A rat model of stavudine-induced hyperalgesia

Stavudine, a nucleoside reverse transcriptase inhibitor (NRTI) used to treat infection by the human immunodeficiency virus (HIV), causes peripheral neuropathy and pain in HIV-positive patients. The mechanisms of this toxic neuropathy are poorly understood, partly because of a lack of animal models of the disease process. I investigated whether long-term daily oral administration of stavudine affects nociception in Sprague-Dawley rats, and whether changes in nociception are accompanied by a general deterioration in the rats’ conditions, as reflected in activity and appetite. Daily stavudine administration induced mechanical hyperalgesia in rats within three weeks without affecting appetite, growth or physical activity, and this hyperalgesia persisted throughout the six weeks of stavudine administration. I then investigated whether central changes underlie the hyperalgesia caused by stavudine in rats by examining inflammatory cytokine secretion and neuronal death in the spinal cord. Daily stavudine administration caused an increase in cytokine-induced neutrophil chemo-attractant (CINC)-1 concentration in the spinal cord after six weeks, but early development of stavudine-induced hyperalgesia did not depend on increases in spinal concentrations of CINC-1 and interleukin (IL)-6, nor on apoptosis or necrosis of spinal neurones. The neurotoxicity of stavudine is thought to derive from mitochondrial toxicity, which has been linked to increased plasma lactate concentration and decreased plasma adiponectin levels caused by lipodystrophy. Thus, I investigated whether a systemic inflammatory response or metabolic dysregulation accompanied stavudine-induced hypernociception by examining plasma adiponectin, lactate, CINC-1 and IL-6 concentrations in rats administered daily stavudine. Plasma adiponectin, lactate, CINC-1 and IL-6 concentrations were unchanged following three or six weeks of daily stavudine administration. Therefore, I have shown that stavudine-induced hyperalgesia is not dependent on spinal cord plasticity, nor on a systemic inflammatory response or extensive metabolic malfunction. Instead, the hyperalgesia I observed may be caused by the adverse effects of stavudine on peripheral neurone functioning. As stavudine administration to healthy rats had no adverse effects besides inducing hyperalgesia and causing a rise in CINC-1 concentration in the spinal cord after six weeks, my results indicate that many other side effects commonly associated with stavudine treatment in HIV-positive patients may arise through interaction with the underlying HIV infection

O processo de educação continuada na visão de enfermeiros de um hospital universitário

O objetivo deste estudo foi analisar a opinião dos enfermeiros sobre a educação continuada da equipe de enfermagem em um hospital universitário. Trata-se de pesquisa descritiva, exploratória, desenvolvida em um hospital universitário com a participação de cinquenta enfermeiros. A coleta deu-se por meio de um instrumento autoaplicável e os dados foram apresentados percentualmente. Os resultados evidenciaram que: os enfermeiros acreditam na educação continuada e a maioria desenvolve essa atividade anualmente; as estratégias de ensino-aprendizagem predominantes são exposição dialogada e problematização de casos; os programas englobam habilidades técnicas e comportamentais e a avaliação é feita por meio de auditoria. Foram sugeridas melhorias na estrutura física, recursos didáticos, planejamento e motivação para maior adesão da equipe. Uma cultura de compartilhamento entre a equipe de enfermagem e instituição seria significativa para o avanço do processo de educação continuada na prática de qualquer modelo assistencial e aquisição de competências profissional e pessoal

Language support for international students of STEM subjects: A course concept for teaching subject-specific learning and study strategies

Für die Zielgruppe der internationalen Studierenden in den MINT-Fächern an deutschen Hochschulen fehlen Curricula und Lehr-Lernmaterialien, die es erlauben, für diese Zielgruppe passgenaue Sprachkurse anzubieten, in denen sie auf die sprachlich-kommunikativen Herausforderungen im Fachstudium vorbereitet werden. Dieser Beitrag präsentiert ein methodisch-didaktisches Kurskonzept zur Fachsprachenvermittlung MINT, das seit 2014 im Bereich Deutsch als Fremdsprache im Zentrum für Fremdsprachenausbildung (DaF/ZFA) der Ruhr-Universität Bochum entwickelt wird. Dabei werden für die Entwicklung der Curricula und Lehr-Lernmaterialien wichtige methodisch-didaktische Aspekte fokussiert, wie die Vermittlung von Strategien, die Arbeit mit authentischen Quellen und die Digitalisierung von Lerninhalten.There is a lack of curricula and teaching materials that cater to the needs of international students studying STEM subjects at German universities, hindering the provision of effective language courses which adequately prepare students for the linguistic and communicative challenges they will encounter in their studies. This article presents a methodological-didactic course concept for teaching subject-specific language skills in STEM fields, which has been developed since 2014 in the field of German as a foreign language at the (DaF/ZFA) of Ruhr-University Bochum. The development of curricula and teaching materials focuses on important methodological-didactic aspects such as teaching strategies, working with authentic sources, and digitizing learning content

