Posthole Sensor Performance in the USArray Transportable Array - Results from Testing and Initial Deployments in Alaska and Canada

NASA Astrophysics Data System (ADS)

Frassetto, A.; Busby, R. W.; Hafner, K.; Sauter, A.; Woodward, R.

2014-12-01

To prepare for the deployment of EarthScope's USArray Transportable Array (TA) in Alaska and adjacent Canada over the next several years, IRIS has evaluated different strategies for emplacing posthole seismometers. The goal of this work has been to maintain or enhance a TA station's noise performance while reducing the weight and logistical considerations required for its installation. Motivating this research are developments in posthole broadband seismometer design and the unique conditions for operating in this region, where many potential sites are located on frost-fractured outcrops or underlain by permafrost, in either case only accessible by helicopter. Current emplacement methods use a portable rig to auger or hammer-drill a hole 2.5-5 meters deep, in unconsolidated materials and permafrost, or by diamond bit coring 1-3 meters into rock. These emplacements are used at new TA installations and upgrades to existing AK network stations, and we compare their performance to the lower-48 TA vault installations. Through July 2014 there are eight TA and six upgraded AK stations operating under USArray; including five since at least October 2012, providing a detailed record of seasonal and/or site-specific behavior. We also discuss testing of different downhole configurations for 13 stations deployed at Piñon Flat Observatory in California since April 2014. Station performance is presented and compared using probability density functions summed from hourly power spectral density calculations. These are computed for the continuous time series of seismic data recorded on each seismic channel. Our results show that the noise performance of seismometers in Alaska with cased- or core- hole installations sometimes exceeds that of the quietest TA stations in the lower-48, particularly for the horizontal channels at long periods. We analyze and discuss the performance of example stations, comparing to other nearby seismometers. We also examine the performance of AK stations before and after they have been converted from surface vault to posthole configuration. At Piñon Flat, different methods for packing the seismometer and clamping its cables within cased holes has guided development of field procedure. The new posthole emplacements generally improve upon the mean performance of the lower-48 TA vaults.

Recent advances in enhanced luminescence upconversion of lanthanide-doped NaYF4 phosphors

NASA Astrophysics Data System (ADS)

Kumar, Deepak; Verma, Kartikey; Verma, Shefali; Chaudhary, Babulal; Som, Sudipta; Sharma, Vishal; Kumar, Vijay; Swart, Hendrik C.

2018-04-01

NaYF4 is regarded as the best upconversion (UC) matrix owing to its low phonon energy, more chemical stability, and a superior refractive index. This review reports on the various synthesis techniques of lanthanide-doped NaYF4 phosphors for UC application. The UC intensity depends on different properties of the matrix and those are discussed in detail. Plasmon-enhanced luminescence UC of the lanthanide-doped NaYF4 core-shells structure is discussed based on a literature survey. The present review provides the information about how the UC intensity can be enhanced. The idea about the UC is then deliberately used for versatile applications such as luminescent materials, display devices, biomedical imaging and different security appliances. In addition, the present review demonstrates the recent trends of NaYF4 UC materials in solar cell devices. The role of NaYF4 phosphor to eradicate the spectral variance among the incident solar spectrum, semiconductor as well as the sub-band gap nature of the semiconductor materials is also discussed in detail. Considering the fact that the research status on NaYF4 phosphor for photovoltaic application is now growing, the present review is therefore very important to the researchers. More importantly, this may promote more interesting research platforms to investigate the realistic use of UC nanophosphors as spectral converters for solar cells.

On thermohydrologic conditions near high-level nuclear wastes emplaced in partially saturated fractured tuff: 1. Simulation studies with explicit consideration of fracture effects

NASA Astrophysics Data System (ADS)

Pruess, K.; Wang, J. S. Y.; Tsang, Y. W.

1990-06-01

We have performed modeling studies on the simultaneous transport of heat, liquid water, vapor, and air in partially saturated, fractured porous rock. Formation parameters were chosen as representative of the potential nuclear waste repository site in the Topopah Spring unit of the Yucca Mountain tuffs. The presence of fractures makes the transport problem very complex, both in terms of flow geometry and physics. The numerical simulator used for our flow calculations takes into account most of the physical effects believed to be important in multiphase fluid and heat flow. It has provisions for handling the extreme nonlinearities that arise in phase transitions, component disappearances, and capillary discontinuities at fracture faces. We model a region around an infinite linear string of nuclear waste canisters, taking into account both the discrete fractures and the porous matrix. Thermohydrologic conditions in the vicinity of the waste packages are found to depend strongly on relative permeability and capillary pressure characteristics of the fractures, which are unknown at the present time. If liquid held on the rough walls of drained fractures is assumed to be mobile, strong heat pipe effects are predicted. Under these conditions the host rock will remain in two-phase conditions right up to the emplacement hole, and formation temperatures will peak near 100°C. If it is assumed that liquid cannot move along drained fractures, the region surrounding the waste packages is predicted to dry up, and formation temperatures will rise beyond 200°C. A substantial fraction of waste heat can be removed if emplacement holes are left open and ventilated, as opposed to backfilled and sealed emplacement conditions. Comparing our model predictions with observations from in situ heater experiments reported by Zimmerman and coworkers, some intriguing similarities are noted. However, for a quantitative evaluation, additional carefully controlled laboratory and field experiments will be needed.

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

PubMed

Parian, Alyssa; Limketkai, Berkeley; Koh, Joyce; Brant, Steven R; Bitton, Alain; Cho, Judy H; Duerr, Richard H; McGovern, Dermot P; Proctor, Deborah D; Regueiro, Miguel D; Rioux, John D; Schumm, Phil; Taylor, Kent D; Silverberg, Mark S; Steinhart, A Hillary; Hernaez, Ruben; Lazarev, Mark

2017-08-01

Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Human umbilical cord mesenchymal stem cells increase interleukin-9 production of CD4+ T cells

PubMed Central

Yang, Zhou Xin; Chi, Ying; Ji, Yue Ru; Wang, You Wei; Zhang, Jing; Luo, Wei Feng; Li, Li Na; Hu, Cai Dong; Zhuo, Guang Sheng; Wang, Li Fang; Han, Zhi-Bo; Han, Zhong Chao

2017-01-01

Mesenchymal stem cells (MSC) are able to differentiate into cells of multiple lineage, and additionally act to modulate the immune response. Interleukin (IL)-9 is primarily produced by cluster of differentiation (CD)4+ T cells to regulate the immune response. The present study aimed to investigate the effect of human umbilical cord derived-MSC (UC-MSC) on IL-9 production of human CD4+ T cells. It was demonstrated that the addition of UC-MSC to the culture of CD4+ T cells significantly enhanced IL-9 production by CD4+ T cells. Transwell experiments suggested that UC-MSC promotion of IL-9 production by CD4+ T cells was dependent on cell-cell contact. Upregulated expression of CD106 was observed in UC-MSC co-cultured with CD4+ T cells, and the addition of a blocking antibody of CD106 significantly impaired the ability of UC-MSC to promote IL-9 production by CD4+ T cells. Therefore, the results of the present study demonstrated that UC-MSC promoted the generation of IL-9 producing cells, which may be mediated, in part by CD106. The findings may act to expand understanding and knowledge of the immune modulatory role of UC-MSC. PMID:29042945

In situ rock strength and far field stress in the Nankai accretionary complex: Integration of downhole data from multiple wells

NASA Astrophysics Data System (ADS)

Huffman, K. A.; Saffer, D. M.

2014-12-01

Knowing the magnitude of tectonic stress and rock strength at seismically active margins is important towards understanding fault strength and failure mechanics, yet both are difficult to measure in situ. Recent work at subduction margins, including Integrated Ocean Drilling Program (IODP) Nankai Trough Subduction Zone Experiment (NanTroSEIZE) drillsites, uses the width of compressional wellbore breakouts (BO), which depends on far field stress conditions, rock strength, and borehole annular pressure (APRS), to estimate the magnitude of horizontal principal stresses (SHmax and Shmin); estimates are problematic due to uncertainty in rock strength (unconfined compressive strength/UCS- for which direct measurements are scarce) and rheology that govern stress distribution at the wellbore. We conduct a novel case study at IODP Site C0002, where a hole was drilled twice with different boundary conditions, providing an opportunity to define in situ stress and strength from field data. Site C0002 is the main deep riser borehole for NanTroSEIZE, located near the seaward edge of the Kumano Basin above the seismogenic plate boundary, ~30 km from the trench. Several boreholes were drilled at the site. During IODP Expedition 314 in 2007, Hole C0002A was drilled with a suite of logging while drilling (LWD) tools to 1401 mbsf in a riserless mode. Hole C0002F, ~70 m away, was drilled to 862 mbsf in riserless mode during Exp. 326 in 2010 and deepened to 2005 mbsf in a riser mode during Expedition 338 in 2012-2013. Increased APRS achieved by riser drilling stabilizes the borehole and suppresses BO, consistent with resistivity imaging data from Exp. 314 that document well-developed, continuous BO throughout the borehole, and data from Expedition 338 indicating few BO. We use a semi-Newtonian approach to solve for stress and UCS consistent with the observed BO width and measured APRS in the two holes over the interval from 862-2005 mbsf. Effective SHmax ranges from ~10-30 MPa and indicate a strike-slip or thrust regime. Our results indicate UCS is higher than predicted by empirical relations and a small suite of laboratory tests by as much as 20 MPa. This apparent discrepancy may indicate that the failure criterion, or assumed distribution of stresses around the wellbore in analyses of far field stress, may not be appropriate in this setting.

Stability and adaptability of popcorn genotypes in the State of Rio de Janeiro, Brazil.

PubMed

Pena, G F; do Amaral, A T; Gonçalves, L S A; Candido, L S; Vittorazzi, C; Ribeiro, R M; Freitas, S P

2012-08-31

This study aimed to obtain estimates of stability and adaptability of phase launched materials and materials recommended in the country, for the northern and northwestern regions of Rio de Janeiro State, Brazil, and made a comparative analysis of different methods to evaluate stability and adaptability of grain yield and popping expansion. To this end, 10 genotypes were evaluated (UNB2U-C3, UNB2U-C4, BRS Angela, Viçosa, Beija-Flor, IAC 112, IAC 125, Zélia, Jade, and UFVM2 Barão de Viçosa) in five environments. The Yates and Cochran method revealed that genotypes UFV2M Barão de Viçosa, BRS Angela and UNB2U-C3 were the most stable for grain yield. This method also indicated superiority of genotypes UNB2U-C3, UNB2U-C4, BRS Angela, Viçosa, IAC 125, and Zélia for popping expansion. The Plaisted and Peterson and Wricke methods demonstrated that genotypes Zélia and UNB2U-C4 were the most productive and stable. These methods indicated genotypes UNB2U-C3 and BRS Angela as the most stable for popping expansion. The Kang and Phan ranking system uses methods based on analysis of variance and classified population UNB2U-C4 as the genotype with the highest stability of grain production and confirmed cultivar BRS Angela as the most stable for popping expansion. Genotypes IAC 112 and UNB2U-C4 were the most stable and adapted for grain yield, according to the Lin and Binns method. The P(i) statistics also ranked UNB2U-C3 and UNB2U-C4 as the genotypes with the best predictability and capacity for popping expansion.

Prevalence of inflammatory bowel disease in two districts of Sri Lanka: a hospital based survey

PubMed Central

2010-01-01

Background Inflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region. Methods To determine prevalence and clinical characteristics of IBD, a hospital-based survey was performed in the Colombo and Gampaha districts (combined population 4.5 million) in Sri Lanka. Patients with established ulcerative colitis (UC) and Crohn's disease (CD), who were permanent residents of these adjoining districts, were recruited from hospital registries and out-patient clinics. Clinical information was obtained from medical records and patient interviews. Results There were 295 cases of IBD (UC = 240, CD = 55), of which 34 (UC = 30, CD = 4) were newly diagnosed during the study year. The prevalence rate for UC was 5.3/100,000 (95% CI 5.0-5.6/100,000), and CD was 1.2/100,000 (95% CI 1.0-1.4/100,000). The incidence rates were 0.69/100,000 (95% CI 0.44-0.94/100,000) for UC and 0.09/100,000 (95% CI 0.002-0.18/100,000) for CD. Female:male ratios were 1.5 for UC and 1.0 for CD. Mean age at diagnosis was (males and females) 36.6 and 38.1y for UC and 33.4 and 36.2y for CD. Among UC patients, 51.1% had proctitis and at presentation 58.4% had mild disease. 80% of CD patients had only large bowel involvement. Few patients had undergone surgery. Conclusions The prevalence of IBD in this population was low compared to Western populations, but similar to some in Asia. There was a female preponderance for UC. UC was mainly mild, distal or left-sided, while CD mainly involved the large bowel. PMID:20302651

Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity.

PubMed

Manolakis, Anastassios C; Kapsoritakis, Andreas N; Kapsoritaki, Anastasia; Tiaka, Elisavet K; Oikonomou, Konstantinos A; Lotis, Vassilis; Vamvakopoulou, Dimitra; Davidi, Ioanna; Vamvakopoulos, Nikolaos; Potamianos, Spyros P

2013-02-01

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

Subsurface geology of a potential waste emplacement site, Salt Valley Anticline, Grand County, Utah

USGS Publications Warehouse

Hite, R.J.

1977-01-01

The Salt Valley anticline, which is located about 32 km northeast of Moab, Utah, is perhaps one of the most favorable waste emplacement sites in the Paradox basin. The site, which includes about 7.8 km 2, is highly accessible and is adjacent to a railroad. The anticline is one of a series of northwest-trending salt anticlines lying along the northeast edge of the Paradox basin. These anticlines are cored by evaporites of the Paradox Member of the Hermosa Formation of Middle Pennsylvanian age. The central core of the Salt Valley anticline forms a ridgelike mass of evaporites that has an estimated amplitude of 3,600 m. The evaporite core consists of about 87 percent halite rock, which includes some potash deposits; the remainder is black shale, silty dolomite, and anhydrite. The latter three lithologies are referred to as 'marker beds.' Using geophysical logs from drill holes on the anticline, it is possible to demonstrate that the marker beds are complexly folded and faulted. Available data concerning the geothermal gradient and heatflow at the site indicate that heat from emplaced wastes should be rapidly dissipated. Potentially exploitable resources of potash and petroleum are present at Salt Valley. Development of these resources may conflict with use of the site for waste emplacement.

Geology and geochemistry of newly discovered Tertiary carbonatite occurrences near Villa Ahumada area, Basin and Range province, Chihuahua, northern Mexico

NASA Astrophysics Data System (ADS)

Nandigam, Ravi Chenchu

This study targets some newly discovered carbonatite occurrences located in the eastern Mexican Basin and Range province, a few kilometers to the east of Villa Ahumada, Chihuahua. The region containing these occurrences experienced compression related to subduction of the Farallon plate until about 32 Ma that was followed by Basin and Range extension. Geological mapping (1:5,000 scale), petrography, study of drill hole cuttings and satellite images, and major and trace element chemical analyses were utilized to understand the intrusive style of the carbonatites, their mineralogy and petrogenesis. The carbonatites, named Yuca, Mariana and El Indio, collectively intrude limestones, granitic intrusives and subduction-related tuffs and lavas mainly as a stock, breccias and dikes. The Yuca carbonatite was emplaced as a 900-m diameter stock, 500 x 350 m breccia body, numerous dikes and networks of fracture fillings. Crosscutting field relationships at Yuca suggest at least two stages of carbonatite emplacement. At Mariana, carbonatite was emplaced as a 750 x 350 m breccia. Four out of nine reverse circulation drill holes penetrated and bottomed in the breccia at an average depth of about 300 m At El Indio, carbonatite was emplaced as a 20 m diameter breccia pipe and a 1m thick sill. Major minerals present are calcite, Fe-rich calcite and hematite. Sporadic presence of fluorite is common. At Mariana, two generations of grossular-rich garnets associated with limestones and granite porphyry respectively are recognized. It is inferred that garnets in granite porphyry represent metasomatic alteration due to the emplacement of carbonatite breccia. Parental magmas of Yuca carbonatites have undergone differentiation under low fO2 conditions during which they were progressively enriched in iron. The carbonatite compositional types recognized based on major element data, in the sequence of least to most highly differentiated, are (1) magnesio-, (2) calcio- and (3) ferrocarbonatites. The concentrations of thorium, uranium, niobium, yttrium and rare earth elements increase with differentiation. Carbonatites are associated with up to 20000 times enrichment of lanthanum and cerium with respect to chondrite. Finally, the Mariana carbonatite breccia is associated with about 7,928,550 short tons of rock with a grade of 0.14% SigmaREE, and primitive mantle normalized trace element plots of carbonatites indicate a mantle origin of their parental melts.

Clinical epidemiology of ulcerative colitis in Arabs based on the Montréal classification.

PubMed

Alharbi, Othman R; Azzam, Nahla A; Almalki, Ahmed S; Almadi, Majid A; Alswat, Khalid A; Sadaf, Nazia; Aljebreen, Abdulrahman M

2014-12-14

To determine the clinical, epidemiological and phenotypic characteristics of ulcerative colitis (UC) in Saudi Arabia by studying the largest cohort of Arab UC patients. Data from UC patients attending gastroenterology clinics in four tertiary care centers in three cities between September 2009 and September 2013 were entered into a validated web-based registry, inflammatory bowel disease information system (IBDIS). The IBDIS database covers numerous aspects of inflammatory bowel disease. Patient characteristics, disease phenotype and behavior, age at diagnosis, course of the disease, and extraintestinal manifestations were recorded. Among 394 UC patients, males comprised 51.0% and females 49.0%. According to the Montréal classification of age, the major chunk of our patients belonged to the A2 category for age of diagnosis at 17-40 years (68.4%), while 24.2% belonged to the A3 category for age of diagnosis at > 40 years. According to the same classification, a majority of patients had extensive UC (42.7%), 35.3% had left-sided colitis and 29.2% had only proctitis. Moreover, 51.3% were in remission, 16.6% had mild UC, 23.4% had moderate UC and 8.6% had severe UC. Frequent relapse occurred in 17.4% patients, infrequent relapse in 77% and 4.8% had chronic disease. A majority (85.2%) of patients was steroid responsive. With regard to extraintestinal manifestations, arthritis was present in 16.4%, osteopenia in 31.4%, osteoporosis in 17.1% and cutaneous involvement in 7.0%. The majority of UC cases were young people (17-40 years), with a male preponderance. While the disease course was found to be similar to that reported in Western countries, more similarities were found with Asian countries with regards to the extent of the disease and response to steroid therapy.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

Characteristics of uranium carbonitride microparticles synthesized using different reaction conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, Chinthaka M; Lindemer, Terrence; Voit, Stewart L

2014-11-01

Three sets of different experimental conditions by changing the cover gases during the sample preparation were tested to synthesize uranium carbonitride (UC1-xNx) microparticles. In the first two sets of experiments using (N2 to N2-4%H2 to Ar) and (Ar to N2 to Ar) environments, single phase UC1-xNx was synthesized. When reducing environments (Ar-4%H2 to N2-4%H2 to Ar-4%H2) were utilized, theoretical densities up to 97% of single phase UC1-xNx kernels were obtained. Physical and chemical characteristics such as density, phase purity, and chemical compositions of the synthesized UC1-xNx materials for the diferent experimental conditions used are provided. In-depth analysis of the microstruturesmore » of UC1-xNx has been carried out and is discussed with the objective of large batch fabrication of high density UC1-xNx kernels.« less

Fluid-inclusion evidence for past temperature fluctuations in the Kilauea East Rift Zone geothermal area, Hawaii

USGS Publications Warehouse

Bargar, K.E.; Keith, T.E.C.; Trusdell, F.A.

1995-01-01

Heating and freezing data were obtained for fluid inclusions in hydrothermal quartz, calcite, and anhydrite from several depths in three scientific observation holes drilled along the lower East Rift Zone of Kilauea volcano, Hawaii. Comparison of measured drill-hole temperatures with fluid-inclusion homogenization-temperature (Th) data indicates that only about 15% of the fluid inclusions could have formed under the present thermal conditions. The majority of fluid inclusions studied must have formed during one or more times in the past when temperatures fluctuated in response to the emplacement of nearby dikes and their subsequent cooling. -from Authors

Polarization-dependent extraordinary optical transmission from upconversion nanoparticles.

PubMed

Wang, Peng Hui; Salcedo, Walter J; Pichaandi, Jothirmayanantham; van Veggel, Frank C J M; Brolo, Alexandre G

2015-11-21

Enhanced upconversion (UC) emission was experimentally demonstrated using gold double antenna nanoparticles coupled to nanoslits in gold films. The transmitted red emission from UC ytterbium and erbium co-doped sodium yttrium fluoride (NaYF4:Yb(3+)/Er(3+)) nanoparticles (UC NPs) at ∼665 nm (excited with a 980 nm diode laser) was enhanced relative to the green emission at ∼550 nm. The relatively enhanced UC NP emission could be tuned by the different polarization-dependent extraordinary optical transmission modes coupled to the gold nanostructures. Finite-difference time-domain calculations suggest that the preferential enhanced UC emission is related to a combination of different surface plasmon mode excitation coupling to cavity Fabry-Perot interactions. A maximum UC enhancement of 6-fold was measured for nanoslit arrays in the absence of the double antennas. In the presence of the double nanoantennas inside the nanoslits, the UC enhancement was between 2- and 4-fold, depending on the experimental conditions.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

PubMed Central

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-01-01

Objective Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. Design We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn’s disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. PMID:26209553

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells.

PubMed

Dardalhon, V; Jaleco, S; Kinet, S; Herpers, B; Steinberg, M; Ferrand, C; Froger, D; Leveau, C; Tiberghien, P; Charneau, P; Noraz, N; Taylor, N

2001-07-31

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4(+) cells proliferated in response to IL-7, whereas naive UC CD4(+) lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G(1b) phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4(+) lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4(+) UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4(+) T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates.

IL-7 differentially regulates cell cycle progression and HIV-1-based vector infection in neonatal and adult CD4+ T cells

PubMed Central

Dardalhon, Valérie; Jaleco, Sara; Kinet, Sandrina; Herpers, Bjorn; Steinberg, Marcos; Ferrand, Christophe; Froger, Delphine; Leveau, Christelle; Tiberghien, Pierre; Charneau, Pierre; Noraz, Nelly; Taylor, Naomi

2001-01-01

Differences in the immunological reactivity of umbilical cord (UC) and adult peripheral blood (APB) T cells are poorly understood. Here, we show that IL-7, a cytokine involved in lymphoid homeostasis, has distinct regulatory effects on APB and UC lymphocytes. Neither naive nor memory APB CD4+ cells proliferated in response to IL-7, whereas naive UC CD4+ lymphocytes underwent multiple divisions. Nevertheless, both naive and memory IL-7-treated APB T cells progressed into the G1b phase of the cell cycle, albeit at higher levels in the latter subset. The IL-7-treated memory CD4+ lymphocyte population was significantly more susceptible to infection with an HIV-1-derived vector than dividing CD4+ UC lymphocytes. However, activation through the T cell receptor rendered UC lymphocytes fully susceptible to HIV-1-based vector infection. These data unveil differences between UC and APB CD4+ T cells with regard to IL-7-mediated cell cycle progression and HIV-1-based vector infectivity. This evidence indicates that IL-7 differentially regulates lymphoid homeostasis in adults and neonates. PMID:11470908

The cooling history and the depth of detachment faulting at the Atlantis Massif oceanic core complex

NASA Astrophysics Data System (ADS)

Schoolmeesters, Nicole; Cheadle, Michael J.; John, Barbara E.; Reiners, Peter W.; Gee, Jeffrey; Grimes, Craig B.

2012-10-01

Oceanic core complexes (OCCs) are domal exposures of oceanic crust and mantle interpreted to be denuded to the seafloor by large slip oceanic detachment faults. We combine previously reported U-Pb zircon crystallization ages with (U-Th)/He zircon thermochronometry and multicomponent magnetic remanence data to determine the cooling history of the footwall to the Atlantis Massif OCC (30°N, MAR) and help establish cooling rates, as well as depths of detachment faulting and gabbro emplacement. We present nine new (U-Th)/He zircon ages for samples from IODP Hole U1309D ranging from 40 to 1415 m below seafloor. These data paired with U-Pb zircon ages and magnetic remanence data constrain cooling rates of gabbroic rocks from the upper 800 m of the central dome at Atlantis Massif as 2895 (+1276/-1162) °C Myr-1 (from ˜780°C to ˜250°C); the lower 600 m of the borehole cooled more slowly at mean rates of ˜500 (+125/-102) °C Myr-1(from ˜780°C to present-day temperatures). Rocks from the uppermost part of the hole also reveal a brief period of slow cooling at rates of ˜300°C Myr-1, possibly due to hydrothermal circulation to ˜4 km depth through the detachment fault zone. Assuming a fault slip rate of 20 mm/yr (from U-Pb zircon ages of surface samples) and a rolling hinge model for the sub-surface fault geometry, we predict that the 780°C isotherm lies at ˜7 km below the axial valley floor, likely corresponding both to the depth at which the semi-brittle detachment fault roots and the probable upper limit of significant gabbro emplacement.

A Proposed Borehole Scientific Laboratory in Quay County, New Mexico, USA

NASA Astrophysics Data System (ADS)

Nielson, Dennis; Eckels, Marc; Mast, Peter; Zellman, Mark; Creed, Robert

2017-04-01

Our team has received funding from the US Department of Energy to initiate a Deep Borehole Field Test that will develop a subsurface test site to evaluate the drilling and scientific aspects of deep borehole disposal of nuclear waste in crystalline rock. Phase 1 of the project will focus on Public Outreach and land acquisition whereas Phase 2 will generate a drilling and testing plan and secure regulatory approvals. Phase 3 will complete the Drilling and Testing Plan and Phase 4 will include the drilling and testing. Phase 5 will be devoted to borehole science and experiments with emplacement technology. Although we are specifically considering issues associated with the disposal of waste, this project is a proof of concept, and no waste will be emplaced at our site. In brief, the concept envisions an 8-1/2 inch open-hole completion at a depth of 5000 m in crystalline rock. There will be an extensive program of sample collection (including core) and analysis as well as geophysical logging and borehole testing. Critical issues will be low permeability in the crystalline rock as well as the ability to manage borehole quality. Our team has proposed a site in Quay County, New Mexico that has an 850 meter thick Paleozoic section overlying homogeneous Precambrian granite. A subsequent phase of the project may drill a second hole with a 17-1/2 inch completion located about 200 m from the first. Our long-term plan is that this site will be managed as a deep scientific observatory that also provides a facility for scientific experiments and testing of borehole infrastructure and drilling equipment.

Antilaminaribioside and antichitobioside antibodies in inflammatory bowel disease.

PubMed

Rejchrt, S; Drahosová, M; Kopácová, M; Cyrany, J; Douda, T; Pintér, M; Bures, J

2008-01-01

Testing antilaminaribioside (ALCA) and antichitobioside (ACCA) antibodies in 89 Crohn's disease (CD), 31 ulcerative colitis (UC) and 50 controls, mean values were 38.6 and 53.0 ELISA units for CD, 34.0 and 32.6 for UC, 34.5 and 36.4 for controls, respectively. There was no significant difference of ALCA values between CD and UC (p = 0.401), CD and control subjects (p = 0.698) or UC and controls (p = 0.898). ACCA were significantly higher in CD compared with UC (p = 0.011) but not with the controls (p = 0.095). No significant difference of ACCA values between UC and controls (p = 0.107) was found. ALCA and ACCA values significantly correlated in CD (r = 0.548, p < 10(-4)) and UC (r = 0.885, p < 10(-4)) but not in controls (r = 0.153, p = 0.287). The positive predictive value for CD was only 20 (ALCA) and 8 % (ACCA), the negative ones (to exclude CD) 25 (ALCA) and 86 % (ACCA). Small and/or large bowel involvement or disease type (i.e. stenosing, perforating or inflammatory) of CD did not differ in the two values. The idea that ALCA and ACCA may be useful either to differentiate between CD, UC and healthy subjects or to stratify CD was not confirmed.

CTLA-4 polymorphisms and susceptibility to inflammatory bowel disease: a meta-analysis.

PubMed

Lee, Young Ho; Kim, Jae-Hoon; Seo, Young Ho; Choi, Sung Jae; Ji, Jong Dae; Song, Gwan Gyu

2014-05-01

The aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) polymorphisms are associated with susceptibility to ulcerative colitis (UC) and Crohn's disease (CD). The authors conducted a meta-analysis on associations between CTLA-4 +49 A/G, -318 C/T, CT60 A/G polymorphisms, and (AT)n repeat in the 3' untranslated region (UTR) and UC and CD susceptibility. A total of 15 comparison studies were considered in our meta-analysis. Meta-analysis revealed no association between UC and the CTLA-4 +49 G and CTLA-4 -318 T alleles in all subjects (OR=0.982, 95% CI=0.851-1.1339, p=0.804; OR=0.500, 95% CI=0.223-1.124, p=0.094). No association was found between UC and the CTLA-4 CT60 A/G polymorphism in Europeans. However, a significant association was observed between the longer allele (⩾118bp) of the (AT)n and UC in Asian population (OR=6.073, 95% CI=4.246-8.684, p=1.0×10(-9)). Meta-analysis of the CTLA-4 +49 A/G, -318 C/T, CT60 A/G polymorphisms showed no association with CD. This meta-analysis demonstrates that the CTLA-4 (AT)n repeat in 3' UTR may be associated with susceptibility to UC in Asians, while no association was found between the CTLA-4 +49 A/G, -318 C/T, and CD60 A/G polymorphism and susceptibility to UC and CD. Copyright © 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Geothermal state and fluid flow within ODP Hole 843B: results from wireline logging

NASA Astrophysics Data System (ADS)

Wiggins, Sean M.; Hildebrand, John A.; Gieskes, Joris M.

2002-02-01

Borehole fluid temperatures were measured with a wireline re-entry system in Ocean Drilling Program Hole 843B, the site of the Ocean Seismic Network Pilot Experiment. These temperature data, recorded more than 7 years after drilling, are compared to temperature data logged during Leg 136, approximately 1 day after drilling had ceased. Qualitative interpretations of the temperature data suggest that fluid flowed slowly downward in the borehole immediately following drilling, and flowed slowly upward 7 years after drilling. Quantitative analysis suggests that the upward fluid flow rate in the borehole is approximately 1 m/h. Slow fluid flow interpreted from temperature data only, however, requires estimates of other unmeasured physical properties. If fluid flows upward in Hole 843B, it may have led to undesirable noise for the borehole seismometer emplaced in this hole as part of the Ocean Seismic Network Pilot Experiment. Estimates of conductive heat flow from ODP Hole 843B are 51 mW/m 2 for the sediment and the basalt. These values are lower than the most recent Hawaiian Arch seafloor heat flow studies.

Coupling of Ag Nanoparticle with Inverse Opal Photonic Crystals as a Novel Strategy for Upconversion Emission Enhancement of NaYF4: Yb(3+), Er(3+) Nanoparticles.

PubMed

Shao, Bo; Yang, Zhengwen; Wang, Yida; Li, Jun; Yang, Jianzhi; Qiu, Jianbei; Song, Zhiguo

2015-11-18

Rare-earth-ion-doped upconversion (UC) nanoparticles have generated considerable interest because of their potential application in solar cells, biological labeling, therapeutics, and imaging. However, the applications of UC nanoparticles were still limited because of their low emission efficiency. Photonic crystals and noble metal nanoparticles are applied extensively to enhance the UC emission of rare earth ions. In the present work, a novel substrate consisting of inverse opal photonic crystals and Ag nanoparticles was prepared by the template-assisted method, which was used to enhance the UC emission of NaYF4: Yb(3+), Er(3+) nanoparticles. The red or green UC emissions of NaYF4: Yb(3+), Er(3+) nanoparticles were selectively enhanced on the inverse opal substrates because of the Bragg reflection of the photonic band gap. Additionally, the UC emission enhancement of NaYF4: Yb(3+), Er(3+) nanoparticles induced by the coupling of metal nanoparticle plasmons and photonic crystal effects was realized on the Ag nanoparticles included in the inverse opal substrate. The present results demonstrated that coupling of Ag nanoparticle with inverse opal photonic crystals provides a useful strategy to enhance UC emission of rare-earth-ion-doped nanoparticles.

Invasive urothelial carcinoma exhibiting basal cell immunohistochemical markers: A variant of urothelial carcinoma associated with aggressive features.

PubMed

Mai, Kien T; Truong, Luan D; Ball, Christopher G; Williams, Phillip; Flood, Trevor A; Belanger, Eric C

2015-08-01

We characterize invasive urothelial carcinoma (UC) exhibiting urothelial basal cell immunohistochemical markers. Consecutive invasive UCs were immunostained with CK20 and urothelial basal cell markers, cytokeratin 5 (CK5)/CD44. Immunostaining for CK5 and CD44 was scored as follows: positive for staining of more than 25% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity. Invasive urothelial carcinoma (UC) exhibiting positive CK5/CD44 staining was designated as basal-like UC (BUC). In this study, of 251 invasive UC (pT1 in 57% and pT2-4 in 43%), BUC accounted for 40% of cases (accounting for most pT2-4 UC) and often presented as non-papillary UC without previous history of UC. In addition, BUC exhibited uniform nuclei with lesser degree of atypia than non BUC and decreased or negative cytokeratin 20 reactivity. Nested and microcystic variants of UC immunohistochemically stained as BUCs. Invasive non-BUCs were often papillary with marked cytologic atypia and pleomorphism, and accounted for most pT1 UC. The rates of perivesical invasion, lymph node and distant metastases were higher for BUC than non-BUC. All nine cases with absent/minimal residual in situ UC in 102 radical cystectomy specimens were from invasive non-BUC. BUC is distinguished from non-BUC due to this aggressive behavior, distinct immunohistochemical profile, and predominant non-papillary architecture. Our findings are consistent with recent studies identifying a subtype of muscle-invasive UC with molecular expression of basal cell and luminal cell molecular profiles. Our study further supports categorizing invasive UCs into these subtypes with different biological behaviors, possibly contributing to better therapeutic strategies. Copyright © 2015 Elsevier GmbH. All rights reserved.

Cytokine treatment optimises the immunotherapeutic effects of umbilical cord-derived MSC for treatment of inflammatory liver disease.

PubMed

de Witte, Samantha F H; Merino, Ana M; Franquesa, Marcella; Strini, Tanja; van Zoggel, Johanna A A; Korevaar, Sander S; Luk, Franka; Gargesha, Madhu; O'Flynn, Lisa; Roy, Debashish; Elliman, Steve J; Newsome, Philip N; Baan, Carla C; Hoogduijn, Martin J

2017-06-08

Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation. Their immunogenicity and immunomodulatory capacity were examined by gene-expression analysis, surface-marker expressions, IDO activity, PGE 2 secretion and inhibition of T cell proliferation and IFNγ production. Furthermore, their activation of NK cell cytotoxicity was investigated via CD107a expression on NK cells. The immunomodulatory capacity, biodistribution and survival of pre-treated ucMSC were investigated in a CCl 4 -induced liver disease mouse model. In addition, capacity of pre-treated MSC to ameliorate liver inflammation was examined in an ex vivo liver inflammation co-culture model. IFN-γ and a multiple cytokine cocktail (MC) consisting of IFN-γ, TGFβ and retinoic acid upregulated the expression of immunomodulatory factor PD-L1 and IDO activity. Subsequently, both treatments enhanced the capacity of ucMSC to inhibit CD4 and CD8 T cell proliferation and IFN-γ production. The susceptibility of ucMSC for NK cell lysis was decreased by IFN-β, TGFβ and MC treatment. In vivo, no immunomodulation was observed by the ucMSC. Four hours after intravenous infusion in mice with CCl 4 -induced inflammatory liver injury, the majority of ucMSC were trapped in the lungs. Rapid clearance of ucMSC(VitB 6 ), ucMSC(Starv + VitB 6 ) and ucMSC(MC) and altered bio-distribution of ucMSC(TGFβ) compared to untreated ucMSC was observed. In the ex vivo co-culture system with inflammatory liver slices ucMSC(MC) showed significantly enhanced modulatory capacity compared to untreated ucMSC. The present study demonstrates the responsiveness of ucMSC to in vitro optimisation treatment. The observed improvements in immunomodulatory capacity as well as immunogenicity after MC treatment may improve the efficacy of ucMSC as immunotherapy targeted towards liver inflammation.

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds.

PubMed

Baumgart, Daniel C; le Claire, Marie

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. DRGs challenge sophisticated IBD care.

Geology and geochemistry of Summitville, Colorado: an epithermal acid sulfate deposit in a volcanic dome

USGS Publications Warehouse

Gray, J.E.; Coolbaugh, M.F.

1994-01-01

Geologic studies during recent open-pit mining at Summitville, Colorado, have provided new information on an epithermal acid sulfate Au-Ag-Cu deposit formed in a volcanic dome. Geologic mapping, geochemical studies of whole-rock samples from blast holes, and geologic and geochemical traverse studies refine the details of the evolution of the Summitville deposit. Six distinct events followed emplacement of the quartz latite volcanic dome and define the development of the Summitville deposit: 1) an early stage of acid sulfate alteration, 2) subsequent Cu sulfide and gold mineralization, 3) widespread hydrothermal brecciation, 4) volumetrically minor, base metal sulfide-bearing barite veining, 5) volumetrically minor, kaolinite matrix brecciation, and finally, 6) supergene oxidation. -from Authors

Enhanced Contribution of HLA in Pediatric Onset Ulcerative Colitis.

PubMed

Venkateswaran, Suresh; Prince, Jarod; Cutler, David J; Marigorta, Urko M; Okou, David T; Prahalad, Sampath; Mack, David; Boyle, Brendan; Walters, Thomas; Griffiths, Anne; Sauer, Cary G; LeLeiko, Neal; Keljo, David; Markowitz, James; Baker, Susan S; Rosh, Joel; Pfefferkorn, Marian; Heyman, Melvin B; Patel, Ashish; Otley, Anthony; Baldassano, Robert; Noe, Joshua; Rufo, Paul; Oliva-Hemker, Maria; Davis, Sonia; Zwick, Michael E; Gibson, Greg; Denson, Lee A; Hyams, Jeffrey; Kugathasan, Subra

2018-03-19

The genetic contributions to pediatric onset ulcerative colitis (UC), characterized by severe disease and extensive colonic involvement, are largely unknown. In adult onset UC, Genome Wide Association Study (GWAS) has identified numerous loci, most of which have a modest susceptibility risk (OR 0.84-1.14), with the exception of the human leukocyte antigen (HLA) region on Chromosome 6 (OR 3.59). To study the genetic contribution to exclusive pediatric onset UC, a GWAS was performed on 466 cases with 2099 healthy controls using UK Biobank array. SNP2HLA was used to impute classical HLA alleles and their corresponding amino acids, and the results are compared with adult onset UC. HLA explained the almost entire association signal, dominated with 191 single nucleotide polymorphisms (SNPs) (p = 5 x 10-8 to 5 x 10-10). Although very small effects, established SNPs in adult onset UC loci had similar direction and magnitude in pediatric onset UC. SNP2HLA imputation identified HLA-DRB1*0103 (odds ratio [OR] = 6.941, p = 1.92*10-13) as the most significant association for pediatric UC compared with adult onset UC (OR = 3.59). Further conditioning showed independent effects for HLA-DRB1*1301 (OR = 2.25, p = 7.92*10-9) and another SNP rs17188113 (OR = 0.48, p = 7.56*10-9). Two HLA-DRB1 causal alleles are shared with adult onset UC, while at least 2 signals are unique to pediatric UC. Subsequent stratified analyses indicated that HLA-DRB1*0103 has stronger association for extensive disease (E4: OR = 8.28, p = 4.66x10-10) and female gender (OR = 8.85, p = 4.82x10-13). In pediatric onset UC, the HLA explains almost the entire genetic associations. In addition, the HLA association is approximately twice as strong in pediatric UC compared with adults, due to a combination of novel and shared effects. We speculate the paramount importance of antigenic stimulation either by infectious or noninfectious stimuli as a causal event in pediatric UC onset.

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis.

PubMed

Lankarani, Kamran B; Karbasi, Ashraf; Kalantari, Tahereh; Yarmohammadi, Hooman; Saberi-Firoozi, Mehdi; Alizadeh-Naeeni, Mahvash; Taghavi, Ali R; Fattahi, Mahammad R; Ghaderi, Abbas

2006-02-01

Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CTLA-4 polymorphism is not associated with UC in the Iranian population.

Dramatic Increase in Incidence of Ulcerative Colitis and Crohn's Disease (1988-2011): A Population-Based Study of French Adolescents.

PubMed

Ghione, Silvia; Sarter, Hélène; Fumery, Mathurin; Armengol-Debeir, Laura; Savoye, Guillaume; Ley, Delphine; Spyckerelle, Claire; Pariente, Benjamin; Peyrin-Biroulet, Laurent; Turck, Dominique; Gower-Rousseau, Corinne

2018-02-01

Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

PubMed

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-10-01

Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

PubMed

Ellinghaus, David; Folseraas, Trine; Holm, Kristian; Ellinghaus, Eva; Melum, Espen; Balschun, Tobias; Laerdahl, Jon K; Shiryaev, Alexey; Gotthardt, Daniel N; Weismüller, Tobias J; Schramm, Christoph; Wittig, Michael; Bergquist, Annika; Björnsson, Einar; Marschall, Hanns-Ulrich; Vatn, Morten; Teufel, Andreas; Rust, Christian; Gieger, Christian; Wichmann, H-Erich; Runz, Heiko; Sterneck, Martina; Rupp, Christian; Braun, Felix; Weersma, Rinse K; Wijmenga, Cisca; Ponsioen, Cyriel Y; Mathew, Christopher G; Rutgeerts, Paul; Vermeire, Séverine; Schrumpf, Erik; Hov, Johannes R; Manns, Michael P; Boberg, Kirsten M; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H

2013-09-01

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. Copyright © 2012 American Association for the Study of Liver Diseases.

Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yong; Dalal, Sushila; Antonopoulos, Dionysios

Background: Ulcerative colitis (UC) only involves the colonic mucosa. Yet, nearly 50% of patients with UC who undergo total proctocolectomy with ileal pouch anal anastomosis develop UC-like inflammation of the ileal pouch (pouchitis). By contrast, patients with familial adenomatous polyposis (FAP) with ileal pouch anal anastomosis develop pouchitis far less frequently. We hypothesized that pathogenic events associated with the development of UC are recapitulated by colonic-metaplastic transcriptomic reprogramming of the UC pouch. Methods: We prospectively sampled pouch and prepouch ileum mucosal biopsies in patients with UC with ileal pouch anal anastomosis 4, 8, and 12 months after their pouch wasmore » in continuity. Mucosal samples were also obtained from patients with FAP. Transcriptional profiles of the UC and FAP pouch and prepouch ileum were investigated via RNA sequencing and compared with data from a previously published microarray study. Results: Unlike patients with FAP, subjects with UC exhibited a large set of differentially expressed genes between the pouch and prepouch ileum as early as 4 months after pouch functionalization. Functional pathway analysis of differentially expressed genes in the UC pouch revealed an enhanced state of immune/inflammatory response and extracellular matrix remodeling. Moreover, >70% of differentially expressed genes mapped to published inflammatory bowel diseases microarray data sets displayed directional changes consistent with active UC but not with Crohn's disease. Conclusions: The UC pouch, well before histologic inflammation, already displays a systems-level gain of colon-associated genes and loss of ileum-associated genes. Patients with UC exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease and may in part explain their susceptibility to the development of pouchitis.« less

Covered Metallic Stents With an Anti-Migration Design vs. Uncovered Stents for the Palliation of Malignant Gastric Outlet Obstruction: A Multicenter, Randomized Trial

PubMed Central

Lee, Hyuk; Min, Byung-Hoon; Lee, Jeong Hoon; Shin, Cheol Min; Kim, Younjoo; Chung, Hyunsoo; Lee, Sang Hyub

2015-01-01

OBJECTIVES: Previous studies reported comparable stent patency between covered self-expandable metallic stents (SEMS) and uncovered SEMS (UCS) for palliation of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the efficacy and safety of the newly developed WAVE-covered SEMS (WCS), which has an anti-migration design, compared with UCS in gastric cancer patients with symptomatic GOO. METHODS: A total of 102 inoperable gastric cancer patients with symptomatic GOO were prospectively enrolled from five referral centers and randomized to undergo UCS or WCS placement. Stent patency and recurrence of obstructive symptoms were assessed at 8 weeks and 16 weeks after stent placement. RESULTS: At the 8-week follow-up, both stent patency rates (72.5% vs. 62.7%) and re-intervention rates (19.6% vs. 19.6%) were comparable between the WCS and the UCS groups. Both stent stenosis (2.4% vs. 8.1%) and migration rates (9.5% vs. 5.4%) were comparable between WCS and UCS groups. At the 16-week follow-up, however, the WCS group had a significantly higher stent patency rate than the UCS group (68.6% vs. 41.2%). Re-intervention rates in the WCS and UCS groups were 23.5% and 39.2%, respectively. Compared with the UCS group, the WCS group had a significantly lower stent restenosis rate (7.1% vs. 37.8%) and a comparable migration rate (9.5% vs. 5.4%). Overall stent patency was significantly longer in the WCS group than in the UCS group. No stent-associated significant adverse events occurred in either the WCS or UCS groups. In the multivariate analysis, WCS placement and chemotherapy were identified as independent predictors of 16-week stent patency. CONCLUSIONS: WCS group showed comparable migration rate and significantly more durable long-term stent patency compared with UCS group for the palliation of GOO in patients with inoperable gastric cancer. PMID:26372507

Morphology evolution and pure red upconversion mechanism of β-NaLuF4 crystals.

PubMed

Lin, Hao; Xu, Dekang; Li, Anming; Teng, Dongdong; Yang, Shenghong; Zhang, Yueli

2016-06-16

A series of β-NaLuF4 crystals were synthesized via a hydrothermal method. Hexagonal phase microdisks, microprisms, and microtubes were achieved by simply changing the amount of citric acid in the initial reaction solution. Pure red upconversion (UC) luminescence can be observed in β-NaLuF4:Yb(3+), Tm(3+), Er(3+) and Li(+) doped β-NaLuF4:20% Yb(3+), 1% Tm(3+), 20% Er(3+). Based on the rate equations, we report the theoretical model about the pure red UC mechanism in Yb(3+)/Tm(3+)/Er(3+) doped system. It is proposed that the pure red UC luminescence is mainly ascribed to the energy transfer UC from Tm(3+):(3)F4 → (3)H6 to Er(3+):(4)I11/2 → (4)F9/2 and the cross-relaxation (CR) effect [Er(3+):(4)S3/2 + (4)I15/2 → (4)I9/2 + (4)I13/2] rather than the long-accepted mechanism [CR process among Er(3+):(4)F7/2 + (4)I11/2 → (4)F9/2 + (4)F9/2]. In addition, compared to the Li(+)-free counterpart, the pure red UC luminescence in β-NaLuF4:20% Yb(3+), 1% Tm(3+), 20% Er(3+) with 15 mol% Li(+) doping is enhanced by 13.7 times. This study provides a general and effective approach to obtain intense pure red UC luminescence, which can be applied to other synthetic strategies.

Morphology evolution and pure red upconversion mechanism of β-NaLuF4 crystals

PubMed Central

Lin, Hao; Xu, Dekang; Li, Anming; Teng, Dongdong; Yang, Shenghong; Zhang, Yueli

2016-01-01

A series of β-NaLuF4 crystals were synthesized via a hydrothermal method. Hexagonal phase microdisks, microprisms, and microtubes were achieved by simply changing the amount of citric acid in the initial reaction solution. Pure red upconversion (UC) luminescence can be observed in β-NaLuF4:Yb3+, Tm3+, Er3+ and Li+ doped β-NaLuF4:20% Yb3+, 1% Tm3+, 20% Er3+. Based on the rate equations, we report the theoretical model about the pure red UC mechanism in Yb3+/Tm3+/Er3+ doped system. It is proposed that the pure red UC luminescence is mainly ascribed to the energy transfer UC from Tm3+:3F4 → 3H6 to Er3+:4I11/2 → 4F9/2 and the cross-relaxation (CR) effect [Er3+:4S3/2 + 4I15/2 → 4I9/2 + 4I13/2] rather than the long-accepted mechanism [CR process among Er3+:4F7/2 + 4I11/2 → 4F9/2 + 4F9/2]. In addition, compared to the Li+-free counterpart, the pure red UC luminescence in β-NaLuF4:20% Yb3+, 1% Tm3+, 20% Er3+ with 15 mol% Li+ doping is enhanced by 13.7 times. This study provides a general and effective approach to obtain intense pure red UC luminescence, which can be applied to other synthetic strategies. PMID:27306720

Rotational Rehybridization and the High Temperature Phase of UC2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen, Xiaodong; Rudin, Sven P.; Batista, Enrique R.

2012-12-03

The screened hybrid approximation (HSE) of density functional theory (DFT) is used to examine the structural, optical, and electronic properties of the high temperature phase, cubic UC(2). This phase contains C(2) units with a computed C-C distance of 1.443 Å which is in the range of a CC double bond; U is formally 4+, C(2) 4-. The closed shell paramagnetic state (NM) was found to lie lowest. Cubic UC(2) is found to be a semiconductor with a narrow gap, 0.4 eV. Interestingly, the C(2) units connecting two uranium sites can rotate freely up to an angle of 30°, indicating amore » hindered rotational solid. Ab-initio molecular dynamic simulations (HSE) show that the rotation of C(2) units in the low temperature phase (tetragonal UC(2)) occurs above 2000 K, in good agreement with experiment. The computed energy barrier for the phase transition from tetragonal UC(2) to cubic UC(2) is around 1.30 eV per UC(2). What is fascinating about this system is that at high temperature, the phase transformation to the cubic phase is associated with a rehybridization of the C atoms from sp to sp(3).« less

A prospective audit on the effect of training and educational workshops on the incidence of urethral catheterization injuries

PubMed Central

Bhatt, Nikita R.; Davis, Niall F.; Quinlan, Mark R.; Flynn, Robert J.; McDermott, T.E.D.; Manecksha, Rustom P.; Thornhill, John A.

2017-01-01

Introduction The incidence of iatrogenic urethral catheterization (UC) injuries is approximately 0.3%. Resultant complications are associated with patient morbidity and unnecessary healthcare costs. Our aim was to investigate whether educational training workshops decreased the incidence of UC-related injuries. Methods A prospective audit was performed to calculate incidence, morbidity, and costs associated with iatrogenic UC injury from January to July 2015. Educational workshops were then conducted with healthcare staff and training modules for junior doctors. UC-related incidence, morbidity, and costs in the subsequent six-month period were recorded prospectively and compared with the previous data. Results The incidence of iatrogenic UC injuries was reduced from 4.3/1000 catheters inserted to 3.8/1000 catheters after the intervention (p=0.59). Morbidity from UC increased in the second half in the form of increase in cumulative additional inpatient hospital stay (22 to 79 days; p=0.25), incidence of urosepsis (n=2 to n=4), and need for operative intervention (n=1 to n=2). The cost of managing UC injuries almost doubled in the period after the training intervention (€50 449 to €90 100). Conclusions Current forms of educational and training interventions for UC did not significantly change morbidity or cost of iatrogenic UC injuries despite a decrease in incidence. Improved and intensive training protocols are necessary for UC to prevent avoidable iatrogenic complications, as well as a safer urethral catheter design. PMID:28761592

High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial.

PubMed

Aoun, Mabel; Makki, Maha; Azar, Hiba; Matta, Hiam; Chelala, Dania Nehme

2017-06-07

Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K 2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K 2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score. This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 μg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks. At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01). Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 μg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K 2 over a longer follow-up period. The clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354 , on August 11, 2016).

Hawaiian lava flows in the third dimension: Identification and interpretation of pahoehoe and 'a'a distribution in the KP-1 and SOH-4 cores

NASA Astrophysics Data System (ADS)

Katz, Melissa G.; Cashman, Katharine V.

2003-02-01

Hawaiian lava flows are classified as pahoehoe or 'a'a by their surface morphology. As surface morphology reflects flow emplacement conditions, the surface distribution of morphologic flow types has been used to study the evolution and eruptive history of basaltic volcanoes. We extend this analysis to the third dimension by determining the distribution of flow types in two deep drill cores, the Scientific Observation Hole-4 (SOH-4) core, drilled near Kilauea's East Rift Zone (ERZ), and the pilot hole (Kahi Puka-1 (KP-1)) for the Hawaiian Scientific Drilling Project (HSDP), drilled through distal flows from Mauna Loa and Mauna Kea. Flows are classified using both internal structures and groundmass textures, with the latter useful when identification based on mesoscopic flow features (e.g., surface morphology and vesicle content and distribution) is ambiguous. We then examine the temporal distribution of pahoehoe and 'a'a flows in proximal (SOH-4) and distal (KP-1) settings. Sequence analysis shows that the two flow types are not randomly distributed in either core but instead are strongly clustered. The proximal SOH-4 core is dominated by thin pahoehoe flows (˜60% by volume), consistent with the common occurrence of surface-fed pahoehoe flows in near-vent settings. The distal KP-1 core has a high proportion of 'a'a (˜58% by volume), although the proportion of pahoehoe and 'a'a varies dramatically throughout the Mauna Kea sequence. Thick inflated pahoehoe flows dominate when the drill site was near sea level, consistent with the numerous inflated pahoehoe fields on the current coastal plains of Kilauea and Mauna Loa. 'A'a flows are abundant when the site was far above sea level. As slope increases from the coastal plains to Mauna Kea's flank, this correlation may reflect the combined effect of long transport distances and increased slopes on flow emplacement. These results demonstrate that flow type and thickness variations in cores provide valuable information about both vent location and local site environment. Observed variations in flow type within the KP-1 core raise interesting questions about feedback between volcano evolution and flow morphology and suggest that flow type is an important variable in models of volcano growth and related models for lava flow hazard assessment.

Transition Metal-Involved Photon Upconversion.

PubMed

Ye, Shi; Song, En-Hai; Zhang, Qin-Yuan

2016-12-01

Upconversion (UC) luminescence of lanthanide ions (Ln 3+ ) has been extensively investigated for several decades and is a constant research hotspot owing to its fundamental significance and widespread applications. In contrast to the multiple and fixed UC emissions of Ln 3+ , transition metal (TM) ions, e.g., Mn 2+ , usually possess a single broadband emission due to its 3 d 5 electronic configuration. Wavelength-tuneable single UC emission can be achieved in some TM ion-activated systems ascribed to the susceptibility of d electrons to the chemical environment, which is appealing in molecular sensing and lighting. Moreover, the UC emissions of Ln 3+ can be modulated by TM ions (specifically d -block element ions with unfilled d orbitals), which benefits from the specific metastable energy levels of Ln 3+ owing to the well-shielded 4 f electrons and tuneable energy levels of the TM ions. The electric versatility of d 0 ion-containing hosts ( d 0 normally viewed as charged anion groups, such as MoO 6 6- and TiO 4 4- ) may also have a strong influence on the electric dipole transition of Ln 3+ , resulting in multifunctional properties of modulated UC emission and electrical behaviour, such as ferroelectricity and oxide-ion conductivity. This review focuses on recent advances in the room temperature (RT) UC of TM ions, the UC of Ln 3+ tuned by TM or d 0 ions, and the UC of d 0 ion-centred groups, as well as their potential applications in bioimaging, solar cells and multifunctional devices.

Transition Metal‐Involved Photon Upconversion

PubMed Central

Song, En‐Hai

2016-01-01

Upconversion (UC) luminescence of lanthanide ions (Ln3+) has been extensively investigated for several decades and is a constant research hotspot owing to its fundamental significance and widespread applications. In contrast to the multiple and fixed UC emissions of Ln3+, transition metal (TM) ions, e.g., Mn2+, usually possess a single broadband emission due to its 3d 5 electronic configuration. Wavelength‐tuneable single UC emission can be achieved in some TM ion‐activated systems ascribed to the susceptibility of d electrons to the chemical environment, which is appealing in molecular sensing and lighting. Moreover, the UC emissions of Ln3+ can be modulated by TM ions (specifically d‐block element ions with unfilled d orbitals), which benefits from the specific metastable energy levels of Ln3+ owing to the well‐shielded 4f electrons and tuneable energy levels of the TM ions. The electric versatility of d 0 ion‐containing hosts (d 0 normally viewed as charged anion groups, such as MoO6 6‐ and TiO4 4‐) may also have a strong influence on the electric dipole transition of Ln3+, resulting in multifunctional properties of modulated UC emission and electrical behaviour, such as ferroelectricity and oxide‐ion conductivity. This review focuses on recent advances in the room temperature (RT) UC of TM ions, the UC of Ln3+ tuned by TM or d 0 ions, and the UC of d 0 ion‐centred groups, as well as their potential applications in bioimaging, solar cells and multifunctional devices. PMID:27981015

Human umbilical cord-derived mesenchymal stem cells suppress proliferation of PHA-activated lymphocytes in vitro by inducing CD4(+)CD25(high)CD45RA(+) regulatory T cell production and modulating cytokine secretion.

PubMed

Yang, Hongna; Sun, Jinhua; Li, Yan; Duan, Wei-Ming; Bi, Jianzhong; Qu, Tingyu

2016-04-01

Bone marrow-derived mesenchymal stem cells (MSCs) are promising candidate cells for therapeutic application in autoimmune diseases due to their immunomodulatory properties. Unused human umbilical cords (UC) offer an abundant and noninvasive source of MSCs without ethical issues and are emerging as a valuable alternative to bone marrow tissue for producing MSCs. We thus investigated the immunomodulation effect of umbilical cord-derived MSCs (UC-MSCs) on human peripheral blood mononuclear cells (PBMCs), T cells in particular, in a co-culture system. We found that UC-MSCs efficiently suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated PBMCs (p<0.01). Kinetic analysis revealed that UC-MSCs primarily inhibited the division of generation 3 (G3) and 4 (G4) of PBMCs. In addition, UC-MSCs augmented the expression of CD127(+) and CD45RA(+) but reduced the expression of CD25(+) in PBMCs stimulated by PHA (p<0.05). Furthermore, UC-MSCs inhibited PHA-resulted increase in the frequency of CD4(+)CD25(+)CD127(low/-) Tregs significantly (p<0.01) but augmented PHA-resulted increase in the frequency of CD4(+)CD25(high)CD45RA(+) Tregs to about three times in PBMCs. The levels of anti-inflammatory cytokines, PEG2, TGF-β, and IL-10 were greatly up-regulated, accompanied by a significant down-regulation of pro-inflammatory IFN-γ in the co-culture (p<0.01). Our results showed that UC-MSCs are able to suppress mitogen-induced PBMC activation and proliferation in vitro by altering T lymphocyte phenotypes, increasing the frequency of CD4(+)CD25(high)CD45RA(+) Tregs, and modulating the associated cytokine production. Further studies are warranted to investigate the therapeutic potential of UC-MSCs in immunologically-diseased conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Featured Image: Making a Rapidly Rotating Black Hole

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2017-10-01

These stills from a simulation show the evolution (from left to right and top to bottom) of a high-mass X-ray binary over 1.1 days, starting after the star on the right fails to explode as a supernova and then collapses into a black hole. Many high-mass X-ray binaries like the well-known Cygnus X-1, the first source widely accepted to be a black hole host rapidly spinning black holes. Despite our observations of these systems, however, were still not sure how these objects end up with such high rotation speeds. Using simulations like that shown above, a team of scientists led by Aldo Batta (UC Santa Cruz) has demonstrated how a failed supernova explosion can result in such a rapidly spinning black hole. The authors work shows that in a binary where one star attempts to explode as a supernova and fails it doesnt succeed in unbinding the star the large amount of fallback material can interact with the companion star and then accrete onto the black hole, spinning it up in the process. You can read more about the authors simulations and conclusions in the paper below.CitationAldo Batta et al 2017 ApJL 846 L15. doi:10.3847/2041-8213/aa8506

Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap.

PubMed

Terao, Chikashi; Matsumura, Takayoshi; Yoshifuji, Hajime; Kirino, Yohei; Maejima, Yasuhiro; Nakaoka, Yoshikazu; Takahashi, Meiko; Amiya, Eisuke; Tamura, Natsuko; Nakajima, Toshiki; Origuchi, Tomoki; Horita, Tetsuya; Matsukura, Mitsuru; Kochi, Yuta; Ogimoto, Akiyoshi; Yamamoto, Motohisa; Takahashi, Hiroki; Nakayamada, Shingo; Saito, Kazuyoshi; Wada, Yoko; Narita, Ichiei; Kawaguchi, Yasushi; Yamanaka, Hisashi; Ohmura, Koichiro; Atsumi, Tatsuya; Tanemoto, Kazuo; Miyata, Tetsuro; Kuwana, Masataka; Komuro, Issei; Tabara, Yasuharu; Ueda, Atsuhisa; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

2015-05-01

Takayasu arteritis (TAK) is a systemic vasculitis affecting large arteries and large branches of the aorta. Ulcerative colitis (UC) is a prevalent autoimmune colitis. Since TAK and UC share HLA-B*52:01 and IL12B as genetic determinants, and since there are case reports of the co-occurrence of these diseases, we hypothesized that UC is a common complication of TAK. We undertook this study to perform a large-scale analysis of TAK, both to evaluate the prevalence of concurrent cases of TAK and UC and to identify and estimate susceptibility genes shared between the 2 diseases. We analyzed a total of 470 consecutive patients with TAK from 14 institutions. We characterized patients with TAK and UC by analyzing clinical manifestations and genetic components. Genetic overlapping of TAK and UC was evaluated with the use of UC susceptibility single-nucleotide polymorphisms by comparing risk directions and effect sizes between susceptibility to the 2 diseases. Thirty of 470 patients with TAK had UC (6.4% [95% confidence interval 4.3-9.0]). This percentage was strikingly higher than that expected from the prevalence of UC in Japan. Patients with TAK complicated with UC developed TAK at an earlier stage of life (P = 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P = 1.0 × 10(-5) ) (odds ratio 12.14 [95% confidence interval 2.96-107.23]). The 110 non-HLA markers of susceptibility to UC significantly displayed common risk directions with susceptibility to TAK (P = 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 × 10(-10) ). UC is a major complication of TAK. These 2 diseases share a significant proportion of their genetic background, and HLA-B*52:01 may play a central role in their co-occurrence. © 2015, American College of Rheumatology.

A ground-based magnetic survey of Frenchman Flat, Nevada National Security Site and Nevada Test and Training Range, Nevada: data release and preliminary interpretation

USGS Publications Warehouse

Phillips, Jeffrey D.; Burton, Bethany L.; Curry-Elrod, Erika; Drellack, Sigmund

2014-01-01

Question 2—Does basin and range normal faulting observed in the hills north of Frenchman Flat continue southward under alluvium and possibly disrupt the Topopah Spring Tuff of the Paintbrush Group (the Topopah Spring welded tuff aquifer or TSA) east of the Pin Stripe underground nuclear test, which was conducted in Emplacement hole U11b?

TRPV2 activation induces apoptotic cell death in human T24 bladder cancer cells: a potential therapeutic target for bladder cancer.

PubMed

Yamada, Takahiro; Ueda, Takashi; Shibata, Yasuhiro; Ikegami, Yosuke; Saito, Masaki; Ishida, Yusuke; Ugawa, Shinya; Kohri, Kenjiro; Shimada, Shoichi

2010-08-01

To investigate the functional expression of the transient receptor potential vanilloid 2 (TRPV2) channel protein in human urothelial carcinoma (UC) cells and to determine whether calcium influx into UC cells through TRPV2 is involved in apoptotic cell death. The expression of TRPV2 mRNA in bladder cancer cell lines (T24, a poorly differentiated UC cell line and RT4, a well-differentiated UC cell line) was analyzed using reverse transcriptase-polymerase chain reaction. The calcium permeability of TRPV2 channels in T24 cells was investigated using a calcium imaging assay that used cannabidiol (CBD), a relatively selective TRPV2 agonist, and ruthenium red (RuR), a nonselective TRPV channel antagonist. The death of T24 or RT4 cells in the presence of CBD was evaluated using a cellular viability assay. Apoptosis of T24 cells caused by CBD was confirmed using an annexin-V assay and small interfering RNA (siRNA) silencing of TRPV2. TRPV2 mRNA was abundantly expressed in T24 cells. The expression level in UC cells was correlated with high-grade disease. The administration of CBD increased intracellular calcium concentrations in T24 cells. In addition, the viability of T24 cells progressively decreased with increasing concentrations of CBD, whereas RT4 cells were mostly unaffected. Cell death occurred via apoptosis caused by continuous influx of calcium through TRPV2. TRPV2 channels in UC cells are calcium-permeable and the regulation of calcium influx through these channels leads directly to the death of UC cells. TRPV2 channels in UC cells may be a potential new therapeutic target, especially in higher-grade UC cells. Copyright 2010 Elsevier Inc. All rights reserved.

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

PubMed

Jabeen, Rukhsana; Miller, Lucy; Yao, Weiguo; Gupta, Sandeep; Steiner, Steven; Kaplan, Mark H

2015-10-01

Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease, and pathogenesis involves a complex interplay among genetic, environmental, and immunological factors. We evaluated isoform expression of the IL-12-activated transcription factor STAT4 in children with CD and UC. We collected biopsy samples from both patients newly diagnosed with CD and with UC. We further collected blood samples from patients newly diagnosed with CD and with UC as well as from patients who had a flare-up after being in clinical remission, and we examined the ratios of STAT4β/STAT4α mRNA. In addition to STAT4 isoforms, we measured the expression of the cytokines TNFα, IFNγ, granulocyte macrophage-colony stimulating factor, and IL-17 using polymerase chain reaction of biopsy samples and multiplex analysis of patient serum samples. Ratios of STAT4β/STAT4α were increased in specific gastrointestinal tract segments in both patients with CD and those with UC that correlate with the location and severity of inflammation. In contrast, we did not observe changes in STAT4β/STAT4α ratios in biopsy specimens from patients with eosinophilic esophagitis. We also observed increased STAT4β/STAT4α ratios in the peripheral blood mononuclear cells of patients with UC and those with CD, compared with healthy controls. Ratios were normalized after patients were treated with steroids. Collectively, these data indicate that STAT4 isoforms could be an important noninvasive biomarker in the diagnosis and treatment of inflammatory bowel disease and that expression of these isoforms might provide further insight into the pathogenesis of IBD.

Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture – a preliminary study

PubMed Central

Yang, Hongna; Sun, Jinhua; Wang, Feng; Li, Yan; Bi, Jianzhong; Qu, Tingyu

2016-01-01

The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4+CD25+CD127low/− Tregs in resting CD4+ T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (−β1, and interleukin-10, along with a reduced interferon-γ production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4+CD25− T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC-primed (naïve) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4+CD25− Teffs was observed in UC-MSC-primed Tregs from MS patients and naïve Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach. PMID:27705922

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds

PubMed Central

Baumgart, Daniel C.; le Claire, Marie

2016-01-01

Background Crohn’s disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. Methods IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Results Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. Conclusions DRGs challenge sophisticated IBD care. PMID:26784027

CONCEPTUAL DESIGN OF A LUNAR REGOLITH CLUSTERED-REACTOR SYSTEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

John Darrell Bess

2009-06-01

It is proposed that a fast-fission, heatpipe-cooled, lunar-surface power reactor system be divided into subcritical units that could be launched safely without the incorporation of additional spectral shift absorbers or other complex means of control. The reactor subunits are to be emplaced directly into the lunar regolith utilizing the regolith not just for shielding but as the reflector material to increase the neutron economy of the system. While a single subunit cannot achieve criticality by itself, coordinated placement of additional subunits will provide a critical reactor system for lunar surface power generation. A lunar regolith clustered-reactor system promotes reliability, safety,more » and ease of manufacture and testing at the cost of a slight increase in launch mass per rated power level and an overall reduction in neutron economy when compared to a single-reactor system. Additional subunits may be launched with future missions to increase the cluster size and power according to desired lunar base power demand and lifetime. The results address the potential uncertainties associated with the lunar regolith material and emplacement of the subunit systems. Physical distance between subunits within the clustered emplacement exhibits the most significant feedback regarding changes in overall system reactivity. Narrow, deep holes will be the most effective in reducing axial neutron leakage from the core. The variation in iron concentration in the lunar regolith can directly influence the overall system reactivity although its effects are less than the more dominant factors of subunit emplacement.« less

Histological and immunological features of appendix in patients with ulcerative colitis.

PubMed

Jo, Yukihiko; Matsumoto, Takayuki; Yada, Shinichiro; Nakamura, Shotaro; Yao, Takashi; Hotokezaka, Masayuki; Mibu, Ryuichi; Iida, Mitsuo

2003-01-01

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Geologic and hydrologic considerations for various concepts of high-level radioactive waste disposal in conterminous United States

USGS Publications Warehouse

Ekren, E.B.; Dinwiddie, G.A.; Mytton, J.W.; Thordarson, William; Weir, J.E.; Hinrichs, E.N.; Schroder, L.J.

1974-01-01

The purpose of this investigation is to evaluate and identify which geohydrologic environments in conterminous United States are best suited for various concepts or methods of underground disposal of high-level radioactive wastes and to establish geologic and hydrologic criteria that are pertinent to high-level waste disposal. The unproven methods of disposal include (1) a very deep drill hole (30,000-50,000 ft or 9,140-15,240 m), (2) a matrix of (an array of multiple) drill holes (1,000-20,000 ft or 305-6,100 m), (3) a mined chamber (1,000-10,000 ft or 305-3,050 m), (4) a cavity with separate manmade structures (1,000-10,000 ft or 305-3,050 m), and (5) an exploded cavity (2,000-20,000 ft or 610-6,100 m) o The geohydrologic investigation is made on the presumption that the concepts or methods of disposal are technically feasible. Field and laboratory experiments in the future may demonstrate whether or not any of the methods are practical and safe. All the conclusions drawn are tentative pending experimental confirmation. The investigation focuses principally on the geohydrologic possibilities of several methods of disposal in rocks other than salt. Disposal in mined chambers in salt is currently under field investigation, and this disposal method has been intensely investigated and evaluated by various workers under the sponsorship of the Atomic Energy Commission. Of the various geohydrologic factors that must be considered in the selection of optimum waste-disposal sites, the most important is hydrologic isolation to assure that the wastes will be safely contained within a small radius of the emplacement zone. To achieve this degree of hydrologic isolation, the host rock for the wastes must have very low permeability and the site must be virtually free of faults. In addition, the locality should be in (1) an area of low seismic risk where the possibility of large earthquakes rupturing the emplacement zone is very low, (2) where the possibility- of flooding by rise is very low, (3) where a possible return of glacial or pluvial climate will not cause potentially hazardous changes in surface- or ground-water regimens, and (4) where danger of exhumation by erosion is nil. The geographic location for an optimum site is one that is far removed from major drainages, lakes, and oceans, where population density is low, and where the topographic relief is gentle in order to avoid steep surface-water drainage gradients that would allow rapid distribution of contaminants in case of accident. The most suitable medium for the unproven deep drill-hole, matrix-holes, and exploded-cavity methods appears to be crystalline rocks, either intrusive igneous or metamorphic because of their potentially low permeabilities and high mechanical strengths. Salt (either in thick beds or stable domes), tuff, and possibly shale appear to be suitable for mined chambers and cavities with separate manmade structures. Salt appears to be suitable because of its very low permeability, high thermal conductivity, and natural plasticity. Tuff and shale appear suitable because of their very low permeabilities and high ion-exchange capacities. Sedimentary rocks other than shale and volcanic rocks, exclusive of tuff, are considered to be generally unsuitable for waste emplacement because of their potentially high permeabilities. Areas that appear to satisfy most geohydrologic requirements for the deep drill hole and the matrix holes include principally (1) the stable continental interior where the sedimentary cover is thin or absent, (2) the shield area of the North-Central States, and (3) the metamorphic belt of Eastern United States--primarily the Piedmont. These areas are possibly suitable also for the exploded cavity and the mined chamber because the possibility of finding rock with very- permeability at depths from 1,000? feet (305? m) to 20,000 feet (6,100 m) appears to be high. The Basin and Range province of Western United States, particula

Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn's Disease from Ulcerative Colitis.

