Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts.

ObjectiveTo compare faecal microbial composition in patients with systemic sclerosis (SSc) from 2 independent cohorts with controls and to determine whether certain genera are associated with SSc-gastrointestinal tract (GIT) symptoms.DesignAdult patients with SSc from the University of California, Los Angeles (UCLA) and Oslo University Hospital (OUH) and healthy controls participated in this study (1:1:1). All participants provided stool specimens for 16S rRNA sequencing. Linear discriminant analysis effect size demonstrated genera with differential expression in SSc. Differential expression analysis for sequence count data identified specific genera associated with GIT symptoms as assessed by the GIT 2.0 questionnaire.ResultsThe UCLA-SSc and OUH-SSc cohorts were similar in age (52.1 and 60.5 years, respectively), disease duration (median (IQR): 6.6 (2.5-16.4) and 7.0 (1.0-19.2) years, respectively), gender distribution (88% and 71%, respectively), and GIT symptoms (mean (SD) total GIT 2.0 scores of 0.7 (0.6) and 0.6 (0.5), respectively). Principal coordinate analysis illustrated significant microbial community differences between SSc and controls (UCLA: p=0.001; OUH: p=0.002). Patients with SSc had significantly lower levels of commensal genera deemed to protect against inflammation, such as Bacteroides (UCLA and OUH), Faecalibacterium (UCLA), Clostridium (OUH); and significantly higher levels of pathobiont genera, such as Fusobacterium (UCLA), compared with controls. Increased abundance of Clostridium was associated with less severe GIT symptoms in both cohorts.ConclusionsThe present analysis detected specific aberrations in the lower GIT microbiota of patients with SSc from 2 geographically and ethnically distinct cohorts. These findings suggest that GIT dysbiosis may be a pathological feature of the SSc disease state

Direct Observation of Plasmon Band Formation and Delocalization in Quasi-Infinite Nanoparticle Chains

Chains of metallic nanoparticles sustain strongly confined surface plasmons with relatively low dielectric losses. To exploit these properties in applications,such as waveguides, the fabrication of long chains of low disorder and a thorough understanding of the plasmon-mode properties, such as dispersion relations, are indispensable. Here, we use a wrinkled template for directed self-assembly to assemble chains of gold nanoparticles. With this up-scalable method, chain lengths from two particles (140 nm) to 20 particles (1500 nm) and beyond can be fabricated. Electron energy-loss spectroscopy supported by boundary element simulations, finite-difference time-domain, and a simplified dipole coupling model reveal the evolution of a band of plasmonic waveguide modes from degenerated single-particle modes in detail. In striking difference from plasmonic rod-like structures, the plasmon band is confined in excitation energy, which allows light manipulations below the diffraction limit. The non-degenerated surface plasmon modes show suppressed radiative losses for efficient energy propagation over a distance of 1500 nm

Diversity and Paleodemography of the Addax (<i>Addax nasomaculatus</i>), a Saharan Antelope on the Verge of Extinction.

Since the 19th century, the addax (Addax nasomaculatus) has lost approximately 99% of its former range. Along with its close relatives, the blue antelope (Hippotragus leucophaeus) and the scimitar-horned oryx (Oryx dammah), the addax may be the third large African mammal species to go extinct in the wild in recent times. Despite this, the evolutionary history of this critically endangered species remains virtually unknown. To gain insight into the population history of the addax, we used hybridization capture to generate ten complete mitochondrial genomes from historical samples and assembled a nuclear genome. We found that both mitochondrial and nuclear diversity are low compared to other African bovids. Analysis of mitochondrial genomes revealed a most recent common ancestor ~32 kya (95% CI 11-58 kya) and weak phylogeographic structure, indicating that the addax likely existed as a highly mobile, panmictic population across its Sahelo-Saharan range in the past. PSMC analysis revealed a continuous decline in effective population size since ~2 Ma, with short intermediate increases at ~500 and ~44 kya. Our results suggest that the addax went through a major bottleneck in the Late Pleistocene, remaining at low population size prior to the human disturbances of the last few centuries

