Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64$\pm$0.14 and 4.50$\pm$0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88$\pm$0.04 and 0.81$\pm$0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions

Treatment of Angular Deformity and Limb Length Discrepancy With a Retrograde Femur Magnetic Intramedullary Nail: A Fixator-assisted, Blocking Screw Technique

Background: Fixator-assisted nailing techniques that incorporate magnetic internal lengthening nails (MILNs) permit acute deformity correction and then gradual limb lengthening without needing postoperative external fixators. Purposes: We sought to investigate the safety and accuracy of a fixator-assisted, blocking screw technique using retrograde MILNs for the correction of LLD and limb malalignment. Methods: Forty-one patients (13 patients with genu varum and 28 patients with genu valgum) with LLD treated with fixator-assisted, blocking screw retrograde MILN reconstruction were included. Preoperative LLD, mechanical axis deviation, and joint orientation angles were compared with values at the end of treatment, and bone healing indices were calculated. Perioperative complications were tracked. Results: Preoperatively, the mean mechanical lateral distal femoral angle of the varus cohort was 98 ± 12°, whereas the mean lateral distal femoral angle of the valgus cohort was 82±4°. Both cohorts had an average 3-cm LLD. 99% of the planned limb lengthening was achieved. Final LDFAs were 91 ± 6° and 89 ± 4° in the varus and valgus cohorts, respectively, and the limb mechanical axis angles were normalized. 10 patients underwent a total of 21 returns to the operating room. Most commonly, this involved percutaneous injection of bone marrow aspirate concentrate to bone regenerate exhibiting delayed union (6 patients). Conclusions: The use of a retrograde MILN with a fixator-assisted, blocking screw technique is an effective means of acute deformity correction and gradual limb lengthening through minimal incisions. The accuracy of deformity correction relies on intraoperative execution of the appropriate nail start site, osteotomy location, and placement of blocking screws

RELICS: Strong Lens Models for Five Galaxy Clusters From the Reionization Lensing Cluster Survey

Strong gravitational lensing by galaxy clusters magnifies background galaxies, enhancing our ability to discover statistically significant samples of galaxies at z>6, in order to constrain the high-redshift galaxy luminosity functions. Here, we present the first five lens models out of the Reionization Lensing Cluster Survey (RELICS) Hubble Treasury Program, based on new HST WFC3/IR and ACS imaging of the clusters RXC J0142.9+4438, Abell 2537, Abell 2163, RXC J2211.7-0349, and ACT-CLJ0102-49151. The derived lensing magnification is essential for estimating the intrinsic properties of high-redshift galaxy candidates, and properly accounting for the survey volume. We report on new spectroscopic redshifts of multiply imaged lensed galaxies behind these clusters, which are used as constraints, and detail our strategy to reduce systematic uncertainties due to lack of spectroscopic information. In addition, we quantify the uncertainty on the lensing magnification due to statistical and systematic errors related to the lens modeling process, and find that in all but one cluster, the magnification is constrained to better than 20% in at least 80% of the field of view, including statistical and systematic uncertainties. The five clusters presented in this paper span the range of masses and redshifts of the clusters in the RELICS program. We find that they exhibit similar strong lensing efficiencies to the clusters targeted by the Hubble Frontier Fields within the WFC3/IR field of view. Outputs of the lens models are made available to the community through the Mikulski Archive for Space TelescopesComment: Accepted to Ap

Using Land-Based Surveys to Assess Sea Duck Abundance and Behavior in Nearshore Waters of Southern New England, USA

Nearshore waters provide very important habitat for sea ducks (Tribe Mergini) during migration and winter, but gathering information on sea duck use of shallow nearshore waters is challenging because traditional aerial and boat-based surveys are expensive, are usually conducted infrequently, and are often not feasible near the coast. The objective of this study was to use land-based surveys to characterize spatiotemporal variation in the abundance and behavior (e.g., foraging, flying) of Common Eider (Somateria mollissima) and scoters (Melanitta spp.) in nearshore waters of southern New England. Surveys (60–120 min per survey, n = 1,044 surveys) were conducted throughout the day from February 2009 to July 2010 to assess diurnal and seasonal variation in sea duck behavior and spatial distribution at nine sites in southern Rhode Island. The density of sea ducks resting or foraging on the water exhibited little diurnal variation, whereas flight activity dramatically increased nearer to sunrise. Sea duck densities and passage rates (individuals/km2/hr) peaked during migration periods from October through November and February through April, although there were important seasonal differences between sites. For example, the highest densities of Common Eider during fall were in a protected estuary, whereas abundance of scoters during fall was greater at a coastal headland. The relative activity of Common Eider on the water and in flight was similar among sites, whereas scoters exhibited highly variable activity among sites, particularly during winter and spring. The spatiotemporal patterns in abundance and behavior of sea ducks in nearshore waters that we detected using land-based surveys provides essential, complementary information to that available from other types of waterfowl and seabird surveys in southern New England

The Impact of the Human DNA Topoisomerase II C-Terminal Domain on Activity

Type II DNA topoisomerases (topos) are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD) of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs

Early stroke-related deep venous thrombosis: risk factors and influence on outcome

