Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis.

Science.gov (United States)

Margolskee, Elizabeth; Hasserjian, Robert P; Hassane, Duane; Tam, Wayne; Mathew, Susan; Ok, Chi Young; Wang, Sa A; Oak, Jean; Arber, Daniel A; Orazi, Attilio

2017-07-01

Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups. MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases. Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.

Science.gov (United States)

Inoue, D; Kitaura, J; Matsui, H; Hou, H-A; Chou, W-C; Nagamachi, A; Kawabata, K C; Togami, K; Nagase, R; Horikawa, S; Saika, M; Micol, J-B; Hayashi, Y; Harada, Y; Harada, H; Inaba, T; Tien, H-F; Abdel-Wahab, O; Kitamura, T

2015-04-01

Mutations in ASXL1 are frequent in patients with myelodysplastic syndrome (MDS) and are associated with adverse survival, yet the molecular pathogenesis of ASXL1 mutations (ASXL1-MT) is not fully understood. Recently, it has been found that deletion of Asxl1 or expression of C-terminal-truncating ASXL1-MTs inhibit myeloid differentiation and induce MDS-like disease in mice. Here, we find that SET-binding protein 1 (SETBP1) mutations (SETBP1-MT) are enriched among ASXL1-mutated MDS patients and associated with increased incidence of leukemic transformation, as well as shorter survival, suggesting that SETBP1-MT play a critical role in leukemic transformation of MDS. We identify that SETBP1-MT inhibit ubiquitination and subsequent degradation of SETBP1, resulting in increased expression. Expression of SETBP1-MT, in turn, inhibited protein phosphatase 2A activity, leading to Akt activation and enhanced expression of posterior Hoxa genes in ASXL1-mutant cells. Biologically, SETBP1-MT augmented ASXL1-MT-induced differentiation block, inhibited apoptosis and enhanced myeloid colony output. SETBP1-MT collaborated with ASXL1-MT in inducing acute myeloid leukemia in vivo. The combination of ASXL1-MT and SETBP1-MT activated a stem cell signature and repressed the tumor growth factor-β signaling pathway, in contrast to the ASXL1-MT-induced MDS model. These data reveal that SETBP1-MT are critical drivers of ASXL1-mutated MDS and identify several deregulated pathways as potential therapeutic targets in high-risk MDS.

GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

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Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

2016-01-27

In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

To chelate or not to chelate in MDS: That is the question!

Science.gov (United States)

Zeidan, Amer M; Griffiths, Elizabeth A

2018-03-08

Myelodysplastic syndromes (MDS) are a heterogeneous group of hemopathies that exhibit physical manifestations with clinical consequences of bone marrow failure and inherent risk of progression to acute myeloid leukemia. Iron overload (IO) is common in MDS due to chronic transfusion support and disease-related alterations in iron metabolism. IO has been conclusively associated with inferior outcomes among MDS patients. Despite lack of randomized trials showing a survival impact of iron chelation therapy (ICT), ICT is recommended by experts and guidelines for select MDS patients with IO and is often used. The availability of effective oral ICT agents has reignited the controversy regarding ICT use in patients with MDS and IO. Here we summarize the studies evaluating the value of ICT in MDS and suggest a practical approach for use of these therapies. We also highlight controversies regarding use of ICT in MDS and discuss some ongoing efforts to answer these questions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unraveling the Pathogenesis of MDS: The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.

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Sallman, David A; Cluzeau, Thomas; Basiorka, Ashley A; List, Alan

2016-01-01

Myelodysplastic syndromes (MDS) are characterized by bone marrow cytological dysplasia and ineffective hematopoiesis in the setting of recurrent somatic gene mutations and chromosomal abnormalities. The underlying pathogenic mechanisms that drive a common clinical phenotype from a diverse array of genetic abnormalities have only recently begun to emerge. Accumulating evidence has highlighted the integral role of the innate immune system in upregulating inflammatory cytokines via NF-κB activation in the pathogenesis of MDS. Recent investigations implicate activation of the NLRP3 inflammasome in hematopoietic stem/progenitor cells as a critical convergence signal in MDS with consequent clonal expansion and pyroptotic cell death though caspase-1 maturation. Specifically, the alarmin S100A9 and/or founder gene mutations trigger pyroptosis through the generation of reactive oxygen species leading to assembly and activation of the redox-sensitive NLRP3 inflammasome and β-catenin, assuring propagation of the MDS clone. More importantly, targeted inhibition of varied steps in this pathway restore effective hematopoiesis. Together, delineation of the role of pyroptosis in the clinical phenotype of MDS patients has identified novel therapeutic strategies that offer significant promise in the treatment of MDS.

Hypotéza o MDS kódech

OpenAIRE

Kesely, Michal

2010-01-01

In this thesis, we study some properties of MDS codes and we mainly focus on the MDS codes conjecture. In the first chapter we define MDS codes, show some examples and basic properties of MDS codes, for example a link between MDS codes and Latin squares or rectangles. Afterwards we state the MDS codes conjecture and prove it in several cases. In the third chapter we can observe the relationship between MDS codes and narcs in projective geometries. Finally we present those known cases, for whi...

Strongly-MDS convolutional codes

NARCIS (Netherlands)

Gluesing-Luerssen, H; Rosenthal, J; Smarandache, R

Maximum-distance separable (MDS) convolutional codes have the property that their free distance is maximal among all codes of the same rate and the same degree. In this paper, a class of MDS convolutional codes is introduced whose column distances reach the generalized Singleton bound at the

Time-dependent changes in mortality and transformation risk in MDS.

Science.gov (United States)

Pfeilstöcker, Michael; Tuechler, Heinz; Sanz, Guillermo; Schanz, Julie; Garcia-Manero, Guillermo; Solé, Francesc; Bennett, John M; Bowen, David; Fenaux, Pierre; Dreyfus, Francois; Kantarjian, Hagop; Kuendgen, Andrea; Malcovati, Luca; Cazzola, Mario; Cermak, Jaroslav; Fonatsch, Christa; Le Beau, Michelle M; Slovak, Marilyn L; Levis, Alessandro; Luebbert, Michael; Maciejewski, Jaroslaw; Machherndl-Spandl, Sigrid; Magalhaes, Silvia M M; Miyazaki, Yasushi; Sekeres, Mikkael A; Sperr, Wolfgang R; Stauder, Reinhard; Tauro, Sudhir; Valent, Peter; Vallespi, Teresa; van de Loosdrecht, Arjan A; Germing, Ulrich; Haase, Detlef; Greenberg, Peter L

2016-08-18

In myelodysplastic syndromes (MDSs), the evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study, we described changes in risk over time, the consequences for basal prognostic scores, and their potential clinical implications. Major MDS prognostic risk scoring systems and their constituent individual predictors were analyzed in 7212 primary untreated MDS patients from the International Working Group for Prognosis in MDS database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. Hazards regarding mortality and acute myeloid leukemia transformation diminished over time from diagnosis in higher-risk MDS patients, whereas they remained stable in lower-risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and were essentially equivalent after 5 years. This fact led to loss of prognostic power of different scoring systems considered, which was more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management, the differing development of risks suggested a reasonable division into lower- and higher-risk MDS based on the IPSS-R at a cutoff of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower-risk patients at diagnosis remain lower risk whereas initially high-risk patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making. © 2016 by The American Society of Hematology.

Lessons from the atomic bomb about secondary MDS.

Science.gov (United States)

Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi

2014-12-01

Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.

MDS MIC Catalog Inputs

Science.gov (United States)

Johnson-Throop, Kathy A.; Vowell, C. W.; Smith, Byron; Darcy, Jeannette

2006-01-01

This viewgraph presentation reviews the inputs to the MDS Medical Information Communique (MIC) catalog. The purpose of the group is to provide input for updating the MDS MIC Catalog and to request that MMOP assign Action Item to other working groups and FSs to support the MITWG Process for developing MIC-DDs.

MDS 3.0 Frequency Report

Data.gov (United States)

U.S. Department of Health & Human Services — The MDS 3.0 Frequency Report summarizes information for active residents currently in nursing homes. The source of these counts is the residents MDS assessment...

New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types.

Science.gov (United States)

Strupp, Corinna; Nachtkamp, Kathrin; Hildebrandt, Barbara; Giagounidis, Aristoteles; Haas, Rainer; Gattermann, Norbert; Bennett, John M; Aul, Carlo; Germing, Ulrich

2017-06-01

Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9% of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively. The difference between the groups with regard to the risk of AML evolution was also impressing. No major changes were made with regard to the MDS-U categories. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible. Copyright © 2017 Elsevier Ltd. All rights reserved.

Progress in the diagnosis of and therapy for MDS.

Science.gov (United States)

Nannya, Yasuhito

2016-01-01

The WHO classification system of MDS 4 th edition was recently updated. This revision includes nomenclature changes, reflecting the policy of the revision team to emphasize morphological features over cytopenias. Other changes are 1) taking SF3B1 mutation status into account for the definition criteria of MDS-RS (ring sideroblasts), 2) allowing for one additional cytogenetic abnormality (excluding -7/del (7q)) to be diagnosed as 'MDS with isolated del (5q)', 3) sub-classifying MDS-U according to the reasons for being included in this category, and 4) changing the diagnostic rules for myeloid neoplasms with erythroid blast predominance. This session also deals with recent topics in hematopoietic stem cell transplantation (HSCT) as an example of progress in therapy for MDS. Although HSCT is the only curative therapy for MDS, high treatment related mortality precludes its applicability especially for elderly patients, for whom demethylating agents are an alternative. Recently, reports on both well-designed retrospective or prospective studies have validated the advantage of HSCT over demethylating agents for patients of comparatively advanced age with higher risk MDS. Optimal intensity of conditioning regimens for HSCT is another controversial topic for which preliminary results of randomized controlled trials have been released and will be introduced in this session.

Myelodysplastic Syndromes (MDS) and autoimmune disorders (AD): cause or consequence?

Science.gov (United States)

Braun, Thorsten; Fenaux, Pierre

2013-12-01

Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) are frequently associated with clinical manifestations of autoimmune disorders (AD) and inflammatory response of the immune system. AD accompanying MDS and CMML include vasculitis, seronegative polyarthritis and neutrophilic dermatosis. Rare AD including relapsing polychondritis is strongly associated with MDS as in a high proportion of those patients MDS is diagnosed during disease course. Antinuclear antibodies (ANA) are frequently found among MDS patients without clinical manifestation of AD. In a subset of patients, MDS and resulting cytopenias appear to be the consequence of auto reactive immunologic activity and may respond to immunosuppressive treatment (IST). Increased release of inflammatory cytokines like tumor necrosis factor-(TNF)-α and interferon (IF)-γ triggers apoptosis of myeloid precursor cells leading to cytopenias. Impaired function of immune cells including cytotoxic, regulatory (Treg), helper (Th17) T cells and NK cells also appears to predict response to IST, outcome and occurrence of AD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in the Apcdel/+ MDS mouse model.

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Stoddart, Angela; Wang, Jianghong; Hu, Chunmei; Fernald, Anthony A; Davis, Elizabeth M; Cheng, Jason X; Le Beau, Michelle M

2017-06-01

There is accumulating evidence that functional alteration(s) of the bone marrow (BM) microenvironment contribute to the development of some myeloid disorders, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In addition to a cell-intrinsic role of WNT activation in leukemia stem cells, WNT activation in the BM niche is also thought to contribute to the pathogenesis of MDS and AML. We previously showed that the Apc -haploinsufficient mice ( Apc del/+ ) model MDS induced by an aberrant BM microenvironment. We sought to determine whether Apc, a multifunctional protein and key negative regulator of the canonical β-catenin (Ctnnb1)/WNT-signaling pathway, mediates this disease through modulating WNT signaling, and whether inhibition of WNT signaling prevents the development of MDS in Apc del/+ mice. Here, we demonstrate that loss of 1 copy of Ctnnb1 is sufficient to prevent the development of MDS in Apc del/+ mice and that altered canonical WNT signaling in the microenvironment is responsible for the disease. Furthermore, the US Food and Drug Administration (FDA)-approved drug pyrvinium delays and/or inhibits disease in Apc del /+ mice, even when it is administered after the presentation of anemia. Other groups have observed increased nuclear CTNNB1 in stromal cells from a high frequency of MDS/AML patients, a finding that together with our results highlights a potential new strategy for treating some myeloid disorders. © 2017 by The American Society of Hematology.

MDS clinical diagnostic criteria for Parkinson's disease in China.

Science.gov (United States)

Li, Jun; Jin, Miao; Wang, Li; Qin, Bin; Wang, Kang

2017-03-01

The Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (MDS-PD Criteria) was introduced by the Movement Disorder Society in 2015 for research purposes. However, its use for clinical diagnosis of Parkinson disease still needs further revision. This study compares the UK-Criteria versus MDS-PD Criteria in the clinical diagnosis of Parkinson disease referred to the China-Japan Friendship Hospital of Beijing, China. To compare the MDS-PD Criteria with the UK-Criteria and discuss the feasibility of the clinical application of MDS-PD Criteria as a general guide to clinical diagnosis of PD in Chinese PD patients. 150 patients of neurology clinic of China-Japan Friendship Hospital of Beijing were recruited in our research. They were divided into three groups: UK-Criteria group, MDS-PD Criteria group and a combined group of UK and MDS-PD Criteria. Clinical history was collected while physical and auxiliary examinations were done by a trained neurologist according to the corresponding criteria. An interrater reliability analysis using the Kappa statistic claimed substantial agreement (κ = 0.626) between the MDS-PD Criteria and the UK-Criteria. The differences between the diagnostic results of these two criteria were statistically significant by paired Chi-square test (p = 0.000). It was found that levodopa-induced dyskinesia had a good positive predictive value, while early bulbar impairment and inspiratory dysfunction presented a negative predictive value. The MDS-PD Criteria emphasize the importance of non-motor symptoms, keeping the motor symptoms as the core for the clinical diagnosis of PD, and establish categories of diagnosis features and levels of certainty which are more complete and organized to be used and replicated by non specialized physicians to evaluated patients with Parkinsonism. The higher sensitivity of MDS-PD Criteria compared with UK-Criteria is worth being widely used in clinical work.

Are the MDS-UPDRS-based composite scores clinically applicable?

Science.gov (United States)

Makkos, Attila; Kovács, Márton; Aschermann, Zsuzsanna; Harmat, Márk; Janszky, József; Karádi, Kázmér; Kovács, Norbert

2018-02-28

The International Parkinson and Movement Disorder Society-sponsored UPDRS (MDS-UPDRS) is a powerful clinical outcome measure. To evaluate the feasibility of various MDS-UPDRS-based composite scores and determine their minimal clinically important difference threshold values. Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Based on the ordinal regression modeling, the MDS-UPDRS II+III, MDS-UPDRS I+II+III, and the total score of MDS-UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS-UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS-UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS-UPDRS were 7.1 points for improvement and 6.3 points for worsening. Our findings support the application of various MDS-UPDRS-based composite scores. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

The MDS-UPDRS Part II (motor experiences of daily living) resulted useful for assessment of disability in Parkinson's disease.

Science.gov (United States)

Rodriguez-Blazquez, Carmen; Rojo-Abuin, Jose Manuel; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G; Martinez-Martin, Pablo

2013-10-01

To evaluate the motor experiences of daily living section of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS M-EDL) for assessing disability in PD patients; to determine the association between disability and quality of life; and to identify cut-off score ranges for no, mild, moderate and severe disability with this measure. International, observational, cross-sectional study of 435 PD patients, assessed with: MDS-UPDRS, Hoehn and Yahr staging, Rapid Assessment of Disability Scale, Clinical Impression of Severity Index for PD, Parkinson's Disease Questionnaire-8 and EQ-5D. Descriptive statistics, Spearman's rank correlation coefficients, Kruskal-Wallis test for group comparisons, ordinal logistic regression analysis for setting cut-off values and a step-wise multiple linear regression model were calculated. MDS-UPDRS M-EDL correlated 0.70-0.80 with other disability measures, and -0.46 to 0.74 with quality of life scales. Scores significantly increased with higher disease duration and severity (p MDS-UPDRS nM-EDL section as the main determinant of M-EDL, followed by the rest of MDS-UPDRS sections (explained variance: 59%). MDS-UPDRS M-EDL proved to be useful for assessing disability in PD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells.

Science.gov (United States)

Li, Jing; Yue, Lanzhu; Wang, Huaquan; Liu, Chunyan; Liu, Hui; Tao, Jinglian; Qi, Weiwei; Wang, Yihao; Zhang, Wei; Fu, Rong; Shao, Zonghong

2016-01-01

Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

[Combination of busulfan with increased-dose of fludarabine as conditioning regimen for MDS and MDS-AML patients with allo-HSCT].

Science.gov (United States)

Yuan, Jing; Ren, Hanyun; Qiu, Zhixiang; Li, Yuan; Wang, Mangju; Liu, Wei; Xu, Weilin; Sun, Yuhua; Wang, Lihong; Liang, Zeyin; Dong, Yujun; Ou, Jinping; Wang, Wensheng; Yin, Yue; Cen, Xinan; Wang, Qian

2015-06-01

To investigate the safety and efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS) and secondary acute myelogenous leukemia (MDS-AML) using conditioning regimen with busulfan (Bu) and increased-dose of fludarabine (ID-Flu). A total of 49 patients with MDS or MDS-AML were treated by allo-HSCT, the clinical data was analyzed retrospectively. All patients achieved hematopoietic reconstitution. Neutrophil engraftment was at 10 - 22 days (median 13 days), and platelet engraftment was at 8 - 66 days (median 16 days). The cumulative incidences of Ⅱ-Ⅳ degree acute graft-versus-host disease (GVHD), hemorrhagic cystitis (HC), and hepatic venous occlusive disease (VOD) were 28.6%, 14.3% and 2.0%, respectively. The transplant-related mortality (TRM) was only 4.1% at 100d and 8.2% at 1-92 months of followed-up (median 14 months) period. Overall survival (OS) and disease free survival (DFS) was 75.5%, 73.5%, respectively. Kaplan-Meier curve showed that 3-year OS and 3-year DFS was (71.1 ± 7.8)%, (66.7 ± 8.3)%, respectively, with a relapse incidence (RI) 16.3%. OS for MDS and MDS-AML was 81.5% and 68.2%, and RI in two settings was 3.7%, 31.8%, respectively. OS for MDS-AML at complete remission (CR) and non-CR subgroup was 83.3% and 50.0%, respectively, while cumulative RR was 16.7% and 50.0%, respectively. OS and RI except for non-CR subgroup were 82.1% and 7.7%. Univariate analysis showed that pre-HSCT disease status had correlation with OS (P=0.031), but age, decitabine in conditioning regimen, stem cell source, HLA matching, patient-donor gender, dose of mononuclear cells and GVHD had no correlation with OS. Bu/ID-Flu conditioning regimen for MDS and MDS-AML has high efficiency, fewer complications, lower toxicity and TRM. The OS and DFS were higher and RI was lower except for refractory MDS-AML patients. The regimen is valuable for clinical application.

Focal Adhesion Kinase as a Potential Target in AML and MDS.

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Carter, Bing Z; Mak, Po Yee; Wang, Xiangmeng; Yang, Hui; Garcia-Manero, Guillermo; Mak, Duncan H; Mu, Hong; Ruvolo, Vivian R; Qiu, Yihua; Coombes, Kevin; Zhang, Nianxiang; Ragon, Brittany; Weaver, David T; Pachter, Jonathan A; Kornblau, Steven; Andreeff, Michael

2017-06-01

Although overexpression/activation of focal adhesion kinase (FAK) is widely known in solid tumors to control cell growth, survival, invasion, metastasis, gene expression, and stem cell self-renewal, its expression and function in myeloid leukemia are not well investigated. Using reverse-phase protein arrays in large cohorts of newly diagnosed acute myeloid leukemia (AML) and myeloid dysplastic syndrome (MDS) samples, we found that high FAK expression was associated with unfavorable cytogenetics ( P = 2 × 10 -4 ) and relapse ( P = 0.02) in AML. FAK expression was significantly lower in patients with FLT3 -ITD ( P = 0.0024) or RAS ( P = 0.05) mutations and strongly correlated with p-SRC and integrinβ3 levels. FAK protein levels were significantly higher in CD34 + ( P = 5.42 × 10 -20 ) and CD34 + CD38 - MDS ( P = 7.62 × 10 -9 ) cells compared with normal CD34 + cells. MDS patients with higher FAK in CD34 + cells tended to have better overall survival ( P = 0.05). FAK expression was significantly higher in MDS patients who later transformed to compared with those who did not transform to AML and in AML patients who transformed from MDS compared with those with de novo AML. Coculture with mesenchymal stromal cells (MSC) increased FAK expression in AML cells. Inhibition of FAK decreased MSC-mediated adhesion/migration and viability of AML cells and prolonged survival in an AML xenograft murine model. Our results suggest that FAK regulates leukemia-stromal interactions and supports leukemia cell survival; hence, FAK is a potential therapeutic target in myeloid leukemia. Mol Cancer Ther; 16(6); 1133-44. ©2017 AACR . ©2017 American Association for Cancer Research.

The emerging role of immune checkpoint based approaches in AML and MDS.

Science.gov (United States)

Boddu, Prajwal; Kantarjian, Hagop; Garcia-Manero, Guillermo; Allison, James; Sharma, Padmanee; Daver, Naval

2018-04-01

The development of immune checkpoint inhibitors represents a major breakthrough in the field of cancer therapeutics. Pursuant to their success in melanoma and numerous solid tumor malignancies, these agents are being investigated in hematological malignancies including acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). Although AML/MDS have traditionally been considered to be less immunogenic than solid tumor malignancies, recent pre-clinical models suggest a therapeutic role for immune checkpoint inhibition in these diseases. CTLA-4 inhibition may be especially effective in treating late post-allogeneic stem cell transplant relapse of AML in patients with limited or no graft versus host disease. Immune checkpoint inhibition, specifically PD-1 inhibition, demonstrated limited single agent efficacy in patients with relapsed AML and with MDS post-hypomethylating therapy. Rationally designed combinations of PD-1 inhibitors with standard anti-leukemic therapy are needed. Hypomethylating agents such as azacitidine, up-regulate PD-1, PD-L1, and PD-L2 in patients with AML/MDS and up-regulation of these genes was associated with the emergence of resistance. The combination of azacitidine and PD-1/PD-L1 inhibition may be a potential mechanism to prevent or overcome resistance to 5-azacitidine. A number of such combinations are being evaluated in clinical trials with early encouraging results. Immune checkpoint inhibition is also an attractive option to improve relapse-free survival or eliminate minimal residual disease post induction and consolidation by enhancing T-cell surveillance in patients with high-risk AML. The ongoing clinical trials with checkpoint inhibitors in AML/MDS will improve our understanding of the immunobiology of these diseases and guide us to the most appropriate application of these agents in the therapy of AML/MDS.

MDS: Recent progress in molecular pathogenesis and clinical aspects.

Science.gov (United States)

Harada, Hironori

2017-01-01

Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

Management of older adults with myelodysplastic syndromes (MDS).

Science.gov (United States)

Luskin, Marlise R; Abel, Gregory A

2017-12-28

The myelodysplastic syndromes (MDS) are a varied group of hematologic neoplasms that lead to bone marrow failure, and also carry a risk of progression to acute myeloid leukemia. Patients with MDS suffer significant impairments to both their quality of life and survival. Age is the dominant risk factor for the development of MDS, with a median age at diagnosis over 70years. Consequently, patients with MDS frequently have concurrent comorbidities and/or frailty which may be coincident or related to the disease itself. Disease characteristics, degree of comorbidity, and presence of frailty all impact prognosis. Treatment of MDS focuses on supportive care, with disease-modifying approaches (chemotherapy and allogeneic hematopoietic cell transplantation) reserved for fit patients with high-risk disease. Care of patients with MDS requires understanding the disease in the context of an older population, and tailoring approaches to both disease risk and patient suitability for therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform.

Science.gov (United States)

Valent, Peter; Stauder, Reinhard; Theurl, Igor; Geissler, Klaus; Sliwa, Thamer; Sperr, Wolfgang R; Bettelheim, Peter; Sill, Heinz; Pfeilstöcker, Michael

2018-02-01

Despite the availability of effective iron chelators, transfusion-related morbidity is still a challenge in chronically transfused patients with myelodysplastic syndromes (MDS). In these patients, transfusion-induced iron overload may lead to organ dysfunction or even organ failure. In addition, iron overload is associated with reduced overall survival in MDS. Areas covered: During the past 10 years, various guidelines for the management of MDS patients with iron overload have been proposed. In the present article, we provide our updated recommendations for the diagnosis, prevention and therapy of iron overload in MDS. In addition, we propose refined treatment response criteria. As in 2006 and 2007, recommendations were discussed and formulated by participants of our Austrian MDS platform in a series of meetings in 2016 and 2017. Expert commentary: Our updated recommendations should support early recognition of iron overload, optimal patient management and the measurement of clinical responses to chelation treatment in daily practice.

Myelodysplastic changes mimicking MDS following treatment for osteosarcoma

DEFF Research Database (Denmark)

Løhmann, Ditte

-MDS/AML) is a feared long-term complication of paediatric cancer including osteosarcoma. Few develop t-MDS/AML, but it is not known how many have significant haematological changes after finishing treatment for osteosarcoma. In this study we reviewed biochemistry from a consecutive series of children for up to two...... years after finishing treatment. We included all children (n=14) who where diagnosed from October 2006 to January 2011 at our department and treated according to the EURAMOS-1 protocol. Four patients relapsed and died before the end of the study period. We found noteworthy changes in MCV, platelets...... for osteosarcoma developed haematological abnormalities similar to early MDS but few developed t-MDS/AML. Close monitoring of patients recovering from osteosarcoma is essential. Keywords: Osteosarcoma, t-MDS/AML, Haematological abnormalities, Children...

Epigenetically Aberrant Stroma in MDS Propagates Disease via Wnt/β-Catenin Activation.

Science.gov (United States)

Bhagat, Tushar D; Chen, Si; Bartenstein, Matthias; Barlowe, A Trevor; Von Ahrens, Dagny; Choudhary, Gaurav S; Tivnan, Patrick; Amin, Elianna; Marcondes, A Mario; Sanders, Mathijs A; Hoogenboezem, Remco M; Kambhampati, Suman; Ramachandra, Nandini; Mantzaris, Iaonnis; Sukrithan, Vineeth; Laurence, Remi; Lopez, Robert; Bhagat, Prafullla; Giricz, Orsi; Sohal, Davendra; Wickrema, Amittha; Yeung, Cecilia; Gritsman, Kira; Aplan, Peter; Hochedlinger, Konrad; Yu, Yiting; Pradhan, Kith; Zhang, Jinghang; Greally, John M; Mukherjee, Siddhartha; Pellagatti, Andrea; Boultwood, Jacqueline; Will, Britta; Steidl, Ulrich; Raaijmakers, Marc H G P; Deeg, H Joachim; Kharas, Michael G; Verma, Amit

2017-09-15

The bone marrow microenvironment influences malignant hematopoiesis, but how it promotes leukemogenesis has not been elucidated. In addition, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands. Stroma derived from 5-azacytidine-treated patients lacked aberrant methylation and DNMTi treatment of primary MDS stroma enhanced its ability to support erythroid differentiation. An integrative expression analysis revealed that the WNT pathway antagonist FRZB was aberrantly hypermethylated and underexpressed in MDS stroma. This result was confirmed in an independent set of sorted, primary MDS-derived mesenchymal cells. We documented a WNT/β-catenin activation signature in CD34 + cells from advanced cases of MDS, where it associated with adverse prognosis. Constitutive activation of β-catenin in hematopoietic cells yielded lethal myeloid disease in a NUP98-HOXD13 mouse model of MDS, confirming its role in disease progression. Our results define novel epigenetic changes in the bone marrow microenvironment, which lead to β-catenin activation and disease progression of MDS. Cancer Res; 77(18); 4846-57. ©2017 AACR . ©2017 American Association for Cancer Research.

Red Blood Cell Transfusion Dependency and Hyperferritinemia Are Associated with Impaired Survival in Patients Diagnosed with Myelodysplastic Syndromes: Results from the First Polish MDS-PALG Registry.

Science.gov (United States)

Waszczuk-Gajda, Anna; Mądry, Krzysztof; Machowicz, Rafał; Drozd-Sokołowska, Joanna; Stella-Hołowiecka, Beata; Mital, Andrzej; Obara, Agata; Szmigielska-Kapłon, Anna; Sikorska, Anna; Subocz, Edyta; Jędrzejczak, Wiesław W; Dwilewicz-Trojaczek, Jadwiga

2016-01-01

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis, cytopenias and a risk of progression to acute myeloid leukemia (AML). Anemia is the most frequent cytopenia diagnosed in patients with MDS. Regular RBC transfusions are the only treatment option for about 40% of patients. Transfusion-dependent patients develop secondary iron overload. The influence of serum ferritin (SF) concentration on survival and acute myeloid leukemia transformation in MDS patients remains controversial. The data for the Central European population is scarce and so far there is no description for Poland. The aim of this study was to perform a retrospective analysis of the relationship of SF concentration with red blood cell transfusion dependency, survival and transformation to acute myeloid leukemia. We retrospectively evaluated the data of the 819 MDS patients (58% male; median age 70 years) included in the MDS Registry of the MDS Section of the Polish Adult Leukemia Group (PALG). Analyses were performed on 190 patients diagnosed with MDS, maximal 6 months before inclusion to the registry in order to avoid selection bias (a shorter survival of higher risk MDS patients). Patients with hyperferritinemia higher than 1000 ng/L vs. patients with SF concentration lower than 1000 ng/L had a median survival of 320 days vs. 568 days, respectively (p log-rank = 0.014). The following factors were found to significantly worsen survival: RBC-transfusion dependence (p = 0.0033; HR 2.67L), platelet transfusion dependence (p = 0.0071; HR 3.321), hemoglobin concentration lower than 10 g/dL (p = 0.0036; HR 2.97), SF concentration higher than 1000 ng/L (p = 0.0023; HR = 2.94), platelet count lower than 10 G/L (p = 0.0081 HR = 5.04), acute leukemia transformation (p = 0.0081; HR 1.968). Taking into account the relatively low number of patients in previous studies exploring hyperferritinemia in MDS, the results of the first Polish

Monitoring the grid with the Globus Toolkit MDS4

International Nuclear Information System (INIS)

Schopf, Jennifer M; Pearlman, Laura; Miller, Neill; Kesselman, Carl; Foster, Ian; D'Arcy, Mike; Chervenak, Ann

2006-01-01

The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

Telomere dynamics in patients with del (5q) MDS before and under treatment with lenalidomide.

Science.gov (United States)

Beier, Fabian; Masouleh, Behzad Kharabi; Buesche, Guntram; Ventura Ferreira, Monica S; Schneider, Rebekka K; Ziegler, Patrick; Wilop, Stefan; Vankann, Lucia; Gattermann, Norbert; Platzbecker, Uwe; Giagounidis, Aristoteles; Götze, Katharina S; Nolte, Florian; Hofmann, Wolf-Karsten; Haase, Detlef; Kreipe, Hans; Panse, Jens; Blasco, Maria A; Germing, Ulrich; Brümmendorf, Tim H

2015-09-21

Myelodysplastic syndrome (MDS) associated with an acquired, isolated deletion of chromosome 5q (del (5q) MDS), represent a clonal disorder of hematopoiesis and a clinically distinct entity of MDS. Treatment of del (5q) MDS with the drug lenalidomide has significantly improved quality of life leading to transfusion independence and complete cytogenetic response rates (CCR) in the majority of patients. Telomeres are located at the end of eukaryotic chromosomes and are linked to replicative history/potential as well as genetic (in) stability of hematopoietic stem cells. Here, we analyzed telomere length (TL) dynamics before and under lenalidomide treatment in the peripheral blood and/or bone marrow of del (5q) patients enrolled in the LEMON-5 study (NCT01081431). Hematopoietic cells from del (5q) MDS patients were characterized by significantly shortened TL compared to age-matched healthy controls. Telomere loss was more accelerated in patients with longer disease duration (>2 years) and more pronounced cytopenias. Sequential analysis under lenalidomide treatment revealed that previously shortened TL in peripheral blood cells was significantly "elongated" towards normal levels within the first six months suggesting a shift from clonal del (5q) cells towards normal hematopoiesis in lenalidomide treated MDS patients. Taken together our findings suggest that the development of the del (5q) clone is associated with accelerated telomere shortening at diagnosis. However, upon induction of CCR and reoccurrence of normal hematopoiesis, the lack of a persistent TL deficit argues against telomere-mediated genetic instability neither as a disease-promoting event of del (5q) MDS nor for lenalidomide mediated development of secondary primary malignancies of the hematopoietic system in responding patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

An improved resource management model based on MDS

Science.gov (United States)

Yuan, Man; Sun, Changying; Li, Pengfei; Sun, Yongdong; He, Rui

2005-11-01

GRID technology provides a kind of convenient method for managing GRID resources. This service is so-called monitoring, discovering service. This method is proposed by Globus Alliance, in this GRID environment, all kinds of resources, such as computational resources, storage resources and other resources can be organized by MDS specifications. However, this MDS is a theory framework, particularly, in a small world intranet, in the case of limit of resources, the MDS has its own limitation. Based on MDS, an improved light method for managing corporation computational resources and storage resources is proposed in intranet(IMDS). Firstly, in MDS, all kinds of resource description information is stored in LDAP, it is well known although LDAP is a light directory access protocol, in practice, programmers rarely master how to access and store resource information into LDAP store, in such way, it limits MDS to be used. So, in intranet, these resources' description information can be stored in RDBMS, programmers and users can access this information by standard SQL. Secondly, in MDS, how to monitor all kinds of resources in GRID is not transparent for programmers and users. In such way, it limits its application scope, in general, resource monitoring method base on SNMP is widely employed in intranet, therefore, a kind of resource monitoring method based on SNMP is integrated into MDS. Finally, all kinds of resources in the intranet can be described by XML, and all kinds of resources' description information is stored in RDBMS, such as MySql, and retrieved by standard SQL, dynamic information for all kinds of resources can be sent to resource storage by SNMP, A prototype resource description, monitoring is designed and implemented in intranet.

Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis.

Science.gov (United States)

Leitch, Heather A; Parmar, Ambica; Wells, Richard A; Chodirker, Lisa; Zhu, Nancy; Nevill, Thomas J; Yee, Karen W L; Leber, Brian; Keating, Mary-Margaret; Sabloff, Mitchell; St Hilaire, Eve; Kumar, Rajat; Delage, Robert; Geddes, Michelle; Storring, John M; Kew, Andrea; Shamy, April; Elemary, Mohamed; Lenis, Martha; Mamedov, Alexandre; Ivo, Jessica; Francis, Janika; Zhang, Liying; Buckstein, Rena

2017-10-01

Analyses suggest iron overload in red blood cell (RBC) transfusion-dependent (TD) patients with myleodysplastic syndrome (MDS) portends inferior overall survival (OS) that is attenuated by iron chelation therapy (ICT) but may be biassed by unbalanced patient-related factors. The Canadian MDS Registry prospectively measures frailty, comorbidity and disability. We analysed OS by receipt of ICT, adjusting for these patient-related factors. TD International Prognostic Scoring System (IPSS) low and intermediate-1 risk MDS, at RBC TD, were included. Predictive factors for OS were determined. A matched pair analysis considering age, revised IPSS, TD severity, time from MDS diagnosis to TD, and receipt of disease-modifying agents was conducted. Of 239 patients, 83 received ICT; frailty, comorbidity and disability did not differ from non-ICT patients. Median OS from TD was superior in ICT patients (5·2 vs. 2·1 years; P MDS, adjusting for age, frailty, comorbidity, disability, revised IPSS, TD severity, time to TD and receiving disease-modifying agents. This provides additional evidence that ICT may confer clinical benefit. © 2017 John Wiley & Sons Ltd.

Therapy with low-dose azacitidine for MDS in children and young adults: a retrospective analysis of the EWOG-MDS study group.

Science.gov (United States)

Cseh, Annamaria M; Niemeyer, Charlotte M; Yoshimi, Ayami; Catala, Albert; Frühwald, Michael C; Hasle, Henrik; van den Heuvel-Eibrink, Mary M; Lauten, Melchior; De Moerloose, Barbara; Smith, Owen P; Bernig, Toralf; Gruhn, Bernd; Kulozik, Andreas E; Metzler, Markus; Olcay, Lale; Suttorp, Meinolf; Furlan, Ingrid; Strahm, Brigitte; Flotho, Christian

2016-03-01

Low-dose azacitidine is efficient and safe in the therapy of malignant myeloid disorders in adults but data in children are lacking. We present a retrospective analysis of 24 children and young adults with myelodysplastic syndrome (MDS) who received azacitidine at the time of first diagnosis or relapse after allotransplant (2 children were treated with azacitidine both initially and for relapse). Diagnoses were refractory cytopenia of childhood (N = 4), advanced primary MDS (N = 9) and secondary MDS (N = 11). The median duration of treatment was four cycles. Azacitidine was well tolerated, but cytopenias led to dose reduction in five cases. Treatment was discontinued in one child because of impaired renal function. Sixteen MDS patients were treated with azacitidine at first diagnosis. One complete clinical remission was observed and one child showed complete marrow remission; six children experienced stable disease with haematological improvement. Ten children received azacitidine for relapsed MDS after transplant: of these, seven experienced stable disease for 2-30 cycles (median 3), including one patient with haematological improvement for seven cycles. In summary, azacitidine is effective in some children with MDS and appears to be a non-toxic option in palliative situations to prolong survival. © 2016 John Wiley & Sons Ltd.

Flow cytometry in the diagnosis of myelodysplastic syndromes (MDS) and the value of myeloid nuclear differentiation antigen (MNDA).

Science.gov (United States)

Bellos, Frauke; Kern, Wolfgang

2014-09-25

Background: Confirming diagnosis of myelodysplastic syndromes (MDS) is often challenging. Standard diagnostic methods are cytomorphology (CM) and cytogenetics (CG). Multiparameter flow cytometry (MFC) is upcoming in MDS diagnostic work up, comparability and investigator experience are critical. Myeloid nuclear differentiation antigen (MNDA) in myelomonocytic cells might be expressed more weakly in patients with MDS. The analysis of MNDA may thus improve diagnostic capabilities of MFC in MDS. Methods: Staining methods and antibody combinations for MFC in MDS are outlined, giving details for interpretation of results in regard to dyspoiesis. MFC results are correlated with CM and CG and with survival data. Use of myeloid nuclear differentiation antigen (MNDA) in MDS diagnostics was evaluated in 239 patients with MDS, AML, other cytopenic conditions and in 30 negative controls. Results: Strong correlation between findings in CM and MFC was found; MFC results correlated well with those of CG. Patients with higher grades of dysplasia in MFC had shorter overall survival. Percentages of granulocytes and monocytes with diminished MNDA expression (%dimG, %dimM) were higher in patients with MDS and AML. Mean fluorescence intensity (MFI) of MNDA in monocytes was lower in MDS and AML. Cut-off values for %dimG (12%) and %dimM (22%) as well as for MFI in monocytes (72) were defined discriminating between MDS and non-MDS. Conclusion: MFC adds significant information on dyspoiesis in the diagnostic work up for MDS and provides prognostic information. MNDA expression can be assessed by MFC and may facilitate evaluation of dyspoiesis when added to MDS MFC panels. © 2014 Clinical Cytometry Society. Copyright © 2014 Clinical Cytometry Society.

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance

NARCIS (Netherlands)

Swart, L. de; Smith, A.; MacKenzie, M.; Symeonidis, A.; Neukirchen, J.; Mikulenkova, D.; Vallespi, T.; Zini, G.; Paszkowska-Kowalewska, M.; Kruger, A.; Saft, L.; Fenaux, P.; Bowen, D.; Hellstrom-Lindberg, E.; Cermak, J.; Stauder, R.; Tatic, A.; Holm, M.S.; Malcovati, L.; Madry, K.; Droste, J.A.; Blijlevens, N.M.; Witte, T.J. de; Germing, U.

2017-01-01

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard

Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS).

Science.gov (United States)

Yao, Chi-Yuan; Hou, Hsin-An; Lin, Tzung-Yi; Lin, Chien-Chin; Chou, Wen-Chien; Tseng, Mei-Hsuan; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Kuo, Yuan-Yeh; Wu, Shang-Ju; Liao, Xiu-Wen; Lin, Chien-Ting; Ko, Bor-Shen; Chen, Chien-Yuan; Hsu, Szu-Chun; Li, Chi-Cheng; Huang, Shang-Yi; Yao, Ming; Tang, Jih-Luh; Tsay, Woei; Liu, Chieh-Yu; Tien, Hwei-Fang

2016-09-27

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS (PMDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients (P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS (P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.

Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone during Xenopus Metamorphosis

Science.gov (United States)

Hasebe, Takashi; Fu, Liezhen; Heimeier, Rachel A.; Das, Biswajit; Ishizuya-Oka, Atsuko; Shi, Yun-Bo

2013-01-01

Background Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells. Methodology/Principal Findings The T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium. Conclusions/Significance Our results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells. PMID:23383234

[VALIDATION OF THE HUNGARIAN MDS-UPDRS: WHY DO WE NEED A NEW PARKINSON SCALE?].

Science.gov (United States)

Horvath, Krisztina; Aschermann Zsuzsanna; Acs, Péter; Bosnyák, Edit; Deli, Gabriella; Pál, Endre; Késmárki, Ildikó; Horváth Réka; Takács, Katalin; Komoly, Sámuel; Bokor, Magdolna; Rigó, Eszter; Lajtos, Júlia; Klivényi, Péter; Dibó, György; Vécsei, László; Takáts, Annamária; Tóth, Adrián; Imre, Piroska; Nagy, Ferenc; Herceg, Mihály; Hidasi, Eszter; Kovács, Norbert

2014-03-30

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been published in 2008 as the successor of the original UPDRS. The MDS-UPDRS organizing team developed guidelines for the development of official non-English translations consisting of four steps: translation/back-translation, cognitive pretesting, large field testing, and clinimetric analysis. The aim of this paper was to introduce the new MDS-UPDRS and its validation process into Hungarian. Two independent groups of neurologists translated the text of the MDS-UPDRS into Hungarian and subsequently back-translated into English. After the review of the back-translated English version by the MDS-UPDRS translation administration team, cognitive pretesting was conducted with ten patients. Based on the results of the initial cognitive pretesting, another round was conducted. For the large field testing phase, the Hungarian official working draft version of MDS-UPDRS was tested with 357 patients with Parkinson's disease (PD). Confirmatory factor analyses (CFA) determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Hungarian Official Draft Version. To become an official translation, the Comparative Fit Index (CFI) had to be ≥ 0.90 compared to the English-language version. For all four parts of the Hungarian MDS-UPDRS, the CFI was ≥ 0.94. The overall factor structure of the Hungarian version was consistent with that of the English version based on the high CFIs for all the four parts of the MDS-UPDRS in the CFA; therefore, this version was designated as the "OFFICIAL GUNGARIAN VERSION OF THE MDS-UPDRS'.

Increased separase activity and occurrence of centrosome aberrations concur with transformation of MDS.

Science.gov (United States)

Ruppenthal, Sabrina; Kleiner, Helga; Nolte, Florian; Fabarius, Alice; Hofmann, Wolf-Karsten; Nowak, Daniel; Seifarth, Wolfgang

2018-01-01

ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome duplication and mitotic sister chromatid separation. Aberrant expression and/or altered separase proteolytic activity are associated with centrosome amplification, aneuploidy, tumorigenesis and disease progression. Since centrosome alterations are a common and early detectable feature in patients with myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role in disease risk stratification, we examined separase activity on single cell level in 67 bone marrow samples obtained from patients with MDS, secondary acute myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy controls by a flow cytometric separase activity assay. The separase activity distribution (SAD) value, a calculated measure for the occurrence of cells with prominent separase activity within the analyzed sample, was tested for correlation with the centrosome, karyotype and gene mutation status. We found higher SAD values in bone marrow cells of sAML patients than in corresponding cells of MDS patients. This concurred with an increased incidence of aberrant centrosome phenotypes in sAML vs. MDS samples. No correlation was found between SAD values and the karyotype/gene mutation status. During follow-up of four MDS patients we observed increasing SAD values after transformation to sAML, in two patients SAD values decreased during azacitidine therapy. Cell culture experiments employing MDS-L cells as an in vitro model of MDS revealed that treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce G2/M arrest, results in decreased SAD values. In conclusion, the appearance of cells with unusual high separase activity levels, as indicated by increased SAD values, concurs with the transformation of MDS to sAML and may reflect separase dysregulation potentially contributing to clonal evolution during MDS progression. Separase activity measurement may therefore be useful as a

[Application of Next Generation Sequencing for AML/MDS Diagnosis and Treatment].

Science.gov (United States)

Cheng, Huan-Chen; Liu, Sheng-Wei; Liu, Yu; Zhao, Xue-Fei; Li, Wei; Qiu, Lin; Ma, Jun

2017-12-01

To detect the mutations of AML/MDS- related genes by using next generation sequencing (NGS), to analyze the mutation levels of each genes in the AML/MDS and the sensitivity of NGS, and to evaluate the feasibility of gene mutations for monitoring the MRD and predicating the progression of diseases. The specimens were collected from primary AML (68 cases) and MDS (57 cases) patients from August 2015 to June 2016 in the Harbin Institute of Hematology and Oncology. The mutations of 22 related genes were detected by using AML/MDS-NGS chips. TET2 gene showed the highest mutation rate in AML (55.9%) and MDS (56.1%). The gene mutations were as follows: CEBPA (11.8%), DNMT3A (7.4%), C-KIT (7.4%) and FLT3-ITD (7.4%) in AML, and U2AF1 (10.5%) and SRSF2 (10.5%) in MDS. All the genes had specific mutation sites except TP53 and CEBPA. The mutations of FLT3, C-KIT and CEBPA became negative in the 5 AML patients in remission when compared with those at primary attack, but the mutation rate of TET2 gene was not obviously changed, whereas the mutation rate of the 5 MDS patients was not significantly changed. The new gene mutations appeared in 3 MDS patients with disease progression, but the mutation rate was not changed significantly in the disease progression. The gene mutation rate still has not been changed significantly even after remission. Both AML and MDS have their own specific mutated genes and sites. Some gene mutations, such as CEBPA, can be used as an effective indicator to monitoring MRD in AML patients, but those only used for the evaluation of the disease progression and prognosis in MDS patients.

Clinical Features and Outcomes of 666 Cases with Therapy-Related Myelodysplastic Syndrome (t-MDS).

Science.gov (United States)

El-Fattah, Mohamed Abd

2018-01-01

Therapy-related myelodysplastic syndrome (t-MDS) is a serious complication of chemoradiotherapy for primary diseases. This cohort was aimed to determine the clinical features and outcomes of t-MDS in comparison with de novo MDS. I retrieved data of 666 cases with t-MDS, and 29,703 cases with de novo MDS diagnosed between 2001 and 2012 from the database of U.S. National Cancer Institute. Survival curves were estimated, and Cox proportional hazards model was constructed. Compared with patients with de novo MDS, patients with t-MDS tended to be young (median age; 65 vs. 76 years, p  MDS than de novo MDS (17.2 months and 22% vs. 31 months and 32%, respectively, p  MDS cases, with a median follow-up of 16 months (range 1-143 months), 521 cases (78.2%) had died. Of which, 78 (15%) cases had died from acute myeloid leukemia, and 66 (12.7%) cases had died from solid cancers. Of the total 66 cases died from solid cancers; 19 cases (28.8%) died from cancer of lung/bronchus, 11 cases (16.7%) breast cancers, and 10 cases (15.2%) ovarian cancer. In a multivariate analysis adjusted for clinical features, calendar period and radiotherapy, the hazard of mortality was significantly low in de novo MDS compared with t-MDS (hazard ratio 0.59; p  MDS is a distinct entity of MDS in terms of clinical characteristics and prognosis.

Minimal clinically important difference on the Motor Examination part of MDS-UPDRS.

