Structural Characterization of Covalently Stabilized Human Cystatin C Oligomers

Human cystatin C (HCC), a cysteine-protease inhibitor, exists as a folded monomer under physiological conditions but has the ability to self-assemble via domain swapping into multimeric states, including oligomers with a doughnut-like structure. The structure of the monomeric HCC has been solved by X-ray crystallography, and a covalently linked version of HCC (stab-1 HCC) is able to form stable oligomeric species containing 10−12 monomeric subunits. We have performed molecular modeling, and in conjunction with experimental parameters obtained from atomic force microscopy (AFM), transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) measurements, we observe that the structures are essentially flat, with a height of about 2 nm, and the distance between the outer edge of the ring and the edge of the central cavity is ~5.1 nm. These dimensions correspond to the height and diameter of one stab-1 HCC subunit and we present a dodecamer model for stabilized cystatin C oligomers using molecular dynamics simulations and experimentally measured parameters. Given that oligomeric species in protein aggregation reactions are often transient and very highly heterogeneous, the structural information presented here on these isolated stab-1 HCC oligomers may be useful to further explore the physiological relevance of different structural species of cystatin C in relation to protein misfolding disease

Confusion after spine injury: cerebral fat embolism after traumatic rupture of a Tarlov cyst: Case report

<p>Abstract</p> <p>Background</p> <p>Acute low back pain is a very common symptom and reason for many medical consultations. In some unusual circumstances it could be linked to a rare aetiology.</p> <p>Case presentation</p> <p>We report a 70-year-old man with an 8-month history of left posterior thigh and leg pain who had sudden confusion after a fall from standing. It was due to cerebral fat embolism suspected by computed tomography scan, later confirmed by brain magnetic resonance imaging (MRI). A spinal MRI scan was then performed and revealed a sacral fracture which drained into an unknown perineurial cyst (Tarlov cyst). Under medical observation the patient fully recovered within three weeks.</p> <p>Conclusions</p> <p>Sacral perineurial cysts are rare, however they remain a potential cause of lumbosacral radiculopathy.</p

The role of neuronavigation in intracranial endoscopic procedures

In occlusive hydrocephalus, cysts and some ventricular tumours, neuroendoscopy has replaced shunt operations and microsurgery. There is an ongoing discussion if neuronavigation should routinely accompany neuroendoscopy or if its use should be limited to selected cases. In this prospective clinical series, the role of neuronavigation during intracranial endoscopic procedures was investigated. In 126 consecutive endoscopic procedures (endoscopic third ventriculostomy, ETV, n = 65; tumour biopsy/resection, n = 36; non-tumourous cyst fenestration, n = 23; abscess aspiration and hematoma removal, n = 1 each), performed in 121 patients, neuronavigation was made available. After operation and videotape review, the surgeon had to categorize the role of neuronavigation: not beneficial; beneficial, but not essential; essential. Overall, neuronavigation was of value in more than 50% of the operations, but its value depended on the type of the procedure. Neuronavigation was beneficial, but not essential in 16 ETVs (24.6%), 19 tumour biopsies/resections (52.7%) and 14 cyst fenestrations (60.9%). Neuronavigation was essential in 1 ETV (2%), 11 tumour biopsies/resections (30.6%) and 8 cyst fenestrations (34.8%). Neuronavigation was not needed/not used in 48 ETVs (73.9%), 6 endoscopic tumour operations (16.7%) and 1 cyst fenestration (4.3%). For ETV, neuronavigation mostly is not required. In the majority of the remaining endoscopic procedures, however, neuronavigation is at least beneficial. This finding suggests integrating neuronavigation into the operative routine in endoscopic tumour operations and cyst fenestrations

D4.2 Final report on trade-off investigations

Research activities in METIS WP4 include several as pects related to the network-level of future wireless communication networks. Thereby, a large variety of scenarios is considered and solutions are proposed to serve the needs envis ioned for the year 2020 and beyond. This document provides vital findings about several trade-offs that need to be leveraged when designing future network-level solutions. In more detail, it elaborates on the following trade- offs: • Complexity vs. Performance improvement • Centralized vs. Decentralized • Long time-scale vs. Short time-scale • Information Interflow vs. Throughput/Mobility enha ncement • Energy Efficiency vs. Network Coverage and Capacity Outlining the advantages and disadvantages in each trade-off, this document serves as a guideline for the application of different network-level solutions in different situations and therefore greatly assists in the design of future communication network architectures.Aydin, O.; Ren, Z.; Bostov, M.; Lakshmana, TR.; Sui, Y.; Svensson, T.; Sun, W.... (2014). D4.2 Final report on trade-off investigations. http://hdl.handle.net/10251/7676

D4.3 Final Report on Network-Level Solutions

Research activities in METIS reported in this document focus on proposing solutions to the network-level challenges of future wireless communication networks. Thereby, a large variety of scenarios is considered and a set of technical concepts is proposed to serve the needs envisioned for the 2020 and beyond. This document provides the final findings on several network-level aspects and groups of solutions that are considered essential for designing future 5G solutions. Specifically, it elaborates on: -Interference management and resource allocation schemes -Mobility management and robustness enhancements -Context aware approaches -D2D and V2X mechanisms -Technology components focused on clustering -Dynamic reconfiguration enablers These novel network-level technology concepts are evaluated against requirements defined by METIS for future 5G systems. Moreover, functional enablers which can support the solutions mentioned aboveare proposed. We find that the network level solutions and technology components developed during the course of METIS complement the lower layer technology components and thereby effectively contribute to meeting 5G requirements and targets.Aydin, O.; Valentin, S.; Ren, Z.; Botsov, M.; Lakshmana, TR.; Sui, Y.; Sun, W.... (2015). D4.3 Final Report on Network-Level Solutions. http://hdl.handle.net/10251/7675

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes