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Find video protocols related to scientific articles indexed in Pubmed.
The role of dendritic cells in the pathogenesis of Whipple's disease.
Infect. Immun.
PUBLISHED: 11-12-2014
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Accumulation of Tropheryma (T.) whipplei-stuffed macrophages in the duodenum, impaired T. whipplei-specific Th1 responses and weak secretion of IL-12 are hallmarks of classical Whipple's disease (CWD). This study addresses dendritic cell (DC) functionality during CWD. We documented composition, distribution and functionality of DC ex vivo or after in vitro maturation by FACS and by immunohistochemistry in situ. A decrease in peripheral DC of untreated CWD patients compared to healthy donors was due to reduced CD11c(high) myeloid DC (M-DC). Decreased maturation markers CD83, CD86 and CCR7 as well as low IL-12 production in response to stimulation disclosed an immature M-DC phenotype. In vitro generated monocyte-derived DC from CWD patients showed normal maturation and T cell-stimulatory capacity under pro-inflammatory conditions, but produced less IL-12 and failed to activate T. whipplei-specific Th1 cells. In duodenal and lymphoid tissues, T. whipplei was found within immature DC-SIGN(+) DC and DC and proliferating lymphocytes were reduced in LN of CWD patients compared to controls. Our results indicate that dysfunctional IL-12 production by DC provides suboptimal conditions for priming of T. whipplei-specific T cells during CWD and that immature DC carrying T. whipplei might contribute to the disseminate the bacterium.
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Proteomics for systems toxicology.
Comput Struct Biotechnol J
PUBLISHED: 08-01-2014
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Current toxicology studies frequently lack measurements at molecular resolution to enable a more mechanism-based and predictive toxicological assessment. Recently, a systems toxicology assessment framework has been proposed, which combines conventional toxicological assessment strategies with system-wide measurement methods and computational analysis approaches from the field of systems biology. Proteomic measurements are an integral component of this integrative strategy because protein alterations closely mirror biological effects, such as biological stress responses or global tissue alterations. Here, we provide an overview of the technical foundations and highlight select applications of proteomics for systems toxicology studies. With a focus on mass spectrometry-based proteomics, we summarize the experimental methods for quantitative proteomics and describe the computational approaches used to derive biological/mechanistic insights from these datasets. To illustrate how proteomics has been successfully employed to address mechanistic questions in toxicology, we summarized several case studies. Overall, we provide the technical and conceptual foundation for the integration of proteomic measurements in a more comprehensive systems toxicology assessment framework. We conclude that, owing to the critical importance of protein-level measurements and recent technological advances, proteomics will be an integral part of integrative systems toxicology approaches in the future.
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Stereological investigation of the posterior hippocampus in affective disorders.
J Neural Transm
PUBLISHED: 07-30-2014
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Hippocampus volumes have been shown to be decreased in patients with major depression, but volume measurements are inconsistent in patients with bipolar disorder. Both disorders are associated with deficits in hippocampus-mediated cognitive functions. However, the underlying pathophysiology is widely unknown. In this post-mortem study, we used design-based stereology on Nissl-stained serial sections to investigate the number of neurons, oligodendrocytes and astrocytes in substructures of the posterior hippocampus in eight patients with major depression, eight patients with bipolar disorder and ten control patients without a neuropsychiatric disorder. Compared to controls, patients with bipolar disorder had significantly more neurons in the cornu ammonis subfield 1 (CA1) and the subiculum, while the number of oligodendrocytes was higher only in CA1. In patients with major depression, the density of oligodendrocytes was higher in CA2/3, CA4 and the subiculum. The dose of antidepressants correlated with the density and number of oligodendrocytes in CA2/3, indicating that antidepressants may affect our results. Treatment with neuroleptics expressed in chlorpromazine equivalents and benzodiazepines expressed in diazepam equivalents correlated negatively with the number of oligodendrocytes in CA2/3 and CA4, respectively, suggesting that treatment with these drugs do not influence cell number. We did not detect alterations in either volumes of substructures or numbers of astrocytes. Increased cell numbers argue for a denser packing of neurons and oligodendrocytes as a result of a decreased neuropils. This neuropathological process may be based on neurodevelopmental disturbances and may contribute to altered microconnectivity and cognitive deficits in affective disorders.
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Survival in Granular Cell Astrocytomas.
J Neurol Surg A Cent Eur Neurosurg
PUBLISHED: 07-29-2014
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Background?Granular cell astrocytomas (GCAs) are rarely encountered aggressive glial neoplasms. Treatment options comprise surgery, radiotherapy, and chemotherapy. Due to the small number of cases, a standard therapeutic regimen for GCA does not exist. Material and Methods?We report on the case of a 64-year-old woman with GCA subjected to tumor biopsy followed by radiochemotherapy with temozolomide. We provide clinical, histopathologic, and magnetic resonance imaging findings as well as a complete follow-up. To assess the relation of age, gender, time of publication, and different treatment options with survival we performed log-rank tests and calculated Cox regression models and hazard ratios in data from all available reports on GCA. Results?A significant difference in survival rates in favor of adjuvant therapy (radiotherapy or radiochemotherapy) at 12 months was found. Age?>?70 years at the time of diagnosis had a significantly unfavorable impact on survival at 12 months. Although not statistically significant, a tendency toward higher probability of survival at 12 months was found in cases reported after 2002. In surgically treated patients, we could not find a significant impact of extent of resection on survival. A significant impact of gender on survival was not found. Conclusion?Adjuvant therapy is significantly related to a higher probability of survival at 12 months and may therefore be recommended for patients with a GCA. Further analysis of these rare neoplasms is warranted.
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Bark in the park: a review of domestic dogs in parks.
Environ Manage
PUBLISHED: 06-07-2014
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The presence of domestic dogs Canis familiaris in public open spaces is increasingly controversial. In our review of the literature, we located 133 publications of various types (papers, reports etc.) that examine some aspect of dogs in parks and open spaces (50 % focussed solely on dogs). There has been an exponential growth in the cumulative number of articles (R (2) = 0.96; 82 % published since 1997); almost all pertain to temperate latitudes (97 %) and most to the northern hemisphere (62 %). Most articles focus on impacts on wildlife (51 %), zoonotic diseases (17 %), and people's perceptions regarding dogs (12 %). Articles mostly describe problems associated with dogs, while reports of low compliance with dog regulations are common. We outline six major findings regarding dogs in parks: (1) there is a paucity of information on dogs in parks, particularly in relation to their interactions with wildlife and regarding their management; (2) published studies are mainly restricted to a handful of locations in developed countries; (3) sectors of societies hold different views over the desirability of dogs in parks; (4) the benefits and risks of dogs to humans and park values are poorly documented and known; (5) dogs represent a notable disease risk in some but not all countries; and (6) coastal parks are over-represented in the literature in terms of potential negative impacts. Park managers globally require better information to achieve conservation outcomes from dog management in parks.
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Prospects and problems of transferring quality-improvement methods from health care to social services: two case studies.
Perm J
PUBLISHED: 05-29-2014
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This study examines the use of quality-improvement (QI) methods in social services. Particularly the key aspects-generalizable knowledge, interprofessional teamwork, and measurements-are studied in projects from the QI program Forum for Values in Sweden.
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[An atypical Stafne cavity-multi-chamber bone lesion with bucal expansion. A case report].
Swiss Dent J
PUBLISHED: 05-24-2014
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In the literature Stafne bone cavities are mostly described for male patients in their fifth and sixth decade. Usually the lingual cavities appear as ovoid lesions located unilateral in the molar region of the lower jaw underneath the inferior alveolar nerve. Classically they contain parts of the submandibular gland. This case study describes a patient who was referred to the authors? clinic with a cavity in the right lower jaw extending over a mesio-distal diameter of 24 mm. Its appearance on panoramic x?ray and cone beam computer tomography (CTBT) was inconclusive. The diagnosis could finally be made after magnetic resonance imaging (MRI). It was based on the content of gland, fat and lymphatic tissue in a lingual open cavity, which is a characteristic feature of Stafne bone cavities. Assumed aetiology and differential diagnosis are discussed.
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Variations in the anatomical positioning of impacted mandibular wisdom teeth and their practical implications.
Swiss Dent J
PUBLISHED: 05-24-2014
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Surgical removal of impacted third molars is one of the most frequent procedures in oral surgery. Here, three-dimensional (3D) imaging is often used, yet its necessity is still being heavily debated. The aim of the study was to describe the variation in the anatomical positioning of third mandibular molars, and, by doing so, examine the necessity of 3D imaging. A retrospective case study was performed with the patients from an oral surgery department from January 2009 to February 2013. The primary focus of the study was on the spatial relationship to the mandibular canal, as well as angulation, root configuration, and developmental stage of the wisdom tooth. Descriptive statistics were calculated for these variables. A total of 1197 wisdom teeth in 699 patients were evaluated. 46.7% exhibited direct contact to the mandibular canal, another 28.7% showed close proximity and 24.6% a measurable distance. In 29.0%, the mandibular canal was vestibular and in 23.8% lingual to the wisdom tooth. In 7.4%, it was interradicular and in 0.6% intraradicular. Most teeth had one (21.3%) or two (55.3%) roots. Others had three (17.6%), four (2.0%) or five (0.2%) roots. In 31.4% of the teeth, the root perforated the lingual compact bone, and in 4.3% the vestibular compact bone. 44.4% of the teeth had mesial angulation, 9.7% distal angulation, 35.3% lingual and 2.9% buccal angulation. Due to the anatomical variety, the use of 3D imaging is recommended before surgical removal of mandibular third molars if conventional imaging cannot exclude complicated conditions.
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Flat, rectangular frequency comb generation with tunable bandwidth and frequency spacing.
Opt Lett
PUBLISHED: 04-03-2014
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The generation of flat, rectangular frequency combs with tunable frequency spacing and bandwidth is demonstrated. Therefore, several lines or sidebands are extracted out of an existing frequency comb, for example a femtosecond fiber laser. Subsequently, these lines are processed via two Mach-Zehnder modulators in order to generate a flat frequency comb with tunable frequency spacing. Optical frequency combs with various spacing and a maximum bandwidth of 260 GHz are generated. However, much higher bandwidth can be reached easily. The overall flatness of the generated combs is within 0.6 dB.
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Advanced REACH Tool: a Bayesian model for occupational exposure assessment.
Ann Occup Hyg
PUBLISHED: 03-24-2014
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This paper describes a Bayesian model for the assessment of inhalation exposures in an occupational setting; the methodology underpins a freely available web-based application for exposure assessment, the Advanced REACH Tool (ART). The ART is a higher tier exposure tool that combines disparate sources of information within a Bayesian statistical framework. The information is obtained from expert knowledge expressed in a calibrated mechanistic model of exposure assessment, data on inter- and intra-individual variability in exposures from the literature, and context-specific exposure measurements. The ART provides central estimates and credible intervals for different percentiles of the exposure distribution, for full-shift and long-term average exposures. The ART can produce exposure estimates in the absence of measurements, but the precision of the estimates improves as more data become available. The methodology presented in this paper is able to utilize partially analogous data, a novel approach designed to make efficient use of a sparsely populated measurement database although some additional research is still required before practical implementation. The methodology is demonstrated using two worked examples: an exposure to copper pyrithione in the spraying of antifouling paints and an exposure to ethyl acetate in shoe repair.
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Nanoliter segmented-flow sampling mass spectrometry with online compartmentalization.
Anal. Chem.
PUBLISHED: 03-21-2014
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We report a microfluidic device, using segmented flow in a two-phase system of immiscible liquids, which delivers aqueous droplets into a modified commercial mass spectrometer. The interface coupling the microfluidics to the mass spectrometer achieves up to 96% sample transfer efficiency to the vacuum chamber. Sample ionization is assisted by multipass infrared laser beam in the interface. The system achieves low femtomole detection limits of several analytes ranging from drugs to proteins. Sample ionization in this segmented-flow sampling was found to be remarkably insensitive to the presence of buffer salts and other matrices.
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The seco-iridoid pathway from Catharanthus roseus.
Nat Commun
PUBLISHED: 03-10-2014
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The (seco)iridoids and their derivatives, the monoterpenoid indole alkaloids (MIAs), form two large families of plant-derived bioactive compounds with a wide spectrum of high-value pharmacological and insect-repellent activities. Vinblastine and vincristine, MIAs used as anticancer drugs, are produced by Catharanthus roseus in extremely low levels, leading to high market prices and poor availability. Their biotechnological production is hampered by the fragmentary knowledge of their biosynthesis. Here we report the discovery of the last four missing steps of the (seco)iridoid biosynthesis pathway. Expression of the eight genes encoding this pathway, together with two genes boosting precursor formation and two downstream alkaloid biosynthesis genes, in an alternative plant host, allows the heterologous production of the complex MIA strictosidine. This confirms the functionality of all enzymes of the pathway and highlights their utility for synthetic biology programmes towards a sustainable biotechnological production of valuable (seco)iridoids and alkaloids with pharmaceutical and agricultural applications.
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The inferior alveolar nerve's loop at the mental foramen and its implications for surgery.
J Am Dent Assoc
PUBLISHED: 03-04-2014
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In this study, the authors aimed to identify and measure the anterior extension of the alveolar loop (aAL) and the caudal extension of the alveolar loop (cAL) of the inferior alveolar nerve by using cone-beam computed tomography (CBCT). They also aimed to provide recommendations for surgery in the anterior mandible.
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Serial crystallography on in vivo grown microcrystals using synchrotron radiation.
IUCrJ
PUBLISHED: 03-01-2014
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Crystal structure determinations of biological macromolecules are limited by the availability of sufficiently sized crystals and by the fact that crystal quality deteriorates during data collection owing to radiation damage. Exploiting a micrometre-sized X-ray beam, high-precision diffractometry and shutterless data acquisition with a pixel-array detector, a strategy for collecting data from many micrometre-sized crystals presented to an X-ray beam in a vitrified suspension is demonstrated. By combining diffraction data from 80 Trypanosoma brucei procathepsin B crystals with an average volume of 9?µm(3), a complete data set to 3.0?Å resolution has been assembled. The data allowed the refinement of a structural model that is consistent with that previously obtained using free-electron laser radiation, providing mutual validation. Further improvements of the serial synchrotron crystallography technique and its combination with serial femtosecond crystallography are discussed that may allow the determination of high-resolution structures of micrometre-sized crystals.
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Quasi-light storage for optical data packets.
J Vis Exp
PUBLISHED: 02-25-2014
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Today's telecommunication is based on optical packets which transmit the information in optical fiber networks around the world. Currently, the processing of the signals is done in the electrical domain. Direct storage in the optical domain would avoid the transfer of the packets to the electrical and back to the optical domain in every network node and, therefore, increase the speed and possibly reduce the energy consumption of telecommunications. However, light consists of photons which propagate with the speed of light in vacuum. Thus, the storage of light is a big challenge. There exist some methods to slow down the speed of the light, or to store it in excitations of a medium. However, these methods cannot be used for the storage of optical data packets used in telecommunications networks. Here we show how the time-frequency-coherence, which holds for every signal and therefore for optical packets as well, can be exploited to build an optical memory. We will review the background and show in detail and through examples, how a frequency comb can be used for the copying of an optical packet which enters the memory. One of these time domain copies is then extracted from the memory by a time domain switch. We will show this method for intensity as well as for phase modulated signals.
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Colon capsule endoscopy: detection of colonic polyps compared with conventional colonoscopy and visualization of extracolonic pathologies.