Science.gov (United States)

Horváth, Krisztina; Aschermann, Zsuzsanna; Ács, Péter; Deli, Gabriella; Janszky, József; Komoly, Sámuel; Balázs, Éva; Takács, Katalin; Karádi, Kázmér; Kovács, Norbert

2015-12-01

Recent studies increasingly utilize the Movement Disorders Society Sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS). However, the minimal clinically important difference (MCID) has not been fully established for MDS-UPDRS yet. To assess the MCID thresholds for MDS-UPDRS Motor Examination (Part III). 728 paired investigations of 260 patients were included. At each visit both MDS-UPDRS and Clinician-reported Global Impression-Improvement (CGI-I) scales were assessed. MDS-UPDRS Motor Examination (ME) score changes associated with CGI-I score 4 (no change) were compared with MDS-UPDRS ME score changes associated with CGI-I score 3 (minimal improvement) and CGI-I score 5 (minimal worsening). Both anchor- and distribution-based techniques were utilized to determine the magnitude of MCID. The MCID estimates for MDS-UPDRS ME were asymmetric: -3.25 points for detecting minimal, but clinically pertinent, improvement and 4.63 points for observing minimal, but clinically pertinent, worsening. MCID is the smallest change of scores that are clinically meaningful to patients. These MCID estimates may allow the judgement of a numeric change in MDS-UPDRS ME on its clinical importance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Handling missing values in the MDS-UPDRS.

Science.gov (United States)

Goetz, Christopher G; Luo, Sheng; Wang, Lu; Tilley, Barbara C; LaPelle, Nancy R; Stebbins, Glenn T

2015-10-01

This study was undertaken to define the number of missing values permissible to render valid total scores for each Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part. To handle missing values, imputation strategies serve as guidelines to reject an incomplete rating or create a surrogate score. We tested a rigorous, scale-specific, data-based approach to handling missing values for the MDS-UPDRS. From two large MDS-UPDRS datasets, we sequentially deleted item scores, either consistently (same items) or randomly (different items) across all subjects. Lin's Concordance Correlation Coefficient (CCC) compared scores calculated without missing values with prorated scores based on sequentially increasing missing values. The maximal number of missing values retaining a CCC greater than 0.95 determined the threshold for rendering a valid prorated score. A second confirmatory sample was selected from the MDS-UPDRS international translation program. To provide valid part scores applicable across all Hoehn and Yahr (H&Y) stages when the same items are consistently missing, one missing item from Part I, one from Part II, three from Part III, but none from Part IV can be allowed. To provide valid part scores applicable across all H&Y stages when random item entries are missing, one missing item from Part I, two from Part II, seven from Part III, but none from Part IV can be allowed. All cutoff values were confirmed in the validation sample. These analyses are useful for constructing valid surrogate part scores for MDS-UPDRS when missing items fall within the identified threshold and give scientific justification for rejecting partially completed ratings that fall below the threshold. © 2015 International Parkinson and Movement Disorder Society.

Explicit MDS Codes with Complementary Duals

DEFF Research Database (Denmark)

Beelen, Duals Peter; Jin, Lingfei

2018-01-01

In 1964, Massey introduced a class of codes with complementary duals which are called Linear Complimentary Dual (LCD for short) codes. He showed that LCD codes have applications in communication system, side-channel attack (SCA) and so on. LCD codes have been extensively studied in literature....... On the other hand, MDS codes form an optimal family of classical codes which have wide applications in both theory and practice. The main purpose of this paper is to give an explicit construction of several classes of LCD MDS codes, using tools from algebraic function fields. We exemplify this construction...

Implication of microRNAs in the Pathogenesis of MDS

Science.gov (United States)

Fang, Jing; Varney, Melinda; Starczynowski, Daniel T.

2016-01-01

MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS. PMID:22571695

Construction of new quantum MDS codes derived from constacyclic codes

Science.gov (United States)

Taneja, Divya; Gupta, Manish; Narula, Rajesh; Bhullar, Jaskaran

Obtaining quantum maximum distance separable (MDS) codes from dual containing classical constacyclic codes using Hermitian construction have paved a path to undertake the challenges related to such constructions. Using the same technique, some new parameters of quantum MDS codes have been constructed here. One set of parameters obtained in this paper has achieved much larger distance than work done earlier. The remaining constructed parameters of quantum MDS codes have large minimum distance and were not explored yet.

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN.

Science.gov (United States)

Jabbour, Elias; Short, Nicholas J; Montalban-Bravo, Guillermo; Huang, Xuelin; Bueso-Ramos, Carlos; Qiao, Wei; Yang, Hui; Zhao, Chong; Kadia, Tapan; Borthakur, Gautam; Pemmaraju, Naveen; Sasaki, Koji; Estrov, Zeev; Cortes, Jorge; Ravandi, Farhad; Alvarado, Yesid; Komrokji, Rami; Sekeres, Mikkael A; Steensma, David P; DeZern, Amy; Roboz, Gail; Kantarjian, Hagop; Garcia-Manero, Guillermo

2017-09-28

Hypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m 2 intravenously/subcutaneously daily or decitabine 20 mg/m 2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% ( P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine ( P = .2). Cytogenetic response rates were 61% and 25% ( P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively ( P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225). © 2017 by The American Society of Hematology.

New Insights into the Pathogenesis of MDS and the rational therapeutic opportunities.

Science.gov (United States)

Abou Zahr, Abdallah; Bernabe Ramirez, Carolina; Wozney, Jocelyn; Prebet, Thomas; Zeidan, Amer M

2016-01-01

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

Some Families of Asymmetric Quantum MDS Codes Constructed from Constacyclic Codes

Science.gov (United States)

Huang, Yuanyuan; Chen, Jianzhang; Feng, Chunhui; Chen, Riqing

2018-02-01

Quantum maximal-distance-separable (MDS) codes that satisfy quantum Singleton bound with different lengths have been constructed by some researchers. In this paper, seven families of asymmetric quantum MDS codes are constructed by using constacyclic codes. We weaken the case of Hermitian-dual containing codes that can be applied to construct asymmetric quantum MDS codes with parameters [[n,k,dz/dx

Modeling Marrow Failure and MDS for Novel Therapeutics

Science.gov (United States)

2017-03-01

syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure syndromes compared to age-matched controls. Prognosis of...Novel Therapeutics W81XWH-16-1-0054 1. Introduction Clonal evolution is a potentially life threatening long-term complication of inherited and...The risk of early progression to myelodysplastic syndrome (MDS) and leukemia is also markedly elevated in patients with inherited marrow failure

CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets.

Science.gov (United States)

Gleason, Michelle K; Ross, Julie A; Warlick, Erica D; Lund, Troy C; Verneris, Michael R; Wiernik, Andres; Spellman, Stephen; Haagenson, Michael D; Lenvik, Alexander J; Litzow, Mark R; Epling-Burnette, Pearlie K; Blazar, Bruce R; Weiner, Louis M; Weisdorf, Daniel J; Vallera, Daniel A; Miller, Jeffrey S

2014-05-08

Myelodysplastic syndromes (MDS) are stem cell disorders that can progress to acute myeloid leukemia. Although hematopoietic cell transplantation can be curative, additional therapies are needed for a disease that disproportionally afflicts the elderly. We tested the ability of a CD16xCD33 BiKE to induce natural killer (NK) cell function in 67 MDS patients. Compared with age-matched normal controls, CD7(+) lymphocytes, NK cells, and CD16 expression were markedly decreased in MDS patients. Despite this, reverse antibody-dependent cell-mediated cytotoxicity assays showed potent degranulation and cytokine production when resting MDS-NK cells were triggered with an agonistic CD16 monoclonal antibody. Blood and marrow MDS-NK cells treated with bispecific killer cell engager (BiKE) significantly enhanced degranulation and tumor necrosis factor-α and interferon-γ production against HL-60 and endogenous CD33(+) MDS targets. MDS patients had a significantly increased proportion of immunosuppressive CD33(+) myeloid-derived suppressor cells (MDSCs) that negatively correlated with MDS lymphocyte populations and CD16 loss on NK cells. Treatment with the CD16xCD33 BiKE successfully reversed MDSC immunosuppression of NK cells and induced MDSC target cell lysis. Lastly, the BiKE induced optimal MDS-NK cell function irrespective of disease stage. Our data suggest that the CD16xCD33 BiKE functions against both CD33(+) MDS and MDSC targets and may be therapeutically beneficial for MDS patients.

Construction of MDS self-dual codes from orthogonal matrices

OpenAIRE

Shi, Minjia; Sok, Lin; Solé, Patrick

2016-01-01

In this paper, we give algorithms and methods of construction of self-dual codes over finite fields using orthogonal matrices. Randomization in the orthogonal group, and code extension are the main tools. Some optimal, almost MDS, and MDS self-dual codes over both small and large prime fields are constructed.

[Establishment of Primary Adult MDS Nested Case-Control Study Cohort and Study of Risk Factors Associated with MDS Evolution to Leukemia].

Science.gov (United States)

Ma, Yan; Chen, Bo-Bin; Wang, Xiao-Qin; Xu, Xiao-Ping; Lin, Guo-Wei

2015-12-01

To establish a nested case-control study cohort in myelodysplastic syndrome (MDS) patients and investigate the clinical characteristics, WHO subtype and risk factors associated with MDS evolution to leukemia of this cohort. All patients, ≥18 years of age, provided by 24 Shanghai hospitals with initial clinical findings consistent with a hematopoietic abnormality between June 2003 and April 2007, were the candidates for inclusion in this study. The blood and bone marrow samples of every patient should be provided at baseline. Diagnosis was made by incorporating morphologic, immunophenotypic, cytogenetic and molecular features according to WHO classification criteria. Cytogenetic analysis was performed using conventional G-banding karyotyping and fluorescence in situ hybridization (FISH) techniques. Cumulative risk of evolution was estimated by Kaplan-Meier method. Prognostic factors were evaluated by univariate Log-rank method and multivariate Cox proportional hazard models. A total of 435 patients were diagnosed as MDS. The median age of MDS onset was 58(18-90) years, with 248 male patients and 187 female patients (male: female 1.33: 1). The percentage of cases with refractory cytopenia with multilineage dysplasia (RCMD) was the highest (65.5%), while that of refraetory anemia (RA) (2.3%), refractory anenia with ring sideroblast (RARS) (1.1%) and 5q-syndrome (0.5%) was lower. Trisomy 8 (+8) was the most common chromosome abnormalities (71 cases, 12.7%). The mean follow-up time was 20.3 (4.2-57.1) months. Cases were patients with evolution by the end of follow-up, while controls were patients without evolution by that time. Case group included 41 patients and control group included 342 patients. Univariate analysis showed that the age, sex, WHO subtype, WBC count, absolute neutrophil count (ANC), IPSS cytogenetic subgroup, IPSS group and bone marrow blast percentage were significant risk factors for leukemia-free survival (LFS). Multivariate analysis of COX model

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro.

Science.gov (United States)

Calkoen, F G J; Vervat, C; van Pel, M; de Haas, V; Vijfhuizen, L S; Eising, E; Kroes, W G M; 't Hoen, P A C; van den Heuvel-Eibrink, M M; Egeler, R M; van Tol, M J D; Ball, L M

2015-03-01

Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n=10 and advanced MDS: n=7) and pediatric controls (n=10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets. Copyright © 2015. Published by Elsevier B.V.

Cytomorphology review of 100 newly diagnosed lower-risk MDS patients in the European LeukemiaNet MDS (EUMDS) registry reveals a high inter-observer concordance.

Science.gov (United States)

de Swart, Louise; Smith, Alex; MacKenzie, Marius; Symeonidis, Argiris; Neukirchen, Judith; Mikulenková, Dana; Vallespí, Teresa; Zini, Gina; Paszkowska-Kowalewska, Malgorzata; Kruger, Anton; Saft, Leonie; Fenaux, Pierre; Bowen, David; Hellström-Lindberg, Eva; Čermák, Jaroslav; Stauder, Reinhard; Tatic, Aurelia; Holm, Mette Skov; Malcovati, Luca; Mądry, Krzysztof; Droste, Jackie; Blijlevens, Nicole; de Witte, Theo; Germing, Ulrich

2017-07-01

The European LeukemiaNet MDS (EUMDS) registry is collecting data of myelodysplastic syndrome (MDS) patients belonging to the IPSS low or intermediate-1 category, newly diagnosed by local cytologists. The diagnosis of MDS can be challenging, and some data report inter-observer variability with regard to the assessment of the MDS subtype. In order to ensure that correct diagnoses were made by the participating centres, blood and bone marrow slides of 10% of the first 1000 patients were reviewed by an 11-person panel of cytomorphologists. All slides were rated by at least 3 panel members (median 8 panel members; range 3-9). Marrow slides from 98 out of 105 patients were of good quality and therefore could be rated properly according to the WHO 2001 classification, including assessment of dysplastic lineages. The agreement between the reviewers whether the diagnosis was MDS or non-MDS was strong with an intra-class correlation coefficient (ICC) of 0.85. Six cases were detected not to fit the entry criteria of the registry, because they were diagnosed uniformly as CMML or AML by the panel members. The agreement by WHO 2001 classification was strong as well (ICC = 0.83). The concordance of the assessment of dysplastic lineages was substantial for megakaryopoiesis and myelopoiesis and moderate for erythropoiesis. Our data show that in general, the inter-observer agreement was high and a very low percentage of misdiagnosed cases had been entered into the EUMDS registry. Further studies including histomorphology are warranted.

Independent Validation of the SEND-PD and Correlation with the MDS-UPDRS Part IA

Directory of Open Access Journals (Sweden)

Mayela Rodríguez-Violante

2014-01-01

Full Text Available Introduction. Neuropsychiatric symptoms in Parkinson’s disease can be assessed by the MDS-UPDRS part IA. The Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s disease (SEND-PD has been recently developed to assess the severity of some neuropsychiatric symptoms. The objective of this study is to compare the performance of the SEND-PD with the corresponding items of the MDS-UPDRS part IA. Methods. Patients with Parkinson’s disease were evaluated using the MDS-UPDRS and the SEND-PD by independent raters. Partial SEND-PD and neuropsychiatric MDS-UPDRS part IA were constructed with equivalent items for comparison. Results. A total of 260 consecutive patients were included. Overall, 61.2% of the patients did not report any psychotic symptom and 83.5% did not report any ICD symptom. On the other hand, 78.5% of the patients did report at least one symptom related to apathy, depression, or anxiety. The partial SEND-PD score was 2.9±3.1 (range from 0 to 16. The neuropsychiatric MDS-UPDRS part IA score was 2.9±3 (range from 0 to 14. The correlation coefficient between corresponding items ranged from 0.67 to 0.98 and between both summary indexes was rs=0.93 (all, P<0.001. Conclusion. A high association between equivalent items of the SEND-PD and the MDS-UPDRS was found.

An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.

Science.gov (United States)

Savona, Michael R; Malcovati, Luca; Komrokji, Rami; Tiu, Ramon V; Mughal, Tariq I; Orazi, Attilio; Kiladjian, Jean-Jacques; Padron, Eric; Solary, Eric; Tibes, Raoul; Itzykson, Raphael; Cazzola, Mario; Mesa, Ruben; Maciejewski, Jaroslaw; Fenaux, Pierre; Garcia-Manero, Guillermo; Gerds, Aaron; Sanz, Guillermo; Niemeyer, Charlotte M; Cervantes, Francisco; Germing, Ulrich; Cross, Nicholas C P; List, Alan F

2015-03-19

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation. © 2015 by The American Society of Hematology.

MDS Nordion - a Canadian success story

International Nuclear Information System (INIS)

Boyd, F.

1998-01-01

MDS Nordion,the world leading supplier of radioisotopes, had its beginnings as a small division of the crown company Eldorado Mining and Refining Ltd. in the late 1940's. With the end of World War II, Eldorado found itself with a supply of radium left over from the production of uranium during the war and set up a small group in Ottawa to sell it. Most of the stock of radium was disposed of when the development of the NRX reactor made reactor produced radioisotopes possible. The company turned to selling these radioisotopes and soon focused on Cobalt 60 for its use in cancer therapy. In 1952, the group transferred to AECL (Atomic Energy of Canada Ltd.), as part of the Commercial Products Division. In 1988, as part of the federal government's move to privatization, the organization was split into two companies, Theratronics, which manufactures the cancer therapy machines and other equipment for the use of radioisotopes, and Nordion International, which continued the primary business of processing, packaging, selling radioisotopes. In 1991 Nordion International was sold to MDS Inc., a large international group of companies in the life and sciences fields with headquarters in Toronto. The name was changed to MDS Nordion in December 1996

[Inhibitory Effect of Decitabine on Proliferation of MDS-L Cells and Its Mechanism].

Science.gov (United States)

Wu, Dong; Zhang, Yao; Zhao, You-Shan; Guo, Juan; Chang, Chun-Kang

2017-10-01

To investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism. LC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m 2 ×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15 INK4B DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit. The blood DAC concentration of MDS patients treated with DAC 20 mg/m 2 ×5 d was 174.08±80.15(84.7-311) ng/ml, which was significantly higher than 89.87±32.94(43.2-165)ng/ml for the group treated with 15 mg/m 2 ×5 d (P=0.014). DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in dose- and- time-dependent manner(r=0.786). However, when DAC concentration was ≥0.1 µg/ml, the proliferation inhibition rates were not significantly different between various dosages. After DAC treatment, MDS-L cells in G 1 phase increased notably, while cells in S phase decreased significantly. Also, the P15 INK4B DNA methylation status of MDS-L cells decreased after being treated with DAC for 96 h, but the difference was not significant between various dosages. DAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in G 1 phase and induce the apoptosis at low concentration (0.1-0.2 µg/ml).

Mouse Drawer System (MDS): An autonomous hardware for supporting mice space research

Science.gov (United States)

Liu, Y.; Biticchi, R.; Alberici, G.; Tenconi, C.; Cilli, M.; Fontana, V.; Cancedda, R.; Falcetti, G.

2005-08-01

For the scientific community the ability of flying mice under weightless conditions in space, compared to other rodents, offers many valuable advantages. These include the option of testing a wide range of wild-type and mutant animals, an increased animal number for flight, and a reduced demand on shuttle resources and crew time. In this study, we describe a spaceflight hardware for mice, the Mouse Drawer System (MDS). MDS can interface with Space Shuttle middeck and International Space Station Express Rack. It consists of Mice Chamber, Liquid Handling Subsystem, Food Delivery Subsystem, Air Conditioning Subsystem, Illumination Subsystem, Observation Subsystem and Payload Control Unit. It offers single or paired containment for 6-8 mice with a mean weight of 40 grams/mouse for a period of up to 3 months. Animal tests were conducted in a MDS breadboard to validate the biocompatibility of various subsystems. Mice survived in all tests of short and long duration. Results of blood parameters, histology and air/waste composition analysis showed that MDS subsystems meet the NIH guidelines for temperature, humidity, food and water access, air quality, odour and waste management.

[mRNA expression of notch ligand-delta-like-1 and jagged-1 in mesenchymal stem cells of MDS patients].

Science.gov (United States)

Fei, Cheng-Ming; Gu, Shu-Cheng; Zhao, You-Shan; Guo, Juan; Li, Xiao; Chang, Chun-Kang

2014-12-01

This study was aimed to investigated the mRNA expression levels of Notch ligands- Delta-like-1 and Jagged-1 in bone marrow mesenchymal stem cells of patients with myelodysplastic syndrome (MDS), and to explore their relation with onset of MDS. Bone marrow mesenchymal stem cells of 38 patients with MDS and 16 normal subjects as control were collected to detect mRNA expression of Delta-like-1 and Jagged-1 by using real-time quantitative polymerase chain reaction. The results showed that the expression levels of Delta-like-1 and Jagged-1 in mesenchymal stem cells of MDS patients were significantly higher than that in normal controls (P MDS patients (r = 0.502, P MDS patients with abnormal karyotypes were significantly higher than those in MDS patients with normal karyotypes (P 0.05). It is concluded that the changes of Delta-like-1 and Jagged-1 expression level in MSC may play a role in the pathogenesis of myelodysplastic syndrome.

Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

Science.gov (United States)

Babushok, Daria V; Bessler, Monica

2015-03-01

Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical and biological significance of isolated Y chromosome loss in myelodysplastic syndromes and chronic myelomonocytic leukemia. A report from the Spanish MDS Group.

Science.gov (United States)

Nomdedeu, Meritxell; Pereira, Arturo; Calvo, Xavier; Colomer, Joan; Sole, Francesc; Arias, Amparo; Gomez, Candida; Luño, Elisa; Cervera, Jose; Arnan, Montserrat; Pomares, Helena; Ramos, Fernando; Oiartzabal, Itziar; Espinet, Blanca; Pedro, Carme; Arrizabalaga, Beatriz; Blanco, María Laura; Tormo, Mar; Hernandez-Rivas, Jesus Maria; Díez-Campelo, María; Ortega, Margarita; Valcárcel, David; Cedena, Maria-Teresa; Collado, Rosa; Grau, Javier; Granada, Isabel; Sanz, Guillermo; Campo, Elias; Esteve, Jordi; Costa, Dolors

2017-12-01

Isolate loss of chromosome Y (-Y) in myelodysplastic syndromes (MDS) is associated to a better outcome but it is also well described as an age-related phenomenon. In this study we aimed to analyze the prognostic impact of -Y in the context of the IPSS-R cytogenetic classification, evaluate the clinical significance of the percentage of metaphases with isolated -Y, and test whether finding -Y may predispose to over-diagnose MDS in patients with borderline morphological features. We evaluated 3581 male patients from the Spanish MDS Registry with a diagnosis of MDS or chronic myelomonocytic leukemia (CMML). -Y was identified in 177 patients (4.9%). Compared with the 2246 male patients with normal karyotype, -Y group showed a reduced risk of leukemic transformation that did not translate into a survival advantage. The overall survival and the risk of leukemic transformation were not influenced by the percentage of metaphases with -Y. The -Y group was not enriched in patients with minor morphologic traits of dysplasia, suggesting that the better outcome in the -Y group cannot be explained by enrichment in cases misdiagnosed as MDS. In conclusion, our results support the current recommendation of classifying patients with -Y within the very good risk category of the IPSS-R for MDS and rule out a selection bias as a possible explanation of this better outcome. An analysis of the molecular basis of MDS with isolated -Y would be of interest as it may provide a biological basis of protection against progression to acute leukemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia.

Science.gov (United States)

Navada, Shyamala C; Fruchtman, Steven M; Odchimar-Reissig, Rosalie; Demakos, Erin P; Petrone, Michael E; Zbyszewski, Patrick S; Holland, James F; Silverman, Lewis R

2018-01-01

This Phase 1/2, dose-escalating study of rigosertib enrolled 22 patients with higher-risk myelodysplastic syndromes (MDS) (n=9) and acute myeloid leukemia (AML; n=13) who had relapsed or were refractory to standard therapy and for whom no second-line therapies were approved. Patients received 3- to 7-day continuous intravenous infusions of rigosertib, an inhibitor of Ras-effector pathways that interacts with the Ras-binding domains, common to several signaling proteins including Raf and PI3 kinase. Rigosertib was administered at doses of 650-1700mg/m 2 /day in 14-day cycles. Initial dose escalation followed a Fibonacci scheme, followed by recommended phase 2 dose confirmation in an expanded cohort. Rigosertib was well tolerated for up to 23 cycles, with no treatment-related deaths and 18% of patients with related serious adverse events (AEs). Common AEs were fatigue, diarrhea, pyrexia, dyspnea, insomnia, and anemia. Rigosertib exhibited biologic activity, with reduction or stabilization of bone marrow blasts and improved peripheral blood counts in a subset of patients. Ten of 19 evaluable patients (53%) demonstrated bone marrow/peripheral blood responses (n=4 MDS, n=1 AML) or stable disease (n=3 MDS, n=2 AML). Median survival was 15.7 and 2.0 months for responders and non-responders, respectively. Additional studies of rigosertib are ongoing in higher-risk MDS (NCT00854646). Copyright © 2017 Elsevier Ltd. All rights reserved.

Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents.

Science.gov (United States)

Lix, Lisa M; Yan, Lin; Blackburn, David; Hu, Nianping; Schneider-Lindner, Verena; Teare, Gary F

2014-01-15

This study assessed the validity of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0 for diagnoses of diabetes and comorbid conditions in residents of long-term care facilities (LTCFs). Hospital inpatient, outpatient physician billing, RAI-MDS, and population registry data for 1997 to 2011 from Saskatchewan, Canada were used to ascertain cases of diabetes and 12 comorbid conditions. Prevalence estimates were calculated for both RAI-MDS and administrative health data. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated using population-based administrative health data as the validation data source. Cohen's κ was used to estimate agreement between the two data sources. 23,217 LTCF residents were in the diabetes case ascertainment cohort. Diabetes prevalence was 25.3% in administrative health data and 21.9% in RAI-MDS data. Overall sensitivity of a RAI-MDS diabetes diagnoses was 0.79 (95% CI: 0.79, 0.80) and the PPV was 0.92 (95% CI: 0.91, 0.92), when compared to administrative health data. Sensitivity of the RAI-MDS for ascertaining comorbid conditions ranged from 0.21 for osteoporosis to 0.92 for multiple sclerosis; specificity was high for most conditions. RAI-MDS clinical assessment data are sensitive to ascertain diabetes cases in LTCF populations when compared to administrative health data. For many comorbid conditions, RAI-MDS data have low validity when compared to administrative data. Risk-adjustment measures based on these comorbidities might not produce consistent results for RAI-MDS and administrative health data, which could affect the conclusions of studies about health outcomes and quality of care across facilities.

Therapy-related AML/MDS after treatment of low-grade B-cell lymphoma

International Nuclear Information System (INIS)

Yanada, Masamitsu

2008-01-01

Described is the therapy-related AML (acute myelogenetic leukemia)/MDS (myelo-dysplasia syndrome), which is manifested after various treatments of low-grade B-cell lymphoma and has strongly attracted attention because of the markedly improved prognosis due to recent advantages of the therapy for the disease. AML/MDS occurs several years after chemotherapy and/or radiation therapy which cause DNA damage in hematopoietic cells, and the AML/MDS risk is known increased in patients undergone especially with autologous transplantation of those cells. AML/MDS has the feature similar to that caused either by alkylating agent or by topoisomerase-2 inhibitor, and the disease by radiation belong to the former. Yet unclear is the problem whether malignant cells causing the disease after therapy are derived from the remaining cells in the graft or in the body. Although irradiations of total body and total lymphaden as well as chemotherapy are said to be related to AML/MDS and local irradiation does not contribute to its risk, the most important factor for the disease is considered to be the autotransplantation as the recurrence occurs in 50% after it. Thus the treatment history should be taken into consideration for suppressing AML/MDS, for which follow up with consideration for the disease is required particularly after autotransplantation. (R.T.)

MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance.

Science.gov (United States)

Kwok, Brian; Hall, Jeff M; Witte, John S; Xu, Yin; Reddy, Prashanti; Lin, Keming; Flamholz, Rachel; Dabbas, Bashar; Yung, Aine; Al-Hafidh, Jenan; Balmert, Emily; Vaupel, Christine; El Hader, Carlos; McGinniss, Matthew J; Nahas, Shareef A; Kines, Julie; Bejar, Rafael

2015-11-19

Establishing a diagnosis in patients suspected of having a myelodysplastic syndrome (MDS) can be challenging and could be informed by the identification of somatic mutations. We performed a prospective study to examine the frequency and types of mutations encountered in 144 patients with unexplained cytopenias. Based on bone marrow findings, 17% were diagnosed with MDS, 15% with idiopathic cytopenias of undetermined significance (ICUS) and some evidence of dysplasia, and 69% with ICUS and no dysplasia. Bone marrow DNA was sequenced for mutations in 22 frequently mutated myeloid malignancy genes. Somatic mutations were identified in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients and no dysplasia. In total, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis. We validated these results in a cohort of 91 lower-risk MDS and 249 ICUS cases identified over a 6-month interval. Mutations were found in 79% of those with MDS, in 45% of those with ICUS with dysplasia, and in 17% of those with ICUS without dysplasia. The spectrum of mutated genes was similar with the exception of SF3B1 which was rarely mutated in patients without dysplasia. Variant allele fractions were comparable between clonal ICUS (CCUS) and MDS as were mean age and blood counts. We demonstrate that CCUS is a more frequent diagnosis than MDS in cytopenic patients. Clinical and mutational features are similar in these groups and may have diagnostic utility once outcomes in CCUS patients are better understood. © 2015 by The American Society of Hematology.

PP2A: The Achilles Heal in MDS with 5q Deletion

Directory of Open Access Journals (Sweden)

David eSallman

2014-09-01

Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

Expanded and independent validation of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

Science.gov (United States)

Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Bergareche-Yarza, Alberto; Chade, Anabel; Garretto, Nelida; Gershanik, Oscar; Kurtis, Monica M; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Moore, Henry P; Rodriguez-Violante, Mayela; Singer, Carlos; Tilley, Barbara C; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G

2013-01-01

The Movement Disorder Society-UPDRS (MDS-UPDRS) was published in 2008, showing satisfactory clinimetric results and has been proposed as the official benchmark scale for Parkinson's disease. The present study, based on the official MDS-UPDRS Spanish version, performed the first independent testing of the scale and adds information on its clinimetric properties. The cross-culturally adapted MDS-UPDRS Spanish version showed a comparative fit index ≥ 0.90 for each part (I-IV) relative to the English-language version and was accepted as the Official MDS-UPDRS Spanish version. Data from this scale, applied with other assessments to Spanish-speaking Parkinson's disease patients in five countries, were analyzed for an independent and complementary clinimetric evaluation. In total, 435 patients were included. Missing data were negligible and moderate floor effect (30 %) was found for Part IV. Cronbach's α index ranged between 0.79 and 0.93 and only five items did not reach the 0.30 threshold value of item-total correlation. Test-retest reliability was adequate with only two sub-scores of the item 3.17, Rest tremor amplitude, reaching κ values lower than 0.60. The intraclass correlation coefficient was higher than 0.85 for the total score of each part. Correlation of the MDS-UPDRS parts with other measures for related constructs was high (≥ 0.60) and the standard error of measurement lower than one-third baseline standard deviation for all subscales. Results confirm those of the original study and add information on scale reliability, construct validity, and precision. The MDS-UPDRS Spanish version shows satisfactory clinimetric characteristics.

Incorporating novel approaches in the management of MDS beyond conventional hypomethylating agents.

Science.gov (United States)

Odenike, Olatoyosi

2017-12-08

In the last decade, the treatment of higher-risk myelodysplastic syndromes (MDS) has revolved around the azanucleosides, azacitidine and decitabine, which at lower doses are postulated to work predominantly via their effects on inhibition of DNA methyltransferases and consequent DNA hypomethylation. For patients who relapse after, or do not respond to, hypomethylating agent therapy, the outcome is dismal, and new agents and approaches that have the potential to alter the natural history of these diseases are desperately needed. Allogeneic stem cell transplant is the only known potentially curative approach in MDS, but its applicability has been limited by the advanced age of patients and attendant comorbidities. There is now an increasing array of new agents under clinical investigation in MDS that aim to exploit our expanding understanding of molecular pathways that are important in the pathogenesis of MDS. This review focuses on a critical appraisal of novel agents being evaluated in higher-risk MDS that go beyond the conventional hypomethylating agent therapies approved by the US Food and Drug Administration. © 2016 by The American Society of Hematology. All rights reserved.

Survey of expert opinions and related recommendations regarding bridging therapy using hypomethylating agents followed by allogeneic transplantation for high-risk MDS.

Science.gov (United States)

Sohn, Sang Kyun; Moon, Joon Ho

2015-08-01

According to current guidelines on therapeutic strategies for myelodysplastic syndrome (MDS), cytoreductive therapies before allogeneic stem cell transplantation (SCT) are not widely recommended for patients with high-risk MDS or refractory anemia with excess blasts (RAEB) who are eligible for allogeneic SCT because of controversial evidence on the role of such therapies. Yet, while treatment with hypomethylating agents (HMAs) has a critical limitation in eradicating MDS clones, the use of HMA treatment as a bridge to allogeneic SCT has become a focus with the hope of improving the SCT outcome based on the chance of achieving complete remission or reducing the blast percentage safely and effectively before allogeneic SCT. However, a consensus needs to be established on the use of HMAs as a bridging therapy for high-risk MDS or RAEB. Thus, the Korean AML/MDS working party group surveyed 34 Korean MDS experts on their bridging therapies for high-risk MDS. Accordingly, this paper presents the survey questionnaire and resulting data, along with a summary of the consensus and related recommendations regarding strategies using HMA treatment and allogeneic SCT based on reported studies and the current survey results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The need for additional genetic markers for MDS stratification: what does the future hold for prognostication?

Science.gov (United States)

Otrock, Zaher K.; Tiu, Ramon V.; Maciejewski, Jaroslaw P.; Sekeres, Mikkael A.

2013-01-01

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of clonal hematopoietic disorders. Metaphase cytogenetics (MC) has been the gold standard for genetic testing in MDS, but it can detect clonal cytogenetic abnormalities in only 50% of cases. New karyotyping tests include fluorescence in situ hybridization (FISH), array-based comparative genomic hybridization (aCGH), and single nucleotide polymorphism arrays (SNP-A). These techniques have increased the detected genetic abnormalities in MDS, many of which confer prognostic significance to overall and leukemia-free survival. This has eventually increased our understanding of MDS genetics. With the help of new technologies, we anticipate that the existing prognostic scoring systems will incorporate mutational data into their parameters. This review discusses the progress in MDS diagnosis through the use of array-based technologies. We also discuss the recently investigated genetic mutation in MDS, and revisit the MDS classification and prognostic scoring systems. PMID:23373781

PD-1 signaling and inhibition in AML and MDS.

Science.gov (United States)

Haroun, Faysal; Solola, Sade A; Nassereddine, Samah; Tabbara, Imad

2017-09-01

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are clinically and molecularly heterogeneous clonal myeloid disorders with a poor prognosis especially in the relapsed refractory setting and in patients above the age of 60. While allogeneic hematopoietic stem cell transplantation (ASCT) is a potentially curative approach, high relapse, morbidity, and mortality rates necessitate the development of alternative therapies. Immune checkpoint inhibitors unmask tumoral immune tolerance and have demonstrated efficacy in the treatment of chemotherapy-resistant hematologic and solid malignancies. The rationale for the investigation of those agents in AML and MDS is supported by an observed increased expression of programmed cell death 1 protein (PD-1) and ligand 1 (PD-L1) in the hematopoietic microenvironment of AML and MDS, and its association with low TP53 and a poor prognosis. Early clinical experience in combination with a hypomethylating agent has shown encouraging responses; however, larger clinical trials are needed to determine the role of checkpoint inhibition in myeloid malignancies.

Cost of transfusion-dependent myelodysplastic syndrome (MDS) from a German payer?s perspective

OpenAIRE

2010-01-01

Abstract No curative treatment exists for patients with myelodysplastic syndrome (MDS) besides allogeneic stem cell transplantation. Hence, palliative treatment is provided for a life time accruing high health care cost. As no study in cost of MDS exists in Germany, the objective of this study was to assess and analyze costs of transfusion-dependent low/intermediate-1-risk MDS in Germany from a payers? perspective. From seven centers, 116 low/intermediate-1-risk transfusion-depende...

75 FR 16512 - Willstaff Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working...

Science.gov (United States)

2010-04-01

... Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., Working On-Site at Tyler Pipe... MDS Industrial Resources, Inc., working on-site at Tyler Pipe Company, Waterworks Division, South... Staffing Agency, Willstaff Crystal, Inc., and MDS Industrial Resources, Inc., working on-site at Tyler Pipe...

Parkinson's disease severity levels and MDS-Unified Parkinson's Disease Rating Scale.

Science.gov (United States)

Martínez-Martín, Pablo; Rodríguez-Blázquez, Carmen; Mario Alvarez; Arakaki, Tomoko; Arillo, Víctor Campos; Chaná, Pedro; Fernández, William; Garretto, Nélida; Martínez-Castrillo, Juan Carlos; Rodríguez-Violante, Mayela; Serrano-Dueñas, Marcos; Ballesteros, Diego; Rojo-Abuin, Jose Manuel; Chaudhuri, Kallol Ray; Merello, Marcelo

2015-01-01

Severity of PD is usually assessed by means of the motor and disability-based Hoehn and Yahr staging (HY), or clinician and patient global perceptions. Scores of more detailed assessments, as the MDS-UPDRS, have not been translated to a grading that allows assignment of score sections to severity levels. The objective of the present study is to determine cut-off points for PD severity levels based on the MDS-UPDRS. International, observational study. Applied assessments were: HY, MDS-UPDRS, Clinical Impression for Severity Index, and Clinical and Patient Global Impression of Severity. The coincidence in severity level (mild, moderate, severe) of at least two clinical classifications plus the patient's gradation was considered "the criterion of severity". Cut-off values for each MDS-UPDRS subscale was determined by triangulation of: 1) percentile 90 of the subscale total score; 2) receiver operating characteristic (ROC) analysis; and 3) ordinal logistic regression (OLR) model. Sample was composed of 452 consecutive PD patients without dementia, 55.3% males, age 65.1 ± 10.7 years and PD duration 8.7 ± 6.3 years. All HY stages were represented. The "criterion", classified 275 patients (60.8% of the sample) as: mild PD, 149 (54.2%); moderate, 82 (29.8%); and severe, 44 (16%). The following MDS-UPDRS cut-off points between mild/moderate and moderate/severe levels were found: Part 1: 10/11 and 21/22; Part 2: 12/13 and 29/30; Part 3: 32/33 and 58/59; and Part 4: 4/5 and 12/13. Cut-off points to classify PD patients as mild, moderate, or severe on the basis of their MDS-UPDRS scores are proposed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

NARCIS (Netherlands)

MC Langemeijer, Saskia; Mariani, Niccolo; Knops, Ruth; Gilissen, Christian; Woestenenk, Rob; de Witte, Theo; Huls, Gerwin; van der Reijden, Bert A.; Jansen, Joop H.

2016-01-01

Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially

Entanglement-assisted quantum MDS codes from negacyclic codes

Science.gov (United States)

Lu, Liangdong; Li, Ruihu; Guo, Luobin; Ma, Yuena; Liu, Yang

2018-03-01

The entanglement-assisted formalism generalizes the standard stabilizer formalism, which can transform arbitrary classical linear codes into entanglement-assisted quantum error-correcting codes (EAQECCs) by using pre-shared entanglement between the sender and the receiver. In this work, we construct six classes of q-ary entanglement-assisted quantum MDS (EAQMDS) codes based on classical negacyclic MDS codes by exploiting two or more pre-shared maximally entangled states. We show that two of these six classes q-ary EAQMDS have minimum distance more larger than q+1. Most of these q-ary EAQMDS codes are new in the sense that their parameters are not covered by the codes available in the literature.

Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

DEFF Research Database (Denmark)

Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed

2010-01-01

This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

Long Term Care Minimum Data Set (MDS)

Data.gov (United States)

U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.

Science.gov (United States)

Dong, Wen; Wu, Lei; Sun, Houfang; Ren, Xiubao; Epling-Burnette, Pearlie K; Yang, Lili

2016-11-01

Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, pMDS using World Health Organization classification (WHO subgroups versus control: RARS, p= 0.009; RCMD, p=0.0002; RAEB1/2, p=0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, pMDS patients (n=20) had significantly higher telomerase activity (p=0.002), higher total hTERT mRNA levels (p=0.001) and hTERT α+β- splice variant expression (pMDS (r=0.58, p=0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.

Mutational profiling in patients with MDS: ready for every-day use in the clinic?

Science.gov (United States)

Bacher, Ulrike; Kohlmann, Alexander; Haferlach, Torsten

2015-03-01

Multiple recurrent somatic mutations were identified in the majority of patients with myelodysplastic syndromes (MDS), but investigating the broad spectrum of molecular markers in MDS exceeds many laboratories' capacity when traditional molecular techniques are used. High-throughput second generation sequencing (=next-generation sequencing, NGS) has proven to be applicable for comprehensive biomarker mutation analyses allowing to increase diagnostic sensitivity and accuracy and to improve risk stratification and prognostication in addition to cytomorphology and cytogenetic analysis in patients with MDS. Amplicon deep-sequencing enables comprehensive biomarker analysis in a multitude of patients per investigation in an acceptable turn-around time and at affordable costs. Comprehensive myeloid marker panels were successfully introduced into diagnostic practice. Therefore, molecular mutation analysis is ready for use in all patients with suspected MDS, may contribute to risk stratification in possible candidates for allogeneic stem cell transplantation, and should become an integral part of clinical research studies in MDS patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Connect MDS/AML: design of the myelodysplastic syndromes and acute myeloid leukemia disease registry, a prospective observational cohort study.

Science.gov (United States)

Steensma, David P; Abedi, Medrdad; Bejar, Rafael; Cogle, Christopher R; Foucar, Kathryn; Garcia-Manero, Guillermo; George, Tracy I; Grinblatt, David; Komrokji, Rami; Ma, Xiaomei; Maciejewski, Jaroslaw; Pollyea, Daniel A; Savona, Michael R; Scott, Bart; Sekeres, Mikkael A; Thompson, Michael A; Swern, Arlene S; Nifenecker, Melissa; Sugrue, Mary M; Erba, Harry

2016-08-19

Registry will be the first prospective, observational, non-interventional study in the United States to collect clinical information, patient-reported outcomes, and tissue samples from patients with MDS, ICUS, or AML receiving multiple therapies. Results from this registry may provide new insights into the relationship between diagnostic practices, treatment regimens, and outcomes in patients with these diseases and identify areas for future investigation. Connect MDS/AML Disease Registry ( NCT01688011 ). Registered 14 September 2012.

Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

Science.gov (United States)

Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

2018-04-01

Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

New q-ary quantum MDS codes with distances bigger than q/2

Science.gov (United States)

He, Xianmang; Xu, Liqing; Chen, Hao

2016-07-01

The construction of quantum MDS codes has been studied by many authors. We refer to the table in page 1482 of (IEEE Trans Inf Theory 61(3):1474-1484, 2015) for known constructions. However, there have been constructed only a few q-ary quantum MDS [[n,n-2d+2,d

A pilot study on the usefulness of peripheral blood flow cytometry for the diagnosis of lower risk myelodysplastic syndromes: the "MDS thermometer".

Science.gov (United States)

Aires, Ana; Teixeira, Maria Dos Anjos; Lau, Catarina; Moreira, Cláudia; Spínola, Ana; Mota, Alexandra; Freitas, Inês; Coutinho, Jorge; Lima, Margarida

2018-01-01

Immunophenotypic analysis of the bone marrow (BM) cells has proven to be helpful in the diagnosis of Myelodysplastic Syndromes (MDS). However, the usefulness of flow cytometry (FCM) for the detection of myelodysplasia in the peripheral blood (PB) still needs to be investigated. The aim of this pilot study was to evaluate the value of FCM-based PB neutrophil and monocyte immunophenotyping for the diagnosis of lower risk MDS (LR-MDS). We evaluated by 8-color FCM the expression of multiple cell surface molecules (CD10, CD11b, CD11c, CD13, CD14, CD15, CD16, CD34, CD45, CD56, CD64 and HLA-DR) in PB neutrophils and monocytes from a series of 14 adult LR-MDS patients versus 14 normal individuals. Peripheral blood neutrophils from patients with LR-MDS frequently had low forward scatter (FSC) and side scatter (SSC) values and low levels of CD11b, CD11c, CD10, CD16, CD13 and CD45 expression, in that order, as compared to normal neutrophils. In addition, patients with LR-MDS commonly display a higher fraction of CD14 + CD56 + and a lower fraction of CD14 + CD16 + monocytes in the PB. Based on these results, we proposed an immunophenotyping score based on which PB samples from patients with LR-MDS could be distinguished from normal PB samples with a sensitivity 93% and a specificity of 100%. In addition, we used this score to construct the MDS Thermometer, a screening tool for detection and monitoring of MDS in the PB in clinical practice. Peripheral blood neutrophil and monocyte immunophenotyping provide useful information for the diagnosis of LR-MDS, as a complement to cytomorphology. If validated by subsequent studies in larger series of MDS patients and extended to non-MDS patients with cytopenias, our findings may improve the diagnostic assessment and avoid invasive procedures in selected groups of MDS patients.

IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

Science.gov (United States)

Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

2015-05-14

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

MDS-UPDRS to assess non-motor symptoms after STN DBS for Parkinson's disease.

Science.gov (United States)

Jafari, Nickey; Pahwa, Rajesh; Nazzaro, Jules M; Arnold, Paul M; Lyons, Kelly E

2016-01-01

To determine if the non-motor sections of the Movement Disorder Society's (MDS) version of the Unified Parkinson's Disease Rating Scale (UPDRS) could supplement the original UPDRS as a patient completed assessment of changes in non-motor symptoms in Parkinson's disease (PD) patients after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS). Thirty PD patients who underwent bilateral STN DBS were assessed using the total UPDRS and the non-motor sections of the MDS-UPDRS prior to surgery and one year following surgery. This study focuses on non-motor symptoms as assessed by Part I of the UPDRS and Part 1A and 1B of the MDS-UPDRS. One year following surgery, no individual non-motor symptoms or the total mentation score of the UPDRS were significantly changed. In comparison, the MDS-UPDRS showed significant improvements in sleep and urinary problems and a trend towards improvement in anxiety, constipation, daytime sleepiness, fatigue and pain. This study provides evidence that the MDS-UPDRS non-motor sections, when completed by the patients, can supplement the original version of the UPDRS as an effective method of measuring changes in non-motor symptoms after DBS. It also reinforces the benefits of bilateral STN DBS on non-motor symptoms of PD.

Resident Assessment Instrument/Minimum Data Set (RAI/MDS)

Data.gov (United States)

Department of Veterans Affairs — The Resident Assessment Instrument/Minimum Data Set (RAI/MDS) is a comprehensive assessment and care planning process used by the nursing home industry since 1990 as...

Impact Of Mutation-derived Antigens In Immune Recognition Of Hematological Malignancies, Specifically Myeloid Dysplastic Syndromes (MDS)

DEFF Research Database (Denmark)

Saini, Sunil Kumar; Dorfmüller, S.; Bjerregaard, Anne-Mette

2016-01-01

Mutation-derived neoepitopes have been suggested as a major component for immune recognition of solid tumors with a high mutational load, e.g. Melanoma and Non-Small-Cell Lung Cancer (NSCLC). Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms characterized by increasing...

[TOPICS-MDS: a versatile resource for generating scientific and social knowledge for elderly care].

Science.gov (United States)

van den Brink, Danielle; Lutomski, Jennifer E; Qin, Li; den Elzen, Wendy P J; Kempen, Gertrudis I J M; Krabbe, Paul F M; Steyerberg, Ewout W; Muntinga, Maaike; Moll van Charante, Eric P; Bleijenberg, Nienke; Olde Rikkert, Marcel G M; Melis, René J F

2015-04-01

Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a standardized questionnaire to collect relevant health care data on quality of life, health services utilization, and informal care use. A proactive approach has been undertaken not only to ensure the standardization and validation of instruments but also the infrastructure for external data requests. Efforts have been made to promote scientifically and socially responsible use of TOPICS-MDS; data has been available for secondary use since early 2014. Through this data sharing initiative, researchers can explore health issues in a broader framework which may have not been possible within individual NPO projects; this broader framework is highly relevant for influencing health policy. In this article, we provide an overview of the development and on-going progress of TOPICS-MDS. We further describe how information derived from TOPICS-MDS can be applied to facilitate future scientific innovations and public health initiatives to improve care for frail older persons and their caregivers.

Studies on the tumor initiation/promotion potential of six middle distillates (MDs) in mouse skin.

