40 CFR 180.475 - Difenoconazole; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., straw 0.05 Beet, sugar 0.3 Beet, sugar, dried pulp 1.9 Brassica, head and stem, subgroup 5A 1.9 Brassica..., oil 25 Corn, sweet, forage 0.01 Corn, sweet, kernel plus cob with husks removed 0.01 Corn, sweet...

40 CFR 180.475 - Difenoconazole; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., straw 0.05 Beet, sugar 0.3 Beet, sugar, dried pulp 1.9 Brassica, head and stem, subgroup 5A 1.9 Brassica..., oil 25 Corn, sweet, forage 0.01 Corn, sweet, kernel plus cob with husks removed 0.01 Corn, sweet...

40 CFR 180.498 - Sulfentrazone; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances... Parts per million Asparagus 0.15 Bean, lima, succulent 0.15 Brassica, head and stem, subgroup 5A 0.20... pesticide under section 18 emergency exemptions granted by EPA. Compliance with the tolerance levels...

Expanding STEM opportunities through inclusive STEM-focused high schools.

PubMed

Means, Barbara; Wang, Haiwen; Wei, Xin; Lynch, Sharon; Peters, Vanessa; Young, Viki; Allen, Carrie

2017-09-01

Inclusive STEM high schools (ISHSs) (where STEM is science, technology, engineering, and mathematics) admit students on the basis of interest rather than competitive examination. This study examines the central assumption behind these schools-that they provide students from subgroups underrepresented in STEM with experiences that equip them academically and attitudinally to enter and stay in the STEM pipeline. Hierarchical modeling was applied to data from student surveys and state longitudinal data records for 5113 students graduating from 39 ISHSs and 22 comprehensive high schools in North Carolina and Texas. Compared to peers from the same demographic group with similar Grade 8 achievement levels, underrepresented minority and female ISHS students in both states were more likely to undertake advanced STEM coursework. Hispanics in Texas and females in both states expressed more STEM career interest in Grade 12 if they attended an ISHS. Positive relationships between ISHS attendance and grade point average were found in the total sample and each subgroup in North Carolina. Positive ISHS advantages in terms of test scores for the total student sample were found for science in both states and for mathematics in Texas. For the various student subgroups, test score differences favored the ISHS samples but attained statistical significance only for African Americans' science achievement scores in the Texas study.

Expanding STEM opportunities through inclusive STEM‐focused high schools

PubMed Central

Wang, Haiwen; Wei, Xin; Lynch, Sharon; Peters, Vanessa; Young, Viki; Allen, Carrie

2017-01-01

Abstract Inclusive STEM high schools (ISHSs) (where STEM is science, technology, engineering, and mathematics) admit students on the basis of interest rather than competitive examination. This study examines the central assumption behind these schools—that they provide students from subgroups underrepresented in STEM with experiences that equip them academically and attitudinally to enter and stay in the STEM pipeline. Hierarchical modeling was applied to data from student surveys and state longitudinal data records for 5113 students graduating from 39 ISHSs and 22 comprehensive high schools in North Carolina and Texas. Compared to peers from the same demographic group with similar Grade 8 achievement levels, underrepresented minority and female ISHS students in both states were more likely to undertake advanced STEM coursework. Hispanics in Texas and females in both states expressed more STEM career interest in Grade 12 if they attended an ISHS. Positive relationships between ISHS attendance and grade point average were found in the total sample and each subgroup in North Carolina. Positive ISHS advantages in terms of test scores for the total student sample were found for science in both states and for mathematics in Texas. For the various student subgroups, test score differences favored the ISHS samples but attained statistical significance only for African Americans’ science achievement scores in the Texas study. PMID:28919649

Influence of aging on the activity of mice Sca-1+CD31- cardiac stem cells.

PubMed

Wu, Qiong; Zhan, Jinxi; Pu, Shiming; Qin, Liu; Li, Yun; Zhou, Zuping

2017-01-03

Therapeutic application of cardiac resident stem/progenitor cells (CSC/CPCs) is limited due to decline of their regenerative potential with donor age. A variety of studies have shown that the cardiac aging was the problem of the stem cells, but little is known about the impact of age on the subgroups CSC/CPCs, the relationship between subgroups CSC/CPCs ageing and age-related dysfunction. Here, we studied Sca-1+CD31- subgroups of CSCs from younger(2~3months) and older(22~24months) age mice, biological differentiation was realized using specific mediums for 14 days to induce cardiomyocyte, smooth muscle cells or endothelial cells and immunostain analysis of differentiated cell resulting were done. Proliferation and cell cycle were measured by flow cytometry assay, then used microarray to dissect variability from younger and older mice. Although the number of CSCs was higher in older mice, the advanced age significantly reduced the differentiation ability into cardiac cell lineages and the proliferation ability. Transcriptional changes in Sca-1+CD31- subgroups of CSCs during aging are related to Vitamin B6 metabolism, circadian rhythm, Tyrosine metabolism, Complement and coagulation cascades. Taking together these results indicate that Cardiac resident stem/progenitor cells have significant differences in their proliferative, pluripotency and gene profiles and those differences are age depending.

Expanding STEM Opportunities through Inclusive STEM-Focused High Schools

ERIC Educational Resources Information Center

Means, Barbara; Wang, Haiwen; Wei, Xin; Lynch, Sharon; Peters, Vanessa; Young, Viki; Allen, Carrie

2017-01-01

Inclusive STEM high schools (ISHSs) (where STEM is science, technology, engineering, and mathematics) admit students on the basis of interest rather than competitive examination. This study examines the central assumption behind these schools--that they provide students from subgroups underrepresented in STEM with experiences that equip them…

40 CFR 180.511 - Buprofezin; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and stem, subgroup 5A 12.0 Canistel 0.90 Cattle, fat 0.05 Cattle, kidney 0.05 Cattle, liver 0.05... and peach 1.9 Goat, fat 0.05 Goat, kidney 0.05 Goat, liver 0.05 Goat, meat 0.05 Goat, meat byproducts 0.05 Grape 2.5 Guava 0.3 Hog, fat 0.05 Hog, kidney 0.05 Hog, liver 0.05 Hog, meat 0.05 Hog, meat...

Signals that regulate the oncogenic fate of neural stem cells and progenitors

PubMed Central

Swartling, Fredrik J.; Bolin, Sara; Phillips, Joanna J.; Persson, Anders I.

2013-01-01

Brain tumors have frequently been associated with a neural stem cell (NSC) origin and contain stem-like tumor cells, so-called brain tumor stem cells (BTSCs) that share many features with normal NSCs. A stem cell state of BTSCs confers resistance to radiotherapy and treatment with alkylating agents. It is also a hallmark of aggressive brain tumors and is maintained by transcriptional networks that are also active in embryonic stem cells. Advances in reprogramming of somatic cells into induced pluripotent stem (iPS) cells have further identified genes that drive stemness. In this review, we will highlight the possible drivers of stemness in medulloblastoma and glioma, the most frequent types of primary malignant brain cancer in children and adults, respectively. Signals that drive expansion of developmentally defined neural precursor cells are also active in corresponding brain tumors. Transcriptomal subgroups of human medulloblastoma and glioma match features of NSCs but also more restricted progenitors. Lessons from genetically-engineered mouse (GEM) models show that temporally and regionally defined NSCs can give rise to distinct subgroups of medulloblastoma and glioma. We will further discuss how acquisition of stem cell features may drive brain tumorigenesis from a non-NSC origin. Genetic alterations, signaling pathways, and therapy-induced changes in the tumor microenvironment can drive reprogramming networks and induce stemness in brain tumors. Finally, we propose a model where dysregulation of microRNAs (miRNAs) that normally provide barriers against reprogramming plays an integral role in promoting stemness in brain tumors. PMID:23376224

40 CFR 180.635 - Spinetoram; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Banana 0.25 Beet, sugar, molasses 0.75 Biriba 0.30 Brassica, head and stem, subgroup 5A 2.0 Brassica... Cherimoya 0.30 Citrus, dried pulp 0.50 Citrus, oil 3.0 Corn, sweet, kernel plus cob with husks removed 0.04... 0.30 Star fruit 0.30 Strawberry 1.0 Sugar apple 0.30 Ti, leaves 10 Vegetable, bulb, group 3, except...

40 CFR 180.635 - Spinetoram; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Banana 0.25 Beet, sugar, molasses 0.75 Biriba 0.30 Brassica, head and stem, subgroup 5A 2.0 Brassica... Cherimoya 0.30 Citrus, dried pulp 0.50 Citrus, oil 3.0 Corn, sweet, kernel plus cob with husks removed 0.04... 0.30 Star fruit 0.30 Strawberry 1.0 Sugar apple 0.30 Ti, leaves 10 Vegetable, bulb, group 3, except...

40 CFR 180.635 - Spinetoram; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Banana 0.25 Beet, sugar, molasses 0.75 Biriba 0.30 Brassica, head and stem, subgroup 5A 2.0 Brassica... Cherimoya 0.30 Citrus, dried pulp 0.50 Citrus, oil 3.0 Corn, sweet, kernel plus cob with husks removed 0.04... 0.30 Star fruit 0.30 Strawberry 1.0 Sugar apple 0.30 Ti, leaves 10 Vegetable, bulb, group 3, except...

Phylogenetic analysis of the complete genome of 11 BKV isolates obtained from allogenic stem cell transplant recipients in Ireland.

PubMed

Drew, Richard John; Walsh, Anne; Laoi, Bairbre Ni; Crowley, Brendan

2012-07-01

BK polyomavirus (family Polyomaviridae) may cause hemorrhagic cystitis (BKV-HC) in hematopoietic stem cell transplant recipients. Eleven complete BKV genomes (GenBank accession numbers: JN192431-JN192441) were sequenced from urine samples of allogenic hematopoietic stem cell transplant recipients and compared to complete BKV genomes in the published literature. Of the 11 isolates, seven (64%) were subgroup Ib-1, three (27%) isolates belonged to subgroup Ib-2 and a single isolate belonged to subtype III. The analysis of single-nucleotide polymorphisms in this study showed that isolates could be subclassified into subtypes I-IV and subgroups Ib-1 and Ib-2 on the basis of VP1 of the first part of the Large T-antigen (LTag). The non-coding control region (NCCR) of the 11 isolates was also sequenced. These sequences showed that there was consistent sequence homology within subgroups Ib-1 and Ib-2. Two new mutations were described in the isolates, G→C at O(84) in isolate SJH-LG-310, and a deletion at R(2-7) in isolate SJH-LG-309. No known transcription factor is thought to be present at the site of either of these mutations. There were no rearrangements seen in isolates and this may be because the patients were not followed up over time. There were five nucleotide positions at which subgroup Ib-1 isolated differed from subgroup Ib-2 isolates in the NCCR sequence, O(41) , P(18) , P(31) , R(4) , and S(18) . The mutation O(41) is present in the promoter granulocyte/macrophage stimulating factor) gene and the P(31) mutation is present in the NF-1 gene. Copyright © 2012 Wiley Periodicals, Inc.

Survival rates and prognostic predictors of high grade brain stem gliomas in childhood: a systematic review and meta-analysis.

PubMed

Hassan, Hadeel; Pinches, Anne; Picton, Susan V; Phillips, Robert S

2017-10-01

Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis.

Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.

PubMed

Pratcorona, Marta; Brunet, Salut; Nomdedéu, Josep; Ribera, Josep Maria; Tormo, Mar; Duarte, Rafael; Escoda, Lourdes; Guàrdia, Ramon; Queipo de Llano, M Paz; Salamero, Olga; Bargay, Joan; Pedro, Carmen; Martí, Josep Maria; Torrebadell, Montserrat; Díaz-Beyá, Marina; Camós, Mireia; Colomer, Dolors; Hoyos, Montserrat; Sierra, Jorge; Esteve, Jordi

2013-04-04

Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (≥0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.

Positron emission tomography response at the time of autologous stem cell transplantation predicts outcome of patients with relapsed and/or refractory Hodgkin’s lymphoma responding to prior salvage therapy

PubMed Central

Devillier, Raynier; Coso, Diane; Castagna, Luca; Brenot Rossi, Isabelle; Anastasia, Antonella; Chiti, Arturo; Ivanov, Vadim; Schiano, Jean Marc; Santoro, Armando; Chabannon, Christian; Balzarotti, Monica; Blaise, Didier; Bouabdallah, Reda

2012-01-01

Background High-dose chemotherapy followed by autologous stem cell transplantation is the standard treatment for relapsed and/or refractory Hodgkin’s lymphoma although half of patients relapse after transplantation. Predictive factors, such as relapse within 12 months, Ann-Arbor stage at relapse, and relapse in previously irradiated fields are classically used to identify patients with poor outcome. Recently, 18-fluorodeoxyglucose positron emission tomography has emerged as a new method for providing information to predict outcome. The aim of this study was to confirm the predictive value of positron emission tomography status after salvage therapy and to compare single versus tandem autologous stem cell transplantation in patients with relapsed and/or refractory Hodgkin’s lymphoma. Design and Methods We report a series of 111 consecutive patients with treatment-sensitive relapsed and/or treatment-refractory Hodgkin’s lymphoma who achieved complete (positron emission tomography-negative group) or partial remission (positron emission tomography-positive group) at positron emission tomography evaluation after salvage chemotherapy and who underwent single or tandem autologous stem cell transplantation. Results Five-year overall and progression-free survival rates were 81% and 64%, respectively. There were significant differences in 5-year progression-free survival (79% versus 23%; P<0.001) and 5-year overall survival (90% versus 55%, P=0.001) between the positron emission tomography-negative and -positive groups, respectively. A complete response, as determined by positron emission tomography evaluation, after salvage therapy predicted significantly better 5-year overall survival rates in both intermediate (91% versus 50%; P=0.029) and unfavorable (89% versus 58%; P=0.026) risk subgroup analyses. In the positron emission tomography-positive subgroup, tandem transplantation improved 5-year progression-free survival from 0% (in the single transplantation group) to 43% (P=0.034). Multivariate analysis showed that positron emission tomography status (hazard ratio: 5.26 [2.57–10.73]) and tandem transplantation (hazard ratio: 0.39 [0.19–0.78]) but not risk factors at relapse (hazard ratio: 1.77 [0.80–3.92]) significantly influenced progression-free survival, while only tomography status significantly influenced overall survival (hazard ratio: 4.03 [1.38–11.75]). Conclusions In patients with relapsed/refractory Hodgkin’s lymphoma responding to prior salvage therapy, positron emission tomography response at time of autologous stem cell transplantation favorably influences outcome and enables identification of patients requiring single or tandem transplantation. PMID:22271893

Brain stem auditory-evoked response of the nonanesthetized dog.

PubMed

Marshall, A E

1985-04-01

The brain stem auditory evoked-response was measured from a group of 24 healthy dogs under conditions suitable for clinical diagnostic use. The waveforms were identified, and analysis of amplitude ratios, latencies, and interpeak latencies were done. The group was subdivided into subgroups based on tranquilization, nontranquilization, sex, and weight. Differences were not observed among any of these subgroups. All dogs responded to the click stimulus from 30 dB to 90 dB, but only 62.5% of the dogs responded at 5 dB. The total number of peaks averaged 1.6 at 5 dB, increased linearly to 6.5 at 50 dB, and remained at 6.5 to 90 dB. Frequency of recognizability of each wave was tabulated for each stimulus intensity tested; recognizability increased with increased stimulus intensity. Amplitudes of waves increased with increasing stimulus intensity, but were highly variable. The 4th wave had the greatest amplitude at the lower stimulus intensities, and the 1st wave had the greatest amplitude at the higher stimulus intensities. Amplitude ratio of the 1st to 5th wave was greater than 1 at less than or equal to 50 dB stimulus intensity, and was 1 for stimulus intensities greater than 50 dB. Interpeak latencies did not change relative to stimulus intensities. Peak latencies of each wave averaged at 5-dB hearing level for the 1st to 6th waves were 2.03, 2.72, 3.23, 4.14, 4.41, and 6.05 ms, respectively; latencies of these 6 waves at 90 dB were 0.92, 1.79, 2.46, 3.03, 3.47, and 4.86 ms, respectively. Latency decreased between 0.009 to 0.014 ms/dB for the waves.

FoxG1 interacts with Bmi1 to regulate self-renewal and tumorigenicity of medulloblastoma stem cells.

PubMed

Manoranjan, Branavan; Wang, Xin; Hallett, Robin M; Venugopal, Chitra; Mack, Stephen C; McFarlane, Nicole; Nolte, Sara M; Scheinemann, Katrin; Gunnarsson, Thorsteinn; Hassell, John A; Taylor, Michael D; Lee, Cathy; Triscott, Joanna; Foster, Colleen M; Dunham, Christopher; Hawkins, Cynthia; Dunn, Sandra E; Singh, Sheila K

2013-07-01

Brain tumors represent the leading cause of childhood cancer mortality, of which medulloblastoma (MB) is the most frequent malignant tumor. Recent studies have demonstrated the presence of several MB molecular subgroups, each distinct in terms of prognosis and predicted therapeutic response. Groups 1 and 2 are characterized by relatively good clinical outcomes and activation of the Wnt and Shh pathways, respectively. In contrast, groups 3 and 4 ("non-Shh/Wnt MBs") are distinguished by metastatic disease, poor patient outcome, and lack a molecular pathway phenotype. Current gene expression platforms have not detected brain tumor-initiating cell (BTIC) self-renewal genes in groups 3 and 4 MBs as BTICs typically comprise a minority of tumor cells and may therefore go undetected on bulk tumor analyses. Since increasing BTIC frequency has been associated with increasing tumor aggressiveness and poor patient outcome, we investigated the subgroup-specific gene expression profile of candidate stem cell genes within 251 primary human MBs from four nonoverlapping MB transcriptional databases (Amsterdam, Memphis, Toronto, Boston) and 74 NanoString-subgrouped MBs (Vancouver). We assessed the functional relevance of two genes, FoxG1 and Bmi1, which were significantly enriched in non-Shh/Wnt MBs and showed these genes to mediate MB stem cell self-renewal and tumor initiation in mice. We also identified their transcriptional regulation through reciprocal promoter occupancy in CD15+ MB stem cells. Our work demonstrates the application of stem cell data gathered from genomic platforms to guide functional BTIC assays, which may then be used to develop novel BTIC self-renewal mechanisms amenable to therapeutic targeting. Copyright © 2013 AlphaMed Press.

MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation.

PubMed

Liu, Hailong; Sun, Qianwen; Sun, Youliang; Zhang, Junping; Yuan, Hongyu; Pang, Shuhuan; Qi, Xueling; Wang, Haoran; Zhang, Mingshan; Zhang, Hongwei; Yu, Chunjiang; Gu, Chunyu

2017-09-01

Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stem-like cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK- or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stem-like cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients. Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma. Mol Cancer Res; 15(9); 1275-86. ©2017 AACR . ©2017 American Association for Cancer Research.

WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma.

PubMed

Zhukova, Nataliya; Ramaswamy, Vijay; Remke, Marc; Martin, Dianna C; Castelo-Branco, Pedro; Zhang, Cindy H; Fraser, Michael; Tse, Ken; Poon, Raymond; Shih, David J H; Baskin, Berivan; Ray, Peter N; Bouffet, Eric; Dirks, Peter; von Bueren, Andre O; Pfaff, Elke; Korshunov, Andrey; Jones, David T W; Northcott, Paul A; Kool, Marcel; Pugh, Trevor J; Pomeroy, Scott L; Cho, Yoon-Jae; Pietsch, Torsten; Gessi, Marco; Rutkowski, Stefan; Bognár, Laszlo; Cho, Byung-Kyu; Eberhart, Charles G; Conter, Cecile Faure; Fouladi, Maryam; French, Pim J; Grajkowska, Wieslawa A; Gupta, Nalin; Hauser, Peter; Jabado, Nada; Vasiljevic, Alexandre; Jung, Shin; Kim, Seung-Ki; Klekner, Almos; Kumabe, Toshihiro; Lach, Boleslaw; Leonard, Jeffrey R; Liau, Linda M; Massimi, Luca; Pollack, Ian F; Ra, Young Shin; Rubin, Joshua B; Van Meir, Erwin G; Wang, Kyu-Chang; Weiss, William A; Zitterbart, Karel; Bristow, Robert G; Alman, Benjamin; Hawkins, Cynthia E; Malkin, David; Clifford, Steven C; Pfister, Stefan M; Taylor, Michael D; Tabori, Uri

2014-12-24

TP53 mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates TP53 related radioresistance and can be used to sensitize TP53 mutant tumors for radiation. We examined the subgroup-specific role of TP53 mutations in a cohort of 314 patients treated with radiation. TP53 wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of TP53 mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/TP53 mutant medulloblastoma had higher 5-year survival than those with SHH/TP53 mutant tumours (100% and 36.6%±8.7%, respectively (p<0.001)). Introduction of TP53 mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89%±2% vs. 57.4%±1.8% (p<0.01)). In contrast, β-catenin mutation sensitized TP53 mutant cells to radiation (p<0.05). Lithium, an activator of the WNT pathway, sensitized TP53 mutant medulloblastoma to radiation (SF2 of 43.5%±1.5% in lithium treated cells vs. 56.6±3% (p<0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33%±8% for lithium treated cells vs. 27%±3% for untreated controls (p=0.05). Poor survival of patients with TP53 mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes TP53 mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.

A Profile of Mexican American, Puerto Rican, and Other Hispanic STEM Doctorates: 1983 TO 1997

NASA Astrophysics Data System (ADS)

Quintana-Baker, Maricel

This article describes the characteristics of Hispanic U. S. citizens who earned doctoral degrees in science, technology, engineering, and mathematics (STEM) from institutions in the United States between 1983 and 1997. The data on this population •were disaggregated by gender and by Hispanic subgroup (i.e., Mexican American, Puerto Rican and other Hispanic). The profile for this population includes parental education, type of financial assistance during time of study, and level of debt on receipt of doctorate. In addition, this research identified and ranked the doctorate-granting institutions according to the absolute number of STEM doctoral degrees they granted to Hispanics during the 15-year period of the study. The results indicate that there are differences among the Hispanic subgroups in this study. Therefore, it is critical thai future researchers understand that studies that analyze Hispanics as one single homogeneous group produce results that are not truly representative and that research, policy, and programmatic efforts must be targeted accordingly.

Detailed Magnetic Resonance Imaging (MRI) Analysis in Infantile Spasms.

PubMed

Harini, Chellamani; Sharda, Sonal; Bergin, Ann Marie; Poduri, Annapurna; Yuskaitis, Christopher J; Peters, Jurriaan M; Rakesh, Kshitiz; Kapur, Kush; Pearl, Phillip L; Prabhu, Sanjay P

2018-05-01

To evaluate initial magnetic resonance imaging (MRI) abnormalities in infantile spasms, correlate them to clinical characteristics, and describe repeat imaging findings. A retrospective review of infantile spasm patients was conducted, classifying abnormal MRI into developmental, acquired, and nonspecific subgroups. MRIs were abnormal in 52 of 71 infantile spasm patients (23 developmental, 23 acquired, and 6 nonspecific) with no correlation to the clinical infantile spasm characteristics. Both developmental and acquired subgroups exhibited cortical gray and/or white matter abnormalities. Additional abnormalities of deep gray structures, brain stem, callosum, and volume loss occurred in the structural acquired subgroup. Repeat MRI showed better definition of the extent of existing malformations. In structural infantile spasms, developmental/acquired subgroups showed differences in pattern of MRI abnormalities but did not correlate with clinical characteristics.

Reduced incidence of interstitial pneumonitis after allogeneic hematopoietic stem cell transplantation using a modified technique of total body irradiation.

PubMed

Chiang, Yun; Tsai, Cheng-Hong; Kuo, Sung-Hsin; Liu, Chieh-Yu; Yao, Ming; Li, Chi-Cheng; Huang, Shang-Yi; Ko, Bor-Sheng; Lin, Chien-Ting; Hou, Hsin-An; Chou, Wen-Chien; Liu, Jia-Hau; Lin, Chien-Chin; Wu, Shang-Ju; Hsu, Szu-Chun; Chen, Yao-Chang; Lin, Kai-Hsin; Lin, Dong-Tsamn; Chou, Hsien-Tang; Lu, Meng-Yu; Yang, Yung-Li; Chang, Hsiu-Hao; Liu, Ming-Chih; Liao, Xiu-Wen; Wu, Jian-Kuen; Chou, Sheng-Chieh; Cheng, Chieh-Lung; Chen, Chien-Yuan; Tsay, Woei; Tien, Hwei-Fang; Tang, Jih-Luh; Chen, Yu-Hsuan

2016-11-10

Allogeneic hematopoietic stem cell transplantation is a curative-intent treatment for patients with high-risk hematologic diseases. However, interstitial pneumonitis (IP) and other toxicities remain major concerns after total body irradiation (TBI). We have proposed using linear accelerators with rice-bag compensators for intensity modulation (IM-TBI), as an alternative to the traditional cobalt-60 teletherapy with lung-shielding technique (Co-TBI). Patients who received a TBI-based myeloablative conditioning regimen between 1995 and 2014 were recruited consecutively. Before March 2007, TBI was delivered using Co-TBI (n = 181); afterward, TBI was administered using IM-TBI (n = 126). Forty-four patients developed IP; of these cases, 19 were idiopathic. The IP-related mortality rate was 50% in the total IP cohort and 63% in the idiopathic subgroup. The 1-year cumulative incidences of IP and idiopathic IP were 16.5% and 7.4%, respectively; both rates were significantly higher in the Co-TBI group than in the IM-TBI group. Multivariate analysis revealed that Co-TBI was an independent prognostic factor for both total and idiopathic IP. In the acute myeloid leukemia subgroup, patients with different TBI techniques had similar outcomes for both overall and relapse-free survival. In conclusion, IM-TBI is an easy and effective TBI technique that could substantially reduce the complication rate of IP without compromising treatment efficacy.

Perturbed hematopoietic stem and progenitor cell hierarchy in myelodysplastic syndromes patients with monosomy 7 as the sole cytogenetic abnormality.

PubMed

Dimitriou, Marios; Woll, Petter S; Mortera-Blanco, Teresa; Karimi, Mohsen; Wedge, David C; Doolittle, Helen; Douagi, Iyadh; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva

2016-11-08

The stem and progenitor cell compartments in low- and intermediate-risk myelodysplastic syndromes (MDS) have recently been described, and shown to be highly conserved when compared to those in acute myeloid leukemia (AML). Much less is known about the characteristics of the hematopoietic hierarchy of subgroups of MDS with a high risk of transforming to AML. Immunophenotypic analysis of immature stem and progenitor cell compartments from patients with an isolated loss of the entire chromosome 7 (isolated -7), an independent high-risk genetic event in MDS, showed expansion and dominance of the malignant -7 clone in the granulocyte and macrophage progenitors (GMP), and other CD45RA+ progenitor compartments, and a significant reduction of the LIN-CD34+CD38low/-CD90+CD45RA- hematopoietic stem cell (HSC) compartment, highly reminiscent of what is typically seen in AML, and distinct from low-risk MDS. Established functional in vitro and in vivo stem cell assays showed a poor readout for -7 MDS patients irrespective of marrow blast counts. Moreover, while the -7 clone dominated at all stages of GM differentiation, the -7 clone had a competitive disadvantage in erythroid differentiation. In azacitidine-treated -7 MDS patients with a clinical response, the decreased clonal involvement in mononuclear bone marrow cells was not accompanied by a parallel reduced clonal involvement in the dominant CD45RA+ progenitor populations, suggesting a selective azacitidine-resistance of these distinct -7 progenitor compartments. Our data demonstrate, in a subgroup of high risk MDS with monosomy 7, that the perturbed stem and progenitor cell compartments resemble more that of AML than low-risk MDS.

Single cell sequencing reveals heterogeneity within ovarian cancer epithelium and cancer associated stromal cells.

PubMed

Winterhoff, Boris J; Maile, Makayla; Mitra, Amit Kumar; Sebe, Attila; Bazzaro, Martina; Geller, Melissa A; Abrahante, Juan E; Klein, Molly; Hellweg, Raffaele; Mullany, Sally A; Beckman, Kenneth; Daniel, Jerry; Starr, Timothy K

2017-03-01

The purpose of this study was to determine the level of heterogeneity in high grade serous ovarian cancer (HGSOC) by analyzing RNA expression in single epithelial and cancer associated stromal cells. In addition, we explored the possibility of identifying subgroups based on pathway activation and pre-defined signatures from cancer stem cells and chemo-resistant cells. A fresh, HGSOC tumor specimen derived from ovary was enzymatically digested and depleted of immune infiltrating cells. RNA sequencing was performed on 92 single cells and 66 of these single cell datasets passed quality control checks. Sequences were analyzed using multiple bioinformatics tools, including clustering, principle components analysis, and geneset enrichment analysis to identify subgroups and activated pathways. Immunohistochemistry for ovarian cancer, stem cell and stromal markers was performed on adjacent tumor sections. Analysis of the gene expression patterns identified two major subsets of cells characterized by epithelial and stromal gene expression patterns. The epithelial group was characterized by proliferative genes including genes associated with oxidative phosphorylation and MYC activity, while the stromal group was characterized by increased expression of extracellular matrix (ECM) genes and genes associated with epithelial-to-mesenchymal transition (EMT). Neither group expressed a signature correlating with published chemo-resistant gene signatures, but many cells, predominantly in the stromal subgroup, expressed markers associated with cancer stem cells. Single cell sequencing provides a means of identifying subpopulations of cancer cells within a single patient. Single cell sequence analysis may prove to be critical for understanding the etiology, progression and drug resistance in ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic characterization of a core collection of flax (Linum usitatissimum L.) suitable for association mapping studies and evidence of divergent selection between fiber and linseed types

PubMed Central

2013-01-01

Background Flax is valued for its fiber, seed oil and nutraceuticals. Recently, the fiber industry has invested in the development of products made from linseed stems, making it a dual purpose crop. Simultaneous targeting of genomic regions controlling stem fiber and seed quality traits could enable the development of dual purpose cultivars. However, the genetic diversity, population structure and linkage disequilibrium (LD) patterns necessary for association mapping (AM) have not yet been assessed in flax because genomic resources have only recently been developed. We characterized 407 globally distributed flax accessions using 448 microsatellite markers. The data was analyzed to assess the suitability of this core collection for AM. Genomic scans to identify candidate genes selected during the divergent breeding process of fiber flax and linseed were conducted using the whole genome shotgun sequence of flax. Results Combined genetic structure analysis assigned all accessions to two major groups with six sub-groups. Population differentiation was weak between the major groups (FST = 0.094) and for most of the pairwise comparisons among sub-groups. The molecular coancestry analysis indicated weak relatedness (mean = 0.287) for most individual pairs. Abundant genetic diversity was observed in the total panel (5.32 alleles per locus), and some sub-groups showed a high proportion of private alleles. The average genome-wide LD (r2) was 0.036, with a relatively fast decay of 1.5 cM. Genomic scans between fiber flax and linseed identified candidate genes involved in cell-wall biogenesis/modification, xylem identity and fatty acid biosynthesis congruent with genes previously identified in flax and other plant species. Conclusions Based on the abundant genetic diversity, weak population structure and relatedness and relatively fast LD decay, we concluded that this core collection is suitable for AM studies targeting multiple agronomic and quality traits aiming at the improvement of flax as a true dual purpose crop. Our genomic scans provide the first insights into candidate regions affected by divergent selection in flax. In combination with AM, genomic scans have the ability to increase the power to detect loci influencing complex traits. PMID:23647851

Genetic characterization of a core collection of flax (Linum usitatissimum L.) suitable for association mapping studies and evidence of divergent selection between fiber and linseed types.

PubMed

Soto-Cerda, Braulio J; Diederichsen, Axel; Ragupathy, Raja; Cloutier, Sylvie

2013-05-06

Flax is valued for its fiber, seed oil and nutraceuticals. Recently, the fiber industry has invested in the development of products made from linseed stems, making it a dual purpose crop. Simultaneous targeting of genomic regions controlling stem fiber and seed quality traits could enable the development of dual purpose cultivars. However, the genetic diversity, population structure and linkage disequilibrium (LD) patterns necessary for association mapping (AM) have not yet been assessed in flax because genomic resources have only recently been developed. We characterized 407 globally distributed flax accessions using 448 microsatellite markers. The data was analyzed to assess the suitability of this core collection for AM. Genomic scans to identify candidate genes selected during the divergent breeding process of fiber flax and linseed were conducted using the whole genome shotgun sequence of flax. Combined genetic structure analysis assigned all accessions to two major groups with six sub-groups. Population differentiation was weak between the major groups (F(ST) = 0.094) and for most of the pairwise comparisons among sub-groups. The molecular coancestry analysis indicated weak relatedness (mean = 0.287) for most individual pairs. Abundant genetic diversity was observed in the total panel (5.32 alleles per locus), and some sub-groups showed a high proportion of private alleles. The average genome-wide LD (r²) was 0.036, with a relatively fast decay of 1.5 cM. Genomic scans between fiber flax and linseed identified candidate genes involved in cell-wall biogenesis/modification, xylem identity and fatty acid biosynthesis congruent with genes previously identified in flax and other plant species. Based on the abundant genetic diversity, weak population structure and relatedness and relatively fast LD decay, we concluded that this core collection is suitable for AM studies targeting multiple agronomic and quality traits aiming at the improvement of flax as a true dual purpose crop. Our genomic scans provide the first insights into candidate regions affected by divergent selection in flax. In combination with AM, genomic scans have the ability to increase the power to detect loci influencing complex traits.

Towards a global human embryonic stem cell bank.

PubMed

Lott, Jason P; Savulescu, Julian

2007-08-01

An increasingly unbridgeable gap exists between the supply and demand of transplantable organs. Human embryonic stem cell technology could solve the organ shortage problem by restoring diseased or damaged tissue across a range of common conditions. However, such technology faces several largely ignored immunological challenges in delivering cell lines to large populations. We address some of these challenges and argue in favor of encouraging contribution or intentional creation of embryos from which widely immunocompatible stem cell lines could be derived. Further, we argue that current immunological constraints in tissue transplantation demand the creation of a global stem cell bank, which may hold particular promise for minority populations and other sub-groups currently marginalized from organ procurement and allocation systems. Finally, we conclude by offering a number of practical and ethically oriented recommendations for constructing a human embryonic stem cell bank that we hope will help solve the ongoing organ shortage problem.

Tomato necrotic streak virus, a novel subgroup 2 ilarvirus

USDA-ARS?s Scientific Manuscript database

A novel plant virus has been identified infecting fresh market tomato plants in south and southeast Florida. The virus causes necrosis of tomato leaves, petioles and stems, and necrotic rings or spots on tomato fruits. Symptomatic tomato plant tissue was used to mechanically inoculate tomato plant...

Profiling first-year students in STEM programs based on autonomous motivation and academic self-concept and relationship with academic achievement.

PubMed

Van Soom, Carolien; Donche, Vincent

2014-01-01

The low success rate of first-year college students in Science, Technology, Engineering, and Mathematics (STEM) programs has spurred many academic achievement studies in which explanatory factors are studied. In this study, we investigated from a person-oriented perspective whether different motivational and academic self-concept profiles could be discerned between male and female first-year college students in STEM and whether differences in early academic achievement were associated with these student groups. Data on autonomous motivation, academic self-concept, and early academic achievement of 1,400 first-year STEM college students were collected. Cluster analyses were used to distinguish motivational profiles based on the relative levels of autonomous motivation and academic self-concept for male and female students. Differences in early academic achievement of the various profiles were studied by means of ANCOVA. Four different motivational profiles were discerned based on the dimensions of autonomous motivation (A) and academic self-concept (S): students scoring high and respectively low on both dimensions (HA-HS or LA-LS), and students scoring high on one dimension and low on the other (HA-LS or LA-HS). Also gender differences were found in this study: male students with high levels of academic self-concept and autonomous motivation had higher academic achievement compared to male students with low levels on both motivational dimensions. For female students, motivational profiles were not associated with academic achievement. The findings partially confirm the internal and external validity of the motivational theories underpinning this study and extend the present insights on identifying subgroup(s) of at risk students in contemporary STEM programs at university level.

Profiling First-Year Students in STEM Programs Based on Autonomous Motivation and Academic Self-Concept and Relationship with Academic Achievement

PubMed Central

Van Soom, Carolien; Donche, Vincent

2014-01-01

The low success rate of first-year college students in Science, Technology, Engineering, and Mathematics (STEM) programs has spurred many academic achievement studies in which explanatory factors are studied. In this study, we investigated from a person-oriented perspective whether different motivational and academic self-concept profiles could be discerned between male and female first-year college students in STEM and whether differences in early academic achievement were associated with these student groups. Data on autonomous motivation, academic self-concept, and early academic achievement of 1,400 first-year STEM college students were collected. Cluster analyses were used to distinguish motivational profiles based on the relative levels of autonomous motivation and academic self-concept for male and female students. Differences in early academic achievement of the various profiles were studied by means of ANCOVA. Four different motivational profiles were discerned based on the dimensions of autonomous motivation (A) and academic self-concept (S): students scoring high and respectively low on both dimensions (HA-HS or LA-LS), and students scoring high on one dimension and low on the other (HA-LS or LA-HS). Also gender differences were found in this study: male students with high levels of academic self-concept and autonomous motivation had higher academic achievement compared to male students with low levels on both motivational dimensions. For female students, motivational profiles were not associated with academic achievement. The findings partially confirm the internal and external validity of the motivational theories underpinning this study and extend the present insights on identifying subgroup(s) of at risk students in contemporary STEM programs at university level. PMID:25390942

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation.

PubMed

Gilis, L; Morisset, S; Billaud, G; Ducastelle-Leprêtre, S; Labussière-Wallet, H; Nicolini, F-E; Barraco, F; Detrait, M; Thomas, X; Tedone, N; Sobh, M; Chidiac, C; Ferry, T; Salles, G; Michallet, M; Ader, F

2014-05-01

BK virus (BKV) reactivation has been increasingly associated with the occurrence of late-onset hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT (allo-HSCT) resulting in morbidity and sometimes mortality. We investigated the incidence, risk factors and outcome of BKV-HC in 323 consecutive adult patients undergoing allo-HSCT over a 5-year period. BK viremia values for HC staging were evaluated, as well as the medico-economic impact of the complication. Forty-three patients developed BKV-HC. In univariate analysis, young age (P=0.028), unrelated donor (P=0.0178), stem cell source (P=0.0001), HLA mismatching (P=0.0022) and BU in conditioning regimen (P=0.01) were associated with a higher risk of developing BKV-HC. In multivariate analysis, patients receiving cord blood units (CBUs) (P=0.0005) and peripheral blood stem cells (P=0.011) represented high-risk subgroups for developing BKV-HC. BK viremia was directly correlated to HC severity (P=0.011) with a 3 to 6-log peak being likely associated with grades 3 or 4 HC. No correlation was found between BKV-HC and acute graft versus host disease or mortality rate. Patients with BKV-HC required a significantly longer duration of hospitalization (P<0.0001), more RBC (P=0.0003) and platelet transfusions (P<0.0001). Over the 5-year study period, the financial cost of the complication was evaluated at \\[euro]2 376 076 ($3 088 899). Strategies to prevent the occurrence of late-onset BKV-HC after allo-HSCT are urgently needed, especially in CBU and peripheral blood stem cell recipients. BK viremia correlates with the severity of the disease. Prospective studies are required to test prophylactic approaches.

Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15.

PubMed

Inukai, Takeshi; Kiyokawa, Nobutaka; Campana, Dario; Coustan-Smith, Elaine; Kikuchi, Akira; Kobayashi, Miyuki; Takahashi, Hiroyuki; Koh, Katsuyoshi; Manabe, Atsushi; Kumagai, Masaaki; Ikuta, Koichiro; Hayashi, Yasuhide; Tsuchida, Masahiro; Sugita, Kanji; Ohara, Akira

2012-02-01

Early T-cell precursor acute lymphoblastic leukaemia (ETP-ALL) is a recently identified subtype of T-ALL with distinctive gene expression and cell marker profiles, poor response to chemotherapy and a very high risk of relapse. We determined the reliability of restricted panel of cell markers to identify EPT-ALL using a previously classified cohort. Then, we applied the cell marker profile that best discriminated ETP-ALL to a cohort of 91 patients with T-ALL enrolled in the Tokyo Children's Cancer Study Group L99-15 study, which included allogeneic stem cell transplantation (allo-SCT) for patients with poor prednisone response. Five of the 91 patients (5·5%) met the ETP-ALL criteria. There were no significant differences in presenting clinical features between these and the remaining 86 patients. Response to early remission induction therapy was inferior in ETP-ALL as compared with T-ALL. The ETP-ALL subgroup showed a significantly poorer event-free survival (4-year rate; 40%) than the T-ALL subgroup (70%, P=0·014). Of note, three of four relapsed ETP-ALL patients survived after allo-SCT, indicating that allo-SCT can be effective for this drug-resistant subtype of T-ALL. © 2011 Blackwell Publishing Ltd.

Donor cell reaction to OKT3 as predictor of chronic graft-vs-host disease in hematopoietic stem cell recipients.

PubMed

Lindemann, Monika; Ottinger, Hellmut D; Elmaagacli, Ahmet H; Trenschel, Rudolf; Rebmann, Vera; Beelen, Dietrich W; Grosse-Wilde, Hans

2006-12-01

In the hematopoietic stem cell transplantation setting, granulocyte colony-stimulating factor (G-CSF) administration can reduce donor cell reactivity in vitro, but the clinical significance of this phenomenon was only sparsely defined. We performed lymphocyte transformation tests in 28 related stem cell donors pre and 5 days post G-CSF treatment, respectively, and correlated proliferative responses of donor peripheral blood mononuclear cells with clinical parameters in the corresponding recipients. In vitro reactions towards 4 mitogens and 12 recall antigens at day 5 post G-CSF administration were predictive for the occurrence of chronic graft-vs-host disease (cGVHD). Here, proliferative responses towards the mitogen anti-CD3 monoclonal antibody (OKT3) above median were most informative; this threshold could be determined by discrimination and receiver operating curve (ROC) analyses. In the whole cohort (18 human leukocyte antigen [HLA]-identical and 10 partially mismatched donor-recipient pairs), OKT3 responses predicted cGVHD with an odds ratio of 33.0, a sensitivity of 79%, and a specificity of 90%. A subgroup analysis of HLA-identical pairs even yielded an odds ratio of 85.0. Furthermore, bivariate analysis defined HLA compatibility and responses towards OKT3 as independent risk factors for cGVHD (p = 0.02 and p = 0.0007, respectively). The proliferative capacity of G-CSF-mobilized donor cells appears as a graft factor that determines the future incidence of cGVHD in the corresponding recipient.

Abundance and Relative Distribution of Frankia Host Infection Groups Under Actinorhizal Alnus glutinosa and Non-actinorhizal Betula nigra Trees.

PubMed

Samant, Suvidha; Huo, Tian; Dawson, Jeffrey O; Hahn, Dittmar

2016-02-01

Quantitative polymerase chain reaction (qPCR) was used to assess the abundance and relative distribution of host infection groups of the root-nodule forming, nitrogen-fixing actinomycete Frankia in four soils with similar physicochemical characteristics, two of which were vegetated with a host plant, Alnus glutinosa, and two with a non-host plant, Betula nigra. Analyses of DAPI-stained cells at three locations, i.e., at a distance of less than 1 m (near stem), 2.5 m (middle crown), and 3-5 m (crown edge) from the stems of both tree species revealed no statistically significant differences in abundance. Frankiae generally accounted for 0.01 to 0.04 % of these cells, with values between 4 and 36 × 10(5) cells (g soil)(-1). In three out of four soils, abundance of frankiae was significantly higher at locations "near stem" and/or "middle crown" compared to "crown edge," while numbers at these locations were not different in the fourth soil. Frankiae of the Alnus host infection group were dominant in all samples accounting for about 75 % and more of the cells, with no obvious differences with distance to stem. In three of the soils, all of these cells were represented by strain Ag45/Mut15. In the fourth soil that was vegetated with older A. glutinosa trees, about half of these cells belonged to a different subgroup represented by strain ArI3. In all soils, the remaining cells belonged to the Elaeagnus host infection group represented by strain EAN1pec. Casuarina-infective frankiae were not found. Abundance and relative distribution of Frankia host infection groups were similar in soils under the host plant A. glutinosa and the non-host plant B. nigra. Results did thus not reveal any specific effects of plant species on soil Frankia populations.

Prognostic Prediction Model for Second Allogeneic Stem-Cell Transplantation in Patients With Relapsed Acute Myeloid Leukemia: Single-Center Report.

PubMed

Park, Sung-Soo; Kim, Hee-Je; Min, Kyoung Il; Min, Gi June; Jeon, Young-Woo; Yoon, Jae-Ho; Yahng, Seung-Ah; Shin, Seung-Hwan; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung

2018-04-01

To identify factors affecting survival outcomes and to develop a prognostic model for second allogeneic stem-cell transplantation (allo-SCT2) for relapsed acute myeloid leukemia (AML) after the first autologous or allogeneic stem-cell transplantation. Seventy-eight consecutive adult AML patients who received allo-SCT2 were analyzed in this retrospective study. The 4-year overall survival (OS) rate was 28.7%. In multivariate analysis, poor cytogenetic risk at diagnosis, circulating blast ≥ 20% at relapse, duration from first transplantation to relapse < 9 months, and failure to achieve morphologic complete remission after allo-SCT2 were factors associated with poor OS. A prognostic model was developed with the following score system: intermediate and poor cytogenetic risk at diagnosis (0.5 and 1 point), peripheral blast ≥ 20% at relapse (1 point), duration from the first transplantation to relapse < 9 months (1 point), and failure to achieve morphologic complete remission after allo-SCT2 (1 point). The model identified 2 subgroups according to the 4-year OS rate: 51.3% in the low-risk group (score < 2) and 2.8% in the high-risk group (score ≥ 2) (P < .001). This prognostic model might be useful to make an appropriate decision for allo-SCT2 in relapsed AML after the first autologous or allogeneic stem-cell transplantation. Copyright © 2018 Elsevier Inc. All rights reserved.

Finding "Los Científicos" within: Latino Male Science Identity Development in the First College Semester

ERIC Educational Resources Information Center

Lu, Charles

2015-01-01

Latino males are the lowest male ethnic subgroup to attain a four-year STEM college degree. This phenomenological qualitative research study used two rounds of interviews with twelve Latino male students in Central Texas to examine their first semester science experiences using a science identity framework. Findings indicate that developing a…

Cross-species genomics matches driver mutations and cell compartments to model ependymoma

PubMed Central

Johnson, Robert A.; Wright, Karen D.; Poppleton, Helen; Mohankumar, Kumarasamypet M.; Finkelstein, David; Pounds, Stanley B.; Rand, Vikki; Leary, Sarah E.S.; White, Elsie; Eden, Christopher; Hogg, Twala; Northcott, Paul; Mack, Stephen; Neale, Geoffrey; Wang, Yong-Dong; Coyle, Beth; Atkinson, Jennifer; DeWire, Mariko; Kranenburg, Tanya A.; Gillespie, Yancey; Allen, Jeffrey C.; Merchant, Thomas; Boop, Fredrick A.; Sanford, Robert. A.; Gajjar, Amar; Ellison, David W.; Taylor, Michael D.; Grundy, Richard G.; Gilbertson, Richard J.

2010-01-01

Understanding the biology that underlies histologically similar but molecularly distinct subgroups of cancer has proven difficult since their defining genetic alterations are often numerous, and the cellular origins of most cancers remain unknown1–3. We sought to decipher this heterogeneity by integrating matched genetic alterations and candidate cells of origin to generate accurate disease models. First, we identified subgroups of human ependymoma, a form of neural tumor that arises throughout the central nervous system (CNS). Subgroup specific alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. To select cellular compartments most likely to give rise to subgroups of ependymoma, we matched the transcriptomes of human tumors to those of mouse neural stem cells (NSCs), isolated from different regions of the CNS at different developmental stages, with an intact or deleted Ink4a/Arf locus. The transcriptome of human cerebral ependymomas with amplified EPHB2 and deleted INK4A/ARF matched only that of embryonic cerebral Ink4a/Arf−/− NSCs. Remarkably, activation of Ephb2 signaling in these, but not other NSCs, generated the first mouse model of ependymoma, which is highly penetrant and accurately models the histology and transcriptome of one subgroup of human cerebral tumor. Further comparative analysis of matched mouse and human tumors revealed selective deregulation in the expression and copy number of genes that control synaptogenesis, pinpointing disruption of this pathway as a critical event in the production of this ependymoma subgroup. Our data demonstrate the power of cross-species genomics to meticulously match subgroup specific driver mutations with cellular compartments to model and interrogate cancer subgroups. PMID:20639864

Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports.

PubMed

Pène, Frédéric; Aubron, Cécile; Azoulay, Elie; Blot, François; Thiéry, Guillaume; Raynard, Bruno; Schlemmer, Benoît; Nitenberg, Gérard; Buzyn, Agnès; Arnaud, Philippe; Socié, Gérard; Mira, Jean-Paul

2006-02-01

Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU). This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003. Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (< or = 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome. Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.

Molecular Cloning and Expression Analysis of Eight PgWRKY Genes in Panax ginseng Responsive to Salt and Hormones.

PubMed

Xiu, Hao; Nuruzzaman, Mohammed; Guo, Xiangqian; Cao, Hongzhe; Huang, Jingjia; Chen, Xianghui; Wu, Kunlu; Zhang, Ru; Huang, Yuzhao; Luo, Junli; Luo, Zhiyong

2016-03-04

Despite the importance of WRKY genes in plant physiological processes, little is known about their roles in Panax ginseng C.A. Meyer. Forty-eight unigenes on this species were previously reported as WRKY transcripts using the next-generation sequencing (NGS) technology. Subsequently, one gene that encodes PgWRKY1 protein belonging to subgroup II-d was cloned and functionally characterized. In this study, eight WRKY genes from the NGS-based transcriptome sequencing dataset designated as PgWRKY2-9 have been cloned and characterized. The genes encoding WRKY proteins were assigned to WRKY Group II (one subgroup II-c, four subgroup II-d, and three subgroup II-e) based on phylogenetic analysis. The cDNAs of the cloned PgWRKYs encode putative proteins ranging from 194 to 358 amino acid residues, each of which includes one WRKYGQK sequence motif and one C₂H₂-type zinc-finger motif. Quantitative real-time PCR (qRT-PCR) analysis demonstrated that the eight analyzed PgWRKY genes were expressed at different levels in various organs including leaves, roots, adventitious roots, stems, and seeds. Importantly, the transcription responses of these PgWRKYs to methyl jasmonate (MeJA) showed that PgWRKY2, PgWRKY3, PgWRKY4, PgWRKY5, PgWRKY6, and PgWRKY7 were downregulated by MeJA treatment, while PgWRKY8 and PgWRKY9 were upregulated to varying degrees. Moreover, the PgWRKY genes increased or decreased by salicylic acid (SA), abscisic acid (ABA), and NaCl treatments. The results suggest that the PgWRKYs may be multiple stress-inducible genes responding to both salt and hormones.

The Biological Activities of Sesterterpenoid-Type Ophiobolins.

PubMed

Tian, Wei; Deng, Zixin; Hong, Kui

2017-07-18

Ophiobolins (Ophs) are a group of tricarbocyclic sesterterpenoids whose structures contain a tricyclic 5-8-5 carbotricyclic skeleton. Thus far, 49 natural Ophs have been reported and assigned into A-W subgroups in order of discovery. While these sesterterpenoids were first characterized as highly effective phytotoxins, later investigations demonstrated that they display a broad spectrum of biological and pharmacological characteristics such as phytotoxic, antimicrobial, nematocidal, cytotoxic, anti-influenza and inflammation-promoting activities. These bioactive molecules are promising drug candidates due to the developments of their anti-proliferative activities against a vast number of cancer cell lines, multidrug resistance (MDR) cells and cancer stem cells (CSCs). Despite numerous studies on the biological functions of Ophs, their pharmacological mechanism still requires further research. This review summarizes the chemical structures, sources, and biological activities of the oph family and discusses its mechanisms and structure-activity relationship to lay the foundation for the future developments and applications of these promising molecules.

Clinical and biological significance of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma.

PubMed

Lu, Chunlai; Xu, Fengkai; Gu, Jie; Yuan, Yunfeng; Zhao, Guangyin; Yu, Xiaofang; Ge, Di

2015-08-01

Esophageal squamous cell carcinoma is one of the most frequent malignant tumors. Cancer stem cells are considered to be responsible for tumor growth, metastasis, and recurrence. Cluster of differentiation 133 (CD133) and C-X-C chemokine receptor type 4 (CXCR4) are frequently applied markers for the identification and isolation of cancer stem cells. However, few studies have investigated the coexpression of CD133 and CXCR4 in esophageal squamous cell carcinoma. This study aims to explore the clinical and biological role of stem-like CD133(+)CXCR4(+) cells in esophageal squamous cell carcinoma. Immunohistochemical staining was performed to detect the expression of CD133 and CXCR4 in esophageal squamous cell carcinoma tissues of patients. Flow cytometry and fluorescence-activated cell sorting were applied to analyze and isolate each subgroup in esophageal squamous cell carcinoma cell line TE-1. The characteristic differences between each subgroup were assayed in vitro. The association between CD133/CXCR4 expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Among 154 patient tissues, concomitant high CD133-CXCR4 expression accounts for 20.78% (32/154). In vitro, CXCR4(+) cells (CD133(+)CXCR4(+) and CD133(-)CXCR4(+)) showed high invasive potential and CD133(+)CXCR4(+) cells showed high proliferative capacity. Clinically, patients with concomitant high CD133-CXCR4 expression had decreased disease-free survival and overall survival (P < .01). Esophageal squamous cell carcinoma cells coexpressing CD133 and CXCR4 possess the characteristics of cancer stem cells. The concomitant high CD133-CXCR4 expression might be a novel marker for predicting the poor prognosis of patients with esophageal squamous cell carcinoma, and CD133 and CXCR4 may serve as potential therapeutic targets. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Successful collection of peripheral blood stem cells upon VIDE chemomobilization in sarcoma patients.

PubMed

Kriegsmann, Katharina; Heilig, Christoph; Cremer, Martin; Novotny, Philipp; Kriegsmann, Mark; Bruckner, Thomas; Müller-Tidow, Carsten; Egerer, Gerlinde; Wuchter, Patrick

2017-11-01

In patients with Ewing sarcoma and some distinct subgroups of soft tissue sarcoma (STS), a quantitatively sufficient autologous peripheral blood stem cell (PBSC) collection for stem cell support might facilitate treatment continuation, dose-intensification, and high-dose chemotherapy. Here, we provide a detailed evaluation of PBSC collection upon vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) chemomobilization. Mobilization and collection parameters of 42 sarcoma patients (Ewing sarcoma n = 35, other STS n = 7) were analyzed retrospectively. Data were evaluated with regard to the number of previous VIDE therapy cycles. All patients reached the collection goal of ≥2.0 × 10 6 CD34 + cells/kg body weight (bw) upon VIDE/G-CSF mobilization, in the majority of cases with one single leukapheresis (LP) session (n = 29, 69%). No significant differences were identified with regard to mobilization and collection variables or the number of previous induction VIDE therapy cycles. However, upon 5 cycles of VIDE, we found the highest relative proportion of patients who required two or three LP sessions. Our data demonstrate the feasibility of successful PBSC collection upon VIDE chemomobilization even after up to five cycles of induction therapy, while at the same time the increasing risk of bone marrow exhaustion with every consecutive cycle is outlined. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the Adenocarcinoma-Associated Gene AGR2 and the Intestinal Stem Cell Marker LGR5 as Biomarkers in Colorectal Cancer

PubMed Central

Valladares-Ayerbes, Manuel; Blanco-Calvo, Moisés; Reboredo, Margarita; Lorenzo-Patiño, María J.; Iglesias-Díaz, Pilar; Haz, Mar; Díaz-Prado, Silvia; Medina, Vanessa; Santamarina, Isabel; Pértega, Sonia; Figueroa, Angélica; Antón-Aparicio, Luis M.

2012-01-01

We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3–pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes. PMID:22605983

Laser versus traditional techniques in cerebral and brain stem gliomas

NASA Astrophysics Data System (ADS)

Lombard, Gian F.

1996-01-01

In medical literature no significant studies have been published on the effectiveness of laser compared with traditional procedures in two series of cerebral gliomas; for this reason we have studied 220 tumors (200 supratentorial -- 20 brain stem gliomas), 110 operated upon with laser, 100 with conventional techniques. Four surgical protocols have been carried out: (1) traditional techniques; (2) carbon dioxide laser free hand; (3) carbon dioxide laser plus microscope; (4) multiple laser sources plus microscope plus neurosector plus CUSA. Two laser sources have been used alone or in combination (carbon dioxide -- Nd:YAG 1.06 or 1.32). Patients have been monitored for Karnofsky scale before and after operation, 12 - 24 and 36 months later; and for survival rate. Tumors were classified by histological examination, dimensions, vascularization, topography (critical or non critical areas). Results for supratentorial gliomas: survival time is the same in both series (laser and traditional). Post- op morbidity is significantly improved in the laser group (high grade sub-group); long term follow-up shows an improvement of quality of life until 36 months in the low grade sub-group.

Perceptions of Depression and Access to Mental Health Care Among Latino Immigrants: Looking Beyond One Size Fits All.

PubMed

Martinez Tyson, Dinorah; Arriola, Nora B; Corvin, Jaime

2016-07-01

Compared with non-Latino Whites, Latino immigrants have a lower prevalence of depression. However, they are also less likely to seek professional mental health services. Our objective was to compare and contrast perceptions of depression and access to mental health care among four of the largest Latino immigrant subgroups in Florida (Puerto Rican, Cuban, Mexican, and Colombian). We conducted a total of 120 interviews (30 men and women from each subgroup). Thematic analysis of qualitative data revealed that participants across the four groups were aware of the signs and symptoms of depression and had similar perceptions of depression. However, notable differences by subgroup emerged with regard to perceptions of access to mental health care. We suggest that the variation stems from differences in life experiences and the immigration context. Understanding the variances and nuances of Latino immigrants' cultural construction of depression and immigration experience will enable practitioners to better serve this community. © The Author(s) 2015.

40 CFR 180.582 - Pyraclostrobin; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., cucurbit, group 9 0.5 Vegetable, foliage of legume, except soybean, subgroup 7A 25.0 Vegetable, fruiting..., except sugar beet 16.0 Vegetable, legume, edible podded, subgroup 6A 0.5 Vegetable, root, except sugar beet, subgroup 1B 0.4 Vegetable, tuberous and corm, subgroup 1C 0.04 Vegetables, foliage of legume...

ICGC PedBrain: Dissecting the genomic complexity underlying medulloblastoma

PubMed Central

Jones, David TW; Jäger, Natalie; Kool, Marcel; Zichner, Thomas; Hutter, Barbara; Sultan, Marc; Cho, Yoon-Jae; Pugh, Trevor J; Hovestadt, Volker; Stütz, Adrian M; Rausch, Tobias; Warnatz, Hans-Jörg; Ryzhova, Marina; Bender, Sebastian; Sturm, Dominik; Pleier, Sabrina; Cin, Huriye; Pfaff, Elke; Sieber, Laura; Wittmann, Andrea; Remke, Marc; Witt, Hendrik; Hutter, Sonja; Tzaridis, Theophilos; Weischenfeldt, Joachim; Raeder, Benjamin; Avci, Meryem; Amstislavskiy, Vyacheslav; Zapatka, Marc; Weber, Ursula D; Wang, Qi; Lasitschka, Bärbel; Bartholomae, Cynthia C; Schmidt, Manfred; von Kalle, Christof; Ast, Volker; Lawerenz, Chris; Eils, Jürgen; Kabbe, Rolf; Benes, Vladimir; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Shih, David; Betts, Matthew J; Russell, Robert B; Coco, Simona; Tonini, Gian Paolo; Schüller, Ulrich; Hans, Volkmar; Graf, Norbert; Kim, Yoo-Jin; Monoranu, Camelia; Roggendorf, Wolfgang; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Maass, Eberhard; Rössler, Jochen; Ebinger, Martin; Schuhmann, Martin U; Frühwald, Michael C; Hasselblatt, Martin; Jabado, Nada; Rutkowski, Stefan; von Bueren, André O; Williamson, Dan; Clifford, Steven C; McCabe, Martin G; Collins, V. Peter; Wolf, Stephan; Wiemann, Stefan; Lehrach, Hans; Brors, Benedikt; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Northcott, Paul A; Taylor, Michael D; Meyerson, Matthew; Pomeroy, Scott L; Yaspo, Marie-Laure; Korbel, Jan O; Korshunov, Andrey; Eils, Roland; Pfister, Stefan M; Lichter, Peter

2013-01-01

Summary Medulloblastoma is an aggressively-growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and displays tremendous biological and clinical heterogeneity1. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently discriminated2,3. WNT tumours, displaying activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens4. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis2. Group 3 & 4 tumours are molecularly less well-characterised, and also present the greatest clinical challenges2,3,5. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs. Tetraploidy was identified as a frequent early event in Group 3 & 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA-sequencing confirmed these alterations, and revealed the expression of the first medulloblastoma fusion genes. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 & 4 patients. PMID:22832583

Use of Bone Marrow-Derived Mesenchymal Stem Cells in Improving Thioacetamide Induced Liver Fibrosis in Rats

NASA Astrophysics Data System (ADS)

Mansour, Fatma A. A.; Shaheed, Iman; Hassan, Nabiha R. A.

Liver fibrosis, is one of big problems usually ends with cirrhosis which considered a life threatening disease as the only way of treatment is the liver transplantation, this study aimed to find a new way for fibrosis treatment by the use of bone marrow isolated Mesenchymal stem cells (MSCs). Thioacetamide (TAA) was used for fibrosis induction in male Sprague Dawely (SD) rats which divided into two random groups: group infused with TAA for fibrosis induction and group as control negative group. MSCs were isolated from bone marrow of twenty five (4-5) weeks male SD rats, and labeled with fluorescent material (PKH26) to confirm the homing of cells. After fibrosis induction, rats were divided into four subgroups to study the effect of MSCs injection in fibrosis treatment. After 4 weeks from MSCs administration, all rats were sacrificed. Liver tissue were collected for histopathological and immunohistopathological studies. In comparison with control groups, the treated groups with MSCs showed improvement in the amount of deposited collagen which decreased compared to control positive group. So MSCs can be used to replace liver transplantation in the treatment of fibrosis.

Osteomacs interact with megakaryocytes and osteoblasts to regulate murine hematopoietic stem cell function.

PubMed

Mohamad, Safa F; Xu, Linlin; Ghosh, Joydeep; Childress, Paul J; Abeysekera, Irushi; Himes, Evan R; Wu, Hao; Alvarez, Marta B; Davis, Korbin M; Aguilar-Perez, Alexandra; Hong, Jung Min; Bruzzaniti, Angela; Kacena, Melissa A; Srour, Edward F

2017-12-12

Networking between hematopoietic stem cells (HSCs) and cells of the hematopoietic niche is critical for stem cell function and maintenance of the stem cell pool. We characterized calvariae-resident osteomacs (OMs) and their interaction with megakaryocytes to sustain HSC function and identified distinguishing properties between OMs and bone marrow (BM)-derived macrophages. OMs, identified as CD45 + F4/80 + cells, were easily detectable (3%-5%) in neonatal calvarial cells. Coculture of neonatal calvarial cells with megakaryocytes for 7 days increased OM three- to sixfold, demonstrating that megakaryocytes regulate OM proliferation. OMs were required for the hematopoiesis-enhancing activity of osteoblasts, and this activity was augmented by megakaryocytes. Serial transplantation demonstrated that HSC repopulating potential was best maintained by in vitro cultures containing osteoblasts, OMs, and megakaryocytes. With or without megakaryocytes, BM-derived macrophages were unable to functionally substitute for neonatal calvarial cell-associated OMs. In addition, OMs differentiated into multinucleated, tartrate resistant acid phosphatase-positive osteoclasts capable of bone resorption. Nine-color flow cytometric analysis revealed that although BM-derived macrophages and OMs share many cell surface phenotypic similarities (CD45, F4/80, CD68, CD11b, Mac2, and Gr-1), only a subgroup of OMs coexpressed M-CSFR and CD166, thus providing a unique profile for OMs. CD169 was expressed by both OMs and BM-derived macrophages and therefore was not a distinguishing marker between these 2 cell types. These results demonstrate that OMs support HSC function and illustrate that megakaryocytes significantly augment the synergistic activity of osteoblasts and OMs. Furthermore, this report establishes for the first time that the crosstalk between OMs, osteoblasts, and megakaryocytes is a novel network supporting HSC function.

Transcriptomes define distinct subgroups of salivary gland adenoid cystic carcinoma with different driver mutations and outcomes

PubMed Central

Frerich, Candace A.; Brayer, Kathryn J.; Painter, Brandon M.; Kang, Huining; Mitani, Yoshitsugu; El-Naggar, Adel K.; Ness, Scott A.

2018-01-01

The relative rarity of salivary gland adenoid cystic carcinoma (ACC) and its slow growing yet aggressive nature has complicated the development of molecular markers for patient stratification. To analyze molecular differences linked to the protracted disease course of ACC and metastases that form 5 or more years after diagnosis, detailed RNA-sequencing (RNA-seq) analysis was performed on 68 ACC tumor samples, starting with archived, formalin-fixed paraffin-embedded (FFPE) samples up to 25 years old, so that clinical outcomes were available. A statistical peak-finding approach was used to classify the tumors that expressed MYB or MYBL1, which had overlapping gene expression signatures, from a group that expressed neither oncogene and displayed a unique phenotype. Expression of MYB or MYBL1 was closely correlated to the expression of the SOX4 and EN1 genes, suggesting that they are direct targets of Myb proteins in ACC tumors. Unsupervised hierarchical clustering identified a subgroup of approximately 20% of patients with exceptionally poor overall survival (median less than 30 months) and a unique gene expression signature resembling embryonic stem cells. The results provide a strategy for stratifying ACC patients and identifying the high-risk, poor-outcome group that are candidates for personalized therapies. PMID:29484115

Medulloblastoma stem cells: Promising targets in medulloblastoma therapy.

PubMed

Huang, Guo-Hao; Xu, Qing-Fu; Cui, You-Hong; Li, Ningning; Bian, Xiu-Wu; Lv, Sheng-Qing

2016-05-01

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Despite great improvements in the therapeutic regimen, relapse and leptomeningeal dissemination still pose great challenges to the long-term survival of MB patients. Developing more effective strategies has become extremely urgent. In recent years, a number of malignancies, including MB, have been found to contain a subpopulation of cancer cells known as cancer stem cells (CSCs), or tumor initiating/propagating cells. The CSCs are thought to be largely responsible for tumor initiation, maintenance, dissemination, and relapse; therefore, their pivotal roles have revealed them to be promising targets in MB therapy. Our growing understanding of the major medulloblastoma molecular subgroups and the derivation of some of these groups from specific stem or progenitor cells adds additional layers to the CSC knowledge base. Herein we review the current knowledge of MB stem cells, highlight the molecular mechanisms relating to MB relapse and leptomeningeal dissemination, and incorporate these with the need to develop more effective and accurate therapies for MB patients. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Leukemia inhibitory factor in the neuroimmune communication pathways in allergic asthma.

PubMed

Lin, Min-Juan; Lao, Xue-Jun; Liu, Sheng-Ming; Xu, Zhen-Hua; Zou, Wei-Feng

2014-03-20

In the pathogenesis of asthma, central sensitization is suggested to be an important neural mechanism, and neurotrophins and cytokines are likely to be the major mediators in the neuroimmune communication pathways of asthma. However, their impact on the central nervous system in allergic asthma remains unclear. We hypothesize that central neurogenic inflammation develops in the pathogenesis of allergic asthma, and nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are important mediators in its development. An asthma model of rats was established by sensitization and challenged with ovalbumin (OVA). For further confirmation of the role of LIF in neurogenic inflammation, a subgroup was pretreated with intraperitoneally (i.p.) LIF antibody before OVA challenge. The levels of LIF and NGF were measured with reverse transcription and polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry stain in lung tissue, airway-specific dorsal root ganglia (DRG, C7-T5) and brain stem of asthmatic rats, anti-LIF pretreated rats and controls. A significantly increased number of LIF- and NGF-immunoreactive cells were detected in lung tissue, DRG and the brain stem of asthmatic rats. In the asthma group a significantly increase level of mRNA encoding LIF and NGF in lung tissue was detected, but not in DRG and the brain stem. Pretreatment with LIF antibody decreased the level of LIF and NGF in all tissues. LIF is an important mediator in the crosstalk between nerve and immune systems. Our study demonstrate that the increased level of LIF and NGF in DRG and brain stem may be not based on result from de novo synthesis, but rather on result from retrograde nerve transport or passage across the blood-brain-barrier. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

78 FR 14461 - Fenpyrazamine; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... berry subgroup 13-07G at 3.0 ppm (PP 1F7841); pistachio at 0.02 ppm; Caneberry subgroup 13-07A at 7.0..., Bushberry Subgroup 13-07B, Caneberry Subgroup 13-07A, Ginseng, and Pistachio'' in docket ID number EPA-HQ..., hulls at 1.5 ppm; pistachio at 0.02 ppm; lettuce, head at 1.5 ppm; lettuce, leaf at 2 ppm; Caneberry...

[Establishment of a new human glioma cell line and analysis of its biological characteristics].

PubMed

Chen, Guilin; Li, Yanyan; Xie, Xueshun; Chen, Jinming; Wu, Tingfeng; Li, Xuetao; Wang, Hangzhou; Zhou, Youxin; Du, Ziwei

2015-02-01

To establish a new glioma cell line and analyze its biological characteristics, and to provide a useful cellular tool with new features for cancer research. Glioma tissue was taken from surgical specimen clinical of a clinical patient. Primary culture was carried out, and a cell line (SHG139) was established after 10 passages. Immunofluorescence staining was performed to detect the expression of proteins, and cell proliferation and cycle were detected by flow cytometry method (FCM). The biological characteristics of SHG139 cells were detected by chromosome karyotype analysis. SHG139s glioma cells derived from SHG139 glioma cell line were cultured with neural stem cell medium. Then stem cell markers were determined. SHG139s cells were induced with serum-containing medium, and their expression of A2B5, GFAP, β-III tubulin, and GalC was detected. Intracranial xenograft tumor of both SHG139 glioma cells and SHG139s glioma stem cell spheres was generated in rats. The expressions of A2B5, GalC, GFAP, S-100, and vimentin in the 20 and 60 passages of SHG139 cells were positive, consistent with the immunohistochemical results and pathological features. SHG139 cells proliferated significantly within 24 h after subculture, and their total number of chromosomes was 68 and mostly multiploid. They were positive for A2B5 (84.12±9.96)%, nestin (73.86±5.01)%, and NG2 (73.37±2.09)%. SHG139s cells were induced, and the ratio of positive cells of GFAP, β-III tubulin and GalC was (92.89±2.24)%, (64.85±4.09)% and (33.57±4.14)%, respectively. SHG139 is an astroglioma cell line, from which SHG139s cells can be successfully obtained by culture with NSCM. SHG139s cells are of A2B5(+)/CD133(-) GSCs subgroup cells, with potentials of self-renewal and multi-directional differentiation. Compared with the intracranial SHG139 xenograft tumor, the intracranial SHG139s xenograft tumor is more malignant and aggressive.

Influence of low-level laser on bone remodeling during induced tooth movement in rats.

PubMed

Cossetin, Eliziane; Janson, Guilherme; de Carvalho, Maria Goretti F; de Carvalho, Rejane A; Henriques, José Fernando Castanha; Garib, Daniela

2013-11-01

To analyze the effect of low-level laser on bone remodeling during induced tooth movement in rats. A diode laser (808 nm, 100 mW, 54 J on an area of 0.0028 cm(2)) was used. The application was continuous, punctual, and with contact. Forty-two 70-day-old Wistar rats had the maxillary left first molar moved using a force level of 25 g. In two experimental subgroups the movement was performed over 7 days and in three subgroups the movement occurred over 14 days. In the 7-day movement subgroups, one subgroup received laser irradiation on day 1 only; the other subgroup received laser irradiation on days 1, 3, and 5. In the 14-day movement subgroups, one subgroup received laser irradiation on day 1 only; the second on days 1, 3, and 5; and the third on days 1, 3, 5, 7, 9, 11, and 13. The control group was also divided into two subgroups, and movement occurred over two different periods of treatment (7 days and 14 days) without laser application; these were used as controls for the respective experimental subgroups. Inter-subgroup comparison was performed with Kruskal-Wallis, followed by Mann-Whitney and analysis of variance, followed by Tukey tests within the 7- and 14-day subgroups. The subgroup with three laser applications showed significantly greater osteoclastic activity and bone resorption than the other subgroups in the 7-day movement subgroups. Low-level laser application significantly increased the osteoclastic but not the osteoblastic activity during the initial phases of tooth movement. In addition, the osteoclastic activity was dose-dependent.

Chemical Composition and Allelopathic Potential of Essential Oils from Tipuana tipu (Benth.) Kuntze Cultivated in Tunisia.

PubMed

El Ayeb-Zakhama, Asma; Sakka-Rouis, Lamia; Bergaoui, Afifa; Flamini, Guido; Jannet, Hichem Ben; Harzallah-Skhiri, Fethia

2016-03-01

In Tunisia, Tipuana tipu (Benth.) Kuntze is an exotic tree, which was introduced many years ago and planted as ornamental street, garden, and park tree. The present work reported, for the first time, the chemical composition and evaluates the allelopathic effect of the hydrodistilled essential oils of the different parts of this tree, viz., roots, stems, leaves, flowers, and pods gathered in the area of Sousse, a coastal region, in the East of Tunisia. In total, 86 compounds representing 89.9 - 94.9% of the whole oil composition, were identified in these oils by GC-FID and GC/MS analyses. The root essential oil was clearly distinguished for its high content in sesquiterpene hydrocarbons (β-caryophyllene, 1 (44); 24.1% and germacrene D, 2 (53); 20.0%), while those obtained from pods, leaves, stems, and flowers were dominated by non-terpene hydrocarbons. The most important ones were n-tetradecane (41, 16.3%, pod oil), 1,7-dimethylnaphthalene (43, 15.6%, leaf oil), and n-octadecane (77, 13.1%, stem oil). The leaf oil was rich in the apocarotene (E)-β-ionone (4 (54); 33.8%), and the oil obtained from flowers was characterized by hexahydrofarnesylacetone (5 (81); 19.9%) and methyl hexadecanoate (83, 10.2%). Principal component and hierarchical cluster analyses separated the five essential oils into three groups and two subgroups, each characterized by the major oil constituents. Contact tests showed that the germination of lettuce seeds was totally inhibited by the root essential oil tested at 1 mg/ml. The inhibitory effect on the shoot and root elongation varied from -1.6% to -32.4%, and from -2.5% to -64.4%, respectively. © 2016 Verlag Helvetica Chimica Acta AG, Zürich.