PubMed

Mortensen, Joachim Høg; Godskesen, Line Elbjerg; Jensen, Michael Dam; Van Haaften, Wouter Tobias; Klinge, Lone Gabriels; Olinga, Peter; Dijkstra, Gerard; Kjeldsen, Jens; Karsdal, Morten Asser; Bay-Jensen, Anne-Christine; Krag, Aleksander

2015-10-01

A hallmark of inflammatory bowel disease [IBD] is chronic inflammation, which leads to excessive extracellular matrix [ECM] remodelling and release of specific protein fragments, called neoepitopes. We speculated that the biomarker profile panel for ulcerative colitis [UC] and Crohn's disease [CD] represent a heterogeneous expression pattern, and may be applied as a tool to aid in the differentiation between UC and CD. Serum biomarkers of degraded collagens I, III-IV [C1M, C3M, and C4M], collagen type 1 and IV formation [P1NP, P4NP], and citrullinated and MMP-degraded vimentin [VICM] were studied with a competitive ELISA assay system in a cohort including 164 subjects [CD n = 72, UC n = 60, and non-IBD controls n = 32] and a validation cohort of 61 subjects [CD n = 46, and UC n = 15]. Receiver operating characteristic curve analysis and logistic regression modelling were carried out to evaluate the discriminative power of the biomarkers. All biomarkers were corrected for confounding factors. VICM and C3M demonstrated the highest diagnostic power, alone, to differentiate CD from UC with an area under the curve [AUC] of 0.77 and 0.69, respectively. Furthermore, the biomarkers C1M [AUC = 0.81], C3M [AUC = 0.83], VICM [AUC = 0.83], and P1NP [AUC = 0.77] were best to differentiate UC from non-IBD. The best combinations of biomarkers to differentiate CD from UC and UC from non-IBD were VICM, C3M, C4M [AUC = 0.90] and VICM, C3M [AUC = 0.98] respectively. Specific extracellular matrix degradation markers are elevated in IBD and can discriminate CD from UC and UC from non-IBD controls with a high diagnostic accuracy. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Near-field transport of {sup 129}I from a point source in an in-room disposal vault

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolar, M.; Leneveu, D.M.; Johnson, L.H.

1995-12-31

A very small number of disposal containers of heat generating nuclear waste may have initial manufacturing defects that would lead to pin-hole type failures at the time of or shortly after emplacement. For sufficiently long-lived containers, only the initial defects need to be considered in modeling of release rates from the disposal vault. Two approaches to modeling of near-field mass transport from a single point source within a disposal room have been compared: the finite-element code MOTIF (A Model Of Transport In Fractured/porous media) and a boundary integral method (BIM). These two approaches were found to give identical results formore » a simplified model of the disposal room without groundwater flow. MOTIF has then been used to study the effects of groundwater flow on the mass transport out of the emplacement room.« less

Characteristics of uranium carbonitride microparticles synthesized using different reaction conditions

NASA Astrophysics Data System (ADS)

Silva, Chinthaka M.; Lindemer, Terrence B.; Voit, Stewart R.; Hunt, Rodney D.; Besmann, Theodore M.; Terrani, Kurt A.; Snead, Lance L.

2014-11-01

Three sets of experimental conditions were tested to synthesize uranium carbonitride (UC1-xNx) kernels from gel-derived urania-carbon microspheres. Primarily, three sequences of gases were used, N2 to N2-4%H2 to Ar, Ar to N2 to Ar, and Ar-4%H2 to N2-4%H2 to Ar-4%H2. Physical and chemical characteristics such as geometrical density, phase purity, and chemical compositions of the synthesized UC1-xNx were measured. Single-phase kernels were commonly obtained with densities generally ranging from 85% to 93% TD and values of x as high as 0.99. In-depth analysis of the microstrutures of UC1-xNx has been carried out and is discussed with the objective of large batch fabrication of high density UC1-xNx kernels.

Fat intake and risk of ulcerative colitis: Systematic review and dose-response meta-analysis of epidemiological studies.

PubMed

Wang, Fan; Lin, Xue; Zhao, Qiu; Li, Jin

2017-01-01

Fat intake is generally thought as a risk factor for onset of ulcerative colitis (UC), while epidemiological data had been controversial. This study aimed to evaluate the role of fat intake in the development of UC. Comprehensive search in PubMed and Embase was conducted to identify all relevant studies, and the role of fat intake in the development of UC was quantitatively assessed by dose-response meta-analysis. Nine studies (four case-control and five prospective cohort) were indentified with a total of 966 UC cases and 171 589 controls. No evidence of a nonlinear dose-response association was found between fat intake and UC risk. Overall, the summary relative risks (RR) for per 30 g increment/day were 1.023 (95%confidence interval [CI]: 0.963-1.087; I 2  = 24%; n = 6) for total fat intake, 1.063 (95%CI: 0.845-1.337; I 2  = 44.5%; n = 4) for saturated fat intake, 1.214 (95%CI: 0.911-1.618; I 2  = 63.1%; n = 4) for monounsaturated fat (MUFA) intake, and 1.247 (95%CI: 0.948-1.640; I 2  = 25.4%; n = 4) for polyunsaturated fat (PUFA) intake, respectively. Subgroup and sensitivity analyses showed inconsistent results on PUFA intake, which was significantly related with UC risk after adjusting for smoking (RR: 1.617, 95%CI: 1.045-2.502; I 2  = 0%; n = 3). For PUFA and MUFA subtypes, no subtypes were significantly associated with UC risk (P > 0.05), and only docosahexaenoic acid showed a potential protective effect in the development of UC (RR for the highest versus lowest intake level: 0.642, 95%CI: 0.403-1.024; I 2  = 34.4%; n = 3) CONCLUSIONS: This meta-analysis suggested a lack of association between fat intake and UC risk, and large-scale prospective designed studies are warranted to confirm our findings. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin

Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted intomore » the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease.« less

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients.

PubMed

Lucendo, Alfredo J; Arias, Ángel; Roncero, Óscar; Hervías, Daniel; Verdejo, Cristina; Naveas-Polo, Carmen; Bouhmidi, Abdelmouneim; Lorente, Rufo; Alcázar, Luis Miguel; Salueña, Irina; García-Quiñones, Julio A; Carrillo-Ramos, María Jesús

2017-04-01

The prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated. Retrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn's disease/ulcerative colitis (CD/UC): 718/560] were collected. Anemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p<0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18-12.10 and 6.55; 95%CI 3.39-12.63, respectively), followed by elevated (≥2mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39-6.97 and 4.58; 95%CI 2.26-9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24-4.02), but a protective one in UC (OR 0.36; 95%CI 0.14-0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36-8.21); in UC, anemia increased with disease extension (E2+E3) (OR 1.80; 95%CI 1.13-2.86). Female sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC. Copyright © 2016. Published by Elsevier Ltd.

A quasi-hexagonal prism-shaped carbon nitride for photoreduction of carbon dioxide under visible light.

PubMed

He, Zhiqiao; Wang, Danfen; Tang, Juntao; Song, Shuang; Chen, Jianmeng; Tao, Xinyong

2017-03-01

A quasi-hexagonal prism-shaped carbon nitride (H-C 3 N 4 ) was synthesized from urea-derived C 3 N 4 (U-C 3 N 4 ) using an alkaline hydrothermal process. U-C 3 N 4 decomposition followed by hydrogen bond rearrangement of hydrolyzed products leads to the formation of a quasi-hexagonal prism-shaped structure. The H-C 3 N 4 catalysts displayed superior activity in the photoreduction of CO 2 with H 2 O compared to U-C 3 N 4 . The enhanced photocatalytic activities can be attributed to the promotion of incompletely coordinated nitrogen atom formation in the C 3 N 4 molecules. Graphical abstract ᅟ.

Monitoring engineered remediation with borehole radar

USGS Publications Warehouse

Lane, J.W.; Day-Lewis, F. D.; Joesten, P.K.

2007-01-01

The success of engineered remediation is predicated on correct emplacement of either amendments (e.g., vegetable-oil emulsion, lactate, molasses, etc.) or permeable reactive barriers (e.g., vegetable oil, zero-valent iron, etc.) to enhance microbial or geochemical breakdown of contaminants and treat contaminants. Currently, site managers have limited tools to provide information about the distribution of injected materials; the existence of gaps or holes in barriers; and breakdown or transformation of injected materials over time. ?? 2007 Society of Exploration Geophysicists.

Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model

PubMed Central

2012-01-01

Background Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. Methods 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. Results At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Conclusions Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels. PMID:22361346

Ultrasonic scalpel causes greater depth of soft tissue necrosis compared to monopolar electrocautery at standard power level settings in a pig model.

PubMed

Homayounfar, Kia; Meis, Johanna; Jung, Klaus; Klosterhalfen, Bernd; Sprenger, Thilo; Conradi, Lena-Christin; Langer, Claus; Becker, Heinz

2012-02-23

Ultrasonic scalpel (UC) and monopolar electrocautery (ME) are common tools for soft tissue dissection. However, morphological data on the related tissue alteration are discordant. We developed an automatic device for standardized sample excision and compared quality and depth of morphological changes caused by UC and ME in a pig model. 100 tissue samples (5 × 3 cm) of the abdominal wall were excised in 16 pigs. Excisions were randomly performed manually or by using the self-constructed automatic device at standard power levels (60 W cutting in ME, level 5 in UC) for abdominal surgery. Quality of tissue alteration and depth of coagulation necrosis were examined histopathologically. Device (UC vs. ME) and mode (manually vs. automatic) effects were studied by two-way analysis of variance at a significance level of 5%. At the investigated power level settings UC and ME induced qualitatively similar coagulation necroses. Mean depth of necrosis was 450.4 ± 457.8 μm for manual UC and 553.5 ± 326.9 μm for automatic UC versus 149.0 ± 74.3 μm for manual ME and 257.6 ± 119.4 μm for automatic ME. Coagulation necrosis was significantly deeper (p < 0.01) when UC was used compared to ME. The mode of excision (manual versus automatic) did not influence the depth of necrosis (p = 0.85). There was no significant interaction between dissection tool and mode of excision (p = 0.93). Thermal injury caused by UC and ME results in qualitatively similar coagulation necrosis. The depth of necrosis is significantly greater in UC compared to ME at investigated standard power levels.

AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells.

PubMed

Qu, Zhiguo; Guo, Shengnan; Fang, Guojun; Cui, Zhenghong; Liu, Ying

2015-04-01

We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8 weeks post fracture for analysis. The fracture line became less defined at 4 weeks and disappeared at 8 weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50% compared to the hUC-MSCs with plasma group and decreased 70% compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.

Investigation of Crohn’s Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship

PubMed Central

ANDERSON, CARL A.; MASSEY, DUNECAN C. O.; BARRETT, JEFFREY C.; PRESCOTT, NATALIE J.; TREMELLING, MARK; FISHER, SHEILA A.; GWILLIAM, RHIAN; JACOB, JEMIMA; NIMMO, ELAINE R.; DRUMMOND, HAZEL; LEES, CHARLIE W.; ONNIE, CLIVE M.; HANSON, CATHERINE; BLASZCZYK, KATARZYNA; RAVINDRARAJAH, RADHI; HUNT, SARAH; VARMA, DHIRAJ; HAMMOND, NAOMI; LEWIS, GREGORY; ATTLESEY, HEATHER; WATKINS, NICK; OUWEHAND, WILLEM; STRACHAN, DAVID; MCARDLE, WENDY; LEWIS, CATHRYN M.; LOBO, ALAN; SANDERSON, JEREMY; JEWELL, DEREK P.; DELOUKAS, PANOS; MANSFIELD, JOHN C.; MATHEW, CHRISTOPHER G.; SATSANGI, JACK; PARKES, MILES

2009-01-01

Background & Aims Identifying shared and disease-specific susceptibility loci for Crohn’s disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. Methods We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. Results Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 × 10-8; odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. Conclusions Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis. PMID:19068216

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

PubMed

Hüppe, Angelika; Langbrandtner, Jana; Häuser, Winfried; Raspe, Heiner; Bokemeyer, Bernd

2018-05-09

 Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDI CD ) and UC (GIBDI UC ) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices.  Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements.  Rank correlations were 0.56 (pMS, GIBDI UC ) and 0.57 (HBI, GIBDI CD ), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories).  There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information. © Georg Thieme Verlag KG Stuttgart · New York.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

PubMed

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-12-14

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. A CCl 4 -induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo . Functionally, the transplantation of hUC-MSCs to CCl 4 -treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl 4 -induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

In vivo hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis

PubMed Central

Zhang, Guo-Zun; Sun, Hui-Cong; Zheng, Li-Bo; Guo, Jin-Bo; Zhang, Xiao-Lan

2017-01-01

AIM To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis. METHODS A CCl4-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR. RESULTS We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes in vivo. Functionally, the transplantation of hUC-MSCs to CCl4-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling via the up-regulation of MMP-13 and down-regulation of TIMP-1. CONCLUSION Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl4-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis. PMID:29290652

Cooperative and non-cooperative sensitization upconversion in lanthanide-doped LiYbF4 nanoparticles.

PubMed

Zou, Qilin; Huang, Ping; Zheng, Wei; You, Wenwu; Li, Renfu; Tu, Datao; Xu, Jin; Chen, Xueyuan

2017-05-18

Lanthanide (Ln 3+ )-doped upconversion nanoparticles (UCNPs) have attracted tremendous interest owing to their potential bioapplications. However, the intrinsic photophysics responsible for upconversion (UC) especially the cooperative sensitization UC (CSU) in colloidal Ln 3+ -doped UCNPs has remained untouched so far. Herein, we report a unique strategy for the synthesis of high-quality LiYbF 4 :Ln 3+ core-only and core/shell UCNPs with tunable particle sizes and shell thicknesses. Energy transfer UC from Er 3+ , Ho 3+ and Tm 3+ and CSU from Tb 3+ were comprehensively surveyed under 980 nm excitation. Through surface passivation, we achieved efficient non-cooperative sensitization UC with absolute UC quantum yields (QYs) of 3.36%, 0.69% and 0.81% for Er 3+ , Ho 3+ and Tm 3+ , respectively. Particularly, we for the first time quantitatively determined the CSU efficiency for Tb 3+ with an absolute QY of 0.0085% under excitation at a power density of 70 W cm -2 . By means of temperature-dependent steady-state and transient UC spectroscopy, we unraveled the dominant mechanisms of phonon-assisted cooperative energy transfer (T > 100 K) and sequential dimer ground-state absorption/excited-state absorption (T < 100 K) for the CSU process in LiYbF 4 :Tb 3+ UCNPs.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment.

PubMed

Cañas-Ventura, Alex; Márquez, Lucia; Ricart, Elena; Domènech, Eugeni; Gisbert, Javier P; García-Sanchez, Valle; Marín-Jiménez, Ignacio; Rodriguez-Moranta, Francisco; Gomollón, Fernando; Calvet, Xavier; Merino, Olga; Garcia-Planella, Esther; Vázquez-Romero, Narcis; Esteve, Maria; Iborra, Marisa; Gutiérrez, Ana; Vera, Maribel; Andreu, Montserrat

2014-10-01

Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain. Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI. Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR 1.5, 95% CI: 1.0-2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5-3.4) and need for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when AZA/MP started in the first 33 months after UC diagnosis. Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Surface drilling technologies for Mars

NASA Technical Reports Server (NTRS)

Blacic, J. D.; Rowley, J. C.; Cort, G. E.

1986-01-01

Rock drilling and coring conceptual designs for the surface activities associated with a manned Mars mission are proposed. Straightforward extensions of equipment and procedures used on Earth are envisioned for the sample coring and shallow high explosive shot holes needed for tunneling and seismic surveying. A novel rocket exhaust jet piercing method is proposed for very rapid drilling of shot holes required for explosive excavation of emergency radiation shelters. Summaries of estimated equipment masses and power requirements are provided, and the indicated rotary coring rigs are scaled from terrestrial equipment and use compressed CO2 from the Martian atmosphere for core bit cooling and cuttings removal. A mass of 120 kg and power of 3 kW(e) are estimated for a 10 m depth capability. A 100 m depth capacity core rig requires about 1150 kg and 32 km(e). The rocket exhaust jet equipment devised for shallow (3m) explosive emplacement shot holes requires no surface power beyond an electrical ignition system, and might have a 15 kg mass.

Environmental factors in infancy and ulcerative colitis in the Central South of Chile: a case-control study.

PubMed

Boneberger, Anja; Weiss, Eduardo Hebel; Calvo, Mario; Torres, Lilibeth; Wagner, Johanna; Kabesch, Michael; Radon, Katja

2011-10-01

Evidence for the role of the hygiene hypothesis and the development of Ulcerative Colitis (UC) is unclear. We aimed to explore the association between environmental factors in infancy and UC. A hospital-based case-control study (52 UC cases, response: 77%, 174 age- , sex and place of living matched controls, response: 62%) was carried out in the Central South of Chile in 2009/2010. Patients or parents underwent a personal interview about early life experiences. High paternal education (adjusted Odds Ratio (aOR): 2.1; 95% CI: 1.0-4.5) as proxy for socioeconomic status was positively associated with case status in the final multivariate logistic regression model. Likewise, having older siblings was a risk factor for UC (aOR: 2.2; 95%CI: 1.1.-4.4). The importance for some early life environmental factors in the development of UC was established. However, the role of the hygiene hypothesis could not be confirmed for all environmental factors. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Results of the exploratory drill hole Ue5n,Frenchman Flat, Nevada Test Site. [Geologic and geophysical parameters of selected locations with anomalous seismic signals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ramspott, L.D.; McArthur, R.D.

1977-02-18

Exploratory hole Ue5n was drilled to a depth of 514 m in central Frenchmam Flat, Nevada Test Site, as part of a program sponsored by the Nuclear Monitoring Office (NMO) of the Advanced Research Projects Agency (ARPA) to determine the geologic and geophysical parameters of selected locations with anomalous seismic signals. The specific goal of drilling Ue5n was to provide the site characteristics for emplacement sites U5b and U5e. We present here data on samples, geophysical logs, lithology and stratigraphy, and depth to the water table. From an analysis of the measurements of the physical properties, a set of recommendedmore » values is given.« less

A randomised translational trial of lifestyle intervention using a 3-tier shared care approach on pregnancy outcomes in Chinese women with gestational diabetes mellitus but without diabetes.

PubMed

Yang, Xilin; Tian, Huiguang; Zhang, Fuxia; Zhang, Cuiping; Li, Yi; Leng, Junhong; Wang, Leishen; Liu, Gongshu; Liu, Gongsu; Dong, Ling; Yu, Zhijie; Hu, Gang; Chan, Juliana Cn

2014-10-28

There are no randomised controlled trials to demonstrate whether lifestyle modifications can improve pregnancy outcomes of gestational diabetes mellitus (GDM) diagnosed by the International Association of Diabetes and Pregnancy Study Group's (IADPSG) criteria. We tested the effectiveness of lifestyle modifications implemented in a 3-tier's shared care (SC) on pregnancy outcomes of GDM. Between December 2010 and October 2012, we randomly assigned 700 women with IADPSG-defined GDM but without diabetes at 26.3 (interquartile range: 25.4-27.3) gestational weeks in Tianjin, China, to receive SC or usual care (UC). The SC group received individual consultations and group sessions and performed regular self-monitoring of blood glucose compared to one hospital-based education session in the UC group. The outcomes were macrosomia defined as birth weight ≥ 4.0 kg and the pregnancy-induced hypertension (PIH). Women in the SC (n = 339) and UC (n = 361) groups delivered their infants at similar gestational weeks. Birth weight of infants in the SC group was lower than that in the UC group (3469 vs. 3371 grams, P = 0.021). The rate of macrosomia was 11.2% (38/339) in the SC group compared to 17.5% (63/361) in the UC group with relative risk (RR) of 0.64 (95% CI: 0.44-0.93). The rate of PIH was 8.0% (27/339) in the SC compared to 4.4% (16/361) in the UC with RR of 1.80 (0.99-3.28). Apgar score at 1 min < 7 was lower but preeclampsia was higher in the SC than in the UC. Lifestyle modifications using a SC system improved pregnancy outcomes in Chinese women with GDM. Clinicaltrials.gov; NCT01565564.

Clinical course of ulcerative colitis patients who develop acute pancreatitis

PubMed Central

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-01-01

AIM To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. METHODS We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. RESULTS Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. CONCLUSION Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent. PMID:28596686

Clinical course of ulcerative colitis patients who develop acute pancreatitis.

PubMed

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-05-21

To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent.

Differential expression of GPR15 on T cells during ulcerative colitis

PubMed Central

Adamczyk, Alexandra; Gageik, Daniel; Frede, Annika; Pastille, Eva; Hansen, Wiebke; Rueffer, Andreas; Buer, Jan; Büning, Jürgen; Langhorst, Jost

2017-01-01

G protein–coupled receptor 15 (GPR15) was recently highlighted as a colon-homing receptor for murine and human CD4+ T cells. The aim of this study was to explore the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and effector T cells (Teffs), and to determine whether GPR15 is the driver for the migration of T cells to the colon during ulcerative colitis (UC). In the peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell subsets produced less IFN-γ and IL-4 but more IL-17 after stimulation and showed a higher migration activity compared with GPR15–CD4+ T cells. In UC patients, GPR15 expression was increased on Tregs in the peripheral blood but not on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on colonic T cells of UC patients in noninflamed biopsies but not in inflamed biopsies. The differential expression of GPR15 in UC patients was accompanied by a significant reduction of bacterial immunoregulatory metabolites in the feces. In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which may have implications for the development of therapeutic approaches to target T cell trafficking to the colon. PMID:28422750

Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.

PubMed

Kevans, D; Tyler, A D; Holm, K; Jørgensen, K K; Vatn, M H; Karlsen, T H; Kaplan, G G; Eksteen, B; Gevers, D; Hov, J R; Silverberg, M S

2016-03-01

There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes. In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction. No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Urinary calculi increase the risk for adverse pregnancy outcomes: a nationwide study.

PubMed

Chung, Shiu-Dong; Chen, Yi-Hua; Keller, Jospeh J; Lin, Ching-Chun; Lin, Herng-Ching

2013-01-01

Using two large-scale nationwide population-based data sets, this study aimed to assess the risk of adverse pregnancy outcomes between mothers with and without urinary calculi. Cross-sectional study. Taiwan. This study included 3694 women who had live singleton births and received a diagnosis of urinary calculi (UC) in the year prior to their delivery, as well as 18 470 matched women without UC, who were used as a comparison group. Conditional logistic regression analyses were performed. Low birthweight, preterm birth, small for gestational age, cesarean section, lower Apgar score and pre-eclampsia/eclampsia. Women with UC had a higher prevalence of low-birthweight neonates (7.4 vs. 6.0%, p = 0.003), preterm births (9.5 vs. 7.3%, p < 0.001) and cesarean sections (43.1 vs. 35.4%, p < 0.001) than women without UC. After adjusting for potential confounding factors, women with UC were more likely than women without UC to have low-birthweight neonates (odds ratio 1.21, 95% confidence interval 1.05-1.39), preterm birth (odds ratio 1.28, 95% confidence interval 1.13-1.43) and cesarean sections (odds ratio 1.37, 95% confidence interval 1.28-1.48). There were increased risks for having low-birthweight, preterm infants and for experiencing cesarean section among women with UC in comparison to women without UC. © 2012 The Authors © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Color-tunable up-conversion emission from Yb{sup 3+}/Er{sup 3+}/Tm{sup 3+} tri-doped T-AgGd(W,Mo){sub 2}O{sub 8} phosphors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jijian; Liu, Ni; Xu, Ling, E-mail: xuling@snnu.edu.cn

Graphical abstract: The doping ions tune the UC luminescence of the T- AgGd(W,Mo){sub 2}O{sub 8}:Yb{sup 3+}/Er{sup 3+}/Tm{sup 3+} material. - Highlights: • AgGd(W,Mo){sub 2}O{sub 8}:Yb{sup 3+}/Er{sup 3+}/Tm{sup 3+} phosphors show color-tunable blue, green, and red UC emissions. • The samples’ UC emission color can be switched with the concentrations of doped ions. • The blue, green and red UC mechanisms are interpreted reasonably as three- and two- photon process. - Abstract: Tetragonal Yb{sup 3+}/Er{sup 3+}/Tm{sup 3+} tri-doped AgGd(W,Mo){sub 2}O{sub 8} phosphors were prepared by the high-temperature solid-state method. When the phosphors were excited at 980 nm, the UC emission ofmore » blue at 475 nm, green at 525 and 550 nm, and red at 656 nm were corresponding to the {sup 1}G{sub 4} → {sup 3}H{sub 6} transition of Tm{sup 3+} ions, the {sup 2}H{sub 11/2},{sup 4}S{sub 3/2} → {sup 4}I{sub 15/2} transitions of Er{sup 3+} ions, and the {sup 4}F{sub 9/2} → {sup 4}I{sub 15/2} transition of Er{sup 3+} ions, respectively. The blue UC emissions originate from a three-photon mechanism, while the green and red ones of Er{sup 3+} from two-photon process. The UC emission color of the Yb{sup 3+}/Er{sup 3+}/Tm{sup 3+} tri-doped AgGdW{sub 2}O{sub 8} samples switched from green to white, and then to red depending on the concentrations of Er{sup 3+} and Tm{sup 3+}. After doping with Mo(VI), tetragonal AgGdW{sub 2}O{sub 8} was transformed into tetragonal AgGdMo{sub 2}O{sub 8}, resulting in a slightly enhanced UC luminescence intensity with the favor of the red emission of Er{sup 3+} ion.« less

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

PubMed

Nomura, E; Kinouchi, Y; Negoro, K; Kojima, Y; Oomori, S; Sugimura, M; Hiroki, M; Takagi, S; Aihara, H; Takahashi, S; Hiwatashi, N; Shimosegawa, T

2004-09-01

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

Efficient up-conversion in Yb:Er:NaT(XO4)2 thermal nanoprobes. Imaging of their distribution in a perfused mouse

PubMed Central

Serrano, María Dolores; Han, Xiumei; Cascales, Concepción; Cantero, Marta; Montoliu, Lluís; Arza, Elvira; Caiolfa, Valeria R.; Zamai, Moreno

2017-01-01

Yb and Er codoped NaT(XO4)2 (T = Y, La, Gd, Lu and X = Mo, W) disordered oxides show a green (Er3+ related) up-conversion (UC) efficiency comparable to that of Yb:Er:β-NaYF4 compound and unless 3 times larger UC ratiometric thermal sensitivity. The similar UC efficiency of Yb:Er doped NaT(XO4)2 and β-NaYF4 compounds allowed testing equal subcutaneous depths of ex-vivo chicken tissue in both cases. This extraordinary behavior for NaT(XO4)2 oxides with large cutoff phonon energy (ħω≈ 920 cm-1) is ascribed to 4F9/2 electron population recycling to higher energy 4G11/2 level by a phonon assisted transition. Crystalline nanoparticles of Yb:Er:NaLu(MoO4)2 have been synthesized by sol-gel with sizes most commonly in the 50–80 nm range, showing a relatively small reduction of the UC efficiency with regards to bulk materials. Fluorescence lifetime and multiphoton imaging microscopies show that these nanoparticles can be efficiently distributed to all body organs of a perfused mouse. PMID:28542327

First Results on High-spin States in ^179Au

NASA Astrophysics Data System (ADS)

Mueller, W. F.; Bingham, C. R.; Reviol, W.; Riedinger, L. L.; Smith, B. H.; Wauters, J.; Ahmad, I.; Amro, H. A.; Blumenthal, D. J.; Carpenter, M. P.; Davids, C. N.; Fischer, S. M.; Hackman, G.; Henderson, D. J.; Janssens, R. V. F.; Khoo, T. L.; Lauritsen, T.; Lister, C. J.; Nisius, D. T.; Seweryniak, D.; Ma, W. C.

1996-05-01

High-spin states in ^179Au were studied for the first time in two experiments at the Argonne uc(atlas) facility. The ^144Sm(^40Ar,p4n)^179Au reaction at 207 MeV was used for the first experiment and ^124Te(^58Ni,p2n)^179Au at 255 MeV in the second. The setup in the first experiment consisted of the Fragment Mass Analyzer (uc(fma)) plus Parallel Plate Avalanche Counter (uc(ppac)) system and 10 Compton-suppressed Ge detectors (CSG's). From this run, several transitions from the yrast bands were established. The latter experiment utilized the uc(fma) + uc(ppac) system in conjunction with the uc(aye-ball) array of 19 Ge detectors (eight >70% efficient CSG's, nine 25% efficient CSG's, and two LEPS; one with Compton suppression) and a double sided silicon strip detector (uc(dssd).) The results from these experiments, including a level scheme, will be presented and discussed.

The Atlantis Bank Gabbro Massif, SW Indian Ridge: the Largest Know Exposure of the Lower Crust in the Oceans

NASA Astrophysics Data System (ADS)

Dick, H. J.; Kvassnes, A. J.; Kinoshita, H.; MacLeod, C. J.; Robinson, P. T.

2017-12-01

Until the discovery of oceanic core complexes little was known and much inferred about the lower ocean crust at slow-spreading ridges. Their study shows the ocean crust isn't simply a uniform layer-cake of pillow lavas, sheeted dikes and gabbros, but is highly variable in thickness, composition and architecture, and even absent over large regions. The 660 km2 Atlantis Bank Gabbro Massif in the rift-mountains of the SW Indian Ridge flanking the Atlantis II Transform is the magmatic end member for ocean core complexes, and best approximates `average' slow-spread crust. Thus it has been a focus for drilling since its discovery in 1986, leading to the current attempt to drill to Moho there (Project SloMo). There are 3 ODP and IODP drill holes on its crest: 1508-m deep Hole 735B, 158-m deep Hole 1105A, and 809.4-m deep Hole U1473. These provide a 200 Kyr view of lower crustal accretion at a slow-spread ocean ridge. Here we extend this view to 2.7 Myr. Mapping and sampling shows the gabbro massif extends nearly the length of a single 2nd order magmatic ridge segment. With numerous inliers of the dike-gabbro transition at numerous locations, and a crust-mantle boundary, traced for 30-km along the transform wall, it would appear to represent a full section of the lower crust. As Moho is at 5.5 ± 1 km mbsf near Hole 735B, and 4.5 km beneath the transform, it is likely a serpentinization front. The crust-mantle boundary was crossed by dives at 4 locations. In each case gabbros at the base of the crust crystallized from melt that had previously fractionated 50% or more from a likely parent. Thus the gabbro massif must be laterally zoned, and the parental mantle melts had to have been emplaced at the center of the paleo-ridge segment, before intruding laterally to the distal end of the complex. Gabbros on a lithospheric flow line down the center of the massif closely resemble those from the drill holes. This shows that while lateral variations in crustal composition and thickness exist at Atlantis Bank, we can extend the conclusions derived from drilling at Hole U1473 that there is a continuum of accretionary magmatic and tectonic processes for 2.7 Myr, and a centrally located deep hole through the lower crust and mantle there will likely be representative of the 660-km2 Atlantis Bank gabbro massif as a whole.

Disposition and metabolism of 2,3-( UC)dichloropropene in rats after inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, J.A.; Medinsky, M.A.; Dutcher, J.S.

1985-01-01

2,3-Dichloropropene (2,3-DCP) is a constituent of some commercially available preplant soil fumigants for the control of plant parasitic nematodes. The purpose of this investigation was to determine the disposition and metabolism of 2,3-( UC)DCP in rats after inhalation. Male Fischer-344 rats were exposed nose-only to a vapor concentration of 250 nmol 2,3-( UC)DCP/liter air (7.5 ppm; 25C, 620 Torr) for 6 hr. Blood samples were taken during exposure, and urine, feces, expired air, and tissues were collected for up to 65 hr after exposure. Urinary excretion was the major route of elimination of UC (55% of estimated absorbed 2,3-DCP). Half-timemore » for elimination of UC in urine was 9.8 +/- 0.05 hr (anti x +/- SE). Half-time for elimination of UC feces (17% of absorbed 2,3-DCP) was 12.9 +/- 0.14 hr (anti x +/- SE). Approximately 1 and 3% of the estimated absorbed 2,3-( UC)DCP were exhaled as either 2,3-( UC)DCP or UCO2, respectively. Concentrations of UC in blood increased during 240 min of exposure, after which no further increases in blood concentration of UC were seen. UC was widely distributed in tissues analyzed after a 6-hr exposure of rats to 2,3-( UC)DCP. Urinary bladder (150 nmol/g), nasal turbinates (125 nmol/g), kidneys (84 nmol/g), small intestine (61 nmol/g), and liver (35 nmol/g) were tissues with the highest concentrations of UC immediately after exposure. Over 90% of the UC in tissues analyzed was 2,3-DCP metabolites. Half-times for elimination of UC from tissues examined ranged from 3 to 11 hr. The data from this study indicate that after inhalation 2,3-DCP is metabolized in tissues and readily excreted. 21 references. 2 figures, 4 tables.« less

Sensor emplacement testing at Poker Flat, Alaska

NASA Astrophysics Data System (ADS)

Reusch, A.; Beaudoin, B. C.; Anderson, K. E.; Azevedo, S.; Carothers, L.; Love, M.; Miller, P. E.; Parker, T.; Pfeifer, M.; Slad, G.; Thomas, D.; Aderhold, K.

2013-12-01

PASSCAL provides equipment and support for temporary seismic projects. Speed and efficiency of deployments are essential. A revised emplacement technique of putting broadband sensors directly into soil (aka direct burial) is being tested. The first phase (fall 2011 to spring 2013) comparing data quality and sensor stability between the direct burial and the traditional 1 m deep temporary PASSCAL-style vault in a wet and noisy site near San Antonio, NM is complete. Results suggest there is little or no difference in sensor performance in the relatively high-noise environment of this initial test. The second phase was started in November 2012 with the goal of making the same comparison, but at Poker Flat, Alaska, in a low-noise, high-signal, cold and wet environment, alongside a Transportable Array (TA) deployment to be used as a performance control. This location is in an accessible and secure area with very low site noise. In addition to benefiting future worldwide PASSCAL deployments, the Poker Flat experiment serves a secondary purpose of testing modifications necessary to successfully deploy and recover broadband stations in a cold environment with the limited logistics anticipated for remote Flexible Array (FA) and PASSCAL Program deployments in Alaska. Developing emplacement techniques that maintain high data quality and data return while minimizing logistics is critical to enable principle investigators to effectively and efficiently co-locate within the future TA Alaska footprint. Three Nanometrics sensors were installed in November 2012 in power-augered holes 76 cm in depth: a Trillium Compact Posthole (PH) and two Trillium 120PH units (one standard PH and one enhanced PHQ). The installations took less than 8 hours in -30°C conditions with 4 hours of usable daylight. The Compact PH and the 120PHQ are delivering data in realtime, while the 120PH is testing standalone power and data collection systems. Preliminary results compare favorably to each other as well as the nearby Trillium 240 in a traditional TA surface vault and a 120PH in a 5 m machine-drilled borehole. This summer, two Trillium 120PA sensors were installed at a depth of 54 cm in traditional PASSCAL-style vaults, adjacent to the Trillium Compact PH, Trillium 120PH and 120PHQ emplacements. Analysis of the data collected from these five sensors will include the use of probability density functions of power spectral density to examine temporal trends in noise, signal-to-noise ratios for local, regional, and teleseismic earthquakes, and coherence of both noise and earthquake signal recordings to compare the data quality of direct burial versus temporary PASSCAL-style vaults sensor emplacements.

Gastroenterologists' Perceptions Regarding Ulcerative Colitis and Its Management: Results from a Large-Scale Survey.

PubMed

Lasch, Karen; Liu, Stephen; Ursos, Lyann; Mody, Reema; King-Concialdi, Kristen; DiBonaventura, Marco; Leberman, Julie; Dubinsky, Marla

2016-10-01

Misperceptions about ulcerative colitis (UC) may influence management strategies and limit opportunities for improving patient outcomes. This study assessed physicians' perceptions of UC, concepts of disease severity and remission, and treatment goals. Gastroenterologists who typically treated ≥10 adults with UC per month were recruited for a large-scale, web-based survey. Participants were asked about their perceptions of UC (often vs. Crohn's disease [CD]), treatment goals, and medication use. Response data were evaluated via descriptive statistics and univariate and multivariable analyses. Gastroenterologists (N = 500) with a mean of 16.5 years (standard deviation, 8.7 years) in practice participated. In comparison to CD, survey respondents perceived UC as being easier to diagnose, having better treatment outcomes, and being associated with later prescribing of biologics. Treatment goals commonly considered to have the greatest importance included quality of life improvement (31.2% of respondents), maintenance of clinical remission (17.4%), and mucosal healing (17.4%). When respondents evaluated the performance of medication classes in achieving these goals, biologics were rated significantly higher than all other classes (P < 0.05). However, the most common drivers for the initiation of biologic therapy were the development of steroid refractoriness (66.8%) and steroid dependency (65.8%). Medication class use by UC severity was generally consistent with the traditional step-up approach to UC therapy, with biologics being used most commonly for severe UC. These results suggest a possible disparity between treatment goals and therapeutic management in UC. An increased awareness of general UC perceptions is an important step toward a better overall understanding of the disease and, ultimately, toward improved management aligned with treatment goals. This study was sponsored by the American Gastroenterological Association (AGA), and the design and conduct of the study as well as article processing charges and the open access fee for this publication were funded by Takeda Pharmaceuticals International, Inc. (TPI).

Gender dimorphism and lack of day/night variation or effects of energy deprivation on undercarboxylated osteocalcin levels in humans.

PubMed

Foo, Joo-Pin; Aronis, Konstantinos N; Chamberland, John P; Thakkar, Bindiya; Hamnvik, Ole-Petter; Brinkoetter, Mary; Zaichenko, Lesya; Mantzoros, Christos S

2013-12-01

Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans. Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels. Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels. The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported. Copyright © 2013 The Obesity Society.

Validation of a urine color scale for assessment of urine osmolality in healthy children.

PubMed

Kavouras, Stavros A; Johnson, Evan C; Bougatsas, Dimitris; Arnaoutis, Giannis; Panagiotakos, Demosthenes B; Perrier, Erica; Klein, Alexis

2016-04-01

Urine color (UC) is a practical tool for hydration assessment. The technique has been validated in adults, but has not been tested in children. The purpose of the study was to test the validity of the urine color scale in young, healthy boys and girls, as a marker of urine concentration, investigate its diagnostic ability of detecting hypohydration and examine the ability of children to self-assess UC. A total of 210 children participated (age: 8-14 years, body mass: 43.4 ± 12.6 kg, height: 1.49 ± 0.13 m, body fat: 25.2 ± 7.8 %). Data collection included: two single urine samples (first morning and before lunch) and 24-h sampling. Hydration status was assessed via urine osmolality (UOsmo) and UC via the eight-point color scale. Mean UC was 3 ± 1 and UOsmo 686 ± 223 mmol kg(-1). UC displayed a positive relationship as a predictor of UOsmo (R (2): 0.45, P < 0.001). Based on the receiver operating curve, UC has good overall classification ability for the three samples (area under the curve 85-92 %), with good sensitivity (92-98 %) and specificity (55-68 %) for detecting hypohydration. The overall accuracy of the self-assessment of UC in the morning or the noon samples ranged from 67 to 78 %. Further threshold analysis indicated that the optimal self-assessed UC threshold for hypohydration was ≥4. The classical eight-point urine color scale is a valid method to assess hydration in children of age 8-14 years, either by researchers or self-assessment.

Incidence and Clinical Outcomes of Inflammatory Bowel Disease in South Korea, 2011-2014: A Nationwide Population-Based Study.

PubMed

Jung, Yoon Suk; Han, Minkyung; Kim, Won Ho; Park, Sohee; Cheon, Jae Hee

2017-08-01

The incidence of inflammatory bowel disease (IBD) is increasing in East Asia; however, population-based data from this region are lacking. We conducted a nationwide, population-based study to examine the incidence and disease course of IBD in South Korea. Using the National Health Insurance claims data, we collected data on patients diagnosed with IBD [10,049 with ulcerative colitis (UC) and 5595 with Crohn's disease (CD)] from 2011 to 2014. During the study period, the average annual incidence of UC was 5.0 per 10 5 , while that of CD was 2.8 per 10 5 . Among patients with UC, the cumulative rates of surgery 1 and 4 years after diagnosis were 1.0 and 2.0%; those among patients with CD were 9.0 and 13.9%, respectively. The 1- and 4-year cumulative rates of moderate- to high-dose corticosteroid use were, respectively, 26.6 and 45.2% among patients with UC, and 29.9 and 50.8% among those with CD. Similarly, the 1- and 4-year cumulative rates of immunomodulator use were 14.1 and 26.4% among patients with UC, and 58.3 and 76.1% among those with CD, respectively. With regard to biologic use, the 1- and 4-year cumulative rates were 3.0 and 9.0% among patients with UC, and 11.1 and 31.7% among those with CD, respectively. The recent incidence of IBD in South Korea has been the highest in East Asia. Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.

Loss of Sh3gl2/Endophilin A1 Is a Common Event in Urothelial Carcinoma that Promotes Malignant Behavior12

PubMed Central

Majumdar, Shyama; Gong, Edward M; Di Vizio, Dolores; Dreyfuss, Jonathan; DeGraff, David J; Hager, Martin H; Park, Peter J; Bellmunt, Joaquim; Matusik, Robert J; Rosenberg, Jonathan E; Adam, Rosalyn M

2013-01-01

Urothelial carcinoma (UC) causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying urothelial cancer development and tumor progression are still largely unknown. Using informatics analysis, we identified Sh3gl2 (endophilin A1) as a bladder urothelium-enriched transcript. The gene encoding Sh3gl2 is located on chromosome 9p, a region frequently altered in UC. Sh3gl2 is known to regulate endocytosis of receptor tyrosine kinases implicated in oncogenesis, such as the epidermal growth factor receptor (EGFR) and c-Met. However, its role in UC pathogenesis is unknown. Informatics analysis of expression profiles as well as immunohistochemical staining of tissue microarrays revealed Sh3gl2 expression to be decreased in UC specimens compared to nontumor tissues. Loss of Sh3gl2 was associated with increasing tumor grade and with muscle invasion, which is a reliable predictor of metastatic disease and cancer-derived mortality. Sh3gl2 expression was undetectable in 19 of 20 human UC cell lines but preserved in the low-grade cell line RT4. Stable silencing of Sh3gl2 in RT4 cells by RNA interference 1) enhanced proliferation and colony formation in vitro, 2) inhibited EGF-induced EGFR internalization and increased EGFR activation, 3) stimulated phosphorylation of Src family kinases and STAT3, and 4) promoted growth of RT4 xenografts in subrenal capsule tissue recombination experiments. Conversely, forced re-expression of Sh3gl2 in T24 cells and silenced RT4 clones attenuated oncogenic behaviors, including growth and migration. Together, these findings identify loss of Sh3gl2 as a frequent event in UC development that promotes disease progression. PMID:23814487

UNC-45/CRO1/She4p (UCS) Protein Forms Elongated Dimer and Joins Two Myosin Heads Near Their Actin Binding Region

DOE Office of Scientific and Technical Information (OSTI.GOV)

H Shi; G Blobel

2011-12-31

UNC-45/CRO1/She4p (UCS) proteins have variously been proposed to affect the folding, stability, and ATPase activity of myosins. They are the only proteins known to interact directly with the motor domain. To gain more insight into UCS function, we determined the atomic structure of the yeast UCS protein, She4p, at 2.9 {angstrom} resolution. We found that 16 helical repeats are organized into an L-shaped superhelix with an amphipathic N-terminal helix dangling off the short arm of the L-shaped molecule. In the crystal, She4p forms a 193-{angstrom}-long, zigzag-shaped dimer through three distinct and evolutionary conserved interfaces. We have identified She4p's C-terminal regionmore » as a ligand for a 27-residue-long epitope on the myosin motor domain. Remarkably, this region consists of two adjacent, but distinct, binding epitopes localized at the nucleotide-responsive cleft between the nucleotide- and actin-filament-binding sites. One epitope is situated inside the cleft, the other outside the cleft. After ATP hydrolysis and Pi ejection, the cleft narrows at its base from 20 to 12 {angstrom} thereby occluding the inside the cleft epitope, while leaving the adjacent, outside the cleft binding epitope accessible to UCS binding. Hence, one cycle of higher and lower binding affinity would accompany one ATP hydrolysis cycle and a single step in the walk on an actin filament rope. We propose that a UCS dimer links two myosins at their motor domains and thereby functions as one of the determinants for step size of myosin on actin filaments.« less

Epidemiology of inflammatory bowel disease among participants of the Millennium Cohort: incidence, deployment-related risk factors, and antecedent episodes of infectious gastroenteritis.

PubMed

Porter, C K; Welsh, M; Riddle, M S; Nieh, C; Boyko, E J; Gackstetter, G; Hooper, T I

2017-04-01

Crohn's disease (CD) and ulcerative colitis (UC) are two pathotypes of inflammatory bowel disease (IBD) with unique pathology, risk factors and significant morbidity. To estimate incidence and identify IBD risk factors in a US military population, a healthy subset of the US population, using information from the Millennium Cohort Study. Incident IBD was identified from medical encounters from 2001 to 2009 or by self-report. Our primary risk factor of interest, infectious gastroenteritis, was identified from medical encounters and self-reported post-deployment health assessments. Other potential risk factors were assessed using self-reported survey responses and military personnel files. Hazard ratios were estimated using Cox proportional hazards analysis. We estimated 23.2 and 21.9 diagnoses per 100 000 person-years, respectively, for CD and UC. For CD, significant risk factors included [adjusted hazard ratio (aHR), 95% confidence interval]: current smoking (aHR: 2.7, 1.4-5.1), two life stressors (aHR: 2.8, 1.4-5.6) and prior irritable bowel syndrome (aHR: 4.7, 1.5-15.2). There was no significant association with prior infectious gastroenteritis. There was an apparent dose-response relationship between UC risk and an increasing number of life stressors. In addition, antecedent infectious gastroenteritis was associated with almost a three-fold increase in UC risk (aHR: 2.9, 1.4-6.0). Moderate alcohol consumption (aHR: 0.4, 0.2-0.6) was associated with lower UC risk. Stressful conditions and the high risk of infectious gastroenteritis in deployment operations may play a role in the development of IBD in military populations. However, observed differences in risk factors for UC and CD warrant further investigation. © 2017 John Wiley & Sons Ltd.

[Urinary catheters prevalence study in a university hospital].

PubMed

Carrouget, J; Legeay, C; Poirier, A; Azzouzi, A-R; Zahar, J-R; Bigot, P

2017-04-01

Urinary tract infection is the most common healthcare-association infection, especially because of urinary catheter. We evaluated our practices concerning catheter insertion and management in our institution. We conducted a single-centre descriptive cross-sectional study during 1 week in September 2014 in all adult departments. We noted prevalence, indications, length, management of urinary catheter (UC) and symptomatic catheter-associated urinary tract infections (SCAUTI). Amongst 1046 patients audited, 125 (12%) had UC. The mean age was 72 years (64.8-79.2). UC prevalence was higher in surgical (88%) and medical (87%) intensive care, urology (50%), geriatrics (18%) and long-term care (18%) departments. The average catheterisation length was 7.8 days (3.8-11.8); it was shorter in surgery than in medicine departments (3.6 vs 9.7 days, P<0.001). Catheters were present for more than 4 days in 60% of the cases. Acute urinary retention was the most frequent indication (59%), significantly more in medical than surgical departments (75% vs 26%). Others indications were perioperative (17%), diuresis monitoring (12%), strict immobilization (4%) and unnecessary indications or staff comfort (4%). A SCAUTI was present in 10% of cases, mostly in medicine department (30% vs 8%). The prevalence of our institution is higher than the national prevalence (8.1%), but still below the European average (17.2%). Control of the risk of CAUTI requires compliance with UC appropriate indications, UC management, and prompt removal of unnecessary UC. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis.

PubMed

Cheng, Yang; Zhu, Yun; Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn's disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.

Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies.

PubMed

Jess, Tine; Rungoe, Christine; Peyrin-Biroulet, Laurent

2012-06-01

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: A pilot study in 71 patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manas, Ana; Glaria, Luis; Pena, Carmen

2006-03-01

Purpose: To assess the impact of bladder instillations of hyaluronic acid (HA) on the prevalence of urinary tract infection (UTI) in patients receiving emergency radiotherapy for metastatic spinal cord compression. Methods and Materials: Patients were recruited consecutively at one center and assigned to usual care (UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation (UC + HA) (Cystistat: 40 mg in 50 mL phosphate-buffered saline) (n = 37; mean age, 63.1 years). All patients had an indwelling catheter and received radiotherapy. UTI status was assessed at baseline and during hospitalization. Results: At baseline, patient groupsmore » were comparable, except for the prevalence of UTI at baseline, which was 11.8% and 0% in the UC and UC + HA patients, respectively (p = 0.0477). During hospitalization, 76.5% (vs. 11.8% at baseline, p < 0.0001) of the UC patients had a UTI compared with 13.5% (vs. 0% at baseline, p = 0.0541) of the UC + HA patients (p < 0.0001). Both groups were hospitalized for similar periods (19.8 days [UC] vs. 18.5 days, p = 0.4769) and received equivalent radiotherapy sessions (4.6 [UC] vs. 5.8 sessions, p = 0.2368). Conclusions: Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the hospitalization period compared to UC patients, suggesting that bladder instillations of HA effectively prevent UTI in patients with indwelling catheters receiving radiotherapy for nerve compression.« less

Direct observation of the core/double-shell architecture of intense dual-mode luminescent tetragonal bipyramidal nanophosphors

NASA Astrophysics Data System (ADS)

Kim, Su Yeon; Jeong, Jong Seok; Mkhoyan, K. Andre; Jang, Ho Seong

2016-05-01

Highly efficient downconversion (DC) green-emitting LiYF4:Ce,Tb nanophosphors have been synthesized for bright dual-mode upconversion (UC) and DC green-emitting core/double-shell (C/D-S) nanophosphors--Li(Gd,Y)F4:Yb(18%),Er(2%)/LiYF4:Ce(15%),Tb(15%)/LiYF4--and the C/D-S structure has been proved by extensive scanning transmission electron microscopy (STEM) analysis. Colloidal LiYF4:Ce,Tb nanophosphors with a tetragonal bipyramidal shape are synthesized for the first time and they show intense DC green light via energy transfer from Ce3+ to Tb3+ under illumination with ultraviolet (UV) light. The LiYF4:Ce,Tb nanophosphors show 65 times higher photoluminescence intensity than LiYF4:Tb nanophosphors under illumination with UV light and the LiYF4:Ce,Tb is adapted into a luminescent shell of the tetragonal bipyramidal C/D-S nanophosphors. The formation of the DC shell on the core significantly enhances UC luminescence from the UC core under irradiation of near infrared light and concurrently generates DC luminescence from the core/shell nanophosphors under UV light. Coating with an inert inorganic shell further enhances the UC-DC dual-mode luminescence by suppressing the surface quenching effect. The C/D-S nanophosphors show 3.8% UC quantum efficiency (QE) at 239 W cm-2 and 73.0 +/- 0.1% DC QE. The designed C/D-S architecture in tetragonal bipyramidal nanophosphors is rigorously verified by an energy dispersive X-ray spectroscopy (EDX) analysis, with the assistance of line profile simulation, using an aberration-corrected scanning transmission electron microscope equipped with a high-efficiency EDX. The feasibility of these C/D-S nanophosphors for transparent display devices is also considered.Highly efficient downconversion (DC) green-emitting LiYF4:Ce,Tb nanophosphors have been synthesized for bright dual-mode upconversion (UC) and DC green-emitting core/double-shell (C/D-S) nanophosphors--Li(Gd,Y)F4:Yb(18%),Er(2%)/LiYF4:Ce(15%),Tb(15%)/LiYF4--and the C/D-S structure has been proved by extensive scanning transmission electron microscopy (STEM) analysis. Colloidal LiYF4:Ce,Tb nanophosphors with a tetragonal bipyramidal shape are synthesized for the first time and they show intense DC green light via energy transfer from Ce3+ to Tb3+ under illumination with ultraviolet (UV) light. The LiYF4:Ce,Tb nanophosphors show 65 times higher photoluminescence intensity than LiYF4:Tb nanophosphors under illumination with UV light and the LiYF4:Ce,Tb is adapted into a luminescent shell of the tetragonal bipyramidal C/D-S nanophosphors. The formation of the DC shell on the core significantly enhances UC luminescence from the UC core under irradiation of near infrared light and concurrently generates DC luminescence from the core/shell nanophosphors under UV light. Coating with an inert inorganic shell further enhances the UC-DC dual-mode luminescence by suppressing the surface quenching effect. The C/D-S nanophosphors show 3.8% UC quantum efficiency (QE) at 239 W cm-2 and 73.0 +/- 0.1% DC QE. The designed C/D-S architecture in tetragonal bipyramidal nanophosphors is rigorously verified by an energy dispersive X-ray spectroscopy (EDX) analysis, with the assistance of line profile simulation, using an aberration-corrected scanning transmission electron microscope equipped with a high-efficiency EDX. The feasibility of these C/D-S nanophosphors for transparent display devices is also considered. Electronic supplementary information (ESI) available: XRD patterns, PL and PLE spectra, SEM and HR-TEM images, PL decay times, photographs showing the transparent nanophosphor solutions and their dual-mode luminescence, and additional EDX data. See DOI: 10.1039/c5nr05722a

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

PubMed

Koch, H; van Bokhoven, M A; Bindels, P J E; van der Weijden, T; Dinant, G J; ter Riet, G

2009-12-01

Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low QoL.

Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial

PubMed Central

Zhang, Jian; Lv, Samei; Liu, Xiaojing; Song, Bin; Shi, Liping

2018-01-01

Background/Aims Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD. Methods Eighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×106 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed. Results Twelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p<0.01, p<0.05, and p<0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed. Conclusions UC-MSCs were effective in the treatment of CD and produced mild side effects. PMID:28873511

Mechanical Implantation of Urothelium Into Periureteral Soft Tissue: A Series of 4 Cases Mimicking High-stage Urothelial Carcinoma.

PubMed

Wobker, Sara E; Aron, Manju; Epstein, Jonathan I

2016-11-01

In the upper genitourinary tract of the ureter and renal pelvis, any invasion of urothelial carcinoma (UC) beyond the thin muscularis is considered pT3 disease, which may prompt adjuvant chemotherapy. Ureteroscopy is commonly used in the workup of these lesions to obtain tissue biopsies and cytology specimens, or to place stents for the relief of obstructive symptoms. The current study describes 4 cases in which the presence of small nests of urothelium in periureteral and peripelvic soft tissue was noted after ureteroscopic instrumentation, mimicking high-stage UC. All 4 cases had a history of ureteral instrumentation with biopsy of the suspected UC. The diagnostic biopsies showed low-grade noninvasive papillary UC (n=2), papillary urothelial neoplasm of uncertain malignant potential (n=1), and benign inverted urothelial papilloma (n=1). In the definitive resection specimens, small nests of bland urothelium were present in the periureteral or peripelvic soft tissue, raising the possibility of pT3 UC. We interpreted these displaced small nests to be the result of mechanical implantation occurring during the ureteroscopic procedure on the basis of the finding of associated linear fibrosis, inflammation, hemorrhage, and foreign body giant cells. In the setting of low-grade or benign urothelial neoplasms in the upper urinary tract, caution is warranted when cytologically bland nests of the urothelium are identified beyond the muscularis that could represent mechanically induced implants as opposed to invasive UC extending into peripelvic or periureteral soft tissue.

Improving work outcomes of dysthymia (persistent depressive disorder) in an employed population.

PubMed

Adler, David A; Lerner, Debra; Visco, Zachary L; Greenhill, Annabel; Chang, Hong; Cymerman, Elina; Azocar, Francisca; Rogers, William H

2015-01-01

To test the effectiveness of a work-focused intervention (WFI) on the work outcomes of employed adults with dysthymia. This subgroup analysis from a randomized controlled trial compares an initial sample of 167 employees (age: ≥45 years), screened for dysthymia using the PC-SAD without current major depressive disorder randomized to WFI (n=85) or usual care (UC) (n=82). Study sites included 19 employers and five additional organizations. Telephone-based WFI counseling (eight, twice monthly 50-min sessions) provided work coaching and modification, care coordination and cognitive behavioral therapy. Adjusted mixed effects models compared the WFI vs. UC group preintervention to 4-month postintervention change in at-work limitations measured by the Work Limitations Questionnaire. Secondary outcome analysis compared the change in self-reported absences and depression symptom severity (Patient Health Questionnaire PHQ-9 scores). Work productivity loss scores improved 43.0% in the WFI group vs. 4.8% in UC (difference in change: P<.001). Absence days declined by 58.3% in WFI vs. 0.0% in UC (difference in change: P=.09). Mean PHQ-9 depression symptom severity declined 44.2% in WFI vs. 5.3% in UC (difference in change: P<.001). At 4 months, the WFI was more effective than UC on two of the three outcomes. It could be an important mental and functional health improvement resource for the employed dysthymic population. Copyright © 2015 Elsevier Inc. All rights reserved.

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

PubMed

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis

PubMed Central

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-01-01

Background Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population. PMID:29511562

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis.

PubMed

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-03-01

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Fan, Ruo-Jing; Guan, Qing; Zhang, Fang; Leng, Jia-Peng; Sun, Tuan-Qi; Guo, Yin-Long

2016-02-18

Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Paving the seafloor: Volcanic emplacement processes during the 2005-2006 eruptions at the fast spreading East Pacific Rise, 9°50‧N

NASA Astrophysics Data System (ADS)

Fundis, A. T.; Soule, S. A.; Fornari, D. J.; Perfit, M. R.

2010-08-01

The 2005-2006 eruptions near 9°50'N at the East Pacific Rise (EPR) marked the first observed repeat eruption at a mid-ocean ridge and provided a unique opportunity to deduce the emplacement dynamics of submarine lava flows. Since these new flows were documented in April 2006, a total of 40 deep-towed imaging surveys have been conducted with the Woods Hole Oceanographic Institution's (WHOI) TowCam system. More than 60,000 digital color images and high-resolution bathymetric profiles of the 2005-2006 flows from the TowCam surveys were analyzed for lava flow morphology and for the presence of kipukas, collapse features, faults and fissures. We use these data to quantify the spatial distributions of lava flow surface morphologies and to investigate how they relate to the physical characteristics of the ridge crest, such as seafloor slope, and inferred dynamics of flow emplacement. We conclude that lava effusion rate was the dominant factor controlling the observed morphological variations in the 2005-2006 flows. We also show that effusion rates were higher than in previously studied eruptions at this site and varied systematically along the length of the eruptive fissure. This is the first well-documented study in which variations in seafloor lava morphology can be directly related to a well documented ridge-crest eruption where effusion rate varied significantly.

Optimization of Deep Borehole Systems for HLW Disposal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, Michael; Baglietto, Emilio; Buongiorno, Jacopo

2015-09-09

This is the final report on a project to update and improve the conceptual design of deep boreholes for high level nuclear waste disposal. The effort was concentrated on application to intact US legacy LWR fuel assemblies, but conducted in a way in which straightforward extension to other waste forms, host rock types and countries was preserved. The reference fuel design version consists of a vertical borehole drilled into granitic bedrock, with the uppermost kilometer serving as a caprock zone containing a diverse and redundant series of plugs. There follows a one to two kilometer waste canister emplacement zone havingmore » a hole diameter of approximately 40-50 cm. Individual holes are spaced 200-300 m apart to form a repository field. The choice of verticality and the use of a graphite based mud as filler between the waste canisters and the borehole wall liner was strongly influenced by the expectation that retrievability would continue to be emphasized in US and worldwide repository regulatory criteria. An advanced version was scoped out using zinc alloy cast in place to fill void space inside a disposal canister and its encapsulated fuel assembly. This excludes water and greatly improves both crush resistance and thermal conductivity. However the simpler option of using a sand fill was found adequate and is recommended for near-term use. Thermal-hydraulic modeling of the low permeability and porosity host rock and its small (≤ 1%) saline water content showed that vertical convection induced by the waste’s decay heat should not transport nuclides from the emplacement zone up to the biosphere atop the caprock. First order economic analysis indicated that borehole repositories should be cost-competitive with shallower mined repositories. It is concluded that proceeding with plans to drill a demonstration borehole to confirm expectations, and to carry out priority experiments, such as retention and replenishment of in-hole water is in order.« less

Three-dimensional spheroid culture of human umbilical cord mesenchymal stem cells promotes cell yield and stemness maintenance.

PubMed

Li, Yi; Guo, Gang; Li, Li; Chen, Fei; Bao, Ji; Shi, Yu-Jun; Bu, Hong

2015-05-01

Mesenchymal stem cell (MSC) transplantation is a promising treatment of many diseases. However, conventional techniques with cells being cultured as a monolayer result in slow cell proliferation and insufficient yield to meet clinical demands. Three-dimensional (3D) culture systems are gaining attention with regard to recreating a complex microenvironment and to understanding the conditions experienced by cells. Our aim is to establish a novel 3D system for the culture of human umbilical cord MSCs (hUC-MSCs) within a real 3D microenvironment but with no digestion or passaging. Primary hUC-MSCs were isolated and grown in serum-free medium (SFM) on a suspension Rocker system. Cell characteristics including proliferation, phenotype and multipotency were recorded. The therapeutic effects of 3D-cultured hUC-MSCs on carbon tetrachloride (CCl4)-induced acute liver failure in mouse models were examined. In the 3D Rocker system, hUC-MSCs formed spheroids in SFM and maintained high viability and active proliferation. Compared with monolayer culture, the 3D-culture system yielded more hUC-MSCs cells within the same volume. The spheroids expressed higher levels of stem cell markers and displayed stronger multipotency. After transplantation into mouse, 3D hUC-MSCs significantly promoted the secretion of interferon-γ and interleukin-6 but inhibited that of tumor necrosis factor-α, thereby alleviating liver necrosis and promoting regeneration following CCl4 injury. The 3D culture of hUC-MSCs thus promotes cell yield and stemness maintenance and represents a promising strategy for hUC-MSCs expansion on an industrial scale with great potential for cell therapy and biotechnology.

Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques.

PubMed

McConville, Christopher; Smith, James M; McCoy, Clare F; Srinivasan, Priya; Mitchell, James; Holder, Angela; Otten, Ron A; Butera, Salvatore; Doncel, Gustavo F; Friend, David R; Malcolm, R Karl

2015-02-01

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside reverse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities considered sufficient to maintain vaginal fluid concentrations at levels 82-860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal transmission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median concentrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo-in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mechanism rather than the expected diffusion-controlled mechanism.

Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis.

PubMed

Narula, Neeraj; Kassam, Zain; Yuan, Yuhong; Colombel, Jean-Frederic; Ponsioen, Cyriel; Reinisch, Walter; Moayyedi, Paul

2017-10-01

Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC. A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported. Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58). Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.

Semi-Individualized Homeopathy Add-On Versus Usual Care Only for Premenstrual Disorders: A Randomized, Controlled Feasibility Study.

PubMed

Klein-Laansma, Christien T; Jong, Mats; von Hagens, Cornelia; Jansen, Jean Pierre C H; van Wietmarschen, Herman; Jong, Miek C

2018-03-22

Premenstrual syndrome and premenstrual dysphoric disorder (PMS/PMDD) bother a substantial number of women. Homeopathy seems a promising treatment, but it needs investigation using reliable study designs. The feasibility of organizing an international randomized pragmatic trial on a homeopathic add-on treatment (usual care [UC] + HT) compared with UC alone was evaluated. A multicenter, randomized, controlled pragmatic trial with parallel groups. The study was organized in general and private homeopathic practices in the Netherlands and Sweden and in an outpatient university clinic in Germany. Women diagnosed as having PMS/PMDD, based on prospective daily rating by the daily record of severity of problems (DRSP) during a period of 2 months, were included and randomized. Women were to receive UC + HT or UC for 4 months. Homeopathic medicine selection was according to a previously tested prognostic questionnaire and electronic algorithm. Usual care was as provided by the women's general practitioner according to their preferences. Before and after treatment, the women completed diaries (DRSP), the measure yourself concerns and well-being, and other questionnaires. Intention-to-treat (ITT) and per protocol (PP) analyses were performed. In Germany, the study could not proceed because of legal limitations. In Sweden, recruitment proved extremely difficult. In the Netherlands and Sweden, 60 women were randomized (UC + HT: 28; UC: 32), data of 47/46 women were analyzed (ITT/PP). After 4 months, relative mean change of DRSP scores in the UC + HT group was significantly better than in the UC group (p = 0.03). With respect to recruitment and different legal status, it does not seem feasible to perform a larger, international, pragmatic randomized trial on (semi-)individualized homeopathy for PMS/PMDD. Since the added value of HT compared with UC was demonstrated by significant differences in symptom score changes, further studies are warranted.

Structural and optical investigation in Er3+ doped Y2MoO6 phosphors

NASA Astrophysics Data System (ADS)

Mondal, Manisha; Rai, Vineet Kumar

2018-05-01

The Er3+ doped Y2MoO6 phosphors have been structurally and optically characterized by X-ray Diffraction (XRD), Field emission scanning electron microscopy (FESEM), UV-Vis absorption spectroscopy and frequency upconversion (UC) emission studies. The crystal and the particles size are found to be ˜ 85 nm and ˜ 200 nm from XRD and FESEM analysis. The intense peak at ˜ 206 nm in the UV-Vis absorption spectroscopy is attributed due to the charge transfer transition between the Mo6+ and the O2- ions in the MoO4 group in the host molybdate. The frequency UC emission studies of the prepared phosphors under 980 nm diode laser excitation shows the intense UC emission in the 0.3 mol% concentrations for the Er3+ ions. In the UC emission spectra, the emission peaks at green (˜ 525 nm and ˜ 546 nm) and red (˜ 656 nm) bands are corresponding to the 2H11/2, 4S3/2 → 4I15/2 and 4F9/2 → 4I15/2 transitions of Er3+ ions. The mechanisms involved in the UC process have been explored with the help of energy level diagram. Moreover, the CIE point (0.31, 0.60) lie in the green colour region which indicates that the developed phosphor have suitable applications in NIR to visible upconverter and in making green light display devices.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

PubMed

Romberg-Camps, Mariëlle; Kuiper, Edith; Schouten, Leo; Kester, Arnold; Hesselink-van de Kruijs, Martine; Limonard, Charles; Bos, Rens; Goedhard, Jelle; Hameeteman, Wim; Wolters, Frank; Russel, Maurice; Stockbrügger, Reinhold; Dagnelie, Pieter

2010-08-01

The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

Vedolizumab induction therapy for inflammatory bowel disease in clinical practice--a nationwide consecutive German cohort study.

PubMed

Baumgart, D C; Bokemeyer, B; Drabik, A; Stallmach, A; Schreiber, S

2016-05-01

Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting α4 β7 integrin. To investigate the real-world efficacy of vedolizumab for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). A consecutive cohort of 212 adult IBD patients with active disease (HBI >7/partial Mayo >4) newly receiving VDZ was prospectively recruited from 7 academic and 17 community centres. The primary endpoint was clinical remission (CRM) (CD HBI ≤4, UC pMayo ≤1) in week 14. Secondary endpoints included steroid-free remission (SFCRM), clinical response (CRS) (HBI/pMayo score drop ≥3), vedolizumab impact on CRP, calprotectin and haemoglobin. Data of 97 CD (71.1% female, HBI 11) and 115 UC (42.6% female, pMayo 6) patients were analysed. Only 5.2% CD and 24.3% UC were anti-TNFα naïve. Most had extensive mucosal involvement (Montreal L3 69.1%/E3 53.9%). At week 14, 23.7% vs. 23.5% of CD vs. UC patients achieved CRM, 19.6% vs. 19.1% SFCRM and 60.8% vs. 57.4% CRS, respectively (all based on NRI). Week 14 CRM in CD was significantly associated with no history of extraintestinal manifestations (P = 0.019), no prior adalimumab use (P = 0.011), no hospitalisation in the past 12 months (P = 0.015) and low HBI score (P = 0.02) and in UC with active or previous smoking (P = 0.044/0.028) and no anti-TNFα (P = 0.023) use. Low HBI (P = 0.019) and no hospitalisation in the past 12 months (P = 0.01) predict CD CRM. The three most common AE were joint pain, acne and nasopharyngitis. Vedolizumab is effective in routine use. © 2016 John Wiley & Sons Ltd.

Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients.

PubMed

Latiano, Anna; Palmieri, Orazio; Latiano, Tiziana; Corritore, Giuseppe; Bossa, Fabrizio; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; Valvano, Maria Rosa; Pastore, Maria; Marseglia, Antonio; D'Incà, Renata; Andriulli, Angelo; Annese, Vito

2011-01-01

Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10(-6)). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10(-5)). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

Enhancement of the Optoelectronic Properties of PEDOT: PSS-PbS Nanoparticles Composite Thin Films Through Nanoparticles' Capping Ligand Exchange

NASA Astrophysics Data System (ADS)

García-Gutiérrez, Diana F.; Hernández-Casillas, Laura P.; Sepúlveda-Guzmán, Selene; Vazquez-Rodriguez, Sofia; García-Gutiérrez, Domingo I.

2018-02-01

The influence of the capping ligand on nanoparticles' optical and electronic properties is a topic of great interest currently being investigated by several research groups in different countries. In the present study, PbS nanoparticles originally synthesized with oleic acid, myristic acid and hexanoic acid underwent a ligand exchange process to replace the original carboxylic acid for uc(l)-cysteine as the capping layer, and were thoroughly characterized by means of transmission electron microscopy and its related techniques, such as energy dispersive x-ray spectroscopy and scanning-transmission electron microscopy, and Fourier transform infrared, Raman and x-ray photoelectron spectroscopy. Afterwards, these PbS nanoparticles were dispersed into a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) matrix to fabricate a composite thin film which displayed the optical absorption properties of the PbS nanoparticles and the electrical transport properties of the PEDOT:PSS matrix, in order to evaluate the impact of the nanoparticles' capping ligand on the optoelectronic properties of the fabricated composite thin films. Composite thin films with PbS nanoparticles showing uc(l)-cysteine as the capping layer displayed clear photoresponse and a threefold increment in their conductivities compared to pristine PEDOT:PSS. The properties of PEDOT:PSS, known as a hole transport layer in most organic photovoltaic devices, were enhanced by adding PbS nanoparticles with different capping ligands, producing a promising composite material for optoelectronic applications by proper selection of the nanoparticles' capping layer.

CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis.

PubMed

Zhao, Jia-Jun; Wang, Di; Yao, Hui; Sun, Da-Wei; Li, Hong-Yu

2015-09-14

To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I(2) tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias. A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001). CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk.

Professional charges not reimbursed to dentists in the U.S.: evidence from Medical Expenditure Panel Survey, 1996.

PubMed

Chattopadhyay, A; Slade, G D; Caplan, D J

2009-12-01

This cross-sectional study examined professional charges not paid to dentists. This analysis used logistic regression in SUDAAN examining the 1996 MEPS data from 12,931 adults. Among people incurring dental care charges, 13.6% had more than $50 of unpaid charge (UC). The percapita UC was $53.30. Total UC was higher for highest income group [45.4% of total] compared to lowest income group [26.0%]. The percapita UC of $76.70 for low income group was significantly greater than for high income group ($47.80, P < 0.01). More Medicaid recipients (52% vs. non-recipients: 12%) incurred at least $50 in UC (P < 0.01). Adjusted odds of incurring UC were greater for those employed (OR = 1.3, 95% CI: 1.0-1.7), and for those with private insurance (OR: 1.5, CI: 1.3-1.9). Number of dental procedure types modified the association between Medicaid recipient and UC (OR = 13.6 for Medicaid recipients undergoing multiple procedure types; OR: 2.3 for Medicaid non-recipients with multiple procedure types; OR: 1.9 for Medicaid recipients receiving single dental procedure. Having private insurance, being unemployed and being Medicaid insured undergoing multiple procedure were strongest predictors of UC.

Recent Changes in UC Admissions Policies. Parent/Student Guide = Unos cambios recientes en los reglamentos de ingreso de la universidad de California. Guia de padres/estudiantes.

ERIC Educational Resources Information Center

EdSource, Inc., Palo Alto, CA.

This parent/student guide describes recent changes in admissions policies at the University of California (UC). Traditionally, UC admitted the top 12.5% of high school graduating seniors, but beginning in 2001, the top 4% of students in the graduating class of every high school are eligible if they have completed 11 specific "a-f"…

Structural and light up-conversion luminescence properties of Er3+-Yb3+-W6+ substituted Bi4Ti3O12

NASA Astrophysics Data System (ADS)

Bokolia, Renuka; Rai, Vineet K.; Chauhan, Lalita; Sreenivas, K.

