An integrated modelling approach to derive the grey water footprint of veterinary antibiotics

Water pollution by veterinary antibiotics (VAs) resulting from livestock production is associated with severe environmental and human health risks. While upward trends in global animal product consumption signal that these risks might exacerbate toward the future, VA related water pollution is currently insufficiently understood. To increase this understanding, the present research assesses processes influencing VA pollution from VA administration to their discharge into freshwater bodies, using an integrated modelling approach (IMA). For the VAs amoxicillin, doxycycline, oxytetracycline, sulfamethazine, and tetracycline we estimate loads administered to livestock, excretion, degradation during manure storage, fate in soil and transport to surface water. Fate and transport are modelled using the VA transport model (VANTOM), which is fed with estimates from the Pan-European Soil Erosion Risk Assessment (PESERA). The grey water footprint (GWF) is used to indicate the severity of water pollution in volumetric terms by combining VA loads and predicted no effect concentrations. We apply our approach to the German-Dutch Vecht river catchment, which is characterized by high livestock densities. Results show a VA mass load decrease larger than 99% for all substances under investigation, from their administration to surface water emission. Due to metabolization in the body, degradation during manure storage and degradation in soil, VA loads are reduced by 45%, 80% and 90% on average, respectively. While amoxicillin and sulfamethazine dissipate quickly after field application, significant fractions of doxycycline, oxytetracycline and tetracycline accumulate in the soil. The overall Vecht catchment's GWF is estimated at 250,000 m3 yr−1, resulting from doxycycline (81% and 19% contribution from the German and Dutch catchment part respectively). Uncertainty ranges of several orders of magnitude, as well as several remaining limitations to the presented IMA, underscore the importance to further develop and refine the approach

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as ‘chemo fog’. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning. This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research

REAP: A two minute cell fractionation method

<p>Abstract</p> <p>Background</p> <p>The translocation or shuttling of proteins between the nucleus and cytoplasm (nucleocytoplasmic transport [NCPT]) is often a rapid event following stimulation with growth factors or in response to stress or other experimental manipulations. Commonly used methods to separate nuclei from cytoplasm employ lengthy steps such as density gradient centrifugation which exposes cells to non-physiological hyperosmotic conditions for extended time periods resulting in varying degrees of leakage between the nucleus and cytoplasm. To help maintain and quantify nuclear:cytoplasmic ratios of proteins, agents such as leptomycin B have been employed to be able to better analyze NCPT by inhibiting nuclear export. To track NCPT in the absence of these experimental manipulations that could introduce unknown artefacts, we have developed a rapid method that appears to produce pure nuclear and cytoplasmic fractions, suitable for obtaining accurate estimates of the nuclear:cytoplasmic ratios of proteins known to undergo NCPT.</p> <p>Findings</p> <p>We have developed a <b>R</b>apid, <b>E</b>fficient <b>A</b>nd <b>P</b>ractical (<b>REAP</b>) method for subcellular fractionation of primary and transformed human cells in culture. The REAP method is a two minute non-ionic detergent-based purification technique requiring only a table top centrifuge, micro-pipette and micro-centrifuge tubes. This inexpensive method has proven to efficiently separate nuclear from cytoplasmic proteins as estimated by no detectible cross-contamination of the nucleoporin and lamin A nuclear markers or the pyruvate kinase and tubulin cytoplasmic markers. REAP fractions also mirrored TNFα induced NF-κB NCPT observed in parallel by indirect immunofluorescence.</p> <p>Conclusions</p> <p>This method drastically reduces the time needed for subcellular fractionation, eliminates detectable protein degradation and maintains protein interactions. The simplicity, brevity and efficiency of this procedure allows for tracking ephemeral changes in subcellular relocalization of proteins while maintaining protein integrity and protein complex interactions.</p

Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study

<p>Abstract</p> <p>Background</p> <p>In planning a randomized controlled trial of acupuncture, we conducted a pilot study using validated outcome measures to assess the feasibility of the protocol, and to obtain preliminary data on efficacy and tolerability of 3 different forms of acupuncture treatment as an adjunct for the treatment of chronic pain in patients with Rheumatoid arthritis (RA).</p> <p>Methods</p> <p>The study employs a randomized, prospective, double-blind, placebo-controlled trial to evaluate the effect of electroacupuncture (EA), traditional Chinese acupuncture (TCA) and sham acupuncture (Sham) in patients with RA. All patients received 20 sessions over a period of 10 weeks. Six acupuncture points were chosen. Primary outcome is the changes in the pain score. Secondary outcomes included the changes in the ACR core disease measures, DAS 28 score and the number of patients who achieved ACR 20 at week 10.</p> <p>Results</p> <p>From 80 eligible patients, 36 patients with mean age of 58 ± 10 years and disease duration of 9.3 ± 6.4 years were recruited. Twelve patients were randomized to each group. Twelve, 10 and 7 patients from the EA, TCA and Sham group respectively completed the study at 20 weeks (p < 0.03); all except one of the premature dropouts were due to lack of efficacy. At week 10, the pain score remained unchanged in all 3 groups. The number of tender joints was significantly reduced for the EA and TCA groups. Physician's global score was significantly reduced for the EA group and patient's global score was significantly reduced for the TCA group. All the outcomes except patient's global score remained unchanged in the Sham group.</p> <p>Conclusion</p> <p>This pilot study has allowed a number of recommendations to be made to facilitate the design of a large-scale trial, which in turn will help to clarify the existing evidence base on acupuncture for RA.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00404443</p