Altered states of consciousness in epilepsy: a DTI study of the brain.

PubMed

Xie, Fangfang; Xing, Wu; Wang, Xiaoyi; Liao, Weihua; Shi, Wei

2017-08-01

A disturbance in the level of consciousness is a classical clinical sign of several seizure types. Recent studies have shown that altered states of consciousness in seizures are associated with structural and functional changes of several brain regions. Prominent among these are the thalamus, the brain stem and the default mode network, which is part of the consciousness system. Our study used diffusion tensor imaging (DTI) to evaluate these brain regions in patients with three different types of epilepsies that are associated with altered consciousness: complex partial seizures (CPS), primary generalized tonic-clonic seizures (PGTCS) or secondary generalized tonic-clonic seizures (SGTCS). Additionally, this study further explores the probable mechanisms underlying impairment of consciousness in seizures. Conventional MRI and DTI scanning were performed in 51 patients with epilepsy and 51 healthy volunteers. The epilepsy group was in turn subdivided into three subgroups: CPS, PGTCS or SGTCS. Each subgroup comprised 17 patients. Each subject involved in the study underwent a DTI evaluation of the brain to measure the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of nine regions of interest: the postero-superior portion of midbrain, the bilateral dorsal thalamus, the bilateral precuneus/posterior cingulate, the bilateral medial pre-frontal gyri and the bilateral supramarginalgyri. The statistical significance of the measured ADC and FA values between the experimental and control groups was analysed using the paired t-test, and one-way analysis of variance was performed for a comparative analysis between the three subgroups. Statistically significantly higher ADC values ( p < 0.01) were observed in the bilateral dorsal thalamus and postero-superior aspect of the midbrain in the three patient subgroups than in the control group. There were no significant changes in the ADC values ( p > 0.05) in the bilateral precuneus/posterior cingulate, bilateral medial pre-frontal gyri or bilateral supramarginalgyri in the experimental group. Among the three patient subgroups and the ADC values of corresponding brain regions, there were no statistically significant changes. Statistically significantly lower FA values ( p < 0.05) were observed in the bilateral dorsal thalamus of the patients in the three subgroups than in the control group. Significantly lowered FA values from the postero-superior aspect of the mid brain ( p < 0.01) were observed in patients with PGTCS compared with the control group. There were no significant changes in the FA values ( p > 0.05) from the bilateral precuneus/posterior cingulate, bilateral medial frontal gyri or bilateral supramarginalgyri in the experimental group. Among the three patient subgroups and the FA values of the corresponding brain regions, there were no statistically significant changes. In epileptic patients with CPS, PGTCS or SGTCS, there seems to be a long-lasting neuronal dysfunction of the bilateral dorsal thalamus and postero-superior aspect of the midbrain. The thalamus and upper brain stem are likely to play a key role in epileptic patients with impaired consciousness.

PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients

PubMed Central

Ussowicz, Marek; Rybka, Blanka; Wendycz-Domalewska, Danuta; Ryczan, Renata; Gorczyńska, Ewa; Kałwak, Krzysztof; Woźniak, Mieczysław

2010-01-01

After stem cell transplantation, human patients are prone to life-threatening opportunistic infections with a plethora of microorganisms. We report a retrospective study on 116 patients (98 children, 18 adults) who were transplanted in a pediatric bone marrow transplantation unit. Blood, urine and stool samples were collected and monitored for adenovirus (AdV) DNA using polymerase chain reaction (PCR) and real-time PCR (RT-PCR) on a regular basis. AdV DNA was detected in 52 (44.8%) patients, with mortality reaching 19% in this subgroup. Variables associated with adenovirus infection were transplantations from matched unrelated donors and older age of the recipient. An increased seasonal occurrence of adenoviral infections was observed in autumn and winter. Analysis of immune reconstitution showed a higher incidence of AdV infections during periods of low T-lymphocyte count. This study also showed a strong interaction between co-infections of AdV and BK polyomavirus in patients undergoing hematopoietic stem cell transplantations. PMID:20848295

Multiparametric Phenotypic Screening System for Profiling Bioactive Compounds Using Human Fetal Hippocampal Neural Stem/Progenitor Cells.

PubMed

Tabata, Yoshikuni; Murai, Norio; Sasaki, Takeo; Taniguchi, Sachie; Suzuki, Shuichi; Yamazaki, Kazuto; Ito, Masashi

2015-10-01

Stem cell research has been progressing rapidly, contributing to regenerative biology and regenerative medicine. In this field, small-molecule compounds affecting stem cell proliferation/differentiation have been explored to understand stem cell biology and support regenerative medicine. In this study, we established a multiparametric screening system to detect bioactive compounds affecting the cell fate of human neural stem/progenitor cells (NSCs/NPCs), using human fetal hippocampal NSCs/NPCs, HIP-009 cells. We examined effects of 410 compounds, which were collected based on mechanisms of action (MOAs) and chemotypes, on HIP-009's cell fate (self-renewal, neuronal and astrocytic differentiation) and morphology by automated multiparametric assays and profiled induced cellular phenotypes. We found that this screening classified compounds with the same MOAs into subgroups according to additional pharmacological effects (e.g., mammalian target of rapamycin complex 1 [mTORC1] inhibitors and mTORC1/mTORC2 dual inhibitors among mTOR inhibitors). Moreover, it identified compounds that have off-target effects under matrix analyses of MOAs and structure similarities (e.g., neurotropic effects of amitriptyline among tri- and tetracyclic compounds). Therefore, this automated, medium-throughput and multiparametric screening system is useful for finding compounds that affect the cell fate of human NSCs/NPCs for supporting regenerative medicine and to fingerprint compounds based on human stem cells' multipotency, leading to understanding of stem cell biology. © 2015 Society for Laboratory Automation and Screening.

78 FR 32246 - Pesticide Products; Registration Applications for New Active Ingredients

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-29

..., crop subgroup 5A; leafy Brassica, greens, crop sub-group 5B; turnip, greens; edible-podded legume..., except soybean, crop subgroups 6C; foliage of legume vegetables, including soybeans, crop group 7, forage green vines; foliage of legume vegetables, including soybean, crop group 7, hay; soybean, seed; fruiting...

Etiological Subgroups of Small-for-Gestational-Age: Differential Neurodevelopmental Outcomes

PubMed Central

Li, Xiuhong; Eiden, Rina D.; Epstein, Leonard H.; Shenassa, Edmond D.; Xie, Chuanbo; Wen, Xiaozhong

2016-01-01

Objectives It remains unclear why substantial variations in neurodevelopmental outcomes exist within small-for-gestational-age (SGA) children. We prospectively compared 5-y neurodevelopmental outcomes across SGA etiological subgroups. Methods Children born SGA (N = 1050) from U.S. Early Childhood Longitudinal Study-Birth Cohort (2001–2007) was divided into etiological subgroups by each of 7 well-established prenatal risk factors. We fit linear regression models to compare 5-y reading, math, gross motor and fine motor scores across SGA subgroups, adjusting for socio-demographic confounders. Results Compared to singleton SGA subgroup, multiple-birth SGA subgroup had lower mean reading (adjusted mean difference, -4.08 [95% confidence interval, -6.10, -2.06]) and math (-2.22 [-3.61, -0.84]) scores. These disadvantages in reading and math existed only among multiple-birth SGA subgroup without ovulation stimulation (reading, -4.50 [-6.64, -2.36]; math, -2.91 [-4.37, -1.44]), but not among those with ovulation stimulation (reading, -2.33 [-6.24, 1.57]; math 0.63 [-1.86, 3.12]). Compared to singleton SGA subgroup without maternal smoking and inadequate gestational weight gain, singleton SGA subgroup with co-occurrence of maternal smoking and inadequate gestational weight gain (GWG) had lower mean reading (-4.81 [-8.50, -1.12]) and math (-2.95 [-5.51, -0.38]) scores. These differences were not mediated by Apgar score. Conclusions Multiple-birth SGA subgroups (vs. singleton SGA) or singleton SGA subgroup with co-occurrence of smoking and inadequate GWG (vs. singleton SGA subgroup without maternal smoking and inadequate gestational weight gain) have poorer cognitive development up to 5 y. PMID:27501456

Intra-Tumour Signalling Entropy Determines Clinical Outcome in Breast and Lung Cancer

PubMed Central

Banerji, Christopher R. S.; Severini, Simone; Caldas, Carlos; Teschendorff, Andrew E.

2015-01-01

The cancer stem cell hypothesis, that a small population of tumour cells are responsible for tumorigenesis and cancer progression, is becoming widely accepted and recent evidence has suggested a prognostic and predictive role for such cells. Intra-tumour heterogeneity, the diversity of the cancer cell population within the tumour of an individual patient, is related to cancer stem cells and is also considered a potential prognostic indicator in oncology. The measurement of cancer stem cell abundance and intra-tumour heterogeneity in a clinically relevant manner however, currently presents a challenge. Here we propose signalling entropy, a measure of signalling pathway promiscuity derived from a sample’s genome-wide gene expression profile, as an estimate of the stemness of a tumour sample. By considering over 500 mixtures of diverse cellular expression profiles, we reveal that signalling entropy also associates with intra-tumour heterogeneity. By analysing 3668 breast cancer and 1692 lung adenocarcinoma samples, we further demonstrate that signalling entropy correlates negatively with survival, outperforming leading clinical gene expression based prognostic tools. Signalling entropy is found to be a general prognostic measure, valid in different breast cancer clinical subgroups, as well as within stage I lung adenocarcinoma. We find that its prognostic power is driven by genes involved in cancer stem cells and treatment resistance. In summary, by approximating both stemness and intra-tumour heterogeneity, signalling entropy provides a powerful prognostic measure across different epithelial cancers. PMID:25793737

40 CFR 180.476 - Triflumizole; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., subgroup 5B 40 Canistel 2.5 Cherry, sweet 1.5 Cherry, tart 1.5 Cilantro, leaves 35 Grape 2.5 Grape, dried... greens subgroup 4A, except spinach 35 Mango 2.5 Papaya 2.5 Pear 0.5 Pineapple 4.0 Sapodilla 2.5 Sapote...

40 CFR 180.476 - Triflumizole; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., subgroup 5B 40 Canistel 2.5 Cherry, sweet 1.5 Cherry, tart 1.5 Cilantro, leaves 35 Grape 2.5 Grape, dried... greens subgroup 4A, except spinach 35 Mango 2.5 Papaya 2.5 Pear 0.5 Pineapple 4.0 Sapodilla 2.5 Sapote...

40 CFR 180.476 - Triflumizole; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., subgroup 5B 40 Canistel 2.5 Cherry, sweet 1.5 Cherry, tart 1.5 Cilantro, leaves 35 Grape 2.5 Grape, dried... greens subgroup 4A, except spinach 35 Mango 2.5 Papaya 2.5 Pear 0.5 Pineapple 4.0 Sapodilla 2.5 Sapote...

40 CFR 180.476 - Triflumizole; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., subgroup 5B 40 Canistel 2.5 Cherry, sweet 1.5 Cherry, tart 1.5 Cilantro, leaves 35 Grape 2.5 Grape, dried... greens subgroup 4A, except spinach 35 Mango 2.5 Papaya 2.5 Pear 0.5 Pineapple 4.0 Sapodilla 2.5 Sapote...

CD271+ cells are diagnostic and prognostic and exhibit elevated MAPK activity in SHH medulloblastoma.

PubMed

Liang, Lisa; Morrison, Ludivine Coudière; Tatari, Nazanin; Stromecki, Margaret; Fresnoza, Agnes; Porter, Christopher J; Del Bigio, Marc R; Hawkins, Cynthia; Chan, Jennifer A; Ryken, Timothy C; Taylor, Michael D; Ramaswamy, Vijay; Werbowetski-Ogilvie, Tamra E

2018-06-21

The extensive heterogeneity both between and within the medulloblastoma (MB) subgroups underscores a critical need for variant-specific biomarkers and therapeutic strategies. We previously identified a role for the CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells in the SHH MB subgroup. Here we demonstrate the utility of CD271 as a novel diagnostic and prognostic marker for SHH MB using immunohistochemical analysis and transcriptome data across 763 primary tumors. RNA sequencing of CD271+ and CD271- cells revealed molecularly distinct, co-existing cellular subsets both in vitro and in vivo. MAPK/ERK signaling was upregulated in the CD271+ population, and inhibiting this pathway reduced endogenous CD271 levels, stem/progenitor cell proliferation, and cell survival as well as cell migration in vitro. Treatment with the MEK inhibitor selumetinib extended survival and reduced CD271 levels in vivo; whereas, treatment with vismodegib, a well-known smoothened (SMO) inhibitor currently in clinical trials for the treatment of recurrent SHH medulloblastoma, had no significant effect in our models. Our study demonstrates the clinical utility of CD271 as both a diagnostic and prognostic tool for SHH MB tumors and reveals a novel role for MEK inhibitors in targeting CD271+ SHH MB cells. Copyright ©2018, American Association for Cancer Research.

Clinical performance of stem cell therapy in patients with acute-on-chronic liver failure: a systematic review and meta-analysis.

PubMed

Xue, Ran; Meng, Qinghua; Dong, Jinling; Li, Juan; Yao, Qinwei; Zhu, Yueke; Yu, Hongwei

2018-05-10

Stem cell therapy has been applied in the treatment of acute-on-chronic liver failure (ACLF). However, its clinical efficiency is still debatable. The aim of this systematic review and meta-analysis is to evaluate the clinical efficiency of stem cell therapy in the treatment of ACLF. The Cochrane Library, OVID, EMBASE, and PUBMED were searched to December 2017. Both randomized and non-randomized studies, assessing stem cell therapy in patients with ACLF, were included. The outcome measures were total bilirubin (TBIL), alanine transaminase (ALT), international normalized ratio (INR), albumin (ALB), and the model for end-stage liver disease (MELD) score. The quality of evidence was assessed by GRADEpro. Four randomized controlled trials and six non-randomized controlled trials were included. The TBIL levels significantly decreased at 1-, 3-, 12-month after the stem cell therapy (p = 0.0008; p = 0.04; p = 0.007). The ALT levels decreased significantly compared with the control group in the short-term (p < 0.00001). There was no obvious change in the INR level compared with the control groups (p = 0.64). The ALB levels increased markedly as compared with the control groups (p < 0.0001). The significant difference can be found in MELD score between stem cell therapy and control groups (p = 0.008). Further subgroup analysis for 3-month clinical performance according to the stem cell types have also been performed. This study suggests that the clinical outcomes of stem cell therapy were satisfied in patients with ACLF in the short-term. MSCs may be better than BM-MNCs in the stem cells transplantation of ACLF. However, more attention should focus on clinical trials in large-volume centers.

Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

PubMed

Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

2014-01-01

Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM. © 2014 S. Karger AG, Basel

Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis

PubMed Central

Schwede, Matthew; Spentzos, Dimitrios; Bentink, Stefan; Hofmann, Oliver; Haibe-Kains, Benjamin; Harrington, David; Quackenbush, John; Culhane, Aedín C.

2013-01-01

Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer. PMID:23536770

Identifying Changes in Youth's Subgroup Membership over Time Based on Their Targeted Communication about Substance Use with Parents and Friends

ERIC Educational Resources Information Center

Kam, Jennifer A.

2011-01-01

Using latent class/transition analyses, this study: (a) identified subgroups of youth based on their targeted communication about substance use with parents and friends, (b) examined subgroup differences in substance use, and (c) considered changes in subgroup membership over four years. Among 5,874 youth, five subgroups emerged, with parents-only…

75 FR 22245 - Imidacloprid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... onion, green, subgroup 3-07B at 2.5 ppm, onion, dry bulb, subgroup 3-07A at 0.15 ppm and grain, cereal... combined residues of imidacloprid in or on onion, green, subgroup 3-07B at 2.5 ppm, onion, dry bulb... acute toxicity via the oral route. It is not an eye or dermal irritant and is not a dermal sensitizer...

Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D.

PubMed

Abbink, Peter; Lemckert, Angelique A C; Ewald, Bonnie A; Lynch, Diana M; Denholtz, Matthew; Smits, Shirley; Holterman, Lennart; Damen, Irma; Vogels, Ronald; Thorner, Anna R; O'Brien, Kara L; Carville, Angela; Mansfield, Keith G; Goudsmit, Jaap; Havenga, Menzo J E; Barouch, Dan H

2007-05-01

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.

Recent developments in testicular germ cell tumor research.

PubMed

van de Geijn, Gert-Jan M; Hersmus, Remko; Looijenga, Leendert H J

2009-03-01

Testicular germ cell tumors of adolescents and adults (TGCTs; the so-called type II variant) are the most frequent malignancies found in Caucasian males between 20 and 40 years of age. The incidence has increased over the last decades. TGCTs are divided into seminomas and nonseminomas, the latter consisting of the subgroups embryonal carcinoma, yolk-sac tumor, teratoma, and choriocarcinoma. The pathogenesis starts in utero, involving primordial germ cells/gonocytes that are blocked in their differentiation, and develops via the precursor lesion carcinoma in situ toward invasiveness. TGCTs are totipotent and can be considered as stem cell tumors. The developmental capacity of their cell of origin, the primordial germ cells/gonocyte, is demonstrated by the different tumor histologies of the invasive TGCTs. Seminoma represents the germ cell lineage, and embryonal carcinoma is the undifferentiated component, being the stem cell population of the nonseminomas. Somatic differentiation is seen in the teratomas (all lineages), whereas yolk-sac tumors and choriocarcinoma represent extra-embryonal differentiation. Seminomas are highly sensitive to irradiation and (DNA damaging) chemotherapy, whereas most nonseminomatous elements are less susceptible to radiation, although still sensitive to chemotherapy, with the exception of teratoma. To allow early diagnosis and follow up, appropriate markers are mandatory to discriminate between the different subgroups. In this review, a summary will be given related to several recent developments in TGCT research, especially selected because of their putative clinical impact.

Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

PubMed

Tyndall, Alan; van Laar, Jacob M

2016-06-01

Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes mellitus have received MSC therapeutically. The possible reasons for this apparent mismatch between expectation and clinical reality will be discussed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Underplating generated A- and I-type granitoids of the East Junggar from the lower and the upper oceanic crust with mixing of mafic magma: Insights from integrated zircon U-Pb ages, petrography, geochemistry and Nd-Sr-Hf isotopes

NASA Astrophysics Data System (ADS)

Liu, Wei; Liu, Xiu-Jin; Liu, Li-Juan

2013-10-01

Whole rock major and trace element, Nd-Sr and zircon Hf isotopic compositions and secondary-ion mass spectrometry zircon U-Pb ages of eleven granitoid intrusions and dioritic rocks from the East Junggar (NW China) were analyzed in this study. The East Junggar granitoids were emplaced during terminal Early to Late Carboniferous (325-301 Ma) following volcanic eruption of the Batamayi Formation. Zircons from the East Junggar granitoids yielded 210 concordant 206Pb/238U ages which are all younger than 334 Ma and exhibit ɛHf(t) values distinctly higher than Devonian arc volcanic-rocks. Seismic P-wave velocities of deep crust of the East Junggar proper resemble those of oceanic crust (OC). These characteristics suggest absence of volcanic rock and volcano-sedimentary rock of Devonian and Early Carboniferous from the source region. The East Junggar granitoids show ɛNd(t) and initial 87Sr/86Sr values substantially overlapping those of the Armantai ophiolite in the area. The Early Paleozoic OC with seamount-like composition as the Zhaheba-Armantai ophiolites remained in the lower crust and formed main source rock of the East Junggar granitoids. Based on petrography and geochemistry, the East Junggar granitoids are classified into peralkaline A-type in the northern subarea, I-type (I1 and I2 subgroups) mainly in the north and A-type in the south of the southern subarea. The perthitic or argillated core and oligoclasic rim with an argillated boundary of feldspar phenocrysts and inclusion of perthites or its overgrowth by matrix plagioclase, in the monzogranites (northern subarea), suggest mixing of peralkaline granitic magma with mafic magma. In the north of the southern subarea, the presence of magmatic microdioritic enclaves (MMEs) in the I1 subgroup granitoids, transfer of plagioclase phenocrysts and hornblendes between host granodiorite and the MME across the boundary and a prominent resorption surface in the plagioclase phenocrysts indicate mixing of crustal magma (I2 subgroup granitoids) with mafic magma. Magma mixing shifted (87Sr/86Sr)i of the I1 subgroup granitoids towards the mantle array. Two generations of hornblende with zonal distribution and similar mineral and geochemical compositions of quartz monzodiorite and hosted MME with unfractionated rare earth elements (REE) suggest extended magma mixing with onset probably at or near source region. These observations imply concurrency of mantle input and the crustal melting and, hence, a causal relationship between underplating/intraplating and the lower OC/upper OC melting. The I-type granitoids experienced plagioclase and hornblende fractionations, whereas fractionated phases of the two groups of A-type granites were alkali feldspar and albite-oligoclase with significant involvement of F--rich fluid. Granodioritic parent magmas of the I2 subgroup granitoids stemmed from the hydrous upper OC. Parent magmas of the two A-type groups possess syenogranitic or quartz syenitic compositions. The peralkaline A-type granites stemmed from the lower OC, whereas the A-type granites from dehydrated upper OC left behind after extensive partial melting and extraction of I-type granitoids. Based on comparison in the ternary system Mg2SiO4-CaAl2SiO6-SiO2, most of the Batamayi volcanic rocks with affinity to ocean-island basalts were derived from asthenospheric upwelling. The gabbro-dioritic rocks with higher light to heavy REE ratios stemmed from metasomatized lithospheric mantle. Both of the above mafic rocks contain subducted slab component.

Genetic Basis for Developmental Homeostasis of Germline Stem Cell Niche Number: A Network of Tramtrack-Group Nuclear BTB Factors

PubMed Central

Chalvet, Fabienne; Netter, Sophie; Dos Santos, Nicolas; Poisot, Emilie; Paces-Fessy, Mélanie; Cumenal, Delphine; Peronnet, Frédérique; Pret, Anne-Marie; Théodore, Laurent

2012-01-01

The potential to produce new cells during adult life depends on the number of stem cell niches and the capacity of stem cells to divide, and is therefore under the control of programs ensuring developmental homeostasis. However, it remains generally unknown how the number of stem cell niches is controlled. In the insect ovary, each germline stem cell (GSC) niche is embedded in a functional unit called an ovariole. The number of ovarioles, and thus the number of GSC niches, varies widely among species. In Drosophila, morphogenesis of ovarioles starts in larvae with the formation of terminal filaments (TFs), each made of 8–10 cells that pile up and sort in stacks. TFs constitute organizers of individual germline stem cell niches during larval and early pupal development. In the Drosophila melanogaster subgroup, the number of ovarioles varies interspecifically from 8 to 20. Here we show that pipsqueak, Trithorax-like, batman and the bric-à-brac (bab) locus, all encoding nuclear BTB/POZ factors of the Tramtrack Group, are involved in limiting the number of ovarioles in D. melanogaster. At least two different processes are differentially perturbed by reducing the function of these genes. We found that when the bab dose is reduced, sorting of TF cells into TFs was affected such that each TF contains fewer cells and more TFs are formed. In contrast, psq mutants exhibited a greater number of TF cells per ovary, with a normal number of cells per TF, thereby leading to formation of more TFs per ovary than in the wild type. Our results indicate that two parallel genetic pathways under the control of a network of nuclear BTB factors are combined in order to negatively control the number of germline stem cell niches. PMID:23185495

Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.

PubMed

Lafage-Pochitaloff, Marina; Baranger, Laurence; Hunault, Mathilde; Cuccuini, Wendy; Lefebvre, Christine; Bidet, Audrey; Tigaud, Isabelle; Eclache, Virginie; Delabesse, Eric; Bilhou-Nabéra, Chrystèle; Terré, Christine; Chapiro, Elise; Gachard, Nathalie; Mozziconacci, Marie-Joelle; Ameye, Geneviève; Porter, Sarah; Grardel, Nathalie; Béné, Marie C; Chalandon, Yves; Graux, Carlos; Huguet, Françoise; Lhéritier, Véronique; Ifrah, Norbert; Dombret, Hervé

2017-10-19

Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization, and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ KMT2A-AFF1 and 14q32/ IGH translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years. © 2017 by The American Society of Hematology.

A comparison of dioctahedral smectite and iodine glycerin cream with topical mouth rinse in treatment of chemotherapy induced oral mucositis: a pilot study.

PubMed

Lin, Jin-Xiang; Fan, Zu-Yan; Lin, Qu; Wu, Dong-Hao; Wu, Xiang-Yuan; Chen, Yan-Ru; Fang, Heng-Ying; Wu, Dong-Bing; Wen, Jing-Yun; Dong, Min; Ma, Xiao-Kun; Wan, Xiang-Bo

2015-04-01

To compare the efficacy of dioctahedral smectite and iodine glycerin (DSIG) cream with topical mouth rinse (composed of saline, gentamicin and Vitamin B12) in treatment of chemotherapy induced oral mucositis (OM). A total of 130 intensive chemotherapy or stem cells transplantation induced OM patients were recruited. Among these patients, 67 patients received topical mouth rinse and 63 patients received DSIG cream treatment. The OM would be treated on the OM appearance and sustained for 5 days. OM severity was measured daily using The American Oncology Nursing Society recommended Oral Assessment Guideline (OAG) score system. Compared with topical mouth rinse treatment, a significant lower OAG score was observed in DSIG cream treated patients. Specifically, the OAG scores were respectively 12.1 ± 1.1, 12.0 ± 1.2, 11.3 ± 1.3 and 10.4 ± 1.3 from day 2 to day 5 in topical mouth rinse treatment subgroup. Correspondingly, the OAG scores were respectively 10.2 ± 1.0, 9.3 ± 0.9, 8.5 ± 0.6 and 8.0 ± 0.2 for DSIG cream treatment subset (all P < 0.05). Importantly, compared with topical mouth rinse treatment, the DSIG cream significantly shortened OM repair time (4.68 ± 0.98 vs. 8.76 ± 1.80 days, P < 0.001). After 5 days treatment, 54 patients (85.7%) obtained complete regression with an OAG score ≤8, and 7 patients (11.1%) had partial regression with an OAG score of 9-10 in DSIG cream treatment subgroup. However, only 2 patients (3.0%) obtained completed regression and 32 patients (47.8%) had partial regression in topical mouth rinse treatment cohort. Moreover, no serious side-effect was observed in both cohorts. Compared with topical mouth rinse, DSIG cream significantly lowered the OAG score and shortened OM duration. Copyright © 2014 Elsevier Ltd. All rights reserved.

77 FR 27130 - Ametoctradin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-09

...; grape at 5.0 ppm; grape, raisin at 8 ppm; hop, dried cones at 9 ppm; onion, bulb, subgroup 3-07A at 1.2 ppm; onion, green, subgroup 3-07B at 16 ppm; vegetable, cucurbit, group 9 at 4.5 ppm; vegetable... 50 ppm; grape at 4.0 ppm; grape, raisin at 8.0 ppm; hop, dried cones at 10 ppm; onion, bulb, subgroup...

Regulatory role of AINTEGUMENTA in organ initiation and growth

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

Krizek, Beth Allyn; Lebioda, Lukasz

2005-03-01

Although several members of the plant-specific AP2/ERF family of transcription factors are important developmental regulators, many genes in this large protein family remain uncharacterized. Here, we present a phylogenetic analysis of the18 genes that make up the AP2 subgroup of this family. We report expression analyses of seven Arabidopsis genes most closely related to the floral development gene AINTEGUMENTA and show that all AINTEGUMENTA-like (AIL) genes are transcribed in multiple tissues during development. They are expressed primarily in young actively dividing tissues of a plant and not in mature leaves or stems. The spatial distribution of AIL5, AIL6, and AIL7more » mRNA in inflorescences was characterized by in situ hybridization. Each of these genes is expressed in a spatially and temporally distinct pattern within inflorescence meristems and flowers. Ectopic expression of AIL5 resulted in a larger floral organ phenotype, similar to that resulting from ectopic expression of ANT. Our results are consistent with AIL genes having roles in specification of meristematic or division-competent states.« less

Differential Response of Acidobacteria Subgroups to Forest-to-Pasture Conversion and Their Biogeographic Patterns in the Western Brazilian Amazon

PubMed Central

Navarrete, Acacio A.; Venturini, Andressa M.; Meyer, Kyle M.; Klein, Ann M.; Tiedje, James M.; Bohannan, Brendan J. M.; Nüsslein, Klaus; Tsai, Siu M.; Rodrigues, Jorge L. M.

2015-01-01

Members of the phylum Acidobacteria are among the most abundant soil bacteria on Earth, but little is known about their response to environmental changes. We asked how the relative abundance and biogeographic patterning of this phylum and its subgroups responded to forest-to-pasture conversion in soils of the western Brazilian Amazon. Pyrosequencing of 16S rRNA genes was employed to assess the abundance and composition of the Acidobacteria community across 54 soil samples taken using a spatially nested sampling scheme at the landscape level. Numerically, Acidobacteria represented 20% of the total bacterial community in forest soils and 11% in pasture soils. Overall, 15 different Acidobacteria subgroups of the current 26 subgroups were detected, with Acidobacteria subgroups 1, 3, 5, and 6 accounting together for 87% of the total Acidobacteria community in forest soils and 75% in pasture soils. Concomitant with changes in soil chemistry after forest-to-pasture conversion—particularly an increase in properties linked to soil acidity and nutrient availability—we observed an increase in the relative abundances of Acidobacteria subgroups 4, 10, 17, and 18, and a decrease in the relative abundances of other Acidobacteria subgroups in pasture relative to forest soils. The composition of the total Acidobacteria community as well as the most abundant Acidobacteria subgroups (1, 3, 5, and 6) was significantly more similar in composition across space in pasture soils than in forest soils. These results suggest that preponderant responses of Acidobacteria subgroups, especially subgroups 1, 3, 4, 5, and 6, to forest-to-pasture conversion effects in soils could be used to define management-indicators of agricultural practices in the Amazon Basin. These acidobacterial responses are at least in part through alterations on acidity- and nutrient-related properties of the Amazon soils. PMID:26733981

Characterization of CaHsp70-1, a Pepper Heat-Shock Protein Gene in Response to Heat Stress and Some Regulation Exogenous Substances in Capsicum annuum L.

PubMed Central

Guo, Meng; Zhai, Yu-Fei; Lu, Jin-Ping; Chai, Lin; Chai, Wei-Guo; Gong, Zhen-Hui; Lu, Ming-Hui

2014-01-01

Pepper (Capsicum annuum L.) is sensitive to heat stress (HS). Heat shock proteins 70 (Hsp70s) play a crucial role in protecting plant cells against HS and control varies characters in different plants. However, CaHsp70-1 gene was not well characterized in pepper. In this study, CaHsp70-1 was cloned from the pepper thermotolerant line R9, which encoded a protein of 652 amino acids, with a molecular weight of 71.54 kDa and an isoelectric point of 5.20. CaHsp70-1 belongs to the cytosolic Hsp70 subgroup, and best matched with tomato SlHsp70. CaHsp70-1 was highly induced in root, stem, leaf and flower in R9 with HS treatment (40 °C for 2 h). In both thermosensitive line B6 and thermotolerant line R9, CaHsp70-1 significantly increased after 0.5 h of HS (40 °C), and maintained in a higher level after 4 h HS. The expression of CaHsp70-1 induced by CaCl2, H2O2 and putrescine (Put) under HS were difference between B6 and R9 lines. The different expression patterns may be related to the differences in promoters of CaHsp70-1 from the two lines. These results suggest that CaHsp70-1 as a member of cytosolic Hsp70 subgroup, may be involved in HS defense response via a signal transduction pathway contained Ca2+, H2O2 and Put. PMID:25356507

Application Guidelines for Quality Assurance Procedures for Hybrid Microcircuits.

DTIC Science & Technology

1983-03-01

INSPECTION LIMITS SYMBOL TEST CONDITIONS UNITS SUBGROUP 6 TC = -55 DEGREES C AVI0 1 SAME AS SUBGROUP 5 -0.1 5 Vpp VOS SAME AS SUBGROUP 4 50 m%LC V0 2 ... 1 . Line Certification 2 . Fabrication Techniques and Material Qualification Procedures 3. Design Guidelines e. Application Guidelines. Items a through... 1 2 . GENERAL ................... ......... ................. 3 2.1 Summary of documents generated ........................ 3 2.2 Contract objectives

Surgical and clinical aspects of cerebellar pilomyxoid-spectrum astrocytomas in children.

PubMed

El Beltagy, Mohamed A; Atteya, Mostafa M E; El-Haddad, Alaa; Awad, Madiha; Taha, Hala; Kamal, Mohamed; El Naga, Sherif Abou

2014-06-01

Cerebellar pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid astrocytomas (IPAs) are collectively called "pilomyxoid-spectrum astrocytomas (PMSAs)." Cerebellar PMSAs are thought to behave more aggressively than pilocytic astrocytomas (PAs). Our objective is to compare PMSAs to PAs in terms of surgical and clinical profiles. This retrospective study included 66 cases (35 males and 31 females) with cerebellar astrocytomas treated between July 2007 and December 2012 at Children's Cancer Hospital Egypt (CCHE 57357) with a mean age of 7 (±1.5) years. Cases were divided into three subgroups as follows: 44 PAs, 10 IPAs, and 12 PMAs. Comparison between all groups was focusing on brain stem invasion, intrinsic necrotic cavitation, extent of resection, recurrence, leptomeningeal dissemination (LD), metastases, need for CSF diversion, and cerebellar mutism (CM). Cerebellar PMAs and IPAs separately and collectively had higher incidence of brain stem invasion, intrinsic necrotic cavitation, tumor recurrence, and LD when compared to PAs (P < 0.001). Gross total resection was 13.6 % in PMSAs versus 90.9 % in PAs (P < 0.001). PMAs had a higher incidence of tumor recurrence than IPAs (66.7 versus 20 %, P < 0.001). Incidence of recurrence in PAs was 9.1 % in partially resected cases. Mean interval to recurrence was 9 (±1.5) months in PMSAs and 42 (±2) months in PAs. Cerebellar PMSAs express an aggressive clinical behavior and impose more operative challenges than PAs. These tumors may represent a clinical spectrum-at its benign end lies PA, while PMA lies at the aggressive end, with IPA lying just behind. Such concepts could be used to guide management in the future.

Change in surface roughness of esthetic restorative materials after exposure to different immersion regimes in a cola drink.

PubMed

Bajwa, Navroop Kaur; Pathak, Anuradha

2014-01-01

Context. An in vitro study carried out to evaluate and compare the effect of Cola drink on surface roughness of esthetic restorative materials. Purpose. To compare the effect of different immersion regimes in a Cola drink on surface roughness of esthetic restorative materials. Method. Two hundred samples were grouped into 4 equal groups of 50 samples each: Group I: conventional glass ionomer, Group II: resin modified glass ionomer, Group III: polyacid-modified resin composite, Group IV: Composite resin. Each group was further subdivided into 5 subgroups of 10 samples each. Subgroup A (Control Subgroup). Samples were kept immersed in artificial saliva. Subgroup B. Samples were immersed in Cola drink once a day. Subgroup C. Samples were immersed in Cola drink, 3 times a day. Subgroup D. Samples were immersed in Cola drink 5 times a day. Subgroup E. Samples were immersed in Cola drink 10 times a day. Each immersion lasted 5 minutes. The immersion protocol was repeated for 7 days. Results. Maximum surface roughness was seen in Group I conventional glass ionomer cement, followed by Group II resin modified glass ionomer, Group III polyacid modified resin composite, and Group IV composite resin samples. Conclusion. Resistance to change in surface roughness is more in resin based restorative materials as compared to glass ionomer based materials.

Change in Surface Roughness of Esthetic Restorative Materials after Exposure to Different Immersion Regimes in a Cola Drink

PubMed Central

Bajwa, Navroop Kaur; Pathak, Anuradha

2014-01-01

Context. An in vitro study carried out to evaluate and compare the effect of Cola drink on surface roughness of esthetic restorative materials. Purpose. To compare the effect of different immersion regimes in a Cola drink on surface roughness of esthetic restorative materials. Method. Two hundred samples were grouped into 4 equal groups of 50 samples each: Group I: conventional glass ionomer, Group II: resin modified glass ionomer, Group III: polyacid-modified resin composite, Group IV: Composite resin. Each group was further subdivided into 5 subgroups of 10 samples each. Subgroup A (Control Subgroup). Samples were kept immersed in artificial saliva. Subgroup B. Samples were immersed in Cola drink once a day. Subgroup C. Samples were immersed in Cola drink, 3 times a day. Subgroup D. Samples were immersed in Cola drink 5 times a day. Subgroup E. Samples were immersed in Cola drink 10 times a day. Each immersion lasted 5 minutes. The immersion protocol was repeated for 7 days. Results. Maximum surface roughness was seen in Group I conventional glass ionomer cement, followed by Group II resin modified glass ionomer, Group III polyacid modified resin composite, and Group IV composite resin samples. Conclusion. Resistance to change in surface roughness is more in resin based restorative materials as compared to glass ionomer based materials. PMID:25006464

Pathogenicity of H5N8 highly pathogenic avian influenza viruses isolated from a wild bird fecal specimen and a chicken in Japan in 2014.

PubMed

Tanikawa, Taichiro; Kanehira, Katsushi; Tsunekuni, Ryota; Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

2016-04-01

Poultry outbreaks caused by H5N8 highly pathogenic avian influenza viruses (HPAIVs) occurred in Japan between December 2014 and January 2015. During the same period; H5N8 HPAIVs were isolated from wild birds and the environment in Japan. The hemagglutinin (HA) genes of these isolates were found to belong to clade 2.3.4.4 and three sub-groups were distinguishable within this clade. All of the Japanese isolates from poultry outbreaks belonged to the same sub-group; whereas wild bird isolates belonged to the other sub-groups. To examine whether the difference in pathogenicity to chickens between isolates of different HA sub-groups of clade 2.3.4.4 could explain why the Japanese poultry outbreaks were only caused by a particular sub-group; pathogenicities of A/chicken/Miyazaki/7/2014 (Miyazaki2014; sub-group C) and A/duck/Chiba/26-372-48/2014 (Chiba2014; sub-group A) to chickens were compared and it was found that the lethality of Miyazaki2014 in chickens was lower than that of Chiba2014; according to the 50% chicken lethal dose. This indicated that differences in pathogenicity may not explain why the Japanese poultry outbreaks only involved group C isolates. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Evaluation of Evidence of Statistical Support and Corroboration of Subgroup Claims in Randomized Clinical Trials.

PubMed

Wallach, Joshua D; Sullivan, Patrick G; Trepanowski, John F; Sainani, Kristin L; Steyerberg, Ewout W; Ioannidis, John P A

2017-04-01

Many published randomized clinical trials (RCTs) make claims for subgroup differences. To evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses. This meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract. Articles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings. Study characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials. The number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses. Sixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null. A minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

40 CFR 180.574 - Fluazinam; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Ginseng 4.5 Lettuce, head 0.02 Lettuce, leaf 2.0 Onion, bulb, subgroup 3-07A 0.20 Pea and bean, dried shelled, except soybean, subgroup 6C, except pea 0.02 Pea and bean, succulent shelled, subgroup 6B, except...

Gene Expression Analyses of the Spatio-Temporal Relationships of Human Medulloblastoma Subgroups during Early Human Neurogenesis

PubMed Central

Hooper, Cornelia M.; Hawes, Susan M.; Kees, Ursula R.; Gottardo, Nicholas G.; Dallas, Peter B.

2014-01-01

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified – WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10–15 and 20–30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies. PMID:25412507

Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.

PubMed

Hooper, Cornelia M; Hawes, Susan M; Kees, Ursula R; Gottardo, Nicholas G; Dallas, Peter B

2014-01-01

Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified - WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options. To address this issue, the gene expression profiles of normal human neural tissues and cell types representing a broad neuro-developmental continuum, were compared to those of two independent cohorts of primary human medulloblastoma specimens. Clustering, co-expression network, and gene expression analyses revealed that WNT and SHH medulloblastoma may be derived from distinct neural stem cell populations during early embryonic development, while the transcriptional profiles of Group 3 and Group 4 medulloblastoma resemble cerebellar granule neuron precursors at weeks 10-15 and 20-30 of embryogenesis, respectively. Our data indicate that Group 3 medulloblastoma may arise through abnormal neuronal differentiation, whereas deregulation of synaptic pruning-associated apoptosis may be driving Group 4 tumorigenesis. Overall, these data provide significant new insight into the spatio-temporal relationships and molecular pathogenesis of the human medulloblastoma subgroups, and provide an important framework for the development of more refined model systems, and ultimately improved therapeutic strategies.

40 CFR 180.658 - Penthiopyrad; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., subgroup 5A 5.0 Brassica, leafy greens, subgroup 5B 50 Buckwheat, grain 0.15 Canola 1.5 Corn, field, forage 40 Corn, field, grain 0.01 Corn, field, refined oil 0.05 Corn, field, stover 15 Corn, pop, grain 0.01 Corn, sweet, kernel plus cob with husks removed 0.01 Cotton, seed 1.5 Cotton, gin byproducts 15 Fruit...

40 CFR 180.658 - Penthiopyrad; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., subgroup 5A 5.0 Brassica, leafy greens, subgroup 5B 50 Buckwheat, grain 0.15 Canola 1.5 Corn, field, forage 40 Corn, field, grain 0.01 Corn, field, refined oil 0.05 Corn, field, stover 15 Corn, pop, grain 0.01 Corn, sweet, kernel plus cob with husks removed 0.01 Cotton, seed 1.5 Cotton, gin byproducts 15 Fruit...

40 CFR 180.658 - Penthiopyrad; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., subgroup 5A 5.0 Brassica, leafy greens, subgroup 5B 50 Buckwheat, grain 0.15 Canola 1.5 Corn, field, forage 40 Corn, field, grain 0.01 Corn, field, refined oil 0.05 Corn, field, stover 15 Corn, pop, grain 0.01 Corn, sweet, kernel plus cob with husks removed 0.01 Cotton, seed 1.5 Cotton, gin byproducts 15 Fruit...

Molecular cloning and expression analysis of WRKY transcription factor genes in Salvia miltiorrhiza.

PubMed

Li, Caili; Li, Dongqiao; Shao, Fenjuan; Lu, Shanfa

2015-03-17

WRKY proteins comprise a large family of transcription factors and play important regulatory roles in plant development and defense response. The WRKY gene family in Salvia miltiorrhiza has not been characterized. A total of 61 SmWRKYs were cloned from S. miltiorrhiza. Multiple sequence alignment showed that SmWRKYs could be classified into 3 groups and 8 subgroups. Sequence features, the WRKY domain and other motifs of SmWRKYs are largely conserved with Arabidopsis AtWRKYs. Each group of WRKY domains contains characteristic conserved sequences, and group-specific motifs might attribute to functional divergence of WRKYs. A total of 17 pairs of orthologous SmWRKY and AtWRKY genes and 21 pairs of paralogous SmWRKY genes were identified. Maximum likelihood analysis showed that SmWRKYs had undergone strong selective pressure for adaptive evolution. Functional divergence analysis suggested that the SmWRKY subgroup genes and many paralogous SmWRKY gene pairs were divergent in functions. Various critical amino acids contributed to functional divergence among subgroups were detected. Of the 61 SmWRKYs, 22, 13, 4 and 1 were predominantly expressed in roots, stems, leaves, and flowers, respectively. The other 21 were mainly expressed in at least two tissues analyzed. In S. miltiorrhiza roots treated with MeJA, significant changes of gene expression were observed for 49 SmWRKYs, of which 26 were up-regulated, 18 were down-regulated, while the other 5 were either up-regulated or down-regulated at different time-points of treatment. Analysis of published RNA-seq data showed that 42 of the 61 identified SmWRKYs were yeast extract and Ag(+)-responsive. Through a systematic analysis, SmWRKYs potentially involved in tanshinone biosynthesis were predicted. These results provide insights into functional conservation and diversification of SmWRKYs and are useful information for further elucidating SmWRKY functions.

Effects of exogenous recombinant human granulocyte colony-stimulating factor (filgrastim, rhG-CSF) on neutrophils of critically ill patients with systemic inflammatory response syndrome depend on endogenous G-CSF plasma concentrations on admission.

PubMed

Weiss, Manfred; Voglic, Sami; Harms-Schirra, Britt; Lorenz, Ingrid; Lasch, Britta; Dumon, Kristoffel; Gross-Weege, Wilhelm; Schneider, Elisabeth Marion

2003-06-01

To investigate the effects of exogenous recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) application on the neutrophils of patients at risk of sepsis following major trauma or operation. Randomized controlled trial. Surgical intensive care unit and research laboratory of a university hospital. Twenty-seven patients with systemic inflammatory response syndrome (SIRS). Thirteen patients were treated with filgrastim (1 micro g.kg.24 h) for 10 days as a continuous infusion. Fourteen patients served as controls. Surface expression of FcgammaR type I (CD64), phagocytosis of E. coli, and the E. coli-induced oxidative burst of neutrophils were tested by flow cytometry. On the first postoperative/posttraumatic day, endogenous G-CSF plasma concentrations were <300 pg/ml in seven controls (subgroup 1) and nine filgrastim patients (subgroup 3), and were already elevated with >500 pg/ml in seven controls (subgroup 2) and four filgrastim patients (subgroup 4). G-CSF values ( P=0.0026, subgroup 1/3; P=0.0167, 2/4), neutrophil counts ( P=0.0026, 1/3; P=0.0167, 2/4), and CD64 expression ( P=0.0013, 1/3) were higher in filgrastim-treated than non-treated subgroups, but not phagocytic and burst activities. From day zero to day 1, phagocytosis decreased in subgroups 1 (5/7 patients) and 3 (5/9), but increased in subgroups 2 (5/7) and 4 (3/4), and respiratory burst activity decreased in subgroup 3 (8/9). Besides activation of neutrophil maturation, low-dose rhG-CSF application in postoperative patients with SIRS has different effects on neutrophil functions, in part depending on already endogenously produced G-CSF.

75 FR 13277 - Notice of Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-19

...]phenyl-1,2-benzenedicarboxamide, in or on vegetable, legume, edible podded, subgroup 6A at 0.5 ppm; pea..., subgroup 6C at 0.8 ppm; vegetable, foliage of legume, except soybean, subgroup 7A at 35 ppm; soybeans...

Discriminating cellular heterogeneity using microwell-based RNA cytometry

PubMed Central

Dimov, Ivan K.; Lu, Rong; Lee, Eric P.; Seita, Jun; Sahoo, Debashis; Park, Seung-min; Weissman, Irving L.; Lee, Luke P.

2014-01-01

Discriminating cellular heterogeneity is important for understanding cellular physiology. However, it is limited by the technical difficulties of single-cell measurements. Here, we develop a two-stage system to determine cellular heterogeneity. In the first stage, we perform multiplex single-cell RNA-cytometry in a microwell array containing over 60,000 reaction chambers. In the second stage, we use the RNA-cytometry data to determine cellular heterogeneity by providing a heterogeneity likelihood score. Moreover, we use Monte-Carlo simulation and RNA-cytometry data to calculate the minimum number of cells required for detecting heterogeneity. We applied this system to characterize the RNA distributions of aging related genes in a highly purified mouse hematopoietic stem cell population. We identified genes that reveal novel heterogeneity of these cells. We also show that changes in expression of genes such as Birc6 during aging can be attributed to the shift of relative portions of cells in the high-expressing subgroup versus low-expressing subgroup. PMID:24667995

Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-2-0032 TITLE: Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis PRINCIPAL...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis 5b...Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The subject of the project is FY14 PRMRP Topic Area – Tinnitus . The broad

40 CFR 180.641 - Spirotetramat; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Strawberry1 0.40 Vegetable, cucurbit, group 9 0.30 Vegetable, foliage of legume, except soybean, subgroup 07A..., legume, group 06, except soybean 2.5 Vegetable, tuberous and corm, subgroup 1C 0.60 Wax jambu 2.5 White...

Health-related quality of life of hematopoietic stem cell transplant childhood survivors: state of the science.

PubMed

Tanzi, Elizabeth M

2011-01-01

The notion of health-related quality of life (HRQoL) holds unique significance in the treatment of patients who have undergone hematopoietic stem cell transplantation (HSCT). Not only is transplant procedure inevitably associated with immediate and late medical effects along with high mortality and morbidity rates, but it can also significantly affect the HRQoL for the patient and family. This review of literature will assist advanced practice nurses and pediatric oncology nurses in distinguishing and targeting interventions for patients and families who are at high risk of encountering distress during and following HSCT. It provides information on the assessment of pre-HSCT variables to identify patient subgroups in need of more aggressive supportive care to improve HRQoL during transplant. Furthermore, it serves as a guideline for developing interventional strategies and the role of the advanced practice nurse and pediatric oncology nurse caring for the patient throughout and following transplant.

The effect of core material, veneering porcelain, and fabrication technique on the biaxial flexural strength and weibull analysis of selected dental ceramics.

PubMed

Lin, Wei-Shao; Ercoli, Carlo; Feng, Changyong; Morton, Dean

2012-07-01

The objective of this study was to compare the effect of veneering porcelain (monolithic or bilayer specimens) and core fabrication technique (heat-pressed or CAD/CAM) on the biaxial flexural strength and Weibull modulus of leucite-reinforced and lithium-disilicate glass ceramics. In addition, the effect of veneering technique (heat-pressed or powder/liquid layering) for zirconia ceramics on the biaxial flexural strength and Weibull modulus was studied. Five ceramic core materials (IPS Empress Esthetic, IPS Empress CAD, IPS e.max Press, IPS e.max CAD, IPS e.max ZirCAD) and three corresponding veneering porcelains (IPS Empress Esthetic Veneer, IPS e.max Ceram, IPS e.max ZirPress) were selected for this study. Each core material group contained three subgroups based on the core material thickness and the presence of corresponding veneering porcelain as follows: 1.5 mm core material only (subgroup 1.5C), 0.8 mm core material only (subgroup 0.8C), and 1.5 mm core/veneer group: 0.8 mm core with 0.7 mm corresponding veneering porcelain with a powder/liquid layering technique (subgroup 0.8C-0.7VL). The ZirCAD group had one additional 1.5 mm core/veneer subgroup with 0.7 mm heat-pressed veneering porcelain (subgroup 0.8C-0.7VP). The biaxial flexural strengths were compared for each subgroup (n = 10) according to ISO standard 6872:2008 with ANOVA and Tukey's post hoc multiple comparison test (p≤ 0.05). The reliability of strength was analyzed with the Weibull distribution. For all core materials, the 1.5 mm core/veneer subgroups (0.8C-0.7VL, 0.8C-0.7VP) had significantly lower mean biaxial flexural strengths (p < 0.0001) than the other two subgroups (subgroups 1.5C and 0.8C). For the ZirCAD group, the 0.8C-0.7VL subgroup had significantly lower flexural strength (p= 0.004) than subgroup 0.8C-0.7VP. Nonetheless, both veneered ZirCAD groups showed greater flexural strength than the monolithic Empress and e.max groups, regardless of core thickness and fabrication techniques. Comparing fabrication techniques, Empress Esthetic/CAD, e.max Press/CAD had similar biaxial flexural strength (p= 0.28 for Empress pair; p= 0.87 for e.max pair); however, e.max CAD/Press groups had significantly higher flexural strength (p < 0.0001) than Empress Esthetic/CAD groups. Monolithic core specimens presented with higher Weibull modulus with all selected core materials. For the ZirCAD group, although the bilayer 0.8C-0.7VL subgroup exhibited significantly lower flexural strength, it had highest Weibull modulus than the 0.8C-0.7VP subgroup. The present study suggests that veneering porcelain onto a ceramic core material diminishes the flexural strength and the reliability of the bilayer specimens. Leucite-reinforced glass-ceramic cores have lower flexural strength than lithium-disilicate ones, while fabrication techniques (heat-pressed or CAD/CAM) and specimen thicknesses do not affect the flexural strength of all glass ceramics. Compared with the heat-pressed veneering technique, the powder/liquid veneering technique exhibited lower flexural strength but increased reliability with a higher Weibull modulus for zirconia bilayer specimens. Zirconia-veneered ceramics exhibited greater flexural strength than monolithic leucite-reinforced and lithium-disilicate ceramics regardless of zirconia veneering techniques (heat-pressed or powder/liquid technique). © 2012 by the American College of Prosthodontists.

EFFECTS OF LIRAGLUTIDE 3.0 MG ON WEIGHT AND RISK FACTORS IN HISPANIC VERSUS NON-HIPANIC POPULATIONS: SUBGROUP ANALYSIS FROM SCALE RANDOMIZED TRIALS.

PubMed

O'Neil, Patrick M; Garvey, W Timothy; Gonzalez-Campoy, J Michael; Mora, Pablo; Ortiz, Rafael Violante; Guerrero, German; Claudius, Birgitte; Pi-Sunyer, Xavier

2016-11-01

Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups. We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m 2 with at least 1 comorbidity, or a minimum BMI of 30 kg/m 2 , at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data. Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo. Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals. A1c = glycated hemoglobin BMI = body mass index CI = confidence interval FPG = fasting plasma glucose GLP-1 = glucagon-like peptide-1 hsCRP = high-sensitivity C-reactive protein SCALE = Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes T2DM = type 2 diabetes mellitus.

Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

DTIC Science & Technology

2017-10-13

AWARD NUMBER: W81XWH-15-2-0032 TITLE: Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-2-0032 5b. GRANT NUMBER Identifying Subgroups of Tinnitus Using Novel Resting State fMRI...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The subject of the project is FY14 PRMRP Topic Area – Tinnitus . The broad goal is

Pay attention to impulsivity: modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats.

PubMed

Tomlinson, Anneka; Grayson, Ben; Marsh, Samuel; Harte, Michael K; Barnes, Samuel A; Marshall, Kay M; Neill, Joanna C

2014-08-01

Varying levels of attention and impulsivity deficits are core features of the three subtypes of adult attention deficit-hyperactivity disorder (ADHD). To date, little is known about the neurobiological correlates of these subtypes. Development of a translational animal model is essential to improve our understanding and improve therapeutic strategies. The 5-choice continuous performance task (5C-CPT) in rats can be used to examine different forms of attention and impulsivity. Adult rats were trained to pre-set 5C-CPT criterion and subsequently separated into subgroups according to baseline levels of sustained attention, vigilance, premature responding and response disinhibition in the 5C-CPT. The behavioural subgroups were selected to represent the different subtypes of adult ADHD. Consequently, effects of the clinically used pharmacotherapies (methylphenidate and atomoxetine) were assessed in the different subgroups. Four subgroups were identified: low-attentive (LA), high-attentive (HA), high-impulsive (HI) and low-impulsive (LI). Methylphenidate and atomoxetine produced differential effects in the subgroups. Methylphenidate increased sustained attention and vigilance in LA animals, and reduced premature responding in HI animals. Atomoxetine also improved sustained attention and vigilance in LA animals, and reduced response disinhibition and premature responding in HI animals. This is the first study using adult rats to demonstrate the translational value of the 5C-CPT to select subgroups of rats, which may be used to model the subtypes observed in adult ADHD. Our findings suggest that this as an important paradigm to increase our understanding of the neurobiological underpinnings of adult ADHD-subtypes and their response to pharmacotherapy. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

34 CFR 200.7 - Disaggregation of data.

Code of Federal Regulations, 2010 CFR

2010-07-01

... disabilities as defined in section 9101(5) of the Act; and students with limited English proficiency as defined... inclusion of all students and student subgroups in § 200.13(b)(7)(ii); and (C) Information regarding the.... (c) Inclusion of subgroups in assessments. If a subgroup under § 200.2(b)(10) is not of sufficient...

Complexities of follicle deviation during selection of a dominant follicle in Bos taurus heifers.

PubMed

Ginther, O J; Baldrighi, J M; Siddiqui, M A R; Araujo, E R

2016-11-01

Follicle deviation during a follicular wave is a continuation in growth rate of the dominant follicle (F1) and decreased growth rate of the largest subordinate follicle (F2). The reliability of using an F1 of 8.5 mm to represent the beginning of expected deviation for experimental purposes during waves 1 and 2 (n = 26 per wave) was studied daily in heifers. Each wave was subgrouped as follows: standard subgroup (F1 larger than F2 for 2 days preceding deviation and F2 > 7.0 mm on the day of deviation), undersized subgroup (F2 did not attain 7.0 mm by the day of deviation), and switched subgroup (F2 larger than F1 at least once on the 2 days before or on the day of deviation). For each wave, mean differences in diameter between F1 and F2 changed abruptly at expected deviation in the standard subgroup but began 1 day before expected deviation in the undersized and switched subgroups. Concentrations of FSH in the wave-stimulating FSH surge and an increase in LH centered on expected deviation did not differ among subgroups. Results for each wave indicated that (1) expected deviation (F1, 8.5 mm) was a reliable representation of actual deviation in the standard subgroup but not in the undersized and switched subgroups; (2) concentrations of the gonadotropins normalized to expected deviation were similar among the three subgroups, indicating that the day of deviation was related to diameter of F1 and not F2; and (3) defining an expected day of deviation for experimental use should consider both diameter of F1 and the characteristics of deviation. Copyright © 2016 Elsevier Inc. All rights reserved.

A food frequency questionnaire validated for estimating dietary flavonoid intake in an Australian population.

PubMed

Somerset, Shawn; Papier, Keren

2014-01-01

Flavonoids, a broad category of nonnutrient food components, are potential protective dietary factors in the etiology of some cancers. However, previous epidemiological studies showing associations between flavonoid intake and cancer risk have used unvalidated intake assessment methods. A 62-item food frequency questionnaire (FFQ) based on usual intake of a representative Australian adult population sample was validated against a 3-day diet diary method in 60 young adults. Spearman's rank correlations showed 17 of 25 individual flavonoids, 3 of 5 flavonoid subgroups, and total flavonoids having strong/moderate correlation coefficients (0.40-0.70), and 8 of 25 individual flavonoids and 2 of 5 flavonoid subgroups having weak/insignificant correlations (0.01-0.39) between the 2 methods. Bland-Altman plots showed most subjects within ±1.96 SD for intakes of flavonoid subgroups and total flavonoids. The FFQ classified 73-90% of participants for all flavonoids except isorhamnetin, cyanidin, delphinidin, peonidin, and pelargonidin; 73.3-85.0% for all flavonoid subgroups except Anthocyanidins; and 86.7% for total flavonoid intake in the same/adjacent quartile determined by the 3-day diary. Weighted kappa values ranged from 0.00 (Isorhamnetin, Pelargonidin) to 0.60 (Myricetin) and were statistically significant for 18 of 25 individual flavonoids, 3 of 5 subgroups, and total flavonoids. This FFQ provides a simple and inexpensive means to estimate total flavonoid and flavonoid subgroup intake.

Evaluation of the zoonotic potential of multiple subgroups of clade 2.3.4.4 influenza A (H5N8) virus.

PubMed

Lee, Yu-Na; Lee, Eun-Kyoung; Song, Byung-Min; Heo, Gyeong-Beom; Woo, Sang-Hee; Cheon, Sun-Ha; Lee, Youn-Jeong

2018-03-01

Clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs in South Korea; group A evolved further into four subgroups. Here, we examined the zoonotic potential, both in vivo and in vitro, of genetically distinct subgroups of H5N8 HPAIVs isolated in South Korea. When compared with other subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe disease in mice at high doses. In ferrets, all H5N8 viruses replicated restrictively in the respiratory tract and did not induce significant clinical signs of influenza infection. In vitro studies, all viruses displayed a hemagglutinin phenotype that was poorly adapted for infection of mammals, although the H2102 virus exhibited higher replication kinetics at 33°C than the others. Although H5N8 HPAIVs have not yet acquired all the characteristics required for adaptation to mammals, their ability to evolve continuously underscores the need for timely risk assessment. Copyright © 2018 Elsevier Inc. All rights reserved.

Amniotic Fluid-Derived Mesenchymal Stem Cells Cut Short the Acuteness of Cisplatin-Induced Nephrotoxicity in Sprague-Dawley Rats.

PubMed

Al-Husseiny, Fatma; Sobh, Mohamed Ahmed; Ashour, Rehab H; Foud, Samah; Medhat, Tarek; El-Gilany, Abdel-Hady; Elghannam, Doaa; Abdel-Ghaffar, Hassan; Saad, Mohamed-Ahdy; Sobh, Mohamed

2016-05-30

Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×10⁶ hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.

Results of a randomized trial comparing high-dose chemotherapy plus Auto-SCT and R-FC in CLL at diagnosis.

PubMed

Magni, M; Di Nicola, M; Patti, C; Scimè, R; Mulè, A; Rambaldi, A; Intermesoli, T; Viero, P; Tarella, C; Gueli, A; Bergui, L; Trentin, L; Barzan, A; Benedetti, F; Ambrosetti, A; Di Raimondo, F; Chiarenza, A; Parvis, G; Billio, A; Attolico, I; Olivieri, A; Montanari, M; Carlo-Stella, C; Matteucci, P; Devizzi, L; Guidetti, A; Viviani, S; Valagussa, P; Gianni, A M

2014-04-01

The importance of early therapy intensification in B-cell CLL (B-CLL) patients remains to be defined. Even though several studies have been published, no randomized trials comparing directly autologous stem cell transplant (ASCT) and the accepted conventional therapy (that is, rituximab, fludarabine and CY; R-FC) have been reported so far. To assess the benefit of a first-line aggressive therapy, we designed a multicenter, randomized, phase 3 trial comparing R-FC and high-dose chemotherapy supported by ASCT in patients under 65 years of age, with stage B(II) or C B-CLL. Primary end point was CR: 96 patients were enrolled (48 in each arm). On an intent-to-treat basis, the CR rates in the ASCT and R-FC arms were 62.5% and 58%, respectively. After 5 years of follow-up, PFS was 60.4% in the ASCT arm and 65.1% in the R-FC arm, time to progression 65.8 and 70.5%, and overall survival 88% vs 88.1%, respectively. Our trial demonstrates, for the first time in a randomized manner, that frontline ASCT does not translate into a survival advantage when compared with benchmark chemoimmunotherapy in B-CLL patients; the possibility of its clinical benefit in certain subgroups remains uncertain.

[Evaluation of bone structure and quality of ovariectomized rats by microcrack].

PubMed

Dai, Ru-chun; Liao, Er-yuan; Yang, Chuan

2003-12-01

To compare microcrack with bone mineral desity (BMD), bone histomorphometry and biomechanics parameters, and to investigate the potential of microcrack in the evaluation of bone biomechanical quality. Eight 10-month-old Sprague-Dawley rats were served as baseline controls, and 90 10-month-old rats were randomly divided into A, B, and C groups. Each group comprised ovariectomized (OVX), 17 beta-estradiol treated [EST, 10 micro/(kg x d)] and sham-operated (SHAM) subgroups. Rats from groups A,B and C were killed at the 3rd, 15th and 21st week post-operatively. Total body and lumbar vertebral BMD were measured before being killed, and BMD of isolated lumbar vertebrae and tibiae were measured after killing. Bone histomorphometry of the proximal end of isolated right tibia was performed,and compression test was carried out on the isolated 5th lumbar vertebra (L5). After fatigue damage, the isolated 4th lumbar vertebra was stained by en bloc basic fuchsin staining, and microcrack density (Cr. Dn) and microcrack surface density (Cr. SDn) were de- termined on the bone tissue sections. Bone parameters in each subgroup of rats were observed at different time. (1) At the 15th and 21st week post-operatively, multi-part BMD, Cr. Dn and Cr. SDn were higher than those at the 3rd week. (2) At the 15th week, trabecular separation (Tb. Sp) increased, trabecular number (Tb. N) decreased, and the maximum loading level and elastic modulus of vertebra reached the peak. (3) At the 3rd week, Tb. Sp, Cr. Dn and Cr. SDn in the OVX subgroup were greater than those in the EST subgroup, while the percentage of trabecular area (TbTr) in the OVX subgroup was lower than that of the EST and SHAM subgroups. No changes of BMDs and biomechanic parameters were observed among the three subgroups. (4) At the 15th week, multi-part BMD and maximum loading level in the OVX and EST subgroups were lower than those in the SHAM subgroup, while elastic modulus, bone histomorphometry parameters, Cr. Dn and Cr. SDn had no change among the three subgroups. (5) At the 21st week, multi-part BMDs, Tb. N and TbTr in the OVX subgroup were smaller than those in the EST and SHAM subgroups. Tb. Sp, bone formation rate, mineral apposition rate, percent labeled perimeter,Cr. Dn and Cr. SDn in the OVX subgroups were greater than those in the EST and SHAM subgroups. Maximum loading level and elastic modulus of vertebra in EST and OVX subgroups were lower than those in the SHAM subgroup. There were no significant differences in all of these parameters Microcrack can be regarded as an alterative between the EST and the SHAM subgroup. Conclusion parameter in the evaluation of bone biomechanical quality.

International travel patterns and travel risks for stem cell transplant recipients.

PubMed

Mikati, Tarek; Griffin, Kenneth; Lane, Dakotah; Matasar, Matthew; Shah, Monika K

2015-01-01

Stem cell transplantation (SCT) is being increasingly utilized for multiple medical illnesses. However, there is limited knowledge about international travel patterns and travel-related illnesses of stem cell transplant recipients (SCTRs). An observational cross-sectional study was conducted among 979 SCTRs at Memorial Sloan Kettering Cancer Center using a previously standardized and validated questionnaire. International travel post SCT, pre-travel health advice, exposure risks, and travel-related illnesses were queried. A total of 516 SCTRs completed the survey (55% response rate); of these, 40% were allogeneic SCTRs. A total of 229 (44.3%) respondents reported international travel outside the United States and Canada post SCT. The international travel incidence was 32% [95% confidence interval CI 28-36] within 2 years after SCT. Using multivariable Cox regression analysis, variables significantly associated with international travel within first 2 years after SCT were history of international travel prior to SCT [hazard ratio (HR) = 5.3, 95% CI 2.3-12.0], autologous SCT (HR = 2.6, 95% CI 1.6-2.8), foreign birth (HR = 2.3, 95% CI 1.5-3.3), and high income (HR = 2.0, 95% CI 1.8-3.7). During their first trip, 64 travelers (28%) had traveled to destinations that may have required vaccination or malaria chemoprophylaxis. Only 56% reported seeking pre-travel health advice. Of those who traveled, 16 travelers (7%) became ill enough to require medical attention during their first trip after SCT. Ill travelers were more likely to have visited high-risk areas (60 vs 26%, p = 0.005), to have had a longer mean trip duration (24 vs 12 days, p = 0.0002), and to have visited friends and relatives (69 vs 21%, p < 0.0001). International travel was common among SCTRs within 2 years after SCT and was mainly to low-risk destinations. Although the overall incidence of travel-related illnesses was low, certain subgroups of travelers were at a significantly higher risk. Pre-travel health counseling and interventions were suboptimal. © 2014 International Society of Travel Medicine.

Clinicopathological features and treatment outcomes of brain stem gliomas in Saudi population

PubMed Central

Bayoumi, Yasser; Sabbagh, Abdulrahman J; Mohamed, Reham; ElShokhaiby, Usama M; Maklad, Ahmed Marzouk; Tunio, Mutahir A; Balbaid, Ali Abdullah O

2014-01-01

AIM: To analyze experiences to identify treatment outcomes and prognostic factors in a Saudi population. METHODS: Medical records of patients with brainstem gliomas treated from July 2001 to December 2012 were reviewed to identify treatment outcomes of surgery, radiation therapy and chemotherapy and associated prognostic factors in a Saudi population. RESULTS: We analyzed 49 brain stem glioma (BSG) patients from July 2001 to December 2012; 31 of them were males (63.3%) with a median age of 12.6 years (range: 8-64 mo). Twenty-two patients (44.9%) had diffuse intrinsic pontine gliomas (DIPG) and 15 (30.6%) presented with focal/tectal BSG. Histopathology was available in 30 patients (61.2%). Median survival time for the whole cohort was 1.5 years. One and two year OS rates were 51.1% and 41.9% respectively. Two year OS rates for focal/tectal, dorsally exophytic, cervicomedullary and DIPG tumors were 60%, 33.3%, 33.3% and 13.6% respectively (P < 0.0001). Significant prognostic factors related to OS were age at diagnosis (worse for > 18 years) P = 0.01, KPS < 70 P = 0.02, duration of symptoms (< 60 d) P = 0.002, histology (better for favorable) P = 0.002, surgery (maximal resection) P = 0.002, and concurrent chemotherapy with radiation therapy in DIPG (better if given) P = 0.01. CONCLUSION: BSG, especially the DIPG subgroup, had a dismal prognosis, needing more aggressive neurosurgical, radiation and chemotherapy techniques, while focal and tectal tumors were found to have a better prognosis. PMID:25493242

Stem cell plasticity enables hair regeneration following Lgr5+ cell loss.

PubMed

Hoeck, Joerg D; Biehs, Brian; Kurtova, Antonina V; Kljavin, Noelyn M; de Sousa E Melo, Felipe; Alicke, Bruno; Koeppen, Hartmut; Modrusan, Zora; Piskol, Robert; de Sauvage, Frederic J

2017-06-01

Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5 + (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5 + cells in mice abrogates hair regeneration but this is reversible. During recovery, CD34 + (CD34 antigen) stem cells activate inflammatory response programs and start dividing. Pharmacological attenuation of inflammation inhibits CD34 + cell proliferation. Subsequently, the Wnt pathway controls the recovery of Lgr5 + cells and inhibition of Wnt signalling prevents Lgr5 + cell and hair germ recovery. Thus, our study uncovers a compensatory relationship between two stem cell populations and the underlying molecular mechanisms that enable hair follicle regeneration.

Molecular phylogenetic study in genus Hydra.

PubMed

Kawaida, Hitomi; Shimizu, Hiroshi; Fujisawa, Toshitaka; Tachida, Hidenori; Kobayakawa, Yoshitaka

2010-11-15

Among 8000-9000 species of Cnidaria, only several dozens of species of Hydrozoa have been found in the fresh water. Hydra is such a fresh water polyp and has been used as a good material for research in developmental biology, regeneration and pattern formation. Although the genus Hydra has only a few ten species, its distribution is cosmopolitan. The phylogenetic relationship between hydra species is fascinating from the aspect of evolutionary biology and biogeography. However, only a few molecular phylogenetic studies have been reported on hydra. Therefore, we conducted a molecular phylogenetic study of the genus Hydra based on mitochondrial and nuclear nucleotide sequences using a hydra collection that has been kept in the National Institute of Genetics (NIG) of Japan. The results support the idea that four species groups comprise the genus Hydra. Within the viridissima group (green hydra) and braueri group, genetic distances between strains were relatively large. In contrast, genetic distances between strains among the vulgaris and oligactis groups were small irrespective of their geographic distribution. The vulgaris group strains were classified at least (as far as our investigated samples) into three sub-groups, vulgaris sub-group, carnea sub-group, and H. sp. (K5 and K6) sub-group. All of the vulgaris sub-group and H. sp. (K5 and K6) sub-group strains were collected in Eurasia. The carnea sub-group strains in NIG collection were all collected in North America. A few newly collected samples in Japan, however, suggested belonging to the carnea sub-group according to the molecular phylogenic analysis. This suggests a trans-Pacific distribution of the carnea sub-group hydra. Copyright © 2010 Elsevier B.V. All rights reserved.

Autologous hematopoietic stem cell transplantation in extranodal natural killer/T cell lymphoma: a multinational, multicenter, matched controlled study.

PubMed

Lee, Jeeyun; Au, Wing-Yan; Park, Min Jae; Suzumiya, Junji; Nakamura, Shigeo; Kameoka, Jun-Ichi; Sakai, Chikara; Oshimi, Kazuo; Kwong, Yok-Lam; Liang, Raymond; Yiu, Harry; Wong, Kam-Hung; Cheng, Hoi-Ching; Ryoo, Baek-Yeol; Suh, Cheolwon; Ko, Young Hyeh; Kim, Kihyun; Lee, Jae-Won; Kim, Won Seog; Suzuki, Ritsuro

2008-12-01

Extranodal natural killer (NK)/T cell lymphoma, nasal type, is a recently recognized distinct entity and the most common type of non-B cell extranodal lymphoma in Asia. This retrospective analysis studied the potential survival benefits of hematopoeitic stem cell transplantation (HSCT) compared with a historical control group. A total of 47 patients from 3 previously published series of HSCT were matched according to NK/T cell lymphoma International Prognostic Index (NKIPI) risk groups and disease status at transplantation with 107 patients from a historical control group for analysis. After a median follow-up of 116.5 months, the median survival time was not determined for the HSCT group, but it was 43.5 months for the control group (95% confidence interval [CI] = 6.7 to 80.3 months; P = .127, log-rank test). In patients who were in complete remission (CR) at the time of HSCT or at surveillance after remission, disease-specific survival rates were significantly higher in the HSCT group compared with the control group (disease-specific 5-year survival rate, 87.3% for HSCT vs 67.8% for non-HSCT; P = .027). In contrast, in subgroup analysis on non-CR patients at the time of HSCT or non-HSCT treatment, disease-specific survival rates were not significantly prolonged in the HSCT group compared with the control group (1-year survival rate, 66.7% for HSCT vs 28.6% for non-HSCT; P = .141). The impact of HSCT on the survival of all patients was significantly retained at the multivariate level with a 2.1-fold (95% CI =1.2- to 3.7-fold) reduced risk of death (P = .006). HSCT seems to confer a survival benefit in patients who attained CR on postremission consolidation therapy. These findings suggest that, in particular, patients in CR with high NKIPI risk scores at diagnosis should receive full consideration for HSCT.

Efficiency of allogeneic hematopoietic SCT from HLA fully-matched non-sibling relatives: a new prospect of exploiting extended family search.

