiota

7openInternationalInternational coauthor/editorThe gut microbiota may modulate the disposition and toxicity of environmental contaminants within a host but, conversely, contaminants may also impact gut bacteria. Such contaminant-gut microbial connections, which could lead to alteration of host health, remain poorly known and are rarely studied in free-ranging wildlife. The polar bear (Ursus maritimus) is a long-lived, wide-ranging apex predator that feeds on a variety of high trophic position seal and cetacean species and, as such, is exposed to among the highest levels of biomagnifying contaminants of all Arctic species. Here, we investigate associations between mercury (THg; a key Arctic contaminant), diet, and the diversity and composition of the gut microbiota of polar bears inhabiting the southern Beaufort Sea, while accounting for host sex, age class and body condition. Bacterial diversity was negatively associated with seal consumption and mercury, a pattern seen for both Shannon and Inverse Simpson alpha diversity indices (adjusted R2 = 0.35, F1,18 = 8.00, P = 0.013 and adjusted R2 = 0.26, F1,18 = 6.04, P = 0.027, respectively). No association was found with sex, age class or body condition of polar bears. Bacteria known to either be involved in THg methylation or considered to be highly contaminant resistant, including Lactobacillales, Bacillales and Aeromonadales, were significantly more abundant in individuals that had higher THg concentrations. Conversely, individuals with higher THg concentrations showed a significantly lower abundance of Bacteroidales, a bacterial order that typically plays an important role in supporting host immune function by stimulating intraepithelial lymphocytes within the epithelial barrier. These associations between diet-acquired mercury and microbiota illustrate a potentially overlooked outcome of mercury accumulation in polar bears.openWatson, S.; McKinney, M.A.; Pindo, M.; Bull, M.; Atwood, T.C.; Hauffe, H.C.; Perkins, S.E.Watson, S.; Mckinney, M.A.; Pindo, M.; Bull, M.; Atwood, T.C.; Hauffe, H.C.; Perkins, S.E

Lymphocytic choriomeningitis, Ljungan and orthopoxvirus seroconversions in patients hospitalized due to acute Puumala hantavirus infection

Background: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. Objective: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity. Study design: We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care. Results: A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively. Conclusion: Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Single-Pion Production in pp Collisions at 0.95 GeV/c (II)

The single-pion production reactions $pp\to d\pi^+$, $pp\to np\pi^+$ and $pp\to pp\pi^0$ were measured at a beam momentum of 0.95 GeV/c ($T_p \approx$ 400 MeV) using the short version of the COSY-TOF spectrometer. The central calorimeter provided particle identification, energy determination and neutron detection in addition to time-of-flight and angle measurements from other detector parts. Thus all pion production channels were recorded with 1-4 overconstraints. Main emphasis is put on the presentation and discussion of the $np\pi^+$ channel, since the results on the other channels have already been published previously. The total and differential cross sections obtained are compared to theoretical calculations. In contrast to the $pp\pi^0$ channel we find in the $np\pi^+$ channel a strong influence of the $\Delta$ excitation already at this energy close to threshold. In particular we find a $(3 cos^2\Theta + 1)$ dependence in the pion angular distribution, typical for a pure s-channel $\Delta$ excitation and identical to that observed in the $d\pi^+$ channel. Since the latter is understood by a s-channel resonance in the $^1D_2$ $pn$ partial wave, we discuss an analogous scenario for the $pn\pi^+$ channel

Pharmacokinetics of pamidronate in patients with bone metastases

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases

Experimental determination of the complete spin structure for anti-proton + proton -> anti-\Lambda + \Lambda at anti-proton beam momentum of 1.637 GeV/c

The reaction anti-proton + proton -> anti-\Lambda + \Lambda -> anti-proton + \pi^+ + proton + \pi^- has been measured with high statistics at anti-proton beam momentum of 1.637 GeV/c. The use of a transversely-polarized frozen-spin target combined with the self-analyzing property of \Lambda/anti-\Lambda decay allows access to unprecedented information on the spin structure of the interaction. The most general spin-scattering matrix can be written in terms of eleven real parameters for each bin of scattering angle, each of these parameters is determined with reasonable precision. From these results all conceivable spin-correlations are determined with inherent self-consistency. Good agreement is found with the few previously existing measurements of spin observables in anti-proton + proton -> anti-\Lambda + \Lambda near this energy. Existing theoretical models do not give good predictions for those spin-observables that had not been previously measured.Comment: To be published in Phys. Rev. C. Tables of results (i.e. Ref. 24) are available at http://www-meg.phys.cmu.edu/~bquinn/ps185_pub/results.tab 24 pages, 16 figure