Can J Gastroenterol Hepatol
PUBLISHED: 02-07-2014
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Conventional colonoscopy (CC) is the gold standard for diagnostic examination of the colon. However, the overall acceptance of this procedure is low due to patient fears of complications or embarrassment. Colon capsule endoscopy (CCE) represents a minimally invasive, patient-friendly procedure that offers complete visualization of the entire intestine.
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A novel ?-xylosidase structure from Geobacillus thermoglucosidasius: the first crystal structure of a glycoside hydrolase family GH52 enzyme reveals unpredicted similarity to other glycoside hydrolase folds.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 02-06-2014
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Geobacillus thermoglucosidasius is a thermophilic bacterium that is able to ferment both C6 and C5 sugars to produce ethanol. During growth on hemicellulose biomass, an intracellular ?-xylosidase catalyses the hydrolysis of xylo-oligosaccharides to the monosaccharide xylose, which can then enter the pathways of central metabolism. The gene encoding a G. thermoglucosidasius ?-xylosidase belonging to CAZy glycoside hydrolase family GH52 has been cloned and expressed in Escherichia coli. The recombinant enzyme has been characterized and a high-resolution (1.7 Å) crystal structure has been determined, resulting in the first reported structure of a GH52 family member. A lower resolution (2.6 Å) structure of the enzyme-substrate complex shows the positioning of the xylobiose substrate to be consistent with the proposed retaining mechanism of the family; additionally, the deep cleft of the active-site pocket, plus the proximity of the neighbouring subunit, afford an explanation for the lack of catalytic activity towards the polymer xylan. Whilst the fold of the G. thermoglucosidasius ?-xylosidase is completely different from xylosidases in other CAZy families, the enzyme surprisingly shares structural similarities with other glycoside hydrolases, despite having no more than 13% sequence identity.
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Stafne bone cavities: systematic algorithm for diagnosis derived from retrospective data over a 5-year period.
Br J Oral Maxillofac Surg
PUBLISHED: 01-27-2014
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Stafne bone cavities are usually found in men 50-70 years old. Typically they appear as lingual, open, ovoid lesions of the molar region of the lower jaw, and most contain parts of the submandibular gland. We have retrospectively examined panoramic radiographs acquired over a 5-year period. All lesions suspected of being Stafne bone cavities were included and analysed further to retrieve statistical information and derive a systematic diagnostic algorithm. We identified 21 Stafne bone cavities among 2928 patients (0.7%). Four of these were confirmed on cone-beam computed tomography (CT). One patient had magnetic resonance imaging (MRI) to confirm the diagnosis. The M:F ratio was 14:7 and the mean age 53 years (range 22-82). All cavities were located in the posterior mandible, 9 on the right and 12 on the left. The mean length was 10.9 (range 4.5-23) mm and height 5.7 (range 3.3-17.3) mm. All cavities were located in the posterior mandible. Sixteen panoramic radiographs (0.6%) were classified as possibly having a Stafne bone cavity but did not fulfil enough criteria to confirm the diagnosis. These 16 were not further analysed. It is rare to diagnose a Stafne bone cavity on a panoramic radiograph. Thorough investigation is essential to exclude differential diagnoses such as keratocystic odontogenic tumour, ameloblastoma, or a metastasis. In atypical presentations 3-dimensional cone-beam CT is helpful to verify the lingual opening. If the diagnosis is still not clear, it can be confirmed by MRI.
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ERG expression in intraductal carcinoma of the prostate: comparison with adjacent invasive prostatic adenocarcinoma.
Mod. Pathol.
PUBLISHED: 01-10-2014
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Intraductal carcinoma of the prostate is a growth pattern of prostatic adenocarcinoma that has not been well characterized from the molecular standpoint. It remains debatable whether intraductal carcinoma of the prostate represents colonization of benign glands by pre-existing conventional prostatic adenocarcinoma, or progression of high-grade prostatic intraepithelial neoplasia. TMPRSS2-ERG is the most common gene fusion in conventional prostatic adenocarcinoma, identified in about 40-70% of cases. In this study, we compared the expression of ERG in intraductal carcinoma of the prostate and adjacent conventional prostatic adenocarcinoma. Thirty-one confirmed cases of intraductal carcinoma of the prostate, with adjacent conventional prostatic adenocarcinoma and available tissue blocks, were identified at our institution. Immunohistochemical stains were performed for ERG using a rabbit anti-ERG monoclonal antibody. The ERG expression in the intraductal carcinoma of the prostate component was compared with that in the adjacent conventional prostatic adenocarcinoma. Mean patient age was 65 years (range: 48-79 years). Positive ERG expression was identified in 11/31 (35%) cases of intraductal carcinoma of the prostate. In all 11/11 (100%) cases with positive ERG expression in the intraductal carcinoma of the prostate component, ERG expression was also positive in the adjacent conventional prostatic adenocarcinoma. In the 20/31 cases with negative ERG expression in the intraductal carcinoma of the prostate component, ERG was also negative in the adjacent conventional prostatic adenocarcinoma. It is highly conceivable that based on the identical ERG expression (positive or negative) in intraductal carcinoma of the prostate and the adjacent conventional prostatic adenocarcinoma, intraductal carcinoma of the prostate most likely represents colonization of benign glands by adjacent pre-existing conventional prostatic adenocarcinoma.
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QuickView video preview software of colon capsule endoscopy: reliability in presenting colorectal polyps as compared to normal mode reading.
Scand. J. Gastroenterol.
PUBLISHED: 12-11-2013
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Abstract Objective. Colon capsule endoscopy (CCE) proved to be highly sensitive in detection of colorectal polyps (CP). Major limitation is the time-consuming video reading. The aim of this prospective, double-center study was to assess the theoretical time-saving potential and its possible impact on the reliability of "QuickView" (QV), in the presentation of CP as compared to normal mode (NM). Methods. During NM reading of 65 CCE videos (mean patient´s age 56 years), all frames showing CPs were collected and compared to the number of frames presented by QV at increasing QV settings (10, 20, ... 80%). Reliability of QV in presenting polyps <6 mm and ?6 mm (significant polyp), and identifying patients for subsequent therapeutic colonoscopy, capsule egestion rate, cleansing level, and estimated time-saving potential were assessed. Results. At a 30% QV setting, the QV video presented 89% of the significant polyps and 86% of any polyps with ?1 frame (per-polyp analysis) identified in NM before. At a 10% QV setting, 98% of the 52 patients with significant polyps could be identified (per-patient analysis) by QV video analysis. Capsule excretion rate was 74% and colon cleanliness was adequate in 85%. QV´s presentation rate correlates to the QV setting, the polyp size, and the number of frames per finding. Conclusions. Depending on its setting, the reliability of QV in presenting CP as compared to NM reading is notable. However, if no significant polyp is presented by QV, NM reading must be performed afterwards. The reduction of frames to be analyzed in QV might speed up identification of candidates for therapeutic colonoscopy.
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Macrophages Accumulate in the Gut Mucosa of Untreated HIV-infected Patients.
J. Infect. Dis.
PUBLISHED: 10-16-2013
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Background.?Mucosal macrophages are involved in the maintenance of epithelial barrier integrity and the elimination of invading pathogens. Although an intestinal barrier defect and microbial translocation are hallmarks of human immunodeficiency virus (HIV) infection, recent data on gut mucosal macrophages in HIV infection are sparse.Methods.?Treatment-naive and treated HIV-infected patients and healthy controls were studied for frequencies and functional parameters of blood monocytes and macrophages in duodenal mucosa.Results.?We found mucosal enrichment of macrophages in untreated HIV infection associated with reduced monocyte counts in blood and increased monocyte expression of the gut-homing molecule integrin ?7. Increased CCR2 density on integrin ?7-expressing monocytes and mucosal secretion of CCL2 suggest that CCR2/CCL2-chemotaxis is involved in enhanced trafficking of blood monocytes to the gut. Secretion of macrophage-related proinflammatory molecules interleukin 1?, CCL5, CXCL9, and CXCL10 was increased in the gut mucosa of untreated patients. Moreover, mucosal macrophages of untreated patients showed reduced phagocytic activity.Conclusions.?These data suggest a role for gut mucosal macrophages in HIV immune pathogenesis: infiltrated macrophages in the intestinal mucosa may promote local inflammation and tissue injury, whereas their low phagocytic activity prevents the efficient elimination of luminal antigens that cross the damaged intestinal barrier.