PubMed

Hamidieh, A A; Dehaghi, M Ostadali; Paragomi, P; Navaei, S; Jalali, A; Eslami, G Ghazizadeh; Behfar, M; Ghavamzadeh, A

2015-04-01

The best donors for hematopoietic SCT (HSCT) are fully-matched siblings. In patients without fully-matched siblings, HLA registries or cord blood banks are alternative strategies with some restrictions. Owing to the high rate of consanguineous marriage in our country, between 2006 and 2013, extended family searches were undertaken in Hematology-Oncology Research Center and Stem Cell Transplantation (HORCSCT), Tehran, Iran, in 523 HSCT candidates with parental consanguinity and no available HLA identical sibling. Fully-matched other-relative donors were found for 109 cases. We retrospectively studied the HSCT outcome in these patients. Median time to neutrophil engraftment was 13 days (range: 9-31days). In 83 patients, full chimerism and in 17 patients, mixed chimerism was achieved. Acute GvHD (aGvHD) grade II-IV appeared in 36 patients (33%). The frequency of aGvHD development in various familial subgroups was NS. Five patients expired before day+100. In the surviving 104 cases, chronic GvHD developed in 20 patients (19.2%). The distantly related subgroup had significantly a higher rate of cGvHD (P=0.04). The 2-year OS and disease-free survival (DFS) were 76.7±4.5% and 71.7±4.7%, respectively. No significant difference in OS (P=0.30) and DFS (P=0.80) was unraveled between various familial relationships. Our considerable rate of fully-matched non-sibling family members and the favorable outcome support the rationale for extended family search in regions where consanguineous marriage is widely practiced.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L.

PubMed

Lee, You-Jeong; Kim, Chung-Hoon; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-11-01

To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L

PubMed Central

Lee, You-Jeong; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-01-01

Objective To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. Methods This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). Results The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). Conclusion TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH. PMID:25469340

Comparative Analysis of the Mechanical Properties between the Fiber-Reinforced Composite and Zirconium Posts.

PubMed

Jurukovska-Shotarovska, Vesna; Kapusevska, Biljana

2015-01-01

To make a comparative analysis of the mechanical properties between FRC and zirconium posts Methods: The patients with FRC and zirconium posts were divided in two groups with three subgroups, each of them composed of 10 samples. Subgroup I with 1.2 mm; Subgroup II with 1.35 mm and Subgroup III with 1.5 mm post diameter. The fracture force, bending and tensile strength of each group were measured with Shimadzu Universal Testing Machine. The fracture force for the first group measured in the first, second and third subgroup was 34.80900N; 67.15390N; 46.53100N and for the second group, first, second and third subgroup was 34.80900N; 46.53100N; 67.15390N correspondingly. The bending strength for the first group measured in the first, second and third subgroup was 401.4420N; 444.6425N; 333.6828N and for the second group, first, second and third subgroup was 307.9352N; 289.1030N; 304.1649N correspondingly. The tensile strength for the first group measured in the first, second and third subgroup was 5.442267N; 4.350545N; 2.943465N and for the second group, first, second and third subgroup was 4.224141N; 3.751466N; 3.168756N correspondingly. The longest diameter of the posts significantly increases the resistance to fracture in relation to the two smaller diameters. The larger diameter, the higher values of the bending strength, as well as the lowest values of the tensile strength of the material contribute to improved mechanical properties of the fiber and zirconium posts.

Efficacy of Tofacitinib for the Treatment of Moderate-to-Severe Chronic Plaque Psoriasis in Patient Subgroups from Two Randomised Phase 3 Trials.

PubMed

Menter, M Alan; Papp, Kim A; Cather, Jennifer; Leonardi, Craig; Pariser, David M; Krueger, James G; Wohlrab, Johannes; Amaya-Guerra, Mario; Kaszuba, Andrzej; Nadashkevich, Oleg; Tsai, Tsen-Fang; Gupta, Pankaj; Tan, Huaming; Valdez, Hernan; Mallbris, Lotus; Tatulych, Svitlana

2016-05-01

Tofacitinib is a Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis. We report efficacy of tofacitinib in patient subgroups based on pooled data from two Phase 3 trials (NCT01276639, NCT01309737).
To assess consistency of treatment effects of tofacitinib versus placebo in subgroups defined by baseline characteristics, and to ascertain whether baseline characteristics are of value in optimizing tofacitinib use.
Pooled data from the two trials were used to evaluate ≥75% reduction in PASI from baseline (PASI75 response) in subgroups defined by age, age at psoriasis onset, gender, race, geographical region, weight, body mass index, diabetes, metabolic syndrome, tobacco/alcohol use, psoriatic arthritis, disease activity, and prior therapy.
Week 16 PASI75 response rates (N=1843) were 43%, 59% and 9% with tofacitinib 5 and 10mg twice daily (BID) and placebo, respectively (each P<0.0001 versus placebo). Tofacitinib 5 and 10mg BID were effective regardless of baseline characteristics. Across subgroups, tofacitinib generally produced greater response rates with the 10 versus 5mg BID dosage. Lower absolute response rates were seen in heavier patients and patients with prior biologic experience.
Both tofacitinib dosages demonstrated consistent efficacy versus placebo across subgroups. Lower response rates were seen in heavier patients and those with prior biologic experience. Tofacitinib 10mg BID resulted in a substantial proportion of responders regardless of baseline characteristics.

J Drugs Dermatol. 2016;15(5):568-580.

Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia.

PubMed

Kuzmina, Zoya; Greinix, Hildegard T; Weigl, Roman; Körmöczi, Ulrike; Rottal, Arno; Frantal, Sophie; Eder, Sandra; Pickl, Winfried F

2011-02-17

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19(+) B cells (165 vs 454 vs 417 × 10⁶L) with elevated CD19(+)CD21(low) immature (16.5%, 7.7%, and 9.1%) and CD19(+)CD21(int-high)CD38(high)IgM(high) transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19(+)CD10(-)CD27(-)CD21(high) naive B cells were highly elevated in all patients with cGVHD. CD19(+)CD27(+)IgD(+) non-class-switched (4 vs 12 vs 11 × 10⁶/L) and class-switched (7 vs 35 vs 42 × 10⁶/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.

A and B antigen levels acquired by group O donor-derived erythrocytes following ABO-non-identical transfusion or minor ABO-incompatible haematopoietic stem cell transplantation.

PubMed

Hult, A K; Dykes, J H; Storry, J R; Olsson, M L

2017-06-01

ABO-incompatible haematopoietic stem cell transplantation (HSCT) presents a challenge to blood component transfusion. The aim of this study was to investigate the weak blood group A or B antigen expression by donor-derived group O red blood cells (RBC) observed following transfusion or minor ABO-incompatible HSCT. In addition, in vitro experiments were performed to elucidate possible mechanisms underlying this phenomenon. A sensitive flow cytometry assay for the semi-quantification of RBC A/B antigen levels was used to assess patient samples and evaluate in vitro experiments. Analysis of blood samples from patients, originally typed as A, B and AB but recently transplanted or transfused with cells from group O donors, revealed the A antigen expression on donor-derived RBC, ranging from very low levels in non-secretor individuals to almost subgroup A x -like profiles in group A secretors. The B antigen expression was less readily detectable. In vitro experiments, in which group O donor RBC were incubated with (i) group A/B secretor/non-secretor donor plasma or (ii) group A/B donor RBC in the absence of plasma, supported the proposed adsorption of A/B antigen-bearing glycolipids from secretor plasma but also indicated a secretor-independent mechanism for A/B antigen acquisition as well as direct cell-to-cell transfer of ABO antigens. The in vivo conversion of donor-derived blood group O RBC to ABO subgroup-like RBC after transfusion or minor ABO-incompatible HSCT raises the question of appropriate component selection. Based on these data, AB plasma should be transfused following ABO-incompatible HSCT. © 2017 British Blood Transfusion Society.

SILAC proteomics of planarians identifies Ncoa5 as a conserved component of pluripotent stem cells.

PubMed

Böser, Alexander; Drexler, Hannes C A; Reuter, Hanna; Schmitz, Henning; Wu, Guangming; Schöler, Hans R; Gentile, Luca; Bartscherer, Kerstin

2013-11-27

Planarian regeneration depends on the presence of pluripotent stem cells in the adult. We developed an in vivo stable isotope labeling by amino acids in cell culture (SILAC) protocol in planarians to identify proteins that are enriched in planarian stem cells. Through a comparison of SILAC proteomes of normal and stem cell-depleted planarians and of a stem cell-enriched population of sorted cells, we identified hundreds of stem cell proteins. One of these is an ortholog of nuclear receptor coactivator-5 (Ncoa5/CIA), which is known to regulate estrogen-receptor-mediated transcription in human cells. We show that Ncoa5 is essential for the maintenance of the pluripotent stem cell population in planarians and that a putative mouse ortholog is expressed in pluripotent cells of the embryo. Our study thus identifies a conserved component of pluripotent stem cells, demonstrating that planarians, in particular, when combined with in vivo SILAC, are a powerful model in stem cell research. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma

PubMed Central

Balakrishnan, Ilango; Harris, Peter; Birks, Diane K; Griesinger, Andrea; Amani, Vladimir; Cristiano, Brian; Remke, Marc; Taylor, Michael D; Handler, Michael; Foreman, Nicholas K; Vibhakar, Rajeev

2014-01-01

Medulloblastoma is a pediatric brain tumor with a variable prognosis due to clinical and genomic heterogeneity. Among the 4 major genomic sub-groups, patients with MYC amplified tumors have a particularly poor prognosis despite therapy with surgery, radiation and chemotherapy. Targeting the MYC oncogene has traditionally been problematic. Here we report that MYC driven medulloblastoma can be targeted by inhibition of the bromodomain protein BRD4. We show that bromodomain inhibition with JQ1 restricts c-MYC driven transcriptional programs in medulloblastoma, suppresses medulloblastoma cell growth and induces a cell cycle arrest. Importantly JQ1 suppresses stem cell associated signaling in medulloblastoma cells and inhibits medulloblastoma tumor cell self-renewal. Additionally JQ1 also promotes senescence in medulloblastoma cells by activating cell cycle kinase inhibitors and inhibiting activity of E2F1. Furthermore BRD4 inhibition displayed an anti-proliferative, pro-senescence effect in a medulloblastoma model in vivo. In clinical samples we found that transcriptional programs suppressed by JQ1 are associated with adverse risk in medulloblastoma patients. Our work indicates that BRD4 inhibition attenuates stem cell signaling in MYC driven medulloblastoma and demonstrates the feasibility BET domain inhibition as a therapeutic approach in vivo. PMID:24796395

Evaluation of effects of busulfan and DMA on SOS in pediatric stem cell recipients.

PubMed

Kerl, Kornelius; Diestelhorst, Christian; Bartelink, Imke; Boelens, Jaap; Trame, Mirjam N; Boos, Joachim; Hempel, Georg

2014-02-01

Busulfan (Bu) is a DNA-alkylating agent used for myeloablative conditioning in stem cell transplantation in children and adults. While the use of intravenous rather than oral administration of Bu has reduced inter-individual variability in plasma levels, toxicity still occurs frequently after hematopoietic stem cell transplantation (HSCT). Toxicity (especially hepatotoxic effects) of intravenous (IV) Bu may be related to both Bu and/or N,N-dimethylacetamide (DMA), the solvent of Bu. In this study, we assessed the relation between the exposure of Bu and DMA with regards to the clinical outcome in children from two cohorts. In a two-centre study Bu and DMA AUC (area under the curve) were correlated in pediatric stem cell recipients to the risk of developing SOS and to the clinical outcome. In patients receiving Bu four times per day Bu levels >1,500 µmol/L minute correlate to an increased risk of developing a SOS. In the collective cohort, summarizing data of all 53 patients of this study, neither high area under the curve (AUC) of Bu nor high AUC of DMA appears to be an independent risk factor for the development of SOS in children. In this study neither Bu nor DMA was observed as an independent risk factor for the development of SOS. To identify subgroups (e.g., infants), in which Bu or DMA might be risk factors for the induction of SOS, larger cohorts have to be evaluated. © 2013 Wiley Periodicals, Inc.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo.

PubMed

Alvero, Ayesha B; Heaton, Andrew; Lima, Eydis; Pitruzzello, Mary; Sumi, Natalia; Yang-Hartwich, Yang; Cardenas, Carlos; Steinmacher, Sahra; Silasi, Dan-Arin; Brown, David; Mor, Gil

2016-06-01

Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44(+)/MyD88(+) ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44(-)/MyD88(-) ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279-90. ©2016 AACR. ©2016 American Association for Cancer Research.

Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

PubMed

Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

2016-08-15

A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and Kopetz, p. 3989. ©2016 American Association for Cancer Research.

Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

PubMed Central

Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

2012-01-01

Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111) PMID:22058209

Divergent strains of human T-lymphotropic virus type 1 (HTLV-1) within the Cosmopolitan subtype in Argentina.

PubMed

Eirin, Maria E; Dilernia, Dario A; Berini, Carolina A; Jones, Leandro R; Pando, Maria A; Biglione, Mirna M

2008-10-01

HTLV-1 Cosmopolitan subtype Transcontinental subgroup A has been described among aboriginal communities from the northwest endemic area of Argentina. Moreover, Transcontinental subgroup A and the Japanese subgroup B were reported among blood donors from the nonendemic central region of the country. We carried out the first HTLV-1 phylogenetic study in individuals residing in Buenos Aires capital city. Phylogenetic analysis performed on the LTR region showed that all 44 new strains clustered within the Cosmopolitan subtype, with 42 (95.4%) belonging to Transcontinental subgroup A. Of them, 20 (45.5%) strains grouped in the large Latin American cluster and 4 (9.1%) in the small Latin American cluster. The majority of them belonged to individuals of nonblack origin, grouped with Amerindian strains. Three (6.8%) were closely related to South African references and two monophyletic clusters including only HIV/HTLV-1 coinfected individuals were observed. Interestingly, two (4.5%) new sequences (divergent strains) branched off from all five known Cosmopolitan subgroups in a well-supported clade. In summary, these findings show that HTLV-1 Cosmopolitan subtype Transcontinental subgroup A is infecting residents of Buenos Aires, a nonendemic area of Argentina, and confirm the introduction of divergent strains in the country.

Methane Flux of Amazonian Peatland Ecosystems: Large Ecosystem Fluxes with Substantial Contribution from Palm (maritia Flexuosa) STEM Emissions

NASA Astrophysics Data System (ADS)

Van Haren, J. L. M.; Cadillo-Quiroz, H.

2015-12-01

Methane (CH4) emissions through plants have long been known in wetlands. However, most measurements have focused on stem tops and leaves. Recently, measurements at the lower parts of stems have shown that stem emissions can exceed soil CH4 emissions in Asian peatlands (Pangala et al. 2013). The addition of stem fluxes to soil fluxes for total ecosystem fluxes has the potential to bridge the discrepancy between modeled to measured and bottom-up to top-down flux estimates. Our measurements in peatlands of Peru show that especially Mauritia flexuosa, a palm species, can emit very large quantities of CH4, although most trees emitted at least some CH4. We used flexible stem chambers to adapt to stems of any size above 5cm in diameter. The chambers were sampled in closed loop with a Gasmet DX4015 for flux measurements, which lasted ~5 minutes after flushing with ambient air. We found that M. flexuosa stem fluxes decrease with height along the stem and were positively correlated with soil fluxes. Most likely CH4 is transported up the stem with the xylem water. Measured M. flexuosa stem fluxes below 1.5m averaged 11.2±1.5 mg-C m-2 h-1 (±95% CI) with a maximum of 123±3.5 mg-C m-2 h-1 (±SE), whereas soil fluxes averaged 6.7±1.7 mg-C m-2 h-1 (±95% CI) with a maximum of 31.6±0.4 mg-C m-2 h-1 (±SE). Significant CH4 fluxes were measured up to 5 m height along the stems. Combined with the high density of ~150 M. flexuosa individuals per hectare in these peatlands and the consistent diameter of ~30cm, the high flux rates add ~20% to the soil flux. With anywhere between 1 and 5 billion M. flexuosa stems across Amazon basin wetlands, stem fluxes from this palm species could represent a major addition to the overall Amazon basin CH4 flux.

Vitamin D is a determinant of mouse intestinal Lgr5 stem cell functions.

PubMed

Peregrina, Karina; Houston, Michele; Daroqui, Cecilia; Dhima, Elena; Sellers, Rani S; Augenlicht, Leonard H

2015-01-01

Lgr5+ intestinal crypt base columnar cells function as stem cells whose progeny populate the villi, and Lgr5+ cells in which Apc is inactivated can give rise to tumors. Surprisingly, these Lgr5+ stem cell properties were abrogated by the lower dietary vitamin D and calcium in a semi-purified diet that promotes both genetically initiated and sporadic intestinal tumors. Inactivation of the vitamin D receptor in Lgr5+ cells established that compromise of Lgr5 stem cell function was a rapid, cell autonomous effect of signaling through the vitamin D receptor. The loss of Lgr5 stem cell function was associated with presence of Ki67 negative Lgr5+ cells at the crypt base. Therefore, vitamin D, a common nutrient and inducer of intestinal cell maturation, is an environmental factor that is a determinant of Lgr5+ stem cell functions in vivo. Since diets used in reports that establish and dissect mouse Lgr5+ stem cell activity likely provided vitamin D levels well above the range documented for human populations, the contribution of Lgr5+ cells to intestinal homeostasis and tumor formation in humans may be significantly more limited, and variable in the population, then suggested by published rodent studies. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Autism Spectrum Disorder and DSM-5: Spectrum or Cluster?].

PubMed

Kienle, Xaver; Freiberger, Verena; Greulich, Heide; Blank, Rainer

2015-01-01

Within the new DSM-5, the currently differentiated subgroups of "Autistic Disorder" (299.0), "Asperger's Disorder" (299.80) and "Pervasive Developmental Disorder" (299.80) are replaced by the more general "Autism Spectrum Disorder". With regard to a patient-oriented and expedient advising therapy planning, however, the issue of an empirically reproducible and clinically feasible differentiation into subgroups must still be raised. Based on two Autism-rating-scales (ASDS and FSK), an exploratory two-step cluster analysis was conducted with N=103 children (age: 5-18) seen in our social-pediatric health care centre to examine potentially autistic symptoms. In the two-cluster solution of both rating scales, mainly the problems in social communication grouped the children into a cluster "with communication problems" (51 % and 41 %), and a cluster "without communication problems". Within the three-cluster solution of the ASDS, sensory hypersensitivity, cleaving to routines and social-communicative problems generated an "autistic" subgroup (22%). The children of the second cluster ("communication problems", 35%) were only described by social-communicative problems, and the third group did not show any problems (38%). In the three-cluster solution of the FSK, the "autistic cluster" of the two-cluster solution differentiated in a subgroup with mainly social-communicative problems (cluster 1) and a second subgroup described by restrictive, repetitive behavior. The different cluster solutions will be discussed with a view to the new DSM-5 diagnostic criteria, for following studies a further specification of some of the ASDS and FSK items could be helpful.

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... to the degree of freedom from harmless extraneous vegetable material, stems, and portions thereof... the stem-flower axis. A defect is a unit where the angle of these two axes exceeds 45 degrees. (5... pitted olive equal to or exceeding the area of a circle 5 mm in diameter. (12) Stem means a stem that...

7 CFR 52.3761 - Defects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... to the degree of freedom from harmless extraneous vegetable material, stems, and portions thereof... the stem-flower axis. A defect is a unit where the angle of these two axes exceeds 45 degrees. (5... pitted olive equal to or exceeding the area of a circle 5 mm in diameter. (12) Stem means a stem that...

Molecular characterization of phytoplasma associated with four important ornamental plant species in India and identification of natural potential spread sources.

PubMed

Gopala; Rao, G P

2018-02-01

Phytoplasma suspected symptoms of phyllody, witches' broom, leaf yellowing, stunting and little leaf were observed in Chrysanthemum morifolium, Bougainvillea glabra, Jasminum sambac and Callistephus chinensis during survey of flower nurseries and experimental ornamental fields at Delhi, Maharashtra, Tamil Nadu and Karnataka from 2014 to 2016. Pleomorphic bodies typical to phytoplasma structures were observed in the phloem sieve elements of ultrathin sections of all the four symptomatic ornamental plants (stem tissue) in transmission electron microscope. Amplification of 1.8 and 1.2 kb phytoplasma DNA products was observed in all the four test plants in PCR assays using universal primer pairs P1/P7 followed by nested primer pair R16F2n/R16R2, respectively. Pairwise sequence comparison, phylogeny and virtual RFLP analysis of 16S rDNA sequences confirmed the association of two phytoplasma subgroups (16SrI-B and 16SrII-D) in four ornamental plant species. ' Ca. P. aurantifolia ' subgroup D (16SrII-D) was found associated with chrysanthemum phyllody and leaf yellowing at Delhi and Tamil Nadu, bougainvillea little leaf and yellowing at Delhi and Chinese aster phyllody at Bengaluru, Karnataka. However, jasmine little leaf and yellowing at Bengaluru, Karnataka and chrysanthemum stunting at Pune were found to be associated with ' Ca . P. asteris ' subgroup B-related strains (16SrI-B). The identification of 16SrII-D subgroup phytoplasma infecting bougainvillea and 16SrI-B subgroup infecting jasmine are the new reports to the world. Besides weed species, Cannabis sativa showing witches' broom in jasmine fields at Bengaluru and Parthenium hysterophorus showing witches' broom symptoms in chrysanthemum fields at Delhi were identified to be caused by phytoplasma strains classified under subgroups 16SrI-B and 16SrII-D, respectively, by PCR assays and 16Sr DNA sequence comparison analysis. Among the three major leafhopper species identified, only Hishimonas phycitis was identified positive for 16SrI-B and 16SrII-D subgroups of phytoplasmas from chrysanthemum fields at Delhi and jasmine fields at Bengaluru, respectively. The identity of similar phytoplasma strains infecting ornamental species in leafhopper and the weed species in the present study suggested that H. phycitis and weeds may act as potential natural sources for secondary spread of the identified phytoplasma strains.

The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthritic subchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein.

PubMed

Maxis, Kelitha; Delalandre, Aline; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Duval, Nicolas; Lajeunesse, Daniel

2006-01-01

Osteoarthritis (OA) is characterized by articular cartilage degradation and hypertrophic bone changes with osteophyte formation and abnormal bone remodeling. Two groups of OA patients were identified via the production of variable and opposite levels of prostaglandin E2 (PGE2) or leukotriene B4 (LTB4) by subchondral osteoblasts, PGE2 levels discriminating between low and high subgroups. We studied whether the expression of 5-lipoxygenase (5-LO) or 5-LO-activating protein (FLAP) is responsible for the shunt from prostaglandins to leukotrienes. FLAP mRNA levels varied in low and high OA groups compared with normal, whereas mRNA levels of 5-LO were similar in all osteoblasts. Selective inhibition of cyclooxygenase-2 (COX-2) with NS-398-stimulated FLAP expression in the high OA osteoblasts subgroup, whereas it was without effect in the low OA osteoblasts subgroup. The addition of PGE2 to the low OA osteoblasts subgroup decreased FLAP expression but failed to affect it in the high OA osteoblasts subgroup. LTB4 levels in OA osteoblasts were stimulated about twofold by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) plus transforming growth factor-beta (TGF-beta), a situation corresponding to their effect on FLAP mRNA levels. Treatments with 1,25(OH)2D3 and TGF-beta also modulated PGE2 production. TGF-beta stimulated PGE2 production in both OA osteoblast groups, whereas 1,25(OH)2D3 alone had a limited effect but decreased the effect of TGF-beta in the low OA osteoblasts subgroup. This modulation of PGE2 production was mirrored by the synthesis of COX-2. IL-18 levels were only slightly increased in a subgroup of OA osteoblasts compared with normal; however, no relationship was observed overall between IL-18 and PGE2 levels in normal and OA osteoblasts. These results suggest that the shunt from the production of PGE2 to LTB4 is through regulation of the expression of FLAP, not 5-LO, in OA osteoblasts. The expression of FLAP in OA osteoblasts is also modulated differently by 1,25(OH)2D3 and TGF-beta depending on their endogenous low and high PGE2 levels.

Different demographic, genetic, and longitudinal traits in language versus memory Alzheimer's subgroups.

PubMed

Mez, Jesse; Cosentino, Stephanie; Brickman, Adam M; Huey, Edward D; Mayeux, Richard

2013-01-01

The study's objective was to compare demographics, APOE genotypes, and rate of rise over time in functional impairment in neuropsychologically defined language, typical, and memory subgroups of clinical Alzheimer's disease (AD). 1,368 participants from the National Alzheimer's Coordinating Center database with a diagnosis of probable AD (CDR 0.5-1.0) were included. A language subgroup (n = 229) was defined as having language performance >1 SD worse than memory performance. A memory subgroup (n = 213) was defined as having memory performance >1 SD worse than language performance. A typical subgroup (n = 926) was defined as having a difference in language and memory performance of <1 SD. Compared with the memory subgroup, the language subgroup was 3.7 years older and more frequently self-identified as African American (OR = 3.69). Under a dominant genetic model, the language subgroup had smaller odds of carrying at least one APOEε4 allele relative to the memory subgroup. While this difference was present for all ages, it was more striking at a younger age (OR = 0.19 for youngest tertile; OR = 0.52 for oldest tertile). Compared with the memory subgroup, the language subgroup rose 35% faster on the Functional Assessment Questionnaire and 44% faster on CDR sum of boxes over time. Among a subset of participants who underwent autopsy (n = 98), the language, memory, and typical subgroups were equally likely to have an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences. The study demonstrates that a language subgroup of AD has different demographics, genetic profile, and disease course in addition to cognitive phenotype.

Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-11-1-0666 TITLE: Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation PRINCIPAL INVESTIGATOR...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation 5b. GRANT NUMBER...several different mouse tissues during the development of chronic gut inflammation. 5. SUBJECT TERMS inflammatory bowel disease; mesenchymal stem

The value of maximum jaw motion measurements for distinguishing between common temporomandibular disorder subgroups.

PubMed

Masumi, S; Kim, Y J; Clark, G T

2002-05-01

The purpose of this study was to determine if mandibular motion measurements could be used to distinguish between common temporomandibular disorder (TMD) subgroups that were established on the basis of only clinical signs and symptoms. Patients were 41 consecutive TMD clinic patients (31 women and 10 men). These patients were divided into 6 typical TMD subgroups. The subgroups were patients with (1) arthromyalgia, (2) arthromyalgia with disk condyle incoordination, (3) disk condyle incoordination only, (4) osteoarthritis, (5) suspected disk displacement without reduction, or (6) other diagnoses. There were no subjects in the other-diagnosis subgroup and only 1 subject with suspected disk displacement without reduction who was dropped without further consideration. The data for mean age showed that the osteoarthritis subgroup (n = 12) was statistically older (17 years) than the disk-condyle-incoordination-only subgroup (n = 11). The mean age of the other 2 groups, arthromyalgia (n = 11) and arthromyalgia with disk condyle incoordination (n = 6), was between the osteoarthritis and the disk-condyle-incoordination-only subgroups. For the 4 TMD subgroups whose data were analyzed, the mean differences between similar jaw opening measurements ranged from 6 to 8 mm with a standard deviation of approximately 8 to 10 mm. The mean left lateral motions were 0.5 to 1.3 mm larger than observed on the right. The widest mean jaw opening (56 mm) occurred in the disk-condyle-incoordination-only group. These differences were not found to be statistically significant. Analysis of opening, lateral and protrusive jaw motion data showed these measurements could not reliably differentiate between patients with osteoarthritis, arthromyalgia, arthromyalgia with disk condyle incoordination and disk condyle incoordination only.

40 CFR 180.544 - Methoxyfenozide; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 9 0.3 Vegetable, foliage of legume, except soybean, subgroup 7A 35 Vegetable, fruiting, group 8 2.0 Vegetable, leaves of root and tuber, group 2 30 Vegetable, legume, edible podded, subgroup 6A 1.5 Vegetable...

40 CFR 180.589 - Boscalid; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., fruiting, group 8 1.2 Vegetable, legume, edible podded, subgroup 6A 1.6 Vegetable, root, subgroup 1A... legume, group 7, forage 1.5 Vegetable, foliage of legume, group 7, hay 2.0 Vegetable, foliage of legume...

40 CFR 180.589 - Boscalid; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., fruiting, group 8 1.2 Vegetable, legume, edible podded, subgroup 6A 1.6 Vegetable, root, subgroup 1A... legume, group 7, forage 1.5 Vegetable, foliage of legume, group 7, hay 2.0 Vegetable, foliage of legume...

Arginine-supplemented enteral nutrition in critically ill diabetic and obese rats: a dose-ranging study evaluating nutritional status and macrophage function.

PubMed

Bonhomme, Sandra; Belabed, Linda; Blanc, Marie-Céline; Neveux, Nathalie; Cynober, Luc; Darquy, Sylviane

2013-01-01

Critically ill diabetic and obese patients are at high risk of complications. Arginine availability is lowered in diabetes and in stress situations, yet arginine is necessary for immune response, mainly by its action through nitric oxide (NO). These facts argue for arginine-supplemented diets in critically ill patients. However, studies have raised concerns about possible adverse effects of such diets in intensive-care patients. We therefore analyzed the metabolic and immunologic effects of an arginine-enriched diet in stressed diabetic-obese rats. Zucker Diabetic Fatty rats (fa/fa) were made endotoxemic by an intraperitoneal injection of lipopolysaccharide and then fed 4-d enteral nutrition enriched with arginine (ARG group) or a non-essential amino acid mix (NEAA group). The two groups each were subdivided into three subgroups: the ARG subgroups received 0.5 g (ARG0.5), 2 g (ARG2), and 5 g (ARG5) of arginine per kilogram daily, and the NEAA groups were made isonitrogenous with the corresponding ARG subgroups (NEAA0.5, NEAA2, and NEAA5). Plasma and urinary biomarkers were measured. Cytokine and NO production levels and inducible NO synthase and arginase protein levels were determined from peritoneal macrophages. The survival rate was lower in the ARG5 and NEAA5 subgroups than in all the other subgroups. The nitrogen balance was higher in the ARG5 group than in the NEAA5 group. Plasma triacylglycerol levels were lower in the ARG2 group than in the NEAA2 group. Interleukin-6, tumor necrosis factor-α, and NO production in the macrophages decreased and arginase-1 was upregulated in the ARG-treated rats. In this model, mortality was increased by the nitrogen burden rather than by arginine per se. Arginine improved nitrogen balance and had an anti-inflammatory action on macrophages by regulating NO production, probably through arginase-1 expression. Copyright © 2013 Elsevier Inc. All rights reserved.

Recent Advances in Lgr5+ Stem Cell Research.

PubMed

Leung, Carly; Tan, Si Hui; Barker, Nick

2018-05-01

The discovery of leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) as both a marker of adult stem cells and a critical modulator of their activity via its role as an effector of Wnt/R-spondin (Rspo) signaling has driven major advances in our understanding of stem cell biology during homeostasis, regeneration, and disease. Exciting new mouse and organoid culture models developed to study the endogenous behavior of Lgr5-expressing cells in health and disease settings have revealed the existence of facultative stem cell populations responsible for tissue regeneration, cancer stem cells (CSCs) driving metastasis in the gut, and Lgr5 + niche cells in the lung. Here we review these recent advances and discuss their impact on efforts to harness the therapeutic potential of adult stem cells and their cancer counterparts in the clinic. Copyright © 2018 Elsevier Ltd. All rights reserved.

Small and similar amounts of micromotion in an anatomical stem and a customized cementless femoral stem in regular-shaped femurs. A 5-year follow-up randomized RSA study.

PubMed

Nysted, Mona; Foss, Olav A; Klaksvik, Jomar; Benum, Pål; Haugan, Kristin; Husby, Otto Schnell; Aamodt, Arild

2014-04-01

High primary stability is important for long-term survival of uncemented femoral stems. Different stem designs are currently in use. The ABG-I is a well-documented anatomical stem with a press-fit design. The Unique stem is designed for a tight customized fit to the cortical bone of the upper femur. This implant was initially developed for patients with abnormal anatomy, but the concept can also be used in patients with normal femoral anatomy. We present 5-year radiostereometric analysis (RSA) results from a randomized study comparing the ABG-I anatomical stem with the Unique femoral stem. 100 hips with regular upper femur anatomy were randomized to either the ABG-I stem or the Unique femoral stem. RSA measurements were performed postoperatively and after 3, 6, 12, 24, and 60 months. RSA measurements from 80 hips were available for analysis at the 5-year follow-up. Small amounts of movement were observed for both stems, with no statistically significant differences between the 2 types. No improvement in long-term stability was found from using a customized stem design. However, no patients with abnormal geometry of the upper femur were included in this study.

Comparison of survival outcome between donor types or stem cell sources for childhood acute myeloid leukemia after allogenic hematopoietic stem cell transplantation: A multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-oncology.

PubMed

Shim, Ye Jee; Lee, Jae Min; Kim, Heung Sik; Jung, Nani; Lim, Young Tak; Yang, Eu Jeen; Hah, Jeong Ok; Lee, Young-Ho; Chueh, Hee Won; Lim, Jae Young; Park, Eun Sil; Park, Jeong A; Park, Ji Kyoung; Park, Sang Kyu

2018-06-19

We compared transplant outcomes between donor types and stem cell sources for childhood acute myeloid leukemia (AML). The medical records of children with AML in the Yeungnam region of Korea from January 2000 to June 2017 were reviewed. In all, 76 children with AML (male-to-female ratio = 46:30) received allogenic hematopoietic stem cell transplantation (allo-HSCT). In total, 29 patients received HSCT from either a matched-related donor or a mismatched-related donor, 32 patients received an unrelated donor, and 15 patients received umbilical cord blood. In term of stem cell sources, bone marrow was used in 15 patients and peripheral blood in 46 patients. For all HSCT cases, the 5-year overall survival (OS) was 73.1% (95% CI: 62.7-83.5) and the 5-year event-free survival (EFS) was 66.1% (95% CI: 54.5-77.7). There was no statistical difference in 5-year OS according to the donor types or stem cell sources (P = .869 and P = .911). There was no statistical difference in 5-year EFS between donor types or stem cell sources (P = .526 and P = .478). For all HSCT cases, the 5-year relapse rate was 16.1% (95% CI: 7.3-24.9) and the 5-year non-relapse mortality (NRM) was 13.3% (95% CI: 5.1-21.5). There was no statistical difference in the 5-year relapse rate according to the donor types or stem cell sources (P = .971 and P = .965). There was no statistical difference in the 5-year NRM between donor types or stem cell sources (P = .461 and P = .470). © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Programming Retinal Stem Cells into Cone Photoreceptors

DTIC Science & Technology

2015-12-01

AWARD NUMBER: W81XWH-14-1-0566 TITLE: Programming Retinal Stem Cells into Cone Photoreceptors PRINCIPAL INVESTIGATOR: Joseph A. Brzezinski IV...SUBTITLE 5a. CONTRACT NUMBER Programming Retinal Stem Cells into Cone Photoreceptors 5b. GRANT NUMBER W81XWH-14-1-0566 5c. PROGRAM ELEMENT NUMBER 6...to program human stem cells directly into cones. Using RNA-seq, we identified several genes that are upregulated in advance of the earliest

Data-Driven Subclassification of Speech Sound Disorders in Preschool Children

PubMed Central

Vick, Jennell C.; Campbell, Thomas F.; Shriberg, Lawrence D.; Green, Jordan R.; Truemper, Klaus; Rusiewicz, Heather Leavy; Moore, Christopher A.

2015-01-01

Purpose The purpose of the study was to determine whether distinct subgroups of preschool children with speech sound disorders (SSD) could be identified using a subgroup discovery algorithm (SUBgroup discovery via Alternate Random Processes, or SUBARP). Of specific interest was finding evidence of a subgroup of SSD exhibiting performance consistent with atypical speech motor control. Method Ninety-seven preschool children with SSD completed speech and nonspeech tasks. Fifty-three kinematic, acoustic, and behavioral measures from these tasks were input to SUBARP. Results Two distinct subgroups were identified from the larger sample. The 1st subgroup (76%; population prevalence estimate = 67.8%–84.8%) did not have characteristics that would suggest atypical speech motor control. The 2nd subgroup (10.3%; population prevalence estimate = 4.3%– 16.5%) exhibited significantly higher variability in measures of articulatory kinematics and poor ability to imitate iambic lexical stress, suggesting atypical speech motor control. Both subgroups were consistent with classes of SSD in the Speech Disorders Classification System (SDCS; Shriberg et al., 2010a). Conclusion Characteristics of children in the larger subgroup were consistent with the proportionally large SDCS class termed speech delay; characteristics of children in the smaller subgroup were consistent with the SDCS subtype termed motor speech disorder—not otherwise specified. The authors identified candidate measures to identify children in each of these groups. PMID:25076005

HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors.

PubMed

Yasuma, Keiko; Matsuzaki, Toshio; Yamano, Yoshihisa; Takashima, Hiroshi; Matsuoka, Masao; Saito, Mineki

2016-08-01

Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.

Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

PubMed

Barker, Nick; Rookmaaker, Maarten B; Kujala, Pekka; Ng, Annie; Leushacke, Marc; Snippert, Hugo; van de Wetering, Marc; Tan, Shawna; Van Es, Johan H; Huch, Meritxell; Poulsom, Richard; Verhaar, Marianne C; Peters, Peter J; Clevers, Hans

2012-09-27

Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Predictive significance of the European LeukemiaNet classification of genetic aberrations in patients with acute myeloid leukaemia undergoing allogeneic stem cell transplantation.

PubMed

Hemmati, Philipp G; Vuong, Lam G; Terwey, Theis H; Jehn, Christian F; le Coutre, Philipp; Penack, Olaf; Na, Il-Kang; Dörken, Bernd; Arnold, Renate

2017-02-01

The purpose of this study was to evaluate the predictive capacity of the European LeukemiaNet (ELN) classification of genetic risk in patients with acute myeloid leukaemia (AML) undergoing allogeneic stem cell transplantation (alloSCT). We retrospectively analysed 274 patients transplanted at our centre between 2004 and 2014. The ELN grouping is comparable to the Southwest Oncology Group/Eastern Cooperative Oncology Group (SWOG/ECOG) stratification in predicting the outcome after alloSCT [overall P = 0.0064 for disease-free survival (DFS), overall P = 0.003 for relapse]. Patients with an intermediate-1 profile have a significantly elevated 5-yr relapse incidence as compared to favourable risk patients, that is 40% vs. 15%, [hazard ratio (HR) 2.58, P = 0.048]. An intermediate-1 risk profile is an independent predictor for relapse as determined by multivariate Cox regression analysis (HR 3.05, P = 0.023). In intermediate-1 patients, the presence of an FLT3 internal tandem duplication (FLT3-ITD) is associated with a significantly increased relapse incidence (P = 0.0323), and a lower DFS (P = 0.0465). FLT3-ITD is an independent predictor for overall survival, DFS and relapse incidence in the intermediate-1 subgroup. The ELN stratification of genetic risk predicts the outcome of patients with AML undergoing alloSCT. Patients with an intermediate-1 profile have a high risk for treatment failure due to relapse, which prompts the development of alternative treatment strategies. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A Mouse Model for Betacoronavirus Subgroup 2c Using a Bat Coronavirus Strain HKU5 Variant

PubMed Central

Agnihothram, Sudhakar; Yount, Boyd L.; Donaldson, Eric F.; Huynh, Jeremy; Menachery, Vineet D.; Gralinski, Lisa E.; Graham, Rachel L.; Becker, Michelle M.; Tomar, Sakshi; Scobey, Trevor D.; Osswald, Heather L.; Whitmore, Alan; Gopal, Robin; Ghosh, Arun K.; Mesecar, Andrew; Zambon, Maria; Heise, Mark; Denison, Mark R.; Baric, Ralph S.

2014-01-01

ABSTRACT Cross-species transmission of zoonotic coronaviruses (CoVs) can result in pandemic disease outbreaks. Middle East respiratory syndrome CoV (MERS-CoV), identified in 2012, has caused 182 cases to date, with ~43% mortality, and no small animal model has been reported. MERS-CoV and Pipistrellus bat coronavirus (BtCoV) strain HKU5 of Betacoronavirus (β-CoV) subgroup 2c share >65% identity at the amino acid level in several regions, including nonstructural protein 5 (nsp5) and the nucleocapsid (N) protein, which are significant drug and vaccine targets. BtCoV HKU5 has been described in silico but has not been shown to replicate in culture, thus hampering drug and vaccine studies against subgroup 2c β-CoVs. We report the synthetic reconstruction and testing of BtCoV HKU5 containing the severe acute respiratory syndrome (SARS)-CoV spike (S) glycoprotein ectodomain (BtCoV HKU5-SE). This virus replicates efficiently in cell culture and in young and aged mice, where the virus targets airway and alveolar epithelial cells. Unlike some subgroup 2b SARS-CoV vaccines that elicit a strong eosinophilia following challenge, we demonstrate that BtCoV HKU5 and MERS-CoV N-expressing Venezuelan equine encephalitis virus replicon particle (VRP) vaccines do not cause extensive eosinophilia following BtCoV HKU5-SE challenge. Passage of BtCoV HKU5-SE in young mice resulted in enhanced virulence, causing 20% weight loss, diffuse alveolar damage, and hyaline membrane formation in aged mice. Passaged virus was characterized by mutations in the nsp13, nsp14, open reading frame 5 (ORF5) and M genes. Finally, we identified an inhibitor active against the nsp5 proteases of subgroup 2c β-CoVs. Synthetic-genome platforms capable of reconstituting emerging zoonotic viral pathogens or their phylogenetic relatives provide new strategies for identifying broad-based therapeutics, evaluating vaccine outcomes, and studying viral pathogenesis. PMID:24667706

Reverse Transcription of a Self-Primed Retrotransposon Requires an RNA Structure Similar to the U5-IR Stem-Loop of Retroviruses

PubMed Central

Lin, Jia-Hwei; Levin, Henry L.

1998-01-01

An inverted repeat (IR) within the U5 region of the Rous sarcoma virus (RSV) mRNA forms a structure composed of a 7-bp stem and a 5-nucleotide (nt) loop. This U5-IR structure has been shown to be required for the initiation of reverse transcription. The mRNA of Tf1, long terminal repeat-containing retrotransposon from fission yeast (Schizosaccharomyces pombe) contains nucleotides with the potential to form a U5-IR stem-loop that is strikingly similar to that of RSV. The putative U5-IR stem-loop of Tf1 consists of a 7-bp stem and a 25-nt loop. Results from mutagenesis studies indicate that the U5-IR stem-loop in the mRNA of Tf1 does form and that it is required for Tf1 transposition. Although the loop is required for transposition, we were surprised that the specific sequence of the nucleotides within the loop was unimportant for function. Additional investigation indicates that the loss of transposition activity due to a reduction in the loop size to 6 nt could be rescued by increasing the GC content of the stem. This result indicates that the large loop in the Tf1 mRNA relative to that of the RSV allows the formation of the relatively weak U5-IR stem. The levels of Tf1 proteins expressed and the amounts of Tf1 RNA packaged into the virus-like particles were not affected by mutations in the U5-IR structure. However, all of the mutations in the U5-IR structure that caused defects in transposition produced low amounts of reverse transcripts. A unique feature in the initiation of Tf1 reverse transcription is that, instead of a tRNA, the first 11 nt of the Tf1 mRNA serve as the minus-strand primer. Analysis of the 5′ end of Tf1 mRNA revealed that the mutations in the U5-IR stem-loop that resulted in defects in reverse transcription caused a reduction in the cleavage activity required to generate the Tf1 primer. Our results indicate that the U5-IR stems of Tf1 and RSV are conserved in size, position, and function. PMID:9774699

Genome-Wide Association Studies of 11 Agronomic Traits in Cassava (Manihot esculenta Crantz)

PubMed Central

Zhang, Shengkui; Chen, Xin; Lu, Cheng; Ye, Jianqiu; Zou, Meiling; Lu, Kundian; Feng, Subin; Pei, Jinli; Liu, Chen; Zhou, Xincheng; Ma, Ping’an; Li, Zhaogui; Liu, Cuijuan; Liao, Qi; Xia, Zhiqiang; Wang, Wenquan

2018-01-01

Cassava (Manihot esculenta Crantz) is a major tuberous crop produced worldwide. In this study, we sequenced 158 diverse cassava varieties and identified 349,827 single-nucleotide polymorphisms (SNPs) and indels. In each chromosome, the number of SNPs and the physical length of the respective chromosome were in agreement. Population structure analysis indicated that this panel can be divided into three subgroups. Genetic diversity analysis indicated that the average nucleotide diversity of the panel was 1.21 × 10-4 for all sampled landraces. This average nucleotide diversity was 1.97 × 10-4, 1.01 × 10-4, and 1.89 × 10-4 for subgroups 1, 2, and 3, respectively. Genome-wide linkage disequilibrium (LD) analysis demonstrated that the average LD was about ∼8 kb. We evaluated 158 cassava varieties under 11 different environments. Finally, we identified 36 loci that were related to 11 agronomic traits by genome-wide association analyses. Four loci were associated with two traits, and 62 candidate genes were identified in the peak SNP sites. We found that 40 of these genes showed different expression profiles in different tissues. Of the candidate genes related to storage roots, Manes.13G023300, Manes.16G000800, Manes.02G154700, Manes.02G192500, and Manes.09G099100 had higher expression levels in storage roots than in leaf and stem; on the other hand, of the candidate genes related to leaves, Manes.05G164500, Manes.05G164600, Manes.04G057300, Manes.01G202000, and Manes.03G186500 had higher expression levels in leaves than in storage roots and stem. This study provides basis for research on genetics and the genetic improvement of cassava. PMID:29725343

Genome-Wide Association Studies of 11 Agronomic Traits in Cassava (Manihot esculenta Crantz).

PubMed

Zhang, Shengkui; Chen, Xin; Lu, Cheng; Ye, Jianqiu; Zou, Meiling; Lu, Kundian; Feng, Subin; Pei, Jinli; Liu, Chen; Zhou, Xincheng; Ma, Ping'an; Li, Zhaogui; Liu, Cuijuan; Liao, Qi; Xia, Zhiqiang; Wang, Wenquan

2018-01-01

Cassava ( Manihot esculenta Crantz) is a major tuberous crop produced worldwide. In this study, we sequenced 158 diverse cassava varieties and identified 349,827 single-nucleotide polymorphisms (SNPs) and indels. In each chromosome, the number of SNPs and the physical length of the respective chromosome were in agreement. Population structure analysis indicated that this panel can be divided into three subgroups. Genetic diversity analysis indicated that the average nucleotide diversity of the panel was 1.21 × 10 -4 for all sampled landraces. This average nucleotide diversity was 1.97 × 10 -4 , 1.01 × 10 -4 , and 1.89 × 10 -4 for subgroups 1, 2, and 3, respectively. Genome-wide linkage disequilibrium (LD) analysis demonstrated that the average LD was about ∼8 kb. We evaluated 158 cassava varieties under 11 different environments. Finally, we identified 36 loci that were related to 11 agronomic traits by genome-wide association analyses. Four loci were associated with two traits, and 62 candidate genes were identified in the peak SNP sites. We found that 40 of these genes showed different expression profiles in different tissues. Of the candidate genes related to storage roots, Manes.13G023300, Manes.16G000800, Manes.02G154700, Manes.02G192500, and Manes.09G099100 had higher expression levels in storage roots than in leaf and stem; on the other hand, of the candidate genes related to leaves, Manes.05G164500, Manes.05G164600, Manes.04G057300, Manes.01G202000, and Manes.03G186500 had higher expression levels in leaves than in storage roots and stem. This study provides basis for research on genetics and the genetic improvement of cassava.

Combined Effects of Vascular Endothelial Growth Factor and Bone Morphogenetic Protein 2 on Odonto/Osteogenic Differentiation of Human Dental Pulp Stem Cells In Vitro.

PubMed

Aksel, Hacer; Huang, George T-J

2017-06-01

The purpose of this study was to investigate whether combined and concerted delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) enhances odonto/osteogenic differentiation of human dental pulp stem cells (DPSCs) in vitro. Various concentrations of VEGF and/or BMP-2 with or without the presence of odonto/osteogenic medium (OM) were added into DPSC cultures for 21 days. The mineral formation in cultures was evaluated using alizarin red stain (ARS). Optimal concentrations of VEGF and BMP-2 were codelivered to DPSCs for total of 21 days with the following experimental groups: (1) group 1: OM only, (2) group 2: OM + VEGF, (3) group 3: OM + BMP-2, and (4) group 4: OM + VEGF + BMP-2 (subgroup 4a: VEGF present the first 7 days, 4b: BMP-2 present the last 14 days, and 4c, both present for 21 days). Cultures were then subjected to quantitative ARS analysis or harvested for quantitative polymerase chain reaction analysis for the expression of core-binding factor alpha 1 (CBFA1), alkaline phosphatase (ALP), and dentin matrix protein 1 (DMP-1). No mineral formation was detected by ARS when VEGF and/or BMP-2 were used without OM. OM + VEGF, but not OM + BMP-2, formed more mineralization than OM (P < .05). In the codelivery groups, the highest mineralization was observed in OM + VEGF and subgroup 4a compared with OM or the other groups (P < .05). Quantitative polymerase chain reaction analysis showed that CBFA1, ALP, and DMP-1 levels were higher in groups 2, 3, and 4a compared with 4b and 4c (P < .05). CBFA1 expressed higher in groups 2, 3, and 4a compared with OM (P < .05). For ALP expression, only subgroup 4a expressed higher than OM (P < .05). No difference was detected between groups 2 and 3 (P > .05) in the expression of the 3 genes. VEGF addition in the early phase rather than a continuous presence of both VEGF and BMP-2 enhances odonto/osteogenic differentiation of DPSCs. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE (HARDESTY CAST IRON RECTANGULAR SLIDE GATE), LOOKING SOUTHWEST - High Mountain Dams in Bonneville Unit, Lost Lake Dam, Kamas, Summit County, UT

Risk of developing invasive breast cancer in Hispanic women: A look across Hispanic subgroups

PubMed Central

Banegas, Matthew P.; Leng, Mei; Graubard, Barry I.; Morales, Leo S.

2012-01-01

Background Current evidence on breast cancer among US Hispanic women indicates a significant public health threat, although few studies assess the heterogeneity in breast cancer risk among Hispanics of different origin. Methods The 2000 and 2005 National Health Interview Survey (NHIS) Cancer Control Modules were used to examine the Breast Cancer Risk Assessment Tool (BCRAT) 5-year and lifetime risk of invasive breast cancer among Mexican/Mexican-American, Puerto Rican, Cuban/Cuban-American, Dominican (Republic), Central/South American, Other Hispanic and non-Hispanic white (NHW) women aged 35-84 years. Multiple linear regression models were used to compare the BCRAT 5-year and lifetime breast cancer risk between: i) Hispanics and NHWs and ii) Hispanic subgroups. Results Hispanics had significantly lower mean BCRAT 5-year and lifetime breast cancer risk compared to NHWs (p<0.001). Among Hispanic subgroups, Cuban/Cuban-Americans had a higher BCRAT 5-year risk (p<0.05), while Dominicans had a higher lifetime risk (p<0.001), compared to Mexican/Mexican-American women. Approximately, 2.6% of Hispanic women were at high-risk for breast cancer (BCRAT 5-year risk ≥1.67%), ranging from 1.0% of Central/South Americans to 3.7% of Puerto Ricans; few Hispanics (0.2%) had a lifetime risk ≥20.0%. Conclusions Our findings indicate that Hispanics had significantly lower risk of breast cancer, compared to NHWs, though BCRAT risk significantly differed between specific Hispanic subgroups. We provide estimates of the number of US Hispanic women, from six subgroups, who would be eligible for prophylactic breast cancer chemoprevention. Future studies should further investigate the heterogeneity in breast cancer risk and risk factors between Hispanic women of different origins. PMID:23224859

Vertical Mandibular Range of Motion in Anesthetized Dogs and Cats

PubMed Central

Gracis, Margherita; Zini, Eric

2016-01-01

The main movement of the temporomandibular joint of dogs and cats is in vertical dimensions (opening and closing the mouth). An objective evaluation of the vertical mandibular range of motion (vmROM) may favor early diagnosis of a number of conditions affecting the joint mobility. vmROM, corresponding to the maximum interincisal opening, was measured in 260 dogs and 127 cats anesthetized between June 2011 and April 2015 because of oral or maxillofacial problems and procedures. Animals with a known history of or having current diseases considered to hamper mandibular extension were excluded from the study. Dogs were divided into four subgroups, based on body weight: subgroup 1 (≤5.0 kg, 51 dogs), subgroup 2 (5.1–10.0 kg, 56 dogs), subgroup 3 (10.1–25 kg, 66 dogs), and subgroup 4 (>25.1 kg, 87 dogs). The mean vmROM of all dogs was 107 ± 30 mm (median 109, range 40–180); in subgroup 1 was 67 ± 15 mm (median 67, range 40–100), in subgroup 2 was 93 ± 15 mm (median 93, range 53–128), in subgroup 3 was 115 ± 19 mm (median 116, range 59–154), and in subgroup 4 was 134 ± 19 mm (median 135, range 93–180). The mean vmROM of the cats was 62 ± 8 mm (median 63, range 41–84). Correlations between vmROM, age, sex, and body weight were evaluated. In dogs, vmROM did not correlate with age, and in cats a weak positive correlation was found. vmROM and body weight were positively correlated in both populations, except dog subgroup 2. Overall, mean vmROM and body weight were significantly higher in male than in female, both in dogs and in cats. However, vmROM did not differ between sexes in any of the canine subgroups, and only in subgroup 4 male dogs were significantly heavier than females. Evaluation of vmROM should be incorporated into every diagnostic examination as it may be valuable in showing changes over time for every single patient. PMID:27446939

Efficacy of various combinations of irrigants and medicaments on Candida albican: An in vitro study.

PubMed

Singh, Mukund; Kasat, Vikrant O

2015-01-01

To evaluate the efficacy of 3% sodium hypochlorite (NaOCl), 17% ethylenediaminetetraacetic acid (EDTA), calcium hydroxide [Ca (OH)2], and 2% chlorhexidine in various combinations on Candida albicans in root canals for 48 h and 10 days. In this in vitro study, 95 extracted teeth were instrumented. MTCC 183 strain of C. albicans was introduced into the root canals and after 7 days, the average value of colony forming units (CFUs)/ml was determined in all the roots. Then the teeth were randomly divided into three groups: Group I (n = 15) was the control group and only saline was added to it. In group II (n = 40), 3% NaOCl was used as the irrigant and in group III (n = 40), 3% NaOCl and 17% EDTA were used as irrigants. Groups II and III were further divided into two subgroups (A and B) having 20 teeth each. After irrigation, Ca (OH)2 was placed in subgroup A and 2% chlorhexidine digluconate (CHX) solution in subgroup B of both groups as intracanal medicament. After 48 h, the CFUs/ml was determined in 45 teeth (5 from the control group and 10 from each subgroup). After 10 days, the CFUs/ml was determined in the remaining 50 teeth (10 from the control group and 10 from each subgroup). For statistical analysis, Statistical Package for Social Sciences (SPSS version 15, Chicago IL, USA) was used. A decrease in CFUs/ml of C. albicans was noted in all subgroups at 48 h, but the combination of NaOCl, EDTA, and CHX (group IIIB) was the most effective showing value of 0.095 × 10(5) CFUs/ml. On the 10(th) day, the CFUs/ml of C. albicans was further decreased in all subgroups; but again, subgroup IIIB was the most effective showing a value of 0.025 × 10(5) CFUs/ml. There was statistically significant difference in CFUs/ml of C. albicans at 48 h and on 10(th) day in all study groups. The antimicrobial activity of irrigant and intracanal medicament has a positive role in controlling the growth of C. albicans.

Human placental PPAR-γ and SOX-2 expression in serologically proved toxoplasmosis.

PubMed

Hasby Saad, M; El-Anwar, N; Lotfy, S; Fouda, M; Hasby, E

2018-06-01

To explore PPAR-γ and SOX-2 transcription factors expression in placenta according to maternal anti-Toxoplasma gondii serological profile during pregnancy and pregnancy outcome. The study included 240 placentas, grouped according to IgM and IgG serostatus and then subgrouped according to pregnancy outcome that varied between miscarriages, premature labour, stillbirth and giving birth to CNS anomaly or apparently healthy neonates. Samples were H&E stained and histopathologically scored blindly. PPAR-γ expression was measured by ELISA, while SOX-2-positive nuclei were stained immunohistochemically to be calculated by ImageJ. The mean pathological score was significantly higher in IgM+ve and IgG rising than IgG-ve and persistent low groups. Former groups showed significantly higher PPAR-γ (mean = 258.63, 227.11). However, PPAR-γ was higher in apparently healthy neonate subgroups. SOX-2 was significantly lower in IgM+ve and IgG rising groups (mean = 12.87, 43.13) and associated with obvious fibrosis. SOX-2 lowest count was in CNS anomaly subgroup. PPAR-γ and SOX-2 changes may give clues of how Toxoplasma induces pathogenesis during vertical transmission. Triggering PPAR-γ expression may be a tool to downregulate the inflammatory response and establish a metabolically permissive cellular environment for Toxoplasma persistence. Low SOX-2 is suspected to disturb placental mesenchymal stem cells pluripotency and neuroectoderm development. © 2018 John Wiley & Sons Ltd.

Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation.

PubMed

Lee, Jae Won; An, Hyoseok; Lee, Kuen Yong

2017-07-01

Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Evolution and estimated age of the C5 Lukala carbonate-evaporite ramp complex in the Lower Congo region (Democratic Republic of Congo): New perspectives in Central Africa

NASA Astrophysics Data System (ADS)

Delpomdor, F.; Van Vliet, N.; Devleeschouwer, X.; Tack, L.; Préat, A.

2018-01-01

New detailed lithological, sedimentological, chemostratigraphic data were obtained from exploration drilling samples on the C5 carbonate-dominated formation of the Neoproterozoic Lukala Subgroup (former Schisto-Calcaire Subgroup) from the West Congo Belt (WCB) in the Democratic Republic of Congo. This formation records the last post-Marinoan sea-level events that occurred in the whole basin, followed by the development of the Araçuaï-West Congo Orogen between 630 and 560 Ma. The C5 Formation consists of back-reef lagoonal and peritidal/sabkha cycles of ∼2.0 m in thickness, that record a short-time marine regression, rapidly flooded by a marine transgression with deposition of organic-rich argillaceous carbonates or shales under dysoxia and anoxia conditions. These dysoxic/anoxic waters were rapidly followed by a regional-scale marine transgression, favouring mixing with well-oxygenated waters, and the development of benthic Tonian to Cambro-Ordovician Obruchevella parva-type 'seagrasses' in the nearshore zones of the lagoons. New δ13C and 87Sr/86Sr isotopic data in the C5 Formation of the Lukala Subgroup are used in the frame of a correlation with the Sete Lagoas Formation in Brazil. Relatively comparable negative to positive δ13C excursions point to marine flooding of the whole basin and allow extension of the debatable Late Ediacaran age of the uppermost Sete Lagoas and C5 formations. Sr isotope ;blind dating; failed due to low Sr concentration related to a dolomitization event close 540 Ma. Several tentative datings of the C5 Formation converge to a Late Ediacaran age ranging between 575 and 540 Ma. As the overlying Mpioka folded Subgroup, the C5 series suffered the Pan African deformation, dated at 566 ± 42 Ma. Unlike the previously generally accepted interpretation, our data suggests that the Mpioka Subgroup was deposited in the Early Cambrian.

Preferential association of interferon regulatory factor 5 gene variants with seronegative rheumatoid arthritis in 2 Swedish case-control studies.

PubMed

Wang, Chuan; Kokkonen, Heidi; Sandling, Johanna K; Johansson, Martin; Seddighzadeh, Maria; Padyukov, Leonid; Rantapää-Dahlqvist, Solbritt; Syvänen, Ann-Christine

2011-10-01

Two interferon regulatory factor 5 (IRF5) gene variants were examined for association with rheumatoid arthritis (RA). A total of 2300 patients with RA and 1836 controls were recruited from 2 independent RA studies in Sweden. One insertion-deletion polymorphism (CGGGG indel) and one single-nucleotide polymorphism (rs10488631) in the IRF5 gene were genotyped and analyzed within RA subgroups stratified by rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA). The CGGGG indel was preferentially associated with the RF-negative (OR 1.29, p = 7.9 × 10(-5)) and ACPA-negative (OR 1.27, p = 7.3 × 10(-5)) RA subgroups compared to the seropositive counterparts. rs10488631 was exclusively associated within the seronegative RA subgroups (RF-negative: OR 1.24, p = 0.016; ACPA-negative: OR 1.27, p = 4.1 × 10(-3)). Both the CGGGG indel and rs10488631 are relevant for RA susceptibility, especially for seronegative RA.

Identification of subgroups of patients with tension type headache with higher widespread pressure pain hyperalgesia.

PubMed

Fernández-de-Las-Peñas, César; Benito-González, Elena; Palacios-Ceña, María; Wang, Kelun; Castaldo, Matteo; Arendt-Nielsen, Lars

2017-12-01

Identification of subgroups of patients with different levels of sensitization and clinical features can help to identify groups at risk and the development of better therapeutic strategies. The aim of this study was to identify subgroups of patients with tension type headache (TTH) with different levels of sensitization, clinical pain features, and psychological outcomes. A total of 197 individuals with TTH participated. Headache intensity, frequency, and duration and medication intake were collected with a 4-weeks diary. Pressure pain thresholds were assessed bilaterally over the temporalis muscle, C5-C6 joint, second metacarpal and tibialis anterior muscle to determine widespread pressure pain hyperalgesia. The Hospital Anxiety and Depression Scale assessed anxiety and depression. The State-Trait Anxiety Inventory evaluated the state and trait levels of anxiety. The Headache Disability Inventory evaluated the burden of headache. Health-related quality of life was determined with the SF-36 questionnaire. Groups were considered as positive (three or more criteria) or negative (less than three criteria) on a clinical prediction rule: headache duration <8.5 h/day; headache frequency <5.5 days/week; bodily pain <47 and vitality <47.5. The ANCOVA revealed that subjects in group 1 (positive rule, n = 89) exhibited longer headache history, shorter headache duration, lower headache frequency, higher widespread pressure hyperalgesia, higher anxiety trait levels, and lower quality of life (all, P < 0.01) than those subjects within group 2 (negative rule, n = 108). Differences were similar between men and women. This study identified a subgroup of patients with TTH with higher sensitization, higher chronicity of headaches and worse quality of life but lower frequency and duration of headache episodes. This subgroup of individuals with TTH may need particular attention and specific therapeutic programs for avoiding potential chronification.

Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report.

PubMed

Chen, Lei; Guo, Shilei; Wei, Cui; Li, Honglan; Wang, Haiya; Xu, Yan

2018-05-01

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=-1.330; 95% confidence interval (CI), -(2.095-0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350-3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157-2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226-2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213-2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Breast Cancer Subtypes: Two decades of Journey from Cell Culture to Patients

PubMed Central

Zhao, Xiangshan; Gurumurthy, Channabasavaiah Basavaraju; Malhotra, Gautam; Mirza, Sameer; Mohibi, Shakur; Bele, Aditya; Quinn, Meghan G; Band, Hamid; Band, Vimla

2014-01-01

Breast cancer remains the second leading cause of cancer-related deaths among women. Clinically breast cancer patients present with distinct diseases with vastly different outcomes. Recent molecular profiling has identified five major subtypes of breast cancers. Importantly, survival analyses have shown significantly different outcomes for patients belonging to various subgroups. These studies strongly support the idea that breast tumor subtypes may represent malignancies of biologically distinct cell types producing distinct disease entities that may also require different treatment strategies. Alternatively, different types of breast cancers may arise from a common precursor based on oncogene-driven reprogramming. Experimental systems that clearly define cancer cell heterogeneity and link this process to cancer stem/progenitor cells have not been developed. It is also unclear if oncogenic transformation of committed progenitors drives them along their committed pathway, and hence the cell of origin determines the histological features of breast cancer, or if different oncogenic pathways can transform the same precursor along distinct phenotypes. One major hurdle to addressing these fundamental questions about the origin and heterogeneity of human breast cancer is the lack of immortal human stem/progenitor cells that could be interrogated with breast cancer-relevant oncogenesis protocols. We have now identified, isolated and immortalized (using hTERT) such mammary stem/progenitor cells that are immortal and still maintain their progenitor/stem cell properties (self-renewal and differentiation into myoepithelial and luminal cells). Our research using these progenitor/stem cells that are highly susceptible to oncogenesis and various models of mammary cell immortalization has allowed us to define several novel cellular pathways and demonstration of their involvement in oncogenesis and breast cancer progression. Given the emerging evidence that stem/progenitor cells are precursors of cancers and distinct subtypes of breast cancer have different survival outcome, these studies are timely and carry the potential of developing novel therapeutics in the future as well as provide potentially novel markers for diagnostic/prognostic use in breast cancer. PMID:21901624

miR-423-5p knockdown enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.

PubMed

Wan, Yi; Fei, Xifeng; Wang, Zhimin; Jiang, Dongyi; Chen, Hanchun; Wang, Mian; Zhou, Shijun

2017-04-01

This study aimed to investigate the effect of miR-423-5p on the sensitivity of glioma stem cells to apigenin and to explore the potential mechanism. Previous research indicated that apigenin can effectively inhibit the proliferation of many cancer cells, including glioma cells, though our data unexpectedly showed that apigenin had no effect on glioma stem cell apoptosis. As many studies have reported that malignant transformation and progression of glioma are due to glioma stem cells, an anti-glioma stem cell approach has become an important direction for glioma treatment. In this study, we found miR-423-5p to be overexpressed in glioma tissues and corresponding glioma stem cells. Downregulation of miR-423-5p repressed glioma stem cell growth but did not cause apoptosis. Based on the concept of "Pharmaco-miR," this study further demonstrated that the combination of miR-423-5p knockdown and apigenin had a notable additive effect on inhibiting proliferation and promoting apoptosis in glioma stem cells. Hoechst staining showed higher apoptosis rates and typical apoptotic morphological changes of the cell nucleus, and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocya-nine iodide) staining revealed reduced mitochondrial membrane potential. Further research demonstrated that the mechanism is associated with a shift in the Bax/Bcl-2 ratio, an increased cytochrome c level, Apaf-1 induction, and caspase-3 activation. In conclusion, this study indicates that downregulation of miR-423-5p enhances the sensitivity of glioma stem cells to apigenin through the mitochondrial pathway.

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation.

PubMed

Sun, Guoqiang; Yu, Ruth T; Evans, Ronald M; Shi, Yanhong

2007-09-25

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359-385, which contains a conserved nuclear receptor-coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1)(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX-HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX-HDAC interactions.

Brain 'Embolism' Detected by Magnetic Resonance Imaging During Percutaneous Mitral Balloon Commissurotomy

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

Rocha, Paulo; Qanadli, Salah D.; Strumza, Pierre

1999-05-15

Purpose: The common finding of thrombi between the bifoil balloons when they were extracted after mitral dilation prompted us to look for evidence of minor brain embolisms using the sensitive technique of BMRI (brain magnetic resonance T2-weighted imaging). Methods: BMRI was performed within 48 hr before and after a percutaneous mitral balloon commissurotomy (PMBC) in each of the 63 patients in this study. Results: There was evidence (hyperintensity foci: HI) of a previous asymptomatic brain embolism in 38 of 63 patients before PMBC and a new HI appeared in 18 of 63 patients after the procedure. New HI signals weremore » found exclusively in the white matter in 8 of 18 patients and in only 3 of 18 were HI signs larger than 1 cm. One patient, with an HI signal >1 cm in the thalamus and another <1 cm in the brain stem, presented diplopia accompanied by other minor clinical signs. The differences in HI rate among four subgroups (1, older vs younger than 43 years; 2, sinus rhythm vs atrial fibrillation; 3, echo score <8 vs >8; 4, patients from western countries vs the others) were not statistically significant, probably because the number of patients in each subgroup was low. Patients in atrial fibrillation had slightly more (not significant) HI before PMBC (15/20, 75%) than patients in sinus rhythm (23/43, 53%), but after PMBC their HI frequencies were similar (atrial fibrillation: 5/20, 25%; sinus rhythm: 13/43, 30%). Conclusion: Brain microembolism is frequent during PMBC, but is often anatomically limited and free from clinical signs in most cases. Brain embolism seems to be related mainly to the procedure itself and not the features of the patient.« less

5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW OF UPRIGHT OUTLET GATE, STEM, STEM GUIDE AND WHEEL (10' HARDESTY CAST IRON VERTICAL LIFT GATE), LOOKING WEST - High Mountain Dams in Bonneville Unit, Weir Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW OF INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE, (12' DIAMETER HARDESTY MODEL 112 CIRCULAR GATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Island Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW SHOWING INCLINED OUTLET GATE WHEEL, STEM AND STEM GUIDE (28' WIDE HARDESTY CAST IRON SLIDE HEADGATE), LOOKING NORTHEAST - High Mountain Dams in Bonneville Unit, Duck Lake Dam, Wasatch National Forest, Kamas, Summit County, UT

Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

PubMed

Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

2016-04-07

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

Longitudinal Monitoring of Patients With Chronic Low Back Pain During Physical Therapy Treatment Using the STarT Back Screening Tool.

PubMed

Medeiros, Flávia Cordeiro; Costa, Leonardo Oliveira Pena; Added, Marco Aurélio Nemitalla; Salomão, Evelyn Cassia; Costa, Lucíola da Cunha Menezes

2017-05-01

Study Design Preplanned secondary analysis of a randomized clinical trial. Background The STarT Back Screening Tool (SBST) was developed to screen and to classify patients with low back pain into subgroups for the risk of having a poor prognosis. However, this classification at baseline does not take into account variables that can influence the prognosis during treatment or over time. Objectives (1) To investigate the changes in risk subgroup measured by the SBST over a period of 6 months, and (2) to assess the long-term predictive ability of the SBST when administered at different time points. Methods Patients with chronic nonspecific low back pain (n = 148) receiving physical therapy care as part of a randomized trial were analyzed. Pain intensity, disability, global perceived effect, and the SBST were collected at baseline, 5 weeks, 3 months, and 6 months. Changes in SBST risk classification were calculated. Hierarchical linear regression models adjusted for potential confounders were built to analyze the predictive capabilities of the SBST when administered at different time points. Results A large proportion of patients (60.8%) changed their risk subgroup after receiving physical therapy care. The SBST improved the prediction for all 6-month outcomes when using the 5-week risk subgroup and the difference between baseline and 5-week subgroup, after controlling for potential confounders. The SBST at baseline did not improve the predictive ability of the models after adjusting for confounders. Conclusion This study shows that many patients change SBST risk subgroup after receiving physical therapy care, and that the predictive ability of the SBST in patients with chronic low back pain increases when administered at different time points. Level of Evidence Prognosis, 2b. J Orthop Sports Phys Ther 2017;47(5):314-323. Epub 29 Mar 2017. doi:10.2519/jospt.2017.7199.

Factorial invariance of child self-report across age subgroups: a confirmatory factor analysis of ages 5 to 16 years utilizing the PedsQL 4.0 Generic Core Scales.

PubMed

Limbers, Christine A; Newman, Daniel A; Varni, James W

2008-01-01

The utilization of health-related quality of life (HRQOL) measurement in an effort to improve pediatric health and well-being and determine the value of health care services has grown dramatically over the past decade. The paradigm shift toward patient-reported outcomes (PROs) in clinical trials has provided the opportunity to emphasize the value and essential need for pediatric patient self-report. In order for HRQOL/PRO comparisons to be meaningful for subgroup analyses, it is essential to demonstrate factorial invariance. This study examined age subgroup factorial invariance of child self-report for ages 5 to 16 years on more than 8,500 children utilizing the PedsQL 4.0 Generic Core Scales. Multigroup Confirmatory Factor Analysis (MGCFA) was performed specifying a five-factor model. Two multigroup structural equation models, one with constrained parameters and the other with unconstrained parameters, were proposed to compare the factor loadings across the age subgroups. Metric invariance (i.e., equal factor loadings) across the age subgroups was demonstrated based on stability of the Comparative Fit Index between the two models, and several additional indices of practical fit including the Root Mean Squared Error of Approximation, the Non-Normed Fit Index, and the Parsimony Normed Fit Index. The findings support an equivalent five-factor structure across the age subgroups. Based on these data, it can be concluded that children across the age subgroups in this study interpreted items on the PedsQL 4.0 Generic Core Scales in a similar manner regardless of their age.

Perfectionism and longitudinal patterns of stress for STEM majors: Implications for academic performance.

PubMed

Rice, Kenneth G; Ray, Merideth E; Davis, Don E; DeBlaere, Cirleen; Ashby, Jeffrey S

2015-10-01

Complementary hypotheses suggest that perfectionism may (a) cause later stress (stress generation) and (b) moderate the effects of stress on subsequent outcomes (stress enhancement). The present study tested these hypotheses with a sample of 432 first-time college freshmen pursuing science, technology, engineering, and math (STEM) majors. Students completed baseline perfectionism scales and repeated measures for perceived academic stress at monthly intervals 3 times in the fall semester and 3 times in the spring semester. Course grade data from institutional records were used to calculate first-year STEM grade point average (GPA) as the distal outcome in analyses. Gender, high school GPA, SAT math scores, and university were covariates. Latent profile analyses supported adaptive, maladaptive, and nonperfectionist classes and latent class growth mixture models identified distinctly low, moderate, and high patterns of academic stress over the year. Latent transition analyses indicated that maladaptive perfectionists were likely to experience moderate or high stress (none transitioned to low stress), and adaptive perfectionists were likely to have low or moderate stress (only 4% transitioned to high stress). Women were substantially more likely than male maladaptive perfectionists to experience high stress. Low-stressed adaptive perfectionists followed by moderately stressed maladaptive perfectionists had relatively higher GPAs than other groups. Subgroups of perfectionists who transitioned to the next higher stress level had substantially lower GPAs than other groups. Overall, results were consistent with stress-generation and stress-enhancement hypotheses regarding perfectionists. Findings suggested implications for prevention and intervention with perfectionistic STEM students that should be implemented early in their college experience. (c) 2015 APA, all rights reserved).

Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0522 TITLE: Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration PRINCIPAL INVESTIGATOR...TITLE AND SUBTITLE Layer-by-Layer Bioprinting of Stem Cells for Retinal Tissue Regeneration 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0522 5c...bioprinting process using stem cells for retinal tissue regeneration. The LBL nature of the bioprinting process matches nicely with the native

Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...CA130273 - Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM...hypothesis, we originally proposed to transform neural stem cells (NSCs) and neural progenitor cells (NPCs) in vivo by expressing an activated form

40 CFR 180.507 - Azoxystrobin; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Sapote, mamey 2.0 Sapote, white 2.0 Sorghum, grain, forage 25 Sorghum, grain, grain 11 Sorghum, grain... Sugarcane, cane 0.2 Sunflower subgroup 20B 0.5 Tamarind 2.0 Tomato, paste 0.6 Tomato subgroup 8-10A 0.2...

40 CFR 180.507 - Azoxystrobin; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Sapote, mamey 2.0 Sapote, white 2.0 Sorghum, grain, forage 25 Sorghum, grain, grain 11 Sorghum, grain... Sugarcane, cane 0.2 Sunflower subgroup 20B 0.5 Tamarind 2.0 Tomato, paste 0.6 Tomato subgroup 8-10A 0.2...

5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW OF UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, LOOKING NORTHWEST - High Mountain Dams in Upalco Unit, Drift Lake Dam, Ashley National Forest, 11.4 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

Antigenic relatedness between glycoproteins of human respiratory syncytial virus subgroups A and B: evaluation of the contributions of F and G glycoproteins to immunity.

PubMed Central

Johnson, P R; Olmsted, R A; Prince, G A; Murphy, B R; Alling, D W; Walsh, E E; Collins, P L

1987-01-01

The degree of antigenic relatedness between human respiratory syncytial virus (RSV) subgroups A and B was estimated from antibody responses induced in cotton rats by respiratory tract infection with RSV. Glycoprotein-specific enzyme-linked immunosorbent assays of antibody responses induced by RSV infection demonstrated that the F glycoproteins of subgroups A and B were antigenically closely related (relatedness, R approximately 50%), whereas the G glycoproteins were only distantly related (R approximately 5%). Intermediate levels of antigenic relatedness (R approximately 25%) were seen in neutralizing antibodies from cotton rats infected with RSV of the two subgroups. Immunity against the F glycoprotein of subgroup A, induced by vaccinia-A2-F, conferred a high level of protection which was of comparable magnitude against challenge by RSV of either subgroup. In comparison, immunity against the G glycoprotein of subgroup A, induced by vaccinia-A2-G, conferred less complete, but significant, protection. Importantly, in vaccinia-A2-G-immunized animals, suppression of homologous challenge virus replication was significantly greater (13-fold) than that observed for the heterologous virus. PMID:3305988

Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents.

PubMed

Al-Hamadani, Mohammed; Hashmi, Shahrukh K; Go, Ronald S

2014-08-01

Very effective combination chemotherapy using novel agents has become available in multiple myeloma (MM). Its impact on the use of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHCT) as part of initial therapy is unknown. Using the National Cancer Data Base, we studied the rate of upfront AHCT use among 137,409 newly diagnosed MM patients from 1998 to 2010 in the United States and determined whether disparity exists among various sociodemographic as well as geographic subgroups. Overall, 12,378 (9.0%) patients received AHCT as part of initial treatment. The use of upfront AHCT increased steadily from 5.2% in 1998 to 12.1% in 2010 (trend test, P < 0.001), with no sign of plateau. This was seen across all socio-geo-demographic subgroups except among patients treated in the Northeast where the rate fell from 8.7% in 1998 to 6.6% in 2010. In multivariable analysis, patients with the following characteristics were the least likely to receive AHCT (odds ratio): year of diagnosis from 1998 to 2003 before the era of novel agents (0.67), older age (0.35), Black race (0.58), Hispanic ethnicity (0.78), low level of education or annual household income (0.55), residence in a metro area (0.66), no or unknown medical insurance (0.30), treatment at a community cancer center (0.16), and treatment facility located in the Northeast region (0.54). Even after the introduction of novel agents, the rate of upfront AHCT in MM continues to increase annually. Significant disparities exist dependent on demographic, social, and geographic factors. © 2014 Wiley Periodicals, Inc.

Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-04-01

For postmenopausal patients with hormone receptor-positive early breast cancer, the optimal subgroup and duration of extended endocrine therapy is not clear yet. The aim of this study using the IDEAL patient cohort was to identify a subgroup for which longer (5 years) extended therapy is beneficial over shorter (2.5 years) extended endocrine therapy. In the IDEAL trial, 1824 patients who completed 5 years of adjuvant endocrine therapy (either 5 years of tamoxifen (12%), 5 years of an AI (29%), or a sequential strategy of both (59%)) were randomized between either 2.5 or 5 years of extended letrozole. For each prior therapy subgroup, the value of longer therapy was assessed for both node-negative and node-positive patients using Kaplan Meier and Cox regression survival analyses. In node-positive patients, there was a significant benefit of 5 years (over 2.5 years) of extended therapy (disease-free survival (DFS) HR 0.67, p = 0.03, 95% CI 0.47-0.96). This effect was only observed in patients who were treated initially with a sequential scheme (DFS HR 0.60, p = 0.03, 95% CI 0.38-0.95). In all other subgroups, there was no significant benefit of longer extended therapy. Similar results were found in patients who were randomized for their initial adjuvant therapy in the TEAM trial (DFS HR 0.37, p = 0.07, 95% CI 0.13-1.06), although this additional analysis was underpowered for definite conclusions. This study suggests that node-positive patients could benefit from longer extended endocrine therapy, although this effect appears isolated to patients treated with sequential endocrine therapy during the first 5 years and needs validation and long-term follow-up.

Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk.

PubMed

Kim, Eunjoo; Davidson, Laurie A; Zoh, Roger S; Hensel, Martha E; Salinas, Michael L; Patil, Bhimanagouda S; Jayaprakasha, Guddadarangavvanahally K; Callaway, Evelyn S; Allred, Clinton D; Turner, Nancy D; Weeks, Brad R; Chapkin, Robert S

2016-11-10

The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5 + ) stem cells, the cells of origin of colon cancer, have not been documented to date. Therefore, we examined the effect of n-3 PUFA and polyphenol (curcumin) combination on Lgr5 + stem cells during tumor initiation and progression in the colon compared with an n-6 PUFA-enriched control diet. Lgr5-EGFP-IRES- creERT2 knock-in mice were fed diets containing n-6 PUFA (control), n-3 PUFA, n-6 PUFA+curcumin or n-3 PUFA+curcumin for 3 weeks, followed by 6 azoxymethane (AOM) injections, and terminated 17 weeks after the last injection. To further elucidate the effects of the dietary bioactives at the tumor initiation stage, Lgr5 + stem cells were also assessed at 12 and 24 h post AOM injection. Only n-3 PUFA+curcumin feeding reduced nuclear β-catenin in aberrant crypt foci (by threefold) compared with control at the progression time point. n-3 PUFA+curcumin synergistically increased targeted apoptosis in DNA-damaged Lgr5 + stem cells by 4.5-fold compared with control at 12 h and maximally reduced damaged Lgr5 + stem cells at 24 h, down to the level observed in saline-treated mice. Finally, RNAseq analysis indicated that p53 signaling in Lgr5 + stem cells from mice exposed to AOM was uniquely upregulated only following n-3 PUFA+curcumin cotreatment. These novel findings demonstrate that Lgr5 + stem cells are uniquely responsive to external dietary cues following the induction of DNA damage, providing a therapeutic strategy for eliminating damaged Lgr5 + stem cells to reduce colon cancer initiation.

Rapidly cycling Lgr5+ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk

PubMed Central

Kim, Eunjoo; Davidson, Laurie A; Zoh, Roger S; Hensel, Martha E; Salinas, Michael L; Patil, Bhimanagouda S; Jayaprakasha, Guddadarangavvanahally K; Callaway, Evelyn S; Allred, Clinton D; Turner, Nancy D; Weeks, Brad R; Chapkin, Robert S

2016-01-01

The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5+) stem cells, the cells of origin of colon cancer, have not been documented to date. Therefore, we examined the effect of n-3 PUFA and polyphenol (curcumin) combination on Lgr5+ stem cells during tumor initiation and progression in the colon compared with an n-6 PUFA-enriched control diet. Lgr5-EGFP-IRES-creERT2 knock-in mice were fed diets containing n-6 PUFA (control), n-3 PUFA, n-6 PUFA+curcumin or n-3 PUFA+curcumin for 3 weeks, followed by 6 azoxymethane (AOM) injections, and terminated 17 weeks after the last injection. To further elucidate the effects of the dietary bioactives at the tumor initiation stage, Lgr5+ stem cells were also assessed at 12 and 24 h post AOM injection. Only n-3 PUFA+curcumin feeding reduced nuclear β-catenin in aberrant crypt foci (by threefold) compared with control at the progression time point. n-3 PUFA+curcumin synergistically increased targeted apoptosis in DNA-damaged Lgr5+ stem cells by 4.5-fold compared with control at 12 h and maximally reduced damaged Lgr5+ stem cells at 24 h, down to the level observed in saline-treated mice. Finally, RNAseq analysis indicated that p53 signaling in Lgr5+ stem cells from mice exposed to AOM was uniquely upregulated only following n-3 PUFA+curcumin cotreatment. These novel findings demonstrate that Lgr5+ stem cells are uniquely responsive to external dietary cues following the induction of DNA damage, providing a therapeutic strategy for eliminating damaged Lgr5+ stem cells to reduce colon cancer initiation. PMID:27831561

Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

PubMed

Oberoi, Sapna; Robinson, Paula D; Cataudella, Danielle; Culos-Reed, S Nicole; Davis, Hailey; Duong, Nathan; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Cabral, Sandra; Dupuis, L Lee; Sung, Lillian

2018-02-01

Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P < 0.00001). Aerobic, neuromotor, resistance and combination exercises were all effective in reducing fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority. Copyright © 2017 Elsevier B.V. All rights reserved.

Internalin profiling and multilocus sequence typing suggest four Listeria innocua subgroups with different evolutionary distances from Listeria monocytogenes

PubMed Central

2010-01-01

Background Ecological, biochemical and genetic resemblance as well as clear differences of virulence between L. monocytogenes and L. innocua make this bacterial clade attractive as a model to examine evolution of pathogenicity. This study was attempted to examine the population structure of L. innocua and the microevolution in the L. innocua-L. monocytogenes clade via profiling of 37 internalin genes and multilocus sequence typing based on the sequences of 9 unlinked genes gyrB, sigB, dapE, hisJ, ribC, purM, gap, tuf and betL. Results L. innocua was genetically monophyletic compared to L. monocytogenes, and comprised four subgroups. Subgroups A and B correlated with internalin types 1 and 3 (except the strain 0063 belonging to subgroup C) and internalin types 2 and 4 respectively. The majority of L. innocua strains belonged to these two subgroups. Subgroup A harbored a whole set of L. monocytogenes-L. innocua common and L. innocua-specific internalin genes, and displayed higher recombination rates than those of subgroup B, including the relative frequency of occurrence of recombination versus mutation (ρ/θ) and the relative effect of recombination versus point mutation (r/m). Subgroup A also exhibited a significantly smaller exterior/interior branch length ratio than expected under the coalescent model, suggesting a recent expansion of its population size. The phylogram based on the analysis with correction for recombination revealed that the time to the most recent common ancestor (TMRCA) of L. innocua subgroups A and B were similar. Additionally, subgroup D, which correlated with internalin type 5, branched off from the other three subgroups. All L. innocua strains lacked seventeen virulence genes found in L. monocytogenes (except for the subgroup D strain L43 harboring inlJ and two subgroup B strains bearing bsh) and were nonpathogenic to mice. Conclusions L. innocua represents a young species descending from L. monocytogenes and comprises four subgroups: two major subgroups A and B, and one atypical subgroup D serving as a link between L. monocytogenes and L. innocua in the evolutionary chain. Although subgroups A and B appeared at approximately the same time, subgroup A seems to have experienced a recent expansion of the population size with higher recombination frequency and effect than those of subgroup B, and might represent the possible evolutionary direction towards adaptation to enviroments. The evolutionary history in the L. monocytogenes-L. innocua clade represents a rare example of evolution towards reduced virulence of pathogens. PMID:20356375

An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.

PubMed

Hayakawa-Yano, Yoshika; Suyama, Satoshi; Nogami, Masahiro; Yugami, Masato; Koya, Ikuko; Furukawa, Takako; Zhou, Li; Abe, Manabu; Sakimura, Kenji; Takebayashi, Hirohide; Nakanishi, Atsushi; Okano, Hideyuki; Yano, Masato

2017-09-15

Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization. Also, our in utero electroporation gain-of-function study suggests that the nuclear-type Qki isoform Qki5 supports the neural stem cell state. We next performed in vivo transcriptome-wide protein-RNA interaction mapping to search for direct targets of Qki5 and elucidate how Qki5 regulates neural stem cell function. Combined with our transcriptome analysis, this mapping analysis yielded a bona fide map of Qki5-RNA interaction at single-nucleotide resolution, the identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent alternative splicing rule in the developing brain. Last, our target gene list provides the first compelling evidence that Qki5 is associated with specific biological events; namely, cell-cell adhesion. This prediction was confirmed by histological analysis of mice in which Qki proteins were genetically ablated, which revealed disruption of the apical surface of the lateral wall in the developing brain. These data collectively indicate that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events and suggest new links between splicing regulation and neural stem cell states. © 2017 Hayakawa-Yano et al.; Published by Cold Spring Harbor Laboratory Press.

Design modifications of the uncemented Furlong hip stem result in minor early subsidence but do not affect further stability: a randomized controlled RSA study with 5-year follow-up.

PubMed

Weber, Erik; Sundberg, Martin; Flivik, Gunnar

2014-12-01

Even small design modifications of uncemented hip stems may alter the postoperative 3-D migration pattern. The Furlong Active is an uncemented femoral stem which, in terms of design, is based on its precursor-the well-proven Furlong HAC-but has undergone several design changes. The collar has been removed on the Active stem along with the lateral fin; it is shorter and has more rounded edges in the proximal part. We compared the migration patterns of the uncemented Furlong HAC stem and the modified Furlong Active stem in a randomized, controlled trial over 5 years using radiostereometry (RSA). 50 patients with primary osteoarthritis were randomized to receive either the HAC stem or the Active stem. The patients underwent repeated RSA examinations (postoperatively, at 3 months, and after 1, 2, and 5 years) and conventional radiography, and they also filled out hip-specific questionnaires. During the first 3 months, the collarless Active stem subsided to a greater extent than the collar-fitted HAC stem (0.99 mm vs. 0.31 mm, p=0.05). There were, however, no other differences in movement measured by RSA or in clinical outcome between the 2 stems. After 3 months, both stem types had stabilized and almost no further migration was seen. The Active stem showed no signs of unfavorable migration. Our results suggest that the osseointegration is not compromised by the new design features.

78 FR 60709 - Methoxyfenozide; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... sunflower subgroup 20B at 1.0 ppm, and to amend the tolerance for herb and spice, group 19, except coriander, leaves at 4.5 ppm to spice subgroup 19B at 4.5 ppm. Upon approval of the proposed tolerances listed under... established tolerance for indirect or inadvertent residues in or on herb and spice, group 19, except coriander...

Using the Integrative Model of Behavioral Prediction to Predict Vegetable Subgroup Consumption among College Students

ERIC Educational Resources Information Center

Senkowski, Valerie; Branscum, Paul; Maness, Sarah; Larson, Daniel

2017-01-01

Background: The United States Department of Agriculture (USDA) currently recommends that young adults consume 2.5-3 cups of vegetables daily, while also providing weekly recommendations for 5 vegetable subgroups: dark green, red and orange, beans and peas, starchy, and other. Purpose: The purpose of this study was to explore theory-based…

40 CFR 180.589 - Boscalid; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., dried shelled, except soybean, subgroup 6C, except cowpea, field pea and grain lupin 2.5 Pea and bean, succulent shelled, subgroup 6B, except cowpea 0.6 Peanut 0.05 Peanut, meal 0.15 Peanut, refined oil 0.15... Cotton, undelinted seed 0.05 Cowpea, seed 0.1 Flax, seed 3.5 Grain, cereal, forage, fodder and straw...

40 CFR 180.589 - Boscalid; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., dried shelled, except soybean, subgroup 6C, except cowpea, field pea and grain lupin 2.5 Pea and bean, succulent shelled, subgroup 6B, except cowpea 0.6 Peanut 0.05 Peanut, meal 0.15 Peanut, refined oil 0.15... Cotton, undelinted seed 0.05 Cowpea, seed 0.1 Flax, seed 3.5 Grain, cereal, forage, fodder and straw...

New evidence of heterogeneity in social anxiety disorder: defining two qualitatively different personality profiles taking into account clinical, environmental and genetic factors.

PubMed

Binelli, C; Muñiz, A; Sanches, S; Ortiz, A; Navines, R; Egmond, E; Udina, M; Batalla, A; López-Sola, C; Crippa, J A; Subirà, S; Martín-Santos, R

2015-01-01

To study qualitatively different subgroups of social anxiety disorder (SAD) based on harm avoidance (HA) and novelty seeking (NS) dimensions. One hundred and forty-two university students with SAD (SCID-DSM-IV) were included in the study. The temperament dimensions HA and NS from the Cloninger's Temperament and Character Inventory were subjected to cluster analysis to identify meaningful subgroups. The identified subgroups were compared for sociodemographics, SAD severity, substance use, history of suicide and self-harm attempts, early life events, and two serotonin transporter gene polymorphisms (5-HTTLPR and STin2.VNTR). Two subgroups of SAD were identified by cluster analysis: a larger (61% of the sample) inhibited subgroup of subjects with "high-HA/low-NS", and a smaller (39%) atypical impulsive subgroup with high-moderate HA and NS. The two groups did not differ in social anxiety severity, but did differ in history of lifetime impulsive-related-problems. History of suicide attempts and self-harm were as twice as frequent in the impulsive subgroup. Significant differences were observed in the pattern of substance misuse. Whereas subjects in the inhibited subgroup showed a greater use of alcohol (P=0.002), subjects in the impulsive subgroup showed a greater use of substances with a high-sensation-seeking profile (P<0.001). The STin2.VNTR genotype frequency showed an inverse distribution between subgroups (P=0.005). Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Mid-term migration analysis of a femoral short-stem prosthesis: a five-year EBRA-FCA-study.

PubMed

Freitag, Tobias; Fuchs, Michael; Woelfle-Roos, Julia V; Reichel, Heiko; Bieger, Ralf

2018-05-01

The objective of this study was to evaluate the mid-term migration pattern of a femoral short stem. Implant migration of 73 femoral short-stems was assessed by Ein-Bild-Roentgen-Analysis Femoral-Component-Analysis (EBRA-FCA) 5 years after surgery. Migration pattern of the whole group was analysed and compared to the migration pattern of implants "at risk" with a subsidence of more than 1.5 mm 2 years postoperative. Mean axial subsidence was 1.1 mm (-5.0 mm to 1.5 mm) after 60 months. There was a statistical significant axial migration until 2 years postoperative with settling thereafter. 2 years after surgery 18 of 73 Implants were classified "at risk." Nevertheless, all stems showed secondary stabilisation in the following period with no implant failure neither in the group of implants with early stabilisation nor the group with extensive early onset migration. In summary, even in the group of stems with more pronounced early subsidence, delayed settling occurred in all cases. The determination of a threshold of critical early femoral short stem subsidence is necessary because of the differing migration pattern described in this study with delayed settling of the Fitmore stem 2 years postoperatively compared to early settling within the first postoperative year described for conventional stems.

Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study.

PubMed

Zammit, Andrea R; Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Muniz-Terrera, Graciela

2018-05-01

The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroup's characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimer's disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).

Molecular subgroups of medulloblastoma identification using noninvasive magnetic resonance spectroscopy.

PubMed

Blüml, Stefan; Margol, Ashley S; Sposto, Richard; Kennedy, Rebekah J; Robison, Nathan J; Vali, Marzieh; Hung, Long T; Muthugounder, Sakunthala; Finlay, Jonathan L; Erdreich-Epstein, Anat; Gilles, Floyd H; Judkins, Alexander R; Krieger, Mark D; Dhall, Girish; Nelson, Marvin D; Asgharzadeh, Shahab

2016-01-01

Medulloblastomas in children can be categorized into 4 molecular subgroups with differing clinical characteristics, such that subgroup determination aids in prognostication and risk-adaptive treatment strategies. Magnetic resonance spectroscopy (MRS) is a widely available, noninvasive tool that is used to determine the metabolic characteristics of tumors and provide diagnostic information without the need for tumor tissue. In this study, we investigated the hypothesis that metabolite concentrations measured by MRS would differ between molecular subgroups of medulloblastoma and allow accurate subgroup determination. MRS was used to measure metabolites in medulloblastomas across molecular subgroups (SHH = 12, Groups 3/4 = 17, WNT = 1). Levels of 14 metabolites were analyzed to determine those that were the most discriminant for medulloblastoma subgroups in order to construct a multivariable classifier for distinguishing between combined Group 3/4 and SHH tumors. Medulloblastomas across molecular subgroups revealed distinct spectral features. Group 3 and Group 4 tumors demonstrated metabolic profiles with readily detectable taurine, lower levels of lipids, and high levels of creatine. SHH tumors showed prominent choline and lipid with low levels of creatine and little or no evidence of taurine. A 5-metabolite subgroup classifier inclusive of creatine, myo-inositol, taurine, aspartate, and lipid 13a was developed that could discriminate between Group 3/4 and SHH medulloblastomas with excellent accuracy (cross-validated area under the curve [AUC] = 0.88). The data show that medulloblastomas of Group 3/4 differ metabolically as measured using MRS when compared with SHH molecular subgroups. MRS is a useful and accurate tool to determine medulloblastoma molecular subgroups. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

5. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW SHOWING UPRIGHT OUTLET GATE WHEEL, STEM AND STEM GUIDE, WITH LOG ACCESS STRUCTURE, LOOKING SOUTHEAST - High Mountain Dams in Upalco Unit, Bluebell Lake Dam, Ashley National Forest, 11.2 miles Northwest of Swift Creek Campground, Mountain Home, Duchesne County, UT

Presence of spermatogonia in 47,XXY men with no spermatozoa recovered after testicular sperm extraction.

PubMed

Van Saen, Dorien; Tournaye, Herman; Goossens, Ellen

2012-02-01

To evaluate the presence of spermatogonia in men diagnosed with Klinefelter syndrome (KS), in whom no testicular spermatozoa were recovered by testicular sperm extraction. Retrospective case series. University hospital. Testicular samples from 22 nonmosaic 47,XXY men, aged 24-43 years, with no spermatozoa at multiple biopsies. Paraffin-embedded testicular tissue was sectioned and stained with hematoxylin-eosin, and immunostainings were performed for both MAGE-A4 and vimentin. The presence of spermatogonia. Massive fibrosis and hyalinization were observed in all men with KS. Spermatogonia were observed in 4 of 22 men with KS, with differentiation up to the spermatocyte level in 2 of them. A few men with KS, having no spermatozoa after testicular sperm extraction, still had few spermatogonia. These patients may eventually benefit from in vitro maturation using spermatogonial stem cells. The adult KS population can thus be divided into three subgroups: one subgroup showing focal spermatogenesis, a second having spermatogonia, and a third group in which no germ cells can be recovered. Further research is necessary to unravel the mechanism leading to these different patterns in patients with KS. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation

PubMed Central

Sun, GuoQiang; Yu, Ruth T.; Evans, Ronald M.; Shi, Yanhong

2007-01-01

TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5-interaction domain was mapped to TLX residues 359–385, which contains a conserved nuclear receptor–coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21CIP1/WAF1(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX-interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX–HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX–HDAC interactions. PMID:17873065

Hippocampal Expression of Connexin36 and Connexin43 during Epileptogenesis in Pilocarpine Model of Epilepsy

PubMed Central

Motaghi, Sahel; Sayyah, Mohammad; Babapour, Vahab; Mahdian, Reza

2017-01-01

Background: Gap junctions (GJs) provide direct intercellular communications that are formed by hexameric protein subunits, called connexin (Cx). The role of Cxs in epileptogenesis has not received sufficient attention. Hippocampus with a critical function in epileptogenesis has a wide network of GJs. We examined the protein expression levels of hippocampal Cx36 (the prominent Cx present between GABAergic interneurons) and Cx43 (the main Cx expressed by astrocytes) during epileptogenesis in the pilocarpine model of epilepsy. Methods: Male Wistar rats received scopolamine (1 mg/kg, s.c.). Pilocarpine (380 mg/kg, i.p.) was administered 30 min thereafter to induce status epilepticus (SE). SE was stopped 2 h later by diazepam (10 mg/kg, i.p.). Cx36 and Cx43 protein expression was assessed by Western blot analysis in the hippocampus of SE-experienced rats, after injection of diazepam (F0 subgroup), after acquisition of focal seizures (F3 subgroup), and after development of generalized seizures (F5 subgroup). The control subgroups, C0, C3, and C5, were aged-matched rats, which received saline (1 ml/kg, i.p.) instead of pilocarpine. Injection of scopolamine and diazepam, and dissection of hippocampi were carried out at the same time interval as the test subgroups. Results: SE emerged in 67.1% of pilocarpine-treated animals. Focal and generalized seizures developed 3.8±0.4 and 7.0±0.5 days after SE, respectively. Cx36 protein abundance was not significantly different between test and control groups in the three time points. However, Cx43 protein level showed 40% increase in F3 subgroup (P<0.05 compared to C3, P<0.01 compared to F0 and F5). Conclusion: Hippocampal Cx43 is overexpressed in pilocarpine model of epileptogenesis after acquisition of focal seizures. PMID:28042145

A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable

PubMed Central

Tian, Hua; Biehs, Brian; Warming, Soren; Leong, Kevin G.; Rangell, Linda; Klein, Ophir D.; de Sauvage, Frederic J.

2014-01-01

The small intestine epithelium renews every 2 to 5 days, making it one of the most regenerative mammalian tissues. Genetic inducible fate mapping studies have identified two principal epithelial stem cell pools in this tissue. One pool consists of columnar Lgr5-expressing cells that cycle rapidly and are present predominantly at the crypt base1. The other pool consists of Bmi1-expressing cells that largely reside above the crypt base2. However, the relative functions of these two pools and their interrelationship are not understood. Here, we specifically ablated Lgr5-expressing cells using a diphtheria toxin receptor (DTR) gene knocked into the Lgr5 locus. We found that complete loss of the Lgr5-expressing cells did not perturb homeostasis of the epithelium, indicating that other cell types can compensate for elimination of this population. After ablation of Lgr5-expressing cells, progeny production by Bmi1-expressing cells increased, suggesting that Bmi1-expressing stem cells compensate for the loss of Lgr5-expressing cells. Indeed, lineage tracing showed that Bmi1-expressing cells gave rise to Lgr5-expressing cells, pointing to a hierarchy of stem cells in the intestinal epithelium. Our results demonstrate that Lgr5-expressing cells are dispensable for normal intestinal homeostasis. In the absence of these cells, the Bmi1-expressing cells can serve as an alternative stem cell pool, providing the first experimental evidence for the interrelationship between these populations. The Bmi1-expressing stem cells may represent both a reserve stem cell pool in case of injury to the small intestine epithelium and a source for replenishment of the Lgr5-expressing cells under non-pathological conditions. PMID:21927002

Evaluation of the secretion and release of vascular endothelial growth factor from two-dimensional culture and three-dimensional cell spheroids formed with stem cells and osteoprecursor cells.

PubMed

Lee, Hyunjin; Lee, Sung-Il; Ko, Youngkyung; Park, Jun-Beom

2018-05-18

Co-culture has been applied in cell therapy, including stem cells, and has been reported to give enhanced functionality. In this study, stem-cell spheroids were formed in concave micromolds at different ratios of stem cells to osteoprecursor cells, and the amount of secretion of vascular endothelial growth factor (VEGF) was evaluated. Gingiva-derived stem cells and osteoprecursor cells in the amount of 6 × 105 were seeded on a 24-well culture plate or concave micromolds. The ratios of stem cells to osteoprecursor cells included: 0:4 (group 1), 1:3 (group 2), 2:2 (group 3), 3:1 (group 4), and 4:0 (group 5). The morphology of cells in a 2-dimensional culture (groups 1-5) showed a fibroblast-like appearance. The secretion of VEGF increased with the increase in stem cells, and a statistically significant increase was noted in groups 3, 4 and 5 when compared with the media-only group (p < 0.05). Osteoprecursor cells formed spheroids in concave microwells, and no noticeable change in the morphology was noted with the increase in stem cells. Spheroids containing stem cells were positive for the stem-cell markers SSEA-4. The secretion of VEGF from cell spheroids increased with the increase in stem cells. This study showed that cell spheroids formed with stem cells and osteoprecursor cells with different ratios, using microwells, had paracrine effects on the stem cells. The secretion of VEGF increased with the increase in stem cells. This stem-cell spheroid may be applied for tissue-engineering purposes.

{sup 18}Fluorodeoxyglucose PET Is Prognostic of Progression-Free and Overall Survival in Locally Advanced Pancreas Cancer Treated With Stereotactic Radiotherapy

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

Schellenberg, Devin; Quon, Andy; Minn, A. Yuriko

2010-08-01

Purpose: This study analyzed the prognostic value of positron emission tomography (PET) for locally advanced pancreas cancer patients undergoing stereotactic body radiotherapy (SBRT). Patients and Methods: Fifty-five previously untreated, unresectable pancreas cancer patients received a single fraction of 25-Gy SBRT sequentially with gemcitabine-based chemotherapy. On the preradiation PET-CT, the tumor was contoured and the maximum standardized uptake value (SUVmax) and metabolic tumor burden (MTB) were calculated using an in-house software application. High-SUVmax and low-SUVmax subgroups were created by categorizing patients above or below the median SUVmax. The analysis was repeated to form high-MTB and low-MTB subgroups as well as clinicallymore » relevant subgroups with SUVmax values of <5, 5-10, or >10. Multivariate analysis analyzing SUVmax, MTB, age, chemotherapy cycles, and pretreatment carbohydrate antigen (CA)19-9 was performed. Results: For the entire population, median survival was 12.7 months. Median survival was 9.8 vs.15.3 months for the high- and low- SUVmax subgroups (p <0.01). Similarly, median survival was 10.1 vs. 18.0 months for the high MTB and low MTB subgroups (p <0.01). When clinical SUVmax cutoffs were used, median survival was 6.4 months in those with SUVmax >10, 9.5 months with SUVmax 5.0-10.0, and 17.7 months in those with SUVmax <5 (p <0.01). On multivariate analysis, clinical SUVmax was an independent predictor for overall survival (p = 0.03) and progression-free survival (p = 0.03). Conclusion: PET scan parameters can predict for length of survival in locally advanced pancreas cancer patients.« less

[Research progress of Lgr5-positive stem cells in the formation of organoid in 3D culture].

PubMed

He, Q Q; Li, A; Wang, M H; Gao, X

2018-06-07

Stem cell is critical to regeneration of tissue or organ of human. How to promote repair or regeneration in the tissues/organ using its pluripotency is always an important issue. Lgr5-possitive cell is one type of the stem cell-like cells capable of pluripotent differentiation in various tissues/organs of both humans and mice. Current study showed that single or small amount Lgr5-possitive stem cells can grow and form a plurality of organs in 3D culture system, and some organs can present similar biological and physiological properties with the progenitor they were derived. These studies provided new insight into future orientation, for example, Lgr5-possitive inner ear cells were confirmed as inner ear pluripotent cells population, the experiences obtained from organoid studies of Lgr5-possitive cells have certainly showed potential in the future study of inner ear stem cells. This review will focus on the recent progress associated with Lgr 5-positive stem cells forming organoids in the 3D culture.

Horizon nomenclature for quartzipsamments in the Carolina and Georgia Sand Hills, South Carolina

USDA-ARS?s Scientific Manuscript database

Quartzipsamments comprise about 189,600 hectare (9.5 percent) of the Carolina and Georgia Sand Hills region (MLRA 137). Official Series Descriptions typically have A - C (Lakeland Series; Typic subgroup) or A - E - E and Bt (Alpin Series; Lamellic subgroup) horizon designation. Horizon colors, alon...

Loss of attentional inhibition in older adults--Does it really exist? An experimental dissociation of inhibitory and memory retrieval processes.

PubMed

Giesen, Carina; Eberhard, Maike; Rothermund, Klaus

2015-06-01

It is commonly assumed that attentional inhibitory functioning decreases with age, even though empirical evidence is mixed. These inconsistencies possibly stem from methodological artifacts: distractor inhibition is typically assessed with the negative priming paradigm, which confounds inhibition and episodic retrieval. In the present study, we investigated age differences in a sequential distractor repetition paradigm (Giesen, Frings, & Rothermund, 2012) that provides independent estimates of distractor inhibition and episodic retrieval processes. Older (60+ yrs) and younger (below 30 years) adults identified target letters that were flanked by distractors (JKJ). Inhibitory processes were preserved in older adults, who showed reliable distractor repetition benefits resulting from persistent distractor inhibition; however, a significant loss of inhibition was apparent for the older subgroup of participants (65+ yrs) compared with a subgroup of young-old participants (60 to 64 years). No age differences were found for episodic retrieval processes of stimulus-response bindings that were indexed by an interaction of distractor repetition and response relation. Findings highlight the importance of dissociating between distractor inhibition and retrieval processes that are differently implicated in age-related cognitive change. (c) 2015 APA, all rights reserved.

Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS

DTIC Science & Technology

2012-10-01

Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS PRINCIPAL INVESTIGATOR: Nicholas J. Maragakis, M.D...Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS 5b. GRANT NUMBER W81XWH-10-1-0520 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...into astrocytes following transplantation. 15. SUBJECT TERMS Stem Cells , iPS cells, astrocytes, familial ALS 16. SECURITY CLASSIFICATION OF

Salmonberry and salal annual aerial stem production: The maintenance of shrub cover in forest stands

USGS Publications Warehouse

Tappeiner, J. C.; Zasada, J.; Huffman, D.; Ganio, L.

2001-01-01

Annual sprouting of aerial stems and ramets enables populations of salmonberry (Rubus spectabilis Pursh), salal (Gaultheria shallon Pursh), and probably other forest shrubs to maintain dense covers (>20 000 stems/ha). We studied annual stem production of salmonberry on cut (all stems cut within 15 cm of the ground) and uncut (stems were not treated) plots for 8 years and salal for 5 years in the understories of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), alder, and riparian stands, as well as clearcuts, which are all common stand types in western Oregon. Mean salmonberry stem production on uncut plots ranged from 4.7 stemsA?ma??2A?yeara??1 (95% CI 2.9a??7.4) in alder stands and clearcuts to 1.6 stemsA?ma??2A?yeara??1 (95% CI 1.0a??2.6) in conifer stands. Mean salal production was greater, ranging from 58 stemsA?ma??2A?yeara??1 (95% CI 25a??135) to 8.6 stemsA?ma??2A?yeara??1 (95% CI 3.7a??20.1) on uncut plots in clearcuts and unthinned Douglas-fir stands, respectively. Annual production of both species was somewhat greater on cut plots. Most stems produced in early spring die by December, but enough are recruited to replace mortality of older stems. Stem density was maintained for 8 years for salmonberry and 5 years for salal on both cut and uncut plots. Based on length of rhizomes and bud density we estimate that only 1a??5% of the buds in the rhizomes are needed to support this annual stem production. Although these species sprout vigorously after their aerial stems are killed, disturbance is not necessary for maintaining a dense cover. It appears that, once established, salal, salmonberry, and probably other clonal forest shrubs can maintain a dense cover that can interfere with establishment of trees and other shrubs in canopy gaps or other openings.

The medical genetics workforce: an analysis of clinical geneticist subgroups.

PubMed

Cooksey, Judith A; Forte, Gaetano; Flanagan, Patricia A; Benkendorf, Judith; Blitzer, Miriam G

2006-10-01

Clinical geneticists with a Doctor of Medicine degree face challenges to meet the growing population demand for genetic services. This study was designed to assist the profession with workforce planning by identifying clinically relevant subgroups of geneticists and describing their professional characteristics and clinical practices. Geneticists' patient care productivity is compared across subgroups and other medical specialists. Part of a comprehensive national study of genetic services and the health workforce, this study uses data from a 2003 survey of geneticists certified by the American Board of Medical Genetics. This study includes 610 clinical geneticists who spend at least 5% of their time in direct patient-care services. An iterative approach was used to identify five subgroups based on the types of new patients seen. We conducted a descriptive analysis of subgroups by demographic, training, professional, and practice characteristics. The subgroups include general (36%), pediatric (28%), reproductive (15%), metabolic (14%), and adult (7%) geneticists. Clinically relevant variations across subgroups were noted in training, professional, and practice parameters. Subgroups vary across patient care hours (median, 15-33 hours/week) and total weekly work hours (52-60 hours). New patient visits (mean, 222-900/year) are higher than follow-up patient visits (mean, 155-405) for all subgroups except metabolic geneticists. Although many geneticists practice as generalist geneticists, this study provides an evidence base for distinguishing clinically relevant subgroups of geneticists. Geneticists provide similar numbers of new patient visits and far fewer follow-up visits than other medical specialists. These findings are relevant to geneticist workforce planning.

Discriminative and predictive validity of the scoliosis research society-22 questionnaire in management and curve-severity subgroups of adolescents with idiopathic scoliosis.

PubMed

Parent, Eric C; Hill, Doug; Mahood, Jim; Moreau, Marc; Raso, Jim; Lou, Edmond

2009-10-15

Prospective cross-sectional measurement study. To determine the ability of the Scoliosis Research Society (SRS)-22 questionnaire to discriminate among management and scoliosis severity subgroups and to correlate with internal and external measures of curve severity. In earlier studies of the SRS-22 discriminative ability, age was not a controlled factor. The ability of the SRS-22 to predict curve severity has not been thoroughly examined. The SRS-22 was completed by 227 females with adolescent idiopathic scoliosis. Using Analysis of covariance analyses controlling for age, the SRS-22 scores were compared among management subgroups (observation, brace, presurgery, and postsurgery) and curve-severity subgroups (in nonoperated subjects: Cobb angles of <30 degrees, 30 degrees -50 degrees, and >50 degrees). A stepwise discriminant analysis was used to identify the SRS-22 domains most discriminative for curve-severity categories. Correlation between SRS-22 scores and radiographic or surface topography measurements was used to determine the predictive ability of the questionnaire. Pain was better for subjects treated with braces than for those planning surgery. Self-image was better for subjects under observation or postsurgery than for those planning surgery. Satisfaction was better for the brace and postsurgery subgroups than for the observation or presurgery subgroups. Statistically significant mean differences between subgroups were all larger than 0.5, which is within the range of minimal clinically important differences recommended for each of the 5-point SRS-22 domain scoring scales. Pain and mental health were worse for those with Cobb angles of >50 degrees than with Cobb angles of 30 degrees to 50 degrees. Self-image and total scores were worse for those with Cobb angles of >50 degrees than both other subgroups. Using discriminant analysis, self-image was the only SRS-22 domain score selected to classify subjects within curve severity subgroups. The percentage of patients accurately classified was 54% when trying to classify within 3 curve severity subgroups. The percentage of patients accurately classified was 73% when classifying simply as those with curves larger or smaller than 50 degrees . Pain, self-image, and satisfaction scores could discriminate among management subgroups, but function, mental health and total scores could not. The total score and all domain scores except satisfaction discriminated among curve-severity subgroups. Using discriminant analysis, self-image was the only domain retained in a model predicting curve-severity categories.

High temperature attenuates the gravitropism of inflorescence stems by inducing SHOOT GRAVITROPISM 5 alternative splicing in Arabidopsis.

PubMed

Kim, Joo-Young; Ryu, Jae Yong; Baek, Kon; Park, Chung-Mo

2016-01-01

In higher plants, gravitropism proceeds through three sequential steps in the responding organs: perception of gravity signals, signal transduction and asymmetric cell elongation. Light and temperature also influence the gravitropic orientation of plant organs. A series of Arabidopsis shoot gravitropism (sgr) mutants has been shown to exhibit disturbed shoot gravitropism. SGR5 is functionally distinct from other SGR members in that it mediates the early events of gravitropic responses in inflorescence stems. Here, we demonstrated that SGR5 alternative splicing produces two protein variants (SGR5α and SGR5β) in modulating the gravitropic response of inflorescence stems at high temperatures. SGR5β inhibits SGR5α function by forming non-DNA-binding heterodimers. Transgenic plants overexpressing SGR5β (35S:SGR5β) exhibit reduced gravitropic growth of inflorescence stems, as observed in the SGR5-deficient sgr5-5 mutant. Interestingly, SGR5 alternative splicing is accelerated at high temperatures, resulting in the high-level accumulation of SGR5β transcripts. When plants were exposed to high temperatures, whereas gravitropic curvature was reduced in Col-0 inflorescence stems, it was uninfluenced in the inflorescence stems of 35S:SGR5β transgenic plants and sgr5-5 mutant. We propose that the thermoresponsive alternative splicing of SGR5 provides an adaptation strategy by which plants protect the shoots from hot air under high temperature stress in natural habitats. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Single-cell Sequencing Reveals Variants in ARID1A, GPRC5A and MLL2 Driving Self-renewal of Human Bladder Cancer Stem Cells.

PubMed

Yang, Zhao; Li, Chong; Fan, Zusen; Liu, Hongjie; Zhang, Xiaolong; Cai, Zhiming; Xu, Liqin; Luo, Jian; Huang, Yi; He, Luyun; Liu, Chunxiao; Wu, Song

2017-01-01

Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis. Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Which subgroups of fire fighters are more prone to work-related diminished health requirements?

PubMed

Plat, Marie-Christine J; Frings-Dresen, Monique H W; Sluiter, Judith K

2012-10-01

To determine whether certain subgroups of fire fighters are prone to work-related diminished health requirements. The health requirements for fire-fighting were tested in a workers' health surveillance (WHS) setting. These health requirements included psychological, physical and sense-related components as well as cardiovascular risk factors. The odds ratio (OR) and 95% confidence interval (95% CI) for the presence of the diminished health requirements were calculated for the subgroups of gender, professionalism and age. The prevalence of diminished psychological requirements was equivalent among the subgroups, and no significant high-risk group was identified. As compared to men fire fighters, women fire fighters were more likely to have diminished physical requirements (OR 28.5; 95% CI 12.1-66.9) and less likely to have cardiovascular risk factors (OR 0.3; 0.1-0.5). As compared to volunteer fire fighters, professionals were less likely to have diminished physical requirements (OR 0.5; 0.3-0.9), but professionals had a higher prevalence of cardiovascular risk factors with an odds ratio of 1.9 (1.1-3.2). As compared to the youngest fire fighters, the oldest fire fighters were more likely to have diminished sense-related requirements (OR 7.1; 3.4-15.2); a similar comparison could be made between oldest and middle-aged fire fighters (OR 5.1; 2.5-10.5). In addition, the oldest fire fighters were more likely to have cardiovascular risk factors when compared to the youngest (OR 4.4; 1.7-11.1) and to the middle-aged fire fighters (OR 3.1; 1.2-7.9). Subgroups (gender, professionalism and age) of fire fighters are prone to at least one specific work-related diminished health requirement. Therefore, parts of the WHS could be applied with more attention to these high-risk groups.

In vivo stem cell tracking with imageable nanoparticles that bind bioorthogonal chemical receptors on the stem cell surface.

PubMed

Lee, Sangmin; Yoon, Hwa In; Na, Jin Hee; Jeon, Sangmin; Lim, Seungho; Koo, Heebeom; Han, Sang-Soo; Kang, Sun-Woong; Park, Soon-Jung; Moon, Sung-Hwan; Park, Jae Hyung; Cho, Yong Woo; Kim, Byung-Soo; Kim, Sang Kyoon; Lee, Taekwan; Kim, Dongkyu; Lee, Seulki; Pomper, Martin G; Kwon, Ick Chan; Kim, Kwangmeyung

2017-09-01

It is urgently necessary to develop reliable non-invasive stem cell imaging technology for tracking the in vivo fate of transplanted stem cells in living subjects. Herein, we developed a simple and well controlled stem cell imaging method through a combination of metabolic glycoengineering and bioorthogonal copper-free click chemistry. Firstly, the exogenous chemical receptors containing azide (-N 3 ) groups were generated on the surfaces of stem cells through metabolic glycoengineering using metabolic precursor, tetra-acetylated N-azidoacetyl-d-mannosamine(Ac 4 ManNAz). Next, bicyclo[6.1.0]nonyne-modified glycol chitosan nanoparticles (BCN-CNPs) were prepared as imageable nanoparticles to deliver different imaging agents. Cy5.5, iron oxide nanoparticles and gold nanoparticles were conjugated or encapsulated to BCN-CNPs for optical, MR and CT imaging, respectively. These imageable nanoparticles bound chemical receptors on the Ac 4 ManNAz-treated stem cell surface specifically via bioorthogonal copper-free click chemistry. Then they were rapidly taken up by the cell membrane turn-over mechanism resulting in higher endocytic capacity compared non-specific uptake of nanoparticles. During in vivo animal test, BCN-CNP-Cy5.5-labeled stem cells could be continuously tracked by non-invasive optical imaging over 15 days. Furthermore, BCN-CNP-IRON- and BCN-CNP-GOLD-labeled stem cells could be efficiently visualized using in vivo MR and CT imaging demonstrating utility of our stem cell labeling method using chemical receptors. These results conclude that our method based on metabolic glycoengineering and bioorthogonal copper-free click chemistry can stably label stem cells with diverse imageable nanoparticles representing great potential as new stem cell imaging technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

PTSD's factor structure and measurement invariance across subgroups with differing count of trauma types.

PubMed

Contractor, Ateka A; Caldas, Stephanie V; Dolan, Megan; Lagdon, Susan; Armour, Chérie

2018-06-01

To investigate the effect of the count of traumatizing event (TE) types on post-trauma mental health, several studies have compared posttraumatic stress disorder (PTSD) severity between individuals experiencing one versus multiple TE types. However, the validity of these studies depends on the establishment of measurement invariance of the construct(s) of interest. The current study examined the stability of the most optimal PTSD Model symptom cluster constructs (assessed by the PTSD Checklist for DSM-5 [PCL-5]) across subgroups experiencing one versus multiple TE types. The sample included university students (n = 556) endorsing at least one TE (Stressful Life Events Screening Questionnaire). Using data from the entire sample, results suggest that the PCL-5-assessed Hybrid Model provided a significantly better fit compared to other models. Results also indicated invariance of factor loadings (metric), and intercepts (scalar) for the PCL-5-assessed Hybrid Model factors across subgroups endorsing one (n = 191) versus multiple TE types (n = 365). Our findings thus support the stability, applicability, and meaningful comparison of the PCL-assessed Hybrid Model factor structure (including subscale severity scores) across subgroups experiencing one versus multiple TE types. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of fasciclin-like arabinogalactan proteins in textile hemp (Cannabis sativa L.): in silico analyses and gene expression patterns in different tissues.

PubMed

Guerriero, Gea; Mangeot-Peter, Lauralie; Legay, Sylvain; Behr, Marc; Lutts, Stanley; Siddiqui, Khawar Sohail; Hausman, Jean-Francois

2017-09-20

The fasciclin-like arabinogalactan proteins (FLAs) belong to the arabinogalactan protein (AGP) superfamily and are known to play different physiological roles in plants. This class of proteins was shown to participate in plant growth, development, defense against abiotic stresses and, notably, cell wall biosynthesis. Although some studies are available on the characterization of FLA genes from different species, both woody and herbaceous, no detailed information is available on the FLA family of textile hemp (Cannabis sativa L.), an economically important fibre crop. By searching the Cannabis genome and EST databases, 23 CsaFLAs have been here identified which are divided into four phylogenetic groups. A real-time qPCR analysis performed on stem tissues (isolated bast fibres and shivs sampled at three heights), hypocotyls (6-9-12-15-17-20 days-old), whole seedlings, roots, leaves and female/male flowers of the monoecious fibre variety Santhica 27, indicates that the identified FLA genes are differentially expressed. Interestingly, some hemp FLAs are expressed during early phases of fibre growth (elongation), while others are more expressed in the middle and base of the stem and thus potentially involved in secondary cell wall formation (fibre thickening). The bioinformatic analysis of the promoter regions shows that the FLAs upregulated in the younger regions of the stem share a conserved motif related to flowering control and regulation of photoperiod perception. The promoters of the FLA genes expressed at higher levels in the older stem regions, instead, share a motif putatively recognized by MYB3, a transcriptional repressor belonging to the MYB family subgroup S4. These results point to the existence of a transcriptional network fine-tuning the expression of FLA genes in the older and younger regions of the stem, as well as in the bast fibres/shivs of textile hemp. In summary, our study paves the way for future analyses on the biological functions of FLAs in an industrially relevant fibre crop.

National economic impact of tirofiban for unstable angina and myocardial infarction without ST elevation; example from the United Kingdom.

PubMed

Bakhai, Ameet; Flather, Marcus D; Collinson, Julian R; Stevens, Warren; Normand, Charles; Alemao, Evo; Itzler, Robbin; Ben-Joseph, Rami

2003-10-01

Acute coronary syndromes without ST elevation are a major health and economic burden. Treatments such as glycoprotein IIb/IIIa antagonists like tirofiban reduce the risk of complications but the cost impact of these agents including cost offsets of avoiding complications are needed particularly in Europe. We used treatment patterns from the Prospective Registry of Acute Ischemic Syndromes in the UK, risk reductions derived from the PRISM-PLUS trial and cost estimates from the CHKS database to estimate the impact of tirofiban on PRAIS-UK patients with and without complications and subgroups at higher risk of complications. These subgroups (and proportions) were patients: (1) aged 60 or over with abnormal electrocardiograms (58%), (2) with ST depression or bundle branch block on admission (30%) and (3) with ST depression, bundle branch block or MI on admission (37%). Total cost of care in the UK at 6 months for the estimated 87339 acute coronary syndromes admissions annually was pound 213 million, which would increase by pound 33 million (15.7%) if tirofiban were given to all patients, avoiding 2422 complications at a mean cost per event avoided of pound 13388. Among the subgroups, the mean cost per event avoided ranges from pound 10856 for subgroup 1 to pound 5953 for subgroup 3. Treating the latter subgroup, would avoid 1977 events at a cost of pound 12 million (5.5%). The use of tirofiban in the UK to treat acute coronary syndromes patients without ST elevation provides an important therapeutic advantage at modest proportional increase in cost, particularly if targeted to higher risk subgroups as recommended in the European guidelines.

Partial Functional Diversification of Drosophila melanogaster Septin Genes Sep2 and Sep5.

PubMed

O'Neill, Ryan S; Clark, Denise V

2016-07-07

The septin family of hetero-oligomeric complex-forming proteins can be divided into subgroups, and subgroup members are interchangeable at specific positions in the septin complex. Drosophila melanogaster has five septin genes, including the two SEPT6 subgroup members Sep2 and Sep5 We previously found that Sep2 has a unique function in oogenesis, which is not performed by Sep5 Here, we find that Sep2 is uniquely required for follicle cell encapsulation of female germline cysts, and that Sep2 and Sep5 are redundant for follicle cell proliferation. The five D. melanogaster septins localize similarly in oogenesis, including as rings flanking the germline ring canals. Pnut fails to localize in Sep5; Sep2 double mutant follicle cells, indicating that septin complexes fail to form in the absence of both Sep2 and Sep5. We also find that mutations in septins enhance the mutant phenotype of bazooka, a key component in the establishment of cell polarity, suggesting a link between septin function and cell polarity. Overall, this work suggests that Sep5 has undergone partial loss of ancestral protein function, and demonstrates redundant and unique functions of septins. Copyright © 2016 O'Neill and Clark.

Improvement over the years of long-term survival in high-risk lymphoma patients treated with hematopoietic stem cell transplantation as consolidation or salvage therapy.

PubMed

Calderón-Cabrera, C; Márquez-Malaver, F J; de la Cruz-Vicente, F; Falantes, F; Carrillo, E; Parody, R; Montero, I; González Campos, J; Martino, M L; Carmona, M; Pérez-Simón, J A; Espigado, I

2013-01-01

The role of hemopoietic stem cell transplantation (HSCT) is not well established in certain types of lymphoma, such as those with a high relapse risk or relapsing after initial therapy. New chemotherapeutic schemes and immunotherapy have improved survival of these patients. Nevertheless, there is not enough evidence regarding whether transplantation is the best therapeutic approach. Moreover, published data on long-term follow-up of high-risk lymphoma patients treated with HSCT are scarce. We analyzed 177 consecutive patients diagnosed with a high risk of relapse or with relapsed lymphoma who underwent HSCT after induction with standard chemotherapy in a tertiary academic center from 1989 to 2013. The median age was 40 years. Diagnoses were Hodgkin disease (n = 56), diffuse large B-cell lymphoma (n = 44), follicular lymphoma (n = 29), mantle cell lymphoma (n = 15), T-cell lymphoma (n = 18), and others (n = 15). Patients received either an autologous graft (n = 154) in first complete remission (1CR; n = 59) or more advanced stages (AS; n = 95), or an allogeneic graft (n = 23) in 1CR (n = 4) or AS (n = 19). In the autologous group, overall survival (OS) at 5 years was 57% and 75% in the periods 1989-2001 and 2002-2013, respectively (P = .05). Patients receiving an allogeneic graft presented an OS of 25% and 43% in the 2 periods. With a mean follow-up of 5 years (95% confidence interval 3.5-6.6), for patients receiving a transplant in 1CR, OS at 5 years was 80%, and for those receiving a transplant in AS it was 59% (P = .003). Nonrelapse mortality (NRM) at 5 years was 3.1% in the autologous group and 27.9% in the allogeneic group (P < .001). The main cause of NRM was infection (44%) in the whole cohort. All this leads to the conclusion that transplantation, as a therapeutic strategy, has shown a high long-term OS in this subgroup of patients with such a poor prognosis. OS improved over the years and reaching 1CR was a good prognostic feature. Infections were the main cause of NRM. Copyright © 2013 Elsevier Inc. All rights reserved.

Distinguishing between Subgroups of Adolescents Who Self-Harm

ERIC Educational Resources Information Center

Hargus, Emily; Hawton, Keith; Rodham, Karen

2009-01-01

The differences in factors associated with subgroups of adolescents in the continuum of deliberate self-harm (DSH) phenomena were investigated. In an anonymous self-report survey of 6,020 adolescents aged 15 and 16 years, 3.2% of adolescents (5.3% females, 1.3% males) reported DSH with intent to die, 2.8% (4.3% females; 1.5% males) reported DSH…

An Analysis of microRNA Expression in the Myelodysplastic Syndromes Using Hematopoietic Stem Cells

DTIC Science & Technology

2014-08-01

AWARD NUMBER: W81XWH-13-1-0082 TITLE: An Analysis of microRNA Expression in the Myelodysplastic Syndromes Using Hematopoietic Stem Cells ... Hematopoietic Stem Cells 5b. GRANT NUMBER W81XWH-13-1-0082 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dr. Stephen Chung 5e. TASK...in MDS hematopoietic stem cells (MDS HSCs) as compared with normal HSCs. MiRNAs differentially expressed between MDS HSCs and normal HSCs overlapped

Gastric Lgr5+ stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice

PubMed Central

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-01-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5+ stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5+ stem cells by the inducible Cre-LoxP system and marked mutant Lgr5+ stem cells and their progeny with Cre-reporter Rosa26tdTomato. Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5+ stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5+ chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5+ cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5+ stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression. PMID:27091432

Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice.

PubMed

Li, Xiu-Bin; Yang, Guan; Zhu, Liang; Tang, Yu-Ling; Zhang, Chong; Ju, Zhenyu; Yang, Xiao; Teng, Yan

2016-07-01

The cellular origin of gastric cancer remains elusive. Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) is the first identified marker of gastric stem cells. However, the role of Lgr5(+) stem cells in driving malignant gastric cancer is not fully validated. Here, we deleted Smad4 and PTEN in murine gastric Lgr5(+) stem cells by the inducible Cre-LoxP system and marked mutant Lgr5(+) stem cells and their progeny with Cre-reporter Rosa26(tdTomato). Rapid onset and progression from microadenoma and macroscopic adenoma to invasive intestinal-type gastric cancer (IGC) were found in the gastric antrum with the loss of Smad4 and PTEN. In addition, invasive IGC developed at the murine gastro-forestomach junction, where a few Lgr5(+) stem cells reside. In contrast, Smad4 and PTEN deletions in differentiated cells, including antral parietal cells, pit cells and corpus Lgr5(+) chief cells, failed to initiate tumor growth. Furthermore, mutant Lgr5(+) cells were involved in IGC growth and progression. In the TCGA (The Cancer Genome Atlas) database, an increase in LGR5 expression was manifested in the human IGC that occurred at the gastric antrum and gastro-esophageal junction. In addition, the concurrent deletion of SMAD4 and PTEN, as well as their reduced expression and deregulated downstream pathways, were associated with human IGC. Thus, we demonstrated that gastric Lgr5(+) stem cells were cancer-initiating cells and might act as cancer-propagating cells to contribute to malignant progression.

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis.

PubMed

Acar, S; Millar, E; Mitkova, M; Mitkov, V

2016-11-01

The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. The following values of Young's modulus were found in subgroup A (adenomyosis): Emean - 72.7 (22.6-274.2) kPa (median, 5-95th percentiles), Emax - 94.8 (29.3-300.0) kPa, SD - 9.9 (2.6-26.3) kPa; in subgroup B (non adenomyosis) - 28.3 (12.7-59.5) kPa, 33.6 (16.0-80.8) kPa, 3.0 (1.4-15.6) kPa; in the control group - 24.4 (17.9-32.4) kPa, 29.8 (21.6-40.8) kPa, 2.3 (1.3-6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis.

Stemming Colorectal Cancer Growth and Metastasis: HOXA5 Forces Cancer Stem Cells to Differentiate.

PubMed

Tan, Si Hui; Barker, Nick

2015-12-14

Wnt signaling drives colorectal cancer stem cells, but effective therapeutics targeting these cells and their signaling pathways are lacking. In this issue of Cancer Cell, Ordóñez-Morán and colleagues describe a promising therapeutic intervention for colorectal cancers that selectively induces cancer stem cell differentiation through HOXA5 expression and Wnt signaling inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

Anterior versus posterior surgery for multilevel cervical myelopathy, which one is better? A systematic review

PubMed Central

Liu, Tao; Xu, Wen; Cheng, Tao

2010-01-01

The objective of the study is to perform a systematic review to compare the clinical outcomes and complications of anterior surgery with posterior surgery for multilevel cervical myelopathy (MCM). MEDLINE, EMBASE databases and other databases were searched for all the relevant original articles published from January 1991 to November 2009 comparing anterior with posterior surgery for MCM. Subgroup analysis was performed according to the follow-up years. The following end points were mainly evaluated: final follow-up JOA (Japanese Orthopaedic Association) scale, recovery rate and complication outcomes. Ten articles fulfilled all inclusion criteria. For multilevel CSM patients, the final follow-up JOA score for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 0.83 [0.24, 1.43]) in the ‘follow-up time ≤5 years’ subgroup, but had no significant differences in the ‘follow-up time >5 years’ subgroup (p > 0.05). The recovery rate for the anterior group was significantly higher than the posterior group (p < 0.05, WMD 10.08 [1.39, 18.78]) in the ‘follow-up time ≤5 years’ subgroup. No study reported the recovery rate for the follow-up time >5 years. For multilevel OPLL patients, the final follow-up JOA score and recovery rate for the anterior group were both significantly higher than the posterior group in the ‘follow-up time ≤5 years’ subgroup (p < 0.05, WMD 2.50 [0.16, 4.85]; p < 0.05, WMD 29.48 [29.09, 29.87], respectively). One study [31] which mean follow-up time was 6 years was enrolled in the ‘follow-up time >5 years’ subgroup. The results showed there was no significant difference in final follow-up JOA score and recovery rate between anterior and posterior group for patients with occupying ratio of OPLL <60% (p > 0.05), while in patients with occupying ratio ≥60%, the final follow-up JOA score and recovery rate of anterior surgery were both superior to that of posterior surgery (p < 0.05). For both multilevel CSM and OPLL patients, the complications for the anterior group were significantly more than the posterior group in the ‘follow-up time ≤5 years’ subgroup (p < 0.05, OR 7.33 [2.96, 18.20] for CSM patients; p < 0.05, OR 4.44 [1.80, 10.98] for OPLL patients), but were similar to the posterior group in the ‘follow-up time >5 years’ subgroup (p > 0.05). In conclusion, anterior surgery had better clinical outcomes and more complications at the early stage after operation for both multilevel CSM and OPLL patients. At the late stage, posterior surgery had similar clinical outcomes and complications to anterior surgery for CSM patients, and OPLL patients with occupying ratio of OPLL <60%. While for OPLL patients with occupying ratio ≥60%, anterior surgery had superior clinical outcome to posterior surgery. PMID:20582710

Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups

PubMed Central

2012-01-01

Background Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). Methods A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. Results The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Conclusions Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High-risk subgroups may be identified automatically from existing geriatric assessment data, especially when combined with domain knowledge in a hybrid classification model. Further work is necessary to validate our approach in a controlled prospective setting. PMID:22417403

Mining geriatric assessment data for in-patient fall prediction models and high-risk subgroups.

PubMed

Marschollek, Michael; Gövercin, Mehmet; Rust, Stefan; Gietzelt, Matthias; Schulze, Mareike; Wolf, Klaus-Hendrik; Steinhagen-Thiessen, Elisabeth

2012-03-14

Hospital in-patient falls constitute a prominent problem in terms of costs and consequences. Geriatric institutions are most often affected, and common screening tools cannot predict in-patient falls consistently. Our objectives are to derive comprehensible fall risk classification models from a large data set of geriatric in-patients' assessment data and to evaluate their predictive performance (aim#1), and to identify high-risk subgroups from the data (aim#2). A data set of n = 5,176 single in-patient episodes covering 1.5 years of admissions to a geriatric hospital were extracted from the hospital's data base and matched with fall incident reports (n = 493). A classification tree model was induced using the C4.5 algorithm as well as a logistic regression model, and their predictive performance was evaluated. Furthermore, high-risk subgroups were identified from extracted classification rules with a support of more than 100 instances. The classification tree model showed an overall classification accuracy of 66%, with a sensitivity of 55.4%, a specificity of 67.1%, positive and negative predictive values of 15% resp. 93.5%. Five high-risk groups were identified, defined by high age, low Barthel index, cognitive impairment, multi-medication and co-morbidity. Our results show that a little more than half of the fallers may be identified correctly by our model, but the positive predictive value is too low to be applicable. Non-fallers, on the other hand, may be sorted out with the model quite well. The high-risk subgroups and the risk factors identified (age, low ADL score, cognitive impairment, institutionalization, polypharmacy and co-morbidity) reflect domain knowledge and may be used to screen certain subgroups of patients with a high risk of falling. Classification models derived from a large data set using data mining methods can compete with current dedicated fall risk screening tools, yet lack diagnostic precision. High-risk subgroups may be identified automatically from existing geriatric assessment data, especially when combined with domain knowledge in a hybrid classification model. Further work is necessary to validate our approach in a controlled prospective setting.

Accounting for Subgroup Structure in Line-Transect Abundance Estimates of False Killer Whales (Pseudorca crassidens) in Hawaiian Waters

PubMed Central

Bradford, Amanda L.; Forney, Karin A.; Oleson, Erin M.; Barlow, Jay

2014-01-01

For biological populations that form aggregations (or clusters) of individuals, cluster size is an important parameter in line-transect abundance estimation and should be accurately measured. Cluster size in cetaceans has traditionally been represented as the total number of individuals in a group, but group size may be underestimated if group members are spatially diffuse. Groups of false killer whales (Pseudorca crassidens) can comprise numerous subgroups that are dispersed over tens of kilometers, leading to a spatial mismatch between a detected group and the theoretical framework of line-transect analysis. Three stocks of false killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian Islands (Hawaiian EEZ): an insular main Hawaiian Islands stock, a pelagic stock, and a Northwestern Hawaiian Islands (NWHI) stock. A ship-based line-transect survey of the Hawaiian EEZ was conducted in the summer and fall of 2010, resulting in six systematic-effort visual sightings of pelagic (n = 5) and NWHI (n = 1) false killer whale groups. The maximum number and spatial extent of subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings were combined with data from similar previous surveys and analyzed within the conventional line-transect estimation framework. The detection function, mean cluster size, and encounter rate were estimated separately to appropriately incorporate data collected using different methods. Unlike previous line-transect analyses of cetaceans, subgroups were treated as the analytical cluster instead of groups because subgroups better conform to the specifications of line-transect theory. Bootstrap values (n = 5,000) of the line-transect parameters were randomly combined to estimate the variance of stock-specific abundance estimates. Hawai’i pelagic and NWHI false killer whales were estimated to number 1,552 (CV = 0.66; 95% CI = 479–5,030) and 552 (CV = 1.09; 95% CI = 97–3,123) individuals, respectively. Subgroup structure is an important factor to consider in line-transect analyses of false killer whales and other species with complex grouping patterns. PMID:24587372

Accounting for subgroup structure in line-transect abundance estimates of false killer whales (Pseudorca crassidens) in Hawaiian waters.

PubMed

Bradford, Amanda L; Forney, Karin A; Oleson, Erin M; Barlow, Jay

2014-01-01

For biological populations that form aggregations (or clusters) of individuals, cluster size is an important parameter in line-transect abundance estimation and should be accurately measured. Cluster size in cetaceans has traditionally been represented as the total number of individuals in a group, but group size may be underestimated if group members are spatially diffuse. Groups of false killer whales (Pseudorca crassidens) can comprise numerous subgroups that are dispersed over tens of kilometers, leading to a spatial mismatch between a detected group and the theoretical framework of line-transect analysis. Three stocks of false killer whales are found within the U.S. Exclusive Economic Zone of the Hawaiian Islands (Hawaiian EEZ): an insular main Hawaiian Islands stock, a pelagic stock, and a Northwestern Hawaiian Islands (NWHI) stock. A ship-based line-transect survey of the Hawaiian EEZ was conducted in the summer and fall of 2010, resulting in six systematic-effort visual sightings of pelagic (n = 5) and NWHI (n = 1) false killer whale groups. The maximum number and spatial extent of subgroups per sighting was 18 subgroups and 35 km, respectively. These sightings were combined with data from similar previous surveys and analyzed within the conventional line-transect estimation framework. The detection function, mean cluster size, and encounter rate were estimated separately to appropriately incorporate data collected using different methods. Unlike previous line-transect analyses of cetaceans, subgroups were treated as the analytical cluster instead of groups because subgroups better conform to the specifications of line-transect theory. Bootstrap values (n = 5,000) of the line-transect parameters were randomly combined to estimate the variance of stock-specific abundance estimates. Hawai'i pelagic and NWHI false killer whales were estimated to number 1,552 (CV = 0.66; 95% CI = 479-5,030) and 552 (CV = 1.09; 95% CI = 97-3,123) individuals, respectively. Subgroup structure is an important factor to consider in line-transect analyses of false killer whales and other species with complex grouping patterns.

Prognostic performance of Emergency Severity Index (ESI) combined with qSOFA score.

PubMed

Kwak, Hyeongkyu; Suh, Gil Joon; Kim, Taegyun; Kwon, Woon Yong; Kim, Kyung Su; Jung, Yoon Sun; Ko, Jung-In; Shin, So Mi

2018-01-31

We conducted this study to investigate whether ESI combined with qSOFA score (ESI+qSOFA) predicts hospital outcome better than ESI alone in the emergency department (ED). This was a retrospective study for patients aged over 15years who visited an ED of a tertiary referral hospital from January 1st, 2015 to December 31st, 2015. We calculated and compared predictive performances of ESI alone and ESI+qSOFA for prespecified outcomes. The primary outcome was hospital mortality, and the secondary outcome was composite outcome of in-hospital mortality and ICU admission. We calculated in-hospital mortality rates by positive qSOFA in each subgroup divided according to ESI levels (1, 2, 3, 4+5). 43,748 patients were enrolled. The area under receiver-operating characteristics curves were higher in ESI+qSOFA than in ESI alone for both mortality and composite outcome (0.786 vs. 0.777, P<.001 for mortality; 0.778 vs. 0.774, P<.001 for composite outcome). In each subgroup divided by ESI levels, patients with positive qSOFA had significantly higher in-hospital mortality rate compared to those with negative qSOFA (20.4% vs. 14.7%, P=.117 in ESI level 1 subgroup; 11.3% vs. 2.7%, P=.001 in ESI level 2 subgroup; 2.3% vs. 0.4%, P<.001 in ESI level 3 subgroup; 0.0% vs. 0.0% in ESI level 4 or 5 subgroup). The prognostic performance of ESI+qSOFA for in-hospital mortality was significantly higher than that of ESI alone. Within each subgroup, patients with positive qSOFA had higher in-hospital mortality compared to those with negative qSOFA. Copyright © 2018 Elsevier Inc. All rights reserved.

A Populus TIR1 gene family survey reveals differential expression patterns and responses to 1-naphthaleneacetic acid and stress treatments

PubMed Central

Shu, Wenbo; Liu, Yingli; Guo, Yinghua; Zhou, Houjun; Zhang, Jin; Zhao, Shutang; Lu, Mengzhu

2015-01-01

The plant hormone auxin is a central regulator of plant growth. TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX (TIR1/AFB) is a component of the E3 ubiquitin ligase complex SCFTIR1/AFB and acts as an auxin co-receptor for nuclear auxin signaling. The SCFTIR1/AFB-proteasome machinery plays a central regulatory role in development-related gene transcription. Populus trichocarpa, as a model tree, has a unique fast-growth trait to which auxin signaling may contribute. However, no systematic analyses of the genome organization, gene structure, and expression of TIR1-like genes have been undertaken in this woody model plant. In this study, we identified a total of eight TIR1 genes in the Populus genome that are phylogenetically clustered into four subgroups, PtrFBL1/PtrFBL2, PtrFBL3/PtrFBL4, PtrFBL5/PtrFBL6, and PtrFBL7/PtrFBL8, representing four paralogous pairs. In addition, the gene structure and motif composition were relatively conserved in each paralogous pair and all of the PtrFBL members were localized in the nucleus. Different sets of PtrFBLs were strongly expressed in the leaves, stems, roots, cambial zones, and immature xylem of Populus. Interestingly, PtrFBL1 and 7 were expressed mainly in vascular and cambial tissues, respectively, indicating their potential but different roles in wood formation. Furthermore, Populus FBLs responded differentially upon exposure to various stresses. Finally, over-expression studies indicated a role of FBL1 in poplar stem growth and response to drought stress. Collectively, these observations lay the foundation for further investigations into the potential roles of PtrFBL genes in tree growth and development. PMID:26442033

Those ubiquitous fertility trends: United States, 1945-1979.

PubMed

Sweet, J A; Rindfuss, R R

1983-01-01

1970-79 US fertility trends among differnet racial, regional, age, educational, parity, and socioeconomic subgroups in the population were examined, using own children data from the 1976 Survey of Income and Education (SIE) and the March Current Population Surveys (CPS) from 1968-80. In addition, cross-sectional differences in fertility for the subgroups were compared for 1970 and 1976, using multiple regression analysis. 1st, the appropriateness of using fertility rates obtained from own children data was assessed by comparing fertility rates obtained from the SIE data with those derived from vital statistic and census data. The comparative analysis confirmed that the SIE data yielded an accurate estimate of period fertility rates for currently married women, provided the subgroup samples were sufficiently large. CPS fertility estimates were also judged to be accurate if data from 3 adjacent survey years was pooled to increase sample size. Fertility trends for 5 educational groups were assessed separately for 1967-73. During this periold, there was a marked decline in fertility for all 5 groups; for the group with 5-8 years of education the decline was only 14%, but for the other 4 groups, which included women with 9-16 or more years of education, the decline in fertility ranged from 26-29%. In assessing the 1970-76 trends, the sample was restricted to own children, aged 3 years or less, of currently married women, under 40 years of age. Among whites, there was an overall 20% decline in fertility between 1970-76 and an overall fertility increase of about 2% between 1976-79. These trends were observed in all 28 white subgroups. A similar pattern was observed for blacks. There was an overall fertility decline of 24% between 1970-76, and this decline was apparent for all subgroups except women with college degrees. Betwen 1976-79, black fertility rates, unlike white rates, continued to decline, but the rate of decline was only 3%. Furthermore, the decline in almost all the black subgroups was markedly less than in the 1970-76 periold, and for many of the subgroups the trend was reversed and fertility increased. In summary, the fertility trends noted for 1970-79 were pervasive for almost all the subgroups for both blacks and whites; i.e., there was a marked decline in fertility between 1970-76 and than a reversal or slowing down of the decline during the 1976-79 for all black and white subgroups. Cross-sectional fertility differences in the subgroups in 1970 and in 1979 were quite similar, and fertility rates differed markedly for the separate subgroups. These differences do not, of course, explain the pervasive trends observed in the analysis of the fertility rates over time. A similar study assessing fertility trends among subgroups for the early 1940's through the late 1960s also revealed the pervasive nature of period fertility trends. Demographers have not as yet been able to explain these shifts in fertility that cut across all subgroups in the US and which also characterize the period fertility rates in other developed countries. Tables provided information on 1) total fertility rates by educational level and by geographical region for 1945-1975; 2) % change in number of own children less than 3 years of age among women under age 40 by maternal age, maternal education, initial parity, geographical region, and husband's income; and 3) mean number of own children less than 3 years of age among women under age 40 by maternal age, education, parity, region, and husband's income.