2016-05-01

The structural and light up-conversion (UC) luminescence properties of W6+ substituted Bi3.79Er0.03Yb0.18Ti3-xWxO12 (0 ≤ x ≤ 0.10) ceramics prepared by solid state reaction method have been investigated. X-ray diffraction (XRD) confirms the formation of single phase material with orthorhombic structure. A decrease in the lattice parameters and unit cell volume is observed with increasing W content. Strong UC luminescence at 527, 548 and 662 nm is seen under an excitation of 980 nm for an optimum W content (x = 0.06) and is attributed to the transitions 2H11/2 →4I15/2, 4S3/2 →4I15/2 and 4F9/2 →4I15/2 respectively. The improved UC luminescence is ascribed to the reduced defects such as oxygen vacancies and change in the crystal field around Er3+ ions due to B-site (Ti4+) substitution with W6+ ions. Enhanced UC emission is observed for an optimum content of w6+ in the prepared composition Bi3.79Er0.03Yb0.18Ti3-xWxO12 for x = 0.06.

Avoidable iatrogenic complications of male urethral catheterisation and inadequate intern training: a 4-year follow-up post implementation of an intern training programme.

PubMed

Sullivan, J F; Forde, J C; Thomas, A Z; Creagh, T A

2015-02-01

To assess the impact of a structured training programme in urethral catheterisation (UC) targeted at newly qualified junior doctors on rates of iatrogenic catheter morbidity within a tertiary care referral centre. Male UC-related morbidities were retrospectively identified from our computerised inpatient urology consultation system over a 1-year period from July 2010 to June 2011. Relevant medical records were also reviewed. Results were compared with an initial study performed between July 2006 and June 2007, prior the introduction of a structured training programme in our institution. An anonymous questionnaire was used for the subjective assessment of interns about confidence in catheterising post introduction of the programme. Of 725 urological consultations, 29 (4%) were related to complications arising from male UC during the 1 year period. This reflected a statistically significant decrease when compared to our 2007 figures, 51/864 (6%) (p < 0.05). Again, the most common indication for UC was monitoring urinary output for acute medical illness (19/29, 66%). The most common complication was urethral trauma (16/29, 55%). Of the 29 cases of UC-related morbidity, 18 (62%) resulted from interns performing UC, a decrease of 12% from our original paper. A drop of 27% was seen in the rates of UC related morbidity attributable to interns during the first 6 months of internship (July-December). Overall, 70% (vs 40% original study) of interns felt that their practical training was adequate since introduction of the programme (p < 0.01) with 53% considering theoretical training adequate (vs 16% original study (p < 0.01). When asked were they confident in performing UC, 63% said they were compared to 35% before introduction of the programme (p < 0.05). UC-related iatrogenic morbidity is not uncommon even in a tertiary-care teaching hospital. Implementation of a structured training programme in UC prior to the commencement of intern year has been shown to result in a significant decrease in the amount of iatrogenic UC related morbidity. Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Observing the San Andreas Fault at Depth

NASA Astrophysics Data System (ADS)

Ellsworth, W.; Hickman, S.; Zoback, M.; Davis, E.; Gee, L.; Huggins, R.; Krug, R.; Lippus, C.; Malin, P.; Neuhauser, D.; Paulsson, B.; Shalev, E.; Vajapeyam, B.; Weiland, C.; Zumberge, M.

2005-12-01

Extending 4 km into the Earth along a diagonal path that crosses the divide between Salinian basement accreted to the Pacific Plate and Cretaceous sediments of North America, the main hole at the San Andreas Fault Observatory at Depth (SAFOD) was designed to provide a portal into the inner workings of a major plate boundary fault. The successful drilling and casing of the main hole in the summer of 2005 to a total vertical depth of 3.1 km make it possible to conduct spatially extensive and long-duration observations of active tectonic processes within the actively deforming core of the San Andreas Fault. In brief, the observatory consists of retrievable seismic, deformation and environmental sensors deployed inside the casing in both the main hole (maximum temperature 135 C) and the collocated pilot hole (1.1 km depth), and a fiber optic strainmeter installed behind casing in the main hole. By using retrievable systems deployed on either wire line or rigid tubing, each hole can be used for a wide range of scientific purposes, with instrumentation that takes maximum advantage of advances in sensor technology. To meet the scientific and technical challenges of building the observatory, borehole instrumentation systems developed for use in the petroleum industry and by the academic community in other deep research boreholes have been deployed in the SAFOD pilot hole and main hole over the past year. These systems included 15Hz omni-directional and 4.5 Hz gimbaled seismometers, micro-electro-mechanical accelerometers, tiltmeters, sigma-delta digitizers, and a fiber optic interferometeric strainmeter. A 1200-m-long, 3-component 80-level clamped seismic array was also operated in the main hole for 2 weeks of recording in May of 2005, collecting continuous seismic data at 4000 sps. Some of the observational highlights include capturing one of the M 2 SAFOD target repeating earthquakes in the near-field at a distance of 420 m, with accelerations of up to 200 cm/s and a static displacement of a few microns. Numerous other local events were observed over the summer by the tilt and seismic instruments in the pilot hole, some of which produced strain offsets of several nanostrain on the fiber optic strainmeter. We were fortunate to observe several episodes of non-volcanic tremor on the 80-level seismic array in May, 2005. These spatially unaliased recordings of the tremor wavefield reveal that the complex tremor time series is comprised of up-and down-going shear waves that produce a spatially stationary interference pattern over time scales of 10s of seconds. All data collected at SAFOD as part of the EarthScope project are open and freely available to all. The Northern California Earthquake Data Center at U.C. Berkeley is the principal data repository for SAFOD. The more than 2 TB of 80-level array data are also available at the IRIS DMC as an assembled data collection.

Study of the Optimum Zone of the Independent Variables of an ORGEL Reactor Connected to a 250-MWeb Power Plant. Self Supporting Fuel Elements Made of UC, with Sap Cladding with Four Fuel Rods and Individual Pressure Tubes; STUDIE DER OPTIMALEN ZONE DER UNABHANGIGEN PARAMETER EINES ORGEL- REAKTORS IN EINEM 250-MWe-KRAFTWERK. SELBST-TRAGENDES BRENNELEMENT AUS UC, SAP-UMHUL-LUNG MIT 4 BRENNSTOFFSTABEN UND INDIVIDUELLEN DRUCKROHREN

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaFontaine, F.; Tauch, P.

The optimum range of the independent variables of and ORGEL reactor connected to a 250-Mw power plant (4 fuel rods of UC with individual pressure tubes), as well as the geometry of the reactor core and the operation of the plant, is described. (auth)

Effects of the background electrolyte on Th(IV) sorption to muscovite mica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmidt, Moritz; Hellebrandt, Stefan; Knope, Karah E.

2015-09-01

The adsorption of tetravalent thorium on the muscovite mica (001) basal plane was studied by X-ray crystal truncation rod (CTR), and resonant anomalous X-ray reflectivity (RAXR) measurements and alpha spectrometry in the presence of perchlorate background electrolytes LiClO 4, NaClO 4, and KClO 4 ([Th(IV)] = 0.1 mM, I = 0.1 M or 0.01 M, pH = 3.3 ± 0.3). RAXR data directly reveal a strong influence of the background electrolyte on the actinide sorption. No significant Th adsorption was observed in 0.1 M NaClO 4, i.e., the Th coverage θ(Th), the number of Th per unit cell area ofmore » the muscovite surface (A UC = 46.72 Å 2), was ≤ 0.01 Th/A UC, whereas limited uptake (θ(Th) ~ 0.04 Th/A UC) was detected at a lower ionic strength (I = 0.01 M). These results are in stark contrast to the behavior of Th in 0.1 M NaCl which showed a coverage of 0.4 Th/A UC (Schmidt et al., 2012a). Th uptake was also influenced by the electrolyte cation. Weak adsorption was observed in 0.1M KClO 4 (θ(Th) ~ 0.07 Th/AUC) similar to the results in NaClO 4 at lower ionic strength. In contrast, strong adsorption was found in 0.1 M LiClO 4, with θ(Th) = 4.9 Th/A UC, a ~10-fold increase compared with that previously reported in NaCl. These differences are confirmed independently by ex situ alpha spectrometry, which shows no measurable Th coverage in 0.1 M NaClO 4 background in contrast to a large coverage of 1.6 Th/A UC in 0.1 M LiClO 4. The CTR/RAXR analyses of Th-LiClO 4 show the sorption structure consisting of Th species that are broadly distributed, centered at heights of 4.1 Å and 29 Å distance from the interface. Neither the very large distribution height of the second species nor the high coverage can be explained with (hydrated) ionic adsorption, suggesting that the enhanced uptake is presumably due to the formation and sorption of Th nanoparticles.« less

Expression Levels of DNA Damage Repair Proteins Are Associated With Overall Survival in Platinum-Treated Advanced Urothelial Carcinoma.

PubMed

Mullane, Stephanie A; Werner, Lillian; Guancial, Elizabeth A; Lis, Rosina T; Stack, Edward C; Loda, Massimo; Kantoff, Philip W; Choueiri, Toni K; Rosenberg, Jonathan; Bellmunt, Joaquim

2016-08-01

Combination platinum chemotherapy is standard first-line therapy for metastatic urothelial carcinoma (mUC). Defining the platinum response biomarkers for patients with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the platinum response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse overall survival (OS) in patients with mUC. We retrospectively identified a clinically annotated cohort of patients with mUC, who had been treated with first-line platinum combination chemotherapy. A tissue microarray was constructed from formalin-fixed paraffin-embedded tissue from the primary tumor before treatment. Immunohistochemical analysis of the following DNA repair proteins was performed: ERCC1, RAD51, BRCA1/2, PAR, and PARP-1. Nuclear and cytoplasmic expression was analyzed using multispectral imaging. Nuclear staining was used for the survival analysis. Cox regression analysis was used to evaluate the associations between the percentage of positive nuclear staining and OS in multivariable analysis, controlling for known prognostic variables. In a cohort of 104 patients with mUC, a greater percentage of nuclear staining of ERCC1 (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .0007), RAD51 (HR, 5.6; 95% CI, 1.7-18.3; P = .005), and PAR (HR, 2.2; 95% CI, 1.1-4.4; P = .026) was associated with worse OS. BRCA1, BRCA2, and PARP-1 expression was not associated with OS (P = .76, P = .38, and P = .09, respectively). A greater percentage of combined ERCC1 and RAD51 nuclear staining was strongly associated with worse OS (P = .005). A high percentage of nuclear staining of ERCC1, RAD51, and PAR, assessed by immunohistochemistry, correlated with worse OS for patients with mUC treated with first-line platinum combination chemotherapy, supporting the evidence of the DNA repair pathways' role in the prognosis of mUC. We also report new evidence that RAD51 and PAR might play a role in the platinum response. Additional prospective studies are required to determine the prognostic or predictive nature of these biomarkers in mUC. Copyright © 2015 Elsevier Inc. All rights reserved.

Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.

PubMed

Sandborn, William J; Regula, Jaroslaw; Feagan, Brian G; Belousova, Elena; Jojic, Njegica; Lukas, Milan; Yacyshyn, Bruce; Krzeski, Piotr; Yeh, Chyon-Hwa; Messer, Christi A; Hanauer, Stephen B

2009-12-01

It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC. A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment. The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events. Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.

High frequency of parasitic and viral stool pathogens in patients with active ulcerative colitis: report from a tropical country.

PubMed

Banerjee, Debabrata; Deb, Rachana; Dar, Lalit; Mirdha, Bijay R; Pati, Sunil K; Thareja, Sandeep; Falodia, Sushil; Ahuja, Vineet

2009-01-01

Diarrhoeal relapses in patients with ulcerative colitis (UC) may be associated with enteric infections and its diagnosis may lessen avoidable exposure to corticosteroids and/or immunosuppressants. The purpose of this study was to assess the frequency of stool pathogens (parasitic and viral) in patients with active UC. This prospective cross-sectional study included 49 consecutive patients (32 M, 17 F, mean age 35.8+/-12 years) with active UC. Three stool samples were collected from each patient and examined for parasitic infection. Rectal biopsies were obtained during sigmoidoscopy to demonstrate cytomegalovirus (CMV) inclusion bodies and to conduct qualitative polymerase chain reaction (PCR) for CMV and herpes simplex virus (HSV) DNA detection. Median duration of illness was 3.9+/-3.7 years and 83.7% of the patients had moderate to severe disease. The prevalence of parasitic infections in UC was 12%. The organisms isolated were Strongyloides stercoralis in 4%, Ankylostoma duodenale in 4%, Cryptosporidium in 2% and Entamoeba histolytica in 2% of the patients. The prevalence of CMV and HSV in rectal biopsies using qualitative PCR was 8% and 10%, respectively. No predictive factor was identified with CMV superinfection in patients with active UC. In India there is a high prevalence of parasitic and viral infections in patients with active UC. The results of the study suggest that, in tropical countries with a known high prevalence of parasitic diseases, aggressive evaluation for parasitic and viral infections should be carried out, as early identification and prompt treatment of such infections can improve the clinical course of patients with active UC.

CD14{sup +} monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Ding, E-mail: qqhewd@gmail.com; TEDA Life and Technology Research Center, Institute of Hematology, Chinese Academy of Medical Sciences, TEDA, Tianjin; Chen, Ke, E-mail: chenke_59@hotmail.com

2010-09-10

Here, the effect of CD14{sup +} monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-{gamma} (IFN-{gamma}) secretion capacities of CD4{sup +} and CD8{sup +} T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E{sub 2} (PGE{sub 2}) as an important soluble mediator. CD14{sup +} monocytes were found to be able to enhance significantly themore » immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1{beta}, either exogenously added or produced by CD14{sup +} monocytes in culture, could trigger expression of high levels of PGE{sub 2} by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE{sub 2} expression, but also reversed the promotional effect of CD14{sup +} monocytes and partially restored CD4{sup +} and CD8{sup +} T cell proliferation and IFN-{gamma} secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.« less

Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More Comparable with that of Patients with Crohn's Disease.

PubMed

Goren, Idan; Yahav, Lior; Tulchinsky, Hagit; Dotan, Iris

2015-10-01

The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis.

PubMed

Sargın, Zeynep Gök; Erin, Nuray; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients' demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

PubMed Central

Sargın, Zeynep Gök; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC. PMID:29232715

Identifying continence options after stroke (ICONS): a cluster randomised controlled feasibility trial.

PubMed

Thomas, Lois H; Watkins, Caroline L; Sutton, Christopher J; Forshaw, Denise; Leathley, Michael J; French, Beverley; Burton, Christopher R; Cheater, Francine; Roe, Brenda; Britt, David; Booth, Joanne; McColl, Elaine

2014-12-23

Urinary incontinence (UI) affects half of patients hospitalised after stroke and is often poorly managed. Cochrane systematic reviews have shown some positive impact of conservative interventions (such as bladder training) in reducing UI, but their effectiveness has not been demonstrated with stroke patients. We conducted a cluster randomised controlled feasibility trial of a systematic voiding programme (SVP) for the management of UI after stroke. Stroke services were randomised to receive SVP (n = 4), SVP plus supported implementation (SVP+, n = 4), or usual care (UC, n = 4).Feasibility outcomes were participant recruitment and retention. The main effectiveness outcome was presence or absence of UI at six and 12 weeks post-stroke. Additional effectiveness outcomes included were the effect of the intervention on different types of UI, continence status at discharge, UI severity, functional ability, quality of life, and death. It was possible to recruit patients (413; 164 SVP, 125 SVP+, and 124 UC) and participant retention was acceptable (85% and 88% at six and 12 weeks, respectively). There was no suggestion of a beneficial effect on the main outcome at six (SVP versus UC: odds ratio (OR) 0.94, 95% CI: 0.46 to 1.94; SVP+ versus UC: OR: 0.62, 95% CI: 0.28 to 1.37) or 12 weeks (SVP versus UC: OR: 1.02, 95% CI: 0.54 to 1.93; SVP+ versus UC: OR: 1.06, 95% CI: 0.54 to 2.09).No secondary outcomes showed a strong suggestion of clinically meaningful improvement in SVP and/or SVP+ arms relative to UC at six or 12 weeks. However, at 12 weeks both intervention arms had higher estimated odds of continence than UC for patients with urge incontinence. The trial has met feasibility outcomes of participant recruitment and retention. It was not powered to demonstrate effectiveness, but there is some evidence of a potential reduction in the odds of specific types of incontinence. A full trial should now be considered. ISRCTN Registry, ISRCTN08609907, date of registration: 7 July 2010.

A long in situ section of the lower ocean crust: results of ODP Leg 176 drilling at the Southwest Indian Ridge

NASA Astrophysics Data System (ADS)

Dick, Henry J. B.; Natland, James H.; Alt, Jeffrey C.; Bach, Wolfgang; Bideau, Daniel; Gee, Jeffrey S.; Haggas, Sarah; Hertogen, Jan G. H.; Hirth, Greg; Holm, Paul Martin; Ildefonse, Benoit; Iturrino, Gerardo J.; John, Barbara E.; Kelley, Deborah S.; Kikawa, Eiichi; Kingdon, Andrew; LeRoux, Petrus J.; Maeda, Jinichiro; Meyer, Peter S.; Miller, D. Jay; Naslund, H. Richard; Niu, Yao-Ling; Robinson, Paul T.; Snow, Jonathan; Stephen, Ralph A.; Trimby, Patrick W.; Worm, Horst-Ulrich; Yoshinobu, Aaron

2000-06-01

Ocean Drilling Program Leg 176 deepened Hole 735B in gabbroic lower ocean crust by 1 km to 1.5 km. The section has the physical properties of seismic layer 3, and a total magnetization sufficient by itself to account for the overlying lineated sea-surface magnetic anomaly. The rocks from Hole 735B are principally olivine gabbro, with evidence for two principal and many secondary intrusive events. There are innumerable late small ferrogabbro intrusions, often associated with shear zones that cross-cut the olivine gabbros. The ferrogabbros dramatically increase upward in the section. Whereas there are many small patches of ferrogabbro representing late iron- and titanium-rich melt trapped intragranularly in olivine gabbro, most late melt was redistributed prior to complete solidification by compaction and deformation. This, rather than in situ upward differentiation of a large magma body, produced the principal igneous stratigraphy. The computed bulk composition of the hole is too evolved to mass balance mid-ocean ridge basalt back to a primary magma, and there must be a significant mass of missing primitive cumulates. These could lie either below the hole or out of the section. Possibly the gabbros were emplaced by along-axis intrusion of moderately differentiated melts into the near-transform environment. Alteration occurred in three stages. High-temperature granulite- to amphibolite-facies alteration is most important, coinciding with brittle-ductile deformation beneath the ridge. Minor greenschist-facies alteration occurred under largely static conditions, likely during block uplift at the ridge transform intersection. Late post-uplift low-temperature alteration produced locally abundant smectite, often in previously unaltered areas. The most important features of the high- and low-temperature alteration are their respective associations with ductile and cataclastic deformation, and an overall decrease downhole with hydrothermal alteration generally ≤5% in the bottom kilometer. Hole 735B provides evidence for a strongly heterogeneous lower ocean crust, and for the inherent interplay of deformation, alteration and igneous processes at slow-spreading ridges. It is strikingly different from gabbros sampled from fast-spreading ridges and at most well-described ophiolite complexes. We attribute this to the remarkable diversity of tectonic environments where crustal accretion occurs in the oceans and to the low probability of a section of old slow-spread crust formed near a major large-offset transform being emplaced on-land compared to sections of young crust from small ocean basins.

Modifying the size and uniformity of upconversion Yb/Er:NaGdF4 nanocrystals through alkaline-earth doping.

PubMed

Lei, Lei; Chen, Daqin; Huang, Ping; Xu, Ju; Zhang, Rui; Wang, Yuansheng

2013-11-21

NaGdF4 is regarded as an ideal upconversion (UC) host material for lanthanide (Ln(3+)) activators because of its unique crystal structure, high Ln(3+) solubility, low phonon energy and high photochemical stability, and Ln(3+)-doped NaGdF4 UC nanocrystals (NCs) have been widely investigated as bio-imaging and magnetic resonance imaging agents recently. To realize their practical applications, controlling the size and uniformity of the monodisperse Ln(3+)-doped NaGdF4 UC NCs is highly desired. Unlike the routine routes by finely adjusting the multiple experimental parameters, herein we provide a facile and straightforward strategy to modify the size and uniformity of NaGdF4 NCs via alkaline-earth doping for the first time. With the increase of alkaline-earth doping content, the size of NaGdF4 NCs increases gradually, while the size-uniformity is still retained. We attribute this "focusing" of size distribution to the diffusion controlled growth of NaGdF4 NCs induced by alkaline-earth doping. Importantly, adopting the Ca(2+)-doped Yb/Er:NaGdF4 NCs as cores, the complete Ca/Yb/Er:NaGdF4@NaYF4 core-shell particles with excellent size-uniformity can be easily achieved. However, when taking the Yb/Er:NaGdF4 NCs without Ca(2+) doping as cores, they could not be perfectly covered by NaYF4 shells, and the obtained products are non-uniform in size. As a result, the UC emission intensity of the complete core-shell NCs increases by about 30 times in comparison with that of the cores, owing to the effective surface passivation of the Ca(2+)-doped cores and therefore protection of Er(3+) in the cores from the non-radiative decay caused by surface defects, whereas the UC intensity of the incomplete core-shell NCs is enhanced by only 3 times.

Mucosal barrier in ulcerative colitis and Crohn's disease.

PubMed

Dorofeyev, A E; Vasilenko, I V; Rassokhina, O A; Kondratiuk, R B

2013-01-01

Background. The mucus layer in the gastrointestinal tract plays important role in host innate defense, regulation of secretion, and absorption processes, maintaining colonization resistance, which composes the integrity of protective mucus barrier in the large intestine. Investigations of mucin expression in the colon mucosa can improve the understanding of protective function of mucosal barrier in ulcerative colitis (UC) and Crohn's disease (CD). Materials and Methods. 77 patients with UC and CD were examined. Histological analysis of colon mucosa was done by standard method (haematoxylin-eosin, alcian blue at pH 1.0 and 2.5 to determine sulfated and nonsulfated glycosaminoglycans and glycoproteins, and goblet cells). To characterize the mucus production the PAS-reaction was performed. Immunohistochemistry was performed using monoclonal mouse antibodies raised against MUC2, MUC3, MUC4, and TFF3 (USBiological, USA). Results. The moderate expression of MUC2 and MUC3 (50.0% and 32.1%, P = 0.03) and high expression of MUC4 and TFF3 in the colon mucosa were observed in all patients with CD. The intensive labeling of MUC4 and TFF3 occurred more often (42.9% and 57.1%, P = 0.03) in patients with CD. The level of expression of secretory MUC2 and transmembrane MUC3 and MUC4 in all patients with UC was low, up to its complete absence (59.2% and 53.1% cases, P = 0.05). TFF3 expression had high and medium staining intensity in patients with UC. Conclusions. Different types of mucins synthesis, secretion, and expression were found in patients with UC and CD. The expression of mucin MUC2, MUC3, MUC4, and TFF3 correlated with the activity of disease and the extent of the inflammatory process in the large intestine. The most pronounced alteration of mucins expression was observed in patients with severe UC and CD.

Impact of MMX® mesalamine on improvement and maintenance of health-related quality of life in patients with ulcerative colitis.

PubMed

Hodgkins, Paul; Yen, Linnette; Yarlas, Aaron; Karlstadt, Robyn; Solomon, Dory; Kane, Sunanda

2013-02-01

Ulcerative colitis (UC) substantially reduces patients' health-related quality of life (HRQoL). The current study examined the burden of disease and the impact of daily multimatrix (MMX®) mesalamine treatment on HRQoL for patients with active or quiescent mild-to-moderate UC. Data were from a two-phase, multicenter, open-label study with mild-to-moderate UC patients. In the acute phase, 132 patients with active disease received MMX mesalamine 2.4-4.8 g/day QD for 8 weeks. In the maintenance phase, 207 patients with quiescent disease received MMX mesalamine 2.4 g/day QD for 12 months. The Short Form-12 (version 2) (SF-12v2) measured HRQoL during each phase. Disease burden was examined by comparing acute-phase baseline scores with a U.S. general population sample. Repeated-measures analyses assessed change in SF-12v2 scores for each phase. Correspondence between HRQoL and disease activity was examined through correlations between SF-12v2 scores with patient-reported symptom measures. Baseline SF-12v2 scores for patients with UC were generally much lower than for the general population sample, indicating a broad disease burden. In the acute phase, significant improvement was observed for most SF-12v2 scores at week 8; a comparison with the matched norms showed a complete elimination of burden. No changes in SF-12v2 scores were observed during the maintenance phase. Changes in symptom measures and SF-12v2 scores were moderately correlated. The sizeable burden of active mild-to-moderate UC on HRQoL was eliminated following 8 weeks' treatment with MMX mesalamine 2.4-4.8 g/day. HRQoL remained stable over 12 months of maintenance treatment in patients with quiescent UC.

Expression of 9-cis-EPOXYCAROTENOID DIOXYGENASE4 Is Essential for Thermoinhibition of Lettuce Seed Germination but Not for Seed Development or Stress Tolerance[C][W

PubMed Central

Huo, Heqiang; Dahal, Peetambar; Kunusoth, Keshavulu; McCallum, Claire M.; Bradford, Kent J.

2013-01-01

Thermoinhibition, or failure of seeds to germinate at warm temperatures, is common in lettuce (Lactuca sativa) cultivars. Using a recombinant inbred line population developed from a lettuce cultivar (Salinas) and thermotolerant Lactuca serriola accession UC96US23 (UC), we previously mapped a quantitative trait locus associated with thermoinhibition of germination to a genomic region containing a gene encoding a key regulated enzyme in abscisic acid (ABA) biosynthesis, 9-cis-EPOXYCAROTENOID DIOXYGENASE4 (NCED4). NCED4 from either Salinas or UC complements seeds of the Arabidopsis thaliana nced6-1 nced9-1 double mutant by restoring germination thermosensitivity, indicating that both NCED4 genes encode functional proteins. Transgenic expression of Salinas NCED4 in UC seeds resulted in thermoinhibition, whereas silencing of NCED4 in Salinas seeds led to loss of thermoinhibition. Mutations in NCED4 also alleviated thermoinhibition. NCED4 expression was elevated during late seed development but was not required for seed maturation. Heat but not water stress elevated NCED4 expression in leaves, while NCED2 and NCED3 exhibited the opposite responses. Silencing of NCED4 altered the expression of genes involved in ABA, gibberellin, and ethylene biosynthesis and signaling pathways. Together, these data demonstrate that NCED4 expression is required for thermoinhibition of lettuce seeds and that it may play additional roles in plant responses to elevated temperature. PMID:23503626

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

PubMed Central

Huang, Xiuping; Zhang, Wei; Han, Zelong; Liu, Side

2015-01-01

Background The associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations. Methods A systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality. Results Thirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models. Conclusions The meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted. PMID:26023918

Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re-Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012).

PubMed

Golovics, Petra A; Lakatos, Laszlo; Mandel, Michael D; Lovasz, Barbara D; Vegh, Zsuzsanna; Kurti, Zsuzsanna; Szita, Istvan; Kiss, Lajos S; Balogh, Mihaly; Pandur, Tunde; Lakatos, Peter L

2015-09-01

Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Posthole Broadband Sensor Emplacement vs. Surface Vaults: Observations of Comparative Noise Performance and Trade-offs

NASA Astrophysics Data System (ADS)

Sweet, J. R.; Beaudoin, B. C.; Barstow, N.; Pfeifer, M.; Anderson, K. R.; Frassetto, A.

2015-12-01

Advances in seismometer design have diversified the range of instruments available for use in temporary field installations. IRIS programs, primarily PASSCAL and the Transportable Array (TA), have helped steer development of these new instruments to meet these evolving needs. PASSCAL operates a small pool of posthole broadband sensors, purpose built for direct burial. Near surface posthole installations are a new, cost effective, and logistically simple technique for broadband emplacement that is an alternative to the vault installations used in portable broadband seismic experiments for nearly 30 years. Direct burial installation is limited to the time and effort required to dig the borehole and emplace the sensor, thus reducing both material costs and time to install. Also, in Alaska, extreme environments and difficult logistics make standard TA tank vaults inappropriate for most sites. TA has developed improved deployment strategies for these environments. There, holes for posthole sensors are hammer- drilled or augered to several meters depth in soil, permafrost, or bedrock and then cased. These emplacement costs are generally less than standard TA vaults. We compare various installation techniques for test cases as well as general deployments of PASSCAL and TA stations. Automated noise performance analyses have been part of the TA throughout its operation, but until recently vault performance for portable installations supported by the PASSCAL program was sparse. In this study, we select a suite of co-located direct burial and surface vault installations and compare their noise performance using probability density functions. Our initial analyses suggest that direct burial sensors have lower noise levels than vault installations on both horizontal and vertical channels across a range of periods spanning <1 s to 100 s. However, most of these initial experiments for PASSCAL were with sensors not purpose built for direct burial and it became obvious that a sensor designed for direct burial was necessary. For the TA, direct emplacement of purpose-built sensors has routinely improved noise levels, particularly beyond about 20 s, by tens of dB. These results suggest that moving towards an instrument pool composed primarily of purpose-built direct burial sensors could yield higher-quality data at lower cost.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colburn, W.A.; Vane, F.M.; Bugge, C.J.

The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of UC-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as UC in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of UC were observed in the healthy subjects whereas they were notmore » seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the UC was 90 hr. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of UC-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.« less

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice

PubMed Central

Wu, Alex G.; Jaja-Chimedza, Asha; Graf, Brittany L.; Waterman, Carrie; Verzi, Michael P.; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC. PMID:28922365

Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice.

PubMed

Kim, Youjin; Wu, Alex G; Jaja-Chimedza, Asha; Graf, Brittany L; Waterman, Carrie; Verzi, Michael P; Raskin, Ilya

2017-01-01

Moringa (Moringa oleifera Lam.) seed extract (MSE) has anti-inflammatory and antioxidant activities. We investigated the effects of MSE enriched in moringa isothiocyanate-1 (MIC-1), its putative bioactive, on ulcerative colitis (UC) and its anti-inflammatory/antioxidant mechanism likely mediated through Nrf2-signaling pathway. Dextran sulfate sodium (DSS)-induced acute (n = 8/group; 3% DSS for 5 d) and chronic (n = 6/group; cyclic rotations of 2.5% DSS/water for 30 d) UC was induced in mice that were assigned to 4 experimental groups: healthy control (water/vehicle), disease control (DSS/vehicle), MSE treatment (DSS/MSE), or 5-aminosalicyic acid (5-ASA) treatment (positive control; DSS/5-ASA). Following UC induction, water (vehicle), 150 mg/kg MSE, or 50 mg/kg 5-ASA were orally administered for 1 or 2 wks. Disease activity index (DAI), spleen/colon sizes, and colonic histopathology were measured. From colon and/or fecal samples, pro-inflammatory biomarkers, tight-junction proteins, and Nrf2-mediated enzymes were analyzed at protein and/or gene expression levels. Compared to disease control, MSE decreased DAI scores, and showed an increase in colon lengths and decrease in colon weight/length ratios in both UC models. MSE also reduced colonic inflammation/damage and histopathological scores (modestly) in acute UC. MSE decreased colonic secretions of pro-inflammatory keratinocyte-derived cytokine (KC), tumor necrosis factor (TNF)-α, nitric oxide (NO), and myeloperoxidase (MPO) in acute and chronic UC; reduced fecal lipocalin-2 in acute UC; downregulated gene expression of pro-inflammatory interleukin (IL)-1, IL-6, TNF-α, and inducible nitric oxide synthase (iNOS) in acute UC; upregulated expression of claudin-1 and ZO-1 in acute and chronic UC; and upregulated GSTP1, an Nrf2-mediated phase II detoxifying enzyme, in chronic UC. MSE was effective in mitigating UC symptoms and reducing UC-induced colonic pathologies, likely by suppressing pro-inflammatory biomarkers and increasing tight-junction proteins. This effect is consistent with Nrf2-mediated anti-inflammatory/antioxidant signaling pathway documented for other isothiocyanates similar to MIC-1. Therefore, MSE, enriched with MIC-1, may be useful in prevention and treatment of UC.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

PubMed

Reissig, Kathrin; Silver, Andrew; Hartig, Roland; Schinlauer, Antje; Walluscheck, Diana; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert; Poehlmann-Nitsche, Angela

2017-01-01

Dysregulation of c-Jun N -terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease

PubMed Central

Wettermark, Björn; Löfberg, Robert; Eriksson, Irene; Sundström, Johan; Lördal, Mikael

2016-01-01

Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. Methods: This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. Results: A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. Conclusions: This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients. PMID:26733406

Associations between NRAMP1 Polymorphisms and Susceptibility to Ulcerative Colitis/Crohn's Disease: A Meta-Analysis.

PubMed

Sun, Manyi; Zhang, Li; Shi, Songli

2016-01-01

Multiple environmental and genetic factors contribute to the risks of ulcerative colitis (UC) and Crohn's disease (CD). Several allelic variants have been identified in natural resistance associated macrophage protein 1 (NRAMP1) gene; however, their association with UC/CD remains conflicting. The purpose of this study was to evaluate whether NRAMP1 polymorphisms are associated with the susceptibility to UC/CD. A meta-analysis on the association between the NRAMP1 polymorphisms and susceptibility to UC/CD was performed. Relevant studies were retrieved from the databases. After eligible data were extracted, Mantel-Haenszel statistics and random/fixed effects model were applied to calculate the pooled odds radio (OR) and 95% confidence interval (95% CI). Seven articles containing 536 UC cases, 997 CD cases, and 1361 controls were collected. No significant association between allele 2 frequency of NRAMP1 and susceptibility to UC/CD was detected in overall population (all p > 0.05). However, increased UC/CD risk for allele 3 was observed in Caucasian population (OR = 1.27, 95% CI = 1.08~1.50, p = 0.04), whereas decreased UC/CD risk was detected in non-Caucasian population (OR = 0.72, 95% CI = 0.60~0.87, p < 0.001), under "allele 3 vs. other alleles" model. Moreover, a significant increase in CD risk for T carrier frequency of -237 C/T (OR = 0.44, 95% CI, 0.26~0.75, p = 0.003) was detected, but not 274 C/T and 1729+55del4 (TGTG) +/del. The polymorphism of -237 C/T is related to the risk of CD; and the association of allele 3 with UC/CD risk differs in Caucasian and non-Caucasian population, which might be the potential biomarkers for clinical diagnosis of UC/CD.

Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis.

PubMed

Ford, Alexander C; Khan, Khurram J; Achkar, Jean-Paul; Moayyedi, Paul

2012-02-01

Efficacy of 5-aminosalicylic acids (5-ASAs) in ulcerative colitis (UC) has been studied previously in meta-analyses. However, no recent meta-analysis has studied the relative efficacies of differing routes of administration. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through May 2011). Eligible trials recruited adults with mildly to moderately active UC, or quiescent UC, and compared oral 5-ASAs with either topical 5-ASAs or a combination of oral and topical 5-ASAs. Dichotomous data were pooled to obtain relative risk (RR) of failure to achieve remission in active UC, and RR of relapse of disease activity in quiescent UC, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. The search identified 3,061 citations, and 12 randomized controlled trials (RCTs) were eligible. Four compared topical with oral 5-ASAs in active UC remission, with an RR of no remission with topical 5-ASAs of 0.82 (95% CI=0.52-1.28). Four trials compared combined with oral 5-ASAs in active UC (RR of no remission=0.65; 95% CI=0.47-0.91; NNT=5). Three RCTs compared intermittent topical with oral 5-ASAs in preventing relapse of quiescent UC (RR=0.64; 95% CI=0.43-0.95; NNT=4), and two compared combined with oral 5-ASAs (RR of relapse=0.48; 95% CI=0.17-1.38). Combined 5-ASA therapy appeared superior to oral 5-ASAs for induction of remission of mildly to moderately active UC. Intermittent topical 5-ASAs appeared superior to oral 5-ASAs for preventing relapse of quiescent UC.

Divert to ULTRA: differences in infused volumes and clearance in two on-line hemodiafiltration treatments.

PubMed

Panichi, Vincenzo; De Ferrari, Giacomo; Saffioti, Stefano; Sidoti, Antonino; Biagioli, Marina; Bianchi, Stefano; Imperiali, Patrizio; Gabbrielli, Claudio; Conti, Paolo; Patrone, Pietro; Falqui, Valeria; Rombolà, Giuseppe; Mura, Carlo; Icardi, Andrea; Mulas, Donatella; Rosati, Alberto; Santori, Francesco; Mannarino, Antonio; Tomei, Valeria; Bertucci, Andrea; Steckiph, Denis; Palla, Roberto

2012-06-01

Mixed diffusive-convective dialysis therapies offer greater removal capabilities than conventional dialysis. The aim of this study was to compare two different on-line, post-dilution hemodiafiltration (HDF) treatments with regard to achieved convective volume and middle-molecule dialysis efficiency: standard volume control (sOL-HDF) and automated control of the transmembrane pressure (TMP) (UC-HDF). We enrolled 30 ESRD patients (55.9 ± 14.0 years, 20/10 M/F) in a randomized, prospective, cross-over study. The patients received a 3-month period of sOL-HDF followed by UC-HDF for a further 3 months, or vice versa, using the same dialysis machine. In sOL-HDF, fixed exchange volumes were set according to a filtration fraction greater than or equal to 25%. In UC-HDF therapy, the exchanged volume was driven by a biofeedback system controlling the TMP and its set point in a double loop. Patients maintained their treatment time, dialyzer, blood flow rate, and anticoagulant regimen unchanged throughout the study. Greater convective volumes were achieved in UC-HDF than in sOL-HDF (23.8 ± 3.9 vs.19.8 ± 4.8 L; p<0.001) with high pre-dialysis Ht value (sOL-HDF 34.0 ± 4.5% and UC-HDF 34.0 ± 4.4%; p = 0.91). The average clearance values of ß2m and P were higher in UC-HDF than in sOL-HDF (respectively 123 ± 24 vs. 111 ± 22 ml/min, p<0.002 and 158 ± 26 vs. 152 ± 25 ml/min, p<0.05). Moreover, the UC-HDF mode led to a significantly increased rate of call-free sessions from 88% to 97% (p<0.0001). This study showed that the biofeedback module, applied to the automatic control of TMP in on-line HDF, results in higher convective volumes and correspondingly higher ß2m and P clearances. By making the HDF treatment more automated and less complex to perform, it significantly reduced the staff workload.

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

PubMed Central

Cho, Judy H.; Nicolae, Dan L.; Gold, Leslee H.; Fields, Carter T.; LaBuda, Michele C.; Rohal, Patrick M.; Pickles, Michael R.; Qin, Li; Fu, Yifan; Mann, Jasdeep S.; Kirschner, Barbara S.; Jabs, Ethylin Wang; Weber, James; Hanauer, Stephen B.; Bayless, Theodore M.; Brant, Steven R.

1998-01-01

The idiopathic inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 × 10−4), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 × 10−5), and at chromosome 1p (MLod = 2.65, P = 2.4 × 10−4) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 × 10−4), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 × 10−3), particularly among Ashkenazim (MLod = 1.51, P = 7.8 × 10−3); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC. PMID:9636179

Patient Perceptions of Telephone vs. In-Person BRCA1/BRCA2 Genetic Counseling

PubMed Central

Peshkin, Beth N.; Kelly, Scott; Nusbaum, Rachel H.; Similuk, Morgan; DeMarco, Tiffani A.; Hooker, Gillian W.; Valdimarsdottir, Heiddis B.; Forman, Andrea D.; Joines, Jessica Rispoli; Davis, Claire; McCormick, Shelley R.; McKinnon, Wendy; Graves, Kristi D.; Isaacs, Claudine; Garber, Judy; Wood, Marie; Jandorf, Lina; Schwartz, Marc D.

2015-01-01

Telephone genetic counseling (TC) for hereditary breast/ovarian cancer risk has been associated with positive outcomes in high risk women. However, little is known about how patients perceive TC. As part of a randomized trial of TC versus usual care (UC; in-person genetic counseling), we compared high risk women’s perceptions of: (1) overall satisfaction with genetic counseling; (2) convenience; (3) attentiveness during the session; (4) counselor effectiveness in providing support; and (5) counselor ability to recognize emotional responses during the session. Among the 554 participants (TC, N=272; UC, N=282), delivery mode was not associated with self-reported satisfaction. However, TC participants found counseling significantly more convenient than UC participants (OR = 4.78, 95% CI = 3.32, 6.89) while also perceiving lower levels of support (OR=0.56, 95% CI=0.40–0.80) and emotional recognition (OR = 0.53, 95% CI = 0.37–0.76). In exploratory analyses, we found that non-Hispanic white participants reported higher counselor support in UC than in TC (69.4% vs. 52.8%; OR = 3.06, 95% CI = 1.39–6.74), while minority women perceived less support in UC vs. TC (58.3% vs. 38.7%; OR = 0.80, 95% CI = 0.39–1.65). We discuss potential research and practice implications of these findings which may further improve the effectiveness and utilization of TC. PMID:26455498

Air Force Office of Scientific Research Technical Report Summaries January - March 1991.

DTIC Science & Technology

1991-04-01

SUS 4SU Uc m W1( -W 0x t - 030 L O F-C-UC W QIMS O-UC tN -C 0 Lo - in 4 LC 4--- 41 UU 00W142 U4 (a 4- C- L 0) -0*-LU0 u ZaW inUi x& Ii- .0 5C4 L US)-L...C 3 L4-in > L 1 4 0 0 4) - DUC 0 L -0M Li nnU 0 3O> C U 0IX 9 z L f -) i- njo e CL .-- w* 1- - .I& - tUn I-. (A in 0 CQ4O 3 041 M -CC 0- LO A A L0...0 ’ 1- - -4-0 -V40 A -- 0 -- W;z a-a 0 Sn C’) 4A OLD tun , z 1’.S oEV mmU OW =3 ) ml > 23 S3 N S 01 1 54 V -0 a0 5 -0 .<Z - 0 4U.~ >jI~S𔃺~.C 42 r - C

Urothelial carcinoma involving the distal penis.

PubMed

Dason, Shawn; Sheikh, Adeel; Wang, Jing Gennie; Tauqir, Syeda; Davies, Timothy O; Shayegan, Bobby

2012-04-01

Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy. Seventeen months prior to presentation, the patient underwent a radical cystectomy with adjuvant chemotherapy. The cystectomy specimen demonstrated a pT4a N2 M0 G3 UC and margins were positive for carcinoma in situ. Follow-up had been negative for recurrence until his presentation with priapism. Incisional biopsy of the glans revealed UC and radical penectomy was performed with negative margins. The penile specimen demonstrated extensive involvement of the corpus spongiosum by UC with lymphovascular invasion and subepidermal involvement. Three months after penectomy, the patient presented with inguinal nodal recurrence. Palliative radiotherapy was administered and the patient passed away eight months after surgery.

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

PubMed

Biancone, Livia; Zuzzi, Sara; Ranieri, Micaela; Petruzziello, Carmelina; Calabrese, Emma; Onali, Sara; Ascolani, Marta; Zorzi, Francesca; Condino, Giovanna; Iacobelli, Simona; Pallone, Francesco

2012-06-01

The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

YouTube as an educational tool regarding male urethral catheterization.

PubMed

Nason, Gregory J; Kelly, Padraig; Kelly, Michael E; Burke, Matthew J; Aslam, Asadullah; Giri, Subhasis K; Flood, Hugh D

2015-04-01

Urethral catheterization (UC) is a common procedure carried out on a daily basis. The aims of this study were to assess the quality of YouTube as an educational tool regarding male UC and to assess the experience of newly qualified doctors regarding UC. YouTube was searched for videos containing relevant information about male UC. A checklist for evaluating content for male UC was devised. The top-ranked video was shown to interns and they were questioned regarding their experience of UC and the usefulness of the video. A total of 100 videos was screened and 49 unique videos were identified. The median length of video was 7 min 15 s (range 1 min 44 s to 26 min 44 s). Regarding the Safe Catheter Insertion Score, the mean score was 5.18 ± 1.64. 9 (18.4%) deemed useful, 24 (49%) somewhat useful and 16 (32.7%) not useful. There was no difference in the number of views (p = 0.487), duration of video (p = 0.364) or number of days online (p = 0.123) between those categorized as useful, somewhat useful and not useful. Twenty-six interns (89.7%) attended the UC teaching session. All reported the video to be a useful educational adjunct. Nine of the respondents (42.9%) had independently inserted a urinary catheter before the educational session. The quality of videos on YouTube regarding male UC is widely variable. Preselected videos are deemed useful by junior doctors regarding male UC and can be used as an educational adjunct before performing hands-on tasks.

Effects of task-specific and impairment-based training compared with usual care on functional walking ability after inpatient stroke rehabilitation: LEAPS Trial.

PubMed

Nadeau, Stephen E; Wu, Samuel S; Dobkin, Bruce H; Azen, Stanley P; Rose, Dorian K; Tilson, Julie K; Cen, Steven Y; Duncan, Pamela W

2013-05-01

After inpatient stroke rehabilitation, many people still cannot participate in community activities because of limited walking ability. To compare the effectiveness of 2 conceptually different, early physical therapy (PT) interventions to usual care (UC) in improving walking 6 months after stroke. The locomotor experience applied post-stroke (LEAPS) study was a single-blind, randomized controlled trial conducted in 408 adults with disabling hemiparetic stroke. Participants were stratified at baseline (2 months) by impairment in walking speed: severe (<0.4 m/s) or moderate (0.4 to <0.8 m/s). Between 2 and 6 months, they received either only UC (n = 143) or UC plus 36 therapist-provided sessions of either (1) walking training on a treadmill using body-weight support and practice overground at clinics (locomotor training program [LTP], n = 139) or (2) impairment-based strength and balance exercise at home (home exercise program [HEP], n = 126). LTP participants were 18% more likely to transition to a higher functional walking level: severe to >0.4 m/s and moderate to >0.8 m/s than UC participants (95% confidence interval [CI] = 7%-29%), and HEP participants were 17% more likely to transition (95% CI = 5%-29%). Mean gain in walking speed in LTP participants was 0.13 m/s greater (95% CI = 0.09-0.18) and in HEP participants, 0.10 m/s greater (95% CI = 0.05-0.14) than in UC participants. Progressive PT, using either walking training on a treadmill and overground, conducted in a clinic, or strength and balance exercises conducted at home, was superior to UC in improving walking, regardless of severity of initial impairment.

Prevalence of Inflammatory Bowel Disease in the Canton of Vaud (Switzerland): A population-based cohort study.

PubMed

Juillerat, Pascal; Pittet, Valérie; Bulliard, Jean-Luc; Guessous, Idris; Antonino, Anca Teodora; Mottet, Christian; Felley, Christian; Vader, John-Paul; Michetti, Pierre

2008-06-01

Because of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Adult IBD patients were identified by a cross-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10(5) inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but males were more represented in elderly UC patients (p=0.008). Thus, being a male was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were found in industrialised countries. Extrapolating our data to all of Switzerland yields an estimate of 12,000 IBD cases for the country, or 1 in 500 inhabitants. Our study gives support to an increase in IBD prevalence in Europe.

Genetic characteristics of inflammatory bowel disease in a Japanese population.

PubMed

Fuyuno, Yuta; Yamazaki, Keiko; Takahashi, Atsushi; Esaki, Motohiro; Kawaguchi, Takaaki; Takazoe, Masakazu; Matsumoto, Takayuki; Matsui, Toshiyuki; Tanaka, Hiroki; Motoya, Satoshi; Suzuki, Yasuo; Kiyohara, Yutaka; Kitazono, Takanari; Kubo, Michiaki

2016-07-01

Crohn's disease (CD) and ulcerative colitis (UC) are two major forms of inflammatory bowel disease (IBD). Meta-analyses of genome-wide association studies (GWAS) have identified 163 susceptibility loci for IBD among European populations; however, there is limited information for IBD susceptibility in a Japanese population. We performed a GWAS using imputed genotypes of 743 IBD patients (372 with CD and 371 with UC) and 3321 controls. Using 100 tag single-nucleotide polymorphisms (SNPs) (P < 5 × 10(-5)), a replication study was conducted with an independent set of 1310 IBD patients (949 with CD and 361 with UC) and 4163 controls. In addition, 163 SNPs identified by a European IBD GWAS were genotyped, and genetic backgrounds were compared between the Japanese and European populations. In the IBD GWAS, two East Asia-specific IBD susceptibility loci were identified in the Japanese population: ATG16L2-FCHSD2 and SLC25A15-ELF1-WBP4. Among 163 reported SNPs in European IBD patients, significant associations were confirmed in 18 (8 CD-specific, 4 UC-specific, and 6 IBD-shared). In Japanese CD patients, genes in the Th17-IL23 pathway showed stronger genetic effects, whereas the association of genes in the autophagy pathway was limited. The association of genes in the epithelial barrier and the Th17-IL23R pathways were similar in the Japanese and European UC populations. We confirmed two IBD susceptibility loci as common for CD and UC, and East Asian-specific. The genetic architecture in UC appeared to be similar between Europeans and East Asians, but may have some differences in CD.

Mucin gene expression in the intestine of ulcerative colitis patients: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2016-11-01

The mucus layer of the colon is the main barrier between luminal microbes and the mucosa, and plays a significant role in the body defense mechanisms. Several studies have examined mucin gene (MUC) expression in ulcerative colitis (UC) without conclusive results. The aim of the study was to establish the knowledge of mucin expression in UC as a basis for further investigation. English medical literature searches were performed for mucin expression in the colonic mucosa of UC patients in comparison with controls. Case-control studies were included. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios (ORs) and 95% confidence intervals were calculated. Altogether, we found 311 eligible studies. Only 10 case-control studies from five countries fulfilled the inclusion criteria. A moderate heterogeneity was found in the studies included: Q=52.703, d.f. (Q)=15.000, I=71.539%. OR for mucin expression in UC patients versus healthy controls was 1.868 with a 95% confidence interval (CI) 1.263-2.764, P=0.002. Thus, we could find a significant increase of 87% of mucin expression in UC patients. OR for MUC2 was 2.520, 95% CI 1.320-4.809, P<0.001. MUC3 was also increased with OR 2.599, 95% CI 1.389-4.861, P=0.003. Funnel plot did not indicate a significant publication bias. We found a global increase in mucin expression in UC patients, specifically in MUC2 and MUC3. Further studies are needed, especially in patients treated with biologics for mucosal healing, to understand the role of mucin expression in the natural history of UC.

Prognostic value of the urea:creatinine ratio in decompensated heart failure and its relationship with acute kidney damage.

PubMed

Josa-Laorden, C; Sola, A; Giménez-López, I; Rubio-Gracia, J; Garcés-Horna, V; Pérez-Calvo, J I

Worsening renal function is associated with an adverse prognosis for patients with acute heart failure (AHF). Urea-creatinine ratio (U:C ratio) might be useful for measuring renal function and could help stratify patients with AHF. An observational and prospective study was conducted to analyse the prognostic value of the U:C ratio, measured during the first 24-28 hours of admission, for patients hospitalised for decompensated Heart failure, and its relationship with estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI). The study included 204 patients, with a mean age of 79.3 years, and a median eGFR of 55 mL/min/1.73m 2 . In the multivariate analysis, an U:C ratio above the median (50) was related to the development of AKI (36.5% vs. 21.9%) and to increased mortality, both overall (OR 2.75) and by HF (OR 3.50) in long term. In combination with eGFR, the U:C ratio showed prognostic value in patients with normal eGFR (mortality of 4.4% for an U:C ratio ≤ 50 vs. 22% for U:C ratio > 50; p=0.01), as well as a better predictive capacity for AKI than each of them separately (AUC, 0.718; 95% CI 0.643-0.793; p>.000). An U:C ratio > 50 is a predictor of increased long-term mortality for patients hospitalised for decompensated HF and with normal eGFR. Given the simplicity of this biomarker, its use in clinical practice should be more systematic. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001

PubMed Central

Lakatos, Laszlo; Mester, Gabor; Erdelyi, Zsuzsanna; Balogh, Mihaly; Szipocs, Istvan; Kamaras, Gyorgy; Lakatos, Peter Laszlo

2004-01-01

AIM: An investigation into inflammatory bowel disease and colorectal cancer in Veszprem Province was conducted from 1977 to 2001. METHODS: Both hospital and outpatient records were collected and reviewed comprehensively. The majority of patients were followed up regularly. RESULTS: The population of the province was decreased from 386000 to 376000 during the period. Five hundred sixty new cases of ulcerative colitis (UC), 212 of Crohn’s disease (CD), and 40 of indeterminate colitis (IC) were diagnosed. The incidence rates increased from 1.66 to 11.01 cases per 100000 persons for UC, from 0.41 to 4.68 for CD and from 0.26 to 0.74 for IC. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9 cases per 100000 persons for CD. The peak onset age in UC patients was between 30 and 40 years, in CD between 20 and 30 years. A family history of IBD was present in 3.4 % in UC and 9.9 % in CD patients. Smoking increased the risk for CD (OR = 1.94) while it decreased the risk for UC (OR = 0.25). Twelve colorectal carcinomas were observed in this cohort, the cumulative colorectal cancer risk after 10 years in UC was 2%, after 20 years 8.8%, after 30 years 13.3%. CONCLUSION: The incidence and prevalence rates of IBD have increased steadily in Veszprem Province, now equivalent to that in Western European countries. Rapid increase in incidence rates supports a probable role for environmental factors. The rate of colorectal cancers in IBD is similar to that observed in Western countries. PMID:14760767

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults

PubMed Central

Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina

2017-01-01

Background Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods One hundred seven frail, obese older adults were randomized into the control (N = 27), diet (N = 26), exercise (N = 26), and diet-exercise (N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2 = 0.140 and 0.107) and diet-exercise (∆R2 = 0.427 and 0.243) groups (P < 0.05 for all). Conclusions Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107. PMID:28951766

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.

PubMed

Colleluori, Georgia; Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina; Villareal, Dennis T

2017-01-01

Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. One hundred seven frail, obese older adults were randomized into the control ( N = 27), diet ( N = 26), exercise ( N = 26), and diet-exercise ( N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). UcOC increased in the diet group (36 ± 11.6%) but not in the other groups ( P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months ( P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only ( R 2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆ R 2 = 0.140 and 0.107) and diet-exercise (∆ R 2 = 0.427 and 0.243) groups ( P < 0.05 for all). Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis: A meta-analysis

PubMed Central

Zhao, Jia-Jun; Wang, Di; Yao, Hui; Sun, Da-Wei; Li, Hong-Yu

2015-01-01

AIM: To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and multi-drug resistance 1 (MDR1) genes polymorphisms with ulcerative colitis (UC) risk. METHODS: PubMed, EMBASE, Web of Science, Cochrane Library, CBM databases, Springerlink, Wiley, EBSCO, Ovid, Wanfang database, VIP database, China National Knowledge Infrastructure, and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4, MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria, the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0 (CMA 2.0) software. The correlations between SNPs of CTLA-4 gene, MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran’s Q-statistic and I2 tests were applied to quantify heterogeneity among studies. Funnel plots, classic fail-safe N and Egger’s linear regression test were inspected for indication of publication bias. RESULTS: A total of 107 studies were initially retrieved and 12 studies were eventually selected for meta-analysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms (SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC (rs3087243 G > A: allele model: OR = 1.365, 95%CI: 1.023-1.822, P = 0.035; dominant model: OR = 1.569, 95%CI: 1.269-1.940, P < 0.001; rs231775 G > A: allele model: OR = 1.583, 95%CI: = 1.306-1.918, P < 0.001; dominant model: OR = 1.805, 95%CI: 1.393-2.340, P < 0.001). In addition, based on our result, SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC (allele model: OR = 1.389, 95%CI: 1.214-1.590, P < 0.001; dominant model: OR = 1.518, 95%CI: 1.222-1.886, P < 0.001). CONCLUSION: CTLA-4 gene rs3087243 G > A and rs231775 G > A, and MDR1 gene rs1045642 C > T might confer an increase for UC risk. PMID:26379408

Plant-based ointments versus usual care in the management of chronic skin diseases: a comparative analysis on outcome and safety.

PubMed

Jong, Miek C; Ermuth, Ulrike; Augustin, Matthias

2013-10-01

To assess the outcome and safety of plant-based ointments versus usual care in the management of chronic skin diseases. Prospective mono-centric comparative analysis. Patients were recruited at an outpatient dermatology clinic and treated with plant-based ointments or care as usual. Main outcome criterion was the response rate, defined as the proportion of patients experiencing 'complete recovery' or 'major improvement' at 6, 12 and 24 months. Secondary outcome criteria were quality of life (SF-12 and EQ-5D), patient satisfaction and safety of treatment. A total of 112 patients with chronic skin diseases were evaluated of which 44 were treated with plant-based ointments (PO) and 68 received usual care (UC). The majority of patients suffered from psoriasis (PO: 50%; UC: 56%) or eczema (PO: 41%; UC: 32%) and were treated with homoeopathic topical ointments containing mahonia or cardiospermum or usual care creams containing calcipotriene and corticosteroids. The only significant difference in baseline status between the two groups was in disease severity score (PO: 1.8±0.7 versus UC: 2.4±0.8, p=0.0004). After two years, the main outcome of responders to treatment was 52.3% (95%-CI: 36.1-64.9) in the ointment and 41.2% (95%-CI: 20.4-42.2) in the UC group. Change in SF-12 (2 years compared to baseline), adjusted for baseline disease severity, was not significantly different between both groups; PO: 5.4 (95%-CI: 3.4-7.3) versus UC: 3.2 (95%-CI: 1.5-4.9). The adjusted EQ-5D was found to be significantly different between the two groups after two years, in favour of the ointment group; PO: 0.113 (95%-CI: 0.052-0.174) and UC: -0.008 (95%-CI: -0.055-0.038). Other secondary outcome parameters such as patient satisfaction and number of adverse drug reactions were comparable. The outcome of this study suggests at least therapeutic equivalence between plant-based ointments and usual care management of chronic skin diseases. As this non-randomised study was open to selection and other bias, further rigorous studies are needed to demonstrate the effectiveness of these topical products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Telemonitoring of CPAP therapy may save nursing time.

PubMed

Anttalainen, Ulla; Melkko, Sari; Hakko, Sirkka; Laitinen, Tarja; Saaresranta, Tarja

2016-12-01

Telemonitoring might enhance continuous positive airway pressure (CPAP) adherence and save nursing time at the commencement of CPAP therapy. We tested wireless telemonitoring (ResTraxx Online System®, ResMed) during the habituation phase of the CPAP therapy in obstructive sleep apnea syndrome (OSAS). In total, 111 consecutive OSAS patients were enrolled. After CPAP titration, patients were followed with the telemonitoring (TM, N = 50) or the usual care (UC, N = 61). The TM group used fixed pressure CPAP device with and the UC group similar device without wireless telemonitoring. Patients and study nurses were unblinded. The evaluated end-points were hours of CPAP use >4 h/day, mask leak <0.4 L/s, and AHI <5/h. Nursing time including extra phone calls, visits, and telemonitoring time was recorded during the habituation phase. CPAP adherence was controlled in the beginning and at the end of the habituation phase and after 1-year of use. TM and UC groups did not differ in terms of patient characteristics. The average length of the habituation phase was 4 weeks in the TM group and fixed 3 months in the UC group. Median nursing time was 39 min (range 12-132 min) in the TM group and shorter compared to that of 58 min (range 40-180 min) (p < 0.001) per patient in the UC group. Both treatment groups had high CPAP usage hours (>4 h/day) and the change in usage at the end of the habituation phase did not differ between the groups (p = 0.39). Patients in both groups were equally satisfied with the treatment protocol. CPAP adherence (6.4 h in TM vs. 6.1 h in UC group, p = 0.63) and residual AHI (1.3 in TM vs. 3.2 in UC group, p = 0.04) were good in both groups at 1-year follow-up. Wireless telemonitoring of CPAP treatment could be relevant in closing the gap between the increasing demand and available health-care resources. It may save nursing time without compromising short- or long-term effectiveness of CPAP treatment in OSAS.

Family partnership and education interventions to reduce dietary sodium by patients with heart failure differ by family functioning.

PubMed

Dunbar, Sandra B; Clark, Patricia C; Stamp, Kelly D; Reilly, Carolyn M; Gary, Rebecca A; Higgins, Melinda; Kaslow, Nadine

2016-01-01

Determine if family functioning influences response to family-focused interventions aimed at reducing dietary sodium by heart failure (HF) patients. Lowering dietary sodium by HF patients often occurs within the home and family context. Secondary analysis of 117 dyads randomized to patient and family education (PFE), family partnership intervention (FPI) or usual care (UC). Dietary sodium measures were obtained from 3-day food record and 24-h urine samples. In the poor family functioning groups, FPI and PFE had lower mean urine sodium than UC (p < .05) at 4 months, and FPI remained lower than UC at 8 months (p < .05). For good family functioning groups, FPI and PFE had lower mean sodium levels by 3-day food record at 4 and 8 months compared to the UC group. Optimizing family-focused interventions into HF clinical care maybe indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic characterization of the UCS and Kex1 loci of Pneumocystis jirovecii.

PubMed

Esteves, F; Tavares, A; Costa, M C; Gaspar, J; Antunes, F; Matos, O

2009-02-01

Nucleotide variation in the Pneumocystis jirovecii upstream conserved sequence (UCS) and kexin-like serine protease (Kex1) loci was studied in pulmonary specimens from Portuguese HIV-positive patients. DNA was extracted and used for specific molecular sequence analysis. The number of UCS tandem repeats detected in 13 successfully sequenced isolates ranged from three (9 isolates, 69%) to four (4 isolates, 31%). A novel tandem repeat pattern and two novel polymorphisms were detected in the UCS region. For the Kex1 gene, the wild-type (24 isolates, 86%) was the most frequent sequence detected among the 28 sequenced isolates. Nevertheless, a nonsynonymous (1 isolate, 3%) and three synonymous (3 isolates, 11%) polymorphisms were detected and are described here for the first time.

Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients

PubMed Central

Latiano, Anna; Palmieri, Orazio; Latiano, Tiziana; Corritore, Giuseppe; Bossa, Fabrizio; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; Valvano, Maria Rosa; Pastore, Maria; Marseglia, Antonio; D'Incà, Renata; Andriulli, Angelo; Annese, Vito

2011-01-01

Background Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Methods Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. Results The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10−6). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10−5). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. Conclusions We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes. PMID:21818367

Quadratic general rotary unitized design for doping concentrations and up-conversion luminescence properties of Er{sup 3+}/Yb{sup 3+} co-doped NaLa(MoO{sub 4}){sub 2} phosphors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jiashi, E-mail: sunjs@dlmu.edu.cn; Shi, Linlin; Li, Shuwei

Highlights: • NaLa(MoO4)2: Er3+/Yb3+ phosphor is synthesized by solid state method. • QGRUD is first applied to the codoping concentration option. • Optimized phosphor presents more stable UC emissions than the commercial phosphor. - Abstract: It is still a great challenge that designing proper codoping concentrations of rare earth ions for achieving intensest expected emission from the studied phosphor. In this work, the quadratic general rotary unitized design (QGRUD) was introduced into the codoping concentration option of NaLa(MoO{sub 4}){sub 2}: Er{sup 3+}/Yb{sup 3+} phosphor for upconversion (UC) applications, and the optimum doping concentrations of Er{sup 3+} and Yb{sup 3+} formore » achieving maximum UC luminescence intensity, which is close to commercial NaYF{sub 4}:Er{sup 3+}/Yb{sup 3+} phosphor, were obtained. The two-photon process was assigned to the green UC emissions in the optimized NaLa(MoO{sub 4}){sub 2}: Er{sup 3+}/Yb{sup 3+} phosphor. It was also demonstrated that the optimized phosphor presented more stable upconversion emissions than the commercial NaYF{sub 4}:Er{sup 3+}/Yb{sup 3+} phosphor.« less

Urinary potassium is a potential biomarker of disease activity in Ulcerative colitis and displays in vitro immunotolerant role.

PubMed

Goyal, Sandeep; Rampal, Ritika; Kedia, Saurabh; Mahajan, Sandeep; Bopanna, Sawan; Yadav, Devesh P; Jain, Saransh; Singh, Amit Kumar; Wari, Md Nahidul; Makharia, Govind; Awasthi, Amit; Ahuja, Vineet

2017-12-22

We evaluated the in-vitro effect of potassium on CD4 + T cells and the role of urinary potassium as a potential biomarker of disease activity in patients with ulcerative colitis (UC). This prospective observational cohort study included healthy controls (n = 18) and UC patients [n = 30, median age: 40 (IQR: 28-46) years, 17 males)] with active disease(assessed by Mayo score) from September 2015-May 2016. Twenty-four hours urinary potassium along with fecal calprotectin (FCP) were estimated in UC patients (at baseline and follow-up after 3-6 months) and controls. In healthy volunteers, we also assessed the effect of potassium on CD4 + T cells differentiated in the presence of Th17 polarizing condition. UC patients had significantly higher FCP (368.2 ± 443.04 vs 12.44 ± 27.51, p < 0.001) and significantly lower urinary potassium (26.6 ± 16.9 vs 46.89 ± 35.91, p = 0.01) levels than controls. At follow-up, a significant increase in urinary potassium among patients who had clinical response [n = 22, 21.4 (14.4-39.7) to 36.5 (20.5-61.6), p = 0.04] and remission [n = 12, 18.7 (9.1-34.3) to 36.5 (23.4-70.5), p = 0.05] was accompanied with a parallel decline in FCP. On in-vitro analysis, potassium under Th17 polarizing conditions significantly inhibited IL-17 and interferon-[Formula: see text] expression while favoring the induction of FoxP3 + T cells. Therefore, urinary potassium levels are inversely associated with disease activity in UC with in-vitro data supporting an immune-tolerant role of potassium.

Appendectomy, smoking habits and the risk of developing ulcerative colitis: a case control study in private practice setting.

PubMed

de Saussure, Philippe; Clerson, Pierre; Prost, Pierre-Louis; Truong Tan, Nghiep; Bouhnik, Yoram; Gil-Rch

2007-05-01

The strongest environmental factors identified for ulcerative colitis (UC) are cigarette smoking and appendectomy. However, most studies have been performed using case-controls from hospital-based populations. The purpose of this study was to compare the history of previous appendectomy and smoking habits in a group of patients with UC and a control group, followed by gastroenterologists in private practice. We performed a case control study in which 100 physicians recruited UC-patients and age and sex matched controls. Data were collected during a single visit. Based on a standardized questionnaire, UC patients and controls were divided into never, former or current smokers, and into subjects with or without a previous history of appendectomy. One hundred and ninety eight age- and sex-matched pairs of UC patients and controls were included. The prevalence of appendectomy in the UC-patients and control group was 12% and 46%, respectively. The pairwise-matched OR of ulcerative colitis for previous appendectomy was 0.10 (95% CI, 0.05-0.21) (P<0.0001). The OR for former and never smokers versus current smokers was 2.40 (95% CI 1.31-4.38) (P=0.004). In UC-patients, the OR of family history of UC compared with controls was 2.80 (95% CI, 1.01-7.77) (P=0.048). This case-control study confirmed a strong negative correlation between both appendectomy and tobacco smoking, and ulcerative colitis in patients followed-up by gastroenterological practitioners.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding

PubMed Central

Silver, Andrew; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert

2017-01-01

Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression. PMID:28751935

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage.

PubMed

Caprodossi, Sara; Lucciarini, Roberta; Amantini, Consuelo; Nabissi, Massimo; Canesin, Giacomo; Ballarini, Patrizia; Di Spilimbergo, Adriana; Cardarelli, Marco Andrea; Servi, Lucilla; Mammana, Gabriele; Santoni, Giorgio

2008-09-01

To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.

Delayed-release oral mesalamine 4.8 g/day (800 mg tablets) compared with 2.4 g/day (400 mg tablets) for the treatment of mildly to moderately active ulcerative colitis: The ASCEND I trial

PubMed Central

Hanauer, Stephen B; Sandborn, William J; Dallaire, Christian; Archambault, André; Yacyshyn, Bruce; Yeh, Chyon; Smith-Hall, Nancy

2007-01-01

BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC), but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease. PATIENTS AND METHODS: A six-week, multicentre, randomized, double-blind, controlled trial assessing the safety and clinical efficacy of a new dose (ASCEND I) of medication randomly assigned 301 adults with mildly to moderately active UC to delayed-release oral mesalamine 2.4 g/day (400 mg tablet [n=154]) or 4.8 g/day (800 mg tablet [n=147]). The primary efficacy end point was overall improvement (ie, treatment success), defined as complete remission or response to therapy from baseline to week 6. Primary safety end points were adverse events and laboratory evaluations. Data were also analyzed separately for the prespecified subgroup of patients with moderate UC at baseline. RESULTS: Treatment success was not statistically different between the treatment groups at week 6; 51% of the group (77 of 150) who received delayed-release oral mesalamine 2.4 g/day and 56% of the group (76 of 136) who received 4.8 g/day reached the efficacy end point (P=0.441). Among the moderate disease subgroup, however, the higher initial dose was more effective; 57% of patients (53 of 93) given delayed-release oral mesalamine 2.4 g/day and 72% of patients (55 of 76) given 4.8 g/day achieved treatment success (P=0.0384). Both regimens were well tolerated. CONCLUSIONS: Delayed-release oral mesalamine is an effective and well-tolerated initial therapy in patients with mildly to moderately active UC, and a 4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day. PMID:18080055

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis

PubMed Central

Nahar, Saifun; Iraha, Atsushi; Hokama, Akira; Uehara, Ayako; Parrott, Gretchen; Ohira, Tetsuya; Kaida, Masatoshi; Kinjo, Tetsu; Kinjo, Takeshi; Hirata, Tetsuo; Kinjo, Nagisa; Fujita, Jiro

2015-01-01

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC). METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex® Kit. Additional clinical and laboratory data were collected from the medical records. RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0.05). CONCLUSION: The multiplex PCR assay that was used to analyze the stool samples in this study may serve as a non-invasive approach that can be used to exclude the possibility of CMV infection in patients with active UC who are treated with immunosuppressive therapy. PMID:26640344

Psychological distress during pregnancy in Miyagi after the Great East Japan Earthquake: The Japan Environment and Children's Study.

PubMed

Watanabe, Zen; Iwama, Noriyuki; Nishigori, Hidekazu; Nishigori, Toshie; Mizuno, Satoshi; Sakurai, Kasumi; Ishikuro, Mami; Obara, Taku; Tatsuta, Nozomi; Nishijima, Ichiko; Fujiwara, Ikuma; Nakai, Kunihiko; Arima, Takahiro; Takeda, Takashi; Sugawara, Junichi; Kuriyama, Shinichi; Metoki, Hirohito; Yaegashi, Nobuo

2016-01-15

To examine psychological distress among pregnant women in Miyagi prefecture which was directly affected by the Great East Japan Earthquake and tsunami and compare other areas of Japan that were less damaged. This study was conducted in conjunction with the Japan Environment and Children's Study (JECS). We examined 10,129 Japanese women using the primary fixed data of the JECS. The Kessler 6-item psychological distress scale (K6) was administered to 7473 eligible women including 998 in Miyagi unit center ('Miyagi UC') and 6475 in the other unit centers ('13UCs'). We compared the prevalence and the risk of distress (K6 ≥ 13) during pregnancy in 'Miyagi UC' and '13UCs'. More women in 'Miyagi UC' (4.9%) suffered psychological distress, compared with '13UCs' (3.1%) (p<0.001). A significantly higher prevalence of women in 'Miyagi UC' (55.5%) had experienced negative life events, whereas '13UCs' showed 42.7% (p<0.0001). In multivariable logistic analyses adjusted for baseline characteristics, there was a significant regional difference of psychological distress (adjusted odds ratio; aOR in Miyagi UC=1.488; 95%CI, 1.059-2.090). After further adjusting for negative life events, the association was diminished (aOR=1.338; 95%CI, 0.949-1.884). The JECS had no data before the earthquake and the extent of damage was not investigated. Possible regional representativeness is also a limitation. After the Great East Japan Earthquake, the prevalence of pregnant women with psychological distress (K6 ≥ 13) were high in Miyagi prefecture. Especially in the coastal area directly affected by tsunami, it is high with or without negative life events experienced. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure, upconversion photoluminescence, and dielectric properties of Ho{sup 3+}- and Yb{sup 3+}-codoped tetragonal tungsten bronze Sr{sub 4}La{sub 2}Ti{sub 4}Nb{sub 6}O{sub 30}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, T., E-mail: weitong.nju@gmail.com; Li, C.P.; Zhou, Q.J.

