349 research outputs found

    Primäres zerebelläres T-Zell-Lymphom

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    Zusammenfassung: Primäre T-Zell-Lymphome des zentralen Nervensystems (ZNS) sind selten. Sie müssen differenzialdiagnostisch von reaktiven Läsionen unterschieden werden. Die Diagnosestellung sollte integrativ unter Verwendung von immunhistochemischen, molekulargenetischen und/oder zytogenetischen Methoden erfolgen. Wir beschreiben den Fall eines 50-jährigen Mannes, bei welchem ein primäres zerebelläres T-Zell-Lymphom diagnostiziert und eine klonale T-Zell-Rezeptorgen-Umlagerung nachgewiesen wurde. Nach 2Zyklen Chemotherapie entwickelte der Patient eine Pneumozystis-carinii-Pneumonie und verstarb 10Wochen nach Diagnosestellung. Die Autopsie ergab keinen Residualtumor im ZN

    Thermography imaging during static and controlled thermoregulation in complex regional pain syndrome type 1: diagnostic value and involvement of the central sympathetic system

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    BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS1) is a clinical diagnosis based on criteria describing symptoms of the disease. The main aim of the present study was to compare the sensitivity and specificity of calculation methods used to assess thermographic images (infrared imaging) obtained during temperature provocation. The secondary objective was to obtain information about the involvement of the sympathetic system in CRPS1. METHODS: We studied 12 patients in whom CRPS1 was diagnosed according to the criteria of Bruehl. High and low whole body cooling and warming induced and reduced sympathetic vasoconstrictor activity. The degree of vasoconstrictor activity in both hands was monitored using a videothermograph. The sensitivity and specificity of the calculation methods used to assess the thermographic images were calculated. RESULTS: The temperature difference between the hands in the CRPS patients increases significantly when the sympathetic system is provoked. At both the maximum and minimum vasoconstriction no significant differences were found in fingertip temperatures between both hands. CONCLUSION: The majority of CRPS1 patients do not show maximal obtainable temperature differences between the involved and contralateral extremity at room temperature (static measurement). During cold and warm temperature challenges this temperature difference increases significantly. As a result a higher sensitivity and specificity could be achieved in the diagnosis of CRPS1. These findings suggest that the sympathetic efferent system is involved in CRPS1

    Interactions between p300 and multiple NF-Y trimers govern cyclin B2 promoter function

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    The CCAAT box is one of the most common elements in eukaryotic promoters and is activated by NF-Y, a conserved trimeric transcription factor with histone-like subunits. Usually one CCAAT element is present in promoters at positions between -60 and -100, but an emerging class of promoters harbor multiple NF-Y sites. In the triple CCAAT-containing cyclin B2 cell-cycle promoter, all CCAAT boxes, independently from their NF-Y affinities, are important for function. We investigated the relationships between NF-Y and p300. Chromatin immunoprecipitation analysis found that NF-Y and p300 are bound to the cyclin B2 promoter in vivo and that their binding is regulated during the cell cycle, positively correlating with promoter function. Cotransfection experiments determined that the coactivator acts on all CCAAT boxes and requires a precise spacing between the three elements. We established the order of in vitro binding of the three NF-Y complexes and find decreasing affinities from the most distal Y1 to the proximal Y3 site. Binding of two or three NF-Y trimers with or without p300 is not cooperative, but association with the Y1 and Y2 sites is extremely stable. p300 favors the binding of NF-Y to the weak Y3 proximal site, provided that a correct distance between the three CCAAT is respected. Our data indicate that the precise spacing of multiple CCAAT boxes is crucial for coactivator function. Transient association to a weak site might be a point of regulation during the cell cycle and a general theme of multiple CCAAT box promoters

    Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

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    PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

    Best of times, worst of times: record fossil-fuel profits, inflation and inequality