Validation d'un nouveau calcul de reference en evolution pour les reacteurs thermiques

NASA Astrophysics Data System (ADS)

Canbakan, Axel

Resonance self-shielding calculations are an essential component of a deterministic lattice code calculation. Even if their aim is to correct the cross sections deviation, they introduce a non negligible error in evaluated parameters such as the flux. Until now, French studies for light water reactors are based on effective reaction rates obtained using an equivalence in dilution technique. With the increase of computing capacities, this method starts to show its limits in precision and can be replaced by a subgroup method. Originally used for fast neutron reactor calculations, the subgroup method has many advantages such as using an exact slowing down equation. The aim of this thesis is to suggest a validation as precise as possible without burnup, and then with an isotopic depletion study for the subgroup method. In the end, users interested in implementing a subgroup method in their scheme for Pressurized Water Reactors can rely on this thesis to justify their modelization choices. Moreover, other parameters are validated to suggest a new reference scheme for fast execution and precise results. These new techniques are implemented in the French lattice scheme SHEM-MOC, composed of a Method Of Characteristics flux calculation and a SHEM-like 281-energy group mesh. First, the libraries processed by the CEA are compared. Then, this thesis suggests the most suitable energetic discretization for a subgroup method. Finally, other techniques such as the representation of the anisotropy of the scattering sources and the spatial representation of the source in the MOC calculation are studied. A DRAGON5 scheme is also validated as it shows interesting elements: the DRAGON5 subgroup method is run with a 295-eenergy group mesh (compared to 361 groups for APOLLO2). There are two reasons to use this code. The first involves offering a new reference lattice scheme for Pressurized Water Reactors to DRAGON5 users. The second is to study parameters that are not available in APOLLO2 such as self-shielding in a temperature gradient and using a flux calculation based on MOC in the self-shielding part of the simulation. This thesis concludes that: (1) The subgroup method is at least more precise than a technique based on effective reaction rates, only if we use a 361-energy group mesh; (2) MOC with a linear source in a geometrical region gives better results than a MOC with a constant model. A moderator discretization is compulsory; (3) A P3 choc law is satisfactory, ensuring a coherence with 2D full core calculations; (4) SHEM295 is viable with a Subgroup Projection Method for DRAGON5.

Clinical Efficacy of a Mouth-Exercising Device Adjunct to Local Ointment Intra-Lesional Injections and Surgical Treatment for Oral Submucous Fibrosis: a Randomized Controlled Trial.

PubMed

Patil, Pravinkumar; Hazarey, Vinay; Chaudhari, Rekha; Nimbalkar-Patil, Smita

2016-01-01

Oral physiotherapy or mouth exercise is considered to be an adjunct but mandatory treatment modality for oral submucous fibrosis (OSMF). This study planned to evaluate the clinical efficacy of a newly designed mouth exercising device (MED) in OSMF patients receiving local ointment, intra-lesional drugs and surgical treatment. A total of 231 OSMF patients were selected and treated with basic regime including topical corticosteroids, oral antioxidants and the icecream-stick exercise regime and allotted randomly to two equal groups A and B. Group-A patients were additionally given MED. Subgroups A1 and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm were managed surgically. IID was measured at baseline and at 6 months recall. The change in IID measurements was calculated and statistically analyzed using 2-way ANOVA and Tukeys multiple post hoc analysis. Average improvement in IID after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53) compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18) compared to 4.8 mm for B3 (n-16) (p<0.01). Use of the MED appears to be effective for increasing oral opening in OMSF patients in conjunction with local, injection and/or surgical treatment.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups.

PubMed

Curtis, Christina; Shah, Sohrab P; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M; Dunning, Mark J; Speed, Doug; Lynch, Andy G; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-04-18

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome.

Patient characteristics in low back pain subgroups based on an existing classification system. A descriptive cohort study in chiropractic practice.

PubMed

Eirikstoft, Heidi; Kongsted, Alice

2014-02-01

Sub-grouping of low back pain (LBP) is believed to improve prediction of prognosis and treatment effects. The objectives of this study were: (1) to examine whether chiropractic patients could be sub-grouped according to an existing pathoanatomically-based classification system, (2) to describe patient characteristics within each subgroup, and (3) to determine the proportion of patients in whom clinicians considered the classification to be unchanged after approximately 10 days. A cohort of 923 LBP patients was included during their first consultation. Patients completed an extensive questionnaire and were examined according to a standardised protocol. Based on the clinical examination, patients were classified into diagnostic subgroups. After approximately 10 days, chiropractors reported whether they considered the subgroup had changed. The most frequent subgroups were reducible and partly reducible disc syndromes followed by facet joint pain, dysfunction and sacroiliac (SI)-joint pain. Classification was inconclusive in 5% of the patients. Differences in pain, activity limitation, and psychological factors were small across subgroups. Within 10 days, 82% were reported to belong to the same subgroup as at the first visit. In conclusion, LBP patients could be classified according to a standardised protocol, and chiropractors considered most patient classifications to be unchanged within 10 days. Differences in patient characteristics between subgroups were very small, and the clinical relevance of the classification system should be investigated by testing its value as a prognostic factor or a treatment effect modifier. It is recommended that this classification system be combined with psychological and social factors if it is to be useful. Copyright © 2013 Elsevier Ltd. All rights reserved.

40 CFR 180.666 - Fluxapyroxad; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

....005 Oilseeds, group 20 (except cottonseed) 0.9 Pea and bean, dried shelled except soybean, subgroup 6C 0.4 Pea and bean, succulent shelled, subgroup 6B 0.5 Peanut 0.01 Peanut, refined oil 0.02 Plum...

Alk5-Mediated Transforming Growth Factor β Signaling Acts Upstream of Fibroblast Growth Factor 10 To Regulate the Proliferation and Maintenance of Dental Epithelial Stem Cells▿

PubMed Central

Zhao, Hu; Li, Sha; Han, Dong; Kaartinen, Vesa; Chai, Yang

2011-01-01

Mouse incisors grow continuously throughout life. This growth is supported by the division of dental epithelial stem cells that reside in the cervical loop region. Little is known about the maintenance and regulatory mechanisms of dental epithelial stem cells. In the present study, we investigated how transforming growth factor β (TGF-β) signaling-mediated mesenchymal-epithelial cell interactions control dental epithelial stem cells. We designed two approaches using incisor organ culture and bromodeoxyuridine (BrdU) pulse-chase experiments to identify and evaluate stem cell functions. We show that the loss of the TGF-β type I receptor (Alk5) in the cranial neural crest-derived dental mesenchyme severely affects the proliferation of TA (transit-amplifying) cells and the maintenance of dental epithelial stem cells. Incisors of Wnt1-Cre; Alk5fl/fl mice lost their ability to continue to grow in vitro. The number of BrdU label-retaining cells (LRCs) was dramatically reduced in Alk5 mutant mice. Fgf10, Fgf3, and Fgf9 signals in the dental mesenchyme were downregulated in Wnt1-Cre; Alk5fl/fl incisors. Strikingly, the addition of exogenous fibroblast growth factor 10 (FGF10) into cultured incisors rescued dental epithelial stem cells in Wnt1-Cre; Alk5fl/fl mice. Therefore, we propose that Alk5 functions upstream of Fgf10 to regulate TA cell proliferation and stem cell maintenance and that this signaling mechanism is crucial for stem cell-mediated tooth regeneration. PMID:21402782

Children's Oncology Group's 2013 blueprint for research: acute myeloid leukemia.

PubMed

Gamis, Alan S; Alonzo, Todd A; Perentesis, John P; Meshinchi, Soheil

2013-06-01

For the 365 children diagnosed with acute myeloid leukemia in the US annually, 5-year survival for patients on COG trials with low, intermediate, and high risk disease is 83%, 62%, and 23%, respectively. Recent advances include improved therapeutic stratification, improved survival with dose intensification, and further elucidation of the heterogeneity specific to childhood AML. These discoveries now guide current strategy incorporating targeted agents to pathways specific to childhood AML as well as evaluating methods to increase the sensitivity of the leukemic stem cell, first in Phase II feasibility trials followed by Phase III efficacy trials of the most promising agents. Acute myeloid leukemia in children, though with similar subgroups to adults, remains uniquely different based upon quite different prevalence of subtypes as well as overall response to therapy. The Children's Oncology Group's research agenda builds upon earlier efforts to better elucidate the leukemogenic steps distinct to childhood AML in order to more scientifically develop and test novel therapeutic approaches to the treatment and ultimate cure for children with this disorder. Pediatr Blood Cancer 2013; 60: 964-971. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Generation of Breast Cancer Stem Cells by the EMT

DTIC Science & Technology

2009-10-01

shift in the type of human breast cancer cells. We began to use experimentally immortalized HMLE cells that were then transformed through...Generation of Breast Cancer Stem Cells by the EMT PRINCIPAL INVESTIGATOR: Robert A. Weinberg, Ph.D. CONTRACTING...Generation of Breast Cancer Stem Cells by the EMT 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0464 5c. PROGRAM ELEMENT NUMBER 6

Adeno-associated viral gene therapy for mucopolysaccharidoses exhibiting neurodegeneration.

PubMed

Lau, Adeline A; Hemsley, Kim M

2017-10-01

The mucopolysaccharidoses (MPS) are a subgroup of lysosomal storage disorders that are caused by mutations in the genes involved in glycosaminoglycan breakdown. Multiple organs and tissues are affected, including the central nervous system. At present, hematopoietic stem cell transplantation and enzyme replacement therapies are approved for some of the (non-neurological) MPS. Treatments that effectively ameliorate the neurological aspects of the disease are being assessed in clinical trials. This review will focus on the recent outcomes and planned viral vector-mediated gene therapy clinical trials, and the pre-clinical data that supported these studies, for MPS-I (Hurler/Scheie syndrome), MPS-II (Hunter syndrome), and MPS-IIIA and -IIIB (Sanfilippo syndrome).

Extending the shelf life of kohlrabi stems by modified atmosphere packaging.

PubMed

Escalona, V H; Aguayo, E; Artés, F

2007-06-01

Kohlrabi stems (without leaves) were stored under modified atmosphere packaging (MAP) for 60 d at 0 degrees C. An additional retail sale period of 3 d at 12 degrees C after each cold storage evaluation (30 and 60 d) was applied. Under high relative humidity (RH) and 0 degrees C, the stems showed low metabolic activity, as no changes in sugars and organic acids were found. From day 21 at 0 degrees C, air-stored stems showed a yellowing of stalks and later they fell down. This disorder severely affected the appearance of stems. A gas composition of 4.5 to 5.5 kPa O(2) plus 11 to 12 kPa CO(2) was reached using antimist oriented polypropylene plastic bags of 20-mum thicknesses. The stems in MAP conditions kept a high sensorial quality. It was enough for commercial purpose of 2 mo. The storage of kohlrabi stems in plastic bags, either MA or in perforated (control) packages, provided an additional protection reducing physical damage. The MAP conditions delayed the weight loss and development of bacterial soft and black rot, extending the shelf life of kohlrabi stems to 60 d at 0 degrees C plus 3 d at 12 degrees C. Stems are not chilling injury sensitive.

Protein arginine methyltransferase 7-mediated microRNA-221 repression maintains Oct4, Nanog, and Sox2 levels in mouse embryonic stem cells.

PubMed

Chen, Tsai-Yu; Lee, Sung-Hun; Dhar, Shilpa S; Lee, Min Gyu

2018-03-16

The stemness maintenance of embryonic stem cells (ESCs) requires pluripotency transcription factors, including Oct4, Nanog, and Sox2. We have previously reported that protein arginine methyltransferase 7 (PRMT7), an epigenetic modifier, is an essential pluripotency factor that maintains the stemness of mouse ESCs, at least in part, by down-regulating the expression of the anti-stemness microRNA (miRNA) miR-24-2. To gain greater insight into the molecular basis underlying PRMT7-mediated maintenance of mouse ESC stemness, we searched for new PRMT7-down-regulated anti-stemness miRNAs. Here, we show that miR-221 gene-encoded miR-221-3p and miR-221-5p are anti-stemness miRNAs whose expression levels in mouse ESCs are directly repressed by PRMT7. Notably, both miR-221-3p and miR-221-5p targeted the 3' untranslated regions of mRNA transcripts of the major pluripotency factors Oct4, Nanog, and Sox2 to antagonize mouse ESC stemness. Moreover, miR-221-5p silenced also the expression of its own transcriptional repressor PRMT7. Transfection of miR-221-3p and miR-221-5p mimics induced spontaneous differentiation of mouse ESCs. CRISPR-mediated deletion of the miR-221 gene, as well as specific antisense inhibitors of miR-221-3p and miR-221-5p, inhibited the spontaneous differentiation of PRMT7-depleted mouse ESCs. Taken together, these findings reveal that the PRMT7-mediated repression of miR-221-3p and miR-221-5p expression plays a critical role in maintaining mouse ESC stemness. Our results also establish miR-221-3p and miR-221-5p as anti-stemness miRNAs that target Oct4 , Nanog , and Sox2 mRNAs in mouse ESCs. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

DTIC Science & Technology

2013-10-01

Fehrenbacher JW et al. Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart. Ann Thorac Surg Sep 2009;88:1036–1043. 45 Payne... mesenchymal stem cells (MSCs) (5). Activation of RhoA-ROCK signaling in cultured MSCs in vitro induces their osteogenesis but Figure 5 Angiogenesis...osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10):1858-66. PMCID

40 CFR 180.609 - Fluoxastrobin; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., subgroup 13-07G 1.9 Corn, field, forage 3.0 Corn, field, grain 0.02 Corn, field, stover 4.5 Leaf petioles subgroup 4B 4.0 Peanut 0.010 Peanut, hay 20.0 Peanut, refined oil 0.030 Soybean, forage 9.0 Soybean, hay 1.2 Soybean, hulls 0.20 Soybean, seed 0.05 Tomato, paste 1.5 Vegetable, fruiting, group 8 1.0...

Utility-value intervention with parents increases students' STEM preparation and career pursuit.

PubMed

Rozek, Christopher S; Svoboda, Ryan C; Harackiewicz, Judith M; Hulleman, Chris S; Hyde, Janet S

2017-01-31

During high school, developing competence in science, technology, engineering, and mathematics (STEM) is critically important as preparation to pursue STEM careers, yet students in the United States lag behind other countries, ranking 35th in mathematics and 27th in science achievement internationally. Given the importance of STEM careers as drivers of modern economies, this deficiency in preparation for STEM careers threatens the United States' continued economic progress. In the present study, we evaluated the long-term effects of a theory-based intervention designed to help parents convey the importance of mathematics and science courses to their high-school-aged children. A prior report on this intervention showed that it promoted STEM course-taking in high school; in the current follow-up study, we found that the intervention improved mathematics and science standardized test scores on a college preparatory examination (ACT) for adolescents by 12 percentile points. Greater high-school STEM preparation (STEM course-taking and ACT scores) was associated with increased STEM career pursuit (i.e., STEM career interest, the number of college STEM courses, and students' attitudes toward STEM) 5 y after the intervention. These results suggest that the intervention can affect STEM career pursuit indirectly by increasing high-school STEM preparation. This finding underscores the importance of targeting high-school STEM preparation to increase STEM career pursuit. Overall, these findings demonstrate that a motivational intervention with parents can have important effects on STEM preparation in high school, as well as downstream effects on STEM career pursuit 5 y later.

Utility-value intervention with parents increases students’ STEM preparation and career pursuit

PubMed Central

Rozek, Christopher S.; Svoboda, Ryan C.; Harackiewicz, Judith M.; Hulleman, Chris S.; Hyde, Janet S.

2017-01-01

During high school, developing competence in science, technology, engineering, and mathematics (STEM) is critically important as preparation to pursue STEM careers, yet students in the United States lag behind other countries, ranking 35th in mathematics and 27th in science achievement internationally. Given the importance of STEM careers as drivers of modern economies, this deficiency in preparation for STEM careers threatens the United States’ continued economic progress. In the present study, we evaluated the long-term effects of a theory-based intervention designed to help parents convey the importance of mathematics and science courses to their high-school–aged children. A prior report on this intervention showed that it promoted STEM course-taking in high school; in the current follow-up study, we found that the intervention improved mathematics and science standardized test scores on a college preparatory examination (ACT) for adolescents by 12 percentile points. Greater high-school STEM preparation (STEM course-taking and ACT scores) was associated with increased STEM career pursuit (i.e., STEM career interest, the number of college STEM courses, and students’ attitudes toward STEM) 5 y after the intervention. These results suggest that the intervention can affect STEM career pursuit indirectly by increasing high-school STEM preparation. This finding underscores the importance of targeting high-school STEM preparation to increase STEM career pursuit. Overall, these findings demonstrate that a motivational intervention with parents can have important effects on STEM preparation in high school, as well as downstream effects on STEM career pursuit 5 y later. PMID:28096393

Adenoma Prevalence and Distribution Among US Latino Subgroups Undergoing Screening Colonoscopy.

PubMed

Chablani, Sumedha V; Jandorf, Lina; DuHamel, Katherine; Lee, Kristen K; Sriphanlop, Pathu; Villagra, Cristina; Itzkowitz, Steven H

2017-06-01

Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.

Severe Graves' ophthalmopathy may be a risk factor for the development of postthyroidectomy hypocalcaemia.

PubMed

Hassan, I; Danila, R; Maurer, E; Osei-Agymang, T; Zielke, A

2008-11-01

The aim of this study was to compare the rate of hypocalcaemia after thyroid resection in patients with versus patients without Graves' Ophthalmopathy (GO). 153 patients following thyroid surgery for Grave's disease were studied. Patients were divided into three groups according to the severity of GO at the time of surgery using the NOSPECS classification. Subgroup I comprised of 70 patients without GO, subgroup II comprised of 63 patients with moderate GO and 20 patients with severe GO were assigned to Subgroup III. Association between severe ophthalmopathy and postoperative hypocalcaemia after thyroidectomy was investigated. 12/70 patients complained transient and 3/70 permanent hypocalcemia within subgroup I. 14/63 patients developed transient and 4/63 patients permanent hypocalcaemia within subgroup II. There were 7/20 patients with transient and 5/20 cases with permanent hypocalcaemia in the patient group with severe GO (subgroup III). The incidence of permanent postthyroidectomy hypocalcaemia was significantly higher in the subgroup III with severe GO when compared to the subgroup I without GO (p=0.004). Although postthyroidectomy hypocalcemia seems to be a multifactorial phenomenon, this study implicates unknown role of severe GO at time of surgery in the development of hypocalcaemia after thyroid surgery for Graves' disease. Therefore, patients with GO should be considered for surgery at high volume centres specialised in thyroid and parathyroid surgery.

Purinergic Receptors in Quiescence and Localization of Leukemic Stem Cells

DTIC Science & Technology

2011-05-01

2011. Ewing’s Sarcoma Gene EWS regulates Hematopoietic Stem Cell Senescence. Blood, 117:1156-66. Conclusion How leukemia stem cells gained...findings contained in this report are those of the author( s ) and should not be construed as an official Department of the Army position, policy or...Receptors in Quiescence and Localization of Leukemic Stem Cells 5b. GRANT NUMBER W81XWH-09-1-0364 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d

Close relationships between Asian American and European American college students.

PubMed

Chen, C; Edwards, K; Young, B; Greenberger, E

2001-02-01

The authors examined attitudes and behaviors regarding close relationships between European and Asian Americans, with a particular emphasis on 5 major subgroups of Asian Americans (Chinese, Japanese, Korean, Vietnamese, and Filipino Americans). Participants were 218 Asian American college students and 171 European American college students attending a culturally diverse university. The European Americans did not differentiate among the various subgroups of Asian Americans. Their attitudes regarding close relationships were less positive toward Asian Americans than toward Mexican and African Americans, a finding contrary to the prediction of social exchange theory (H. Tajfel, 1975). In contrast to the European Americans' view of homogeneity among Asian Americans, the 5 major subgroups of Asian Americans expressed a distinctive hierarchy of social preference among themselves. Results are discussed in terms of their implications for future research on interethnic relations involving Asian Americans.

Replacement of Lost Lgr5-Positive Stem Cells through Plasticity of Their Enterocyte-Lineage Daughters.

PubMed

Tetteh, Paul W; Basak, Onur; Farin, Henner F; Wiebrands, Kay; Kretzschmar, Kai; Begthel, Harry; van den Born, Maaike; Korving, Jeroen; de Sauvage, Frederic; van Es, Johan H; van Oudenaarden, Alexander; Clevers, Hans

2016-02-04

Intestinal crypts display robust regeneration upon injury. The relatively rare secretory precursors can replace lost stem cells, but it is unknown if the abundant enterocyte progenitors that express the Alkaline phosphate intestinal (Alpi) gene also have this capacity. We created an Alpi-IRES-CreERT2 (Alpi(CreER)) knockin allele for lineage tracing. Marked clones consist entirely of enterocytes and are all lost from villus tips within days. Genetic fate-mapping of Alpi(+) cells before or during targeted ablation of Lgr5-expressing stem cells generated numerous long-lived crypt-villus "ribbons," indicative of dedifferentiation of enterocyte precursors into Lgr5(+) stems. By single-cell analysis of dedifferentiating enterocytes, we observed the generation of Paneth-like cells and proliferative stem cells. We conclude that the highly proliferative, short-lived enterocyte precursors serve as a large reservoir of potential stem cells during crypt regeneration. Copyright © 2016 Elsevier Inc. All rights reserved.

Conditional mutation of Smc5 in mouse embryonic stem cells perturbs condensin localization and mitotic progression.

PubMed

Pryzhkova, Marina V; Jordan, Philip W

2016-04-15

Correct duplication of stem cell genetic material and its appropriate segregation into daughter cells are requisites for tissue, organ and organism homeostasis. Disruption of stem cell genomic integrity can lead to developmental abnormalities and cancer. Roles of the Smc5/6 structural maintenance of chromosomes complex in pluripotent stem cell genome maintenance have not been investigated, despite its important roles in DNA synthesis, DNA repair and chromosome segregation as evaluated in other model systems. Using mouse embryonic stem cells (mESCs) with a conditional knockout allele of Smc5, we showed that Smc5 protein depletion resulted in destabilization of the Smc5/6 complex, accumulation of cells in G2 phase of the cell cycle and apoptosis. Detailed assessment of mitotic mESCs revealed abnormal condensin distribution and perturbed chromosome segregation, accompanied by irregular spindle morphology, lagging chromosomes and DNA bridges. Mutation of Smc5 resulted in retention of Aurora B kinase and enrichment of condensin on chromosome arms. Furthermore, we observed reduced levels of Polo-like kinase 1 at kinetochores during mitosis. Our study reveals crucial requirements of the Smc5/6 complex during cell cycle progression and for stem cell genome maintenance. © 2016. Published by The Company of Biologists Ltd.

Photosynthetic Bradyrhizobia Are Natural Endophytes of the African Wild Rice Oryza breviligulata

PubMed Central

Chaintreuil, Clémence; Giraud, Eric; Prin, Yves; Lorquin, Jean; Bâ, Amadou; Gillis, Monique; de Lajudie, Philippe; Dreyfus, Bernard

2000-01-01

We investigated the presence of endophytic rhizobia within the roots of the wetland wild rice Oryza breviligulata, which is the ancestor of the African cultivated rice Oryza glaberrima. This primitive rice species grows in the same wetland sites as Aeschynomene sensitiva, an aquatic stem-nodulated legume associated with photosynthetic strains of Bradyrhizobium. Twenty endophytic and aquatic isolates were obtained at three different sites in West Africa (Senegal and Guinea) from nodal roots of O. breviligulata and surrounding water by using A. sensitiva as a trap legume. Most endophytic and aquatic isolates were photosynthetic and belonged to the same phylogenetic Bradyrhizobium/Blastobacter subgroup as the typical photosynthetic Bradyrhizobium strains previously isolated from Aeschynomene stem nodules. Nitrogen-fixing activity, measured by acetylene reduction, was detected in rice plants inoculated with endophytic isolates. A 20% increase in the shoot growth and grain yield of O. breviligulata grown in a greenhouse was also observed upon inoculation with one endophytic strain and one Aeschynomene photosynthetic strain. The photosynthetic Bradyrhizobium sp. strain ORS278 extensively colonized the root surface, followed by intercellular, and rarely intracellular, bacterial invasion of the rice roots, which was determined with a lacZ-tagged mutant of ORS278. The discovery that photosynthetic Bradyrhizobium strains, which are usually known to induce nitrogen-fixing nodules on stems of the legume Aeschynomene, are also natural true endophytes of the primitive rice O. breviligulata could significantly enhance cultivated rice production. PMID:11097925

Mesenchymal Stem Cell Based Therapy for Prostate Cancer

DTIC Science & Technology

2015-11-01

Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING...TITLE AND SUBTITLE Mesenchymal Stem Cell-Based Therapy for Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-13-1-0304 5c. PROGRAM ELEMENT...effective therapy for castrate resistant metastatic prostate cancer (CRPC). Based upon a substantial published literature from multiple groups, as well as

Targeting Tumor Oct4 to Deplete Prostate Tumor- and Metastasis-Initiating Cells

DTIC Science & Technology

2015-10-01

and stem cell To investigate whether POU5F1B overrxpression can induce cancer stem cell -related genes expression, we did cancer stem cell ...future 15. SUBJECT TERMS OCT4, cancer stem cells , prostate cancer, metastasis, tumor formation 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...described in last report. Here we describe some findings previously not reported. 1.1 POU5F1B expression in prostatic tissue As cancer stem cell marker

Environmental Impact on Intestinal Stem Cell Functions in Mucosal Homeostasis and Tumorigenesis.

PubMed

Augenlicht, Leonard H

2017-05-01

Multiple cell compartments at or near the base of the intestinal crypt have been identified as contributing intestinal stem cells for homeostasis of the rapidly turning over intestinal mucosa and cells that can initiate tumor development upon appropriate genetic changes. There is a strong literature establishing the importance of the frequently dividing Lgr5+ crypt base columnar cells as the fundamental cell in providing these stem cell-associated functions, but there are also clear data that more quiescent cells from other compartments can be mobilized to provide these stem cell functions upon compromise of Lgr5+ cells. We review the data that vitamin D, a pleiotropic hormone, is essential for Lgr5 stem cell functions by signaling through the vitamin D receptor. Moreover, we discuss the implications of this role of vitamin D and its impact on relatively long-lived stem cells in regards to the fact that virtually all the data on normal functioning of mouse Lgr5 stem cells is derived from mice exposed to vitamin D levels well above those that characterize the human population. Thus, there are still many questions regarding how dietary and environmental factors influence the complement of cells providing stem cell functions and the mechanisms by which this is determined, and the importance of this in human colorectal tumor development. J. Cell. Biochem. 118: 943-952, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Efficacy of albendazole chitosan microspheres against Echinococcus granulosus infection in mice].

PubMed

Liang, Wen; Wang, Xin-Chun; Wu, Xiang-Wei; Zhang, Shi-Jie; Sun, Hong; Ma, Xin; Peng, Xin-Yu

2014-06-01

To observe the therapeutic effect of albendazole chitosan microspheres (ABZ-CS-MPs) on cystic echinococcosis in mice. Two hundred male kunming mice were each infected by intraperitoneal inoculation of about 5 000 viable protoscoleces of Echinococcus granulosus. Another 20 mice were kept as blank control. After 12 weeks post infection, the mice were randomly divided into four groups named as infection control group (n = 20), ABZ-CS-MPs group, albendazole liposome (L-ABZ) group, and albendazole tablet group. The latter three treatment groups were then each divided into three subgroups (n = 20) by given the dose of 37.5, 75.0, and 150.0 mg/kg for three times per week, respectively. After 12 weeks of treatment, all mice were sacrificed. The weight of hydatid cysts was measured and the inhibition rate were calculated. Mouse liver was observed. The histopathological changes of E. granulosus were observed by microscopy. The concentration of albendazole sulfoxide in plasma and liver tissues was determined by high-performance liquid chromatography. Compared with the other treatment groups, the turbidity of contained fluid, the consolidation level and calcification level of hydatid cysts in ABZ-CS-MPs group were higher. The average weight of hydatid cysts in each treatment group was lower than that of infection control group [(3.19 +/- 2.94) g] (P < 0.05). The cyst weight in 37.5, 75.0, and 150.0 mg/kg ABZ-CS-MPs group [(0.28 +/- 0.28), (0.24 +/- 0.22), and (0.20 +/- 0.19) g, respectively] was lower than that of albendazole tablet groups [(0.77 +/- 0.74), (0.55 +/- 0.42), (0.76 +/- 0.35) g] (P < 0.05). Among the same dosage groups, the inhibition rate in ABZ-CS-MPs group (from low to high dosage sub-group: 91.1%, 92.6%, and 93.7%, respectively) was highest. In 75.0 mg/kg ABZ-CS-MPs group, there were 15 mice with class I (degeneration) and II (necrosis) pathological changes of E. granulosus hydatid. The number of mice with class I and II pathological changes in each dosage ABZ-CS-MPs sub-group and L-ABZ sub-group was more than that of albendazole tablet group (P<0.05). Plasma concentration of albendazole sulfoxide in 75.0 and 150.0 mg/kg ABZ-CS-MPs sub-groups [(0.83 +/- 0.39), (0.80 +/- 0.5) microg/ml] were higher than that of L-ABZ sub-groups [(0.34 +/- 0.03), (0.43 +/- 0.15) microg/ml] and albendazole tablet sub-groups [(0.31 +/- 0.02), (0.40 +/- 0.10) microg/ml] (P < 0.05). Compared with 37.5, 75.0, and 150.0 mg/kg albendazole tablet sub-groups [(0.04 +/- 0.02), (0.07 +/- 0.04), (0.04 +/- 0.0) microg/g], the albendazole sulfoxide concentration in liver tissue was higher in ABZ-CS-MPs sub-groups [(0.33 +/- 0.06), (0.45 +/- 0.31), (0.50 +/- 0.30) microg/g] (P < 0.05). In 37.5 mg/kg dosage sub-group, the albendazole sulfoxide concentration in liver tissue in ABZ-CS-MPs group was higher than that of L-ABZ group [(0.14 +/- 0.19) microg/g] (P < 0.05). ABZ-CS-MPs can reduce the weight of hydatid cyst and increase the concentration of al-bendazole sulfoxide in plasma and liver tissue of mice.

Differences in problem behaviour among ethnic minority and majority preschoolers in the Netherlands and the role of family functioning and parenting factors as mediators: the Generation R Study.

PubMed

Flink, Ilse J E; Jansen, Pauline W; Beirens, Tinneke M J; Tiemeier, Henning; van IJzendoorn, Marinus H; Jaddoe, Vincent W V; Hofman, Albert; Raat, Hein

2012-12-19

Studies have shown that, compared to native counterparts, preschoolers from ethnic minorities are at an increased risk of problem behaviour. Socio-economic factors only partly explain this increased risk. This study aimed to further unravel the differences in problem behaviour among ethnic minority and native preschoolers by examining the mediating role of family functioning and parenting factors. We included 4,282 preschoolers participating in the Generation R Study, an ethnically-diverse cohort study with inclusion in early pregnancy. At child age 3 years, parents completed the Child Behavior Checklist (CBCL/1,5-5); information on demographics, socio-economic status and measures of family functioning (maternal psychopathology; general family functioning) and parenting (parenting stress; harsh parenting) were retrieved from questionnaires. CBCL Total Problems scores in each ethnic subgroup were compared with scores in the Dutch reference population. Mediation was evaluated using multivariate regression models. After adjustment for confounders, preschoolers from ethnic minorities were more likely to present problem behaviour than the Dutch subgroup (e.g. CBCL Total Problems Turkish subgroup (OR 7.0 (95% CI 4.9; 10.1)). When considering generational status, children of first generation immigrants were worse off than the second generation (P<0.01). Adjustment for socio-economic factors mediated the association between the ethnic minority status and child problem behaviour (e.g. attenuation in OR by 54.4% (P<0.05) from OR 5.1 (95% CI 2.8; 9.4) to OR 2.9 (95% CI 1.5; 5.6) in Cape Verdean subgroup). However, associations remained significant in most ethnic subgroups. A final adjustment for family functioning and parenting factors further attenuated the association (e.g. attenuation in OR by 55.5% (P<0.05) from OR 2.2 (95% CI 1.3; 4.4) to OR 1.5 (95% CI 1.0; 2.4) in European other subgroup). This study showed that preschoolers from ethnic minorities and particularly children of first generation immigrants are at an increased risk of problem behaviour compared to children born to a Dutch mother. Although socio-economic factors were found to partly explain the association between the ethnic minority status and child problem behaviour, a similar part was explained by family functioning and parenting factors. Considering these findings, it is important for health care workers to also be attentive to symptoms of parental psychopathology (e.g. depression), poor family functioning, high levels of parenting stress or harsh parenting in first and second generation immigrants with young children.

Aging and stem cell therapy: AMPK as an applicable pharmacological target for rejuvenation of aged stem cells and achieving higher efficacy in stem cell therapy.

PubMed

Khorraminejad-Shirazi, Mohammadhossein; Farahmandnia, Mohammad; Kardeh, Bahareh; Estedlal, Alireza; Kardeh, Sina; Monabati, Ahmad

2017-10-19

In recent years, tissue regeneration has become a promising field for developing stem cell-based transplantation therapies for human patients. Adult stem cells are affected by the same aging mechanisms that involve somatic cells. One of the mechanisms involved in cellular aging is hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and disruption of 5' adenosine monophosphate-activated protein kinase (AMPK). Aging of stem cells results in their impaired regenerative capacity and depletion of stem cell pools in adult tissue, which results in lower efficacy of stem cell therapy. By utilizing an effective therapeutic intervention for aged stem cells, stem cell therapy can become more promising for future application. mTORC1 inhibition is a practical approach to preserve the stem cell pool. In this article, we review the dynamic interaction between sirtuin (silent mating type information regulation 2 homolog) 1, AMPK, and mTORC1. We propose that using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide, A769662, metformin, and oxidized nicotinamide adenine dinucleotide (NAD + ) are practical ways to be employed for achieving better optimized results in stem cell-based transplantation therapies. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Hesperetin Alleviates the Inhibitory Effects of High Glucose on the Osteoblastic Differentiation of Periodontal Ligament Stem Cells

PubMed Central

Kim, So Yeon; Lee, Jin-Yong; Park, Yong-Duk; Kang, Kyung Lhi; Lee, Jeong-Chae; Heo, Jung Sun

2013-01-01

Hesperetin (3′,5,7-trihydroxy-4-methoxyflavanone) is a metabolite of hesperidin (hesperetin-7-O-rutinoside), which belongs to the flavanone subgroup and is found mainly in citrus fruits. Hesperetin has been reported to be an effective osteoinductive compound in various in vivo and in vitro models. However, how hesperetin effects osteogenic differentiation is not fully understood. In this study, we investigated the capacity of hesperetin to stimulate the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and to relieve the anti-osteogenic effect of high glucose. Osteogenesis of PDLSCs was assessed by measurement of alkaline phosphatase (ALP) activity, and evaluation of the mRNA expression of ALP, runt-related gene 2 (Runx2), osterix (OSX), and FRA1 as osteogenic transcription factors, as well as assessment of protein expression of osteopontin (OPN) and collagen type IA (COLIA). When PDLSCs were exposed to a high concentration (30 mM) of glucose, osteogenic activity decreased compared to control cells. Hesperetin significantly increased ALP activity at doses of 1, 10, and 100 µM. Pretreatment of cells with hesperetin alleviated the high-glucose-induced suppression of the osteogenic activity of PDLSCs. Hesperetin scavenged intracellular reactive oxygen species (ROS) produced under high glucose condition. Furthermore, hesperetin increased the activity of the PI3K/Akt and β-catenin pathways. Consistent with this, blockage of Akt or β-catenin diminished the protective effect of hesperetin against high glucose-inhibited osteogenic differentiation. Collectively, our results suggest that hesperetin alleviates the high glucose-mediated suppression of osteogenic differentiation in PDLSCs by regulating ROS levels and the PI3K/Akt and β-catenin signaling pathways. PMID:23840726

Essential role of FBXL5-mediated cellular iron homeostasis in maintenance of hematopoietic stem cells

PubMed Central

Muto, Yoshiharu; Nishiyama, Masaaki; Nita, Akihiro; Moroishi, Toshiro; Nakayama, Keiichi I.

2017-01-01

Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion. Transcriptomic analysis shows abnormal activation of oxidative stress responses and the cell cycle in FBXL5-deficient mouse HSCs as well as downregulation of FBXL5 expression in HSCs of patients with myelodysplastic syndrome. Suppression of iron regulatory protein 2 (IRP2) accumulation in FBXL5-deficient mouse HSCs restores stem cell function, implicating IRP2 as a potential therapeutic target for human hematopoietic diseases associated with FBXL5 downregulation. PMID:28714470

Tanshinone IIA inhibits cervix carcinoma stem cells migration and invasion via inhibiting YAP transcriptional activity.

PubMed

Qin, Jinghao; Shi, Hongbing; Xu, Yanjie; Zhao, Fang; Wang, Qing

2018-06-14

This study aims to explore the effects and related mechanisms of Tanshinone IIA in cervix carcinoma (CC) stemness-like cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that Tanshinone IIA suppressed CC stemness-like cells migration and invasion in a concentration- and time-dependent manner. And consistent results were obtained in CC cells stemness characterized as the decrease of CC stemness markers expression and cells spheroid formation ability. Mechanistically, we found that Tanshinone IIA suppressed RNA binding protein HuR translocation from nuclear to cytoplasm, and thus reduced YAP mRNAs stability and transcriptional activity. Importantly, overexpression YAP-5SA rescued the inhibition of Tanshinone IIA on CC cells stemness. Furthermore, Tanshinone IIA enhanced adriamycin sensitivity in CC stemness-like cells, this effect was attenuated by YAP-5SA overexpression too. Therefore, Tanshinone IIA could suppress CC stemness-like cells migration and invasion by inhibiting YAP transcriptional activity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Use of generalized regression tree models to characterize vegetation favoring Anopheles albimanus breeding.

PubMed

Hernandez, J E; Epstein, L D; Rodriguez, M H; Rodriguez, A D; Rejmankova, E; Roberts, D R

1997-03-01

We propose the use of generalized tree models (GTMs) to analyze data from entomological field studies. Generalized tree models can be used to characterize environments with different mosquito breeding capacity. A GTM simultaneously analyzes a set of predictor variables (e.g., vegetation coverage) in relation to a response variable (e.g., counts of Anopheles albimanus larvae), and how it varies with respect to a set of criterion variables (e.g., presence of predators). The algorithm produces a treelike graphical display with its root at the top and 2 branches stemming down from each node. At each node, conditions on the value of predictors partition the observations into subgroups (environments) in which the relation between response and criterion variables is most homogeneous.

The Stem Cell Marker Lgr5 Defines a Subset of Postmitotic Neurons in the Olfactory Bulb.

PubMed

Yu, Yiqun; Moberly, Andrew H; Bhattarai, Janardhan P; Duan, Chen; Zheng, Qian; Li, Fangqi; Huang, Hugh; Olson, William; Luo, Wenqin; Wen, Tieqiao; Yu, Hongmeng; Ma, Minghong

2017-09-27

Lgr5, leucine-rich repeat-containing G-protein coupled receptor 5, is a bona fide biomarker for stem cells in multiple tissues. Lgr5 is also expressed in the brain, but the identities and properties of these Lgr5 + cells are still elusive. Using an Lgr5-EGFP reporter mouse line, we found that, from early development to adulthood, Lgr5 is highly expressed in the olfactory bulb (OB), an area with ongoing neurogenesis. Immunostaining with stem cell, glial, and neuronal markers reveals that Lgr5 does not label stem cells in the OB but instead labels a heterogeneous population of neurons with preference in certain subtypes. Patch-clamp recordings in OB slices reveal that Lgr5-EGFP + cells fire action potentials and display spontaneous excitatory postsynaptic events, indicating that these neurons are integrated into OB circuits. Interestingly, R-spondin 3, a potential ligand of Lgr5, is also expressed in the adult OB. Collectively, our data indicate that Lgr5-expressing cells in the OB are fully differentiated neurons and imply distinct roles of Lgr5 and its ligand in postmitotic cells. SIGNIFICANCE STATEMENT Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) is a bona fide stem cell marker in many body organs. Here we report that Lgr5 is also highly expressed in the olfactory bulb (OB), the first relay station in the brain for processing odor information and one of the few neural structures that undergo continuous neurogenesis. Surprisingly, Lgr5 is not expressed in the OB stem cells, but instead in a few subtypes of terminally differentiated neurons, which are incorporated into the OB circuit. This study reveals that Lgr5 + cells in the brain represent a nonstem cell lineage, implying distinct roles of Lgr5 in postmitotic neurons. Copyright © 2017 the authors 0270-6474/17/379403-12$15.00/0.

Contribution of Dietary Supplements to Nutritional Adequacy by Socioeconomic Subgroups in Adults of the United States.

PubMed

Blumberg, Jeffrey B; Frei, Balz; Fulgoni, Victor L; Weaver, Connie M; Zeisel, Steven H

2017-12-22

Many Americans have inadequate intakes of several nutrients, and the Dietary Guidelines for Americans 2015-2020 identified vitamins A, C, D, and E, in addition to calcium, magnesium, iron, potassium, choline, and fiber as "underconsumed nutrients". Based on nationally representative data on 10,698 adults from National Health and Nutrition Examination Surveys (NHANES), 2009-2012, assessments were made of socioeconomic differences, based on the Poverty Income Ratio (PIR), in terms of the association of dietary supplement use on nutrient intake and nutrient inadequacies. Compared to food alone, the use of any dietary supplement plus food was associated with significantly ( p < 0.01) higher intakes of 15-16 of 19 nutrients examined in all socioeconomic groups; and significantly reduced rates of inadequacy for 10/17 nutrients in the subgroup PIR > 1.85 (not poor), but only 4-5/17 nutrients (calcium and vitamins A, C, D, E) for the poor and nearly poor subgroups (PIR < 1.35 and PIR 1.35 to ≤1.85, respectively). An increased prevalence of intakes above the Tolerable Upper Intake Level (UL) was seen for 3-9/13 nutrients, but all were less than 5% in the PIR subgroups. In conclusion, dietary supplement use was associated with an increased micronutrient intake, decreased inadequacies, and a slight increase in the prevalence of intakes above the UL, with greater benefits seen in the PIR > 1.85 subgroup.

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia.

PubMed

Giustacchini, Alice; Thongjuea, Supat; Barkas, Nikolaos; Woll, Petter S; Povinelli, Benjamin J; Booth, Christopher A G; Sopp, Paul; Norfo, Ruggiero; Rodriguez-Meira, Alba; Ashley, Neil; Jamieson, Lauren; Vyas, Paresh; Anderson, Kristina; Segerstolpe, Åsa; Qian, Hong; Olsson-Strömberg, Ulla; Mustjoki, Satu; Sandberg, Rickard; Jacobsen, Sten Eirik W; Mead, Adam J

2017-06-01

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis.

Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy

PubMed Central

Andreano, Anita; Pui, Ching-Hon; Hunger, Stephen P.; Schrappe, Martin; Moericke, Anja; Biondi, Andrea; Escherich, Gabriele; Silverman, Lewis B.; Goulden, Nicholas; Taskinen, Mervi; Pieters, Rob; Horibe, Keizo; Devidas, Meenakshi; Locatelli, Franco; Valsecchi, Maria Grazia

2016-01-01

Purpose We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL). Patients and Methods We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission. Using a random effects model, with CRT as a dichotomous covariate, we performed a single-arm meta-analysis to compare event-free survival and cumulative incidence of isolated or any CNS relapse and isolated bone marrow relapse in high-risk subgroups of patients who either did or did not receive CRT. Results Although there was significant heterogeneity in all outcome end points according to trial, CRT was associated with a reduced risk of relapse only in the small subgroup of patients with overt CNS disease at diagnosis, who had a significantly lower risk of isolated CNS relapse (4% with CRT v 17% without CRT; P = .02) and a trend toward lower risk of any CNS relapse (7% with CRT v 17% without CRT; P = .09). However, this group had a relatively high rate of events regardless of whether or not they received CRT (32% [95% CI, 26% to 39%] v 34% [95% CI, 19% to 54%]; P = .8). Conclusion CRT does not have an impact on the risk of relapse in children with ALL treated on contemporary protocols. PMID:26755523

Control of plant stem cell function by conserved interacting transcriptional regulators

PubMed Central

Zhou, Yun; Liu, Xing; Engstrom, Eric M.; Nimchuk, Zachary L.; Pruneda-Paz, Jose L.; Tarr, Paul T.; Yan, An; Kay, Steve A.; Meyerowitz, Elliot M.

2014-01-01

SUMMARY Plant stem cells in the shoot apical meristem (SAM) and root apical meristem (RAM) provide for postembryonic development of above-ground tissues and roots, respectively, while secondary vascular stem cells sustain vascular development1–4. WUSCHEL (WUS), a homeodomain transcription factor expressed in the rib meristem of the SAM, is a key regulatory factor controlling stem cell populations in the Arabidopsis SAM5–6 and is thought to establish the shoot stem cell niche via a feedback circuit with the CLAVATA3 (CLV3) peptide signaling pathway7. WUSCHEL-RELATED HOMEOBOX5 (WOX5), specifically expressed in root quiescent center (QC), defines QC identity and functions interchangeably with WUS in control of shoot and root stem cell niches8. WOX4, expressed in Arabidopsis procambial cells, defines the vascular stem cell niche9–11. WUS/WOX family proteins are evolutionarily and functionally conserved throughout the plant kingdom12 and emerge as key actors in the specification and maintenance of stem cells within all meristems13. However, the nature of the genetic regime in stem cell niches that centers on WOX gene function has been elusive, and molecular links underlying conserved WUS/WOX function in stem cell niches remain unknown. Here we demonstrate that the Arabidopsis HAIRY MERISTEM (HAM)family transcription regulators act as conserved interacting co-factors with WUS/WOX proteins. HAM and WUS share common targets in vivo and their physical interaction is important in driving downstream transcriptional programs and in promoting shoot stem cell proliferation. Differences in the overlapping expression patterns of WOX and HAM family members underlie the formation of diverse stem cell niche locations, and the HAM family is essential for all of these stem cell niches. These findings establish a new framework for the control of stem cell production during plant development. PMID:25363783

Type 2 Diabetes: Identifying High Risk Asian American Subgroups in a Clinical Population

PubMed Central

Wang, Elsie J.; Wong, Eric C.; Dixit, Anjali A.; Fortmann, Stephen P.; Linde, Randolph B.; Palaniappan, Latha P.

2011-01-01

Aims We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. Methods A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Results Age-adjusted prevalence ranged from 5.8%-18.2% (women) and 8.1%-25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Conclusions Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. PMID:21665315

Type 2 diabetes: identifying high risk Asian American subgroups in a clinical population.

PubMed

Wang, Elsie J; Wong, Eric C; Dixit, Anjali A; Fortmann, Stephen P; Linde, Randolph B; Palaniappan, Latha P

2011-08-01

We compared the prevalence and treatment of type 2 diabetes across Asian American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and Non-Hispanic Whites (NHWs) in a Northern California healthcare system. A three-year, cross-sectional sample of patient electronic health records was accessed to compare diabetes prevalence in 21,816 Asian and 73,728 NHWs aged 35+ years. Diabetes was classified through ICD-9 codes, abnormal laboratory values, or use of oral anti-diabetic medication. Multivariate adjusted prevalence rates for each Asian subgroup, and adjusted odds ratios (OR) relative to NHWs, were compared. Age-adjusted prevalence ranged from 5.8% to 18.2% (women) and 8.1 to 25.3% (men). Age-adjusted ORs of Asian subgroups ranged 1.11-3.94 (women) and 1.14-4.56 (men). The odds of diabetes were significantly higher in Asian Indians (women OR 3.44, men OR 3.54) and Filipinos (women OR 3.94, men OR 4.56), compared to NHWs. Results for Asian Indians and Filipinos were similar with age-and-BMI adjustment. Treatment rates across subgroups were 59.7-82.0% (women) and 62.9-79.4% (men). Heterogeneity exists in the prevalence of diabetes across Asian subgroups, independent of obesity prevalence. Asian Indian and Filipino subgroups had particularly high prevalence of diabetes when compared to NHWs. Future studies should explore these clinically important differences among Asian subgroups. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups

PubMed Central

Curtis, Christina; Shah, Sohrab P.; Chin, Suet-Feung; Turashvili, Gulisa; Rueda, Oscar M.; Dunning, Mark J.; Speed, Doug; Lynch, Andy G.; Samarajiwa, Shamith; Yuan, Yinyin; Gräf, Stefan; Ha, Gavin; Haffari, Gholamreza; Bashashati, Ali; Russell, Roslin; McKinney, Steven; Langerød, Anita; Green, Andrew; Provenzano, Elena; Wishart, Gordon; Pinder, Sarah; Watson, Peter; Markowetz, Florian; Murphy, Leigh; Ellis, Ian; Purushotham, Arnie; Børresen-Dale, Anne-Lise; Brenton, James D.; Tavaré, Simon; Caldas, Carlos; Aparicio, Samuel

2012-01-01

The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (copy number variants and single nucleotide polymorphisms) and acquired somatic copy number aberrations (CNAs) were associated with expression in ~40% of genes, with the landscape dominated by cis- and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP and MAP2K4. Unsupervised analysis of paired DNA–RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, oestrogen-receptor-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the ‘CNA-devoid’ subgroup and a basal-specific chromosome 5 deletion-associated mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic CNAs on the transcriptome. PMID:22522925

Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0644 TITLE: Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells PRINCIPAL INVESTIGATOR: Chun-Ju...U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release...Targeting Cell Polarity Machinery to Exhaust Breast Cancer Stem Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0644 5c. PROGRAM ELEMENT

[Evaluation and trend analysis of prepregnancy nutrition in Chinese women of reproductive age during 2010-2012].

PubMed

Sun, Lizhou; Wang, Qiaomei; Shen, Haiping; Liu, Min; Ma, Xu; Ye, Hanfeng; Liu, Xinyan; Pan, Hui; Du, Zhongdong; Zhang, Yiping; Yan, Donghai; Wang, Yuanyuan; Pan, Yi; Zhang, Shikun

2015-01-20

To evaluate the prepregnancy nutritional status and analyze its trend in Chinese women of reproductive age during the period of 2010-2012. Analyses of prepregnancy nutritional indicators were conducted for a total of 2 120 131women of reproductive age (aged 21-49 years) from 220 pilot counties of 31 provinces who participated in National Free Prepregnancy Health Examination Project from January 1, 2010 to December 31, 2012. The nutritional indicators involving body mass index (BMI), hemoglobin (HB) concentration and fasting plasma glucose (FBG) were statistically analyzed with SPSS 17.0 software. There were a sustained increase in prepregnancy HB concentration and declined levels of prepregnancy BMI and FBG during 2010-2012. The clinical data were categorized into 4 subgroups. The data of age composition showed the age group of 25-34 years was the largest proportion of the cohort. The prevalence in prepregnancy low-BMI population subgroup increased from 10.4% in 2010 to 14.14% in 2012. The prepregnancy obesity and overweight subgroups revealed the lowest prevalences of 10.65% and 2.32% respectively in 2012. A decreased prevalence of prepregnancy low FBG subgroup occurred from 5.45% in 2010 to 5.23% in 2012. The prevalences of prepregnancy impaired fasting plasma glucose and diabetes subgroups decreased year-on-year from 3.17% and 1.64% in 2010 to 2.71% and 1.05% in 2012 respectively. The prevalences of prepregnancy mild and severe anemia subgroups decreased from 12.29% and 0.95% to 9.62% and 0.78% respectively during the period 2010-2012. High hemoglobin concentration subgroup also exhibited a decreasing prevalence. Statistical analysis indicated significant differences (P < 0.001) in the evaluation and trend analysis of prepregnancy nutrition in Chinese women of reproductive age. Chinese women of reproductive age show a fair status of prepregnancy nutrition. And there are decreasing prevalences in obesity, anemia and diabetes.

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid.

PubMed

Aihara, Eitaro; Mahe, Maxime M; Schumacher, Michael A; Matthis, Andrea L; Feng, Rui; Ren, Wenwen; Noah, Taeko K; Matsu-ura, Toru; Moore, Sean R; Hong, Christian I; Zavros, Yana; Herness, Scott; Shroyer, Noah F; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A; Montrose, Marshall H

2015-11-24

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5(+)) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5(+) cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration.

Characterization of stem/progenitor cell cycle using murine circumvallate papilla taste bud organoid

PubMed Central

Aihara, Eitaro; Mahe, Maxime M.; Schumacher, Michael A.; Matthis, Andrea L.; Feng, Rui; Ren, Wenwen; Noah, Taeko K.; Matsu-ura, Toru; Moore, Sean R.; Hong, Christian I.; Zavros, Yana; Herness, Scott; Shroyer, Noah F.; Iwatsuki, Ken; Jiang, Peihua; Helmrath, Michael A.; Montrose, Marshall H.

2015-01-01

Leucine-rich repeat-containing G-protein coupled receptor 5-expressing (Lgr5+) cells have been identified as stem/progenitor cells in the circumvallate papillae, and single cultured Lgr5+ cells give rise to taste cells. Here we use circumvallate papilla tissue to establish a three-dimensional culture system (taste bud organoids) that develops phenotypic characteristics similar to native tissue, including a multilayered epithelium containing stem/progenitor in the outer layers and taste cells in the inner layers. Furthermore, characterization of the cell cycle of the taste bud progenitor niche reveals striking dynamics of taste bud development and regeneration. Using this taste bud organoid culture system and FUCCI2 transgenic mice, we identify the stem/progenitor cells have at least 5 distinct cell cycle populations by tracking within 24-hour synchronized oscillations of proliferation. Additionally, we demonstrate that stem/progenitor cells have motility to form taste bud organoids. Taste bud organoids provides a system for elucidating mechanisms of taste signaling, disease modeling, and taste tissue regeneration. PMID:26597788

Chemical composition and anti-inflammatory activities of the essential oils from Acacia mearnsii de Wild.

PubMed

Avoseh, Opeyemi N; Oyedeji, Ope-oluwa O; Aremu, Kayode; Nkeh-Chungag, Benedicta N; Songca, Sandile P; Oluwafemi, Samuel O; Oyedeji, Adebola O

2015-01-01

The volatile oils of the leaves and the stem bark of Acacia mearnsii de Wild obtained by hydro-distillation were analysed by gas chromatography-mass spectrometry. A total of 20, 38, 29 and 38 components accounted for 93.8%, 92.1%, 78.5% and 90.9% of the total oils of the fresh, dry leaves and fresh, dry stem bark, respectively. The major components of the oil were octadecyl alcohol (25.5%) and phytol (10.5%); cis-verbenol (29.5%); phytol (10.1%) and phytol (23.4%) for the fresh leaves, dried leaves, fresh stem, dry stem bark, respectively. Oral administration of essential oils at a dose of 2% showed significant (p < 0.05) anti-inflammatory properties in the albumin-induced test model in rats. Oils from the fresh leaves and dry stems inhibited inflammation beyond 4 h post treatment. The potent anti-inflammatory activity of essential oils of A. mearnsii hereby confirmed its traditional use in treating various inflammatory diseases.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction.

PubMed

Keefe, Richard S E; Nomikos, George; Zhong, Wei; Christensen, Michael Cronquist; Jacobson, William

2018-05-01

We evaluated vortioxetine's effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions-Severity of Illness). Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45-54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions-Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. clinicaltrials.gov: NCT01564862.

Cemented or cementless humeral fixation in reverse total shoulder arthroplasty? a systematic review.

PubMed

Phadnis, J; Huang, T; Watts, A; Krishnan, J; Bain, G I

2016-01-01

To date, there is insufficient evidence available to compare the outcome of cemented and uncemented fixation of the humeral stem in reverse shoulder arthroplasty (RSA). A systemic review comprising 41 clinical studies was performed to compare the functional outcome and rate of complications of cemented and uncemented stems in RSA. These included 1455 cemented and 329 uncemented shoulders. The clinical characteristics of the two groups were similar. Variables were compared using pooled frequency-weighted means and relative risk ratios (RR). Uncemented stems had a significantly higher incidence of early humeral stem migration (p < 0.001, RR 18.1, 95% confidence interval (CI) 5.0 to 65.2) and non-progressive radiolucent lines (p < 0.001, RR 2.4, 95% CI 1.7 to 3.4), but a significantly lower incidence of post-operative fractures of the acromion compared with cemented stems (p = 0.004, RR 14.3, 95% CI 0.9 to 232.8). There was no difference in the risk of stem loosening or revision between the groups. The cemented stems had a greater relative risk of infection (RR 3.3, 95% CI 0.8 to 13.7), nerve injury (RR 5.7, 95% CI 0.7 to 41.5) and thromboembolism (RR 3.9, 95% CI 0.2 to 66.6). The functional outcome and range of movement were equivalent in the two groups. RSA performed with an uncemented stem gives them equivalent functional outcome and a better complication profile than with a cemented stem. The natural history and clinical relevance of early stem migration and radiolucent lines found with uncemented stems requires further long-term study. This study demonstrates that uncemented stems have at least equivalent clinical and radiographic outcomes compared with cemented stems when used for reverse total shoulder arthroplasty. ©2016 The British Editorial Society of Bone & Joint Surgery.

Tailoring the implementation of new biomarkers based on their added predictive value in subgroups of individuals.

PubMed

van Giessen, A; Moons, K G M; de Wit, G A; Verschuren, W M M; Boer, J M A; Koffijberg, H

2015-01-01

The value of new biomarkers or imaging tests, when added to a prediction model, is currently evaluated using reclassification measures, such as the net reclassification improvement (NRI). However, these measures only provide an estimate of improved reclassification at population level. We present a straightforward approach to characterize subgroups of reclassified individuals in order to tailor implementation of a new prediction model to individuals expected to benefit from it. In a large Dutch population cohort (n = 21,992) we classified individuals to low (< 5%) and high (≥ 5%) fatal cardiovascular disease risk by the Framingham risk score (FRS) and reclassified them based on the systematic coronary risk evaluation (SCORE). Subsequently, we characterized the reclassified individuals and, in case of heterogeneity, applied cluster analysis to identify and characterize subgroups. These characterizations were used to select individuals expected to benefit from implementation of SCORE. Reclassification after applying SCORE in all individuals resulted in an NRI of 5.00% (95% CI [-0.53%; 11.50%]) within the events, 0.06% (95% CI [-0.08%; 0.22%]) within the nonevents, and a total NRI of 0.051 (95% CI [-0.004; 0.116]). Among the correctly downward reclassified individuals cluster analysis identified three subgroups. Using the characterizations of the typically correctly reclassified individuals, implementing SCORE only in individuals expected to benefit (n = 2,707,12.3%) improved the NRI to 5.32% (95% CI [-0.13%; 12.06%]) within the events, 0.24% (95% CI [0.10%; 0.36%]) within the nonevents, and a total NRI of 0.055 (95% CI [0.001; 0.123]). Overall, the risk levels for individuals reclassified by tailored implementation of SCORE were more accurate. In our empirical example the presented approach successfully characterized subgroups of reclassified individuals that could be used to improve reclassification and reduce implementation burden. In particular when newly added biomarkers or imaging tests are costly or burdensome such a tailored implementation strategy may save resources and improve (cost-)effectiveness.

Subgroups of Adult Basic Education Learners with Different Profiles of Reading Skills

ERIC Educational Resources Information Center

MacArthur, Charles A.; Konold, Timothy R.; Glutting, Joseph J.; Alamprese, Judith A.

2012-01-01

The purpose of this study was to identify subgroups of adult basic education (ABE) learners with different profiles of skills in the core reading components of decoding, word recognition, spelling, fluency, and comprehension. The analysis uses factor scores of those 5 reading components from on a prior investigation of the reliability and…

[Disease perception in patients with wet age-related macular degeneration].

PubMed

Kostadinov, F; Valmaggia, C

2015-04-01

The disease perception of the patients treated with intravitreal injections of anti-vascular endothelial growth factor due to wet age-related macular degeneration was investigated. 177 questionnaires focusing on the development of the perceived visual acuity and the quality of life were evaluated. The subgroup 1 included 125 patients (70.6%) with a unilateral wet age-related macular degeneration. The subgroup 2 included 52 patients (29.4%) with a bilateral wet age-related macular degeneration. Patients would almost always recommend the therapy to a friend (97.2%). The critical remarks are related to the uncertain course of the disease (22.8%) and the uncertain duration of the treatment (19%). There was a discrepancy between the measured visual outcome and the perceived one in 5.6% in the subgroup 1, and in 38.5% in the subgroup 2. This difference was statistically significant (chi-square test with p<0.01). The treatment of wet age-related macular degeneration with intravitreal injections of anti-vascular endothelial growth factor is judged positively. Binocular affected patients have a higher disease perception and therefore a poorer self-assessment of their visual acuity and their quality of life compared with monocular affected patients. Georg Thieme Verlag KG Stuttgart · New York.

Does Surface Topography Play a Role in Taper Damage in Head-neck Modular Junctions?

PubMed

Pourzal, Robin; Hall, Deborah J; Ha, Nguyen Q; Urban, Robert M; Levine, Brett R; Jacobs, Joshua J; Lundberg, Hannah J

2016-10-01

There are increasing reports of total hip arthroplasty failure subsequent to modular taper junction corrosion. The surfaces of tapers are machined to have circumferential machining marks, resulting in a surface topography of alternating peaks and valleys on the scale of micrometers. It is unclear if the geometry of this machined surface topography influences the degree of fretting and corrosion damage present on modular taper junctions or if there are differences between modular taper junction material couples. (1) What are the differences in damage score and surface topography between CoCr/CoCr and CoCr/Ti modular junctions? (2) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/CoCr couples? (3) How are initial surface topography, flexural rigidity, taper angle mismatch, and time in situ related to visual taper damage scores for CoCr/Ti couples? Damage on stem and head tapers was evaluated with a modified Goldberg score. Differences in damage scores were determined between a group of 140 CoCr/CoCr couples and 129 CoCr/Ti couples using a chi-square test. For a subgroup of 70 retrievals, selected at random, we measured five variables, including initial stem taper machining mark height and spacing, initial head taper roughness, flexural rigidity, and taper angle mismatch. All retrievals were obtained at revision surgeries. None were retrieved as a result of metal-on-metal failures or were recalled implants. Components were chosen so there was a comparable number of each material couple and damage score. Machining marks around the circumference of the tapers were measured using white light interferometry to characterize the initial stem taper surface topography in terms of the height of and spacing between machining mark peaks as well as initial head taper roughness. The taper angle mismatch was assessed with a coordinate measuring machine. Flexural rigidity was determined based on measurements of gross taper dimensions and material properties. Differences of median or mean values of all variables between material couples were determined (Wilcoxon rank-sum tests and t-tests). The effect of all five variables along with time in situ on stem and head taper damage scores was tested with a multiple regression model. With 70 retrievals, a statistical power of 0.8 could be achieved for the model. Damage scores were different between CoCr/CoCr and CoCr/Ti modular taper junction material couples. CoCr/CoCr stem tapers were less likely to be mildly damaged (11%, p = 0.006) but more likely to be severely damaged (4%, p = 0.02) than CoCr/Ti stem tapers (28% and 1%, respectively). CoCr/CoCr couples were less likely to have moderately worn head tapers (7% versus 17%, p = 0.003). Stem taper machining mark height and spacing and head taper roughness were 11 (SD 3), 185 (SD 46), and 0.57 (SD 0.5) for CoCr/CoCr couples and 10 (SD 3), 170 (SD 56), and 0.64 (SD 0.4) for CoCr/Ti couples, respectively. There was no difference (p = 0.09, p = 0.1, p = 0.16, respectively) for either factor between material couples. Larger stem taper machining mark heights (p = 0.001) were associated with lower stem taper damage scores, and time in situ (p = 0.006) was associated with higher stem taper damage scores for CoCr/CoCr material couples. Stem taper machining marks that had higher peaks resulted in slower damage progression over time. For CoCr/Ti material couples, head taper roughness was associated with higher stem (p = 0.001) and head taper (p = 0.003) damage scores, and stem taper machining mark height, but not time in situ, was associated with lower stem taper damage scores (p = 0.007). Stem taper surface topography was related to damage scores on retrieved head-neck modular junctions; however, it affected CoCr/CoCr and CoCr/Ti couples differently. A taper topography of circumferential machining marks with higher peaks appears to enable slower damage progression and, subsequently, a reduction of the reported release of corrosion products. This may be of interest to implant designers and manufacturers in an effort to reduce the effects of metal release from modular femoral components.

Acute B lymphoblastic leukaemia-propagating cells are present at high frequency in diverse lymphoblast populations

PubMed Central

Rehe, Klaus; Wilson, Kerrie; Bomken, Simon; Williamson, Daniel; Irving, Julie; den Boer, Monique L; Stanulla, Martin; Schrappe, Martin; Hall, Andrew G; Heidenreich, Olaf; Vormoor, Josef

2013-01-01

Leukaemia-propagating cells are more frequent in high-risk acute B lymphoblastic leukaemia than in many malignancies that follow a hierarchical cancer stem cell model. It is unclear whether this characteristic can be more universally applied to patients from non-‘high-risk’ sub-groups and across a broad range of cellular immunophenotypes. Here, we demonstrate in a wide range of primary patient samples and patient samples previously passaged through mice that leukaemia-propagating cells are found in all populations defined by high or low expression of the lymphoid differentiation markers CD10, CD20 or CD34. The frequency of leukaemia-propagating cells and their engraftment kinetics do not differ between these populations. Transcriptomic analysis of CD34high and CD34low blasts establishes their difference and their similarity to comparable normal progenitors at different stages of B-cell development. However, consistent with the functional similarity of these populations, expression signatures characteristic of leukaemia propagating cells in acute myeloid leukaemia fail to distinguish between the different populations. Together, these findings suggest that there is no stem cell hierarchy in acute B lymphoblastic leukaemia. PMID:23229821

Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells.

PubMed

Hitoshi, Seiji; Ishino, Yugo; Kumar, Akhilesh; Jasmine, Salma; Tanaka, Kenji F; Kondo, Takeshi; Kato, Shigeaki; Hosoya, Toshihiko; Hotta, Yoshiki; Ikenaka, Kazuhiro

2011-07-17

Signaling mediated by Notch receptors is crucial for the development of many organs and the maintenance of various stem cell populations. The activation of Notch signaling is first detectable by the expression of an effector gene, Hes5, in the neuroepithelium of mouse embryos at embryonic day (E) 8.0-8.5, and this activation is indispensable for the generation of neural stem cells. However, the molecular mechanism by which Hes5 expression is initiated in stem-producing cells remains unknown. We found that mammalian Gcm1 and Gcm2 (glial cells missing 1 and 2) are involved in the epigenetic regulation of Hes5 transcription by DNA demethylation independently of DNA replication. Loss of both Gcm genes and subsequent lack of Hes5 upregulation in the neuroepithelium of E7.5-8.5 Gcm1(-/-); Gcm2(-/-) mice resulted in the impaired induction of neural stem cells. Our data suggest that Hes5 expression is serially activated first by Gcms and later by the canonical Notch pathway.

Risk stratification using stress echocardiography: incremental prognostic value over historic, clinical, and stress electrocardiographic variables across a wide spectrum of bayesian pretest probabilities for coronary artery disease.

PubMed

Bangalore, Sripal; Gopinath, Devi; Yao, Siu-Sun; Chaudhry, Farooq A

2007-03-01

We sought to evaluate the risk stratification ability and incremental prognostic value of stress echocardiography over historic, clinical, and stress electrocardiographic (ECG) variables, over a wide spectrum of bayesian pretest probabilities of coronary artery disease (CAD). Stress echocardiography is an established technique for the diagnosis of CAD. However, data on incremental prognostic value of stress echocardiography over historic, clinical, and stress ECG variables in patients with known or suggested CAD is limited. We evaluated 3259 patients (60 +/- 13 years, 48% men) undergoing stress echocardiography. Patients were grouped into low (<15%), intermediate (15-85%), and high (>85%) pretest CAD likelihood subgroups using standard software. The historical, clinical, stress ECG, and stress echocardiographic variables were recorded for the entire cohort. Follow-up (2.7 +/- 1.1 years) for confirmed myocardial infarction (n = 66) and cardiac death (n = 105) was obtained. For the entire cohort, an ischemic stress echocardiography study confers a 5.0 times higher cardiac event rate than the normal stress echocardiography group (4.0% vs 0.8%/y, P < .0001). Furthermore, Cox proportional hazard regression model showed incremental prognostic value of stress echocardiography variables over historic, clinical, and stress ECG variables across all pretest probability subgroups (global chi2 increased from 5.1 to 8.5 to 20.1 in the low pretest group, P = .44 and P = .01; from 20.9 to 28.2 to 116 in the intermediate pretest group, P = .47 and P < .0001; and from 17.5 to 36.6 to 61.4 in the high pretest group, P < .0001 for both groups). A normal stress echocardiography portends a benign prognosis (<1% event rate/y) in all pretest probability subgroups and even in patients with high pretest probability and yields incremental prognostic value over historic, clinical, and stress ECG variables across all pretest probability subgroups. The best incremental value is, however, in the intermediate pretest probability subgroup.

Stability of a stem-loop involving the initiator AUG controls the efficiency of internal initiation of translation on hepatitis C virus RNA.

PubMed Central

Honda, M; Brown, E A; Lemon, S M

1996-01-01

The initiation of translation on the positive-sense RNA genome of hepatitis C virus (HCV) is directed by an internal ribosomal entry site (IRES) that occupies most of the 341-nt 5' nontranslated RNA (5'NTR). Previous studies indicate that this IRES differs from picornaviral IRESs in that its activity is dependent upon RNA sequence downstream of the initiator AUG. Here, we demonstrate that the initiator AUG of HCV is located within a stem-loop (stem-loop IV) involving nt -12 to +12 (with reference to the AUG). This structure is conserved among HCV strains, and is present in the 5'NTR of the phylogenetically distant GB virus B. Mutant, nearly genome-length RNAs containing nucleotide substitutions predicted to enhance the stability of stem-loop IV were generally deficient in cap-independent translation both in vitro and in vivo. Additional mutations that destabilize the stem-loop restored translation to normal. Thus, the stability of the stem-loop is strongly but inversely correlated with the efficiency of internal initiation of translation. In contrast, mutations that stabilize this stem-loop had comparatively little effect on translation of 5' truncated RNAs by scanning ribosomes, suggesting that internal initiation of translation follows binding of the 40S ribosome directly at the site of stem-loop IV. Because stem-loop IV is not required for internal entry of ribosomes but is able to regulate this process, we speculate that it may be stabilized by interactions with a viral protein, providing a mechanism for feedback regulation of translation, which may be important for viral persistence. PMID:8849773

WNT signaling in stem cell biology and regenerative medicine.

PubMed

Katoh, Masaru

2008-07-01

WNT family members are secreted-type glycoproteins to orchestrate embryogenesis, to maintain homeostasis, and to induce pathological conditions. FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, and ROR2 are transmembrane receptors transducing WNT signals based on ligand-dependent preferentiality for caveolin- or clathrin-mediated endocytosis. WNT signals are transduced to canonical pathway for cell fate determination, and to non-canonical pathways for regulation of planar cell polarity, cell adhesion, and motility. MYC, CCND1, AXIN2, FGF20, WISP1, JAG1, DKK1 and Glucagon are target genes of canonical WNT signaling cascade, while CD44, Vimentin and STX5 are target genes of non-canonical WNT signaling cascades. However, target genes of WNT signaling cascades are determined in a context-dependent manner due to expression profile of transcription factors and epigenetic status. WNT signaling cascades network with Notch, FGF, BMP and Hedgehog signaling cascades to regulate the balance of stem cells and progenitor cells. Here WNT signaling in embryonic stem cells, neural stem cells, mesenchymal stem cells, hematopoietic stem cells, and intestinal stem cells will be reviewed. WNT3, WNT5A and WNT10B are expressed in undifferentiated human embryonic stem cells, while WNT6, WNT8B and WNT10B in endoderm precursor cells. Wnt6 is expressed in intestinal crypt region for stem or progenitor cells. TNF/alpha-WNT10B signaling is a negative feedback loop to maintain homeostasis of adipose tissue and gastrointestinal mucosa with chronic inflammation. Recombinant WNT protein or WNT mimetic (circular peptide, small molecule compound, or RNA aptamer) in combination with Notch mimetic, FGF protein, and BMP protein opens a new window to tissue engineering for regenerative medicine.

40 CFR 180.544 - Methoxyfenozide; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 9 0.3 Vegetable, foliage of legume, except soybean, subgroup 7A 35 Vegetable, fruiting, group 8 2.0 Vegetable, leaves of root and tuber, group 2 30 Vegetable, legume, edible podded, subgroup 6A 1.5 Vegetable..., group 17 10.0 09/30/10 Herb and spice, group 19 10.0 09/30/10 Vegetable, foliage of legume, group 7 10.0...

Gibberellins and stem growth in Arabidopsis thaliana. Effects of photoperiod on expression of the GA4 and GA5 loci.

PubMed

Xu, Y L; Gage, D A; Zeevaart, J A

1997-08-01

Arabidopsis thaliana (L.) Heynh. is a quantitative long-day (LD) rosette plant in which stem growth is mediated by gibberellins (CAs). Application of GAs to plants in short-day (SD) conditions resulted in rapid stem elongation and flower formation, with GA4 and GA9 being equally effective, and GA1 showing lower activity. The effects of photoperiod on the levels of endogenous GAs were measured by combined gas chromatography-mass spectrometry with selected ion monitoring. When plants were transferred from SD to LD conditions there was a slight decrease in the level of GA53 and an increase in the levels of C19-GAs, GA9, GA20, GA1, and GA8, indicating that GA 20-oxidase activity is stimulated in LD conditions. Expression of GA5, which encodes GA 20-oxidase, was highest in elongating stems and was correlated with the rate of stem elongation. By contrast, GA4, which encodes 3 beta-hydroxylase, showed low expression in stems and its expression was not correlated with the rate of stem elongation. We conclude that stem elongation in LD conditions is at least in part due to increased expression of GA5, whereas expression of GA4 is not under photoperiodic control.

