Roles of interleukin-17 in uveitis

Th17 cells, a CD4+ T-cell subset, produce interleukin (IL)-17, a pro-inflammatory cytokine that has been shown to be involved in several forms of infectious and noninfectious uveitis. Here, we explore the roles of this IL in uveitic disorders as well as in experimental autoimmune uveitis, the possible pathogenic implications of several cytokines associated with IL-17 and analyze the current outcomes and goals for drugs aiming for the IL-17 pathway.info:eu-repo/semantics/publishedVersio

Prospective evaluation of BDProbeTec strand displacement amplification (SDA) system for diagnosis of tuberculosis in non-respiratory and respiratory samples.

Nucleic acid amplification techniques (NAATs) have been demonstrated to make significant improvements in the diagnosis of tuberculosis (TB), particularly in the time to diagnosis and the diagnosis of smear-negative TB. The BD ProbeTec strand displacement amplification (SDA) system for the diagnosis of pulmonary and non-pulmonary tuberculosis was evaluated. A total of 689 samples were analysed from patients with clinically suspected TB. Compared with culture, the sensitivity and specificity for pulmonary samples were 98 and 89 %, and against final clinical diagnosis 93 and 92 %, respectively. This assay has undergone limited evaluation for non-respiratory samples and so 331 non-respiratory samples were tested, identifying those specimens that were likely to yield a useful result. These were CSF (n = 104), fine needle aspirates (n = 64) and pus (n = 41). Pleural fluid (n = 47) was identified as a poor specimen. A concern in using the SDA assay was that low-positive samples were difficult to interpret; 7.8 % of specimens fell into this category. Indeed, 64 % of the discrepant results, when compared to final clinical diagnosis, could be assigned as low-positive samples. Specimen type did not predict likelihood of a sample being in the low-positive zone. Although the manufacturers do not describe the concept of a low-positive zone, we have found that it aids clinical diagnosis

Sortilin is associated with the chlamydial inclusion and is modulated during infection

© 2016. Published by The Company of Biologists Ltd. Chlamydia species are obligate intracellular pathogens that have a major impact on human health. The pathogen replicates within an intracellular niche called an inclusion and is thought to rely heavily on host-derived proteins and lipids, including ceramide. Sortilin is a transmembrane receptor implicated in the trafficking of acid sphingomyelinase, which is responsible for catalysing the breakdown of sphingomyelin to ceramide. In this study, we examined the role of sortilin in Chlamydia trachomatis L2 development. Western immunoblotting and immunocytochemistry analysis revealed that endogenous sortilin is not only associated with the inclusion, but that protein levels increase in infected cells. RNAimediated depletion of sortilin, however, had no detectable impact on ceramide delivery to the inclusion or the production of infectious progeny. This study demonstrates that whilst Chlamydia redirects sortilin trafficking to the chlamydial inclusion, RNAi knockdown of sortilin expression is insufficient to determine if this pathway is requisite for the development of the pathogen

Is blue dye still required during sentinel lymph node biopsy for breast cancer?

BACKGROUND: In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. METHODS: Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. RESULTS: A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. CONCLUSION: The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation

Diffusion tensor imaging reveals changes in microstructural integrity along compressed nerve roots that correlate with chronic pain symptoms and motor deficiencies in elderly stenosis patients

Age-related degenerative changes in the lumbar spine frequently result in nerve root compression causing severe pain and disability. Given the increasing incidence of lumbar spinal disorders in the aging population and the discrepancies between the use of current diagnostic imaging tools and clinical symptoms, novel methods of nerve root assessment are needed. We investigated elderly patients with stenosis at L4-L5 or L5-S1 levels. Diffusion tensor imaging (DTI) was used to quantify microstructure in compressed L5 nerve roots and investigate relationships to clinical symptoms and motor neurophysiology. DTI metrics (i.e. FA, MD, AD and RD) were measured at proximal, mid and distal segments along compressed (i.e. L5) and intact (i.e. L4 or S1) nerve roots. FA was significantly reduced in compressed nerve roots and MD, AD and RD were significantly elevated in the most proximal segment of the nerve root studied. FA was significantly correlated with electrophysiological measures of root function: minimum F-wave latency and peripheral motor conduction time (PMCT). In addition, FA along the compressed root also correlated with leg pain and depression score. There was also a relationship between RD and anxiety, leg pain and disability score and AD correlated with depression score. Taken together, these data show that DTI metrics are sensitive to nerve root compression in patients with stenosis as a result of age-related lumbar degeneration. Critically, they show that the changes in microstructural integrity along compressed L5 nerve roots are closely related to a number of clinical symptoms associated with the development of chronic pain as well as neurophysiological assessments of motor function. These inherent relationships between nerve root damage and phenotype suggest that the use DTI is a promising method as a way to stratify treatment selection and predict outcomes

