Developments in the synovial biology field 2006

Synovial pathophysiology is a complex and synergistic interplay of different cell populations with tissue components, mediated by a variety of signaling mechanisms. All of these mechanisms drive the affected joint into inflammation and drive the subsequent destruction of cartilage and bone. Each cell type contributes significantly to the initiation and perpetuation of this deleterious concert, especially in rheumatoid arthritis. Rheumatoid arthritis synovial fibroblasts and macrophages, both cell types with pivotal roles in inflammation and destruction, but also T cells and B cells are crucial for complex network in the inflamed synovium. An even more complex cellular crosstalk between these key players maintains a process of chronic inflammation. As outlined in the present review, in the past year substantial progress has been made to elucidate further details of the rich pathophysiology of rheumatoid arthritis, which may also facilitate the identification of novel targets for future therapeutic strategies

Metadaten für Open Educational Resources (OER). Eine Handreichung für die öffentliche Hand, erstellt von der Technischen Informationsbibliothek (TIB)

"Im Zuge der weiteren Verbreitung der Social Media und der internetbasierten Lehre, gewinnen eLearning Inhalte immer mehr an Bedeutung. In den Kontext von eLearning und internetbasierter Lehre gehören auch Open Educational Resources (OER). OER sind digitale Lern- und Lehrmaterialien, die frei für Lehrende und Studierende zugänglich sind und auch frei verbreitet werden dürfen. [...] Um OER auszutauschen, zu finden, zu beschaffen und sie auf einer breiten Basis zugänglich zu machen, insbesondere auch über Suchmaschinen und dadurch verwenden zu können, werden für die jeweiligen Materialien Metadaten benötigt. [...] Um die Frage nach dem Handlungs- und Forschungsbedarf zum Thema Metadaten für Open Educational Resources zu untersuchen, wird zunächst ein Überblick über die momentan bestehenden nationalen und internationalen Metadatenstandards für eLearning Objekte gegeben. [...] Hieraus ergeben sich Empfehlungen, welche Metadaten-Standards für die weitere Nutzung und Förderung geeignet sein könnten. Es werden außerdem die Möglichkeiten der Erstellung eines neuen Metadaten-Standards sowie eines gemeinsamen Portals für OER erörtert. Hierbei wird vor allem auf die zu erwartenden Probleme und die damit verbundenen Anforderungen eingegangen." (DIPF/Orig.

Clinically relevant advances in rheumatoid arthritis therapy

Owing to the success of biologics in the treatment of rheumatoid arthritis (RA), several novel drugs have been introduced in the therapeutic armamentarium, although not all of them have been approved in all countries worldwide. Among the drugs are tumour necrosis factor (TNF) inhibitors such as certolizumab pegol and golimumab (the latter of which was the first TNF blocker shown to be effective in patients who had been unsuccessfully treated with other TNF blockers and which can be applied only once a month), and the interleukin-6 receptor antagonist tocilizumab, which not only opens up a completely new field of anti-inflammatory modulation of RA pathophysiology, but also highlights the challenge of novel potential side effects. Moreover, aside from clinical studies showing efficacy in the inhibition of osteoclast activation by the anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody denosumab, an improved form of steroid application known as slow-release ‘tempus tablet’ for treatment of RA and several developments in the small-molecule area have been addressed by clinical trials

Thermal stability test of sugar alcohols as phase change materials for medium temperature energy storage application

Sugar alcohols are potential phase change materials candidates as they present high phase change enthalpy values, are non-toxic and low cost products. Three promising sugar-alcohols were selected: D-mannitol, myo-inositol and dulcitol under high melting enthalpy and temperature criterion. Thermal cycling tests were performed to study its cycling stability which can be determining when selecting the suitable phase change material. D-mannitol and dulcitol present poor thermal stability. Myo-inositol shows almost no decrease in thermal properties after 50 cycles for the heating process, however in the solidification part a decrease of 20 % of enthalpy and 11 % of temperature values is observed.The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement 296006