Subgrouping of risky behaviors among Iranian college students: a latent class analysis

PubMed Central

Safiri, Saeid; Rahimi-Movaghar, Afarin; Yunesian, Masud; Sadeghi-Bazargani, Homayoun; Shamsipour, Mansour; Mansournia, Mohammad Ali; Fotouhi, Akbar

2016-01-01

Background Risky behaviors may interrupt development or cause considerable morbidity or mortality. This study’s purpose was to determine subgroups of students based on risky behaviors and assess the prevalence of risky behaviors in each of the subgroups. Participants and methods This anonymous cross-sectional study was carried out in October 2015 and November 2015, with 1,777 students from Tabriz University of Medical Sciences, through multistage random sampling method. The data were analyzed by latent class analysis. Results The prevalence rates of cigarette smoking (more than or equal to ten cigarettes), hookah use (≥1 time/month), and alcohol consumption (≥1 time/month) during the last year were 12.4% (95% confidence interval [CI]: 10.9–14.0), 11.6% (95% CI: 10.0–13.1), and 4.9% (95% CI: 3.8–5.9), respectively. The prevalence rates of illicit opioids (1.8%, 95% CI: 1.2–2.5), cannabis (1.2%, 95% CI: 0.7–1.7), methamphetamine (1.1%, 95% CI: 0.6–1.6), methylphenidate (2.5%, 95% CI: 1.7–3.2), and extramarital sex (5.5%, 95% CI: 4.5–6.6) over the last year were also estimated. Three latent classes were determined: 1) low risk; 2) cigarette and hookah smoker; and 3) high risk. It is worth mentioning that 3.7% of males and 0.4% of females were in the high risk group. Conclusion Subgrouping of college students showed that a considerable percentage of them, especially males, were classified into the high risk and cigarette and hookah smoker groups. Appropriate preventive measures that consider multiple different risky behaviors simultaneously are needed for this part of the population. PMID:27524898

METHOD OF SEPARATING TETRAVALENT PLUTONIUM VALUES FROM CERIUM SUB-GROUP RARE EARTH VALUES

DOEpatents

Duffield, R.B.; Stoughton, R.W.

1959-02-01

A method is presented for separating plutonium from the cerium sub-group of rare earths when both are present in an aqueous solution. The method consists in adding an excess of alkali metal carbonate to the solution, which causes the formation of a soluble plutonium carbonate precipitate and at the same time forms an insoluble cerium-group rare earth carbonate. The pH value must be adjusted to bctween 5.5 and 7.5, and prior to the precipitation step the plutonium must be reduced to the tetravalent state since only tetravalent plutonium will form the soluble carbonate complex.

A new grading system focusing on neurological outcomes for brain metastases treated with stereotactic radiosurgery: the modified Basic Score for Brain Metastases.

PubMed

Serizawa, Toru; Higuchi, Yoshinori; Nagano, Osamu; Matsuda, Shinji; Ono, Junichi; Saeki, Naokatsu; Hirai, Tatsuo; Miyakawa, Akifumi; Shibamoto, Yuta

2014-12-01

The Basic Score for Brain Metastases (BSBM) proposed by Lorenzoni and colleagues is one of the best grading systems for predicting survival periods after stereotactic radiosurgery (SRS) for brain metastases. However, it includes no brain factors and cannot predict neurological outcomes, such as preservation of neurological function and prevention of neurological death. Herein, the authors propose a modified BSBM, adding 4 brain factors to the original BSBM, enabling prediction of neurological outcomes, as well as of overall survival, in patients undergoing SRS. To serve as neurological prognostic scores (NPSs), the authors scored 4 significant brain factors for both preservation of neurological function (qualitative survival) and prevention of neurological death (neurological survival) as 0 or 1 as described in the following: > 10 brain tumors = 0 or ≤ 10 = 1, total tumor volume > 15 cm(3) = 0 or ≤ 15 cm(3) = 1, MRI findings of localized meningeal dissemination (yes = 0 or no = 1), and neurological symptoms (yes = 0 or no = 1). According to the sum of NPSs, patients were classified into 2 subgroups: Subgroup A with a total NPS of 3 or 4 and Subgroup B with an NPS of 0, 1, or 2. The authors defined the modified BSBM according to the NPS subgroup classification applied to the original BSBM groups. The validity of this modified BSBM in 2838 consecutive patients with brain metastases treated with SRS was verified. Patients included 1868 with cancer of the lung (including 1604 with non-small cell lung cancer), 355 of the gastrointestinal tract, 305 of the breast, 176 of the urogenital tract, and 134 with other cancers. Subgroup A had 2089 patients and Subgroup B 749. Median overall survival times were 2.6 months in BSBM 0 (382 patients), 5.7 in BSBM 1 (1143), 11.4 in BSBM 2 (1011) and 21.7 in BSBM 3 (302), and pairwise differences between the BSBM groups were statistically significant (all p < 0.0001). One-year qualitative survival rates were 64.6% (modified BSBM 0A, 204 patients), 45.0% (0B, 178), 82.5% (1A, 825), 63.3% (1B, 318), 86.4% (2A, 792), 73.7% (2B, 219), 91.4% (3A, 268), and 73.5% (3B, 34). One-year neurological survival rates were 82.6% (0A), 52.4% (0B), 90.5% (1A), 78.1% (1B), 91.1% (2A), 83.2% (2B), 93.9% (3A), and 76.3% (3B), where A and B identify the subgroup. Statistically significant differences in both qualitative and neurological survivals between Subgroups A and B were detected in all BSBM groups. The authors' new index, the modified BSBM, was found to be excellent for predicting neurological outcomes, independently of life expectancy, in SRS-treated patients with brain metastases.

Analysis of efficacy and safety of treatment with collagenase Clostridium histolyticum among subgroups of patients with Dupuytren contracture.

PubMed

Raven, Raymond B; Kushner, Harvey; Nguyen, Dat; Naam, Nash; Curtin, Catherine

2014-09-01

Collagenase Clostridium histolyticum (CCH) injection is a nonoperative treatment of hand contractures from Dupuytren disease. This study assessed the efficacy and safety of CCH in several subgroups of patients with increased surgical risk.Data were pooled from 3 randomized, placebo-controlled, double-blind trials. This analysis included 271 patients with metacarpophalangeal (n = 167) or proximal interphalangeal (n = 104) joint contractures greater than or equal to 20 degrees treated with CCH (0.58 mg collagenase per injection). Subgroups included age, sex, and diabetes status. End points included rate of clinical success (reduction in contracture to 0-5 degrees of normal) and percentage of adverse events.There was no significant difference in clinical success by age, diabetes status, or sex with 63% reaching the end point. There was no difference in adverse events among the subgroups, with peripheral edema, contusion, and injection-site hemorrhage being most common.High-risk subgroups do not demonstrate differences in efficacy or safety with CCH treatment of Dupuytren-related contractures.

Mass media effect on vaccines uptake during silent polio outbreak.

PubMed

Sagy, Iftach; Novack, Victor; Gdalevich, Michael; Greenberg, Dan

2018-03-14

During 2013, isolation of a wild type 1 poliovirus from routine sewage sample in Israel, led to a national OPV campaign. During this period, there was a constant cover of the outbreak by the mass media. To investigate the association of media exposure and OPV and non-OPV vaccines uptake during the 2013 silent polio outbreak in Israel. We received data on daily immunization rates during the outbreak period from the Ministry of Health (MoH). We conducted a multivariable time trend analysis to assess the association between daily media exposure and vaccines uptake. Analysis was stratified by ethnicity and socio-economic status (SES). During the MoH supplemental immunization activity, 138,799 OPV vaccines were given. There was a significant association between media exposure and OPV uptake, most prominent in a lag of 3-5 days from the exposure among Jews (R.R 1.79C.I 95% 1.32-2.41) and high SES subgroups (R.R 1.71C.I 95% 1.27-2.30). These subgroups also showed increased non-OPV uptake in a lag of 3-5 days from the media exposure, in all vaccines except for MMR. Lower SES and non-Jewish subgroups did not demonstrate the same association. Our findings expand the understanding of public behaviour during outbreaks. The public response shows high variability within specific subgroups. These findings highlight the importance of tailored communication strategies for each subgroup. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases

PubMed Central

Hubert, Amy; Henderson, Jordana M.; Ross, Kelly G.; Cowles, Martis W.; Torres, Jessica; Zayas, Ricardo M.

2013-01-01

Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5–1 and mll5–2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5–2 are required for regeneration and that set1, trr-1 and mll5–2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo. PMID:23235145

Epigenetic regulation of planarian stem cells by the SET1/MLL family of histone methyltransferases.

PubMed

Hubert, Amy; Henderson, Jordana M; Ross, Kelly G; Cowles, Martis W; Torres, Jessica; Zayas, Ricardo M

2013-01-01

Chromatin regulation is a fundamental mechanism underlying stem cell pluripotency, differentiation, and the establishment of cell type-specific gene expression profiles. To examine the role of chromatin regulation in stem cells in vivo, we study regeneration in the freshwater planarian Schmidtea mediterranea. These animals possess a high concentration of pluripotent stem cells, which are capable of restoring any damaged or lost tissues after injury or amputation. Here, we identify the S. mediterranea homologs of the SET1/MLL family of histone methyltransferases and COMPASS and COMPASS-like complex proteins and investigate their role in stem cell function during regeneration. We identified six S. mediterranea homologs of the SET1/MLL family (set1, mll1/2, trr-1, trr-2, mll5-1 and mll5-2), characterized their patterns of expression in the animal, and examined their function by RNAi. All members of this family are expressed in the stem cell population and differentiated tissues. We show that set1, mll1/2, trr-1, and mll5-2 are required for regeneration and that set1, trr-1 and mll5-2 play roles in the regulation of mitosis. Most notably, knockdown of the planarian set1 homolog leads to stem cell depletion. A subset of planarian homologs of COMPASS and COMPASS-like complex proteins are also expressed in stem cells and implicated in regeneration, but the knockdown phenotypes suggest that some complex members also function in other aspects of planarian biology. This work characterizes the function of the SET1/MLL family in the context of planarian regeneration and provides insight into the role of these enzymes in adult stem cell regulation in vivo.

Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults

PubMed Central

Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

2016-01-01

Background: Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. Methods: A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t-test. Results: There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group. Conclusions: Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population. PMID:27174324

Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults.

PubMed

Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

2016-05-20

Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage <30%). Altogether 207 healthy adults were chosen as the control group. All patients and the control group took lumbosacral lateral radiographs. Seven sagittal lumbosacral parameters, including PI, pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), L5 incidence, L5 slope, and sacral table angle (STA), were measured in the lateral radiographs. All the parameters aforementioned were compared between the two subgroups and between the spondylolysis group and the control group with independent-sample t- test. There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P < 0.05) in the spondylolysis group than those in the control group, but STA was lower (P < 0.001) in the spondylolysis group. Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population.

Styrax americanus Lam.

Treesearch

K.F Connor

2004-01-01

American snowbell, also known as mock orange or storax, is a deciduous shrub or small tree with a widely branched crown. It reaches 3 to 5 m in height, and the stems can reach 7.5 cm in diameter. While the bark on the stems is smooth and dark grey to brown, branches range in color from green to grey to red-brown. Young stems are pubescent, becoming glabrous with age....

Internal working models and adjustment of physically abused children: the mediating role of self-regulatory abilities.

PubMed

Hawkins, Amy L; Haskett, Mary E

2014-01-01

Abused children's internal working models (IWM) of relationships are known to relate to their socioemotional adjustment, but mechanisms through which negative representations increase vulnerability to maladjustment have not been explored. We sought to expand the understanding of individual differences in IWM of abused children and investigate the mediating role of self-regulation in links between IWM and adjustment. Cluster analysis was used to subgroup 74 physically abused children based on their IWM. Internal working models were identified by children's representations, as measured by a narrative story stem task. Self-regulation was assessed by teacher report and a behavioral task, and adjustment was measured by teacher report. Cluster analyses indicated two subgroups of abused children with distinct patterns of IWMs. Cluster membership predicted internalizing and externalizing problems. Associations between cluster membership and adjustment were mediated by children's regulation, as measured by teacher reports of many aspects of regulation. There was no support for mediation when regulation was measured by a behavioral task that tapped more narrow facets of regulation. Abused children exhibit clinically relevant individual differences in their IWMs; these models are linked to adjustment in the school setting, possibly through children's self-regulation. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.

Volatile Constituents of Three Piper Species from Vietnam.

PubMed

Hieua, Le D; Hoic, Tran M; Thangda, Tran D; Ogunwande, Isiaka A

2015-11-01

The chemical compositions of the essential oils obtained by hydrodistillation of three Piper plants grown in Vietnam are reported. The analysis was achieved by means of gas chromatography with flame ionization detection (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS). The main constituents of the leaf oil of Piper majusculum Blume were β-caryophyllene (20.7%), germacrene D (18.6%) and β-elemene (11.3%). The quantitatively significant compounds of the volatile oils of P. harmandii C. DC were sabinene (leaves, 14.5%; stems, 16.2%), benzyl benzoate (leaves, 20.0%; stems, 29.40%) and benzyl salicylate (leaves, 14.1%; stems, 24.3%). Also, α-cadinol (17.0%) was identified in large proportion in the leaf oil. However, sabinene (leaves, 17.9%; stems, 13.5%), benzyl benzoate (leaves, 20.5%; stems, 32.5%) and β-eudesmol (leaves, 13.8%; stems, 8.4%) were the main constituents of P. brevicaule C. DC. This is the first report on the volatile constituents of both P. harmandii and P. brevicaule.

1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells.

PubMed

Okolotowicz, Karl J; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Mercola, Mark; Cashman, John R

2015-09-01

Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure-activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

1,5-Disubstituted benzimidazoles that direct cardiomyocyte differentiation from mouse embryonic stem cells

PubMed Central

Okolotowicz, Karl J.; Bushway, Paul; Lanier, Marion; Gilley, Cynthia; Cynthia, Mark; Cashman, John R.

2016-01-01

Cardiomyopathy is the leading cause of death worldwide. Despite progress in medical treatments, heart transplantation is one of the only current options for those with infarcted heart muscle. Stem cell differentiation technology may afford cell-based therapeutics that may lead to the generation of new, healthy heart muscle cells from undifferentiated stem cells. Our approach is to use small molecules to stimulate stem cell differentiation. Herein, we describe a novel class of 1,5-disubstituted benzimidazoles that induce differentiation of stem cells into cardiac cells. We report on the evaluation in vitro for cardiomyocyte differentiation and describe structure–activity relationship results that led to molecules with drug-like properties. The results of this study show the promise of small molecules to direct stem cell lineage commitment, to probe signaling pathways and to develop compounds for the stimulation of stem cells to repair damaged heart tissue. PMID:26278027

Tumor necrosis factor alpha gene promoter -238G/A polymorphism increases the risk of psoriasis vulgaris in Indian patients.

PubMed

Rajesh, Deepa; Gurumurthy, Rajesh; Kutty, A V Moideen; Balakrishna, Sharath

2017-03-01

Tumor necrosis factor alpha (TNFα) gene -238G/A polymorphism (rs361525) is associated with psoriasis in several populations worldwide. To the best of our knowledge, there is no information about this polymorphism in Indian psoriatic patients. This study was undertaken to fill the gap in knowledge. This case-control study involved 72 patients with psoriasis vulgaris (PsV) and 72 age and gender matched healthy individuals. TNFα -238G/A polymorphism was genotyped by PCR-RFLP method. TNFα -238A allele was 5 times commoner in PsV patients than in the control group (P = 4.1 × 10 -7 ; odds ratio [OR] = 6.5 [0.95 CI: 2.9-14.6]). Distribution of the genotypes in the two groups showed statistically significant difference in dominant genetic model (P = 2.3 × 10 -7 ) and not in recessive genetic model (P = 2.5 × 10 -1 ). Odds ratio for the occurrence of -238A genotype in PsV patients was 8.8 (0.95 CI: 3.5-20.2). The association showed no major difference when PsV patients were subgrouped into type I and type II categories and tested separately. Subgroup analysis on the basis of disease severity showed higher association with the moderate-severe subgroup (P = 2.4 × 10 -9 , OR 15.4 [0.95 CI: 5.8-41.0]) than with mild subgroup (P = 1.3 × 10 -2 , OR 3.8 [0.95 CI: 1.3-10.9]). Our results indicate that TNFα gene -238G/A polymorphism increases the risk of developing psoriasis vulgaris among Indians. Also, the data show that severity and not the type affects the strength of association in this population. © 2017 The International Society of Dermatology.

Stalking influenza by vaccination with pre-fusion headless HA mini-stem.

PubMed

Valkenburg, Sophie A; Mallajosyula, V Vamsee Aditya; Li, Olive T W; Chin, Alex W H; Carnell, George; Temperton, Nigel; Varadarajan, Raghavan; Poon, Leo L M

2016-03-07

Inaccuracies in prediction of circulating viral strain genotypes and the possibility of novel reassortants causing a pandemic outbreak necessitate the development of an anti-influenza vaccine with increased breadth of protection and potential for rapid production and deployment. The hemagglutinin (HA) stem is a promising target for universal influenza vaccine as stem-specific antibodies have the potential to be broadly cross-reactive towards different HA subtypes. Here, we report the design of a bacterially expressed polypeptide that mimics a H5 HA stem by protein minimization to focus the antibody response towards the HA stem. The HA mini-stem folds as a trimer mimicking the HA prefusion conformation. It is resistant to thermal/chemical stress, and it binds to conformation-specific, HA stem-directed broadly neutralizing antibodies with high affinity. Mice vaccinated with the group 1 HA mini-stems are protected from morbidity and mortality against lethal challenge by both group 1 (H5 and H1) and group 2 (H3) influenza viruses, the first report of cross-group protection. Passive transfer of immune serum demonstrates the protection is mediated by stem-specific antibodies. Furthermore, antibodies induced by these HA stems have broad HA reactivity, yet they do not have antibody-dependent enhancement activity.

Mechanical aspects of degree of cement bonding and implant wedge effect.

PubMed

Yoon, Yong-San; Oxland, Thomas R; Hodgson, Antony J; Duncan, Clive P; Masri, Bassam A; Choi, Donok

2008-11-01

The degree of bonding between the femoral stem and cement in total hip replacement remains controversial. Our objective was to determine the wedge effect by debonding and stem taper angle on the structural behavior of axisymmetric stem-cement-bone cylinder models. Stainless steel tapered plugs with a rough (i.e. bonded) or smooth (i.e. debonded) surface finish were used to emulate the femoral stem. Three different stem taper angles (5 degrees , 7.5 degrees , 10 degrees ) were used for the debonded constructs. Non-tapered and tapered (7.5 degrees ) aluminum cylindrical shells were used to emulate the diaphyseal and metaphyseal segments of the femur. The cement-aluminum cylinder interface was designed to have a shear strength that simulated bone-cement interfaces ( approximately 8MPa). The test involved applying axial compression at a rate of 0.02mm/s until failure. Six specimens were tested for each combination of the variables. Finite element analysis was used to enhance the understanding of the wedge effect. The debonded stems sustained about twice as much load as the bonded stem, regardless of taper angle. The metaphyseal model carried 35-50% greater loads than the diaphyseal models and the stem taper produced significant differences. Based on the finite element analysis, failure was most probably by shear at the cement-bone interface. Our results in this simplified model suggest that smooth (i.e. debonded) stems have greater failure loads and will incur less slippage or shear failure at the cement-bone interface than rough (i.e. bonded) stems.

Value of ultrasound shear wave elastography in the diagnosis of adenomyosis

PubMed Central

Millar, E; Mitkova, M; Mitkov, V

2016-01-01

Background The aim of the study was to assess the accuracy of ultrasound shear wave elastography in the diagnosis of adenomyosis. Methods One hundred and fifty three patients were examined. Ninety-seven patients were with suspected adenomyosis and 56 patients were with unremarkable myometrium. Adenomyosis was confirmed in 39 cases (A subgroup) and excluded in 14 cases (B subgroup) in the main group based on morphological examination. All patients underwent ultrasound examination using an Aixplorer (Supersonic Imagine, France) scanner with application of shear wave elastography during transvaginal scanning. Retrospective analysis of the elastography criteria against the findings from morphological/histological examination was performed. Results The following values of Young’s modulus were found in subgroup A (adenomyosis): Emean – 72.7 (22.6–274.2) kPa (median, 5–95th percentiles), Emax – 94.8 (29.3–300.0) kPa, SD – 9.9 (2.6–26.3) kPa; in subgroup B (non adenomyosis) – 28.3 (12.7–59.5) kPa, 33.6 (16.0–80.8) kPa, 3.0 (1.4–15.6) kPa; in the control group – 24.4 (17.9–32.4) kPa, 29.8 (21.6–40.8) kPa, 2.3 (1.3–6.1) kPa, respectively (P < 0.05 for all comparison with subgroup В and the control group). The Emean cut-off value for adenomyosis diagnosis was 34.6 kPa. The sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) were 89.7%, 92.9%, 97.2%, 76.5% and 0.908. The Emax cut-off value was 45.4 kPa (89.7%, 92.9%, 97.2%, 76.5% and 0.907, respectively). Conclusion This study showed a significant increase of the myometrial stiffness estimated with shear wave elastography use in patients with adenomyosis. PMID:27847535

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

PubMed

Frejo, L; Martin-Sanz, E; Teggi, R; Trinidad, G; Soto-Varela, A; Santos-Perez, S; Manrique, R; Perez, N; Aran, I; Almeida-Branco, M S; Batuecas-Caletrio, A; Fraile, J; Espinosa-Sanchez, J M; Perez-Guillen, V; Perez-Garrigues, H; Oliva-Dominguez, M; Aleman, O; Benitez, J; Perez, P; Lopez-Escamez, J A

2017-12-01

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials. © 2017 John Wiley & Sons Ltd.

On the chemical composition of L-chondrites

NASA Technical Reports Server (NTRS)

Neal, C. W.; Dodd, R. T.; Jarosewich, E.; Lipschutz, M. E.

1980-01-01

Radiochemical neutron activation analysis of Ag, As, Au, Bi, Co, Cs, Ga, In, Rb, Sb, Te, Tl, and Zn and major element data in 14 L4-6 and 3 LL5 chondrites indicates that the L group is unusually variable and may represent at least 2 subgroups differing in formation history. Chemical trends in the S/Fe rich subgroup support textural evidence indicating late loss of a shock formed Fe-Ni-S melt; the S/Fe poor subgroup seemingly reflects nebular fractionation only. Highly mobile In and Zn apparently reflect shock induced loss from L chondrites. However, contrasting chemical trends in several L chondrite sample sets indicate that these meteorites constitute a more irregular sampling of, or more heterogeneous parent material than do carbonaceous or enstatite chondrites. Data for 15 chondrites suggest higher formation temperatures and/or degrees of shock than for LL5 chondrites.

Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.

PubMed

Swisher, Elizabeth M; Lin, Kevin K; Oza, Amit M; Scott, Clare L; Giordano, Heidi; Sun, James; Konecny, Gottfried E; Coleman, Robert L; Tinker, Anna V; O'Malley, David M; Kristeleit, Rebecca S; Ma, Ling; Bell-McGuinn, Katherine M; Brenton, James D; Cragun, Janiel M; Oaknin, Ana; Ray-Coquard, Isabelle; Harrell, Maria I; Mann, Elaina; Kaufmann, Scott H; Floquet, Anne; Leary, Alexandra; Harding, Thomas C; Goble, Sandra; Maloney, Lara; Isaacson, Jeff; Allen, Andrew R; Rolfe, Lindsey; Yelensky, Roman; Raponi, Mitch; McNeish, Iain A

2017-01-01

Poly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor. ARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing. 256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p<0·0001) and LOH high (0·62, 0·42-0·90, p=0·011) subgroups compared with the LOH low subgroup. The most common grade 3 or worse treatment-emergent adverse events were anaemia or decreased haemoglobin (45 [22%] patients), and elevations in alanine aminotransferase or aspartate aminotransferase (25 [12%]). Common serious adverse events included small intestinal obstruction (10 [5%] of 204 patients), malignant neoplasm progression (10 [5%]), and anaemia (nine [4%]). Three patients died during the study (two because of disease progression and one because of sepsis and disease progression). No treatment-related deaths occurred. In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas. Our results suggest that assessment of tumour LOH can be used to identify patients with BRCA wild-type platinum-sensitive ovarian cancers who might benefit from rucaparib. These results extend the potential usefulness of PARP inhibitors in the treatment setting beyond BRCA mutant tumours. Clovis Oncology, US Department of Defense Ovarian Cancer Research Program, Stand Up To Cancer-Ovarian Cancer Research Fund Alliance-National Ovarian Cancer Coalition Dream Team Translational Research Grant, and V Foundation Translational Award. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prognostic value of LGR5 in colorectal cancer: a meta-analysis.

PubMed

Chen, Qing; Zhang, Xin; Li, Wei-Min; Ji, Yu-Qiang; Cao, Hao-Zhe; Zheng, Pengsheng

2014-01-01

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) has recently been reported to be a marker of cancer stem cells (CSCs) in colorectal cancer (CRC), and the prognostic value of LGR5 in CRC has been evaluated in several studies. However, the conclusions remain controversial. In this study, we aimed to evaluate the association between the expression of LGR5 and the outcome of CRC patients by performing a meta-analysis. We systematically searched for relevant studies published up to February 2014 using the PubMed, Web of Science, EMBASE and Wangfang databases. Only articles in which LGR5 expression was detected by immunohistochemistry were included. A meta-analysis was performed using STATA 12.0, and pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate the strength of the association between LGR5 expression and the prognosis of CRC patients. A total of 7 studies comprising 1833 CRC patients met the inclusion criteria, including 6 studies comprising 1781 patients for overall survival (OS) and 3 studies comprising 528 patients for disease-free survival (DFS). Our results showed that high LGR5 expression was significantly associated with poor prognosis in terms of OS (HR: 1.87, 95% CI: 1.23-2.84; P = 0.003) and DFS (HR: 2.44, 95% CI: 1.49-3.98; P<0.001). Further subgroup analysis revealed that many factors, including the study region, number of patients, follow-up duration and cutoff value, affected the significance of the association between LGR5 expression and a worse prognosis in patients with CRC. In addition, there was no evidence of publication bias, as suggested by Begg's and Egger's tests. The present meta-analysis indicated that high LGR5 expression was associated with poor prognosis in patients with CRC and that LGR5 is an efficient prognostic factor in CRC.

G-protein coupled receptor expression patterns delineate medulloblastoma subgroups

PubMed Central

2013-01-01

Background Medulloblastoma is the most common malignant brain tumor in children. Genetic profiling has identified four principle tumor subgroups; each subgroup is characterized by different initiating mutations, genetic and clinical profiles, and prognoses. The two most well-defined subgroups are caused by overactive signaling in the WNT and SHH mitogenic pathways; less is understood about Groups 3 and 4 medulloblastoma. Identification of tumor subgroup using molecular classification is set to become an important component of medulloblastoma diagnosis and staging, and will likely guide therapeutic options. However, thus far, few druggable targets have emerged. G-protein coupled receptors (GPCRs) possess characteristics that make them ideal targets for molecular imaging and therapeutics; drugs targeting GPCRs account for 30-40% of all current pharmaceuticals. While expression patterns of many proteins in human medulloblastoma subgroups have been discerned, the expression pattern of GPCRs in medulloblastoma has not been investigated. We hypothesized that analysis of GPCR expression would identify clear subsets of medulloblastoma and suggest distinct GPCRs that might serve as molecular targets for both imaging and therapy. Results Our study found that medulloblastoma tumors fall into distinct clusters based solely on GPCR expression patterns. Normal cerebellum clustered separately from the tumor samples. Further, two of the tumor clusters correspond with high fidelity to the WNT and SHH subgroups of medulloblastoma. Distinct over-expressed GPCRs emerge; for example, LGR5 and GPR64 are significantly and uniquely over-expressed in the WNT subgroup of tumors, while PTGER4 is over-expressed in the SHH subgroup. Uniquely under-expressed GPCRs were also observed. Our key findings were independently validated using a large international dataset. Conclusions Our results identify GPCRs with potential to act as imaging and therapeutic targets. Elucidating tumorigenic pathways is a secondary benefit to identifying differential GPCR expression patterns in medulloblastoma tumors. PMID:24252460

Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells

DTIC Science & Technology

2013-04-01

0240 TITLE: Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells PRINCIPAL INVESTIGATOR: Donna M...TITLE AND SUBTITLE I Identification of Epigenetic Changes in Prostate Cancer using 5a. CONTRACT NUMBER Induced Pluripotent Stem Cells ... stem cells (iPSCs). Comparison of gene and protein expression of these prostatic iPSCs and embryonic stem cells (ESCs) revealed similarities but

Longitudinal Examination of Symptom Profiles among Breast Cancer Survivors

PubMed Central

Avis, Nancy E.; Levine, Beverly; Marshall, Sarah A.; Ip, Edward H.

2017-01-01

Context Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. Objectives To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Methods Secondary analyses of data from 653 breast cancer survivors recruited within 8 months of diagnosis who completed questionnaires at five timepoints. Hidden Markov modeling was used to: 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer, and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to: 3) identify patient characteristics related to subgroup membership, and 4) evaluate the relationship between symptom subgroup and QOL. Results A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological; and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Conclusion Cancer survivors can be differentiated by their symptom profiles. PMID:28042076

Identification of Candidate Genes Responsible for Stem Pith Production Using Expression Analysis in Solid-Stemmed Wheat.

PubMed

Oiestad, A J; Martin, J M; Cook, J; Varella, A C; Giroux, M J

2017-07-01

The wheat stem sawfly (WSS) is an economically important pest of wheat in the Northern Great Plains. The primary means of WSS control is resistance associated with the single quantitative trait locus (QTL) , which controls most stem solidness variation. The goal of this study was to identify stem solidness candidate genes via RNA-seq. This study made use of 28 single nucleotide polymorphism (SNP) makers derived from expressed sequence tags (ESTs) linked to contained within a 5.13 cM region. Allele specific expression of EST markers was examined in stem tissue for solid and hollow-stemmed pairs of two spring wheat near isogenic lines (NILs) differing for the QTL. Of the 28 ESTs, 13 were located within annotated genes and 10 had detectable stem expression. Annotated genes corresponding to four of the ESTs were differentially expressed between solid and hollow-stemmed NILs and represent possible stem solidness gene candidates. Further examination of the 5.13 cM region containing the 28 EST markers identified 260 annotated genes. Twenty of the 260 linked genes were up-regulated in hollow NIL stems, while only seven genes were up-regulated in solid NIL stems. An -methyltransferase within the region of interest was identified as a candidate based on differential expression between solid and hollow-stemmed NILs and putative function. Further study of these candidate genes may lead to the identification of the gene(s) controlling stem solidness and an increased ability to select for wheat stem solidness and manage WSS. Copyright © 2017 Crop Science Society of America.

NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.

PubMed

Narayan, Satya; Jaiswal, Aruna S; Sharma, Ritika; Nawab, Akbar; Duckworth, Lizette Vila; Law, Brian K; Zajac-Kaye, Maria; George, Thomas J; Sharma, Jay; Sharma, Arun K; Hromas, Robert A

2017-08-22

The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents. In the present study, we have identified a novel orphan molecule NSC30049 (NSC49L) that is effective alone, and in combination potentiates 5-FU-mediated growth inhibition of CRC heterogeneous bulk and FOLFOX-resistant cell lines in culture with minimal effect on normal colonic epithelial cells. It also inhibits the sphere forming activity of CRC stem cells, and decreases the expression levels of mRNAs of CRC stem cell marker genes. Results showed that NSC49L induces 5-FU-mediated S-phase cell cycle arrest due to increased load of DNA damage and increased γ-H2AX staining as a mechanism of cytotoxicity. The pharmacokinetic analysis showed a higher bioavailability of this compound, however, with a short plasma half-life. The drug is highly tolerated by animals with no pathological aberrations. Furthermore, NSC49L showed very potent activity in a HDTX model of CRC stem cell tumors either alone or in combination with 5-FU. Thus, NSC49L as a single agent or combined with 5-FU can be developed as a therapeutic agent by targeting the Chk1 pathway in 5-FU-resistant CRC heterogeneous bulk and CRC stem cell populations.

Pigmentation Is Associated with Stemness Hierarchy of Progenitor Cells Within Cultured Limbal Epithelial Cells.

PubMed

Liu, Lei; Nielsen, Frederik Mølgaard; Emmersen, Jeppe; Bath, Chris; Hjortdal, Jesper Østergaard; Riis, Simone; Fink, Trine; Pennisi, Cristian Pablo; Zachar, Vladimir

2018-05-20

Ex-vivo cultured human limbal epithelial stem/progenitor cells (hLESCs) are the main source for regenerative therapy of limbal stem cell deficiency (LSCD), which is worldwide one of the major causes of corneal blindness. Despite many stemness-associated markers have been identified within the limbal niche, the phenotype of the earliest hLESCs has not been hitherto identified. We sought to confirm or refute the use of tumor protein p63 (p63) and ATP binding cassette subfamily B member 5 (ABCB5) as surrogate markers for hLESCs early within the limbal differentiation hierarchy. Based on a robust fluorescence-activated cell sorting (FACS) and subsequent RNA isolation protocol, a comprehensive transcriptomic profile was obtained from four subpopulations of cultured hLESCs. The subpopulations were defined by co-expression of two putative stem/progenitor markers, the p63 and ABCB5, and the corneal differentiation marker cytokeratin 3 (CK3). A comparative transcriptomic analysis yielded novel data that indicated association between pigmentation and differentiation, with the p63 positive populations being the most pigmented and immature of the progenitors. In contrast, ABCB5, either alone or in co-expression patterns, identified more committed progenitor cells with less pigmentation. In conclusion, p63 is superior to ABCB5 as a marker for stemness. This article is protected by copyright. All rights reserved. © 2018 AlphaMed Press.

Colon Transit Time Test in Korean Children with Chronic Functional Constipation

PubMed Central

Yoo, Ha Yeong; Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung

2016-01-01

Purpose Each ethnic group has a unique life style, including diets. Life style affects bowel movement. The aim of this study is to describe the results of colon transit time (CTT) tests in Korean children who had chronic functional constipation based on highly refined data. Methods One hundred ninety (86 males) out of 415 children who performed a CTT test under the diagnosis of chronic constipation according to Rome III criteria at Konkuk University Medical Center from January 2006 through March 2015 were enrolled in this study. Two hundreds twenty-five children were excluded on the basis of CTT test result, defecation diary, and clinical setting. Shapiro-Wilk and Mann-Whitney U, and chi-square tests were used for statistical analysis. Results The median value and interquartile range (IQR) of CTT was 54 (37.5) hours in Encopresis group, and those in non-encopresis group was 40.2 (27.9) hours (p<0.001). The frequency of subtype between non-encopresis group and encopresis was statistically significant (p=0.002). The non-encopresis group (n=154, 81.1%) was divided into normal transit subgroup (n=84, 54.5%; median value and IQR of CTT=26.4 [9.6] hours), outlet obstruction subgroup (n=18, 11.7%; 62.4 [15.6] hours), and slow transit subgroup (n=52, 33.8%; 54.6 [21.0] hours]. The encopresis group (n=36, 18.9%) was divided into normal transit subgroup (n=8, 22.2%; median value and IQR of CTT=32.4 [9.9] hours), outlet obstruction subgroup (n=8, 22.2%; 67.8 [34.8] hours), and slow transit subgroup (n=20, 55.6%; 59.4 [62.7]hours). Conclusion This study provided the basic pattern and value of the CTT test in Korean children with chronic constipation. PMID:27064388

Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas

DTIC Science & Technology

2015-07-01

AWARD NUMBER: W81XWH-14-1-0115 TITLE: Cell of Origin and Cancer Stem Cell Phenotype in Medulloblastomas PRINCIPAL INVESTIGATOR: Kyuson Yun...YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE July 2015 2. REPORT TYPE Annual 3. DATES COVERED 1 Jul 2014 - 30 Jun 2015 4. TITLE AND SUBTITLE Cell ...of Origin and Cancer Stem Cell Phenotype in Medulloblastomas 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0115 5c. PROGRAM ELEMENT NUMBER 6

Effects of Postconditioning on Skeletal Muscle Injury and Apoptosis Induced by Partial Ischemia and Reperfusion in Rats.

PubMed

Lintz, José Alves; Dalio, Marcelo Bellini; Tirapelli, Luiz Fernando; Ribeiro, Maurício Serra; Joviliano, Edwaldo Edner; Piccinato, Carlos Eli

2017-04-01

Analyze the effects of ischemic postconditioning on skeletal muscle injury and apoptosis produced by partial ischemia and reperfusion in rats. An experimental study was designed using 70 Wistar rats divided in 3 groups: Sham; Control-submitted to ischemia and reperfusion; and Postconditioning-submitted to ischemia and reperfusion with ischemic postconditioning. Subgroups (n = 10) were divided by duration of ischemia (4, 5, or 6 hr). A partial ischemia model using aortic clamping was used. The postconditioning protocol consisted of 3 cycles of clamping the aorta for 1 min and releasing for another minute. Skeletal muscle injury was evaluated by measuring serum levels of releasing cytoplasmic enzymes: aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and total creatine phosphokinase (CPK). Lipid peroxidation was evaluated by muscular levels of malondialdehyde (MDA). Energetic cell storage was evaluated by muscular glycogen levels. Apoptosis was evaluated analyzing the expression of caspase 3 and protein B-cell lymphoma 2 (Bcl-2) by immunohistochemistry. AST levels in Sham group were 109.80 units/L, in Control subgroups were 4h 200.60 units/L/5h 392.30 units/L/6h 118.82 units/L, whereas in Postconditioning subgroups were: 4h 316.10 units/L/5h 268.40 units/L/6h 267.00 units/L. There was a 2-3-fold increase in Control and Postconditioning groups compared with Sham group (P = 0.003) There was no difference between groups with the same ischemic injury time. LDH, CPK, and MDA levels were similar in Sham, Control, and Postconditioning groups. Subgroups with the same ischemic injury time were also similar. Glycogen levels in Sham group were 0.629 mg%, in Control subgroups were 4h 0.323 mg%/5h 0.348 mg%/6h 0.183 mg%, whereas in Postconditioning subgroups were: 4h 0.443 mg%/5h 0.270 mg%/6h 0.324 mg%. Control and Postconditioning groups were decreased by half in relation with the Sham group (P = 0.002), with no difference between groups with the same ischemic injury time. For both caspase 3 and Bcl-2, the percentage of positive cells increased more than 2-fold in Control and Postconditioning groups when compared with Sham group (P < 0.001). The greater the ischemic injury time, the greater was the percent of positive cells (P < 0.0005), with no difference between subgroups with the same ischemic injury time. Ischemic postconditioning had neither protective effect on skeletal muscle injury nor avoided apoptosis induction in rats submitted to partial ischemia and reperfusion. Copyright © 2017 Elsevier Inc. All rights reserved.

[Effects of n-hexane exposure on human serum myelin basic proteins].

PubMed

Zhou, Wei; Yi, Juan; Huang, Hui-Ping; Xiang, Ying-Ping; He, Jia-Xi; Liu, Qing-Jun; Huang, Xian-Qing

2011-06-01

To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure.

Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.

PubMed

Tabernero, Josep; Van Cutsem, Eric; Lakomý, Radek; Prausová, Jana; Ruff, Paul; van Hazel, Guy A; Moiseyenko, Vladimir M; Ferry, David R; McKendrick, Joseph J; Soussan-Lazard, Karen; Chevalier, Soazig; Allegra, Carmen J

2014-01-01

The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome.

PubMed

Sökeland, J

2000-09-01

To test the hypothesis that in patients with benign prostatic hyperplasia (BPH), the outcome of drug therapy with finasteride may be predictable from the baseline prostate volume and that positive clinical effects might be expected only in patients with prostate volumes of > 40 mL, using a subgroup analysis of results from a previously reported clinical trial of finasteride and phytotherapy. A subgroup of 431 patients was analysed from a randomized, multicentre, double-blind clinical trial involving 543 patients with the early stages of BPH. Patients received a fixed combination of extracts of saw palmetto fruit (Serenoa repens) and nettle root (Urtica dioica) (PRO 160/120) or the synthetic 5alpha-reductase inhibitor finasteride. The patients assessed had valid ultrasonographic measurements and baseline prostate volumes of either 40 mL. All 516 patients were included in the safety analysis. The results of the original trial showed equivalent efficacy for both treatments. The mean (SD) maximum urinary flow (the main outcome variable) increased (from baseline values) after 24 weeks by 1.9 (5.6) mL/s with PRO 160/120 and by 2.4 (6.3) mL/s with finasteride. There were no statistically significant group differences (P = 0.52). The subgroups with small prostates ( 40 mL were similar, at 2.3 (6.1) and 2. 2 (5.3) mL/s, respectively. There were improvements in the International Prostate Symptom Score in both treatment groups, with no statistically significant differences. The subgroup analysis showed slightly better results for voiding symptoms in the patients with prostates of > 40 mL, but there were also improvements in the subgroup with smaller prostates. The safety analysis showed that more patients in the finasteride group reported adverse events and also there were more adverse events in this group than in patients treated with PRO 160/120. The present analysis showed that the efficacy of both PRO 160/120 and finasteride was equivalent and unrelated to prostate volume. However, PRO 160/120 had better tolerability than finasteride.

The influence of storage time and pH variation on water sorption by different composite resins.

PubMed

Gusmão, George Mário de Araújo Silva; De Queiroz, Thiago Vinicius Veras; Pompeu, Guilherme Ferrer; Menezes Filho, Paulo Fonseca; da Silva, Cláudio Heliomar Vicente

2013-01-01

The objective of this work was to assess the influence of storage time and pH cycling on water sorption by different composite resins. Nine resin brands were selected and divided into groups: G1-ROK (SDI), G2-ICE (SDI), G3-GLACIER (SDI), G4-Z350 (3M/ESPE), G5-Z250 (3M/ESPE), G6-TPH 3 (DENTSPLY), G7-ESTHET X (DENTSPLY), G8-SUPRAFILL (SSWHITE), and G9-MASTERFILL (BIODINΒMICS). Ninety specimens, ten per group, were obtained using an aluminum matrix. Specimens measured 10 mm diameter × 2 mm width. The groups were divided into subgroups according to the immersion solution: A - control (n = 05) stored in artificial saliva pH = 7.0 and B-test (n = 05) submitted to seven consecutive days of pH cycling (cariogenic challenger) that consisted of immersion in a pH° = 4.3 solution for 6 h followed by immersion in a pH¹ =7.0 solution for 18 h and stored in artificial saliva pH = 7.0 until the end of the experiment. The specimens were weighed on six occasions: T 0 (after fabrication), T 1 (24 h), T 2 (7 days), T 3 (15 days), T 4 (30 days), T 5 (60 days), and then analyzed. The water sorption was determined by the weight difference between the specimens at the time intervals. The mean weight gain was exactly the same for both the subgroups within group G4. The highest means for the control subgroup were found in groups: G1, G5, G7, G8, and G9. For the pH cycling subgroup, the highest means were found in G2, G3, and G6; however, significant differences between the subgroups compared to the mean-weight gain were found for G1, G5, and G7. The water sorption of composite resins is dependent upon their storage time. The pH cycling created a significant impact on resins G1, G5, and G7. The sorption and solubility of composite resins vary according to their chemical composition.

Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

PubMed

Wang, P-H; Ko, J-L

2006-01-01

The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

Effect of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of certain plasma enzymes in CCl4-induced liver injury in low-protein fed rats.

PubMed

Nkosi, C Z; Opoku, A R; Terblanche, S E

2005-04-01

The effects of pumpkin seed (Cucurbita pepo) protein isolate on the activity levels of lactate dehydrogenase (LD), alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) against carbon tetrachloride (CCl4)-induced acute liver injury in low-protein fed rats were investigated. A group of male Sprague-Dawley rats maintained on a low-protein diet for 5 days were divided into three subgroups. Two subgroups were injected with carbon tetrachloride and the other group with an equivalent amount of olive oil. Two hours after CCl4 intoxication one of the two subgroups was administered with pumpkin seed protein isolate. All three subgroups of rats were maintained on the low-protein diet for the duration of the investigation. Groups of rats from the different subgroups were killed at 24, 48 and 72 h after their respective treatments. After 5 days on the low-protein diet the activity levels of all four enzymes were significantly higher than their counterparts on a normal balanced diet. CCl4 intoxication resulted in significant increases in the activity levels of all four enzymes investigated. The administration of pumpkin seed protein isolate after CCl4 intoxication resulted in significantly reduced activity levels of all four enzymes. It is concluded that pumpkin seed protein isolate administration was effective in alleviating the detrimental effects associated with protein malnutrition. (c) 2005 John Wiley & Sons, Ltd.

Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue

PubMed Central

Yee, Karen K.; Li, Yan; Redding, Kevin M.; Iwatsuki, Ken; Margolskee, Robert F.; Jiang, Peihua

2013-01-01

Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knock-in allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of circumvallate and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue. PMID:23377989

Lgr5-EGFP marks taste bud stem/progenitor cells in posterior tongue.

PubMed

Yee, Karen K; Li, Yan; Redding, Kevin M; Iwatsuki, Ken; Margolskee, Robert F; Jiang, Peihua

2013-05-01

Until recently, reliable markers for adult stem cells have been lacking for many regenerative mammalian tissues. Lgr5 (leucine-rich repeat-containing G-protein-coupled receptor 5) has been identified as a marker for adult stem cells in intestine, stomach, and hair follicle; Lgr5-expressing cells give rise to all types of cells in these tissues. Taste epithelium also regenerates constantly, yet the identity of adult taste stem cells remains elusive. In this study, we found that Lgr5 is strongly expressed in cells at the bottom of trench areas at the base of circumvallate (CV) and foliate taste papillae and weakly expressed in the basal area of taste buds and that Lgr5-expressing cells in posterior tongue are a subset of K14-positive epithelial cells. Lineage-tracing experiments using an inducible Cre knockin allele in combination with Rosa26-LacZ and Rosa26-tdTomato reporter strains showed that Lgr5-expressing cells gave rise to taste cells, perigemmal cells, along with self-renewing cells at the bottom of trench areas at the base of CV and foliate papillae. Moreover, using subtype-specific taste markers, we found that Lgr5-expressing cell progeny include all three major types of adult taste cells. Our results indicate that Lgr5 may mark adult taste stem or progenitor cells in the posterior portion of the tongue. Copyright © 2013 AlphaMed Press.

Preoperative digital planning versus postoperative outcomes in total hip arthroplasty using a calcar-guided short stem: frequent valgization can be avoided.

PubMed

Kutzner, Karl Philipp; Pfeil, Joachim; Kovacevic, Mark Predrag

2017-07-01

Modern total hip arthroplasty is largely dependent on the successful preservation of hip geometry. Thus, a successful implementation of the preoperative planning is of great importance. The present study evaluates the accuracy of anatomic hip reconstruction predicted by 2D digital planning using a calcar-guided short stem of the newest generation. A calcar-guided short stem was implanted in 109 patients in combination with a cementless cup using the modified anterolateral approach. Preoperative digital planning was performed including implant size, caput-collum-diaphyseal angle, offset, and leg length using mediCAD II software. A coordinate system and individual scale factors were implemented. Postoperative outcome was evaluated accordingly and was compared to the planning. Intraoperatively used stem sizes were within one unit of the planned stem sizes. The postoperative stem alignment showed a minor and insignificant (p = 0.159) mean valgization of 0.5° (SD 3.79°) compared to the planned caput-collum-diaphyseal angles. Compared to the planning, mean femoral offset gained 2.18 (SD 4.24) mm, while acetabular offset was reduced by 0.78 (SD 4.36) mm during implantation resulting in an increased global offset of 1.40 (SD 5.51) mm (p = 0.0094). Postoperative femoroacetabular height increased by a mean of 5.00 (SD 5.98) mm (p < 0.0001) compared to preoperative measures. Two-dimensional digital preoperative planning in calcar-guided short-stem total hip arthroplasty assures a satisfying implementation of the intended anatomy. Valgization, which has been frequently observed in previous short-stem designs, negatively affecting offset, can be avoided. However, surgeons have to be aware of a possible leg lengthening.

Northeast Tennessee Educators' Perception of STEM Education Implementation

NASA Astrophysics Data System (ADS)

Turner, Kristin Beard

A quantitative nonexperimental survey study was developed to investigate Northeast Tennessee K-8 educators' perceptions of STEM education. This study was an examination of current perceptions of STEM education. Perceived need, current implementation practices, access to STEM resources, definition of STEM, and the current condition of STEM in Northeast Tennessee were also examined. The participating school districts are located in the Northeast Region of Tennessee: Bristol City Schools, Hamblen County Schools, Johnson City Schools, Johnson County Schools, Kingsport City Schools, Sullivan County Schools, and Washington County Schools. Educational professionals including both administrators and teachers in the elementary and/or middle school setting were surveyed. The closed and open form survey consisted of 20 research items grouped by 5 core research questions. Quantitative data were analyzed using single sample t tests. A 4 point Likert scale was used to measure responses with a 2.5 point of neutrality rating. The open-ended question was summarized and recorded for frequency. Research indicated that Northeast Tennessee K-8 educators perceive a need for STEM education to a significant extent. However, many do not feel prepared for implementation. Lack of professional development opportunities and STEM assets were reported as areas of need. Teachers reported implementation of inquiry-based, problem solving activities in their classrooms. The majority of participants reported that the current condition of STEM education in Northeast Tennessee is not meeting the needs of 21st century learners. Challenges facing STEM instruction include: funding designated for STEM is too low, professional development for STEM teacher is insufficient, and STEM Education in K-8 is lacking or inadequate.

Agreement Between Deoxyribonucleic Acid Base Composition and Taxometric Classification of Gram-Positive Cocci1

PubMed Central

Silvestri, L. G.; Hill, L. R.

1965-01-01

Silvestri, L. G. (Università Statale, Milan, Italy), and L. R. Hill. Agreement between deoxyribonucleic acid base composition and taxometric classification of gram-positive cocci. J. Bacteriol. 90:136–140. 1965.—It had been previously proposed, from taxometric analyses, that gram-positive, catalase-positive cocci be divided into two subgroups. Thirteen strains, representative of both subgroups, were examined for deoxyribonucleic acid (DNA) base composition, determined from melting temperatures. Per cent GC (guanine + cytosine/total bases) values fell into two groups: 30.8 to 36.5% GC and 69 to 75% GC. Strains with low per cent GC values belonged to the Staphylococcus aureus–S. saprophyticus–S. lactis taxometric subgroups, and those with high per cent GC values belonged to the S. roseus–S. afermentans subgroup. The hypothetical nature of any classification is emphasized, and, in the present work, the hypothesis derived from taxometric analyses of division into two subgroups is confirmed by the study of DNA base ratios. The two subgroups correspond, respectively, to the genera Staphylococcus and Micrococcus. PMID:16562008

Dissection and staining of Drosophila larval ovaries.

PubMed

Maimon, Iris; Gilboa, Lilach

2011-05-13

Many organs depend on stem cells for their development during embryogenesis and for maintenance or repair during adult life. Understanding how stem cells form, and how they interact with their environment is therefore crucial for understanding development, homeostasis and disease. The ovary of the fruit fly Drosophila melanogaster has served as an influential model for the interaction of germ line stem cells (GSCs) with their somatic support cells (niche) (1, 2). The known location of the niche and the GSCs, coupled to the ability to genetically manipulate them, has allowed researchers to elucidate a variety of interactions between stem cells and their niches (3-12). Despite the wealth of information about mechanisms controlling GSC maintenance and differentiation, relatively little is known about how GSCs and their somatic niches form during development. About 18 somatic niches, whose cellular components include terminal filament and cap cells (Figure 1), form during the third larval instar (13-17). GSCs originate from primordial germ cells (PGCs). PGCs proliferate at early larval stages, but following the formation of the niche a subgroup of PGCs becomes GSCs (7, 16, 18, 19). Together, the somatic niche cells and the GSCs make a functional unit that produces eggs throughout the lifetime of the organism. Many questions regarding the formation of the GSC unit remain unanswered. Processes such as coordination between precursor cells for niches and stem cell precursors, or the generation of asymmetry within PGCs as they become GSCs, can best be studied in the larva. However, a methodical study of larval ovary development is physically challenging. First, larval ovaries are small. Even at late larval stages they are only 100μm across. In addition, the ovaries are transparent and are embedded in a white fat body. Here we describe a step-by-step protocol for isolating ovaries from late third instar (LL3) Drosophila larvae, followed by staining with fluorescent antibodies. We offer some technical solutions to problems such as locating the ovaries, staining and washing tissues that do not sink, and making sure that antibodies penetrate into the tissue. This protocol can be applied to earlier larval stages and to larval testes as well.

Moderate clinical improvement after revision arthroplasty of the severely stiff knee.

PubMed

Heesterbeek, P J C; Goosen, J H M; Schimmel, J J P; Defoort, K C; van Hellemondt, G G; Wymenga, A B

2016-10-01

Revision of the severe stiff total knee arthroplasty (TKA) is challenging, and clinical outcome is inferior to other indications for revision. The purpose of the present study was to determine clinical outcome of TKA revision in patients with severe stiffness (range of motion (ROM) ≤ 70°) and evaluate a possible influence of accompanying findings, such as component malposition, aseptic loosening or instability. A prospective cohort of 40 patients with a preoperative ROM ≤ 70° and a minimum of 2-year follow-up after total system revision (Genesis or Legion stemmed condylar implant) was evaluated. ROM, Knee Society Scoring System (KSS) and visual analogue scale (VAS) pain scores were obtained preoperatively and at 2 years. Patient satisfaction and complication rate were assessed. Component malposition was most frequently reported as accompanying finding (n = 27). Comparisons between pre- and postoperative outcome (p < 0.05) and between different subgroups (component malposition, aseptic loosening, and instability) based on accompanying findings were made (no statistical comparison). ROM, KSS and VAS pain scores improved significantly (p < 0.001): median ROM at two years 85° (range 10-125) and median gain 25° (range -10 to +85). Median VAS satisfaction was 53.5 points (range 15-98). Seventeen patients reported at least one complication, including one re-revision. Six patients underwent manipulation under anaesthesia, and five were referred to the pain clinic. No clear differences between subgroups were observed. TKA revision in patients with severe stiffness resulted in a moderate but significant improved clinical outcome after 2 years. Accompanying abnormalities such as component malposition, aseptic loosening or instability did not influence clinical outcome. Realistic patient counselling on the moderate outcome and possible remaining limitations in daily life might help to improve patient satisfaction. Therapeutic studies-case series with no comparison group, Level IV.

An Effective Model of Developing Teacher Leaders in STEM Education

ERIC Educational Resources Information Center

Sublette, Heidi

2013-01-01

In the last 5 years, industries have begun to recognize a growing gap in the production of college graduates in areas of STEM. Researchers in various industries believe this gap will create a significant loss of competitive edge in the STEM fields, which will leave the United States pursuing STEM graduates from foreign countries and may ultimately…

The NSL chromatin-modifying complex subunit KANSL2 regulates cancer stem-like properties in glioblastoma that contribute to tumorigenesis

PubMed Central

Ferreyra-Solari, Nazarena; Belforte, Fiorella S.; Canedo, Lucía; Videla-Richardson, Guillermo A.; Espinosa, Joaquín M.; Rossi, Mario; Serna, Eva; Riudavets, Miguel A.; Martinetto, Horacio; Sevlever, Gustavo; Perez-Castro, Carolina

2016-01-01

KANSL2 is an integral subunit of the Non-Specific Lethal (NSL) chromatin-modifying complex which contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. PMID:27406830

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer

PubMed Central

Deplanque, G.; Demarchi, M.; Hebbar, M.; Flynn, P.; Melichar, B.; Atkins, J.; Nowara, E.; Moyé, L.; Piquemal, D.; Ritter, D.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Hammel, P.

2015-01-01

Background Masitinib is a selective oral tyrosine–kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). Patients and methods Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m2) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. Results Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl–CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the ‘ACOX1’ subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the ‘pain’ subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. Conclusions The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. Trial Registration ClinicalTrials.gov:NCT00789633. PMID:25858497

The effect of a radial neck notch on press-fit stem stability: a biomechanical study on 7 cadavers.

PubMed

Shukla, Dave R; Sahu, Dipit C; Fitzsimmons, James S; An, Kai-Nan; O'Driscoll, Shawn W

2018-03-01

Minimal micromotion is necessary for osteointegration of cementless radial head prostheses. When radial head fractures extend longitudinally, where the neck cut for prosthetic replacement should be made is uncertain. We hypothesized that complete resection of the notched portion of a radial neck confers no advantage in initial stability compared with not resecting the defect and inserting the implant into a notched radial neck. The radii of 7 cadavers underwent radial head resection and implantation with a 25-mm-long press-fit radial head stem. Before implantation, a 5-mm-long notch that was less than 1-mm wide was made in the radial neck. After the stem-bone micromotion was recorded, the proximal 5 mm of radial neck, incorporating the entire notch, was cut away, the stem was inserted 5 mm further, and the resulting micromotion was recorded. The mean micromotion measured in the presence of a cortical notch was 51 ± 6 µm. After the neck was circumferentially cut and the stem was advanced, the micromotion (46 ± 9 µm) was not statistically significantly different. Initial stability of an adequately sized cementless stem in the presence of a 5-mm-long cortical notch was well within the threshold needed for bone ingrowth (<100 µm). In addition, there was no reduction of micromotion after the notch-containing portion of the radial neck was resected and the stem was advanced. Making a neck cut distal to a 5-mm-long, 1-mm-wide cortical notch does not confer added stability. Thus, surgeons can preserve bone stock and avoid an aggressive neck cut. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

PubMed

Kiss, István; Tibold, Antal; Halmosi, Róbert; Bartha, Eva; Koltai, Katalin; Orsós, Zsuzsanna; Bujdosó, László; Ember, István

2010-06-01

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

Characteristics of US Students That Pursued a STEM Major and Factors That Predicted Their Persistence in Degree Completion

ERIC Educational Resources Information Center

Mau, Wei-Cheng J.

2016-01-01

Low participation and completion rates in the science, technology, engineering, or mathematics (STEM) careers are a world-wide concern. This study tracked American college students over a 5-year period and identifies factors that lead to choosing a STEM major and in turn successfully earning a STEM degree. Characteristics of female and minority…

Targeting of Cancer Stem Cells and Their Microenvironment in Early-Stage MutantK-ras Lung Cancer

DTIC Science & Technology

2015-10-01

a combination of SHH/ALDH/ NOTCH3 as potential stem cell markers. We will also test the hypothesis that SHH+ cell population may be a quiescent stem...and SHH are expressed within the same cell population. We will also test NOTCH3 in combination with 5E1-647 alone or in combination with 5E1-647 and...Aldefluor assays. Anti- NOTCH3 antibody will be labeled with Alexa Fluor 594 (red color spectrum) in an analogous manner to 5E1-594. As ALDH+ and

An improved sensor for precision detection of in situ stem water content using a frequency domain fringing capacitor.

PubMed

Zhou, Haiyang; Sun, Yurui; Tyree, Melvin T; Sheng, Wenyi; Cheng, Qiang; Xue, Xuzhang; Schumann, Henrik; Schulze Lammers, Peter

2015-04-01

One role of stems is that of water storage. The water content of stems increases and decreases as xylem water potential increases and decreases, respectively. Hence, a nondestructive method to measure stem water content (StWC) = (volume of water) : (volume of stem), could be useful in monitoring the drought stress status of plants. We introduce a frequency domain inner fringing capacitor-sensor for measuring StWC which operates at 100 MHz frequency. The capacitor-sensor consists of two wave guides (5-mm-wide braided metal) that snugly fit around the surface of a stem with a spacing of 4-5 mm between guides. Laboratory measurements on analog stems reveals that the DC signal output responds linearly to the relative dielectric constant of the analog stem, is most sensitive to water content between the waveguides to a depth of c. 3 mm from the stem surface, and calibrations based on the gravimetric water loss of excised stems of plants revealed a resolution in StWC of < ± 0.001 v/ v. The sensor performed very well on whole plants with a 100-fold increased resolution compared with previous frequency domain and time domain reflectometry methods and, hence, may be very useful for future research requiring nondestructive measurements of whole plants. © European Union 2014. New Phytologist © 2014 New Phytologist Trust.

A Higher Proportion of the EGFR T790M Mutation May Contribute to the Better Survival of Patients with Exon 19 Deletions Compared with Those with L858R.

PubMed

Ke, E-E; Zhou, Qing; Zhang, Qiu-Yi; Su, Jian; Chen, Zhi-Hong; Zhang, Xu-Chao; Xu, Chong-Rui; Yang, Jin-Ji; Tu, Hai-Yan; Yan, Hong-Hong; Zhang, Yi-Chen; Niu, Fei-Yu; Wu, Yi-Long

2017-09-01

Increasing evidence has demonstrated that exon 19 deletions (Del19) and L858R mutation in EGFR have different prognostic and predictive roles in NSCLC. We aimed to investigate whether these two mutations produced differences in mechanisms of resistance to EGFR tyrosine kinase inhibitors. Consecutive patients with advanced EGFR-mutant NSCLC who acquired resistance to EGFR tyrosine kinase inhibitors and underwent postprogression biopsy were enrolled. Mechanisms including T790M mutation, mesenchymal-epithelial transition proto-oncogene (MET) amplification, and histological transformation, as well as KRAS, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA) mutation, and anaplastic lymphoma receptor tyrosine kinase gene (ALK) fusion, were analyzed. The prevalence of T790M mutation was significantly higher in the Del19 subgroup than that in L858R subgroup (50.4% versus 36.5%, p = 0.043). Apart from this, there was no difference in other mechanisms including MET amplification and histological transformation. The median overall survival (OS) of patients with T790M mutation was 36.0 months (95% confidence interval [CI]: 30.9-41.2), which was significantly longer than the 26.5 months (95% CI: 24.0-29.0) in MET-positive patients, 19.7 months (95% CI: 18.2-21.2) in patients with histological transformation, and 23.0 months (95% CI: 17.4-28.6) in the KRAS/PIK3CA/ALK-altered population (p = 0.021). The hazard ratios of the MET-amplification subgroup and subgroup with histological transformation were 1.809-fold and 2.370-fold higher than that in T790M-positive subgroup. The median OS times were months 33.3 (95% CI: 28.9-37.7) in the Del19 subgroup and 26.4 months (95% CI: 23.2-29.6) in the L858R subgroup (p = 0.028). However, in multivariable analysis adjusted for T790M genotype, the EGFR mutation subtype was no longer found to be significant. Significant OS benefit was observed in patients with T790M mutation, suggesting that a larger proportion of T790M mutation might contribute to the better survival of patients with Del19. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

PubMed

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

Flagellin preconditioning enhances the efficacy of mesenchymal stem cells in an irradiation-induced proctitis model.

PubMed

Linard, Christine; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Benderitter, Marc

2016-09-01

The success of mesenchymal stem cell transplantation for proctitis depends not only on cell donors but also on host microenvironmental factors, which play a major role in conditioning mesenchymal stem cell immunosuppressive action and repair. This study sought to determine if flagellin, a TLR5 ligand, can enhance the mesenchymal stem cell treatment efficacy in radiation-induced proctitis. With the use of a colorectal model of 27 Gy irradiation in rats, we investigated and compared the effects on immune capacity and remodeling at 28 d after irradiation of the following: 1) systemic mesenchymal stem cell (5 × 10(6)) administration at d 7 after irradiation, 2) administration of flagellin at d 3 and systemic mesenchymal stem cell administration at d 7, and 3) in vitro preconditioning of mesenchymal stem cells with flagellin, 24 h before their administration on d 7. The mucosal CD8(+) T cell population was normalized after treatment with flagellin-preconditioned mesenchymal stem cells or flagellin plus mesenchymal stem cells, whereas mesenchymal stem cells alone did not alter the radiation-induced elevation of CD8(+) T cell frequency. Mesenchymal stem cell treatment returned the irradiation-elevated frequency of CD25(+) cells in the mucosa-to-control levels, whereas both flagellin-preconditioned mesenchymal stem cell and flagellin-plus-mesenchymal stem cell treatment each significantly increased not only CD25(+) cell frequency but also forkhead box p3 and IL-2Rα expression. Specifically, IL-10 was overexpressed after flagellin-preconditioned mesenchymal stem cell treatment. Analysis of collagen expression showed that the collagen type 1/collagen type 3 ratio, an indicator of wound-healing maturation, was low in the irradiated and mesenchymal stem cell-treated groups and returned to the normal level only after the flagellin-preconditioned mesenchymal stem cell treatment. This was associated with a reduction in myofibroblast accumulation. In a proctitis model, flagellin-preconditioned mesenchymal stem cells improved colonic immune capacity and enhanced tissue remodeling. © Society for Leukocyte Biology.

Constipation incidence and impact in medical critical care patients: importance of the definition criterion.

PubMed

Prat, Dominique; Messika, Jonathan; Avenel, Alexandre; Jacobs, Frédéric; Fichet, Jérome; Lemeur, Matthieu; Ricard, Jean-Damien; Sztrymf, Benjamin

2016-03-01

Constipation incidence and impact remain controversial in the ICU. This may depend on the definition criterion used in the previous studies on the field. We aimed to determine the frequency and significance of constipation according to its definition criterion. This is a prospective observational study. Adult patients without a cause of transit time modification and laxative intake within the first 3 days were screened. Constipation was defined by a first stool passage occurring after 3 days of ICU stay. Thereafter, we identified two subgroups of patients: absence of stool passage more than 3 days but less than 6 days (3-day subgroup), and no stool passage for 6 days or more (6-day subgroup). Survival, length of stay and time spent under mechanical ventilation (MV) were compared according to constipation status. Among 189 included patients [age 60.8 (49.5-74.2) years, SAPS II 44 (34-53)], 98 (51.9%) exhibited constipation (3-day subgroup n=53, 6-day subgroup n=45). Constipated patients were more likely to receive MV, sedation, vasopressors, enteral nutrition and neuromuscular blocking agents. ICU length of stay and time spent under MV was longer in the 6-day subgroup but not in the 3-day subgroup of patients. With regard to outcomes, defining constipation by the absence of stool passage less than 6 days after ICU admission does not identify a specific subset of population. Further studies on the management of this condition should focus on these 'long-term' constipated patients.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction

PubMed Central

Keefe, Richard S E; Nomikos, George; Zhong, Wei; Christensen, Michael Cronquist; Jacobson, William

2018-01-01

Abstract Background We evaluated vortioxetine’s effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder. Methods This was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions–Severity of Illness). Results Greater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45–54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions–Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]). Conclusions Our findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups. Clinical Trial Registry clinicaltrials.gov: NCT01564862 PMID:29546401

Comparative analysis of the efficacy of astigmatic correction after wavefront-guided and wavefront-optimized LASIK in low and moderate myopic eyes

PubMed Central

Khalifa, Mounir A.; Alsahn, Mahmoud F.; Shaheen, Mohamed Shafik; Pinero, David P.

2017-01-01

AIM To evaluate and compare the efficacy of the astigmatic correction achieved with laser in situ keratomileusis (LASIK) in eyes with myopic astigmatism using wavefront-guided (WFG) and wavefront-optimized (WFO) ablation profiles. METHODS Prospective study included 221 eyes undergoing LASIK: 99 and 122 eyes with low and moderate myopic astigmatism (low and moderate myopia groups). Two subgroups were differentiated in each group according to the ablation profile: WFG subgroup, 109 eyes (45/64, low/moderate myopia groups) treated using the Advanced CustomVue platform (Abbott Medical Optics Inc.), and WFO subgroup, 112 eyes (54/58, low/moderate myopia groups) treated using the EX-500 platform (Alcon). Clinical outcomes were evaluated during a 6-month follow-up, including a vector analysis of astigmatic changes. RESULTS Significantly better postoperative uncorrected visual acuity and efficacy index was found in the WFG subgroups of each group (P≤0.041). Postoperative spherical equivalent and cylinder were significantly higher in WFO subgroups (P≤0.003). In moderate myopia group, a higher percentage of eyes with a postoperative cylinder ≤0.25 D was found in the WFG subgroup (90.6% vs 65.5%, P=0.002). In low and moderate myopia groups, the difference vector was significantly higher in the WFO subgroup compared to WFG (P<0.001). In moderate myopia group, the magnitude (P=0.008) and angle of error (P<0.001) were also significantly higher in the WFO subgroup. Significantly less induction of high order aberrations were found with WFG treatments in both low and moderate myopia groups (P≤0.006). CONCLUSION A more efficacious correction of myopic astigmatism providing a better visual outcome is achieved with WFG LASIK compared to WFO LASIK. PMID:28251090

Texture analysis of intermediate-advanced hepatocellular carcinoma: prognosis and patients' selection of transcatheter arterial chemoembolization and sorafenib

PubMed Central

Fu, Sirui; Chen, Shuting; Liang, Changhong; Liu, Zaiyi; Zhu, Yanjie; Li, Yong; Lu, Ligong

2017-01-01

Transcatheter arterial chemoembolization (TACE) and sorafenib combination treatment for unselected hepatocellular carcinoma (HCC) is controversial. We explored the potential of texture analysis for appropriate patient selection. There were 261 HCCs included (TACE group: n = 197; TACE plus sorafenib (TACE+Sorafenib) group n = 64). We applied a Gabor filter and wavelet transform with 3 band-width responses (filter 0, 1.0, and 1.5) to portal-phase computed tomography (CT) images of the TACE group. Twenty-one textural parameters per filter were extracted from the region of interests delineated around tumor outline. After testing survival correlations, the TACE group was subdivided according to parameter thresholds in receiver operating characteristic curves and compared to TACE+Sorafenib group survival. The Gabor-1-90 (filter 0) was most significantly correlated with TTP. The TACE group was accordingly divided into the TACE-1 (Gabor-1-90 ≤ 3.6190) and TACE-2 (Gabor-1-90 > 3.6190) subgroups; TTP was similar in the TACE-1 subgroup and TACE+Sorafenib group, but shorter in the TACE-2 subgroup. Only wavelet-3-D (filter 1.0) correlated with overall survival (OS), and was used for subgrouping. The TACE-5 (wavelet-3-D ≤ 12.2620) subgroup and the TACE+Sorafenib group showed similar OS, while the TACE-6 (wavelet-3-D > 12.2620) subgroup had shorter OS. Gabor-1-90 and wavelet-3-D were consistent. In dependent of tumor number or size, CT textural parameters are correlated with TTP and OS. Patients with lower Gabor-1-90 (filter 0) and wavelet-3-D (filter 1.0) should be treated with TACE and sorafenib. Texture analysis holds promise for appropriate selection of HCCs for this combination therapy. PMID:27911268

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder

PubMed Central

Josiassen, Richard C.; Kane, John M.; Liang, Grace S.; Burke, Joshua; O’Brien, Christopher F.

2017-01-01

Background The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. Methods The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. Results The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant. Conclusion Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder). PMID:28839341

Long-Term Safety and Tolerability of Valbenazine (NBI-98854) in Subjects with Tardive Dyskinesia and a Diagnosis of Schizophrenia or Mood Disorder.

PubMed

Josiassen, Richard C; Kane, John M; Liang, Grace S; Burke, Joshua; O'Brien, Christopher F

2017-08-01

The short-term safety profile of once-daily valbenazine (NBI-98854) has been evaluated in several double-blind, placebo-controlled (DBPC) trials in adults with tardive dyskinesia (TD) who had a diagnosis of schizophrenia/schizoaffective (SCHZ) disorder or mood disorder. Studies with longer treatment duration (up to 48 weeks) were conducted to evaluate the long-term safety of this novel drug in subjects with TD. The pooled long-term exposure (LTE) population included valbenazine-treated subjects from 3 studies: KINECT (NCT01688037: 6-week DBPC, 6-week open-label); KINECT 3 (NCT02274558: 6-week DBPC, 42-week blinded extension, 4-week drug-free follow-up); KINECT 4 (NCT02405091: 48-week open-label, 4-week drug-free follow-up). Safety assessments included adverse events (AEs), laboratory tests, vital signs, electrocardiograms (ECGs), and extrapyramidal symptom (EPS) scales. Psychiatric stability was monitored using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) (SCHZ subgroup), as well as the Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) (mood subgroup). All data were analyzed descriptively. The LTE population included 430 subjects (KINECT, n = 46; KINECT 3, n = 220; KINECT 4, n = 164), 71.7% with SCHZ and 28.3% with a mood disorder; 85.5% were taking an antipsychotic (atypical only, 69.8%; typical only or typical + atypical, 15.7%). In the LTE population, treatment-emergent AEs (TEAEs) and discontinuations due to AEs were reported in 66.5% and 14.7% of subjects, respectively. The TEAE incidence was lower in the SCHZ subgroup (64.4%) than in the mood subgroup (71.9%). The 3 most common TEAEs in the SCHZ subgroup were urinary tract infection (UTI, 6.1%), headache (5.8%), and somnolence (5.2%). The 3 most common TEAEs in the mood subgroup were headache (12.4%), UTI (10.7%), and somnolence (9.1%). Mean score changes from baseline to end of treatment (Week 48) indicated that psychiatric stability was maintained in the SCHZ subgroup (PANSS Total, -3.4; PANSS Positive, -1.1; PANSS Negative, -0.1; PANSS General Psychopathology, -2.2; CDSS total, -0.4) and the mood subgroup (MADRS Total, 0.0; YMRS Total, -1.2). These scores remained generally stable during the 4-week drug-free follow-up periods. In the LTE population, mean changes in laboratory parameters, vital signs, ECG, and EPS scales were generally minimal and not clinically significant. Valbenazine appeared to be well tolerated in adults with TD who received up to 48 weeks of treatment. In addition to long-term efficacy results (presented separately), these results suggest that valbenazine may be appropriate for the long-term management of TD regardless of underlying psychiatric diagnosis (SCHZ disorder or mood disorder).

Measuring student learning using initial and final concept test in an STEM course

NASA Astrophysics Data System (ADS)

Kaw, Autar; Yalcin, Ali

2012-06-01

Effective assessment is a cornerstone in measuring student learning in higher education. For a course in Numerical Methods, a concept test was used as an assessment tool to measure student learning and its improvement during the course. The concept test comprised 16 multiple choice questions and was given in the beginning and end of the class for three semesters. Hake's gain index, a measure of learning gains from pre- to post-tests, of 0.36 to 0.41 were recorded. The validity and reliability of the concept test was checked via standard measures such as Cronbach's alpha, content and criterion-related validity, item characteristic curves and difficulty and discrimination indices. The performance of various subgroups such as pre-requisite grades, transfer students, gender and age were also studied.