The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study

Abstract: Background: Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA, and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study, we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun metagenomic sequence data were also used to identify protein-encoding genes within the SEED database, and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results: The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and inactive GPA patients and household controls (P = 0.0168 and P = 0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long-term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion: Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species

Rehabilitation of Upper Extremity Nerve Injuries Using Surface EMG Biofeedback: Protocols for Clinical Application

Motor recovery following nerve transfer surgery depends on the successful re-innervation of the new target muscle by regenerating axons. Cortical plasticity and motor relearning also play a major role during functional recovery. Successful neuromuscular rehabilitation requires detailed afferent feedback. Surface electromyographic (sEMG) biofeedback has been widely used in the rehabilitation of stroke, however, has not been described for the rehabilitation of peripheral nerve injuries. The aim of this paper was to present structured rehabilitation protocols in two different patient groups with upper extremity nerve injuries using sEMG biofeedback. The principles of sEMG biofeedback were explained and its application in a rehabilitation setting was described. Patient group 1 included nerve injury patients who received nerve transfers to restore biological upper limb function (n = 5) while group 2 comprised patients where biological reconstruction was deemed impossible and hand function was restored by prosthetic hand replacement, a concept today known as bionic reconstruction (n = 6). The rehabilitation protocol for group 1 included guided sEMG training to facilitate initial movements, to increase awareness of the new target muscle, and later, to facilitate separation of muscular activities. In patient group 2 sEMG biofeedback helped identify EMG activity in biologically “functionless” limbs and improved separation of EMG signals upon training. Later, these sEMG signals translated into prosthetic function. Feasibility of the rehabilitation protocols for the two different patient populations was illustrated. Functional outcome measures were assessed with standardized upper extremity outcome measures [British Medical Research Council (BMRC) scale for group 1 and Action Research Arm Test (ARAT) for group 2] showing significant improvements in motor function after sEMG training. Before actual movements were possible, sEMG biofeedback could be used. Patients reported that this visualization of muscle activity helped them to stay motivated during rehabilitation and facilitated their understanding of the re-innervation process. sEMG biofeedback may help in the cognitively demanding process of establishing new motor patterns. After standard nerve transfers individually tailored sEMG biofeedback can facilitate early sensorimotor re-education by providing visual cues at a stage when muscle activation cannot be detected otherwise

Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

Objective To assess the frequency of venous thromboembolism (VTE) events in the Rituximab in Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis (RAVE) trial and identify novel potential risk factors. Methods VTE events in 197 patients enrolled in the RAVE trial were analyzed. Baseline demographic and clinical characteristics were recorded, and univariate and multivariate analyses were performed to identify factors associated with VTE in ANCA-associated vasculitis (AAV). Results VTE occurred in 16 patients (8.1%) with an overall average time to event of 1.5 months (range 1.0-2.75). In univariate analyses with calculation of hazard ratios (HRs) and 95% confidence intervals (95% CIs), heart involvement (HR 17.408 [95% CI 2.247-134.842]; P = 0.006), positive proteinase 3 (PR3)-ANCA (HR 7.731 [95% CI 1.021-58.545]; P = 0.048), pulmonary hemorrhage (HR 3.889 [95% CI 1.448-10.448]; P = 0.008), and the presence of red blood cell casts (HR 15.617 [95% CI 3.491-69.854]; P <0.001) were associated with the onset of VTE. In multivariate models adjusted for age and sex, the significant associations between VTE events and heart involvement (HR 21.836 [95% CI 2.566-185.805]; P = 0.005), PR3-ANCA (HR 9.12 [95% CI 1.158-71.839]; P = 0.036), pulmonary hemorrhage (HR 3.91 [95% CI 1.453-10.522]; P = 0.007), and urinary red blood cell casts (HR 16.455 [95% CI 3.607-75.075]; P <0.001) remained. Conclusion Patients diagnosed as having AAV with pulmonary hemorrhage, positive PR3-ANCA, heart involvement, and the presence of red blood cell casts are at an increased risk to develop VTE. Further studies are needed to confirm and expand these findings and to explore the mechanisms of hypercoagulability in these patients with the aim of informing potential targets for therapeutic intervention