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Generation of ultra-narrow, stable and tunable millimeter- and terahertz- waves with very low phase noise.
Opt Express
PUBLISHED: 10-10-2013
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The interference between two spectral lines of the frequency comb of a fiber femtosecond laser is used to generate millimeter-wave and terahertz tones. The two lines are selected by stimulated Brillouin scattering (SBS) amplification. All other modes are strongly rejected based on polarization discrimination, using the polarization-pulling effect that is associated with SBS. The inherent high spectral quality of a femtosecond fiber laser comb allows generation of millimeter- and terahertz waves with linewidths below 1 Hz, and a phase noise of -105 dBc/Hz at 10 kHz offset. The generation, free-space transmission and detection of continuous waves at 1 THz are demonstrated as well. Lastly, the generated millimeter-wave carriers are modulated by 40 Gbit/s data. The entire system consists of a fiber laser and standard equipment of optical telecommunications. Besides metrology, spectroscopy and astronomy, the method can be utilized for the emergent field of wireless millimeter-wave and THz-communications at ultra-high data rates.
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Tunable microwave-photonic filter using frequency-to-time mapping-based delay lines.
Opt Express
PUBLISHED: 10-10-2013
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A new implementation of microwave-photonic filters (MPFs) based on tunable optical delay lines is proposed and demonstrated. The variable delay is based on mapping of the spectral components of an incoming waveform onto the time domain, the application of linearly-varying temporal phase offsets, and an inverse mapping back to the frequency domain. The linear phase correction is equivalent to a frequency offset, and realized though suppressed-carrier single-sideband modulation by a radio-frequency sine wave. The variable delay element, controlled by the selected frequency, is used in one arm of a two-tap MPF. In a proof-of-concept experiment, the free spectral range (FSR) of the MPF was varied by over a factor of four: between 1.2 GHz and 5.3 GHz.
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Self-digitization of samples into a high-density microfluidic bottom-well array.
Anal. Chem.
PUBLISHED: 10-07-2013
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This paper describes a sample digitization method that generates tens of thousands of nanoliter-sized droplets in a high-density array in a matter of minutes. We show that the sample digitization depends on both the geometric design of the microfluidic device and the viscoelastic forces between the aqueous sample and a continuous oil phase. Our design avoids sample loss: Samples are split into tens of thousands of discrete volumes with close to 100% efficiency without the need for any expensive valving or pumping systems. We envision this technology will have broad applications that require simple sample digitization within minutes, such as digital polymerase chain reactions and single-cell studies.
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Brillouin optical spectrum analyzer monitoring of subcarrier-multiplexed fiber-optic signals.
Appl Opt
PUBLISHED: 10-03-2013
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Optical spectral analysis of closely spaced, subcarrier multiplexed fiber-optic transmission is performed, based on stimulated Brillouin scattering (SBS). The Brillouin gain window of a single, continuous-wave pump is scanned across the spectral extent of the signal under test. The polarization pulling effect associated with SBS is employed to improve the rejection ratio of the analysis by an order of magnitude. Ten tones, spaced by only 10 MHz and each carrying random-sequence on-off keying data, are clearly resolved. The measurement identifies the absence of a single subcarrier, directly in the optical domain. The results are applicable to the monitoring of optical orthogonal frequency domain multiplexing and radio over fiber transmission.
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Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.
PLoS Pathog.
PUBLISHED: 10-01-2013
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Latency-associated nuclear antigen (LANA) mediates ?2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of Epstein-Barr virus EBNA1. A predicted DNA binding surface is present and opposite this interface is a positive electrostatic patch. Targeted DNA recognition substitutions eliminated DNA binding, while certain charged patch mutations reduced bromodomain protein, BRD4, binding. Virus containing LANA abolished for DNA binding was incapable of viable latent infection in mice. Virus with mutations at the charged patch periphery exhibited substantial deficiency in expansion of latent infection, while central region substitutions had little effect. This deficiency was independent of BRD4. These results elucidate the LANA DNA binding domain structure and reveal a unique charged region that exerts a critical role in viral latent infection, likely acting through a host cell protein(s).
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Effects of cannabis and familial loading on subcortical brain volumes in first-episode schizophrenia.
Eur Arch Psychiatry Clin Neurosci
PUBLISHED: 09-01-2013
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Schizophrenia is a severe neuropsychiatric disorder with familial loading as heritable risk factor and cannabis abuse as the most relevant environmental risk factor up to date. Cannabis abuse has been related to an earlier onset of the disease and persisting cannabis consumption is associated with reduced symptom improvement. However, the underlying morphological and biochemical brain alterations due to these risk factors as well as the effects of gene-environmental interaction are still unclear. In this magnetic resonance imaging (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control subjects, we investigated effects of previous cannabis abuse and increased familial risk on subcortical brain regions such as hippocampus, amygdala, caudate nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a subsequent single-volume (1)H-magnetic resonance spectroscopy study, we investigated spectra in the left hippocampus and putamen to detect metabolic alterations. Compared to healthy controls, schizophrenia patients displayed decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus as well as an increased area of the midsagittal CC1 segment of the corpus callosum. Patients fulfilling the criteria for cannabis abuse at admission showed an increased area of the CC2 segment compared to those who did not fulfill the criteria. Patients with a family history of schizophrenia combined with previous cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to all other patients, implicating an interaction between the genetic background and cannabis abuse as environmental factor. Patients with cannabis abuse also had higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a possible neuroprotective effect in this area. However, antipsychotic medication prior to MRI acquisition and gender effects may have influenced our results. Future longitudinal studies in first-episode patients with quantification of cannabis abuse and assessment of schizophrenia risk genes are warranted.
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Validation of an rpoB gene PCR assay for detection of Tropheryma whipplei: 10 years experience in a National Reference Laboratory.
J. Clin. Microbiol.
PUBLISHED: 08-21-2013
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The performance of a real-time PCR assay targeting the Tropheryma whipplei rpoB gene was evaluated using test strains and 1,236 clinical specimens in a national reference laboratory. The novel rpoB-PCR assay proved to be specific, revealed improved analytical sensitivity, and substantially accelerated detection of T. whipplei DNA in clinical specimens.
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The integrin inhibitor cilengitide affects meningioma cell motility and invasion.
Clin. Cancer Res.
PUBLISHED: 08-15-2013
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Meningiomas are frequent intracranial or spinal neoplasms, which recur frequently and can show aggressive clinical behaviour. We elucidated the impact of the integrin inhibitor cilengitide on migration, proliferation, and radiosensitization of meningioma cells.
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Matching p-i-n-junctions and optical modes enables fast and ultra-small silicon modulators.
Opt Express
PUBLISHED: 07-12-2013
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In this article a new method is presented that allows for low loss implementation of fast carrier transport structures in diffraction limited photonic crystal resonators. We utilize a node-matched doping process in which precise silicon doping results in comb-like shaped, highly-doped diode areas that are matched to the spatial field distribution of the optical modes of a Fabry-Pérot resonator. While the doping is only applied to areas with low optical field strength, the intrinsic diode region overlaps with an optical field maximum. The presented node-matched diode-modulators, combining small size, high-speed, thermal stability and energy-efficient switching could become the centerpiece for monolithically integrated transceivers.
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Inflammatory myopathy with abundant macrophages (IMAM): The immunology revisited.
Neuromuscul. Disord.