2015-04-15

Highlights: • TTB-type SLTN: Ho-Ybx with space group P4/mbm was determined. • UC photoluminescence of SLTN: Ho-Ybx ceramics was first reported. • Bright UC green emission was observed at room temperature. • Two-photon energy transfer process was confirmed for the UC processes. • Temperature stability of dielectric permittivity was improved for SLTN: Ho-Ybx. - Abstract: Ho{sup 3+}- and Yb{sup 3+}-codoped Sr{sub 4}La{sub 2}Ti{sub 4}Nb{sub 6}O{sub 30} (Sr{sub 4}La{sub 1.94–x}Ho{sub 0.06}Yb{sub x}Ti{sub 4}Nb{sub 6}O{sub 30}, abbreviated as SLTN: Ho-Ybx) ceramics have been synthesized, and their structural, up-conversion (UC) photoluminescence, and dielectric properties have been carefully investigated. Through Rietveld structural refinement, SLTN:more » Ho-Ybx samples are determined as single tetragonal tungsten bronze (TTB) phase with space group P4/mbm in which larger Sr{sup 2+} ions fill the A{sub 2}-sites, relative smaller La{sup 3+}, Ho{sup 3+}, and Yb{sup 3+} ions occupy the A{sub 1}-sites, while Ti{sup 4+} and Nb{sup 4+} ions fill the B-sites. Under 980 nm near infrared (NIR) excitation, bright UC green emission, relatively weak red and near-infrared (NIR) emissions, originating from {sup 5}F{sub 4}/{sup 5}S{sub 2} → {sup 5}I{sub 8}, {sup 5}F{sub 5} → {sup 5}I{sub 8}, and {sup 5}F{sub 4}/{sup 5}S{sub 2} → {sup 5}I{sub 7} transitions of Ho{sup 3+} ions, are confirmed for SLTN: Ho-Ybx. Two-photon energy transfer process is proved through pumping laser power dependence of emission intensity measurement. Furthermore, the influence of Ho{sup 3+}- and Yb{sup 3+}- ions on the dielectric properties of SLTN: Ho-Ybx is also investigated and the temperature stability of dielectric permittivity is improved.« less

Constraints on the magnitude and rate of carbon dioxide dissolution at Bravo Dome natural gas field

NASA Astrophysics Data System (ADS)

Sathaye, K.; Hesse, M. A.

2013-12-01

The Bravo Dome field in northeastern New Mexico contains at least 10 trillion cubic feet (tcf) of magmatic CO2. The CO2 has been emplaced in the reservoir for at least 10,000 years, providing a useful analog for geologic CO2 storage. The reservoir is comprised of a CO2 gas layer overlying brine water in a sandstone reservoir. Previous estimates have used differences in the CO2/3He ratio in the gas to infer that locally, half of the CO2 originally emplaced has dissolved into the underlying brine. This study presents the first estimate of the total amount of CO2 dissolved. We incorporate gas pressure, reservoir geometry, and gas layer thickness to show that over 80% of the CO2 originally emplaced is still present in the gas layer. It is generally assumed that the dissolution of CO2 is driven by convective currents in the brine. We present an alternative hypothesis for the spatial differences of the CO2/3He ratio seen in this reservoir. Gas injection theory predicts that as gas displaces a liquid, relatively insoluble gas components will become enriched at the front of the displacement. If the emplacement occurred from west to east this would cause 3He enrichment in the eastern portion of the Bravo Dome field overlying the brine. This effect could be responsible for the spatial differences in the CO2/3He ratio. Mass per area in the gas layer of the reservoir is seen in the 2 right panes. The measured bottom hole pressure data from 1981 is used in combination with CO2/3He measurements to estimate the mass of CO2 originally in place. The water thickness is inversely correlated with the CO2/3He ratio, suggesting that there may be convective dissolution occurring in the eastern part of the reservoir. Present day mass of CO2 is roughly 83% of the original total.

Florid urticarial vasculitis heralding a flare up of ulcerative colitis.

PubMed

Boules, Evon; Lyon, Calum

2014-12-22

A 75-year-old man with ulcerative colitis (UC) and diet controlled diabetes mellitus presented with a 3-week history of slightly itchy, red plaques on both lower limbs ascending gradually to cover the trunk and arms. One week later, he developed a flare up of his UC. Routine blood tests showed modest drop in haemoglobin (122 g/L) and C reactive protein (85 mg/L). Serology was remarkable for high antiproteinase 3 (c-ANCA). Serum electrophoresis showed a mildly positive paraprotein band (γ region). Stool culture was negative. Urine analysis showed proteinuria. Skin biopsy showed features of urticarial vasculitis (UV). He underwent a flexible sigmoidoscopy after the flare up showed mildly active UC. The patient was given hydrocortisone for 7 days and then prednisolone. Both rash and UC subsided. Electrophoresis was repeated 4 weeks later showing normal pattern. Prednisolone has been gradually reduced. Although rare, UV can be considered as one of the skin manifestations of UC. 2014 BMJ Publishing Group Ltd.

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis.

PubMed

Manguso, F; Balzano, A

2007-07-01

Beclomethasone dipropionate (BDP) is a second-generation steroid with topical effects and minimal systemic activity for patients with ulcerative colitis (UC). To review all available literature to assess the efficacy of enema/foam BDP compared with enema/foam 5-aminosalicylic acid (5-ASA) in the control of left-sided mild-moderate UC. We selected randomized controlled trials of enema/foam BDP compared with enema/foam 5-ASA treatment in patients with UC. Two reviewers assessed trial quality and extracted data independently. Four trials involving 428 UC patients, 209 treated with 5-ASA (1-4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention-to-treat analysis showed that 5-ASA induced improvement/remission of UC in 146 (69.9%) patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was not significant and Mantel-Haenszel pooled estimate of odds ratio was 1.23 (95% CI = 0.82-1.85). The results did not change when analysis was performed on a per-protocol basis. The randomized controlled trials identified in this review showed that rectal BDP has equal effect as 5-ASA to control symptoms in UC.

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

PubMed Central

Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

2015-01-01

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

Interns reflect: the effect of formative assessment with feedback during pre-internship.

PubMed

McKenzie, Susan; Burgess, Annette; Mellis, Craig

2017-01-01

It is widely known that the opportunity for medical students to be observed and to receive feedback on their procedural skills performance is variable in the senior years. To address this problem, we provided our Pre-Intern (PrInt) students with "one-to-one" formative feedback on their ability to perform urethral catheterization (U/C) and hypothesized that their future practice of U/C as interns would benefit. This study sought to evaluate the performance and practice of interns in U/C 4-5 months after having received feedback on their performance of U/C as PrInt students. Between 2013 and 2014, two cohorts of interns, (total n=66) who had received recent formative feedback on their U/C performance as PrInt students at Central Clinical School, were invited to complete an anonymous survey. The survey contained nine closed unvalidated questions and one open-ended question, designed to allow interns to report on their current practice of U/C. Forty-one out of 66 interns (62%) completed the survey. Thirty-five out of 41 respondents (85%) reported that the assessment with feedback during their PrInt term was beneficial to their practice. Thirty of 41 (73%) reported being confident to perform U/C independently. Eleven out of 41 respondents (27%) reported that they had received additional training at intern orientation. Nine of the 11 interns (82%) reported that they had a small, but a significant, increase in confidence to perform U/C when compared with the 30 of the 41 respondents (73%) who had not ( p =0.03). Our results substantiate our hypothesis that further education by assessment with feedback in U/C during PrInt was of benefit to interns' performance. Additional educational reinforcement in U/C during intern orientation further improved intern confidence. Our results indicate that extra pre- and post-graduation procedural skills training, with feedback, should be universal.

Interns reflect: the effect of formative assessment with feedback during pre-internship

PubMed Central

McKenzie, Susan; Burgess, Annette; Mellis, Craig

2017-01-01

Background It is widely known that the opportunity for medical students to be observed and to receive feedback on their procedural skills performance is variable in the senior years. To address this problem, we provided our Pre-Intern (PrInt) students with “one-to-one” formative feedback on their ability to perform urethral catheterization (U/C) and hypothesized that their future practice of U/C as interns would benefit. This study sought to evaluate the performance and practice of interns in U/C 4–5 months after having received feedback on their performance of U/C as PrInt students. Methods Between 2013 and 2014, two cohorts of interns, (total n=66) who had received recent formative feedback on their U/C performance as PrInt students at Central Clinical School, were invited to complete an anonymous survey. The survey contained nine closed unvalidated questions and one open-ended question, designed to allow interns to report on their current practice of U/C. Results Forty-one out of 66 interns (62%) completed the survey. Thirty-five out of 41 respondents (85%) reported that the assessment with feedback during their PrInt term was beneficial to their practice. Thirty of 41 (73%) reported being confident to perform U/C independently. Eleven out of 41 respondents (27%) reported that they had received additional training at intern orientation. Nine of the 11 interns (82%) reported that they had a small, but a significant, increase in confidence to perform U/C when compared with the 30 of the 41 respondents (73%) who had not (p=0.03). Conclusion Our results substantiate our hypothesis that further education by assessment with feedback in U/C during PrInt was of benefit to interns’ performance. Additional educational reinforcement in U/C during intern orientation further improved intern confidence. Our results indicate that extra pre- and post-graduation procedural skills training, with feedback, should be universal. PMID:28138270

Extracellular Vesicles Released from Human Umbilical Cord-Derived Mesenchymal Stromal Cells Prevent Life-Threatening Acute Graft-Versus-Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Wang, Li; Gu, Zhenyang; Zhao, Xiaoli; Yang, Nan; Wang, Feiyan; Deng, Ailing; Zhao, Shasha; Luo, Lan; Wei, Huaping; Guan, Lixun; Gao, Zhe; Li, Yonghui; Wang, Lili; Liu, Daihong; Gao, Chunji

2016-12-15

Mesenchymal stromal cells (MSCs) are attractive agents for the prophylaxis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, safety concerns remain about their clinical application. In this study, we explored whether extracellular vesicles released from human umbilical cord-derived MSCs (hUC-MSC-EVs) could prevent aGVHD in a mouse model of allo-HSCT. hUC-MSC-EVs were intravenously administered to recipient mice on days 0 and 7 after allo-HSCT, and the prophylactic effects of hUC-MSC-EVs were assessed by observing the in vivo manifestations of aGVHD, histologic changes in target organs, and recipient mouse survival. We evaluated the effects of hUC-MSC-EVs on immune cells and inflammatory cytokines by flow cytometry and ProcartaPlex™ Multiplex Immunoassays, respectively. The in vitro effects of hUC-MSC-EVs were determined by mitogen-induced proliferation assays. hUC-MSC-EVs alleviated the in vivo manifestations of aGVHD and the associated histologic changes and significantly reduced the mortality of the recipient mice. Recipients treated with hUC-MSC-EVs had significantly lower frequencies and absolute numbers of CD3 + CD8 + T cells; reduced serum levels of IL-2, TNF-α, and IFN-γ; a higher ratio of CD3 + CD4 + and CD3 + CD8 + T cells; and higher serum levels of IL-10. An in vitro experiment demonstrated that hUC-MSC-EVs inhibited the mitogen-induced proliferation of splenocytes in a dose-dependent manner, and the cytokine changes were similar to those observed in vivo. This study indicated that hUC-MSC-EVs can prevent life-threatening aGVHD by modulating immune responses. These data provide the first evidence that hUC-MSC-EVs represent an ideal alternative in the prophylaxis of aGVHD after allo-HSCT.

The risk of bladder cancer in patients with urinary calculi: a meta-analysis.

PubMed

Yu, Zhang; Yue, Wu; Jiuzhi, Li; Youtao, Jiang; Guofei, Zhang; Wenbin, Guo

2018-01-05

The objective of this meta-analysis was to evaluate the association between a history of urinary calculi (UC) and the risk of bladder cancer (BC). A literature search was performed from inception until July 2017. Studies that reported odds ratios (OR), relative risks or hazard ratios comparing the risk of BC in patients with the history of UC vs those without the history of UC were included. Pooled odds ratios and 95% confidence interval (CI) were calculated using a random-effect or fixed-effect method. Thirteen studies were included in our analysis to assess the association between a history of UC and risk of BC. The pooled OR of BC in patients with UC was 1.87 (95% CI, 1.45-2.41). Bladder calculi [OR, 2.17 (95% CI, 1.52-3.08)] had a higher risk of BC than kidney calculi [OR, 1.39 (95% CI, 1.06-1.82)]. The subjects had a history of UC that was associated with increased BC risk both in males [OR, 2.04 (95% CI, 1.41-2.96)] and in females [OR, 2.99 (95% CI, 2.37-3.76)]. The subgroup analysis demonstrated that UC increasing risk of BC both in case-control studies [OR, 1.75 (95% CI, 1.25-2.45)] and cohort studies [OR, 2.27 (95% CI, 1.55-3.32)]. The pooled OR of BC risk in patients with UC were 1.60 (95% CI, 1.15-2.24) in America, 1.36 (95% CI, 1.14-1.64) in Europe and 3.05 (95% CI, 2.21-4.21) in Asia, respectively. Our study demonstrates a significant increased risk of BC in patients with prior UC. This finding suggests that a history of UC is associated with BC and may impact clinical management and cancer surveillance. Further studies still needed to confirm the findings.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis.

PubMed

Fumery, Mathurin; Dulai, Parambir S; Gupta, Samir; Prokop, Larry J; Ramamoorthy, Sonia; Sandborn, William J; Singh, Siddharth

2017-05-01

Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). We performed a systematic literature review through June 1, 2016, to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% confidence interval [CI], 0.4-1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9-2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (odds ratio [OR], 3.4; 95% CI, 1.5-7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0-3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1-3.7), and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5-8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8-33). In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

PubMed Central

Civini, Sara; Pacelli, Consiglia; Dieng, Mame Massar; Lemieux, William; Jin, Ping; Bazin, Renée; Patey, Natacha; Marincola, Francesco M.; Moldovan, Florina; Zaouter, Charlotte; Trudeau, Louis-Eric; Benabdhalla, Basma; Louis, Isabelle; Beauséjour, Christian; Stroncek, David; Le Deist, Françoise; Haddad, Elie

2016-01-01

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to-DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation. PMID:27070086

Ground motion analysis of OSSY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swift, R.P.; Snell, C.M.

1993-11-01

The On Site Seismic Yield experiment, OSSY, was performed to investigate the viability of a high-explosive technique to help estimate the yield of nuclear explosions. We have analyzed recorded data and conducted numerical simulations of the 100-pound OSSY experiments performed in hole UE-10 ITS No. 3 at the Nevada Test Site. Particle velocity wave forms from these experiments show a distinct dual-pulse structure in the close-in and far-field regions, with the amplitude of the second pulse being as large as or larger than the first pulse. To gain some insight into the cause of the dual-pulse feature, we examine howmore » the explosion-induced close-in response is affected by (1) certain features of inelastic rock/soil constitutive models applied in the near-field region, (2) the large length-to-diameter charge ratio of 8, (3) the charge and gauge package emplacement, and (4) geology (e.g., layering) in the vicinity of the explosion. Our results from 1-D and 2-D simulations show the following: (a) the response, measured by accelerometers located above the charges, is significantly influenced by the charge length-to-diameter ratio out to a distance of 8 m. (b) the grout emplacement of the charge has very little effect on the response. (c) the geologic layering serves mainly to phase the arrival of the pulses. (d) the second pulse can be best accounted for by applying a dilatant feature that allows for pore recovery during unloading. Other material property variations do not provide any contribution to the formation of a second pulse.« less

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

PubMed

De Vos, Martine; Dhooghe, Barbara; Vermeire, Severine; Louis, Edouard; Mana, Fazia; Elewaut, Ann; Bossuyt, Peter; Baert, Filip; Reenaers, Catherine; Van Gossum, Marc; Macken, Elisabeth; Ferrante, Marc; Hindryckx, Pieter; Dewit, Olivier; Holvoet, Tom; Franchimont, Denis

2018-04-01

Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Enhancement of 800 nm upconversion emission in a thulium doped tellurite microstructured fiber pumped by a 1560 nm femtosecond fiber laser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jia, Zhixu; Zheng, Kezhi; State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012

We report enhanced upconversion (UC) fluorescence in Tm{sup 3+} doped tellurite microstructured fibers (TDTMFs) fabricated by using a rod-in-tube method. Under the pumping of a 1560 nm femtosecond fiber laser, ultrabroadband supercontinuum light expanding from ∼1050 to ∼2700 nm was generated in a 4 cm long TDTMF. Simultaneously, intense 800 nm UC emission from the {sup 3}H{sub 4} → {sup 3}H{sub 6} transition of Tm{sup 3+} was observed in the same TDTMF. Compared to that pumped by a 1560 nm continuous wave fiber laser, the UC emission intensity was enhanced by ∼4.1 times. The enhancement was due to the spectral broadening in the TDTMF under themore » pumping of the 1560 nm femtosecond fiber laser.« less

Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study.

PubMed

Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori

2015-12-01

Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative Colitis: A Simulation Model.

PubMed

Scott, Frank I; Shah, Yash; Lasch, Karen; Luo, Michelle; Lewis, James D

2018-01-18

Vedolizumab, an α4β7 integrin monoclonal antibody inhibiting gut lymphocyte trafficking, is an effective treatment for ulcerative colitis (UC). We evaluated the optimal position of vedolizumab in the UC treatment paradigm. Using Markov modeling, we assessed multiple algorithms for the treatment of UC. The base case was a 35-year-old male with steroid-dependent moderately to severely active UC without previous immunomodulator or biologic use. The model included 4 different algorithms over 1 year, with vedolizumab use prior to: initiating azathioprine (Algorithm 1), combination therapy with infliximab and azathioprine (Algorithm 2), combination therapy with an alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3), and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life-year (QALY) estimates were derived from the published literature. Primary analyses included simulating 100 trials of 100,000 individuals, assessing clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons and ranges for all variables. Algorithm 1 (vedolizumab use prior to all other therapies) was the preferred strategy, resulting in 8981 additional individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious infections per 100,000 patients compared with last-line use (A4). Algorithm 1 also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This benefit increased with longer time horizons. Algorithm 1 was preferred in all sensitivity analyses. The model suggests that treatment algorithms positioning vedolizumab prior to other therapies should be considered for individuals with moderately to severely active steroid-dependent UC. Further prospective research is needed to confirm these simulated results. © 2018 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The emplacement, geochemistry and petrogenesis of two central Morocco Hercynian granites. Geotectonic implications

NASA Astrophysics Data System (ADS)

Giuliani, G.; Cheilletz, A.; Zimmermann, J. L.

New field, petrographic and geochemical data including REE, Rb-Sr, and K-Ar, are presented concerning the emplacement and petrogenesis of two calc-alkaline Moroccan Hercynian granites: the Zaër pluton and the Djebel Aouam stocks. Zonation in the Zaër pluton does not appear to result from simple fractional crystallization nor from hydrothermal alteration but is rather the diapiric intrusion of two interlocked bodies. REE geochemistry supports the interpretation that the biotite-granodiorite magma (301 ± 8.2 M.a.) and the Djebel Aouam stocks appear to have been derived by fusion of crustal materials with possible mantle contamination ( Initial87Sr/ 86Srratio = 0.70514 ). The second two-mica granitic magma (283.4 ± 6.2 M.a.) corresponds to a peraluminous granite (1.22 < A/ CNK < 1.33) generated by fusion of continental crust including mature sedimentarr materials (Initial 87Sr/ 86Sr ratio = 0.70836). These granites are compared to the Acadian granites of north Appalachian and classified in the «post-collision, uplift environmentå type. An illustrative four step model presenting the generation and emplacement of these two granites together with the associated W-Sn-Pb-Zn-Ag mineralizations is proposed: (1) first magma generation, (2) first melt emplacement, (3) second melt emplacement, (4) late convective flow.

Carbohydrate and protein intake and risk of ulcerative colitis: Systematic review and dose-response meta-analysis of epidemiological studies.

PubMed

Wang, Fan; Feng, Juerong; Gao, Qian; Ma, Minxing; Lin, Xue; Liu, Jing; Li, Jin; Zhao, Qiu

2017-10-01

Dietary carbohydrate and protein intake is generally thought as risk factors for onset of ulcerative colitis (UC), while epidemiological data had been controversial. This study aimed to evaluate the role of carbohydrate and protein intake in the development of UC. Comprehensive search in PubMed and Embase was conducted to identify all relevant studies, and the role of carbohydrate and protein intake in the development of UC was quantitatively assessed by dose-response meta-analysis. Nine studies (5 case-control and 4 prospective cohort) were identified with a total of 975 UC cases and 239352 controls. The summary relative risks (RR) for per 10 g increment/day were 1.005 (95%CI: 0.991-1.019, I 2  = 31.5%, n = 5) for total carbohydrate intake, 1.001 (95%CI: 0.971-1.032, I 2  = 0.0%, n = 7) for the subtype of fiber intake, 1.029 (95%CI: 0.962-1.101, I 2  = 68.9%, n = 2) for the subtype of sugar intake, and 1.010 (95%CI: 0.975-1.047, I 2  = 12.4%, n = 7) for total protein intake. Among sugar subtypes, only sucrose intake was found positively related with UC risk (RR for per 10 g increment/day: 1.098, 95%CI: 1.024-1.177, I 2  = 0.0%, n = 3). No evidence of a non-linear dose-response association was found between the nutrient intake and UC risk, except for the subtype of sucrose (P for non-linear trend = 0.032). Subgroup analyses showed consistent results. This meta-analysis suggested a lack of association between dietary carbohydrate or protein intake and the risk of UC, except for the subtype of sucrose which played a significant role in the development of UC. Large-scale prospective designed studies are needed to confirm our findings. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

46 CFR 56.60-2 - Limitations on materials.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Boiler and Pressure Vessel Code * ASTM specifications Source of allowable stress Notes Ferrous Materials...-5. 2 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME.... 4 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME Boiler...

46 CFR 56.60-2 - Limitations on materials.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Boiler and Pressure Vessel Code * ASTM specifications Source of allowable stress Notes Ferrous Materials...-5. 2 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME.... 4 Allowable stresses shall be the same as those listed in UCS23 of section VIII of the ASME Boiler...

Study of visible luminescence spectra from Nd3+ doped TPO glass upon 808 nm excitation

NASA Astrophysics Data System (ADS)

Azam, Mohd; Rai, Vineet Kumar

2018-05-01

The Nd3+ doped TPO glasses have been prepared by melting and quenching method using the high temperature electric furnace. The upconversion (UC) spectra of Nd3+ doped TPO glasses at different concentration of rare ions have been recorded in the 400-700 nm wavelength range upon 808 nm laser excitation source. In the UC emission process, there are four bands centered at ˜495 nm, 546 nm, 602 nm and 653 nm respectively in the visible range were observed. But the green and red bands centered at˜546 nm and ˜653 nm corresponding to the 4G7/2 → 4I9/2 and 4G7/2 → 4I13/2 transitions respectively have been observed as the strong bands. The UC emission mechanism was observed as two photon process. The material can be used as a good NIR to visible upconverter and non-colour tunable display.

Upconversion luminescence of CsScF4 crystals doped with erbium and ytterbium

NASA Astrophysics Data System (ADS)

Ikonnikov, D. A.; Voronov, V. N.; Molokeev, M. S.; Aleksandrovsky, A. S.

2016-10-01

Tetragonal CsScF4 crystals doped with (5 at.%) Er and Er/Yb (0.5 at.%/5 at.%) are grown and their crystal structure is determined to belong to Pmmn space group. Er and Yb ions are shown to occupy distorted octahedral Sc sites with the center of inversion. Bright visible upconversion luminescence was observed under 970-980 nm pumping with red (4F9/2), yellow (4S3/2) and green (2H11/2) bands of comparable intensity. UCL tuning curves maximize at 972 nm (CSF:Er) and at 969.7 nm (CSF:Er,Yb) pumping wavelengths. Different ratios between yellow-green and red luminescence intensities in CSF:Er and CSF:Er, Yb are explained by contribution of cross-relaxation in CSF:Er UCL. UC in CSF:Er is a three stage process while UC in CSF:Er, Yb is a two stage process. The peculiarities of power dependences are explained by the power-dependent repopulation between starting levels of UC.

Inflammatory bowel disease associations with HLA Class II genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castro, R.; Yang, H.; Targan, S.

1994-09-01

A PCR-SSOP assay has been used to analyze HLA-Class II DRB1 and DQB1 alleles in 378 Caucasians from a population in Southern California. The data has been analyzed separately for the Ashkenasi Jews and non-Jewish patients (n=286) and controls (n=92). Two common clinical forms of inflammatory bowel disease (IBD) have been studied: ulcerative colitis (UC) and Crohn`s disease (CD). In CD, we observed a susceptible effect with the rare DR1 allele - DRB*0103 [O.R.=4.56; 95% CI (0.96, 42.97); p=0.03]; a trend for an increase in DRB1*0103 was also observed in UC patients. A susceptible effect with DRB1*1502 [O.R.=5.20; 95% CImore » (1.10, 48.99); p=0.02] was observed in non-Jewish UC patients. This susceptible effect was restricted to UC ANCA-positive (antineutrophil cytoplasmic antibodies) patients. In addition, a significant association with DRB1*1101-DQB1*0301 [O.R.=9.46; 95% CI (1.30, 413.87); p=0.01] was seen with UC among non-Jewish patients: this haplotype was increased with CD among non-Jewish patients. Two protective haplotypes were detected among CD non-Jewish patients: DRB1*1301-DQB1*0603 [O.R.=0.34; 95% CI (0.09, 1.09); p=0.04], and DRB*0404-DQB1*0302 [O.R.=<0.08; 95% CI (0.0, 0.84); p=0.01]. When the same data were analyzed at the serology level, we observed a positive association in UC with DR2 [O.R.6.77; 95% CI (2.47, 22.95); p=2 x 10{sup -4}], and a positive association in CD with DR1 [O.R.=2.63; 95% CI (1.14, 6.62); p=0.01] consistent with previous reports. Thus, some IBD disease associations appear to be common to both UC and CD, while some are unique to one disease.« less

Online disease management of diabetes: engaging and motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.

PubMed

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-05-01

To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational 'nuggets' dispensed electronically by the care team. A1C was the primary outcome variable. Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12 months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204.

Online disease management of diabetes: Engaging and Motivating Patients Online With Enhanced Resources-Diabetes (EMPOWER-D), a randomized controlled trial

PubMed Central

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-01-01

Objective To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Materials and methods Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational ‘nuggets’ dispensed electronically by the care team. A1C was the primary outcome variable. Results Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (−1.32% INT vs −0.66% UC; p<0.001). At 12 months, the differences were not significant (−1.14% INT vs −0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). Conclusions A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204 PMID:23171659

Overweight and obesity in children with newly diagnosed inflammatory bowel disease.

PubMed

Pituch-Zdanowska, Aleksandra; Banaszkiewicz, Aleksandra; Dziekiewicz, Marcin; Łazowska-Przeorek, Izabella; Gawrońska, Agnieszka; Kowalska-Duplaga, Kinga; Iwańczak, Barbara; Klincewicz, Beata; Grzybowska-Chlebowczyk, Urszula; Walkowiak, Jarosław; Albrecht, Piotr

2016-03-01

Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as ≥85th BMI percentile and obesity as ≥95th BMI percentile. 675 patients were evaluated: 368 with Crohn's disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effectiveness of vitamin K2 on osteoporosis in adults with cerebral palsy.

PubMed

Kodama, Yuichi; Okamoto, Yasuhiro; Kubota, Tomohiro; Hiroyama, Yoshifumi; Fukami, Hiroshi; Matsushita, Kensuke; Kawano, Yoshifumi

2017-11-01

Osteoporosis can lead to spontaneous fractures in adults with cerebral palsy (CP). Undercarboxylated osteocalcin (ucOC) is a useful marker for vitamin K insufficiency in osteoporosis. The primary objective of this study was to determine the effect of vitamin K2 on bone mineral density (BMD) in adults with CP and vitamin K insufficiency. Sixteen adults, median age of 56years, with CP and osteoporosis in whom the serum ucOC concentration exceeded 4.5ng/mL were included. All patients received 45mg of vitamin K2 per day. BMD was measured and presented as a percentage of the young adult mean (%YAM). Serum levels of ucOC and BMD were measured at baseline and after 6 and 12months. Serum levels of ucOC decreased from 7.8ng/mL (range, 4.9-32) at baseline to 3.9ng/mL (range, 1.9-6.8) after 6months (P=0.001). BMD increased from 59%YAM (range, 45-67) at baseline to 68%YAM (range, 50-79) after 12months (P=0.003). Vitamin K2 had a positive effect on BMD in osteoporotic adults with CP and high serum concentrations of ucOC, and might be useful as a first line treatment for osteoporotic adults with CP and vitamin K insufficiency. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Small financial incentives increase smoking cessation in homeless smokers: a pilot study.

PubMed

Businelle, Michael S; Kendzor, Darla E; Kesh, Anshula; Cuate, Erica L; Poonawalla, Insiya B; Reitzel, Lorraine R; Okuyemi, Kolawole S; Wetter, David W

2014-03-01

Although over 70% of homeless individuals smoke, few studies have examined the effectiveness of smoking cessation interventions in this vulnerable population. The purpose of this pilot study was to compare the effectiveness of shelter-based smoking cessation clinic usual care (UC) to an adjunctive contingency management (CM) treatment that offered UC plus small financial incentives for smoking abstinence. Sixty-eight homeless individuals in Dallas, Texas (recruited in 2012) were assigned to UC (n=58) or UC plus financial incentives (CM; n=10) groups and were followed for 5 consecutive weeks (1 week pre-quit through 4 weeks post-quit). A generalized linear mixed model regression analysis was conducted to compare biochemically-verified abstinence rates between groups. An additional model examined the interaction between time and treatment group. The participants were primarily male (61.8%) and African American (58.8%), and were 49 years of age on average. There was a significant effect of treatment group on abstinence overall, and effects varied over time. Follow-up logistic regression analyses indicated that CM participants were significantly more likely than UC participants to be abstinent on the quit date (50% vs. 19% abstinent) and at 4 weeks post-quit (30% vs. 1.7% abstinent). Offering small financial incentives for smoking abstinence may be an effective way to facilitate smoking cessation in homeless individuals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy

PubMed Central

Dong, Huajiang; Li, Gang; Shang, Chongzhi; Yin, Huijuan; Luo, Yuechen; Meng, Huipeng; Li, Xiaohong; Wang, Yali; Lin, Ling; Zhao, Mingliang

2018-01-01

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy. PMID:29636880

Spectral management and morphology evolution of β-NaGdF4:Yb3+,Er3+ by tuning the concentration of citric acid

NASA Astrophysics Data System (ADS)

Yao, Lu; Xu, Dekang; Lin, Hao; Yang, Shenghong; Zhang, Yueli

2018-05-01

β-NaGdF4:Yb3+,Er3+ upconversion (UC) particles were prepared by a facile hydrothermal process with assistance of citric acid (CA). The morphologies of β-NaGdF4 UC particles were controlled by changing the doses of CA in precursor. With an increase CA concentration in precursor, increase sizes of crystals were observed, resulting in the increasing of luminescence intensity. The energy transfer ET mechanism was analyzed in detail.

[NEOCAT, surveillance network of catheter-related bloodstream infections in neonates: 2010 data].

PubMed

L'Hériteau, F; Lacavé, L; Leboucher, B; Decousser, J-W; De Chillaz, C; Astagneau, P; Aujard, Y

2012-09-01

The NEOCAT surveillance network was implemented in 2006 in order to address catheter-associated bloodstream infections (BSIs) in neonates. The results for 2010 surveillance are presented herein. Neonatal intensive care units (NICUs) participated in the study on a voluntary basis. Umbilical catheters (UCs) and central venous catheters (CVCs) were analyzed separately. In 2010, 26NICUs participated. Overall, 2953 neonates were included (median weight, 1550 g; median gestational age, 32 weeks). These neonates had 2551UCs (median insertion duration, 4 days) and 2147CVCs (median insertion duration, 12 days). Thirty-three BSIs associated with UCs were reported, yielding a 2.9/1000UC-day incidence density, 95% confidence interval (95%CI) (1.9-3.8). UC-associated BSIs appeared after a median period of 5 days after UC insertion. The main microorganism isolated from blood cultures was coagulase negative staphylococci (CNS, n=27), S. aureus (n=3), and Enterobacteriaceae (n=5). Three hundred and six CVC-associated BSIs were recorded, yielding a 11.2/1000 CVC-day incidence density (95%CI, 10.0-12.5). These BSIs occurred after a median period of 12 days after CVC insertion. The main microorganisms were CNS (83%), S. aureus (6%), and Enterobacteriaceae (5%). The NEOCAT network provides a useful benchmark for participating wards. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

NaLa(MoO{sub 4}){sub 2}: RE{sup 3+} (RE{sup 3+} = Eu{sup 3+}, Sm{sup 3+}, Er{sup 3+}/Yb{sup 3+}) microspheres: the synthesis and optical properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Zhiyi; Wang, Zhiying; Fu, Linlin

The strong green upconversion (UC) emission were observed in various Er{sup 3+}, Yb{sup 3+} co-doped NaLa(MoO{sub 4}){sub 2} samples synthesized via a hydrothermal route. The UC intensity depends on the dopant concentration, and the optimal UC emission was obtained in NaLa(MoO{sub 4}){sub 2}: 0.02Er{sup 3+}/0.10 Yb{sup 3+}. - Highlights: • The NaLa(MoO{sub 4}){sub 2} microspheres doped with Eu{sup 3+}, Sm{sup 3+} and Er{sup 3+}/Yb{sup 3+} were synthesized by a hydrothermal method. • The effects of the EDTA in the initial solution crystal phase and morphology were studied. • The down-conversion luminescence properties of NaLa(MoO{sub 4}){sub 2}: RE{sup 3+} (RE{sup 3+}more » = Eu{sup 3+}, Sm{sup 3+}) were investigated. • The UC luminescence properties and mechanism of Er{sup 3+}/Yb{sup 3+} co-doped NaLa(MoO{sub 4}){sub 2} was discussed. - Abstract: NaLa(MoO{sub 4}){sub 2}: RE{sup 3+} (RE{sup 3+} = Eu{sup 3+}, Sm{sup 3+}) microspheres have been synthesized at 180 °C via a facile EDTA-mediated hydrothermal route. X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), photoluminescence (PL) spectra were employed to characterize the samples. It was found that the amount of EDTA in the initial solution was responsible for crystal phase and shape determination. The effect of Eu{sup 3+} and Sm{sup 3+} doping concentrations on the luminescent intensity was also investigated in details. Furthermore, the up-conversion (UC) emissions have been observed in a series of Er{sup 3+}/Yb{sup 3+} co-doped NaLa(MoO{sub 4}){sub 2} samples. Concentration dependent studies revealed that the optimal composition was realized for a 2% Er{sup 3+} and 10% Yb{sup 3+}-doping concentration.« less

Carbohydrate Intake in the Etiology of Crohn's Disease and Ulcerative Colitis

PubMed Central

Luben, Robert; van Schaik, Fiona; Oldenburg, Bas; Bueno-de-Mesquita, H. Bas; Hallmans, Göran; Karling, Pontus; Lindgren, Stefan; Grip, Olof; Key, Timothy; Crowe, Francesca L.; Bergmann, Manuela M.; Overvad, Kim; Palli, Domenico; Masala, Giovanna; Khaw, Kay-Tee; Racine, Antoine; Carbonnel, Franck; Boutron-Ruault, Marie-Christine; Olsen, Anja; Tjonneland, Anne; Kaaks, Rudolf; Tumino, Rosario; Trichopoulou, Antonia; Hart, Andrew R.

2014-01-01

Background: Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). Methods: A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. Results: One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, Ptrend = 0.70; UC, Ptrend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, Ptrend = 0.50; UC, Ptrend = 0.71) or starch (CD, Ptrend = 0.69; UC, Ptrend = 0.17). Conclusions: The lack of associations with these nutrients is in agreement with many case–control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect. PMID:25265262

Carbohydrate intake in the etiology of Crohn's disease and ulcerative colitis.

PubMed

Chan, Simon S M; Luben, Robert; van Schaik, Fiona; Oldenburg, Bas; Bueno-de-Mesquita, H Bas; Hallmans, Göran; Karling, Pontus; Lindgren, Stefan; Grip, Olof; Key, Timothy; Crowe, Francesca L; Bergmann, Manuela M; Overvad, Kim; Palli, Domenico; Masala, Giovanna; Khaw, Kay-Tee; Racine, Antoine; Carbonnel, Franck; Boutron-Ruault, Marie-Christine; Olsen, Anja; Tjonneland, Anne; Kaaks, Rudolf; Tumino, Rosario; Trichopoulou, Antonia; Hart, Andrew R

2014-11-01

Diet may have a role in the etiology of inflammatory bowel disease. In previous studies, the associations between increased intakes of carbohydrates, sugar, starch, and inflammatory bowel disease are inconsistent. However, few prospective studies have investigated the associations between these macronutrients and incident Crohn's disease (CD) or ulcerative colitis (UC). A total of 401,326 men and women were recruited between 1991 and 1998. At recruitment, dietary intakes of carbohydrate, sugar, and starch were measured using validated food frequency questionnaires. The cohort was monitored identifying participants who developed incident CD or UC. Cases were matched with 4 controls, and odds ratios were calculated for quintiles of total carbohydrate, sugar, and starch intakes adjusted for total energy intake, body mass index, and smoking. One hundred ten participants developed CD, and 244 participants developed UC during follow-up. The adjusted odds ratio for the highest versus the lowest quintiles of total carbohydrate intake for CD was 0.87, 95% CI = 0.24 to 3.12 and for UC 1.46, 95% CI = 0.62 to 3.46, with no significant trends across quintiles for either (CD, P trend = 0.70; UC, P trend = 0.41). Similarly, no associations were observed with intakes of total sugar (CD, P trend = 0.50; UC, P trend = 0.71) or starch (CD, P trend = 0.69; UC, P trend = 0.17). The lack of associations with these nutrients is in agreement with many case-control studies that have not identified associations with CD or UC. As there is biological plausibility for how specific carbohydrates could have an etiological role in inflammatory bowel disease, future epidemiological work should assess individual carbohydrates, although there does not seem to be a macronutrient effect.

Albumin as a prognostic marker for ulcerative colitis

PubMed Central

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Trivedi, Chinmay; Yang, Yu-Xiao

2017-01-01

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis. PMID:29259376

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.

PubMed

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-10-27

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. © European Crohn’s and Colitis Organisation (ECCO) 2017.

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis

PubMed Central

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-01-01

Abstract Background and Aims Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Methods Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Results Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Conclusions Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. PMID:28981629

Medical resource utilization and associated costs in patients with ulcerative colitis in the UK: a chart review analysis.

PubMed

Bodger, Keith; Yen, Linnette; Szende, Agota; Sharma, Gunjan; Chen, Yaozhu J; McDermott, John; Hodgkins, Paul

2014-02-01

Limited evidence is available on the economic burden of ulcerative colitis (UC) in the UK, particularly relating to the impact of relapse frequency on direct medical costs. This study identifies and assesses medical resource utilization (MRU) and associated direct costs in mild and moderate UC patients in the UK. A retrospective chart review of patients with mild-to-moderate UC diagnosed at least 1 year before the study was performed. From 33 general practitioner (GP) and 34 gastroenterologist sites, charts of the last three UC patients fulfilling the inclusion criteria were reviewed. Descriptive statistics were calculated for MRU and 2011 costs (GB£) by number of relapses. The study population included 201 patients with a mean age of 39.9 years; 44% were women and the mean disease duration was 7.4 years. UC-related costs of each MRU category increased with the number of relapses. Comparing patients without relapse with those with more than two relapses, the mean annual UC-related costs were £14 versus £2556 for hospitalizations; £218 versus £988 for visits (including nurse, GP, specialist, and other visits); £21 versus £1303 for procedures; £17 versus £188 for diagnostics; and £1168 versus £6660 for all-cause total costs. Age, sex, and site of data reporting (GP vs. gastroenterologist) were not associated with MRU or costs. Patients with mild-to-moderate UC incurred considerable costs that increased markedly with the number of relapses. These findings support the importance of maintenance therapies in UC that reduce or prevent relapses. Quantifying the relationship between relapse rate and costs will inform future health economic studies.

Ulcerative colitis in a multiracial Asian country: Racial differences and clinical presentation among Malaysian patients

PubMed Central

Tan, Yan-Mei; Goh, Khean-Lee

2005-01-01

AIM: TO determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. METHODS: Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. RESULTS: There were 45 confirmed cases of UC, of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0 ± 10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; c2 = 15.45,P < 0.001) and 3.06 (CI = 1.24-7.78; c2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; c2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). CONCLUSION: UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease. PMID:16270398

Thermochronology of the Cornubian batholith in southwest England: Implications for pluton emplacement and protracted hydrothermal mineralization

USGS Publications Warehouse

Chesley, J.T.; Halliday, A.N.; Snee, L.W.; Mezger, K.; Shepherd, T.J.; Scrivener, R.C.

1993-01-01

The metalliferous ore deposits of southwest England are associated with biotite-muscovite granites that intruded upper Paleozoic sediments and volcanic rocks at the end of the Hercynian Orogeny. The hydrothermal mineralization can be subdivided into four stages: 1. (1) exoskarns 2. (2) high-temperature tin and tungsten oxide-bearing sheeted greisen bordered veins and Sn-bearing tourmaline veins and breccias 3. (3) polymetallic quartz-tourmaline-chlorite-sulfide-fluorite-bearing fissure veins, which represent the main episode of economic mineralization 4. (4) late-stage, low-temperature polymetallic fluorite veins. U-Pb dating of monazite and xenotime and 40Ar 39Ar dating of muscovite were used to determine emplacement ages and cooling times for individual plutons within the Cornubian batholith, as well as separate intrusive phases within the plutons. In addition, 40Ar 39Ar ages from hornblende and secondary muscovite and Sm-Nd isochron ages from fluorite were employed to determine the relationship between pluton emplacement and different stages of mineralization. The U-Pb ages indicate that granite magmatism was protracted from ~300 Ma down to ~275 Ma with no evidence of a major hiatus. There is no systematic relation between the age of a pluton and its location within the batholith. The U-Pb ages for separate granite phases within a single pluton are resolvable and indicate that magma emplacement within individual plutons occurred over periods of as much as 4.5 myrs. Felsic porphyry dike emplacement was coeval with plutonism, but continued to ~270 Ma. The geochronologic data suggest that the Cornubian batholith originated from repeated melting events over 30 myrs and was formed by a series of small coalescing granitic bodies. Cooling rates of the main plutons are unrelated to emplacement age, but decrease from the southwest to the northeast from ~210??C myr-1 to ~60??C myr-1 with a mean of 100??C myr-1. These slow cooling rates appear to reflect the addition of heat from multiple intrusive episodes. The mineralization history is distinct for each pluton and ranges from coeval with, to up to 40 myrs younger than the cooling age for the host pluton. Stage 2 mineralization is broadly synchronous with the emplacement of granite magmas, is dominated by fluids expelled during crystallization, and may be repeated by the emplacement of younger magmas within the same pluton. Sm-Nd isochrons for fluorite from stage 3 polymetallic mineralization give ages of 259 ?? 7, 266 ?? 3 and 267 ?? 12 Ma, postdating stage 2 mineralization by up to 25 myrs within the same deposit. The similarity in age of the main polymetallic mineralization hosted by the oldest and youngest plutons, suggests that this stage of mineralization is unlikely to be related to hydrothermal circulation driven by the emplacement and cooling of the host granite. The mineralization is more likely the product of regional hydrothermal circulation driven by heat from the emplacement and crystallization of younger buried pulses of magma. ?? 1993.

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.

PubMed

Martinez-Chamorro, A; Moreno, A; Gómez-García, M; Cabello, M J; Martin, J; Lopez-Nevot, M Á

2016-06-01

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found. © 2016 British Society for Immunology.

Time to Remission for Depression with Collaborative Care Management (CCM) in Primary Care.

PubMed

Garrison, Gregory M; Angstman, Kurt B; O'Connor, Stephen S; Williams, Mark D; Lineberry, Timothy W

2016-01-01

Collaborative care management (CCM) has been shown to have superior outcomes to usual care (UC) for depressed patients with a fixed end point. This study was a survival analysis over time comparing CCM with UC using remission (9-item Patient Health Questionnaire [PHQ-9] score <5) and persistent depressive symptoms (PDSs; PHQ-9 score ≥10) as end points. A retrospective cohort study of 7340 patients with depression cared for at 4 outpatient primary care clinics was conducted from March 2008 through June 2013. All adult patients diagnosed with depression (International Classification of Diseases, 9th Revision [ICD-9], codes 296.2-3) or dysthymia (ICD-9 code 300.4) with an initial PHQ-9 score ≥10 were included. CCM was implemented at all clinics between 2008 and 2010. Kaplan-Meyer survival curves for time to remission and PDSs were plotted. A Cox proportional hazards model was used to adjust for expected differences between patients choosing CCM versus UC. Median time to remission was 86 days (95% confidence interval [CI], 81-91 days) for the CCM group versus 614 days (95% CI, 565-692 days) for the UC group. Likewise, median duration of PDSs was 31 days (95% CI, 30-33 days) for the CCM group versus 154 days (95% CI, 138-182 days) for the UC group. In the Cox proportional hazards model, which controlled for covariates such as age, sex, race, diagnosis, and initial PHQ-9 score, CCM was associated with faster remission (hazard ratio of the CCM group [HRCCM], 2.48; 95% CI, 2.31-2.65). This study demonstrated that patients enrolled in CCM have a faster rate of remission and a shorter duration of PDSs than patients choosing UC. © Copyright 2016 by the American Board of Family Medicine.

Evaluation of the Role of Umbilical Cord Serum and Autologous Serum Therapy in Reepithelialization After Keratoplasty: A Randomized Controlled Clinical Trial.

PubMed

Kamble, Neha; Sharma, Namrata; Maharana, Prafulla K; Bandivadekar, Pooja; Nagpal, Ritu; Agarwal, Tushar; Velpandian, Thirumurthy; Mittal, Suneeta; Vajpayee, Rasik B

2017-09-01

To evaluate the role of umbilical cord serum (UCS) and autologous serum (AS) therapy in reepithelialization of corneal graft after keratoplasty in a randomized controlled trial. A total of 105 eyes with epithelial defect (ED) after keratoplasty (penetrating keratoplasty-67 and anterior lamellar keratoplasty-38) on the first postoperative day were included in the study. The eyes were randomized into three groups: UCS (n=35), AS (n=35), and artificial tears (AT) (n=35). All patients received standard postoperative medical therapy. The primary outcome measure was time to epithelialization, and secondary outcome measures were best-corrected visual acuity and graft clarity. The ED healed completely in 103 eyes. The mean time for complete reepithelialization was 2.5±2.1, 3.1±2.2, and 4.5±1.4 days in UCS, AS, and AT groups, respectively. The mean percentage decrease in the size of the ED was significantly better in the UCS and AS groups as compared with the AT group (P=0.001). The rate of reepithelialization was comparable between the AS and UCS groups (P=0.3). On bivariate analysis, significant correlation was found between the mean size of postoperative ED, grade of the donor cornea (P=0.001), and the presence of preoperative ED (P=0.001). No complications were associated with the use of serum therapy. Most of the cases of postkeratoplasty corneal ED can be managed with AT only. The serum therapy (AS/UCS) helps in the faster reepithelialization of postkeratoplasty ED as compared with AT and may be considered as a treatment option for early epithelial healing.

Maintenance therapy options for ulcerative colitis.

PubMed

Chaparro, María; Gisbert, Javier P

2016-07-01

Medical therapy is the cornerstone of the management of ulcerative colitis (UC) and the goal of the treatment is the induction and maintenance of remission. Mesalamine is the first line treatment in patients with mild to moderate UC. Despite having different formulations available, clinically significant differences in pharmacokinetics and exposure to these drugs have not been observed. Evidence supporting the efficacy of azathioprine and mercaptopurine for maintaining remission is UC patients come from both observational cohorts and clinical trials. The main limitation of the treatment with thiopurines is the onset of adverse events that occur in over one-third of patients. Infliximab, adalimumab and golimumab are anti-TNF drugs, which are generally used for more severe or refractory cases. Finally, vedolizumab, a drug directed against the integrins α4β7 has been shown to be effective for the induction and maintenance of remission in moderate-to-severe UC patients. Several new drugs have enriched the therapeutic armamentarium of UC. Whether the administration of biologics earlier on in the course of the disease would have an impact on the natural history of the disease, avoiding the need for colectomy, remains unknown.

The helium flux from the continents and ubiquity of low-3He/4He recycled crust and lithosphere

NASA Astrophysics Data System (ADS)

Day, James M. D.; Barry, Peter H.; Hilton, David R.; Burgess, Ray; Pearson, D. Graham; Taylor, Lawrence A.

2015-03-01

New helium isotope and trace-element abundance data are reported for pyroxenites and eclogites from South Africa, Siberia, and the Beni Bousera Massif, Morocco that are widely interpreted to form from recycled oceanic crustal protoliths. The first He isotope data are also presented for Archaean peridotites from the Kaapvaal (South Africa), Slave (Canada), and Siberian cratons, along with recently emplaced off-craton peridotite xenoliths from Kilbourne Hole, San Carlos (USA) and Vitim (Siberia), to complement existing 3He/4He values obtained for continental and oceanic peridotites. Helium isotope compositions of peridotite xenoliths vary from 7.3 to 9.6 RA in recently (<10 kyr) emplaced xenoliths, to 0.05 RA in olivine from cratonic peridotite xenoliths of the 1179 Ma Premier kimberlite, South Africa. The helium isotope compositions of the peridotites can be explained through progressive sampling of 4He produced from radiogenic decay of U and Th in the mineral lattice in the older emplaced peridotite xenoliths. Ingrowth of 4He is consistent with generally higher 4He concentrations measured in olivine from older emplaced peridotite xenoliths relative to those from younger peridotite xenoliths. Collectively, the new data are consistent with pervasive open-system behaviour of He in peridotite xenoliths from cratons, mobile belts and tectonically-active regions. However, there is probable bias in the estimate of the helium isotope composition of the continental lithospheric mantle (6.1 ± 2.1 RA), since previously published databases were largely derived from peridotite xenoliths from non-cratonic lithosphere, or phenocrysts/xenocrysts obtained within continental intraplate alkaline volcanics that contain a contribution from asthenospheric sources. Using the new He isotope data for cratonic peridotites and assuming that significant portions (>50%) of the Archaean and Proterozoic continental lithospheric mantle are stable and unaffected by melt or fluid infiltration on geological timescales (>0.1 Ga), and that U and Th contents vary between cratonic lithosphere and non-cratonic lithosphere, calculations yield a 3He flux of 0.25-2.2 atoms/s/cm2 for the continental lithospheric mantle. These estimates differ by a factor of ten from non-cratonic lithospheric mantle and are closer to the observed 3He flux from the continents (<1 atoms/s/cm2). Pyroxenites and eclogites from the continental regions are all characterized by 3He/4He (0.03-5.6 RA) less than the depleted upper mantle, and relatively high U and Th contents. Together with oceanic and continental lithospheric peridotites, these materials represent reservoirs with low time-integrated 3He/(U + Th) in the mantle. Pyroxenites and eclogites are also characterized by higher Fe/Mg, more radiogenic Os-Pb isotope compositions, and more variable δ18O values (∼3‰ to 7‰), compared with peridotitic mantle. These xenoliths are widely interpreted to be the metamorphic/metasomatic equivalents of recycled oceanic crustal protoliths. The low-3He/4He values of these reservoirs and their distinctive compositions make them probable end-members to explain the compositions of some low-3He/4He OIB, and provide an explanation for the low-3He/4He measured in most HIMU lavas. Continental lithospheric mantle and recycled oceanic crust protoliths are not reservoirs for high-3He/4He and so alternative, volumetrically significant, He-rich reservoirs, such as less-degassed (lower?) mantle, are required to explain high-3He/4He signatures measured in some intraplate lavas. Recycling of oceanic crust represents a fundamental process for the generation of radiogenic noble gases in the mantle, and can therefore be used effectively as tracers for volatile recycling.

Costs of ulcerative colitis from a societal perspective in a regional health care area in Spain: A database study.

PubMed

Aldeguer, Xavier; Sicras-Mainar, Antoni

2016-01-01

To estimate the management of UC associated costs from the societal perspective in Spain. Observational, longitudinal study with retrospective data collection based on reviews of outpatient health records. Socio-demographic, clinical and sick leave information was gathered. Patients diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a minimum of 12 months post diagnosis, with at least two clinical and use of resources data recorded, were included. 285 UC patients [51.2% men; 44.5 (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6 (2.5) years disease follow-up] participated. More than half (65.6%) were active workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70) times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC-related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct and indirect annual cost per UC patient were €1754.10 (95%CI: 1473.37-2034.83) and €399.32 (282.31-422.69), respectively. Absenteeism was estimated at €88.21(32.72-50.06) per patient per year, in which sick-leaves were the main component of indirect costs (88.2%). Age, UC family history, diarrhea at diagnosis, blood and blood-forming organs diseases and psychological disorders were the main predictors of indirect costs. UC is a costly disease for the society and the Spanish National Healthcare System. Indirect costs imply a major burden by affecting the most productive years of patients. Further research is needed considering all components of productivity loss, including presenteeism-associated costs. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis.

PubMed

Lu, Xiaohong; Yu, Yuanjie; Tan, Shiyun

2017-10-25

Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians. p53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

CAMPARE and Cal-Bridge: Two Institutional Networks Increasing Diversity in Astronomy

NASA Astrophysics Data System (ADS)

Rudolph, Alexander L.; Smecker-Hane, Tammy A.

2017-01-01

We describe two programs, CAMPARE and Cal-Bridge, with the common mission of increasing participation of groups traditionally underrepresented in astronomy, through summer research opportunities, in the case of CAMPARE, scholarships in the case of Cal-Bridge, and significant mentoring in both programs, creating a national impact on their numbers successfully pursuing a PhD in the field.In 7 years, the CAMPARE program has sent 80 students, >80% from underrepresented groups, to conduct summer research at one of 14 major research institutions throughout the country. The graduation rate among CAMPARE scholars is 98%, and of the CAMPARE scholars who have graduated with a Bachelor’s degree, more than 60% have completed or are pursuing graduate education in astronomy or a related field, at institutions including UCLA, UC Riverside, UC Irvine, UC Santa Barbara, USC, Stanford, Univ. of Arizona, Univ. of Washington, and the Fisk-Vanderbilt Master’s-to-PhD program.Now entering its third year, the Cal-Bridge program is a CSU-UC Bridge program comprised of over 75 physics and astronomy faculty from 5 University of California (UC), 9 California State University (CSU), and 14 California Community College (CCC) campuses in Southern California. In the first three years, 22 Cal-Bridge Scholars have been selected, including 11 Hispanic, 3 African-American and 8 female students, 5 of whom are from URM groups. Nineteen (19) of the 22 Cal-Bridge Scholars are first-generation college students. The entire first cohort of 4 Cal-Bridge scholars was accepted to one or more PhD programs in astronomy or physics, including UC Irvine, UC Santa Cruz, UC Davis, Michigan State, and Georgia State Universities. The second cohort of 8 Cal-Bridge scholars is applying to graduate schools this fall.Cal-Bridge provides much deeper mentoring and professional development experiences over the last two years of undergraduate and first year of graduate school to students from this diverse network of higher education institutions. Cal-Bridge Scholars benefit from substantial financial support, intensive, joint mentoring by CSU and UC faculty, professional development workshops, and exposure to research opportunities at the participating UC campuses.

Rapid response to vedolizumab therapy in biologic-naïve patients with inflammatory bowel diseases.

PubMed

Feagan, Brian G; Lasch, Karen; Lissoos, Trevor; Cao, Charlie; Wojtowicz, Abigail M; Khalid, Javaria Mona; Colombel, Jean-Frédéric

2018-05-29

Vedolizumab, a humanized monoclonal antibody against α4β7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists. We performed a post-hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (n=374) or CD (n=784). We collected data on patient-reported symptoms (rectal bleeding and stool frequency for patients with UC, abdominal pain and loose stool frequency for patients with CD) reported at weeks 2, 4, and 6 of treatment. We reported mean percentage score changes from baseline and proportions of patients who achieved predefined scores. We performed multivariate logistic regression analysis to identify factors associated with an early response (at week 2). In patients with UC (overall or naïve to TNF antagonist therapy), a significantly greater percentage of patients given vedolizumab achieved the predefined composite symptom score at weeks 2, 4, and 6 compared to those given placebo. In patients with CD who were naïve to TNF antagonists, a significantly greater percentage of patients given vedolizumab achieved the predefined score at weeks 2 and 4 compared to those given placebo. Among patients with UC given vedolizumab, 19.1% (overall) and 22.3% (TNF antagonist naïve) achieved a composite score of rectal bleeding of 0 and stool frequency ≤1 at week 2 compared to 10% (overall) and 6.6% (TNF antagonist naïve) of those receiving placebo. Among TNF antagonist-naïve patients with CD, 15.0% of those given vedolizumab achieved an average daily composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 (compared to 7.9% given placebo), and 23.8% of those given vedolizumab achieved these by week 4 (compared to 10.3% given placebo). In a post-hoc analysis of data from phase 3 clinical trials, vedolizumab significantly improved patient-reported symptoms of UC and CD as early as week 2 of treatment, continuing through the first 6 weeks-especially when given as first-line biologic therapy. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

A case of pyoderma gangrenosum with ulcerative colitis treated with mesalazine.

PubMed

Lee, Jae In; Park, Hyun Jeong; Lee, Jun Young; Cho, Baik Kee

2010-11-01

Pyoderma gangrenosum (PG) manifests as recurrent deep ulceration of the skin and PG is associated with a variety of disorders. Approximately 30% of the cases of PG develop in patients with inflammatory bowel disease. A 34-year-old woman presented with a one-week history of recurrent ulcers on the right cheek and back. She was diagnosed with ulcerative colitis (UC) 4 years previously and with PG 1 year previously. The clinical course of the skin lesions followed the status of her UC. The patient's skin lesions and bowel symptoms were not improved with prednisolone. After she was started on mesalazine, we observed rapid resolution of skin lesions and bowel symptoms. Herein, we report a case of recurrent PG with UC, and we discuss the possible association between these two conditions, and the efficacy of mesalazine therapy for the treatment of PG combined with UC.

Specific immunotherapy ameliorates ulcerative colitis.

PubMed

Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

2016-01-01

Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course.

PubMed

Paul, S; Boschetti, G; Rinaudo-Gaujous, M; Moreau, A; Del Tedesco, E; Bonneau, J; Presles, E; Mounsef, F; Clavel, L; Genin, C; Flourié, B; Phelip, J-M; Nancey, S; Roblin, X

2015-06-01

The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51U/ml] and anti-laminarin [> 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77U/ml [OR = 4.3; p = 0.002], ASCA > 63U/ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52U/ml [OR = 3.4; p = 0.04] and ACCA > 25U/ml [OR = 3.0; p < 0.04]. Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Smoking, breastfeeding, physical inactivity, contact with animals, and size of the family influence the risk of inflammatory bowel disease: A Slovak case-control study.

PubMed

Hlavaty, Tibor; Toth, Jozef; Koller, Tomas; Krajcovicova, Anna; Oravcova, Stanislava; Zelinkova, Zuzana; Huorka, Martin

2013-04-01

The aetiology of inflammatory bowel disease (IBD) is not known but is likely to involve a combination of genetic predisposition and environmental risk factors. Smoking has been associated consistently with a higher risk of Crohn's disease (CD), while appendectomy and smoking appear to diminish the risk of ulcerative colitis (UC). The roles of other environmental factors are unclear. The aim of the present study was to evaluate the association of CD and UC with several environmental risk factors. This case-control study included 338 patients (190 CD, 148 UC) and 355 controls. All subjects completed a detailed questionnaire regarding breastfeeding duration, history of helminthic infections, allergic diseases, appendectomy, household size, housing type, contact with specific domestic animals, physical activity, and smoking. Associations between risk factors and CD and UC were investigated by univariate and multivariate analysis. On multivariate analysis, CD associated with smoking at diagnosis (odds ratio, OR, 3.7, 95% CI 2.2-6.2; p < 0.001), being breastfed for <6 months (OR 2.7, 95% CI 1.7-4.4; p < 0.001), and less than two childhood sporting activities weekly (OR 2.7, 95% CI 1.5-5.0; p < 0.001) and inversely associated with frequent contact with cats in childhood (OR 0.6, 95% CI 0.4-0.9; p < 0.03). UC associated with less than two sporting weekly activities in childhood (OR 2.0, 95% CI 1.1-3.5, p = 0.02), fewer household members in childhood (OR 0.8, 95% CI 0.7-0.98, p = 0.03), and being breastfed for <6 months (OR 1.7, 95% CI 1.02-2.8, p = 0.04). A composite environmental risk index for CD revealed that 47 and 14% of the controls and patients with CD had no risk factors, respectively, and that 14 and 38% of the controls and patients with CD had at least two risk factors, respectively. CD and UC associated with infrequent childhood sports activities and short breastfeeding. Furthermore, CD associated with smoking and infrequent contact with animals in childhood. UC associated with a smaller family size in childhood.

Department of the Air Force Supporting Data for Fiscal Year 1995 Research, Development, Test and Evaluation Descriptive Summaries

DTIC Science & Technology

1994-02-01

c CLIOU 0 V ONj 00 . ca % 4 .) en 4...AD-A279 096 oci 00 o Io lef 1-4 00 .00 >~-4 C ) .tU E4.~ -4; ’.) .0 4-- -. Eu ca--- CU. >0 LU .e >. 060 U.U> m W CA *0E c00 &MU)%~ z ~0 0 U co o w) 0...0O o E~ ’= C E . M u-L od \\cu~ CU-L 4w) uC~ >0 oo CQ O 0 t ~ C /) ~ C MI 0 U *-’-’ cu. Cu~ 0%oU .E O 4uC). 0 0cl .20 0ý 0uU (U ~ U) toU 00 -Z 0 a 0

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.

PubMed

Brar, Jaspreet S; Ganguli, Rohan; Pandina, Gahan; Turkoz, Ibrahim; Berry, Sally; Mahmoud, Ramy

2005-02-01

Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Vedolizumab: an α4β7 integrin antagonist for ulcerative colitis and Crohn’s disease

PubMed Central

Cherry, Lauren N.; Yunker, Nancy S.; Lambert, Erika R.; Vaughan, DaleMarie

2015-01-01

Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted. PMID:26336591

Role of Tetrasomy for the Diagnosis of Urothelial Carcinoma Using UroVysion Fluorescent In Situ Hybridization.

PubMed

Zhou, Amy G; Liu, Yuxin; Cyr, Maryann St; Garver, Joanne; Woda, Bruce A; Cosar, Ediz F; Hutchinson, Lloyd M

2016-06-01

-UroVysion fluorescent in situ hybridization (FISH) is routinely used to detect urothelial carcinoma (UC). A positive threshold is defined as chromosome polysomy in 4 or more cells, which also includes tetrasomy, a natural product of cell division. -To evaluate tetrasomy for UC detection and explore the relation to the surgical diagnosis or patient history. -The FISH was performed on 1532 urine samples from patients with cytology results and 4 or more years of follow-up. We created separate polysomy and tetrasomy categories and constructed receiver operating curves to determine appropriate thresholds using biopsy (n = 194) as the gold standard. Standard FISH and a novel assay integrating cytomorphology and FISH (Target-FISH) were compared. Matching tissue biopsies of urine samples with 10 or more tetrasomy cells were analyzed. -No significant threshold was found for tetrasomy cells. Exclusion of tetrasomy from the polysomy category changed the threshold from 8.5 to 4.5 cells, increased specificity (59.2% to 78.9%), but reduced sensitivity (78.9% to 65.9%). In Target-FISH, the same approach yielded a specificity of 93.7% and sensitivity of 65.2%. Similarly, specificity improved significantly for low- and high-grade UC, but sensitivity decreased for low-grade UC. No evidence of UC was observed in 95% (52 of 55) of the patients referred for screening who had 10 or more tetrasomy cells by FISH. Matching biopsies for urines containing 10 or more tetrasomy cells showed few or no tetrasomy cells. -Tetrasomy is a nonspecific finding frequently encountered in urine FISH and should be excluded from the polysomy classification. Target-FISH is an optimal approach, offering the ability to detect rare tetrasomy tumors.

Ultrasound contrast and real-time perfusion in conjunction with supine bicycle stress echocardiography for comprehensive evaluation of surgically corrected congenital heart disease.

PubMed

Kutty, Shelby; Olson, Joan; Danford, Christopher J; Sandene, Erin K; Xie, Feng; Fletcher, Scott E; Erickson, Christopher C; Kugler, John D; Danford, David A; Porter, Thomas R

2012-06-01

We sought to evaluate the efficacy of ultrasound contrast (UC) and low mechanical index real-time perfusion (RTP) in the haemodynamic and anatomic assessment of repaired congenital heart disease (CHD) at rest and during supine bicycle stress echocardiography (BSE). Patients with CHD (n = 51, median age 21.5 years) were prospectively studied. All had compromised image quality, 20 (39%) had arrhythmias, and 10 (20%) had pacemakers. RTP was performed at rest and during BSE using Definity and Contrast Pulse Sequencing, with assessment of Doppler pressure gradients. Diagnoses included tetralogy of Fallot (n = 27), transposition of the great arteries (TGA) atrial switch (n = 10), TGA arterial switch (n = 2), aortic valve disease (n = 4), Fontan (n = 4), and Kawasaki disease (n = 4). UC with RTP improved endocardial border definition, with increased number of left ventricular (LV) and right ventricular (RV) segments visualized at rest (P < 0.0001) and during stress. LV ejection fraction (EF) and RV fractional area change (FAC) were measurable at rest and peak stress, RV FAC correlating closely with same-day magnetic resonance EFs (r = 0.72; P < 0.001). UC enhanced Doppler signals, enabling subpulmonary ventricular systolic pressure measurements at rest and stress. In six patients, marked elevations of subpulmonary ventricular systolic pressure were detected with UC during BSE, and quantifiable ventricular dysfunction. No adverse events occurred, other than transient low back pain in one patient. UC at rest and with supine BSE enables safe and comprehensive assessment of anatomy, haemodynamics, and biventricular functional and perfusion reserve in adolescents and young adults with surgically modified CHD.

Development of a UC781 releasing polyethylene vinyl acetate vaginal ring.

PubMed

McConville, Christopher; Major, Ian; Friend, David R; Clark, Meredith R; Malcolm, R Karl

2012-12-01

UC781 is potent, hydrophobic, non-nucleotide reverse transcriptase inhibitor (NNRTI) against the human immunodeficiency virus (HIV). UC781 is currently being investigated for use as a potential HIV microbicide. A study in rhesus macaques demonstrated that a 100-mg UC781-loaded silicone elastomer vaginal ring released limited amounts of UC781 into the vaginal fluid and tissue after 28 days. The reason for this was due to the hydrophobic nature and limited aqueous solubility of UC781. This study describes the manufacture of UC781-loaded polyethylene vinyl acetate (PEVA) vaginal rings, which have an improved in vitro release rate of UC781 when compared to UC781-loaded silicone elastomer vaginal rings. The study demonstrates that the UC781 in the PEVA rings is mostly in its amorphous form due to the rings being manufactured above UC781's melting point. Furthermore, the rings do not show any signs of UC781 degradation, such as the presence of UC22.

What Made Berkeley Great? The Sources of Berkeley's Sustained Academic Excellence. Research & Occasional Paper Series CSHE.3.11

ERIC Educational Resources Information Center

Breslauer, George W.

2011-01-01

University of California (UC) Berkeley's chief academic officer explores the historical sources of Berkeley' academic excellence. He identifies five key factors: (1) wealth from many sources; (2) supportive and skilled governors; (3) leadership from key UC presidents; (4) the pioneering ethos within the State of California; and (5) a process of…

77 FR 58150 - Rene Casanova, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... matter of statutory interpretation logically encompass the factors listed in Sec. 824(a).'' ALJ at 32- 33... usual course of professional practice.'' (ALJ Ex. 1 at 2.) In particular, the OSC alleged that in... greater detail its allegations related to the visits by UC1 and UC2 (e.g., ALJ Ex. 4 at 6-16; ALJ Ex. 7 at...

Interleukin-17 immunity in pediatric Crohn disease and ulcerative colitis.

PubMed

Hölttä, Veera; Klemetti, Paula; Salo, Harri M; Koivusalo, Antti; Pakarinen, Mikko; Westerholm-Ormio, Mia; Kolho, Kaija-Leena; Vaarala, Outi

2013-09-01

The present understanding of inflammatory bowel disease pathogenesis mainly relies on studies of adult patients. Therefore, we studied the balance between T-effector and regulatory cells in pediatric inflammatory bowel disease. Quantitative polymerase chain reaction and immunohistochemistry served to quantify the expression of immunological markers in mucosal biopsies and flow cytometry analysis was used in peripheral blood mononuclear cells. Colonic interleukin (IL)-17+, IL-22, and IL-6 mRNA upregulation and increase in the number of colonic IL-17 cells were demonstrated in both Crohn disease (CD) and ulcerative colitis (UC). Likewise, colonic forkhead box P3 (FOXP3+) mRNA expression and the number of colonic FOXP3 cells were increased both in CD and in UC and were accompanied in CD also with increased numbers of FOXP3+CD25 High CD4 cells in peripheral blood. Ileal relation of IL-17/CD4 cells was increased only in CD. We showed activation of colonic IL-17/IL-22 axis and upregulation of FOXP3 to occur both in pediatric CD and in UC, indicating shared immunological characteristics. Upregulation of IL-17 was restricted to colon in UC, but existed in the ileum and in the colon in active CD.

Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.

PubMed

Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Tian, Hongliang; Ding, Chao; Gu, Lili; Li, Ning; Li, Jieshou

2016-11-03

Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. Current Controlled Trial NCT02016469 . Registered 10 November 2013.

Umbilical Cord Tissue-Derived Mesenchymal Stem Cells Induce T Lymphocyte Apoptosis and Cell Cycle Arrest by Expression of Indoleamine 2, 3-Dioxygenase

PubMed Central

Li, Xiuying; Xu, Zhuo; Bai, Jinping; Yang, Shuyuan; Zhao, Shuli; Zhang, Yingjie; Chen, Xiaodong

2016-01-01

It has been reported that human mesenchymal stem cells are able to inhibit T lymphocyte activation; however, the discrepancy among different sources of MSCs is not well documented. In this study, we have compared the MSCs from bone marrow (BM), adipose tissue (AT), placenta (PL), and umbilical cord (UC) to determine which one displayed the most efficient immunosuppressive effects on phytohemagglutinin-induced T cell proliferation. Among them we found that hUC-MSC has the strongest effects on inhibiting T cell proliferation and is chosen to do the further study. We observed that T lymphocyte spontaneously released abundant IFN-γ. And IFN-γ secreted by T lymphocyte could induce the expression of indoleamine 2, 3-dioxygenase (IDO) in hUC-MSCs. IDO was previously reported to induce T lymphocyte apoptosis and cell cycle arrest in S phase. When cocultured with hUC-MSCs, T lymphocyte expression of caspase 3 was significantly increased, while Bcl2 and CDK4 mRNA expression decreased dramatically. Addition of 1-methyl tryptophan (1-MT), an IDO inhibitor, restored T lymphocyte proliferation, reduced apoptosis, and induced resumption of the cell cycle. In addition, the changes in caspase 3, CDK4, and Bcl2 expression were reversed by 1-MT. These findings demonstrate that hUC-MSCs induce T lymphocyte apoptosis and cell cycle arrest by expressing abundant IDO and provide an explanation for some of the immunomodulatory effects of MSCs. PMID:27418932

A lunar/Martian anchor emplacement system

NASA Astrophysics Data System (ADS)

Clinton, Dustin; Holt, Andrew; Jantz, Erik; Kaufman, Teresa; Martin, James; Weber, Reed

On the Moon or Mars, it is necessary to have an anchor, or a stable, fixed point able to support the forces necessary to rescue a stuck vehicle, act as a stake for a tent in a Martian gale, act as a fulcrum in the erection of general construction poles, or support tent-like regolith shields. The anchor emplacement system must be highly autonomous. It must supply the energy and stability for anchor deployment. The goal of the anchor emplacement system project is to design and build a prototype anchor and to design a conceptual anchor emplacement system. Various anchors were tested in a 1.3 cubic meter test bed containing decomposed granite. A simulated lunar soil was created by adjusting the moisture and compaction characteristics of the soil. We conducted tests on emplacement torque, amount of force the anchor could withstand before failure, anchor pull out force at various angles, and soil disturbances caused by placing the anchor. A single helix auger anchor performed best in this test bed based on energy to emplace, and the ultimate holding capacity. The anchor was optimized for ultimate holding capacity, minimum emplacement torque, and minimum soil disturbance in sandy soils yielding the following dimensions: helix diameter (4.45 cm), pitch (1.27 cm), blade thickness (0.15 cm), total length (35.56 cm), shaft diameter (0.78 cm), and a weight of 212.62 g. The experimental results showed that smaller diameter, single-helix augers held more force than larger diameter augers for a given depth. The emplacement system consists of a flywheel and a motor for power, sealed in a protective box supported by four legs. The flywheel system was chosen over a gear system based on its increased reliability in the lunar environment.