Practical Propagation of Trust in Risk Management Systems

Using risk management systems for large-scale asset management is not without risk itself. Systems that collect measurement from a geographically diverse area, across many organisations, contain many interacting components that can fail in many different ways. In this chapter these systems are discussed from a risk assessment point of view, using practical examples. It provides suggestions how trust can propagate between interacting components of risk management systems by making information needed for risk assessment information explicit

On the probabilistic description of a multipartite correlation scenario with arbitrary numbers of settings and outcomes per site

We consistently formalize the probabilistic description of multipartite joint measurements performed on systems of any nature. This allows us: (1) to specify in probabilistic terms the difference between nonsignaling, the Einstein- Podolsky-Rosen (EPR) locality and Bell's locality; (2) to introduce the notion of an LHV model for an S_{1}x...xS_{N}-setting N-partite correlation experiment, with outcomes of any spectral type, discrete or continuous, and to prove both general and specific "quantum" statements on an LHV simulation in an arbitrary multipartite case; (3) to classify LHV models for a multipartite quantum state, in particular, to show that any N-partite quantum state, pure or mixed, admits an Sx1x...x1 -setting LHV description; (4) to evaluate a threshold visibility for a noisy bipartite quantum state to admit an S_{1}xS_ {2}-setting LHV description under any generalized quantum measurements of two parties. In a sequel to this paper, we shall introduce a single general representation incorporating in a unique manner all Bell-type inequalities for either joint probabilities or correlation functions that have been introduced or will be introduced in the literature.Comment: 26 pages; added section Conclusions and some references for section

Metadaten für Open Educational Resources (OER) : eine Handreichung für die öffentliche Hand

[no abstract available

A phospho-deficient α3 glycine receptor mutation alters synaptic glycine and GABA release in mouse spinal dorsal horn neurons

Glycine receptors (GlyRs), together with GABA$_{A}$ receptors, mediate postsynaptic inhibition in most spinal cord and hindbrain neurons. In several CNS regions, GlyRs are also expressed in presynaptic terminals. Here, we analysed the effects of a phospho-deficient mutation (S346A) in GlyR α3 subunits on inhibitory synaptic transmission in superficial spinal dorsal horn neurons, where this subunit is abundantly expressed. Unexpectedly, we found that not only were the amplitudes of evoked glycinergic inhibitory postsynaptic currents (IPSCs) significantly larger in GlyRα3(S346A) mice than in mice expressing wild-type α3GlyRs (GlyRα3(WT) mice), but so were those of GABAergic IPSCs. Decreased frequencies of spontaneously occurring glycinergic and GABAergic miniature IPSCs (mIPSCs) with no accompanying change in mIPSC amplitudes suggested a change in presynaptic transmitter release. Paired-pulse experiments on glycinergic IPSCs revealed an increased paired-pulse ratio and a smaller coefficient of variation in GlyRα3(S346A) mice, which together indicate a reduction in transmitter release probability and an increase in the number of releasable vesicles. Paired-pulse ratios of GABAergic IPSCs recorded in the presence of strychnine were not different between genotypes, while the coefficient of variation was smaller in GlyRα3(S346A) mice, demonstrating that the decrease in release probability was readily reversible by GlyR blockade, while the difference in the size of the pool of releasable vesicles remained. Taken together, our results suggest that presynaptic α3 GlyRs regulate synaptic glycine and GABA release in superficial dorsal horn neurons, and that this effect is potentially regulated by their phosphorylation status. KEY POINTS: A serine-to-alanine point mutation was introduced into the glycine receptor α3 subunit of mice. This point mutation renders α3 glycine receptors resistant to protein kinase A mediated phosphorylation but has otherwise only small effects on receptor function. Patch-clamp recordings from neurons in mouse spinal cord slices revealed an unexpected increase in the amplitudes of both glycinergic and GABAergic evoked inhibitory postsynaptic currents (IPSCs). Miniature IPSCs, paired-pulse ratios and synaptic variation analyses indicate a change in synaptic glycine and GABA release. The results strongly suggest that α3 subunit-containing glycine receptors are expressed on presynaptic terminals of inhibitory dorsal horn neurons where they regulate transmitter release

