3,520 research outputs found

    Where do we stand On Organ Printing

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    Abstract Attitude towards organ donation and the risks associated with organ transplantation drive the search for alternatives. One such alternative, albeit a conceptual level, could be the generation of an organ replacement in a controlled setting. For instance, growing suitable cells onto a printed matrix under appropriate conditions would then lead to the formation of a functional organ. How about the practical issues surrounding either duplication or de novo generation of an organ with, say, a device to print a suitable matrix and grow and differentiate cells on it? Here, we wish to outline selected safety-related questions arising from the ex vivo growth, differentiation and maintenance of cells or cell systems

    Public-good experiments with large groups

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    Many of real-world public-goods are characterized by a marginal per capita return (MPCR) close to zero and have to be provided by large groups. Up until now, there is almost no evidence on how large groups facing a low MPCR behave in controlled public-good laboratory experiments involving financial incentives. Connecting four experimental laboratories located in four di€erent German universities via Internet, we are able to run such experiments. In ad-dition to the group size (60 and 100 subjects), we vary the MPCR which is as small as 0:02 or 0:04. Our data reveal a strong MPCR effect, but almost no group-size e€ect. Our data demonstrates that, even in large groups and for low MPCRs, considerable contributions to public goods can be expected. Interestingly, the contribution patterns observed in large and very small groups are very similar. To the best of our knowledge, this study is the first one that includes large-group laboratory experiments with a small MPCR under conditions comparable to previous small-group standard public-good experiments

    An Abraded Surface Of Oxorubicin-loaded Surfactant-containing Drug Delivery Systems Effectively Reduces The Survival Of Carcinoma Cells

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    An effective antitumor remedy is yet to be developed. All previous approaches for a targeted delivery of anticancer medicine have relied on trial and error. The goal of this study was to use structural insights gained from the study of delivery systems and malignant cells to provide for a systematic approach to the development of next-generation drugs. We used doxorubicin (Dox) liposomal formulations. We assayed for cytotoxicity via the electrical current exclusion method. Dialysis of the samples yielded information about their drug release profiles. Information about the surface of the delivery systems was obtained through synchrotron small-angle X-ray scattering (SAXS) measurements. SAXS measurements revealed that Dox-loading yielded an abraded surface of our Dox liposomal formulation containing soybean oil, which also correlated with an effective reduction of the survival of carcinoma cells. Furthermore, a dialysis assay revealed that a higher burst of Dox was released from soybean oil-containing preparations within the first five hours. We conclude from our results that an abraded surface of Dox-loaded drug delivery system increases their efficacy. The apparent match between surface geometry of drug delivery systems and target cells is suggested as a steppingstone for refined development of drug delivery systems. This is the first study to provide a systematic approach to developing next-generation drug carrier systems using structural insights to guide the development of next-generation drug delivery systems with increased efficacy and reduced side effects.4

    HPM-Detektionssystem mit Frequenzbestimmung

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    In allen Bereichen unserer Gesellschaft hĂ€lt moderne und komplexe Elektronik Einzug. Mit zunehmender KomplexitĂ€t und Vernetzung wĂ€chst auch das Potential fĂŒr Bedrohung solcher kritischer Infrastruktur durch Hochleistungsmikrowellen (HPM), die solche Systeme zeitweise stören oder permanent außer Kraft setzen können. In der Vergangenheit wurde am Fraunhofer INT ein HPM-Detektionssystem entwickelt, dass ĂŒber die FĂ€higkeiten einfacher WarnempfĂ€nger zur einfachen Anzeige von gefĂ€hrlichen HPM-Ereignissen hinausgeht. In einem nĂ€chsten Schritt wurde mit einem vierkanaligen System die Detektion der Richtung eines HPM-Angriffs realisiert. Der Beitrag gliedert sich wie folgt: VorĂŒberlegungen fĂŒr die HPM-Detektion (die zu einer analogen AusfĂŒhrung des Detektors fĂŒhren); Konzept zur HPM-Amplitudenmessung: Der Frequenzbereich erstreckt sich von 500 MHz bis etwa 4 GHz, die Messdynamik umfasst 60 dB, beginnend bei etwa 10 V/m. Die Schirmung des Demonstrators wurde erfolgreich bis 1 kV/m ausgemessen. Gepulste Signale konnten bis zu einer KĂŒrze von 10 ns gemessen werden; Konzept zur HPM-Frequenzmessung (Prinzipschaltbild des HPM-Frequenzdiskriminators); Realisierung eines HPM-Detektionssystems mit Frequenzbestimmung (hierzu 5 Abb.: Kennlinie des Frequenzdiskriminators; Ausgangsimpuls des Frequenzdiskriminators, HF-PulslĂ€nge = 100 ns; Blockschaltbild des HF-Teils des HPM-Detektors mit Frequenzmessung; Demonstrator des Konzeptes der Frequenzerkennung und einkanaliger Amplitudenmessung; Blockschaltbild des gesamten HPM-Detektors mit Frequenzmessung) sowie Softwarekonzept (BenutzeroberflĂ€che). Das Konzept eines kompakten Gesamtsystems mit integrierter Spannungsversorgung und SignalĂŒbertragung per Lichtwellenleiter wurde im Labor, wie auch bei Freifeldmessungen, erfolgreich bestĂ€tigt