PUBLISHED: 07-08-2013
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We describe a patient with a clinically atypical presentation of inflammatory myopathy with abundant macrophages (IMAM) but with convincing muscle biopsy features of this subform of inflammatory myopathy. IMAM is characterized mainly by a conspicuous infiltration of muscle and connective tissue by numerous macrophages remote from necrotic and basophilic regenerating muscle fibers. Typically few, mostly CD4(+) T helper (Th) cells are also present. Here, we report a patient with IMAM and demonstrate, that most macrophages express the macrophage mannose receptor 1 (CD206) corresponding to alternatively activated (M2) polarization. Accordingly, signal transducer and activator of transcription 6 (STAT6), involved in Th2-M2 immunity, was expressed at high levels in skeletal muscle. However, TNF?, IFN? and STAT1, mediators of the T helper 1-classically activated (M1) response were elevated in skeletal muscle and in blood, while expression of CD206 was elevated in skeletal muscle only. Our results argue that IMAM could be a distinct entity between the inflammatory myopathies rather than a subform of dermatomyositis.
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Capsule endoscopy in a network cooperation: assessment of the experience in 822 patients.
Scand. J. Gastroenterol.
PUBLISHED: 07-08-2013
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Capsule endoscopy (CE) is firmly established as a standard procedure in the diagnostic algorithm of occult or obscure gastrointestinal bleeding and Crohns disease. Despite its excellent diagnostic yield, missing expertise, reading time and financial expenditure limit an area-wide availability. A multicentric cooperation might compensate these disadvantages.
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Evaluation of arginine metabolism for the analysis of M1/M2 macrophage activation in human clinical specimens.
Inflamm. Res.
PUBLISHED: 05-29-2013
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Macrophage heterogeneity reflects their plasticity in response to environmental stimuli. Usually human macrophages are characterized by analysis of surface molecules or cytokine expression while functional assays are established in the mouse system but lacking for various human specimens.
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Optical sinc-shaped Nyquist pulses of exceptional quality.
Nat Commun
PUBLISHED: 05-27-2013
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Sinc-shaped Nyquist pulses possess a rectangular spectrum, enabling data to be encoded in a minimum spectral bandwidth and satisfying by essence the Nyquist criterion of zero inter-symbol interference (ISI). This property makes them very attractive for communication systems since data transmission rates can be maximized while the bandwidth usage is minimized. However, most of the pulse-shaping methods reported so far have remained rather complex and none has led to ideal sinc pulses. Here a method to produce sinc-shaped Nyquist pulses of very high quality is proposed based on the direct synthesis of a rectangular-shaped and phase-locked frequency comb. The method is highly flexible and can be easily integrated in communication systems, potentially offering a substantial increase in data transmission rates. Further, the high quality and wide tunability of the reported sinc-shaped pulses can also bring benefits to many other fields, such as microwave photonics, light storage and all-optical sampling.
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CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia.
Eur Arch Psychiatry Clin Neurosci
PUBLISHED: 04-24-2013
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Affective deficits are one common denominator of schizophrenia (SZ), bipolar disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated as one of the major structures involved in emotion regulation. Previous findings of differences in amygdala volume between healthy controls and patients with SZ, BD or OCD diverge with respect to the affected hemisphere, size and direction of the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as structural and functional variation in the amygdala in healthy people and patients with BD. We were interested to investigate whether amygdala volumes differ between hemispheres, diagnostic or genotype groups, and whether any interactive effects exist. We combined genotyping of SNP rs1006737 in CACNA1C with structural MRI measurements of relative gray matter (GM) amygdala volume in patients with SZ, BD or OCD as well as healthy controls (N Total = 72). The CACNA1C genotype showed a significant effect on relative GM amygdala volume in patients with SZ. There was a significant left versus right relative GM amygdala volume decrease in patients with SZ or BD. The effects of hemisphere and diagnosis (controls vs. patients with SZ) on relative GM amygdala volume were genotype specific. Our data suggest that the CACNA1C genotype may account for some heterogeneity in the effects of hemisphere and diagnosis on amygdala volume when comparing patients with SZ and controls and point to disturbed Ca(2+)-signaling as a plausible mechanism contributing to the pathology in patients with SZ.
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SCEDS: protein fragments for molecular replacement in Phaser.
Acta Crystallogr. D Biol. Crystallogr.
PUBLISHED: 04-11-2013
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A method is described for generating protein fragments suitable for use as molecular-replacement (MR) template models. The template model for a protein suspected to undergo a conformational change is perturbed along combinations of low-frequency normal modes of the elastic network model. The unperturbed structure is then compared with each perturbed structure in turn and the structurally invariant regions are identified by analysing the difference distance matrix. These fragments are scored with SCEDS, which is a combined measure of the sphericity of the fragments, the continuity of the fragments with respect to the polypeptide chain, the equality in number of atoms in the fragments and the density of C(?) atoms in the triaxial ellipsoid of the fragment extents. The fragment divisions with the highest SCEDS are then used as separate template models for MR. Test cases show that where the protein contains fragments that undergo a change in juxtaposition between template model and target, SCEDS can identify fragments that lead to a lower R factor after ten cycles of all-atom refinement with REFMAC5 than the original template structure. The method has been implemented in the software Phaser.
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Elderly- versus younger-onset rheumatoid arthritis: higher levels of ultrasound-detected inflammation despite comparable clinical disease activity.
Arthritis Care Res (Hoboken)
PUBLISHED: 03-26-2013
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To compare ultrasound-verified joint inflammation between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA) patients.
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The potential impact of droplet microfluidics in biology.
Anal. Chem.
PUBLISHED: 03-15-2013
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Droplet microfluidics, which involves micrometer-sized emulsion droplets on a microfabricated platform, is an active research endeavor that evolved out of the larger field of microfluidics. Recently, this subfield of microfluidics has started to attract greater interest because researchers have been able to demonstrate applications of droplets as miniaturized laboratories for biological measurements. This perspective explores the recent developments and the potential future biological applications of droplet microfluidics.
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Medication error-related issues in nursing practice.
Medsurg Nurs
PUBLISHED: 03-09-2013
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Professional nurses are more exposed to civil claims for negligence than in the past. Issues related to medication errors, and strategies to decrease them, are addressed.
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Thermal ablation of malignant lung tumors.
Dtsch Arztebl Int
PUBLISHED: 02-18-2013
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About 50 000 new cases of non-small-cell carcinoma of the lung are diagnosed in Germany each year. More than 20% of the affected patients cannot be offered radical resection because of comorbidity alone. The lung is also the second most common site of distant metastases of extrathoracic tumors; it is the only site of such metastases in 20% of cases. In recent years, image-guided thermoablation has been used with increasing frequency in patients who are unable to undergo surgery for medical reasons.
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Uniform polymer microspheres: monodispersity criteria, methods of formation and applications.
Nanomedicine (Lond)
PUBLISHED: 02-12-2013
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For many applications, polymer microspheres (MS) should possess a monodisperse size distribution. With such uniformity they are able to deliver precise amounts of drug per MS, optimize the release kinetics of an encapsulated drug, obtain repeatable in vivo biodistributions to different organs and tissues, and obtain the maximum protection of (protein) drugs from degradation. This review classifies monodisperse polymer MS according to their methods of production and gives examples of the formation of uniform MS and their applications in the medical field. In the literature, the term monodisperse is often used inaccurately, and this article attempts to rectify this by clearly defining monodispersity in terms of the coefficient of variation and the polydispersity index, the two statistical quantities most frequently used to describe the size distribution of MS.
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Extended resection of a plasmocytoma of bone and an amyloidoma of the chest wall.
Ann. Thorac. Surg.
PUBLISHED: 02-03-2013
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Solitary plasmocytoma of bone is a rare condition of plasma cell neoplasia that presents as a single lesion. Amyloidoma of the chest wall is an uncommon presentation of solitary tissue amyloid deposition in the absence of systemic light-chain amyloidosis. This report describes a patient with both uncommon conditions. The tumor originated from the spine and invaded the right lung. In this exceedingly rare case, radiotherapy and a two-step resection of the right lower lobe, full-thickness chest wall, diaphragm, and vertebral body of T9 provided local control of the tumor. Spondylodesis of T7 to T11 provided spine stability.
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Immunopathology of immune reconstitution inflammatory syndrome in Whipples disease.
J. Immunol.
PUBLISHED: 01-30-2013
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During antimicrobial treatment of classic Whipples disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4(+) T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3(+), predominantly CD45RO(+)CD4(+) T cells. In the periphery, initial reduction of CD4(+) cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4(+) T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4(+) T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei-specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4(+) T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.
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A similar but distinctive pattern of impaired cortical excitability in first-episode schizophrenia and ADHD.
Neuropsychobiology
PUBLISHED: 01-04-2013
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First-episode schizophrenia (FE-SZ) and attention deficit hyperactivity disorder (ADHD) are both neuropsychiatric disorders associated with an impaired dopaminergic transmission. Though displaying different clinical phenotypes, a common pathophysiological pathway is discussed controversially. Several studies using transcranial magnetic stimulation (TMS) revealed abnormalities in human motor cortex excitability in both schizophrenia and ADHD patients. Studies on cortical excitability comparing these two diseases directly are lacking.
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Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipples disease.
J. Infect.
PUBLISHED: 01-03-2013
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There is no agreement on how and for how long Whipples disease should be treated. In a randomized trial it was shown that patients can be cured with ceftriaxone or meropenem followed by trimethoprim-sulfamethoxazole for 12 months. The present study tested whether trimethoprim-sulfamethoxazole for three months is sufficient.
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The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23.
PLoS ONE
PUBLISHED: 01-01-2013
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Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4(+) and CD8(+) T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs), which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S) 19, which has previously been employed successfully to vaccinate cattle.
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High frequency of Tropheryma whipplei in culture-negative endocarditis.
J. Clin. Microbiol.
PUBLISHED: 11-30-2011
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"Classical" Whipples disease (cWD) is caused by Tropheryma whipplei and is characterized by arthropathy, weight loss, and diarrhea. T. whipplei infectious endocarditis (TWIE) is rarely reported, either in the context of cWD or as isolated TWIE without signs of systemic infection. The frequency of TWIE is unknown, and systematic studies are lacking. Here, we performed an observational cohort study on the incidence of T. whipplei infection in explanted heart valves in two German university centers. Cardiac valves from 1,135 patients were analyzed for bacterial infection using conventional culture techniques, PCR amplification of the bacterial 16S rRNA gene, and subsequent sequencing. T. whipplei-positive heart valves were confirmed by specific PCR, fluorescence in situ hybridization, immunohistochemistry, histological examination, and culture for T. whipplei. Bacterial endocarditis was diagnosed in 255 patients, with streptococci, staphylococci, and enterococci being the main pathogens. T. whipplei was the fourth most frequent pathogen, found in 16 (6.3%) cases, and clearly outnumbered Bartonella quintana, Coxiella burnetii, and members of the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In this cohort, T. whipplei was the most commonly found pathogen associated with culture-negative infective endocarditis.
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Cold acclimation induces changes in Arabidopsis tonoplast protein abundance and activity and alters phosphorylation of tonoplast monosaccharide transporters.
Plant J.
PUBLISHED: 11-16-2011
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Because they are immotile organisms, higher plants have developed efficient strategies for adaptation to temperature changes. During cold acclimation, plants accumulate specific types of solutes to enhance freezing tolerance. The vacuole is a major solute storage organelle, but until now the role of tonoplast proteins in cold acclimation has not been investigated. In a comparative tonoplast proteome analysis, we identified several membrane proteins with altered abundance upon cold acclimation. We found an increased protein abundance of the tonoplast pyrophosphatase and subunits of the vacuolar V-ATPase and a significantly increased V-ATPase activity. This was accompanied by increased vacuolar concentrations of dicarbonic acids and soluble sugars. Consistently, the abundance of the tonoplast dicarbonic acid transporter was also higher in cold-acclimatized plants. However, no change in the protein abundance of tonoplast monosaccharide transporters was detectable. However, a generally higher cold-induced phosphorylation of members of this sugar transporter sub-group was observed. Our results indicate that cold-induced solute accumulation in the vacuole is mediated by increased acidification of this organelle. Thus solute transport activity is either modulated by increased protein amounts or by modification of proteins via phosphorylation.
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Advanced REACH Tool (ART): overview of version 1.0 and research needs.
Ann Occup Hyg
PUBLISHED: 11-15-2011
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This paper provides an outline of the Advanced REACH Tool (ART) version 1.0 and a discussion of how it could be further developed. ART is a higher tier exposure assessment tool that combines mechanistically modelled inhalation exposure predictions with available exposure data using a Bayesian approach. ART assesses exposure for scenarios across different plants and sites. Estimates are provided for different percentiles of the exposure distribution and confidence intervals around the estimate. It also produces exposure estimates in the absence of data, but uncertainty of the estimates will decrease when results of exposure measurements are included. The tool has been calibrated using a broad range of exposure data and provides estimates for exposure to vapours, mists, and dusts. ART has a robust and stable conceptual basis but will be refined in the future and should therefore be considered an evolving system. High-priority areas for future research are identified in this paper and include the integration of partially analogous measurement series, inclusion of company and site-specific assessments, user decision strategies linked to ART predictions, evaluation of validity and reliability of ART, exploring the possibilities for incorporating the dermal route and integration of ART predictions with tools for modelling internal dose. ART is initially developed in the scope of REACH but is equally useful for exposure assessment in other areas.
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Hippocampal integrity and neurocognition in first-episode schizophrenia: A multidimensional study.
World J. Biol. Psychiatry
PUBLISHED: 11-02-2011
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Abstract Objectives. Impairments in memory and executive function are key components of schizophrenia. These disturbances have been linked to several subcortical and cortical networks. For example, anatomical and functional changes in the hippocampus have been linked to deficits in these cognitive domains. However, the association between hippocampal morphometry, neurochemistry and function is controversial. Therefore, we aimed to investigate the relationship between hippocampal anomalies and their functional relevance. Methods. Fifty-seven first-episode schizophrenia patients (FE-SZ) and 61 healthy control subjects (HC) participated in this study. Hippocampal volumes were investigated using structural magnetic resonance imaging (sMRI) and hippocampal neurochemistry was determined using proton magnetic resonance spectroscopy (1H MRS). Verbal memory was used as a hippocampus-dependent cognitive task whereas working memory and cognitive flexibility assessed frontal lobe function. Results. FE-SZ presented smaller volumes of the left hippocampus, with a significant correlation between left hippocampal volume and verbal memory performance (immediate recall). There was also an inverse correlation between neurochemical ratios (NAA/Cho and Cho/Cr) and verbal memory (delayed recognition). Tests of cognitive flexibility and working memory were not correlated with MRI and 1H MRS values. Compared to HC, FE-SZ demonstrated reduced performance in all of the assessed neurocognitive domains. Conclusions. These results point to a relationship between verbal memory and hippocampal integrity in schizophrenia patients which might be independent from deficits in other memory domains. Disturbed verbal memory functions in FE-SZ might be linked specifically to hippocampal function.
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Advanced Reach Tool (ART): development of the mechanistic model.
Ann Occup Hyg
PUBLISHED: 10-14-2011
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This paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure for workers sharing similar operational conditions across different industries and locations in Europe. The ART mechanistic model is based on a conceptual framework that adopts a source receptor approach, which describes the transport of a contaminant from the source to the receptor and defines seven independent principal modifying factors: substance emission potential, activity emission potential, localized controls, segregation, personal enclosure, surface contamination, and dispersion. ART currently differentiates between three different exposure types: vapours, mists, and dust (fumes, fibres, and gases are presently excluded). Various sources were used to assign numerical values to the multipliers to each modifying factor. The evidence used to underpin this assessment procedure was based on chemical and physical laws. In addition, empirical data obtained from literature were used. Where this was not possible, expert elicitation was applied for the assessment procedure. Multipliers for all modifying factors were peer reviewed by leading experts from industry, research institutes, and public authorities across the globe. In addition, several workshops with experts were organized to discuss the proposed exposure multipliers. The mechanistic model is a central part of the ART tool and with advancing knowledge on exposure, determinants will require updates and refinements on a continuous basis, such as the effect of worker behaviour on personal exposure, best practice values that describe the maximum achievable effectiveness of control measures, the intrinsic emission potential of various solid objects (e.g. metal, glass, plastics, etc.), and extending the applicability domain to certain types of exposures (e.g. gas, fume, and fibre exposure).