A lunar/Martian anchor emplacement system

NASA Technical Reports Server (NTRS)

Clinton, Dustin; Holt, Andrew; Jantz, Erik; Kaufman, Teresa; Martin, James; Weber, Reed

1993-01-01

On the Moon or Mars, it is necessary to have an anchor, or a stable, fixed point able to support the forces necessary to rescue a stuck vehicle, act as a stake for a tent in a Martian gale, act as a fulcrum in the erection of general construction poles, or support tent-like regolith shields. The anchor emplacement system must be highly autonomous. It must supply the energy and stability for anchor deployment. The goal of the anchor emplacement system project is to design and build a prototype anchor and to design a conceptual anchor emplacement system. Various anchors were tested in a 1.3 cubic meter test bed containing decomposed granite. A simulated lunar soil was created by adjusting the moisture and compaction characteristics of the soil. We conducted tests on emplacement torque, amount of force the anchor could withstand before failure, anchor pull out force at various angles, and soil disturbances caused by placing the anchor. A single helix auger anchor performed best in this test bed based on energy to emplace, and the ultimate holding capacity. The anchor was optimized for ultimate holding capacity, minimum emplacement torque, and minimum soil disturbance in sandy soils yielding the following dimensions: helix diameter (4.45 cm), pitch (1.27 cm), blade thickness (0.15 cm), total length (35.56 cm), shaft diameter (0.78 cm), and a weight of 212.62 g. The experimental results showed that smaller diameter, single-helix augers held more force than larger diameter augers for a given depth. The emplacement system consists of a flywheel and a motor for power, sealed in a protective box supported by four legs. The flywheel system was chosen over a gear system based on its increased reliability in the lunar environment.

A Cluster-Randomized, Community-Based, Tribally Delivered Oral Health Promotion Trial in Navajo Head Start Children.

PubMed

Braun, P A; Quissell, D O; Henderson, W G; Bryant, L L; Gregorich, S E; George, C; Toledo, N; Cudeii, D; Smith, V; Johs, N; Cheng, J; Rasmussen, M; Cheng, N F; Santo, W; Batliner, T; Wilson, A; Brega, A; Roan, R; Lind, K; Tiwari, T; Shain, S; Schaffer, G; Harper, M; Manson, S M; Albino, J

2016-10-01

The authors tested the effectiveness of a community-based, tribally delivered oral health promotion (OHP) intervention (INT) at reducing caries increment in Navajo children attending Head Start. In a 3-y cluster-randomized trial, we developed an OHP INT with Navajo input that was delivered by trained Navajo lay health workers to children attending 52 Navajo Head Start classrooms (26 INT, 26 usual care [UC]). The INT was designed as a highly personalized set of oral health-focused interactions (5 for children and 4 for parents), along with 4 fluoride varnish applications delivered in Head Start during academic years of 2011 to 2012 and 2012 to 2013. The authors evaluated INT impact on decayed, missing, and filled tooth surfaces (dmfs) increment compared with UC. Other outcomes included caries prevalence and caregiver oral health-related knowledge and behaviors. Modified intention-to-treat and per-protocol analyses were conducted. The authors enrolled 1,016 caregiver-child dyads. Baseline mean dmfs/caries prevalence equaled 19.9/86.5% for the INT group and 22.8/90.1% for the UC group, respectively. INT adherence was 53% (i.e., ≥3 child OHP events, ≥1 caregiver OHP events, and ≥3 fluoride varnish). After 3 y, dmfs increased in both groups (+12.9 INT vs. +10.8 UC; P = 0.216), as did caries prevalence (86.5% to 96.6% INT vs. 90.1% to 98.2% UC; P = 0.808) in a modified intention-to-treat analysis of 897 caregiver-child dyads receiving 1 y of INT. Caregiver oral health knowledge scores improved in both groups (75.1% to 81.2% INT vs. 73.6% to 79.5% UC; P = 0.369). Caregiver oral health behavior scores improved more rapidly in the INT group versus the UC group (P = 0.006). The dmfs increment was smaller among adherent INT children (+8.9) than among UC children (+10.8; P = 0.028) in a per-protocol analysis. In conclusion, the severity of dental disease in Navajo Head Start children is extreme and difficult to improve. The authors argue that successful approaches to prevention may require even more highly personalized approaches shaped by cultural perspectives and attentive to the social determinants of oral health (ClinicalTrials.gov NCT01116739). © International & American Associations for Dental Research 2016.

Co-operative energy transfer in Yb3+-Er3+ co-doped SrGdxOy upconverting phosphor

NASA Astrophysics Data System (ADS)

Kumar, Ashwini; Pathak, Trilok K.; Dhoble, S. J.; . Terblans, J. J.; Swart, H. C.

2018-04-01

Upconversion nanoparticles (UCNPs) have shown considerable interest in many fields; however, low upconversion efficiency of UCNPs is still the most severe limitation of their applications. Yb3+ and Er3+ co-doped SrGd4O7/Gd2O3(SGO) upconversion (UC) phosphors were synthesized by a modified co-precipitation process. The UC properties were investigated by direct excitation with a 980 nm laser. It was observed that the as prepared materials showed relatively strong green emission, while upon the incorporation of the Er3+ ion, there was an increase in the upconversion luminescence intensity for the red component. The effect of different doping concentration of Er3+on the emission spectra and X-ray diffraction patterns of the UC materials have also been studied. The luminescence lifetimes and Commission Internationale de L'Eclairage coordinates for these as prepared samples were determined to understand the energy transfer (ET) mechanisms occurring between Yb3+ and Er3+ in the SGO host matrix. The UC luminescence intensity as a function of laser pump power was monitored and it was confirmed that the UC process in SGO:Yb3+/Er3+is a two-photon absorption process. The findings reported here are expected to provide a better approach for understanding of the ET mechanisms in the oxide based Yb3+/Er3+ co-doped UC phosphors. This study might be helpful in precisely defined applications where optical transitions are essential criterion and this can be easily achieved by smart tuning of the emission properties of Yb3+/Er3+ co-doped UC phosphors.

Upconversion improvement in KLaF4:Yb3+/Er3+ nanoparticles by doping Al3+ ions

NASA Astrophysics Data System (ADS)

Zhou, Haifang; Wang, Xiechun; Lai, Yunfeng; Cheng, Shuying; Zheng, Qiao; Yu, Jinlin

2017-10-01

Rare-earth ion-doped upconversion (UC) materials show great potential applications in optical and optoelectronic devices due to their novel optical properties. In this work, hexagonal KLaF4:Yb3+/Er3+ nanoparticles (NPs) were successfully synthesized by a hydrothermal method, and remarkably enhanced upconversion luminescence in green and red emission bands in KLaF4:Yb3+/Er3+ NPs has been achieved by doping Al3+ ions under 980 nm excitation. Compared to the aluminum-free KLaF4:Yb3+/Er3+ NPs sample, the UC fluorescence intensities of the green and red emissions of NPs doped with 10 at.% Al3+ ions were significantly enhanced by 5.9 and 7.3 times, respectively. Longer lifetimes of the doped samples were observed for the 4S3/2 state and 4F9/2 state. The underlying reason for the UC enhancement by doping Al3+ ions was mainly ascribed to distortion of the local symmetry around Er3+ ions and adsorption reduction of organic ligands on the surface of NPs. In addition, the influence of doping Al3+ ions on the structure and morphology of the NPs samples was also discussed.

Emplacement of Pahoehoe Toe Networks: Observations of May, 2010 Tube-fed Flows at Kilauea Volcano, Hawai'i

NASA Astrophysics Data System (ADS)

Crown, D. A.; Ramsey, M.; Hon, K.

2010-12-01

Pahoehoe lava flows are compound features that consist of multiple overlapping and interfingering lobes and exhibit morphologically diverse surfaces characterized by channelized zones, smooth-surfaced sheets, and numerous, small toe networks. Previous work compiled detailed planform maps of solidified pahoehoe toe networks to document their morphology, morphometry and connective relationships in order to provide constraints on lava transport models. In order to expand this research to active flow emplacement, we observed slow-moving, tube-fed pahoehoe flows on the coastal plain near Kalapana, Hawaii in May, 2010. The evolution of pahoehoe toe and toe network characteristics over their emplacement history was examined and the role of small-scale flow inflation on the advance of pahoehoe lobes evaluated. We collected both visible video footage and high-speed, high-precision thermal infrared (TIR) data using a FLIR S-40 camera. The TIR data provide surface temperature maps that can be easily used to identify formation of new toes and track their growth and surface cooling. From these maps, lobe development, connective relationships, and frontal and lateral spreading rates can be analyzed. Preliminary results suggest that regular cycles of activity characterize the development of these pahoehoe lobes: 1) emplacement of new toes in local topographic lows at the front, margin, and within the interior of an active lobe forming small interconnected networks, 2) decline and sometimes temporary cessation in the production of new pahoehoe toes, 3) inflation of the recently emplaced flow surface, either partially or en masse depending on the rate of influx of new lava, the degree of irregularity of the pre-flow surface, and/or the slope across the recently emplaced lava surface, and 4) fracturing of the recently emplaced surface crust that feeds emplacement of new toes. Inflation fractures typically cut across several previously emplaced toes and can occur at the front, along the margins, or within the active lobe, even at significant distances behind the flow front.

Mutation of the Ser18 phosphorylation site on the sole Saccharomyces cerevisiae UCS protein, She4, can compromise high-temperature survival.

PubMed

Gomez-Escalante, Susana; Piper, Peter W; Millson, Stefan H

2017-01-01

Folding of the myosin head often requires the joint actions of Hsp90 and a dedicated UNC45, Cro1, She4 (UCS) domain-containing cochaperone protein. Relatively weak sequence conservation exists between the single UCS protein of simple eukaryotes (She4 in budding yeast) and the two UCS proteins of higher organisms (the general cell and smooth muscle UNC45s; UNC45-GC and UNC45-SM respectively). In vertebrates, UNC45-GC facilitates cytoskeletal function whereas the 55% identical UNC45-SM assists in the assembly of the contractile apparatus of cardiac and skeletal muscles. UNC45-SM, unlike UNC45-GC, shares with yeast She4 an IDSL sequence motif known to be a site of in vivo serine phosphorylation in yeast. Investigating this further, we found that both a non-phosphorylatable (S18A) and a phosphomimetic (S18E) mutant form of She4 could rescue the type 1 myosin localisation and endocytosis defects of the yeast she4Δ mutant at 39 °C. Nevertheless, at higher temperature (45 °C), only She4 (S18A), not She4(S18E), could substantially rescue the cell lysis defect of she4Δ mutant cells. In the yeast two-hybrid system, the non-phosphorylatable S18A and S251A mutant forms of She4 and UNC45-SM still displayed the stress-enhanced in vivo interaction with Hsp90 seen with the wild-type She4 and UNC45-SM. Such high-temperature enforcement to interaction was though lost with the phosphomimetic mutant forms (She4(S18E) and UNC45-SM (S251E)), an indication that phosphorylation might suppress these increases in She4/Hsp90 and UNC45-SM/Hsp90 interaction with stress.

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

PubMed Central

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Umbilical choline and related methylamines betaine and dimethylglycine in relation to birth weight.

PubMed

Hogeveen, Marije; den Heijer, Martin; Semmekrot, Ben A; Sporken, Jan M; Ueland, Per M; Blom, Henk J

2013-06-01

Low birth weight (LBW) is associated with increased morbidity and mortality for the newborn and risk of chronic disease in adulthood. Choline plays an essential role in the integrity of cell membranes, methylation reactions, and memory development. We examined whether choline, betaine, and dimethylglycine (DMG) concentrations were associated with LBW in Dutch women. Blood was sampled from umbilical cords (UCs) at delivery in singleton pregnancies (n = 1,126). Maternal blood was sampled at 30-34 wk of gestational age (GA) (n = 366). We calculated birth weights standardized for GA and defined LBW as standardized birth weight ≤ 2,500 g. Maternal concentrations were lower as compared with UC concentrations and were not associated with birth weight. UC choline and betaine were inversely associated with birth weight (β = -60 (-89, -31) and β = -65 (-94, -36), respectively), whereas UC DMG was positively associated with birth weight (β = 35 (6.1, 63)). Odds ratios for LBW were 4.12 (1.15, 14.78), 5.68 (1.24, 25.91), and 0.48 (0.09, 2.65) for the highest UC choline, betaine, and DMG quartiles, respectively, as compared with the lowest quartiles. We observed an increased risk of LBW with increased umbilical choline and betaine in venous UC blood. These results might reflect a change in choline consumption or metabolism or a disturbed placental function.

Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

PubMed

Isene, Rune; Bernklev, Tomm; Høie, Ole; Munkholm, Pia; Tsianos, Epameonondas; Stockbrügger, Reinhold; Odes, Selwyn; Palm, Øyvind; Småstuen, Milada; Moum, Bjørn

2015-03-01

In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: a meta-analysis.

PubMed

Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

2014-11-14

To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also showed that UC patients had higher serum IL-17 levels than healthy controls (SMD = 5.95, 95%CI: 4.25-7.65, P < 0.001). Furthermore, serum IL-17 levels significantly correlated with the severity of UC (moderate vs mild: SMD = 2.59, 95%CI: 0.03-5.16, P < 0.05; severe vs mild: SMD = 7.09, 95%CI: 3.96-10.23, P < 0.001; severe vs moderate: SMD = 5.84, 95%CI: 5.09-6.59, P < 0.001). The NOS score was ≥ 5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Neither the Begger's funnel plots nor Egger's test displayed strong statistical evidence for publication bias (IL-17A/F genetic polymorphisms: t = -2.60, P = 0.019; serum IL-17 levels: t = -1.54, P = 0.141). The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC.

Structural and optical characterization of NaGdF{sub 4}: Ho{sup 3+}/Yb{sup 3+} UC nano-particles for lateral finger mark detections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, A., E-mail: ak.phy87@gmail.com; Tiwari, S. P.; Krishna, K. M.

2016-05-23

Ho{sup 3+}/Yb{sup 3+} co-doped NaGdF{sub 4} up-conversion (UC) nano-particles were synthesized by thermal decomposition method. X-ray diffraction and FE-SEM image analysis were done to confirm the structure, morphology and determination of particle size. The UC emission spectra for as prepared as well as 100°C, 200°C, 300°C, 400°C, 800°C, 1000°C and 1200°C heated for 3h samples were recorded and there emission intensities were compared at a constant pump power of excitations 98.1 W/cm{sup 2}. The effect of emission intensity on decay time was also studied through focused and unfocused excitations. The synthesized material was successfully utilized in lateral finger mark detections onmore » the glass substrate through powder dusting method.« less

A gene encoding an abscisic acid biosynthetic enzyme (LsNCED4) collocates with the high temperature germination locus Htg6.1 in lettuce (Lactuca sp.)

PubMed Central

Argyris, Jason; Truco, María José; Ochoa, Oswaldo; McHale, Leah; Dahal, Peetambar; Van Deynze, Allen; Michelmore, Richard W.

2010-01-01

Thermoinhibition, or failure of seeds to germinate when imbibed at warm temperatures, can be a significant problem in lettuce (Lactuca sativa L.) production. The reliability of stand establishment would be improved by increasing the ability of lettuce seeds to germinate at high temperatures. Genes encoding germination- or dormancy-related proteins were mapped in a recombinant inbred line population derived from a cross between L. sativa cv. Salinas and L. serriola accession UC96US23. This revealed several candidate genes that are located in the genomic regions containing quantitative trait loci (QTLs) associated with temperature and light requirements for germination. In particular, LsNCED4, a temperature-regulated gene in the biosynthetic pathway for abscisic acid (ABA), a germination inhibitor, mapped to the center of a previously detected QTL for high temperature germination (Htg6.1) from UC96US23. Three sets of sister BC3S2 near-isogenic lines (NILs) that were homozygous for the UC96US23 allele of LsNCED4 at Htg6.1 were developed by backcrossing to cv. Salinas and marker-assisted selection followed by selfing. The maximum temperature for germination of NIL seed lots with the UC96US23 allele at LsNCED4 was increased by 2–3°C when compared with sister NIL seed lots lacking the introgression. In addition, the expression of LsNCED4 was two- to threefold lower in the former NIL lines as compared to expression in the latter. Together, these data strongly implicate LsNCED4 as the candidate gene responsible for the Htg6.1 phenotype and indicate that decreased ABA biosynthesis at high imbibition temperatures is a major factor responsible for the increased germination thermotolerance of UC96US23 seeds. Electronic supplementary material The online version of this article (doi:10.1007/s00122-010-1425-3) contains supplementary material, which is available to authorized users. PMID:20703871

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis

PubMed Central

Grewal, Suman; LaComb, Joseph F.; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M.; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E.; Frank, Daniel N.; Li, Ellen

2018-01-01

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients. PMID:29385143

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

PubMed

Mintz, Michael; Khair, Shanawaj; Grewal, Suman; LaComb, Joseph F; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E; Frank, Daniel N; Li, Ellen

2018-01-01

Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Web-Based Intervention for Transitioning Smokers From Inpatient to Outpatient Care: An RCT.

PubMed

Kathleen F, Harrington; Young-Il, Kim; Meifang, Chen; Rekha, Ramachandran; Maria, Pisu; Rajani S, Sadasivam; Thomas K, Houston; William C, Bailey

2016-10-01

Smoking-cessation follow-up care after hospitalization is known to be effective. Cost-effective and disseminable interventions adoptable by hospitals are needed. RCT. Fourteen hundred eighty-eight current smokers recruited during a tertiary care hospital stay were randomly assigned to Usual Care (UC) or Usual Care plus Web-Based Intervention (WI). Data were collected in 2011-2013 and analyzed in 2014-2015. UC provided brief bedside advice to quit, a quit plan template, and quitline contact information. WI included access to a website with asynchronous e-message communication with a tobacco counselor, use of interactive self-assessments, helpful cessation information, and access to additional web resources, as well as automated e-mail messages tailored for health concern and readiness to quit. Self-reported 30-day abstinence at 6 months was the primary outcome; a subset was verified by saliva cotinine. Six-month follow-up was completed by 83% of participants. No difference was found between study arms for self-reported abstinence rates in intent-to-treat (25.4% WI vs 26.8% UC) and complete case (31.3% WI vs 31.4% UC) analyses. Reduced smoking was reported by 45.5% (WI, n=276) and 47% (UC, n=296) of non-abstinent responders (p=0.59). Using a 10-ng/mL cotinine cut off, abstinence was verified in 52.1% of WI and 62.5% of UC (p=0.11). Significant covariates associated with abstinence at 6 months were being male, not smoking during hospitalization, being very confident in quitting, planning to quit/stay quit, smoking fewer days in the past 30 days, fewer years of smoking, and having cerebrovascular or connective tissue rheumatic disease as primary hospital diagnosis. Lack of difference between treatment arms suggests a strong effect for UC, WI was not effective, or both. Low intervention engagement may be partially responsible. Self-reported abstinence rates were relatively high in both arms, although the biochemically verified rates indicate over-reporting of abstinence. These findings suggest brief bedside counseling for all hospitalized smokers is beneficial. This study is registered at www.clinicaltrials.gov NCT01277250. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Assessment of Atrial Electromechanical Delay and Left Atrial Mechanical Functions in Patients with Ulcerative Colitis.

PubMed

Nar, Gokay; Ergul, Bilal; Aksan, Gokhan; Inci, Sinan

2016-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease causing systemic inflammation, which may also affect the cardiovascular system, as well as other organ systems. The aim of the current study was to evaluate left atrial (LA) mechanical functions and duration of atrial electromechanical delay (AEMD) with echocardiography in patients with UC. A total of 91 patients, 45 with UC (Group 1) and 46 healthy individuals as control (Group 2) were included in the study. The demographic and laboratory data were recorded, and echocardiographic measurements were taken for all patients. In the evaluation of basal clinical and laboratory findings, no difference was detected between the two groups, except for white blood cell count (WBC) (8.26 ± 2.71 vs. 7.06 ± 1.70, P = 0.013) and high-sensitivity C-reactive protein (Hs-CRP; 3.4 ± 1.7 vs. 1.0 ± 0.8, P < 0.001). The echocardiographic assessment revealed that the diastolic parameters such as E-, E/A-, and E- waves decreased in the UC group when compared to the control group. LA mechanical functions were different between groups, except for left atrial (LA) maximal volume: LA minimum volume (22.2 ± 12.9 vs. 15.3 ± 4.7, P = 0.001), LA volume before atrial systole (29.9 ± 14.2 vs. 24.2 ± 4.9, P = 0.021), LA ejection fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA total emptying volume (17.9 ± 6.9 vs. 21.9 ± 5.9, P = 0.004), LA active emptying fraction (27.4 ± 16.5 vs. 38.6 ± 10.1, P < 0.001), LA active emptying volume (7.7 ± 3.6 vs. 9.4 ± 2.9, P = 0.013), LA passive emptying fraction (26.8 ± 10.2 vs. 33.2 ± 9.2, P = 0.002), and LA passive emptying volume (10.3 ± 4.9 vs. 12.5 ± 4.5, P = 0.029). There was a significant difference between the groups in terms of AEMD durations, except time interval from the onset of the P-wave on the surface ECG to the peak of the late diastolic wave (PA) of the tricuspid valve. The correlation analysis revealed that age and duration of disease were correlated with AEMD. The current study reported that LA volume and mechanical functions degenerated and AEMD increased in patients with UC when compared to the control group. These findings demonstrate that UC may have effects on LA electromechanical functions related to duration of disease. © 2016, Wiley Periodicals, Inc.

Altered expression of transmembrane mucins, MUC1 and MUC4, in bladder cancer: pathological implications in diagnosis.

PubMed

Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G; Horn, Adam J; Lele, Subodh M; Theodorescu, Dan; Batra, Surinder K

2014-01-01

Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma.

Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials.

PubMed

Hulten, Edward; Pickett, Christopher; Bittencourt, Marcio Sommer; Villines, Todd C; Petrillo, Sara; Di Carli, Marcelo F; Blankstein, Ron

2013-02-26

The aim of the study was to systematically review and perform a meta-analysis of randomized, controlled trials of coronary computed tomography angiography (CCTA) versus usual care (UC) triage of acute chest pain in the emergency department (ED). CCTA allows rapid evaluation of patients presenting to the ED with acute chest pain syndromes; however, the impact of such testing on patient management and downstream testing has emerged as a concern. We systematically searched for randomized, controlled trials of CCTA in the ED and performed a meta-analysis of clinical outcomes. Four randomized, controlled trials were included, with 1,869 patients undergoing CCTA and 1,397 undergoing UC. There were no deaths and no difference in the incidence of myocardial infarction, post-discharge ED visits, or rehospitalizations. Four studies reported decreased length of stay with CCTA and 3 reported cost savings; 8.4% of patients undergoing CCTA versus 6.3% of those receiving UC underwent invasive coronary angiography (ICA), whereas 4.6% of patients undergoing CCTA versus 2.6% of those receiving UC underwent coronary revascularization. The odds ratio of ICA for CCTA patients versus UC patients was 1.36 (95% confidence interval [CI]: 1.03 to 1.80, p = 0.030), and for revascularization, it was 1.81 (95% CI: 1.20 to 2.72, p = 0.004). The absolute increase in ICA after CCTA was 21 per 1,000 CCTA patients (95% CI: 1.8 to 44.9), and the number needed to scan was 48. The absolute increase in revascularization after CCTA was 20 per 1,000 patients (95% CI: 5.0 to 41.4); the number needed to scan was 50. Both percutaneous coronary intervention and coronary artery bypass graft surgery independently contributed to the significant increase in revascularization. Compared with UC, the use of CCTA in the ED is associated with decreased ED cost and length of stay but increased ICA and revascularization. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Distinct kinetics in the frequency of peripheral CD4+ T cells in patients with ulcerative colitis experiencing a flare during treatment with mesalazine or with a herbal preparation of myrrh, chamomile, and coffee charcoal.

PubMed

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J; Westendorf, Astrid M

2014-01-01

We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. EU Clinical Trials Register 2007-007928-18/DE.

Distinct Kinetics in the Frequency of Peripheral CD4+ T Cells in Patients with Ulcerative Colitis Experiencing a Flare during Treatment with Mesalazine or with a Herbal Preparation of Myrrh, Chamomile, and Coffee Charcoal

PubMed Central

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J.; Westendorf, Astrid M.

2014-01-01

Background We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. Aim To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Methods Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. Results A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25medeffector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. Conclusions In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. Trial Registration EU Clinical Trials Register 2007-007928-18/DE PMID:25144293

Noise Characteristics of EarthScope Transportable Array Posthole Sensor Emplacements in Alaska and Canada

NASA Astrophysics Data System (ADS)

Aderhold, K.; Frassetto, A.; Busby, R. W.; Enders, M.; Bierma, R. M.; Miner, J.; Woodward, R.

2016-12-01

From 2011 to 2015, IRIS has built or upgraded 67 broadband seismic stations in Alaska and western Canada as part of the EarthScope Transportable Array (TA) program. An additional 72 stations will be completed by the fall of 2016. Nearly all use new posthole seismometers, emplaced at 3 m depth in cased holes within fractured bedrock outcrops, permafrost, or soil. Based on initial tests in Alaska, New Mexico, and California, this emplacement technique was chosen to streamline logistics in challenging, remote conditions as well as optimize station performance. A versatile drill capable of operating with a hammer bit or auger was developed specifically for the TA and is light enough to be transported by helicopter in a single load. The drilling system is ideal for TA deployment logistics in Alaska, but could be adapted to many regional or permanent network operations because it is easily transported on a flatbed truck and manuevered into tight working locations. The TA will complete another 73 installations in 2017 and operate the full network of 268 real-time stations through at least 2019. The removal of some TA stations is planned for 2020, but upgrades to existing stations are permanent contributions to these networks. The TA stations are a proof of concept for a new approach to emplacement of seismometers across a large network and will enable high-quality scientific research as well as advances in hazard monitoring. To evaluate the new and upgraded stations, we use probability density functions of hourly power spectral density computed by the IRIS DMC MUSTANG metric service for the continuous data recorded through 2016. Our results show that the noise performance of TA postholes in Alaska and Canada show significant improvement over the tank vaults of the lower-48 TA. With an ideal posthole drilled into bedrock or permafrost, noise levels can approach the quality of GSN stations particularly on the horizontal channels at long periods [>70 seconds]. Stations also display a strong but expected regional and seasonal variation. We provide notable examples of station performance, focusing on regional trends as well as the performance of stations upgraded from surface vault to posthole configuration.

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

PubMed

Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

2017-05-01

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care

PubMed Central

Chiarelli, Anna M; Muradali, Derek; Blackmore, Kristina M; Smith, Courtney R; Mirea, Lucia; Majpruz, Vicky; O'Malley, Frances P; Quan, May Lynn; Holloway, Claire MB

2017-01-01

Background: Timely coordinated diagnostic assessment following an abnormal screening mammogram reduces patient anxiety and may optimise breast cancer prognosis. Since 1998, the Ontario Breast Screening Program (OBSP) has offered organised assessment through Breast Assessment Centres (BACs). For OBSP women seen at a BAC, an abnormal mammogram is followed by coordinated referrals through the use of navigators for further imaging, biopsy, and surgical consultation as indicated. For OBSP women seen through usual care (UC), further diagnostic imaging is arranged directly from the screening centre and/or through their physician; results must be communicated to the physician who is then responsible for arranging any necessary biopsy and/or surgical consultation. This study aims to evaluate factors associated with diagnostic wait times for women undergoing assessment through BAC and UC. Methods: Of the 2 147 257 women aged 50–69 years screened in the OBSP between 1 January 2002 and 31 December 2009, 155 866 (7.3%) had an abnormal mammogram. A retrospective design identified two concurrent cohorts of women diagnosed with screen-detected breast cancer at a BAC (n=4217; 47%) and UC (n=4827; 53%). Multivariable logistic regression analyses examined associations between wait times and assessment and prognostic characteristics by pathway. A two-sided 5% significance level was used. Results: Screened women with breast cancer were two times more likely to be diagnosed within 7 weeks when assessed through a BAC vs UC (OR=1.91, 95% CI=1.73–2.10). In addition, compared with UC, women assessed through a BAC were significantly more likely to have their first assessment procedure within 3 weeks of their abnormal mammogram (OR=1.25, 95% CI=1.12–1.39), ⩽3 assessment procedures (OR=1.54, 95% CI=1.41–1.69), ⩽2 assessment visits (OR=1.86, 95% CI=1.70–2.05), and ⩾2 procedures per visit (OR=1.41, 95% CI=1.28–1.55). Women diagnosed through a BAC were also more likely than those in UC to have imaging (OR=1.99, 95% CI=1.44–2.75) or a biopsy (OR=3.69, 95% CI=2.64–5.15) vs consultation only at their first assessment visit, and two times more likely to have a core or FNA biopsy than a surgical biopsy (OR=2.08, 95% CI=1.81–2.40). Having ⩽2 assessment visits was more likely to reduce time to diagnosis for women assessed through a BAC compared with UC (BAC OR=10.58, 95% CI=8.96–12.50; UC OR=4.47, 95% CI=3.94–5.07), as was having ⩽3 assessment procedures (BAC OR=4.97, 95% CI=4.26–5.79; UC OR=2.95, 95% CI=2.61–3.33). Income quintile affected wait times only in women diagnosed in UC, with those in the two highest quintiles more likely to receive a diagnosis in 7 weeks. Conclusions: Women with screen-detected breast cancer in OBSP were more likely to have shorter wait times if they were diagnosed through organised assessment. This might be as a result of women diagnosed through a BAC having more procedures per visit, procedures scheduled in shorter intervals, and imaging or biopsy on their first visit. Given the significant improvement in timeliness to diagnosis, women with abnormal mammograms should be managed through organised assessment. PMID:28359079

Evaluating wait times from screening to breast cancer diagnosis among women undergoing organised assessment vs usual care.

PubMed

Chiarelli, Anna M; Muradali, Derek; Blackmore, Kristina M; Smith, Courtney R; Mirea, Lucia; Majpruz, Vicky; O'Malley, Frances P; Quan, May Lynn; Holloway, Claire Mb

2017-05-09

Timely coordinated diagnostic assessment following an abnormal screening mammogram reduces patient anxiety and may optimise breast cancer prognosis. Since 1998, the Ontario Breast Screening Program (OBSP) has offered organised assessment through Breast Assessment Centres (BACs). For OBSP women seen at a BAC, an abnormal mammogram is followed by coordinated referrals through the use of navigators for further imaging, biopsy, and surgical consultation as indicated. For OBSP women seen through usual care (UC), further diagnostic imaging is arranged directly from the screening centre and/or through their physician; results must be communicated to the physician who is then responsible for arranging any necessary biopsy and/or surgical consultation. This study aims to evaluate factors associated with diagnostic wait times for women undergoing assessment through BAC and UC. Of the 2 147 257 women aged 50-69 years screened in the OBSP between 1 January 2002 and 31 December 2009, 155 866 (7.3%) had an abnormal mammogram. A retrospective design identified two concurrent cohorts of women diagnosed with screen-detected breast cancer at a BAC (n=4217; 47%) and UC (n=4827; 53%). Multivariable logistic regression analyses examined associations between wait times and assessment and prognostic characteristics by pathway. A two-sided 5% significance level was used. Screened women with breast cancer were two times more likely to be diagnosed within 7 weeks when assessed through a BAC vs UC (OR=1.91, 95% CI=1.73-2.10). In addition, compared with UC, women assessed through a BAC were significantly more likely to have their first assessment procedure within 3 weeks of their abnormal mammogram (OR=1.25, 95% CI=1.12-1.39), ⩽3 assessment procedures (OR=1.54, 95% CI=1.41-1.69), ⩽2 assessment visits (OR=1.86, 95% CI=1.70-2.05), and ⩾2 procedures per visit (OR=1.41, 95% CI=1.28-1.55). Women diagnosed through a BAC were also more likely than those in UC to have imaging (OR=1.99, 95% CI=1.44-2.75) or a biopsy (OR=3.69, 95% CI=2.64-5.15) vs consultation only at their first assessment visit, and two times more likely to have a core or FNA biopsy than a surgical biopsy (OR=2.08, 95% CI=1.81-2.40). Having ⩽2 assessment visits was more likely to reduce time to diagnosis for women assessed through a BAC compared with UC (BAC OR=10.58, 95% CI=8.96-12.50; UC OR=4.47, 95% CI=3.94-5.07), as was having ⩽3 assessment procedures (BAC OR=4.97, 95% CI=4.26-5.79; UC OR=2.95, 95% CI=2.61-3.33). Income quintile affected wait times only in women diagnosed in UC, with those in the two highest quintiles more likely to receive a diagnosis in 7 weeks. Women with screen-detected breast cancer in OBSP were more likely to have shorter wait times if they were diagnosed through organised assessment. This might be as a result of women diagnosed through a BAC having more procedures per visit, procedures scheduled in shorter intervals, and imaging or biopsy on their first visit. Given the significant improvement in timeliness to diagnosis, women with abnormal mammograms should be managed through organised assessment.

Hybrid constructs for tridimensional correction of the thoracic spine in adolescent idiopathic scoliosis: a comparative analysis of universal clamps versus hooks.

PubMed

Ilharreborde, Brice; Even, Julien; Lefevre, Yan; Fitoussi, Franck; Presedo, Ana; Penneçot, Georges-François; Mazda, Keyvan

2010-02-01

Retrospective study of prospectively collected data. Compare Universal Clamps (UCs) and hooks for the thoracic correction of adolescent idiopathic scoliosis (AIS). In scoliosis surgery, sagittal correction is as important as frontal correction due to the risk of junctional kyphosis. Compared to all-screw constructs, hybrid constructs with lumbar pedicle screws and thoracic hooks or sublaminar wires have been shown to achieve similar coronal correction while providing superior postoperative thoracic kyphosis. The authors used a novel sublaminar thoracic implant, the UC with improvements over sublaminar wires. Hybrid constructs using thoracic UCs were compared to those with thoracic hooks. This series involved 150 patients treated for AIS with hybrid constructs. A total of 75 consecutive patients operated from 2001 to 2003, who had thoracic hooks with in situ contouring, distraction, and compression (Group 1), were compared to 75 consecutive patients operated from 2004 to 2006, who had thoracic UCs with posteromedial translation (Group 2). All had intraoperative somatosensory/motor-evoked potential monitoring and at least 2-years follow-up. Except for follow-up (longer in Group 1), the 2 groups were similar before surgery. The UCs achieved better thoracic coronal correction (P < 0.001), Cincinnati index (P < 0.001), kyphosis (P = 0.02), and apical rotation (P < 0.001). In normokyphotic or hypokyphotic patients, the UC corrected thoracic kyphosis by 11.2 degrees (55%) versus 0.4 degrees (2%) achieved by hooks (P < 0.0001). These differences were stable at last follow-up. There were no intraoperative complications or changes in somatosensory/motor-evoked potentials. UC reduced operative time by 20% (60 minutes; P < 0.001) and blood loss by 23% (250 mL; P < 0.001). Although both of these hybrid constructs efficaciously corrected the coronal and axial deformities in AIS, the results of the UC technique were superior to those achieved with hooks in all 3 planes, especially the sagittal plane. Moreover, the UC technique is straightforward and safe, reducing both operative duration and blood loss.

Long Noncoding RNA uc002yug.2 Activates HIV-1 Latency through Regulation of mRNA Levels of Various RUNX1 Isoforms and Increased Tat Expression.

PubMed

Huan, Chen; Li, Zhaolong; Ning, Shanshan; Wang, Hong; Yu, Xiao-Fang; Zhang, Wenyan

2018-05-01

The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long noncoding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. In this study, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 replication and latency. uc002yug.2 potentially enhances HIV-1 replication, long terminal repeat (LTR) activity, and the activation of latent HIV-1 in both cell lines and CD4 + T cells from patients. Further investigation revealed that uc002yug.2 activates latent HIV-1 through downregulating RUNX1b and -1c and upregulating Tat protein expression. The accumulated evidence supports our model that the Tat protein has the key role in the uc002yug.2-mediated regulatory effect on HIV-1 reactivation. Moreover, uc002yug.2 showed an ability to activate HIV-1 similar to that of suberoylanilide hydroxamic acid or phorbol 12-myristate 13-acetate using latently infected cell models. These findings improve our understanding of lncRNA regulation of HIV-1 replication and latency, providing new insights into potential targeted therapeutic interventions. IMPORTANCE The latent viral reservoir is the primary obstacle to curing HIV-1 disease. To date, only a few lncRNAs, which play major roles in various biological processes, including viral infection, have been identified as regulators in HIV-1 latency. In this study, we demonstrated that lncRNA uc002yug.2 is important for both HIV-1 replication and activation of latent viruses. Moreover, uc002yug.2 was shown to activate latent HIV-1 through regulating alternative splicing of RUNX1 and increasing the expression of Tat protein. These findings highlight the potential merit of targeting lncRNA uc002yug.2 as an activating agent for latent HIV-1. Copyright © 2018 American Society for Microbiology.

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Gonczi, Lorant; Golovics, Petra Anna; Lovasz, Barbara Dorottya; Szita, Istvan; Balogh, Mihaly; Pandur, Tunde; Vavricka, Stephan R; Rogler, Gerhard; Lakatos, Laszlo; Lakatos, Peter Laszlo

2016-07-01

The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

Ulcerative colitis in a multiracial Asian country: racial differences and clinical presentation among Malaysian patients.

PubMed

Tan, Yan-Mei; Goh, Khean-Lee

2005-10-07

Inflammatory bowel disease appears to be uncommon among Asians. This study was conducted to determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. Three major Asian races: Malay, Chinese, and Indian co-exist in Malaysia and we sought to determine if there were any racial differences in the prevalence and presentation of disease. Racial differences for several other gastrointestinal diseases have previously been observed and found to be extremely interesting. Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. There were 45 confirmed cases of UC of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0+/-10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; chi2 = 15.45, P<0.001) and 3.06 (CI = 1.24-7.78; chi2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; chi2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease.

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

PubMed

Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

2013-04-01

Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up

PubMed Central

van der Valk, Mirthe E.; Mangen, Marie-Josée J.; Severs, Mirjam; van der Have, Mike; Dijkstra, Gerard; van Bodegraven, Ad A.; Fidder, Herma H.; de Jong, Dirk J.; van der Woude, C. Janneke; Romberg-Camps, Mariëlle J. L.; Clemens, Cees H. M.; Jansen, Jeroen M.; van de Meeberg, Paul C.; Mahmmod, Nofel; van der Meulen-de Jong, Andrea E.; Ponsioen, Cyriel Y.; Bolwerk, Clemens; Vermeijden, J. Reinoud; Siersema, Peter D.; Leenders, Max; Oldenburg, Bas

2016-01-01

Background With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02–3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61–13.86)). Conclusions BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC. PMID:27099937

Collaborative care for depression symptoms in an outpatient cardiology setting: A randomized clinical trial.

PubMed

Carney, Robert M; Freedland, Kenneth E; Steinmeyer, Brian C; Rubin, Eugene H; Ewald, Gregory

2016-09-15

Depression is a risk factor for morbidity and mortality in patients with coronary heart disease. Finding effective methods for identifying and treating depression in these patients is a high priority. The purpose of this study was to determine whether collaborative care (CC) for patients who screen positive for depression during an outpatient cardiology visit results in greater improvement in depression symptoms and better medical outcomes than seen in patients who screen positive for depression but receive only usual care (UC). Two hundred-one patients seen in an outpatient cardiology clinic who screened positive for depression during an outpatient visit were randomized to receive either CC or UC. Recommendations for depression treatment and ongoing support and monitoring of depression symptoms were provided to CC patients and their primary care physicians (PCPs) for up to 6months. There were no differences between the arms in mean Beck Depression Inventory-II scores(CC, 15.9; UC, 17.4; p=.45) or in depression remission rates(CC, 32.5%; UC, 26.2%; p=0.34) after 6months, or in the number of hospitalizations after 12months (p=0.73). There were fewer deaths among the CC (1/100) than UC patients (8/101) (p=0.03). This trial did not show that CC produces better depression outcomes than UC. Screening led to a higher rate of depression treatment than was expected in the UC group, and delays in obtaining depression treatment from PCPs may have reduced treatment effectiveness for the CC patients. A different strategy for depression treatment following screening in outpatient cardiology services is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mucosal Transcriptomics Implicates Under Expression of BRINP3 in the Pathogenesis of Ulcerative Colitis

PubMed Central

Smith, Philip J.; Levine, Adam P.; Dunne, Jenny; Guilhamon, Paul; Turmaine, Mark; Sewell, Gavin W.; O'Shea, Nuala R.; Vega, Roser; Paterson, Jennifer C.; Oukrif, Dahmane; Beck, Stephan; Bloom, Stuart L.; Novelli, Marco; Rodriguez-Justo, Manuel; Smith, Andrew M.

2014-01-01

Background: Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC). We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls, taken from macroscopically noninflamed tissue from the terminal ileum and 3 colonic locations with the objective of identifying abnormal molecules that might be involved in disease development. Methods: Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 patients with UC, 26 healthy controls, and 14 patients with Crohn's disease. Differential gene expression analysis was performed at each tissue location separately, and results were then meta-analyzed. Significantly, differentially expressed genes were validated using quantitative polymerase chain reaction. The location of gene expression within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing. Results: Only 4 probes were abnormally expressed throughout the colon in patients with UC with Bone morphogenetic protein/Retinoic acid Inducible Neural-specific 3 (BRINP3) being the most significantly underexpressed. Attenuated expression of BRINP3 in UC was independent of current inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy an average of 22 months later. BRINP3 is localized to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter. Conclusions: Genome-wide expression analysis of noninflamed mucosal biopsies from patients with UC identified BRINP3 as significantly underexpressed throughout the colon in a large subset of patients with UC. Low levels of this gene could predispose or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition. PMID:25171508

Causes of false-negative for high-grade urothelial carcinoma in urine cytology.

PubMed

Lee, Paul J; Owens, Christopher L; Lithgow, Marie Y; Jiang, Zhong; Fischer, Andrew H

2016-12-01

The Paris System for classifying urine cytology emphasizes identification of high-grade urothelial carcinoma (HGUC). The causes of false-negative urine cytologies (UC) within this system are not well described. We identified 660 cases between 2005 and 2013 with both UC and subsequent cystoscopic biopsies. UC were classified as either Negative for HGUC or "Abnormal" ("Atypical", "Suspicious", and "Malignant"). Apparent false-negative cases were reviewed in a nonblinded fashion by two cytopathologists and two subspecialized genitourinary pathologists. A total of 199 of the 660 cases (30%) were histologically diagnosed as HGUC. The UC were "Abnormal" in 170/199 cases (sensitivity/specificity of 86%/71%). Twenty four apparent false negative cases were available for retrospective review. Five of 24 (21%) cystoscopic biopsies were found not to be HGUC on review (one false positive and four low-grade urothelial carcinoma (LGUC on review). Of the remaining 19 UC, 7 (29%) cytology samples were found to be truly negative on review, 11 (46%) were found to be Atypical, and 1 (4%) suspicious. Of the 12 UC that were at least "Atypical" with histologic HGUC on review: six misses (half) were attributed to obscuring inflammation/blood, four to poor preservation, eight to paucity of abnormal cells, and 1 case to interpretive error; many cases demonstrated overlapping reasons. About one fifth of apparent false negative diagnoses for HGUC can be because of overdiagnosis of HGUC by surgical pathologists. If poor preservation or obscured samples are called nondiagnostic, the sensitivity/specificity of UC for HGUC can be as high as 94%/71%. Diagn. Cytopathol. 2016;44:994-999. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A case-control study of the association between ulcerative colitis and hyperthyroidism in an Asian population.

PubMed

Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

2017-06-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P<.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24-1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27-2.05). Furthermore, we analysed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18-39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04-3.79). This study demonstrated an association between UC and hyperthyroidism. © 2017 John Wiley & Sons Ltd.

The polymorphisms K469E and G261R of intercellular adhesion molecule-1 and susceptibility to inflammatory bowel disease: a meta-analysis.

PubMed

Song, Gwan Gyu; Lee, Young Ho

2015-01-01

The aim of this study was to explore whether polymorphisms of intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to Crohn's disease (CD) and ulcerative colitis (UC). The authors conducted a meta-analysis on the associations between the polymorphisms K469E and G241R of ICAM-1 and susceptibility to CD and UC. A total of 8 studies with 801 patients with CD, 672 patients with UC, and 1,828 controls were included in the meta-analysis. The meta-analysis revealed no association between CD and the ICAM-1 469E allele among the subjects (OR = 1.175, 95% CI = 0.901-1.533, p = 0.233). However, stratification by ethnicity indicated an association between the ICAM-1 469E allele and CD in Europeans (OR = 1.425, 95% CI = 1.013-2.002, p = 0.042). Meta-analysis using the homozygosity also showed an association with CD in Europeans (OR = 2.054, 95% CI = 1.036-4.073, p = 0.039). The meta-analysis revealed no association between UC and the ICAM-1 K469E polymorphism. No association between CD or UC and the ICAM-1 G241R polymorphism was observed. This meta-analysis demonstrates that the ICAM-1 K469E polymorphism may be associated with susceptibility to CD in Europeans, but no association was found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not found to be associated with susceptibility to either CD or UC.

Impact of inflammatory bowel disease on pubertal growth.

PubMed

Mason, A; Malik, S; Russell, R K; Bishop, J; McGrogan, P; Ahmed, S F

2011-01-01

Puberty is thought to be commonly affected in adolescents with inflammatory bowel disease (IBD). To determine the impact of Crohn's disease (CD) and ulcerative colitis (UC) on the pubertal growth spurt. Retrospective study of 30 boys with CD (CD-M), 11 girls with CD (CD-F), 14 boys with UC (UC-M) and 12 girls with UC (UC-F). Pubertal growth was assessed by calculating peak height velocity SDS (PHV SDS), height SDS at diagnosis (Ht(Diag)) and height SDS at PHV (Ht(PHV)) and age at PHV (Age(PHV)). Systemic markers of disease activity were also collected. Altered parameters of pubertal growth were observed in the CD groups compared to the normal population: in the CD-M group, median Ht(Diag) was -0.56 (p = 0.001) and median Age(PHV) was 14.45 years (p = 0.004), and in the CD-F group, median Ht(Diag) was -1.14 (p = 0.007) and Ht(PHV) was -0.79 (p = 0.039). Individually, 8/30 CD-M cases had one or more parameter affected: 2 boys had Ht(Diag )<-2, 3 boys had Ht(PHV) <-2, 2 boys had an Age(PHV) >2 years above population mean, and 2 boys had a PHV SDS <-2. In the whole group, Age(PHV) showed an association with erythrocyte sedimentation rate (r = 0.4; p = 0.005) and an inverse association with BMI (r = 0.4; p = 0.001). Disorders of pubertal growth are more likely to occur in CD and, particularly, in boys. Copyright © 2011 S. Karger AG, Basel.

Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases.

PubMed

Karrasch, T; Obermeier, F; Straub, R H

2014-06-01

Acute and chronic intestinal inflammation stimulates innate and adaptive immune systems, thereby increasing energy demand of activated immune cells. Energy regulation by systemically released mediators is of critical importance for homeostasis. We wanted to find out how systemic metabolic mediators are affected during intestinal inflammation. A total of 123 patients suffering from Crohn's disease (CD), 76 patients with ulcerative colitis (UC), and 21 healthy controls were recruited. Patients receiving systemic steroids or therapy regimens including biologicals (anti-TNF) were excluded from the study. Serum levels of IL-6, CRP, insulin, glucose, free fatty acid, and RBP-4 were measured by ELISA and RIA. Intestinal inflammation was accompanied by elevated systemic inflammatory para-meters such as IL-6 and CRP in UC and CD and, concomitantly, with elevated insulin levels and increased insulin/glucose ratio in patients with UC. This indicates insulin resistance in liver, muscle, and fat. In addition, intestinal inflammation was associated with elevated levels of circulating free fatty acids in UC and CD, indicating an activation of the organism's appeal for energy-rich substrates (energy appeal reaction). RBP-4 serum levels were also high in acute and chronic intestinal inflammation in UC and CD, which can support insulin resistance. The organism's "energy appeal reaction" in response to acute and chronic inflammation provides free energy in the circulation, which is needed by inflammatory cells. A major mechanism of the redirection program is insulin resistance. New therapeutic strategies might be developed in the future, directly impacting on the storage and utilization of energy-rich fuels. © Georg Thieme Verlag KG Stuttgart · New York.

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-06-01

Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC.A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome.Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6-39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events.FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT.

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis

PubMed Central

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-01-01

Abstract Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC. A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome. Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6–39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I2 = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events. FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT. PMID:27281075

Biochemical and dietary factors of uric acid stone formation.

PubMed

Trinchieri, Alberto; Montanari, Emanuele

2018-04-01

The aim of this study was to compare the clinical characteristics of "pure" uric acid renal stone formers (UA-RSFs) with that of mixed uric acid/calcium oxalate stone formers (UC-RSFs) and to identify which urinary and dietary risk factors predispose to their formation. A total of 136 UA-RSFs and 115 UC-RSFs were extracted from our database of renal stone formers. A control group of 60 subjects without history of renal stones was considered for comparison. Data from serum chemistries, 24-h urine collections and 24-h dietary recalls were considered. UA-RSFs had a significantly (p = 0.001) higher body mass index (26.3 ± 3.6 kg/m 2 ) than UC-RSFs, whereas body mass index of UA-RSFs was higher but not significantly than in controls (24.6 ± 4.7) (p = 0.108). The mean urinary pH was significantly lower in UA-RSFs (5.57 ± 0.58) and UC-RSFs (5.71 ± 0.56) compared with controls (5.83 ± 0.29) (p = 0.007). No difference of daily urinary uric acid excretion was observed in the three groups (p = 0.902). Daily urinary calcium excretion was significantly (p = 0.018) higher in UC-RSFs (224 ± 149 mg/day) than UA-RSFs (179 ± 115) whereas no significant difference was observed with controls (181 ± 89). UA-RSFs tend to have a lower uric acid fractional excretion (0.083 ± 0.045% vs 0.107+/-0.165; p = 0.120) and had significantly higher serum uric acid (5.33 ± 1.66 vs 4.78 ± 1.44 mg/dl; p = 0.007) than UC-RSFs. The mean energy, carbohydrate and vitamin C intakes were higher in UA-SFs (1987 ± 683 kcal, 272 ± 91 g, 112 ± 72 mg) and UC-SFs (1836 ± 74 kcal, 265 ± 117, 140 ± 118) with respect to controls (1474 ± 601, 188 ± 84, 76 ± 53) (p = 0.000). UA-RSFs should be differentiated from UC-RSFs as they present lower urinary pH, lower uric acid fractional excretion and higher serum uric acid. On the contrary, patients with UC-RSFs show urinary risk factors more similar to those for calcium oxalate stones. The dietary approach in patients forming uric acid stones should be reconsidered with more attention to the quantity and quality of carbohydrate intake.

Environmental and microbial factors influencing methane and nitrous oxide fluxes in Mediterranean cork oak woodlands: trees make a difference.

PubMed

Shvaleva, Alla; Siljanen, Henri M P; Correia, Alexandra; Costa E Silva, Filipe; Lamprecht, Richard E; Lobo-do-Vale, Raquel; Bicho, Catarina; Fangueiro, David; Anderson, Margaret; Pereira, João S; Chaves, Maria M; Cruz, Cristina; Martikainen, Pertti J

2015-01-01

Cork oak woodlands (montado) are agroforestry systems distributed all over the Mediterranean basin with a very important social, economic and ecological value. A generalized cork oak decline has been occurring in the last decades jeopardizing its future sustainability. It is unknown how loss of tree cover affects microbial processes that are consuming greenhouse gases in the montado ecosystem. The study was conducted under two different conditions in the natural understory of a cork oak woodland in center Portugal: under tree canopy (UC) and open areas without trees (OA). Fluxes of methane and nitrous oxide were measured with a static chamber technique. In order to quantify methanotrophs and bacteria capable of nitrous oxide consumption, we used quantitative real-time PCR targeting the pmoA and nosZ genes encoding the subunit of particulate methane mono-oxygenase and catalytic subunit of the nitrous oxide reductase, respectively. A significant seasonal effect was found on CH4 and N2O fluxes and pmoA and nosZ gene abundance. Tree cover had no effect on methane fluxes; conversely, whereas the UC plots were net emitters of nitrous oxide, the loss of tree cover resulted in a shift in the emission pattern such that the OA plots were a net sink for nitrous oxide. In a seasonal time scale, the UC had higher gene abundance of Type I methanotrophs. Methane flux correlated negatively with abundance of Type I methanotrophs in the UC plots. Nitrous oxide flux correlated negatively with nosZ gene abundance at the OA plots in contrast to that at the UC plots. In the UC soil, soil organic matter had a positive effect on soil extracellular enzyme activities, which correlated positively with the N2O flux. Our results demonstrated that tree cover affects soil properties, key enzyme activities and abundance of microorganisms and, consequently net CH4 and N2O exchange.

Design and synthesis of a novel multifunctional stabilizer for highly stable uc(dl)-tetrahydropalmatine nanosuspensions and in vitro study

NASA Astrophysics Data System (ADS)

Yan, Beibei; Wang, Yancai; Wang, Lulu; Zhou, Yuqi; Shang, Xueyun; Zhao, Juan; Liu, Yangyang; Du, Juan

2018-05-01

The present study aimed to prepare stable uc(dl)-tetrahydropalmatine (uc(dl)-THP) nanosuspensions of optimized formulation with PEGylated chitosan as a multifunctional stabilizer using the antisolvent precipitation method. A central composite design project of three factors and five-level full factorial (53) was applied to design the experimental program, and response surface methodology analysis was used to optimize the experimental conditions. The effects of critical influencing factors such as PEGylated chitosan concentration, operational temperature, and ultrasonic energy on particle size and zeta potential were investigated. Under the optimization nanosuspension formulation, the particle size was 269 nm and zeta potential was at 37.4 mV. Also, the uc(dl)-THP nanosuspensions maintained good physical stability after 2 months, indicating the potential ability of the multifunctional stabilizer for stable nanosuspension formulation. Hence, the present findings indicated that PEGylated chitosan could be used as the ideal stabilizer to form a physically stable nanosuspension formulation.

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

PubMed Central

Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

2016-01-01

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

Estimation of quality of life in Cypriot patients with inflammatory bowel disease.

PubMed

Tsoukka, Maria; Jelastopulu, Eleni; Lavranos, Giagkos; Charalambous, George

2017-01-07

To investigate the health-related quality of life (HRQoL) of patients suffering with idiopathic inflammatory bowel disease (IBD). The Greek validated version of the Short Inflammatory Bowel Disease Questionnaire was used for evaluating the quality of life of IBD patients. The questionnaire was distributed to 100 consecutive patients suffering from IBD and presenting for a clinic appointment at the endoscopy unit of Larnaca General Hospital during the period from October to November 2012. The criteria for participating in this study were constituted by the documented diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) after endoscopy and histologic examination at least 6 months before the study, adult patients (18 years old or older), the capability of verbal communication and the patient's written consent for attending this study. The majority of the questionnaires were completed by a nurse practitioner who specializes in IBD patient care. Regarding the physical dimension in patients with UC, males scored significantly higher than females (4.2 vs 3.4, P = 0.023). Higher scores were also observed in UC patients younger than 35 or older than 50 years (4.0 and 4.2 vs 3.2, respectively, P = 0.021). The psychological dimension revealed similar results in patients with UC, with males, and older ages scoring higher (5.0 vs 3.0, P = 0.01 and 4.7 vs 2.7, P < 0.5, respectively), whereas regarding CD higher scores were observed in married compared to unmarried (3.83 vs 2.33, P = 0.042). No statistical differences in any parameters in the social dimension were observed. Regarding the treatment of, patients with CD, overall higher scores were observed when treated with biological factors compared to standard therapy in all dimensions but with statistical significant difference in the social dimension (5.00 vs 3.25, P = 0.045). The study reveals a negative impact of IBD on HRQoL. Increased risks are age and gender in patients with UC and family status in patients with CD.

On the Supermassive Black Hole-Galaxy Coevolution

NASA Astrophysics Data System (ADS)

Hegde, Sahil; Zhang, Shawn; Rodriguez, Aldo; Primack, Joel R.

2017-01-01

In recent years, a major focus of astronomy has been the study of the effects of supermassive black holes (SMBH) on their host galaxies. Recent results have found strong correlations between SMBH mass and host galaxy properties, most notably in the bulge velocity dispersion and galaxy stellar mass. We utilize these relations along with a novel convolution method to construct number density models of different galaxy properties. Using these models, we compare two fundamental methods for constructing a black hole mass function (BHMF) with the M⊙-σ and M⊙-M* relations. With these methods, we estimate the redshift evolution of the BHMF and, based on that, compare mass growth histories of central black holes and their host galaxies. Additionally, we utilize a data compilation of over 500 galaxies with individual measurements of galaxy properties (BH mass, stellar velocity dispersion, stellar mass, etc.) and classify galaxies by their morphologies in order to shed light on the controversial Shankar et al. (2016) argument that observations are biased in favor of massive SMBHs. We find that such a bias has little impact on the SMBH-galaxy relations.We conclude that the galaxy sample is a fair representation of the local universe and argue that our BH number density and scaling relations can be employed in the future to constrain relevant mechanisms for galaxy formation. We emphasize that this is the most comprehensive and accurate study of SMBH-galaxy coevolution as of now. Most of this work was carried out by high school students working under the auspices of the Science Internship Program at UC Santa Cruz.

Genetic characterization of UCS region of Pneumocystis jirovecii and construction of allelic profiles of Indian isolates based on sequence typing at three regions.

PubMed

Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Kumar, Lalit; Luthra, Kalpana; Agarwal, Sanjay Kumar; Sreenivas, Vishnubhatla

2013-01-01

Pneumocystis jirovecii is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. To study the genetic diversity of P. jirovecii in India the upstream conserved sequence (UCS) region of Pneumocystis genome was amplified, sequenced and genotyped from a set of respiratory specimens obtained from 50 patients with a positive result for nested mitochondrial large subunit ribosomal RNA (mtLSU rRNA) PCR during the years 2005-2008. Of these 50 cases, 45 showed a positive PCR for UCS region. Variations in the tandem repeats in UCS region were characterized by sequencing all the positive cases. Of the 45 cases, one case showed five repeats, 11 cases showed four repeats, 29 cases showed three repeats and four cases showed two repeats. By running amplified DNA from all these cases on a high-resolution gel, mixed infection was observed in 12 cases (26.7%, 12/45). Forty three of 45 cases included in this study had previously been typed at mtLSU rRNA and internal transcribed spacer (ITS) region by our group. In the present study, the genotypes at those two regions were combined with UCS repeat patterns to construct allelic profiles of 43 cases. A total of 36 allelic profiles were observed in 43 isolates indicating high genetic variability. A statistically significant association was observed between mtLSU rRNA genotype 1, ITS type Ea and UCS repeat pattern 4. Copyright © 2012 Elsevier B.V. All rights reserved.

Improving Work Outcomes of Dysthymia (Persistent Depressive Disorder) in an Employed Population

PubMed Central

Adler, David A.; Lerner, Debra; Visco, Zachary L.; Greenhill, Annabel; Chang, Hong; Cymerman, Elina; Azocar, Francisca; Rogers, William H.

2015-01-01

Objective To test the effectiveness of a work-focused intervention (WFI) on the work outcomes of employed adults with dysthymia. Method This subgroup analysis from a randomized controlled trial compares an initial sample of 167 employees (age ≥ 45 years), screened for dysthymia using the PC-SAD without current major depressive disorder randomized to WFI (n=85) or usual care (UC) (n=82). Study sites included 19 employers and five additional organizations. Telephone-based WFI counseling (eight, twice monthly 50-minute sessions) provided work coaching and modification, care coordination and cognitive-behavioral therapy (CBT). Adjusted mixed effects models compared the WFI versus UC group pre-intervention to four-month post-intervention change in at-work limitations measured by the Work Limitations Questionnaire. Secondary outcome analysis compared the change in self-reported absences and depression symptom severity (PHQ-9 scores). Results Work productivity loss scores improved 43.0% in the WFI group vs. 4.8% in UC (difference in change P < 0.001). Absence days declined by 58.3% in WFI vs. 0.0% in UC (difference in change P = .09). Mean PHQ-9 depression symptom severity declined 44.2% in WFI vs. 5.3% in UC (difference in change P < 0.001). Conclusion At four months, the WFI was more effective than UC on two of the three outcomes. It could be an important mental and functional health improvement resource for the employed dysthymic population. PMID:25892151

Partners of patients with ulcerative colitis exhibit a biologically relevant dysbiosis in fecal microbial metacommunities.

PubMed

Chen, Guang-Lan; Zhang, Ye; Wang, Wang-Yue; Ji, Xue-Liang; Meng, Fei; Xu, Pei-Song; Yang, Ning-Min; Ye, Fu-Qiang; Bo, Xiao-Chen

2017-07-07

To investigate alterations in the fecal microbiome using 16S rRNA amplicon sequencing in couples in the same cohabitation environment. Fecal samples were collected from eight ulcerative colitis (UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant. Fecal microbial communities were more similar among UC patients than their healthy partners ( P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes , especially Blautia , Clostridium , Coprococcus and Roseburia ( P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam , Bacteroides , Escherichia , Lactobacillales , Klebsiella and Parabacteroides . The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners. Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.

Down-Regulation of Glucose-Regulated Protein (GRP) 78 Potentiates Cytotoxic Effect of Celecoxib in Human Urothelial Carcinoma Cells

PubMed Central

Huang, Kuo-How; Kuo, Kuan-Lin; Chen, Shyh-Chyan; Weng, Te-I; Chuang, Yuan-Ting; Tsai, Yu-Chieh; Pu, Yeong-Shiau; Chiang, Chih-Kang; Liu, Shing-Hwa

2012-01-01

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has been reported to elicit anti-proliferative response in various tumors. In this study, we aim to investigate the antitumor effect of celecoxib on urothelial carcinoma (UC) cells and the role endoplasmic reticulum (ER) stress plays in celecoxib-induced cytotoxicity. The cytotoxic effects were measured by MTT assay and flow cytometry. The cell cycle progression and ER stress-associated molecules were examined by Western blot and flow cytometry. Moreover, the cytotoxic effects of celecoxib combined with glucose-regulated protein (GRP) 78 knockdown (siRNA), (−)-epigallocatechin gallate (EGCG) or MG132 were assessed. We demonstrated that celecoxib markedly reduces the cell viability and causes apoptosis in human UC cells through cell cycle G1 arrest. Celecoxib possessed the ability to activate ER stress-related chaperones (IRE-1α and GRP78), caspase-4, and CCAAT/enhancer binding protein homologous protein (CHOP), which were involved in UC cell apoptosis. Down-regulation of GRP78 by siRNA, co-treatment with EGCG (a GRP78 inhibitor) or with MG132 (a proteasome inhibitor) could enhance celecoxib-induced apoptosis. We concluded that celecoxib induces cell cycle G1 arrest, ER stress, and eventually apoptosis in human UC cells. The down-regulation of ER chaperone GRP78 by siRNA, EGCG, or proteosome inhibitor potentiated the cytotoxicity of celecoxib in UC cells. These findings provide a new treatment strategy against UC. PMID:22438966

Physician Perspectives on Unresolved Issues in the Management of Ulcerative Colitis: The UC Horizons Project.

PubMed

Gisbert, Javier P; Barreiro-de Acosta, Manuel; Esteve, María; García-Sánchez, Valle; Gomollón, Fernando; Guardiola, Jordi; Hinojosa, Joaquin; Martín Arranz, Maria-Dolores; Minguez, Miguel; Taxonera, Carlos; Vera, Isabel

2016-03-01

There is still uncertainty about what constitutes the best therapeutic practice in ulcerative colitis (UC). The purpose of the "UC Horizons Project" was to raise a series of questions regarding the management of UC to provide responses based on the best scientific evidence available. The 11 members of the scientific committee prepared draft answers to the 10 questions from available evidence after a literature search. A total of 48 Spanish gastroenterology specialists nationwide participated in the project. The national meeting discussed the 10 issues in working groups and reached consensus regarding the recommendations by anonymous, interactive vote following the Delphi methodology. Final answers were developed, based on evidence and clinical experience of the participants. All the recommendations achieved a high level of agreement in the plenary vote, although the quality of the evidence was markedly heterogeneous. The lowest percentage of agreement corresponded to the questions with the weakest level of evidence, highlighting the necessity of conducting further studies in these areas. The recommendations focused on (1) aminosalicylates therapy (regarding dose and appropriateness of coadministration with thiopurines), (2) corticosteroid therapy (regarding dose and route of administration), (3) thiopurine treatment (regarding indications and possibility of withdrawal), (4) anti-tumor necrosis factor therapy (regarding appropriateness of combination with thiopurines, intensification, or discontinuation of treatment), and (5) colorectal cancer (regarding risk and time trends). The UC Horizons Project raised a series of eminently practical questions about the management of UC and provided responses based on the best scientific evidence available.

Back to the Future: Freshman Admissions at the University of California, 1994 to the Present and Beyond. Research & Occasional Paper Series: CSHE.4.14

ERIC Educational Resources Information Center

Geiser, Saul

2014-01-01

The past five years have seen unprecedented changes in freshman admissions at the University of California, reflecting steep cuts in state funding that UC sustained during that period as well as changes in UC's definition of who is eligible to enter the university. The number of California applicants who were "not" admitted to the UC…

Laser Induced Patterning of Transparent Ceramics and Metallic Thin Films for Photonic and Sensing Applications

DTIC Science & Technology

2014-01-31

Department Chair Mechanical Engineering UC Riverside gaguilar@engr.ucr.edu Javier Garay Program Chair Materials and Engineering UC Riverside...Students: Miroslava Cano-Lara (PhD CICESE) # Yasmin Esqueda-Barron ( MSc , PhD CICESE)* Gabriel Castillo-Vega ( MSc CICESE, PhD USAL) # Rene Rodriguez...Beltran ( MSc , CICESE) # Lidia Sanchez-Hernandez (BSc UAEM) # Adela Reyes-Contreras (BSc UAEM) # Postdocs: Israel Perez (Postdoc, 4 months) USA

Seven Years Later. Education and Work: A 1977 Survey of Students Who Entered the University of California in 1970.

ERIC Educational Resources Information Center

Pace, C. Robert; Rosenstein, Carolyn

Based on a national followup survey of college freshmen conducted by the Higher Education Research Institute, the University of California (UC) respondents were singled out for examination. In the spring of 1977, the national survey was sent to freshmen who had entered college in the fall of 1970. The UC sample of 4,240 freshmen attended either…

Induction of the tumor-suppressor p16(INK4a) within regenerative epithelial crypts in ulcerative colitis.

PubMed

Furth, Emma E; Gustafson, Karen S; Dai, Charlotte Y; Gibson, Steven L; Menard-Katcher, Paul; Chen, Tina; Koh, Jim; Enders, Greg H

2006-06-01

p16(INK4a) is a major tumor-suppressor protein, but its regulation and settings of fuction remain poorly understood. To explore the notion that p16 is induced in vivo in response to replicative stress, we examined p16 expression in tissues from human ulcerative colitis (UC; n = 25) and normal controls (n = 20). p16 was expressed strongly in UC-associated neoplasms (n = 17), as seen previously in sporadic colonic neoplasms. In non-neoplastic UC epithelium, p16 was expressed in 33% of crypts (the proliferative compartment) compared to < 1% of normal controls. p16 expression did not correlate with degree of inflammation but did correlate with the degree of crypt architecture distortion (P = .002)-a reflection of epithelial regeneration. In coimmunofluorescence studies with Ki67, p16 expression was associated with cell cycle arrest (P < .001). Both UC and normal crypts displayed evidence for the activation of the DNA damage checkpoint pathway, and p16 was induced in primary cultures of normal epithelial cells by ionizing irradiation (IR). However, induction by IR displayed delayed kinetics, implying that p16 is not an immediate target of the checkpoint pathway. These findings support a model in which p16 is induced as an "emergency brake" in cells experiencing sustained replicative stress.

From intestinal stem cells to inflammatory bowel diseases

PubMed Central

Gersemann, Michael; Stange, Eduard Friedrich; Wehkamp, Jan

2011-01-01

The pathogenesis of both entities of inflammatory bowel disease (IBD), namely Crohn’s disease (CD) and ulcerative colitis (UC), is still complex and under investigation. The importance of the microbial flora in developing IBD is beyond debate. In the last few years, the focus has changed from adaptive towards innate immunity. Crohn’s ileitis is associated with a deficiency of the antimicrobial shield, as shown by a reduced expression and secretion of the Paneth cell defensin HD5 and HD6, which is related to a Paneth cell differentiation defect mediated by a diminished expression of the Wnt transcription factor TCF4. In UC, the protective mucus layer, acting as a physical and chemical barrier between the gut epithelium and the luminal microbes, is thinner and in part denuded as compared to controls. This could be caused by a missing induction of the goblet cell differentiation factors Hath1 and KLF4 leading to immature goblet cells. This defective Paneth and goblet cell differentiation in Crohn’s ileitis and UC may enable the luminal microbes to invade the mucosa and trigger the inflammation. The exact molecular mechanisms behind ileal CD and also UC must be further clarified, but these observations could give rise to new therapeutic strategies based on a stimulation of the protective innate immune system. PMID:21912468

Prevalence of inflammatory bowel disease related dysplasia and cancer in 1500 colonoscopies from a referral center in northwestern Greece.

PubMed

Katsanos, Konstantinos H; Stamou, Paraskevi; Tatsioni, Athina; Tsianos, Vasileios E; Zoumbas, Stefanos; Kavvadia, Spyridoula; Giga, Anna; Vagias, Ioannis; Christodoulou, Dimitrios K; Tsianos, Epameinondas V

2011-02-01

To report on the prevalence of inflammatory bowel disease (IBD) related intestinal dysplasia and cancer in northwestern Greece. Single referral center retrospective study. The policy among all gastroenterologists of the area regarding medical treatment, patient follow up and bowel surveillance strategies including risk factors is the same. We analyzed 1494 colonoscopies from 696 consecutive IBD patients (494 UC). The follow up time [median, IQR] was 16 [8-23] years and the age at diagnosis was 28 [21-49] years. The number of patient years at risk was 16.219. Disease location for UC was: pancolitis 761 (59%), left sided colitis 455 (35%), and proctitis 69 (6%). Disease location for CD was: colitis 142 (66%), ileitis 45 (22%) and ileocolitis 21 (10%). Disease activity was in remission in 1240 (83%) of them. In total, 498 (72%) patients were on mesalazine, 169(24%) on immunosuppression and 29 (4%) on biologicals. Biopsies were taken randomly in 1429 (96%) endoscopies and were targeted in 65 (4%) of them. We recorded 69 (9.4%) cases with dysplasia and 10 (1.4%) cases with intestinal cancer (9 in UC). No difference was found for dysplasia and cancer in patients who followed up for 10-20 years or for more than 20 years. The prevalence of dysplasia and cancer is increased in UC compared to CD but the prevalence of high-grade dysplasia is comparatively low. Intestinal cancer prevalence is increasing after the first decade and then practically remains stable. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Genetic and Transcriptomic Bases of Intestinal Epithelial Barrier Dysfunction in Inflammatory Bowel Disease.