Science.gov (United States)

Jungen, H; Mellert, W; Wenzel-Hartung, R

1995-08-01

Six middle distillates (MDs) were tested for tumor initiating/promoting activity after application to the skin of 30 male CD-1 (ICR) BR mice per group. As the control, 7,12-dimethylbenz[a]-anthracene (DMBA) was used for initiation followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) for promotion. For assessing the tumor-initiating activity, 50 microliters of neat MDs was administered for 5 days with subsequent TPA promotion. In the promotion bioassay, after DMBA initiation 50 microliters of the neat MDs was administered twice weekly until Week 28. For the examination of complete carcinogenic activity, one MD was given without DMBA initiation. Hyperkeratosis, hyperplasia, and dermal inflammation, occurring during the initiation with the MDs, were completely reversible during the 2-week treatment-free period after initiation. Similar skin findings were observed during promotion with the MDs. Regarding the number of affected animals and the severity of the response, TPA was more irritating than the MDs. The initiation study revealed skin tumors for the DMBA/TPA control (30/30), MD 57,389 (14/30), MD 57,396 (5/30), MD 57,383 (4/30) and MD 57,324 (2/30). The promotion study revealed tumor induction by MDs 57,389 (9/30), 57,324 (1/30), 57,393 (1/30), and 57,396 (1/30). Two of 30 animals treated with MD 57,389 developed tumors without DMBA initiation thus indicating that it also is a complete carcinogen. MD 57,399 caused neither initiating nor promoting effects. The tumors observed were diagnosed histopathologically predominantly as squamous cell papillomas.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes of CD34(+) and CD71(+)CD45(-) cell levels in bone marrow of MDS and AA patients].

Science.gov (United States)

Yan, Zhen-Yu; Tian, Xu; Li, Ying; Yang, Mei-Rong; Zhang, Song; Wang, Xie-Ming; Zhang, Hai-Xia; Cheng, Nai-Yao

2014-04-01

This study was aimed to investigate the changes of CD34(+) and CD71(+)CD45(-) cell levels in MDS and AA patients. A total of 25 cases MDS and 43 cases of AA (18 cases SAA and 25 cases of NSAA) from January 2010 to October 2013 in the Department of Hematology, affiliated hospital of Hebei United University were enrolled in this study. The complete blood count, bone marrow smears, bone marrow biopsy, karyotype analysis and bone marrow blood cell immune genotyping (mainly the proportion of CD34(+) cells, CD71(+)CD45(-) cells in nucleated cells) were carried out for all patients; the changes of CD34(+) and CD71(+)CD45(-) cell levels in patients with MDS and AA (SAA NSAA) were compared; the differences of white blood cell count, platelet count and hemoglobin concentration in patients with count of CD71(+)CD45(-) ≥ 15% or MDS group was higher than that in AA (NSAA and SAA) group (P MDS group was higher than that in SAA (P MDS group. In MDS group with CD71(+)CD45(-) ≥ 15%, the platelet count was significantly higher than that in NSAA group (P MDS and NSAA group with CD71(+)CD45(-) 0.05). It is concluded that the count of CD34(+) cells in MDS patients is significantly higher than that in AA and SAA patients. The count of CD71(+)CD45(-) cells in MDS group is significantly higher than that of SAA group. The platelet count in MDS patients with CD71(+)CD45(-) cells ≥ 15% is significantly higher than that of the NSAA group.

Azacitidine improves outcome in higher-risk MDS patients with chromosome 7 abnormalities: a retrospective comparison of GESMD and GFM registries.

Science.gov (United States)

Díez-Campelo, María; Lorenzo, Jose I; Itzykson, Raphael; Rojas, Silvia M; Berthon, Céline; Luño, Elisa; Beyne-Rauzy, Odile; Perez-Oteyza, Jaime; Vey, Norbert; Bargay, Joan; Park, Sophie; Cedena, Teresa; Bordessoule, Dominique; Muñoz, Juan A; Gyan, Emmanuel; Such, Esperanza; Visanica, Sorin; López-Cadenas, Félix; de Botton, Stéphane; Hernández-Rivas, Jesús M; Ame, Shanti; Stamatoullas, Aspasia; Delaunay, Jacques; Salanoubat, Celia; Isnard, Françoise; Guieze, Romain; Pérez Guallar, Joan; Badiella, Llorenc; Sanz, Guillermo; Cañizo, Consuelo; Fenaux, Pierre

2018-05-01

Treatment with azacitidine (AZA) has been suggested to be of benefit for higher-risk myelodysplastic syndrome (HR-MDS) patients with chromosome 7 abnormalities (Abn 7). This retrospective study of 235 HR-MDS patients with Abn 7 treated with AZA (n = 115) versus best supportive care (BSC; n = 120), assessed AZA treatment as a time-varying variable in multivariable analysis. A Cox Regression model with time-interaction terms of overall survival (OS) at different time points confirmed that, while chromosome 7 cytogenetic categories (complex karyotype [CK] versus non-CK) and International Prognostic Scoring System risk (high versus intermediate-2) retained poor prognosis over time, AZA treatment had a favourable impact on OS during the first 3 years of treatment compared to BSC (Hazard ratio [HR] 0·5 P MDS and cytogenetic abnormalities involving chromosome 7, especially for those with CK. © 2018 John Wiley & Sons Ltd.

EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development.

Science.gov (United States)

Okada, Morihiro; Shi, Yun-Bo

2018-01-01

The gene ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI encode zinc-finger proteins that have been recognized as important oncogenes in various types of cancer. In contrast to the established role of EVI and MDS/EVI in cancer development, their potential function during vertebrate postembryonic development, especially in organ-specific adult stem cells, is unclear. Amphibian metamorphosis is strikingly similar to postembryonic development around birth in mammals, with both processes taking place when plasma thyroid hormone (T3) levels are high. Using the T3-dependent metamorphosis in Xenopus tropicalis as a model, we show here that high levels of EVI and MDS/EVI are expressed in the intestine at the climax of metamorphosis and are induced by T3. By using the transcription activator-like effector nuclease gene editing technology, we have knocked out both EVI and MDS/EVI and have shown that EVI and MDS/EVI are not essential for embryogenesis and premetamorphosis in X. tropicalis On the other hand, knocking out EVI and MDS/EVI causes severe retardation in the growth and development of the tadpoles during metamorphosis and leads to tadpole lethality at the climax of metamorphosis. Furthermore, the homozygous-knockout animals have reduced adult intestinal epithelial stem cell proliferation at the end of metamorphosis (for the few that survive through metamorphosis) or during T3-induced metamorphosis. These findings reveal a novel role of EVI and/or MDS/EVI in regulating the formation and/or proliferation of adult intestinal adult stem cells during postembryonic development in vertebrates.-Okada, M., Shi, Y.-B. EVI and MDS/EVI are required for adult intestinal stem cell formation during postembryonic vertebrate development. © FASEB.

TOPICS-MDS: Veelzijdige bron voor wetenschappelijke en maatschappelijke kennisgeneratie ten behoeve van de ouderenzorg

NARCIS (Netherlands)

van den Brink, D.; Lutomski, J.E.; Qin, L.; den Elzen, W.P.J.; Kempen, G.I.J.M.; Krabbe, P.F.M.; Steyerberg, E.W.; Muntinga, M.E.; Moll van Charante, E.P.; Bleijenberg, N.; Olde Rikkert, M.G.M.; Melis, R.J.F.

2015-01-01

Developed as part of the National Care for the Elderly Programme (NPO), TOPICS-MDS is a uniform, national database on the health and wellbeing of the older persons and caregivers who participated in NPO-funded projects. TOPICS-MDS Consortium has gained extensive experience in constructing a

Gene expression profiling in MDS and AML: potential and future avenues

DEFF Research Database (Denmark)

Theilgaard-Mönch, K; Boultwood, J; Ferrari, S

2011-01-01

Today, the classification systems for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) already incorporate cytogenetic and molecular genetic aberrations in an attempt to better reflect disease biology. However, in many MDS/AML patients no genetic aberrations have been identified yet...... with regard to diagnosis, prediction of clinical outcome, discovery of novel subclasses and identification of novel therapeutic targets and novel drugs. As many challenges remain ahead, we discuss the pitfalls of this technology and its potential including future integrative studies with other genomics...

Cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC in myelodysplastic syndrome (MDS

Directory of Open Access Journals (Sweden)

Myrna Candelaria-Hernández

2017-06-01

Full Text Available ABSTRACTIntroductionMyelodysplastic syndrome (MDS comprises a group of clonal hematological disorders, characterized by ineffective hematopoiesis and progressive bone marrow failure. It increases the risk of transformation to acute myeloid leukemia (AML. Therapeutic benefit should include overall survival increase (OS, hematological improvement, transfusion dependence and time to progression to AML decrease.ObjectiveAssess, from a Mexican health-care perspective, the cost-effectiveness of azacitidine compared with low-doses of chemotherapy (LDC plus best supportive care (BSC for the treatment of adult patients with intermediate-2 and high-risk MDS, who are not eligible for hematopoietic stem-cell transplantation. We developed a cost-effectiveness survival analysis model of three stages: MDS, AML, and death. OS and costs are extrapolated beyond three-year time horizon. Discount rate of 5% was applied. To estimate the model cycle probability transition to mortality state, survival curves were constructed for each treatment arm using individual patient-level data from Study AZA-001. Unitary costs are from public price list, and profiles for the management of MDS and AML were collected separately using a structured questionnaire. Probabilistic sensitivity analyses (PSA were conducted by simultaneously sampling from estimated probability distributions of model parameters.ResultsOverall survival was projected to increase by 72.26 weeks with azacitidine. Incremental expected total costs for azacitidine compared to LDC was MXN$68,045. However, the cost of the drug therapy was lower with azacitidine. The incremental cost-effectiveness ratio (ICER for azacitidine compared to LDC was MXN$48,932 per life-year gained (LYG. PSA showed that azacitidine was a highly cost-effective option in 96.49% of the simulated cases in MXN$180,000/LYG willingness-to-pay.ConclusionsCompared with LDC, azacitidine represents a cost-effective treatment alternative in patients

Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

Science.gov (United States)

Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

2018-01-01

The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

The Mice Drawer System (MDS experiment and the space endurance record-breaking mice.

Directory of Open Access Journals (Sweden)

Ranieri Cancedda

Full Text Available The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS, contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS. The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th, 2009. MDS returned to Earth on November 27(th, 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice.

Science.gov (United States)

Cancedda, Ranieri; Liu, Yi; Ruggiu, Alessandra; Tavella, Sara; Biticchi, Roberta; Santucci, Daniela; Schwartz, Silvia; Ciparelli, Paolo; Falcetti, Giancarlo; Tenconi, Chiara; Cotronei, Vittorio; Pignataro, Salvatore

2012-01-01

The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.

Relationship between the MDS-UPDRS and Quality of Life: A large multicenter study of 3206 patients.

Science.gov (United States)

Skorvanek, Matej; Martinez-Martin, Pablo; Kovacs, Norbert; Zezula, Ivan; Rodriguez-Violante, Mayela; Corvol, Jean-Christophe; Taba, Pille; Seppi, Klaus; Levin, Oleg; Schrag, Anette; Aviles-Olmos, Iciar; Alvarez-Sanchez, Mario; Arakaki, Tomoko; Aschermann, Zsuzsanna; Benchetrit, Eve; Benoit, Charline; Bergareche-Yarza, Alberto; Cervantes-Arriaga, Amin; Chade, Anabel; Cormier, Florence; Datieva, Veronika; Gallagher, David A; Garretto, Nelida; Gdovinova, Zuzana; Gershanik, Oscar; Grofik, Milan; Han, Vladimir; Kadastik-Eerme, Liis; Kurtis, Monica M; Mangone, Graziella; Martinez-Castrillo, Juan Carlos; Mendoza-Rodriguez, Amelia; Minar, Michal; Moore, Henry P; Muldmaa, Mari; Mueller, Christoph; Pinter, Bernadette; Poewe, Werner; Rallmann, Karin; Reiter, Eva; Rodriguez-Blazquez, Carmen; Singer, Carlos; Valkovic, Peter; Goetz, Christopher G; Stebbins, Glenn T

2018-03-28

The relationship between Health-Related Quality of Life (HRQoL) and MDS-UPDRS has not been fully studied so far. The aim of this study was to evaluate the relationship between all MDS-UPDRS components and HRQoL in a representative international cohort of PD patients. We collected demographic and disease-related data as well as MDS-UPDRS and PDQ8 scales. Data were analyzed using correlations between PDQ8 and all MDS-UPDRS items, subsequently two hierarchical multiple regressions were performed, first between the scores of the MDS-UPDRS Parts and PDQ8 and second between individual items from those Parts demonstrating significant relationship to PDQ8 scores in the first regression. LASSO regression analyses were performed to evaluate the relationship between PDQ8 and all individual MDS-UPDRS items. A total of 3206 PD patients were included in the study. In the first regression analysis, PDQ8 was significantly related to MDS-UPDRS parts I and II, but not to III and IV. In the second regression model, significant contributions to PDQ8 were found for Part I items Fatigue, Pain, Depressed mood, Apathy; and Part II items Dressing, Doing hobbies, Freezing, Speech and Tremor. In the LASSO analysis, six Part I, seven Part II, three Part III and one Part IV items contributed to PDQ8 scores. The five items most significantly related to the model were Depressed mood, Dressing, Apathy, Pain and Fatigue. This is so far the largest study related to HRQoL issues in PD. Restrictions in activities of daily living and non-motor symptoms significantly contribute to HRQoL in PD. Copyright © 2018. Published by Elsevier Ltd.

MDS 2.0 Public Quality Indicator and Resident Reports

Data.gov (United States)

U.S. Department of Health & Human Services — The Minimum Data Set (MDS) is part of the federally mandated process for clinical assessment of all residents in Medicare or Medicaid certified nursing homes. This...

SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

Science.gov (United States)

Mortera-Blanco, Teresa; Dimitriou, Marios; Woll, Petter S; Karimi, Mohsen; Elvarsdottir, Edda; Conte, Simona; Tobiasson, Magnus; Jansson, Monika; Douagi, Iyadh; Moarii, Matahi; Saft, Leonie; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva

2017-08-17

Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal ( SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro-B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS. © 2017 by The American Society of Hematology.

The Mice Drawer System Tissue Sharing Program (MDS-TSP)

Science.gov (United States)

Biticchi, Roberta; Cancedda, Ranieri; Cilli, Michele; Cotronei, Vittorio; Costa, Delfina; Liu, Yi; Piccardi, Federica; Pignataro, Salvatore; Ruggiu, Alessandra; Tasso, Roberta; Tavella, Sara

obtain from the animals sent to the ISS as much as possible information including also microgravity induced modifications of tissues other than bone, we associated to the MDS experiment several international group from Italian, American, Japanese Universities and from NASA and JAXA labs and we created a Tissue Sharing Program (TSP). In total 17 groups from 6 countries were involved in the program. The MDS payload containing three PTN-transgenic mice (Tg) and three wild type (Wt) mice was launched with the Shuttle STS-128, on August, 28 2009 and the MDS transferred to the ISS for three months. The payload re-entry was with the Shuttle STS-129 on November, 27 2009 in Florida. Unfortunately during this period 3 mice (two Wt and one Tg) died due to a spinal cord lesion probably occurred during the shuttle lift off, a liver pathology and a failure of the food delivery system respectively. All the three dead mice were however frozen for subsequent skeletal analysis. The remaining 3 mice had a normal behavior during the flight and appeared in excellent health conditions at the time of landing. During the MDS stay at the ISS several physical parameters were under daily check. With regard to the animal health status checking, the daily water consumption for each individual mouse revealed to be one of the most important parameter. Immediately after landing the mice were sacrificed, blood parameter were measured and all different tissues were dissected. Samples from almost the entire organism are now under investigation by the TSP team. A ground replica of the flight experiment ("ground control") was performed at the University of Genova from November 2009 to the second week of February 2010. Some of the initial results from the flight and the ground control experiments are presented in the individual abstracts.

Differential response to hypomethylating agents based on sex: a report on behalf of the MDS Clinical Research Consortium (MDS CRC).

Science.gov (United States)

DeZern, Amy E; Zeidan, Amer M; Barnard, John; Hand, Wesley; Al Ali, Najla; Brown, Francis; Zimmerman, Cassie; Roboz, Gail J; Garcia-Manero, Guillermo; Steensma, David P; Komrokji, Rami S; Sekeres, Mikkael A

2017-06-01

First-line therapy for higher-risk myelodysplastic syndromes (MDS) includes decitabine (DAC) or azacitidine (AZA). Variables have not identified differential response rates between these. We assessed the influence of patient sex on outcomes including overall survival (OS) in 642 patients with higher-risk MDS treated with AZA or DAC. DAC-treated patients (35% of females, 31% of males) had marginally better OS than AZA-treated patients (p = .043), (median OS of 18.7 months versus 16.4 months), but the difference varied strongly by sex. Female patients treated with DAC had a longer median OS (21.1 months, 95% CI: 16.0-28.0) than female patients treated with AZA (13.2 months, 95% CI: 11.0-15.9; p = .0014), while for males there was no significant difference between HMAs (median OS 18.3 months with DAC versus 17.9 months for AZA, p = .59). The biological reason for this variability is unclear, but may be a consequence of differences in cytidine deaminase activity between men and women.

Safety and efficacy of the CD95-ligand inhibitor asunercept in transfusion-dependent patients with low and intermediate risk MDS.

Science.gov (United States)

Boch, Tobias; Luft, Thomas; Metzgeroth, Georgia; Mossner, Maximilian; Jann, Johann-Christoph; Nowak, Daniel; Meir, Franziska La; Schumann, Christiane; Klemmer, Jennifer; Brendel, Susanne; Fricke, Harald; Kunz, Claudia; Weiß, Christel; Hofmann, Wolf-Karsten; Nolte, Florian

2018-05-01

In low risk MDS, increased apoptosis of erythroid progenitors mediated via CD95 (Fas) activation has been described to result in peripheral cytopenia. Blockade of the CD95 system can improve erythropoiesis in MDS. Asunercept (APG101) is a fusion protein consisting of the extracellular domain of human CD95 and the Fc domain of human IgG1 blocking the interaction between CD95 and its ligand. Here we report on results from a phase I study in 20 transfusion-dependent low and intermediate risk MDS patients treated with intravenous asunercept (EudraCT 2012-003027-37). Primary objectives were safety and tolerability as well as pharmacodynamic effects. Secondary objectives were hematologic improvement, incidence and time to leukemic progression as well as overall survival. Frequency and severity of adverse events were in range of what could be expected in a patient cohort comprising of elderly MDS patients. Two patients experienced a serious adverse event with a suspected relationship to asunercept. The incidence of disease progression was low. In the 20 patients a decrease of the transfusion need from a mean of 10,8 (±5,1) pRBCs during the 12 weeks treatment phase to a mean of 10,0 (±4,2) pRBCs at the end of the study was observed. In conclusion, asunercept was well tolerated and showed efficacy in transfusion-dependent low and intermediate risk MDS patients. Further clinical investigation is warranted, particularly in combination with erythropoiesis stimulating agents (ESAs). Copyright © 2018. Published by Elsevier Ltd.

The development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): a large-scale data sharing initiative.

Science.gov (United States)

Lutomski, Jennifer E; Baars, Maria A E; Schalk, Bianca W M; Boter, Han; Buurman, Bianca M; den Elzen, Wendy P J; Jansen, Aaltje P D; Kempen, Gertrudis I J M; Steunenberg, Bas; Steyerberg, Ewout W; Olde Rikkert, Marcel G M; Melis, René J F

2013-01-01

In 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons' health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu). A working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden). Between 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies. TOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations

MDS 3.0 for Nursing Homes and Swing Bed Providers

Data.gov (United States)

U.S. Department of Health & Human Services — The MDS is a powerful tool for implementing standardized assessment and for facilitating care management in nursing homes (NHs) and non-critical access hospital...

Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro

Directory of Open Access Journals (Sweden)

F.G.J. Calkoen

2015-03-01

An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.

Relationship between the MDS-UPDRS domains and the health-related quality of life of Parkinson's disease patients.

Science.gov (United States)

Martínez-Martín, P; Rodríguez-Blázquez, C; Forjaz, M J; Alvarez-Sánchez, M; Arakaki, T; Bergareche-Yarza, A; Chade, A; Garretto, N; Gershanik, O; Kurtis, M M; Martínez-Castrillo, J C; Mendoza-Rodríguez, A; Moore, H P; Rodríguez-Violante, M; Singer, C; Tilley, B C; Huang, J; Stebbins, G T; Goetz, C G

2014-03-01

The Movement Disorder Society sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive instrument for assessing Parkinson's disease (PD). The present study was aimed at determining the relationships between MDS-UPDRS components and health-related quality of life (HRQoL) evaluations in PD patients. An international, multicenter, cross-sectional study was carried out of 435 PD patients assessed with the MDS-UPDRS, Hoehn and Yahr (HY), Clinical Impression Severity for PD, EQ-5D and PD Questionnaire - eight items (PDQ-8). Spearman's rank correlation coefficients, exploratory factor analysis and multiple linear regression models (dependent variables EQ-5D and PDQ-8) were performed. The participants' age was 66.71 ± 10.32 years (51.5% men). PD duration was 8.52 ± 6.14, and median HY was 2 (range 1-5). The correlation between the EQ-5D index and the MDS-UPDRS ranged from -0.46 (Part IV) to -0.72 (Part II) and for the PDQ-8 index from 0.47 (Part III) to 0.74 (Part II). In multiple regression models with the MDS-UPDRS domains as independent variables, the main determinant for both the EQ-5D index and the PDQ-8 was Part II followed by Part I. After factorial grouping of the cardinal PD manifestations embedded in the MDS-UPDRS Parts III and IV for inclusion into multiple regression models, a factor formed by M-EDL, nM-EDL and fluctuations was the main determinant for both the EQ-5D and PDQ-8 indexes. The MDS-UPDRS component most tightly related with the HRQoL measures was a combination of motor and non-motor experiences of daily living. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

The MDS challenging behavior profile for long-term care

NARCIS (Netherlands)

Gerritsen, D. L.; Achterberg, W. P.; Steverink, N.; Frijters, D. H. M.; Ribbe, M. W.

2008-01-01

The objective was to construct a reliable and valid challenging behavior scale with items from the Minimum Data Set (MDS). Exploratory factor analyses of a sample of 656 nursing home residents yielded a 16-item Behavior Profile containing four internally consistent and valid subscales measuring

Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier.

Science.gov (United States)

Li, Qiang; Gu, Yu; Jia, Jing

2017-01-30

Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS) and support vector machine (SVM) algorithms in a quartz crystal microbalance (QCM)-based electronic nose (e-nose) we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3%) showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN) classifier (93.3%) and moving average-linear discriminant analysis (MA-LDA) classifier (87.6%). The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization) performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

Classification of Multiple Chinese Liquors by Means of a QCM-based E-Nose and MDS-SVM Classifier

Directory of Open Access Journals (Sweden)

Qiang Li

2017-01-01

Full Text Available Chinese liquors are internationally well-known fermentative alcoholic beverages. They have unique flavors attributable to the use of various bacteria and fungi, raw materials, and production processes. Developing a novel, rapid, and reliable method to identify multiple Chinese liquors is of positive significance. This paper presents a pattern recognition system for classifying ten brands of Chinese liquors based on multidimensional scaling (MDS and support vector machine (SVM algorithms in a quartz crystal microbalance (QCM-based electronic nose (e-nose we designed. We evaluated the comprehensive performance of the MDS-SVM classifier that predicted all ten brands of Chinese liquors individually. The prediction accuracy (98.3% showed superior performance of the MDS-SVM classifier over the back-propagation artificial neural network (BP-ANN classifier (93.3% and moving average-linear discriminant analysis (MA-LDA classifier (87.6%. The MDS-SVM classifier has reasonable reliability, good fitting and prediction (generalization performance in classification of the Chinese liquors. Taking both application of the e-nose and validation of the MDS-SVM classifier into account, we have thus created a useful method for the classification of multiple Chinese liquors.

Prognostic classification of MDS is improved by the inclusion of FISH panel testing with conventional cytogenetics.

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Kokate, Prajakta; Dalvi, Rupa; Koppaka, Neeraja; Mandava, Swarna

2017-10-01

Cytogenetics is a critical independent prognostic factor in myelodysplastic syndromes (MDS). Conventional cytogenetics (CC) and Fluorescence in situ hybridization (FISH) Panel Testing are extensively used for the prognostic stratification of MDS, although the FISH test is not yet a bona fide component of the International Prognostic Scoring System (IPSS). The present study compares the utility of CC and FISH to detect chromosomal anomalies and in prognostic categorization. GTG-Banding and FISH Panel Testing specifically for -5/-5q, -7/-7q, +8 and -20q was performed on whole blood or bone marrow samples from 136 patients with MDS. Chromosomal anomalies were found in 40 cases by CC, including three novel translocations. FISH identified at least one anomaly in 54/136 (39.7%) cases. More than one anomaly was found in 18/54 (33.3%) cases, therefore, overall FISH identified 75 anomalies of which 32 (42.6%) were undetected by CC. FISH provided additional information in cases with CC failure and in cases with a normal karyotype. Further, in ten cases with an abnormal karyotype, FISH could identify additional anomalies, increasing the number of abnormalities per patient. Although CC is the gold standard in the cytogenetic profiling of MDS, FISH has proven to be an asset in identifying additional abnormalities. The number of anomalies per patient can predict the prognosis in MDS and hence, FISH contributed towards prognostic re-categorization. The FISH Panel testing should be used as an adjunct to CC, irrespective of the adequacy of the number of metaphases in CC, as it improves the prognostic classification of MDS. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease.

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Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P

2015-01-01

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS-UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS-UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS-UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS-UPDRS parts II, I and IV respectively, but not to part III. Individual MDS-UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS-UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS-UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of FISH 7q in MDS patients without monosomy 7 or 7q deletion by conventional G-banding cytogenetics: does -7/7q- detection by FISH have prognostic value?

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Ademà, Vera; Hernández, Jesús María; Abáigar, María; Lumbreras, Eva; Such, Esperanza; Calull, Anna; Dominguez, Esther; Arenillas, Leonor; Mallo, Mar; Cervera, José; Marugán, Isabel; Tormo, Mar; García, Francisca; González, Teresa; Luño, Elisa; Sanzo, Carmen; Martín, María Luisa; Fernández, Manuela; Costa, Dolors; Blázquez, Beatriz; Barreña, Beatriz; Marco, Fernando; Batlle, Ana; Buño, Ismael; Martínez-Laperche, Carolina; Noriega, Víctor; Collado, Rosa; Ivars, David; Carbonell, Félix; Vallcorba, Isabel; Melero, Josefa; Delgado, Elena; Vargas, María Teresa; Grau, Javier; Salido, Marta; Espinet, Blanca; Melero, Carme; Florensa, Lourdes; Pedro, Carmen; Solé, Francesc

2013-04-01

Chromosomal abnormalities are detected in 40-60% of patients with de novo myelodysplastic syndromes (MDS). This study used the FISH technique in 773 patients with de novo MDS without evidence of monosomy 7 (-7) or 7q deletion (7q-) by conventional G-banding cytogenetics (CC) to analyze their prognostic impact by FISH alone. FISH detected -7/7q- in 5.2% of patients. Presence of -7/7q- was associated with shorter overall survival than absence of such aberrations. Our results suggest that FISH 7q could be beneficial in patients with intermediate WHO morphologic risk stratification and no evidence of -7/7q- by CC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Therapy Related AML/MDS Following Treatment for Childhood Cancer: Experience from a Tertiary Care Centre in North India.

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Vyas, Chintan; Jain, Sandeep; Kapoor, Gauri

2018-01-01

Therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) is a devastating late effect of cancer treatment. There is limited data on incidence of t-AML/MDS from India. We retrospectively studied pediatric t AML/MDS at our institute between January 1996 and December 2015. Among 1285 children, 8 patients developed t-AML with a median age of 15.5 years. Overall incidence of t-AML/MDS was 0.62% [0.99% (4/402) in solid tumours and 0.45% (4/883) in leukemia/lymphoma, P  = 0.26] with 6390 patient years of follow up. Primary malignancy included sarcoma [bone (2), soft tissue (2)], B-non-Hodgkin lymphoma (2) and acute lymphoblastic leukemia (2). The median cumulative equivalent doses of cyclophosphamide, doxorubicin and etoposide were 6.8, 270 and 2.5 gm/m 2 respectively. Two patients received radiotherapy [rhabdomyosarcoma (50 Gy), synovial sarcoma (45 Gy)]. The median latency period to develop t-AML/MDS was 24 months (range 16.5-62 months). Most common FAB morphology was M4/M5 (7/8) and cytogenetic abnormality was MLL rearrangement (4/8). Five patients opted for treatment, 4 achieved remission out of which 2 patients are alive and disease free. Short latency periods, absence of pre-leukemic phase and 11q23 translocations were characteristic in the patients with t-AML/MDS. In view of poor outcome with conventional therapy, novel strategies and prevention need to be considered.

Development of a Minimum Data Set (MDS) for C-Section Anesthesia Information Management System (AIMS).

Science.gov (United States)

Sheykhotayefeh, Mostafa; Safdari, Reza; Ghazisaeedi, Marjan; Khademi, Seyed Hossein; Seyed Farajolah, Seyedeh Sedigheh; Maserat, Elham; Jebraeily, Mohamad; Torabi, Vahid

2017-04-01

Caesarean section, also known as C-section, is a very common procedure in the world. Minimum data set (MDS) is defined as a set of data elements holding information regarding a series of target entities to provide a basis for planning, management, and performance evaluation. MDS has found a great use in health care information systems. Also, it can be considered as a basis for medical information management and has shown a great potential for contributing to the provision of high quality care and disease control measures. The principal aim of this research was to determine MDS and required capabilities for Anesthesia information management system (AIMS) in C-section in Iran. Data items collected from several selected AIMS were studied to establish an initial set of data. The population of this study composed of 115 anesthesiologists was asked to review the proposed data elements and score them in order of importance by using a five-point Likert scale. The items scored as important or highly important by at least 75% of the experts were included in the final list of minimum data set. Overall 8 classes of data (consisted of 81 key data elements) were determined as final set. Also, the most important required capabilities were related to airway management and hypertension and hypotension management. In the development of information system (IS) based on MDS and identification, because of the broad involvement of users, IS capabilities must focus on the users' needs to form a successful system. Therefore, it is essential to assess MDS watchfully by considering the planned uses of data. Also, IS should have essential capabilities to meet the needs of its users.

Design and rationale of the QUAZAR Lower-Risk MDS (AZA-MDS-003) trial: a randomized phase 3 study of CC-486 (oral azacitidine) plus best supportive care vs placebo plus best supportive care in patients with IPSS lower-risk myelodysplastic syndromes and poor prognosis due to red blood cell transfusion-dependent anemia and thrombocytopenia.

Science.gov (United States)

Garcia-Manero, Guillermo; Almeida, Antonio; Giagounidis, Aristoteles; Platzbecker, Uwe; Garcia, Regina; Voso, Maria Teresa; Larsen, Stephen R; Valcarcel, David; Silverman, Lewis R; Skikne, Barry; Santini, Valeria

2016-01-01

CC-486 is an oral formulation of the epigenetic modifier azacitidine. In an expanded phase 1 trial, CC-486 demonstrated clinical and biological activity in patients with International Prognostic Scoring System (IPSS) lower-risk (low- and intermediate-1-risk) myelodysplastic syndromes (MDS) with poor prognostic features including anemia and/or thrombocytopenia who may have required red blood cell or platelet transfusions. The overall response rate was 40 %, including hematologic improvement in 28 % of patients and RBC transfusion independence sustained for 56 days in 47 % of patients with baseline transfusion dependence. Based on the results of this study, the randomized, placebo-controlled phase 3 QUAZAR Lower-Risk MDS trial (AZA-MDS-003) was initiated. The design and rationale for this trial comparing CC-486 with placebo for the treatment of patients with IPSS lower-risk MDS with poor prognostic features are described. Patients must have IPSS lower-risk MDS with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia. Eligible patients are randomized 1:1 to receive 300 mg of CC-486 or placebo once daily for the first 21 days of 28-day treatment cycles. Disease status assessments occur at the end of cycle 6 and patients may continue to receive treatment unless there is evidence of progressive disease, lack of efficacy, or unacceptable toxicity. The primary endpoint is RBC transfusion independence for ≥ 84 days, assessed according to International Working Group 2006 criteria. Secondary endpoints include overall survival, hematologic response including platelet response and erythroid response, RBC transfusion independence for ≥ 56 days, duration of RBC transfusion independence, time to RBC transfusion independence, rate of acute myeloid leukemia (AML) progression, time to AML progression, clinically significant bleeding events, safety, health-related quality of life, and healthcare resource utilization. This study will provide data

A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

Science.gov (United States)

Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

2017-07-01

To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

Minimum variance and variance of outgoing quality limit MDS-1(c1, c2) plans

Science.gov (United States)

Raju, C.; Vidya, R.

2016-06-01

In this article, the outgoing quality (OQ) and total inspection (TI) of multiple deferred state sampling plans MDS-1(c1,c2) are studied. It is assumed that the inspection is rejection rectification. Procedures for designing MDS-1(c1,c2) sampling plans with minimum variance of OQ and TI are developed. A procedure for obtaining a plan for a designated upper limit for the variance of the OQ (VOQL) is outlined.

Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

Science.gov (United States)

Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M

2017-04-01

MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study.

Science.gov (United States)

Stauder, Reinhard; Yu, Ge; Koinig, Karin A; Bagguley, Tim; Fenaux, Pierre; Symeonidis, Argiris; Sanz, Guillermo; Cermak, Jaroslav; Mittelman, Moshe; Hellström-Lindberg, Eva; Langemeijer, Saskia; Holm, Mette Skov; Mądry, Krzysztof; Malcovati, Luca; Tatic, Aurelia; Germing, Ulrich; Savic, Aleksandar; van Marrewijk, Corine; Guerci-Bresler, Agnès; Luño, Elisa; Droste, Jackie; Efficace, Fabio; Smith, Alex; Bowen, David; de Witte, Theo

2018-03-06

In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (p MDS patients (p MDS-related restrictions in the dimension mobility were most prominent in males, and in older people (p MDS experience a pronounced reduction in HRQoL and a clustering of restrictions in distinct dimensions of HRQoL as compared with reference populations.

Comparison of clinical outcomes and prognostic utility of risk stratification tools in patients with therapy-related vs de novo myelodysplastic syndromes: a report on behalf of the MDS Clinical Research Consortium.

Science.gov (United States)

Zeidan, A M; Al Ali, N; Barnard, J; Padron, E; Lancet, J E; Sekeres, M A; Steensma, D P; DeZern, A; Roboz, G; Jabbour, E; Garcia-Manero, G; List, A; Komrokji, R

2017-06-01

While therapy-related (t)-myelodysplastic syndromes (MDS) have worse outcomes than de novo MDS (d-MDS), some t-MDS patients have an indolent course. Most MDS prognostic models excluded t-MDS patients during development. The performances of the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R), MD Anderson Global Prognostic System (MPSS), WHO Prognostic Scoring System (WPSS) and t-MDS Prognostic System (TPSS) were compared among patients with t-MDS. Akaike information criteria (AIC) assessed the relative goodness of fit of the models. We identified 370 t-MDS patients (19%) among 1950 MDS patients. Prior therapy included chemotherapy alone (48%), chemoradiation (31%), and radiation alone in 21%. Median survival for t-MDS patients was significantly shorter than for d-MDS (19 vs 46 months, PMDS (PMDS had a significantly higher hazard of death relative to d-MDS in every risk model, and had inferior survival compared to patients with d-MDS within all risk group categories. AIC Scores (lower is better) were 2316 (MPSS), 2343 (TPSS), 2343 (IPSS-R), 2361 (WPSS) and 2364 (IPSS). In conclusion, subsets of t-MDS patients with varying clinical outcomes can be identified using conventional risk stratification models. The MPSS, TPSS and IPSS-R provide the best predictive power.

T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

DEFF Research Database (Denmark)

Vries, A.C. de; Langerak, A.W.; Verhaaf, B.

2008-01-01

(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which...... the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vbeta CDR3 region. We investigated retrospectively the frequency...... and the discriminative value of TCR Vbeta CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vbeta heteroduplex PCR analysis of extracted...

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

International Nuclear Information System (INIS)

Tobiasson, M; Dybedahl, I; Holm, M S; Karimi, M; Brandefors, L; Garelius, H; Grövdal, M; Högh-Dufva, I; Grønbæk, K; Jansson, M; Marcher, C; Nilsson, L; Kittang, A O; Porwit, A; Saft, L; Möllgård, L; Hellström-Lindberg, E

2014-01-01

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a transfusion need of ⩾4 units over 8 weeks were included. Aza 75 mg m −2 d −1 , 5/28 days, was given for six cycles; non-responding patients received another three cycles combined with Epo 60 000 units per week. Primary end point was transfusion independence (TI). All patients underwent targeted mutational screen for 42 candidate genes. Thirty enrolled patients received ⩾one cycle of Aza. Ten patients discontinued the study early, 7 due to adverse events including 2 deaths. Thirty-eight serious adverse events were reported, the most common being infection. Five patients achieved TI after six cycles and one after Aza+Epo, giving a total response rate of 20%. Mutational screening revealed a high frequency of recurrent mutations. Although no single mutation predicted for response, SF3A1 (n=3) and DNMT3A (n=4) were only observed in non-responders. We conclude that Aza can induce TI in severely anemic MDS patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations

Utility of 5-Methylcytosine Immunohistochemical Staining to Assess Global DNA Methylation and Its Prognostic Impact in MDS Patients

Science.gov (United States)

Chandra, Dinesh; Tyagi, Seema; Singh, Jasdeep; Deka, Roopam; Manivannan, Prabhu; Mishra, Pravas; Pati, Hara Prasad; Saxena, Renu

2017-12-29

Background: DNA methylation plays a vital role in the pathogenesis of the myelodysplastic syndrome (MDS), a heterogeneous group of clonal hematopoietic stem cell (HSC) disorders. It is reported to be an independent prognostic factor affecting overall survival (OS). Our aim was to analyze the role of global DNA methylation using an anti-5-methylcytosine (5-MC) antibody by immunohistochemistry (IHC) of bone marrow biopsy (BM Bx) specimens in MDS patients, assessing correlations with various clinical and biological prognostic factors. Material and methods: A total of 59 MDS cases, classified as per the World Health Organization (WHO) 2008 guidelines, were evaluated over a period of 4 years. Clinical data were retrieved from departmental case records and anti-5-MC expression was analyzed with formalin fixed paraffin embedded sections of BM Bx specimens of MDS patients and controls. Results: The median age at diagnosis was 52 years (15-85years). Patients were categorized into low risk (59%) and high risk (41%) according to International Prognostic Scoring System (IPSS). The median follow-up time was 10 months (1 to 37 months). We generated a methylation score (M-score) using anti-5-MC and with the derived cut-off of 30.5 from the receiver operator curve (ROC), there was a significant difference between the two groups in the percentage of BM blasts (p=0.01), WHO sub-type (p=0.01), IPSS (p=0.004), progression to AML (p=0.04) on univariate analysis. Interestingly, patients showing a high M-score (M-score ≥ 30.5) demonstrated a significantly shorter OS and progression to AML. However, on multivariate analysis, only BM blasts (p=0.01) and IPSS (p=0.02) remained independent variables for progression to AML and OS respectively. Conclusion: Immunostaining with anti-5-MC antibody with BM Bx samples is a simple and cost effective technique to detect global methylation, a powerful tool to predict overall survival in patients with MDS. Creative Commons Attribution License

Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

DEFF Research Database (Denmark)

Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease.

Science.gov (United States)

Tobiasson, Magnus; Abdulkadir, Hani; Lennartsson, Andreas; Katayama, Shintaro; Marabita, Francesco; De Paepe, Ayla; Karimi, Mohsen; Krjutskov, Kaarel; Einarsdottir, Elisabet; Grövdal, Michael; Jansson, Monika; Ben Azenkoud, Asmaa; Corddedu, Lina; Lehmann, Sören; Ekwall, Karl; Kere, Juha; Hellström-Lindberg, Eva; Ungerstedt, Johanna

2017-04-25

Azacitidine (Aza) is first-line treatment for patients with high-risk myelodysplastic syndromes (MDS), although its precise mechanism of action is unknown. We performed the first study to globally evaluate the epigenetic effects of Aza on MDS bone marrow progenitor cells assessing gene expression (RNA seq), DNA methylation (Illumina 450k) and the histone modifications H3K18ac and H3K9me3 (ChIP seq). Aza induced a general increase in gene expression with 924 significantly upregulated genes but this increase showed no correlation with changes in DNA methylation or H3K18ac, and only a weak association with changes in H3K9me3. Interestingly, we observed activation of transcripts containing 15 endogenous retroviruses (ERVs) confirming previous cell line studies. DNA methylation decreased moderately in 99% of all genes, with a median β-value reduction of 0.018; the most pronounced effects seen in heterochromatin. Aza-induced hypomethylation correlated significantly with change in H3K9me3. The pattern of H3K18ac and H3K9me3 displayed large differences between patients and healthy controls without any consistent pattern induced by Aza. We conclude that the marked induction of gene expression only partly could be explained by epigenetic changes, and propose that activation of ERVs may contribute to the clinical effects of Aza in MDS.

Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS

DEFF Research Database (Denmark)

Holm, Mette; Dybedahl, I; Holm, Mette

2014-01-01

This prospective phase II study evaluated the efficacy of azacitidine (Aza)+erythropoietin (Epo) in transfusion-dependent patients with lower-risk myelodysplastic syndrome (MDS). Patients ineligible for or refractory to full-dose Epo+granulocyte colony stimulation factors for >8 weeks and a trans...... patients, but efficacy is limited, toxicity substantial and most responses of short duration. This treatment cannot be generally recommended in lower-risk MDS. Mutational screening revealed a high frequency of mutations....

Role of casein kinase 1A1 in the biology and targeted therapy of del(5q) MDS

Science.gov (United States)

Schneider, Rebekka K.; Ademà, Vera; Heckl, Dirk; Järås, Marcus; Mallo, Mar; Lord, Allegra M.; Chu, Lisa P.; McConkey, Marie E.; Kramann, Rafael; Mullally, Ann; Bejar, Rafael; Solé, Francesc; Ebert, Benjamin L.

2014-01-01

Summary The Casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage whereas homozygous deletion induces hematopoietic stem cell failure. Based on this finding, we found that heterozygous inactivation of Csnk1a1 sensitizes cells to a CSNK1 inhibitor relative to cells with two intact alleles. In addition, we identified recurrent somatic mutations in CSNK1A1 on the non-deleted allele of patients with del(5q) MDS. These studies demonstrate that CSNK1A1 plays a central role in the biology of del(5q) MDS and is a promising therapeutic target. PMID:25242043

Spliceosomal gene aberrations are rare, coexist with oncogenic mutations, and are unlikely to exert a driver effect in childhood MDS and JMML

NARCIS (Netherlands)

S. Hirabayashi (Shinsuke); C. Flotho (Christian); J. Moetter (Jessica); M. Heuser (Michael); H. Hasle (Henrik); B. Gruhn (Bernd); T. Klingebiel (Thomas); F. Thol (Felicitas); B. Schlegelberger (Brigitte); I. Baumann (Irith); B. Strahm (Brigitte); J. Stary (Jan); F. Locatelli (Franco); M. Zecca (Marco); E. Bergstraesser (Eva); M.N. Dworzak (Michael); M.M. van den Heuvel-Eibrink (Marry); B. de Moerloose (Barbara); S. Ogawa (Susumu); C.M. Niemeyer (Charlotte); M. Wlodarski (Marcin)

2012-01-01

textabstractSomatic mutations of the spliceosomal machinery occur frequently in adult patients with myelodysplastic syndrome (MDS). We resequenced SF3B1, U2AF35, and SRSF2 in 371 children with MDS or juvenile myelomonocytic leukemia. We found missense mutations in 2 juvenile myelomonocytic leukemia

Age-related changes of healthy bone marrow cell signaling in response to growth factors provide insight into low risk MDS.

Science.gov (United States)

Kornblau, Steven M; Cohen, Aileen C; Soper, David; Huang, Ying-Wen; Cesano, Alessandra

2014-11-01

Single Cell Network Profiling (SCNP) is a multiparametric flow cytometry-based assay that quantifiably and simultaneously measures changes in intracellular signaling proteins in response to in vitro extracellular modulators at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous clonal disorder of hematopoietic stem cells that occurs in elderly subjects and is characterized by dysplasia and ineffective hematopoiesis. The functional responsiveness of MDS bone marrow (BM) hematopoietic cells, including functionally distinct myeloid and erythroid precursor subsets, to hematopoietic growth factors (HGF) and the relationship of modulated signaling to disease characteristics is poorly understood. SCNP was used first to examine the effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34 expressing cell subsets in healthy BM (n = 15). SCNP was then used to map functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to signaling in samples from healthy donors and to probe signaling associations within clinically defined subgroups. In healthy BM samples, signaling responses to HGF were quite homogeneous (i.e., tightly regulated) with age-dependent effects observed in response to EPO but not to GCSF. Despite the relatively small number of samples assayed in the study, LR MDS could be classified into distinct subgroups based on both cell subset frequency and signaling profiles. As a correlate of underlying genetic abnormalities, signal transduction analyses may provide a functional and potentially clinically relevant classification of MDS. Further evaluation in a larger cohort is warranted. © 2013 Clinical Cytometry Society.

Impact of chromosome alterations, genetic mutations and clonal hematopoiesis of indeterminate potential (CHIP) on the classification and risk stratification of MDS.

Science.gov (United States)

Ganguly, Bani Bandana; Banerjee, Debasis; Agarwal, Mohan B

2018-03-01

The advent of technological development has undoubtedly advanced biological and molecular inputs for better understanding the heterogeneous hematopoietic pre-malignant disorder of the stem cells known as myelodysplastic syndromes (MDS). Chromosomal rearrangements, including del(3q/5q/7q/11q/12p/20q), loss of 5/7/Y, trisomy 8/19, i(17q), etc. frequently detected in MDS with variable frequencies and combinations, are the integral components of the 5-tier risk-stratification and WHO-2016 classification. Observations on mutations in genes involved in RNA-splicing, DNA methylation, chromatin modification, transcription factor, signal transduction/kinases, RAS pathway, cohesin complex, DNA repair and other pathways have given insights in independent effects and biological interaction of co-occurrence on disease-phenotype and treatment outcome. However, recent concepts of clonal hematopoiesis of indeterminate potential (CHIP) and idiopathic cytopenia of undetermined significance (ICUS) have urged a re-definition of mutational events in non-clonal cytopenia and non-MDS healthy elderly but with a higher risk of overt leukemia. Considering gene mutations, chromosomal alterations, CHIP, ICUS and their significance in classification and risk-scoring certainly presents a comprehensive picture of disease-phenotype towards better understanding of MDS-pathogenesis, its evolution to AML and its response to therapeutic agents. The present review summarizes chromosomal and gene mutations, co-existence of mutational complexity, and WHO-2016 classification and risk-stratifications of MDS to facilitate a better understanding of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Wormhole Detection Based on Ordinal MDS Using RTT in Wireless Sensor Network

Directory of Open Access Journals (Sweden)

Saswati Mukherjee

2016-01-01

Full Text Available In wireless communication, wormhole attack is a crucial threat that deteriorates the normal functionality of the network. Invasion of wormholes destroys the network topology completely. However, most of the existing solutions require special hardware or synchronized clock or long processing time to defend against long path wormhole attacks. In this work, we propose a wormhole detection method using range-based topology comparison that exploits the local neighbourhood subgraph. The Round Trip Time (RTT for each node pair is gathered to generate neighbour information. Then, the network is reconstructed by ordinal Multidimensional Scaling (MDS followed by a suspicion phase that enlists the suspected wormholes based on the spatial reconstruction. Iterative computation of MDS helps to visualize the topology changes and can localize the potential wormholes. Finally, a verification phase is used to remove falsely accused nodes and identify real adversaries. The novelty of our algorithm is that it can detect both short path and long path wormhole links. Extensive simulations are executed to demonstrate the efficacy of our approach compared to existing ones.