Monitorización intersticial de glucosa en pacientes pediátricos con diabetes mellitus tipo I

Introducción: Un buen control metabólico de la diabetes mellitus tipo I se asocia con una disminución de las complicaciones a largo plazo. Actualmente, existen dispositivos que ayudan a tomar decisiones terapéuticas para mantener la glucemia en los valores objetivos. Objetivos: Valorar el impacto de los dispositivos en la mejoría del perfil glucémico de los pacientes, comparando la evolución previa a la colocación con los datos en el primer mes, a los 6 y 12 meses siguientes. Además, valorar el uso del dispositivo por parte del paciente o sus familiares. Material y métodos: Estudio observacional retrospectivo, desde septiembre de 2017 hasta noviembre de 2019. Mediante el acceso a los datos clínicos codificados de los pacientes que están en seguimiento por la consulta de Endocrinología Pediátrica del Hospital Universitario de Canarias y que disponen de monitores de glucosa intersticial de tipo intermitente o continuo. Resultados: Se observó una mejoría de la media de hemoglobina glicosilada a los 12 meses (7,17 %; DE 0,75) respecto a la previa a la colocación del sensor (7,428 %; DE 1,37). Se encontró, que los que partían de una hemoglobina glicosilada previa más elevada eran los que la seguían teniendo mayor a los 6 y 12 meses (p=0,000) y los que presentaban menor porcentaje de glucemia en rango objetivo al mes (p=0,000), a los 6 meses ( p<0.001) y a los 12 meses (p<0.001). Disminuyó el porcentaje en hipoglucemia en el grupo de monitor flash a pesar de no disponer alarmas, aunque el tiempo en hipoglucemia mostró un empeoramiento a los 6 meses con respecto al primer mes, que posteriormente mejoró. La variabilidad glucémica mejoró a los 12 meses, pero la media sigue siendo superior a las recomendaciones. Se observó un aumento progresivo del uso de los dispositivos, que se objetiva en la media del tiempo activo, en las descargas realizadas y en la introducción de datos. Conclusiones: Se observó una mejoría del perfil glucémico de los pacientes portadores de los dispositivos de monitorización y un notable aumento del uso de dicha tecnología.Background: Good metabolic control of type I diabetes mellitus is associated with a decrease in long-term complications. There are devices that help making therapeutic decisions to keep the blood glucose in the target range. Objective: To value the impact of the devices in the improvement of the glycemic profile of the patients, comparing the previous evolution to the sensor placement with the data of the 6 and 12 following months. In addition, the use of the device by the patient or by their relatives is also valued. Material and methods: This is a retrospective observational study, from September 2017 to November 2019, by accessing to the encoded clinical data of patients who are being followed by the Pediatric Endocrinology Service of the Hospital Universitario de Canarias and which have an intermittent or continuous type of interstitial glucose monitor. Results: An improvement of the mean glycosylated hemoglobin was observed at 12 months (7.17%; SD 0.75) compared to the glycosylated hemoglobin prior to the placement of the sensor (7.428%; SD 1.37). It was found that those who started with a higher previous glycosylated hemoglobin were those who continued to have it higher at 6 and 12 months (p = 0.000) and those who had a lower percentage of glycemia in the target range at the first month after placement, (p = 0.000), at 6 (p <0.001) and at 12 months (p <0.001). The percentage of hypoglycemia decreased in the flash monitor group despite of not having alarms, although the time in hypoglycemia showed a worsening at 6 months compared to the first month, which subsequently improved. Glycemic variability improved after 12 months, but the mean is still higher than the recommendations. A progressive increase in the use of the devices was observed, which is shown in the mean active time, the downloads and the introduction of data. Conclusions: An improvement in the glycemic profile of patients wearing monitoring devices and a notable increase in the use of this technology were observed