PubMed

Vancamelbeke, Maaike; Vanuytsel, Tim; Farré, Ricard; Verstockt, Sare; Ferrante, Marc; Van Assche, Gert; Rutgeerts, Paul; Schuit, Frans; Vermeire, Séverine; Arijs, Ingrid; Cleynen, Isabelle

2017-10-01

Intestinal barrier defects are common in patients with inflammatory bowel disease (IBD). To identify which components could underlie these changes, we performed an in-depth analysis of epithelial barrier genes in IBD. A set of 128 intestinal barrier genes was selected. Polygenic risk scores were generated based on selected barrier gene variants that were associated with Crohn's disease (CD) or ulcerative colitis (UC) in our study. Gene expression was analyzed using microarray and quantitative reverse transcription polymerase chain reaction. Influence of barrier gene variants on expression was studied by cis-expression quantitative trait loci mapping and comparing patients with low- and high-risk scores. Barrier risk scores were significantly higher in patients with IBD than controls. At single-gene level, the associated barrier single-nucleotide polymorphisms were most significantly enriched in PTGER4 for CD and HNF4A for UC. As a group, the regulating proteins were most enriched for CD and UC. Expression analysis showed that many epithelial barrier genes were significantly dysregulated in active CD and UC, with overrepresentation of mucus layer genes. In uninflamed CD ileum and IBD colon, most barrier gene levels restored to normal, except for MUC1 and MUC4 that remained persistently increased compared with controls. Expression levels did not depend on cis-regulatory variants nor combined genetic risk. We found genetic and transcriptomic dysregulations of key epithelial barrier genes and components in IBD. Of these, we believe that mucus genes, in particular MUC1 and MUC4, play an essential role in the pathogenesis of IBD and could represent interesting targets for treatment.

Randomised clinical trial: evaluation of the efficacy of mesalazine (mesalamine) suppositories in patients with ulcerative colitis and active rectal inflammation -- a placebo-controlled study.

PubMed

Watanabe, M; Nishino, H; Sameshima, Y; Ota, A; Nakamura, S; Hibi, T

2013-08-01

Mesalazine suppositories are recommended and widely used as the standard therapy in induction and maintenance of remission for proctitis. To evaluate the efficacy of mesalazine suppositories in patients with ulcerative colitis (UC) and rectal inflammation; and in patient groups categorised by the extent of lesions. This study was a phase III multicentre, randomised, double-blind, placebo-controlled, parallel-group study. Mild-to-moderate UC patients with rectal inflammation were randomly assigned either a 1 g mesalazine or placebo suppository. The suppository was administered in the rectum once daily for 4 weeks. The primary efficacy end point was the rate of endoscopic remission (mucosal score of 0 or 1) after 4 weeks. The endoscopic remission rates after 4 weeks in the mesalazine and placebo suppository groups were 81.5% and 29.7%, respectively, and the superiority of mesalazine to placebo was confirmed (P < 0.0001, chi-squared test). For proctitis, the endoscopic remission rates after 4 weeks were 83.8% and 36.1% in the mesalazine and placebo suppository groups, respectively, and the corresponding rates for all other types of UC were 78.6% and 21.4%, respectively. The superiority of mesalazine to placebo was confirmed in both subgroups (P < 0.0001, Fisher's exact test). The percentage of patients without bleeding was significantly higher in the mesalazine group than the placebo group from Day 3 of treatment (P = 0.0001, Fisher's exact test). The effectiveness of mesalazine suppositories in all types of UC patients with rectal inflammation was confirmed for the first time in a double-blind, placebo-controlled, parallel-group study (JapicCTI- 111421). © 2013 John Wiley & Sons Ltd.

ZnMoO4:Er3+,Yb3+ phosphor with controlled morphology and enhanced upconversion through alkali ions doping

NASA Astrophysics Data System (ADS)

Luitel, Hom Nath; Chand, Rumi; Watari, Takanori

2018-04-01

A facile hydrothermal method was used to synthesize ZnMoO4:Er3+,Yb3+ nanoparticles. The shapes and sizes of the nanoparticles were well tuned by simply monitoring the pH of the starting solution. Microballs consisting of agglomerated nanograins were observed at strong acidic condition. At mild pH, plates and rectangular particles were realized, while strong basic pH stabilized rods. Further increasing pH to extremely basic conditions (pH > 13), rods changed to fragile hairy structures. The nucleation and growth mechanism of nanograins to form different morphology nanoparticles were studied and illustrated. XRD patterns confirmed well crystalline, triclinic structure despite small amount of aliovalent metal ions doping. Under 980 nm excitation, the ZnMoO4:Er3+,Yb3+ nanophosphor exhibited strong green (centered at 530 and 560 nm) and weak red (centered at 660 nm) upconversion (UC) emissions. Substitution of part of the Zn2+ ions by monovalent alkali ions intensified the UC emission intensities drastically. The order of intensification was K+>Na+>Li+>Rb+>no alkali ion. When Zn2+ ions were substituted with 10 at% K+ ions, the green and red UC emissions intensities increased by more than 50 and 15 folds, respectively. Time dependent measurements confirmed efficient Yb to Er energy transfer in the ZnMoO4:Er3+,Yb3+,K+ nanophosphor. The optimized ZnMoO4:Er3+,Yb3+,K+ phosphor exhibited intense UC emissions with 0.31% quantum yield. The upconverted light is visible to naked eye while pumping by laser of less than 1 mW power and opens door for variety of novel applications.

Magnetic and upconverted luminescent properties of multifunctional lanthanide doped cubic KGdF4 nanocrystals.

PubMed

Yang, L W; Zhang, Y Y; Li, J J; Li, Y; Zhong, J X; Chu, Paul K

2010-12-01

Lanthanide (Ln3+) doped KGdF4 (Ln=Yb3+, Er3+, Ho3+, Tm3+) nanocrystals with a mean diameter of approximately 12 nm were synthesized by a hydrothermal method using oleic acid as a stabilizing agent at 180 °C. The nanocrystals crystallize in the cubic phase as α-NaGdF4. When excited by a 980 nm laser, these Ln3+ doped nanocrystals exhibit multicolor up-conversion (UC) emissions in red, yellow, blue and white. The calculated color coordinates demonstrate that white UC emission (CIE-X=0.352, CIE-Y=0.347) can be obtained by varying the dopant concentrations in the Yb3+/Ho3+/Tm3+ triply-doped nanocrystals to yield different RGB emission intensities. The measured field dependence of magnetization (M-H curves) of the KGdF4 nanocrystals shows their paramagnetic characteristics that can be ascribed to the non-interacting localized nature of the magnetic moment of Gd3+ ions. Moreover, low temperature thermal treatment can enhance UC properties, magnetization and magnetic mass susceptibility of Ln3+ doped KGdF4 nanocrystals. The multifunctional Ln3+ doped KGdF4 nanocrystals have potential applications in color displays, bioseparation, and optical-magnetic dual modal nanoprobes in biomedical imaging.

Magnetic and upconverted luminescent properties of multifunctional lanthanide doped cubic KGdF4nanocrystals

NASA Astrophysics Data System (ADS)

Yang, L. W.; Zhang, Y. Y.; Li, J. J.; Li, Y.; Zhong, J. X.; Chu, Paul K.

2010-12-01

Lanthanide (Ln3+) doped KGdF4 (Ln = Yb3+, Er3+, Ho3+, Tm3+) nanocrystals with a mean diameter of approximately 12 nm were synthesized by a hydrothermal method using oleic acid as a stabilizing agent at 180 °C. The nanocrystals crystallize in the cubic phase as α-NaGdF4. When excited by a 980 nm laser, these Ln3+ doped nanocrystals exhibit multicolor up-conversion (UC) emissions in red, yellow, blue and white. The calculated color coordinates demonstrate that white UC emission (CIE-X = 0.352, CIE-Y = 0.347) can be obtained by varying the dopant concentrations in the Yb3+/Ho3+/Tm3+ triply-doped nanocrystals to yield different RGB emission intensities. The measured field dependence of magnetization (M-H curves) of the KGdF4nanocrystals shows their paramagnetic characteristics that can be ascribed to the non-interacting localized nature of the magnetic moment of Gd3+ ions. Moreover, low temperature thermal treatment can enhance UC properties, magnetization and magnetic mass susceptibility of Ln3+ doped KGdF4nanocrystals. The multifunctional Ln3+ doped KGdF4nanocrystals have potential applications in color displays, bioseparation, and optical-magnetic dual modal nanoprobes in biomedical imaging.

Highly efficient saturated visible up-conversion photoluminescent Y 2 O 3 :Er 3+ microspheres pumped with a 1.55 μm laser diode

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Jinbo; Wu, Lili; Zhang, Chuanjiang

2017-01-01

Highly efficient saturation up-conversion (UC) luminescent Y2O3:Er3+ microspheres have been successfully prepared via a hydrothermal-homogeneous precipitation method. Bright visible luminescence can be clearly seen with a 1.55 mu m laser diode excitation power as low as similar to 0.03 W cm(-2). The up-conversion (UC) emission spectra indicate that the strongest red emission with a peak situated at similar to 660 nm originated from the I-4(9/2) -> I-4(15/2) transition of Er3+. The peaks situated at similar to 520 and 550 nm can be assigned to the transition from H-2(11/2)/S-4(3/2) state to the ground state of Er3+. The high efficient saturation up-conversionmore » emission is related to the highly crystalline structure. These results indicate a new way to enhance UC radiation in rare-earth ion-doped materials prepared using a hydrothermal-homogeneous precipitation method.« less

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation].

PubMed

Lopès, P; Rimbault, F; Scheffler, M; André, C; Cappelletti, M-C; Marès, P

2014-11-01

In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Thermochronology of the Cornubian batholith in southwest England: Implications for pluton emplacement and protracted hydrothermal mineralization

NASA Astrophysics Data System (ADS)

Chesley, J. T.; Halliday, A. N.; Snee, L. W.; Mezger, K.; Shepherd, T. J.; Scrivener, R. C.

1993-04-01

The metalliferous ore deposits of southwest England are associated with biotite-muscovite granites that intruded upper Paleozoic sediments and volcanic rocks at the end of the Hercynian Orogeny. The hydrothermal mineralization can be subdivided into four stages: (1) exoskarns (2) high-temperature tin and tungsten oxide-bearing sheeted greisen bordered veins and Sn-bearing tourmaline veins and breccias (3) polymetallic quartz-tourmaline-chlorite-sulfide-fluorite-bearing fissure veins, which represent the main episode of economic mineralization (4) late-stage, low-temperature polymetallic fluorite veins. U-Pb dating of monazite and xenotime and 40Ar /39Ar dating of muscovite were used to determine emplacement ages and cooling times for individual plutons within the Cornubian batholith, as well as separate intrusive phases within the plutons. In addition, 40Ar /39Ar ages from hornblende and secondary muscovite and Sm-Nd isochron ages from fluorite were employed to determine the relationship between pluton emplacement and different stages of mineralization. The U-Pb ages indicate that granite magmatism was protracted from ~300 Ma down to ~275 Ma with no evidence of a major hiatus. There is no systematic relation between the age of a pluton and its location within the batholith. The U-Pb ages for separate granite phases within a single pluton are resolvable and indicate that magma emplacement within individual plutons occurred over periods of as much as 4.5 myrs. Felsic porphyry dike emplacement was coeval with plutonism, but continued to ~270 Ma. The geochronologic data suggest that the Cornubian batholith originated from repeated melting events over 30 myrs and was formed by a series of small coalescing granitic bodies. Cooling rates of the main plutons are unrelated to emplacement age, but decrease from the southwest to the northeast from ~210°C myr -1 to ~60°C myr -1 with a mean of 100°C myr -1. These slow cooling rates appear to reflect the addition of heat from multiple intrusive episodes. The mineralization history is distinct for each pluton and ranges from coeval with, to up to 40 myrs younger than the cooling age for the host pluton. Stage 2 mineralization is broadly synchronous with the emplacement of granite magmas, is dominated by fluids expelled during crystallization, and may be repeated by the emplacement of younger magmas within the same pluton. Sm-Nd isochrons for fluorite from stage 3 polymetallic mineralization give ages of 259 ± 7, 266 ± 3 and 267 ± 12 Ma, postdating stage 2 mineralization by up to 25 myrs within the same deposit. The similarity in age of the main polymetallic mineralization hosted by the oldest and youngest plutons, suggests that this stage of mineralization is unlikely to be related to hydrothermal circulation driven by the emplacement and cooling of the host granite. The mineralization is more likely the product of regional hydrothermal circulation driven by heat from the emplacement and crystallization of younger buried pulses of magma.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

PubMed

Merra, Giuseppe; Gasbarrini, Giovanni; Laterza, Lucrezia; Pizzoferrato, Marco; Poscia, Andrea; Scaldaferri, Franco; Arena, Vincenzo; Fiore, Francesca; Cittadini, Achille; Sgambato, Alessandro; Franceschi, Francesco; Gasbarrini, Antonio

2012-09-28

To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

PubMed Central

Merra, Giuseppe; Gasbarrini, Giovanni; Laterza, Lucrezia; Pizzoferrato, Marco; Poscia, Andrea; Scaldaferri, Franco; Arena, Vincenzo; Fiore, Francesca; Cittadini, Achille; Sgambato, Alessandro; Franceschi, Francesco; Gasbarrini, Antonio

2012-01-01

AIM: To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. METHODS: Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn’s disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. RESULTS: All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. CONCLUSION: PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients. PMID:23049215

Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis

PubMed Central

Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

2014-01-01

AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also showed that UC patients had higher serum IL-17 levels than healthy controls (SMD = 5.95, 95%CI: 4.25-7.65, P < 0.001). Furthermore, serum IL-17 levels significantly correlated with the severity of UC (moderate vs mild: SMD = 2.59, 95%CI: 0.03-5.16, P < 0.05; severe vs mild: SMD = 7.09, 95%CI: 3.96-10.23, P < 0.001; severe vs moderate: SMD = 5.84, 95%CI: 5.09-6.59, P < 0.001). The NOS score was ≥ 5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Neither the Begger’s funnel plots nor Egger’s test displayed strong statistical evidence for publication bias (IL-17A/F genetic polymorphisms: t = -2.60, P = 0.019; serum IL-17 levels: t = -1.54, P = 0.141). CONCLUSION: The findings strongly suggest that IL-17A/F genetic polymorphisms and serum IL-17 levels contribute to the development and progression of UC. PMID:25400476

Managing ulcerative colitis in remission phase: usefulness of Casperome®, an innovative lecithin-based delivery system of Boswellia serrata extract.

PubMed

Pellegrini, L; Milano, E; Franceschi, F; Belcaro, G; Gizzi, G; Feragalli, B; Dugall, M; Luzzi, R; Togni, S; Eggenhoffner, R; Giacomelli, L

2016-06-01

Boswellia serrata extracts (BSE) have been traditionally used for the treatment of several inflammatory diseases. The aim of this study was to evaluate the efficacy of a novel delivery form of BSE (Casperome®) in Ulcerative Colitis (UC) during minimally symptomatic remission phase. In this open-label, observational, registry study, informed participants with UC in remission phase (n = 43) freely decided to receive the oral daily Casperome® supplementation (n = 22) or no supplementation (n = 21) for 4 weeks. Several parameters associated with minimally symptomatic UC in remission were evaluated at the inclusion and the end of the study. A significant beneficial effect of Casperome® was observed for all the parameters evaluated, namely: diffuse intestinal pain, evident and occult blood in stools, bowel movements and cramps, watery stools, malaise, anemia, rectal involvement, number of white blood cells as well as need for concomitant drugs and medical attention. Faecal concentration of calprotectin, a marker of bowel inflammation, resulted ameliorated in Casperome® supplemented patients. Our study showed that Casperome® supplementation attenuates symptoms associated with mild UC in remission, reducing the use of drugs and medical consultations. Therefore, our study suggests that Casperome® supplementation could represent a promising alternative approach to manage minimally symptomatic UC and maintain the remission phase.

The safety of vedolizumab for the treatment of ulcerative colitis.

PubMed

Novak, Gregor; Hindryckx, Pieter; Khanna, Reena; Jairath, Vipul; Feagan, Brian G

2017-04-01

Vedolizumab is a humanized monoclonal antibody to the α4β7-integrin that blocks lymphocyte trafficking to the gut and is approved for treatment of patients with moderate-to-severe ulcerative colitis (UC). The gut-selective mechanism of action has the potential to improve vedolizumab's safety profile compared to other approved biologic drugs. Areas covered: We review the mechanism of action, efficacy and safety of vedolizumab treatment for UC. The positioning of vedolizumab in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of vedolizumab restricts immunosuppressive effects to the gut. Vedolizumab is efficacious as induction and maintenance therapy in UC patients who are naïve or refractory to tumor necrosis factor antagonists. No clinically important safety signals have been identified. Infusion reactions are reported in <5% of cases. The rates of adverse events (AE), serious AEs, and serious infections were not different between patients treated with placebo and those who received vedolizumab in a pooled analysis of six randomized controlled trials. Rates of malignancy and mortality in vedolizumab-exposed patients are similar to those of the general UC patient population. Progressive multifocal leukoencephalopathy has not been observed. Vedolizumab is a safe and effective therapy for UC with a unique mechanism of action.

The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis.

PubMed

Peng, Jiang-Chen; Shen, Jun; Zhu, Qi; Ran, Zhi-Hua

2015-01-01

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.

From Crustal Anatexis to Pluton Emplacement: High-Precision Zircon Geochronology Reveals the Thermal History of the Larderello-Travale Geothermal System (Italy)

NASA Astrophysics Data System (ADS)

Farina, F.; Dini, A.; Ovtcharova, M.; Davies, J.; Bouvier, A. S.; Baumgartner, L. P.; Caricchi, L.; Schaltegger, U.

2017-12-01

Late Miocene to recent post-collisional extension in Tuscany (Italy) led to the emplacement of shallow-level granitic plutons and to the eruption of small rhyolitic bodies. The intrusion of peraluminous two-mica and tourmaline-bearing granites triggered the formation of the steam-dominated Larderello-Travale geothermal system. In this study, zircon crystals from granite samples obtained from drill holes at 3.0-4.5 km depth were investigated by combining in-situ oxygen isotopes analysis and high-precision CA-ID-TIMS U-Pb age determinations to gain insight into the nature of the magmatic heat source fuelling the geothermal field. Magmatic zircon crystals display δ18O values ranging from 8.6 to 13.5‰ and crystals from individual samples exhibit inter- and intra-grain oxygen isotope variability exceeding 3‰. The geochronological data indicates the existence of three magmatic pulses with ages between 3.637 ± 0.008 and 1.671 ± 0.004 Ma. More importantly, zircon crystals from individual samples exhibit an age spread as large as 200-400 ky. This age dispersion, which is more than one order of magnitude greater than the uncertainty on a single date, suggest that most of the zircon did not crystallize at the emplacement level, but within isolated and isotopically distinct magma batches before large-scale homogenization in a magmatic reservoir at depth. The rate of assembly and final volume of this reservoir is estimated using the distribution of precise U-Pb zircon dates following the approach of Caricchi et al. (2014). Thermal modelling indicates that the heat flow at the surface in the geothermal field cannot be sustained by the inferred reservoir or by heat advection from the mantle. Our data suggest the existence of a younger shallow-level intrusion, whose occurrence also accounts for the existence of confined magmatic fluids at the top of the Larderello-Travale intrusion. We conclude that a multi-disciplinary approach, integrating high-precision zircon dating, in-situ oxygen isotopes and thermal modelling can be used to resolve the thermal structure of the crust in active geothermal systems. Ref: Caricchi et al., (2014). Nature, 511, 457-461. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 701494.

Comparison of ultrasonic energy, bipolar thermal energy, and vascular clips for the hemostasis of small-, medium-, and large-sized arteries.

PubMed

Harold, K L; Pollinger, H; Matthews, B D; Kercher, K W; Sing, R F; Heniford, B T

2003-08-01

Advanced laparoscopic procedures have necessitated the development of new technology for vascular control. Suture ligation can be time-consuming and cumbersome during laparoscopic dissection. Titanium clips have been used for hemostasis, and recently plastic clips and energy sources such as ultrasonic coagulating shears and bipolar thermal energy devices have become popular. The purpose of this study was to compare the bursting pressure of arteries sealed with ultrasonic coagulating shears (UCS), electrothermal bipolar vessel sealer (EBVS), titanium laparoscopic clips (LCs), and plastic laparoscopic clips (PCs). In addition, the spread of thermal injury from the UCS and the EBVS was compared. Arteries in three size groups (2-3, 4-5 and 6-7 mm) were harvested from freshly euthanized pigs. Each of the four devices was used to seal 16 specimens from each size group for burst testing. A 5-Fr catheter was placed into the open end of the specimen and secured with a purse-string suture. The catheter was connected to a pressure monitor and saline was infused until there was leakage from the sealed end. This defined the bursting pressure in mmHg. The ultrasonic shears and bipolar thermal device were used to seal an additional 8 vessels in each size group, which were sent for histologic examination. These were examined with hematoxylin and eosin stains, and the extent of thermal injury, defined by coagulation necrosis, was measured in millimeters. Analysis of variance was performed and, where appropriate, a Tukey's test was also performed. The EBVS's mean burst pressure was statistically higher than that of the UCS at 4 or 5 mm (601 vs 205 mmHg) and 6 or 7 mm (442 vs 175 mmHg). EBVS had higher burst pressures for the 4 or 5-mm group (601 mmHg) and 6 or 7-mm group (442 mmHg) compared with its pressure at 2 or 3 mm (128 mmHg) ( p = 0.0001). The burst pressures of the UCS and EBVS at 2 or 3 mm were not significantly different. Both clips were statistically stronger than the thermal devices except at 4 or 5 mm, in which case the EBVS was as strong as the LC (601 vs 593 mmHg). The PC and LC were similar except at 4 or 5 mm, where the PC was superior (854 vs 593 mmHg). The PC burst pressure for 4 or 5 mm (854 mmHg) was statistically higher than that for vessels 2 or 3 mm (737 mmHg) but not different from the 6 or 7 mm pressure (767 mmHg). Thermal spread was not statistically different when comparing EBVS and UCS at any size (EBVS mean = 2.57 mm vs UCS mean = 2.18 mm). Both the PC and LC secured all vessel sizes to well above physiologic levels. The EBVS can be used confidently in vessels up to 7 mm. There is no difference in the thermal spread of the LigaSure vessel sealer and the UCS.

Deep Borehole Field Test Research Activities at LBNL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobson, Patrick; Tsang, Chin-Fu; Kneafsey, Timothy

The goal of the U.S. Department of Energy Used Fuel Disposition’s (UFD) Deep Borehole Field Test is to drill two 5 km large-diameter boreholes: a characterization borehole with a bottom-hole diameter of 8.5 inches and a field test borehole with a bottom-hole diameter of 17 inches. These boreholes will be used to demonstrate the ability to drill such holes in crystalline rocks, effectively characterize the bedrock repository system using geophysical, geochemical, and hydrological techniques, and emplace and retrieve test waste packages. These studies will be used to test the deep borehole disposal concept, which requires a hydrologically isolated environment characterizedmore » by low permeability, stable fluid density, reducing fluid chemistry conditions, and an effective borehole seal. During FY16, Lawrence Berkeley National Laboratory scientists conducted a number of research studies to support the UFD Deep Borehole Field Test effort. This work included providing supporting data for the Los Alamos National Laboratory geologic framework model for the proposed deep borehole site, conducting an analog study using an extensive suite of geoscience data and samples from a deep (2.5 km) research borehole in Sweden, conducting laboratory experiments and coupled process modeling related to borehole seals, and developing a suite of potential techniques that could be applied to the characterization and monitoring of the deep borehole environment. The results of these studies are presented in this report.« less

Involvement of WNT Signaling in the Regulation of Gestational Age-Dependent Umbilical Cord-Derived Mesenchymal Stem Cell Proliferation

PubMed Central

Shono, Akemi; Yoshida, Makiko; Yamana, Keiji; Thwin, Khin Kyae Mon; Kuroda, Jumpei; Kurokawa, Daisuke; Koda, Tsubasa; Nishida, Kosuke; Ikuta, Toshihiko; Mizobuchi, Masami; Taniguchi-Ikeda, Mariko

2017-01-01

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation. PMID:29138639

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, R.A.; Cron, J.

This design analysis has shown that, on a conceptual level, the emplacement of drip shields is feasible with current technology and equipment. A plan for drip shield emplacement was presented using a Drip Shield Transporter, a Drip Shield Emplacement Gantry, a locomotive, and a Drip Shield Gantry Carrier. The use of a Drip Shield Emplacement Gantry as an emplacement concept results in a system that is simple, reliable, and interfaces with the numerous other exising repository systems. Using the Waste Emplacement/Retrieval System design as a basis for the drip shield emplacement concept proved to simplify the system by using existingmore » equipment, such as the gantry carrier, locomotive, Electrical and Control systems, and many other systems, structures, and components. Restricted working envelopes for the Drip Shield Emplacement System require further consideration and must be addressed to show that the emplacement operations can be performed as the repository design evolves. Section 6.1 describes how the Drip Shield Emplacement System may use existing equipment. Depending on the length of time between the conclusion of waste emplacement and the commencement of drip shield emplacement, this equipment could include the locomotives, the gantry carrier, and the electrical, control, and rail systems. If the exisiting equipment is selected for use in the Drip Shield Emplacement System, then the length of time after the final stages of waste emplacement and start of drip shield emplacement may pose a concern for the life cycle of the system (e.g., reliability, maintainability, availability, etc.). Further investigation should be performed to consider the use of existing equipment for drip shield emplacement operations. Further investigation will also be needed regarding the interfaces and heat transfer and thermal effects aspects. The conceptual design also requires further design development. Although the findings of this analysis are accurate for the assumptions made, further refinements of this analysis are needed as the project parameters change. The designs of the drip shield, the Emplacement Drift, and the other drip shield emplacement equipment all have a direct effect on the overall design feasibility.« less

Blytheville AFB, Arkansas, Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F.

DTIC Science & Technology

1987-10-01

A USAFETAC Air Weather Service (MAC) 3SSTAe’ REVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS BLYTHEVILLE AFB AR MSC 1723408 IC N 35 58 W...I IE C It I 1-3 4-b I-Il It 1 7-2 1 2 - 4- UC 4 1-4 7 4F - U S5 1(IA " SAN I9 I 1. . 217 2.0 .i D I .lF I .2 1.? .7 1 .1 1 .2 .2- 0.1I 7 I AIR4 3tf...o o o , . . .. . . .o ..oo.o.. 17-, -7 5C.-. 1-7 ’-, F t tt 71*1. Li I I L C1.2 4 t 7 1L 1 4 uC I* I. A .o o.....oo. oo ~ oo o ooo ...... ...... .o. o

Extending the horizon in chronic heart failure: effects of multidisciplinary, home-based intervention relative to usual care.

PubMed

Inglis, Sally C; Pearson, Sue; Treen, Suzette; Gallasch, Tamara; Horowitz, John D; Stewart, Simon

2006-12-05

The long-term impact of chronic heart failure management programs over the typical life span of affected individuals is unknown. The effects of a nurse-led, multidisciplinary, home-based intervention (HBI) in a typically elderly cohort of patients with chronic heart failure initially randomized to either HBI (n=149) or usual postdischarge care (UC) (n=148) after a short-term hospitalization were studied for up to 10 years of follow-up (minimum 7.5 years of follow-up). Study end points were all-cause mortality, event-free survival (event was defined as death or unplanned hospitalization), recurrent hospital stay, and cost per life-year gained. Median survival in the HBI cohort was almost twice that of UC (40 versus 22 months; P<0.001), with fewer deaths overall (HBI, 77% versus 89%; adjusted relative risk, 0.74; 95% CI, 0.53 to 0.80; P<0.001). HBI was associated with prolonged event-free survival (median, 7 versus 4 months; P<0.01). HBI patients had more unplanned readmissions (560 versus 550) but took 7 years to overtake UC; the rates of readmission (2.04+/-3.23 versus 3.66+/-7.62 admissions; P<0.05) and related hospital stay (14.8+/-23.0 versus 28.4+/-53.4 days per patient per year; P<0.05) were significantly lower in the HBI group. HBI was associated with 120 more life-years per 100 patients treated compared with UC (405 versus 285 years) at a cost of 1729 dollars per additional life-year gained when we accounted for healthcare costs including the HBI. In altering the natural history of chronic heart failure relative to UC (via prolonged survival and reduced frequency of recurrent hospitalization), HBI is a remarkably cost- and time-effective strategy over the longer term.

[Effect of Electroacupuncture Stimulation of "Guanyuan" (CV 4) and "Zusanli" (ST 36) on Spleen Lymphocytes Treg/Th 17 Immune Balance in Ulcerative Colitis Mice].

PubMed

Wang, Cheng-yu-lin; Zeng, Lin-lan; Geng, Yu; Wang, Xiang; Zhang, He-jiao; Yang, Hui; Wu, Qiao- feng; Yu, Shu-guang

2016-02-01

To observe the effect of electroacupuncture (EA) intervention on spleen T-helper 17 (Th 17) and regulatory T (Treg) cell levels in mice with ulcerative colitis (UC), so as to reveal its mechanisms underlying improvement of UC. METHODS Kunming mice were randomized into control, UC model and EA groups, with 8 mice in each group. The UC model was established by giving the mice with 3% Dextran Sulfate Sodium (DSS) for 5 days. EA (15 Hz/25 Hz, 0.1-0.2 mA) was applied at "Guanyuan" (CV 4) and bilateral "Zusanli" (ST 36, used alternatively) for 10 min, once a day for 5 days. The animals' disease activity index [DAl, = (body weight index score + stool score + bleeding score)/3; 0-4 points] were calculated. The pathological changes of colon tissues were observed by light microscopy after H. E. stain, and spleen Treg (CD⁴⁺ CD²⁵⁺ Foxp³⁺ Treg) and Th 17 (CD³⁺ CD⁸⁺ IL-17⁺ Th 17) lymphocyte levels were determined by flow cytometry. Compared to the control group, the DAl score and the ratio of Th 17/CD⁸⁺ T cells were significantly increased, while the ratio of Treg/CD⁴⁺ T cells obviously decreased in the model group (P < 0.05). After EA intervention, the increased DAI score and the ratio of Th 17/CD⁸⁺ T cells and the decreased Treg/CD⁴⁺ T cells were reversed (P < 0.05), and the inflammatory cell infiltration degree of the colon tissue was attenuated. EA intervention can improve the, UC rats' symptoms of activity state, bloody or viscidity stool and colonic inflammation, probably by regulating the balance between the spleenic Treg and Th 17 lymphocytes.

Chronic Disease Management for Tobacco Dependence

PubMed Central

Joseph, Anne M.; Fu, Steven S.; Lindgren, Bruce; Rothman, Alexander J.; Kodl, Molly; Lando, Harry; Doyle, Brandon; Hatsukami, Dorothy

2014-01-01

Background Tobacco dependence disorder is a chronic relapsing condition, yet treatment is delivered in discrete episodes of care that yield disappointing long-term quit rates. Methods We conducted a randomized controlled trial from June 1, 2004, through May 31, 2009, to compare telephone-based chronic disease management (1 year; longitudinal care [LC]) with evidence-based treatment (8 weeks; usual care [UC]) for tobacco dependence. A total of 443 smokers each received 5 telephone counseling calls and nicotine replacement therapy by mail for 4 weeks. They were then randomized to UC(2 additional calls) or LC(continued counseling and nicotine replacement therapy for an additional 48 weeks). Longitudinal care targeted repeat quit attempts and interim smoking reduction for relapsers. The primary outcome was 6 months of prolonged abstinence measured at 18 months of follow-up. Results At 18 months, 30.2% of LC participants reported 6 months of abstinence from smoking, compared with 23.5% in UC (unadjusted, P=.13). Multivariate analysis showed that LC (adjusted odds ratio, 1.74; 95% CI, 1.08–2.80), quit attempts in past year (1.75; 1.06–2.89), baseline cigarettes per day (0.95; 0.92–0.99), and smoking in the 14- to 21-day interval post-quit (0.23; 0.14–0.38) predicted prolonged abstinence at 18 months. The LC participants who did not quit reduced smoking more than UC participants (significant only at 12 months). The LC participants received more counseling calls than UC participants (mean, 16.5 vs 5.8 calls; P<.001), longer total duration of counseling (283 vs 117 minutes; P<.001), and more nicotine replacement therapy (4.7 vs 2.4 boxes of patches; P<.001). Conclusion A chronic disease management approach increases both short- and long-term abstinence from smoking. Trial Registration clinicaltrials.gov Identifier: NCT00309296 PMID:22123795

High quality polyacrylic acid modified multifunction luminescent nanorods for tri-modality bioimaging, in vivo long-lasting tracking and biodistribution

NASA Astrophysics Data System (ADS)

Yi, Zhigao; Lu, Wei; Liu, Hongrong; Zeng, Songjun

2014-12-01

Polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er upconversion nanorods (denoted as PAA-UCNRs) are demonstrated for tri-modal upconversion (UC) optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI). The hydrophilic PAA-UCNRs were obtained from hydrophobic oleic acid (OA) capped UCNRs (denoted as OA-UCNRs) using a ligand exchange method. The as-prepared UCNRs with a hexagonal phase structure present high monodispersity. These PAA-UCNRs are successfully used as ideal probes for in vivo UC luminescence bioimaging and synergistic X-ray and UC bioimaging. Moreover, X-ray CT imaging reveals that PAA-UCNRs can act as contrast agents for improved detection of the liver and spleen. In addition, a significant signal enhancement in the liver is observed in in vivo MRI, indicating that PAA-UCNRs are ideal T1-weighted MRI agents. More importantly, in vivo long-term tracking based on these PAA-UCNRs in the live mice and the corresponding ex vivo bioimaging of isolated organs also verify the translocation of PAA-UCNRs from the liver to the spleen, and the observed intense UC signals from the feces reveal the biliary excretion mechanism of these UCNRs. These findings contribute to understanding of the translocation and potential route for excretion of PAA-UCNRs, which can provide an important guide for the diagnosis and detection of diseases based on these UCNRs.Polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er upconversion nanorods (denoted as PAA-UCNRs) are demonstrated for tri-modal upconversion (UC) optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI). The hydrophilic PAA-UCNRs were obtained from hydrophobic oleic acid (OA) capped UCNRs (denoted as OA-UCNRs) using a ligand exchange method. The as-prepared UCNRs with a hexagonal phase structure present high monodispersity. These PAA-UCNRs are successfully used as ideal probes for in vivo UC luminescence bioimaging and synergistic X-ray and UC bioimaging. Moreover, X-ray CT imaging reveals that PAA-UCNRs can act as contrast agents for improved detection of the liver and spleen. In addition, a significant signal enhancement in the liver is observed in in vivo MRI, indicating that PAA-UCNRs are ideal T1-weighted MRI agents. More importantly, in vivo long-term tracking based on these PAA-UCNRs in the live mice and the corresponding ex vivo bioimaging of isolated organs also verify the translocation of PAA-UCNRs from the liver to the spleen, and the observed intense UC signals from the feces reveal the biliary excretion mechanism of these UCNRs. These findings contribute to understanding of the translocation and potential route for excretion of PAA-UCNRs, which can provide an important guide for the diagnosis and detection of diseases based on these UCNRs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr05161k

Measurement of in-situ strength using projectile penetration: Tests of a new launching system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hearst, J.R.; Newmark, R.L.; Charest, J.A.

1987-10-01

The Lawrence Livermore National Laboratory has a continuing need to measure rock strength in situ, both for simple prediction of cavity size, and as input to computational models. In a previous report we compared two methods for measuring formation strength in situ: projectile penetration and a cone penetrometer. We determined that the projectile method was more promising for application to our large-diameter (2-4-m) hole environment. A major practical problem has been the development of a launcher and an apparatus for measuring depth of penetration that would be suitable for use in large-diameter holes. We are developing a gas-gun launcher systemmore » that will be capable of measuring both depth of penetration and deceleration of a reusable projectile. The current version of the launcher is trailer-mounted for testing at our Nevada Test Site (NTS) in tunnels and outcrops, but its design is such that it can be readily adapted for emplacement hole use. We test the current launcher on 60-cm cubes of gypsum cement, mixed to provie a range of densities (1.64 to 2.0 g/cc) and strengths (3 to 17 MPa). We compared depth of penetration of a 84-g projectile from a ''Betsy'' seismic gun - traveling on the order of 500 m/s - with the depth of penetration of a 13-kg projectile from the gas gun - traveling on the order of 30 m/s. For projectiles with the same nose size and shape, impacting targets of approximately constant strength, penetration depth was proportional to projectile kinetic energy. The ratio of kinetic energy to penetration depth was approximately proportional to target strength. Tests in tuffs with a wide range of strengths at NTS gave a similar linear relationship between the ratio of kinetic energy to penetration and target strength, and also a linear relationship between deceleration and strength. It appears that penetration can indeed be used as a semiquantitative measure of strength.« less

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers

PubMed Central

2013-01-01

Background UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. Methods This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. Results After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Conclusions Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities. PMID:24153020

Undenatured type II collagen (UC-II®) for joint support: a randomized, double-blind, placebo-controlled study in healthy volunteers.

PubMed

Lugo, James P; Saiyed, Zainulabedin M; Lau, Francis C; Molina, Jhanna Pamela L; Pakdaman, Michael N; Shamie, Arya Nick; Udani, Jay K

2013-10-24

UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects who reported knee pain after participating in a standardized stepmill performance test were randomized to receive placebo (n = 28) or the UC-II (40 mg daily, n = 27) product for 120 days. Joint function was assessed by changes in degree of knee flexion and knee extension as well as measuring the time to experiencing and recovering from joint pain following strenuous stepmill exertion. After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3º vs 74.0 ± 2.2º; p = 0.011) and to baseline (81.0 ± 1.3º vs 73.2 ± 1.9º; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9º vs 73.2 ± 1.9º; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature.

PubMed

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-03-20

Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4(+) lymphocytes, ICAM-1(+) and iNOS(+) microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients.

Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature

PubMed Central

Scioli, Maria Giovanna; Stasi, Maria Antonietta; Passeri, Daniela; Doldo, Elena; Costanza, Gaetana; Camerini, Roberto; Fociani, Paolo; Arcuri, Gaetano; Lombardo, Katia; Pace, Silvia; Borsini, Franco; Orlandi, Augusto

2014-01-01

Objectives: Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. Methods: To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-α-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Results: Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4+ lymphocytes, ICAM-1+ and iNOS+ microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-α-stimulated HIMECs, PLC restored β-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of β-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Conclusions: Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial β-oxidation and function, and reduces mucosal inflammation in UC patients. PMID:24646507

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab.

PubMed

Rosario, Maria; Dirks, Nathanael L; Milch, Catherine; Parikh, Asit; Bargfrede, Michael; Wyant, Tim; Fedyk, Eric; Fox, Irving

2017-11-01

Vedolizumab is a humanized anti-α 4 β 7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α 4 β 7 -mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations. At therapeutic concentrations, vedolizumab primarily undergoes linear elimination. From population pharmacokinetic modeling, the vedolizumab terminal elimination half-life (t ½ β) was estimated to be 25.5 days; linear clearance (CL L ) was similar for patients with UC (0.159 L/day) and CD (0.155 L/day). Extreme low albumin concentrations and extreme high body weight values were potentially clinically important predictors of vedolizumab CL L . Other factors, including concomitant therapy use (methotrexate, azathioprine, mercaptopurine, or aminosalicylates) or prior tumor necrosis factor-α (TNF-α) antagonist use, had no clinically relevant effects on CL L . A positive exposure-efficacy relationship for clinical remission and clinical response was apparent for vedolizumab induction therapy in patients with UC or CD. On average, patients with higher albumin, lower fecal calprotectin (UC only), lower C-reactive protein (CD only), and no prior TNF-α antagonist use had a higher probability of remission. Off drug, 10% of patients with UC or CD were positive for anti-drug antibodies. This article provides a comprehensive review of the clinical pharmacokinetics, pharmacodynamics, exposure-efficacy relationships, and immunogenicity of vedolizumab.

Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis.

PubMed

Shah, Shailja C; Colombel, Jean-Frederic; Sands, Bruce E; Narula, Neeraj

2016-09-01

The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH. We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks. We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy. In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Incidence and Prevalence of Crohn's Disease and Ulcerative Colitis in Olmsted County, Minnesota From 1970 Through 2010.

PubMed

Shivashankar, Raina; Tremaine, William J; Harmsen, W Scott; Loftus, Edward V

2017-06-01

The incidence and prevalence of inflammatory bowel diseases (IBD) continue to increase worldwide. We sought to update incidence rates of Crohn's disease (CD) and ulcerative colitis (UC) in a well-defined United States population, calculating values for Olmsted County, Minnesota through 2010. We also calculated prevalence values. The resources of the Rochester Epidemiology Project were used to identify county residents who were diagnosed with IBD (CD or UC), based on previously set criteria. Those with new diagnoses of CD or UC between 1970 and 2010 were identified as incidence cases, and those meeting diagnostic criteria on January 1, 2011, were identified as prevalence cases. Incidence rates were estimated (adjusted for age and sex to the US white population in 2010). Trends in incidence based on age at diagnosis, sex, and year of diagnosis were evaluated by Poisson regression. The incidence cohort included 410 patients with CD (51% female) and 483 individuals with UC (56% male). Median age of diagnosis was 29.5 years for persons with CD (range, 4-93 years) and 34.9 years for UC (range, 1-91 years). From 2000 through 2010, the adjusted annual incidence rate for CD was 10.7 cases per 100,000 person-years (95% confidence interval [CI], 9.1-12.3 person-years) and for UC was 12.2 per 100,000 (95% CI, 10.5-14.0 person-years). On January 1, 2011, there were 380 residents with CD, with an adjusted prevalence of 246.7 cases per 100,000 persons (95% CI, 221.7-271.8 cases per 100,000 persons), and 435 residents with UC, with an adjusted prevalence of 286.3 (95% CI, 259.1-313.5 cases per 100,000 persons). Male sex was significantly associated with a higher incidence rate of UC, and younger age was significantly associated with a higher incidence rate of CD. Estimated incidence rates for UC and CD in Olmsted County are among the highest in the United States. Extrapolating the adjusted prevalence to the most recent US Census, there could be approximately 1.6 million persons in the United States with IBD. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

PubMed

Masuda, Hideki; Ishii, Ukimoto; Aoki, Nobuhiko; Nakayama, Hisashi; Sato, Fumii; Karube, Hideaki; Suzuki, Shigeru; Kondo, Toshihiko

2002-01-01

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort.

PubMed

Hiroz, Philippe; Vavricka, Stephan R; Fournier, Nicolas; Safroneeva, Ekaterina; Pittet, Valérie; Rogler, Gerhard; Schoepfer, Alain M

2014-10-01

Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Differentiation of human umbilical cord mesenchymal stromal cells into low immunogenic hepatocyte-like cells.

PubMed

Zhao, Qinjun; Ren, Hongying; Li, Xiyuan; Chen, Zhong; Zhang, Xiangyu; Gong, Wei; Liu, Yongjun; Pang, Tianxiang; Han, Zhong Chao

2009-01-01

Mesenchymal stromal cells (MSC) isolated from several human tissues have been known to differentiate into the hepatic lineage in vitro, but the immunogenicity of the differentiated hepatocyte-like cells (DHC) has not been reported. Umbilical cord (UC) MSC are thought to be an attractive cell source for cell therapy because of their young age and low infection rate compared with adult tissue MSC. Hepatic differentiation of UC-MSC was induced with a 2-step protocol. The expressions of hepatic markers were detected by RT-PCR and immunofluorescence staining. Albumin production and urea secretion were measured by ELISA and colorimetric assay respectively. The immunosuppressive properties of DHC was detected by mixed lymphocyte culture. After incubation with specific growth factors, including hepatocyte growth factor (HGF) and basic fibroblast growth factor (bFGF), UC MSC exhibited a high hepatic differentiation ability in an adherent culture condition. The differentiated UC MSC showed hepatocyte-like morphology and expressed several liver-specific markers at gene and protein levels. Furthermore, the DHC exhibited hepatocyte-specific functions, including albumin secretion, low-density lipoprotein uptake and urea production. More importantly, DHC did not express major histocompatibility complex (MHC) II antigen and were not able to induce lymphocyte proliferation in mixed lymphocyte culture, as undifferentiated UC MSC did. Our results indicate that UC MSC are able to differentiate into functional hepatocyte-like cells that still retain their low immunogenicity in vitro. More importantly, DHC incorporated into the parenchyma of liver when transplanted into mice with CCl(4)-induced liver injury. Therefore, DHC may be an ideal source for cell therapy of liver diseases.

Clostridium difficile infection worsens the prognosis of ulcerative colitis

PubMed Central

Negrón, María E; Barkema, Herman W; Rioux, Kevin; De Buck, Jeroen; Checkley, Sylvia; Proulx, Marie-Claude; Frolkis, Alexandra; Beck, Paul L; Dieleman, Levinus A; Panaccione, Remo; Ghosh, Subrata; Kaplan, Gilaad G

2014-01-01

BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC) patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients. OBJECTIVE: To determine whether C difficile infection is associated with undergoing an emergent colectomy and experiencing postoperative complications. METHODS: The present population-based case-control study identified UC patients admitted to Calgary Health Zone hospitals for a flare between 2000 and 2009. C difficile toxin tests ordered in hospital or 90 days before hospital admission were provided by Calgary Laboratory Services (Calgary, Alberta). Hospital records were reviewed to confirm diagnoses and to extract clinical data. Multivariate logistic regression analyses were performed among individuals tested for C difficile to examine the association between C difficile infection and emergent colectomy and diagnosis of any postoperative complications and, secondarily, an infectious postoperative complication. Estimates were presented as adjusted ORs with 95% CIs. RESULTS: C difficile was tested in 278 (58%) UC patients and 6.1% were positive. C difficile infection was associated with an increased risk for emergent colectomy (adjusted OR 3.39 [95% CI 1.02 to 11.23]). Additionally, a preoperative diagnosis of C difficile was significantly associated with the development of postoperative infectious complications (OR 4.76 [95% CI 1.10 to 20.63]). CONCLUSION: C difficile diagnosis worsened the prognosis of UC by increasing the risk of colectomy and postoperative infectious complications following colectomy. Future studies are needed to explore whether early detection and aggressive management of C difficile infection will improve UC outcomes. PMID:25157528

Risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and inflammatory bowel diseases: a meta-analysis.

PubMed

Liang, Meilan; Xu, Xinyu; Gong, Yaoyao; Tang, Yurong; Lin, Lin

2012-09-01

Extensive investigation of the NF-κB1 -94ins/delATTG promoter polymorphism for risk association with ulcerative colitis (UC) and Crohn's disease (CD) risk has yielded conflicting results. The objective of this meta-analysis was to evaluate the risk association between the NF-κB1 -94ins/delATTG promoter polymorphism and UC and CD. All eligible case-control studies of the association of NF-κB1 -94ins/delATTG promoter polymorphism with UC and CD were identified in the Pubmed and Embase databases. From these data, odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Meta-analysis was performed for alleles (D vs. W) and genotypes (DD + WD vs. WW, DD vs. WW + WD, DD vs. WW, WD vs. WW) in a fixed/random effects model. Nine case-control studies that included 4,447 cases (2,631 UC and 1,816 CD) and 2,195 controls were identified. Results indicated increased risk association of D allele carriers with UC (D vs. W: OR = 1.08, 95 % CI = 1.01-1.17, P = 0.03; DD vs. WW + WD: OR = 1.16, 95 % CI = 1.01-1.32, P = 0.04 and DD vs. WW: OR = 1.20, 95 % CI = 1.03-1.39, P = 0.02). No risk association was identified with CD. This meta-analysis indicated that the NF-κB1 -94ins/delATTG promoter polymorphism is a risk factor for UC but not CD.

Similar risk of Depression and Anxiety following surgery or hospitalization for Crohn’s disease and Ulcerative colitis

PubMed Central

Ananthakrishnan, Ashwin N.; Gainer, Vivian S.; Cai, Tianxi; Perez, Raul Guzman; Cheng, Su-Chun; Savova, Guergana; Chen, Pei; Szolovits, Peter; Xia, Zongqi; De Jager, Philip L; Shaw, Stanley; Churchill, Susanne; Karlson, Elizabeth W.; Kohane, Isaac; Perlis, Roy H; Plenge, Robert M.; Murphy, Shawn N.; Liao, Katherine P.

2013-01-01

Introduction Psychiatric co-morbidity is common in Crohn’s disease (CD) and ulcerative colitis (UC). IBD-related surgery or hospitalizations represent major events in the natural history of disease. Whether there is a difference in risk of psychiatric co-morbidity following surgery in CD and UC has not been examined previously. Methods We used a multi-institution cohort of IBD patients without a diagnosis code for anxiety or depression preceding their IBD-related surgery or hospitalization. Demographic, disease, and treatment related variables were retrieved. Multivariate logistic regression analysis was performed to individually identify risk factors for depression and anxiety. Results Our study included a total of 707 CD and 530 UC patients who underwent bowel resection surgery and did not have depression prior to surgery. The risk of depression 5 years after surgery was 16% and 11% in CD and UC respectively. We found no difference in the risk of depression following surgery in CD and UC patients (adjusted OR 1.11, 95%CI 0.84 – 1.47). Female gender, co-morbidity, immunosuppressant use, perianal disease, stoma surgery, and early surgery within 3 years of care predicted depression after CD-surgery; only female gender and co-morbidity predicted depression in UC. Only 12% of the CD cohort had ≥ 4 risk factors for depression, but among them nearly 44% were subsequently received a diagnosis code for depression. Conclusion IBD-related surgery or hospitalization is associated with a significant risk for depression and anxiety with a similar magnitude of risk in both diseases. PMID:23337479

Advanced fuels modeling: Evaluating the steady-state performance of carbide fuel in helium-cooled reactors using FRAPCON 3.4

NASA Astrophysics Data System (ADS)

Hallman, Luther, Jr.

Uranium carbide (UC) has long been considered a potential alternative to uranium dioxide (UO2) fuel, especially in the context of Gen IV gas-cooled reactors. It has shown promise because of its high uranium density, good irradiation stability, and especially high thermal conductivity. Despite its many benefits, UC is known to swell at a rate twice that of UO2. However, the swelling phenomenon is not well understood, and we are limited to a weak empirical understanding of the swelling mechanism. One suggested cladding for UC is silicon carbide (SiC), a ceramic that demonstrates a number of desirable properties. Among them are an increased corrosion resistance, high mechanical strength, and irradiation stability. However, with increased temperatures, SiC exhibits an extremely brittle nature. The brittle behavior of SiC is not fully understood and thus it is unknown how SiC would respond to the added stress of a swelling UC fuel. To better understand the interaction between these advanced materials, each has been implemented into FRAPCON, the preferred fuel performance code of the Nuclear Regulatory Commission (NRC); additionally, the material properties for a helium coolant have been incorporated. The implementation of UC within FRAPCON required the development of material models that described not only the thermophysical properties of UC, such as thermal conductivity and thermal expansion, but also models for the swelling, densification, and fission gas release associated with the fuel's irradiation behavior. This research is intended to supplement ongoing analysis of the performance and behavior of uranium carbide and silicon carbide in a helium-cooled reactor.

Approaches to improve the stability of the antiviral agent UC781 in aqueous solutions.

PubMed

Damian, Festo; Fabian, Judit; Friend, David R; Kiser, Patrick F

2010-08-30

In this work, we evaluated the chemical stability profiles of UC781 based solutions to identify excipients that stabilize the microbicidal agent UC781. When different antioxidants were added to UC781 in sulfobutylether-beta-cyclodextrin (SBE-beta-CD) solutions and subjected to a 50 degrees C stability study, it was observed that EDTA was a better stabilizing agent than sodium metabisulfite, glutathione or ascorbic acid. Some antioxidants accelerated the degradation of UC781, suggesting metal-catalyzed degradation of UC781. Furthermore, we observed substantial degradation of UC781 when stored in 1% Tween 80 and 1% DMSO solutions alone or in those with 10mM EDTA. On the other hand, improved stability of UC781 in the presence of 100 and 200mM of EDTA was observed in these solutions. The addition of both EDTA and citric acid in the stock solutions resulted in recovery of more than 60% of UC781 after 12 weeks. Generally, 10% SBE-beta-CD in the presence of EDTA and citric acid stabilized UC781 solutions: the amount of UC781 recovered approaching 95% after 12 weeks of storage at 40 degrees C. We also showed that the desulfuration reaction of the UC781 thioamide involves oxygen by running solution stability studies in deoxygenated media. Improved stability of UC781 in the present study indicates that the incorporation of EDTA, citric acid and SBE-beta-CD and the removal of oxygen in formulations of this drug will aid in increasing the stability of UC781 where solutions of the drug are required. Published by Elsevier B.V.

Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis.

PubMed

Kane, Sunanda; Katz, Seymour; Jamal, M Mazen; Safdi, Michael; Dolin, Ben; Solomon, Dory; Palmen, Mary; Barrett, Karen

2012-06-01

This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were ≥ 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were ≥ 80% adherent and 36.1% of patients with <80% adherence (P = 0.05 [post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

The role of centralized reading of endoscopy in a randomized controlled trial of mesalamine for ulcerative colitis.

PubMed

Feagan, Brian G; Sandborn, William J; D'Haens, Geert; Pola, Suresh; McDonald, John W D; Rutgeerts, Paul; Munkholm, Pia; Mittmann, Ulrich; King, Debra; Wong, Cindy J; Zou, Guangyong; Donner, Allan; Shackelton, Lisa M; Gilgen, Denise; Nelson, Sigrid; Vandervoort, Margaret K; Fahmy, Marianne; Loftus, Edward V; Panaccione, Remo; Travis, Simon P; Van Assche, Gert A; Vermeire, Séverine; Levesque, Barrett G

2013-07-01

Interobserver differences in endoscopic assessments contribute to variations in rates of response to placebo in ulcerative colitis (UC) trials. We investigated whether centralized review of images could reduce these variations. We performed a 10-week, randomized, double-blind, placebo-controlled study of 281 patients with mildly to moderately active UC, defined by an Ulcerative Colitis Disease Activity Index (UCDAI) sigmoidoscopy score ≥2, that evaluated the efficacy of delayed-release mesalamine (Asacol 800-mg tablet) 4.8 g/day. Endoscopic images were reviewed by a single expert central reader. The primary outcome was clinical remission (UCDAI, stool frequency and bleeding scores of 0, and no fecal urgency) at week 6. The primary outcome was achieved by 30.0% of patients treated with mesalamine and 20.6% of those given placebo, a difference of 9.4% (95% confidence interval [CI], -0.7% to 19.4%; P = .069). Significant differences in results from secondary analyses indicated the efficacy of mesalamine. Thirty-one percent of participants, all of whom had a UCDAI sigmoidoscopy score ≥2 as read by the site investigator, were considered ineligible by the central reader. After exclusion of these patients, the remission rates were 29.0% and 13.8% in the mesalamine and placebo groups, respectively (difference of 15%; 95% CI, 3.5%-26.0%; P = .011). Although mesalamine 4.8 g/day was not statistically different from placebo for induction of remission in patients with mildly to moderately active UC, based on an intent-to-treat analysis, the totality of the data supports a benefit of treatment. Central review of endoscopic images is critical to the conduct of induction studies in UC; ClinicalTrials.gov Number, NCT01059344. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Altered Expression of Transmembrane Mucins, MUC1 and MUC4, in Bladder Cancer: Pathological Implications in Diagnosis

PubMed Central

Kaur, Sukhwinder; Momi, Navneet; Chakraborty, Subhankar; Wagner, David G.; Horn, Adam J.; Lele, Subodh M.; Theodorescu, Dan; Batra, Surinder K.

2014-01-01

Purpose Radical changes in both expression and glycosylation pattern of transmembrane mucins have been observed in various malignancies. We and others have shown that MUC1 and MUC4, two transmembrane mucins, play a sentinel role in cell signaling events that drive several epithelial malignancies. In the present study, we investigated the expression profile of MUC1 and MUC4 in the non-neoplastic bladder urothelium, in various malignant neoplasms of bladder and in bladder carcinoma cell lines. Material and Methods Immunohistochemistry was performed on tissue sections from the urinary bladder biopsies, resection samples and tissue microarrays (TMAs) with monoclonal antibodies specific for MUC1 and MUC4. We also investigated their expression in bladder carcinoma cell lines by RT-PCR and immunoblotting. Results MUC1 is expressed on the apical surface or in umbrella cells of the normal non-neoplastic bladder urothelium. Strong expression of MUC1 was also observed in urothelial carcinoma (UC). MUC1 staining increased from normal urothelium (n = 27, 0.35±0.12) to urothelial carcinoma (UC, n = 323, H-score, 2.4±0.22, p≤0.0001). In contrast to MUC1, MUC4 was expressed in all the layers of non-neoplastic bladder urothelium (n = 14, 2.5±0.28), both in the cell membrane and cytoplasm. In comparison to non-neoplastic urothelium, the loss of MUC4 expression was observed during urothelial carcinoma (n = 211, 0.56±0.06). However, re-expression of MUC4 was observed in a subset of metastatic cases of urothelial carcinoma (mean H-score 0.734±0.9). Conclusion The expression of MUC1 is increased while that of MUC4 decreased in UC compared to the normal non-neoplastic urothelium. Expression of both MUC1 and MUC4, however, are significantly higher in urothelial carcinoma metastatic cases compared to localized UC. These results suggest differential expression of MUC1 and MUC4 during development and progression of bladder carcinoma. PMID:24671186

Effect of a Food Supplement Containing L-Methionine on Urinary Tract Infections in Pregnancy: A Prospective, Multicenter Observational Study.

PubMed

Passaro, Mario; Mainini, Giampaolo; Ambrosio, Francesco; Sgambato, Raimondo; Balbi, Giancarlo

2017-06-01

Adjuvants or alternatives to antibiotics in urinary tract infections (UTIs) during pregnancy seem advisable because of possible fetal stress. The present study assessed the effectiveness of a food supplement containing L-methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a treatment for symptomatic UTIs in pregnancy. Pregnant patients with symptomatic cystitis were screened for UTIs in three different clinical centers. Those unwilling to take antibiotics were offered two alternative treatments: (A) a 1-week treatment with the food supplement or (B) a week in which they were advised to increase their fluid consumption to more than 1.5 L daily. After 1 week, group B patients who still had positive urine cultures (UCs) or had no UC performed took the food supplement for an additional week. UCs were performed on all patients at the first visit (w0) and on most of them at 7 days (w1). Patients who were still positive at w1 or had no UC performed at w1 had UC performed 14 days (w2) thereafter. Of 264 pregnant women enrolled, 216 joined group A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those in group B had negative UCs (p = 0.003). The reduction of bacterial load was 42.2% ± 8.0% and 4.5% ± 9.2%, respectively (p < 0.0001). At w1, symptoms disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B (p = 0.03). At w2, 30 of 32 group B patients who switched to taking the supplement for the second week had negative UCs, including 20 who had been positive at w1. At w2, all group A patients had negative UCs. No side effects were reported. The food supplement provided effective treatment and might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in pregnancy.

Human Umbilical Cord Mesenchymal Stem Cells: Subpopulations and Their Difference in Cell Biology and Effects on Retinal Degeneration in RCS Rats.

PubMed

Wang, L; Li, P; Tian, Y; Li, Z; Lian, C; Ou, Q; Jin, C; Gao, F; Xu, J-Y; Wang, J; Wang, F; Zhang, J; Zhang, J; Li, W; Tian, H; Lu, L; Xu, G-T

2017-01-01

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential candidates for treating retinal degeneration (RD). To further study the biology and therapeutic effects of the hUC-MSCs on retinal degeneration. Two hUC-MSC subpopulations, termed hUC-MSC1 and hUC-MSC2, were isolated by single-cell cloning method and their therapeutic functions were compared in RCS rat, a RD model. Although both subsets satisfied the basic requirements for hUC-MSCs, they were significantly different in morphology, proliferation rate, differentiation capacity, phenotype and gene expression. Furthermore, only the smaller, fibroblast-like, faster growing subset hUC-MSC1 displayed stronger colony forming potential as well as adipogenic and osteogenic differentiation capacities. When the two subsets were respectively transplanted into the subretinal spaces of RCS rats, both subsets survived, but only hUC-MSC1 expressed RPE cell markers Bestrophin and RPE65. More importantly, hUC-MSC1 showed stronger rescue effect on the retinal function as indicated by the higher b-wave amplitude on ERG examination, thicker retinal nuclear layer, and decreased apoptotic photoreceptors. When both subsets were treated with interleukin-6, mimicking the inflammatory environment when the cells were transplanted into the eyes with degenerated retina, hUC-MSC1 expressed much higher levels of trophic factors in comparison with hUC-MSC2. The data here, in addition to prove the heterogeneity of hUC-MSCs, confirmed that the stronger therapeutic effects of hUC-MSC1 were attributed to its stronger anti-apoptotic effect, paracrine of trophic factors and potential RPE cell differentiation capacity. Thus, the subset hUC-MSC1, not the other subset or the ungrouped hUC-MSCs should be used for effective treatment of RD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Treatability Study Report for In SITU Lead Immobilization Using Phosphate-Based Binders

DTIC Science & Technology

2008-05-01

include lead, zinc, copper, cadmium, nickel, uranium, barium, cesium, strontium, plutonium, thorium, and other lanthanide and actinide metals. There...Density Bulk density is the measure of the mass per unit volume of the whole soil specimen. American Society for Testing and Materials (ASTM) D 698...Where: m = mass of the soil (grams) V = Volume of sample (cm3) 4.2.2.1.3 Unconfined Compressive Strength (UCS) The UCS test was used to

Undernutrition and serum and urinary urea nitrogen of white-tailed deer during winter

USGS Publications Warehouse

DelGiudice, G.D.; Mech, L.D.; Seal, U.S.

1994-01-01

Direct, practical means of assessing undernutrition in deer (Odocoileus spp.) and other ungulates during winter are needed in areas of research and management. We examined the relationship between mass loss and serum urea nitrogen (SUN) and urinary urea nitrogen:creatinine (U:C) in captive white-tailed deer (O. virginianus). During 4 February-5 May 1988, we maintained 7 adult white-tailed deer on various feeding regimes to simulate natural nutritional restriction during winter. Mass loss was greater (P = 0.037) in deer (17.0-32.2%) fed restricted amounts of a low protein low energy diet versus control deer (7.0-17.4%) fed the same diet ad libitum. Serum triiodothyronine (T3) concentrations did not differ (P = 0.191) between groups, but declined (P = 0.001) as nutrition declined. Slopes of percent mass lossSUN and urinary U:C relationships were positive (P = 0.008 and 0.055) in 7 and 6 deer, respectively. Mean U:C was directly related (r2 = 0.52, P = 0.040) to mean cumulative mass loss, whereas mean SUN was not (r2 = 0.29, P = 0.125). Data presented support the potential of urinary U:C as an index of winter nutritional condition of white-tailed deer; however, additional research is required to provide a complete understanding of this index's utility under field conditions.

Induction of the Tumor-Suppressor p16INK4a within Regenerative Epithelial Crypts in Ulcerative Colitis1

PubMed Central

Furth, Emma E; Gustafson, Karen S; Dai, Charlotte Y; Gibson, Steven L; Menard-Katcher, Paul; Chen, Tina; Koh, Jim; Enders, Greg H

2006-01-01

Abstract p16INK4a is a major tumor-suppressor protein, but its regulation and settings of fuction remain poorly understood. To explore the notion that p16 is induced in vivo in response to replicative stress, we examined p16 expression in tissues from human ulcerative colitis (UC; n = 25) and normal controls (n = 20). p16 was expressed strongly in UC-associated neoplasms (n = 17), as seen previously in sporadic colonic neoplasms. In non-neoplastic UC epithelium, p16 was expressed in 33% of crypts (the proliferative compartment) compared to < 1% of normal controls. p16 expression did not correlate with degree of inflammation but did correlate with the degree of crypt architecture distortion (P = .002)—a reflection of epithelial regeneration. In coimmunofluorescence studies with Ki67, p16 expression was associated with cell cycle arrest (P < .001). Both UC and normal crypts displayed evidence for the activation of the DNA damage checkpoint pathway, and p16 was induced in primary cultures of normal epithelial cells by ionizing irradiation (IR). However, induction by IR displayed delayed kinetics, implying that p16 is not an immediate target of the checkpoint pathway. These findings support a model in which p16 is induced as an “emergency brake” in cells experiencing sustained replicative stress. PMID:16820088

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases.

PubMed

Smith, Michael A; Mohammad, Rima A

2014-12-01

To review the pharmacology, efficacy, and safety of vedolizumab in the treatment of patients with ulcerative colitis (UC) and Crohn's disease (CD). A literature search through clinicialtrials.gov, EMBASE and MEDLINE was conducted (January 1966-June 2014) using the terms vedolizumab and MLN0002. References from retrieved articles were reviewed for any additional material. Additionally, the prescribing information was retrieved. Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of vedolizumab were identified. Vedolizumab, an α4β7 integrin inhibitor, was recently approved for adult patients with moderate to severe active UC or CD who are refractory or intolerant to standard therapies or who are dependent on corticosteroids. Trial data have demonstrated that vedolizumab 300 mg at weeks 0, 2, and 6 followed by every 8 weeks is effective at inducing and maintaining clinical response and remission, improving mucosal appearance, and achieving corticosteroid-free remission in patients with UC. This regimen is also effective at achieving clinical response, remission, and corticosteroid-free remission in patients with CD. Patients treated with vedolizumab, unadjusted for exposure, reported experiencing nasopharyngitis, headache, nausea, arthralgias, pyrexia, upper-respiratory-tract infections, fatigue, and cough. Vedolizumab is an effective agent at inducing and maintaining remission in patients with UC or CD. Vedolizumab is generally well tolerated and has not been associated with progressive multifocal leukoencephalopathy. © The Author(s) 2014.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

PubMed

Safroneeva, E; Vavricka, S; Fournier, N; Seibold, F; Mottet, C; Nydegger, A; Ezri, J; Straumann, A; Rogler, G; Schoepfer, A M

2015-09-01

Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. © 2015 John Wiley & Sons Ltd.

Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors.

PubMed

Zakko, Salam F; Gordon, Glenn L; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-01-01

A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, UC flare, or UC-related adverse event (AE). Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728.

Receptivity of a Cryogenic Coaxial Gas-Liquid Jet to Acoustic Disturbances (Briefing Charts)

DTIC Science & Technology

2014-03-01

meas = Δt Δs Uc,meas 2/12/1 0 2/12/1 0 , i iio thc UUU      DISTRIBUTION STATEMENT A. Approved for public release; distribution unlimited...this point, dynamic pressures are approximately equal. Uc Uo – Uc Uc – Ui (Uo > Ui) 2/12/1 2/12/1 io iioo c UUU      St = Uc fnatD If St, D, Uc

Long-term outcome of patients with distal ulcerative colitis and inflammation of the appendiceal orifice.

PubMed

Naves, Juan E; Lorenzo-Zúñiga, Vicente; Marín, Laura; Mañosa, Míriam; Oller, Blanca; Moreno, Vicente; Zabana, Yamile; Boix, Jaume; Cabré, Eduard; Domènech, Eugeni

2011-12-01

Skip inflammation of the appendiceal orifice has been described in distal UC (UC-IAO) but long-term clinical outcomes are poorly established. Our aim was to evaluate the long-term clinical outcomes of UC-IAO as compared to classic distal UC. Patients with UC-IAO were identified from the local IBD database. Disease outcome and therapeutic requirements during follow-up were accurately collected, and compared with a control group of patients with distal UC without peri-appendiceal involvement matched by disease extent (proctitis/distal), smoking habit, and date and age at diagnosis. Fourteen UC patients were found to have UC-IAO, most of them with initial extent of UC limited to the rectum. All patients were initially managed with mesalazine administered orally (28.5%), topically (28.5%), or in combination (43%). After a median follow-up of 78 months (interquartile range--IQR 45-123) most UC-IAO patients were successfully managed with oral and/or topical aminosalicylates. Only one of them developed proximal disease progression. As compared to controls, no differences in clinical outcomes or therapeutic requirements were found. Patients with UC-IAO tend to present a mild course, with a low probability to develop proximal progression of disease extent or to require immunosuppressive therapy or colectomy.

Receptivity of a Cryogenic Coaxial Liquid Jet to Acoustic Disturbances

DTIC Science & Technology

2014-05-21

i iio thc UUU DISTRIBUTION STATEMENT A. Approved for public release; distribution unlimited. PA Clearance 14208 12Place Proper DISTRIBUTION STATEMENT...dynamic pressures are approximately equal. Uc Uo – Uc Uc – Ui (Uo > Ui) 2/12/1 2/12/1 io iioo c UUU St = Uc fnatD If St, D, Uc are held constant then

Ulcerative colitis-associated colorectal cancer

PubMed Central

Yashiro, Masakazu

2014-01-01

The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. PMID:25469007

Multifunctional hydroxyapatite/Na(Y/Gd)F4:Yb3+,Er3+ composite fibers for drug delivery and dual modal imaging.

PubMed

Liu, Min; Liu, Hui; Sun, Shufen; Li, Xuejiao; Zhou, Yanmin; Hou, Zhiyao; Lin, Jun

2014-02-04

Porous hydroxyapatite (HAp) composite fibers functionalized with up-conversion (UC) luminescent and magnetic Na(Y/Gd)F4:Yb(3+),Er(3+) nanocrystals (NCs) have been fabricated via electrospinning. After transferring hydrophobic oleic acid-capped Na(Y/Gd)F4:Yb(3+),Er(3+) NCs into aqueous solution, these water-dispersible NCs were dispersed into precursor electrospun solution containing CTAB. Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers were fabricated by the high temperature treatment of the electrospun Na(Y/Gd)F4:Yb(3+),Er(3+) NCs decorated precursor fibers. The biocompatibility test on MC 3T3-E1 cells using MTT assay shows that the HAp composite fibers have negligible cytotoxity, which reveals the HAp composite fibers could be a drug carrier for drug delivery. Because the contrast brightening is enhanced at increased concentrations of Gd(3+), the HAp composite fibers can serve as T1 magnetic resonance imaging contrast agents. In addition, the composites uptaken by MC 3T3-E1 cells present the UC luminescent emission of Er(3+) under the excitation of a 980 nm near-infrared laser. The above findings reveal Na(Y/Gd)F4:Yb(3+),Er(3+)@HAp composite fibers have potential applications in drug storage/release and magnetic resonance/UC luminescence imaging.

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

PubMed

Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy

PubMed Central

2011-01-01

Background Concomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective. Methods A Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research. Results PREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty. Conclusions Based on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY). PMID:22051143

Epidemiological and clinical characteristics of inflammatory bowel diseases in Cairo, Egypt.

PubMed

Esmat, Serag; El Nady, Mohamed; Elfekki, Mohamed; Elsherif, Yehia; Naga, Mazen

2014-01-21

To study the natural history, patterns and clinical characteristics of inflammatory bowel diseases (IBD) in Egypt. We designed a case-series study in the gastroenterology centre of the Internal Medicine department of Cairo University, which is a tertiary care referral centre in Egypt. We included all patients in whom the diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) was confirmed by clinical, laboratory, endoscopic, histological and/or radiological criteria over the 15 year period from 1995 to 2009, and we studied their sociodemographic and clinical characteristics. Endoscopic examinations were performed by 2 senior experts. This hospital centre serves patients from Cairo, as well as patients referred from all other parts of Egypt. Our centre received 24156 patients over the described time period for gastro-intestinal consultations and/or interventions. A total of 157 patients with established IBD were included in this study. Of these, 135 patients were diagnosed with UC (86% of the total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the frequency of both UC and CD diagnoses during the most recent 10 years of the 15 year period studied. Regarding the gender distribution, the male:female ratio was 1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with UC was 6.2 ± 5.18 years, while the mean duration of follow up for patients with CD was 5.52 ± 2.83 years. For patients with UC we found no correlation between the severity of the disease and the presence of extraintestinal manifestations. Eleven patients had surgical interventions during the studied years: 4 cases of total colectomy and 7 cases of anal surgery. We observed a ratio of 6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt.