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Classification of occupational activities for assessment of inhalation exposure.
Ann Occup Hyg
PUBLISHED: 09-15-2011
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There is a large variety of activities in workplaces that can lead to emission of substances. Coding systems based on determinants of emission have so far not been developed. In this paper, a system of Activity Classes and Activity Subclasses is proposed for categorizing activities involving chemical use. Activity Classes share their so-called emission generation mechanisms and physical state of the product handled and the underlying determinants of emission. A number of (industrial) stakeholders actively participated in testing and fine-tuning the system. With the help of these stakeholders, it was found to be relatively easy to allocate a large number of activities to the Activity Classes and Activity Subclasses. The system facilitates a more structured classification of activities in exposure databases, a structured analysis of the analogy of exposure activities, and a transparent quantification of the activity emission potential in (new) exposure assessment models. The first use of the system is in the Advanced REACH Tool.
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Modulation of the CD4+ T-cell response by Helicobacter pylori depends on known virulence factors and bacterial cholesterol and cholesterol ?-glucoside content.
J. Infect. Dis.
PUBLISHED: 09-15-2011
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Helicobacter pylori blocks the proliferation of human CD4(+) T cells, facilitated by vacuolating exotoxin (VacA) and ?-glutamyl transpeptidase (GGT). H. pylori-triggered T-cell reactions in mice correlate with bacterial cholesterol and cholesterol ?-glucoside content but their role in human cells is unclear. We characterized the effect of VacA, GGT, and cholesterol on T-helper 1, T-helper 2, T-regulatory and T-helper 17 associated cytokines and T-cell proliferation. VacA, GGT, and bacterial cholesterol content exhibited differential and synergistic inhibitory effects on the expression of activation markers CD25 and CD69 and on interleukin 2, interleukin 4, interleukin 10, and interferon ? production. These factors did not affect the H. pylori-mediated abrogation of transforming growth factor ? secretion or increased interleukin 6 production. Cholesterol ?-glucosyltransferase-deficient bacteria exerted strongly reduced antiproliferative effects on primary human CD4(+) T cells. In conclusion, H. pylori shapes rather than suppresses human CD4(+) T-cell responses, and glucosylated cholesterol is a relevant bacterial component involved in this modulation.
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Regulatory T cells in patients with Whipples disease.
J. Immunol.
PUBLISHED: 09-14-2011
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Classical Whipples disease (CWD) is caused by chronic infection with Tropheryma whipplei that seems to be associated with an underlying immune defect. The pathognomonic hallmark of CWD is a massive infiltration of the duodenal mucosa with T. whipplei-infected macrophages that disperse systemically to many other organ systems. An alleviated inflammatory reaction and the absence of T. whipplei-specific Th1 reactivity support persistence and systemic spread of the pathogen. In this article, we hypothesized that regulatory T cells (T(reg)) are involved in immunomodulation in CWD, and we asked for the distribution, activation, and regulatory capacity of T(reg) in CWD patients. Whereas in the lamina propria of CWD patients before treatment numbers of T(reg) were increased, percentages in the peripheral blood were similar in CWD patients and healthy controls. However, peripheral T(reg) of CWD patients were more activated than those of controls. Elevated secretion of IL-10 and TGF-? in the duodenal mucosa of CWD patients indicated locally enhanced T(reg) activity. Enhanced CD95 expression on peripheral memory CD4(+) T cells combined with reduced expression of IFN-? and IL-17A upon polyclonal stimulation by CD4(+) cells from untreated CWD patients further hinted to T(reg) activity-related exhaustion of effector CD4(+) T cells. In conclusion, increased numbers of T(reg) can be detected within the duodenal mucosa in untreated CWD, where huge numbers of T. whipplei-infected macrophages are present. Thus, T(reg) might contribute to the chronic infection and systemic spread of T. whipplei in CWD but in contrast prevent mucosal barrier defect by reducing local inflammation.
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Reduction of gyrification index in the cerebellar vermis in schizophrenia: a post-mortem study.
World J. Biol. Psychiatry
PUBLISHED: 09-13-2011
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In schizophrenia, alterations of the gyrification index (GI) have been measured in cortical brain regions and are related to neurodevelopmental disturbances. Cerebellar regions have been implicated in the pathophysiology of schizophrenia; however, the GI has not been investigated here so far.
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Dual role of the mitochondrial protein frataxin in astrocytic tumors.
Lab. Invest.
PUBLISHED: 08-22-2011
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The mitochondrial protein frataxin (FXN) is known to be involved in mitochondrial iron homeostasis and iron-sulfur cluster biogenesis. It is discussed to modulate function of the electron transport chain and production of reactive oxygen species (ROS). FXN loss in neurons and heart muscle cells causes an autosomal-dominant mitochondrial disorder, Friedreichs ataxia. Recently, tumor induction after targeted FXN deletion in liver and reversal of the tumorigenic phenotype of colonic carcinoma cells following FXN overexpression were described in the literature, suggesting a tumor suppressor function. We hypothesized that a partial reversal of the malignant phenotype of glioma cells should occur after FXN transfection, if the mitochondrial protein has tumor suppressor functions in these brain tumors. In astrocytic brain tumors and tumor cell lines, we observed reduced FXN levels compared with non-neoplastic astrocytes. Mitochondrial content (citrate synthase activity) was not significantly altered in U87MG glioblastoma cells stably overexpressing FXN (U87-FXN). Surprisingly, U87-FXN cells exhibited increased cytoplasmic ROS levels, although mitochondrial ROS release was attenuated by FXN, as expected. Higher cytoplasmic ROS levels corresponded to reduced activities of glutathione peroxidase and catalase, and lower glutathione content. The defect of antioxidative capacity resulted in increased susceptibility of U87-FXN cells against oxidative stress induced by H(2)O(2) or buthionine sulfoximine. These characteristics may explain a higher sensitivity toward staurosporine and alkylating drugs, at least in part. On the other hand, U87-FXN cells exhibited enhanced growth rates in vitro under growth factor-restricted and hypoxic conditions and in vivo using tumor xenografts in nude mice. These data contrast to a general tumor suppressor function of FXN but suggest a dual, pro-proliferative but chemosensitizing role in astrocytic tumors.
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Quasi-light-storage enhancement by reducing the Brillouin gain bandwidth.
Appl Opt
PUBLISHED: 08-12-2011
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The quasi-light-storage (QLS) is a method for the variable and almost distortion free storage of optical data which is based on stimulated Brillouin scattering (SBS). The natural gain bandwidth of SBS limits the storage time of this method to up to 100?ns. We overcome this limit by the superposition of the SBS gain bandwidth with two losses. With this narrowed gain bandwidth, we were able to enhance the storage time for the QLS by 40%.
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Selective antimicrobial activity associated with sulfur nanoparticles.
J Biomed Nanotechnol
PUBLISHED: 08-12-2011
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Many sulfur compounds are known to exhibit widespread antimicrobial activity. The latter is often the result of an intricate redox biochemistry whereby reactive sulfur species, such as organic polysulfanes, interact with pivotal cellular signaling pathways. The S8 unit in elemental sulfur resembles certain aspects of the chemistry of polysulfanes. As a consequence, water-soluble S8-sulfur nanoparticles are active against some smaller organisms, including nematodes, yet are non-toxic against human cells. In contrast, selenium and tellurium nanoparticles are less active. Together, the ease of production of the sulfur nanoparticles, their chemical stability in aqueous dispersion, amenable physical properties and selective toxicity, turn sulfur nanoparticles into promising antimicrobial prototypes for medical as well as agricultural applications.
