Evaluation of cystatin C for the detection of chronic kidney disease in cats

BackgroundSerum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. ObjectivesTo evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). AnimalsNinety cats were included: 49 CKD and 41 healthy cats. MethodsSerum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT<1.7mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling. ResultsCats with CKD had significantly higher meanSD sCysC (1.4 +/- 0.5mg/L) (P<.001) and uCysC/urinary creatinine (uCr) (291 +/- 411mg/mol) (P<.001) compared to healthy cats (sCysC 1.0 +/- 0.3 and uCysC/uCr 0.32 +/- 0.97). UCysC was detected in 35/49 CKD cats. R-2 values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr=+GFR+epsilon). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr. ConclusionSerum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats

Noiseless Linear Amplification and Distillation of Entanglement

The idea of signal amplification is ubiquitous in the control of physical systems, and the ultimate performance limit of amplifiers is set by quantum physics. Increasing the amplitude of an unknown quantum optical field, or more generally any harmonic oscillator state, must introduce noise. This linear amplification noise prevents the perfect copying of the quantum state, enforces quantum limits on communications and metrology, and is the physical mechanism that prevents the increase of entanglement via local operations. It is known that non-deterministic versions of ideal cloning and local entanglement increase (distillation) are allowed, suggesting the possibility of non-deterministic noiseless linear amplification. Here we introduce, and experimentally demonstrate, such a noiseless linear amplifier for continuous-variables states of the optical field, and use it to demonstrate entanglement distillation of field-mode entanglement. This simple but powerful circuit can form the basis of practical devices for enhancing quantum technologies. The idea of noiseless amplification unifies approaches to cloning and distillation, and will find applications in quantum metrology and communications.Comment: Submitted 10 June 200

Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses

Fasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection

Antibody engineering & therapeutics, the annual meeting of the antibody society December 7-10, 2015, San Diego, CA, USA

The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries

Postural loads during walking after an imbalance of occlusion created with unilateral cotton rolls

<p>Abstract</p> <p>Background</p> <p>It was showed that stomatognathic functions correlate with alterations in locomotion, that are detectable through the analysis of loading during walking. For example, subjects with symptoms of Temporomandibular disorders (TMDs) showed a significant higher load pressure on the two feet, respect to health subjects, when cotton rolls were inserted. This previous study appeared to suggest that the alteration of postural loads associated to a particular alteration of stomatognathic condition (in this case, the cotton rolls inserted between the two dental arches) is detectable only in TMD's subjects, while it resulted not detectable in health subjects, because in that study, health subjects did not show any significant alteration of postural loads related to the different stomatognathic tested conditions. In other words, in that previous study, in the group of health subjects, no significant difference in postural loads was observed among the different test conditions; while TMD subjects showed a significant higher load pressure on the two feet when cotton rolls were inserted, respect to all the other tested conditions. Thus, the aim of this study was to better investigate these correlations in health subjects without TMD's symptoms, testing other different intra-oral conditions, and to verifywhether an experimentally induced imbalance of occlusion, obtained putting an unilateral cotton roll, could cause an alteration of postural loading on feet during walking.</p> <p>Findings</p> <p>In a sample of thirty Caucasian adult females (mean age 28.5 ± 4.5), asymptomatic for TMDs, when a cotton roll was positioned on the left or the right sides of dental arches, so causing a lateral shift of the mandible, the percentage of loading and the loading surface of the ipsi-lateral foot, left or right, were found to be significantly lower than in habitual occlusion (p < 0.05). Males were not included because of their different postural attitude respect to females. Further studies in a sample of males will be presented.</p> <p>Conclusions</p> <p>This study showed that in health subjects without TMD's symptoms, an experimentally induced imbalance of the occlusion, obtained through an unilateral cotton roll, is associated to detectable alterations in the distribution of loading on feet surface, during walking.</p

A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

© 2016 cThe Author(s). Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases

Contrast‐enhanced ultrasound assessed renal microvascular perfusion may predict postoperative renal complications following colorectal surgery

Colorectal surgery is associated with an above‐average mortality rate of ~15%. During surgery, maintenance of vital organ perfusion is essential in order to reduce postoperative mortality and morbidity, with renal perfusion of particular importance. Oesophageal Doppler monitors (ODM) are commonly used to try and provide accurate measures of fluid depletion during surgery, however it is unclear to what extent they reflect organ perfusion. In addition, it is not known whether macro‐ and/ or microvascular perfusion indices are associated with renal complications following colorectal surgery. Thirty‐two participants scheduled for colorectal surgery had three measures of macro‐ and microvascular renal blood flow via contrast enhanced ultrasound (CEUS), and simultaneous measures of cardiac output indicies via ODM: i) pre‐operatively; ii) intra‐operatively at the mid‐point of operation, and iii) after the conclusion of surgery. The Postoperative Morbidity Survey (POMS) was used to assess postoperative complications. Intra‐operatively, there was a significant correlation between renal microvascular flow (RT) and renal macrovascular flow (TTI) (rho=0.52; p=0.003). Intra‐operative TTI, but not RT, was associated with cardiac index (rho= ‐0.50; p=0.0003). Intra‐operative RT predicted increases in renal complications (OR 1.46; 95% CI 1.03 to 2.09) with good discrimination (C‐statistic, 0.85). Complications were not predicted by TTI or ODM‐derived indices. There was no relationship between RT and TTI before or after surgery. ODM measures of haemodynamic status do not correlate with renal microvascular blood flow, and as such are likely not suitable to determine vital organ perfusion. Only CEUS‐derived measures of microvascular perfusion were predictive of postoperative renal complications

Network analysis of human muscle adaptation to aging and contraction.

This is the final version. Available from Impact Journals via the DOI in this record. Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we employed a network-driven pipeline to identify putative molecular drivers of muscle aging and contraction mode responses. RNA-sequencing data was generated from young (21±1 y) and older (70±1 y) human skeletal muscle before and following acute unilateral concentric and contralateral eccentric contractions. Application of weighted gene co-expression network analysis identified 33 distinct gene clusters ('modules') with an expression profile regulated by aging, contraction and/or linked to muscle strength. These included two contraction 'responsive' modules (related to 'cell adhesion' and 'transcription factor' processes) that also correlated with the magnitude of post-exercise muscle strength decline. Module searches for 'hub' genes and enriched transcription factor binding sites established a refined set of candidate module-regulatory molecules (536 hub genes and 60 transcription factors) as possible contributors to muscle aging and/or contraction responses. Thus, network-driven analysis can identify new molecular candidates of functional relevance to muscle aging and contraction mode adaptations.Wellcome Trust Institutional Strategic Support AwardBiotechnology and Biological Sciences Research Counci