Identification of the byproducts of the oxygen evolution reaction on rutile-type oxides under dynamic conditions

Peer reviewedPostprin

Emergency intraosseous access in a helicopter emergency medical service: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Intraosseous access (IO) is a method for providing vascular access in out-of-hospital resuscitation of critically ill and injured patients when traditional intravenous access is difficult or impossible. Different intraosseous techniques have been used by our Helicopter Emergency Medical Services (HEMS) since 2003. Few articles document IO use by HEMS physicians. The aim of this study was to evaluate the use of intraosseous access in pre-hospital emergency situations handled by our HEMS.</p> <p>Methods</p> <p>We reviewed all medical records from the period May 2003 to April 2010, and compared three different techniques: Bone Injection Gun (B.I.G^®- Waismed), manual bone marrow aspiration needle (Inter V - Medical Device Technologies) and EZ-IO^®(Vidacare), used on both adults and paediatric patients.</p> <p>Results</p> <p>During this seven-year period, 78 insertion attempts were made on 70 patients. Overall success rates were 50% using the manual needle, 55% using the Bone Injection Gun, and 96% using the EZ-IO^®. Rates of success on first attempt were significantly higher using the EZ-IO^®compared to the manual needle/Bone Injection Gun (p < 0.01/p < 0.001). Fifteen failures were due to insertion-related problems (19.2%), with four technical problems (5.1%) and three extravasations (3.8%) being the most frequent causes. Intraosseous access was primarily used in connection with 53 patients in cardiac arrest (75.7%), including traumatic arrest, drowning and SIDS. Other diagnoses were seven patients with multi-trauma (10.0%), five with seizures/epilepsy (7.1%), three with respiratory failure (4.3%) and two others (2.9%). Nearly one third of all insertions (n = 22) were made in patients younger than two years. No cases of osteomyelitis or other serious complications were documented on the follow-up.</p> <p>Conclusions</p> <p>Newer intraosseous techniques may enable faster and more reliable vascular access, and this can lower the threshold for intraosseous access on both adult and paediatric patients in critical situations. We believe that all emergency services that handle critically ill or injured paediatric and adult patients should be familiar with intraosseous techniques.</p

Long Term Exposure to Malaria and Development: Disaggregate Evidence for Contemporaneous Africa

Malaria afflicts mankind since thousands of years and still imposes serious health impediments and considerable mortality on the affected populations. Empirical investigations of the role of malaria for economic development at the country level deliver mixed findings, however. We study the role of long-term malaria exposure on development today using disaggregate within-country variation for the whole of Africa with 1 × 1 degree cells as units of observation. Local development is measured by light density at night. Based on insights from epidemiology, which documents that genetic and acquired immunities reduce Malaria risk for adults in holoendemic areas, the effect is hypothesized to be nonlinear, with a peak for intermediate rather than high exposure to the pathogen. The empirical findings support this hypothesis. The results also suggest the existence of a significant moderating effect of genetic immunities measured by the prevalence of the sickle cell trait in the population

Functional megalin is expressed in renal cysts in a mouse model of adult polycystic kidney disease

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of cysts and a decline of renal function. The clinical feasibility of the number of potential disease-modifying drugs is limited by systemic adverse effects. We hypothesize that megalin, a multiligand endocytic receptor expressed in the proximal tubule, may be used to facilitate drug uptake into cysts, thereby allowing for greater efficacy and fewer side effects. METHODS: The cyst expression of various tubular markers, including megalin and aquaporin 2 (AQP2), was analysed by immunohistochemistry (IHC) of kidney sections from the ADPKD mouse model (PKD1(RC/RC)) at different post-natal ages. The endocytic function of megalin in cysts was examined by IHC of kidney tissue from mice injected with the megalin ligand aprotinin. RESULTS: Cyst lining epithelial cells expressing megalin were observed at all ages; however, the proportion decreased with age. Concomitantly, an increasing proportion of cysts revealed expression of AQP2, partial expression of megalin and/or AQP2 or no expression of the examined markers. Endocytic uptake of aprotinin was evident in megalin-positive cysts, but only in those that remained connected to the renal tubular system. CONCLUSIONS: Megalin-expressing cysts were observed at all ages, but the proportion decreased with age, possibly due to a switch in tubular origin, a merging of cysts of different tubular origin and/or a change in the expression pattern of cyst lining cells. Megalin expressed in cysts was functional, suggesting that megalin-mediated endocytosis is a potential mechanism for drug targeting in ADPKD if initiated early in the disease