The drift-flux correlation package MDS

International Nuclear Information System (INIS)

Hoeld, A.

2001-01-01

Based on the SONNENBURG drift-flux correlation, developed at GRS/Garching (Germany), a comprehensive drift-flux correlation package (MDS) has been established. Its aim is to support thermal-hydraulic mixture-fluid models, models being used for the simulation of the steady state and transient behaviour of characteristic thermal-hydraulic parameters of single- or two-phase fluids flowing along coolant channels of different types (being, e.g., parts of NPP-s, steam generators etc.). The characteristic properties of this package with respect to the behaviour at co- and counter-current flow, its inverse solutions needed for steady state simulations, its behaviour when approaching the lower or upper boundary of a two-phase region, its verification and behaviour with respect to other correlations will be discussed. An adequate driver code, MDSDRI, has been established too, allowing to test the package very thoroughly out of the complex thermal-hydraulic codes. (author)

The drift-flux correlation package MDS

Energy Technology Data Exchange (ETDEWEB)

Hoeld, A. [Bernaysstr. 16A, Munich, F.R. (Germany)

2001-07-01

Based on the SONNENBURG drift-flux correlation, developed at GRS/Garching (Germany), a comprehensive drift-flux correlation package (MDS) has been established. Its aim is to support thermal-hydraulic mixture-fluid models, models being used for the simulation of the steady state and transient behaviour of characteristic thermal-hydraulic parameters of single- or two-phase fluids flowing along coolant channels of different types (being, e.g., parts of NPP-s, steam generators etc.). The characteristic properties of this package with respect to the behaviour at co- and counter-current flow, its inverse solutions needed for steady state simulations, its behaviour when approaching the lower or upper boundary of a two-phase region, its verification and behaviour with respect to other correlations will be discussed. An adequate driver code, MDSDRI, has been established too, allowing to test the package very thoroughly out of the complex thermal-hydraulic codes. (author)

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

Science.gov (United States)

Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

2016-01-01

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

CMS MDS 3.0 Section M Skin Conditions in Long-term Care: Pressure Ulcers, Skin Tears, and Moisture-Associated Skin Damage Data Update.

Science.gov (United States)

Ayello, Elizabeth A

2017-09-01

The purpose of this learning activity is to provide information about the updates to the Centers for Medicare & Medicaid Services (CMS) MDS 3.0 Section M, Skin Conditions documentation in long-term care. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Explain the use of the CMS MDS 3.0 tool for documenting skin problems in long-term care.2. Demonstrate examples of proper documentation for specific skin problems. This manuscript reviews some of the key parts of the October 2016 revised Long-term Care Resident Assessment Instrument manual for Minimum Data Set (MDS) 3.0 Section M Skin Conditions. It also reports the Centers for Medicare & Medicaid's publicly reported frequency data in long-term care for selected items on the MDS 3.0 Section M Skin Conditions. Percentages and trends of pressure ulcers/injuries, skin tears, and moisture-associated skin damage are assessed.

Investigation of porosity and fractal properties of the sintered metal and semiconductor layers in the MDS capacitor structure

Directory of Open Access Journals (Sweden)

Skatkov Leonid

2012-01-01

Full Text Available MDS capacitor (metal - dielectric - semiconductor is a structure in which metal plate is represented by compact bulk-porous pellets of niobium sintered powder, and semiconductor plate - by pyrolytic layer of MnO2. In the present paper we report the results of investigation of microporosity of sintered Nb and pyrolytic MnO2 and also the fractal properties of semiconductor layer.

Meta-Analytical Online Repository of Gene Expression Profiles of MDS Stem Cells

Science.gov (United States)

2015-12-01

lymphoid cell percentages in these samples. We observed that most of the MDS samples had lymphoid and neutrophil percentages that were in the normal...pathways involved in chemokine signaling, cytokine-cytokine receptor interaction, innate immunity signaling, hematopoietic cell lineage regulation, and...transcription factors are important for survival of cancer stem cells .2,34-36 IL8 is also an important regulator of innate immunity. Recent data have shown

Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

International Nuclear Information System (INIS)

Litt, P.

2000-01-01

Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world

Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease.

Science.gov (United States)

Berg, Daniela; Postuma, Ronald B; Bloem, Bastiaan; Chan, Piu; Dubois, Bruno; Gasser, Thomas; Goetz, Christopher G; Halliday, Glenda M; Hardy, John; Lang, Anthony E; Litvan, Irene; Marek, Kenneth; Obeso, José; Oertel, Wolfgang; Olanow, C Warren; Poewe, Werner; Stern, Matthew; Deuschl, Günther

2014-04-01

With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration. © 2014 International Parkinson and Movement Disorder Society.

Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

Science.gov (United States)

Camerino, Giulia M.; Bianchini, Elisa; Ciciliot, Stefano; Danieli-Betto, Daniela; Dobrowolny, Gabriella; Furlan, Sandra; Germinario, Elena; Goto, Katsumasa; Gutsmann, Martina; Kawano, Fuminori; Nakai, Naoya; Ohira, Takashi; Ohno, Yoshitaka; Picard, Anne; Salanova, Michele; Schiffl, Gudrun; Blottner, Dieter; Musarò, Antonio; Ohira, Yoshinobu; Betto, Romeo; Conte, Diana; Schiaffino, Stefano

2012-01-01

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures. PMID:22470446

Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

Directory of Open Access Journals (Sweden)

Dorianna Sandonà

Full Text Available The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day spaceflights. The mice drawer system (MDS program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1 into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+-activated K(+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

Downregulation but lack of promoter hypermethylation or somatic mutations of the potential tumor suppressor CXXC5 in MDS and AML with deletion 5q

DEFF Research Database (Denmark)

Treppendahl, Marianne Bach; Möllgård, L; Hellström-Lindberg, E

2013-01-01

During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells, identify......During recent years mutations in epigenetic modulators have been identified in several human cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS)[1]. CXXC5 has been found to be necessary for retinoic acid induced differentiation of myelocytic leukemia cells...

Wheat Mds-1 encodes a heat-shock protein and governs susceptibility towards the Hessian fly gall midge

Science.gov (United States)

Plant pests including insects must manipulate plants in order to utilize the nutrition and environment of the host. Here, we show that the heat-shock protein gene Mayetiola destructor susceptibility gene-1 (Mds-1) is a major susceptibility gene in wheat that allows the gall midge M. destructor, com...

Aplicación del Escalamiento Multidimensional (MDS al análisis del discurso mediático. El caso de la cobertura periodística a los ‘escraches’

Directory of Open Access Journals (Sweden)

Xabier Albizu Landa

2014-06-01

Full Text Available En el presente artículo se discuten las posibilidades que ofrece la técnica de análisis multivariante conocida como Escalamiento Multidimensional (MDS para el análisis del discurso periodístico y la determinación de los frames presentes en este. En una primera parte se repasan las tradiciones de los análisis de framing y de la aplicación del MDS. En una segunda parte se presenta un caso práctico en el que el MDS es utilizado para la determinación de los frames presentes en la cobertura periodística a los escraches protagonizados en la primavera de 2013 por el movimiento contra los desahucios.

MDS system increases drilling safety and efficiency

Energy Technology Data Exchange (ETDEWEB)

Chevallier, J.; Turner, L. (Sedco Forex, Paris (FR))

1989-09-01

There's a great deal of data recorded during drilling operations on rigs these days, but it is seldom well utilized. The operator's company person relies upon mud loggers for collecting and recording most information. The methods used to process and display this information are often inadequate for those who need it the most the driller and toolpusher. Drilling contractor personnel usually have only rudimentary displays of drilling parameters, and practically no serious method of analysis except for daily paper reports. These are cumbersome to use and provide only incomplete data, after the fact. The MDS system, presented in this article, is a new information and alarm network, which rectifies this situation by bringing to the rig, for the first time, the latest in sensor and computer technologies. This system acquires key drilling data on the rig floor, pump room, and return line, and displays it in a clear graphical format to both the driller and the toolpusher in real time. It also provides the toolpusher with a workstation for easy access to the same information for evaluation and planning of the drilling program.

Defining AML and MDS second cancer risk dynamics after diagnoses of first cancers treated or not with radiation

NARCIS (Netherlands)

Radivoyevitch, T.; Sachs, R. K.; Gale, R. P.; Molenaar, R. J.; Brenner, D. J.; Hill, B. T.; Kalaycio, M. E.; Carraway, H. E.; Mukherjee, S.; Sekeres, M. A.; Maciejewski, J. P.

2016-01-01

Risks of acute myeloid leukemia (AML) and/or myelodysplastic syndromes (MDS) are known to increase after cancer treatments. Their rise-and-fall dynamics and their associations with radiation have, however, not been fully characterized. To improve risk definition we developed SEERaBomb R software for

Toward a new task assignment and path evolution (TAPE) for missile defense system (MDS) using intelligent adaptive SOM with recurrent neural networks (RNNs).

Science.gov (United States)

Wang, Chi-Hsu; Chen, Chun-Yao; Hung, Kun-Neng

2015-06-01

In this paper, a new adaptive self-organizing map (SOM) with recurrent neural network (RNN) controller is proposed for task assignment and path evolution of missile defense system (MDS). We address the problem of N agents (defending missiles) and D targets (incoming missiles) in MDS. A new RNN controller is designed to force an agent (or defending missile) toward a target (or incoming missile), and a monitoring controller is also designed to reduce the error between RNN controller and ideal controller. A new SOM with RNN controller is then designed to dispatch agents to their corresponding targets by minimizing total damaging cost. This is actually an important application of the multiagent system. The SOM with RNN controller is the main controller. After task assignment, the weighting factors of our new SOM with RNN controller are activated to dispatch the agents toward their corresponding targets. Using the Lyapunov constraints, the weighting factors for the proposed SOM with RNN controller are updated to guarantee the stability of the path evolution (or planning) system. Excellent simulations are obtained using this new approach for MDS, which show that our RNN has the lowest average miss distance among the several techniques.

Isotopes and innovation: MDS Nordion's first fifty years, 1946-1996

Energy Technology Data Exchange (ETDEWEB)

Litt, P

2000-07-01

Few people realize that Canada leads in the world in the production of radio isotopes, the raw material of nuclear medicine and high-tech scanners, and in their use in medicine and industry. In Isotopes and Innovation the author gives an in-depth look at MDS Nordion, a company that started as the radium sales department of Eldorado Mining and Refining, the Canadian uranium producer that was a key strategic resource for the Allies during the race to build the nuclear bomb, and went on to become the world?s leading producer of radioisotopes. When radium began to be used as a cancer treatment, Eldorado quickly became familiar with the medical marketplace and adept at developing products that could solve clinical problems and, more important, save lives. When Canadian nuclear reactors at Chalk River began producing radioisotopes that outperformed radium, Eldorado's radium sales department was transferred to a new crown corporation, Atomic Energy of Canada Limited, created to manage Canada's nuclear research establishment. The new company developed many useful applications for radioisotopes, including cobalt-60 cancer therapy machines and industrial sterilization plants. Bought by Medical Data Services Inc. in the early 1990s, MDS Nordion was a runaway success, creator and sole proprietor of several market-leading products. Isotopes and Innovation describes how a company capitalized on the byproducts of Canada's unique nuclear research program to attain a commanding international position in extremely specialized and demanding high-tech markets, a saga in which innovative research and enterprising global marketing have brought commercial success and saved countless lives around the world.

Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: an evaluation of different methods.

Science.gov (United States)

Kremser, Andreas; Dressig, Julia; Grabrucker, Christine; Liepert, Anja; Kroell, Tanja; Scholl, Nina; Schmid, Christoph; Tischer, Johanna; Kufner, Stefanie; Salih, Helmut; Kolb, Hans Jochem; Schmetzer, Helga

2010-01-01

Myeloid-leukemic cells (AML, MDS, CML) can be differentiated to leukemia-derived dendritic cell [DC (DCleu)] potentially presenting the whole leukemic antigen repertoire without knowledge of distinct leukemia antigens and are regarded as promising candidates for a vaccination strategy. We studied the capability of 6 serum-free DC culture methods, chosen according to different mechanisms, to induce DC differentiation in 137 cases of AML and 52 cases of MDS. DC-stimulating substances were cytokines ("standard-medium", "MCM-Mimic", "cytokine-method"), bacterial lysates ("Picibanil"), double-stranded RNA ["Poly (I:C)"] or a cytokine bypass method ("Ca-ionophore"). The quality/quantity of DC generated was estimated by flow cytometry studying (co) expressions of "DC"antigens, costimulatory, maturation, and blast-antigens. Comparing these methods on average 15% to 32% DC, depending on methods used, could be obtained from blast-containing mononuclear cells (MNC) in AML/MDS cases with a DC viability of more than 60%. In all, 39% to 64% of these DC were mature; 31% to 52% of leukemic blasts could be converted to DCleu and DCleu-proportions in the suspension were 2% to 70% (13%). Average results of all culture methods tested were comparable, however not every given case of AML could be differentiated to DC with 1 selected method. However performing a pre-analysis with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-ionophore) we could generate DC in any given case. Functional analyses provided proof, that DC primed T cells to antileukemia-directed cytotoxic cells, although an anti-leukemic reaction was not achieved in every case. In summary our data show that a successful, quantitative DC/DCleu generation is possible with the best of 3 previously tested methods in any given case. Reasons for different functional behaviors of DC-primed T cells must be evaluated to design a practicable DC-based vaccination strategy.

Validation of the Care-Related Quality of Life Instrument in different study settings: findings from The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS).

Science.gov (United States)

Lutomski, J E; van Exel, N J A; Kempen, G I J M; Moll van Charante, E P; den Elzen, W P J; Jansen, A P D; Krabbe, P F M; Steunenberg, B; Steyerberg, E W; Olde Rikkert, M G M; Melis, R J F

2015-05-01

Validity is a contextual aspect of a scale which may differ across sample populations and study protocols. The objective of our study was to validate the Care-Related Quality of Life Instrument (CarerQol) across two different study design features, sampling framework (general population vs. different care settings) and survey mode (interview vs. written questionnaire). Data were extracted from The Older Persons and Informal Caregivers Minimum DataSet (TOPICS-MDS, www.topics-mds.eu ), a pooled public-access data set with information on >3,000 informal caregivers throughout the Netherlands. Meta-correlations and linear mixed models between the CarerQol's seven dimensions (CarerQol-7D) and caregiver's level of happiness (CarerQol-VAS) and self-rated burden (SRB) were performed. The CarerQol-7D dimensions were correlated to the CarerQol-VAS and SRB in the pooled data set and the subgroups. The strength of correlations between CarerQol-7D dimensions and SRB was weaker among caregivers who were interviewed versus those who completed a written questionnaire. The directionality of associations between the CarerQol-VAS, SRB and the CarerQol-7D dimensions in the multivariate model supported the construct validity of the CarerQol in the pooled population. Significant interaction terms were observed in several dimensions of the CarerQol-7D across sampling frame and survey mode, suggesting meaningful differences in reporting levels. Although good scientific practice emphasises the importance of re-evaluating instrument properties in individual research studies, our findings support the validity and applicability of the CarerQol instrument in a variety of settings. Due to minor differential reporting, pooling CarerQol data collected using mixed administration modes should be interpreted with caution; for TOPICS-MDS, meta-analytic techniques may be warranted.

Relationship between the non-motor items of the MDS-UPDRS and Quality of Life in patients with Parkinson's disease

NARCIS (Netherlands)

Skorvanek, Matej; Rosenberger, Jaroslav; Minar, Michal; Grofik, Milan; Han, Vladimir; Groothoff, Johan W.; Valkovic, Peter; Gdovinova, Zuzana; van Dijk, Jitse P.

2015-01-01

The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship

Context Matters: Distinct Disease Outcomes as a Result of Crebbp Hemizygosity in Different Mouse Bone Marrow Compartments.

Directory of Open Access Journals (Sweden)

Ting Zhou

Full Text Available Perturbations in CREB binding protein (CREBBP are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS. Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U, and a proportion goes on to develop acute myeloid leukemia (AML. We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells. We now report that transplantation of unfractionated Crebbp+/- bone marrow into wild-type recipients resulted in either early-onset AML or late-onset MDS and MDS/MPN-U. In contrast, purified Lin-Sca-1+c-Kit++ cells primarily gave rise to MDS with occasional transformation to AML. Furthermore, Crebbp+/- common myeloid progenitors and granulocyte/macrophage progenitors could trigger skewed myelopoiesis, myelodysplasia and late-onset AML. Surprisingly, the phenotypically abnormal cells were all of wild-type origin. MDS, MPN and AML can thus all be transferred from Crebbp+/- BM to wild-type hosts but fractionated bone marrow does not recapitulate the full disease spectrum of whole bone marrow, indicating that not only mutational status but also cellular context contribute to disease outcome. This has important consequences for structuring and interpreting future investigations into the underlying mechanisms of myeloid malignancies as well as for their treatment.

An International MDS/MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

Science.gov (United States)

Mughal, Tariq I.; Cross, Nicholas C.P.; Padron, Eric; Tiu, Ramon V.; Savona, Michael; Malcovati, Luca; Tibes, Raoul; Komrokji, Rami S.; Kiladjian, Jean-Jacques; Garcia-Manero, Guillermo; Orazi, Attilio; Mesa, Ruben; Maciejewski, Jaroslaw P.; Fenaux, Pierre; Itzykson, Raphael; Mufti, Ghulam; Solary, Eric; List, Alan F.

2015-01-01

In the 2008 WHO classification, chronic myeloid malignancies that share both myelodysplastic and myeloproliferative features define the myelodysplastic/myeloproliferative group, which includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ring sideroblasts and thrombocytosis, and myelodysplastic/myeloproliferative unclassified. With the notable exception of refractory anemia with ring sideroblasts and thrombocytosis, there is much overlap among the various subtypes at the molecular and clinical levels, and a better definition of these entities, an understanding of their biology and an identification of subtype-specific molecular or cellular markers are needed. To address some of these challenges, a panel comprised of laboratory and clinical experts in myelodysplastic/myeloproliferative was established, and four independent academic MDS/MPN workshops were held on: 9th March 2013, in Miami, Florida, USA; 6th December 2013, in New Orleans, Louisiana, USA; 13th June 2014 in Milan, Italy; and 5th December 2014 in San Francisco, USA. During these meetings, the current understanding of these malignancies and matters of biology, diagnosis and management were discussed. This perspective and the recommendations on molecular pathogenesis, diagnosis and clinical characterization for adult onset myelodysplastic/myeloproliferative is the result of a collaborative project endorsed and supported by the MDS Foundation. PMID:26341525

To change or not to change - translating and culturally adapting the paediatric version of the Moral Distress Scale-Revised (MDS-R).

Science.gov (United States)

Af Sandeberg, Margareta; Wenemark, Marika; Bartholdson, Cecilia; Lützén, Kim; Pergert, Pernilla

2017-02-20

Paediatric cancer care poses ethically difficult situations that can lead to value conflicts about what is best for the child, possibly resulting in moral distress. Research on moral distress is lacking in paediatric cancer care in Sweden and most questionnaires are developed in English. The Moral Distress Scale-Revised (MDS-R) is a questionnaire that measures moral distress in specific situations; respondents are asked to indicate both the frequency and the level of disturbance when the situation arises. The aims of this study were to translate and culturally adapt the questionnaire to the context of Swedish paediatric cancer care. In doing so we endeavoured to keep the content in the Swedish version as equivalent to the original as possible but to introduce modifications that improve the functional level and increase respondent satisfaction. The procedure included linguistic translation and cultural adaptation of MDS-R's paediatric versions for Physicians, Nurses and Other Healthcare Providers to the context of Swedish paediatric cancer care. The process of adjustment included: preparation, translation procedure and respondent validation. The latter included focus group and cognitive interviews with healthcare professionals in paediatric cancer care. To achieve a Swedish version with a good functional level and high trustworthiness, some adjustments were made concerning design, language, cultural matters and content. Cognitive interviews revealed problems with stating the level of disturbance hypothetically and items with negations caused even more problems, after having stated that the situation never happens. Translation and cultural adaptation require the involvement of various types of specialist. It is difficult to combine the intention to keep the content as equivalent to the original as possible with the need for modifications that improve the functional level and increase respondent satisfaction. The translated and culturally adapted Swedish MDS-R seems

The DVB Channel Coding Application Using the DSP Development Board MDS TM-13 IREF

Directory of Open Access Journals (Sweden)

M. Slanina

2004-12-01

Full Text Available The paper deals with the implementation of the channel codingaccording to DVB standard on DSP development board MDS TM-13 IREF andPC. The board is based on Philips Nexperia media processor andintegrates hardware video ADC and DAC. The program libraries featuresused for MPEG based video compression are outlined and then thealgorithms of channel decoding (FEC protection against errors arepresented including the flowchart diagrams. The paper presents thepartial hardware implementation of the simulation system that coversselected phenomena of DVB baseband processing and it is used for realtime interactive demonstration of error protection influence ontransmitted digital video in laboratory and education.

Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation; Myeloablative Radioimmuntherapien zur Konditionierung bei Patienten mit AML, MDS und multiplem Myelom vor Stammzelltransplantation

Energy Technology Data Exchange (ETDEWEB)

Buchmann, I. [Abt. fuer Nuklearmedizin, Universitaetsklinik Heidelberg (Germany)

2008-06-15

Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. {sup 90}Y, {sup 188}Re and {sup 131}I are the most frequently used {beta}{sup -}-particles. Of these, {sup 90}Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate {sup 90}Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The {sup 90}Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow < 25%. The specific doses (Gy/GBq) are 10.2 {+-} 1.8 (bone marrow), 2.7 {+-} 2 (liver) and < 1 (kidneys). In contrast, radiolabeled anti-CD33- and anti-CD45-antibodies bind to both, most of white blood cells and

Large enhancement of highly energetic electrons in the outer radiation belt and its transport into the inner radiation belt inferred from MDS-1 satellite observations

Science.gov (United States)

Obara, T.; Matsumoto, H.

2016-03-01

We have examined a large increase of relativistic electrons in the outer radiation belt and its penetration into the inner radiation belt over slot region using the MDS-1 satellite observations. Result of analyses demonstrates that a large increase took place in the spring and autumn seasons, and we have newly confirmed that the penetration of outer belt electrons to the inner radiation zone took place during the big magnetic storms by examining a pitch angle distribution of the penetrating electrons.

Multidimensional assessment of patient condition and mutational analysis in peripheral blood, as tools to improve outcome prediction in myelodysplastic syndromes: A prospective study of the Spanish MDS group.

Science.gov (United States)

Ramos, Fernando; Robledo, Cristina; Pereira, Arturo; Pedro, Carmen; Benito, Rocío; de Paz, Raquel; Del Rey, Mónica; Insunza, Andrés; Tormo, Mar; Díez-Campelo, María; Xicoy, Blanca; Salido, Eduardo; Sánchez-Del-Real, Javier; Arenillas, Leonor; Florensa, Lourdes; Luño, Elisa; Del Cañizo, Consuelo; Sanz, Guillermo F; María Hernández-Rivas, Jesús

2017-09-01

The International Prognostic Scoring System and its revised form (IPSS-R) are the most widely used indices for prognostic assessment of patients with myelodysplastic syndromes (MDS), but can only partially account for the observed variation in patient outcomes. This study aimed to evaluate the relative contribution of patient condition and mutational status in peripheral blood when added to the IPSS-R, for estimating overall survival and the risk of leukemic transformation in patients with MDS. A prospective cohort (2006-2015) of 200 consecutive patients with MDS were included in the study series and categorized according to the IPSS-R. Patients were further stratified according to patient condition (assessed using the multidimensional Lee index for older adults) and genetic mutations (peripheral blood samples screened using next-generation sequencing). The change in likelihood-ratio was tested in Cox models after adding individual covariates. The addition of the Lee index to the IPSS-R significantly improved prediction of overall survival [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.96-4.66, P < 0.001), and mutational analysis significantly improved prediction of leukemic evolution (HR 2.64, 1.56-4.46, P < 0.001). Non-leukemic death was strongly linked to patient condition (HR 2.71, 1.72-4.25, P < 0.001), but not to IPSS-R score (P = 0.35) or mutational status (P = 0.75). Adjustment for exposure to disease-modifying therapy, evaluated as a time-dependent covariate, had no effect on the proposed model's predictive ability. In conclusion, patient condition, assessed by the multidimensional Lee index and patient mutational status can improve the prediction of clinical outcomes of patients with MDS already stratified by IPSS-R. © 2017 Wiley Periodicals, Inc.

The prognostic value of monosomal karyotype (MK) in higher-risk patients with myelodysplastic syndromes treated with 5-Azacitidine. A retrospective analysis of the Hellenic (Greek) MDS Study Group.

Science.gov (United States)

Papageorgiou, Sotirios G; Vasilatou, Diamantina; Kontos, Christos K; Kotsianidis, Ioannis; Symeonidis, Argiris; Galanopoulos, Athanasios G; Hatzimichael, Eleftheria; Megalakaki, Aekaterini; Poulakidas, Elias; Diamantopoulos, Panagiotis; Vassilakopoulos, Theodoros; Zikos, Panagiotis; Papadaki, Helen; Mparmparousi, Despoina; Bouronikou, Eleni; Panayiotidis, Panayiotis; Viniou, Nora-Athina; Pappa, Vassiliki

2018-04-16

In this study, we investigated the incidence and prognostic impact of monosomal karyotype (MK) in 405 higher-risk MDS patients treated with 5-AZA. The MK was present in 66 out of 405 (16.3%) patients, most of whom had complex karyotype (CK). MK was strongly associated with CK and the cytogenetic risk defined according to IPSS-R, as well as with high-risk disease, according to IPSS (P=0.029), IPSS-R (PMDS treated with 5-AZA. Furthermore, we showed that in MDS with high or very-high IPSS-R risk score, MK can further distinguish patients with worse outcome. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Azacitidine-lenalidomide (ViLen) combination yields a high response rate in higher risk myelodysplastic syndromes (MDS)-ViLen-01 protocol.

Science.gov (United States)

Mittelman, Moshe; Filanovsky, Kalman; Ofran, Yishai; Rosenbaum, Hanna; Raanani, Pia; Braester, Andrei; Goldschmidt, Neta; Kirgner, Ilya; Herishanu, Yair; Perri, Chava; Ellis, Martin; Oster, Howard S

2016-10-01

Azacitidine treatment is effective in higher risk MDS (HR-MDS), with less than 50 % response, lasting 2 years. Aza and lenalidomide (Len) have a potential synergistic effect. ViLen-01 phase IIa trial includes 6-month induction (Aza 75 mg/m(2)/day, days 1-5, Len 10 mg/day, days 6-21, every 28 days), 6-month consolidation (Aza 75 mg/m(2)/day, days 1-5, every 28 days), and 12-month maintenance (Len 10 mg/day, days 1-21, every 28 days). Response was evaluated according to IWG criteria. Totally, 25 patients enrolled, with an average of 76.3 years old (60-87), and 88 % with major comorbidities. Thirteen patients completed induction, 7 proceeded for consolidation, and 2 for maintenance. The overall response rate (ORR) was 72 % (18/25), with 6 (24 %) for CR, 3 (12 %) for marrow CR, and 9 (36 %) for hematologic improvement (HI). The 7 non-responding patients were on the study 3 days to 4.1 months. At 6 months, 4 of 6 evaluable patients achieved complete cytogenetic response and 2 with del (5q) at diagnosis. Adverse events (AEs) were as expected in these patients: grades III-IV, mainly hematologic-thrombocytopenia (20 patients) and neutropenia (13 patients). The common non-hematologic AEs were infections (14 patients), nausea (7), vomiting (7), diarrhea (7), and skin reactions (5). The median progression-free survival (PFS) was 12 ± 1.36 months, with median overall survival (OS) of 12 ± 1.7 months. Quality of life (FACT questionnaire) data were available for 12 patients with a tendency towards improved QoL. This trial with elderly HR-MDS patients with an expected poor prognosis demonstrates a high (72 %) response rate and a reasonable expected safety profile but a relatively short PFS and OS.

Myeloablative radioimmunotherapies in the conditioning of patients with AML, MDS and multiple myeloma prior to stem cell transplantation

International Nuclear Information System (INIS)

Buchmann, I.

2008-01-01

Aggressive consolidation chemotherapy and hematopoietic stem cell transplantation have improved the prognosis of patients with acute myeloid leukemia (AML), myelodyplastic syndrome (MDS) and multiple myeloma. Nevertheless, only a minor fraction of patients achieve long-term disease-free survival after stem cell transplantation with disease recurrence being the most common cause of treatment failure. In addition, therapy-related effects such as toxicity of chemotherapy and complications of stem cell transplantation increase mortality rates significantly. Myeloablative radioimmunotherapy uses radiolabeled monoclonal antibodies (mAb) with affinity for the hematopoietic marrow. It applies high radiation doses in the bone marrow but spares normal organs. Adding myeloablative radioimmunotherapy to the conditioning schemes of AML, MDS and multiple myeloma before stem cell transplantation allows for the achievement of a pronounced antileukemic/antimyeloma effect for the reduction of relapse rates without significant increase of acute organ toxicity and therapy-related mortality. In order to optimise therapy, a rational design of the nuclide-antibody combination is necessary. 90 Y, 188 Re and 131 I are the most frequently used β - -particles. Of these, 90 Y is the most qualified nuclide for myeloablation. Backbone stabilised DTPA are ideal chelators to stably conjugate 90 Y to antibodies so far. For myeloablative conditioning, anti-CD66-, -45- and -33-mAb are used. The anti-CD66-antibody BW250/183 binds to normal hematopoietic cells but not to leukemic blasts and myeloma cells. The 90 Y-2B3M-DTPA-BW250/183 is the most suited radioimmunoconjugate for patients with an infiltration grade of leukemic blasts in the bone marrow 90 Y-anti-CD45-mAb YAML568 are 6.4 ± 1.2 (bone marrow), 3.9 ± 1.4 (liver) and 1.1 ± 0.4 (kidneys). CD45 is expressed also on the extramedullar clonogenic myeloma progenitor cell that circulates in the peripheral blood. Thus, the conditioning of

Aplastic Anemia and MDS International Foundation (AAMDSIF): Bone marrow failure disease scientific symposium 2016.

Science.gov (United States)

Zeidan, Amer M; Battiwalla, Minoo; Berlyne, Deborah; Winkler, Thomas

2017-02-01

Patients with acquired and inherited bone marrow failure syndromes (BMFS) have ineffective hematopoiesis due to impairments of the hematopoietic stem cell compartment. Common manifestations of BMFS include varying degrees of peripheral blood cytopenias and, sometimes, progression to acute myelogenous leukemia. Research efforts have been made all over the world to improve understanding of the pathogenesis of these diseases and their clinical implications. The Aplastic Anemia and MDS International Foundation (AAMDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize recent scientific discoveries in several BMFS that were presented at the fifth International Bone Marrow Failure Disease Scientific Symposium 2016 that AAMDSIF sponsored on March 17-18, 2016, in Rockville, Maryland. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions

DEFF Research Database (Denmark)

Nilsson-Ehle, Herman; Birgegård, Gunnar; Samuelsson, Jan

2011-01-01

Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels...... has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L....

Paclitaxel Induced MDS and AML: A Case Report and Literature Review

Directory of Open Access Journals (Sweden)

Udit Bhaskar Bhatnagar

2016-01-01

Full Text Available Therapy related acute myelogenous leukemia (AML and myelodysplastic syndromes (MDS have been classically linked to alkylating agents and topoisomerase inhibitors. They constitute about 1% of all AMLs. There is less evidence on association of taxanes (paclitaxel and docetaxel with these myeloid neoplasms. We present a case of paclitaxel therapy related acute myelogenous leukemia after treatment of endometrial cancer with a regimen containing paclitaxel and carboplatin. A 63-year-old female underwent surgery followed by a total of 6 cycles of chemotherapy with carboplatin and paclitaxel. Six months after last cycle of chemotherapy, she was diagnosed with myelodysplastic syndrome with refractory anemia and excess blasts. Six weeks later, she had worsening anemia and thrombocytopenia which prompted a bone marrow biopsy which revealed acute myelomonocytic leukemia. A thorough literature review revealed 12 other case reports where taxanes have been implicated in the development of therapy related myeloid neoplasm. Based on the timeline of events in our patient, paclitaxel is the likely culprit in the pathogenesis of this myeloid neoplasm. This rare but significantly grave adverse effect should be kept in consideration when deciding on treatment options for gynecological malignancies.

The impact of older person's frailty on the care-related quality of life of their informal caregiver over time: results from the TOPICS-MDS project.

Science.gov (United States)

Oldenkamp, Marloes; Hagedoorn, Mariët; Wittek, Rafael; Stolk, Ronald; Smidt, Nynke

2017-10-01

To examine the impact of changes in an older person's frailty on the care-related quality of life of their informal caregiver. Five research projects in the TOPICS-MDS database with data of both older person and informal caregiver at baseline and after 12 months follow-up were selected. Frailty was measured in five health domains (functional limitations, psychological well-being, social functioning, health-related quality of life, self-rated health). Care-related quality of life was measured with the Care-Related Quality of Life instrument (CarerQoL-7D), containing two positive (fulfilment, perceived support) and five negative dimensions (relational problems, mental health problems, physical health problems, financial problems, problems combining informal care with daily activities). 660 older person/caregiver couples were included. Older persons were on average 79 (SD 6.9) years of age, and 61% was female. Caregivers were on average 65 (SD 12.6) years of age, and 68% was female. Results of the multivariable linear and logistic regression analyses showed that an increase in older person's frailty over time was related to a lower total care-related quality of life of the caregiver, and to more mental and physical health problems, and problems with combining informal care with daily activities at follow-up. A change in the older person's psychological well-being was most important for the caregiver's care-related quality of life, compared to the other health domains. Health professionals observing decreasing psychological well-being of an older person and increasing hours of informal care provision should be aware of the considerable problems this may bring to their informal caregiver, and should tailor interventions to support informal caregivers according to their specific needs and problems.

2C-Methyl- D- erythritol 2,4-cyclodiphosphate synthase from Stevia rebaudiana Bertoni is a functional gene.

Science.gov (United States)

Kumar, Hitesh; Singh, Kashmir; Kumar, Sanjay

2012-12-01

Stevia [Stevia rebaudiana (Bertoni)] is a perennial herb which accumulates sweet diterpenoid steviol glycosides (SGs) in its leaf tissue. SGs are synthesized by 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Of the various enzymes of the MEP pathway, 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (MDS) (encoded by MDS) catalyzes the cyclization of 4-(cytidine 5' diphospho)-2C-methyl-D-erythritol 2-phosphate into 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Complementation of the MDS knockout mutant strain of Escherichia coli, EB370 with putative MDS of stevia (SrMDS) rescued the lethal mutant, suggesting SrMDS to be a functional gene. Experiments conducted in plant growth chamber and in the field suggested SrMDS to be a light regulated gene. Indole 3-acetic acid (IAA; 50, 100 μM) down-regulated the expression of SrMDS at 4 h of the treatment, whereas, abscisic acid did not modulate its expression. A high expression of SrMDS was observed during the light hours of the day as compared to the dark hours. The present work established functionality of SrMDS and showed the role of light and IAA in regulating expression of SrMDS.

Mediterranean and Nordic diet scores and long-term changes in body weight and waist circumference: results from a large cohort study.

Science.gov (United States)

Li, Yingjun; Roswall, Nina; Ström, Peter; Sandin, Sven; Adami, Hans-Olov; Weiderpass, Elisabete

2015-12-28

Dietary patterns, which represent a broader picture of food and nutrient consumption, have gained increasing interest over the last decades. In a cohort design, we followed 27 544 women aged 29-49 years from baseline in 1991-1992. We collected data from an FFQ at baseline and body weight (BW) and waist circumference (WC) data both at baseline and at follow-up in 2003. We calculated the Mediterranean diet score (MDS, ranging from 0 to 9) and the Nordic diet score (NDS, ranging from 0 to 6). We used linear regression to examine the association between MDS and NDS (exposures) with subsequent BW change (ΔBW) and WC change (ΔWC) (outcomes) both continuously and categorically. Higher adherence to the MDS or NDS was not associated with ΔBW. The multivariable population average increment in BW was 0·03 kg (95 % CI -0·03, 0·09) per 1-point increase in MDS and 0·04 kg (95 % CI -0·02, 0·10) per 1-point increase in NDS. In addition, higher adherence to the MDS was not associated with ΔWC, with the multivariable population average increment per 1-point increase in MDS being 0·05 cm (95 % CI -0·03, 0·13). Higher adherence to the NDS was not significantly associated with gain in WC when adjusted for concurrent ΔBW. In conclusion, a higher adherence to the MDS or NDS was not associated with changes in average BW or WC in the present cohort followed for 12 years.

Multidimensional scaling for large genomic data sets

Directory of Open Access Journals (Sweden)

Lu Henry

2008-04-01

Full Text Available Abstract Background Multi-dimensional scaling (MDS is aimed to represent high dimensional data in a low dimensional space with preservation of the similarities between data points. This reduction in dimensionality is crucial for analyzing and revealing the genuine structure hidden in the data. For noisy data, dimension reduction can effectively reduce the effect of noise on the embedded structure. For large data set, dimension reduction can effectively reduce information retrieval complexity. Thus, MDS techniques are used in many applications of data mining and gene network research. However, although there have been a number of studies that applied MDS techniques to genomics research, the number of analyzed data points was restricted by the high computational complexity of MDS. In general, a non-metric MDS method is faster than a metric MDS, but it does not preserve the true relationships. The computational complexity of most metric MDS methods is over O(N2, so that it is difficult to process a data set of a large number of genes N, such as in the case of whole genome microarray data. Results We developed a new rapid metric MDS method with a low computational complexity, making metric MDS applicable for large data sets. Computer simulation showed that the new method of split-and-combine MDS (SC-MDS is fast, accurate and efficient. Our empirical studies using microarray data on the yeast cell cycle showed that the performance of K-means in the reduced dimensional space is similar to or slightly better than that of K-means in the original space, but about three times faster to obtain the clustering results. Our clustering results using SC-MDS are more stable than those in the original space. Hence, the proposed SC-MDS is useful for analyzing whole genome data. Conclusion Our new method reduces the computational complexity from O(N3 to O(N when the dimension of the feature space is far less than the number of genes N, and it successfully

Additive Construction with Mobile Emplacement (ACME) / Automated Construction of Expeditionary Structures (ACES) Materials Delivery System (MDS)

Science.gov (United States)

Mueller, R. P.; Townsend, I. I.; Tamasy, G. J.; Evers, C. J.; Sibille, L. J.; Edmunson, J. E.; Fiske, M. R.; Fikes, J. C.; Case, M.

2018-01-01

The purpose of the Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) project is to incorporate the Liquid Goods Delivery System (LGDS) into the Dry Goods Delivery System (DGDS) structure to create an integrated and automated Materials Delivery System (MDS) for 3D printing structures with ordinary Portland cement (OPC) concrete. ACES 3 is a prototype for 3-D printing barracks for soldiers in forward bases, here on Earth. The LGDS supports ACES 3 by storing liquid materials, mixing recipe batches of liquid materials, and working with the Dry Goods Feed System (DGFS) previously developed for ACES 2, combining the materials that are eventually extruded out of the print nozzle. Automated Construction of Expeditionary Structures, Phase 3 (ACES 3) is a project led by the US Army Corps of Engineers (USACE) and supported by NASA. The equivalent 3D printing system for construction in space is designated Additive Construction with Mobile Emplacement (ACME) by NASA.

Is working memory working against suggestion susceptibility? Results from extended version of DRM paradigm

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Maciaszek Patrycja

2016-04-01

Full Text Available The paper investigates relationship between working memory efficiency, defined as the result of its’ processing & storage capacity (Oberauer et al., 2003 and the tendency to (1 create assosiative memory distortions (false memories, FM; (2 yield under the influence of external, suggesting factors. Both issues were examined using extended version of Deese-Roediger-McDermott procedure (1959, 1995, modified in order to meet the study demands. Suggestion was contained in an ostentatious feedback information the participants (N=88 received during the DRM procedure. Working memory (WM was measured by standardized tasks (n-back, Jaeggi et al., 2010; automatic-ospan, Unsworth et al., 2005. Study included 3 conditions, differing in the quality of suggestion (positive, negative or neutral. Participants were assigned into 3 groups, depending on results they achieved completing the WM tasks. Obtained results alongside the previously set hypothesis, revealed that (1 WM impacts individuals’ tendency to create false memories in DRM and (2 that the individuals showing higher rates in WM tasks are less willing to yield to suggestion compared to those with lesser ones. It also showed that the greater amount to shift (Gudjonsson, 2003, emerges under the negative suggestion condition (collating positive. Notwithstanding that the interaction effect did not achieve saliency, both analyzed factors (WM and suggesting content are considered as meaningful to explain memory suggestion susceptibility in presented study. Although, obtained results emphasize the crucial role of WM efficiency, that is believed to decide the magnitude of feedback that is influential in every subject. Therefore, issue demands further exploration.

Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome

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O'Brien Susan

2010-11-01

Full Text Available Abstract Background Myelodysplastic syndrome (MDS may be induced by certain mutagenic environmental or chemotherapeutic toxins; however, the role of susceptibility genes remains unclear. The G/G genotype of the single-nucleotide polymorphism (SNP rs1617640 in the erythropoietin (EPO promoter has been shown to be associated with decreased EPO expression. We examined the association of rs1617640 genotype with MDS. Methods We genotyped the EPO rS1617640 SNP in 189 patients with MDS, 257 with acute myeloid leukemia (AML, 106 with acute lymphoblastic leukemia, 97 with chronic lymphocytic leukemia, 353 with chronic myeloid leukemia, and 95 healthy controls. Results The G/G genotype was significantly more common in MDS patients (47/187; 25.1% than in controls (6/95; 6.3% or in patients with other leukemias (101/813; 12.4% (all P P = 0.03. Time to neutrophils recovery after therapy was significantly longer in MDS patients with the G/G genotype (P = 0.02. Conclusions These findings suggest a strong association between the rs1617640 G/G genotype and MDS. Further studies are warranted to investigate the utility of screening for this marker in individuals exposed to environmental toxins or chemotherapy.

PAS positivity of erythroid precursor cells is associated with a poor prognosis in newly diagnosed myelodysplastic syndrome patients.

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Masuda, Kenta; Shiga, Shuichi; Kawabata, Hiroshi; Takaori-Kondo, Akifumi; Ichiyama, Satoshi; Kamikubo, Yasuhiko

2018-07-01

Myelodysplastic syndrome (MDS) is a group of clonal stem cell disorders characterized by hematopoietic insufficiency. The accurate risk stratification of patients with MDS is essential for selection of appropriate therapies. We herein conducted a retrospective cohort study to examine the prognostic value of periodic acid-Schiff (PAS) reaction-positive erythroblasts in MDS patients. We examined the PAS positivity of the bone marrow erythroblasts of 144 patients newly diagnosed with MDS; 26 (18.1%) of them had PAS-positive erythroblasts, whereas 118 (81.9%) did not. The PAS-positive group showed significantly poorer karyotypes as defined in the revised International Prognostic Scoring System (IPSS-R) and higher scores in age-adjusted IPSS-R (IPSS-RA) than the PAS-negative group. Overall survival (OS) and leukemia-free survival (LFS) were also significantly shorter in the PAS-positive group than in the PAS-negative group. Similar results were obtained when only high- and very high risk groups were analyzed using IPSS-RA. This retrospective study suggested that the PAS positivity of erythroblasts is an additional prognostic factor combined with other risk scores for OS and LFS in MDS, and our results may contribute to improved clinical decision-making and rapid risk stratification.

Depletion of cytotoxic T-cells does not protect NUP98-HOXD13 mice from myelodysplastic syndrome but reveals a modest tumor immunosurveillance effect.

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Sheryl M Gough

Full Text Available Myelodysplastic syndrome (MDS and aplastic anemia (AA patients both present with symptoms of bone marrow failure. In many AA patients, these features are thought to result from an oligoclonal expansion of cytotoxic T-cells that destroy haematopoietic stem or progenitor cells. This notion is supported by the observation that AA patients respond to immunosuppressive therapy. A fraction of MDS patients also respond well to immunosuppressive therapy suggesting a similar role for cytotoxic T-cells in the etiology of MDS, however the role of cytotoxic T-cells in MDS remains unclear. Mice that express a NUP98-HOXD13 (NHD13 transgene develop a MDS that closely mimics the human condition in terms of dysplasia, ineffective hematopoiesis, and transformation to acute myeloid leukemia (AML. We followed a cohort of NHD13 mice lacking the Rag1 protein (NHD13/Rag1KO to determine if the absence of lymphocytes might 1 delay the onset and/or diminish the severity of the MDS, or 2 effect malignant transformation and survival of the NHD13 mice. No difference was seen in the onset or severity of MDS between the NHD13 and NHD13/Rag1KO mice. However, NHD13/Rag1KO mice had decreased survival and showed a trend toward increased incidence of transformation to AML compared to the NHD13 mice, suggesting protection from AML transformation by a modest immuno-surveillance effect. In the absence of functional Tcrb signaling in the NHD13/Rag1KO T-cell tumors, Pak7 was identified as a potential Tcrb surrogate survival signal.

Simultaneous Presentation of Giant Cell Arteritis and Myelodysplastic Syndrome in an Elderly Japanese Man.

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Senjo, Hajime; Higuchi, Takakazu; Morimoto, Masaya; Koyamada, Ryosuke; Yanaoka, Chisun; Okada, Sadamu

2018-05-18

An 81-year-old Japanese man presented with constitutional symptoms and anemia and was diagnosed with giant cell arteritis (GCA) and myelodysplastic syndrome (MDS) simultaneously. His symptoms and anemia improved promptly with steroids; however, the MDS rapidly progressed to overt leukemia. While MDS patients are at an increased risk of autoimmune diseases, an association with GCA has rarely been reported. This case illustrates the importance of considering GCA as a cause of anemia in elderly patients if MDS is already diagnosed, even in countries where the prevalence of GCA is very low. The simultaneous development of GCA and MDS suggests a common pathogenetic link between these two diseases.

Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

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Ostendorf, Benjamin N; Flenner, Eva; Flörcken, Anne; Westermann, Jörg

2018-01-01

Recent reports have revealed myelodysplastic syndromes (MDS) to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

Phenotypic characterization of aberrant stem and progenitor cell populations in myelodysplastic syndromes.

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Benjamin N Ostendorf

Full Text Available Recent reports have revealed myelodysplastic syndromes (MDS to arise from cancer stem cells phenotypically similar to physiological hematopoietic stem cells. Myelodysplastic hematopoiesis maintains a hierarchical organization, but the proportion of several hematopoietic compartments is skewed and multiple surface markers are aberrantly expressed. These aberrant antigen expression patterns hold diagnostic and therapeutic promise. However, eradication of MDS requires targeting of early myelodysplasia propagating stem cells. This warrants an exact assessment of the differentiation stage at which aberrant expression occurs in transformed hematopoiesis. Here, we report results on the prospective and extensive dissection of the hematopoietic hierarchy in 20 patients with either low-risk MDS or MDS with excess blasts and compare it to hematopoiesis in patients with non-malignancy-associated cytopenia or B cell lymphoma without bone marrow infiltration. We found patients with MDS with excess blasts to exhibit characteristic expansions of specific immature progenitor compartments. We also identified the aberrant expression of several markers including ALDH, CLL-1, CD44, and CD47 to be specific features of hematopoiesis in MDS with excess blasts. We show that amongst these, aberrant CLL-1 expression manifested at the early uncommitted hematopoietic stem cell level, suggesting a potential role as a therapeutic target.

New polymorphisms of Xeroderma Pigmentosum DNA repair genes in myelodysplastic syndrome.

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Santiago, Sabrina Pinheiro; Junior, Howard Lopes Ribeiro; de Sousa, Juliana Cordeiro; de Paula Borges, Daniela; de Oliveira, Roberta Taiane Germano; Farias, Izabelle Rocha; Costa, Marília Braga; Maia, Allan Rodrigo Soares; da Nóbrega Ito, Mayumi; Magalhães, Silvia Maria Meira; Pinheiro, Ronald Feitosa

2017-07-01

The association between Xeroderma Pigmentosum DNA repair genes (XPA rs1800975, XPC rs2228000, XPD rs1799793 and XPF rs1800067) polymorphisms and myelodysplastic syndrome (MDS) have not been reported. To assess the functional role between these polymorphisms and MDS, we evaluated 189 samples stratified in two groups: 95 bone marrow samples from MDS patients and 94 from healthy elderly volunteers used as controls. Genotypes for all polymorphisms were identified in DNA samples in an allelic discrimination experiment by real-time polymerase chain reaction (qPCR). We also studied the mRNA expression of XPA and XPC genes to evaluate if its polymorphisms were functional in 53 RNAm MDS patients by qPCR methodologies. To the rs2228000 polymorphism, the CT and TT polymorphic genotype were associated with increased odds ratio (OR) of more profound cytopenia (hemoglobin and neutrophils count). To the rs1799793 polymorphism, we found that the GG homozygous wild-type genotype was associated with a decreased chance of developing MDS. We observed low expression of XPA in younger patients, in hypoplastic MDS and patients with abnormal karyotype when presented AG or AA polymorphic genotypes. We also found that there was a statistically significant interaction between the presence of micromegakaryocyte on down regulation of XPC regarding the CT heterozygous genotype of the rs1800975 polymorphism. Our results suggest that new functional polymorphisms of Xeroderma Pigmentosum DNA repair genes in MDS are related to its pathogenesis and prognosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thyroid function appears to be significantly reduced in Space-borne MDS mice

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Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

Quantitative Detection of ID4 Gene Aberrant Methylation in the Differentiation of Myelodysplastic Syndrome from Aplastic Anemia

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Mian-Yang Li

2015-01-01

Full Text Available Background: The diagnosis of myelodysplastic syndrome (MDS, especially hypoplastic MDS, and MDS with low blast counts or normal karyotype may be problematic. This study characterized ID4 gene methylation in patients with MDS and aplastic anemia (AA. Methods: The methylation status of ID4 was analyzed by bisulfite sequencing polymerase chain reaction (PCR and quantitative real-time methylation-specific PCR (MethyLight PCR in 100 patients with MDS and 31 patients with AA. Results: The MDS group had a higher ID4 gene methylation positivity rate (22.22% and higher methylation levels (0.21 [0-3.79] than the AA group (P < 0.05. Furthermore, there were significant differences between the hypoplastic MDS and AA groups, the MDS with low blast count and the AA groups, and the MDS with normal karyotype and the AA groups. The combination of genetic and epigenetic markers was used in much more patients with MDS (62.5% [35/56] than the use of genetic markers only (51.79% [29/56]. Conclusions: These results showed that the detection of ID4 methylation positivity rates and levels could be a useful biomarker for MDS diagnosis.

Endothelial Progenitor Cell Dysfunction in Myelodysplastic Syndromes: Possible Contribution of a Defective Vascular Niche to Myelodysplasia

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Luciana Teofili

2015-05-01

Full Text Available We set a model to replicate the vascular bone marrow niche by using endothelial colony forming cells (ECFCs, and we used it to explore the vascular niche function in patients with low-risk myelodysplastic syndromes (MDS. Overall, we investigated 56 patients and we observed higher levels of ECFCs in MDS than in healthy controls; moreover, MDS ECFCs were found variably hypermethylated for p15INK4b DAPK1, CDH1, or SOCS1. MDS ECFCs exhibited a marked adhesive capacity to normal mononuclear cells. When normal CD34+ cells were co-cultured with MDS ECFCs, they generated significant lower amounts of CD11b+ and CD41+ cells than in co-culture with normal ECFCs. At gene expression profile, several genes involved in cell adhesion were upregulated in MDS ECFCs, while several members of the Wingless and int (Wnt pathways were underexpressed. Furthermore, at miRNA expression profile, MDS ECFCs hypo-expressed various miRNAs involved in Wnt pathway regulation. The addition of Wnt3A reduced the expression of intercellular cell adhesion molecule-1 on MDS ECFCs and restored the defective expression of markers of differentiation. Overall, our data demonstrate that in low-risk MDS, ECFCs exhibit various primary abnormalities, including putative MDS signatures, and suggest the possible contribution of the vascular niche dysfunction to myelodysplasia.

Potential environmental benefits of improving recycling of polyolefines – LCA of Magnetic density separation (MDS) developed in the EU FP7 funded project W2Plastic

DEFF Research Database (Denmark)

Olsen, Stig Irving; Bonou, Alexandra

2012-01-01

identify eco-design criteria for the development and secondly to document the potential environmental improvement of polyolefin recycling using the MDS technology. A preliminary study focusing solely on the carbon footprint benefits of recycling plastic waste compared to virgin production of polymers...... showed that there are large benefits to recycling. However, including other uses of the waste illustrates that the benefits to a large extent depend on that the recycled plastic have such high quality that it can actually replace virgin plastic and also to some extent depends on which energy systems e.......g. energy recovery from incineration substitutes....

Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial

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John Porter

2012-01-01

Full Text Available Treatment of iron overload using deferoxamine (DFO is associated with significant deficits in patients' health-related quality of life (HRQOL and low treatment satisfaction. The current article presents patient-reported HRQOL, satisfaction, adherence, and persistence data from β-thalassemia (n=274 and myelodysplastic syndrome (MDS patients (n=168 patients participating in the Evaluation of Patients' Iron Chelation with Exjade (EPIC study (NCT00171821; a large-scale 1-year, phase IIIb study investigating the efficacy and safety of the once-daily oral iron chelator, deferasirox. HRQOL and satisfaction, adherence, and persistence to iron chelation therapy (ICT data were collected at baseline and end of study using the Medical Outcomes Short-Form 36-item Health Survey (SF-36v2 and the Satisfaction with ICT Questionnaire (SICT. Compared to age-matched norms, β-thalassemia and MDS patients reported lower SF-36 domain scores at baseline. Low levels of treatment satisfaction, adherence, and persistence were also observed. HRQOL improved following treatment with deferasirox, particularly among β-thalassemia patients. Furthermore, patients reported high levels of satisfaction with deferasirox at end of study and greater ICT adherence, and persistence. Findings suggest deferasirox improves HRQOL, treatment satisfaction, adherence, and persistence with ICT in β-thalassemia and MDS patients. Improving such outcomes is an important long-term goal for patients with iron overload.

Impact of azacitidine on red blood cell alloimmunisation in myelodysplastic syndrome.

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Ortiz, Sebastián; Orero, Maria T; Javier, Karla; Villegas, Carolina; Luna, Irene; Pérez, Pedro; Roig, Mónica; López, María; Costa, Sofía; Carbonell, Félix; Collado, Rosa; Ivars, David; Linares, Mariano

2017-09-01

The incidence of alloimmunisation in myelodysplastic syndromes (MDS) during the era of supportive treatment ranges from 9 to 56%. However, it is unknown if the widespread use of hypomethylating agents has changed the risk of immunisation. The aim of this study is to evaluate the impact of azacitidine (AZA) therapy on red blood cell (RBC) alloimmunisation in transfused patients with MDS, myelodysplastic syndromes/myeloproliferative syndromes (MDS/MPS) and secondary acute myeloid leukaemia (AML). We have analysed retrospectively all patients with MDS, MDS/MPS and secondary AML from MDS, who received their first transfusion in our hospital between January 1995 and December 2014. We have assessed the impact of age, sex, RBC and platelets units transfused, and AZA treatment on developing alloantibodies. In our study, the number of RBC units transfused increased the risk of developing alloantibodies. However aging and the treatment with AZA were associated with a lower rate of alloimmunisation. Patients with MDS, MDS/MPS and secondary AML who received treatment with AZA developed RBC antibodies at a lower rate than control group. We suggest that aging and immunosuppression due to AZA therapy could develop an immunological tolerance with a weak response to allotransfusions.

Replication Improves Sorting-Task Results Analyzed by DISTATIS in a Consumer Study of American Bourbon and Rye Whiskeys.

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Lahne, Jacob; Collins, Thomas S; Heymann, Hildegarde

2016-05-01

In consumer food-sensory studies, sorting and closely related methods (for example, projective mapping) have often been applied to large product sets which are complex and fatiguing for panelists. Analysis of sorting by Multi-Dimensional Scaling (MDS) is common, but this method discards relevant individual decisions; analysis by DISTATIS, which accounts for individual differences, is gaining acceptance. This research posits that replication can improve DISTATIS analysis by stabilizing consumer sensory maps, which are often extremely unstable. As a case study a fatiguing product set was sorted: 10 American whiskeys-5 bourbons and 5 ryes-were sorted into groups by 21 consumers over 2 replications. These products were chosen because American whiskeys are some of the most important distilled beverages in today's market; in particular, "bourbon" (mashbill more than 50% corn) and "rye" (more than 50% rye) whiskeys are important and assumed to be products with distinct sensory attributes. However, there is almost no scientific information about their sensory properties. Data were analyzed using standard and aggregated DISTATIS and MDS. No significant relationship between mashbill and consumer categorization in whiskeys was found; instead, there was evidence of producer and aging effects. aggregated DISTATIS was found to provide more stable results than without replication, and DISTATIS results provided a number of benefits over MDS, including bootstrapped confidence intervals for product separation. In addition, this is the first published evidence that mashbill does not determine sensory properties of American whiskey: bourbons and ryes, while legally distinct, were not separated by consumers. © 2016 Institute of Food Technologists®

Interpreting small treatment differences from quality of life data in cancer trials: an alternative measure of treatment benefit and effect size for the EORTC-QLQ-C30.

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Khan, Iftekhar; Bashir, Zahid; Forster, Martin

2015-11-14

The EORTC-QLQ-C30 is a widely used health related quality of life (HRQoL) questionnaire in lung cancer patients. Small HRQoL treatment effects are often reported as mean differences (MDs) between treatments, which are rarely justified or understood by patients and clinicians. An alternative approach using odds ratios (OR) for reporting effects is proposed. This may offer advantages including facilitating alignment between patient and clinician understanding of HRQoL effects. Data from six CRUK sponsored randomized controlled lung cancer trials (2 small cell and 4 in non-small cell, in 2909 patients) were used to HRQoL effects. Results from Beta-Binomial (BB) standard mixed effects were compared. Preferences for ORs vs MDs were determined and Time to Deterioration (TD) was also compared. HRQoL effects using ORs offered coherent interpretations: MDs >0 resulted in ORs >1 and vice versa; effect sizes were classified as 'Trivial' if the OR was between 1 ± 0.05 (i.e. 0.95 to 1.05); 'Small': for 1 ± 0.1; 'Medium': 1 ± 0.2 and 'Large': OR 1.20. Small HRQoL effects on the MD scale may translate to important treatment differences on the OR scale: for example, a worsening in symptoms (MD) by 2.6 points (p = 0.1314) would be a 17 % deterioration (p small ORs are unlikely to yield large MDs because methods based on OR model skewed data well. Initial evidence also suggests oncologists prefer ORs over MDs since interpretation is similar to hazard ratios. Reporting HRQoL benefits as MDs can be misleading. Estimates of HRQoL treatment effects in terms of ORs are preferred over MDs. Future analysis of QLQ-C30 and other HRQoL measures should consider reporting HRQoL treatment effects as ORs.

Understanding Adolescents' Categorisation of Animal Species.

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Connor, Melanie; Lawrence, Alistair B

2017-08-30

Categorisations are a means of investigating cognitive maps. The present study, for the first time, investigates adolescents' spontaneous categorisation of 34 animal species. Furthermore, explicit evaluations of 16 selected animals in terms of their perceived utility and likeability were analysed. 105 British adolescents, 54% female, mean age 14.5 (SD = 1.6) participated in the study. Results of multidimensional scaling (MDS) techniques indicate 3-dimensional data representation regardless of gender or age. Property fittings show that affect and perceived utility of animals explain two of the MDS dimensions, and hence partly explain adolescents' categorisation. Additionally, hierarchical cluster analyses show a differentiation between farm animals, birds, pet animals, and wild animals possibly explaining MDS dimension 3. The results suggest that utility perceptions predominantly underlie adolescents' categorisations and become even more dominant in older adolescents, which potentially has an influence on attitudes to animals with implications for animal welfare, conservation, and education.

Synthesis of protons exchange polymeric membranes via co-poly-esters doped with sodium dodecyl sulfate for application in PEM fuel cells; Sintese de membranas polimericas condutoras de protons por imobilizacao de MDs em copoliesteres para aplicacao em PEM-FC

Energy Technology Data Exchange (ETDEWEB)

Fiuza, R.A.; Brioude, M.M.; Bresciani, D.; Jose, N.M.; Boaventura, J.S. [Universidade Federal da Bahia (IQ/UFBA), Salvador, BA (Brazil). Inst. de Quimica

2008-07-01

Polymers are largely studied for use in PEM-type fuel cell (Proton Exchange membrane, PEMFC). These fuel cells are based on polymer membranes as electrolyte, also called protons conductor. This work developed co-polyesters made electrical conductors by doping with sodium dodecyl sulfate. The copolymers were synthesized from the copolymerization of terephthalic and adipic acids with glycerol. The material was processed in a reactor and shaped by hot pressing, yielding homogeneous and flexible plates, with excellent surface finish. The co-polyesters were analyzed by SEM, FTIR, TG, DSC, and XRD. The thermal analysis showed that the composites were thermally stable up to about 250 deg C. The micrographics revealed the MDS homogeneously dispersed in the polymeric matrix. These copolymers showed electrical conductivity between 10-7 to 10-1 S/cm, suggesting strong potential use in PEM fuel cells. (author)

Temporal and Geographic variation in the validity and internal consistency of the Nursing Home Resident Assessment Minimum Data Set 2.0.

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Mor, Vincent; Intrator, Orna; Unruh, Mark Aaron; Cai, Shubing

2011-04-15

Medicare hospital diagnoses and MDS based diagnoses were between .6 and .7 for major diagnoses like CHF, hypertension, diabetes. Internal consistency, as measured by PPV, of the MDS ADL items with other MDS items measuring impairments and symptoms exceeded .9. The Activities of Daily Living (ADL) long form summary scale achieved an alpha inter-consistency level exceeding .85 and multi-item scale alpha levels of .65 were achieved for well being and mood, and .55 for behavior, levels that were sustained even after stratification by ADL and cognition. The Changes in Health, End-stage disease and Symptoms and Signs (CHESS) index, a summary measure of frailty was highly predictive of one year survival. The MDS demonstrates a reasonable level of consistency both in terms of how well MDS diagnoses correspond to hospital discharge diagnoses and in terms of the internal consistency of functioning and behavioral items. The level of alpha reliability and validity demonstrated by the scales suggest that the data can be useful for research and policy analysis. However, while improving, the MDS discharge tracking record should still not be used to indicate Medicare hospitalizations or mortality. It will be important to monitor the performance of the MDS 3.0 with respect to consistency, reliability and validity now that it has replaced version 2.0, using these results as a baseline that should be exceeded.

Myelodysplastic syndromes and acute myeloid leukemia in cats infected with feline leukemia virus clone33 containing a unique long terminal repeat.

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Hisasue, Masaharu; Nagashima, Naho; Nishigaki, Kazuo; Fukuzawa, Isao; Ura, Shigeyoshi; Katae, Hiromi; Tsuchiya, Ryo; Yamada, Takatsugu; Hasegawa, Atsuhiko; Tsujimoto, Hajime

2009-03-01

Feline leukemia virus (FeLV) clone33 was obtained from a domestic cat with acute myeloid leukemia (AML). The long terminal repeat (LTR) of this virus, like the LTRs present in FeLV from other cats with AML, differs from the LTRs of other known FeLV in that it has 3 tandem direct 47-bp repeats in the upstream region of the enhancer (URE). Here, we injected cats with FeLV clone33 and found 41% developed myelodysplastic syndromes (MDS) characterized by peripheral blood cytopenias and dysplastic changes in the bone marrow. Some of the cats with MDS eventually developed AML. The bone marrow of the majority of cats with FeLV clone33 induced MDS produced fewer erythroid and myeloid colonies upon being cultured with erythropoietin or granulocyte-macrophage colony-stimulating factor (GM-SCF) than bone marrow from normal control cats. Furthermore, the bone marrow of some of the cats expressed high-levels of the apoptosis-related genes TNF-alpha and survivin. Analysis of the proviral sequences obtained from 13 cats with naturally occurring MDS reveal they also bear the characteristic URE repeats seen in the LTR of FeLV clone33 and other proviruses from cats with AML. Deletions and mutations within the enhancer elements are frequently observed in naturally occurring MDS as well as AML. These results suggest that FeLV variants that bear URE repeats in their LTR strongly associate with the induction of both MDS and AML in cats.

The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts

International Nuclear Information System (INIS)

Kang, Min-Gu; Kim, Hye-Ran; Seo, Bo-Young; Lee, Jun Hyung; Choi, Seok-Yong; Kim, Soo-Hyun; Shin, Jong-Hee; Suh, Soon-Pal; Ahn, Jae-Sook; Shin, Myung-Geun

2015-01-01

Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS. The online version of this article (doi:10.1186/s12885-015-1493-5) contains supplementary material, which is available to authorized users

Official Japanese Version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale: validation against the original English version.

Science.gov (United States)

Kashihara, Kenichi; Kondo, Tomoyoshi; Mizuno, Yoshikuni; Kikuchi, Seiji; Kuno, Sadako; Hasegawa, Kazuko; Hattori, Nobutaka; Mochizuki, Hideki; Mori, Hideo; Murata, Miho; Nomoto, Masahiro; Takahashi, Ryosuke; Takeda, Atsushi; Tsuboi, Yoshio; Ugawa, Yoshikazu; Yamanmoto, Mitsutoshi; Yokochi, Fusako; Yoshii, Fumihito; Stebbins, Glenn T; Tilley, Barbara C; Luo, Sheng; Wang, Lu; LaPelle, Nancy R; Goetz, Christopher G

2014-09-01

The Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease (PD) Rating Scale (UPDRS) (MDS-UPDRS) has been developed and is now available in English. Part of the overall program includes the establishment of official non-English translations of the MDS-UPDRS. We present the process for completing the official Japanese translation of the MDS-UPDRS with clinimetric testing results. In this trial, the MDS-UPDRS was translated into Japanese, underwent cognitive pre-testing, and the translation was modified after taking the results into account. The final translation was approved as Official Working Draft of the MDS-UPDRS Japanese version and tested in 365 native-Japanese-speaking patients with PD. Confirmatory analyses were used to determine whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Official Working Draft of the Japanese translation. As a secondary analysis, we used exploratory factor analyses to examine the underlying factor structure without the constraint of a pre-specified factor organization. Confirmatory factor analysis revealed that Comparative Fit Index for all Parts of the MDS-UPDRS exceeded the minimal standard of 0.90 relative to the English version and therefore Japanese translation met the pre-specified criterion to be designated called an OFFICIAL MDS TRANSLATION. Secondary analyses revealed some differences between the English-language MDS-UPDRS and the Japanese translation, however, these differences were considered to be within an acceptable range. The Japanese version of the MDS-UPDRS met the criterion as an Official MDS Translation and is now available for use (www.movementdisorders.org).

Outcome of Allogeneic Stem Cell Transplantation for Patients Transformed to Myelodysplastic Syndrome or Leukemia from Severe Aplastic Anemia: A Report from the MDS Subcommittee of the Chronic Malignancies Working Party and the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

NARCIS (Netherlands)

Hussein, A.A.; Halkes, C.M.; Socie, G.; Tichelli, A.; Borne, P.A. von dem; Schaap, M.N.; Foa, R.; Ganser, A.; Dufour, C.; Bacigalupo, A.; Locasciulli, A.; Aljurf, M.; Peters, C.; Robin, M.; Biezen, A.A. van; Volin, L.; Witte, T.J. de; Marsh, J.; Passweg, J.R.; Kroger, N.; et al.,

2014-01-01

One hundred and forty patients who had undergone hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) transformation after treatment of severe aplastic anemia (SAA) were identified in the European Group for Blood and Marrow

Knockdown of HSPA9 induces TP53-dependent apoptosis in human hematopoietic progenitor cells.

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Tuoen Liu

Full Text Available Myelodysplastic syndromes (MDS are the most common adult myeloid blood cancers in the US. Patients have increased apoptosis in their bone marrow cells leading to low peripheral blood counts. The full complement of gene mutations that contribute to increased apoptosis in MDS remains unknown. Up to 25% of MDS patients harbor and acquired interstitial deletion on the long arm of chromosome 5 [del(5q], creating haploinsufficiency for a large set of genes including HSPA9. Knockdown of HSPA9 in primary human CD34+ hematopoietic progenitor cells significantly inhibits growth and increases apoptosis. We show here that HSPA9 knockdown is associated with increased TP53 expression and activity, resulting in increased expression of target genes BAX and p21. HSPA9 protein interacts with TP53 in CD34+ cells and knockdown of HSPA9 increases nuclear TP53 levels, providing a possible mechanism for regulation of TP53 by HSPA9 haploinsufficiency in hematopoietic cells. Concurrent knockdown of TP53 and HSPA9 rescued the increased apoptosis observed in CD34+ cells following knockdown of HSPA9. Reduction of HSPA9 below 50% results in severe inhibition of cell growth, suggesting that del(5q cells may be preferentially sensitive to further reductions of HSPA9 below 50%, thus providing a genetic vulnerability to del(5q cells. Treatment of bone marrow cells with MKT-077, an HSPA9 inhibitor, induced apoptosis in a higher percentage of cells from MDS patients with del(5q compared to non-del(5q MDS patients and normal donor cells. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to TP53 activation and increased apoptosis observed in del(5q-associated MDS.

MR imaging findings of the femoral marrow in myelodysplastic syndrome

International Nuclear Information System (INIS)

Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun

1995-01-01

MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author)

MR imaging findings of the femoral marrow in myelodysplastic syndrome

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Osamu; Takagi, Shojiro; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun [Jichi Medical School, Minamikawachi, Tochigi (Japan)

1995-10-01

MR imaging of the femoral marrow was performed in 30 patients with myelodysplastic syndrome (MDS), 11 cases of which evolved to acute myeloid leukemia (AML). The MRI appearance was classified into five patterns: fatty marrow; faint signal; nodular pattern; heterogeneous infiltration; and diffuse infiltration. For each type of MDS, MRI patterns of the femoral marrow were evaluated and compared with those in normal subjects as well as in patients with aplastic anemia. Signal intensity alteration, a low signal on T1-weighted SE image and a high signal on STIR image, began in the proximal femoral marrow almost symmetrically in patients with MDS. The area of abnormal signal intensity tended to gradually extend towards the distal portion of the femur as the disease progressed. MRI patterns of the femoral marrow correlated with marrow cellularity, and diffuse marrow infiltration was noted in patients with a more advanced type of MDS or with severe anemia. There were limitations to making an accurate diagnosis of the MDS type on the basis of the MRI pattern. Progression of the MRI appearance in the course of MDS was thought to be a sign suggesting evolution to AML. It was difficult to differentiate hypoplastic MDS from aplastic anemia, although the nodular pattern was commonly seen in the latter disease. (author).

Types of suggestibility: Relationships among compliance, indirect, and direct suggestibility.

Science.gov (United States)

Polczyk, Romuald; Pasek, Tomasz

2006-10-01

It is commonly believed that direct suggestibility, referring to overt influence, and indirect suggestibility, in which the intention to influence is hidden, correlate poorly. This study demonstrates that they are substantially related, provided that they tap similar areas of influence. Test results from 103 students, 55 women and 48 men, were entered into regression analyses. Indirect suggestibility, as measured by the Sensory Suggestibility Scale for Groups, and compliance, measured by the Gudjonsson Compliance Scale, were predictors of direct suggestibility, assessed with the Barber Suggestibility Scale. Spectral analyses showed that indirect suggestibility is more related to difficult tasks on the BSS, but compliance is more related to easy tasks on this scale.

Medical doctors and complementary and alternative medicine: the context of holistic practice.

Science.gov (United States)

Winnick, Terri A

2006-04-01

Consumers, health care financing, external and internal competition are factors identified in the medical literature as prompting change within medicine. I test these factors to determine if they also prompt regular doctors to define themselves as 'holistic MDs' and align themselves with complementary and alternative medicine (CAM). State-level regression analyses on the number of MDs advertising in referral directories for CAM therapies find holistic practice a function of practice locale. The proportion of holistic MDs increases in states with an older population, where more patients survive despite serious disabilities, and where non-physician providers pose a competitive threat. Consumer demand, specialization and licensing do not significantly influence adoption of CAM treatments in these analyses. Health care financing has disparate effects. Indemnity insurance constrains holistic practice while HMO penetration enhances it. These results suggest that holistic practice may be an integral part of the regular profession's ongoing professionalization project.

Development and implementation of the waste diversion program at MDS Nordion's Cobalt Operations Facility

International Nuclear Information System (INIS)

Wasiak, T.

2004-01-01

Historically, the MDS Nordion (MDSN) Cobalt Operations Facility sent solid waste for disposal to Atomic Energy of Canada Ltd.'s Chalk River Laboratories (AECL-CRL). A large portion of this waste was not contaminated. Because this non-contaminated waste originated in the 'active area' of the MDSN facility, it was routinely disposed of as low-level active waste. In 2002, MDSN undertook an initiative to develop and implement a more sophisticated and more economical waste management program. The Waste Diversion Program (WDP) ensures continued environmental and public protection, and reduces the demand on Canada's limited capacity for storage of radioactive material and the associated operating costs. The goal of the WDP is to reduce the volume of waste currently being shipped to AECL-CRL's Waste Management Operation as low-level active waste. The presentation discusses key elements of both the development and the implementation of WDP. It focuses on the following areas: the regulatory environment surrounding the waste disposal issues in Canada and abroad. Methods used by MDSN for determination of radionuclides, which could be present in the facility. Choice of equipment and calculation of individual alarm levels for each identified radionuclide. Key elements of the practical implementation of the program. CNSC Regulatory approval process. The bottom line - dollars and cents. The primary objective of the WDP is to ensure that only waste, which meets regulatory requirements, is diverted from the solid active waste stream. This has been successfully accomplished in MDSN's Cobalt Operations Facility. The objective of the presentation is to share the knowledge and experience obtained in the development process, and thus provide a guideline for other nuclear facilities interested in establishing similar proactive and cost effective programs. (author)

Chromosomal instability and the abrogated G2/M arrest in x-irradiated myelodysplastic syndrome cells

International Nuclear Information System (INIS)

Ban, S.; Sudo, H.; Saegusa, K.; Sagara, M.; Imai, T.; Kimura, A.

2003-01-01

A preliminary epidemiological study demonstrated that myelodysplastic syndrome (MDS) has an excess relative risk per sievert of 13 in atomic bomb survivors in Hiroshima. MDS is the only other radiogenic blood disease apart from leukemia. Clinically, MDS involves dysplastic hematopoiesis and an increased risk of leukemic transformation. Because it is uncertain whether MDS pathogenesis affects lymphoid progenitor cells as well as myeloid progenitor cells, we investigated the karyotypes of bone marrow cells and the micronucleus (MN) frequency in peripheral T lymphocytes of twenty- three atomic bomb survivors with MDS and five normal individuals. Aneuploidy was observed in 10 of 23 patients. Chromosome aberrations were observed in 3 of 12 patients with mild symptoms, and six of 11 patients of severe symptoms. The spontaneous- and X-ray-induced-MN frequencies were significantly higher in MDS patients than in normal individuals. Interestingly, radiation sensitivity increased along with the severity of MDS clinical subtypes. Because many of the patients in this study had not been exposed to chemo- or radiation- therapy, their unusual radiosensitivity may be related to their chromosomal or genomic instability. Immortalized lymphoid cell lines were established from B-lymphocytes infected with Epstein-Barr virus in vitro. The abrogation of radiation-induced-G2/M arrest was observed in 10 of 12 MDS-B lymphoid cell lines, but not in the normal B lymphoid cell lines. Our data suggest that the control of chromosomal stability is impaired in pluripotent stem cells of MDS patients, and that the abrogated G2/M arrest may be involved in the pathophysiology of disease progression and the high radiation sensitivity of patients

Nucleon resonance electroproduction at high momentum transers: Results from SLAC and suggestions for CEBAF

Energy Technology Data Exchange (ETDEWEB)

Keppel, C. [Virginia Union Univ., Richmond, VA (United States)

1994-04-01

Nucleon resonance electroproduction results from SLAC Experiment E14OX are presented. A CEBAF facility with doubled energy would enable similar high momentum transfer measurements to be made with greater accuracy. Of particular interest are the Delta P{sub 33}(1232) resonance form factor and R = {sigma}{sub L}/{sigma}{sub T}, the ratio of the longitudinal and transverse components of the cross section. A suggestion is made to study these quantities in conjunction with Bloom-Gilman duality.

MDS G(N) fast differentiation between natural and artificial gamma radiation with a new class of mobile instruments

International Nuclear Information System (INIS)

Katzung, W.; Bottcher, J.

2009-01-01

A State-of-the-Art tool used for detecting and tracking artificial gamma radiation out of a helicopter or a vehicle is the MDS G(N) - Mobile Detection System. A highly sensitive scintillation detector detects a significant artificial gamma radiation on the ground even if the helicopter is travelling at high speed. The GPS-aided system visualizes the measured values on a moveable map displayed on the screen of a notebook every second. The colours of the continuously entered points do represent adjustable alarm thresholds. This way, location and intensity of an unknown radioactive source or a radioactive contamination can be determined very quickly. The NBR-technology (Natural Background Rejection) which is used here leads to expressive measurement results differentiating between artificial and natural gamma radiation. Additional He-3 detectors allow simultaneously the detection of neutrons. The NBR principle - developed by Thermo Scientific - stands out for its very short response times. Thus, artificial radiation can be detected reliably within seconds - even when the unit is operated by untrained staff. Unlike traditional analytic measuring techniques, the NBR method is able to detect artificial radiation sources hidden or strongly shielded gamma sources clearly from the natural background radiation. The measuring range from 1 nSv/h to 20 ?Sv/h and is extended to 1 Sv/h with a Geiger Mueller counting tube. The sensitivity amounts to max. 20000 cps (referred to 1 ?Sv/h for Cs-137). The NBR- technique is well-proven and tested for: tracking hidden radiation sources, even such ones with low activity or which are shielded, detection of artificial radiation portions in the range of the natural background, reliably measuring the ambient equivalent dose rate in the range of the natural background, fast detection of artificial radioactivity out of helicopters and vehicles.(author)

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

Science.gov (United States)

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

MM-MDS: a multidimensional scaling database with similarity ratings for 240 object categories from the Massive Memory picture database.

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Michael C Hout

Full Text Available Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of "sameness" among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16-17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of "sameness."

MM-MDS: a multidimensional scaling database with similarity ratings for 240 object categories from the Massive Memory picture database.

Science.gov (United States)

Hout, Michael C; Goldinger, Stephen D; Brady, Kyle J

2014-01-01

Cognitive theories in visual attention and perception, categorization, and memory often critically rely on concepts of similarity among objects, and empirically require measures of "sameness" among their stimuli. For instance, a researcher may require similarity estimates among multiple exemplars of a target category in visual search, or targets and lures in recognition memory. Quantifying similarity, however, is challenging when everyday items are the desired stimulus set, particularly when researchers require several different pictures from the same category. In this article, we document a new multidimensional scaling database with similarity ratings for 240 categories, each containing color photographs of 16-17 exemplar objects. We collected similarity ratings using the spatial arrangement method. Reports include: the multidimensional scaling solutions for each category, up to five dimensions, stress and fit measures, coordinate locations for each stimulus, and two new classifications. For each picture, we categorized the item's prototypicality, indexed by its proximity to other items in the space. We also classified pairs of images along a continuum of similarity, by assessing the overall arrangement of each MDS space. These similarity ratings will be useful to any researcher that wishes to control the similarity of experimental stimuli according to an objective quantification of "sameness."

Prognostic factors in de novo myelodysplastic syndrome in young and middle-aged people

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Наталья Николаевна Климкович

2015-01-01

Full Text Available We spent multivariate analysis of clinical and laboratory parameters for the prediction of de-novo myelodysplastic syndromes (MDS patients aged 18-60 years. The results of clinical application of prognostic systems in MDS show that there is a large variability within individual risk groups, especially at low-risk MDS. So now hematologists conduct research aimed at identifying additional adverse risk MDS. This is done so that patients with low-risk MDS embodiments and unfavorable prognosis could benefit from early therapeutic intervention, and not only be clinician monitored until disease progression. We found that additional adverse risk factors for the development of MDS are the expression of CD95 in bone marrow ≤40 % and FLT3≥60 %. The expression level of CD95 in bone marrow cells≤40 % and FLT3≥60 % can be considered as a prognostic marker progression of MDS and time start specific therapy

Nuclear Nox4-Derived Reactive Oxygen Species in Myelodysplastic Syndromes

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Marianna Guida

2014-01-01

Full Text Available A role for intracellular ROS production has been recently implicated in the pathogenesis and progression of a wide variety of neoplasias. ROS sources, such as NAD(PH oxidase (Nox complexes, are frequently activated in AML (acute myeloid leukemia blasts and strongly contribute to their proliferation, survival, and drug resistance. Myelodysplastic syndromes (MDS comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop AML. The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is the genomic instability. NADPH oxidases are now recognized to have specific subcellular localizations, this targeting to specific compartments for localized ROS production. Local Nox-dependent ROS production in the nucleus may contribute to the regulation of redox-dependent cell growth, differentiation, senescence, DNA damage, and apoptosis. We observed that Nox1, 2, and 4 isoforms and p22phox and Rac1 subunits are expressed in MDS/AML cell lines and MDS samples, also in the nuclear fractions. Interestingly, Nox4 interacts with ERK and Akt1 within nuclear speckle domain, suggesting that Nox4 could be involved in regulating gene expression and splicing factor activity. These data contribute to the elucidation of the molecular mechanisms used by nuclear ROS to drive MDS evolution to AML.

Effect of 90-day space flight (MDS-ISS) on immunological parameters in mice: lymphocyte distribution and function

Science.gov (United States)

Roberts, Arthur; Lhuillier, Andrew; Liu, Yi; Ruggiu, Alessandra; Shi, Yufang

Elucidation of the effects of space flight on the immune system of astronauts and other animal species is important for the survival and success of manned space flight, especially long-term missions. Space flight exposes astronauts to microgravity, galactic cosmic radiation (GCR), and various psycho-social stressors. Blood samples from astronauts returning from space flight have shown changes in the numbers and types of circulating leukocytes. Similarly, normal lym-phocyte homeostasis has been shown to be severely affected in mice using ground-based models of microgravity and GCR exposure, as demonstrated by profound effects on several immuno-logical parameters examined by other investigators and ourselves. In particular, lymphocyte numbers are significantly reduced and subpopulation distribution is altered in the spleen, thy-mus, and peripheral blood following hindlimb unloading (HU) in mice. Lymphocyte depletion was found to be mediated through corticosteroid-induced apoptosis, although the molecular mechanism of apoptosis induction is still under investigation. The proliferative capacity of TCR-stimulated lymphocytes was also inhibited after HU. We have similarly shown that mice exposed to high-energy 56Fe ion radiation have decreased lymphocyte numbers and perturba-tions in proportions of various subpopulations, including CD4+ and CD8+ T cells, and B cells in the spleen, and maturation stages of immature T cells in the thymus. To compare these ground-based results to the effects of actual space-flight, fresh spleen and thymus samples were recently obtained from normal and transgenic mice immediately after 90 d. space-flight in the MDS, and identically-housed ground control mice. Total leukocyte numbers in each organ were enumerated, and subpopulation distribution was examined by flow cytometric analysis of CD3, CD4, CD8, CD19, CD25, DX-5, and CD11b. Splenic T cells were stimulated with anti-CD3 and assessed for proliferation after 2-4 d., and production of

Myelodysplastic syndromes in Chernobyl clean-up workers.

Science.gov (United States)

Gluzman, Daniil F; Sklyarenko, Lilia M; Koval, Stella V; Rodionova, Nataliia K; Zavelevich, Michael P; Ivanivskaya, Tetiana S; Poludnenko, Liudmyla Yu; Ukrainskaya, Nataliia I

2015-10-01

The studies of the recent decades posed the question of the association between radiation exposure and myelodysplastic syndromes (MDS). This association has been proved in secondary MDS originating upon exposure to chemotherapeutics and/or radiation therapy. The long-term study in Japanese atomic (A)-bomb survivors demonstrated the significant linear dose-response for MDS confirming the link between radiation exposure and this form of hematopoietic malignancies. All these findings provide the strong basis for studying MDS in the persons exposed to radiation following the Chernobyl disaster, especially those in the cohort of Chernobyl clean-up workers of 1986-1987. The data on MDS among Chernobyl clean-up workers (1986-1987) diagnosed in 1996-2012 at the reference laboratory of RE Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology are summarized. MDS cases were diagnosed in 23 persons (21 males and 2 females) having been exposed to radiation as clean-up workers of 1986-1987. Refractory anemia (RA) has been detected in 13, refractory anemia with ring sideroblasts (RARS)-in 2, and refractory anemia with excess blasts (RAEB)-in 8 patients. The median age of those MDS patients was 62.0 years. In addition, 5 cases of chronic myelomonocytic leukemia (CMML) were recorded in the group of Chernobyl clean-up workers with the median time of 14.8 years from 1986-1987 to diagnosis. The association between radiation exposure and MDS is discussed. The suggested life-long risk for myelodysplastic syndromes among A-bomb survivors in Japan highlights the importance of the continuing follow-up studies in the affected populations in the post-Chernobyl period.

Mediterranean Diet Adherence and Genetic Background Roles within a Web-Based Nutritional Intervention: The Food4Me Study

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Rodrigo San-Cristobal

2017-10-01

Full Text Available Mediterranean Diet (MedDiet adherence has been proven to produce numerous health benefits. In addition, nutrigenetic studies have explained some individual variations in the response to specific dietary patterns. The present research aimed to explore associations and potential interactions between MedDiet adherence and genetic background throughout the Food4Me web-based nutritional intervention. Dietary, anthropometrical and biochemical data from volunteers of the Food4Me study were collected at baseline and after 6 months. Several genetic variants related to metabolic risk features were also analysed. A Genetic Risk Score (GRS was derived from risk alleles and a Mediterranean Diet Score (MDS, based on validated food intake data, was estimated. At baseline, there were no interactions between GRS and MDS categories for metabolic traits. Linear mixed model repeated measures analyses showed a significantly greater decrease in total cholesterol in participants with a low GRS after a 6-month period, compared to those with a high GRS. Meanwhile, a high baseline MDS was associated with greater decreases in Body Mass Index (BMI, waist circumference and glucose. There also was a significant interaction between GRS and the MedDiet after the follow-up period. Among subjects with a high GRS, those with a high MDS evidenced a highly significant reduction in total carotenoids, while among those with a low GRS, there was no difference associated with MDS levels. These results suggest that a higher MedDiet adherence induces beneficial effects on metabolic outcomes, which can be affected by the genetic background in some specific markers.

Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

Science.gov (United States)

Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

2014-08-07

Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

Development of Megawatt Demand Setter for Plant Operating Flexibility

International Nuclear Information System (INIS)

Kim, Se Chang; Hah, Yeong Joon; Song, In Ho; Lee, Myeong Hun; Chang, Do Ik; Choi, Jung In

1993-05-01

The Conceptual design of the Megawatt Demand Setter (MDS) is presented for the Korean Standardized Nuclear Power Plant. The MDS is a digital supervisory limitation system. The MDS assures that the plant does not exceed the operating limits by regulating the plant operations through monitoring the operating margins of the critical parameters. MDS is aimed at increasing the operating flexibility which allow the nuclear plant to meet the grid demand in very efficient manner. It responds to the grid demand without penalizing plant availability by limiting the load demand when the operating limits are approached or violated. MDS design concepts were tested using simulation responses of Yonggwang Units 3, 4. The design of the Yonggwang Units 3, 4 would be used as a reference which designs of Korean Standardized Nuclear Power Plants would be based upon. The simulation results illustrate that the MDS can be used to improve operating flexibility. (Author)

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

Science.gov (United States)

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bone marrow MRI in patients with myelodysplastic syndromes

International Nuclear Information System (INIS)

Chen Zhao; Guo You; Wang Renfa; Zou Mingli; Liu Wenli; Xia Liming; Wang Chengyuan

2004-01-01

Objective: To observe the MR imaging of bone marrow in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), and to reveal the rule of bone marrow infiltration and the role of MRI in diagnosing and predicting the prognosis of myelodysplastic syndromes. Methods: Thirty patients received MRI after the diagnosis based on clinic and FAB subtype study, including 16 with MDS and 14 with AML. MR image was obtained by T 1 -weighted spin echo and shot time inversion recovery in pelvis and femur. The examining results of morphology and blood routine were collected at the same time. 30 age-matched volunteers were selected as controls. Results: The MRI appearance was classified into their patterns based on scope of focus. MRI patterns from grade 1 to grade 3 was observed in patients with MDS. All patients with AML distributed in grade 2 to grade 3. The distribution of patterns had no significant difference between MDS and AML (P>0.05). The marrow ratio had significant difference among MDS, AML, and controls (P<0.05). The MRI grade was consistent with the clinic diagnostic indexes. Conclusion: MRI can provide a better understanding of the difference between MDS and AML. MRI can estimate the extent of disease in the marrow as a whole. MRI of bone marrow can provide imaging basis in diagnosis and predicting the prognosis for patients with MDS

Assessing treatment motivation among patients receiving antiretroviral therapy: A multidimensional approach

Science.gov (United States)

Houston, Eric; McKirnan, David J.; Cervone, Daniel; Johnson, Matthew S.; Sandfort, Theo G.M.

2011-01-01

Using multidimensional scaling analysis (MDS), this study examined how patient conceptualisations of treatment motivation compare with theoretically-based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n = 39) rated for similarity all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach, and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivation often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively-valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivation. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence. PMID:21942538

Assessing treatment motivation among patients receiving antiretroviral therapy: a multidimensional approach.

Science.gov (United States)

Houston, Eric; McKirnan, David J; Cervone, Daniel; Johnson, Matthew S; Sandfort, Theo G M

2012-01-01

Using multidimensional scaling (MDS) analysis, this study examined how patient conceptualisations of treatment motivation compare with theoretically based assumptions used in current assessment approaches. Patients undergoing antiretroviral therapy for HIV/AIDS (n=39) rated for similarity between all possible pairings of 23 treatment descriptions, including descriptors of intrinsic, extrinsic, approach and avoidance motivation. MDS analyses revealed that patient perceptions of intrinsic and extrinsic motivations often differ from those based on definitions derived from common interpretations of self-determination theory. Findings also showed that patients reported motivation for avoiding treatment when they associated their medication regimens with side effects and other negatively valenced outcomes. The study describes new applications of MDS in assessing how patients perceive the relationship between treatment behaviours and specific forms of motivation, such as intrinsic and extrinsic motivations. In addition, the study suggests how MDS may be used to develop behavioural strategies aimed at helping patients follow their regimens consistently by identifying treatment conceptualisations and contexts that facilitate or impede adherence.

Delayed globin synthesis leads to excess heme and the macrocytic anemia of Diamond Blackfan anemia and del(5q) myelodysplastic syndrome.

Science.gov (United States)

Yang, Zhantao; Keel, Siobán B; Shimamura, Akiko; Liu, Li; Gerds, Aaron T; Li, Henry Y; Wood, Brent L; Scott, Bart L; Abkowitz, Janis L

2016-05-11

Diamond Blackfan anemia (DBA) and myelodysplastic syndrome (MDS) with isolated del(5q) are severe macrocytic anemias; although both are associated with impaired ribosome assembly, why the anemia occurs is not known. We cultured marrow cells from DBA (n = 3) and del(5q) MDS (n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. We show that globin translation initiates slowly, whereas heme synthesis proceeds normally. This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. Consistent with these observations, treatment with 10 μM succinylacetone, a specific inhibitor of heme synthesis, improved the erythroid cell output of DBA and del(5q) MDS marrow cultures by 68 to 95% (P = 0.03 to 0.05), whereas the erythroid cell output of concurrent control marrow cultures decreased by 4 to 13%. Our studies demonstrate that erythropoiesis fails when heme exceeds globin. Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. Copyright © 2016, American Association for the Advancement of Science.

Ge-on-Si films obtained by epitaxial growing: edge dislocations and their participation in plastic relaxation

International Nuclear Information System (INIS)

Bolkhovityanov, Yu B; Sokolov, L V

2012-01-01

Pure edge 90° misfit dislocations (MDs) are the most effective linear defects that combine the substrate and the film with different lattice parameters. A system consisting of a nonstressed film and a substrate approaches the perfect case in terms of the structural transition from one lattice parameter to the other if imperfections in the form of an ordered network of edge MDs are located exclusively at the interface, while threading dislocations are practically absent. The path to this perfect case goes through studying the possibilities of creating such an ordered network of edge MDs. The mechanism of formation of edge MDs proposed previously by Kvam et al (1990 J. Mater. Res. 5 1900) is discussed. This mechanism involves induced formation of a complementary pair of 60° MDs whose coalescence at the interface creates an edge MD. Some publications are presented, which demonstrate on the basis of experimental data that this mechanism under certain conditions can be the basic mechanism responsible for plastic relaxation of Ge-on-Si films. A cardinal method for decreasing the number of defects at the initial stages of growth of Ge/Si heterosystems is a set of procedures that allow a specified number of MDs to be inserted into the stressed film earlier than conditions of spontaneous nucleation of MDs from the film surface in the 2D–3D transition occur. When the low-temperature/high-temperature strategy of growth is used, the low-temperature GeSi seed layer tuned with respect to the growth temperature, composition and thickness can serve as a source of 60° dislocations, which facilitate earlier formation of edge MDs at the initial stage of plastic relaxation of the GeSi or Ge main layer. Results of some recent publications that report reaching high structural perfection of thin (∼1 µm and less) Ge-on-Si films are discussed. The proposed explanation of these results is based on postulates of controlled insertion of MDs and formation of edge MDs by the model of

Iron overload in patients with myelodysplastic syndromes: An updated overview.

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Moukalled, Nour M; El Rassi, Fuad A; Temraz, Sally N; Taher, Ali T

2018-06-15

Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by a broad clinical spectrum related to ineffective hematopoiesis leading to unilineage or multilineage cytopenias, with a high propensity for transformation to acute myeloid leukemia. Iron overload has been recently identified as one of the important conditions complicating the management of these diverse disorders. The accumulation of iron is mainly related to chronic transfusions; however, evidence suggests a possible role for ineffective erythropoiesis and increased intestinal absorption of iron, related to altered hepcidin and growth differentiation factor-15 levels in the development of hemosiderosis in patients with MDS. In addition to its suggested role in the exacerbation of ineffective erythropoiesis, multiple reports have identified a prognostic implication for the development of iron overload in patients with MDS, with an improvement in overall survival after the initiation of iron chelation therapy. This review includes a detailed discussion of iron overload in patients with MDS whether they are undergoing supportive therapy or curative hematopoietic stem cell transplantation, with a focus on the mechanism, diagnosis, and effect on survival as well as the optimal management of this highly variable complication. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Rescue of TET2 Haploinsufficiency in Myelodysplastic Syndrome Patients Using Turbo Cosubstrate

Science.gov (United States)

2017-07-01

prevalent in a number of myeloid malignancies such as MDS-myeloproliferative neoplasms (MDS-MPN) and acute myeloid leukemia derived from MDS and MDS...Myelodysplastic syndromes (MDS), MDS-myeloproliferative neoplasms (MDS-MPN), Acute myeloid leukemia (AML), 5-methylcytosine (5mC), Mutation...normal initially, with age, develop diverse myeloid malignancies similar to humans. The objective in this project is to develop effective strategies

Dynamic MRI of the lumbar spine for the evaluation of microcirculation during anti-angiogenetic therapy in patients with myelodysplastics syndromes

International Nuclear Information System (INIS)

Scherer, A.; Wittsack; Strupp, C.; Engelbrecht, V.

2002-01-01

Material and Methods: In 20 healthy normal persons and 28 MDS patients a dynamic contrast-enhanced MRI (d-MRI) of the lumbar spine was performed. After the initial d-MRI-investigation 24 of the 28 MDS patients received an antiangiogenetic therapy with thalidomide. With an average of 4.2 months after the beginning of therapy a d-MRI-follow-up examination in 9 of these patients was performed. The amplitude and exchange-rate constant were calculated and a statistical comparison of these values between healthy persons and MDS patients as well as a correlation with the clinical course was executed. Results: Compared with the normal controls the MDS patients showed a higher amplitude (normal persons: 14.4±5.2, MDS: 24.8±8.1) and exchange-rate constant (normal persons: 0.124±0.042, MDS: 0.136±0.036). In 7 of 9 MDS patients undergoing thalidomide therapy a reduction of the amplitude and exchange rate constant values was evident in the d-MRI follow-up examinations. Clinically these patients showed a therapy response with complete or partial disease remission. (orig.) [de

The Minimum Data Set 3.0 Cognitive Function Scale.

Science.gov (United States)

Thomas, Kali S; Dosa, David; Wysocki, Andrea; Mor, Vincent

2017-09-01

The Minimum Data Set (MDS) 3.0 introduced the Brief Interview for Mental Status (BIMS), a short performance-based cognitive screener for nursing home (NH) residents. Not all residents are able to complete the BIMS and are consequently assessed by staff. We designed a Cognitive Function Scale (CFS) integrating self-report and staff-report data and present evidence of the scale's construct validity. A retrospective cohort study. The subjects consisted of 3 cohorts: (1) long-stay NH residents (N=941,077) and (2) new admissions (N=2,066,580) during 2011-2012, and (3) residents with the older MDS 2.0 assessment in 2010 and the newer MDS 3.0 assessment (n=688,511). MDS 3.0 items were used to create a single, integrated 4-category hierarchical CFS that was compared with residents' prior MDS 2.0 Cognitive Performance Scale scores and other concurrent MDS 3.0 measures of construct validity. The new CFS suggests that 28% of the long-stay cohort in 2011-2012 were cognitively intact, 22% were mildly impaired, 33% were moderately impaired, and 17% were severely impaired. For the admission cohort, the CFS noted 56% as cognitively intact, 23% as mildly impaired, 17% as moderately impaired, and 4% as severely impaired. The CFS corresponded closely with residents' prior MDS 2.0 Cognitive Performance Scale scores and with performance of Activities of Daily Living, and nurses' judgments of function and behavior in both the admission and long-stay cohorts. The new CFS is valuable to researchers as it provides a single, integrated measure of NH residents' cognitive function, regardless of the mode of assessment.

Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

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Romuald Polczyk

2016-05-01

Full Text Available Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence for the existence of the two factors has been scarce. In the present study, more sophisticated and reliable tools for measuring suggestibility were applied than in the previous research, in the hope that better measurement would reveal the factor structure of suggestibility. Two tests of direct suggestibility were used: the Harvard Group Scale of Hypnotic Susceptibility, Form A, measuring hypnotic susceptibility, and the Barber Suggestibility Scale, measuring non-hypnotic direct imaginative suggestibility. Three tests served to measure indirect suggestibility: the Sensory Suggestibility Scale, measuring indirect suggestibility relating to perception; the Gudjonsson Suggestibility Scale, measuring the tendency to yield to suggestive questions and changing answers after negative feedback; and the Emotional Dialogs Tests, measuring the tendency to perceive nonexistent aggression. Participants and procedure In sum, 115 participants were tested, 69 women, 49 men, mean age 22.20 years, SD = 2.20. Participants were tested in two sessions, lasting for a total of four hours. Results Confirmatory factor analyses confirmed the existence of two uncorrelated factors of suggestibility: direct and indirect. Conclusions Suggestibility may indeed involve two factors, direct and indirect, and failure to discover them in previous research may be due to methodological problems.

Physical exercise and oxidative stress in muscular dystrophies: is there a good balance?

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Chico, L; Ricci, G; Cosci O Di Coscio, M; Simoncini, C; Siciliano, G

2017-07-01

The effect of oxidative stress on muscle damage inducted by physical exercise is widely debated. It is generally agreed that endurance and intense exercise can increase oxidative stress and generate changes in antioxidant power inducing muscle damage; however, regular and moderate exercise can be beneficial for the health improving the antioxidant defense mechanisms in the majority of cases. Growing evidences suggest that an increased oxidative/nitrosative stress is involved in the pathogenesis of several muscular dystrophies (MDs). Notably, physical training has been considered useful for patients with these disorders. This review will focus on the involvement of oxidative stress in MDs and on the possible effects of physical activities to decrease oxidative damage and improve motor functions in MDs patients.

Masculine Discrepancy Stress and Psychosocial Maladjustment: Implications for Behavioral and Mental Health of Adolescent Boys.

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Reidy, Dennis E; Smith-Darden, Joanne P; Vivolo-Kantor, Alana M; Malone, Carolyn A; Kernsmith, Poco D

2017-01-01

Gender role discrepancy (GRD), or nonconformity to socially prescribed gender roles, has been linked to a multitude of adverse mental and behavioral health outcomes. Masculine discrepancy stress (MDS), stress about being perceived not to conform to one's gender role, may explain the relationship between GRD and deleterious health outcomes. However, research on MDS has primarily been restricted to adult males. This leaves a critical gap pertaining to the potential effect of MDS on adolescent boys, who may be more malleable and susceptible to the influence and pressures of gender socialization. In the current study, data are drawn from a sample of adolescent male students ( N = 592) who completed self-report questionnaires. We employed structural equation modeling to test the effects of GRD and MDS on psychosocial maladjustment measured via sexual behavior, substance use, violence, mood disorder symptoms, and hopelessness. In addition, we controlled for critical risk factors including sociodemographic characteristics, adverse childhood experiences, trauma symptoms, and neighborhood disorganization. Findings indicate significant potentiating effects of MDS on maladjustment while there were direct protective effects of GRD. These data suggest that developing prevention strategies that incorporate social norms pertaining to gender socialization may have an impact on multiple behavioral and mental health problems.

Reversion of mtDNA depletion in a patient with TK2 deficiency.

Science.gov (United States)

Vilà, M R; Segovia-Silvestre, T; Gámez, J; Marina, A; Naini, A B; Meseguer, A; Lombès, A; Bonilla, E; DiMauro, S; Hirano, M; Andreu, A L

2003-04-08

Mutations in the thymidine kinase 2 (TK2) gene cause a myopathic form of the mitochondrial DNA depletion syndrome (MDS). Here, the authors report the unusual clinical, biochemical, and molecular findings in a 14-year-old patient in whom pathogenic mutations were identified in the TK2 gene. This report extends the phenotypic expression of primary TK2 deficiency and suggests that factors other than TK2 may modify expression of the clinical phenotype in patients with MDS syndrome.

Awareness of breathing: the structure of language descriptors of respiratory sensations.

Science.gov (United States)

Petersen, Sibylle; Orth, Bernhard; Ritz, Thomas

2008-01-01

Recent research suggests that dyspnea is not a single sensation but a multidimensional construct reflected in different verbal descriptors that can provide useful diagnostic information. In this study superordinated clusters of dyspnea were investigated in combination with a dimensional approach. We examined the use of 20 respiratory symptom descriptors by healthy volunteers who completed a protocol of seven experimental conditions: Quiet breathing, breath holding, paced breathing, climbing stairs, resistive load breathing, voluntary hyperinflation, and voluntary hyperventilation. We analyzed the ratings of these descriptors with multidimensional scaling (MDS) and cluster analysis. While similarities with prior studies were found on a lower fusion level, we were able to demonstrate the usefulness of interpreting higher fusion levels with four clusters related to work of breathing, coordination, suffocation, and struggling for air, merging into two superordinated clusters, effort and air hunger that are compatible with widely accepted primary components of dyspnea. MDS results also suggested that future studies should consider further breathing sensations related to cognitive control of breathing.

Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications

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Lisa Pleyer

2016-04-01

Full Text Available Abstract Background The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20–30 % bone marrow blasts (AML20–30, formerly MDS-RAEB-t to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20–30 and AML30+ was made by regulatory agencies by initially restricting approval of azacitidine to AML20–30. Thus, uncertainty prevails regarding the diagnosis, prognosis and optimal treatment timing and strategy for patients with AML20–30. Here, we aim to provide clarification for patients treated with azacitidine front-line. Methods The Austrian Azacitidine Registry is a multicentre database (ClinicalTrials.gov: NCT01595295. For this analysis, we selected 339 patients treated with azacitidine front-line. According to the WHO classification 53, 96 and 190 patients had MDS-RAEB-I, MDS-RAEB-II and AML (AML20–30: n = 79; AML30+: n = 111, respectively. According to the FAB classification, 131, 101 and 111 patients had MDS-RAEB, MDS-RAEB-t and AML, respectively. Results The median ages of patients with MDS and AML were 72 (range 37–87 and 77 (range 23–93 years, respectively. Overall, 80 % of classifiable patients (≤30 % bone marrow blasts had intermediate-2 or high-risk IPSS scores. Most other baseline, treatment and response characteristics were similar between patients diagnosed with MDS or AML. WHO-classified patients with AML20–30 had significantly worse OS than patients with MDS-RAEB-II (13.1 vs 18.9 months; p = 0.010, but similar OS to patients with AML30+ (10.9 vs 13.1 months; p = 0.238. AML patients that showed MDS-related features did not have worse outcomes compared with patients who did not (13.2 vs 8.9 months; p = 0.104. FAB-classified patients with MDS-RAEB-t had similar survival to patients with AML30+ (12.8 vs 10.9 months; p = 0.376, but significantly worse OS than patients with MDS-RAEB (10

Mobbing Experiences of Instructors: Causes, Results, and Solution Suggestions

Science.gov (United States)

Celep, Cevat; Konakli, Tugba

2013-01-01

In this study, it was aimed to investigate possible mobbing problems in universities, their causes and results, and to attract attention to precautions that can be taken. Phenomenology as one of the qualitative research methods was used in the study. Sample group of the study was selected through the criteria sampling method and eight instructors…

Impact of pozzolanic binder addition on stabilization of polluted dredged sediments on its potential reuse as a new material resource for road construction in Basse Normandie, France

Science.gov (United States)

Silitonga, E.

2018-02-01

Due to the increase of the amount of marine dredged sediments (MDS) and the cost of managing the disposal site is very high, a reutilization of dredged sediment is urgently needed in France. The primary goal of this research is to find a domain for reuse of MDS materials as a new material regarding the environmental issues, and other requirement needed. In this study, the MDS was used as replacement material in road construction. Hence, various tests need to be realized to identify if MDS could achieve the requirement needed in this domain. The secondary objective is to enhance the geotechnical characteristic and to reduce the pollution content of the MDS, by incorporating binders and sediments, and revealed the geotechnical characteristic. The geotechnical test result shows that the stabilization by hydraulics binders improve the geotechnical characteristic and could fulfil the requirement needed. The present of Fly Ash and Silica Fume in this study is aimed to reduce the pollution level, especially the heavy metal content. After the geotechnical study in laboratory results shows as expected then the study to identify the chemical characteristic was realized. In order to evaluate the environmental impacts, leaching test was performed. The Leaching test result shows that with 7% of Silica Fume and 10% of Fly Ash capable to fulfil the criteria needed, hence, the use of MDS is consider safe in term of geotechnical and environmental impact, as a new material in road construction

Normal Hematopoietic Progenitor Subsets Have Distinct Reactive Oxygen Species, BCL2 and Cell-Cycle Profiles That Are Decoupled from Maturation in Acute Myeloid Leukemia.

Directory of Open Access Journals (Sweden)

Naeem Khan

Full Text Available In acute myeloid leukemia (AML quiescence and low oxidative state, linked to BCL2 mitochondrial regulation, endow leukemic stem cells (LSC with treatment-resistance. LSC in CD34+ and more mature CD34- AML have heterogeneous immunophenotypes overlapping with normal stem/progenitor cells (SPC but may be differentiated by functional markers. We therefore investigated the oxidative/reactive oxygen species (ROS profile, its relationship with cell-cycle/BCL2 for normal SPC, and whether altered in AML and myelodysplasia (MDS. In control BM (n = 24, ROS levels were highest in granulocyte-macrophage progenitors (GMP and CD34- myeloid precursors but megakaryocyte-erythroid progenitors had equivalent levels to CD34+CD38low immature-SPC although they were ki67high. BCL2 upregulation was specific to GMPs. This profile was also observed for CD34+SPC in MDS-without-excess-blasts (MDS-noEB, n = 12. Erythroid CD34- precursors were, however, abnormally ROS-high in MDS-noEB, potentially linking oxidative stress to cell loss. In pre-treatment AML (n = 93 and MDS-with-excess-blasts (MDS-RAEB (n = 14, immunophenotypic mature-SPC had similar ROS levels to co-existing immature-SPC. However ROS levels varied between AMLs; Flt3ITD+/NPM1wild-type CD34+SPC had higher ROS than NPM1mutated CD34+ or CD34- SPC. An aberrant ki67lowBCL2high immunophenotype was observed in CD34+AML (most prominent in Flt3ITD AMLs but also in CD34- AMLs and MDS-RAEB, suggesting a shared redox/pro-survival adaptation. Some patients had BCL2 overexpression in CD34+ ROS-high as well as ROS-low fractions which may be indicative of poor early response to standard chemotherapy. Thus normal SPC subsets have distinct ROS, cell-cycle, BCL2 profiles that in AML /MDS-RAEB are decoupled from maturation. The combined profile of these functional properties in AML subpopulations may be relevant to differential treatment resistance.

Resveratrol Suppresses Growth and Migration of Myelodysplastic Cells by Inhibiting the Expression of Elevated Cyclin D1 (CCND1).

Science.gov (United States)

Zhou, Wei; Xu, Shilin; Ying, Yi; Zhou, Ruiqing; Chen, Xiaowei

2017-11-01

Myelodysplastic syndromes (MDS) are a group of heterogeneous diseases characterized by poorly formed blood cells. We wanted to elucidate the underlying molecular mechanism to better determine pathogenesis, prognosis, diagnosis, and treatment for patients with MDS. We compared gene expression levels between normal and MDS tissue samples by immunohistochemical analysis. We studied the proliferation, survival, and migration of MDS cells using the EDU assay, colony formation, and transwell assays. We assessed the apoptotic rate and cell cycle status using flow cytometry and Hoechst staining. Finally, we evaluated RNA and protein expressions using polymerase chain reaction and Western blots, respectively. We found that resveratrol suppressed SKM-1 (an advanced MDS cell line) proliferation in a dose-dependent manner. Consistent with this finding, the EDU and colony formation assays also showed that resveratrol inhibited SKM-1 growth. Moreover, flow cytometry and Hoechst 33258 staining demonstrated that resveratrol induced apoptosis and a change in cell cycle status in SKM-1 cells, while the transwell assay showed that resveratrol reduced the migratory ability of SKM-1 cells. Resveratrol also decreased the expression of CCND1 (a gene that encodes the cyclin D1 protein) and increased expressions of KMT2A [lysine (K)-specific methyltransferase 2A] and caspase-3, suggesting that resveratrol exerts its effect by regulating CCND1 in SKM-1 cells. In addition, a combination of resveratrol and the PI3K/AKT inhibitor LY294002 exhibited a stronger inhibitory effect on the SKM-1 cells, compared with resveratrol alone. Our study proved that resveratrol suppresses SKM-1 growth and migration by inhibiting CCND1 expression. This finding provides novel insights into the pathogenesis of MDS and might help develop new diagnosis and treatment for patients with MDS.

The Differencies in Adult and Pediatric Myelodysplastic Syndrome: A Review

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Vasekova P

2016-08-01

Full Text Available Myelodysplastic syndrome (MDS represent very heterogenous group of clonal stem cell bone marrow disorders with ineffective haematopoesis leading to cytopenias in peripheral blood and increased risk of blastic transformation and evolution of acute myeloid leukemia. MDS is a disease of older age mostly, in children it seems to be very rare. There are several significant morphological, cytogenetic and prognostic differencies of the disease in adults and in children. Adult MDS patients most commonly manifest with symptoms of anemia, bleeding and infection are uncommon. In childhood, MDS manifests predominantly by neutropenia and thrombocytopenia. In addition, some pediatric MDS patients present also with constitutional disease’s signs and symptoms. Early and correct diagnosis in both age groups is essential for the choice of appropriate therapy and also for next life of patients. However, the diagnosis of MDS is challenging, complex and requiring close correlation of clinical symptoms, laboratory parameters and standardized examination of BM biopsies. The authors present an overview focused on biology of MDS in adults and children, on the differences in the incidence, clinical presentation and treatment. They summarize the possibilities and limits of histopathological diagnosis and differential diagnosis of the disease in different age groups. A major problem in the morphological diagnosis of MDS remains the determination, whether the myelodysplasia is due to clonal disorder. It might result also from some other factors, as significant dysplasia can also occur in reactive conditions, and vice versa, only discrete dysplasia is sometimes observed in MDS patients. Although histomorphological and immunohistochemical analysis of BM biopsy is invasive and time-consuming examination, it has its value in the diagnosis, differential diagnosis and evaluation of therapeutic effect.

New Insights on Iron Study in Myelodysplasia

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Noha M. El Husseiny

2014-12-01

Full Text Available OBJECTIVE: Hepcidin plays a pivotal role in iron homeostasis. It is predominantly produced by hepatocytes and inhibits iron release from macrophages and iron uptake by intestinal epithelial cells. Competitive ELISA is the current method of choice for the quantification of serum hepcidin because of its lower detection limit, low costs, and high throughput. This study aims to discuss the role of hepcidin in the pathogenesis of iron overload in recently diagnosed myelodysplasia (MDS cases. METHODS: The study included 21 recently diagnosed MDS patients and 13 healthy controls. Ferritin, hepcidin, and soluble transferrin receptor (sTFR were measured in all subjects. RESULTS: There were 7 cases of hypocellular MDS, 8 cases of refractory cytopenia with multilineage dysplasia, and 6 cases of refractory anemia with excess blasts. No difference was observed among the 3 MDS subtypes in terms of hepcidin, sTFR, and ferritin levels (p>0.05. Mean hepcidin levels in the MDS and control groups were 55.8±21.5 ng/mL and 19.9±2.6 ng/ mL, respectively. Mean sTFR was 45.7±8.8 nmol/L in MDS patients and 31.1±5.6 nmol/L in the controls. Mean ferritin levels were significantly higher in MDS patients than in controls (539.14±83.5 ng/mL vs. 104.6±42.9 ng/mL, p0.05. CONCLUSION: Hepcidin may not be the main cause of iron overload in MDS. Further studies are required to test failure of production or peripheral unresponsiveness to hepcidin in MDS cases.

Suggestibility and suggestive modulation of the Stroop effect.

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Kirsch, Irving

2011-06-01

Although the induction of a hypnotic state does not seem necessary for suggestive modulation of the Stroop effect, this important phenomenon has seemed to be dependent on the subject's level of hypnotic suggestibility. Raz and Campbell's (2011) study indicates that suggestion can modulate the Stroop effect substantially in very low suggestible subjects, as well as in those who are highly suggestible. This finding casts doubt on the presumed mechanism by which suggestive modulation is brought about. Research aimed at uncovering the means by which low suggestible individuals are able to modulate the Stroop effect would be welcome, as would assessment of this effect in moderately suggestible people. Copyright © 2010 Elsevier Inc. All rights reserved.

Microdeletions of chromosome 17p13.3 markers in an unselected survey of probands with type I lissencephaly

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Giannakoudis, J.; Wrisch, A.; Farber, C. [and others

1994-09-01

Type I lissencephaly (MIM No.247200, McKusick, 1992), a brain malformation characterized by a smooth cerebral surface, exhibits a four-layered cortex and leads to mental retardation and other neurological anomalies. Lissencephaly, type I occurs either isolated (ILS) or in association with dysmorphic facial features (Miller-Dieker syndrome, MDS). Microdeletions were detected within a 350 kb critical segment in 17p13.3 in about 13% of patients with ILS and about 90% with MDS. Most of these patients were selected for molecular analysis, however, by an already known abnormal karyotype. Therefore, the diagnostic value of microsatellite and VNTR markers to identify deletions in unselected ILS/MDS patients is still unknown. We have tested the respective significance of a novel (CA)17 VNDR element (D17S379) and of the VNTR marker YNZ22 (D17S5) to identify deletions in an unselected survey of 28 ILS/MDS patients. For D17S379, 50% of our patients were heterozygous, while 46% were uninformative with respect to segregation of alleles within their family. One patient (3.6%) was shown to be deleted for a paternal allele. PCR for D17S5, which maps proximal to the ILS region, disclosed a deletion in 3 patients (10.7%), including the one seen also by D17S379. Altogether, 75% were heterozygous and only 14% uninformative for this locus. Our results suggest that the combined PCR analysis for two of the most significant markers within the ILS/MDS region disclose a deletion in about 10% of unselected patients with features of type I lissencephaly. The low frequency of deletions detected may reflect different mutation mechanisms, genetic heterogeneity, the need for more densely spaced markers around the critical region, and/or more strict clinical criteria for defining the study group.

Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes

DEFF Research Database (Denmark)

Musto, Pellegrino; Lanza, Francesco; Balleari, Enrico

2005-01-01

Thirty-seven anaemic subjects with low-to-intermediate risk myelodysplastic syndrome (MDS) received the highly glycosylated, long-acting erythropoiesis-stimulating molecule darbepoetin-alpha (DPO) at the single, weekly dose of 150 microg s.c. for at least 12 weeks. Fifteen patients (40.5%) achieved......, no excess of blasts and hypoplastic bone marrow. This study suggests that DPO, at the dose and schedule used, can be safely given in low-intermediate risk MDS and may be effective in a significant proportion of these patients....

Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-κB Gene Network

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Jing Fang

2014-09-01

Full Text Available Chromosome 5q deletions (del[5q] are common in high-risk (HR myelodysplastic syndrome (MDS and acute myeloid leukemia (AML; however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q HR MDS/AML and miR-146a−/− hematopoietic stem/progenitor cells (HSPCs results in TRAF6/NF-κB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62, expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-κB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-κB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-κB to sustain TRAF6/NF-κB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q MDS/AML.

Pollutant content in marine debris and characterization by thermal decomposition

International Nuclear Information System (INIS)

Iñiguez, M.E.; Conesa, J.A.; Fullana, A.

2017-01-01

Marine debris (MDs) produces a wide variety of negative environmental, economic, safety, health and cultural impacts. Most marine litter has a very low decomposition rate (plastics), leading to a gradual accumulation in the coastal and marine environment. Characterization of the MDs has been done in terms of their pollutant content: PAHs, ClBzs, ClPhs, BrPhs, PCDD/Fs and PCBs. The results show that MDs is not a very contaminated waste. Also, thermal decomposition of MDs materials has been studied in a thermobalance at different atmospheres and heating rates. Below 400–500 K, the atmosphere does not affect the thermal degradation of the mentioned waste. However, at temperatures between 500 and 800 K the presence of oxygen accelerates the decomposition. Also, a kinetic model is proposed for the combustion of the MDs, and the decomposition is compared with that of their main constituents, i.e., polyethylene (PE), polystyrene (PS), polypropylene (PP), nylon and polyethylene-terephthalate (PET). - Highlights: • The analysis and characterization of waste from marine environment were performed. • Its pollutant content has been determined, considering PAHs, PCDD/Fs and dl-PCBs. • Thermal decomposition of MDs was studied at different atmospheres and heating rates. • Kinetic models for the combustion of the five main plastics of MDs were proposed. • Composition of the waste is calculated using thermal behavior of different plastics.

Pollutant content in marine debris and characterization by thermal decomposition.

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Iñiguez, M E; Conesa, J A; Fullana, A

2017-04-15

Marine debris (MDs) produces a wide variety of negative environmental, economic, safety, health and cultural impacts. Most marine litter has a very low decomposition rate (plastics), leading to a gradual accumulation in the coastal and marine environment. Characterization of the MDs has been done in terms of their pollutant content: PAHs, ClBzs, ClPhs, BrPhs, PCDD/Fs and PCBs. The results show that MDs is not a very contaminated waste. Also, thermal decomposition of MDs materials has been studied in a thermobalance at different atmospheres and heating rates. Below 400-500K, the atmosphere does not affect the thermal degradation of the mentioned waste. However, at temperatures between 500 and 800K the presence of oxygen accelerates the decomposition. Also, a kinetic model is proposed for the combustion of the MDs, and the decomposition is compared with that of their main constituents, i.e., polyethylene (PE), polystyrene (PS), polypropylene (PP), nylon and polyethylene-terephthalate (PET). Copyright © 2017 Elsevier Ltd. All rights reserved.

Classification of hadith into positive suggestion, negative suggestion, and information

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Faraby, Said Al; Riviera Rachmawati Jasin, Eliza; Kusumaningrum, Andina; Adiwijaya

2018-03-01

As one of the Muslim life guidelines, based on the meaning of its sentence(s), a hadith can be viewed as a suggestion for doing something, or a suggestion for not doing something, or just information without any suggestion. In this paper, we tried to classify the Bahasa translation of hadith into the three categories using machine learning approach. We tried stemming and stopword removal in preprocessing, and TF-IDF of unigram, bigram, and trigram as the extracted features. As the classifier, we compared between SVM and Neural Network. Since the categories are new, so in order to compare the results of the previous pipelines, we created a baseline classifier using simple rule-based string matching technique. The rule-based algorithm conditions on the occurrence of words such as “janganlah, sholatlah, and so on” to determine the category. The baseline method achieved F1-Score of 0.69, while the best F1-Score from the machine learning approach was 0.88, and it was produced by SVM model with the linear kernel.

Deferasirox in iron-overloaded patients with transfusion-dependent myelodysplastic syndromes: Results from the large 1-year EPIC study

DEFF Research Database (Denmark)

Gattermann, Norbert; Finelli, Carlo; Porta, Matteo Della

2010-01-01

The prospective 1-year EPIC study enrolled 341 patients with myelodysplastic syndromes (MDS); although baseline iron burden was >2500ng/mL, approximately 50% were chelation-naïve. Overall median serum ferritin decreased significantly at 1 year (p=0.002). Decreases occurred irrespective of whether...

Deepening Sleep by Hypnotic Suggestion

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Cordi, Maren J.; Schlarb, Angelika A.; Rasch, Björn

2014-01-01

Study Objectives: Slow wave sleep (SWS) plays a critical role in body restoration and promotes brain plasticity; however, it markedly declines across the lifespan. Despite its importance, effective tools to increase SWS are rare. Here we tested whether a hypnotic suggestion to “sleep deeper” extends the amount of SWS. Design: Within-subject, placebo-controlled crossover design. Setting: Sleep laboratory at the University of Zurich, Switzerland. Participants: Seventy healthy females 23.27 ± 3.17 y. Intervention: Participants listened to an auditory text with hypnotic suggestions or a control tape before napping for 90 min while high-density electroencephalography was recorded. Measurements and Results: After participants listened to the hypnotic suggestion to “sleep deeper” subsequent SWS was increased by 81% and time spent awake was reduced by 67% (with the amount of SWS or wake in the control condition set to 100%). Other sleep stages remained unaffected. Additionally, slow wave activity was significantly enhanced after hypnotic suggestions. During the hypnotic tape, parietal theta power increases predicted the hypnosis-induced extension of SWS. Additional experiments confirmed that the beneficial effect of hypnotic suggestions on SWS was specific to the hypnotic suggestion and did not occur in low suggestible participants. Conclusions: Our results demonstrate the effectiveness of hypnotic suggestions to specifically increase the amount and duration of slow wave sleep (SWS) in a midday nap using objective measures of sleep in young, healthy, suggestible females. Hypnotic suggestions might be a successful tool with a lower risk of adverse side effects than pharmacological treatments to extend SWS also in clinical and elderly populations. Citation: Cordi MJ, Schlarb AA, Rasch B. Deepening sleep by hypnotic suggestion. SLEEP 2014;37(6):1143-1152. PMID:24882909

Testing increases suggestibility for narrative-based misinformation but reduces suggestibility for question-based misinformation.

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LaPaglia, Jessica A; Chan, Jason C K

2013-01-01

A number of recent studies have found that recalling details of an event following its occurrence can increase people's suggestibility to later presented misinformation. However, several other studies have reported the opposite result, whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the present study, we investigated whether differences in the way misinformation is presented can modulate the effects of testing on suggestibility. Participants watched a video of a robbery and some were questioned about the event immediately afterwards. Later, participants were exposed to misinformation in a narrative (Experiment 1) or in questions (Experiment 2). Consistent with previous studies, we found that testing increased suggestibility when misinformation was presented via a narrative. Remarkably, when misinformation was presented in questions, testing decreased suggestibility. Copyright © 2013 John Wiley & Sons, Ltd.

Multidimensional scaling of emotional responses to music in patients with temporal lobe resection.

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Dellacherie, D; Bigand, E; Molin, P; Baulac, M; Samson, S

2011-10-01

The present study investigated emotional responses to music by using multidimensional scaling (MDS) analysis in patients with right or left medial temporal lobe (MTL) lesions and matched normal controls (NC). Participants were required to evaluate emotional dissimilarities of nine musical excerpts that were selected to express graduated changes along the valence and arousal dimensions. For this purpose, they rated dissimilarity between pairs of stimuli on an eight-point scale and the resulting matrices were submitted to an MDS analysis. The results showed that patients did not differ from NC participants in evaluating emotional feelings induced by the musical excerpts, suggesting that all participants were able to distinguish refined emotions. We concluded that the ability to detect and use emotional valence and arousal when making dissimilarity judgments was not strongly impaired by a right or left MTL lesion. This finding has important clinical implications and is discussed in light of current neuropsychological studies on emotion. It suggests that emotional responses to music can be at least partially preserved at a non-verbal level in patients with unilateral temporal lobe damage including the amygdala. Copyright © 2011 Elsevier Srl. All rights reserved.

Reinventing suggestion systems for continuous improvement

NARCIS (Netherlands)

Schuring, R.W.; Luijten, Harald

2001-01-01

This article reports an experiment to increase the effectiveness of a suggestion system by deliberately applying principles of the kaizen and performance management. Design rules for suggestion systems are derived from these theories. The suggestion system that resulted differs from traditional

A study of megakaryocyte morphology in bone marrow aspiration smears of cases of thrombocytopenia

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Shashikala Vinayakamurthy

2017-01-01

Full Text Available Background: Thrombocytopenia may be encountered in various hematological and nonhematological conditions and may be associated with dysplastic megakaryocytes which is a feature of myelodysplastic syndrome (MDS, even though they can be observed in non-MDS hematological conditions. Objective: To study the morphological variations of megakaryocytes on bone marrow aspiration smears in non-MDS-related thrombocytopenia in a Medical College in Bengaluru, Karnataka. Materials and Methods: It was a prospective study of 86 cases of non-MDS thrombocytopenia whose bone marrow aspirates were studied morphologically. Results: The most common cause of thrombocytopenia was acute leukemia followed by other systemic malignancies, megaloblastic anemia, and idiopathic thrombocytopenic purpura. Both dysplastic and nondysplastic features were observed in the above-mentioned conditions. The most common dysplastic feature was nuclear segmentation followed by micromegakaryocytes and hypogranular forms. Among nondysplastic features, the most common were immature forms, bare nuclei, and hypolobation. Emperipolesis and cytoplasmic vacuoles were noted in a case of pyrexia of unknown origin. Conclusion: Dysplastic megakaryocytes are common in non-MDS-related thrombocytopenia and their mere presence should not lead to the diagnosis of MDS. Hence, proper diagnosis should be made on megakaryocyte morphology, patient's clinical findings, and other hematological parameters. This understanding can improve the diagnostic accuracy for wide range of hematological disorders.

Hypnosis, suggestion, and suggestibility: an integrative model.

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Lynn, Steven Jay; Laurence, Jean-Roch; Kirsch, Irving

2015-01-01

This article elucidates an integrative model of hypnosis that integrates social, cultural, cognitive, and neurophysiological variables at play both in and out of hypnosis and considers their dynamic interaction as determinants of the multifaceted experience of hypnosis. The roles of these variables are examined in the induction and suggestion stages of hypnosis, including how they are related to the experience of involuntariness, one of the hallmarks of hypnosis. It is suggested that studies of the modification of hypnotic suggestibility; cognitive flexibility; response sets and expectancies; the default-mode network; and the search for the neurophysiological correlates of hypnosis, more broadly, in conjunction with research on social psychological variables, hold much promise to further understanding of hypnosis.

Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

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Bartesaghi, Stefano; Betts-Henderson, Joanne; Cain, Kelvin; Dinsdale, David; Zhou, Xiaoshan; Karlsson, Anna; Salomoni, Paolo; Nicotera, Pierluigi

2010-05-01

Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated with progressive myopathy, hepatopathy and/or encephalopathy, depending in part on the underlying nuclear genetic defect. Mutations of TK2 have previously been associated with an isolated myopathic form of MDS (OMIM 609560). However, more recently, neurological phenotypes have been demonstrated in patients carrying TK2 mutations, thus suggesting that loss of TK2 results in neuronal dysfunction. Here, we directly address the role of TK2 in neuronal homeostasis using a knockout mouse model. We demonstrate that in vivo loss of TK2 activity leads to a severe ataxic phenotype, accompanied by reduced mtDNA copy number and decreased steady-state levels of electron transport chain proteins in the brain. In TK2-deficient cerebellar neurons, these abnormalities are associated with impaired mitochondrial bioenergetic function, aberrant mitochondrial ultrastructure and degeneration of selected neuronal types. Overall, our findings demonstrate that TK2 deficiency leads to neuronal dysfunction in vivo, and have important implications for understanding the mechanisms of neurological impairment in MDS.

The Effects of Suggestibility on Relaxation.

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Rickard, Henry C.; And Others

1985-01-01

Selected undergraduates (N=32) on the basis of Creative Imagination Scale scores and randomly assigned high and low suggestibility subjects to progressive relaxation (PR) and suggestions of relaxation (SR) training modes. Results revealed a significant pre-post relaxation effect, and main efffects for both suggestibility and training mode. (NRB)

Immune Mechanisms in Myelodysplastic Syndrome

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Andreas Glenthøj

2016-06-01

Full Text Available Myelodysplastic syndrome (MDS is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS.

Greater Independence in Activities of Daily Living is Associated with Higher Health-Related Quality of Life Scores in Nursing Home Residents with Dementia

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Charice S. Chan

2015-06-01

Full Text Available Health-related quality of life (HRQL for nursing home residents is important, however, the concept of quality of life is broad, encompasses many domains and is difficult to assess in people with dementia. Basic activities of daily living (ADL are measured routinely in nursing homes using the Resident Assessment Instrument-Minimum Data Set Version 2.0 (RAI-MDS and Functional Independence Measure (FIM instrument. We examined the relationship between HRQL and ADL to assess the future possibility of ADL dependency level serving as a surrogate measure of HRQL in residents with dementia. To assess ADL, measures derived from the RAI-MDS and FIM data were gathered for 111 residents at the beginning of our study and at 6-month follow-up. Higher scores for independence in ADL were correlated with higher scores for a disease-specific HRQL measure, the Quality of Life—Alzheimer’s Disease Scale. Preliminary evidence suggests that FIM-assessed ADL is associated with HRQL for these residents. The associations of the dressing and toileting items with HRQL were particularly strong. This finding suggests the importance of ADL function in HRQL. The RAI-MDS ADL scales should be used with caution to evaluate HRQL.

Comprehending Adverbs Of Doubt And Certainty In Health Communication: A Multidimensional Scaling Approach

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Norman S. Segalowitz

2016-05-01

Full Text Available This research explored the feasibility of using multidimensional scaling (MDS analysis in novel combination with other techniques to study comprehension of epistemic adverbs expressing doubt and certainty (e.g., evidently, obviously, probably as they relate to health communication in clinical settings. In Study 1, Australian English speakers performed a dissimilarity-rating task with sentence pairs containing the target stimuli, presented as doctors' opinions. Ratings were analyzed using a combination of cultural consensus analysis (factor analysis across participants, weighted-data classical-MDS, and cluster analysis. Analyses revealed strong within-community consistency for a 3-dimensional semantic space solution that took into account individual differences, strong statistical acceptability of the MDS results in terms of stress and explained variance, and semantic configurations that were interpretable in terms of linguistic analyses of the target adverbs. The results confirmed the feasibility of using MDS in this context. Study 2 replicated the results with Canadian English speakers on the same task. Semantic analyses and stress decomposition analysis were performed on the Australian and Canadian data sets, revealing similarities and differences between the two groups. Overall, the results support using MDS to study comprehension of words critical for health communication, including in future studies, for example, second language speaking patients and/or practitioners. More broadly, the results indicate that the techniques described should be promising for comprehension studies in many communicative domains, in both clinical settings and beyond, and including those targeting other aspects of language and focusing on comparisons across different speech communities.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country.

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Velloso, E D R P; Chauffaille, M L; Peliçario, L M; Tanizawa, R S S; Toledo, S R C; Gaiolla, R D; Lopes, L F

2013-01-01

Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED). We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome). Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

[Progress of cytogenetic detection in myelodysplastic syndromes].

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Zhou, Qing-Bing; Hu, Xiao-Mei; Liu, -Feng; Ma, Rou

2011-12-01

In recent years, significant progresses have been got in study on pathogenesis, treatment and prognosis of myelodysplastic syndromes (MDS), especially on use of new technology, that has great importance for cytogenetics of MDS. Recently, the progress of cytogenetic detection in MDS is very remarkable. Based on the metaphase cytogenetics (MC) method, prognostic significance of cytogenetics in MDS was clarified gradually. For example, people have known the prognostic significance of 12 p-, 11 q-, +21, t(11(q23)), although these genetic abnormalities are rare in the MDS. In addition, chromosome mutation emerged in the process of MDS may indicate the poor prognosis. On the other hand, with the use of SNP-A and aCGH in the study of genetics, MDS cytogenetic abnormality detection rate has been further improved and can reach to 78%. At the same time, some of MDS patients with the "normal karyotype" detected by MC have new hidden aberrations through the SNP or CGH detection, and these patients have a poorer prognosis. In this review, the advances of study on cytogenetic detection for MDS based on MC and SNP-A or aCGH methods are summarized.

Aberrant Methylation-Mediated Suppression of APAF1 in Myelodysplastic Syndrome.

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Zaker, Farhad; Nasiri, Nahid; Amirizadeh, Naser; Razavi, Seyed Mohsen; Yaghmaie, Marjan; Teimoori-Toolabi, Ladan; Maleki, Ali; Bakhshayesh, Masoumeh

2017-04-01

Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials and Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS. Gene expression was analyzed by using real time RT-PCR. Results: 42.6% of patient samples were methylated in promoter region of APAF1analyzed, while methylation of the gene was not seen in controls (P<0.05). Methylation of APAF1was significantly associated with the suppression of its mRNA expression (P=0.00). The methylation status of APAF1in advanced-stage MDS patients (80%) was significantly higher than that of the early-stage MDS patients (28.2%) (P=0.001). The difference in frequency of hypermethylatedAPAF1 gene was significant between good (37.5%) and poor (85.71%) cytogenetic risk groups (P=0.043). In addition, a higher frequency of APAF1hypermethylation was observed in higher-risk MDS group (69.2%) compared to lower-risk MDS group (34.14%) (P=0.026). Conclusion: Our study indicated that APAF1hypermethylation in MDS was associated to high-risk disease classified according to the IPSS, WHO and cytogenetic risk.

Megakaryocytic alterations in thrombocytopenia: A bone marrow aspiration study

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Muhury Manas

2009-10-01

Full Text Available Context: Dysplastic changes are well documented in myelodysplastic syndromes (MDS. However, they are also observed in non-MDS hematological conditions. Aims: To evaluate the megakaryocytic alterations in the bone marrow aspirations in cases of non-MDS related thrombocytopenia. Setting and Design: A prospective study of 144 bone marrow aspirates was conducted in the department of pathology, Kasturba Medical College, Mangalore. The aspirates were studied to assess the number and morphology of the megakaryocytes in non-MDS related thrombocytopenia and evaluate their significance when compared to changes in MDS. Materials and Methods: The bone marrow aspiration smears were stained with Leishman stain and examined under light microscope. Statistical Analysis Used: Fisher′s exact test. A P value less than 0.05 was considered significant. Sensitivity and specificity was calculated for those features which were significant in the relevant hematological disorders. Results: The sensitivity of immature megakaryocytes, dysplastic forms and micromegakaryocytes in cases of immune thrombocytopenic purpura was 100%, 89% and 42% respectively. The specificity of emperipolesis was 74%. In cases of infection-associated thrombocytopenia, immature megakaryocytes had a sensitivity of 100% and cytoplasmic vacuolization were 86% specific. The sensitivity of the dysplastic forms in megaloblastic anemia was 75%. However, no platelet budding was observed. The presence of micromegakaryocyte had a specificity of 83% in MDS, and was statistically significant when compared to cases of non-MDS conditions (P< 0.05. Conclusions: Careful understanding of the morphological changes of megakaryocytes in bone marrow aspirates can improve the diagnostic accuracy for a wide range of hematological disorders thereby enabling proper therapeutic interventions.

Facultative methanotrophy: false leads, true results, and suggestions for future research.

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Semrau, Jeremy D; DiSpirito, Alan A; Vuilleumier, Stéphane

2011-10-01

Methanotrophs are a group of phylogenetically diverse microorganisms characterized by their ability to utilize methane as their sole source of carbon and energy. Early studies suggested that growth on methane could be stimulated with the addition of some small organic acids, but initial efforts to find facultative methanotrophs, i.e., methanotrophs able to utilize compounds with carbon-carbon bonds as sole growth substrates were inconclusive. Recently, however, facultative methanotrophs in the genera Methylocella, Methylocapsa, and Methylocystis have been reported that can grow on acetate, as well as on larger organic acids or ethanol for some species. All identified facultative methanotrophs group within the Alphaproteobacteria and utilize the serine cycle for carbon assimilation from formaldehyde. It is possible that facultative methanotrophs are able to convert acetate into intermediates of the serine cycle (e.g. malate and glyoxylate), because a variety of acetate assimilation pathways convert acetate into these compounds (e.g. the glyoxylate shunt of the tricarboxylic acid cycle, the ethylmalonyl-CoA pathway, the citramalate cycle, and the methylaspartate cycle). In this review, we summarize the history of facultative methanotrophy, describe scenarios for the basis of facultative methanotrophy, and pose several topics for future research in this area. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Molecular modeling and structural analysis of two-pore domain potassium channels TASK1 interactions with the blocker A1899

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David Mauricio Ramirez

2015-03-01

Full Text Available A1899 is a potent and highly selective blocker of the Two-pore domain potassium (K2P channel TASK-1, it acts as an antagonist blocking the K+ flux and binds to TASK-1 in the inner cavity and shows an activity in nanomolar order. This drug travels through the central cavity and finally binds in the bottom of the selectivity filter with some threonines and waters molecules forming a H-bond network and several hydrophobic interactions. Using alanine mutagenesis screens the binding site was identify involving residues in the P1 and P2 pore loops, the M2 and M4 transmembrane segments, and the halothane response element; mutations were introduced in the human TASK-1 (KCNK3, NM_002246 expressed in Oocytes from anesthetized Xenopus laevis frogs. Based in molecular modeling and structural analysis as such as molecular docking and binding free energy calculations a pose was suggested using a TASK-1 homology models. Recently, various K2P crystal structures have been obtained. We want redefined – from a structural point of view – the binding mode of A1899 in TASK-1 homology models using as a template the K2P crystal structures. By computational structural analysis we describe the molecular basis of the A1899 binding mode, how A1899 travel to its binding site and suggest an interacting pose (Figure 1. after 100 ns of molecular dynamics simulation (MDs we found an intra H-Bond (80% of the total MDs, a H-Bond whit Thr93 (42% of the total MDs, a pi-pi stacking interaction between a ring and Phe125 (88% of the total MDs and several water bridges. Our experimental and computational results allow the molecular understanding of the structural binding mechanism of the selective blocker A1899 to TASK-1 channels. We identified the structural common and divergent features of TASK-1 channel through our theoretical and experimental studies of A1899 drug action.

Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

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Iriyama, Chisako [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Tomita, Akihiro, E-mail: atomita@med.nagoya-u.ac.jp [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Hoshino, Hideaki; Adachi-Shirahata, Mizuho [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan); Furukawa-Hibi, Yoko; Yamada, Kiyofumi [Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Nagoya (Japan); Kiyoi, Hitoshi; Naoe, Tomoki [Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya (Japan)

2012-03-23

Highlights: Black-Right-Pointing-Pointer Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. Black-Right-Pointing-Pointer Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. Black-Right-Pointing-Pointer Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. Black-Right-Pointing-Pointer Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3-9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic

Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome

International Nuclear Information System (INIS)

Iriyama, Chisako; Tomita, Akihiro; Hoshino, Hideaki; Adachi-Shirahata, Mizuho; Furukawa-Hibi, Yoko; Yamada, Kiyofumi; Kiyoi, Hitoshi; Naoe, Tomoki

2012-01-01

Highlights: ► Circulating DNAs (CDs) can be used to detect genetic/epigenetic abnormalities in MDS. ► Epigenetic changes can be detected more sensitively when using plasma DNA than PBMNC. ► Mutation ratio in CDs may reflect the ratio in stem cell population in bone marrow. ► Using CDs can be a safer alternate strategy compared to bone marrow aspiration. -- Abstract: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disorder. Several genetic/epigenetic abnormalities are deeply associated with the pathogenesis of MDS. Although bone marrow (BM) aspiration is a common strategy to obtain MDS cells for evaluating their genetic/epigenetic abnormalities, BM aspiration is difficult to perform repeatedly to obtain serial samples because of pain and safety concerns. Here, we report that circulating cell-free DNAs from plasma and serum of patients with MDS can be used to detect genetic/epigenetic abnormalities. The plasma DNA concentration was found to be relatively high in patients with higher blast cell counts in BM, and accumulation of DNA fragments from mono-/di-nucleosomes was confirmed. Using serial peripheral blood (PB) samples from patients treated with hypomethylating agents, global methylation analysis using bisulfite pyrosequencing was performed at the specific CpG sites of the LINE-1 promoter. The results confirmed a decrease of the methylation percentage after treatment with azacitidine (days 3–9) using DNAs from plasma, serum, and PB mono-nuclear cells (PBMNC). Plasma DNA tends to show more rapid change at days 3 and 6 compared with serum DNA and PBMNC. Furthermore, the TET2 gene mutation in DNAs from plasma, serum, and BM cells was quantitated by pyrosequencing analysis. The existence ratio of mutated genes in plasma and serum DNA showed almost equivalent level with that in the CD34+/38- stem cell population in BM. These data suggest that genetic/epigenetic analyses using PB circulating DNA can be a safer and painless alternative to using BM

Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms.

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Gabriela Silva

Full Text Available BACKGROUND: Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS and acute myeloid leukaemia (AML. Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. METHODOLOGY/PRINCIPAL FINDINGS: Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+ cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3 and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1 and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. CONCLUSION: This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

Vorinostat induces apoptosis and differentiation in myeloid malignancies: genetic and molecular mechanisms.