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    The 2022 oil and gas crisis resulted in record fossil-fuel profits globally that rehabilitated the oil and gas industry, obstructed the energy transition and contributed to inflation, but their magnitude and beneficiaries have been insufficiently understood. Here we show the size of profits across countries and their distribution across socio-economic groups within the United States, using company income statements, comprehensive ownership data and a network model for propagating profits via shareholdings. We estimate that globally, net income in publicly listed oil and gas companies alone reached US916billionin2022,withtheUnitedStatesthebiggestbeneficiarywithclaimsonUS916 billion in 2022, with the United States the biggest beneficiary with claims on US301 billion, more than U.S. investments of US$267 billion in the low carbon economy that year. In a network of U.S. shareholdings with 252,433 nodes including privately held U.S. companies, 50 % of profits went to the wealthiest 1 % of individuals, predominantly through direct shareholdings and private company ownership. In contrast the bottom 50 % only received 1 %. The incremental U.S. fossil-fuel profits in 2022 relative to 2021 were enough to increase the disposable income of the wealthiest Americans by several percent and compensate a substantial part of their purchasing power loss from inflation that year, thereby exacerbating inflation inequality. These profits also reinforced existing racial and ethnic inequalities and inequalities between groups with different educational attainments. We discuss how an excess profit tax could be used to both lower inequality and accelerate the energy transition as increasing geopolitical tensions and climate impacts threaten continued volatility in oil and gas markets

    Knowledge and attitude of final - year medical students in Germany towards palliative care - an interinstitutional questionnaire-based study

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    <p>Abstract</p> <p>Background</p> <p>To care for terminally ill and dying patients requires a thorough medical education, encompassing skills, knowledge, and attitudes in the field of palliative care. Undergraduate medical students in Germany will receive mandatory teaching in palliative care in the near future driven by recent changes in the Medical Licensure Act. Before new curricula can be implemented, the knowledge of medical students with respect to palliative care, their confidence to handle palliative care situations correctly, their therapeutic attitude, and their subjective assessment about previous teaching practices have to be better understood.</p> <p>Method</p> <p>We designed a composite, three-step questionnaire (self estimation of confidence, knowledge questions, and opinion on the actual and future medical curriculum) conducted online of final - year medical students at two universities in Germany.</p> <p>Results</p> <p>From a total of 318 enrolled students, 101 responded and described limited confidence in dealing with specific palliative care issues, except for pain therapy. With regard to questions examining their knowledge base in palliative care, only one third of the students (33%) answered more than half of the questions correctly. Only a small percentage of students stated they had gained sufficient knowledge and experience in palliative care during their studies, and the vast majority supported the introduction of palliative care as a mandatory part of the undergraduate curriculum.</p> <p>Conclusion</p> <p>This study identifies medical students' limited confidence and knowledge base in palliative care in 2 German universities, and underlines the importance of providing a mandatory palliative care curriculum.</p

    LiBAT: A High-Performance AC Battery System for Transport Applications

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    The paper proposes a novel battery design for high-performance transport applications that is immersion-cooled and switched by a multi-level inverter. Advantages of the proposed AC battery design in terms of weight, modularity, scalability, performance, reliability and safety are presented. To demonstrate the applicability of the design, an electrically powered glider use case is addressed. The derived battery system is evaluated by means of theoretical analysis, simulation and prototyping. Simulations showed that the used multi-level inverter (MLI) power electronics modules could successfully run the motor without additional power electronics and charge batteries from a 110 V AC source. The prototype implementation with a motor-driven propeller demonstrated power levels of up to 3.3 kW, with a behavior in accordance with simulations. Guidelines to further advance the technology readiness level including control strategies and hardware design were derived to overcome limitations in the prototype realization that could not be addressed within the project budget. Finally, research topics to evaluate additional performance metrics such as efficiency and aging behavior are suggested

    Increased endothelin-1 and diminished nitric oxide levels in blister fluids of patients with intermediate cold type complex regional pain syndrome type 1

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    BACKGROUND: In complex regional pain syndrome type 1 (CRPS1) pro-inflammatory mediators and vascular changes play an important role in the sustained development and outcome of the disease. The aim of this study was to determine the involvement of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) during early chronic CRPS1. METHODS: Included were 29 patients with CRPS 1 who were diagnosed during the acute stage of their disease and observed during follow-up visits. Disease activity and impairment were determined and artificial suction blisters were made on the CRPS1 and the contralateral extremities for measurements of IL-6, TNF-α, ET-1 and nitrate/nitrite (NOx). RESULTS: The levels of IL-6, TNF-α and ET-1 in blister fluid in the CRPS1 extremity versus the contralateral extremity were significantly increased and correlated with each other, whereas NOx levels were decreased. CONCLUSION: The NOx/ET-1 ratio appears to be disturbed in the intermediate stage of CRPS, resulting in vasoconstriction and consequently in a diminished tissue blood distribution
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