Thermally stable mesoporous tetragonal zirconia through surfactant-controlled synthesis and Si-stabilization

Thermally stable, highly mesoporous Si-stabilized ZrO₂ was prepared by sol–gel-synthesis. By utilizing the surfactant dodecylamine (DDA), large mesopores with a pore width of ∼9.4 nm are formed. Combined with an NH₃-treatment on the hydrogel, a high specific surface area of up to 225 m² g⁻¹ and pore volume up to 0.46 cm³ g⁻¹ are obtained after calcination at 973 K. The individual contributions of Si-addition, DDA surfactant and the NH₃-treatment on the resulting pore system were studied by inductively coupled plasma with optical emission spectrometry (ICP-OES), X-ray diffraction (XRD), N₂ sorption, and transmission electron microscopy (TEM). Electron tomography was applied to visualize and investigate the mesopore network in 3D space. While Si prevents the growth of ZrO₂ crystallites and stabilizes the t-ZrO₂ phase, DDA generates a homogeneous mesopore network within the zirconia. The NH₃-treatment unblocks inaccessible pores, thereby increasing specific surface area and pore volume while retaining the pore width distribution

Wind Power Persistence Characterized by Superstatistics

Mitigating climate change demands a transition towards renewable electricity generation, with wind power being a particularly promising technology. Long periods either of high or of low wind therefore essentially define the necessary amount of storage to balance the power system. While the general statistics of wind velocities have been studied extensively, persistence (waiting) time statistics of wind is far from well understood. Here, we investigate the statistics of both high- and low-wind persistence. We find heavy tails and explain them as a superposition of different wind conditions, requiring q-exponential distributions instead of exponential distributions. Persistent wind conditions are not necessarily caused by stationary atmospheric circulation patterns nor by recurring individual weather types but may emerge as a combination of multiple weather types and circulation patterns. This also leads to Fréchet instead of Gumbel extreme value statistics. Understanding wind persistence statistically and synoptically may help to ensure a reliable and economically feasible future energy system, which uses a high share of wind generation

Enterocolic lymphocytic phlebitis of the cecal pole and appendix vermiformis with increase of IgG4-positive plasma cells

Here we describe the clinicopathological course of a 20-year-old female patient with enterocolic lymphocytic phlebitis (ELP) of the appendix vermiformis and cecal pole with increase of IgG4-positive plasma cells. The patient presented with acute abdomen, suspicious of acute appendicitis. Diagnostic laparoscopy showed tumefaction of the cecal pole and appendix vermiformis. Histologic examination revealed mural thickening and a dense lymphoplasmocytic, partly obliterative infiltrate of the veins with sparing of the arteries, diagnostic of ELP. In addition, we found an elevated number of IgG4-positive plasma cells blended in with the lymphocytes. The IgG4-to-IgG ratio accounted for >40%. This case meets the histopathological criteria requested for IgG4-related disease (IgG4-RD) and thus opens the possibility that ELP might be part of the IgG4-RD spectrum

Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models

HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection

Применение дуговой сварки при строительстве нефтяных резервуаров в условиях Крайнего Севера

Целью выпускной квалификационной работы является разработка технологического процесса сборки и дуговой сварки центральной части днища нефтяного резервуара объемом 5000м? в условиях Крайнего Севера. Путем сравнения способов сварки в специфических климатических условиях была предложена механизированная сварка самозащитной порошковой проволокой.The aim of the bachelor's work is the development of the technological process of assembling and arc welding of the central part of the bottom of the oil reservoir with the volume of 5000 m? in the conditions of the Far North. By comparing the welding methods in specific climatic conditions, a mechanized self-shielded flux cored wire was proposed