Gravitropism in Higher Plant Shoots 1

PubMed Central

Mueller, Wesley J.; Salisbury, Frank B.; Blotter, P. Thomas

1984-01-01

Dimensional changes during gravitropic bending of cocklebur (Xanthium strumarium L.) dicot stems were measured using techniques of stereo photogrammetry. The differential growth is from an increased growth rate on the bottom of the stem and a stopping or contraction of the top. Contraction of the top was especially evident upon release and immediate bending of horizontal stems that had been restrained between stiff wires for 36 hours. The energy for this could have been stored in both the top and bottom, since the bottom elongated, and the top contracted. Forces developed during bending were measured by fastening a stem tip to the end of a bar with attached strain gauges and recording electrical output from the strain gauges. Restrained mature cocklebur stems continued to accumulate potential energy for bending for about 120 hours, after which the recorded force reached a maximum. Pressures within castor bean (Ricinus communis L.) stems were also measured with 3.5-millimeter diameter pressure transducers. As expected, the pressure on the bottom of the restrained plants increased with time; pressures decreased in vertical controls, tops of restrained stems, and bottoms of free-bending stems. Pressures increased in tops of free-bending stems. When restrained plants were released, pressure on the bottom decreased and pressure on the top increased. Results suggest a possible role for cell contraction in the top of stems bending upward in response to gravity. Images Fig. 5 Fig. 11 PMID:16663987

DNA homology among diverse spiroplasma strains representing several serological groups.

PubMed

Lee, I M; Davis, R E

1980-11-01

Deoxyribonucleic acid (DNA) homology among 10 strains of spiroplasma associated with plants and insects was assessed by analysis of DNA-DNA hybrids with single strand specific S1 nuclease. Based on DNA homology, the spiroplasmas could be divided into three genetically distinct groups (designated I, II, and III), corresponding to three separate serogroups described previously. DNA sequence homology between the three groups was less than or equal to 5%. Based on DNA homology, group I could be divided into three subgroups (A, B, and C) that corresponded to three serological subgroups of serogroup I. Subgroup A contained Spiroplasma citri strains Maroc R8A2 and C 189; subgroup B contained strains AS 576 from honey bee and G 1 from flowers; subgroup C contained corn stunt spiroplasma strains I-747 and PU 8-17. There was 27-54% DNA sequence homology among these three subgroups. Group II contained strains 23-6 and 27-31 isolated from flowers of tulip tree (Liriodendron tulipifera L.). Group III contained strains SR 3 and SR 9, other isolates from flowers of tulip tree. Based on thermal denaturation, guanine plus cytosine contents of DNA from five type strains representing all groups and subgroups were estimated to be close to 26 mol% for group I strains, close to 25 mol% for group II strains, and close to 29 mol% for group III strains. The genome molecular weights of these five type strains were all estimated to bae about 10(9).

Recombination in the evolution of enterovirus C species sub-group that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99.

PubMed

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C) species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A-C). In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5'UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses.

In Vitro Evaluation of the Effect of Chemical and Thermal Stress of the Mechanical Properties of Periodontal Curettes under Simulated Conditions of Sharpening Wear.

PubMed

De Pedro, Daniel; Puglisi, Rosario; Levi, Paul; Pascual, Andrés; Nart, José

To determine whether chemical and thermal stress as well as sharpening are aspects that must be considered to determine when a curette has become too weak to be used safely without the threat of breakage. A total sample of 35 curette blades was divided into 2 principal groups, control (groups 1 to 3) and experimental (groups 4 to 6). The control group was divided into 3 colour-coded groups of 19 similar curette blades and was only subjected to progressive sharpening wear (not sterilised). The test group included 16 Gracey curette blades that were subjected to various degrees of progressive wear and different numbers of sterilisation cycles in 3 subgroups (subgroup 4 had 5 sterilisation cycles; subgroup 5 had 30 cycles and experimental subgroup 6 had 55 cycles). Using a universal testing machine, all blades were tested for strength until they fractured. No evidence was found that the simple presence or absence of sterilisation cycles produced a statistically significant difference between the two studied groups (sterilised and not sterilised). However, when comparing the six subgroups that underwent different numbers of sterilisation cycles, the analysis showed that the more sterilisation cycles a curette underwent, the more likely the curette was to fracture (p = 0.047). Sterilisation by itself does not produce a significant change in the fracture strength, whereas the number of sterilisation cycles clearly weakens the instrument. Sterilisation is a factor to control when evaluating the life of a periodontal curette for the patients' and professionals' safety.

Frequency of subgroups of the antigen “a” among volunteer donors

PubMed

Parra-Jaramillo, Katherine; Chiriboga-Ponce, Rosa F

2018-01-01

The presence of weak variants of blood type A represents a challenge in the practice of immunohematology for discrepancies in the time of the classification. It is common in blood banks to perform a forward and reverse typing for the purpose of confirming the blood type, but not all the people with a subgroup A2 have developed anti-A1 antibodies. We present a descriptive, observational and transversal study that establishes the proportion of subgroups of A antigen with the analysis of manual tube technique and monoclonal antibodies like anti-A, anti-A1 (Dolichus biflorus lectins extract) and anti-H. The analysis involved a total of 818 samples of voluntary blood donor, selected by random sampling, which were initially classified as 737 of Type A, and 81 as Type AB, with a confidence level of 95% (alpha error of 5% and 3% of precision). The present study evaluated the existence of the subgroups A1, A2, A1B, A2B, A intermediate and A intB. It is recommended the identification of subgroups in different types of blood in the laboratory and blood banks. Copyright: © 2018 SecretarÍa de Salud

Federal Science, Technology, Engineering, and Mathematics (STEM) Education: 5-Year Strategic Plan. A Report from the Committee on STEM Education National Science and Technology Council

ERIC Educational Resources Information Center

Executive Office of the President, 2013

2013-01-01

Given that many jobs of the future will be STEM jobs, that our K-12 system is "middle of the pack" in international comparisons, and that progress on STEM education at multiple levels is critical to building a just and inclusive society, there is an urgent need to continue to improve STEM education in the United States. Much knowledge…

Placenta accreta is associated with decreased decidual natural killer (dNK) cells population: a comparative pilot study.

PubMed

Laban, Mohamed; Ibrahim, Eman Abdel-Salam; Elsafty, Mohammed Saeed Eldin; Hassanin, Alaa Sayed

2014-10-01

Placenta accreta is a general term describes abnormal adherent placenta to the uterine wall. When the chorionic villi invade the myometrium, the term placenta increta is appropriate. Nowadays, it is one of the increasing causes of materno-fetal morbidities and mortality. The aim of this research was to evaluate density of decidual natural killer cells (dNK, CD56+(bright)) in decidua basalis in patients with placenta accreta. We recruited 76 patients from Ain Shams Maternity Hospital between June 2012 to August 2013, they were divided into study subgroup (A) which included 10 patients who underwent cesarean hysterectomy due to unseparated placenta accreta, study subgroup (B) included 16 patients with separated placenta accreta, a comparison group included 25 patients with placenta previa and a control group included 25 patients with normally situated placenta. All patients underwent elective cesarean delivery. Decidual biopsies were taken during the operation. An immunohistochemical staining for (dNK, CD56+(bright)) and a semi quantitative scoring were done. One-way ANOVA and Fisher Exact tests were used for statistical correlation. The mean dNK cells scores were (0.4±0.5, 1.9±1, 3.3±0.5 and 3.5±0.5) for study subgroups (A), (B) comparison and control groups respectively) with a highly significant statistical difference (P<0.001). There was a significant statistical difference between study subgroups (A) and (B) P=0.002 .There was an insignificant statistical correlation between dNK scores and number of previous uterine scars (P=0.46). These findings suggest that low dNK score was associated with cases of morbidly adherent placenta accreta. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Diffuse alveolar hemorrhage: retrospective review of clinical outcome in allogeneic transplant recipients treated with aminocaproic acid.

PubMed

Wanko, Sam O; Broadwater, Gloria; Folz, Rodney J; Chao, Nelson J

2006-09-01

Diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (HSCT) is often fatal. Standard therapy with high-dose corticosteroid is not always effective. There is paucity of data in the literature about other potentially useful agents, such as aminocaproic acid (Amicar) in the post-transplantation setting. We retrospectively reviewed our data on 115 consecutive patients who underwent HSCT and had pulmonary complications, with the aim of determining the overall clinical outcome in recipients of allogeneic transplants and in the subgroup of these patients who were treated with concomitant Solu-Medrol and aminocaproic acid. Aminocaproic acid was added at the discretion of the attending physician. We identified 14 allogeneic transplant recipients (median age, 41 years) with 15 episodes of DAH who were treated with Solu-Medrol (250 mg to 1 g intravenously per day). Of these, 8 patients also received concomitant aminocaproic acid at 1000 mg intravenously every 6 hours. Failure to improve was the most common reason for adding aminocaproic acid. The incidence of DAH was 12.2% (10.3% in myeloablative versus 1.9% in nonmyeloablative recipients). The overall 100-day DAH mortality and median transplantation survival were 60% and 99 days, respectively. Among the subset of patients treated with the combination of Solu-Medrol and aminocaproic acid, we observed a 100-day DAH mortality and median transplantation survival of 44% and 167 days, respectively, compared with 83% and 96.5 days in those treated with Solu-Medrol alone. The median time to DAH was 40.5 days, and the median time to death was 53 days in the combined treatment group compared with 29.5 days in those treated with steroid alone. There were no significant differences in coagulation parameters between subsets. Infections (yeast, respiratory syncytial virus, herpes simplex virus, and parainfluenza) were isolated and treated from 6 diagnostic bronchial alveolar lavage samples and were more common in the subgroup treated with Solu-Medrol only. Respiratory failure was the documented cause of death in 89% of patients. There were no clinically significant side effects from aminocaproic acid. Although these historically lower DAH outcomes are intriguing, prospective studies are needed to confirm the role of aminocaproic acid in DAH occurring in the allogeneic transplantation setting.

Discovery and characterization of two new stem rust resistance genes in Aegilops sharonensis.

PubMed

Yu, Guotai; Champouret, Nicolas; Steuernagel, Burkhard; Olivera, Pablo D; Simmons, Jamie; Williams, Cole; Johnson, Ryan; Moscou, Matthew J; Hernández-Pinzón, Inmaculada; Green, Phon; Sela, Hanan; Millet, Eitan; Jones, Jonathan D G; Ward, Eric R; Steffenson, Brian J; Wulff, Brande B H

2017-06-01

We identified two novel wheat stem rust resistance genes, Sr-1644-1Sh and Sr-1644-5Sh in Aegilops sharonensis that are effective against widely virulent African races of the wheat stem rust pathogen. Stem rust is one of the most important diseases of wheat in the world. When single stem rust resistance (Sr) genes are deployed in wheat, they are often rapidly overcome by the pathogen. To this end, we initiated a search for novel sources of resistance in diverse wheat relatives and identified the wild goatgrass species Aegilops sharonesis (Sharon goatgrass) as a rich reservoir of resistance to wheat stem rust. The objectives of this study were to discover and map novel Sr genes in Ae. sharonensis and to explore the possibility of identifying new Sr genes by genome-wide association study (GWAS). We developed two biparental populations between resistant and susceptible accessions of Ae. sharonensis and performed QTL and linkage analysis. In an F 6 recombinant inbred line and an F 2 population, two genes were identified that mapped to the short arm of chromosome 1S sh , designated as Sr-1644-1Sh, and the long arm of chromosome 5S sh , designated as Sr-1644-5Sh. The gene Sr-1644-1Sh confers a high level of resistance to race TTKSK (a member of the Ug99 race group), while the gene Sr-1644-5Sh conditions strong resistance to TRTTF, another widely virulent race found in Yemen. Additionally, GWAS was conducted on 125 diverse Ae. sharonensis accessions for stem rust resistance. The gene Sr-1644-1Sh was detected by GWAS, while Sr-1644-5Sh was not detected, indicating that the effectiveness of GWAS might be affected by marker density, population structure, low allele frequency and other factors.

miR-335 negatively regulates osteosarcoma stem cell-like properties by targeting POU5F1.

PubMed

Guo, Xiaodong; Yu, Ling; Zhang, Zhengpei; Dai, Guo; Gao, Tian; Guo, Weichun

2017-01-01

Evidence is accumulating to link cancer stem cells to the pathogenesis and progression of osteosarcoma. The aim of this study is to investigate the role of miR-335 in osteosarcoma stem cells. Tumor spheroid culture and flow cytometry were applied to screen out osteosarcoma stem cells. Real-time quantitative PCR was used to detect the expression level of miR-335 in MG63, U2OS and 143B osteosarcoma stem cells. The relationship of miR-335 expression with osteosarcoma stem cells was then analyzed. Transwell assay and transplantation assay were performed to elucidate biological effects of miR-335 on cell invasion and vivo tumor formation. Western Blot and luciferase assays were executed to investigate the regulation of POU5F1 by miR-335. The expression of miR-335 in osteosarcoma stem cells was lower than their differentiated counterparts. Cells expressing miR-335 possessed decreased stem cell-like properties. Gain or loss of function assays were applied to find that miR-335 antagonist promoted stem cell-like properties as well as invasion. Luciferase report and transfection assay showed that POU5F1 was downregulated by miR-335. Pre-miR-335 resulted in tumor enhanced sensitivity to traditional chemotherapy, whereas anti-miR-335 promoted chemoresistance. Finally, the inhibitory effect of miR-335 on in vivo tumor formation showed that combination of pre-miR-335 with cisplatin further reduced the tumor size, and miR-335 brought down the sphere formation capacity induced by cisplatin. The current study demonstrates that miR-335 negatively regulates osteosarcoma stem cell-like properties by targeting POU5F1, and miR-335 could target CSCs to synergize with traditional chemotherapeutic agents to overcome osteosarcoma.

Stem cell exhaustion due to Runx1 deficiency is prevented by Evi5 activation in leukemogenesis

PubMed Central

Jacob, Bindya; Yamashita, Namiko; Wang, Chelsia Qiuxia; Taniuchi, Ichiro; Littman, Dan R.; Asou, Norio

2010-01-01

The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1−/− mice do not develop spontaneous leukemia. Here we show that maintenance of Runx1−/− HSCs is compromised, progressively resulting in HSC exhaustion. In leukemia development, the stem cell exhaustion was rescued by additional genetic changes. Retroviral insertional mutagenesis revealed Evi5 activation as a cooperating genetic alteration and EVI5 overexpression indeed prevented Runx1−/− HSC exhaustion in mice. Moreover, EVI5 was frequently overexpressed in human RUNX1-related leukemias. These results provide insights into the mechanism for maintenance of pre-leukemic stem cells and may provide a novel direction for therapeutic applications. PMID:20008790

Longitudinal Examination of Symptom Profiles Among Breast Cancer Survivors.

PubMed

Avis, Nancy E; Levine, Beverly; Marshall, Sarah A; Ip, Edward H

2017-04-01

Identification of cancer patients with similar symptom profiles may facilitate targeted symptom management. To identify subgroups of breast cancer survivors based on differential experience of symptoms, examine change in subgroup membership over time, and identify relevant characteristics and quality of life (QOL) among subgroups. Secondary analyses of data from 653 breast cancer survivors recruited within eight months of diagnosis who completed questionnaires at five time points. Hidden Markov modeling was used to 1) formulate symptom profiles based on prevalence and severity of eight symptoms commonly associated with breast cancer and 2) estimate probabilities of changing subgroup membership over 18 months of follow-up. Ordinal repeated measures were used to 3) identify patient characteristics related to subgroup membership and 4) evaluate the relationship between symptom subgroup and QOL. A seven-subgroup model provided the best fit: 1) low symptom burden, 2) mild fatigue, 3) mild fatigue and mild pain, 4) moderate fatigue and moderate pain, 5) moderate fatigue and moderate psychological, 6) moderate fatigue, mild pain, mild psychological, and 7) high symptom burden. Seventy percent of survivors remained in the same subgroup over time. In multivariable analyses, chemotherapy and greater illness intrusiveness were significantly related to greater symptom burden, while not being married or partnered, no difficulty paying for basics, and greater social support were protective. Higher symptom burden was associated with lower QOL. Survivors who reported psychological symptoms had significantly lower QOL than did survivors with pain symptoms. Cancer survivors can be differentiated by their symptom profiles. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Effect of Dimethyl Sulfoxide on Bond Strength of a Self-Etch Primer and an Etch and Rinse Adhesive to Surface and Deep Dentin.

PubMed

Sharafeddin, Farahnaz; Salehi, Raha; Feizi, Negar

2016-09-01

Composite bond to dentin is crucial in many clinical conditions particularly in deep cavities without enamel margins due to insufficient penetration of adhesive into demineralized dentin. The aim of this study was to assess the shear bond strength (SBS) of a methacrylate-based and a silorane-based composite resin to surface and deep dentin after pretreatment with dimethyl sulfoxide (DMSO). Eighty extracted human premolars were randomly divided into two groups of flat occlusal dentin with different cuts as A: surface group (sections just below the dentinoenamel junction (DEJ) and B: deep group (2 mm below DEJ). Each group was randomly assigned to 4 subgroups and their samples were restored with Adper Single bond (ASB) and Filtek Z350 or Silorane system Adhesive (SA) and Filtek P90 composite resins, using a 3×3mm cylindrical plastic mold. following these steps , the subgroups were assigned as SubgroupA 1 : surface dentin+ Silorane System Primer (SSP)+ Silorane System Bonding (SSB)+ P90; Subgroup A 2 : surface dentin+ 37% etchant (E37%) + Adper Single Bond (ASB)+ Z350; Subgroup A 3 : surface dentin+ DMSO+ SSP+ SSB+ P90; Subgroup A 4 : surface dentin+ E37%+ DMSO+ ASB+ Z350; Subgroup B 1 : deep dentin+ SSP+ SSB+ P90; Subgroup B 2 : deep dentin+ E37%+ ASB+ Z350; Subgroup B 3 : deep dentin+ DMSO+ SSP+ SSB+ P90; Subgroup B 4 :dentin +E37% +DMSO +ASB +Z350. The specimens were thermocycled at 5± 2/55± 2°C for 1000 cycles and then tested for SBS. Using DMSO as dentin conditioner increased SBS of ASB to deep dentin (p< 0.001) and SBS of SA to surface dentin (p= 0.003) but had no effect on SBS of SA to deep dentin (p= 1.00). The ability of DMSO to increase SBS of ASB to deep dentin provides a basis for improving bonding of this composite resin in deep cavities.

Strengthening STEM Education through Community Partnerships

PubMed Central

Lopez, Colleen A.; Rocha, Jon; Chapman, Matthew; Rocha, Kathleen; Wallace, Stephanie; Baum, Steven; Lawler, Brian R.; Mothé, Bianca R.

2017-01-01

California State University San Marcos (CSUSM) and San Marcos Elementary Schools have established a partnership to offer a large-scale community service learning opportunity to enrich science curriculum for K-5 students. It provides an opportunity for science, technology, engineering, and math (STEM) majors to give back to the community, allowing them to experience teaching in an elementary classroom setting, in schools that lack the resources and science instructor specialization needed to instill consistent science curricula. CSUSM responded to this need for more STEM education by mobilizing its large STEM student body to design hands-on, interactive science lessons based on Next Generation Science Standards (NGSS). Since 2012, the program has reached out to over four thousand K-5 students, and assessment data have indicated an increase in STEM academic performance and interest. PMID:28725512

Strengthening STEM Education through Community Partnerships.

PubMed

Lopez, Colleen A; Rocha, Jon; Chapman, Matthew; Rocha, Kathleen; Wallace, Stephanie; Baum, Steven; Lawler, Brian R; Mothé, Bianca R

2016-01-01

California State University San Marcos (CSUSM) and San Marcos Elementary Schools have established a partnership to offer a large-scale community service learning opportunity to enrich science curriculum for K-5 students. It provides an opportunity for science, technology, engineering, and math (STEM) majors to give back to the community, allowing them to experience teaching in an elementary classroom setting, in schools that lack the resources and science instructor specialization needed to instill consistent science curricula. CSUSM responded to this need for more STEM education by mobilizing its large STEM student body to design hands-on, interactive science lessons based on Next Generation Science Standards (NGSS). Since 2012, the program has reached out to over four thousand K-5 students, and assessment data have indicated an increase in STEM academic performance and interest.

Attitude of A Sample of Iranian Researchers toward The Future of Stem Cell Research.

PubMed

Lotfipanah, Mahdi; Azadeh, Fereydoon; Totonchi, Mehdi; Omani-Samani, Reza

2018-10-01

Stem cells that have unlimited proliferation potential as well as differentiation potency are considered to be a promising future treatment method for incurable diseases. The aim of the present study is to evaluate the future trend of stem cell researches from researchers' viewpoints. This was a cross-sectional descriptive study on researchers involved in stem cell research at Royan Institute. We designed a questionnaire using a qualitative study based on expert opinion and a literature review. Content validity was performed using three rounds of the Delphi method with experts. Face validity was undertaken by a Persian literature expert and a graphics designer. The questionnaire was distributed among 150 researchers involved in stem cell studies in Royan Institute biology laboratories. We collected 138 completed questionnaires. The mean age of participants was 31.13 ± 5.8 years; most (60.9%) were females. Participants (76.1%) considered the budget to be the most important issue in stem cell research, 79.7% needed financial support from the government, and 77.5% felt that charities could contribute substantially to stem cell research. A total of 90.6% of participants stated that stem cells should lead to commercial usage which could support future researches (86.2%). The aim of stem cell research was stipulated as increasing health status of the society according to 92.8% of the participants. At present, among cell types, importance was attached to cord blood and adult stem cells. Researchers emphasized the importance of mesenchymal stem cells (MSCs) rather than hematopoietic stem cells (HSCs, 57.73%). The prime priorities were given to cancer so that stem cell research could be directed to sphere stem cell research whereas the least preference was given to skin research. Regenerative medicine is considered the future of stem cell research with emphasis on application of these cells, especially in cancer treatment. Copyright© by Royan Institute. All rights reserved.

Associations between religiosity and anxiety, depressive symptoms, and well-being in Korean adults living with epilepsy.

PubMed

Lee, Sang-Ahm; Ryu, Han Uk; Choi, Eun-Ju; Ko, Myung-Ah; Jeon, Ji-Ye; Han, Su-Hyun; Lee, Gha-Hyun; Lee, Moon Kyu; Jo, Kwang-Deog

2017-10-01

Religiosity can be important in the everyday life of persons with epilepsy (PWE). How PWE live with religiosity can be influenced by their cultural background. We determined whether religiosity is associated with anxiety, depressive symptoms, and well-being in Korean adults with epilepsy. This multicenter cross-sectional study was conducted in the outpatient clinics of five university hospitals in Korea. Religiosity was assessed using the five-item Duke University Religion Index (DUREL). The WHO-Five Well-Being Index (WHO-5) and Hospital Anxiety Depression Scale were used. The participants were categorized into three subgroups bounded by the 33rd and 66th percentiles of their DUREL scores. Of a total of 226 participants, 61.1% declared that they had religious affiliation. The median DUREL score was 11 (interquartile ranges 6, 18). All three subscales of the DUREL were significantly related to WHO-5 (p<0.01). Non-organizational religious activities such as prayer and meditation were also inversely related to anxiety (p<0.05) and depressive symptoms (p<0.01). After controlling for confounding variables, anxiety and depressive symptoms were more extensive in the low religiosity subgroup than in the high or no religiosity subgroup (p<0.01) and well-being was higher in the high or low religiosity subgroup than in the no religiosity subgroup (p<0.05). Religiosity is significantly associated with anxiety, depressive symptoms, and well-being in Korean adults with epilepsy. Copyright © 2017 Elsevier Inc. All rights reserved.

Spatial and temporal heterogeneity of infectious hematopoietic necrosis virus in Pacific Northwest salmonids

USGS Publications Warehouse

Breyta, Rachel; Black, Allison; Kaufman, John; Kurath, Gael

2016-01-01

The aquatic rhaboviral pathogen infectious hematopoietic necrosis virus (IHNV) causes acute disease in juvenile fish of a number of populations of Pacific salmonid species. Heavily managed in both marine and freshwater environments, these fish species are cultured during the juvenile stage in freshwater conservation hatcheries, where IHNV is one of the top three infectious diseases that cause serious morbidity and mortality. Therefore, a comprehensive study of viral genetic surveillance data representing 2590 field isolates collected between 1958 and 2014 was conducted to determine the spatial and temporal patterns of IHNV in the Pacific Northwest of the contiguous United States. Prevalence of infection varied over time, fluctuating over a rough 5–7 year cycle. The genetic analysis revealed numerous subgroups of IHNV, each of which exhibited spatial heterogeneity. Within all subgroups, dominant genetic types were apparent, though the temporal patterns of emergence of these types varied among subgroups. Finally, the affinity or fidelity of subgroups to specific host species also varied, where UC subgroup viruses exhibited a more generalist profile and all other subgroups exhibited a specialist profile. These complex patterns are likely synergistically driven by numerous ecological, pathobiological, and anthropogenic factors. Since only a few anthropogenic factors are candidates for managed intervention aimed at improving the health of threatened or endangered salmonid fish populations, determining the relative impact of these factors is a high priority for future studies.

Stem Cells News Update: A Personal Perspective

PubMed Central

Wong, SC

2013-01-01

This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy. PMID:24778557

Stem cells news update: a personal perspective.

PubMed

Wong, Sc

2013-12-01

This article is a follow-up to a previous Commentary published in 2011. It updates some of the events mentioned in that Commentary and continues with more interesting and exciting news on stem cell research and the emerging field of Regenerative Medicine. Some of the news includes: 1) the 2012 Nobel Prize for Medicine awarded to John B. Gurdon and Shinya Yamanaka; 2) the cloning of human embryonic stem cells; 3) the continued search for truly pluripotent adult stem cells via in vitro and in vivo protocols; 4) the breakthrough in organ replacements; 5) the global stem cell race; 6) the global stem cell cryo-preservation business; 7) the worldwide stem cell donor registries, and 8) the issue of government regulation on stem cell therapy.

Phase diagram of (Li(1-x)Fe(x))OHFeSe: a bridge between iron selenide and arsenide superconductors.

PubMed

Dong, Xiaoli; Zhou, Huaxue; Yang, Huaixin; Yuan, Jie; Jin, Kui; Zhou, Fang; Yuan, Dongna; Wei, Linlin; Li, Jianqi; Wang, Xinqiang; Zhang, Guangming; Zhao, Zhongxian

2015-01-14

Previous experimental results have shown important differences between iron selenide and arsenide superconductors which seem to suggest that the high-temperature superconductivity in these two subgroups of iron-based families may arise from different electronic ground states. Here we report the complete phase diagram of a newly synthesized superconducting (SC) system, (Li1-xFex)OHFeSe, with a structure similar to that of FeAs-based superconductors. In the non-SC samples, an antiferromagnetic (AFM) spin-density-wave (SDW) transition occurs at ∼127 K. This is the first example to demonstrate such an SDW phase in an FeSe-based superconductor system. Transmission electron microscopy shows that a well-known √5×√5 iron vacancy ordered state, resulting in an AFM order at ∼500 K in AyFe2-xSe2 (A = metal ions) superconductor systems, is absent in both non-SC and SC samples, but a unique superstructure with a modulation wave vector q = (1)/2(1,1,0), identical to that seen in the SC phase of KyFe2-xSe2, is dominant in the optimal SC sample (with an SC transition temperature Tc = 40 K). Hence, we conclude that the high-Tc superconductivity in (Li1-xFex)OHFeSe stems from the similarly weak AFM fluctuations as FeAs-based superconductors, suggesting a universal physical picture for both iron selenide and arsenide superconductors.

7 CFR 319.56-52 - Tomatoes with stems from the Republic of Korea.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Tomatoes with stems from the Republic of Korea. 319.56... Vegetables § 319.56-52 Tomatoes with stems from the Republic of Korea. Fresh tomatoes with stems (Solanum... not be allowed to enter the United States. (d) Commercial consignments. Tomatoes with stems from the...

7 CFR 319.56-52 - Tomatoes with stems from the Republic of Korea.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Tomatoes with stems from the Republic of Korea. 319.56... Vegetables § 319.56-52 Tomatoes with stems from the Republic of Korea. Fresh tomatoes with stems (Solanum... not be allowed to enter the United States. (d) Commercial consignments. Tomatoes with stems from the...

7 CFR 319.56-52 - Tomatoes with stems from the Republic of Korea.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Tomatoes with stems from the Republic of Korea. 319.56... Vegetables § 319.56-52 Tomatoes with stems from the Republic of Korea. Fresh tomatoes with stems (Solanum... not be allowed to enter the United States. (d) Commercial consignments. Tomatoes with stems from the...

Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway

PubMed Central

Zhang, Xin; Peng, Yao; Ye, Ziyu; Ma, Yan; Liang, Yangfang; Cao, Longbin; Li, Xiangyong; Li, Ronggang; Sun, Lixia; Liu, Qiongru; Wu, Jinhua; Zhou, Keyuan; Zeng, Jincheng

2017-01-01

Emerging studies indicated that cancer stem cells represent a subpopulation of cells within the tumor that is responsible for chemotherapeutic resistance. However, the underlying mechanism is still not clarified yet. Here we report that miR-196b-5p is dramatically upregulated in CRC tissues and high expression of miR-196b-5p correlates with poor survival in CRC patients. Moreover, recurrent gains (amplification) contribute to the miR-196b-5p overexpression in CRC tissues. Silencing miR-196b-5p suppresses spheroids formation ability, the fraction of SP cells, expression of stem cell factors and the mitochondrial potential, and enhances the apoptosis induced by 5-fluorouracil in CRC cells; while ectopic expression of miR-196b-5p yields an opposite effect. In addition, downregulation of miR-196b-5p resensitizes CRC cells to 5-fluorouracil in vivo. Our results further demonstrate that miR-196b-5p promotes stemness and chemoresistance of CRC cells to 5-fluorouracil via targeting negative regulators SOCS1 and SOCS3 of STAT3 signaling pathway, giving rise to activation of STAT3 signaling. Interestingly, miR-196b-5p is highly enriched in the serum exosomes of patients with CRC compared to the healthy control subjects. Thus, our results unravel a novel mechanism of miR-196b-5p implicating in the maintenance of stem cell property and chemotherapeutic resistance in CRC, offering a potential rational registry of anti-miR-196b-5p combining with conventional chemotherapy against CRC. PMID:28591704

Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5 Monoclonal Antibody

DTIC Science & Technology

2013-02-01

1 AD_________________ Award Number: W81XWH-11-1-0151 TITLE: Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5...Annual Summary 3. DATES COVERED 15-January-2012 – 14-January-2013 4. TITLE AND SUBTITLE Sensitivity of Breast Cancer Stem Cells to TRA-8 Anti-DR5...release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Basal-like breast cancers (BLBCs) generally become resistant to

MiR-146b-5p overexpression attenuates stemness and radioresistance of glioma stem cells by targeting HuR/lincRNA-p21/β-catenin pathway

PubMed Central

Yang, Wei; Yu, Hongquan; Shen, Yueming; Liu, Yingying; Yang, Zhanshan; Sun, Ting

2016-01-01

A stem-like subpopulation existed in GBM cells, called glioma stem cells (GSCs), might contribute to cancer invasion, angiogenesis, immune evasion, and therapeutic resistance, providing a rationale to eliminate GSCs population and their supporting niche for successful GBM treatment. LincRNA-p21, a novel regulator of cell proliferation, apoptosis and DNA damage response, is found to be downregulated in several types of tumor. However, little is known about the role of lincRNA-p21 in stemness and radioresistance of GSCs and its regulating mechanisms. In this study, we found that lincRNA-p21 negatively regulated the expression and activity of β-catenin in GSCs. Downregulation of lincRNA-p21 in GSCs was resulted from upregulation of Hu antigen R (HuR) expression caused by miR-146b-5p downregulation. MiR-146b-5p overexpression increased apoptosis and radiosensitivity, decreased cell viability, neurosphere formation capacity and stem cell marker expression, and induced differentiation in GSCs. Moreover, knock-down lincRNA-p21 or HuR and β-catenin overexpression could rescue the phenotypic changes resulted from miR-146b-5p overexpression in GSCs. These findings suggest that targeting the miR-146b-5p/HuR/lincRNA-p21/β-catenin signaling pathway may be valuable therapeutic strategies against glioma. PMID:27166258

Complete sequence of two tick-borne flaviviruses isolated from Siberia and the UK: analysis and significance of the 5' and 3'-UTRs.

PubMed

Gritsun, T S; Venugopal, K; Zanotto, P M; Mikhailov, M V; Sall, A A; Holmes, E C; Polkinghorne, I; Frolova, T V; Pogodina, V V; Lashkevich, V A; Gould, E A

1997-05-01

The complete nucleotide sequence of two tick-transmitted flaviviruses, Vasilchenko (Vs) from Siberia and louping ill (LI) from the UK, have been determined. The genomes were respectively, 10928 and 10871 nucleotides (nt) in length. The coding strategy and functional protein sequence motifs of tick-borne flaviviruses are presented in both Vs and LI viruses. The phylogenies based on maximum likelihood, maximum parsimony and distance analysis of the polyproteins, identified Vs virus as a member of the tick-borne encephalitis virus subgroup within the tick-borne serocomplex, genus Flavivirus, family Flaviviridae. Comparative alignment of the 3'-untranslated regions revealed deletions of different lengths essentially at the same position downstream of the stop codon for all tick-borne viruses. Two direct 27 nucleotide repeats at the 3'-end were found only for Vs and LI virus. Immediately following the deletions a region of 332-334 nt with relatively conserved primary structure (67-94% identity) was observed at the 3'-non-coding end of the virus genome. Pairwise comparisons of the nucleotide sequence data revealed similar levels of variation between the coding region, and the 5' and 3'-termini of the genome, implying an equivalent strong selective control for translated and untranslated regions. Indeed the predicted folding of the 5' and 3'-untranslated regions revealed patterns of stem and loop structures conserved for all tick-borne flaviviruses suggesting a purifying selection for preservation of essential RNA secondary structures which could be involved in translational control and replication. The possible implications of these findings are discussed.

Is there still a place for the cemented titanium femoral stem?

PubMed Central

2012-01-01

Background and purpose Despite the fact that there have been some reports on poor performance, titanium femoral stems intended for cemented fixation are still used at some centers in Europe. In this population-based registry study, we examined the results of the most frequently used cemented titanium stem in Norway. Patients and methods 11,876 cases implanted with the cemented Titan stem were identified for the period 1987–2008. Hybrid arthroplasties were excluded, leaving 10,108 cases for this study. Stem survival and the influence of age, sex, stem offset and size, and femoral head size were evaluated using Cox regression analyses. Questionnaires were sent to the hospitals to determine the surgical technique used. Results Male sex, high stem offset, and small stem size were found to be risk factors for stem revision, (adjusted RR = 2.5 (1.9–3.4), 3.3 (2.3–4.8), and 2.2 (1.4–3.5), respectively). Patients operated in the period 2001–2008 had an adjusted relative risk (RR) of 4.7 (95% CI: 3.0–7.4) for stem revision due to aseptic stem loosening compared to the period 1996–2000. Changes in broaching technique and cementing technique coincided with deterioration of the results in some hospitals. Interpretation The increased use of small stem sizes and high-offset stems could only explain the deterioration of results to a certain degree since the year 2000. The influence of discrete changes in surgical technique over time could not be fully evaluated in this registry study. We suggest that this cemented titanium stem should be abandoned. The results of similar implants should be carefully evaluated. PMID:22206445

Subgroup-Elimination Transcriptomics Identifies Signaling Proteins that Define Subclasses of TRPV1-Positive Neurons and a Novel Paracrine Circuit

PubMed Central

Isensee, Jörg; Wenzel, Carsten; Buschow, Rene; Weissmann, Robert; Kuss, Andreas W.; Hucho, Tim

2014-01-01

Normal and painful stimuli are detected by specialized subgroups of peripheral sensory neurons. The understanding of the functional differences of each neuronal subgroup would be strongly enhanced by knowledge of the respective subgroup transcriptome. The separation of the subgroup of interest, however, has proven challenging as they can hardly be enriched. Instead of enriching, we now rapidly eliminated the subgroup of neurons expressing the heat-gated cation channel TRPV1 from dissociated rat sensory ganglia. Elimination was accomplished by brief treatment with TRPV1 agonists followed by the removal of compromised TRPV1(+) neurons using density centrifugation. By differential microarray and sequencing (RNA-Seq) based expression profiling we compared the transcriptome of all cells within sensory ganglia versus the same cells lacking TRPV1 expressing neurons, which revealed 240 differentially expressed genes (adj. p<0.05, fold-change>1.5). Corroborating the specificity of the approach, many of these genes have been reported to be involved in noxious heat or pain sensitization. Beyond the expected enrichment of ion channels, we found the TRPV1 transcriptome to be enriched for GPCRs and other signaling proteins involved in adenosine, calcium, and phosphatidylinositol signaling. Quantitative population analysis using a recent High Content Screening (HCS) microscopy approach identified substantial heterogeneity of expressed target proteins even within TRPV1-positive neurons. Signaling components defined distinct further subgroups within the population of TRPV1-positive neurons. Analysis of one such signaling system showed that the pain sensitizing prostaglandin PGD2 activates DP1 receptors expressed predominantly on TRPV1(+) neurons. In contrast, we found the PGD2 producing prostaglandin D synthase to be expressed exclusively in myelinated large-diameter neurons lacking TRPV1, which suggests a novel paracrine neuron-neuron communication. Thus, subgroup analysis based on the elimination rather than enrichment of the subgroup of interest revealed proteins that define subclasses of TRPV1-positive neurons and suggests a novel paracrine circuit. PMID:25551770

Results of press-fit stems in revision knee arthroplasties.

PubMed

Wood, Gavin C; Naudie, Douglas D R; MacDonald, Steven J; McCalden, Richard W; Bourne, Robert B

2009-03-01

The ideal method of stem fixation in revision knee arthroplasty is controversial with advantages and disadvantages for cemented and press-fit designs. Studies have suggested cemented revision knee stems may provide better long-term survival. The aim of this study was to report our experience with press-fit uncemented stems and metaphyseal cement fixation in a selected series of patients undergoing revision total knee arthroplasty. One hundred twenty-seven patients (135 knees) who underwent revision total knee arthroplasty using a press-fit technique (press-fit diaphyseal fixation and cemented metaphyseal fixation) were reviewed. Minimum followup was 2 years (mean, 5 years; range, 2-12 years). A Kaplan-Meier survivorship analysis using an end point of revision surgery or radiographic loosening was used to determine probability of survival at 5 and 10 years. Of the 127 patients (135 knees), 31 patients (36 knees) died and two patients (two knees) were lost to followup. Six patients (six knees) had revisions at a mean of 3.5 years (range, 1-8 years). Kaplan-Meier survivorship analysis revealed a probability of survival free of revision for aseptic loosening of 98% at 12 years. Survivorship of press-fit stems for revision knee arthroplasty is comparable to reported survivorship of cemented stem revision knee arthroplasty. Radiographic analysis has shown continued satisfactory appearances regardless of constraint, stem size, and augmentations.

Clinical outcomes after combined therapy with dutasteride plus tamsulosin or either monotherapy in men with benign prostatic hyperplasia (BPH) by baseline characteristics: 4-year results from the randomized, double-blind Combination of Avodart and Tamsulosin (CombAT) trial.

PubMed

Roehrborn, Claus G; Barkin, Jack; Siami, Paul; Tubaro, Andrea; Wilson, Timothy H; Morrill, Betsy B; Gagnier, R Paul

2011-03-01

• To investigate the influence of baseline variables on the 4-year incidence of acute urinary retention (AUR), benign prostatic hyperplasia (BPH)-related surgery and overall clinical progression in men treated with tamsulosin, dutasteride, or a combination of both. • The 4-year Combination of Avodart® and Tamsulosin (CombAT) study was a multicenter, randomized, double-blind, parallel-group study of clinical outcomes in men aged ≥ 50 years with symptomatic (International Prostate Symptom Score [IPSS]≥ 12) BPH, with prostate-specific antigen (PSA) levels of ≥ 1.5 ng/mL and ≤ 10 ng/mL, and a prostate volume (PV) of ≥ 30 mL. • Eligible patients received tamsulosin 0.4 mg, dutasteride 0.5 mg, or a combination of both. • The primary endpoint was time to first AUR or BPH-related surgery. Secondary endpoints included clinical progression of BPH and symptoms. Posthoc analyses of the influence of baseline variables (including age, IPSS health-related quality of life [HRQL], PV, PSA, IPSS, peak urinary flow rate [Q(max) ] and body-mass index [BMI]) on the incidence of AUR or BPH-related surgery, clinical progression of BPH, and symptoms were performed. • There were 4844 men in the intent-to-treat population. Overall baseline characteristics were similar across all patient groups. • Regardless of baseline subgroup, the incidence of AUR or BPH-related surgery was higher in men treated with tamsulosin than in those treated with dutasteride or combined therapy. • Combined therapy was statistically better than tamsulosin in reducing the risk of AUR or BPH-related surgery in subgroups of baseline PV > 42.0 mL, in all subgroups of baseline PSA level, and all other baseline subgroups (P ≤ 0.001). • Across treatment groups, the incidence of clinical progression was highest in men with a baseline IPSS of < 20 or IPSS HRQL score of < 4. The incidence of clinical progression was also higher in men receiving tamsulosin than dutasteride or combined therapy in all baseline subgroups, except for men with a baseline PV of < 40 mL. Combined therapy reduced the relative risk (RR) of clinical progression compared with tamsulosin across all baseline subgroups and compared with dutasteride across most baseline subgroups. • Symptom deterioration was the most common progression event in each treatment group regardless of baseline subgroup, except in those men with an IPSS of ≥ 20 at baseline. Combined therapy reduced the RR of symptom deterioration compared with tamsulosin across all but one baseline subgroup (the reduction was not significant for men with a baseline PV of < 40 mL) and compared with dutasteride in most subgroups. • Men with a baseline PV of ≥ 40 mL and any baseline PSA level of ≥1.5 ng/mL had greater reductions in the RR of AUR or BPH-related surgery and greater reductions in the RR of clinical progression and symptom deterioration on combined therapy or dutasteride monotherapy than on tamsulosin monotherapy. • These analyses support the long-term use of combined therapy with dutasteride plus tamsulosin in men with moderate-to-severe BPH symptoms and a slightly enlarged prostate. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Change in Psychosocial Health Status Over 5 Years in Relation to Adults' Hearing Ability in Noise.

PubMed

Stam, Mariska; Smit, Jan H; Twisk, Jos W R; Lemke, Ulrike; Smits, Cas; Festen, Joost M; Kramer, Sophia E

The aim of this study was to establish the longitudinal relationship between hearing ability in noise and psychosocial health outcomes (i.e., loneliness, anxiety, depression, distress, and somatization) in adults aged 18 to 70 years. An additional objective was to determine whether a change in hearing ability in noise over a period of 5 years was associated with a change in psychosocial functioning. Subgroup effects for a range of factors were investigated. Longitudinal data of the web-based Netherlands Longitudinal Study on Hearing (NL-SH) (N = 508) were analyzed. The ability to recognize speech in noise (i.e., the speech-reception-threshold [SRTn]) was measured with an online digit triplet test at baseline and at 5-year follow-up. Psychosocial health status was assessed by online questionnaires. Multiple linear regression analyses and longitudinal statistical analyses (i.e., generalized estimating equations) were performed. Poorer SRTn was associated longitudinally with more feelings of emotional and social loneliness. For participants with a high educational level, the longitudinal association between SRTn and social loneliness was significant. Changes in hearing ability and loneliness appeared significantly associated only for specific subgroups: those with stable pattern of hearing aid nonuse (increased emotional and social loneliness), who entered matrimony (increased social loneliness), and low educational level (less emotional loneliness). No significant longitudinal associations were found between hearing ability and anxiety, depression, distress, or somatization. Hearing ability in noise was longitudinally associated with loneliness. Decline in hearing ability in noise was related to increase in loneliness for specific subgroups of participants. One of these subgroups included participants whose hearing deteriorated over 5 years, but who continued to report nonuse of hearing aids. This is an important and alarming finding that needs further investigation.

26 CFR 1.1502-95 - Rules on ceasing to be a member of a consolidated group (or loss subgroup).

Code of Federal Regulations, 2010 CFR

2010-04-01

... (other than the L1 and L2 stock), asset 1 with an adjusted basis of $40 and a fair market value of $15... of the L2 stock to M. At that time, asset 5, which has appreciated in value, has a fair market value... reference to a subgroup section 382 limitation. (2) Election by common parent. Only the common parent (not...

Lower periprosthetic bone loss and good fixation of an ultra-short stem compared to a conventional stem in uncemented total hip arthroplasty.

PubMed

Salemyr, Mats; Muren, Olle; Ahl, Torbjörn; Bodén, Henrik; Eisler, Thomas; Stark, André; Sköldenberg, Olof

2015-01-01

We hypothesized that an ultra-short stem would load the proximal femur in a more physiological way and could therefore reduce the adaptive periprosthetic bone loss known as stress shielding. 51 patients with primary hip osteoarthritis were randomized to total hip arthroplasty (THA) with either an ultra-short stem or a conventional tapered stem. The primary endpoint was change in periprosthetic bone mineral density (BMD), measured with dual-energy x-ray absorptiometry (DXA), in Gruen zones 1 and 7, two years after surgery. Secondary endpoints were change in periprosthetic BMD in the entire periprosthetic region, i.e. Gruen zones 1 through 7, stem migration measured with radiostereometric analysis (RSA), and function measured with self-administered functional scores. The periprosthetic decrease in BMD was statistically significantly lower with the ultra-short stem. In Gruen zone 1, the mean difference was 18% (95% CI: -27% to -10%). In zone 7, the difference was 5% (CI: -12% to -3%) and for Gruen zones 1-7 the difference was also 5% (CI: -9% to -2%). During the first 6 weeks postoperatively, the ultra-short stems migrated 0.77 mm more on average than the conventional stems. 3 months after surgery, no further migration was seen. The functional scores improved during the study and were similar in the 2 groups. Up to 2 years after total hip arthroplasty, compared to the conventional tapered stem the ultra-short uncemented anatomical stem induced lower periprosthetic bone loss and had equally excellent stem fixation and clinical outcome.

Targeting the Adipocyte-Tumor Cell Interaction in Prostate Cancer Treatment

DTIC Science & Technology

2014-10-01

cell of origin 5, it would be of great interest to further investigate whether p62 regulates mesenchymal stem cells in PCa. To start addressing this...Signaling Promotes Inflammation and Tumorigenesis. Cancer Cell 26, 121-135 (2014). 5. Uccelli, A., Moretta, L. & Pistoia, V. Mesenchymal stem cells ...chemotherapeutic approaches. Tasks 6.7. (Aim 2.3) Determine the role of adipose- stem cells (ASC). Since fibroblasts and adipocytes have the same

Intercontinental spread of asian-origin H5N8 to North America through Beringia by migratory birds

USGS Publications Warehouse

Lee, Dong-Hun; Kim Torchetti, Mia; Winker, Kevin; Ip, Hon S.; Swayne, David E.; Song, Chang-Seon

2015-01-01

Phylogenetic network analysis and understanding of waterfowl migration patterns suggest the Eurasian H5N8 clade 2.3.4.4 avian influenza virus emerged in late 2013 in China, spread in early 2014 to South Korea and Japan, and reached Siberia and Beringia by summer 2014 via migratory birds. Three genetically distinct subgroups emerged and subsequently spread along different flyways during fall 2014 into Europe, North America, and East Asia, respectively. All three subgroups reappeared in Japan, a wintering site for waterfowl from Eurasia and parts of North America.

High Blood Pressure Increases the Risk of Poor Outcome at Discharge and 12-month Follow-up in Patients with Symptomatic Intracranial Large Artery Stenosis and Occlusions: Subgroup analysis of the CICAS Study.

PubMed

Yu, Dan-Dan; Pu, Yue-Hua; Pan, Yue-Song; Zou, Xin-Ying; Soo, Yannie; Leung, Thomas; Liu, Li-Ping; Wang, David Z; Wong, Ka-Sing; Wang, Yi-Long; Wang, Yong-Jun

2015-06-01

The purpose of this study was to discuss the relationship between blood pressure and prognosis of patients with symptomatic intracranial arterial stenosis. Data on 2426 patients with symptomatic intracranial large artery stenosis and occlusion who participated in the Chinese Intracranial Atherosclerosis (CICAS) study were analyzed. According to the JNC 7 criteria, blood pressure of all patients was classified into one of the four subgroups: normal, prehypertension, hypertension stage I, and hypertension stage II. Poor outcomes were defined as death and functional dependency (mRS 3-5) at discharge or at 1 year. For patients with intracranial stenosis of 70% to 99%, the rate of poor outcome at discharge was 19.3%, 23.5%, 26.8%, and 39.8% (P = 0.001) for each blood pressure subgroup. For patients with intracranial large artery occlusion, the rates were 17.6%, 22.1%, 29.5%, and 49.8%, respectively (P < 0.0001). The rate of poor outcome at 12-month follow-up was 12.6%, 15.3%, 28.5%, and 27.9% (P = 0.0038) in patients with stenosis of 70% to 99% for each blood pressure subgroup and 11.6%, 21.5%, 23.9%, 35.1% (P < 0.0001) in patients with occlusion. For patients with severe intracranial arterial stenosis or occlusion, higher hypertension stages are associated with an increased risk of poor outcome at discharge and 12-month follow-up. © 2015 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

A novel class of small RNAs bind to MILI protein in mouse testes.

PubMed

Aravin, Alexei; Gaidatzis, Dimos; Pfeffer, Sébastien; Lagos-Quintana, Mariana; Landgraf, Pablo; Iovino, Nicola; Morris, Patricia; Brownstein, Michael J; Kuramochi-Miyagawa, Satomi; Nakano, Toru; Chien, Minchen; Russo, James J; Ju, Jingyue; Sheridan, Robert; Sander, Chris; Zavolan, Mihaela; Tuschl, Thomas

2006-07-13

Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.

The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

PubMed

Ferreyra Solari, Nazarena E; Belforte, Fiorella S; Canedo, Lucía; Videla-Richardson, Guillermo A; Espinosa, Joaquín M; Rossi, Mario; Serna, Eva; Riudavets, Miguel A; Martinetto, Horacio; Sevlever, Gustavo; Perez-Castro, Carolina

2016-09-15

KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use. Cancer Res; 76(18); 5383-94. ©2016 AACR. ©2016 American Association for Cancer Research.

Diabetes mellitus is an independent risk factor for atrial fibrillation in a general Chinese population.

PubMed

Sun, Guozhe; Ma, Mingfeng; Ye, Ning; Wang, Jun; Chen, Yintao; Dai, Dongxue; Sun, Yingxian

2016-09-01

To explore the association between atrial fibrillation (AF) and diabetes mellitus in a general Chinese population, and the influence of hypertension. From January 2013 to August 2013, we carried out a cross-sectional study involving 11,956 permanent residents aged ≥35 years from the general population in the Liaoning province of China (response rate 85.3%). Each participant completed a questionnaire, had a physical examination, and underwent an electrocardiogram and echocardiogram. AF was diagnosed on the basis of the electrocardiogram findings. Logistic regression analyses were carried out to estimate the associations between diabetes mellitus and AF. The associations were also analyzed in hypertensive and normotensive subgroups. There was a higher prevalence of AF in participants with diabetes mellitus than those without diabetes mellitus (1.2 vs 0.5%; P = 0.004). In the hypertensive subgroup, the prevalence of AF in participants with diabetes mellitus was significantly higher than in participants without diabetes mellitus (1.5 vs 0.6%; P = 0.008); however, the prevalences were similar in the normotensive subgroup (0.3 vs 0.4%; P = 1.000). Similar trends were present in both men and women. After adjustment for cardiovascular risk factors, the independent association between diabetes mellitus and AF remained in the total sample (odds ratio 2.33, 95% confidence interval 1.20-4.54) and hypertensive subgroup (odds ratio 3.15, 95% confidence interval 1.52-6.56), but not in the normotensive subgroup (odds ratio 0.64, 95% confidence interval 0.08-5.31). Diabetes mellitus is an independent risk factor for AF in the general population in China, this association was present in total and hypertensive participants, but not in normotensive participants. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

High School STEM Teachers' Perceptions of the Work Environment

ERIC Educational Resources Information Center

Pedersen, Daphne E.; West, Robert R.

2017-01-01

How do secondary STEM teachers perceive the environments in which they teach? To what degree is STEM teaching at the secondary level situated in a gendered workplace organization? Using data from the 1999-2000 Schools and Staffing Survey, we examined how men and women who were full-time secondary school teachers in STEM fields (N = 5,617)…

76 FR 3913 - Advisory Council on Blood Stem Cell Transplantation; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-21

... Council on Blood Stem Cell Transplantation; Notice of Meeting In accordance with section 10(a)(2) of the...: Advisory Council on Blood Stem Cell Transplantation. Date and Time: February 4, 2011, from 3 p.m. to 5 p.m. EST. ACTION: Notice of Advisory Council on Blood Stem Cell Transplantation (ACBSCT) Meeting to be Held...

Stem geometry changes initial femoral fixation stability of a revised press-fit hip prosthesis: A finite element study.

PubMed

Russell, Robert D; Huo, Michael H; Rodrigues, Danieli C; Kosmopoulos, Victor

2016-11-14

Stable femoral fixation during uncemented total hip arthroplasty is critical to allow for subsequent osseointegration of the prosthesis. Varying stem designs provide surgeons with multiple options to gain femoral fixation. The purpose of this study was to compare the initial fixation stability of cylindrical and tapered stem implants using two different underreaming techniques (press-fit conditions) for revision total hip arthroplasty (THA). A finite element femur model was created from three-dimensional computed tomography images simulating a trabecular bone defect commonly observed in revision THA. Two 18-mm generic femoral hip implants were modeled using the same geometry, differing only in that one had a cylindrical stem and the other had a 2 degree tapered stem. Surgery was simulated using a 0.05-mm and 0.01-mm press-fit and tested with a physiologically relevant loading protocol. Mean contact pressure was influenced more by the surgical technique than by the stem geometry. The 0.05-mm press-fit condition resulted in the highest contact pressures for both the cylindrical (27.35 MPa) and tapered (20.99 MPa) stems. Changing the press-fit to 0.01-mm greatly decreased the contact pressure by 79.8% and 78.5% for the cylindrical (5.53 MPa) and tapered (4.52 MPa) models, respectively. The cylindrical stem geometry consistently showed less relative micromotion at all the cross-sections sampled as compared to the tapered stem regardless of press-fit condition. This finite element analysis study demonstrates that tapered stem results in lower average contact pressure and greater micromotion at the implant-bone interface than a cylindrical stem geometry. More studies are needed to establish how these different stem geometries perform in such non-ideal conditions encountered in revision THA cases where less bone stock is available.

Sox2+ Stem Cells Contribute to All Epithelial Lineages of the Tooth via Sfrp5+ Progenitors

PubMed Central

Juuri, Emma; Saito, Kan; Ahtiainen, Laura; Seidel, Kerstin; Tummers, Mark; Hochedlinger, Konrad; Klein, Ophir D.; Thesleff, Irma; Michon, Frederic

2012-01-01

SUMMARY The continuously growing mouse incisor serves as a valuable model to study stem cell regulation during organ renewal. Epithelial stem cells are localized in the proximal end of the incisor in the labial cervical loop. Here, we show that the transcription factor Sox2 is a specific marker for these stem cells. Sox2+ cells became restricted to the labial cervical loop during tooth morphogenesis, and they contributed to the renewal of enamel-producing ameloblasts as well as all other epithelial cell lineages of the tooth. The early progeny of Sox2-positive stem cells transiently expressed the Wnt inhibitor Sfrp5. Sox2 expression was regulated by the tooth initiation marker FGF8 and specific miRNAs, suggesting a fine-tuning to maintain homeostasis of the dental epithelium. The identification of Sox2 as a marker for the dental epithelial stem cells will facilitate further studies on their lineage segregation and differentiation during tooth renewal. PMID:22819339

Victimization and health risk factors among weapon-carrying youth.

PubMed

Stayton, Catherine; McVeigh, Katharine H; Olson, E Carolyn; Perkins, Krystal; Kerker, Bonnie D

2011-11-01

To compare health risks of 2 subgroups of weapon carriers: victimized and nonvictimized youth. 2003-2007 NYC Youth Risk Behavior Surveys were analyzed using bivariate analyses and multinomial logistic regression. Among NYC teens, 7.5% reported weapon carrying without victimization; 6.9% reported it with victimization. Both subgroups were more likely than non-weapon carriers to binge drink, use marijuana, smoke, fight, and have multiple sex partners; weapon carriers with victimization also experienced persistent sadness and attempted suicide. Subgroups of weapon carriers have distinct profiles. Optimal response should pair disciplinary action with screening for behavioral and mental health concerns and victimization.

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

PubMed Central

Feng, Yongjia; Barrett, Meredith; Hou, Yue; Yoon, Hong Keun; Ochi, Takanori

2015-01-01

Feeding strategies to care for patients who transition from enteral nutrient deprivation while on total parenteral nutrition (TPN) to enteral feedings generally proceed to full enteral nutrition once the gastrointestinal tract recovers; however, an increasing body of literature suggests that a subgroup of patients may actually develop an increased incidence of adverse events, including death. To examine this further, we studied the effects of acute refeeding in a mouse model of TPN. Interestingly, refeeding led to some beneficial effects, including prevention in the decline in intestinal epithelial cell (IEC) proliferation. However, refeeding led to a significant increase in mucosal expression of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), as well as an upregulation in Toll-like receptor 4 (TLR-4). Refeeding also failed to prevent TPN-associated increases in IEC apoptosis, loss of epithelial barrier function, and failure of the leucine-rich repeat-containing G protein-coupled receptor 5-positive stem cell expression. Transitioning from TPN to enteral feedings led to a partial restoration of the small bowel microbial population. In conclusion, while acute refeeding led to some restoration of normal gastrointestinal physiology, enteral refeeding led to a significant increase in mucosal inflammatory markers and may suggest alternative strategies to enteral refeeding should be considered. PMID:26635320

Relationship between biometric characteristics and stem size of uncemented hip prostheses.

PubMed

De Clerico, Manuela; Bordini, Barbara; Stea, Susanna; Viceconti, Marco; Toni, Aldo

2007-06-01

The authors examined 2329 uncemented hip prosthesis stems (AncaFit stem, Wright Medical Technology, Arlington, TN, USA) implanted between 1996 and 2004 due to primary coxarthrosis. This is the most commonly used stem in the Emilia-Romagna region, in northern Italy, according to data from the Register of Orthopaedic Prosthetic Implants (RIPO). It is produced in eight sizes for each side. We analyzed the relationship between stem size and anthropometric data. Among the patients, 49.5% were men and 50.5% were women; mean age at surgery was 64.1 years (SD 9.1); mean height was 167 cm (SD 8.4), and mean weight was 75.7 kg (SD 12.7). Multifactorial analysis demonstrated that stem size was influenced by sex, age, and height, but not by weight. Besides this, there was an interaction between sex and age: in women, but not in men, the stem size increased with aging.

Reproducibility of femoral offset following short stem and straight stem total hip arthroplasty.

PubMed

von Roth, Philipp; Perka, Carsten; Mayr, Hermann O; Preininger, Bernd; Ziebula, Friedrich; Matziolis, Georg; Hube, Robert

2014-07-01

Bone stock-preserving short stem prostheses have gained importance in total hip arthroplasty (THA) with the use of minimally invasive surgical procedures. Because of their metaphyseal fixation and their dependency on the calcar radius, it is unknown whether the femoral offset can be reproduced with the same accuracy following short stem vs standard stem THA. This study clarifies whether it is possible to restore the femoral offset using a short stem prosthesis (Fitmore; Zimmer, Warsaw, Indiana) compared with a conventional straight stem prosthesis (CLS; Zimmer) following minimally invasive implantation using an anterolateral approach. In a prospective, randomized, double-blinded study, 80 patients underwent THA using a short stem (SS group; n=40) or CLS implant (control group; n=40). Follow-up examinations were conducted 6 weeks postoperatively. Radiological and functional outcomes were measured. Subjective assessment of quality of life was evaluated using the Harris Hip Score (HHS), the Short Form 36-item health survey (SF-36), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pre- and postoperative comparison of the groups' change in offset showed no significant differences (SS group difference from pre- to postoperative, 6.1±6.5 mm; control group difference from pre- to postoperative, 6.5±7.1 mm; P=.93). Group comparison after 6 weeks revealed no significant differences in HHS, SF-36, or WOMAC. Based on these data, an equivalent reproducibility of the femoral offset was demonstrated following short stem and straight stem THA using a minimally invasive anterolateral approach. If the long-term results of short stems show a comparable survival, they represent a sensible alternative to standard stems. Copyright 2014, SLACK Incorporated.

Early subsidence of shape-closed hip arthroplasty stems is associated with late revision. A systematic review and meta-analysis of 24 RSA studies and 56 survival studies.

PubMed

van der Voort, Paul; Pijls, Bart G; Nieuwenhuijse, Marc J; Jasper, Jorrit; Fiocco, Marta; Plevier, Josepha W M; Middeldorp, Saskia; Valstar, Edward R; Nelissen, Rob G H H

2015-01-01

Few studies have addressed the association between early migration of femoral stems and late aseptic revision in total hip arthroplasty. We performed a meta-regression analysis on 2 parallel systematic reviews and meta-analyses to determine the association between early migration and late aseptic revision of femoral stems. Of the 2 reviews, one covered early migration data obtained from radiostereometric analysis (RSA) studies and the other covered long-term aseptic revision rates obtained from survival studies with endpoint revision for aseptic loosening. Stems were stratified according to the design concept: cemented shape-closed, cemented force-closed, and uncemented. A weighted regression model was used to assess the association between early migration and late aseptic revision, and to correct for confounders. Thresholds for acceptable and unacceptable migration were determined in accordance with the national joint registries (≤ 5% revision at 10 years) and the NICE criteria (≤ 10% revision at 10 years). 24 studies (731 stems) were included in the RSA review and 56 studies (20,599 stems) were included in the survival analysis review. Combining both reviews for the 3 design concepts showed that for every 0.1-mm increase in 2-year subsidence, as measured with RSA, there was a 4% increase in revision rate for the shape-closed stem designs. This association remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. The threshold for acceptable migration of shape-closed designs was defined at 0.15 mm; stems subsiding less than 0.15 mm in 2 years had revision rates of less than 5% at 10 years, while stems exceeding 0.15 mm subsidence had revision rates of more than 5%. There was a clinically relevant association between early subsidence of shape-closed femoral stems and late revision for aseptic loosening. This association can be used to assess the safety of shape-closed stem designs. The published research is not sufficient to allow us to make any conclusions regarding such an association for the force-closed and uncemented stems.

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

PubMed Central

Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

2014-01-01

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

Primary cultures of human colon cancer as a model to study cancer stem cells.

PubMed

Koshkin, Sergey; Danilova, Anna; Raskin, Grigory; Petrov, Nikolai; Bajenova, Olga; O'Brien, Stephen J; Tomilin, Alexey; Tolkunova, Elena

2016-09-01

The principal cause of death in cancer involves tumor progression and metastasis. Since only a small proportion of the primary tumor cells, cancer stem cells (CSCs), which are the most aggressive, have the capacity to metastasize and display properties of stem cells, it is imperative to characterize the gene expression of diagnostic markers and to evaluate the drug sensitivity in the CSCs themselves. Here, we have examined the key genes that are involved in the progression of colorectal cancer and are expressed in cancer stem cells. Primary cultures of colorectal cancer cells from a patient's tumors were studied using the flow cytometry and cytological methods. We have evaluated the clinical and stem cell marker expression in these cells, their resistance to 5-fluorouracil and irinotecan, and the ability of cells to form tumors in mice. The data shows the role of stem cell marker Oct4 in the resistance of primary colorectal cancer tumor cells to 5-fluorouracil.

Reactive oxygen species in human semen in relation to leukocyte contamination.

PubMed

Oborna, Ivana; Fingerova, Helena; Novotny, Jiri; Brezinova, Jana; Svobodova, Magda; Aziz, Nabil

2009-03-01

Excessive production of reactive oxygen species (ROS) in semen has been linked to male infertility. Main sources of ROS in male genital tract are immature and/or damaged spermatozoa and a subpopulation of leukocytes known as polymorphonuclear neutrophils (PMN). Study group included male partners of infertile couples, 67 normospermic males (group B) and 98 males with sperm abnormalities in one or more parameters (group C), 36 fertile volunteers (group A) served as controls. Sperm parameters were determined according to WHO guidelines. The ROS production was measured by chemiluminiscence in sperm suspension in phosphate buffered saline. All fertile volunteers in the control group had seminal PMN concentrations below 0.5x10(6)/ml. Therefore study subjects, 67 normospermic and 98 men with sperm abnormalities, were further subdivided into two subgroups of PMN concentrations: (1) < 0.5x10(6)/ml and (2) 0.5 to 1.0x10(6)/ml. The ROS production in individuals varied greatly from 1.0x10(2) to 1.7 x10(7) RLU/min per 20x10(6) spermatozoa. The ROS production in both subgroups of normospermic men and the subgroup (1) of men with sperm abnormalities was not different from the ROS production in fertile controls. The ROS production in the subgroup (2) with sperm abnormalities was significantly higher than in controls (P = 0.00004). Our findings suggest that the contribution of PMN to the ROS production in semen is negligible only up to a concentration of 0.5x10(6)/ml. This suggests that the current WHO Guidelines threshold of 1.0x10(6) PMN per ml of semen is too high and might be re-evaluated.

Efficacy of 1% Metformin Gel in Patients With Moderate and Severe Chronic Periodontitis: A Randomized Controlled Clinical Trial.

PubMed

Pradeep, A R; Patnaik, Kaushik; Nagpal, Kanika; Karvekar, Shruti; Guruprasad, C N; Kumaraswamy, K M

2017-10-01

The aim of this study is to investigate efficacy of metformin (MF) 1% gel as an adjunct to scaling and root planing (SRP) in the treatment of moderate and severe chronic periodontitis (CP). Seventy patients were categorized into two treatment groups: 1) SRP plus 1% MF and 2) SRP plus placebo. Clinical parameters were recorded at baseline and 3, 6, and 9 months. They included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). Radiologic assessment of intrabony defects (IBDs) and percentage defect depth reduction (DDR%) was done at baseline and 6- and 9-month intervals using computer-aided software. PD, CAL, and DDR% were evaluated in two subgroups in both the placebo and MF group: 1) initial PD of 5 to 7 mm and 2) initial PD of >7 mm. Mean PD reduction and mean CAL gain was found to be greater in the MF group than the placebo group at all visits. Clinical parameters (PD, CAL) in both subgroups, with initial PDs of 5 to 7 and >7 mm, showed significant improvement in the 1% MF group compared with the placebo group. A significantly greater mean DDR% was found in the MF group than the placebo group at 6 and 9 months in both subgroups, 5 to 7 and >7 mm of initial PD. There was a greater decrease in PD and more CAL gain with significant IBD depth reduction at sites treated with SRP plus locally delivered MF in patients with CP in both initial PD = 5 to 7 and >7 mm subgroups compared with placebo.

Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking

PubMed Central

Taniguchi Ishikawa, E.; Chang, K.H.; Nayak, R.; Olsson, H.A; Ficker, A.; Dunn, S.K.; Madhu, M.; Sengupta, A.; Whitsett, J.A.; Grimes, H.L.; Cancelas, J.A.

2013-01-01

Kruppel-like factor 5 (Klf5) regulates pluripotent stem cell self-renewal but its role in somatic stem cells is unknown. Here we show that Klf5 deficient haematopoietic stem cells and progenitors (HSC/P) fail to engraft after transplantation. This HSC/P defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, and with decreased adhesion to fibronectin and expression of membrane-bound β1/β2-integrins. In vivo inducible gain-of-function of Klf5 in HSCs increases HSC/P adhesion. The expression of Rab5 family members, mediators of β1/β2-integrin recycling in the early endosome, is decreased in Klf5Δ/Δ HSC/Ps. Klf5 binds directly to the promoter of Rab5a/b and overexpression of Rab5b rescues the expression of activated β1/β2-integrins, adhesion and bone marrow homing of Klf5Δ/Δ HSC/Ps. Altogether, these data indicate that Klf5 is indispensable for adhesion, homing, lodging and retention of HSC/Ps in the bone marrow through Rab5-dependent post-translational regulation of β1/β2 integrins. PMID:23552075

Detection of siRNA Mediated Target mRNA Cleavage Activities in Human Cells by a Novel Stem-Loop Array RT-PCR Analysis

DTIC Science & Technology

2016-09-07

sequences of the target mRNA, and a double stranded stem at the 5′ end that forms a stem -loop to function as a forceps to stabilize the secondary...E-mjournal homepage: www.elsevier.com/locate/bbrepDetection of siRNA-mediated target mRNA cleavage activities in human cells by a novel stem -loop...challenges for the accurate and efficient detection and verification of cleavage sites on target mRNAs. Here we used a sensitive stem -loop array reverse

Application of adipocyte-derived stem cells in treatment of cutaneous radiation syndrome.

PubMed

Riccobono, Diane; Agay, Diane; Scherthan, Harry; Forcheron, Fabien; Vivier, Mylène; Ballester, Bruno; Meineke, Viktor; Drouet, Michel

2012-08-01

Cutaneous radiation syndrome caused by local high dose irradiation is characterized by delayed outcome and incomplete healing. Recent therapeutic management of accidentally irradiated burn patients has suggested the benefit of local cellular therapy using mesenchymal stem cell grafting. According to the proposed strategy of early treatment, large amounts of stem cells would be necessary in the days following exposure and hospitalization, which would require allogeneic stem cells banking. In this context, the authors compared the benefit of local autologous and allogeneic adipocyte-derived stem cell injection in a large animal model. Minipigs were locally irradiated using a 60Co gamma source at a dose of 50 Gy and divided into three groups. Two groups were grafted with autologous (n = 5) or allogeneic (n = 5) adipocyte-derived stem cells four times after the radiation exposure, whereas the control group received the vehicle without cells (n = 8). A clinical score was elaborated to compare the efficiency of the three treatments. All controls exhibited local inflammatory injuries leading to a persistent painful necrosis, thus mimicking the clinical evolution in human victims. In the autologous adipocyte-derived stem cells group, skin healing without necrosis or uncontrollable pain was observed. In contrast, the clinical outcome was not significantly different in the adipocyte-derived stem cell allogeneic group when compared with controls. This study suggests that autologous adipocyte-derived stem cell grafting improves cutaneous radiation syndrome wound healing, whereas allogeneic adipocyte derived stem cells do not. Further studies will establish whether manipulation of allogeneic stem cells will improve their therapeutic potential.

Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia in adult rats.

PubMed

Omori, Yoshinori; Honmou, Osamu; Harada, Kuniaki; Suzuki, Junpei; Houkin, Kiyohiro; Kocsis, Jeffery D

2008-10-21

The systemic injection of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has therapeutic benefits after cerebral artery occlusion in rats, and may have multiple therapeutic effects at various sites and times within the lesion as the cells respond to a particular pathological microenvironment. However, the comparative therapeutic benefits of multiple injections of hMSCs at different time points after cerebral artery occlusion in rats remain unclear. In this study, we induced middle cerebral artery occlusion (MCAO) in rats using intra-luminal vascular occlusion, and infused hMSCs intravenously at a single 6 h time point (low and high cell doses) and various multiple time points after MCAO. From MRI analyses lesion volume was reduced in all hMSC cell injection groups as compared to serum alone injections. However, the greatest therapeutic benefit was achieved following a single high cell dose injection at 6 h post-MCAO, rather than multiple lower cell infusions over multiple time points. Three-dimensional analysis of capillary vessels in the lesion indicated that the capillary volume was equally increased in all of the cell-injected groups. Thus, differences in functional outcome in the hMSC transplantation subgroups are not likely the result of differences in angiogenesis, but rather from differences in neuroprotective effects.

Conditioning a segmented stem profile model for two diameter measurements

Treesearch

Raymond L. Czaplewski; Joe P. Mcclure

1988-01-01

The stem profile model of Max and Burkhart (1976) is conditioned for dbh and a second upper stem measurement. This model was applied to a loblolly pine data set using diameter outside bark at 5.3m (i.e., height of 17.3 foot Girard form class) as the second upper stem measurement, and then compared to the original, unconditioned model. Variance of residuals was reduced...

Psychostimulants: Influence on Body Mass Index and Height in a Pediatric Population with Attention-Deficit/Hyperactivity Disorder?

PubMed

Lentferink, Yvette E; van de Garde, Ewoudt M W; Knibbe, Catherijne A J; van der Vorst, Marja M J

2018-05-16

Attention-deficit/hyperactivity disorder (ADHD) is often treated with psychostimulants. Psychostimulants' adverse effects on body mass index standard deviation score (BMI-sds) and height in children/adolescents with ADHD have been reported. However, literature is inconsistent, and it is unclear whether the observed effects are dosage- and/or BMI-dependent. Therefore, the aim of this retrospective observational study is to evaluate the influence of psychostimulants on BMI-sds and height-sds in a pediatric cohort with ADHD from an outpatient clinic, and to study the correlation between psychostimulant dosage and BMI-sds and height-sds change. Participants ≤18 years of age diagnosed with ADHD who started with psychostimulants (methylphenidate) were studied. Changes in BMI-sds and height-sds over an 18-month treatment period were assessed in subgroups according to baseline BMI-sds, gender, and age. Furthermore, correlations between BMI-sds, height-sds, and psychostimulant dose were studied. In total, 298 participants [median age 9.8 years, height-sds 0.0, BMI-sds 0.5, psychostimulant dosage 0.5 (0.2-1.4) mg/kg/day] were analyzed, with an underweight, overweight, and obesity prevalence of 5%, 21%, and 7%, respectively. After 18 months of treatment a significant decline in BMI-sds (-0.4) and height-sds (-0.2) was observed. These effects were consistent in all subgroups except for no change in BMI-sds in the underweight subgroup and no change in height-sds in the overweight subgroup. Medication dosage was weakly correlated with change in BMI-sds [r = -0.3 (-0.9 to +0.5); p < 0.01] and height-sds [r = -0.2 (-0.4 to -0.1); p = 0.01]. After 18 months of psychostimulant treatment, a significant decline in BMI-sds and height-sds was observed. However, the correlation with psychostimulant dosage was weak, and the decline was not observed in all subgroups. Therefore, further studies on the etiology of BMI-change are warranted, particularly with regard to the ADHD symptoms.

Mechanism and stem-cell activity of 5-carboxycytosine decarboxylation determined by isotope tracing.