Digestibility in selected rainbow trout families and modelling of growth from the specific intake of digestible protein

The experiments aimed to clarify variations in digestibility of dietary nutrients in rainbow trout. Furthermore, the objective was to study how differences in digestibility might be related to growth and feed utilisation at various growth rates. When comparing the results from the experiments it appeared that particularly protein digestibility was closely related to specific growth rate and feed conversion ratio at high growth rates. As a tool to visualise the relationship between protein digestibility and growth of rainbow trout a growth model was developed based on the specific intake of digestible protein, and general assumptions on protein content and protein retention efficiency in rainbow trout. The model indicated that increased protein digestibility only partly explained growth increase and that additional factors were important for growth increment

Amyloid fibril length distribution quantified by atomic force microscopy single-particle image analysis

Amyloid fibrils are proteinaceous nano-scale linear aggregates. They are of key interest not only because of their association with numerous disorders, such as type II diabetes mellitus, Alzheimer's and Parkinson's diseases, but also because of their potential to become engineered high-performance nano-materials. Methods to characterise the length distribution of nano-scale linear aggregates such as amyloid fibrils are of paramount importance both in understanding the biological impact of these aggregates and in controlling their mechanical properties as potential nano-materials. Here, we present a new quantitative approach to the determination of the length distribution of amyloid fibrils using tapping-mode atomic force microscopy. The method described employs single-particle image analysis corrected for the length-dependent bias that is a common problem associated with surface-based imaging techniques. Applying this method, we provide a detailed characterisation of the length distribution of samples containing long-straight fibrils formed in vitro from β2-microglobulin. The results suggest that the Weibull distribution is a suitable model in describing fibril length distributions, and reveal that fibril fragmentation is an important process even under unagitated conditions. These results demonstrate the significance of quantitative length distribution measurements in providing important new information regarding amyloid assembly

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods

Multicomponent analysis of T1 relaxation in bovine articular cartilage at low magnetic fields

European Union’s Horizon 2020 Research and Innovation Programme; Grant/Award number 668119 (project “IDentIFY”).Peer reviewedPublisher PD

Discrete molecular dynamics simulations of peptide aggregation

We study the aggregation of peptides using the discrete molecular dynamics simulations. At temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multi-layer parallel beta-sheet structure. This structure has an inter-strand distance of 0.48 nm and an inter-sheet distance of 1.0 nm, which agree with experimental observations. In this model, the hydrogen bond interactions give rise to the inter-strand spacing in beta-sheets, while the Go interactions among side chains make beta-strands parallel to each other and allow beta-sheets to pack into layers. The aggregates also contain free edges which may allow for further aggregation of model peptides to form elongated fibrils.Comment: 15 pages, 8 figure

Tight regulation of unstructured proteins: from transcript synthesis to protein degradation

Altered abundance of several intrinsically unstructured proteins ( IUPs) has been associated with perturbed cellular signaling that may lead to pathological conditions such as cancer. Therefore, it is important to understand how cells precisely regulate the availability of IUPs. We observed that regulation of transcript clearance, proteolytic degradation, and translational rate contribute to controlling the abundance of IUPs, some of which are present in low amounts and for short periods of time. Abundant phosphorylation and low stochasticity in transcription and translation indicate that the availability of IUPs can be finely tuned. Fidelity in signaling may require that most IUPs be available in appropriate amounts and not present longer than needed.Royal Society; MRC Special Training Fellowship; Medical Research Council [MC_U105161047, MC_U105185859, G0600158]info:eu-repo/semantics/publishedVersio