Comparison of the onset of uterine contractions determined from tocodynamometry and maternal perception.

PubMed

Ying Wang; Pei Gao; Qian Qiu; Yang An; Dongmei Hao; Fangwei Yang; Xiya Zhou; Lin Yang; Yimin Yang; Xuwen Li; Song Zhang; Dingchang Zheng

2017-07-01

The aim of this study was to investigate the time difference (TD) between the onset of uterine contraction (UC) determined from tocodynamometry (TOCO) and identified by maternal perception. The online available Icelandic database was used to calculate TD, which was defined as the difference between when it was felt by a pregnant woman and the starting point on the UC signal recorded by a TOCO. A total of 295 TDs from 78 recordings (from a total of 33 participants; among them, 13 participants included at least 3 recordings from different gestational weeks) were analyzed with the overall mean±SD of TD calculated. For each individual participant with at least 3 recordings, regression analysis was then performed to investigate the relationship between the mean TD from each recording with gestational week, with their overall slope calculated. The results showed that 85.4% of TDs was within [-40, 40] s, with an overall mean TD of 3.04 s (p>0.05), indicating that there was no significant difference between the UC onset determined from TOCO and maternal perception. It was also noticed that 61.5% recordings (48 out of 78 recordings) had all positive or negative TD for all the UCs analyzed within a recording. Furthermore, the regression analysis showed that the regression line slope was negative for 10 out of the 13 participants with at least 3 recordings from different gestational weeks, resulting in that the overall slope (-2.85±5.58) was significantly negative (p<;0.05), and indicating that UC onset TD decreased with gestational weeks. In summary, this study quantitatively investigated the TD between the onset of UCs determined from TOCO and maternal perception, providing scientific evidence for future studies to understand the underlying mechanism of the time sequence of UC activity determined from different techniques.

miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.

PubMed

Benderska, Natalya; Dittrich, Anna-Lena; Knaup, Sabine; Rau, Tilman T; Neufert, Clemens; Wach, Sven; Fahlbusch, Fabian B; Rauh, Manfred; Wirtz, Ralph M; Agaimy, Abbas; Srinivasan, Swetha; Mahadevan, Vijayalakshmi; Rümmele, Petra; Rapti, Emmanouela; Gazouli, Maria; Hartmann, Arndt; Schneider-Stock, Regine

2015-09-01

Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis. Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation. miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases. We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.

Systematic review with meta-analysis: Comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn’s disease and ulcerative colitis controlled trials

PubMed Central

Cholapranee, Aurada; Hazlewood, Glen S; Kaplan, Gilaad G.; Peyrin-Biroulet, Laurent; Ananthakrishnan, Ashwin N

2017-01-01

Background Mucosal healing is an important therapeutic endpoint in the management of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data exists regarding the comparative efficacy of various therapies in achieving this outcome. Methods We performed a systematic review and meta-analysis of randomized controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumor necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pair-wise treatment comparisons evaluated using a Bayesian network meta-analysis. Results A total of 12 RCTs were included in the meta-analysis (CD – 2 induction, 4 maintenance; UC – 8 induction, 5 maintenance). Duration of follow-up was 6–12 weeks for induction and 32–54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing (28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51 – 110.84). In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab (OR 0.45, 95% credible interval (CrI) 0.25 – 0.82) and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12 – 0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Conclusion Anti-TNF and anti-integrin biologic agents are effective in inducing mucosal healing in UC with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. PMID:28326566

Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

PubMed

Paramsothy, Sudarshan; Paramsothy, Ramesh; Rubin, David T; Kamm, Michael A; Kaakoush, Nadeem O; Mitchell, Hazel M; Castaño-Rodríguez, Natalia

2017-10-01

Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel disease [IBD]. We thus performed a systematic review and meta-analysis assessing the effectiveness and safety of FMT in IBD. A systematic review was conducted until January 2017. Studies were excluded if patients had co-infection or data were pooled across disease subtypes (ulcerative colitis [UC], Crohn's disease [CD], pouchitis). Clinical remission was established as the primary outcome. Pooled effect sizes and 95% confidence intervals were obtained using the random effects model. In all, 53 studies were included [41 in UC, 11 in CD, 4 in pouchitis]. Overall, 36% [201/555] of UC, 50.5% [42/83] of CD, and 21.5% [5/23] of pouchitis patients achieved clinical remission. Among cohort studies, the pooled proportion achieving clinical remission was 33% (95% confidence interval [CI] = 23%-43%] for UC and 52% [95% CI = 31%-72%] for CD, both with moderate risk of heterogeneity. For four RCTs in UC, significant benefit in clinical remission (pooled odds ratios [[P-OR] = 2.89, 95% CI = 1.36-6.13, p = 0.006) with moderate heterogeneity [Cochran's Q, p = 0.188; I2 = 37%] was noted. Sub-analyses suggest remission in UC improved with increased number of FMT infusions and lower gastrointestinal tract administration. Most adverse events were transient gastrointestinal complaints. Microbiota analysis was performed in 24 studies, with many identifying increased diversity and a shift in recipient microbiota profile towards the donor post-FMT. FMT appears effective in UC remission induction, but long-term durability and safety remain unclear. Additional well-designed controlled studies of FMT in IBD are needed, especially in CD and pouchitis. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Systematic review with meta-analysis: comparative efficacy of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis controlled trials.

PubMed

Cholapranee, A; Hazlewood, G S; Kaplan, G G; Peyrin-Biroulet, L; Ananthakrishnan, A N

2017-05-01

Mucosal healing is an important therapeutic endpoint in the management of Crohn's disease (CD) and ulcerative colitis (UC). Limited data exist regarding the comparative efficacy of various therapies in achieving this outcome. To perform a systematic review and meta-analysis of biologics for induction and maintenance of mucosal healing in Crohn's disease and ulcerative colitis. We performed a systematic review and meta-analysis of randomised controlled trials (RCT) examining mucosal healing as an endpoint of immunosuppressives, anti-tumour necrosis factor α (anti-TNF) or anti-integrin monoclonal antibody therapy for moderate-to-severe CD or UC. Pooled effect sizes for induction and maintenance of mucosal healing were calculated and pairwise treatment comparisons evaluated using a Bayesian network meta-analysis. A total of 12 RCTs were included in the meta-analysis (CD - 2 induction, 4 maintenance; UC - 8 induction, 5 maintenance). Duration of follow-up was 6-12 weeks for induction and 32-54 weeks for maintenance trials. In CD, anti-TNFs were more effective than placebo for maintaining mucosal healing [28% vs. 1%, Odds ratio (OR) 19.71, 95% confidence interval (CI) 3.51-110.84]. In UC, anti-TNFs and anti-integrins were more effective than placebo for inducing (45% vs. 30%) and maintaining mucosal healing (33% vs. 18%). In network analysis, adalimumab therapy was inferior to infliximab [OR 0.45, 95% credible interval (CrI) 0.25-0.82] and combination infliximab-azathioprine (OR 0.32, 95% CrI 0.12-0.84) for inducing mucosal healing in UC. There was no statistically significant pairwise difference between vedolizumab and anti-TNF agents in UC. Anti-TNF and anti-integrin biological agents are effective in inducing mucosal healing in UC, with adalimumab being inferior to infliximab or combination therapy. Infliximab and adalimumab were similar in CD. © 2017 John Wiley & Sons Ltd.

Epidemiological and clinical characteristics of inflammatory bowel diseases in Cairo, Egypt

PubMed Central

Esmat, Serag; El Nady, Mohamed; Elfekki, Mohamed; Elsherif, Yehia; Naga, Mazen

2014-01-01

AIM: To study the natural history, patterns and clinical characteristics of inflammatory bowel diseases (IBD) in Egypt. METHODS: We designed a case-series study in the gastroenterology centre of the Internal Medicine department of Cairo University, which is a tertiary care referral centre in Egypt. We included all patients in whom the diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) was confirmed by clinical, laboratory, endoscopic, histological and/or radiological criteria over the 15 year period from 1995 to 2009, and we studied their sociodemographic and clinical characteristics. Endoscopic examinations were performed by 2 senior experts. This hospital centre serves patients from Cairo, as well as patients referred from all other parts of Egypt. Our centre received 24156 patients over the described time period for gastro-intestinal consultations and/or interventions. RESULTS: A total of 157 patients with established IBD were included in this study. Of these, 135 patients were diagnosed with UC (86% of the total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the frequency of both UC and CD diagnoses during the most recent 10 years of the 15 year period studied. Regarding the gender distribution, the male:female ratio was 1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with UC was 6.2 ± 5.18 years, while the mean duration of follow up for patients with CD was 5.52 ± 2.83 years. For patients with UC we found no correlation between the severity of the disease and the presence of extraintestinal manifestations. Eleven patients had surgical interventions during the studied years: 4 cases of total colectomy and 7 cases of anal surgery. CONCLUSION: We observed a ratio of 6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt. PMID:24574754

Emplacement of Volcanic Domes on Venus and Europa

NASA Technical Reports Server (NTRS)

Quick, Lynnae C.; Glaze, Lori S.; Baloga, Steve M.

2015-01-01

Placing firmer constraints on the emplacement timescales of visible volcanic features is essential to obtaining a better understanding of the resurfacing history of Venus. Fig. 1 shows a Magellan radar image and topography for a putative venusian lava dome. 175 such domes have been identified, having diameters that range from 19 - 94 km, and estimated thicknesses as great as 4 km [1-2]. These domes are thought to be volcanic in origin [3], having formed by the flow of a viscous fluid (i.e., lava) onto the surface. Among the unanswered questions surrounding the formation of Venus steep-sided domes are their emplacement duration, composition, and the rheology of the lava. Rheologically speaking, maintenance of extremely thick, 1-4 km flows necessitates higher viscosity lavas, while the domes' smooth upper surfaces imply the presence of lower viscosity lavas [2-3]. Further, numerous quantitative issues, such as the nature and duration of lava supply, how long the conduit remained open and capable of supplying lava, the volumetric flow rate, and the role of rigid crust in influencing flow and final morphology all have implications for subsurface magma ascent and local surface stress conditions. The surface of Jupiter's icy moon Europa exhibits many putative cryovolcanic constructs [5-7], and previous workers have suggested that domical positive relief features imaged by the Galileo spacecraft may be volcanic in origin [5,7-8] (Fig. 2). Though often smaller than Venus domes, if emplaced as a viscous fluid, formation mechanisms for europan domes may be similar to those of venusian domes [7]. Models for the emplacement of venusian lava domes (e.g. [9-10]) have been previously applied to the formation of putative cryolava domes on Europa [7].

Cost-Effectiveness of Multidisciplinary Management Program and Exercise Training Program in Heart Failure.

PubMed

Dang, Weixiong; Yi, Anji; Jhamnani, Sunny; Wang, Shi-Yi

2017-10-15

Heart failure causes significant health and financial burdens for patients and society. Multidisciplinary management program (MMP) and exercise training program (ETP) have been reported as cost-effective in improving health outcomes, yet no study has compared the 2 programs. We constructed a Markov model to simulate life year (LY) gained and total costs in usual care (UC), MMP, and ETP. The probability of transitions between states and healthcare costs were extracted from previous literature. We calculated the incremental cost-effectiveness ratio (ICER) over a 10-year horizon. Model robustness was assessed through 1-way and probabilistic sensitivity analyses. The expected LY for patients treated with UC, MMP, and ETP was 7.6, 8.2, and 8.4 years, respectively. From a societal perspective, the expected cost of MMP was $20,695, slightly higher than the cost of UC ($20,092). The cost of ETP was much higher ($48,378) because of its high implementation expense and the wage loss it incurred. The ICER of MMP versus UC was $976 per LY gained, and the ICER of ETP versus MMP was $165,702 per LY gained. The results indicated that, under current cost-effectiveness threshold, MMP is cost-effective compared with UC, and ETP is not cost-effective compared with MMP. However, ETP is cost-effective compared with MMP from a healthcare payer's perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women.

PubMed

Centi, Amanda J; Booth, Sarah L; Gundberg, Caren M; Saltzman, Edward; Nicklas, Barbara; Shea, M Kyla

2015-12-01

Osteocalcin (OC) is a vitamin K-dependent bone protein used as a marker of bone formation. Mouse models have demonstrated a role for the uncarboxylated form of OC (ucOC) in energy metabolism, including energy expenditure and adiposity, but human data are equivocal. The purpose of this study was to determine the associations between changes in measures of OC and changes in body weight and percent body fat in obese, but otherwise healthy post-menopausal women undergoing a 20-week weight loss program. All participants received supplemental vitamins K and D and calcium. Body weight and body fat percentage (%BF) were assessed before and after the intervention. Serum OC [(total (tOC), ucOC, percent uncarboxylated (%ucOC)], and procollagen type 1N-terminal propeptide (P1NP; a measure of bone formation) were measured. Women lost an average of 10.9 ± 3.9 kg and 4 %BF. Serum concentrations of tOC, ucOC, %ucOC, and P1NP did not significantly change over the twenty-week intervention, nor were these measures associated with changes in weight (all p > 0.27) or %BF (all p > 0.54). Our data do not support an association between any serum measure of OC and weight or %BF loss in post-menopausal women supplemented with nutrients implicated in bone health.

Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

PubMed

Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

2016-01-01

Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

A randomized controlled trial of very early rehabilitation in speech after stroke.

PubMed

Godecke, Erin; Armstrong, Elizabeth A; Rai, Tapan; Middleton, Sandy; Ciccone, Natalie; Whitworth, Anne; Rose, Miranda; Holland, Audrey; Ellery, Fiona; Hankey, Graeme J; Cadilhac, Dominique A; Bernhardt, Julie

2016-07-01

The efficacy of rehabilitation therapy for aphasia caused by stroke is uncertain. The Very Early Rehabilitation of Speech (VERSE) trial aims to determine if intensive prescribed aphasia therapy (VERSE) is more effective and cost saving than non-prescribed, intensive (usual care-plus) and non-intensive usual care (UC) therapy when started within 15 days of stroke onset and continued daily over four weeks. We hypothesize that aphasia therapy when started very early after stroke and delivered daily could enhance recovery of communication compared with UC. A total of 246 participants (82 per arm) will provide 80% power to detect a 4.4% improvement on aphasia quotient between VERSE and UC plus at a significance level of α = 0.05. Acute-care hospitals and accompanying rehabilitation services throughout Australia, 2014-2017. Three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment (PROBE) trial. Acute stroke in previous 14 days and aphasia diagnosed by aphasia quotient (AQ) of the Western Aphasia Battery (WAB). Computer-generated blocked randomization procedure stratified by aphasia severity according to Western Aphasia Battery, to one of three arms. All participants receive UC-usual ward-based aphasia therapy. Arm 1: UC-no additional therapy; Arm 2: UC-plus usual ward-based therapy; Arm 3: VERSE therapy-a prescribed and structured aphasia therapy program. Arms 2 and 3 receive a total of 20 additional sessions (45-60 min, provided daily) of aphasia therapy. The additional intervention must be provided before day 50 post stroke. The aphasia quotient of Western Aphasia Battery at 12 weeks post stroke. Secondary outcomes include discourse measures, the Stroke and Aphasia Quality of Life Scale-39 and the Aphasia Depression Rating Scale at 12 and 26 weeks. Incremental cost-effectiveness ratios at 26 weeks will be reported. This trial is designed to test whether the intensive and prescribed VERSE intervention is effective in promoting maximum recovery and preventing costly health complications in a vulnerable population of survivors of stroke. It will also provide novel, prospective, aphasia specific cost-effectiveness data to guide future policy development for this population. © 2016 World Stroke Organization.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumari, Astha, E-mail: asthaguru90@gmail.com; Rai, Vineet Kumar, E-mail: vineetkrrai@yahoo.co.in

Upconversion is an interesting optical property, generally shown by rare-earth doped materials. This unusual optical behavior shown by these rare-earths doped materials are due to their peculiar atomic configuration and electronic transitions. Here, the Tm{sup 3+}-Yb{sup 3+} codoped BaTiO{sub 3} glass with TeO{sub 2} as former has been prepared by conventional melt and quench technique and the upconversion property has been investigated with the help of near infrared (NIR) to Visible UC study. The generation of the visible UC bands around ∼ 476 nm, ∼ 653 nm, ∼ 702 nm and one NIR UC band at ∼795 nm are assignedmore » due to the {sup 1}G{sub 4}→ {sup 3}H{sub 6}, {sup 1}G{sub 4}→ {sup 3}F{sub 4}, {sup 3}F{sub 2}→ {sup 3}H{sub 6} and {sup 3}H{sub 4}→ {sup 3}H{sub 6} transitions respectively. The generations of these upconversion bands have been discussed in detail with the help of energy level diagram. The colour coordinates corresponding to the prepared material have been shown with the help of CIE chromaticity diagram. These glasses can be very appropriately used in the fabrication of solid state laser and as NIR to blue light upconverter.« less

Epidemiology and gene markers of ulcerative colitis in the Chinese

PubMed Central

Yun, Jun; Xu, Chang-Tai; Pan, Bo-Rong

2009-01-01

Inflammatory bowel disease (IBD) includes two similar yet distinct conditions called ulcerative colitis (UC) and Crohn's disease (CD). These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD: TNF-308A, CARD15 (NOD2), MIF-173, N-acetyltransferase 2 (NAT2), NKG2D (natural killer cell 2D), STAT6 (signal transducer and activator of transcription 6), CTLA-4 (cytotoxic T lymphocyte antigen-4), MICA-MICB (major histocompatibility complex A and B), HLA-DRB1, HLA class-II, IL-18, IL-4, MICA-A5, CD14, TLR4, Fas-670, p53 and NF-κB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD (UC and CD). PMID:19230040

The homing of human umbilical cord-derived mesenchymal stem cells and the subsequent modulation of macrophage polarization in type 2 diabetic mice.

PubMed

Yin, Yaqi; Hao, Haojie; Cheng, Yu; Gao, Jieqing; Liu, Jiejie; Xie, Zongyan; Zhang, Qi; Zang, Li; Han, Weidong; Mu, Yiming

2018-07-01

Umbilical cord-derived mesenchymal stem cells (UC-MSCs), with both immunomodulatory and pro-regenerative properties, are promising for the treatment of type 2 diabetes mellitus (T2DM). As efficient cell therapy largely relies on appropriate homing to target tissues, knowing where and to what extent injected UC-MSCs have homed is critically important. However, bio-distribution data for UC-MSCs in T2DM subjects are extremely limited. Beneficial effects of UC-MSCs on T2DM subjects are associated with increased M2 macrophages, but no systemic evaluation of M2 macrophages has been performed in T2DM individuals. In this study, we treated T2DM mice with CM-Dil-labelled UC-MSCs. UC-MSC infusion not only exerted anti-diabetic effects but also alleviated dyslipidemia and improved liver function in T2DM mice. To compare UC-MSC migration between T2DM and normal subjects, a collection of normal mice also received UC-MSC transplantation. UC-MSCs homed to the lung, liver and spleen in both normal and T2DM recipients. Specifically, the spleen harbored the largest number of UC-MSCs. Unlike normal mice, a certain number of UC-MSCs also homed to pancreatic islets in T2DM mice, which suggested that UC-MSC homing may be closely related to tissue damage. Moreover, the number of M2 macrophages in the islets, liver, fat and muscle significantly increased after UC-MSC infusion, which implied a strong link between the increased M2 macrophages and the improved condition in T2DM mice. Additionally, an M2 macrophage increase was also observed in the spleen, suggesting that UC-MSCs might exert systemic effects in T2DM individuals by modulating macrophages in immune organs. Copyright © 2018 Elsevier B.V. All rights reserved.

Comprehensive gene expression analysis of canine invasive urothelial bladder carcinoma by RNA-Seq.

PubMed

Maeda, Shingo; Tomiyasu, Hirotaka; Tsuboi, Masaya; Inoue, Akiko; Ishihara, Genki; Uchikai, Takao; Chambers, James K; Uchida, Kazuyuki; Yonezawa, Tomohiro; Matsuki, Naoaki

2018-04-27

Invasive urothelial carcinoma (iUC) is a major cause of death in humans, and approximately 165,000 individuals succumb to this cancer annually worldwide. Comparative oncology using relevant animal models is necessary to improve our understanding of progression, diagnosis, and treatment of iUC. Companion canines are a preferred animal model of iUC due to spontaneous tumor development and similarity to human disease in terms of histopathology, metastatic behavior, and treatment response. However, the comprehensive molecular characterization of canine iUC is not well documented. In this study, we performed transcriptome analysis of tissue samples from canine iUC and normal bladders using an RNA sequencing (RNA-Seq) approach to identify key molecular pathways in canine iUC. Total RNA was extracted from bladder tissues of 11 dogs with iUC and five healthy dogs, and RNA-Seq was conducted. Ingenuity Pathway Analysis (IPA) was used to assign differentially expressed genes to known upstream regulators and functional networks. Differential gene expression analysis of the RNA-Seq data revealed 2531 differentially expressed genes, comprising 1007 upregulated and 1524 downregulated genes, in canine iUC. IPA revealed that the most activated upstream regulator was PTGER2 (encoding the prostaglandin E 2 receptor EP2), which is consistent with the therapeutic efficiency of cyclooxygenase inhibitors in canine iUC. Similar to human iUC, canine iUC exhibited upregulated ERBB2 and downregulated TP53 pathways. Biological functions associated with cancer, cell proliferation, and leukocyte migration were predicted to be activated, while muscle functions were predicted to be inhibited, indicating muscle-invasive tumor property. Our data confirmed similarities in gene expression patterns between canine and human iUC and identified potential therapeutic targets (PTGER2, ERBB2, CCND1, Vegf, and EGFR), suggesting the value of naturally occurring canine iUC as a relevant animal model for human iUC.

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF

PubMed Central

Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-01-01

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs. PMID:27917866

Umbilical Cord-derived Mesenchymal Stem Cells Instruct Monocytes Towards an IL10-producing Phenotype by Secreting IL6 and HGF.

PubMed

Deng, Yinan; Zhang, Yingcai; Ye, Linsen; Zhang, Tong; Cheng, Jintao; Chen, Guihua; Zhang, Qi; Yang, Yang

2016-12-05

Human UC-MSCs are regarded as an attractive alternative to BM-MSCs for clinical applications due to their easy preparation, higher proliferation and lower immunogenicity. However, the mechanisms underlying immune suppression by UC-MSCs are still unclear. We studied the mechanism of inhibition by UC-MSCs during the differentiation of monocytes into DCs and focused on the specific source and the role of the involved cytokines. We found that UC-MSCs suppressed monocyte differentiation into DCs and instructed monocytes towards other cell types, with clear decreases in the expression of co-stimulatory molecules, in the secretion of inflammatory factors and in allostimulatory capacity. IL6, HGF and IL10 might be involved in this process because they were detected at higher levels in a coculture system. UC-MSCs produce IL-6 and HGF, and neutralization of IL-6 and HGF reversed the suppressive effect of UC-MSCs. IL10 was not produced by UC-MSCs but was exclusively produced by monocytes after exposure to UC-MSCs, IL-6 or HGF. In summary, we found that the UC-MSC-mediated inhibitory effect was dependent on IL6 and HGF secreted by UC-MSCs and that this effect induced monocyte-derived cells to produce IL10, which might indirectly strengthen the suppressive effect of UC-MSCs.

A brief history of the Bioengineering Institute of California and the UC System-wide Symposia.

PubMed

Chien, Shu

2011-04-01

The plan to establish a Multicampus Research Unit (MRU) on Bioengineering in the University of California (UC) System started in August 1999. The cooperative efforts of the UC campuses led to the formal establishment of the Bioengineering Institute of California (BIC) in October 2003. Three years prior to the BIC establishment, the System-wide Annual Bioengineering Symposium was started at UC Davis. The Symposia were then hosted sequentially by UC Santa Barbara, UC Berkeley, UCSD, UC Santa Cruz, UC Irvine, UCSF, UCLA, and UC Riverside, with the completion of the first cycle of a decade in the newest campus of UC Merced in 2009. The second cycle began in 2010 with the Symposium returning again to UC Davis. Each campus hosted a wonderful Symposium, with the active participation of students and faculty from all campuses, with the motto of "Ten campuses united as one, learning and growing together." These Symposia have contributed significantly to the collaborative research and training of students and young scientists in bioengineering, as well as fruitful interactions with industry and government agencies, which have provided strong support for these valuable meetings. The BIC will endeavor to further enhance these efforts by fostering research collaborations and joint education and training activities, with the ultimate goal of advancing bioengineering for the improvement of human health and wellbeing.

Lanthanide-doped NaScF4 nanoprobes: crystal structure, optical spectroscopy and biodetection

NASA Astrophysics Data System (ADS)

Ai, Yu; Tu, Datao; Zheng, Wei; Liu, Yongsheng; Kong, Jintao; Hu, Ping; Chen, Zhuo; Huang, Mingdong; Chen, Xueyuan

2013-06-01

Trivalent lanthanide ions (Ln3+)-doped inorganic nanoparticles (NPs) as potential luminescent bioprobes have been attracting tremendous interest because of their unique upconversion (UC) and downconversion (DC) luminescence properties. NaScF4, as an important host material, has been rarely reported and its crystal structure remains unclear. Herein, based on the single crystal X-ray diffraction, the space group of NaScF4 crystals was determined to be P31 containing multiple sites of Sc3+ with crystallographic site symmetry of C1, which was verified by high-resolution photoluminescence spectroscopy of Eu3+ at low temperature (10 K). Furthermore, monodisperse and size-controllable NaScF4:Ln3+ NPs were synthesized via a facile thermal decomposition method. The biotinylated NaScF4:Er3+/Yb3+ NPs were demonstrated for their applications as a heterogeneous UC luminescence bioprobe to detect avidin with a detection limit of 180 pM. After bioconjugation with amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), NaScF4:Ln3+ NPs also exhibited specific recognition of cancer cells overexpressed with uPA receptor (uPAR, an important marker of tumor biology and metastasis), showing great potentials in tumor-targeted bioimaging.Trivalent lanthanide ions (Ln3+)-doped inorganic nanoparticles (NPs) as potential luminescent bioprobes have been attracting tremendous interest because of their unique upconversion (UC) and downconversion (DC) luminescence properties. NaScF4, as an important host material, has been rarely reported and its crystal structure remains unclear. Herein, based on the single crystal X-ray diffraction, the space group of NaScF4 crystals was determined to be P31 containing multiple sites of Sc3+ with crystallographic site symmetry of C1, which was verified by high-resolution photoluminescence spectroscopy of Eu3+ at low temperature (10 K). Furthermore, monodisperse and size-controllable NaScF4:Ln3+ NPs were synthesized via a facile thermal decomposition method. The biotinylated NaScF4:Er3+/Yb3+ NPs were demonstrated for their applications as a heterogeneous UC luminescence bioprobe to detect avidin with a detection limit of 180 pM. After bioconjugation with amino-terminal fragment (ATF) of urokinase plasminogen activator (uPA), NaScF4:Ln3+ NPs also exhibited specific recognition of cancer cells overexpressed with uPA receptor (uPAR, an important marker of tumor biology and metastasis), showing great potentials in tumor-targeted bioimaging. Electronic supplementary information (ESI) available: Crystallographic data (CCDC 931481) in CIF format. EDX analysis of NaScF4:Er3+/Yb3+ NPs. 10 K PL excitation spectra of NaScF4:Eu3+ microcrystals. Selected bond lengths and angles for NaScF4 crystals. Atomic coordinates and equivalent isotropic displacement parameters for NaScF4 crystals. UC quantum yield data of NaScF4:Er3+/Yb3+ NPs. See DOI: 10.1039/c3nr01529g

46 CFR 54.25-10 - Low temperature operation-ferritic steels (replaces UCS-65 through UCS-67).

Code of Federal Regulations, 2010 CFR

2010-10-01

... this temperature range are satisfied. Range percent Si 0.10-0.50 Maximum S 0.035 P 0.035 Ni 0.80 Cr 0... service temperature A-203, 21/4 percent, Ni, normalized −80 °F. for Grade A.−75 °F. for Grade B. A-203, 31/2 percent, Ni, normalized −130 °F. for Grade D.−110 °F. for Grade E. 5 percent Ni, normalized...

46 CFR 54.25-10 - Low temperature operation-ferritic steels (replaces UCS-65 through UCS-67).

Code of Federal Regulations, 2011 CFR

2011-10-01

... this temperature range are satisfied. Range percent Si 0.10-0.50 Maximum S 0.035 P 0.035 Ni 0.80 Cr 0... service temperature A-203, 21/4 percent, Ni, normalized −80 °F. for Grade A.−75 °F. for Grade B. A-203, 31/2 percent, Ni, normalized −130 °F. for Grade D.−110 °F. for Grade E. 5 percent Ni, normalized...

Arkhangelsk, USSR. Limited Surface Observations Climatic Summary (LISOCS). Parts A-F.

DTIC Science & Technology

1988-01-01

MSC *225500 N 64 35 E 040 30 ELEV 43 FT ULAA PARTS A - F HOURS SUMMARIZED: SYNOPTIC HRS PERIOD 0- RECORD: HOURLY OBSERVATIONS: OCT 77 - SEP 87 SUMMARY...C/OR WicBSI TOTAL LESTI I ORIZZLL C/OR SLEET PRECIP HAZE SNOW SAND 10 ORS DRIZZLE VISION uc -02 .7 41.2 42.0 13.1 13.1 274 1,3-OS A 1.1 41.6 42.7 12.3...57.6 58.2 58.2 58.6 5-.9 58.9 59.2 59.2 59.2 54.2 GE 15LOI 17.4 45.1 49.3 58.6 63.5 66.1 67.4 68.4 68.4 68.8 69.1 69.4 69.7 p9.7 69.7 69.7 uC 1CO 19.1

Implications for crustal accretion at fast spreading ridges from observations in Jurassic oceanic crust in the western Pacific

NASA Astrophysics Data System (ADS)

Pockalny, Robert A.; Larson, Roger L.

2003-01-01

Downhole logging data and basement stratigraphy interpretations are used to determine the spreading environment and crustal accretion history of the ocean basement cored at ODP Hole 801C located in the Jurassic Magnetic Quiet Zone of the western Pacific. High-resolution microresistivity data obtained with the Formation MicroScanner are used to measure the dip of the extrusive layers and indicate a 10°-30° increase in dip down the drill hole with lava flow contacts dipping back toward the original ridge axis. This structural pattern and the high proportion of massive flows relative to pillow units are consistent with prevailing crustal accretion models proposed for faster spreading ridges (e.g., >60 km/m.y., full-rate). A detailed analysis of the age data, basement lithology, related geochemistry, and structural attitudes suggest the shallowest 100 m of the drilled section (e.g., Sequences I-III) were emplaced just off the ridge (Sequence III) or significantly farther off-axis up to 5-15 m.y. later (Sequences I and II). The remainder of the drilled section (e.g., Sequences IV-VIII) has geochemical, lithological and physical trends that are assumed to be representative of crust created at faster spreading ridges. The pattern of dipping lava flow contacts from this deeper section of the drill hole suggests lava flows emanating from the ridge axis are limited to 1-2 km off-axis. Our results suggest ocean crust drilled at Hole 801C was created at faster spreading rates; however, caution should be used when incorporating Sequences I-III into geochemical reference sections for faster spreading ridges.

[Basic biological characteristics of mesenchymal stem cells derived from bone marrow and human umbilical cord].

PubMed

Han, Zhen-Xia; Shi, Qing; Wang, Da-Kun; Li, Dong; Lyu, Ming

2013-10-01

Bone marrow (BM) and umbilical cord (UC) are the major sources of mesenchymal stem cells for therapeutics. This study was aimed to compare the basic biologic characteristics of bone marrow-derived and umbilical cord derived-mesenchymal stem cells (BM-MSC and UC-MSC) and their immunosuppressive capability in vitro. The BM-MSC and UC-MSC were cultured and amplified under same culture condition. The growth kinetics, phenotypic characteristics and immunosuppressive effects of UC-MSC were compared with those of BM-MSC.Gene chip was used to compare the genes differentially expressed between UC-MSC and BM-MSC. The results showed that UC-MSC shared most of the characteristics of BM-MSC, including morphology and immunophenotype. UC-MSC could be ready expanded for 30 passages without visible changes. However, BM-MSC grew slowly, and the mean doubling time increased notably after passage 6. Both UC-MSC and BM-MSC could inhibit phytohemagglutinin-stimulated peripheral blood mononuclear cell proliferation, in which BM-MSC mediated more inhibitory effect. Compared with UC-MSC, BM-MSC expressed more genes associated with immune response. Meanwhile, the categories of up-regulated genes in UC-MSC were concentrated in organ development and growth. It is concluded that the higher proliferation capacity, low human leukocyte antigen-ABC expression and immunosuppression make UC-MSC an excellent alternative to BM-MSC for cell therapy. The differences between BM-MSC and UC-MSC gene expressions can be explained by their ontogeny and different microenvironment in origin tissue. These differences can affect their efficacy in different therapeutic applications.

Compassionate access anti-tumour necrosis factor-α therapy for ulcerative colitis in Australia: the benefits to patients.

PubMed

Costello, S P; Ghaly, S; Beswick, L; Pudipeddi, A; Agarwal, A; Sechi, A; O'Connor, S; Connor, S J; Sparrow, M P; Bampton, P; Walsh, A J; Andrews, J M

2015-06-01

The efficacy of infliximab has been demonstrated in patients with both acute severe and moderate-severe ulcerative colitis (UC). However, there is a need for 'real-life data' to ensure that conclusions from trial settings are applicable in usual care. We therefore examined the national experience of anti-tumour necrosis factor-α (TNF-α) therapy in UC. Case notes review of patients with UC who had received compassionate access (CA) anti-TNF-α therapy from prospectively maintained inflammatory bowel disease databases of six Australian adult teaching hospitals. Patients either received drug for acute severe UC (ASUC) failing steroids (n = 29) or for medically refractory UC (MRUC) (n = 35). In ASUC, the treating physicians judged that anti-TNF-α therapy was successful in 20/29 patients (69%); in these cases, anti-TNF-α was able to be discontinued (after 1-3 infusions in 19/20 responders) as clinical remission was achieved. Consistent with this perceived benefit, only 7/29 (24%) subsequently underwent colectomy during a median follow up of 12 months (interquartile range (IQR) 5-16). Eight of the 35 patients with MRUC (23%) required colectomy during a median follow up of 28 months (IQR 11-43). The majority of these patients (20/35 or 57%) had anti-TNF-α therapy for ≥4 months, whereas, 27/29 (93%) of ASUC patients had CA for ≤3 months. These data show an excellent overall benefit for anti-TNF-α therapy in both ASUC and MRUC. In particular, only short-duration anti-TNF-α was required in ASUC. These real-life data thus support the clinical trial data and should lead to broader use of this therapy in UC. © 2015 Royal Australasian College of Physicians.

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy.

PubMed

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-02-09

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20-44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79-4.00]), GSTT gene (GMR: 0.68 [0.52-0.80]), consumption of tap water (GMR: 1.35 [1.02-1.77]), seafood (GMR: 1.44 [1.11-1.88]), whole milk (GMR: 1.34 [1.04-1.73]), and fruit/vegetables (GMR: 1.37 [1.03-1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources.

Ulcerative colitis in northern Portugal and Galicia in Spain.

PubMed

Barreiro-de Acosta, Manuel; Magro, Fernando; Carpio, Daniel; Lago, Paula; Echarri, Ana; Cotter, José; Pereira, Santos; Gonçalves, Raquel; Lorenzo, Aurelio; Carvalho, Laura; Castro, Javier; Barros, Luisa; Dias, Jorge Amil; Rodrigues, Susana; Portela, Francisco; Dias, Camila; da Costa-Pereira, Altamiro

2010-07-01

Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. A cross-sectional study was conducted during a 15-month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846-4.058; OR 5.799, 95% CI: 3.433-9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641-15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

PubMed

Vivio, Emily E; Kanuri, Navya; Gilbertsen, Joanna J; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M; Ciorba, Matthew A

2016-04-01

Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice

PubMed Central

Vivio, Emily E.; Kanuri, Navya; Gilbertsen, Joanna J.; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M.

2016-01-01

Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn’s Disease Activity Index (p = 0.04) and Harvey–Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. PMID:26681763

Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography

PubMed Central

Liu, Mei-Juan; Men, Yan-Ming; Zhang, Yong-Lin; Zhang, Yu-Xi; Liu, Hao

2017-01-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules. PMID:28693244

Improvement of diagnostic efficiency in distinguishing the benign and malignant thyroid nodules via conventional ultrasound combined with ultrasound contrast and elastography.

PubMed

Liu, Mei-Juan; Men, Yan-Ming; Zhang, Yong-Lin; Zhang, Yu-Xi; Liu, Hao

2017-07-01

We aimed to evaluate the diagnostic values of conventional ultrasound (US), ultrasound contrast (UC) and ultrasound elastography (UE) in distinguishing the benign and malignant thyroid nodules. A total of 100 patients with thyroid nodules receiving operative treatment were selected; they underwent the conventional US, UE and UC examinations before operation, respectively. The nodules received pathological examination after operation to distinguish benign from malignant lesions. The sensitivity, specificity and diagnostic accordance rate of each diagnostic method was evaluated by receiver operating characteristic (ROC) curve, and the area under the curve (AUC) of ROC was calculated. The manifestations of malignant thyroid nodules in conventional US examination were mostly the hypoecho, heterogeneous echo, irregular shape, unclear boundary, aspect ratio <1, microcalcification and irregular peripheral echo halo, and there were statistically significant differences compared with the benign nodules (P<0.05). UE showed that the differences between benign and malignant nodules in 2, 3 and 4 points were statistically significant (P<0.05). The manifestations of malignant nodules in UC were mostly the irregular shape, obscure boundary, no obvious enhancement, heterogeneous enhancement and visible perfusion defects, and there were statistically significant differences compared with the benign nodules (P<0.05). ROC curve showed that both sensitivity and specificity of UE and UC were superior to those of conventional US. AUC was the largest (AUC = 0.908) and the diagnostic value was the highest in the conventional US combined with UE and UC. Conventional US combined with elastography and UC can significantly improve the sensitivity, specificity and accuracy of diagnosis of benign and malignant thyroid nodules.

Assessing the potential of the Woman's Condom for vaginal drug delivery

PubMed Central

Kramzer, Lindsay F.; Cohen, Jessica; Schubert, Jesse; Dezzutti, Charlene S.; Moncla, Bernard J.; Friend, David; Rohan, Lisa C.

2015-01-01

Background The Woman's Condom is a new female condom that uses a dissolvable polyvinyl alcohol (PVA) capsule to simplify vaginal insertion. This preclinical study assessed the feasibility to incorporate an antiviral drug, UC781, into the Woman's Condom capsule, offering a unique drug delivery platform. Study Design UC781 capsules were fabricated using methods from the development of the Woman's Condom capsules as well as those used in vaginal film development. Capsules were characterized to evaluate physical/chemical attributes, Lactobacillus compatibility, in vitro safety and bioactivity, and condom compatibility. Results Two UC781 capsule platforms were assessed. Capsule masses (mg; mean ± SD) for platforms 1 and 2 were 116.50 ± 18.22 and 93.80 ± 8.49, respectively. Thicknesses were 0.0034 ± 0.0004 in and 0.0033 ± 0.0004 in. Disintegration times were 11 ± 3 sec and 5 ± 1 sec. Puncture strengths were 21.72 ± 3.30 N and 4.02 ± 0.83 N. Water content measured 6.98 ± 1.17 % and 7.04 ± 1.92 %. UC781 content was 0.59 ± 0.05 mg and 0.77 ± 0.11 mg. Both platforms retained in vitro bioactivity and were non-toxic to TZM-bl cells and Lactobacillus. Short-term storage of UC781 capsules with the Woman's Condom pouch did not decrease condom mechanical integrity. Conclusions UC781 was loaded into a polymeric capsule similar to that of the Woman's Condom product. This study highlights the potential use of the Woman's Condom as a platform for vaginal delivery of drugs relevant to sexual/reproductive health, including those for short or long-acting HIV prevention. PMID:25998936

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

PubMed

Bopanna, Sawan; Kedia, Saurabh; Das, Prasenjit; Dattagupta, S; Sreenivas, V; Mouli, V Pratap; Dhingra, Rajan; Pradhan, Rajesh; Kumar, N Suraj; Yadav, Dawesh P; Makharia, Govind; Ahuja, Vineet

2017-08-01

As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Randomized noninferiority trial of telephone versus in-person genetic counseling for hereditary breast and ovarian cancer.

PubMed

Schwartz, Marc D; Valdimarsdottir, Heiddis B; Peshkin, Beth N; Mandelblatt, Jeanne; Nusbaum, Rachel; Huang, An-Tsun; Chang, Yaojen; Graves, Kristi; Isaacs, Claudine; Wood, Marie; McKinnon, Wendy; Garber, Judy; McCormick, Shelley; Kinney, Anita Y; Luta, George; Kelleher, Sarah; Leventhal, Kara-Grace; Vegella, Patti; Tong, Angie; King, Lesley

2014-03-01

Although guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery. Participants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n = 334) or telephone counseling (TC; n = 335). UC participants received in-person pre- and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC. TC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d = 0.03; lower bound of 97.5% CI, -0.61), perceived stress (d = -0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d = -0.16; lower bound of 97.5% CI, -0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d = 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d = -1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient. Genetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Urinary Arsenic in Human Samples from Areas Characterized by Natural or Anthropogenic Pollution in Italy

PubMed Central

Minichilli, Fabrizio; Bianchi, Fabrizio; Ronchi, Anna Maria; Gorini, Francesca; Bustaffa, Elisa

2018-01-01

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20–44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79–4.00]), GSTT gene (GMR: 0.68 [0.52–0.80]), consumption of tap water (GMR: 1.35 [1.02–1.77]), seafood (GMR: 1.44 [1.11–1.88]), whole milk (GMR: 1.34 [1.04–1.73]), and fruit/vegetables (GMR: 1.37 [1.03–1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources. PMID:29425136

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

PubMed

Singh, Sunny; Al-Darmaki, Ahmed; Frolkis, Alexandra D; Seow, Cynthia H; Leung, Yvette; Novak, Kerri L; Ghosh, Subrata; Eksteen, Bertus; Panaccione, Remo; Kaplan, Gilaad G

2015-10-01

There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Risk for Overall Infection with Anti-TNF and Anti-integrin Agents Used in IBD: A Systematic Review and Meta-analysis.

PubMed

Shah, Eric D; Farida, Jeremy P; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2017-04-01

The overall risk for infection with contemporary biological agents in treating Crohn's disease (CD) and ulcerative colitis (UC) has not been systematically assessed. We performed a PubMed and Cochrane database literature search to evaluate randomized, placebo-controlled trials of biologics in treating UC and CD. Meta-analysis was performed using a DerSimonian and Laird random effects model. We determined relative risk (RR) of harm against placebo; number needed to harm (NNH) was reported when appropriate. Heterogeneity and publication bias were assessed. Fourteen trials (6 UC and 8 CD) evaluating 5107 patients were included. For anti-tumor necrosis factor agents used in the treatment of UC, golimumab {NNH of 9.3, RR = 1.4 (95% confidence interval [CI], 1.04-1.8)} and pooled studies of infliximab and adalimumab (NNH = 17.2, RR = 1.2 [95% CI, 1.0-1.3]) had a statistically significant higher risk for any infection versus placebo. Risk was not significantly increased in anti-tumor necrosis factor trials in CD (RR = 1.1 [95% CI, 0.8-1.5]). By contrast, anti-integrin agents in UC (RR = 1.0 [95% CI, 0.9-1.2]) or CD (RR = 1.1 [95% CI, 0.97-1.3]) did not confer a statistically significant excess risk of infection versus placebo. Anti-tumor necrosis factor therapy but not anti-integrin therapy is associated with a greater infection risk than placebo in treating UC. Neither class of therapy is associated with increased infection risk over placebo in treating CD. Our findings can help guide patient-centered discussions regarding the risk for infection with biological agents.

Logistics Modeling of Emplacement Rate and Duration of Operations for Generic Geologic Repository Concepts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalinina, Elena Arkadievna; Hardin, Ernest

This study identified potential geologic repository concepts for disposal of spent nuclear fuel (SNF) and (2) evaluated the achievable repository waste emplacement rate and the time required to complete the disposal for these concepts. Total repository capacity is assumed to be approximately 140,000 MT of spent fuel. The results of this study provide an important input for the rough-order-of-magnitude (ROM) disposal cost analysis. The disposal concepts cover three major categories of host geologic media: crystalline or hard rock, salt, and argillaceous rock. Four waste package sizes are considered: 4PWR/9BWR; 12PWR/21BWR; 21PWR/44BWR, and dual purpose canisters (DPCs). The DPC concepts assumemore » that the existing canisters will be sealed into disposal overpacks for direct disposal. Each concept assumes one of the following emplacement power limits for either emplacement or repository closure: 1.7 kW; 2.2 kW; 5.5 kW; 10 kW; 11.5 kW, and 18 kW.« less

Local-scale stratigraphy of grooved terrain on Ganymede

NASA Technical Reports Server (NTRS)

Murchie, Scott L.; Head, James W.; Helfenstein, Paul; Plescia, Jeffrey B.

1987-01-01

The surface of the Jovian satellite, Ganymede, is divided into two main units, dark terrain cut by arcuate and subradial furrows, and light terrain consisting largely of areas with pervasive U-shaped grooves. The grooved terrain may be subdivided on the basis of pervasive morphology of groove domains into four terrain types: (1) elongate bands of parallel grooves (groove lanes); (2) polygonal domains of parallel grooves (grooved polygons); (3) polygonal domains of two orthogonal groove sets (reticulate terrain); and (4) polygons having two to several complexly cross-cutting groove sets (complex grooved terrain). Reticulate terrain is frequently dark and not extensively resurfaced, and grades to a more hummocky terrain type. The other three grooved terrain types have almost universally been resurfaced by light material during their emplacement. The sequence of events during grooved terrain emplacement has been investigated. An attempt is made to integrate observed geologic and tectonic patterns to better constrain the relative ages and styles of emplacement of grooved terrain types. A revised model of grooved terrain emplacement is proposed and is tested using detailed geologic mapping and measurement of crater density.

Thermocouple psychrometer measurements of in situ water potential changes in heated welded tuff

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao, Nai-hsien; Wang, H.F.

1991-05-01

Ten thermocouple psychrometers (TCPs) to measure water potential (WP) were installed in three holes in G-Tunnel at the Nevada Test Site as part of the Prototype Engineered Barrier System Field Tests. These integrated tests measured several parameters as a function of location and time within a few meters of a heater emplaced in welded tuff. The primary goal of the TCP experiment was to find out whether the combination of laboratory calibration and field use of the TCP can provide useful data for determining the change of moisture condition in the field. We calibrated the TCPs in NaCl solutions upmore » to 80{degree}C(176{degree}F) in the laboratory. In two holes, we used rubber sleeves and packers to house TCPs, and in the third hole, we used foam. All three holes were grouted behind the TCP assemblages. Field results of the heater test showed that small temperature gradients were present for all measurements. Nevertheless, the WP calibration made the necessary correction for the nonisothermal condition. A drying and re-wetting cycle peaked at about day 140 with a WP of -65 bar in borehole P3, located below the heater. A similar cycle but reduced in scale was found at about day 175 with a WP of -45 bar in borehole P2, above the heater. This difference in drying behavior above and below the heater was also observed from neutron data and was explained as a gravity effect. As temperatures increased, the evaporation rate of pore water increased, In unfractured rock, the gas-phase flow was primarily outward. Water condensed above the heater would drain back to keep the boiling region wet, but water condensed below the heater would drain away from the boiling region. This conceptual model explained both the time and magnitude differences for data from holes above and below the heater. 7 refs., 14 figs., 2 tabs.« less

Glans size is an independent risk factor for urethroplasty complications after hypospadias repair.

PubMed

Bush, Nicol C; Villanueva, Carlos; Snodgrass, Warren

2015-12-01

We hypothesized small glans size could increase urethroplasty complications (UC) following hypospadias repair. To test this, we measured glans width at its widest point in consecutive patients with hypospadias, and following a protocol for surgical decision-making, we then assessed post-operative UC using pre-determined definitions. We now report analysis of glans size as a potential additional independent risk factor for UC after hypospadias repair. Consecutive prepubertal patients undergoing hypospadias repair (2009-2013) had maximum glans width measured using calipers (Fig. 1). There were no differences in surgical technique for urethroplasty or glansplasty in this series based on the measured size of the glans. Multivariate logistic regression analyzed UC (fistula, glans dehiscence, diverticulum, stricture and/or meatal stenosis) based on glans size while adjusting for patient age, meatus (distal or midshaft/proximal), type of repair (TIP, inlay, 2-stage), surgeon, and primary or reoperative repair. Glans size was analyzed as both a continuous and dichotomous variable, with small glans defined as <14 mm. Mean glans size was 15 mm (10-27 mm) in 490 boys (mean 1.5 years) undergoing 432 primary repairs (380d/19mid/33prox), and 58 reoperations (28d/7mid/23prox). Increasing age between 3 months and 10 years did not correlate with increasing glans size (R = 0.01, p = 0.18). 17% had small glans <14 mm. UC occurred in 61 (13%) primary TIP, 2-stage, and reoperative repairs, including 20/81 (25%) patients with small glans <14 mm, versus 41/409 (10%) in patients with glans width ≥14 mm (p = 0.0003). On multivariate analysis, small glans size (OR 3.5, 95% CI 1.8-6.8), reoperations (OR 3.0, 95% CI 1.4-6.5) and mid/proximal meatus (OR 3.1, 95% CI 1.6-6.2) were independent risk factors for UC. Surgeon, repair type, and patient age did not impact risk for UC. Analysis with glans size as a continuous variable demonstrated each 1 mm increase in size decreased odds of UC (OR 0.8, 95% CI 0.7-0.9). Our analysis of prospectively-collected data from a standardized management protocol in 490 consecutive boys undergoing hypospadias repair adds small glans size, defined as width <14 mm, to proximal meatal location and reoperation as an independent risk factor for UC. Best means to modify this factor remain to be determined. Our data suggest that others analyzing potential risks for hypospadias UC should similarly measure and report glans width. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

UCS protein Rng3p activates actin filament gliding by fission yeast myosin-II

PubMed Central

Lord, Matthew; Pollard, Thomas D.

2004-01-01

We purified native Myo2p/Cdc4p/Rlc1p (Myo2), the myosin-II motor required for cytokinesis by Schizosaccharomyces pombe. The Myo2p heavy chain associates with two light chains, Cdc4p and Rlc1p. Although crude Myo2 supported gliding motility of actin filaments in vitro, purified Myo2 lacked this activity in spite of retaining full Ca-ATPase activity and partial actin-activated Mg-ATPase activity. Unc45-/Cro1p-/She4p-related (UCS) protein Rng3p restored the full motility and actin-activated Mg-ATPase activity of purified Myo2. The COOH-terminal UCS domain of Rng3p alone restored motility to pure Myo2. Thus, Rng3p contributes directly to the motility activity of native Myo2. Consistent with a role in Myo2 activation, Rng3p colocalizes with Myo2p in the cytokinetic contractile ring. The absence of Rlc1p or mutations in the Myo2p head or Rng3p compromise the in vitro motility of Myo2 and explain the defects in cytokinesis associated with some of these mutations. In contrast, Myo2 with certain temperature-sensitive forms of Cdc4p has normal motility, so these mutations compromise other functions of Cdc4p required for cytokinesis. PMID:15504913

Eruption and emplacement dynamics of a thick trachytic lava flow of the Sancy volcano (France)

NASA Astrophysics Data System (ADS)

Latutrie, Benjamin; Harris, Andrew; Médard, Etienne; Gurioli, Lucia

2017-01-01

A 70-m-thick, 2200-m-long (51 × 106 m3) trachytic lava flow unit underlies the Puy de Cliergue (Mt. Dore, France). Excellent exposure along a 400-m-long and 60- to 85-m-high section allows the flow interior to be accessed on two sides of a glacial valley that cuts through the unit. We completed an integrated morphological, structural, textural, and chemical analysis of the unit to gain insights into eruption and flow processes during emplacement of this thick silicic lava flow, so as to elucidate the chamber and flow dynamic processed that operate during the emplacement of such systems. The unit is characterized by an inverse chemical stratification, where there is primitive lava beneath the evolved lava. The interior is plug dominated with a thin basal shear zone overlying a thick basal breccia, with ramping affecting the entire flow thickness. To understand these characteristics, we propose an eruption model that first involves processes operating in the magma chamber whereby a primitive melt is injected into an evolved magma to create a mixed zone at the chamber base. The eruption triggered by this event first emplaced a trachytic dome, into which banded lava from the chamber base was injected. Subsequent endogenous dome growth led to flow down the shallow slope to the east on which the highly viscous (1012 Pa s) coulée was emplaced. The flow likely moved extremely slowly, being emplaced over a period of 4-10 years in a glacial manner, where a thick (>60-m) plug slid over a thin (5-m-thick) basal shear zone. Excellent exposure means that the Puy de Cliergue complex can be viewed as a case type location for understanding and defining the eruption and emplacement of thick, high-viscosity, silicic lava flow systems.

Ultra-fast pump-probe determination of electron-phonon coupling in cuprate superconductors

NASA Astrophysics Data System (ADS)

Mihailovic, Dragan

2010-03-01

Fresh femtosecond spectroscopy experiments show the electron-phonon interaction strength λ to be 0.7 and 1.4 for YBCO and LSCO respectively and not around 0.2 as previously reported [1]. The revised estimates arise primarily from improved time-resolution, and also partly from improved modeling. Comparison with classical superconductors and pnictides shows non-monotonic correlation of λ with Tc. Systematic new measurements of the condensate vaporization energy (Uv) in cuprates [2] and pnictides reveals a power-law dependence on Tc with exponent 2. However, Uc is 16-18 times greater than the BCS condensation energy Uc, implying that a significant heat capacity of the ``bosonic glue.'' In contrast, charge-density wave systems with electronically driven ordering transitions have Uv˜Uc. The data suggest BCS and Eliashberg-based models to be inappropriate for describing the physics of high-temperature superconductors, and point towards polaron models which consider strong or intermediate λ.[4pt] [1] C.Gadermeier et al., arXiv:0902.1636[0pt] [2] P.Kusar et al., Phys. Rev. Lett. 101, 227001 (2008)

A transcribed ultraconserved noncoding RNA, Uc.173, is a key molecule for the inhibition of lead-induced neuronal apoptosis

PubMed Central

Chen, Lijian; Liu, Meiling; Zhang, Nan; Zhang, Li; Luo, Yuanwei; Liu, Zhenzhong; Dai, Lijun; Jiang, Yiguo

2016-01-01

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury. PMID:26683706

Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

PubMed

Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

2016-01-01

Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

Evidence of volcanic and glacial activity in Chryse and Acidalia Planitiae, Mars

USGS Publications Warehouse

Martinez-Alonso, Sara; Mellon, Michael T.; Banks, Maria E.; Keszthelyi, Laszlo P.; McEwen, Alfred S.

2011-01-01

Chryse and Acidalia Planitiae show numerous examples of enigmatic landforms previously interpreted to have been influenced by a water/ice-rich geologic history. These landforms include giant polygons bounded by kilometer-scale arcuate troughs, bright pitted mounds, and mesa-like features. To investigate the significance of the last we have analyzed in detail the region between 60°N, 290°E and 10°N, 360°E utilizing HiRISE (High Resolution Imaging Science Experiment) images as well as regional-scale data for context. The mesas may be analogous to terrestrial tuyas (emergent sub-ice volcanoes), although definitive proof has not been identified. We also report on a blocky unit and associated landforms (drumlins, eskers, inverted valleys, kettle holes) consistent with ice-emplaced volcanic or volcano-sedimentary flows. The spatial association between tuya-like mesas, ice-emplaced flows, and further possible evidence of volcanism (deflated flow fronts, volcanic vents, columnar jointing, rootless cones), and an extensive fluid-rich substratum (giant polygons, bright mounds, rampart craters), allows for the possibility of glaciovolcanic activity in the region.Landforms indicative of glacial activity on Chryse/Acidalia suggest a paleoclimatic environment remarkably different from today's. Climate changes on Mars (driven by orbital/obliquity changes) or giant outflow channel activity could have resulted in ice-sheet-related landforms far from the current polar caps.

Reduced risk of UC in families affected by appendicitis: a Danish national cohort study.

PubMed

Nyboe Andersen, Nynne; Gørtz, Sanne; Frisch, Morten; Jess, Tine

2017-08-01

The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. A cohort of 7.1 million individuals was established by linkage of national registers in Denmark with data on kinship and diagnoses of appendicitis and UC. Poisson regression models were used to calculate first hospital contact rate ratios (RR) for UC with 95% CIs between individuals with or without relatives with a history of appendicitis. During 174 million person-years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question a previously hypothesised direct protective influence of appendicitis on inflammation of the large bowel. Rather, genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs.

PubMed

Deparle, L A; Gupta, R C; Canerdy, T D; Goad, J T; D'Altilio, M; Bagchi, M; Bagchi, D

2005-08-01

DeParle L. A., Gupta R. C., Canerdy T. D., Goad J. T., D'Altilio M., Bagchi M., Bagchi D. Efficacy and safety of glycosylated undenatured type-II collagen (UC-II) in therapy of arthritic dogs. J. vet. Pharmacol. Therap.28, 385-390. In large breed dogs, arthritis is very common because of obesity, injury, aging, immune disorder, or genetic predispositions. This study was therefore undertaken to evaluate clinical efficacy and safety of undenatured type-II collagen (UC-II) in obese-arthritic dogs. Fifteen dogs in three groups received either no UC-II (Group I) or UC-II with 1 mg/day (Group II) or 10 mg/day (Group III) for 90 days. Lameness and pain were measured on a weekly basis for 120 days (90 days treatment plus 30 days post-treatment). Blood samples were assayed for creatinine and blood urea nitrogen (markers of renal injury); and alanine aminotransferase and aspartate aminotransferase (evidence of hepatic injury). Dogs receiving 1 mg or 10 mg UC-II/day for 90 days showed significant declines in overall pain and pain during limb manipulation and lameness after physical exertion, with 10 mg showed greater improvement. At either dose of UC-II, no adverse effects were noted and no significant changes were noted in serum chemistry, suggesting that UC-II was well tolerated. In addition, dogs receiving UC-II for 90 days showed increased physical activity level. Following UC-II withdrawal for a period of 30 days, all dogs experienced a relapse of overall pain, exercise-associated lameness, and pain upon limb manipulation. These results suggest that daily treatment of arthritic dogs with UC-II ameliorates signs and symptoms of arthritis, and UC-II is well tolerated as no adverse effects were noted.

Second-hand smoke exposure in 4-year-old children in Spain: Sources, associated factors and urinary cotinine.

PubMed

Aurrekoetxea, Juan José; Murcia, Mario; Rebagliato, Marisa; Guxens, Mònica; Fernández-Somoano, Ana; López, María José; Lertxundi, Aitana; Castilla, Ane Miren; Espada, Mercedes; Tardón, Adonina; Ballester, Ferran; Santa-Marina, Loreto

2016-02-01

Second-hand smoke exposure (SHS) in children remains as a major pollution problem, with important consequences for children's health. This study aimed to identify the sources of exposure to SHS among 4-year-old children, comparing self-reports to a urinary biomarker of exposure, and characterize the most important variables related to SHS exposure in this population. 4-year-old children's exposure to SHS was assessed by a parental-reported questionnaire and by urinary cotinine (UC) measurements in 1757 participants from 4 different areas of the Spanish INMA (INfancia y Medio Ambiente - Environment and Childhood) Project. The questionnaire about SHS included information about smoking habits at home by household members, and about exposure to SHS in other places including other homes, bars, restaurants or transportation. The association between quantified UC levels (>4ng/ml) and sociodemographic variables and the different sources of SHS exposure was examined using logistic regression. Based on parental reports, 21.6% of the children were exposed to SHS at home and 47.1% elsewhere; making a total 55.9% of the children exposed to SHS. In addition, 28.2% of the children whose parents reported being not regularly exposed to SHS had quantified UC values. Children from younger mothers (<34 vs. ≥39.4 y) had a higher odds of exposure to SHS [OR (95% CI): 2.28 (1.70-3.05) per year], as well as from families with a lower educational level [OR secondary: 2.12 (1.69-2.65); primary or less: 2.91 (2.19-3.88)]. The odds of quantifiable UC in children dropped after the smoking ban in public places [OR=0.59 (0.42-0.83)]. Regarding the sources of SHS exposure we observed that quantifiable UC odds was increased in children whose parents smoked at home in their presence [OR mother occasionally: 13.39 (7.03-25.50); mother often: 18.48 (8.40-40.66); father occasionally: 10.98 (6.52-18.49); father often: 11.50 (5.96-22.20)] or in children attending other confined places, mainly other houses where people smoked [OR: 2.23 (1.78-2.80)]. Children's SHS exposure is nowadays an unresolved major public health problem in Spain. After the ban of smoking in public places health care professionals should put more emphasis to the parents on the importance of controlling the exposure of their children in private spaces. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study.

PubMed

Jess, Tine; Frisch, Morten; Jørgensen, Kristian Tore; Pedersen, Bo Vestergaard; Nielsen, Nete Munk

2012-09-01

An association between endometriosis and certain autoimmune diseases has been suggested. However, the impact of endometriosis on risk of inflammatory bowel disease (IBD) remains unknown. To assess the risk of Crohn's disease (CD) and ulcerative colitis (UC) in an unselected nationwide Danish cohort of women with endometriosis. By use of national registers, 37 661 women hospitalised with endometriosis during 1977-2007 were identified. The relative risk of developing IBD after an endometriosis diagnosis was calculated as observed versus expected numbers and presented as standardised incidence ratios (SIRs) with 95% CIs. Women with endometriosis had a increased risk of IBD overall (SIR=1.5; 95% CI 1.4 to 1.7) and of UC (SIR=1.5; 95% CI 1.3 to 1.7) and CD (SIR=1.6; 95% CI 1.3 to 2.0) separately, even 20 years after a diagnosis of endometriosis (UC: SIR=1.5; 95% CI 1.1 to 2.1; CD: SIR=1.8; 95% CI 1.1 to 3.2). Restricting analyses to women with surgically verified endometriosis suggested even stronger associations (UC: SIR=1.8; 95% CI 1.4 to 2.3; CD: SIR=1.7; 95% CI 1.2 to 2.5). The risk of IBD in women with endometriosis was increased even in the long term, hence suggesting a genuine association between the diseases, which may either reflect common immunological features or an impact of endometriosis treatment with oral contraceptives on risk of IBD.

Update on the management of ulcerative colitis: treatment and maintenance approaches focused on MMX® mesalamine

PubMed Central

Nanda, Kavinderjit; Moss, Alan C

2012-01-01

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon that typically manifests as diarrhea, abdominal pain, and bloody stool. Complications, such as colorectal cancer and extraintestinal manifestations, may also develop. The goals of management are to induce and maintain clinical remission and to screen for complications of this disease. Mesalamine is a 5-aminosalicylic acid compound that is the first-line therapy to induce and maintain clinical remission in patients with mild-to-moderate UC. For patients who are refractory to mesalamine or have more severe disease, steroids, azathioprine/mercaptopurine, cyclosporine, or infliximab may be used, induce and/or maintain remission. The various formulations of mesalamine available are primarily differentiated by the methods of delivery of the active compound of the drug to the colon. Mesalamine with Multi-Matrix System® (MMX) technology (Cosmo SpA, Milan, Italy) is an oral (1.2 g), once-daily tablet formulation of mesalamine used for the treatment of UC (Lialda® or Mezavant®, Shire Pharmaceuticals Inc, Wayne, PA). In clinical studies, MMX mesalamine (taken as a once-daily dose of 2.4 or 4.8 g) effectively induced and maintained clinical remission in patients with active mild-to-moderate UC. The overall safety profile of MMX mesalamine is similar to other oral mesalamine formulations. The use of such once-daily formulations has led to intense interest in whether simplified pill regimens can improve patient adherence to mesalamine therapy. PMID:22888278

Metallic conductance at the interface of tri-color titanate superlattices

NASA Astrophysics Data System (ADS)

Kareev, M.; Cao, Yanwei; Liu, Xiaoran; Middey, S.; Meyers, D.; Chakhalian, J.

2013-12-01

Ultra-thin tri-color (tri-layer) titanate superlattices ([3 u.c. LaTiO3/2 u.c. SrTiO3/3 u.c. YTiO3], u.c. = unit cells) were grown in a layer-by-layer way on single crystal TbScO3 (110) substrates by pulsed laser deposition. High sample quality and electronic structure were characterized by the combination of in-situ photoelectron and ex-situ structure and surface morphology probes. Temperature-dependent sheet resistance indicates the presence of metallic interfaces in both [3 u.c. LaTiO3/2 u.c. SrTiO3] bi-layers and all the tri-color structures, whereas a [3 u.c. YTiO3/2 u.c. SrTiO3] bi-layer shows insulating behavior. Considering that in the bulk YTiO3 is ferromagnetic below 30 K, the tri-color titanate superlattices provide an opportunity to induce tunable spin-polarization into the two-dimensional electron gas with Mott carriers.

Novel genetic risk markers for ulcerative colitis in the IL2/IL21 region are in epistasis with IL23R and suggest a common genetic background for ulcerative colitis and celiac disease.

PubMed

Glas, Jürgen; Stallhofer, Johannes; Ripke, Stephan; Wetzke, Martin; Pfennig, Simone; Klein, Wolfram; Epplen, Jörg T; Griga, Thomas; Schiemann, Uwe; Lacher, Martin; Koletzko, Sibylle; Folwaczny, Matthias; Lohse, Peter; Göke, Burkhard; Ochsenkühn, Thomas; Müller-Myhsok, Bertram; Brand, Stephan

2009-07-01

Recently, a genome-wide association study showed that single-nucleotide polymorphisms (SNPs) in the chromosome 4q27 region containing IL2 and IL21 are associated with celiac disease. Given the increased prevalence of inflammatory bowel disease (IBD) among celiac disease patients, we investigated the possible involvement of these SNPs in IBD. Five SNPs strongly associated with celiac disease within the KIAA1109/TENR/IL2/IL21 linkage disequilibrium block on chromosome 4q27 and one coding SNP within the IL21 gene were analyzed in a large German IBD cohort. The study population comprised a total of 2,948 Caucasian individuals, including 1,461 IBD patients (ulcerative colitis (UC): n=514, Crohn's disease (CD): n=947) and 1,487 healthy unrelated controls. Three of the five celiac disease risk markers had a protective effect on UC susceptibility, and this effect remained significant after correcting for multiple testing: rs6840978: P=0.0082, P(corr)=0.049, odds ratio (OR) 0.77, 95% confidence interval (CI) 0.63-0.93; rs6822844: P=0.0028, P(corr)=0.017, OR 0.73, 95% CI 0.59-0.90; rs13119723: P=0.0058, P(corr)=0.035, OR 0.75, 95% CI 0.61-0.92. A haplotype consisting of the six SNPs tested was markedly associated with UC susceptibility (P=0.0025, P(corr)=0.015, OR 0.72, 95% CI 0.58-0.89). Moreover, in UC, epistasis was observed between the IL23R SNP rs1004819 and three SNPs in the KIAA1109/TENR/IL2/IL21 block (rs13151961, rs13119723, and rs6822844). Similar to other autoimmune diseases such as celiac disease, rheumatoid arthritis, type 1 diabetes, Graves' disease, and psoriatic arthritis, genetic variation in the chromosome 4q27 region predisposes to UC, suggesting a common genetic background for these diseases.

Evaluation of skeletal maturity using maxillary canine, mandibular second and third molar calcification stages.

PubMed

Trakinienė, Giedrė; Smailienė, Dalia; Kučiauskienė, Ainė

2016-08-01

The objective of this study was to evaluate whether the calcification stages of maxillary canine, mandibular second molar, and mandibular third molar can be used for assessment of growth phase. The study group consisted of 274 subjects. Pre-treatment digital panoramic and lateral cephalometric radiographs of the patients were analysed. The patients' age was ranging from 7 to 19 years. Right maxillary canine, mandibular second molar and third molar were used as a sample. The teeth mineralization was assessed using modification of Gleiser and Hunt method. The skeletal maturation was assessed by the cervical vertebrae maturation (CVM) method. A significant association was found between CVM stage 2 and maxillary canine (UC) stage 4, mandibular second molar (LM2) stage 4, and mandibular third molar (LM3) stage 1. CVM stage 3 corresponded with UC stage 5, LM2 stage 5, LM3 stage 2. CVM stage 4 matched with UC stage 5, LM2 stage 6 and LM3 stage 3. The highest correlations between CVM and calcification stages were in the group of the maxillary canine (r = 0.812, P < 0.01) and mandibular second molar (r = 0.824, P < 0.01). Limitation of our study was that the study sample was not very big and the distribution value in the groups was very high, so it was impossible to check more statistical parameters. The calcification stages of UC, LM2, and LM3 as indicators of skeletal maturity could be clinically used with caution, until this method is verified with a larger sample group. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib.

PubMed

Winthrop, Kevin L; Melmed, Gil Y; Vermeire, Séverine; Long, Millie D; Chan, Gary; Pedersen, Ronald D; Lawendy, Nervin; Thorpe, Andrew J; Nduaka, Chudy I; Su, Chinyu

2018-05-30

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib is approved for rheumatoid arthritis and psoriatic arthritis, where it has been shown to increase herpes zoster (HZ) risk. We evaluated HZ risk among UC patients using tofacitinib. HZ cases were identified in tofacitinib phase II/III/ongoing, open-label, long-term extension (OLE) UC trials. We calculated HZ incidence rates (IRs) per 100 patient-years of tofacitinib exposure within phase III maintenance (Maintenance Cohort) and phase II/III/OLE (Overall Cohort) studies, stratified by baseline demographics and other factors. HZ risk factors were evaluated in the Overall Cohort using Cox proportional hazard models. Overall, 65 (5.6%) patients developed HZ. Eleven patients had multidermatomal involvement (2 nonadjacent or 3-6 adjacent dermatomes), and 1 developed encephalitis (resolved upon standard treatment). Five (7.7%) events led to treatment discontinuation. HZ IR (95% confidence interval [CI]) in the Overall Cohort was 4.07 (3.14-5.19) over a mean (range) of 509.1 (1-1606) days, with no increased risk observed with increasing tofacitinib exposure. IRs (95% CI) were highest in patients age ≥65 years, 9.55 (4.77-17.08); Asian patients, 6.49 (3.55-10.89); patients with prior tumor necrosis factor inhibitor (TNFi) failure, 5.38 (3.86-7.29); and patients using tofacitinib 10 mg twice daily, 4.25 (3.18-5.56). Multivariate analysis identified older age and prior TNFi failure as independent risk factors. In tofacitinib-treated UC patients, there was an elevated risk of HZ, although complicated HZ was infrequent. Increased HZ rates occurred in patients who were older, Asian, or had prior TNFi failure (NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612).

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Task Order 22 – Engineering and Technical Support, Deep Borehole Field Test. AREVA Summary Review Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denton, Mark A.