    Late-Onset Prosthetic Endocarditis with Paraaortic Abscess Caused by Cutibacterium acnes

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    Cutibacterium acnes, an integral component of the skin’s customary bacterial flora, represents a Gram-positive anaerobic bacterium characterized by its low virulence. Despite its low virulence, the pathogen can cause profound-seated infections as well as infections linked to medical devices. We report a case study of a prosthesis endocarditis accompanied by a paraaortic abscess caused by C. acnes, a development occurring five years prior to composite aortic root and valve replacement. At the point of admission, the patient presented with a combination of symptoms hinting at a subacute progression, such as weight loss, chest pain, and limitations of cardiopulmonary functionality. An anaerobic pathogen, namely C. acnes, was detected in a singular blood culture vial. Since first-line imaging modalities such as echocardiography did not reveal any signs of inflammation, and in the case of a suspected diagnosis for IE, did not show high pretest probability, further diagnostic imaging such as 18F-FDG PET CT was put to use. Here, a highly elevated glucose metabolism around the aortic valve ring was detected, pointing to an inflammatory process. The patient received adjusted intravenous antibiotic therapy over a course of six weeks; he then underwent surgical therapy via re-replacement of the aortic root and valve using a composite conduit. Advanced microbiological analyses, including the amplification of PCR and valve sequencing via 16S rDNA, mainly detected one pathogen: C. acnes. Delayed onset with mild symptoms and laboratory findings is characteristic of infective endocarditis by C. acnes. Due to its high rate of complications, mortality, and morbidity, an infection should not be disregarded as contamination. Recommendations from different studies underline a combination of a positive blood culture and microbiological evidence to differentiate between contamination and true infection in the case of an infection involving C. acnes. Serial blood cultures with prolonged incubation, advanced microbiological analyses, and modified Duke criteria including second-line imaging techniques should be utilized for further evaluation

    Living Long and Well: Prospects for a Personalized Approach to the Medicine of Ageing.

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    Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large-scale cohort studies in humans, similar systematic 56 studies in model organisms, and detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains, or genetic reference populations of mice. Combining both, the comprehensive picture of the various determinants of ageing and healthspan can be studied in detail, and an appreciation of the relevance of results from model organisms to humans emerges. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of healthspan enables us to refocus healthcare spending on individual prevention starting in late adulthood, and on the brief period of morbidity at very old age

    Plasma Lipocalin 2 in Alzheimer’s disease: potential utility in the differential diagnosis and relationship with other biomarkers

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    Background Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer's disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer's disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer's disease, differential diagnoses, other biomarkers, and clinical data. Methods For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer's disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer's disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results Plasma Lipocalin-2 was significantly lower in Alzheimer's disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer's pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer's disease and healthy controls were 0.783 (95%CI: 0.712-0.855) in the study cohort and 0.766 (95%CI: 0.627-0.905) in the validation cohort. The area under the curve for Alzheimer's disease versus vascular dementia was 0.778 (95%CI: 0.667-0.890) in the study cohort. In Alzheimer's disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer's disease (p = 0.013). Conclusions Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer's disease and seems to be independent from currently employed biomarkers
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