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia

SIRF: Synergistic Image Reconstruction Framework

The combination of positron emission tomography (PET) with magnetic resonance (MR) imaging opens the way to more accurate diagnosis and improved patient management. At present, the data acquired by PET-MR scanners are essentially processed separately, but the opportunity to improve accuracy of the tomographic reconstruction via synergy of the two imaging techniques is an active area of research. In this paper, we present Release 2.1.0 of the CCP-PETMR Synergistic Image Reconstruction Framework (SIRF) software suite, providing an open-source software platform for efficient implementation and validation of novel reconstruction algorithms. SIRF provides user-friendly Python and MATLAB interfaces built on top of C++ libraries. SIRF uses advanced PET and MR reconstruction software packages and tools. Currently, for PET this is Software for Tomographic Image Reconstruction (STIR); for MR, Gadgetron and ISMRMRD; and for image registration tools, NiftyReg. The software aims to be capable of reconstructing images from acquired scanner data, whilst being simple enough to be used for educational purposes

SIRF: Synergistic Image Reconstruction Framework

The combination of positron emission tomography (PET) with magnetic resonance (MR) imaging opens the way to more accurate diagnosis and improved patient management. At present, the data acquired by PET-MR scanners are essentially processed separately, but the opportunity to improve accuracy of the tomographic reconstruction via synergy of the two imaging techniques is an active area of research. In this paper, we present Release 2.1.0 of the CCP-PETMR Synergistic Image Reconstruction Framework (SIRF) software suite, providing an open-source software platform for efficient implementation and validation of novel reconstruction algorithms. SIRF provides user-friendly Python and MATLAB interfaces built on top of C++ libraries. SIRF uses advanced PET and MR reconstruction software packages and tools. Currently, for PET this is Software for Tomographic Image Reconstruction (STIR); for MR, Gadgetron and ISMRMRD; and for image registration tools, NiftyReg. The software aims to be capable of reconstructing images from acquired scanner data, whilst being simple enough to be used for educational purposes. The most recent version of the software can be downloaded from http://www.ccppetmr.ac.uk/downloads and https://github.com/CCPPETMR/. Program summary: Program Title: Synergistic Image Reconstruction Framework (SIRF) Program Files DOI: http://dx.doi.org/10.17632/s45f5jh55j.1 Licensing provisions: GPLv3 and Apache-2.0 Programming languages: C++, C, Python, MATLAB Nature of problem: In current practice, data acquired by PET-MR scanners are processed separately. Methods for improving the accuracy of the tomographic reconstruction using the synergy of the two imaging techniques are actively being investigated by the PET-MR research and development community, however, practical application is heavily reliant on software. Open-source software available to the PET-MR community – such as the PET package (STIR) (Thielemans et al., 2012) and the MR package Gadgetron (Hansen and Sørensen, 2013) – provide a basis for new synergistic PET-MR software. However, these two software packages are independent and have very different software architectures. They are mostly written in C++ but many researchers in the PET-MR community are more familiar with script-style languages, such as Python and MATLAB, which enable rapid prototyping of novel reconstruction algorithms. In the current situation it is difficult for researchers to exploit any synergy between PET and MR data. Furthermore, techniques from one field cannot easily be applied in the other. Solution method: In SIRF, the bulk of computation is performed by available advanced open-source reconstruction and registration software (currently STIR, Gadgetron and NiftyReg) that can use multithreading and GPUs. The SIRF C++ code provides a thin layer on top of these existing libraries. The SIRF layer has unified data-containers and access mechanisms. This C++ layer provides the basis for a simple and intuitive Python and MATLAB interface, enabling users to quickly develop and test their reconstruction algorithms using these scripting languages only. At the same time, advanced users proficient in C++ can directly utilise wider SIRF functionality via the SIRF C++ libraries that we provide