Under Task Order 22 of the industry Advisory and Assistance Services (A&AS) Contract to the Department of Energy (DOE) DE-NE0000291, AREVA has been tasked with providing assistance with engineering, analysis, cost estimating, and design support of a system for disposal of radioactive wastes in deep boreholes (without the use of radioactive waste). As part of this task order, AREVA was requested, through a letter of technical direction, to evaluate Sandia National Laboratory’s (SNL’s) waste package borehole emplacement system concept recommendation using input from DOE and SNL. This summary review report (SRR) documents this evaluation, with its focus on the primarymore » input document titled: “Deep Borehole Field Test Specifications/M2FT-15SN0817091” Rev. 1 [1], hereafter referred to as the “M2 report.” The M2 report focuses on the conceptual design development for the Deep Borehole Field Test (DBFT), mainly the test waste packages (WPs) and the system for demonstrating emplacement and retrieval of those packages in the Field Test Borehole (FTB). This SRR follows the same outline as the M2 report, which allows for easy correlation between AREVA’s review comments, discussion, potential proposed alternatives, and path forward with information established in the M2 report. AREVA’s assessment focused on three primary elements of the M2 report: the conceptual design of the WPs proposed for deep borehole disposal (DBD), the mode of emplacement of the WP into DBD, and the conceptual design of the DBFT. AREVA concurs with the M2 report’s selection of the wireline emplacement mode specifically over the drill-string emplacement mode and generically over alternative emplacement modes. Table 5-1 of this SRR compares the pros and cons of each emplacement mode considered viable for DBD. The primary positive characteristics of the wireline emplacement mode include: (1) considered a mature technology; (2) operations are relatively simple; (3) probability of a radiological release due to off-normal events are relatively low; (4) costs are relatively low; and (5) maintenance activities are relatively simple. The primary drawback associated with the wireline emplacement mode for DBD is the number of emplacement trips-in to the borehole, which results in a relatively higher probability for a drop event. Fortunately, the WPs can be engineered with impact limiters that will minimize the likelihood of a breach of the WP due to a drop. The WP designs presented in the M2 report appear to be focused on compatibility with the drill-string emplacement mode (e.g., the threaded connections). With the recommendation that the wireline emplacement mode be utilized for the DBFT, some changes may be warranted to these WPs. For example, the development of a WP release connection that is more reliable than the currently credited connection, which is considered to have a high failure probability, and the integration of an impact limiter into its design. The M2 report states the engineering demonstration of the DBFT will occur in the FTB over a 4-year period. AREVA recommends development and testing of the WP emplacement handling equipment occur separately (but concurrently, if not earlier) from the FTB at a mock-up facility. The separation of this activity would prevent schedule interference between the science and engineering thrusts of the project. Performing tests in a mock-up facility would allow additional control and observation compared to the FTB. The mock-up facility could also be utilized as a training facility for future operations. Terminal velocity and impact limiter testing would require the FTB for testing, since these areas would be difficult to reproduce in a limited depth mock-up. Although only at the end of the conceptual stage of design development, DBD appears to be a viable solution for some waste forms produced by the nuclear industry. However, regulatory requirements have yet to be established for pre- and post-closure performance of DBD and should be established as soon as possible. Some of the main areas of focus from a regulatory perspective include: (1) establishing acceptable performance requirements for the long-term behavior of DBD; (2) determining acceptable borehole abandonment criteria; (3) establishing retrievability requirements; (4) developing a consensus on the factor of safety (FoS) for the emplacement mode and WP; and (5) establishing safety and safeguards performance requirements for DBD. Although conservative requirements have been utilized to provide the foundation for the conceptual design of DBD, regulatory requirements and feedback are necessary to confirm recommendations made herein and to ensure the long-term performance of DBD is acceptable. The combination of the M2 report and this SRR is intended to facilitate the completion of the conceptual design for DBD for the Cs and Sr capsules and calcined waste forms. Using the conceptual design, preliminary design activities (the second stage of a three-stage process described in the M2 report) can proceed and the DBFT utilized to support, demonstrate, and confirm engineering elements of this design.« less

High Israeli mortality rates from diabetes and renal failure - Can international comparison of multiple causes of death reflect differences in choice of underlying cause?

PubMed

Goldberger, Nehama; Applbaum, Yael; Meron, Jill; Haklai, Ziona

2015-01-01

The age-adjusted mortality rate in Israel is low compared to most Western countries although mortality rates from diabetes and renal failure in Israel are amongst the highest, while those from cardiovascular diseases (CVD) are amongst the lowest. This study aims to assess validity of choice of underlying causes (UC) in Israel by analyzing Israeli and international data on the prevalence of these diseases as multiple causes of death (MCOD) compared to UC, and data on comorbidity (MCOD based). Age-adjusted death rates were calculated for UC and MCOD and the corresponding ratio of multiple to underlying cause of death (SRMU) for available years between 1999 and 2012. Comorbidity was explored by calculating cause of death association indicators (CDAI) and frequency of comorbid disease. These results were compared to data from USA, France, Italy, Australia and the Czech Republic for 2009 or other available year. Mortality rates for all these diseases except renal failure have decreased in Israel between 1999 and 2012 as UC and MCOD. In 2009, the SRMU for diabetes was 2.7, slightly lower than other Western countries (3.0-3.5) showing more frequent choice as UC. Similar results were found for renal failure. In contrast, the SRMU for ischemic heart disease (IHD) and cerebrovascular disease were 2.0 and 2.6, respectively, higher than other countries (1.4-1.6 and 1.7-1.9, respectively), showing less frequent choice as UC. CDAI data showed a strong association between heart and cerebrovascular disease, and diabetes in all countries. In Israel, 40 % of deaths with UC diabetes had IHD and 24 % had cerebrovascular disease. Renal disease was less strongly associated with IHD. This international comparison suggests that diabetes and renal failure may be coded more frequently in Israel as UC, sometimes instead of heart and cerebrovascular disease. Even with some changes in coding, mortality rates would be high compared to other countries, similar to the comparatively high diabetes prevalence in Israel at older ages and high rate of end-stage renal failure. This study highlights the importance of physician training on death certification practice and need for further progress towards automation in recording and coding death causes.

Gold decorated NaYF4:Yb,Er/NaYF4/silica (core/shell/shell) upconversion nanoparticles for photothermal destruction of BE(2)-C neuroblastoma cells

NASA Astrophysics Data System (ADS)

Qian, Li Peng; Zhou, Li Han; Too, Heng-Phon; Chow, Gan-Moog

2011-02-01

Gold decorated NaYF4:Yb,Er/NaYF4/silica (core/shell/shell) upconversion (UC) nanoparticles ( 70-80 nm) were synthesized using tetraethyl orthosilicate and chloroauric acid in a one-step reverse microemulsion method. Gold nanoparticles ( 6 nm) were deposited on the surface of silica shell of these core/shell/shell nanoparticles. The total upconversion emission intensity (green, red, and blue) of the core/shell/shell nanoparticles decreased by 31% after Au was deposited on the surface of silica shell. The upconverted green light was coupled with the surface plasmon of Au leading to rapid heat conversion. These UC/silica/Au nanoparticles were very efficient to destroy BE(2)-C cancer cells and showed strong potential in photothermal therapy.

Differential Alteration in Intestinal Epithelial Cell Expression of Toll-Like Receptor 3 (TLR3) and TLR4 in Inflammatory Bowel Disease

PubMed Central

Cario, Elke; Podolsky, Daniel K.

2000-01-01

Initiation and perpetuation of the inflammatory intestinal responses in inflammatory bowel disease (IBD) may result from an exaggerated host defense reaction of the intestinal epithelium to endogenous lumenal bacterial flora. Intestinal epithelial cell lines constitutively express several functional Toll-like receptors (TLRs) which appear to be key regulators of the innate response system. The aim of this study was to characterize the expression pattern of TLR2, TLR3, TLR4, and TLR5 in primary intestinal epithelial cells from patients with IBD. Small intestinal and colonic biopsy specimens were collected from patients with IBD (Crohn's disease [CD], ulcerative colitis [UC]) and controls. Non-IBD specimens were assessed by immunofluorescence histochemistry using polyclonal antibodies specific for TLR2, TLR3, TLR4, and TLR5. Primary intestinal epithelial cells (IEC) of normal mucosa constitutively expressed TLR3 and TLR5, while TLR2 and TLR4 were only barely detectable. In active IBD, the expression of TLR3 and TLR4 was differentially modulated in the intestinal epithelium. TLR3 was significantly downregulated in IEC in active CD but not in UC. In contrast, TLR4 was strongly upregulated in both UC and CD. TLR2 and TLR5 expression remained unchanged in IBD. These data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that alterations in the innate response system may contribute to the pathogenesis of these disorders. PMID:11083826

Publications - GMC 310 | Alaska Division of Geological & Geophysical

Science.gov Websites

approximations of core (4,309.5'-4,409') from the BP Exploration (Alaska) Inc. Milne Point G-1 well Authors UCS approximations of core (4,309.5'-4,409') from the BP Exploration (Alaska) Inc. Milne Point G-1

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

PubMed

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Urethral catheters and medical malpractice: a legal database review from 1965 to 2015.

PubMed

Awad, Mohannad A; Osterberg, E Charles; Chang, Helena; Gaither, Thomas W; Alwaal, Amjad; Fox, Ryan; Breyer, Benjamin N

2016-10-01

Urethral catheters (UCs) are commonly used in medicine and are associated with complications such as urinary tract infections (UTIs) and trauma. Given UC complications and their ubiquitous usage in healthcare, there is a potential for liability risk. We aim to explore litigation involving UC-related complications. The LexisNexis legal database was queried for all state and federal cases from January 1965 through October 2015 using the terms "urethral catheter" or "Foley catheter" in combination with "medical malpractice", "negligence", "medical error", and "trauma". Each case was reviewed for reported medical characteristics and legal aspects, including the outcome of the case. Our search yielded 29 cases. Urologists were the most common providers cited as defendants (21%), all of whom were successful in their defense. The most common malpractice claim was for traumatic insertion (48%). Pain was the most common type of damage claimed by plaintiffs (28%), followed by UTI (24%). Nineteen (66%) cases favored defendants, while 10 (34%) cases favored the plaintiffs, of which 2 (7%) were settled out of the court. In settled cases, the mean settlement received by plaintiffs was $55,750 (range, $25,000-$86,500). The mean award to plaintiffs for cases determined by the court was $112,991 (range, $4,000-$325,000). Despite widespread usage of UC over a 50-year period, lawsuits centered on UC misuse are rare at the state and federal court levels. Of litigated cases, urologists are commonly involved yet have successful defenses.

[Ulcerative colitis in remission with cerebral abscess and septic pulmonary emboli: a case report].

PubMed

Yamauchi, Takahiro; Katsumura, Hirotoshi; Noguchi, Yoshiyuki; Kikuta, Ken-ichiro

2013-12-01

A 69-year-old man with a 4-year history of ulcerative colitis (UC) presented at our hospital with high fever, dysarthria, and right hemiparesis. Computed tomography (CT) of the head revealed a low-density area in the left temporal lobe. Chest CT exposed multiple pulmonary nodules in his right lung. Gadolinium-enhanced magnetic resonance imaging (MRI) indicated a 3-cm tumor with ring enhancement located in the left temporal lobe. The patient was diagnosed with a brain abscess and septic pulmonary emboli (SPE); antibiotic therapy was initiated. Shrinkage of the brain abscess was not observed in a follow-up MRI;thus, he underwent aspiration and drainage of the abscess 11 days after his hospitalization. Intravenous antibiotic therapy was continued for 6 weeks after the operation. Follow-up chest CT performed 48 days after his hospitalization revealed disappearance of the SPE. Follow-up head MRI conducted 63 days after his hospitalization indicated that the cyst had almost disappeared. Occurrence of a brain abscess in patients with UC has been very rarely reported in Japan. To the best of our knowledge, this is the first report of a case of a brain abscess in conjunction with UC and SPE. It is believed that patients with UC have compromised immunity and exhibit activation of the blood coagulation system. Our report suggests that medical practitioners should consider the possibility of a brain abscess and SPE for patients with UC.

Reprogramming human umbilical cord mesenchymal stromal cells to islet-like cells with the use of in vitro-synthesized pancreatic-duodenal homebox 1 messenger RNA.

PubMed

Wang, Xiao Li; Hu, Pei; Guo, Xing Rong; Yan, Ding; Yuan, Yahong; Yan, Shi Rong; Li, Dong Sheng

2014-11-01

Human umbilical cord mesenchymal stromal cells (hUC-MSCs) hold great potential as a therapeutic candidate to treat diabetes, owing to their unlimited source and ready availability. In this study, we differentiated hUC-MSCs with in vitro-synthesized pancreatic-duodenal homebox 1 (PDX1) messenger (m)RNA into islet-like cell clusters. hUC-MSCs were confirmed by both biomarker detection and functional differentiation. In vitro-synthesized PDX1 messenger RNA can be transfected into hUC-MSCs efficiently. The upregulated expression of PDX1 protein can be detected 4 h after transfection and remains detectable for 36 h. The induction of islet-like structures was confirmed by means of morphology and dithizone staining. Reverse transcriptase-polymerase chain reaction results revealed the expression of some key pancreatic transcription factors, such as PDX1, NeuroD, NKX6.1, Glut-2 and insulin in islet-like cell clusters. Immunofluorescence analysis showed that differentiated cells express both insulin and C-peptide. Enzyme-linked immunosorbent assay analysis validated the insulin secretion of islet-like cell clusters in response to the glucose stimulation. Our results demonstrate the use of in vitro-synthesized PDX1 messenger RNA to differentiate hUC-MSCs into islet-like cells and pave the way toward the development of reprogramming and directed-differentiation methods for the expression of encoded proteins. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

[Meta-analysis on causes of ulcerative colitis].

PubMed

Luo, Ruili; Huo, Lijuan; Zhang, Jie; Zhang, Qiannan

2015-12-01

To analyze the main influencing factor of ulcerative colitis (UC). Literature retrieval was conducted by using English databases (PubMed, Cochrane and Embase) and Chinese databases (CNKI, Wanfang, SinoMed and VIP) to collect the studies on the influencing factors of UC published both at home and abroad from January 2000 to October 2014. According to the inclusion and exclusion criteria, data were extracted and methodological quality was assessed. Then, a Meta-analysis was performed with Stata 12.0 software. A total of 24 case-control studies were included, involving 5 653 patients and 20 218 controls. The results of Meta-analysis showed that the influencing factors of UC would include family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk, fat diet, appendectomy, smoking and high educational level, with the pooled OR values as 4.68 (95%CI:3.59-6.11) , 1.81 (95%CI: 1.58-2.09) , 5.10 (95%CI: 2.38-10.92) , 2.26 (95%CI: 1.65-3.09) , 2.21 (95%CI: 1.49-3.27) , 0.40 (95%CI:0.32-0.51) , 0.44 (95%CI:0.32-0.60) and 0.50 (95%CI:0.36-0.69) , respectively. Current evidence showed that the risk factors influencing the incidence of UC were family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk and fat diet, whereas appendectomy, smoking and high educational level were protective factors for UC.

Stuttgart, Germany. Revised Uniform Summary of Surface Weather Observations (RUSSWO)

DTIC Science & Technology

1988-07-01

4rREVISED UNIFORM SUMMARY OF SURFACE WEATHER OBSERVATIONS STUTTGART GERMANY MSC # 107380 N 48 41 K 009 13 ELEV 1300 FT EDOC PARTS A - F HOURS SUMMARIZED 0000...1 .. L. b I.E 725O0 14.2 24.A 26.4 32.3 32.1 33.6 34.2 36.7 37.7 9.2 39.c 39.5 39.7 𔄃.e 40. 1 I. . GE 6’ UC 1 14.4 25.3 27.0 30.6 32.8 34. 2 34*. 37.4...28.9 30.1 33.8 35.8 36.7 37.3 39.1 39.6 40.0 40.2 60.5 60.6 60.7 41.1 1.9 6E 8- uC l7.9 3L. b 31 .9 35.838 V.. 39. 139 . 7- 6’.6 - 42. 1-62. 7 42.9 4

Tn4556, a 6.8-kilobase-pair transposable element of Streptomyces fradiae.

PubMed Central

Chung, S T

1987-01-01

A 6.8-kilobase-pair (kbp) transposable element (Tn4556) was found in a neomycin-producing strain of Streptomyces fradiae. This element was first observed in two 30.3-kbp plasmids (pUC1123 and pUC1124) which arose when a thiostrepton resistance gene (1 kbp) was ligated with the BclI-2 fragment (22.5 kbp) that contains the origin of replication of phage SF1. The Tn4556 segment was deleted when these plasmids were transduced into another S. fradiae host with phage SF1. These deletion plasmids (pUC1210 and pUC1211) had copy numbers of less than 1 per chromosome and were unstable. In contrast, pUC1123 and pUC1124, with copy numbers of 12 to 15 per chromosome, respectively, were relatively stable. When pUC1210 and pUC1211 were reintroduced into S. fradiae by protoplast transformation, the Tn4556 element transposed again to the plasmids at numerous new locations in either of two orientations. A copy of Tn4556 was found in the S. fradiae chromosome by hybridization studies. It appears that Tn4556 originated from the chromosome, transposed into unstable pUC1210 and pUC1211, and made stable plasmids. A temperature-sensitive hybrid plasmid carrying a viomycin resistance derivative of Tn4556 (pMT660::Tn4556::vph) was constructed. When Streptomyces lividans UC8390 containing the hybrid plasmid was grown at 39 degrees C, Tn4556::vph (Tn4560) transposed to random positions in the host chromosome. Images PMID:2820925

Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.

PubMed

Hamanaka, Shinsaku; Nakagawa, Tomoo; Hiwasa, Takaki; Ohta, Yuki; Kasamatsu, Shingo; Ishigami, Hideaki; Taida, Takashi; Okimoto, Kenichiro; Saito, Keiko; Maruoka, Daisuke; Matsumura, Tomoaki; Takizawa, Hirotaka; Kashiwado, Koichi; Kobayashi, Sohei; Matsushita, Kazuyuki; Matsubara, Hisahiro; Katsuno, Tatsuro; Arai, Makoto; Kato, Naoya

2018-06-05

The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC. Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. Of 66 candidate protein antigens screened by ProtoArray™, 6 were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1 (TCEAL1), and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases. The serum titers of anti-PARG, anti-TCEAL1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission. This article is protected by copyright. All rights reserved.

Clinical usefulness of endoscopic ultrasonography for the evaluation of ulcerative colitis-associated tumors

PubMed Central

Kobayashi, Kiyonori; Kawagishi, Kana; Ooka, Shouhei; Yokoyama, Kaoru; Sada, Miwa; Koizumi, Wasaburo

2015-01-01

AIM: To evaluate the clinical usefulness of endoscopic ultrasonography (EUS) for the diagnosis of the invasion depth of ulcerative colitis-associated tumors. METHODS: The study group comprised 13 patients with 16 ulcerative colitis (UC)-associated tumors for which the depth of invasion was preoperatively estimated by EUS. The lesions were then resected endoscopically or by surgical colectomy and were examined histopathologically. The mean age of the subjects was 48.2 ± 17.1 years, and the mean duration of UC was 15.8 ± 8.3 years. Two lesions were treated by endoscopic resection and the other 14 lesions by surgical colectomy. The depth of invasion of UC-associated tumors was estimated by EUS using an ultrasonic probe and was evaluated on the basis of the deepest layer with narrowing or rupture of the colonic wall. RESULTS: The diagnosis of UC-associated tumors by EUS was carcinoma for 13 lesions and dysplasia for 3 lesions. The invasion depth of the carcinomas was intramucosal for 8 lesions, submucosal for 2, the muscularis propria for 2, and subserosal for 1. Eleven (69%) of the 16 lesions arose in the rectum. The macroscopic appearance was the laterally spreading tumor-non-granular type for 4 lesions, sessile type for 4, laterally spreading tumor-granular type for 3, semi-pedunculated type (Isp) for 2, type 1 for 2, and type 3 for 1. The depth of invasion was correctly estimated by EUS for 15 lesions (94%) but was misdiagnosed as intramucosal for 1 carcinoma with high-grade submucosal invasion. The 2 lesions treated by endoscopic resection were intramucosal carcinoma and dysplasia, and both were diagnosed as intramucosal lesions by EUS. CONCLUSION: EUS provides a good estimation of the invasion depth of UC-associated tumors and may thus facilitate the selection of treatment. PMID:25759538

Decreased undercarboxylated osteocalcin in children with type 2 diabetes mellitus.

PubMed

Takaya, Junji; Tanabe, Yuko; Kuroyanagi, Yuichi; Kaneko, Kazunari

2016-08-01

Osteocalcin (OC) is a bone-specific protein secreted by osteoblasts and often used as a bone formation biomarker. OC undergoes post-translational carboxylation to yield carboxylated osteocalcin (Gla-OC) and undercarboxylated osteocalcin (uc-OC) molecules. The aim of this study was to explore the association between bone and glucose metabolism by evaluating OC, ionized cations, and markers of glucose metabolism in children with obesity and type 2 diabetes mellitus (DM2). The subjects were nine children with DM2 [six males, three females; age 15.7±4.1 years; duration of disease 3.2±1.2 years], 18 children with simple obesity [12 males, six females; age 12.6±4.1 years], and 12 controls [eight males, four females; age 12.3±3.2 years]. Serum Gla-OC and uc-OC levels were determined using an enzyme-linked immunosorbent assay (ELISA). Patients with DM2 (0.65±0.46 ng/mL), but not with obesity (1.11±0.55 ng/mL), had lower uc-OC levels than controls (1.25±0.49 ng/mL). Serum uc-OC was negatively correlated with mean serum glucose levels (r=-0.447, p=0.013) and hemoglobin A1c (HbA1c) (r=-0.455, p=0.012) in all subjects. Serum Gla-OC was correlated with serum alkaline phosphatase (r=0.601, p<0.001) and inorganic phosphorus (r=0.686, p<0.001), yet negatively correlated with age (r=-0.383, p=0.030). Mean serum ionized magnesium was lower in DM2 subjects than in controls. Mean serum ionized calcium was higher in obese subjects than in controls. In all subjects, mean serum ionized magnesium was negatively correlated with mean serum glucose levels. Osteoblast-derived protein OC, especially uc-OC, may have a role in the pathophysiology of diabetes by being associated with blood glucose homeostasis.

Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG).

PubMed

Eriksson, Carl; Marsal, Jan; Bergemalm, Daniel; Vigren, Lina; Björk, Jan; Eberhardson, Michael; Karling, Pontus; Söderman, Charlotte; Myrelid, Pär; Cao, Yang; Sjöberg, Daniel; Thörn, Mari; Karlén, Per; Hertervig, Erik; Strid, Hans; Ludvigsson, Jonas F; Almer, Sven; Halfvarson, Jonas

Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48). Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

Randomized Trial Comparing Telephone Versus In-Person Weight Loss Counseling on Body Composition and Circulating Biomarkers in Women Treated for Breast Cancer: The Lifestyle, Exercise, and Nutrition (LEAN) Study.

PubMed

Harrigan, Maura; Cartmel, Brenda; Loftfield, Erikka; Sanft, Tara; Chagpar, Anees B; Zhou, Yang; Playdon, Mary; Li, Fangyong; Irwin, Melinda L

2016-03-01

Obesity is associated with a higher risk of breast cancer mortality. The gold standard approach to weight loss is in-person counseling, but telephone counseling may be more feasible. We examined the effect of in-person versus telephone weight loss counseling versus usual care on 6-month changes in body composition, physical activity, diet, and serum biomarkers. One hundred breast cancer survivors with a body mass index ≥ 25 kg/m(2) were randomly assigned to in-person counseling (n = 33), telephone counseling (n = 34), or usual care (UC) (n = 33). In-person and telephone counseling included 11 30-minute counseling sessions over 6 months. These focused on reducing caloric intake, increasing physical activity, and behavioral therapy. Body composition, physical activity, diet, and serum biomarkers were measured at baseline and 6 months. The mean age of participants was 59 ± 7.5 years old, with a mean BMI of 33.1 ± 6.6 kg/m(2), and the mean time from diagnosis was 2.9 ± 2.1 years. Fifty-one percent of the participants had stage I breast cancer. Average 6-month weight loss was 6.4%, 5.4%, and 2.0% for in-person, telephone, and UC groups, respectively (P = .004, P = .009, and P = .46 comparing in-person with UC, telephone with UC, and in-person with telephone, respectively). A significant 30% decrease in C-reactive protein levels was observed among women randomly assigned to the combined weight loss intervention groups compared with a 1% decrease among women randomly assigned to UC (P = .05). Both in-person and telephone counseling were effective weight loss strategies, with favorable effects on C-reactive protein levels. Our findings may help guide the incorporation of weight loss counseling into breast cancer treatment and care. © 2015 by American Society of Clinical Oncology.

Effect of threatening life experiences and adverse family relations in ulcerative colitis: analysis using structural equation modeling and comparison with Crohn's disease.

PubMed

Slonim-Nevo, Vered; Sarid, Orly; Friger, Michael; Schwartz, Doron; Sergienko, Ruslan; Pereg, Avihu; Vardi, Hillel; Singer, Terri; Chernin, Elena; Greenberg, Dan; Odes, Shmuel

2017-05-01

We published that threatening life experiences and adverse family relations impact Crohn's disease (CD) adversely. In this study, we examine the influence of these stressors in ulcerative colitis (UC). Patients completed demography, economic status (ES), the Patient-Simple Clinical Colitis Activity Index (P-SCCAI), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Short-Form Health Survey (SF-36), the Brief Symptom Inventory (BSI), the Family Assessment Device (FAD), and the List of Threatening Life Experiences (LTE). Analysis included multiple linear and quantile regressions and structural equation modeling, comparing CD. UC patients (N=148, age 47.55±16.04 years, 50.6% women) had scores [median (interquartile range)] as follows: SCAAI, 2 (0.3-4.8); FAD, 1.8 (1.3-2.2); LTE, 1.0 (0-2.0); SF-36 Physical Health, 49.4 (36.8-55.1); SF-36 Mental Health, 45 (33.6-54.5); Brief Symptom Inventory-Global Severity Index (GSI), 0.5 (0.2-1.0). SIBDQ was 49.76±14.91. There were significant positive associations for LTE and SCAAI (25, 50, 75% quantiles), FAD and SF-36 Mental Health, FAD and LTE with GSI (50, 75, 90% quantiles), and ES with SF-36 and SIBDQ. The negative associations were as follows: LTE with SF-36 Physical/Mental Health, SIBDQ with FAD and LTE, ES with GSI (all quantiles), and P-SCCAI (75, 90% quantiles). In structural equation modeling analysis, LTE impacted ES negatively and ES impacted GSI negatively; LTE impacted GSI positively and GSI impacted P-SCCAI positively. In a split model, ES had a greater effect on GSI in UC than CD, whereas other path magnitudes were similar. Threatening life experiences, adverse family relations, and poor ES make UC patients less healthy both physically and mentally. The impact of ES is worse in UC than CD.

Effect of Tai Chi on physical function, fall rates and quality of life among older stroke survivors.

PubMed

Taylor-Piliae, Ruth E; Hoke, Tiffany M; Hepworth, Joseph T; Latt, L Daniel; Najafi, Bijan; Coull, Bruce M

2014-05-01

To examine the effect of a 12-week Tai Chi (TC) intervention on physical function and quality of life. Single-blind, randomized controlled trial. General community. Community-dwelling survivors of stroke (N=145; 47% women; mean age, 70y; time poststroke: 3y; ischemic stroke: 66%; hemiparesis: 73%) who were aged ≥50 years and were ≥3 months poststroke. Yang style 24-posture short-form TC (n=53), strength and range of movement exercises (SS) (n=44), or usual care (UC) (n=48) for 12 weeks. The TC and SS groups attended a 1-hour class 3 times per week, whereas the UC group had weekly phone calls. Physical function: Short Physical Performance Battery, fall rates, and 2-minute step test; quality of life: Medical Outcomes Study 36-Item Short-Form Health Survey, Center for Epidemiologic Studies Depression Scale, and Pittsburgh Sleep Quality Index. During the intervention, TC participants had two thirds fewer falls (5 falls) than the SS (14 falls) and UC (15 falls) groups (χ(2)=5.6, P=.06). There was a significant group by time interaction for the 2-minute step test (F2,142=4.69, P<.01). Post hoc tests indicated that the TC (t53=2.45, P=.02) and SS (t44=4.63, P<.01) groups had significantly better aerobic endurance over time, though not in the UC group (t48=1.58, P=.12). Intervention adherence rates were 85%. TC and SS led to improved aerobic endurance, and both are suitable community-based programs that may aid in stroke recovery and community reintegration. Our data suggest that a 12-week TC intervention was more effective in reducing fall rates than SS or UC interventions. Future studies examining the effectiveness of TC as a fall prevention strategy for community-dwelling survivors of stroke are recommended. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Infrastructure for deployment of power systems

NASA Technical Reports Server (NTRS)

Sprouse, Kenneth M.

1991-01-01

A preliminary effort in characterizing the types of stationary lunar power systems which may be considered for emplacement on the lunar surface from the proposed initial 100-kW unit in 2003 to later units ranging in power from 25 to 825 kW is presented. Associated with these power systems are their related infrastructure hardware including: (1) electrical cable, wiring, switchgear, and converters; (2) deployable radiator panels; (3) deployable photovoltaic (PV) panels; (4) heat transfer fluid piping and connection joints; (5) power system instrumentation and control equipment; and (6) interface hardware between lunar surface construction/maintenance equipment and power system. This report: (1) presents estimates of the mass and volumes associated with these power systems and their related infrastructure hardware; (2) provides task breakdown description for emplacing this equipment; (3) gives estimated heat, forces, torques, and alignment tolerances for equipment assembly; and (4) provides other important equipment/machinery requirements where applicable. Packaging options for this equipment will be discussed along with necessary site preparation requirements. Design and analysis issues associated with the final emplacement of this power system hardware are also described.

Preventing Overweight in USAF Personnel: Minimal Contract Program

DTIC Science & Technology

2005-05-01

Allowable Weight (MAW) and heavier. Effectiveness of MCBT + UC is compared to UC in terms of weight loss . Outcomes are being measured at 6 and 12 months...while those assigned to UC actually gained weight . Also, greater fise of the treatment website was associated with significantly more weight loss over...Effectiveness of MCBT + UC will be compared to UC in terms of weight loss . Outcomes are measured at 6 and 12 months. The ultimate goal of this study is to

[An operative case of ulcerative colitis associated with hyperthyroidism].

PubMed

Kohyama, Atsushi; Funayama, Yuji; Fukushima, Kouhei; Shibata, Chikashi; Miura, Koh; Takahashi, Ken-ichi; Ogawa, Hitoshi; Ueno, Tatsuya; Sasaki, Iwao; Hiwatashi, Nobuo

2009-06-01

We encountered a rare operative case of hyperthyroidism followed by ulcerative colitis (UC). A 26-year-old mam was referred to our department to undergo an operation. We suspected the possible complication of adrenal insufficiency, since he suffered from severe weight loss, a high fever and palpitation on admission. We diagnosed hyperthyroidism, however, based on the presence of high serum free T3 and T4 levels and a decreased TSH level. After improving the symptoms and the thyroid function by administering thiamazole, we then performed a total proctocolectomy. Although a high rate of association of autoimmune thyroid diseases with UC has been suggested, only 9 cases of hyperthyroidism coexisting with UC have so far been reported in Japan. A common immunological process has been suggested to be implicated in the pathogenesis of this association, however, the exact mechanism needs to be elucidated in the future.

Study of chromosomal region 5p13.1 in Crohn's disease, ulcerative colitis, and rheumatoid arthritis.

PubMed

Perdigones, Nieves; Martín, Ezequiel; Robledo, Gema; Lamas, José Ramón; Taxonera, Carlos; Díaz-Rubio, Manuel; de la Concha, Emilio G; López-Nevot, Miguel Angel; García, Antonio; Gómez-García, María; Fernández-Gutiérrez, Benjamín; Martín, Javier; Urcelay, Elena

2010-08-01

Chromosomal region 5p13 includes regulatory elements of the prostaglandin receptor EP4 (PTGER4) gene and is associated with inflammatory bowel disease (IBD) susceptibility. We aimed at corroborating the association of the PTGER4 risk variant in IBD. Given the proinflammatory activity of prostaglandin E(2) in rheumatoid arthritis (RA), the reduction in incidence and severity of collagen-induced arthritis observed in mice deficient in the prostaglandin receptor EP4, and a modest signal of association found in an RA genome-wide scan, we proposed to extend the investigation of this locus to RA patients. A total of 709 Crohn's disease (CD) patients, 662 ulcerative colitis (UC) patients, and 1369 control subjects were genotyped for rs17234657. This polymorphism was also analyzed in 605 RA patients, and rs6871834 was studied in the RA patient group. Replication of the previous finding in CD was achieved in our independent collections, although with a milder effect (odds ratios = 1.23) than that originally described. No further association of the previously mentioned polymorphisms was detected with either UC or RA patients. We validated this 5p13 signal as a genuine susceptibility factor for CD in Caucasian populations. Our data seem to rule out a major influence of these polymorphisms on UC or RA predisposition. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

PTGER4 modulating variants in Crohn's disease.

PubMed

Prager, Matthias; Büttner, Janine; Büning, Carsten

2014-08-01

Variants modulating expression of the prostaglandin receptor 4 (PTGER4) have been reported to be associated with Cohn's disease (CD), but the clinical impact remains to be elucidated. We analyzed these variants in a large German inflammatory bowel disease (IBD) cohort and searched for a potential phenotype association. The variants rs4495224 and rs7720838 were studied in adult German IBD patients (CD, n = 475; ulcerative colitis (UC), n = 293) and healthy controls (HC, n = 467). Data were correlated to results from NOD2 genotyping and to clinical characteristics. We found a significant association for the rs7720838 variant with overrepresentation of the T allele to CD (p = 0.0058; OR 0.7703, 95 % CI 0.641-0.926) but not to UC. Furthermore, logistic regression analysis revealed that the presence of the T allele was associated with stricturing disease behavior in CD patients (p = 0.03; OR 1.84, 95 % CI 1.07-3.16). Interestingly, the chance for developing stricturing disease behavior was enhanced if mutant alleles in both rs7720838 and NOD2 were present (OR 2.87, 95 % CI 1.42-5.81; p = 0.003). No overall association to CD or UC was found for the rs4495224 variant. The PTGER4 modulating variant rs7720838 increases susceptibility for CD and might resemble a risk factor for stricturing disease behavior.

Synthesis of novel branched β-NaLuF4: Yb/Er upconversion luminescence material and investigation of its optical properties

NASA Astrophysics Data System (ADS)

Ding, Yanli; Yang, Tonghui; Yin, Naiqiang; Shu, Fangjie; Zhao, Ying; Zhang, Xiaodan

2018-05-01

Branched β-NaLuF4: Yb/Er was synthesized using a simple hydrothermal method by controlling the NaF/Ln molar ratio. In contrast to the β-NaYF4: Yb/Er hexagonal disks, the branched β-NaLuF4: Yb/Er has stronger emission intensity. The integrated intensities of green and red emission bands were as 6.2 and 3.3 times as that of NaYF4, respectively. The branched β-NaLuF4: Yb/Er has the smaller unit cell volume, the higher absorption intensity around 980 nm and the lower crystal field symmetry than NaYF4, which made a significant contribution to the stronger upconversion (UC) fluorescence emissions. The results indicate that the branched β-NaLuF4: Yb/Er is an excellent UC luminescence material. The current research has a great potential in improving near-infrared conversion efficiency of solar cells.

Approach to cytomegalovirus infections in patients with ulcerative colitis

PubMed Central

Park, Sung Chul; Jeen, Yoon Mi; Jeen, Yoon Tae

2017-01-01

Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or ‘an innocent bystander’ in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC. PMID:28490715

Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

PubMed

Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

2016-03-01

In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American Cancer Society. © 2015 American Cancer Society.

The UAS control segment architecture: an overview

NASA Astrophysics Data System (ADS)

Gregory, Douglas A.; Batavia, Parag; Coats, Mark; Allport, Chris; Jennings, Ann; Ernst, Richard

2013-05-01

The Under Secretary of Defense (Acquisition, Technology and Logistics) directed the Services in 2009 to jointly develop and demonstrate a common architecture for command and control of Department of Defense (DoD) Unmanned Aircraft Systems (UAS) Groups 2 through 5. The UAS Control Segment (UCS) Architecture is an architecture framework for specifying and designing the softwareintensive capabilities of current and emerging UCS systems in the DoD inventory. The UCS Architecture is based on Service Oriented Architecture (SOA) principles that will be adopted by each of the Services as a common basis for acquiring, integrating, and extending the capabilities of the UAS Control Segment. The UAS Task Force established the UCS Working Group to develop and support the UCS Architecture. The Working Group currently has over three hundred members, and is open to qualified representatives from DoD-approved defense contractors, academia, and the Government. The UCS Architecture is currently at Release 2.2, with Release 3.0 planned for July 2013. This paper discusses the current and planned elements of the UCS Architecture, and related activities of the UCS Community of Interest.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Desmocollin 2 is a new immunohistochemical marker indicative of squamous differentiation in urothelial carcinoma.

PubMed

Hayashi, Tetsutaro; Sentani, Kazuhiro; Oue, Naohide; Anami, Katsuhiro; Sakamoto, Naoya; Ohara, Shinya; Teishima, Jun; Noguchi, Tsuyoshi; Nakayama, Hirofumi; Taniyama, Kiyomi; Matsubara, Akio; Yasui, Wataru

2011-10-01

Urothelial carcinoma (UC) with squamous differentiation tends to present at higher stages than pure UC. To distinguish UC with squamous differentiation from pure UC, a sensitive and specific marker is needed. Desmocollin 2 (DSC2) is a protein localized in desmosomal junctions of stratified epithelium, but little is known about its biological significance in bladder cancer. We examined the utility of DSC2 as a diagnostic marker. We analysed the immunohistochemical characteristics of DSC2, and studied the relationship of DSC2 expression with the expression of the known markers uroplakin III (UPIII), cytokeratin (CK)7, CK20, epidermal growth factor receptor (EGFR), and p53. DSC2 staining was detected in 24 of 25 (96%) cases of UC with squamous differentiation, but in none of 85 (0%) cases of pure UC. DSC2 staining was detected only in areas of squamous differentiation. DSC2 expression was mutually exclusive of UPIII expression, and was correlated with EGFR expression. Furthermore, DSC2 expression was correlated with higher stage (P = 0.0314) and poor prognosis (P = 0.0477). DSC2 staining offers high sensitivity (96%) and high specificity (100%) for the detection of squamous differentiation in UC. DSC2 is a useful immunohistochemical marker for separation of UC with squamous differentiation from pure UC. 2011 Blackwell Publishing Limited.

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics.

PubMed

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-09-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules.

Comparison of particle morphology between commercial- and research-grade calcium hydroxide in endodontics

PubMed Central

Komabayashi, Takashi; Ahn, Chul; Spears, Robert; Zhu, Qiang

2014-01-01

Ca(OH)2 aqueous slurry is widely used as an inter-appointment antimicrobial dressing in root canal treatment. The aim of this study was to quantify the particle size and shape of commercial-grade UltraCal XS (UC) and to compare it with that of research-grade Ca(OH)2 (RG) using a flow particle image analyzer (FPIA). The morphology and penetration inside the dentin tubules of the UC and RG particles were examined using a scanning electron microscope (SEM). UC and RG (10 mg) were mixed with 15 mL of alcohol, and were sonicated. Five milliliters of the dispersion was subjected to FPIA, and particle length, width, perimeter and aspect ratio were analyzed. In addition, UC paste and RG aqueous slurry were agitated on dentin discs and were prepared for SEM examination. There were significant differences between UC and RG with regard to the frequency of different length groups (P < 0.0001). UC contained smaller particles than RG (P < 0.0001). Under SEM, the agitated UC and RG particles occluded the opening of dentin tubules and penetrated inside the dentin tubules. The size of UC particles is smaller than those of RG. Both UC and RG particles were able to penetrate into open dentin tubules. PMID:25231145

Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice.

PubMed

Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

2016-11-14

To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. Treg cells, Treg cell subsets, Th17 cells, and CD4 + CD25 + FoxP3 + IL-17 + cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased ( P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4 + CD45RA + FoxP3 low ) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4 + CD45RA - FoxP3 high ) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4 + CD45RA - FoxP3 low ) and CD4 + CD25 + FoxP3 + IL-17A + cells was increased. FoxP3 mRNA levels in CD4 + CD45RA - FoxP3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4 + CD45RA - FoxP3 high , and CD4 + CD45RA - FoxP3 low cells was higher in LPC relative to other tissues. Increased numbers of CD4 + CD45RA - FoxP3 low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

Increased CD4+CD45RA-FoxP3low cells alter the balance between Treg and Th17 cells in colitis mice

PubMed Central

Ma, Ya-Hui; Zhang, Jie; Chen, Xue; Xie, You-Fu; Pang, Yan-Hua; Liu, Xin-Juan

2016-01-01

AIM To investigate the role of regulatory T cell (Treg) subsets in the balance between Treg and T helper 17 (Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis. METHODS Treg cells, Treg cell subsets, Th17 cells, and CD4+CD25+FoxP3+IL-17+ cells from the lamina propria of colon (LPC) and other ulcerative colitis (UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3 (FoxP3), interleukin 17A (IL-17A), and RORC mRNA levels were assessed by real-time PCR, while interleukin-10 (IL-10) and IL-17A levels were detected with a Cytometric Beads Array. RESULTS In peripheral blood monocytes (PBMC), mesenteric lymph node (MLN), lamina propria of jejunum (LPJ) and LPC from UC mice, Treg cell numbers were increased (P < 0.05), and FoxP3 and IL-10 mRNA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17A levels in PBMC, LPJ, and serum. The number of FrI subset cells (CD4+CD45RA+FoxP3low) was increased in the spleen, MLN, LPJ, and LPC. FrII subset cells (CD4+CD45RA-FoxP3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of FrIII cells (CD4+CD45RA-FoxP3low) and CD4+CD25+FoxP3+IL-17A+ cells was increased. FoxP3 mRNA levels in CD4+CD45RA-FoxP3low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17A and RORC mRNA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP3high, and CD4+CD45RA-FoxP3low cells was higher in LPC relative to other tissues. CONCLUSION Increased numbers of CD4+CD45RA-FoxP3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues. PMID:27895423

Investigating the anisotropy of magnetic susceptibility and other rock magnetic properties of the Beaver River Diabase in northeastern Minnesota

NASA Astrophysics Data System (ADS)

Hariri, Samer H.

The Beaver River Diabase (BRD) is a series of mafic dikes and sills within the Beaver Bay Complex (BBC) of northern Minnesota, which formed during the development of the ~1.1 Ga Midcontinent Rift (MCR). The BRD is one of the youngest and most extensive intrusive phases of the BBC. The BRD dikes and sills were emplaced into the medial levels of the 6-10 kilometer-thick North Shore Volcanic Group and occur over an arcuate area extending 120 by 20 kilometers. The BRD is composed of fine- to medium-grained ophitic olivine gabbro and does not display obvious foliation or lineation features and rarely displays modal layering. Without obvious magmatic internal structures, it is difficult to determine emplacement properties such as flow direction using standard geologic mapping or petrographic techniques. For this reason, we measured the anisotropy of magnetic susceptibility (AMS), in conjunction with other rock magnetic properties, to better understand the BRD's emplacement and deformation history in the context of the MCR. AMS measures the directional dependence of low-field magnetic susceptibility, and is used to infer a shape-preferred orientation of magnetic minerals within a rock, which can be related to specific emplacement mechanisms (e.g. directional flow or settling). Preliminary analysis of AMS at 20 sites within the southern half of the BRD (with 4-7 samples per site) shows maximum susceptibility values between 4.48 x 10-6 and 2.22 x 10-4 m 3/kg (1165 and 65400 μSI). Most specimens display nearly isotropic AMS ellipsoids (Pj < 1.15) with minor degrees of prolateness and oblateness. However, about 20% of specimens have higher anisotropies (Pj between 1.15 and 1.67) and higher degrees of oblateness and prolateness. Variations in AMS properties may reflect differences in concentration and composition of magnetic minerals, as well as emplacement mechanisms. Measurements of susceptibility as a function of temperature yield Curie points between 470 and 570 °C, indicating the presence of low-titanium titanomagnetite. Major hysteresis loops show coercivities between 1 and 25 mT, consistent with titanomagnetite as the dominant remanence carrier.

Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel diseases risk

PubMed Central

Ferguson, Lynnette R; Huebner, Claudia; Petermann, Ivonne; Gearry, Richard B; Barclay, Murray L; Demmers, Pieter; McCulloch, Alan; Han, Dug Yeo

2008-01-01

AIM: To investigate the role that single nucleotide polymorphisms (SNPs) in the promoter of the tumour necrosis factor-alpha (TNF-α) gene play in the risk of inflammatory bowel diseases (IBDs) in a New Zealand population, in the context of international studies. METHODS: DNA samples from 388 patients with Crohn’s disease (CD), 405 ulcerative colitis (UC), 27 indeterminate colitis (IC) and 201 randomly selected controls, from Canterbury, New Zealand were screened for 3 common polymorphisms in the TNF-α receptor: -238 G→A, -308 G→A and -857C→T, using a TaqmanR assay. A meta-analysis was performed on the data obtained on these polymorphisms combined with that from other published studies. RESULTS: Individuals carrying the -308 G/A allele had a significantly (OR = 1.91, χ2 = 17.36, P < 0.0001) increased risk of pancolitis, and a 1.57-fold increased risk (OR = 1.57, χ2 = 4.34, P = 0.037) of requiring a bowel resection in UC. Carrying the -857 C/T variant decreased the risk of ileocolonic CD (OR = 0.56, χ2 = 4.32, P = 0.037), and the need for a bowel resection (OR = 0.59, χ2 = 4.85, P = 0.028). The risk of UC was reduced in individuals who were smokers at diagnosis, (OR = 0.48, χ2 = 4.86, P = 0.028). CONCLUSION: TNF-α is a key cytokine known to play a role in inflammatory response, and the locus for the gene is found in the IBD3 region on chromosome 6p21, known to be associated with an increased risk for IBD. The -308 G/A SNP in the TNF-α promoter is functional, and may account in part for the increased UC risk associated with the IBD3 genomic region. The -857 C/T SNP may decrease IBD risk in certain groups. Pharmaco- or nutrigenomic approaches may be desirable for individuals with such affected genotypes. PMID:18698679

Effects of a high fat or a balanced omega 3/omega 6 diet on cytokines levels and DNA damage in experimental colitis.

PubMed

Vieira de Barros, Karina; Gomes de Abreu, Gilclay; Xavier, Roberta Araujo Navarro; Real Martinez, Carlos Augusto; Ribeiro, Marcelo Lima; Gambero, Alessandra; de Oliveira Carvalho, Patrícia; Silveira, Vera Lúcia Flor

2011-02-01

High-fat diets have been shown to be a risk factor for ulcerative colitis (UC). Omega-6 polyunsaturated fatty acids are considered to increase lipid peroxidation, while the omega-3 polyunsaturated fatty acid exerts a chemopreventative effect. We evaluated the effect of high-fat diets (20%) enriched with fish or soybean oil on colonic inflammation and DNA damage in dextran sulfate sodium-induced colitis. Male Wistar rats (28-30 days) were fed an American Institute of Nutrition (AIN)-93 diet for 47 days and divided into five groups: control normal fat non-colitic (C) or control colitis (CC), high soybean fat group (HS) colitis, high fish fat group colitis, or high-fat soybean plus fish oil colitis. UC was induced from day 35 until day 41 by 3% dextran sulfate sodium. On day 47, the rats were anesthetized; blood samples collected for corticosterone determination, and the distal colon was excised to quantify interleukin-4 (IL-4), IL-10, and interferon-gamma levels, myeloperoxidase activity, histological analyses, and DNA damage. The disease activity index was recorded daily. The disease activity index, histological analysis, myeloperoxidase activity, IL-4, interferon-gamma, and corticosterone levels did not differ among the colitic groups. IL-10 was significantly increased by the high fish fat group diet in relation to HS, but only the high soybean-fish fat diet increased the IL-10/IL-4 ratio (anti-inflammatory/pro-inflammatory) to levels closer to the C group and reduced DNA damage compared to the HS group (P<0.05). The data show that high-fat diets did not exacerbate UC and suggest that the soybean and fish oil mixture, more than the fish oil alone, could be a complementary therapy to achieve a cytokine balance in UC. Copyright © 2011 Elsevier Inc. All rights reserved.

Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis.

PubMed

Castaño-Milla, C; Chaparro, M; Gisbert, J P

2014-04-01

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate. To assess the risk of CRC in UC patients by systematic review and meta-analysis. A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle-Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub-analyses were performed to identify factors associated with an increased risk of developing CRC. A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient-years (py) [95% confidence interval (CI), 1.39–1.76]. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population-based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade. The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.

3g mesalazine granules are superior to 9mg budesonide for achieving remission in active ulcerative colitis: a double-blind, double-dummy, randomised trial.

PubMed

Gross, Volker; Bunganic, Ivan; Belousova, Elena A; Mikhailova, Tatyana L; Kupcinskas, Limas; Kiudelis, Gediminas; Tulassay, Zsolt; Gabalec, Libor; Dorofeyev, Andrey E; Derova, Jelena; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2011-04-01

Budesonide may be an effective therapy for mild-to-moderately active ulcerative colitis (UC). This study aimed to demonstrate non-inferiority for oral 9mg budesonide once daily (OD) versus 3g mesalazine granules OD. This was an eight-week randomised, double-blind, double-dummy, multicentre study in which patients with mild-to-moderately active UC, defined as Clinical Activity Index (CAI) ≥6 and Endoscopic Index (EI) ≥4, received budesonide (Budenofalk® 3mg capsules×3) or mesalazine (Salofalk® 1000mg granules×3). The primary endpoint was clinical remission at week 8 (CAI ≤4 with stool frequency and rectal bleeding subscores of "0"). 343 patients were randomised (177 budesonide, 166 mesalazine). Fewer patients achieved the primary endpoint with budesonide versus mesalazine (70/177 [39.5%] versus 91/166 [54.8%]) with a difference in proportions of -15.3% (95% CI [-25.7%, -4.8%]; p=0.520 for non-inferiority). The median time to first resolution of symptoms was 14.0 days (budesonide) and 11.0 days (mesalazine) (hazard ratio 1.19; 95% CI [0.94, 1.51]). Mucosal healing was observed in 54/177 (30.5%) budesonide patients versus 65/166 (39.2%) mesalazine patients, a difference of -8.6% (95% CI [-18.7%, 1.4%]; p=0.093). The incidences of adverse events (budesonide 26.6%, mesalazine 25.3%) and serious adverse events (budesonide 1.7%, mesalazine 1.2%) were similar. Once-daily 3g mesalazine administered as granules is superior to 9mg budesonide OD administered as capsules for achieving remission in mild-to-moderately active UC. However, it is noteworthy that remission of UC was attained in about 40% of budesonide-treated patients with a rapid onset of resolution. Copyright © 2010. Published by Elsevier B.V.

MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1.

PubMed

Lv, Bo; Liu, Zhihui; Wang, Shuping; Liu, Fengbin; Yang, Xiaojun; Hou, Jiangtao; Hou, Zhengkun; Chen, Bin

2014-01-01

While it's widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC. The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated. In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3'UTR of mcl-1 and mutation in this binding site on the 3'UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1. miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.

Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function.

PubMed

Zhao, Xiaoqin; Rong, Can; Pan, Fenghui; Xiang, Lizhi; Wang, Xinlei; Hu, Yun

2018-06-28

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes. © 2018 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Huang, Chao-Yuan

Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain riskmore » factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.« less

Geochronological, geochemical and mineralogical constraints of emplacement depth of TTG suite from the Sinassi Batholith in the Central African Fold Belt (CAFB) of northern Cameroon: Implications for tectonomagmatic evolution

NASA Astrophysics Data System (ADS)

Houketchang Bouyo, M.; Penaye, J.; Njel, U. O.; Moussango, A. P. I.; Sep, J. P. N.; Nyama, B. A.; Wassouo, W. J.; Abaté, J. M. E.; Yaya, F.; Mahamat, A.; Ye, Hao; Wu, Fei

2016-04-01

The Sinassi Batholith in the Central African Fold Belt (CAFB) of northern Cameroon represents the largest volume of plutonic rocks or granitoids massif of the Western Cameroonian Domain. It is made up dominantly of tonalite-trondhjemite-granodiorite (TTG) suite and lesser granite which are locally more or less deformed, and composed of varying proportions of quartz, plagioclase, K-feldspar, biotite, hornblende, sphene, magnetite, apatite and zircon. Major and trace element compositions of fifteen rock samples of granitoids (Djourdé granodiorite, Sinassi quartz diorite and orthogneisses groups) indicate that investigated rocks from the Sinassi Batholith are characterized by medium- to high-K calc-alkaline affinity and metaluminous I-type signature. In addition, their chondrite- and primitive mantle-normalized trace element patterns are strongly fractionated ((La/Yb)N = 2.96-61.40) and show respectively enrichment in LREE relative to HREE and enrichment in LILE compared to HFSE with moderate to slight negative Nb-Ta, Ti and Eu anomalies consistent with a continental magmatic arc setting related to a subduction zone. Geothermobarometric calculations using hornblende-plagioclase thermometry and aluminum-in-hornblende barometry on eleven rock samples indicate that plutons from Sinassi Batholith were emplaced at average temperatures and pressures ranging between 698 and 720 °C and 4.06-5.82 kbar (Djourdé granitoids), 698-728 °C and 4.04-5.34 kbar (Sinassi granitoids) and 667-670 and 4.23-4.76 kbar (orthogneisses group) respectively. The average emplacement depths estimates for the investigated granitoids is constrained at ca 16-18 km, indicating that at least 16 km of crustal rocks of the Sinassi Batholith must have been eroded or uplifted at approximately exhumation rates of 0.08-0.10 mm/year. Regardless of their Th/U ratios, geochronological results highlight three main events characterizing the Neoproterozoic tectonomagmatic evolution within the Sinassi Batholith at the northern margin of CAFB of northern Cameroon: (1) inherited magmatic sources ranging from one group to another at ca 692, 713, 722, 746 and 772 Ma; (2) successive emplacement ages at ca 670-686 Ma (orthogneisses group), ca 661-666 Ma (synchronous emplacement of the Djourdé and Sinassi groups) and ca 644 Ma (emplacement age of eyespots quartz diorite in the Sinassi group); and (3) post-magmatic alteration or metamorphism at ca 600 Ma. Correlations with the neighboring Mayo Kebbi Batholith in southwestern Chad show geochemical and geochronological similarities, demonstrating that the Sinassi and Mayo Kebbi granitoids beyond political boundaries are parts of a unique Sinassi-Mayo Kebbi Batholith witnessing a Neoproterozoic subduction-related continental magmatic arc setting of Andean-type.

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

PubMed

Brant, Steven R; Okou, David T; Simpson, Claire L; Cutler, David J; Haritunians, Talin; Bradfield, Jonathan P; Chopra, Pankaj; Prince, Jarod; Begum, Ferdouse; Kumar, Archana; Huang, Chengrui; Venkateswaran, Suresh; Datta, Lisa W; Wei, Zhi; Thomas, Kelly; Herrinton, Lisa J; Klapproth, Jan-Micheal A; Quiros, Antonio J; Seminerio, Jenifer; Liu, Zhenqiu; Alexander, Jonathan S; Baldassano, Robert N; Dudley-Brown, Sharon; Cross, Raymond K; Dassopoulos, Themistocles; Denson, Lee A; Dhere, Tanvi A; Dryden, Gerald W; Hanson, John S; Hou, Jason K; Hussain, Sunny Z; Hyams, Jeffrey S; Isaacs, Kim L; Kader, Howard; Kappelman, Michael D; Katz, Jeffry; Kellermayer, Richard; Kirschner, Barbara S; Kuemmerle, John F; Kwon, John H; Lazarev, Mark; Li, Ellen; Mack, David; Mannon, Peter; Moulton, Dedrick E; Newberry, Rodney D; Osuntokun, Bankole O; Patel, Ashish S; Saeed, Shehzad A; Targan, Stephan R; Valentine, John F; Wang, Ming-Hsi; Zonca, Martin; Rioux, John D; Duerr, Richard H; Silverberg, Mark S; Cho, Judy H; Hakonarson, Hakon; Zwick, Michael E; McGovern, Dermot P B; Kugathasan, Subra

2017-01-01

The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10 -8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10 -6 ): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lavas and Sills in the Ferrar Large Igneous Province: Field and Geochemical Evidence for the Order of Emplacement.

NASA Astrophysics Data System (ADS)

Elliot, D. H.; Fleming, T. H.

2005-12-01

Many large igneous provinces, particularly those associated with Gondwana break-up, include major sill complexes as well as flood basalt fields. In the Ferrar province, radiometric dates of lavas and sills are indistinguishable. Nevertheless, in north Victoria Land (NVL) field evidence suggests the lavas had to have been erupted first in order to create the overburden needed for emplacement at shallow depths of thick sills, lacking vesicles, in a thin (100 m) Upper Triassic sedimentary sequence overlying basement. Elsewhere in the Transantarctic Mountains sills occur almost exclusively in a thick (2-2.5 km) Devonian-Triassic sedimentary sequence (Beacon Supergroup) that was possibly capped by 500+m of lavas before sill emplacement. For south Victoria Land (SVL), Marsh (2004) proposed that the most evolved rocks were erupted first as lavas, and sills were emplaced at progressively greater depth as increasingly more magnesian magmas and crystal mushes were injected into supracrustal and finally basement rocks. In NVL most lavas have MgO between 6-8% with a few as low as 4.5% MgO, whereas analyzed chilled margins of sills range from 3.7-5.6% MgO. In the Prince Albert Mountains (PAM), SVL, lava and sill compositions overlap (3.9-7.3% MgO). In the greater Dry Valleys region (SVL) lavas at Carapace Nunatak range from 3.6-6.7% MgO; chilled margins of Dry Valleys sills range from about 4.2 to 7.2% MgO. In the Queen Alexandra Range, central Transantarctic Mountains (CTM), lavas are predominantly 2.6-5.7% MgO; sills in the region range from 4.5% to 10.7% MgO. In the Otway Massif region (head of the Shackleton Glacier, CTM) most lavas are strongly evolved (2.7-3.4% MgO); sills in the Shackleton Glacier region range from 4.3-7.3% MgO. Nowhere do lavas show unequivocal systematic temporal change in MgO, and notably in CTM the initial flows are the most mafic (7.5-8.0% MgO). Olivine dolerite sills (chilled margins: -9% MgO) tend to occur low in the stratigraphic section. Except for NVL where Beacon strata exposures are limited, sills are thicker (100-200 m) and more regular in lower stratigraphic levels. Sills with orthopyroxene crystal-mush tongues are not known outside the Dry Valleys except perhaps the Warren Range (SVL). No province-wide systematic relationship is apparent between compositions of lavas and sill chilled margins. Nevertheless, in CTM most lavas are significantly more evolved than the sills; within the sills there is no clear relationship between MgO and stratigraphy, and some less evolved compositions occur at relatively high stratigraphic levels. In SVL compositional overlap is almost complete; locally, cross-cutting relations show more mafic sills and sheets cutting less mafic compositions. In NVL the chemical relations between lavas and sills are opposite from those that have been advocated for SVL. Interpretation is compounded by sills that exchange stratigraphic position or climb stratigraphically. Factors affecting magma emplacement include magma density, lithostatic pressure, overpressures required for lateral emplacement, and rock physical properties; when and where the evolving source was tapped may play an equal role in the emplacement order. Further, detailed work on the sills will show whether crystallization might have yielded lower density residual liquids that could have migrated and formed distal fingers of sills or migrated to higher stratigraphic levels.

Temporal and structural evolution of the Early Palæogene rocks of the Seychelles microcontinent.

PubMed

Shellnutt, J Gregory; Yeh, Meng-Wan; Suga, Kenshi; Lee, Tung-Yi; Lee, Hao-Yang; Lin, Te-Hsien

2017-03-14

The Early Palæogene Silhouette/North Island volcano-plutonic complex was emplaced during the rifting of the Seychelles microcontinent from western India. The complex is thought to have been emplaced during magnetochron C28n. However, the magnetic polarities of the rocks are almost entirely reversed and inconsistent with a normal polarity. In this study we present new in situ zircon U/Pb geochronology of the different intrusive facies of the Silhouette/North Island complex in order to address the timing of emplacement and the apparent magnetic polarity dichotomy. The rocks from Silhouette yielded weighted mean 206 Pb/ 238 U ages from 62.4 ± 0.9 Ma to 63.1 ± 0.9 Ma whereas the rocks from North Island yielded slightly younger mean ages between 60.6 ± 0.7 Ma to 61.0 ± 0.8 Ma. The secular latitudinal variation from Silhouette to North Island is consistent with the anticlockwise rotation of the Seychelles microcontinent and the measured polarities. The rocks from Silhouette were emplaced across a polarity cycle (C26r-C27n-C27r) and the rocks from North Island were emplaced entirely within a magnetic reversal (C26r). Moreover, the rocks from North Island and those from the conjugate margin of India are contemporaneous and together mark the culmination of rift-related magmatism.

Solidified structure and leaching properties of metallurgical wastewater treatment sludge after solidification/stabilization process.

PubMed

Radovanović, Dragana Đ; Kamberović, Željko J; Korać, Marija S; Rogan, Jelena R

2016-01-01

The presented study investigates solidification/stabilization process of hazardous heavy metals/arsenic sludge, generated after the treatment of the wastewater from a primary copper smelter. Fly ash and fly ash with addition of hydrated lime and Portland composite cement were studied as potential binders. The effectiveness of the process was evaluated by unconfined compressive strength (UCS) testing, leaching tests (EN 12457-4 and TCLP) and acid neutralization capacity (ANC) test. It was found that introduction of cement into the systems increased the UCS, led to reduced leaching of Cu, Ni and Zn, but had a negative effect on the ANC. Gradual addition of lime resulted in decreased UCS, significant reduction of metals leaching and high ANC, due to the excess of lime that remained unreacted in pozzolanic reaction. Stabilization of more than 99% of heavy metals and 90% of arsenic has been achieved. All the samples had UCS above required value for safe disposal. In addition to standard leaching tests, solidificates were exposed to atmospheric conditions during one year in order to determine the actual leaching level of metals in real environment. It can be concluded that the EN 12457-4 test is more similar to the real environmental conditions, while the TCLP test highly exaggerates the leaching of metals. The paper also presents results of differential acid neutralization (d-AN) analysis compared with mineralogical study done by scanning electron microscopy and X-ray diffraction analysis. The d-AN coupled with Eh-pH (Pourbaix) diagrams were proven to be a new effective method for analysis of amorphous solidified structure.

Studies on the organization and regeneration of bone marrow: origin, growth, and differentiation of endocloned hematopoietic colonies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lambertsen, R.H.; Weiss, L.

1983-04-01

Hematopoietic colonies were studied by light microscopy in the marrow of alternate fraction x-irradiated mice (C576J/B1) to investigate the microenvironmental organization of marrow and identify early hematopoietic cell-stromal cell interactions. Undifferentiated colonies (UC) were detected at 3 days postirradiation, showed a marked predilection for bone surfaces, and disappeared as differentiated colonies developed. Some UC occurred along marrow arteries. Neutrophilic granulocyte colonies (GC) occurred in all areas at 3 days but grew rapidly only subosteally. Few eosinophilic colonies (GCe) occurred. Erythrocytic colonies (EC) appeared at 4 days as dispersed populations of motile cells within a localized area of marrow; these tendedmore » to proliferate initially in intermediate and central marrow zones. Macrophage colonies (M phi C) of two ''subtypes'' were detected, peaking in relative frequency at 4 days. These appeared active in stromal repair and monocytopoiesis. Megakaryocyte colonies (MC) originated along bone and differentiated away from bone. These results were interpreted as evidence that in x-irradiated marrow: (1) hematopoietic microenvironments (HMs) for stem-cell proliferation and commitment to differentiation, with the possible exception of HMs determining erythroid differentiation, occur in endosteal and periarterial regions; (2) a proliferative and/or chemotactic stimulus to erythroid progenitors exists in intermediate and central marrow regions; and (3) some subosteal regions may exclude erythropoiesis, or preferentially support nonerythroid differentiation. Elaborate associations occurred between macrophages and early UC, GC, and EC, but not MC hematopoietic cells. UC and GC often associated with osteoclasts. Reticular and other fibroblastic cells associated with the cells of all colony types.« less

Preservation of Immune Function in Cervical Cancer Patients during Chemoradiation using a Novel Integrative Approach

PubMed Central

Lutgendorf, Susan K.; Mullen-Houser, Elizabeth; Russell, Daniel; DeGeest, Koen; Jacobson, Geraldine; Hart, Laura; Bender, David; Anderson, Barrie; Buekers, Thomas E.; Goodheart, Michael J.; Antoni, Michael H.; Sood, Anil K.; Lubaroff, David M.

2010-01-01

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for 1) supporting cellular immunity, 2) improving mood and quality of life (QOL), and 3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p=0.018). HT patients showed greater decreases in 2 different indicators of depressed mood (CESD depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p < 0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known. PMID:20600809

A preliminary assessment of vitamin K1 intakes and serum undercarboxylated osteocalcin levels in 11-13 year old Irish girls.

PubMed

Collins, Aoife; Cashman, Kevin D; Kiely, Máiréad

2006-11-01

Low vitamin K1 intakes have been associated with low bone mineral density in women and reduced bone turnover in girls. No European data exist on the relationship between vitamin K1 and serum undercarboxylated osteocalcin (ucOC), an indicator of K1 status in adolescents. The aim of the current study was to assess intakes of vitamin K1 in relation to serum ucOC status in Irish girls. A detailed dietary history method, which measured habitual intakes from a typical 14-day period, was used to estimate vitamin K1 intakes in 18 girls aged 11-13 years. Recently compiled and validated food composition data for vitamin K1 were used to determine vitamin K1 intakes. An enzyme immunoassay was used to measure ucOC in fasting serum samples. The mean (+/- SD) intake of vitamin K1 in the girls was 72.4 microg/day (SD 34.4). Vegetables (particularly broccoli, composite dishes, and lettuce) contributed 53% of total vitamin K1 intakes. Thirty-Seven percent of the girls failed to meet the current U.S. adequate intake for adolescents of 60 microg/day vitamin K1. Serum ucOC levels were inversely related to body weight-adjusted vitamin K1 intakes, controlling for energy intake (partial correlation r = -0.538; p = 0.026). The data indicate that large-scale studies to examine relationships between vitamin K1 (and green vegetable) intakes and bone growth and development in adolescents are warranted.

Lunar base habitat designs: Characterizing the environment, and selecting habitat designs for future trade-offs

NASA Technical Reports Server (NTRS)

Ganapathi, Gani B.; Ferrall, Joseph; Seshan, P. K.

1993-01-01

A survey of distinct conceptual lunar habitat designs covering the pre- and post-Apollo era is presented. The impact of the significant lunar environmental challenges such as temperature, atmosphere, radiation, soil properties, meteorites, and seismic activity on the habitat design parameters are outlined. Over twenty habitat designs were identified and classified according to mission type, crew size; total duration of stay, modularity, environmental protection measures, and emplacement. Simple selection criteria of (1) post-Apollo design, (2) uniqueness of the habitat design, (3) level of thoroughness in design layout, (4) habitat dimensions are provided, and (5) materials of construction for the habitat shell are specified, are used to select five habitats for future trade studies. Habitat emplacement scenarios are created to examine the possible impact of emplacement of the habitat in different locations, such as lunar poles vs. equatorial, above ground vs. below ground, etc.

Dissociation between implicit and explicit responses in postconditioning UCS revaluation after fear conditioning in humans

PubMed Central

Schultz, Douglas H.; Balderston, Nicholas L.; Geiger, Jennifer A.; Helmstetter, Fred J.

2014-01-01

The nature of the relationship between explicit and implicit learning is a topic of considerable debate. In order to investigate this relationship we conducted two experiments on postconditioning revaluation of the unconditional stimulus (UCS) in human fear conditioning. In Experiment 1, the intensity of the UCS was decreased following acquisition for one group (devaluation) and held constant for another group (control). A subsequent test revealed that even though both groups exhibited similar levels of UCS expectancy, the devaluation group had significantly smaller conditional skin conductance responses. The devaluation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. In Experiment 2, the value of the UCS was increased following acquisition for one group (inflation) and held constant for another group (control). Test performance revealed that UCS inflation did not alter expectancy ratings, but the inflation group exhibited larger learned skin conductance responses than the control group. The inflation effect was not explained by differences in the explicit estimates of UCS probability or explicit knowledge that the UCS intensity had changed. The SCR revaluation effect was not dependent on explicit memory processes in either experiment. In both experiments we found differences on an implicit measure of learning in the absence of changes in explicit measures. Together, the differences observed between expectancy measures and skin conductance support the idea that these responses might reflect different types of memory formed during the same training procedure and be supported by separate neural systems. PMID:23731073

First-principles study of uranium carbide: Accommodation of point defects and of helium, xenon, and oxygen impurities

NASA Astrophysics Data System (ADS)

Freyss, Michel

2010-01-01

Point defects and volatile impurities (helium, xenon, oxygen) in uranium monocarbide UC are studied by first-principles calculations. Preliminarily, bulk properties of UC and of two other uranium carbide phases, UC2 and U2C3 , are calculated in order to compare them to experimental data and to get confidence in the use of the generalized gradient approximation for this class of compounds. The subsequent study of different types of point defects shows that the carbon sublattice best accommodates the defects. The perturbation of the crystal structure induced by the defects is weak and the interaction between defects is found short range. Interstitial carbon dumbbells possibly play an important role in the diffusion of carbon atoms. The most favorable location of diluted helium, xenon, and oxygen impurities in the UC crystal lattice is then determined. The rare-gas atoms occupy preferably a uranium substitution site or a uranium site in a U-C bivacancy. But their incorporation in UC is, however, not energetically favorable, especially for xenon, suggesting their propensity to diffuse in the material and/or form bubbles. On the other hand, oxygen atoms are very favorably incorporated as diluted atoms in the UC lattice, confirming the easy oxidation of UC. The oxygen atoms preferably occupy a carbon substitution site or the carbon site of a U-C bivacancy. Our results are compared to available experimental data on UC and to similar studies by first-principles calculations for other carbides and nitrides with the rock-salt structure.

Multi-Matrix System (MMX®) mesalamine for the treatment of mild-to-moderate ulcerative colitis.

PubMed

Horst, Sara N; Kane, Sunanda

2012-10-01

Ulcerative colitis (UC) is an inflammatory disease of the colon characterized by periods of active disease and remission. The pathogenesis of this disease is likely a complex interaction of genetic predisposition, environmental factors, and immune system dysregulation, and is not completely understood. A Multi-MatriX (MMX®) system formulation of mesalamine, MMX mesalamine (SPD476; Lialda®; Mesavancol®; Mezavant®), allows for high-dose, once-daily dosing for patients with mild-to-moderate UC. Mesalamine is a topically active agent with anti-inflammatory properties. Available literature regarding MMX mesalamine is extensively reviewed in this article, covering its chemical makeup, mechanism of action, pharmaceutics and pharmacokinetics, clinical efficacy, and safety and tolerability. A dose of 2.4 and 4.8 g was used in large Phase III clinical trials and was efficacious for induction of clinical and endoscopic remission in UC. MMX mesalamine was also efficacious in large multicenter maintenance studies for the maintenance of clinical and endoscopic remission. The introduction of the first once-daily mesalamine has given practitioners and patients more flexibility in dosing administration, which will ultimately lead to higher satisfaction and improved clinical outcomes.

Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

PubMed

Nohara, Hiroaki; Saito, Yuki; Higaki, Singo; Okayama, Naoko; Hamanaka, Yuichiro; Okita, Kiwamu; Hinoda, Yuji

2002-11-01

Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

Anti-TNF-A therapy about infliximab and adalimamab for the effectiveness in ulcerative colitis compared with conventional therapy: a meta-analysis.

PubMed

Zhou, Zheng; Dai, Cong; Liu, Wei-Xin

2015-01-01

TNF-α has an important role in the pathogenesis of ulcerative colitis (UC). It seems that anti-TNF-α therapy is beneficial in the treatment of UC. The aim was to assess the effectiveness of Infliximab and Adalimamab with UC compared with conventional therapy. The Pubmed and Embase databases were searched for studies investigating the efficacy of infliximab and adalimumab on UC. Infliximab had a statistically significant effects in induction of clinical response (RR = 1.67; 95% CI 1.12 to 2.50) of UC compared with conventional therapy, but those had not a statistically significant effects in clinical remission (RR = 1.63; 95% CI 0.84 to 3.18) and reduction of colectomy rate (RR = 0.54; 95% CI 0.26 to 1.12) of UC. And adalimumab had a statistically significant effects in induction of clinical remission (RR = 1.82; 95% CI 1.24 to 2.67) and clinical response (RR = 1.36; 95% CI 1.13 to 1.64) of UC compared with conventional therapy. Our meta-analyses suggested that Infliximab had a statistically significant effects in induction of clinical response of UC compared with conventional therapy and adalimumab had a statistically significant effects in induction of clinical remission and clinical response of UC compared with conventional therapy.