PubMed

Schiesser, Stefan; Hackner, Benjamin; Pfaffeneder, Toni; Müller, Markus; Hagemeier, Christian; Truss, Matthias; Carell, Thomas

2012-06-25

Eraserhead: Stem cells seem to erase epigenetic information by decarboxylation of the newly discovered epigenetic base 5-carboxycytosine (caC; see picture). This reaction is likely to involve a nucleophilic attack of the C5-C6 double bond. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Brain stem serotonin protects blood pressure in neonatal rats exposed to episodic anoxia.

PubMed

Yang, Hsiao T; Cummings, Kevin J

2013-12-01

In neonatal rodents, a loss of brain stem serotonin [5-hydroxytryptamine (5-HT)] in utero or at birth compromises anoxia-induced gasping and the recovery of heart rate (HR) and breathing with reoxygenation (i.e., autoresuscitation). How mean arterial pressure (MAP) is influenced after an acute loss of brain stem 5-HT content is unknown. We hypothesized that a loss of 5-HT for ∼1 day would compromise MAP during episodic anoxia. We injected 6-fluorotryptophan (20 mg/kg ip) into rat pups (postnatal days 9-10 or 11-13, n = 22 treated, 24 control), causing a ∼70% loss of brain stem 5-HT. Pups were exposed to a maximum of 15 anoxic episodes, separated by 5 min of room air to allow autoresuscitation. In younger pups, we measured breathing frequency and tidal volume using "head-out" plethysmography and HR from the electrocardiogram. In older pups, we used whole body plethysmography to detect gasping, while monitoring MAP. Gasp latency and the time required for respiratory, HR, and MAP recovery following each episode were determined. Despite normal gasp latency, breathing frequency and a larger tidal volume (P < 0.001), 5-HT-deficient pups survived one-half the number of episodes as controls (P < 0.001). The anoxia-induced decrease in MAP experienced by 5-HT-deficient pups was double that of controls (P = 0.017), despite the same drop in HR (P = 0.48). MAP recovery was delayed ∼10 s by 5-HT deficiency (P = 0.001). Our data suggest a loss of brain stem 5-HT leads to a pronounced, premature loss of MAP in response to episodic anoxia. These data may help explain why some sudden infant death syndrome cases die from what appears to be cardiovascular collapse during apparent severe hypoxia.

Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia.

PubMed

Sun, Heng; Miao, Zhengqiang; Zhang, Xin; Chan, Un In; Su, Sek Man; Guo, Sen; Wong, Chris Koon Ho; Xu, Xiaoling; Deng, Chu-Xia

2018-06-01

The mammary gland is very intricately and well organized into distinct tissues, including epithelia, endothelia, adipocytes, and stromal and immune cells. Many mammary gland diseases, such as breast cancer, arise from abnormalities in the mammary epithelium, which is mainly composed of two distinct lineages, the basal and luminal cells. Because of the limitation of traditional transcriptome analysis of bulk mammary cells, the hierarchy and heterogeneity of mammary cells within these two lineages remain unclear. To this end, using single-cell RNA-Seq coupled with FACS analysis and principal component analysis, we determined gene expression profiles of mammary epithelial cells of virgin and pregnant mice. These analyses revealed a much higher heterogeneity among the mammary cells than has been previously reported and enabled cell classification into distinct subgroups according to signature gene markers present in each group. We also identified and verified a rare CDH5 + cell subpopulation within a basal cell lineage as quiescent mammary stem cells (MaSCs). Moreover, using pseudo-temporal analysis, we reconstructed the developmental trajectory of mammary epithelia and uncovered distinct changes in gene expression and in biological functions of mammary cells along the developmental process. In conclusion, our work greatly refines the resolution of the cellular hierarchy in developing mammary tissues. The discovery of CDH5 + cells as MaSCs in these tissues may have implications for our understanding of the initiation, development, and pathogenesis of mammary tumors. © 2018 Sun et al.

A single clone of Acinetobacter baumannii, ST22, is responsible for high antimicrobial resistance rates of Acinetobacter spp. isolates that cause bacteremia and urinary tract infections in Korea.

PubMed

Park, Young Kyoung; Lee, Gyu Hong; Baek, Jin Yang; Chung, Doo Ryeon; Peck, Kyong Ran; Song, Jae-Hoon; Ko, Kwan Soo

2010-06-01

We investigated the characteristics of a total of 96 Acinetobacter spp. isolates that were shown to cause bacteremia and urinary tract infections (UTIs) from 10 university hospitals located in various regions of Korea from November 2006 to August 2007. The antimicrobial susceptibilities of these isolates were determined using a broth microdilution method, and the species were identified using molecular identification. In addition, we performed multilocus sequence typing for Acinetobacter baumannii subgroup A isolates. A. baumannii subgroup A was the most prevalent in patients with both bacteremia (32 isolates, 53.3%) and UTIs (20 isolates, 55.6%), followed by Acinetobacter genomic species 13TU (15.0% and 27.8% in bacteremia and UTIs, respectively). A. baumannii subgroup B and Acinetobacter junii were found exclusively in isolates causing bacteremia (seven and five isolates, respectively). Among 96 Acinetobacter spp. isolates, 19.8% were resistant to imipenem and 25.0% were resistant to meropenem. Most carbapenem-resistant A. baumannii isolates contained PER or oxacillinase-23-like enzymes (65.2% and 78.3%, respectively). In addition, 13.5% were resistant to polymyxin B and 17.7% were resistant to colistin. A. baumannii subgroup A isolates (52 isolates, 54.2%) showed higher resistance rates to most antimicrobial agents than other species, but not to colistin. Among A. baumannii subgroup A isolates, ST22 was the most prevalent genotype (33 isolates, 63.5%) and showed higher resistance rates to all antimicrobial agents than the other genotypes. In addition, four out of five polymyxin-resistant A. baumannii group A isolates belonged to ST22. Thus, dissemination of the main clone of A. baumannii, ST22, may contribute to the high resistance rates of Acinetobacter isolates to antimicrobials, including carbapenems, in Korea.

Characterization of genes encoding ABA 8'-hydroxylase in ethylene-induced stem growth of deepwater rice (Oryza sativa L.).

PubMed

Yang, Seung-Hwan; Choi, Dongsu

2006-11-24

Ethylene and submergence enhance stem elongation of deepwater rice, at least in part, by reducing in the internode the endogenous abscisic acid (ABA) content and increasing the level of gibberellin A1 (GA1). We cloned and characterized the CYP707A5 and CYP707A6 genes, which encode putative ABA 8'-hydroxylase, the enzyme that catalyzes the oxidation of ABA. Expression of CYP707A5 was upregulated significantly by ethylene treatment, whereas that of CYP707A6 was not altered. Recombinant proteins from both genes expressed in yeast cells showed activity of ABA 8'-hydroxylase. This finding indicates that CYP707A5 may play a role in ABA catabolism during submergence- or ethylene-induced stem elongation in deepwater rice. Taken together, these results provide links between the molecular mechanisms and physiological phenomena of submergence- and ethylene-induced stem elongation in deepwater rice.

Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide.

PubMed

Arango, Marcos; Combariza, Juan F

2017-06-01

Noninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients. A retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out. Thirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5h (range, 9.5-100h) and median peak temperature was 39.0°C (range, 38.1-40.5°C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion. Fever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Evaluation of the correlation between insulin like factor 3, polycystic ovary syndrome, and ovarian maldescent.

PubMed

Seyam, Emaduldin; Hefzy, Enas

2018-06-01

The aim of this study was to investigate a proposed correlation between the incidentally discovered undescended ovaries and their confirmed diagnosis as a polycystic ovary disease (PCOD) for all cases included, and to evaluate the role of estimated insulin like factor 3 (INSL3) circulating level in the pathogenesis of both abnormal findings. The study group (A) comprised 35 women whose ovaries had been incidentally found to be undescended during the routine laparoscopy for infertility causes, and all had been diagnosed as PCOD. The control category included two subgroups; subgroup (B) included 35 women group, diagnosed as PCOD but with normally allocated ovaries in the true pelvis, and subgroup (C) included 35 healthy women with regular menses and no signs of hyperandrogenism. Correlations between the level of INSL3 and other PCOD relevant biochemical tests: [e.g. BMI, waist-to-hip ratio (WHR), LH, FSH, androstendione (A), total and free testosterone (T & Ft), DHEA-S, and SHBG] had been also investigated. INSL3 levels were significantly higher in PCOD groups (A) and (B) compared to the healthy fertile control subgroup (C) (80.5 ± 29.4, 65.11 ± 15.6, and 41.11 ± 10.2 pg/mL, respectively), and was highest in group (A). Moreover, we identified a strong correlation between INSL3 and androstenedione (r = 0.42, p = 0.0012), and free (r = 0.42, p = .0123) and total testosterone (r = 0.41, p = .004) in the PCOD (A) and (B) subgroup compared to the levels in subgroup (C). LH was significantly higher in all PCOD women in groups (A&B) (12. 3 ± 3.4, and 11.2 ± 1.4 mIU/L, respectively) compared to those in group (A) (5.7 ± 2.5 mIU/L), with a fair correlation with INSL3. However, there was no statistically significant correlation between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR in all PCOD women. The strong positive correlation between INSL3, and high ovarian androgens levels in all PCOD women, which appeared clearly in undescended polycystic ovaries could support the proposed syndrome hypothesis between those abnormal findings.

Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases.

PubMed

Maas, Roderick P P W M; Muller-Hansma, Annemarie H G; Esselink, Rianne A J; Murk, Jean-Luc; Warnke, Clemens; Killestein, Joep; Wattjes, Mike P

2016-10-01

The implementation of a variety of immunosuppressive therapies has made drug-associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug-related PML lesions.

[The effects of infrasound on the blood coagulation function of guinea pigs].

PubMed

Ma, Wen-min; Qi, Peng; Zhang, Jian-zhong; Yi, Yong; Chen, Xing-ming; Zhang, Jun; Han, Rui-gang

2011-03-01

To study the change of the blood coagulation function of guinea pigs exposed to 16 Hz/120 dB, 16 Hz/125 dB infrasound and to explore the mechanism of circulation system damage. Seventy-two guinea pigs were divided into 3 groups: the control group, the group exposed to 16 Hz/120 dB infrasound for 1.5 h a day and the group exposed to 16 Hz/125 dB infrasound for 1.5 h a day. Each exposure group was divided into 4 sub-groups (8 guinea pigs a sub-group) which were exposed to infrasound for 1, 7, 14 and 21 d, respectively. The coagulation function and serum nitric oxide (NO) were measured for control group and all sub-groups after exposure to infrasound. The prothrombin time (PT), international normalized ratio (INR) and serum NO of group exposed to 16 Hz/125 dB infrasound were (31.16 ± 3.05) s, 2.53 ± 1.21 and (88.304 ± 52.601) µmol/L, respectively, which were significantly higher than those [(21.36 ± 0.10) s, 1.65 ± 0.07 and (30.943 ± 26.864) µmol/L] of control group (P < 0.05). PT and INR of sub-groups exposed to 16 Hz/125 dB infrasound for 14 and 21 d were significantly higher than those of control group. NO of sub-groups exposed to 16 Hz/125 dB infrasound for 1 week and 2 weeks were significantly higher than that of control group (P < 0.05), but NO of sub-group exposed to 16 Hz/125 dB infrasound for 3 weeks decreased slightly. The blood coagulation function of guinea pigs exposed to 16 Hz/125 dB infrasound decreased, PT and INR may be used as the indexes to assess of blood coagulation function change induced by the infrasound exposure.

Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

How young can children reliably and validly self-report their health-related quality of life?: an analysis of 8,591 children across age subgroups with the PedsQL 4.0 Generic Core Scales.

PubMed

Varni, James W; Limbers, Christine A; Burwinkle, Tasha M

2007-01-03

The last decade has evidenced a dramatic increase in the development and utilization of pediatric health-related quality of life (HRQOL) measures in an effort to improve pediatric patient health and well-being and determine the value of healthcare services. The emerging paradigm shift toward patient-reported outcomes (PROs) in clinical trials has provided the opportunity to further emphasize the value and essential need for pediatric patient self-reported outcomes measurement. Data from the PedsQL DatabaseSM were utilized to test the hypothesis that children as young as 5 years of age can reliably and validly report their HRQOL. The sample analyzed represented child self-report age data on 8,591 children ages 5 to 16 years from the PedsQL 4.0 Generic Core Scales DatabaseSM. Participants were recruited from general pediatric clinics, subspecialty clinics, and hospitals in which children were being seen for well-child checks, mild acute illness, or chronic illness care (n = 2,603, 30.3%), and from a State Children's Health Insurance Program (SCHIP) in California (n = 5,988, 69.7%). Items on the PedsQL 4.0 Generic Core Scales had minimal missing responses for children as young as 5 years old, supporting feasibility. The majority of the child self-report scales across the age subgroups, including for children as young as 5 years, exceeded the minimum internal consistency reliability standard of 0.70 required for group comparisons, while the Total Scale Scores across the age subgroups approached or exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scale scores. Construct validity was demonstrated utilizing the known groups approach. For each PedsQL scale and summary score, across age subgroups, including children as young as 5 years, healthy children demonstrated a statistically significant difference in HRQOL (better HRQOL) than children with a known chronic health condition, with most effect sizes in the medium to large effect size range. The results demonstrate that children as young as the 5 year old age subgroup can reliably and validly self-report their HRQOL when given the opportunity to do so with an age-appropriate instrument. These analyses are consistent with recent FDA guidelines which require instrument development and validation testing for children and adolescents within fairly narrow age groupings and which determine the lower age limit at which children can provide reliable and valid responses across age categories.

Organotypic distribution of stem cell markers in formalin-fixed brain harboring glioblastoma multiforme.

PubMed

Schrot, Rudolph J; Ma, Joyce H; Greco, Claudia M; Arias, Angelo D; Angelastro, James M

2007-11-01

The role of stem cells in the origin, growth patterns, and infiltration of glioblastoma multiforme is a subject of intense investigation. One possibility is that glioblastoma may arise from transformed stem cells in the ventricular zone. To explore this hypothesis, we examined the distribution of two stem cell markers, activating transcription factor 5 (ATF5) and CD133, in an autopsy brain specimen from an individual with glioblastoma multiforme. A 41-year-old male with a right posterior temporal glioblastoma had undergone surgery, radiation, and chemotherapy. The brain was harvested within several hours after death. After formalin fixation, sectioning, and mapping of tumor location in the gross specimen, histologic specimens were prepared from tumor-bearing and grossly normal hemispheres. Fluorescence immunohistochemistry and colorimetric staining were performed for ATF5 and CD133. Both markers co-localized to the ependymal and subependymal zones on the side of the tumor, but not in the normal hemisphere or more rostrally in the affected hemisphere. ATF5 staining was especially robust within the diseased hemisphere in histologically normal ependyma. To our knowledge, this is the first in situ demonstration of stem cell markers in whole human brain. These preliminary results support the hypothesis that some glioblastomas may arise from the neurogenic zone of the lateral ventricle. The robust staining for ATF5 and CD133 in histologically normal ventricular zone suggests that an increase in periventricular stem cell activity occurred in this patient on the side of the tumor, either as a localized response to brain injury or as an integral component of oncogenesis and tumor recurrence.

Characterization and ethanol potential from giant cassava (Manihot esculenta) stem waste biomass

NASA Astrophysics Data System (ADS)

Septia, E.; Supriadi; Suwinarti, W.; Amirta, R.

2018-04-01

Manihot esculenta stem waste biomass is promising material for ethanol production since it is unutilized substance from cassava production. Nowadays, cassava is the most common food in Indonesian society. The aims of this study were to identify availability and characteristic of giant cassava (M. esculenta) stem waste biomass for ethanol feedstock. In term of that, four plots with the size of 5m x 5m were made to calculate the total stem biomass obtained after harvesting process. In this study, various concentrations of alkaline were used to degrade lignin from the substrate. The effects of alkaline pretreatment were investigated using TAPPI method and the ethanol yield was estimated using modified NREL protocol. The results showed that the potential dry stem waste biomass from harvesting of M. esculenta was approximately 10.5 ton/ha. Further, alkaline pretreatment of stem waste biomass with 2% of NaOH coupled with the enzymatic saccharification process using meicelase was showed the highest production of sugar to reach of 38.49 % of total reduction sugar and estimated potentially converted to 2,62 L/ha of ethanol. We suggested M. esculenta stem waste biomass could be used as sustainable feedstock for ethanol production in Indonesia.

Dynamic methylation and expression of Oct4 in early neural stem cells.

PubMed

Lee, Shih-Han; Jeyapalan, Jennie N; Appleby, Vanessa; Mohamed Noor, Dzul Azri; Sottile, Virginie; Scotting, Paul J

2010-09-01

Neural stem cells are a multipotent population of tissue-specific stem cells with a broad but limited differentiation potential. However, recent studies have shown that over-expression of the pluripotency gene, Oct4, alone is sufficient to initiate a process by which these can form 'induced pluripotent stem cells' (iPS cells) with the same broad potential as embryonic stem cells. This led us to examine the expression of Oct4 in endogenous neural stem cells, as data regarding its expression in neural stem cells in vivo are contradictory and incomplete. In this study we have therefore analysed the expression of Oct4 and other genes associated with pluripotency throughout development of the mouse CNS and in neural stem cells grown in vitro. We find that Oct4 is still expressed in the CNS by E8.5, but that this expression declines rapidly until it is undetectable by E15.5. This decline is coincident with the gradual methylation of the Oct4 promoter and proximal enhancer. Immunostaining suggests that the Oct4 protein is predominantly cytoplasmic in location. We also found that neural stem cells from all ages expressed the pluripotency associated genes, Sox2, c-Myc, Klf4 and Nanog. These data provide an explanation for the varying behaviour of cells from the early neuroepithelium at different stages of development. The expression of these genes also provides an indication of why Oct4 alone is sufficient to induce iPS formation in neural stem cells at later stages.

Latent Profile Analysis and Conversion to Psychosis: Characterizing Subgroups to Enhance Risk Prediction.

PubMed

Healey, Kristin M; Penn, David L; Perkins, Diana; Woods, Scott W; Keefe, Richard S E; Addington, Jean

2018-02-15

Groups at clinical high risk (CHR) of developing psychosis are heterogeneous, composed of individuals with different clusters of symptoms. It is likely that there exist subgroups, each associated with different symptom constellations and probabilities of conversion. Present study used latent profile analysis (LPA) to ascertain subgroups in a combined sample of CHR (n = 171) and help-seeking controls (HSCs; n = 100; PREDICT study). Indicators in the LPA model included baseline Scale of Prodromal Symptoms (SOPS), Calgary Depression Scale for Schizophrenia (CDSS), and neurocognitive performance as measured by multiple instruments, including category instances (CAT). Subgroups were further characterized using covariates measuring demographic and clinical features. Three classes emerged: class 1 (mild, transition rate 5.6%), lowest SOPS and depression scores, intact neurocognitive performance; class 2 (paranoid-affective, transition rate 14.2%), highest suspiciousness, mild negative symptoms, moderate depression; and class 3 (negative-neurocognitive, transition rate 29.3%), highest negative symptoms, neurocognitive impairment, social cognitive impairment. Classes 2 and 3 evidenced poor social functioning. Results support a subgroup approach to research, assessment, and treatment of help-seeking individuals. Class 3 may be an early risk stage of developing schizophrenia.

Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo

PubMed Central

Ren, Wenwen; Lewandowski, Brian C.; Watson, Jaime; Aihara, Eitaro; Iwatsuki, Ken; Bachmanov, Alexander A.; Margolskee, Robert F.; Jiang, Peihua

2014-01-01

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5+) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5+ or Lgr6+ cells from taste tissue can generate continuously expanding 3D structures (“organoids”). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2’-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5+ cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6+ cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5+ or Lgr6+ cells, validating the use of this model for the study of taste cell generation. PMID:25368147

Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo.

PubMed

Ren, Wenwen; Lewandowski, Brian C; Watson, Jaime; Aihara, Eitaro; Iwatsuki, Ken; Bachmanov, Alexander A; Margolskee, Robert F; Jiang, Peihua

2014-11-18

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5(+)) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5(+) or Lgr6(+) cells from taste tissue can generate continuously expanding 3D structures ("organoids"). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2'-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5(+) cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6(+) cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5(+) or Lgr6(+) cells, validating the use of this model for the study of taste cell generation.

Clinical and radiological features of Marchiafava–Bignami disease

PubMed Central

Dong, Xiaoyu; Bai, Chaobo; Nao, Jianfei

2018-01-01

Abstract Marchiafava–Bignami disease (MBD) is a rare neurological disease usually associated with chronic alcoholism and characterized by demyelination and necrosis. Our aims were to describe the clinicoradiological features and identify factors that may affect the prognosis of patients with MBD. We examined clinical manifestations, laboratory results, and neuroradiological features of 9 patients with MBD. The patients were classified into 2 subgroups (favorable and poor outcome subgroups) based on the Modified Oxford Handicap Scale (MOSH). In addition, we compared the clinical and neuroimaging features between the 2 subgroups. Nine adult male patients (age of onset range 37–62 years, with a mean age of 47.00 ± 14.50 years) were included in this study. According to MOSH, 4 patients were placed in the poor outcome subgroup (MOHS ≥ 3), 5 patients were placed in the favorable outcome subgroup (MOHS ≤ 2). Relatively high score of MAST-C (≥6) (P = .008), extracallosal lesions (P = .048), GCS (P = .026), cerebral lobe impairment (P = .048) was significantly more common in the poor outcome subgroup. Clinical manifestations of MBD are variable and lack specificity. Early diagnosis by relatively specific performance of bisymmetric lesions in corpus callosum of diffusion-weighted imaging (DWI) may affect the prognosis. The prognosis of patients with severe disturbance of consciousness, heavy alcohol consumption, extracallosal lesions, cerebral lobe impairment is probably unfavorable. PMID:29384842

The Association between Care Experiences and Parent Ratings of Care for Different Racial, Ethnic, and Language Groups in a Medicaid Population

PubMed Central

Wilkins, Victoria; Elliott, Marc N; Richardson, Andrea; Lozano, Paula; Mangione-Smith, Rita

2011-01-01

Objective To examine the association between care experiences and parent ratings of care within racial/ethnic/language subgroups. Data Source National Consumer Assessment of Healthcare Providers and Systems Benchmarking Database 3.0 (2003–2006). Sample Characteristics 111,139 parents of minor Medicaid managed care enrollees. Study Design Cross-sectional observational study predicting “poor” (0–5 on 0–10 scale) parent ratings of personal doctor, specialist, health care, and health plan from care experiences for different parent race/ethnicity/language subgroups (Latino/Spanish, Latino/English, white, and black). Principal Findings Care experiences had similar associations with the probability of poor parent ratings of care across the four racial/ethnic/language subgroups (p>.20). A one standard deviation improvement in the doctor communication care experience was associated with about half the frequency of poor ratings of care for personal doctor and health care in all subgroups (p<.05). Sensitivity analysis of individual communication items found that failure to provide explanations to children predicted poor ratings of care only among whites, who also weighed the length of physician interaction more heavily than other subgroups. Conclusions Communication-based interventions may improve experiences and ratings of care for all subgroups, although implementation of these interventions may need to consider preferences associated with race, ethnicity, and language. PMID:21275987

The Elite-Plus stem migrates more than the flanged Charnley stem

PubMed Central

Sanzén, Lennart; Besjakov, Jack; Carlsson, Åke

2010-01-01

Background and purpose The Charnley Elite-Plus stem was introduced in 1993 as a presumed improvement of the flanged Charnley stem. We started this study in 1996 to investigate the migratory pattern of the Elite-Plus stem. Patients and methods We followed 114 patients with osteoarthritis and a primary total hip replacement with the Elite-Plus stem. Mean age at the time of operation was 64 (50–76) years. The mean follow-up time was 6.5 (2–7) years. Radiographs were evaluated with respect to cementing technique, migration, and wear measured by radiostereometry (RSA). Results The stem survival was 98% (CI: 96–100) at 7 years and 92% (CI: 86–97) at 10 years. Mean migration of the femoral head was 0.35 mm (SD 0.3) medially, 0.51 mm (SD 0.6) distally, and 1.1 mm (SD 1.8) in the dorsal direction. Mean total point motion was 1.7 mm (SD 1.7). The migration of the stems stabilized after 5 years in the medial and dorsal directions, but continued to subside slightly. Migration along any of the axes was higher if the cementing technique was inferior. Interpretation Patients with a Charnley Elite-Plus stem and defects in the cement mantle or other signs of inferior implantation technique should be carefully monitored. PMID:20367422

Mining Health App Data to Find More and Less Successful Weight Loss Subgroups

PubMed Central

2016-01-01

Background More than half of all smartphone app downloads involve weight, diet, and exercise. If successful, these lifestyle apps may have far-reaching effects for disease prevention and health cost-savings, but few researchers have analyzed data from these apps. Objective The purposes of this study were to analyze data from a commercial health app (Lose It!) in order to identify successful weight loss subgroups via exploratory analyses and to verify the stability of the results. Methods Cross-sectional, de-identified data from Lose It! were analyzed. This dataset (n=12,427,196) was randomly split into 24 subsamples, and this study used 3 subsamples (combined n=972,687). Classification and regression tree methods were used to explore groupings of weight loss with one subsample, with descriptive analyses to examine other group characteristics. Data mining validation methods were conducted with 2 additional subsamples. Results In subsample 1, 14.96% of users lost 5% or more of their starting body weight. Classification and regression tree analysis identified 3 distinct subgroups: “the occasional users” had the lowest proportion (4.87%) of individuals who successfully lost weight; “the basic users” had 37.61% weight loss success; and “the power users” achieved the highest percentage of weight loss success at 72.70%. Behavioral factors delineated the subgroups, though app-related behavioral characteristics further distinguished them. Results were replicated in further analyses with separate subsamples. Conclusions This study demonstrates that distinct subgroups can be identified in “messy” commercial app data and the identified subgroups can be replicated in independent samples. Behavioral factors and use of custom app features characterized the subgroups. Targeting and tailoring information to particular subgroups could enhance weight loss success. Future studies should replicate data mining analyses to increase methodology rigor. PMID:27301853

Lower periprosthetic bone loss and good fixation of an ultra-short stem compared to a conventional stem in uncemented total hip arthroplasty

PubMed Central

Salemyr, Mats; Muren, Olle; Ahl, Torbjörn; Bodén, Henrik; Eisler, Thomas; Stark, André; Sköldenberg, Olof

2015-01-01

Background and purpose — We hypothesized that an ultra-short stem would load the proximal femur in a more physiological way and could therefore reduce the adaptive periprosthetic bone loss known as stress shielding. Patients and methods — 51 patients with primary hip osteoarthritis were randomized to total hip arthroplasty (THA) with either an ultra-short stem or a conventional tapered stem. The primary endpoint was change in periprosthetic bone mineral density (BMD), measured with dual-energy x-ray absorptiometry (DXA), in Gruen zones 1 and 7, two years after surgery. Secondary endpoints were change in periprosthetic BMD in the entire periprosthetic region, i.e. Gruen zones 1 through 7, stem migration measured with radiostereometric analysis (RSA), and function measured with self-administered functional scores. Results — The periprosthetic decrease in BMD was statistically significantly lower with the ultra-short stem. In Gruen zone 1, the mean difference was 18% (95% CI: −27% to −10%). In zone 7, the difference was 5% (CI: −12% to −3%) and for Gruen zones 1–7 the difference was also 5% (CI: −9% to −2%). During the first 6 weeks postoperatively, the ultra-short stems migrated 0.77 mm more on average than the conventional stems. 3 months after surgery, no further migration was seen. The functional scores improved during the study and were similar in the 2 groups. Interpretation — Up to 2 years after total hip arthroplasty, compared to the conventional tapered stem the ultra-short uncemented anatomical stem induced lower periprosthetic bone loss and had equally excellent stem fixation and clinical outcome. PMID:26134386

Steady advance of stem cell therapies: report from the 2011 World Stem Cell Summit, Pasadena, California, October 3-5.

PubMed

Swan, Melanie

2011-12-01

Stem cell research and related therapies (including regenerative medicine and cellular therapies) could have a significant near-term impact on worldwide public health and aging. One reason is the industry's strong linkage between policy, science, industry, and patient advocacy, as was clear in the attendance and programming at the 7(th) annual World Stem Cell Summit held in Pasadena, California, October 3-5, 2011. A special conference session sponsored by the SENS Foundation discussed how stem cell therapies are being used to extend healthy life span. Stem cells are useful not only in cell-replacement therapies, but also in disease modeling, drug discovery, and drug toxicity screening. Stem cell therapies are currently being applied to over 50 diseases, including heart, lung, neurodegenerative, and eye disease, cancer, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Dozens of companies are developing therapeutic solutions that are in different stages of clinical use and clinical trials. Some high-profile therapies include Dendreon's Provenge for prostate cancer, Geron's first-ever embryonic stem cell trials for spinal cord injury, Fibrocell's laViv cellular therapy for wrinkles, and well-established commercial skin substitutes (Organogenesis' Apligraf and Advanced BioHealing's Dermagraft). Stem cell policy issues under consideration include medical tourism, standards for large-scale stem cell manufacturing, and lingering ethical debates over the use of embryonic stem cells. Contemporary stem cell science advances include a focus on techniques for the direct reprogramming of cells from one lineage to another without returning to pluripotency as an intermediary step, improved means of generating and characterizing induced pluripotent cells, and progress in approaches to neurodegenerative disease.

Barium-cross-linked alginate-gelatine microcapsule as a potential platform for stem cell production and modular tissue formation.

PubMed

Alizadeh Sardroud, Hamed; Nemati, Sorour; Baradar Khoshfetrat, Ali; Nabavinia, Mahbobeh; Beygi Khosrowshahi, Younes

2017-08-01

Influence of gelatine concentration and cross-linker ions of Ca 2+ and Ba 2+ was evaluated on characteristics of alginate hydrogels and proliferation behaviours of model adherent and suspendable stem cells of fibroblast and U937 embedded in alginate microcapsules. Increasing gelatine concentration to 2.5% increased extent of swelling to 15% and 25% for barium- and calcium-cross-linked hydrogels, respectively. Mechanical properties also decreased with increasing swelling of hydrogels. Both by increasing gelatine concentration and using barium ions increased considerably the proliferation of encapsulated model stem cells. Barium-cross-linked alginate-gelatine microcapsule tested for bone building block showed a 13.5 ± 1.5-fold expansion for osteoblast cells after 21 days with deposition of bone matrix. The haematopoietic stem cells cultured in the microcapsule after 7 days also showed up to 2-fold increase without adding any growth factor. The study demonstrates that barium-cross-linked alginate-gelatine microcapsule has potential for use as a simple and efficient 3D platform for stem cell production and modular tissue formation.

Survey of Basal Stem Rot Disease on Oil Palms (Elaeis guineensis Jacq.) in Kebun Bukit Kijang,North Sumatera, Indonesia

NASA Astrophysics Data System (ADS)

Lisnawita; Hanum, H.; Tantawi, A. R.

2016-08-01

Basal stem rot disease caused by Ganoderma sp. is a significant disease on oil palm plantations in Indonesia, especially in North Sumatera. Currently, the pathogen does not only attack the plants that have produced (old plants) but also attacks the plants that have not produced in the first generation yet. A survey of the distribution of the basal stem rot disease in the plantation of the community has been completed in order to illustrate the distribution and the incidence of the basal stem rot disease in 5 locations of the oil palm plantation of the community in Desa Bukit Kijang, Region of Asahan, North Sumatera, Indonesia. From the research, it is revealed that the basal stem rot disease has spread to all of the observed locations with the level of disease incidence between 0.71% in Kebun Bukit Kijang 3 to 50% in the 17 years old oil palm in Kebun Bukit Kijang 4 and Bukit Kijang 5. The observable symptoms of the basal stem rot disease are chlorotic leaves, the appearance of fruiting body, collapsed plants, and the existence of holes on the basal stem. The incidence of basal stem rot disease is higher on land due to a high sand content (>50%).

False-Positive [18F]fluorodeoxyglucose-avid lymph nodes on positron emission tomography-computed tomography after allogeneic but not autologous stem-cell transplantation in patients with lymphoma.

PubMed

Ulaner, Gary A; Lilienstein, Joshua; Gönen, Mithat; Maragulia, Jocelyn; Moskowitz, Craig H; Zelenetz, Andrew D

2014-01-01

Determine the clinical significance of [(18)F]fluorodeoxyglucose (FDG)-avid lesions in patients with lymphoma treated with stem-cell transplantation. All patients who underwent stem-cell transplantation for lymphoma at Memorial Sloan-Kettering Cancer Center between January 2005 and December 2009 and had post-transplantation FDG positron emission tomography/computed tomography (PET/CT) examinations were included. PET/CT examinations were evaluated for FDG-avid lesions suggestive of disease. Clinical records, biopsy results, and subsequent imaging examinations were evaluated for malignancy. Two hundred fifty-one patients were identified, 107 with allogeneic and 144 with autologous stem-cell transplantation. Of allogeneic stem-cell transplantation recipients, 50 had FDG-avid lesions suggestive of lymphoma, defined as FDG-avidity greater than liver background. However, only 29 of these 50 demonstrated lymphoma on biopsy, whereas biopsy attempts were benign in the other 21 patients. Sensitivity analysis determined that a 1.5-cm short axis nodal measurement distinguished patients with malignant from nonmalignant biopsies. In 21 of 22 patients with FDG-avid lymph nodes ≤ 1.5 cm, biopsy attempts were benign. In the absence of treatment, these nodes either resolved or were stable on repeat imaging. Disease-free survival of patients with FDG-avid ≤ 1.5 cm lymph nodes was comparable with patients without FDG-avid lesions. In comparison, autologous stem-cell transplantation patients rarely demonstrated FDG-avid lesions suggestive of disease without malignant pathology. Twenty percent (21 of 107) of patients with an allogeneic stem-cell transplantation demonstrated FDG-avid lymph nodes up to 1.5 cm in short axis on PET/CT, which did not represent active lymphoma. After allogeneic stem-cell transplantation of patients with lymphoma, benign FDG-avid ≤ 1.5 cm lymph nodes can mimic malignancy.

Joint morphogenetic cells in the adult mammalian synovium

PubMed Central

Roelofs, Anke J.; Zupan, Janja; Riemen, Anna H. K.; Kania, Karolina; Ansboro, Sharon; White, Nathan; Clark, Susan M.; De Bari, Cosimo

2017-01-01

The stem cells that safeguard synovial joints in adulthood are undefined. Studies on mesenchymal stromal/stem cells (MSCs) have mainly focused on bone marrow. Here we show that lineage tracing of Gdf5-expressing joint interzone cells identifies in adult mouse synovium an MSC population largely negative for the skeletal stem cell markers Nestin-GFP, Leptin receptor and Gremlin1. Following cartilage injury, Gdf5-lineage cells underpin synovial hyperplasia through proliferation, are recruited to a Nestin-GFPhigh perivascular population, and contribute to cartilage repair. The transcriptional co-factor Yap is upregulated after injury, and its conditional ablation in Gdf5-lineage cells prevents synovial lining hyperplasia and decreases contribution of Gdf5-lineage cells to cartilage repair. Cultured Gdf5-lineage cells exhibit progenitor activity for stable chondrocytes and are able to self-organize three-dimensionally to form a synovial lining-like layer. Finally, human synovial MSCs transduced with Bmp7 display morphogenetic properties by patterning a joint-like organ in vivo. Our findings further the understanding of the skeletal stem/progenitor cells in adult life. PMID:28508891

The case for and against initiating either hydroxyurea therapy, blood transfusion therapy or hematopoietic stem cell transplant in asymptomatic children with sickle cell disease.

PubMed

Kassim, Adetola A; DeBaun, Michael R

2014-02-01

The perception of an asymptomatic sickle cell disease (SCD) state is a misnomer. Children without overt symptoms, likely have subclinical disease beginning in infancy with progression into adulthood. Predictive models of SCD severity are unable to predict a subgroup of asymptomatic children likely to develop severe SCD. The introduction of penicillin prophylaxis, conjugated pneumococcal and Haemophilus influenzae type B vaccines have dramatically decreased the rate of life-threatening infections, while use of hydroxyurea in children has decreased pain and acute chest syndrome events. Use of transcranial Doppler coupled with regular blood transfusion therapy has decreased the rate of overt strokes and premature death associated with strokes. Currently, therapy for asymptomatic children includes hydroxyurea, regular blood transfusion or allogeneic hematopoietic stem cell transplant (allo-HSCT). The pros and cons of initiating hydroxyurea, regular blood transfusion or allo-HSCT in asymptomatic children with SCD. Emerging evidence from observational studies indicates that hydroxyurea prolongs survival in children and adults with sickle cell anemia. Regular blood transfusions reduce incidence of strokes, acute chest and pain episodes, but is associated with the burden of monthly visits and excessive iron stores. Although curative, the perceived risk:benefit ratio associated with allo-HSCT limits its use in asymptomatic children.

Participation of the elderly, women, and minorities in pivotal trials supporting 2011-2013 U.S. Food and Drug Administration approvals.

PubMed

Downing, Nicholas S; Shah, Nilay D; Neiman, Joseph H; Aminawung, Jenerius A; Krumholz, Harlan M; Ross, Joseph S

2016-04-14

Pivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public. We conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity. We identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6-60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5-34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3-55.2 %) and female (mean 49.7 %, 95 % CI 44.7-54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9-82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5-9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2-9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4-7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3-16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications. Although women are equally represented in pivotal trials supporting recent novel therapeutic approvals by the FDA, elderly patients and those from racial and ethnic minorities are underrepresented. FDA reviewers generally perform subgroup efficacy analyses by age, sex, and race and make these subgroup analyses available to the public.

Migration characteristics and early clinical results of the NANOS® short-stem hip arthroplasty.

PubMed

Kaipel, Martin; Grabowiecki, Phillip; Sinz, Katrina; Farr, Sebastian; Sinz, Günter

2015-05-01

Femoral short stems promise essential advantages in total hip arthroplasty. Up to now, only short- and midterm clinical studies exist. Data on early stem migration that could predict later aseptic loosening at an early stage are rare. The purpose of this study was to assess migration patterns and clinical outcome 2 years after hip replacement by a metaphyseal anchored cementless short stem. Migration data and clinical results were prospectively assessed in 49 patients. Clinical outcome was measured using the Harris Hip Score (HHS). Migration analyses were performed using the computer-assisted Einzel-Bild-Roentgen-Analyse (EBRA) system. At 2 years after surgery, none of the implants needed revision, and HHS increased from 47.9 up to 98.1. Of 49 patients, 5 (10%) showed increased vertical stem migration (1.5 mm/2a) that might predict late aseptic loosening. Of 49 stems, 44 (90%) showed stable migration patterns indicating a beneficial long-term outcome. Results of this study confirm the excellent clinical data of previous works. Migration patterns strongly suggest that short-stem arthroplasty is not only an innovative but also a reliable strategy in total hip replacement.

Genome at Juncture of Early Human Migration: A Systematic Analysis of Two Whole Genomes and Thirteen Exomes from Kuwaiti Population Subgroup of Inferred Saudi Arabian Tribe Ancestry

PubMed Central

Alsmadi, Osama; Hebbar, Prashantha; Antony, Dinu; Behbehani, Kazem; Thanaraj, Thangavel Alphonse

2014-01-01

Population of the State of Kuwait is composed of three genetic subgroups of inferred Persian, Saudi Arabian tribe and Bedouin ancestry. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels and 39,762 structural variations. Of the identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic indels, and 374,959 (74.08%) non-exomic indels are ‘novel’. Up to 8,070 (79.9%) of the reported novel biallelic exomic SNPs are seen in low frequency (minor allele frequency <5%). We observe 5,462 known and 1,004 novel potentially deleterious nonsynonymous SNPs. Allele frequencies of common SNPs from the 15 exomes is significantly correlated with those from genotype data of a larger cohort of 48 individuals (Pearson correlation coefficient, 0.91; p <2.2×10−16). A set of 2,485 SNPs show significantly different allele frequencies when compared to populations from other continents. Two notable variants having risk alleles in high frequencies in this subgroup are: a nonsynonymous deleterious SNP (rs2108622 [19:g.15990431C>T] from CYP4F2 gene [MIM:*604426]) associated with warfarin dosage levels [MIM:#122700] required to elicit normal anticoagulant response; and a 3′ UTR SNP (rs6151429 [22:g.51063477T>C]) from ARSA gene [MIM:*607574]) associated with Metachromatic Leukodystrophy [MIM:#250100]. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman) is observed in the exome data. The mitochondrial haplogroup profiles of the 15 individuals are consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource imperative for designing future genetic studies in Saudi Arabian tribe subgroup. The full-length genome sequences and the identified variants are available at ftp://dgr.dasmaninstitute.org and http://dgr.dasmaninstitute.org/DGR/gb.html. PMID:24896259

The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma

DTIC Science & Technology

2012-12-01

hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep . Hepatology, 46: 1935-1945, 2007. 4. Jongsma, J., van...Mice with Pleural Mesothelioma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0574 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jonathan M

The sagittal stem alignment and the stem version clearly influence the impingement-free range of motion in total hip arthroplasty: a computer model-based analysis.

PubMed

Müller, Michael; Duda, Georg; Perka, Carsten; Tohtz, Stephan

2016-03-01

The component alignment in total hip arthroplasty influences the impingement-free range of motion (ROM). While substantiated data is available for the cup positioning, little is known about the stem alignment. Especially stem rotation and the sagittal alignment influence the position of the cone in relation to the edge of the socket and thus the impingement-free functioning. Hence, the question arises as to what influence do these parameters have on the impingement-free ROM? With the help of a computer model the influence of the sagittal stem alignment and rotation on the impingement-free ROM were investigated. The computer model was based on the CT dataset of a patient with a non-cemented THA. In the model the stem version was set at 10°/0°/-10° and the sagittal alignment at 5°/0°/-5°, which resulted in nine alternative stem positions. For each position, the maximum impingement-free ROM was investigated. Both stem version and sagittal stem alignment have a relevant influence on the impingement-free ROM. In particular, flexion and extension as well as internal and external rotation capability present evident differences. In the position intervals of 10° sagittal stem alignment and 20° stem version a difference was found of about 80° in the flexion and 50° in the extension capability. Likewise, differences were evidenced of up to 72° in the internal and up to 36° in the external rotation. The sagittal stem alignment and the stem torsion have a relevant influence on the impingement-free ROM. To clarify the causes of an impingement or accompanying problems, both parameters should be examined and, if possible, a combined assessment of these factors should be made.

STEM Girls Night In at Goddard

NASA Image and Video Library

2016-11-04

Girls Night In was held at Goddard on Nov 4-5, 2016. This is a pilot program which reinvigorates, Girls Night In was held at Goddard on Nov 4-5, inspires and engages high school girls who may be struggling or not fully engaged in STEM

A pseudo-tetragonal tungsten bronze superstructure: a combined solution of the crystal structure of K6.4(Nb,Ta)(36.3)O94 with advanced transmission electron microscopy and neutron diffraction.

PubMed

Paria Sena, Robert; Babaryk, Artem A; Khainakov, Sergiy; Garcia-Granda, Santiago; Slobodyanik, Nikolay S; Van Tendeloo, Gustaaf; Abakumov, Artem M; Hadermann, Joke

2016-01-21

The crystal structure of the K6.4Nb28.2Ta8.1O94 pseudo-tetragonal tungsten bronze-type oxide was determined using a combination of X-ray powder diffraction, neutron diffraction and transmission electron microscopy techniques, including electron diffraction, high angle annular dark field scanning transmission electron microscopy (HAADF-STEM), annular bright field STEM (ABF-STEM) and energy-dispersive X-ray compositional mapping (STEM-EDX). The compound crystallizes in the space group Pbam with unit cell parameters a = 37.468(9) Å, b = 12.493(3) Å, c = 3.95333(15) Å. The structure consists of corner sharing (Nb,Ta)O6 octahedra forming trigonal, tetragonal and pentagonal tunnels. All tetragonal tunnels are occupied by K(+) ions, while 1/3 of the pentagonal tunnels are preferentially occupied by Nb(5+)/Ta(5+) and 2/3 are occupied by K(+) in a regular pattern. A fractional substitution of K(+) in the pentagonal tunnels by Nb(5+)/Ta(5+) is suggested by the analysis of the HAADF-STEM images. In contrast to similar structures, such as K2Nb8O21, also parts of the trigonal tunnels are fractionally occupied by K(+) cations.

LGR5 receptor promotes cell-cell adhesion in stem cells and colon cancer cells via the IQGAP1-Rac1 pathway.

PubMed

Carmon, Kendra S; Gong, Xing; Yi, Jing; Wu, Ling; Thomas, Anthony; Moore, Catherine M; Masuho, Ikuo; Timson, David J; Martemyanov, Kirill A; Liu, Qingyun J

2017-09-08

Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts, and is highly up-regulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro ; however, deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear. Here, we show that LGR5 interacts with IQ motif-containing GTPase-activating protein 1 (IQGAP1), an effector of Rac1/CDC42 GTPases, in the regulation of actin cytoskeleton dynamics and cell-cell adhesion. Specifically, LGR5 decreased levels of IQGAP1 phosphorylation at Ser-1441/1443, leading to increased binding of Rac1 to IQGAP1 and thus higher levels of cortical F-actin and enhanced cell-cell adhesion. LGR5 ablation in colon cancer cells and crypt stem cells resulted in loss of cortical F-actin, reduced cell-cell adhesion, and disrupted localization of adhesion-associated proteins. No evidence of LGR5 coupling to any of the four major subtypes of heterotrimeric G proteins was found. These findings suggest that LGR5 primarily functions via the IQGAP1-Rac1 pathway to strengthen cell-cell adhesion in normal adult crypt stem cells and colon cancer cells. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

AtMMS21, an SMC5/6 complex subunit, is involved in stem cell niche maintenance and DNA damage responses in Arabidopsis roots.

PubMed

Xu, Panglian; Yuan, Dongke; Liu, Ming; Li, Chunxin; Liu, Yiyang; Zhang, Shengchun; Yao, Nan; Yang, Chengwei

2013-04-01

Plants maintain stem cells in meristems to sustain lifelong growth; these stem cells must have effective DNA damage responses to prevent mutations that can propagate to large parts of the plant. However, the molecular links between stem cell functions and DNA damage responses remain largely unexplored. Here, we report that the small ubiquitin-related modifier E3 ligase AtMMS21 (for methyl methanesulfonate sensitivity gene21) acts to maintain the root stem cell niche by mediating DNA damage responses in Arabidopsis (Arabidopsis thaliana). Mutation of AtMMS21 causes defects in the root stem cell niche during embryogenesis and postembryonic stages. AtMMS21 is essential for the proper expression of stem cell niche-defining transcription factors. Moreover, mms21-1 mutants are hypersensitive to DNA-damaging agents, have a constitutively increased DNA damage response, and have more DNA double-strand breaks (DSBs) in the roots. Also, mms21-1 mutants exhibit spontaneous cell death within the root stem cell niche, and treatment with DSB-inducing agents increases this cell death, suggesting that AtMMS21 is required to prevent DSB-induced stem cell death. We further show that AtMMS21 functions as a subunit of the STRUCTURAL MAINTENANCE OF CHROMOSOMES5/6 complex, an evolutionarily conserved chromosomal ATPase required for DNA repair. These data reveal that AtMMS21 acts in DSB amelioration and stem cell niche maintenance during Arabidopsis root development.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

4G/5G Variant of Plasminogen Activator Inhibitor-1 Gene and Severe Pregnancy-Induced Hypertension: Subgroup Analyses of Variants of Angiotensinogen and Endothelial Nitric Oxide Synthase

PubMed Central

Kobashi, Gen; Ohta, Kaori; Yamada, Hideto; Hata, Akira; Minakami, Hisanori; Sakuragi, Noriaki; Tamashiro, Hiko; Fujimoto, Seiichiro

2009-01-01

Background Pregnancy-induced hypertension (PIH) is a common cause of perinatal mortality. It is believed to result from the interaction of several factors, including those related to the blood coagulation system. We performed genotyping and subgroup analyses to determine if the 4G/5G genotypes of the plasminogen activator inhibitor-1 gene (PAI-1) play a role in the pathogenesis of PIH, and to evaluate possible interactions of the PAI-1 polymorphisms with those of the angiotensinogen gene (AGT) and the endothelial nitric oxide synthase gene (NOS3). Methods An association study of PAI-1 polymorphism, and subgroup analyses of common variants of AGT and NOS3, among 128 patients with PIH and 376 healthy pregnant controls. Results No significant differences were found between the cases and controls in the frequencies of allele 4G or the 4G/4G genotype. In subgroup analyses, after adjustment for multiple comparison, a significant association with the AGT TT genotype was found among women with the PAI-1 4G/4G genotype, and an association with the NOS3 GA+AA genotype was found among women with the 5G/5G or 4G/5G genotypes. Conclusions Our findings suggest that there are at least 2 pathways in the pathogenesis of severe PIH. However, with respect to early prediction and prevention of severe PIH, although the PAI-1 4G/4G genotype alone was not a risk factor for severe PIH, the fact that PAI-1 genotypes are associated with varying risks for severe PIH suggests that PAI-1 genotyping of pregnant women, in combination with other tests, may be useful in the development of individualized measures that may prevent severe PIH. PMID:19838007

Cardiovascular disease guideline adherence and self-reported statin use in longstanding type 1 diabetes: results from the Canadian study of longevity in diabetes cohort.

PubMed

Bai, Johnny W; Boulet, Geneviève; Halpern, Elise M; Lovblom, Leif E; Eldelekli, Devrim; Keenan, Hillary A; Brent, Michael; Paul, Narinder; Bril, Vera; Cherney, David Z I; Weisman, Alanna; Perkins, Bruce A

2016-01-25

Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. The 309 participants had mean ± SD age 65.7 ± 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 ± 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin-system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to the secondary prevention subgroup, adjusting for age, sex, hypertension history, body mass, HbA1c, cholesterol, microvascular complications, acetylsalicylic acid use, and renin-angiotensin system inhibitor use. Despite good self-reported adherence to general CVD prevention guidelines, against the principles of these guidelines we found that statin use was substantially lower in those without CVD history. Interventions are needed to improve statin use in older type 1 diabetes patients without a history of CVD.

Insurance Expansion and the Utilization of Inpatient Surgery: Evidence for a "Woodwork" Effect?

PubMed

Ellimoottil, Chandy; Miller, Sarah; Davis, Matthew; Miller, David C

2015-12-01

The impact of insurance expansion on the currently insured population is largely unknown. We examine rates of elective surgery in previously insured individuals before and after Massachusetts health care reform. Using the State Inpatient Databases for Massachusetts and 2 control states (New York and New Jersey) that did not expand coverage, we identified patients aged 69 and older who underwent surgery from January 1, 2003, through December 31, 2010. We studied 5 elective operations (knee and hip replacement, transurethral resection of prostate, inguinal hernia repair, back surgery). We examined statewide utilization rates before and after implementation of health care reform, using a difference-in-differences technique to adjust for secular trends. We also performed subgroup analyses according to race and income strata. We observed no increase in the overall rate of selected discretionary inpatient surgeries in Massachusetts versus control states for the entire population (-1.4%, P = .41), as well as among the white (-1.6%, P = .43) and low-income (-2.2%, P = .26) subgroups. We did, however, find evidence for a woodwork effect in the subgroup of nonwhite elderly patients, among whom the rate of these procedures increased by 20.5% (P = .001). Among nonwhites, the overall result reflected increased utilization of all 5 individual procedures, with statistically significant changes for knee replacement (18%, P < .01), back surgery (18%, P = .05), transurethral resection of the prostate (28%, P = .05), and hernia repair (71%, P = .03). Our findings suggest that national insurance expansion may increase the use of elective surgery among subgroups of previously insured patients. © The Author(s) 2015.

Isolation and characterization of the trophectoderm from the Arabian camel (Camelus dromedarius).

PubMed

Saadeldin, Islam M; Swelum, Ayman Abdel-Aziz; Elsafadi, Mona; Moumen, Abdullah F; Alzahrani, Faisal A; Mahmood, Amer; Alfayez, Musaad; Alowaimer, Abdullah N

2017-09-01

We isolated and characterized trophoblast from in vivo-derived camel embryos and compared with embryonic stem-like cells. Camel embryos were flushed on day 8 post-insemination and used to derive trophectoderm and embryonic stem-like cells under feeder-free culture conditions using a basement membrane matrix. Embryos were evaluated for the expression of POU5F1, MYC, KLF4, SOX2, CDX2, and KRT8 mRNA transcripts by relative quantitative polymerase chain reaction. Camel embryos grew and expanded to ∼4.5 mm and maintained their vesicular shape in vitro for 21 days post-insemination. Trophoblast and embryonic stem-like cell lines grew under feeder-free culture conditions and showed distinct morphological criteria and normal chromosomal counts. Embryonic stem-like cells showed positive staining in the alkaline phosphatase reaction. Trophoblast cells showed a significant increase in CDX2, KRT8, KLF4, and SOX2 expression compared with embryonic stem-like cells and whole embryos. Embryonic stem-like cells showed a significant decrease in CDX2 expression and increase in SOX2 and KRT8 expression compared to embryonic expression. POU5F1 and MYC expression showed no difference between embryos and both cell lines. We characterized embryo survival in vitro, particularly the derivation of trophectoderm and embryonic stem-like cells, providing a foundation for further analysis of early embryonic development and placentation in camels. Copyright © 2017 Elsevier Ltd. All rights reserved.

An observational study identifying obese subgroups among older adults at increased risk of mobility disability: do perceptions of the neighborhood environment matter?

PubMed

King, Abby C; Salvo, Deborah; Banda, Jorge A; Ahn, David K; Gill, Thomas M; Miller, Michael; Newman, Anne B; Fielding, Roger A; Siordia, Carlos; Moore, Spencer; Folta, Sara; Spring, Bonnie; Manini, Todd; Pahor, Marco

2015-12-18

Obesity is an increasingly prevalent condition among older adults, yet relatively little is known about how built environment variables may be associated with obesity in older age groups. This is particularly the case for more vulnerable older adults already showing functional limitations associated with subsequent disability. The Lifestyle Interventions and Independence for Elders (LIFE) trial dataset (n = 1600) was used to explore the associations between perceived built environment variables and baseline obesity levels. Age-stratified recursive partitioning methods were applied to identify distinct subgroups with varying obesity prevalence. Among participants aged 70-78 years, four distinct subgroups, defined by combinations of perceived environment and race-ethnicity variables, were identified. The subgroups with the lowest obesity prevalence (45.5-59.4%) consisted of participants who reported living in neighborhoods with higher residential density. Among participants aged 79-89 years, the subgroup (of three distinct subgroups identified) with the lowest obesity prevalence (19.4%) consisted of non-African American/Black participants who reported living in neighborhoods with friends or acquaintances similar in demographic characteristics to themselves. Overall support for the partitioned subgroupings was obtained using mixed model regression analysis. The results suggest that, in combination with race/ethnicity, features of the perceived neighborhood built and social environments differentiated distinct groups of vulnerable older adults from different age strata that differed in obesity prevalence. Pending further verification, the results may help to inform subsequent targeting of such subgroups for further investigation. Clinicaltrials.gov Identifier =  NCT01072500.

Influence of rotational speed, torque and operator proficiency on failure of Greater Taper files.

PubMed

Yared, G M; Dagher, F E Bou; Machtou, P; Kulkarni, G K

2002-01-01

The purpose of this study was to evaluate the influence of rotational speed. torque, and operator experience on the incidence of locking, deformation, and separation of instruments when using a specific Ni-Ti rotary instrumentation technique in extracted human teeth. Greater Taper Ni-Ti rotary instruments (GT) were used in a crown-down technique. In one group (rotational speed evaluation) of canals (n = 300) speeds of 150, 2 50 and 350 r.p.m. (subgroups 1, 2 and 3) were used. Each one of the subgroups included 100 canals. In a second group (evaluation of torque) (n = 300) torque was set at 20, 30 and 55 Ncm (subgroups 4, 5 and 6). In the third group (evaluation of operator proficiency) (n = 300 three operators with varying experience (subgroups 7, 8 and 9) were also compared. Each subgroup included the use of 10 sets of GT rotary instruments and 100 canals of extracted human molars. Each set of instruments was used in up to 10 canals and sterilized before each case. NaOCl 2.5% was used as an irrigant. The number of locked, deformed, and separated instruments was recorded for each group. Statistical analysis was carried out with pairwise comparisons using Fisher's exact tests for each of the failure type. When the influence of rotational speed was evaluated, instrument deformation and separation did not occur in subgroups 1 (150) r.p.m.), 2 (250 r.p.m.), and 3 (350) r.p.m.). Instrument locking occurred in subgroup 3 only. Statistical analysis demonstrated a significant difference between the 150 and 350 r.p.m. groups and between the 250 and 350 r.p.m. groups with respect to instrument locking. In torque evaluation, neither separation, deformation nor locking occurred during the use of the instruments, at 150 r.p.m., and at the different torque values. When the operators were compared, although two instruments were separated in canals prepared by the least experienced operator. Fisher's exact tests did not demonstrate a significant difference between the three subgroups. Instrument locking, deformation, and separation did not occur with the most experienced operator. None of the instruments separated with the trained operator. Preclinical training in the use of the GT rotary instruments when used with a crown-down technique at 150 r.p.m. was crucial in avoiding instrument separation and reducing the incidence of instrument locking and deformation.

40 CFR 180.476 - Triflumizole; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., tart 1.5 Cilantro, leaves 35 Fruit, pome, group 11-10 0.50 Fruit, small, vine climbing, except fuzzy... Hazelnut 0.05 Hop, dried cones 50 Leafy greens subgroup 4A, except spinach 35 Mango 2.5 Papaya 2.5...

5-Azacytidine delivered by mesoporous silica nanoparticles regulates the differentiation of P19 cells into cardiomyocytes

NASA Astrophysics Data System (ADS)

Cheng, Jin; Ding, Qian; Wang, Jia; Deng, Lin; Yang, Lu; Tao, Lei; Lei, Haihong; Lu, Shaoping

2016-01-01

Heart disease is one of the deadliest diseases causing mortality due to the limited regenerative capability of highly differentiated cardiomyocytes. Stem cell-based therapy in tissue engineering is one of the most exciting and rapidly growing areas and raises promising prospects for cardiac repair. In this study, we have synthesized FITC-mesoporous silica nanoparticles (FMSNs) based on a sol-gel method (known as Stöber's method) as a drug delivery platform to transport 5-azacytidine in P19 embryonic carcinoma stem cells. The surfactant CTAB is utilized as a liquid crystal template to self-aggregate into micelles, resulting in the synthesis of MSNs. Based on the cell viability assay, treatment with FMSNs + 5-azacytidine resulted in much more significant inhibition of the proliferation than 5-azacytidine alone. To study the mechanism, we have tested the differentiation genes and cardiac marker genes in P19 cells and found that these genes have been up-regulated in P19 embryonic carcinoma stem cells treated with FMSNs + 5-azacytidine + poly(allylamine hydrochloride) (PAH), with the changes of histone modifications on the regulatory region. In conclusion, with FMSNs as drug delivery platforms, 5-azacytidine can be more efficiently delivered into stem cells and can be used to monitor and track the transfection process in situ to clarify their effects on stem cell functions and the differentiation process, which can serve as a promising tool in tissue engineering and other biomedical fields.

Pre-Engineering Program: Science, Technology, Engineering and Mathematics (STEM)

DTIC Science & Technology

2013-08-29

educators in the Urbana-Champaign area. 15. SUBJECT TERMS STEM: science, technology , engineering, mathematics 16. SECURITY CLASSIFICATION OF: 19a. NAME...9132T-13-1-0002 4. TITLE AND SUBTITLE Pre-Engineering Program: Science, Technology , Engineering and Mathematics (STEM) 5c. PROGRAM ELEMENT NUMBER N...project was focused on underserved children in grades 1-6 who need, but have limited access to, out-of-school time STEM (science, technology

Tobacco price increase and smoking behaviour changes in various subgroups: a nationwide longitudinal 7-year follow-up study among a middle-aged Japanese population

PubMed Central

Fujiwara, Takeo; Shinozaki, Tomohiro

2017-01-01

Objective Few longitudinal studies have examined the effect of tobacco price increase on both cessation among smokers and relapse among quitters. Our objective was to investigate the differential impact of the tobacco price increase on the changes in smoking status in the total population and various subgroups. Methods We analysed data from a Japanese nationally representative longitudinal study of 30 773 individuals aged 50–59 years (weighted sum of discrete-time number = 215 411) with smoking information, using inverse probability weighting to account for non-response at follow-up. Generalised estimating equation models were used to calculate the odds ratios (ORs) for smoking behavioural changes (cessation among smokers and relapse among quitters), using discrete-time design. Stratified analyses were conducted according to demographic, socioeconomic and health behavioural characteristics. Results From 2005 to 2012, current smoker prevalence among the middle-aged Japanese population decreased from 30.5% to 24.3%. Of all the factors surveyed, only the tobacco price increase in 2010 (up by 37%, the highest increase during the period) was significantly associated with both cessation among smokers (OR 2.14, 95% confidence interval 1.90 to 2.41) and prevention of relapse among quitters (0.60, 0.46 to 0.77). Regarding the subgroup analysis, the tobacco price increase was associated with a significant reduction in relapse in the lowest income, recent quitters and very poor health subgroups. However, different associations were observed for cessation; a significant association between price increase and cessation was observed among all subgroups except for the heavy smoker and recently unemployed subgroups. Conclusions We confirmed that the tobacco price rise was associated with increasing cessation and decreasing relapse concurrently. Furthermore, this price rise was associated with favourable smoking changes in nearly all population subgroups; a large differential impact was not observed across the various subgroups. PMID:26880743

[Diagnostic approach and therapeutic strategy in 133 infertile patients with astheno-necrozoospermia].

PubMed

Vicari, E

1999-02-01

One-hundred thirty-three patients (aged 22 to 48, median 27 years) found affected by repetitive severe astheno-necrozoospermia (ASNE) (forward sperm motility < 10%; viable forms < 25%) in their ejaculates detected by both conventional viability tests (eosin Y exclusion and HOS tests) associated with oligo (51.1%), poly (3.7%), terato- (82.7%), -zoospermia, hyperdesfoliation of seminal spermatids (36.8%), hypospermia (11.3%), a comprehensive (history analysis; physical examination; lab: hormonal, microbiological, hemato-chemical blood screening, ultrasound scans at didymo-epididymal and prostato-vesicular glands, genital venous doppler) work-up allowed to recognize the following possible causes of ASNE: infectious (24.1%), spermiotoxyc (16.5%), hormonal (15.0%), iatrogenic (12.8%), chronic extratesticular diseases (CETD) (10.9%), varicocele (6.8%), idiopathic (14.3%). Overall population, except CETD patients gave their written informed consent about trial options for a three month period: a. rational, evidence-based treatment, group-standardised for doses and lenght (treated patients = subgroups T: total number = 71); b. short-term treatment/no treatment, (matched-control = subgroups Co: total number = 47). Follow-up semen data performed after completion of the assigned trial, together detected a conventionally normal percentage (> 25%) of viable sperm (necrozoospermic-responders (NR) in 37 (52.1%) out of subgroup-T patients. All subgroups-T patient, excepted subgroup-T patient affected by idiophathic ASNE (NR = 0%), exhibited NR rate (range 50-69.2%) values always significantly higher than subgroups-Co (NR = 0%, in all subgroups). Moreover, in each subgroup-T patients the percentages of viable and forward motile sperms values were significantly higher than matched-controls. The results of this study indicate that in patients affected by ASNE an andrological comprehensive work-up is mandatory because ASNE has a heterogeneous pathogenesis and a favourable prognosis, in terms of viable forms sperm improvement is possible after evidence-based therapeutic strategy.

Farming system and wheat cultivar affect infestation of, and parasitism on, Cephus cinctus in the Northern Great Plains.

PubMed

Adhikari, Subodh; Seipel, Tim; Menalled, Fabian D; Weaver, David K

2018-03-26

Cephus cinctus infestation causes $350 million in annual losses in the Northern Great Plains. We compared infestation and parasitism of C. cinctus in spring (including Kamut; Triticum turgidum ssp. turanicum) and winter wheat cultivars grown in organic and conventional fields in Montana, USA. In the greenhouse, we compared C. cinctus preference and survival in Kamut, Gunnison, and Reeder spring wheat cultivars. Stems cut by C. cinctus varied by farming system and the seasonality of the wheat crop. No stems of Kamut in organic fields were cut by C. cinctus, but 1.5% [±0.35% standard error (SE)] of stems in conventional spring wheat, 5% (±0.70% SE) of stems in organic winter wheat, and 20% (±0.93% SE) of stems in conventional winter wheat fields were cut by C. cinctus. More larvae of C. cinctus were parasitized in organic (27 ± 0.03% SE) compared with conventional (5 ± 0.01% SE) winter wheat fields. Cephus cinctus oviposition, survival, and the number of stems cut were lowest in Kamut compared with Gunnison and Reeder. Cephus cinctus infestation was more common in winter wheat than in spring wheat. Organic fields with fewer cut stems also supported more parasitoids. Kamut is a genetic resource for developing C. cinctus-resistant cultivars. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Exploring Student Engagement in STEM Education: An Examination of STEM Schools, STEM Programs, and Traditional Schools

ERIC Educational Resources Information Center

Franco, M. Suzanne; Patel, Nimisha H.

2017-01-01

High school students' perceptions and experiences regarding student engagement were investigated using 32 focus group sessions across 4 different types of STEM education settings in 2 metropolitan areas in the Midwest. Students' understandings and experiences related to student engagement were reflected via 5 categories: students' thinking of…

Apelin: an endogenous peptide essential for cardiomyogenic differentiation of mesenchymal stem cells via activating extracellular signal-regulated kinase 1/2 and 5.

PubMed

Wang, Li; Zhu, Zhi-Ming; Zhang, Ning-Kun; Fang, Zhi-Rong; Xu, Xiao-Hong; Zheng, Nan; Gao, Lian-Ru

2016-05-01

Growing evidence has shown that apelin/APJ system functions as a critical mediator of cardiac development as well as cardiovascular function. Here, we investigated the role of apelin in the cardiomyogenic differentiation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cord in vitro. In this research, we used RNA interference methodology and gene transfection technique to regulate the expression of apelin in Wharton's jelly-derived mesenchymal stem cells and induced cells with a effective cardiac differentiation protocol including 5-azacytidine and bFGF. Four weeks after induction, induced cells assumed a stick-like morphology and myotube-like structures except apelin-silenced cells and the control group. The silencing expression of apelin in Wharton's jelly-derived mesenchymal stem cells decreased the expression of several critical cardiac progenitor transcription factors (Mesp1, Mef2c, NKX2.5) and cardiac phenotypes (cardiac α-actin, β-MHC, cTnT, and connexin-43). Meanwhile, endogenous compensation of apelin contributed to differentiating into cells with characteristics of cardiomyocytes in vitro. Further experiment showed that exogenous apelin peptide rescued the cardiomyogenic differentiation of apelin-silenced mesenchymal stem cells in the early stage (1-4 days) of induction. Remarkably, our experiment indicated that apelin up-regulated cardiac specific genes in Wharton's jelly-derived mesenchymal stem cells via activating extracellular signal-regulated kinase (ERK) 1/2 and 5. © 2016 International Federation for Cell Biology.

miR-1915 and miR-1225-5p Regulate the Expression of CD133, PAX2 and TLR2 in Adult Renal Progenitor Cells

PubMed Central

Costantino, Vincenzo; Curci, Claudia; Cox, Sharon N.; De Palma, Giuseppe; Schena, Francesco P.

2013-01-01

Adult renal progenitor cells (ARPCs) were recently identified in the cortex of the renal parenchyma and it was demonstrated that they were positive for PAX2, CD133, CD24 and exhibited multipotent differentiation ability. Recent studies on stem cells indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of ARPCs with that of mesenchymal stem cells (MSCs) and renal proximal tubular cells (RPTECs) finding distinct sets of miRNAs that were specifically expressed in ARPCs. In particular, miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX2 depends on lower miR-1915 levels and that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, miR-1915 and miR-1225-5p seem to regulate important traits of renal progenitors: the stemness and the repair capacity. PMID:23861881

Stem-Cell Therapy Advances in China.

PubMed

Hu, Lei; Zhao, Bin; Wang, Songlin

2018-02-01

Stem-cell therapy is a promising method for treating patients with a wide range of diseases and injuries. Increasing government funding of scientific research has promoted rapid developments in stem-cell research in China, as evidenced by the substantial increase in the number and quality of publications in the past 5 years. Multiple high-quality studies have been performed in China that concern cell reprogramming, stem-cell homeostasis, gene modifications, and immunomodulation. The number of translation studies, including basic and preclinical investigations, has also increased. Around 100 stem-cell banks have been established in China, 10 stem-cell drugs are currently in the approval process, and >400 stem cell-based clinical trials are currently registered in China. With continued state funding, advanced biotechnical support, and the development of regulatory standards for the clinical application of stem cells, further innovations are expected that will lead to a boom in stem-cell therapies. This review highlights recent achievements in stem-cell research in China and discusses future prospects.

Intercontinental Spread of Asian-Origin H5N8 to North America through Beringia by Migratory Birds.

PubMed

Lee, Dong-Hun; Torchetti, Mia Kim; Winker, Kevin; Ip, Hon S; Song, Chang-Seon; Swayne, David E

2015-06-01

Phylogenetic network analysis and understanding of waterfowl migration patterns suggest that the Eurasian H5N8 clade 2.3.4.4 avian influenza virus emerged in late 2013 in China, spread in early 2014 to South Korea and Japan, and reached Siberia and Beringia by summer 2014 via migratory birds. Three genetically distinct subgroups emerged and subsequently spread along different flyways during fall 2014 into Europe, North America, and East Asia, respectively. All three subgroups reappeared in Japan, a wintering site for waterfowl from Eurasia and parts of North America. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration

PubMed Central

Flores, Natasha M.; Oviedo, Néstor J.; Sage, Julien

2016-01-01

The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians. PMID:27542689

Essential role for the planarian intestinal GATA transcription factor in stem cells and regeneration.

PubMed

Flores, Natasha M; Oviedo, Néstor J; Sage, Julien

2016-10-01

The cellular turnover of adult tissues and injury-induced repair proceed through an exquisite integration of proliferation, differentiation, and survival signals that involve stem/progenitor cell populations, their progeny, and differentiated tissues. GATA factors are DNA binding proteins that control stem cells and the development of tissues by activating or repressing transcription. Here we examined the role of GATA transcription factors in Schmidtea mediterranea, a freshwater planarian that provides an excellent model to investigate gene function in adult stem cells, regeneration, and differentiation. Smed-gata4/5/6, the homolog of the three mammalian GATA-4,-5,-6 factors is expressed at high levels in differentiated gut cells but also at lower levels in neoblast populations, the planarian stem cells. Smed-gata4/5/6 knock-down results in broad differentiation defects, especially in response to injury. These defects are not restricted to the intestinal lineage. In particular, at late time points during the response to injury, loss of Smed-gata4/5/6 leads to decreased neoblast proliferation and to gene expression changes in several neoblast subpopulations. Thus, Smed-gata4/5/6 plays a key evolutionary conserved role in intestinal differentiation in planarians. These data further support a model in which defects in the intestinal lineage can indirectly affect other differentiation pathways in planarians. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The impact of subgroup type and subgroup configurational properties on work team performance.

PubMed

Carton, Andrew M; Cummings, Jonathon N

2013-09-01

Scholars have invoked subgroups in a number of theories related to teams, yet certain tensions in the literature remain unresolved. In this article, we address 2 of these tensions, both relating to how subgroups are configured in work teams: (a) whether teams perform better with a greater number of subgroups and (b) whether teams perform better when they have imbalanced subgroups (majorities and minorities are present) or balanced subgroups (subgroups are of equal size). We predict that the impact of the number and balance of subgroups depends on the type of subgroup-whether subgroups are formed according to social identity (i.e., identity-based subgroups) or information processing (i.e., knowledge-based subgroups). We first propose that teams are more adversely affected by 2 identity-based subgroups than by any other number, yet the uniquely negative impact of a 2-subgroup configuration is not apparent for knowledge-based subgroups. Instead, a larger number of knowledge-based subgroups is beneficial for performance, such that 2 subgroups is worse for performance when compared with 3 or more subgroups but better for performance when compared with no subgroups or 1 subgroup. Second, we argue that teams perform better when identity-based subgroups are imbalanced yet knowledge-based subgroups are balanced. We also suggest that there are interactive effects between the number and balance of subgroups-however, the nature of this interaction depends on the type of subgroup. To test these predictions, we developed and validated an algorithm that measures the configurational properties of subgroups in organizational work teams. Results of a field study of 326 work teams from a multinational organization support our predictions. PsycINFO Database Record (c) 2013 APA, all rights reserved

Recombination in the Evolution of Enterovirus C Species Sub-Group that Contains Types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99

PubMed Central

Smura, Teemu; Blomqvist, Soile; Vuorinen, Tytti; Ivanova, Olga; Samoilovich, Elena; Al-Hello, Haider; Savolainen-Kopra, Carita; Hovi, Tapani; Roivainen, Merja

2014-01-01

Genetic recombination is considered to be a very frequent phenomenon among enteroviruses (Family Picornaviridae, Genus Enterovirus). However, the recombination patterns may differ between enterovirus species and between types within species. Enterovirus C (EV-C) species contains 21 types. In the capsid coding P1 region, the types of EV-C species cluster further into three sub-groups (designated here as A–C). In this study, the recombination pattern of EV-C species sub-group B that contains types CVA-21, CVA-24, EV-C95, EV-C96 and EV-C99 was determined using partial 5′UTR and VP1 sequences of enterovirus strains isolated during poliovirus surveillance and previously published complete genome sequences. Several inter-typic recombination events were detected. Furthermore, the analyses suggested that inter-typic recombination events have occurred mainly within the distinct sub-groups of EV-C species. Only sporadic recombination events between EV-C species sub-group B and other EV-C sub-groups were detected. In addition, strict recombination barriers were inferred for CVA-21 genotype C and CVA-24 variant strains. These results suggest that the frequency of inter-typic recombinations, even within species, may depend on the phylogenetic position of the given viruses. PMID:24722726