Understanding vehicular routing behavior with location-based service data

This is the final published version, also available from Springer Nature via the DOI in this record.Properly extracting patterns of individual mobility with high resolution data sources such as the one extracted from smartphone applications offers important opportunities. Potential opportunities not offered by call detailed records (CDRs), which offer resolutions triangulated from antennas, are route choices, travel modes detection and close encounters. Nowadays, there is not a standard and large scale data set collected over long periods that allows us to characterize these. In this work we thoroughly examine the use of data from smartphone applications, also referred to as location-based services (LBS) data, to extract and understand the vehicular route choice behavior. Taking the Dallas-Fort Worth metroplex as an example, we first extract the vehicular trips with simple rules and reconstruct the origin-destination matrix by coupling the extracted vehicular trips of the active LBS users and the United States census data. We then present a method to derive the commonly used routes by individuals from the LBS traces with varying sample rate intervals. We further inspect the relation between the number of routes and the trip characteristics, including the departure time, trip length and travel time. Specifically, we consider the travel time index and buffer index for the LBS users taking different number of routes. Empirical results demonstrate that during the peak hours, travelers tend to reduce the impact of traffic congestion by taking alternative routes. Overall, the proposed data analysis framework is cost-effective to treat sparse data generated from the use of smartphones to inform routing behavior. The potential in practice is to inform demand management strategies, by targeting individual users while generating large scale estimates of congestion mitigation.MIT Energy InitiativeBerkeley Deep Drive consortiu

Local stressors mask the effects of warming in freshwater ecosystems

Climate warming is a ubiquitous stressor in freshwater ecosystems, yet its interactive effects with other stressors are poorly understood. We address this knowledge gap by testing the ability of three contrasting null models to predict the joint impacts of warming and a range of other aquatic stressors using a new database of 296 experimental combinations. Despite concerns that stressors will interact to cause synergisms, we found that net impacts were usually best explained by the effect of the stronger stressor alone (the dominance null model), especially if this stressor was a local disturbance associated with human land use. Prediction accuracy depended on stressor identity and how asymmetric stressors were in the magnitude of their effects. These findings suggest we can effectively predict the impacts of multiple stressors by focusing on the stronger stressor, as habitat alteration, nutrients and contamination often override the biological consequences of higher temperatures in freshwater ecosystems

Optically Generated Ultrasound for Intracoronary Imaging

Conventional intravascular ultrasound (IVUS) devices use piezoelectric transducers to electrically generate and receive US. With this paradigm, there are numerous challenges that restrict improvements in image quality. First, with miniaturization of the transducers to reduce device size, it can be challenging to achieve the sensitivities and bandwidths required for large tissue penetration depths and high spatial resolution. Second, complexities associated with manufacturing miniaturized electronic transducers can have significant cost implications. Third, with increasing interest in molecular characterization of tissue in-vivo, it has been challenging to incorporate optical elements for multimodality imaging with photoacoustics (PA) or near-infrared spectroscopy (NIRS) whilst maintaining the lateral dimensions suitable for intracoronary imaging. Optical Ultrasound (OpUS) is a new paradigm for intracoronary imaging. US is generated at the surface of a fiber optic transducer via the photoacoustic effect. Pulsed or modulated light is absorbed in an engineered coating on the fiber surface and converted to thermal energy. The subsequent temperature rise leads to a pressure rise within the coating, which results in a propagating ultrasound wave. US reflections from imaged structures are received with optical interferometry. With OpUS, high bandwidths (31.5 MHz) and pressures (21.5 MPa) have enabled imaging with axial resolutions better than 50 μm and at depths >20 mm. These values challenge those of conventional 40 MHz IVUS technology and show great potential for future clinical application. Recently developed nanocomposite coating materials, that are highly transmissive at light wavelengths used for PA and NIRS light, can facilitate multimodality imaging, thereby enabling molecular characterization

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction