Commentary – ordering lab tests for suspected rheumatic disease

One of the least-appreciated advances in pediatric rheumatology over the past 25 years has been the delineation of the many ways in which children with rheumatic disease differ from adults with the same illnesses. Furthermore, we are now learning that paradigms that are useful in evaluating adults with musculoskeletal complaints have limited utility in children. Nowhere is that more true than in the use of commonly used laboratory tests, particularly antinuclear antibody (ANA) and rheumatoid factor (RF) assays. This short review will provide the practitioner with the evidence base that supports a more limited use of ANA and RF testing in children

Comparing two approaches for parsimonious vegetation modelling in semiarid regions using satellite data

[EN] Large portions of Earth's terrestrial surface are arid or semiarid. As in these regions, the hydrological cycle and the vegetation dynamics are tightly interconnected, a coupled modelling of these two systems is needed to fully reproduce the ecosystem behaviour. In this paper, the performance of two parsimonious dynamic vegetation models, suitable for the inclusion in operational ecohydrological models and based on well-established but different approaches, is compared in a semiarid Aleppo Pine region. The first model [water use efficiency (WUE) model] links growth to transpiration through WUE; the second model [light use efficiency (LUE) model] simulates biomass increase in relation to absorbed photosynthetically active radiation and LUE. Furthermore, an analysis of the information contained in MODIS products is presented to indicate the best vegetation indices to be used as observational verification for the models. Enhanced Vegetation Index is reported in literature to be highly correlated with leaf area index, so it is compared with modelled LAI(mod) (rWUE model = 0.45; rLUE model = 0.57). In contrast, Normalized Difference Vegetation Index appears highly linked to soil moisture, through the control exerted by this variable on chlorophyll production, and is therefore used to analyze LAI*(mod), models' output corrected by plant water stress (rWUE model = 0.62; rLUE model = 0.59). Moderate-resolution imaging spectroradiometer Leaf Area Index and evapotranspiration are found to be unrealistic in the studied area. The performance of both models in this semiarid region is found to be reasonable. However, the LUE model presents the advantages of a better performance, the possibility to be used in a wider range of climates and to have been extensively tested in literature. (C) Copyright 2014 John Wiley & Sons, Ltd.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness through the research projects FLOOD-MED (ref. CGL2008-06474-C02-02), SCARCE-CONSOLIDER (ref. CSD2009-00065) and ECO-TETIS (ref. CGL2011-28776-C02-01), and from the European Community's Seventh Framework Programme (FP7 2007-2013) under grant agreement no. 238366. The MODIS data were obtained through the online Data Pool at the NASA Land Processes Distributed Active Archive Centre (LP DAAC), USGS/Earth Resources Observation and Science (EROS) Centre, Sioux Falls, South Dakota (https://lpdaac.usgs.gov/get_data). The meteorological data were provided by the Spanish National Weather Agency (AEMET). The authors thank Antonio Del Campo Garcia and Maria Gonzalez Sanchis at the Universitat Politecnica de Valencia for their support and valuable comments.Pasquato, M.; Medici, C.; Friend, A.; Francés, F. (2015). Comparing two approaches for parsimonious vegetation modelling in semiarid regions using satellite data. Ecohydrology. 8(6):1024-1036. https://doi.org/10.1002/eco.1559S102410368

The evoked compound nerve action potential is shaped by the electrical pulse-width

Introduction: Despite its central role in medicine electrical stimulation (ES) is still limited by its selectivity. Different reports did assess effects of different waveforms, intensities, and frequency on the activation threshold of nerve fibres with different diameters. We aimed to extend this knowledge by investigating the effect of short monophasic rectangular pulses (1, 2, 5, 10, 50, 100 and 200 μs) on the recruitment order. Methods:The sciatic nerve of rats was stimulated, and the evoked compound nerve action potential (CNAP) measured at two sites on the tibialis nerve, using epineural electrodes. Changes in delay, amplitude, and the shape of the CNAP were analyzed. Results:The amplitude and delay of the CNAP were significantly affected by the pulse-width (PW). The delay and duration of the compound nerve action potential increased with longer PW, while the amplitude decreased. Discussion:Found changes are likely caused by changes in the time point of excitation of individual neuron fibres, depending on electrical field strength and exposure time. This might be of particular interest when selecting PWs for design and validation of stimulation patterns and analysis of experimental and clinical observations

The complete mitochondrial genome of the foodborne parasitic pathogen Cyclospora cayetanensis

Cyclospora cayetanensis is a human-specific coccidian parasite responsible for several food and water-related outbreaks around the world, including the most recent ones involving over 900 persons in 2013 and 2014 outbreaks in the USA. Multicopy organellar DNA such as mitochondrion genomes have been particularly informative for detection and genetic traceback analysis in other parasites. We sequenced the C. cayetanensis genomic DNA obtained from stool samples from patients infected with Cyclospora in Nepal using the Illumina MiSeq platform. By bioinformatically filtering out the metagenomic reads of non-coccidian origin sequences and concentrating the reads by targeted alignment, we were able to obtain contigs containing Eimeria-like mitochondrial, apicoplastic and some chromosomal genomic fragments. A mitochondrial genomic sequence was assembled and confirmed by cloning and sequencing targeted PCR products amplified from Cyclospora DNA using primers based on our draft assembly sequence. The results show that the C. cayetanensis mitochondrion genome is 6274 bp in length, with 33% GC content, and likely exists in concatemeric arrays as in Eimeria mitochondrial genomes. Phylogenetic analysis of the C. cayetanensis mitochondrial genome places this organism in a tight cluster with Eimeria species. The mitochondrial genome of C. cayetanensis contains three protein coding genes, cytochrome (cytb), cytochrome C oxidase subunit 1 (cox1), and cytochrome C oxidase subunit 3 (cox3), in addition to 14 large subunit (LSU) and nine small subunit (SSU) fragmented rRNA genes

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice

Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process that is facilitated by the neuronal specific K+/Cl− co-transporter KCC2. Its activity is also a determinant of the anticonvulsant efficacy of the canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 activity is implicated in the pathophysiology of status epilepticus (SE), a medical emergency that rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small molecules that directly bind to and activate KCC2, which leads to reduced neuronal Cl− accumulation and excitability. KCC2 activation does not induce any overt effects on behavior but prevents the development of and terminates ongoing BDZ-RSE. In addition, KCC2 activation reduces neuronal cell death following BDZ-RSE. Collectively, these findings demonstrate that KCC2 activation is a promising strategy to terminate BDZ-resistant seizures and limit the associated neuronal injury

A case of panuveitis with hypopyon due to presumed ocular leishmaniasis in a HIV patient.

BACKGROUND: Post-kala-azar dermal leishmaniasis is a well-known immunologic cutaneous reaction. There are few case reports of ocular leishmaniasis. It is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. Ocular leishmaniasis panuveitis can present with severe inflammation in patients with highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome. FINDINGS: A case of a 40-year-old man, human immunodeficiency virus (HIV) positive on HAART, with a presumed diagnosis of ocular leishmaniasis, is presented. He had a past history of visceral leishmaniasis and was referred to the uveitis service with rapidly worsening panuveitis and counting fingers vision in both eyes. On empirical anti-leishmania therapy and systemic steroids, the visual acuity of the left eye improved to 6/9 but remained poor in the right eye. Based on the medical history, improvement with therapy and the exclusion of other common infections, a presumed diagnosis of ocular leishmaniasis-related panuveitis was made. CONCLUSIONS: A major immune reaction against lingering parasites may play a key role in the pathogenesis of this sight-threatening and rapidly progressive condition. Both the infection and the immune reaction should be treated

Understanding voltage decay in lithium-excess layered cathode materials through oxygen-centred structural arrangement

Lithium-excess 3d-transition-metal layered oxides (Li1+xNiyCozMn1-x-y-zO2, &gt; 250 mAh g(-1)) suffer from severe voltage decay upon cycling, which decreases energy density and hinders further research and development. Nevertheless, the lack of understanding on chemical and structural uniqueness of the material prevents the interpretation of internal degradation chemistry. Here, we discover a fundamental reason of the voltage decay phenomenon by comparing ordered and cation-disordered materials with a combination of X-ray absorption spectroscopy and transmission electron microscopy studies. The cation arrangement determines the transition metal-oxygen covalency and structural reversibility related to voltage decay. The identification of structural arrangement with de-lithiated oxygen-centred octahedron and interactions between octahedrons affecting the oxygen stability and transition metal mobility of layered oxide provides the insight into the degradation chemistry of cathode materials and a way to develop high-energy density electrodes

A Visual Pathway Links Brain Structures Active during Magnetic Compass Orientation in Migratory Birds

The magnetic compass of migratory birds has been suggested to be light-dependent. Retinal cryptochrome-expressing neurons and a forebrain region, “Cluster N”, show high neuronal activity when night-migratory songbirds perform magnetic compass orientation. By combining neuronal tracing with behavioral experiments leading to sensory-driven gene expression of the neuronal activity marker ZENK during magnetic compass orientation, we demonstrate a functional neuronal connection between the retinal neurons and Cluster N via the visual thalamus. Thus, the two areas of the central nervous system being most active during magnetic compass orientation are part of an ascending visual processing stream, the thalamofugal pathway. Furthermore, Cluster N seems to be a specialized part of the visual wulst. These findings strongly support the hypothesis that migratory birds use their visual system to perceive the reference compass direction of the geomagnetic field and that migratory birds “see” the reference compass direction provided by the geomagnetic field

Cyborg Activism: Exploring the reconfigurations of democratic subjectivity in Anonymous

This article develops the concept of cyborg activism as novel configuration of democratic subjectivity in the Information Age by exploring the online collectivity Anonymous as a prototype. By fusing elements of human/machine and organic/digital the cyborg disrupts modern logics of binary thinking. Cyborg activism emerges as the reconfiguration of equality/hierarchy, reason/emotion, and nihilism/idealism. Anonymous demonstrates how through the use of contingent and ephemeral digital personae hierarchies in cyborg activism prove more volatile than in face-to-face settings. Emotions appear as an essential part of a politics of passion, which enables pursuing laughter and joy, expressing anger, and experiencing empowerment as part of a reasoned, strategic politics. Anonymous’ political content reconfigures nihilist sentiments, frustration, and political disenchantment on the one hand with idealist world views on the other. This enables the cohabitation and partial integration of a great diversity of political claims rooted in various ideologies