Deep venous thrombosis (DVT) is a serious complication of various medical conditions including acute stroke. Our aim was to identify the occurrence of early stroke-related DVT, risk factors for its development and the influence on outcome. The study involved consecutive patients admitted to our center due to acute ischaemic (n = 278) or haemorrhagic (n = 12) stroke during a 16-month period. We collected data on their pre-stroke health status, neurological deficit on admission and baseline serum CRP and fibrinogen level. Ultrasonographic imaging was performed at the 3rd (IQR: 2–4) and 9th (IQR: 8–9) day after stroke. Patients thrombosis occurring between the first and second examination comprised the newly developed early stroke-related DVT group. We found DVT in 8.0% (24/299) of patients at initial evaluation. Newly developed DVT was present in 3.0% (9/299) of patients, and was predominantly distal (7 of 9 cases). It was associated with elevated serum CRP level (OR 8.75; 95%CI: 1.61–47.6), which was verified in a model adjusted for stroke severity and pre-stroke dependency (3–5 pts. in mRS). In a multivariate model, newly developed DVT significantly increased the risk of 3-month mortality (OR 12.4; 95%CI: 1.72–89.4), without affecting the combined risk of dependency and death (OR 2.57; 95%CI: 0.39–17.0). Early stroke-related DVT is an infrequent complication. However, it may be an independent risk factor for 3-month mortality. Increased serum CRP level combined with normal fibrinogen level seems predictive for development of DVT. It may be reasonable to provide those patients with additional DVT prophylaxis

A infância representada no livro escolar: tipos de textos e estereótipos sociais

Esta investigação inscreve-se dominantemente no âmbito dos estudos da criança e ancora a sua área específica nas questões linguísticas, assumindo os pressupostos teóricos e metodológicos da análise do discurso (de tradição francófona), considerando também contributos de áreas conexas. Analisa textos de manuais/livros escolares usados no sistema de ensino português, pretendendo tornar visíveis as imagens que estes constroem das crianças e da infância, bem como os recursos linguísticos mais relevantes associados a tal construção. Procura desvendar a representatividade das tipologias textuais nos manuais e de que forma estas contribuem para a construção das referidas imagens. Conclui que as crianças dos textos são seres sem voz e sem poder, consumidoras, mas não coprodutoras de cultura, com os textos inculcando valores conformadores da manutenção da ordem social estabelecida, sendo a forma como as tipologias textuais estão organizadas contribuidora para se alcançar esse propósito.This research forms primarily part of the child studies and is based on its specific field of linguistic issues, assuming the theoretical and methodological assumptions of the speech analysis (of French-speaking tradition), having also regard the inputs of related fields. It analyses texts from handbooks/textbooks used on the Portuguese educational system, intending to reveal pictures that these books construct about children and childhood, as well as the most relevant linguistic resources associated with such construction. This paper aims at unravelling the representation of the text typologies in the handbooks and how these can contribute for building of such pictures. From this, one can conclude that children from the texts are voiceless and have no power, they are consumers but not co-producers of culture, with these texts instilling conservative values for maintaining the established social order, but also that the way texts typologies are organized to contribute for reaching that propose.Esta investigación se ensere en el ámbito de los estudios del niño y más precisamente en la área de las cuestiones lingüísticas, asumiendo los presupuestos teóricos e metodológicos de la análisis del discurso (de tradición francófona), considerando también aportes de las áreas conexas. Analiza textos de manuales/libros escolares usados en el sistema de enseñanza portugués, pretendiendo tornar visibles las imágenes que este construyen de los niños y de la infancia, bien como los recursos lingüísticos más relevantes asociados a esa construcción. Busca desvendar la representatividad de las tipologías textuales en los manuales y de qué forma contribuyen para la construcción de las referidas imágenes. Concluye que los niños de los textos son seres sin voz y sin poder, consumidores, pero no coproductores de cultura y que los textos inculcan valores conformadores de manutención del orden social establecido, mas también que la forma como las tipologías textuales están organizadas contribuye para alcanzar ese propósito.CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT), Portugal. Fundos Nacionais através da FCT (Fundação para a Ciência e a Tecnologia) e cofinanciado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) através do COMPETE 2020 – Programa Operacional Competitividade e Internacionalização (POCI) no âmbito do CIEC (Centro de Investigação em Estudos da Criança, da Universidade do Minho) com a referência POCI-01-0145-FEDER-007562info:eu-repo/semantics/publishedVersio

Bile Acid-Induced Virulence Gene Expression of Vibrio parahaemolyticus Reveals a Novel Therapeutic Potential for Bile Acid Sequestrants

Vibrio parahaemolyticus, a bacterial pathogen, causes human gastroenteritis. A type III secretion system (T3SS2) encoded in pathogenicity island (Vp-PAI) is the main contributor to enterotoxicity and expression of Vp-PAI encoded genes is regulated by two transcriptional regulators, VtrA and VtrB. However, a host-derived inducer for the Vp-PAI genes has not been identified. Here, we demonstrate that bile induces production of T3SS2-related proteins under osmotic conditions equivalent to those in the intestinal lumen. We also show that bile induces vtrA-mediated vtrB transcription. Transcriptome analysis of bile-responsive genes revealed that bile strongly induces expression of Vp-PAI genes in a vtrA-dependent manner. The inducing activity of bile was diminished by treatment with bile acid sequestrant cholestyramine. Finally, we demonstrate an in vivo protective effect of cholestyramine on enterotoxicity and show that similar protection is observed in infection with a different type of V. parahaemolyticus or with non-O1/non-O139 V. cholerae strains of vibrios carrying the same kind of T3SS. In summary, these results provide an insight into how bacteria, through the ingenious action of Vp-PAI genes, can take advantage of an otherwise hostile host environment. The results also reveal a new therapeutic potential for widely used bile acid sequestrants in enteric bacterial infections