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Molecular plasmonics: light meets molecules at the nanoscale.
Philos Trans A Math Phys Eng Sci
PUBLISHED: 08-03-2011
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Certain metal nanoparticles exhibit the effect of localized surface plasmon resonance when interacting with light, based on collective oscillations of their conduction electrons. The interaction of this effect with molecules is of great interest for a variety of research disciplines, both in optics and in the life sciences. This paper attempts to describe and structure this emerging field of molecular plasmonics, situated between the molecular world and plasmonic effects in metal nanostructures, and demonstrates the potential of these developments for a variety of applications.
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Brillouin scattering gain bandwidth reduction down to 3.4MHz.
Opt Express
PUBLISHED: 06-07-2011
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We present a simple method for the stimulated Brillouin scattering (SBS) gain bandwidth reduction in an optical fiber. We were able to reduce the natural bandwidth of 20 MHz to around 3.4 MHz by a superposition of the gain with two losses produced by the same source. This reduced bandwidth can drastically enhance the performance of many different applications which up to now were limited by the minimum of the natural SBS bandwidth.
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Localized leishmanial lymphadenopathy: an unusual manifestation of leishmaniasis in a traveler in southern Europe.
Vector Borne Zoonotic Dis.
PUBLISHED: 05-25-2011
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A 38-year-old male patient presented with enlarged nuchal and sinistral supraclavicular lymph nodes of about 1-month history. He had no further signs or symptoms of disease and was not immunocompromised. His travel history included India, South America, and Africa but only southern Europe during more recent years. Leishmania parasites were histologically detected in a lymph node and Leishmania (Leishmania) infantum, the causative species of leishmaniasis in the European Mediterranean area, was identified by PCR and sequencing. Leishmanial infection should be included in the differential diagnosis of localized lymph node enlargement in returnees from endemic countries including southern Europe.
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Non-small cell lung cancer induces an immunosuppressive phenotype of dendritic cells in tumor microenvironment by upregulating B7-H3.
J Thorac Oncol
PUBLISHED: 05-21-2011
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Tumors may shift the phenotype and function of dendritic cells (DC) toward the induction of tolerance. In the status of full maturity, DC express a multitude of T cell costimulatory molecules enabling them to induce immune reactions, whereas nonactivated resident DC lack these T cell stimulating capacities. Therefore, we investigated the changes in DC phenotype and expression of B7-H molecules induced by non-small cell lung cancer (NSCLC).
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Systematic investigation of droplet generation at T-junctions.
Lab Chip
PUBLISHED: 05-17-2011
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Droplet microfluidics has attracted much attention in recent years. For many droplet-based applications, researchers want to predict the size of the droplets in a certain experimental condition. To meet this need, van Steijn and colleagues proposed an elegant theoretical model that predicts the volume of droplets generated in a common channel configuration for forming a steady-state, continuous stream of droplets, the T-junction geometry. To determine the accuracy of this model in predicting droplet volume, we performed a systematic experimental study over two orders of magnitude in capillary number. We found that this model, albeit elegant, has a limited range of interfacial tension over which it can predict accurately the droplet volume. Our experimental results, together with fluid dynamic simulations, allowed us to highlight the importance of physical fluid properties when employing theoretical models.
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No improvement after chronic ibuprofen treatment in the 5XFAD mouse model of Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 05-03-2011
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Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that has been reported to reduce the risk of developing Alzheimers disease (AD). Its preventive effects in AD are likely pleiotropic as ibuprofen displays both anti-inflammatory activity by inhibition of cyclooxygenases and anti-amyloidogenic activity by modulation of ?-secretase. In order to study the anti-inflammatory properties of ibuprofen independent of its anti-amyloidogenic activity, we performed a long-term treatment study with ibuprofen in 5XFAD mice expressing a presenilin-1 mutation that renders this AD model resistant to ?-secretase modulation. As expected, ibuprofen treatment for 3 months resulted in a reduction of the inflammatory reaction in the 5XFAD mouse model. Importantly, an unchanged amyloid beta (A?) plaque load, an increase in soluble A?42 levels, and an aggravation of some behavioral parameters were noted, raising the question whether suppression of inflammation by nonsteroidal anti-inflammatory drug is beneficial in AD.
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Impaired long-term depression in schizophrenia: a cathodal tDCS pilot study.
Brain Stimul
PUBLISHED: 04-27-2011
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Neural plasticity involves the reorganization of synaptic connections and represents the ability of the brain to adjust its function in response to challenge. Disturbed cortical plasticity has been linked to the pathophysiology of schizophrenia, with indirect evidence for disturbed plasticity in the disease state having been provided by postmortem studies and various animal models. However, glutamate-dependent long-term depression (LTD)-like cortical plasticity has not yet been investigated.
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Getting the foot out of the pelvis: modeling problems affecting use of SNOMED CT hierarchies in practical applications.
J Am Med Inform Assoc
PUBLISHED: 04-21-2011
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(a) To determine the extent and range of errors and issues in the Systematised Nomenclature of Medicine-Clinical Terms (SNOMED CT) hierarchies as they affect two practical projects. (b) To determine the origin of issues raised and propose methods to address them.
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Cleaning of occluded pancreatic duct endoprostheses: a new indication for extracorporeal shock wave lithotripsy?
Gastrointest. Endosc.
PUBLISHED: 04-20-2011
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Pancreatic duct stenting is widely performed for bridging main pancreatic duct obstruction in patients with chronic pancreatitis. The major limitation is early stent occlusion, making regular stent exchange necessary.
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Effects of chemical and physical parameters in the generation of microspheres by hydrodynamic flow focusing.
Colloids Surf B Biointerfaces
PUBLISHED: 04-20-2011
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Hydrodynamic flow focusing is a seminal, easy-to-use technology for micro- and nanodroplet generation. It is characterized by the co-axial focusing of two (or more) immiscible liquid streams forced through a small orifice. In this method, the outer continuous phase has a much higher flow velocity than the inner disperse phase. While passing through the orifice, the prevailing pressure drop and shear stress force the inner phase to break up into uniform droplets. Using a biodegradable poly(lactide-co-glycolide) (PLGA) polymer solution as the disperse phase, monodisperse and user-defined polymer micro- and nanospheres can be generated. Here we present a consecutive parameter study of hydrodynamic flow focusing to study the effect of chemical and physical parameters that effect the dispersity of the droplets generated in the 1-5 ?m range. The parameter study shows the applicability and challenges of hydrodynamic flow focusing in the preparation of biodegradable microspheres. Applications for microspheres made with this method can be found in the medical, pharmaceutical and technical fields.
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Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation.
Blood
PUBLISHED: 04-12-2011
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Norovirus (NV) infections are a frequent cause of gastroenteritis (GE), but data on this disease in immunocompromised patients are limited. We analyzed an NV outbreak, which affected immunosuppressed patients in the context of chemotherapy or HSCT. On recognition, 7 days after admission of the index patient, preventive measures were implemented. Attack rates were only 3% (11/334) and 10% (11/105) among patients and staff members, respectively. The median duration of symptoms was 7 days in patients compared with only 3 days in staff members (P = .02). Three patients died of the NV infection. Commonly used clinical diagnostic criteria (Kaplan-criteria) were unsuitable because they applied to 11 patients with proven NV-GE but also to 15 patients without NV-GE. With respect to the therapeutic management, it is important to differentiate intestinal GVHD from NV-GE. Therefore, we analyzed the histopathologic patterns in duodenal biopsies, which were distinctive in both conditions. Stool specimens in patients remained positive for NV-RNA for a median of 30 days, but no transmission was observed beyond an asymptomatic interval of 48 hours. NV-GE is a major threat to patients with chemotherapy or HSCT, and meticulous measures are warranted to prevent transmission of NV to these patients.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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