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Silva, Gabriela; Cardoso, Bruno A; Belo, Hélio; Almeida, António Medina

2013-01-01

Aberrant epigenetic patterns are central in the pathogenesis of haematopoietic diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). Vorinostat is a HDACi which has produced responses in these disorders. The purpose of this study was to address the functional effects of vorinostat in leukemic cell lines and primary AML and MDS myeloid cells and to dissect the genetic and molecular mechanisms by which it exerts its action. Functional assays showed vorinostat promoted cell cycle arrest, inhibited growth, and induced apoptosis and differentiation of K562, HL60 and THP-1 and of CD33(+) cells from AML and MDS patients. To explore the genetic mechanism for these effects, we quantified gene expression modulation by vorinostat in these cells. Vorinostat increased expression of genes down-regulated in MDS and/or AML (cFOS, COX2, IER3, p15, RAI3) and suppressed expression of genes over-expressed in these malignancies (AXL, c-MYC, Cyclin D1) and modulated cell cycle and apoptosis genes in a manner which would favor cell cycle arrest, differentiation, and apoptosis of neoplastic cells, consistent with the functional assays. Reporter assays showed transcriptional effect of vorinostat on some of these genes was mediated by proximal promoter elements in GC-rich regions. Vorinostat-modulated expression of some genes was potentiated by mithramycin A, a compound that interferes with SP1 binding to GC-rich DNA sequences, and siRNA-mediated SP1 reduction. ChIP assays revealed vorinostat inhibited DNA binding of SP1 to the proximal promoter regions of these genes. These results suggest vorinostat transcriptional action in some genes is regulated by proximal promoter GC-rich DNA sequences and by SP1. This study sheds light on the effects of vorinostat in AML and MDS and supports the implementation of clinical trials to explore the use of vorinostat in the treatment of these diseases.

DNA (cytosine-5-methyltransferase 3B (DNMT 3B polymorphism and risk of Down syndrome offspring

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Cláudia Melo de Moura

2018-01-01

Full Text Available Down syndrome (DS is the most common form of human genetic mental retardation. Several polymorphisms in genes coding folic acid cycle enzymes have been associated to the risk of bearing a DS child; however, the results are controversial. S-adenosyl-l-methionine (SAM is an important intermediate of folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5-methyltransferase 3B (DNMT3B – EC 2.1.1.37 de novo methylation processes during embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B in maternal genotype may be associated with a decreased risk of having a DS child. We herein investigate the association of this polymorphism with the occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS infants (MDS and 212 control mothers (CM through PCR-RFLP. The observed genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC = 0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T = 0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed, and both DNMT 3B rs2424913 genotype (χ2 = 4.53; DF = 1; P = 0.03 and allelic (χ2 = 4.90; DF = 1; P = 0.03 frequencies show significant differences between MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of bearing a DS child (OR = 0.69; 95% CI: 0.50–0.96; P = 0.03, and the risk is diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95% CI: 0.31–0.96; P = 0.04. Our results suggest that women harboring the single nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS pregnancy, and further studies are necessary to confirm this protective effect.

Influence of crop load on almond tree water status and its importance in irrigation scheduling

Science.gov (United States)

Puerto Conesa, Pablo; Domingo Miguel, Rafael; Torres Sánchez, Roque; Pérez Pastor, Alejandro

2014-05-01

reserve sugar concentration were also evaluated. Trees were drip irrigated in order to satisfy the maximum crop water requirements. Variations in MDS were compared with changes in Ψs and VPD10-15 in the three treatments at the end of fruit growth stage (stage III), kernel filling stage (stage IV) and postharvest (stage V). Our results highlighted that crop load affects almond tree water status. We observed a greater effect of crop load on MDS and TGR than on Ψs. In T0 trees, Ψs was 16% higher than in T50 and T100. MDS was 36% and 49% lower in the low (T50) and almost nil-cropping trees (T0) than in the high-cropping trees (T100). The slope of MDS vs VPD10-15 forced to the origin increased with crop load, suggesting that different relationships are needed to estimate tree water status. TGR was 33% higher in T0 than in the cropping trees. In the same way, the presence of fruits, as reflected by the source/sink relationship, increased gas exchange parameters. Also pruning weights reflected competition between fruits and shoots for photoassimilates. Nevertheless the reserve sugar concentration at the base of the main branches was unaffected by the crop load. All this implies that it is necessary to consider the crop load in irrigation scheduling based on MDS signal intensity.

Cytogenetic studies of Brazilian pediatric myelodysplastic syndrome cases: challenges and difficulties in a large and emerging country

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E.D.R.P. Velloso

2013-01-01

Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

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E.D.R.P. Velloso

2013-11-01

Full Text Available Myelodysplastic syndromes (MDS and juvenile myelomonocytic leukemia (JMML are rare hematopoietic stem cell diseases affecting children. Cytogenetics plays an important role in the diagnosis of these diseases. We report here the experience of the Cytogenetic Subcommittee of the Brazilian Cooperative Group on Pediatric Myelodysplastic Syndromes (BCG-MDS-PED. We analyzed 168 cytogenetic studies performed in 23 different cytogenetic centers; 84 of these studies were performed in patients with confirmed MDS (primary MDS, secondary MDS, JMML, and acute myeloid leukemia/MDS+Down syndrome. Clonal abnormalities were found in 36.9% of the MDS cases and cytogenetic studies were important for the detection of constitutional diseases and for differential diagnosis with other myeloid neoplasms. These data show the importance of the Cooperative Group for continuing education in order to avoid a late or wrong diagnosis.

Familiarity, opinions, experiences and knowledge about scalp cooling: a Dutch survey among breast cancer patients and oncological professionals

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Mijke Peerbooms

2015-01-01

Full Text Available Objective: Scalp cooling (SC is applied to reduce chemotherapy-induced alopecia (CIA. The aim of this study was to investigate patients′ familiarity and opinions and oncological professionals′ attitude and knowledge about SC in the Netherlands. Methods: Ex breast cancer patients, nurses and medical oncologists (MDs from SC and non-SC hospitals filled out questionnaires. Results: The majority of MDs and nurses were satisfied with the results of SC, as were SC patients. Over 33% of MDs and nurses perceived their knowledge level insufficient to inform patients about effectiveness, which was over 43% for information about safety. MDs main reason to not apply SC was doubt about effectiveness and safety. Nurses generally offered SC to a minority of eligible patients. Patients were frequently unfamiliar with SC before diagnosis. Seventy percent of SC patients with insufficient results (20/52 reported to mind it very much. With expected success rates of 35% and 50%, respectively, 36% and 54% of patients would use SC again. Conclusion: Room for improvement has been shown for both patients′ familiarity and oncological professionals′ knowledge about SC. Sharing knowledge about results, safety and patients′ experiences will improve patient counseling and SC availability. The results of this survey led to the development of a national standard on CIA and SC.

NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

DEFF Research Database (Denmark)

Andersen, Morten Tolstrup; Andersen, Mette Klarskov; Christiansen, D.H.

2008-01-01

Frameshift mutations of the nucleophosmin gene (NPM1) were recently reported as a frequently occurring abnormality in patients with de novo acute myeloid leukemia (AML). To evaluate the frequency of NPM1 mutations in patients with therapy-related myelodysplasia (t-MDS) and therapy-related AML (t......-/-7, the most frequent abnormalities of t-MDS/t-AML, were not observed (P=0.002). This raises the question whether some of the cases presenting NPM1 mutations were in fact cases of de novo leukemia. The close association to class I mutations and the inverse association to class II mutations suggest...

Multiparameter flow cytometry reveals myelodysplasia-related aberrant antigen expression in myelodysplastic/myeloproliferative neoplasms.

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Kern, Wolfgang; Bacher, Ulrike; Schnittger, Susanne; Alpermann, Tamara; Haferlach, Claudia; Haferlach, Torsten

2013-05-01

Within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) category of the WHO (2008), only chronic myelomonocytic leukemia was so far evaluated by multiparameter flow cytometry (MFC). To investigate the potential of MFC for MDS/MPNs, unclassifiable (MDS/MPNu), and refractory anemia associated with ring sideroblasts and marked thrombocytosis (RARS-T), we studied 91 patients with these entities (60 males/31 females; 35.3-87.4 years) for MDS-related aberrant immunophenotypes (≥ 2 different cell lineages with ≥ 3 aberrantly expressed antigens). Data were correlated with cytomorphology and cytogenetics. MFC identified MDS-related immunophenotypes in 54/91 (59.3%) of patients. Patients with or without MDS-related immunophenotype did not differ significantly by demographic characteristics, blood values, or median overall survival. MDS-related immunophenotype cases showed a higher number of aberrantly expressed antigens (mean ± SD, 4.9 ± 2.4 vs. 2.0 ± 1.4; P MPNu and RARS-T. MFC therefore may be helpful to separate cases into more "MDS-like" or "MPN-like" subgroups. Copyright © 2012 International Clinical Cytometry Society.

BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders.

Science.gov (United States)

Damm, Frederik; Chesnais, Virginie; Nagata, Yasunobu; Yoshida, Kenichi; Scourzic, Laurianne; Okuno, Yusuke; Itzykson, Raphael; Sanada, Masashi; Shiraishi, Yuichi; Gelsi-Boyer, Véronique; Renneville, Aline; Miyano, Satoru; Mori, Hiraku; Shih, Lee-Yung; Park, Sophie; Dreyfus, François; Guerci-Bresler, Agnes; Solary, Eric; Rose, Christian; Cheze, Stéphane; Prébet, Thomas; Vey, Norbert; Legentil, Marion; Duffourd, Yannis; de Botton, Stéphane; Preudhomme, Claude; Birnbaum, Daniel; Bernard, Olivier A; Ogawa, Seishi; Fontenay, Michaela; Kosmider, Olivier

2013-10-31

Patients with low-risk myelodysplastic syndromes (MDS) that rapidly progress to acute myeloid leukemia (AML) remain a challenge in disease management. Using whole-exome sequencing of an MDS patient, we identified a somatic mutation in the BCOR gene also mutated in AML. Sequencing of BCOR and related BCORL1 genes in a cohort of 354 MDS patients identified 4.2% and 0.8% of mutations respectively. BCOR mutations were associated with RUNX1 (P = .002) and DNMT3A mutations (P = .015). BCOR is also mutated in chronic myelomonocytic leukemia patients (7.4%) and BCORL1 in AML patients with myelodysplasia-related changes (9.1%). Using deep sequencing, we show that BCOR mutations arise after mutations affecting genes involved in splicing machinery or epigenetic regulation. In univariate analysis, BCOR mutations were associated with poor prognosis in MDS (overall survival [OS]: P = .013; cumulative incidence of AML transformation: P = .005). Multivariate analysis including age, International Prognostic Scoring System, transfusion dependency, and mutational status confirmed a significant inferior OS to patients with a BCOR mutation (hazard ratio, 3.3; 95% confidence interval, 1.4-8.1; P = .008). These data suggest that BCOR mutations define the clinical course rather than disease initiation. Despite infrequent mutations, BCOR analyses should be considered in risk stratification.

Immune Mechanisms in Myelodysplastic Syndrome

DEFF Research Database (Denmark)

Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner

2016-01-01

diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients......-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune...... mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS....

Two cases of therapy-related myelodysplastic syndrome after concurrent oral cancer chemoradiotherapy

International Nuclear Information System (INIS)

Doi, Katsuyuki; Asano, Takanori; Kinoshita, Takashi

2010-01-01

Therapy-related myelodysplastic syndrome (t-MDS) and therapy-related leukemia (TRL) are reported increasingly often, and we report two cases of T-MDS after concurrent chemoradiotherapy (CCRT) with oral cancer. Patients underwent CCRT with cisplatin (CDDP) or carboplatin (CBDCA). The interval between primary CCRT and t-MDS was 11 months in 1 case and 14 years in the other. Chromosomal analysis indicated abnormal karyotypes. Platinum has a relatively lower t-MDS risk than alkylating agents or topoisomerase II inhibitors, but our experience supports concurrent use of radiotherapy with platinum affects the risk of t-MDS. If pancytopenia is detected after CCRT, bone marrow and cytogenetic examinations should be conducted to rule out t-MDS. (author)

Determination of boundary layer top on the basis of the characteristics of atmospheric particles

Science.gov (United States)

Liu, Boming; Ma, Yingying; Gong, Wei; Zhang, Ming; Yang, Jian

2018-04-01

The planetary boundary layer (PBL) is the lowest layer of the atmosphere that can be directly influenced with the Earth's surface. This layer can also respond to surface forcing. The determination of the PBL is significant to environmental and climate research. PBL can also serve as an input parameter for further data processing with atmospheric models. Traditional detection algorithms are susceptible to errors associated with the vertical distribution of aerosol concentrations. To overcome this limitation, a maximum difference search (MDS) algorithm was proposed to calculate the top of the boundary layer based on differences in particle characteristics. The top positions of the PBL from MDS algorithm under different convection states were compared with those from conventional methods. Experimental results demonstrated that the MDS method can determine the top of the boundary layer precisely. The proposed algorithm can also be used to calculate the top of the PBL accurately under weak convection conditions where the traditional methods cannot be applied. Finally, experimental data from June 2015 to December 2015 were analysed to verify the reliability of the MDS algorithm. The correlation coefficients R2 (RMSE) between the results of MDS algorithm and radiosonde measurements were 0.53 (115 m), 0.79 (141 m) and 0.96 (43 m) under weak, moderate and strong convections, respectively. These findings indicated that the proposed method possessed a good feasibility and stability.

The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/incision at base damage in eukaryotic cells

International Nuclear Information System (INIS)

Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Kozmin, S.G.; Sedletska, Y.; Reynaud-Angelin, A.; Sage, E.; Gasparutto, D.

2009-01-01

It has been stipulated that repair of clustered DNA lesions may be compromised, possibly leading to the formation of double-strand breaks (DSB) and, thus, to deleterious events. Using a variety of model multiply damaged sites (MDS), we investigated parameters that govern the formation of DSB during the processing of MDS. Duplexes carrying MDS were inserted into replicative or integrative vectors, and used to transform yeast Saccharomyces cerevisiae. Formation of DSB was assessed by a relevant plasmid survival assay. Kinetics of excision/incision and DSB formation at MDS was explored using yeast cell extracts. We show that MDS composed of two uracils or abasic sites, were rapidly incised and readily converted into DSB in yeast cells. In marked contrast, none of the MDS carrying opposed oG and hU separated by 38 bp gave rise to DSB, despite the fact that some of them contained preexisting single-strand break (a 1-nt gap). Interestingly, the absence of DSB formation in this case correlated with slow excision/incision rates of lesions. We propose that the kinetics of the initial repair steps at MDS is a major parameter that direct towards the conversion of MDS into DSB. Data provides clues to the biological consequences of MDS in eukaryotic cells. (authors)

New Options for AV in Telecommunications

Science.gov (United States)

Gelman, Morrie

1974-01-01

A discussion of MDS, a multi-point distribution service which is a recently evolved supplementary telecommunications service that suggests new possibilities for improving the reach, impact and effectiveness of audio-visual communications. (Author)

Temozolomide-Induced Myelodysplasia

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Ethan A. Natelson

2010-01-01

Full Text Available A patient who had received temozolomide (TMZ as a single agent in treatment of malignant glioma developed therapy-induced myelodysplasia (T-MDS. TMZ is an orally active imidazotetrazine which methylates guanine residues in DNA, ultimately causing single and double-strand DNA breaks leading to apoptotic cell death. TMZ does not chemically cross-link DNA and is considered a nonclassical alkylating agent, similar in structure and activity to dacarbazine. Observations on this patient, and on similarly treated others, suggest that the cumulative dose threshold (CDT for TMZ that predisposes to T-MDS and which may potentially lead to acute myeloid leukemia (T-AML is around 18000 to 20000 mg/sq m. Although the incidence of T-MDS and the predisposing CDT of TMZ may differ from that of other potentially leukemogenic compounds currently and formerly used as chemotherapeutic agents, all alkylating agents, including TMZ, should be considered potentially leukemogenic when administered long term.

Information Needs, Infobutton Manager Use, and Satisfaction by Clinician Type: A Case Study

Science.gov (United States)

Collins, Sarah A.; Currie, Leanne M.; Bakken, Suzanne; Cimino, James J.

2009-01-01

To effectively meet clinician information needs at the point of care, we must understand how their needs are dependent on both context and clinician type. The Infobutton Manager (IM), accessed through a clinical information system, anticipates the clinician's questions and provides links to pertinent electronic resources. We conducted an observational usefulness case study of medical residents (MDs), nurse practitioners (NPs), registered nurses (RNs), and a physician assistant (PA), using the IM in a laboratory setting. Generic question types and success rates for each clinician's information needs were characterized. Question type frequency differed by clinician type. All clinician types asked for institution-specific protocols. The MDs asked about unfamiliar domains, RNs asked about physician order rationales, and NPs asked questions similar to both MDs and RNs. Observational data suggest that IM success rates may be improved by tailoring anticipated questions to clinician type. Clinicians reported that a more visible Infobutton may increase use. PMID:18952943

Investigations of aircrews exposure to cosmic radiation - results, conclusions and suggestions

CERN Document Server

Bilski, P; Horwacik, T; Marczewska, B; Ochab, E; Olko, P

2002-01-01

In frame of a research project undertaken in collaboration with Polish airlines LOT, analysis of aircrews exposure to cosmic radiation has been performed. The applied methods included measurements of radiation doses with thermoluminescent detectors (MTS-N, MCP-N) and track detectors (CR-39) and also calculations of route doses with the CARI computer code. The obtained results indicate that aircrews of nearly all airplanes, with exception of these flying only on ATR aircraft, exceed regularly or may exceed in some conditions, effective doses of 1 mSv. In case of Boeing-767 aircrews such exceeding occurs always, independently of solar activity. Investigations revealed, that during these periods of the solar cycle, when intensity of cosmic radiation is high, exceeding of 6 mSv level is also possible. These results indicate, that according to Polish and European regulations it is necessary for airlines to provide regular estimations of radiation exposure of aircrews. Basing on the obtained results a system for pe...

Maternal depression and child BMI: longitudinal findings from a US sample.

Science.gov (United States)

Duarte, C S; Shen, S; Wu, P; Must, A

2012-04-01

To examine the association between maternal depression and child body mass index (BMI) from Kindergarten (K) to fifth grade. Analysis of four waves of data from the Early Childhood Longitudinal Study - Kindergarten spanning K to fifth grade. Maternal depressive symptoms (MDSs) were measured by a brief version of the Center for Epidemiological Studies Depression scale. Data were analyzed using multiple regression analyses, adjusting for key covariates and potential confounders. The analytic sample was restricted to children of normal birth weight. The relationship between MDS and child BMI varies by child gender and age. Among girls, severe MDS at K was related to lower BMI at third grade (but not later at fifth grade) and to an increase in BMI from K to third and K to fifth grades. Among boys, severe MDS at K was related to higher boys' BMI at fifth grade. When severe MDS occurred at third grade, it was related to higher BMI at fifth grade among girls whereas no statistically significant relationship was found for boys. Low levels of physical activity in comparison to peers at fifth grade and more screen time on weekends at third grade are likely mediators of the relationship between MDS and child BMI among girls, while among boys the relationship appears to be mediated by unhealthy eating habits. Our findings, indicating developmental and gender differences in the relationship between maternal depression and child BMI, if confirmed, suggest that interventions addressing maternal depression may have concomitant impact on childhood obesity. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

Hypnotic suggestibility predicts the magnitude of the imaginative word blindness suggestion effect in a non-hypnotic context.

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Parris, Benjamin A; Dienes, Zoltan

2013-09-01

The present study investigated how the magnitude the word blindness suggestion effect on Stroop interference depended on hypnotic suggestibility when given as an imaginative suggestion (i.e. not post-hypnotic suggestion) and under conditions in which hypnosis was not mentioned. Hypnotic suggestibility is shown to be a significant predictor of the magnitude of the imaginative word blindness suggestion effect under these conditions. This is therefore the first study to show a linear relationship between the imaginative word blindness suggestion effect and hypnotic suggestibility across the whole hypnotizability spectrum. The results replicate previous findings showing that highs respond to the word blindness suggestion to a greater extent than lows but extend previous work by showing that the advantage for those higher on the hypnotizability spectrum occurs even in a non-hypnotic context. Negative attitudes about hypnosis may not explain the failure to observe similar effects of the word blindness suggestion in less hypnotizable individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Falls documentation in nursing homes: agreement between the minimum data set and chart abstractions of medical and nursing documentation.

Science.gov (United States)

Hill-Westmoreland, Elizabeth E; Gruber-Baldini, Ann L

2005-02-01

To assess the agreement between falls as recorded in the Minimum Data Set (MDS) and fall events abstracted from chart documentation of elderly nursing home (NH) residents. Secondary analysis of data from a longitudinal panel study. Fifty-six randomly selected NHs in Maryland stratified by facility size and geographic region. Four hundred sixty-two NH residents, aged 65 and older, in NHs for 1 year. Falls were abstracted from resident charts and compared with MDS fall variables. Fall events data obtained from other sources of chart documentation were matched for the corresponding periods of 30 and 180 days before the 1-year MDS assessment date. For a 30-day period, concordance between the MDS and chart abstractions of falls occurred in 65% of cases, with a kappa coefficient of 0.29 (Pfalls the MDS missed indicated that these residents had significantly more activity of daily living impairment and significantly less unsteady gait and cane/walker use. The MDS underreported falls. Nurses completing MDS assessments must carefully review residents' medical records for falls documentation. Future studies should use caution when employing MDS data as the only indicator of falls.

LSD enhances suggestibility in healthy volunteers.

Science.gov (United States)

Carhart-Harris, R L; Kaelen, M; Whalley, M G; Bolstridge, M; Feilding, A; Nutt, D J

2015-02-01

Lysergic acid diethylamide (LSD) has a history of use as a psychotherapeutic aid in the treatment of mood disorders and addiction, and it was also explored as an enhancer of mind control. The present study sought to test the effect of LSD on suggestibility in a modern research study. Ten healthy volunteers were administered with intravenous (i.v.) LSD (40-80 μg) in a within-subject placebo-controlled design. Suggestibility and cued mental imagery were assessed using the Creative Imagination Scale (CIS) and a mental imagery test (MIT). CIS and MIT items were split into two versions (A and B), balanced for 'efficacy' (i.e. A ≈ B) and counterbalanced across conditions (i.e. 50 % completed version 'A' under LSD). The MIT and CIS were issued 110 and 140 min, respectively, post-infusion, corresponding with the peak drug effects. Volunteers gave significantly higher ratings for the CIS (p = 0.018), but not the MIT (p = 0.11), after LSD than placebo. The magnitude of suggestibility enhancement under LSD was positively correlated with trait conscientiousness measured at baseline (p = 0.0005). These results imply that the influence of suggestion is enhanced by LSD. Enhanced suggestibility under LSD may have implications for its use as an adjunct to psychotherapy, where suggestibility plays a major role. That cued imagery was unaffected by LSD implies that suggestions must be of a sufficient duration and level of detail to be enhanced by the drug. The results also imply that individuals with high trait conscientiousness are especially sensitive to the suggestibility-enhancing effects of LSD.

General practitioners' management of mental disorders: A rewarding practice with considerable obstacles

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Fleury Marie-Josée

2012-03-01

Full Text Available Abstract Background Primary care improvement is the cornerstone of current reforms. Mental disorders (MDs are a leading cause of morbidity worldwide and widespread in industrialised countries. MDs are treated mainly in primary care by general practitioners (GPs, even though the latter ability to detect, diagnose, and treat patients with MDs is often considered unsatisfactory. This article examines GPs' management of MDs in an effort to acquire more information regarding means by which GPs deal with MD cases, impact of such cases on their practices, factors that enable or hinder MD management, and patient-management strategies. Methods This study employs a mixed-method approach with emphasis on qualitative investigation. Based on a previous survey of 398 GPs in Quebec, Canada, 60 GPs representing a variety of practice settings were selected for further study. A 10-minute-long questionnaire comprising 27 items was administered, and 70-minute-long interviews were conducted. Quantitative (SPSS and qualitative (NVivo analyses were performed. Results At least 20% of GP visits were MD-related. GPs were comfortable managing common MDs, but not serious MDs. GPs' based their treatment of MDs on pharmacotherapy, support therapy, and psycho-education. They used clinical intuition with few clinical tools, and closely followed their patients with MDs. Practice features (salary or hourly fees payment; psycho-social teams on-site; strong informal networks, and GPs' individual characteristics (continuing medical education; exposure and interest in MDs; traits like empathy favoured MD management. Collaboration with psychologists and psychiatrists was considered key to good MD management. Limited access to specialists, system fragmentation, and underdeveloped group practice and shared-care models were impediments. MD management was seen as burdensome because it required more time, flexibility, and emotional investment. Strategies exist to reduce the burden (one

Perception and attitude of medical doctors in Dhaka, Bangladesh, with regard to Ayurvedic medicine.

Science.gov (United States)

Yoshida, Yoshitoku; Alim, Md Abdul; Alam, Zakia; Asaduzzaman, Mohammad; Yoshida, Yasuko; Manikdrs, Shahabuddin

2017-02-01

The World Health Organization (WHO) Traditional Medicine Strategy (2014-2023) aimed to help member states promote the safe and effective use of traditional medicine. While economic conditions have markedly improved in Bangladesh, the country is experiencing significant public health problems. Because of limited medical resources, there is a strong incentive to enhance complementary and alternative medicine usage in Bangladesh. Therefore, this study aimed to confirm the perceptions and attitudes of medical doctors (MDs) in Dhaka, Bangladesh, with regard to Ayurvedic medicine (AM). A total number of 159 MDs in Dhaka were interviewed by face-to-face between February and June 2015. The study revealed that 62.0% of MDs had treated patients with AM and 55.3% believed that AM should be regarded as its own specialty, whereas 39.7% of MDs believed that AM should be part of the conventional medical curriculum and 32.7% thought that AM did not seem scientific. In terms of gender, 45.3% of male MDs agreed or strongly agreed that AM only had a placebo effect. On the other hand, 65.8% of female MDs disagreed or strongly disagreed it. In terms of age, 77.0% of MDs aged 36 or elder (elder MDs) believed they were more likely to recommend AM use and 80.3% of elder MDs believed that the government should encourage more initiatives to promote AM. To enhance AM use, scientifically robust information on the efficacy, safety and scientific basis of AM should be more effectively conveyed to male MDs.

Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

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Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L. [Department of Hematology, Shanghai Clinical Research Center, Chinese Academy of Sciences, Shanghai Xuhui District Central Hospital, Shanghai (China)

2015-01-20

The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS.

Cytokine expression patterns and mesenchymal stem cell karyotypes from the bone marrow microenvironment of patients with myelodysplastic syndromes

International Nuclear Information System (INIS)

Xiong, H.; Yang, X.Y.; Han, J.; Wang, Q.; Zou, Z.L.

2015-01-01

The purpose of this study was to explore cytokine expression patterns and cytogenetic abnormalities of mesenchymal stem cells (MSCs) from the bone marrow microenvironment of Chinese patients with myelodysplastic syndromes (MDS). Bone marrow samples were obtained from 30 cases of MDS (MDS group) and 30 healthy donors (control group). The expression pattern of cytokines was detected by customized protein array. The karyotypes of MSCs were analyzed using fluorescence in situ hybridization. Compared with the control group, leukemia inhibitory factor, stem cell factor (SCF), stromal cell-derived factor (SDF-1), bone morphogenetic protein 4, hematopoietic stem cell (HSC) stimulating factor, and transforming growth factor-β in the MDS group were significantly downregulated (P<0.05), while interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and programmed death ligand (B7-H1) were significantly upregulated (P<0.05). For chromosome abnormality analysis, the detection rate of abnormal karyotypes (+8, -8, -20, 20q-, -Y, -7, 5q-) was 30% in the MDS group and 0% in the control group. In conclusion, the up- and downregulated expression of these cytokines might play a key role in the pathogenesis of MDS. Among them, SCF and SDF-1 may play roles in the apoptosis of HSCs in MDS; and IFN-γ, TNF-α, and B7-H1 may be associated with apoptosis of bone marrow cells in MDS. In addition, the abnormal karyotypes might be actively involved in the pathogenesis of MDS. Further studies are required to determine the role of abnormal karyotypes in the occurrence and development of MDS

[Characteristic and function of peripheral blood mononuclear cells-induced macrophages in patients with myelodysplastic syndrome].

Science.gov (United States)

Han, Y; Wang, H Q; Fu, R; Qu, W; Ruan, E B; Wang, X M; Wang, G J; Wu, Y H; Liu, H; Song, J; Guan, J; Xing, L M; Li, L J; Jiang, H J; Liu, H; Wang, Y H; Liu, C Y; Zhang, W; Shao, Z H

2017-08-14

Objective: To explore characteristic and function of peripheral blood mononuclear cells (PBMNC) -induced macrophages in patients with myelodysplastic syndrome (MDS) to couple with its progression. Methods: A total of 24 MDS patients (11 low-risk patients and 13 high-risk group patients) referred to Department of Hematology of Tianjin Medical University General Hospital and normal controls were enrolled from September 2014 to December 2015. PBMNC was stimulated with GM-CSF to transform to macrophages. The morphology of macrophages was observed by microscope. The quantity of macrophages, CD206 and SIRPα on surface of macrophages were detected by flow cytometry. The phagocytic function of macrophages was analyzed by fluorescence microscopy and flow cytometry. Results: The morphology of macrophages from MDS patients was abnormal. The percentage of transformed macrophages was (5.17±3.47) % in patients with MDS, which was lower than that in controls significantly[ (66.18±13.43) %, t =3.529, P =0.001]. The expression of CD206 on macrophages from MDS patients was significantly lower than that of controls[ (9.73±2.59) % vs (51.15±10.82) %, t =4.551, P patients was significantly lower than that of controls [ (0.51±0.09) % vs (0.77±0.06) %, t =2.102, P =0.043]. The phagocytic index and the percentage of phagocytic of macrophages from MDS patients were significantly lower than those of macrophages from normal controls[0.45±0.08 vs 0.92±0.07, t =-6.253, P =0.008; (23.69±3.22) % vs (42.75±2.13) %, t =-6.982, P =0.006 respectively]by flow cytometry. The phagocytic index of MDS patients was significantly lower than that of controls (0.24±0.04 vs 0.48±0.96, t =3.464, P =0.001) by fluorescence microscopy. Conclusion: The quantity, recognization receptors and phagocytosis of PBMNC-induced macrophages decreased in MDS patients.

657del5 mutation of the NBS1 gene in myelodysplastic syndrome

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Bunjevacki Vera

2014-01-01

Full Text Available Myelodysplastic syndromes (MDS are clonal hematologic stem cell disorders with an as yet unknown molecular pathology. Genetic instability has been proposed as a cause of MDS. Mutations in the NBS1 gene, whose product nibrin (p95 is involved in DNA damage repair and cell-cycle control, might be associated with an elevated predisposition to the development of MDS. The aim of the study was to examine truncating 5 bp deletion (657del5, the most frequent NBS1 gene mutation in Slavic populations, in MDS patients. Among 71 MDS patients, we found one case that was heterozygous for the NBS1 657del5 mutation. To the best of our knowledge, this is the first report of a NBS1 mutation in MDS. [Projekat Ministarstva nauke Republike Srbije, br. 175091

The influence of suggestibility on memory.

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Nicolas, Serge; Collins, Thérèse; Gounden, Yannick; Roediger, Henry L

2011-06-01

We provide a translation of Binet and Henri's pioneering 1894 paper on the influence of suggestibility on memory. Alfred Binet (1857-1911) is famous as the author who created the IQ test that bears his name, but he is almost unknown as the psychological investigator who generated numerous original experiments and fascinating results in the study of memory. His experiments published in 1894 manipulated suggestibility in several ways to determine effects on remembering. Three particular modes of suggestion were employed to induce false recognitions: (1) indirect suggestion by a preconceived idea; (2) direct suggestion; and (3) collective suggestion. In the commentary we suggest that Binet and Henri's (1894) paper written over 115 years ago is still highly relevant even today. In particular, Binet's legacy lives on in modern research on misinformation effects in memory, in studies of conformity, and in experiments on the social contagion of memory. Copyright © 2010 Elsevier Inc. All rights reserved.

A methodology for a minimum data set for rare diseases to support national centers of excellence for healthcare and research

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Choquet, Rémy; Maaroufi, Meriem; de Carrara, Albane; Messiaen, Claude; Luigi, Emmanuel; Landais, Paul

2015-01-01

Background Although rare disease patients make up approximately 6–8% of all patients in Europe, it is often difficult to find the necessary expertise for diagnosis and care and the patient numbers needed for rare disease research. The second French National Plan for Rare Diseases highlighted the necessity for better care coordination and epidemiology for rare diseases. A clinical data standard for normalization and exchange of rare disease patient data was proposed. The original methodology used to build the French national minimum data set (F-MDS-RD) common to the 131 expert rare disease centers is presented. Methods To encourage consensus at a national level for homogeneous data collection at the point of care for rare disease patients, we first identified four national expert groups. We reviewed the scientific literature for rare disease common data elements (CDEs) in order to build the first version of the F-MDS-RD. The French rare disease expert centers validated the data elements (DEs). The resulting F-MDS-RD was reviewed and approved by the National Plan Strategic Committee. It was then represented in an HL7 electronic format to maximize interoperability with electronic health records. Results The F-MDS-RD is composed of 58 DEs in six categories: patient, family history, encounter, condition, medication, and questionnaire. It is HL7 compatible and can use various ontologies for diagnosis or sign encoding. The F-MDS-RD was aligned with other CDE initiatives for rare diseases, thus facilitating potential interconnections between rare disease registries. Conclusions The French F-MDS-RD was defined through national consensus. It can foster better care coordination and facilitate determining rare disease patients’ eligibility for research studies, trials, or cohorts. Since other countries will need to develop their own standards for rare disease data collection, they might benefit from the methods presented here. PMID:25038198

Measuring change in activities of daily living in nursing home residents with moderate to severe cognitive impairment

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Fries Brant E

2006-04-01

Full Text Available Abstract Background The objective of this study was to assess the responsiveness of the Minimum Data Set Activities of Daily Living (MDS-ADL Scale to change over time by examining the change in physical function in adults with moderate to severe dementia with no comorbid illness who had been resident in a nursing home for over 90 days. Methods Longitudinal data were collected on nursing home residents with moderate (n = 7001 or severe (n = 4616 dementia in one US state from the US national Minimum Data Set (MDS. Severity of dementia was determined by the MDS Cognitive Performance Scale (CPS. Physical function was assessed by summing the seven items (bed mobility, transfer, locomotion, dressing, eating, toilet use, personal hygiene on the MDS activities of daily living (ADL Long Form scale. Mean change over time of MDS-ADL scores were estimated at three and six months for residents with moderate (CPS score of 3 and severe (CPS score of 4 or 5 dementia. Results Physical function in residents with moderate cognitive impairment deteriorated over six months by an average of 1.78 points on the MDS-ADL Long Form scale, while those with severe cognitive impairment declined by an average of 1.70 points. Approximately one quarter of residents in both groups showed some improvement in physical function over the six month period. Residents with moderate cognitive impairment experienced the greatest deterioration in early-loss and mid-loss ADL items (personal hygiene, dressing, toilet use and residents with severe cognitive impairment showed the greatest deterioration in activities related to eating, a late loss ADL. Conclusion The MDS-ADL Long Form scale detected clinically meaningful change in physical function in a large cohort of long-stay nursing home residents with moderate to severe dementia, supporting its use as a research tool in future studies.

Measuring change in activities of daily living in nursing home residents with moderate to severe cognitive impairment

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Carpenter, G Iain; Hastie, Charlotte L; Morris, John N; Fries, Brant E; Ankri, Joel

2006-01-01

Background The objective of this study was to assess the responsiveness of the Minimum Data Set Activities of Daily Living (MDS-ADL) Scale to change over time by examining the change in physical function in adults with moderate to severe dementia with no comorbid illness who had been resident in a nursing home for over 90 days. Methods Longitudinal data were collected on nursing home residents with moderate (n = 7001) or severe (n = 4616) dementia in one US state from the US national Minimum Data Set (MDS). Severity of dementia was determined by the MDS Cognitive Performance Scale (CPS). Physical function was assessed by summing the seven items (bed mobility, transfer, locomotion, dressing, eating, toilet use, personal hygiene) on the MDS activities of daily living (ADL) Long Form scale. Mean change over time of MDS-ADL scores were estimated at three and six months for residents with moderate (CPS score of 3) and severe (CPS score of 4 or 5) dementia. Results Physical function in residents with moderate cognitive impairment deteriorated over six months by an average of 1.78 points on the MDS-ADL Long Form scale, while those with severe cognitive impairment declined by an average of 1.70 points. Approximately one quarter of residents in both groups showed some improvement in physical function over the six month period. Residents with moderate cognitive impairment experienced the greatest deterioration in early-loss and mid-loss ADL items (personal hygiene, dressing, toilet use) and residents with severe cognitive impairment showed the greatest deterioration in activities related to eating, a late loss ADL. Conclusion The MDS-ADL Long Form scale detected clinically meaningful change in physical function in a large cohort of long-stay nursing home residents with moderate to severe dementia, supporting its use as a research tool in future studies. PMID:16584565

The experience of caregivers of people living with serious mental disorders: a study from rural Ghana

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Kenneth Ayuurebobi Ae-Ngibise

2015-05-01

Full Text Available Background: Families and friends who give care to people with mental disorders (MDs are affected in a variety of ways and degrees. The interplay of caregiving consequences: poverty, discrimination and stigma, lack of support from others, diminished social relationships, depression, emotional trauma, and poor or interrupted sleep are associated caregiver burden. Objective: The burden of care on caregivers of people living with MDs was assessed in two districts located in the middle part of Ghana. Coping strategies and available support for caregivers of MDs were also assessed. Design: A qualitative study was carried out involving 75 caregivers of participants with MDs registered within the Kintampo Health and Demographic Surveillance Systems. Data were gathered from caregivers about their experiences in providing care for their relations with MDs. Results: Caregivers reported various degrees of burden, which included financial, social exclusion, emotional, depression, and inadequate time for other social responsibilities. Responsibilities around caregiving were mostly shared among close relatives but to a varying and limited extent. Religious prayers and the anticipation of cure were the main coping strategies adopted by caregivers, with expectation of new treatments being discovered. Conclusions: Emotional distress, stigma, financial burden, lack of support networks, social exclusion, health impact, and absence of decentralised mental health services were experienced by family caregivers. These findings highlight the need for interventions to support people with MDs and their caregivers. This might include policy development and implementation that will decentralise mental health care provision including psychosocial support for caregivers. This will ameliorate families’ financial and emotional burden, facilitate early diagnosis and management, reduce travel time to seek care, and improve the quality of life of family caregivers of persons

Maternal depressive symptoms are negatively associated with child growth and development: Evidence from rural India.

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Nguyen, Phuong Hong; Friedman, Jed; Kak, Mohini; Menon, Purnima; Alderman, Harold

2018-05-17

Maternal depression has been suggested as a risk factor for both poor child growth and development in many low- and middle-income countries, but the validity of many studies is hindered by small sample sizes, varying cut-offs used in depression diagnostics, and incomplete control of confounding factors. This study examines the association between maternal depressive symptoms (MDSs) and child physical growth and cognitive development in Madhya Pradesh, India, where poverty, malnutrition, and poor mental health coexist. Data were from a baseline household survey (n = 2,934) of a randomized controlled trial assessing an early childhood development programme. Multivariate linear and logistic regression analyses were conducted, adjusting for socio-economic factors to avoid confounding the association of mental health and child outcomes. MDS (measured using the Center for Epidemiologic Studies Short Depression Scale) was categorized as low, medium, and high in 47%, 42%, and 10% of mothers, respectively. The prevalence of child developmental delay ranged from 16% to 27% for various development domains. Compared with children of mothers with low MDS, those of high MDS mothers had lower height-for-age, weight-for-age, and weight-for-height z-scores (0.22, 0.21, and 0.15, respectively), a higher rate of stunting and underweight (~1.5 times), and higher rate of developmental delay (partial adjusted odds ratio ranged from 1.3-1.8 for different development domains and fully adjusted odds ratio = 1.4 for fine motor). Our results-that MDS is significantly associated with both child undernutrition and development delay-add to the call for practical interventions to address maternal depression to simultaneously address multiple outcomes for both women and children. © 2018 The Authors. Maternal & Child Nutrition Published by John Wiley & Sons, Ltd.

Open to Suggestion.

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Journal of Reading, 1987

1987-01-01

Offers (1) suggestions for improving college students' study skills; (2) a system for keeping track of parent, teacher, and community contacts; (3) suggestions for motivating students using tic tac toe; (4) suggestions for using etymology to improve word retention; (5) a word search grid; and (6) suggestions for using postcards in remedial reading…

The biology of myelodysplastic syndromes: unity despite heterogeneity

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Azra Raza

2010-06-01

Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

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Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

2013-03-01

Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS. © 2012 John Wiley & Sons A/S.

Myelodysplastic Syndromes (MDS)

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... talk about donating their baby's cord blood College football player stays true to his commitment Be the ... appointment, the transplant doctor will: Review your medical history Talk with you about your treatment options Discuss ...

MDS Quality Measures

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U.S. Department of Health & Human Services — A list of the quality measures displayed on Nursing Home Compare, excluding Measures of Rehospitalization, Emergency Room Visit, and Community Discharge. Each row...

Validation of the Italian version of the Movement Disorder Society--Unified Parkinson's Disease Rating Scale.

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Antonini, Angelo; Abbruzzese, Giovanni; Ferini-Strambi, Luigi; Tilley, Barbara; Huang, Jing; Stebbins, Glenn T; Goetz, Christopher G; Barone, Paolo; Bandettini di Poggio, Monica; Fabbrini, Giovanni; Di Stasio, Flavio; Tinazzi, Michele; Bovi, Tommaso; Ramat, Silvia; Meoni, Sara; Pezzoli, Gianni; Canesi, Margherita; Martinelli, Paolo; Maria Scaglione, Cesa Lorella; Rossi, Aroldo; Tambasco, Nicola; Santangelo, Gabriella; Picillo, Marina; Morgante, Letterio; Morgante, Francesca; Quatrale, Rocco; Sensi, MariaChiara; Pilleri, Manuela; Biundo, Roberta; Nordera, Giampietro; Caria, Antonella; Pacchetti, Claudio; Zangaglia, Roberta; Lopiano, Leonardo; Zibetti, Maurizio; Zappia, Mario; Nicoletti, Alessandra; Quattrone, Aldo; Salsone, Maria; Cossu, Gianni; Murgia, Daniela; Albanese, Alberto; Del Sorbo, Francesca

2013-05-01

The Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has been available in English since 2008. As part of this process, the MDS-UPDRS organizing team developed guidelines for development of official non-English translations. We present here the formal process for completing officially approved non-English versions of the MDS-UPDRS and specifically focus on the first of these versions in Italian. The MDS-UPDRS was translated into Italian and tested in 377 native-Italian speaking PD patients. Confirmatory and exploratory factor analyses determined whether the factor structure for the English-language MDS-UPDRS could be confirmed in data collected using the Italian translation. To be designated an 'Official MDS translation,' the Comparative Fit Index (CFI) had to be ≥0.90 relative to the English-language version. For all four parts of the Italian MDS-UPDRS, the CFI, in comparison with the English-language data, was ≥0.94. Exploratory factor analyses revealed some differences between the two datasets, however these differences were considered to be within an acceptable range. The Italian version of the MDS-UPDRS reaches the criterion to be designated as an Official Translation and is now available for use. This protocol will serve as outline for further validation of this in multiple languages.

Alternate Mediterranean diet score is positively associated with skeletal muscle mass index in middle-aged adults.

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Tian, Hui-Yuan; Qiu, Rui; Jing, Li-Peng; Chen, Zhan-Yong; Chen, Geng-Dong; Chen, Yu-Ming

2017-04-01

Researches have suggested Mediterranean diet might lower the risk of chronic diseases, but data on skeletal muscle mass (SMM) are limited. This community-based cross-sectional study examined the association between the alternate Mediterranean diet score (aMDS) and SMM in 2230 females and 1059 males aged 40-75 years in Guangzhou, China. General information and habitual dietary information were assessed in face-to-face interviews conducted during 2008-2010 and 3 years later. The aMDS was calculated by summing the dichotomous points for the items of higher intakes of whole grain, vegetables, fruits, legumes, nuts, fish and ratio of MUFA:SFA, lower red meat and moderate ethanol consumption. The SMM of the whole body, limbs, arms and legs were measured using dual-energy X-ray absorptiometry during 2011-2013. After adjusting for potential covariates, higher aMDS was positively associated with skeletal muscle mass index (SMI, SMM/height2, kg/m2) at all of the studied sites in males (all P trend0·05). Age-stratified analyses showed that the favourable associations tended to be more pronounced in the younger subjects aged less than the medians of 59·2 and 62·2 years in females and males (P interaction>0·10). In conclusion, the aMDS shows protective associations with SMM in Chinese adults, particularly in male and younger subjects.

Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis—Masters of Survival and Clonality?

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Pleyer, Lisa; Valent, Peter; Greil, Richard

2016-01-01

Myelodysplastic syndromes (MDS) are malignant hematopoietic stem cell disorders that have the capacity to progress to acute myeloid leukemia (AML). Accumulating evidence suggests that the altered bone marrow (BM) microenvironment in general, and in particular the components of the stem cell niche, including mesenchymal stem cells (MSCs) and their progeny, play a pivotal role in the evolution and propagation of MDS. We here present an overview of the role of MSCs in the pathogenesis of MDS, with emphasis on cellular interactions in the BM microenvironment and related stem cell niche concepts. MSCs have potent immunomodulatory capacities and communicate with diverse immune cells, but also interact with various other cellular components of the microenvironment as well as with normal and leukemic stem and progenitor cells. Moreover, compared to normal MSCs, MSCs in MDS and AML often exhibit altered gene expression profiles, an aberrant phenotype, and abnormal functional properties. These alterations supposedly contribute to the “reprogramming” of the stem cell niche into a disease-permissive microenvironment where an altered immune system, abnormal stem cell niche interactions, and an impaired growth control lead to disease progression. The current article also reviews molecular targets that play a role in such cellular interactions and possibilities to interfere with abnormal stem cell niche interactions by using specific targeted drugs. PMID:27355944

Longitudinal beam parameters and quality checks of the LHC beam in the SPS: further results and comparisons

CERN Document Server

Papotti, G; Linnecar, T; Shaposhnikova, E; Tückmantel, Joachim; CERN. Geneva. AB Department

2008-01-01

Controlled longitudinal emittance blow up is used, along with other measures, to stabilize the nominal LHC beam in the SPS. Two Machine Development studies (MDs) were carried out in 2007 to evaluate the effectiveness of different noise settings for the longitudinal blow up of the beam. The noise settings are affected by both the presence of the 800 MHz RF system and intensity effects which modify the synchrotron frequency distribution inside the bunch. The results for the first MD are reported in Note [1]. This Note reports on the results of the second MD, carried out on 2007-10-17, as well as the comparison between the two in order to analyse the differences between the two occasions. Figures of merit are used that allow rapid evaluation of the quality of the beam as for example stability and bunch length uniformity across batches.

Are You Suggesting That's My Hand? The Relation Between Hypnotic Suggestibility and the Rubber Hand Illusion.

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Walsh, E; Guilmette, D N; Longo, M R; Moore, J W; Oakley, D A; Halligan, P W; Mehta, M A; Deeley, Q

2015-01-01

Hypnotic suggestibility (HS) is the ability to respond automatically to suggestions and to experience alterations in perception and behavior. Hypnotically suggestible participants are also better able to focus and sustain their attention on an experimental stimulus. The present study explores the relation between HS and susceptibility to the rubber hand illusion (RHI). Based on previous research with visual illusions, it was predicted that higher HS would lead to a stronger RHI. Two behavioral output measures of the RHI, an implicit (proprioceptive drift) and an explicit (RHI questionnaire) measure, were correlated against HS scores. Hypnotic suggestibility correlated positively with the implicit RHI measure contributing to 30% of the variation. However, there was no relation between HS and the explicit RHI questionnaire measure, or with compliance control items. High hypnotic suggestibility may facilitate, via attentional mechanisms, the multisensory integration of visuoproprioceptive inputs that leads to greater perceptual mislocalization of a participant's hand. These results may provide insight into the multisensory brain mechanisms involved in our sense of embodiment.

Longitudinal Analysis of DNA Methylation in CD34+ Hematopoietic Progenitors in Myelodysplastic Syndrome

DEFF Research Database (Denmark)

Wong, Yan Fung; Micklem, Chris N; Taguchi, Masataka

2014-01-01

Myelodysplastic syndrome (MDS) is a disorder of hematopoietic stem cells (HSCs) that is often treated with DNA methyltransferase 1 (DNMT1) inhibitors (5-azacytidine [AZA], 5-aza-2'-deoxycytidine), suggesting a role for DNA methylation in disease progression. How DNMT inhibition retards disease...... regulators not expressed within the hematopoietic compartment and was distinct from that observed between healthy hematopoietic cell types. After AZA treatment, we observed only limited DNA demethylation at sites that varied between patients. This suggests that a subset of the stem cell population...... is resistant to AZA and provides a basis for disease relapse. Using gene expression data from patient samples and an in vitro AZA treatment study, we identified differentially methylated genes that can be activated following treatment and that remain silent in the CD34+ stem cell compartment of high-risk MDS...

Clinicopathological associations of acquired erythroblastopenia.

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Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

2015-01-01

Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated.

Factor structure of suggestibility revisited: new evidence for direct and indirect suggestibility

OpenAIRE

Romuald Polczyk

2016-01-01

Background Yielding to suggestions can be viewed as a relatively stable individual trait, called suggestibility. It has been long proposed that there are two kinds of suggestible influence, and two kinds of suggestibility corresponding to them: direct and indirect. Direct suggestion involves overt unhidden influence, while indirect suggestion concerns influence that is hidden, and the participant does not know that the suggestibility is being measured. So far however, empirical evidence ...

HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study.

Science.gov (United States)

De Souza, Geane Felix; Ribeiro, Howard Lopes; De Sousa, Juliana Cordeiro; Heredia, Fabíola Fernandes; De Freitas, Rivelilson Mendes; Martins, Manoel Ricardo Alves; Gonçalves, Romélia Pinheiro; Pinheiro, Ronald Feitosa; Magalhães, Silvia Maria Meira

2015-04-03

A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011. IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry. The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions. We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress

Genes that bias Mendelian segregation.

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Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

2014-01-01

Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

Radiotherapy- and Chemotherapy-Induced Myelodysplasia Syndrome

Science.gov (United States)

Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

2015-01-01

Abstract This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT). We performed a nested case–control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33–1.77; CT: OR = 1.51; 95% CI = 1.25–1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details. This population-based nested case–control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used. PMID:25929909

Radiotherapy- and chemotherapy-induced myelodysplasia syndrome: a nationwide population-based nested case-control study.

Science.gov (United States)

Sun, Li-Min; Lin, Cheng-Li; Lin, Ming-Chia; Liang, Ji-An; Kao, Chia-Hung

2015-05-01

This study explored which kinds of cancer are related to a higher incidence of subsequent myelodysplastic syndrome (MDS) after radiotherapy (RT) and chemotherapy (CT).We performed a nested case-control study by using data from the Taiwanese National Health Insurance (NHI) system. The case group included cancer patients who developed MDS. For the control group, 4 cancer patients without MDS were frequency-matched with each MDS case by age, sex, year of cancer diagnosis, and MDS index year. A multivariable logistic regression analysis was conducted, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.Overall, cancer patients who received RT or CT exhibited secondary MDS more frequently than did those who did not (RT: OR = 1.53; 95% CI = 1.33-1.77; CT: OR = 1.51; 95% CI = 1.25-1.82). Analysis by cancer site showed that RT increased the risk of MDS for patients with stomach, colorectal, liver, breast, endometrial, prostate, and kidney cancers. By contrast, CT was more likely to increase the risk of MDS for patients with lung, endometrial, and cervical cancers. Further analysis revealed that RT and CT seemed to have a positive interaction. The major limitation of this study was the lack of certain essential data in the NHI Research Database, such as data regarding cancer stage and treatment dose details.This population-based nested case-control study determined that RT and CT predisposed patients in Taiwan to the development of MDS. This effect was more prominent when both modalities were used.

The Effect of Memory Trace Strength on Suggestibility.

Science.gov (United States)

Pezdek, Kathy; Roe, Chantal

1995-01-01

Examined the conditions under which children's memory is resistant to suggestibility versus vulnerable to suggestibility. Results suggest that children have more accurate memory for an event that occurred to them frequently, and that they are less vulnerable to suggestive influences such as biased interviewing procedures than they would be for an…

Effects of Counselor Facilitative Level on Client Suggestibility

Science.gov (United States)

Murphy, Harry B.; Rowe, Wayne

1977-01-01

University students (N=48) were individually tested for suggestibility in one of three conditions. Results indicated subjects of higher rated experimenters would demonstrate more suggestibility than subjects of lower rated experimenters. Results did not indicate that subject interaction with lower rated experimenters would elicit less…

The relationships between suggestibility, influenceability, and relaxability.

Science.gov (United States)

Polczyk, Romuald; Frey, Olga; Szpitalak, Malwina

2013-01-01

This research explores the relationships between relaxability and various aspects of suggestibility and influenceability. The Jacobson Progressive Muscle Relaxation procedure was used to induce relaxation. Tests of direct suggestibility, relating to the susceptibility of overt suggestions, and indirect suggestibility, referring to indirect hidden influence, as well as self-description questionnaires on suggestibility and the tendency to comply were used. Thayer's Activation-Deactivation Adjective Check List, measuring various kinds of activation and used as a pre- and posttest, determined the efficacy of the relaxation procedure. Indirect, direct, and self-measured suggestibility proved to be positively related to the ability to relax, measured by Thayer's subscales relating to emotions. Compliance was not related to relaxability. The results are discussed in terms of the aspects of relaxation training connected with suggestibility.

Meeting report: Vienna 2008 Workshop of the German–Austrian Working Group for Studying Prognostic Factors in Myelodysplastic Syndromes

OpenAIRE

Valent , Peter; Hofmann , Wolf-Karsten; Büsche , Guntram; Sotlar , Karl; Horny , Hans-Peter; Haase , Detlef; Haferlach , Torsten; Kern , Wolfgang; Bettelheim , Peter; Baumgartner , Christian; Sperr , Wolfgang R.; Nösslinger , Thomas; Wimazal , Friedrich; Giagounidis , Aristoteles A.; Lübbert , Michael

2009-01-01

Abstract Criteria, scoring systems, and treatment algorithms for myelodysplastic syndromes (MDS) have been updated repeatedly in recent years. This apparently results from increased awareness and early recognition of the disease, an increasing number of new diagnostic and prognostic markers and tools, and new therapeutic options that may change the course and thus prognosis in MDS. To address these challenges and to create useful new diagnostic and prognostic parameters and scores,...

Study of RpI22 in MDS and AML

Science.gov (United States)

2016-12-01

developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22þ/þ control mice. But, unlike Rpl22þ/þ or Rpl22þ...hypoxia (31). Alternatively, we did not observe obvious necrosis in the center of the large thymic tumors from Rpl22-deficent mice, suggesting Rpl22...Orthop Res 2004;22:1175–81. 32. Loeffler S, Fayard B, Weis J, Weissenberger J. Interleukin-6 induces tran- scriptional activation of vascular endothelial

Measuring Children's Suggestibility in Forensic Interviews.

Science.gov (United States)

Volpini, Laura; Melis, Manuela; Petralia, Stefania; Rosenberg, Melina D

2016-01-01

According to the scientific literature, childrens' cognitive development is not complete until adolescence. Therefore, the problems inherent in children serving as witnesses are crucial. In preschool-aged children, false memories may be identified because of misinformation and insight bias. Additionally, they are susceptible of suggestions. The aim of this study was to verify the levels of suggestibility in children between three and 5 years of age. Ninety-two children were examined (44 male, 48 female; M = 4.5 years, SD = 9.62). We used the correlation coefficient (Pearson's r) and the averages variance by SPSS statistical program. The results concluded that: younger children are almost always more susceptible to suggestibility. The dimension of immediate recall was negatively correlates with that of total suggestibility (r = -0.357 p suggestibility, because older children shift their answers more often (r = 0.394 p < 0.001). Younger children change their answers more times (r = -0.395 p < 0.001). © 2016 American Academy of Forensic Sciences.

Suggestibility and negative priming: two replication studies.

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David, Daniel; Brown, Richard J

2002-07-01

Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

Multidimensional Scaling for Orthodontic Root Resorption

Directory of Open Access Journals (Sweden)

Cristina Teodora Preoteasa

2013-01-01

Full Text Available The paper investigates the risk factors for the severity of orthodontic root resorption. The multidimensional scaling (MDS visualization method is used to investigate the experimental data from patients who received orthodontic treatment at the Department of Orthodontics and Dentofacial Orthopedics, Faculty of Dentistry, “Carol Davila” University of Medicine and Pharmacy, during a period of 4 years. The clusters emerging in the MDS plots reveal features and properties not easily captured by classical statistical tools. The results support the adoption of MDS for tackling the dentistry information and overcoming noise embedded into the data. The method introduced in this paper is rapid, efficient, and very useful for treating the risk factors for the severity of orthodontic root resorption.

Should elderly patients with higher-risk myelodysplastic syndromes undergo allogeneic hematopoietic stem cell transplantation?

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Zeidan, Amer M; Gore, Steven D

2013-10-01

Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies characterized by dysplastic changes, ineffective hematopoiesis and variable risk of leukemic progression. At diagnosis, 86% of MDS patients are ≥60 years. Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients, adds a median of only 9.5 months to life. Allogeneic stem cell transplantation (alloSCT) remains the only potentially curative approach. Despite recent improvements including use of reduced intensity conditioning (RIC) that decrease transplant-related mortality, alloSCT continues to be used rarely in elderly MDS. There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS patients, especially in direct comparison with azanucleosides. In this paper, the authors discuss the recent Markov decision analysis by Koreth et al. in which investigators demonstrated superior survival of patients with HR-MDS aged 60-70 years who underwent RIC alloSCT in comparison with those who were treated with azanucleosides.

Fundamentals of applied multidimensional scaling for educational and psychological research

CERN Document Server

Ding, Cody S

2018-01-01

This book explores the fundamentals of multidimensional scaling (MDS) and how this analytic method can be used in applied setting for educational and psychological research. The book tries to make MDS more accessible to a wider audience in terms of the language and examples that are more relevant to educational and psychological research and less technical so that the readers are not overwhelmed by equations. The goal is for readers to learn the methods described in this book and immediately start using MDS via available software programs. The book also examines new applications that have previously not been discussed in MDS literature. It should be an ideal book for graduate students and researchers to better understand MDS. Fundamentals of Applied Multidimensional Scaling for Educational and Psychological Research is divided into three parts. Part I covers the basic and fundamental features of MDS models pertaining to applied research applications. Chapters in this section cover the essential features of da...

Impaired Expression of Focal Adhesion Kinase in Mesenchymal Stromal Cells from Low-Risk Myelodysplastic Syndrome Patients

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Yuenv Wu

2017-08-01

Full Text Available The pathogenic role of mesenchymal stromal cells (MSCs in myelodysplastic syndromes (MDS development and progression has been investigated by numerous studies, yet, it remains controversial in some aspects (1, 2. In the present study, we found distinct features of MSCs from low-risk (LR-MDS stromal microenvironment as compared to those from healthy subjects. At the molecular level, focal adhesion kinase, a key tyrosine kinase in control of cell proliferation, survival, and adhesion process, was found profoundly suppressed in expression and activation in LR-MDS MSC. At a functional level, LR-MDS MSCs showed impaired growth and clonogenic capacity, which were independent of cellular senescence and apoptosis. The pro-adipogenic differentiation and attenuated osteogenic capacity along with reduced SDF-1 expression could be involved in creating an unfavorable microenvironment for hematopoiesis. In conclusion, our experiments support the theory that the stromal microenvironment is fundamentally altered in LR-MDS, and these preliminary data offer a new perspective on LR-MDS pathophysiology.

Zimbabwe's Human Resources for health Information System (ZHRIS)-an assessment in the context of establishing a global standard.

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Waters, Keith P; Zuber, Alexandra; Simbini, Tungamirirai; Bangani, Zwashe; Krishnamurthy, Ramesh S

2017-04-01

There have been numerous global calls to action to utilize human resources information systems (HRIS) to improve the availability and quality of data for strengthening the regulation and deployment of health workers. However, with no normative guidance in existence, the development of HRIS has been inconsistent and lacking in standardization, hindering the availability and use of data for health workforce planning and decision making (Riley et al., 2012). CDC and WHO partnered with the Ministry of Health in several countries to conduct HRIS functional requirements analyses and establish a Minimum Data Set (MDS) of elements essential for a global standard HRIS. As a next step, CDC advanced a study to examine the alignment of one of the HRIS it supports (in Zimbabwe) against this MDS. For this study, we created a new data collection and analysis tool to assess the extent to which Zimbabwe's CDC-supported HRIS was aligned with the WHO MDS. We performed systematic "gap analyses" in order to make prioritized recommendations for addressing the gaps, with the aim of improving the availability and quality of data on Zimbabwe's health workforce. The majority of the data elements outlined in the WHO MDS were present in the ZHRIS databases, though they were found to be missing various applicable elements. The lack of certain elements could impede functions such as health worker credential verification or equitable in-service training allocation. While the HRIS MDS treats all elements equally, our assessment revealed that not all the elements have equal significance when it comes to data utilization. Further, some of the HRIS MDS elements exceeded the current needs of regulatory bodies and the Ministry of Health and Child Care (MOHCC) in Zimbabwe. The preliminary findings of this study helped inspire the development of a more recent HRH Registry MDS subset, which is a shorter list of priority data elements recommended as a global standard for HRIS. The field-tested assessment

Energy-momentum spectroscopy of the outervalence 3 {sigma} and 1{pi} states of hydrogen fluoride: a reanalysis

Energy Technology Data Exchange (ETDEWEB)

Nicholson, R.; McCarthy, I.E.; Weigold, E.; Brunger, M.J.

1996-03-01

We highlight and examine in detail a discrepancy that exists between the results of various single-channel and multiparameter electron momentum spectroscopy (EMS) studies into the outervalence states of hydrogen fluoride (HF). In an attempt to elucidate the nature of this problem and the disagreement that exists between the best available theoretical momentum distributions (MDs), as calculated in the plane-wave-impulse-approximation with wavefunctions at the near-Hartree-Fock limit, and the most accurate experimental MDs, we have adapted a method, originally applied to extract atomic orbital information from Compton profiles to our 3{sigma} and 1{pi} experimental MDs. In addition we have also applied this technique to the 2s and 2p orbitals of neon, which is isoelectronic with HF, with the ramifications of the results of this investigation to HF also being outlined. (authors). 17 refs., 3 tabs., 5 figs.

Integrating open-source software applications to build molecular dynamics systems.

Science.gov (United States)

Allen, Bruce M; Predecki, Paul K; Kumosa, Maciej

2014-04-05

Three open-source applications, NanoEngineer-1, packmol, and mis2lmp are integrated using an open-source file format to quickly create molecular dynamics (MD) cells for simulation. The three software applications collectively make up the open-source software (OSS) suite known as MD Studio (MDS). The software is validated through software engineering practices and is verified through simulation of the diglycidyl ether of bisphenol-a and isophorone diamine (DGEBA/IPD) system. Multiple simulations are run using the MDS software to create MD cells, and the data generated are used to calculate density, bulk modulus, and glass transition temperature of the DGEBA/IPD system. Simulation results compare well with published experimental and numerical results. The MDS software prototype confirms that OSS applications can be analyzed against real-world research requirements and integrated to create a new capability. Copyright © 2014 Wiley Periodicals, Inc.

Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases

International Nuclear Information System (INIS)

Michels, S.D.; McKenna, R.W.; Arthur, D.C.; Brunning, R.D.

1985-01-01

This study consists of 65 patients (pts) who developed a myelodysplastic syndrome (MDS) (39 pts) or acute myeloid leukemia (AML) (26 pts) following chemotherapy and/or radiotherapy; the interval from the onset of therapy to bone marrow abnormality ranged from 11 to 192 months (median, 58). Thirty-three patients had been previously treated for lymphoproliferative diseases, 29 for carcinoma, and three for a nonneoplastic disorder. Approximately 30% of the cases presenting in the MDS phase evolved to AML in one to 12 months (median, 3.5). The AML in 49% of the cases was not readily classified according to French-American-British (FAB) criteria; the primary difficulty in classification related to the involvement of multiple cell lines. Among the cases that could be classified, all FAB types were represented except for M1; M2 was the most frequent type. Clonal chromosome abnormalities were found in marrow specimens from 22 of 24 (92%) patients studied with G banding; 11 had abnormalities of chromosomes 5 and/or 7. The median survival for all patients was four months with no significant difference between those treated and not treated with antileukemic therapy. The median survival was three months for the patients presenting with AML, six months for the patients with AML following an MDS, and four months for the patients with an MDS that did not evolve to AML. The findings in the present study suggest that there are three stages of therapy-related panmyelosis: (1) pancytopenia with associated myelodysplastic changes, (2) a frank MDS, and (3) overt AML. Many patients will present in the stage of overt AML that differs from de novo AML primarily by the high incidence of trilineage involvement, difficulty in classification, frequent cytogenetic abnormalities, and poor response to antileukemic therapy

Challenges in the Assessment of Medical Devices: The MedtecHTA Project.

Science.gov (United States)

Tarricone, Rosanna; Torbica, Aleksandra; Drummond, Michael

2017-02-01

Assessing medical devices (MDs) raises challenges which require us to reflect on whether current methods are adequate. Major features of devices are: (i) device-operator interaction can generate learning curve effects; (ii) incremental nature of innovation needs to be addressed by careful identification of the alternatives for comparative and incremental cost-effectiveness analysis; and (iii) broader organizational impact in terms of training and infrastructure, coupled with dynamic pricing, requires a more flexible approach to costing. The objective of the MedtecHTA project was to investigate improvements in HTA methods to allow for more comprehensive evaluation of MDs. It consisted of several work packages concerning (i) the available evidence on the currently adopted approaches for regulation and HTA of medical devices; (ii) the geographical variation in access to MDs; (iii) the development of methodological frameworks for conducting comparative effectiveness research and economic evaluation of MDs; and (iv) the organizational impact of MDs. This introductory paper summarizes the main results of the project and draws out the main overarching themes. This supplement represents a comprehensive report of all the main findings of the MedtecHTA project, and it is intended to be the main source for researchers and policy makers wanting information on the project. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd. © 2017 The Authors. Health Economics Published by John Wiley & Sons, Ltd.

Index-Based Dietary Patterns and Colorectal Cancer Risk: A Systematic Review123

Science.gov (United States)

Steck, Susan E; Guinter, Mark; Zheng, Jiali; Thomson, Cynthia A

2015-01-01

Colorectal cancer (CRC) is the third most common cancer in both men and women in the United States. Various a priori dietary patterns that take into account diet complexity have been associated with CRC risk. This systematic review augments the evidence for an association between CRC risk and the Mediterranean Diet Score (MDS) and the Healthy Eating Index (HEI), and provides new evidence for a novel Dietary Inflammatory Index (DII). Human studies published in English after 31 December 2008 were reviewed. Five case-control studies and 7 prospective cohort studies conducted in the United States and Europe were identified. Five of the studies examined the MDS, 4 examined the HEI, and 4 examined the DII. Comparing highest to lowest score groups, higher MDSs were associated with an 8–54% lower CRC risk, and higher HEI scores were associated with a 20–56% lower CRC risk. More proinflammatory diet scores were associated with a 12–65% higher CRC risk compared with more anti-inflammatory diets in studies that used the DII. The results reported by sex suggested similar associations for men and women. This review builds upon the evidence supporting the association between higher overall diet quality and lower risk of CRC. Increasing scores of MDS and HEI and anti-inflammatory DII scores are characterized by high intake of plant-based foods and low intake of animal products. Future studies in more diverse populations and with consistent scoring calculations are recommended. PMID:26567200

Cytogenetic as an Important Tool for Diagnosis and Prognosis for Patients with Hypocellular Primary Myelodysplastic Syndrome

Directory of Open Access Journals (Sweden)

Daiane Corrêa de Souza

2014-01-01

Full Text Available We analyzed cytogenetically 105 patients with hypocellular primary MDS and their clinical implications. The main chromosomal abnormalities found were del(5q/−5, del(6q/+6, del(7q/−7, del(11q, and del(17p. Pediatric patients had a higher frequency of abnormal karyotypes compared with adult patients (P < 0,05. From our patients, 18% showed evolution of the disease. The chromosomal abnormalities presented in the diagnosis of patients who evolved to AML included numerical (−7, +8 and structural del(6q, del(7q, i(7q, t(7;9, i(9q, and del(11q abnormalities and complex karyotypes. Although the frequency of evolution from hypocellular MDS to AML is low, our results suggest that some chromosomal alterations may play a critical role during this process. We applied the IPSS in our patients because this score system has been proved to be useful for predicting evolution of disease. When we considered the patients according to group 1 (intermediate-1 and group 2 (intermediate-2 and high risk, we showed that group 2 had a high association with respect to the frequency of abnormal karyotypes (P < 0,0001, evolution of disease (P < 0,0001, and mortality (P < 0,001. In fact, the cytogenetic analysis for patients with hypocellular primary MDS is an important tool for diagnosis, prognosis, in clinical decision-making and in follow-up.

Enumerating bone marrow blasts from nonerythroid cellularity improves outcome prediction in myelodysplastic syndromes and permits a better definition of the intermediate risk category of the Revised International Prognostic Scoring System (IPSS-R).

Science.gov (United States)

Calvo, Xavier; Arenillas, Leonor; Luño, Elisa; Senent, Leonor; Arnan, Montserrat; Ramos, Fernando; Pedro, Carme; Tormo, Mar; Montoro, Julia; Díez-Campelo, María; Blanco, María Laura; Arrizabalaga, Beatriz; Xicoy, Blanca; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Meritxell; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

2017-07-01

The Revised International Prognostic Scoring System (IPSS-R) has been recognized as the score with the best outcome prediction capability in MDS, but this brought new concerns about the accurate prognostication of patients classified into the intermediate risk category. The correct enumeration of blasts is essential in prognostication of MDS. Recent data evidenced that considering blasts from nonerythroid cellularity (NECs) improves outcome prediction in the context of IPSS and WHO classification. We assessed the percentage of blasts from total nucleated cells (TNCs) and NECs in 3924 MDS patients from the GESMD, 498 of whom were MDS with erythroid predominance (MDS-E). We assessed if calculating IPSS-R by enumerating blasts from NECs improves prognostication of MDS. Twenty-four percent of patients classified into the intermediate category were reclassified into higher-risk categories and showed shorter overall survival (OS) and time to AML evolution than those who remained into the intermediate one. Likewise, a better distribution of patients was observed, since lower-risk patients showed longer survivals than previously whereas higher-risk ones maintained the outcome expected in this poor prognostic group (median OS < 20 months). Furthermore, our approach was particularly useful for detecting patients at risk of dying with AML. Regarding MDS-E, 51% patients classified into the intermediate category were reclassified into higher-risk ones and showed shorter OS and time to AML. In this subgroup of MDS, IPSS-R was capable of splitting our series in five groups with significant differences in OS only when blasts were assessed from NECs. In conclusion, our easy-applicable approach improves prognostic assessment of MDS patients. © 2017 Wiley Periodicals, Inc.

Validation of the Hebrew version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale.

Science.gov (United States)

Zitser, Jennifer; Peretz, Chava; Ber David, Aya; Shabtai, Herzl; Ezra, Adi; Kestenbaum, Meir; Brozgol, Marina; Rosenberg, Alina; Herman, Talia; Balash, Yakov; Gadoth, Avi; Thaler, Avner; Stebbins, Glenn T; Goetz, Christopher G; Tilley, Barbara C; Luo, Sheng T; Liu, Yuanyuan; Giladi, Nir; Gurevich, Tanya

2017-12-01

The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. The MDS-UPDRS questionnaire was translated to Hebrew and was tested on 389 patients with PD, treated at the Movement Disorders Unit at Tel-Aviv Medical Center. The MDS-UPDRS is made up of four sections. The higher the score, the worst the clinical situation of the patient is. Confirmatory and explanatory factor analysis were applied to determine if the factor structure of the English version could be confirmed in the Hebrew version. The Hebrew version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Hebrew-version was satisfactory, with Cronbach's alpha values 0.79, 0.90, 0.93, 0.80, for parts 1 to 4 respectively. In the confirmatory factor analysis, all four parts had high (greater than 0.90) comparative fit index (CFI) in comparison to the original English MDS-UPDRS with high factor structure (0.96, 0.99, 0.94, 1.00, respectively), thus confirming the pre-specified English factor structure. Explanatory factor analysis yielded that the Hebrew responses differed from the English one within an acceptable range: in isolated item differences in factor structure and in the findings of few items having cross loading on multiple factors. The Hebrew version of the MDS-UPDRS meets the requirements to be designated as the Official Hebrew Version of the MDS-UPDRS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Beliefs of rehabilitation professionals towards guided self-rehabilitation contracts for post stroke hemiparesis.

Science.gov (United States)

Marsal, Claire; Gracies, Jean-Michel; Dean, Catherine; Mesure, Serge; Bayle, Nicolas

2017-12-01

Purpose To investigate the beliefs of physiotherapy students (ST), professionals (PT) and physicians (MD) about engaging patients with post-stroke hemiparesis into Guided Self-Rehabilitation Contracts (GSC), to increase their exercise intensity and responsibility level. Method A survey examining beliefs about post-stroke rehabilitation was completed by first (n = 95), second (n = 105), and third (n = 48) year STs; PTs (n = 129) and MDs (n = 65) in France. Results The belief about whether a patient may exercise alone varied between the professional groups with more STs and MDs finding it acceptable: 62% of PTs vs. 74% of STs (p = 0.005) and 79% of MDs (p = 0.02). For 93% of therapists (STs and PTs together), the caregiver may take part in physical therapy sessions. The appropriate weekly duration of exercises in chronic hemiparesis should be over 5 h for 19% of PTs, 37% of STs, and 51% of MDs (MDs vs. PTs, p < 0.005). After stroke, functional progress through rehabilitation is possible all lifelong for 11% of STs, 19% of PTs (p < 0.05, STs vs. PTs), and 29% of MDs (MD vs. PT, NS). Conclusions The strategy of asking patients to perform exercises alone, in the practice or at home, is still not accepted by a large proportion of physical therapy professionals as compared with students or with physicians. Most therapists still see a <5-h weekly duration of exercise as sufficient after stroke. Few therapists are ready to utilize the persistence of behavior-induced brain plasticity regardless of age or delay after the lesion.

Attitudes of Nurses and Physicians About Clinical Autopsy in Neonatal and Adult Hospital Care: A Survey in Sweden.

Science.gov (United States)

Mjörnheim, Berit; Rosendahl, Anders; Eriksson, Lennart C; Takman, Christina

2015-01-01

The rate of autopsies has dropped to low levels in Western countries. The aim of this study was to describe the experiences and attitudes of registered nurses (RNs) and physicians (MD) toward clinical autopsies in neonatal and adult hospital care in Sweden. RNs and MDs in neonatal and adult care specialized clinics at a university-affiliated hospital in Sweden were surveyed. Survey responses were tallied, and free-text comments were assessed with qualitative content analysis. Three hundred thirty-six surveys were distributed; the response rate was 35%. Most RNs and 14% of the MDs had limited or no experience participating in an autopsy. Notably, few RNs and approximately one third of the MDs were familiar with the autopsy processes and the treatment of the deceased person's body after an autopsy. More than one third of RNs had experience with talking to relatives regarding autopsy. Most agreed that an autopsy could be supportive for relatives during the grieving process and beneficial for the quality of healthcare. Most MDs (70%) thought that autopsies should be performed more frequently. Qualitative results emphasized that RNs and MDs thought that autopsy information supported the grieving process of relatives-especially parents who had lost a child. The survey data confirm belief in the value of clinical autopsies in neonatal and adult hospital care. RNs and MDs should receive training about the autopsy process and procedures for obtaining consent for an autopsy. RNs are in a position to support the decision making of relatives about providing consent for autopsy and have an opportunity to take a more active role in the autopsy process.

Service provider perceptions of telerehabilitation as an additional service delivery option within an Australian neurosurgical and orthopaedic physiotherapy screening clinic: A qualitative study.

Science.gov (United States)

Cottrell, Michelle A; Hill, Anne J; O'Leary, Shaun P; Raymer, Maree E; Russell, Trevor G

2017-12-01

The Neurosurgical & Orthopaedic Physiotherapy Screening Clinic and Multidisciplinary Service (N/OPSC&MDS) originated as a complementary, non-surgical pathway for patients referred to public neurosurgical and orthopaedic specialist services. Patient access to the N/OPSC&MDS could potentially be improved with the implementation of telerehabilitation as an additional method of service delivery. To evaluate service provider's views on (1) current barriers to patients' accessing N/OPSC & MD services, and (2) the implementation of telerehabilitation within the N/OPSC&MDS. Qualitative descriptive study design. Healthcare providers (n = 26) were recruited from six N/OPSC&MD services located throughout Queensland, Australia. Semi-structured interviews were conducted to explore service providers' views with respect to existing barriers to patients accessing the N/OPSC&MDS, and if telerehabilitation could be feasibly adopted to address current barriers. Template analysis resulted in six themes: (1) barriers to some patients' accessing current N/OPSC&MD services are complex & multifaceted; (2) telerehabilitation could improve patient access to appropriate management for their musculoskeletal condition; (3) telerehabilitation may have limitations when compared to face-to-face healthcare; (4) the delivery of telerehabilitation needs to be flexible; (5) perceived barriers, and (6) facilitators to the successful implementation of telerehabilitation within the N/OPSC&MDS. This study represents a critical step in determining the readiness of service providers for the implementation of telerehabilitation within the N/OPSC&MDS. Although cautious, service providers are overall accepting of the implementation of telerehabilitation, acknowledging that it could eliminate several current barriers, subsequently achieving more equitable access to the service. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Iron overload may promote alteration of NK cells and hematopoietic stem/progenitor cells by JNK and P38 pathway in myelodysplastic syndromes.

Science.gov (United States)

Hua, Yanni; Wang, Chaomeng; Jiang, Huijuan; Wang, Yihao; Liu, Chunyan; Li, Lijuan; Liu, Hui; Shao, Zonghong; Fu, Rong

2017-08-01

The objective of the study was to examine levels of intracellular iron, reactive oxygen species (ROS) and the expression of JNK and p38MAPK in NK cells and hematopoietic stem/progenitor cells (HSPCs) in MDS patients, and explore potential mechanisms by which iron overload (IOL) promotes MDS progression. Thirty-four cases of MDS and six cases of AML transformed from MDS (MDS/AML) were included. HSPCs and NK cells were isolated by magnetic absorption cell sorting. We used flow cytometry to detect the levels of ROS and intracellular JNK and P38 in NK cells and HSPCs. Total RNA and protein were extracted from NK cells and CD34 + cells to examine the expression of JNK and p38MAPK using RT-PCR and Western blotting. Intracellular iron concentration was detected. Data were analyzed by SPSS 21 statistical software. Intracellular iron concentration and ROS were increased in both NK cells and HSPCs in MDS patients with iron overload (P overload had higher JNK expression and lower p38 expression in NK cells, and higher p38 expression in HSPCs compared with non-iron overload group. IOL may cause alterations in NK cells and HSPCs through the JNK and p38 pathways, and play a role in the transformation to AML from MDS.

The mutation frequency of 8-oxo-7,8 dihydroguanine (8-oxoG) situated in a multiply damaged site: comparison of a single and two closely opposed 8-oxodG in Escherichia coli

International Nuclear Information System (INIS)

Malyarchuk, S.G.; Youngblood, R.C.; Landry, A.M.; Quillin, E.; Harrison, L.

2003-01-01

Full text: A multiply damaged site (MDS) is defined as >= two lesions within a distance of 10-15 base pairs (bp). MDS generated by ionizing radiation contains oxidative base damage, and in vitro studies have indicated that if the base damage is less than 3 bp apart, repair of one lesion is inhibited until repair of the lesion in the opposite strand is completed. Inhibition of repair could result in an increase in the mutation frequency of the base damage. We have designed an assay to determine whether a closely opposed lesion causes an increase in adenine insertion opposite an 8-oxodG in bacteria. The double-stranded oligonucleotides (with no damage, each single 8-oxodG or the MDS) were ligated into the firefly luciferase coding region of a reporter vector and transformed into wild type or MutY-deficient bacteria. The MDS contained an 8-oxodG in the transcribed strand (T) and a second 8-oxodG immediately 5' to this lesion in the non-transcribed strand (NT). During two rounds of replication, insertion of adenine opposite the 8-oxodG in the T or NT strand results in a translation termination codon at position 444 or 445, respectively. In wild-type bacteria, we detected a translation stop at a frequency of 0.15% (codon 444) and 0.09% (codon 445) with a single 8-oxodG in the T or NT strand, respectively. This was enhanced ∼3 fold when single lesions were replicated in MutY-deficient bacteria. Positioning an 8-oxodG in the T strand within the MDS enhanced the mutation frequency by ∼2 fold in wild-type bacteria and 8 fold in Mut Y-deficient bacteria, while the mutation frequency of the 8-oxodG in the NT strand increased by 6 fold in Mut Y-deficient bacteria. This enhancement of mutation frequency supports the in vitro MDS studies, which demonstrated the inability of base excision repair to completely repair closely opposed lesions

Identity modulates short-term memory for facial emotion.

Science.gov (United States)

Galster, Murray; Kahana, Michael J; Wilson, Hugh R; Sekuler, Robert

2009-12-01

For some time, the relationship between processing of facial expression and facial identity has been in dispute. Using realistic synthetic faces, we reexamined this relationship for both perception and short-term memory. In Experiment 1, subjects tried to identify whether the emotional expression on a probe stimulus face matched the emotional expression on either of two remembered faces that they had just seen. The results showed that identity strongly influenced recognition short-term memory for emotional expression. In Experiment 2, subjects' similarity/dissimilarity judgments were transformed by multidimensional scaling (MDS) into a 2-D description of the faces' perceptual representations. Distances among stimuli in the MDS representation, which showed a strong linkage of emotional expression and facial identity, were good predictors of correct and false recognitions obtained previously in Experiment 1. The convergence of the results from Experiments 1 and 2 suggests that the overall structure and configuration of faces' perceptual representations may parallel their representation in short-term memory and that facial identity modulates the representation of facial emotion, both in perception and in memory. The stimuli from this study may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.

Hypnotic suggestibility, cognitive inhibition, and dissociation.

Science.gov (United States)

Dienes, Zoltán; Brown, Elizabeth; Hutton, Sam; Kirsch, Irving; Mazzoni, Giuliana; Wright, Daniel B

2009-12-01

We examined two potential correlates of hypnotic suggestibility: dissociation and cognitive inhibition. Dissociation is the foundation of two of the major theories of hypnosis and other theories commonly postulate that hypnotic responding is a result of attentional abilities (including inhibition). Participants were administered the Waterloo-Stanford Group Scale of Hypnotic Susceptibility, Form C. Under the guise of an unrelated study, 180 of these participants also completed: a version of the Dissociative Experiences Scale that is normally distributed in non-clinical populations; a latent inhibition task, a spatial negative priming task, and a memory task designed to measure negative priming. The data ruled out even moderate correlations between hypnotic suggestibility and all the measures of dissociation and cognitive inhibition overall, though they also indicated gender differences. The results are a challenge for existing theories of hypnosis.

Motor Importance of motor assessment in school children: analysis of the reliability of the motor development scale

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Kassandra Nunes Amaro

2010-09-01

Full Text Available The objective of this study was to investigate the motor performance of school chil-dren aged 6 to 10 years without learning difficulties (n=101, and to analyze the reliability of the Motor Development Scale (MDS (Rosa Neto, 2002. Descriptive statistics with calculation of the mean, standard deviation, and range was used for data analysis. The internal consistency of the MDS was assessed using Cronbach’s alpha coefficient, and the correlation between variables was determined by Pearson’s linear correlation, with p<0.05. The results showed (1 that motor development was within normal limits in 96% of the children, and (2 a high correlation betwe-en chronological age and general motor age, indicating good internal consistency. These data demonstrate the logic and structured design of the MDS, confirming its reliability.

Motor Importance of motor assessment in school children: analysis of the reliability of the motor development scale doi: 10.5007/1980-0037.2010v12n6p422

Directory of Open Access Journals (Sweden)

Francisco Rosa Neto

2010-09-01

Full Text Available The objective of this study was to investigate the motor performance of school chil-dren aged 6 to 10 years without learning difficulties (n=101, and to analyze the reliability of the Motor Development Scale (MDS (Rosa Neto, 2002. Descriptive statistics with calculation of the mean, standard deviation, and range was used for data analysis. The internal consistency of the MDS was assessed using Cronbach’s alpha coefficient, and the correlation between variables was determined by Pearson’s linear correlation, with p<0.05. The results showed (1 that motor development was within normal limits in 96% of the children, and (2 a high correlation betwe-en chronological age and general motor age, indicating good internal consistency. These data demonstrate the logic and structured design of the MDS, confirming its reliability.

Responding to hypnotic and nonhypnotic suggestions: performance standards, imaginative suggestibility, and response expectancies.

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Meyer, Eric C; Lynn, Steven Jay

2011-07-01

This study examined the relative impact of hypnotic inductions and several other variables on hypnotic and nonhypnotic responsiveness to imaginative suggestions. The authors examined how imaginative suggestibility, response expectancies, motivation to respond to suggestions, and hypnotist-induced performance standards affected participants' responses to both hypnotic and nonhypnotic suggestions and their suggestion-related experiences. Suggestions were administered to 5 groups of participants using a test-retest design: (a) stringent performance standards; (b) lenient performance standards; (c) hypnosis test-retest; (d) no-hypnosis test-retest; and (e) no-hypnosis/hypnosis control. The authors found no support for the influence of a hypnotic induction or performance standards on responding to suggestions but found considerable support for the role of imaginative suggestibility and response expectancies in predicting responses to both hypnotic and nonhypnotic suggestions.

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

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Saumell, Sílvia; Solé, Francesc; Arenillas, Leonor; Montoro, Julia; Valcárcel, David; Pedro, Carme; Sanzo, Carmen; Luño, Elisa; Giménez, Teresa; Arnan, Montserrat; Pomares, Helena; De Paz, Raquel; Arrizabalaga, Beatriz; Jerez, Andrés; Martínez, Ana B; Sánchez-Castro, Judith; Rodríguez-Gambarte, Juan D; Raya, José M; Ríos, Eduardo; Rodríguez-Rivera, María; Espinet, Blanca; Florensa, Lourdes

2015-01-01

Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS) in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8) can be found as a constitutional mosaicism (cT8M). We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC) and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH). In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

Sequential acquisition of mutations in myelodysplastic syndromes.

Science.gov (United States)

Makishima, Hideki

2017-01-01

Recent progress in next-generation sequencing technologies allows us to discover frequent mutations throughout the coding regions of myelodysplastic syndromes (MDS), potentially providing us with virtually a complete spectrum of driver mutations in this disease. As shown by many study groups these days, such driver mutations are acquired in a gene-specific fashion. For instance, DDX41 mutations are observed in germline cells long before MDS presentation. In blood samples from healthy elderly individuals, somatic DNMT3A and TET2 mutations are detected as age-related clonal hematopoiesis and are believed to be a risk factor for hematological neoplasms. In MDS, mutations of genes such as NRAS and FLT3, designated as Type-1 genes, may be significantly associated with leukemic evolution. Another type (Type-2) of genes, including RUNX1 and GATA2, are related to progression from low-risk to high-risk MDS. Overall, various driver mutations are sequentially acquired in MDS, at a specific time, in either germline cells, normal hematopoietic cells, or clonal MDS cells.

Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not?

Directory of Open Access Journals (Sweden)

Sílvia Saumell

Full Text Available Isolated trisomy 8 is not considered presumptive evidence of myelodysplastic syndrome (MDS in cases without minimal morphological criteria. One reason given is that trisomy 8 (+8 can be found as a constitutional mosaicism (cT8M. We tried to clarify the incidence of cT8M in myeloid neoplasms, specifically in MDS, and the diagnostic value of isolated +8 in MDS. Twenty-two MDS and 10 other myeloid neoplasms carrying +8 were studied. Trisomy 8 was determined in peripheral blood by conventional cytogenetics (CC and on granulocytes, CD3+ lymphocytes and oral mucosa cells by fluorescence in situ hybridization (FISH. In peripheral blood CC, +8 was seen in 4/32 patients. By FISH, only one patient with chronic myelomonocytic leukemia showed +8 in all cell samples and was interpreted as a cT8M. In our series +8 was acquired in all MDS. Probably, once discarded cT8M by FISH from CD3+ lymphocytes and non-hematological cells, +8 should be considered with enough evidence to MDS.

Biochemical compositions and fatty acid profiles in four species of microalgae cultivated on household sewage and agro-industrial residues.

Science.gov (United States)

Calixto, Clediana Dantas; da Silva Santana, Jordana Kaline; de Lira, Evandro Bernardo; Sassi, Patrícia Giulianna Petraglia; Rosenhaim, Raul; da Costa Sassi, Cristiane Francisca; da Conceição, Marta Maria; Sassi, Roberto

2016-12-01

The potential of four regional microalgae species was evaluated in relation to their cell growth and biomass production when cultured in the following alternative media: bio-composts of fruit/horticultural wastes (HB), sugarcane waste and vinasse (VB) chicken excrements (BCE), raw chicken manure (RCM), and municipal domestic sewage (MDS). The cultures were maintained under controlled conditions and their growth responses, productivities, biochemical compositions, and the ester profiles of their biomasses were compared to the results obtained in the synthetic media. The MDS and HB media demonstrated promising results for cultivation, especially of Chlorella sp., Chlamydomonas sp., and Lagerheimia longiseta, which demonstrated productivities superior to those seen when grown on the control media. The highest lipid levels were obtained with the HB medium. The data obtained demonstrated the viability of cultivating microalgae and producing biomass in alternative media prepared from MDS and HB effluents to produce biodiesel. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suicidality and interrogative suggestibility.

Science.gov (United States)

Pritchard-Boone, Lea; Range, Lillian M

2005-01-01

All people are subject to memory suggestibility, but suicidal individuals may be especially so. The link between suicidality and suggestibility is unclear given mixed findings and methodological weaknesses of past research. To test the link between suicidality and interrogative suggestibility, 149 undergraduates answered questions about suicidal thoughts and reasons for living, and participated in a direct suggestibility procedure. As expected, suggestibility correlated with suicidality but accounted for little overall variance (4%). Mental health professionals might be able to take advantage of client suggestibility by directly telling suicidal persons to refrain from suicidal thoughts or actions.

The Nursing Home Minimum Data Set Assessment Instrument: Manifest Functions and Unintended Consequences--Past, Present, and Future

Science.gov (United States)

Rahman, Anna N.; Applebaum, Robert A.

2009-01-01

The Minimum Data Set (MDS) is a uniform instrument used in nursing homes to assess residents. In January 2008, the Centers for Medicare and Medicaid Services published a draft of a new MDS--version 3.0. This article traces the instrument's development and the design decisions that shaped it, discusses the MDS's manifest functions--data collection…

Impairment of FOS mRNA stabilization following translation arrest in granulocytes from myelodysplastic syndrome patients.

Science.gov (United States)

Feng, Xiaomin; Shikama, Yayoi; Shichishima, Tsutomu; Noji, Hideyoshi; Ikeda, Kazuhiko; Ogawa, Kazuei; Kimura, Hideo; Takeishi, Yasuchika; Kimura, Junko

2013-01-01

Although quantitative and qualitative granulocyte defects have been described in myelodysplastic syndromes (MDS), the underlying molecular basis of granulocyte dysfunction in MDS is largely unknown. We recently found that FOS mRNA elevation under translation-inhibiting stimuli was significantly smaller in granulocytes from MDS patients than in healthy individuals. The aim of this study is to clarify the cause of the impaired FOS induction in MDS. We first examined the mechanisms of FOS mRNA elevation using granulocytes from healthy donors cultured with the translation inhibitor emetine. Emetine increased both transcription and mRNA stability of FOS. p38 MAPK inhibition abolished the emetine-induced increase of FOS transcription but did not affect FOS mRNA stabilization. The binding of an AU-rich element (ARE)-binding protein HuR to FOS mRNA containing an ARE in 3'UTR was increased by emetine, and the knockdown of HuR reduced the FOS mRNA stabilizing effect of emetine. We next compared the emetine-induced transcription and mRNA stabilization of FOS between MDS patients and healthy controls. Increased rates of FOS transcription by emetine were similar in MDS and controls. In the absence of emetine, FOS mRNA decayed to nearly 17% of initial levels in 45 min in both groups. In the presence of emetine, however, 76.7±19.8% of FOS mRNA remained after 45 min in healthy controls, versus 37.9±25.5% in MDS (Pknowledge, this is the first report demonstrating attenuation of stress-induced FOS mRNA stabilization in MDS granulocytes.

Polymorphisms of Interlukin-1β rs16944 confer susceptibility to myelodysplastic syndromes.

Science.gov (United States)

Yin, Congcong; He, Na; Li, Peng; Zhang, Chen; Yu, Jie; Hua, Mingqiang; Ji, Chunyan; Ma, Daoxin

2016-11-15

Genetic factors have been shown to be associated with Myelodysplastic syndromes (MDS) susceptibility. In recent years, the role of inflammation in the promotion of tumor growth is supported by a broad range of experimental and clinical evidence. But the relationship between polymorphisms in NOD-like receptor protein 3 (NLRP3) inflammasome and MDS is rarely reported. Thus, we conducted a case-control study, and genotyped five single nucleotide polymorphisms (SNPs) (NLRP3, IL-1β, IL-18, CARD8, and NF-κB) in MDS patients and healthy controls. The association of different genotypes with patient characteristics was analyzed. Comparing MDS patients with controls, GG genotype of IL-1β (rs16944) was observed to be associated with a significantly increased risk of MDS 78/166 (48.8%) vs 26/96 (27.0%), OR=2.1, CI (1.0-4.4). No significant association was identified regarding the rest of investigated polymorphisms and MDS susceptibility. Complex karyotypes were more frequent in patients with GG genotype of IL-1β (rs16944). Patients with IL-1β polymorphisms (rs16944) GG and GA had lower hemoglobin than those without. Patients with IL-1β polymorphisms (rs16944) GG had higher IPSS scores than those without IL-1β polymorphisms. In conclusion, our present data shows that the IL-1β polymorphisms (rs16944) GG were frequently occurred in MDS. IL-1β (rs16944) GG genotype might serve as a novel biomarker and potential targets for MDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Fluorescence in situ hybridization of TP53 for the detection of chromosome 17 abnormalities in myelodysplastic syndromes.

Science.gov (United States)

Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; García-Cerecedo, Tomás; López, Ricard; Talavera, Elisabeth; Fernández-Ruiz, Sara; Ademà, Vera; Marugan, Isabel; Luño, Elisa; Sanzo, Carmen; Vallespí, Teresa; Arenillas, Leonor; Marco Buades, Josefa; Batlle, Ana; Buño, Ismael; Martín Ramos, María Luisa; Blázquez Rios, Beatriz; Collado Nieto, Rosa; Vargas, Ma Teresa; González Martínez, Teresa; Sanz, Guillermo; Solé, Francesc

2015-01-01

Conventional G-banding cytogenetics (CC) detects chromosome 17 (chr17) abnormalities in 2% of patients with de novo myelodysplastic syndromes (MDS). We used CC and fluorescence in situ hybridization (FISH) (LSI p53/17p13.1) to assess deletion of 17p in 531 patients with de novo MDS from the Spanish Group of Hematological Cytogenetics. FISH detected - 17 or 17p abnormalities in 13 cases (2.6%) in whom no 17p abnormalities were revealed by CC: 0.9% of patients with a normal karyotype, 0% in non-informative cytogenetics, 50% of patients with a chr17 abnormality without loss of 17p and 4.7% of cases with an abnormal karyotype not involving chr17. Our results suggest that applying FISH of 17p13 to identify the number of copies of the TP53 gene could be beneficial in patients with a complex karyotype. We recommend using FISH of 17p13 in young patients with a normal karyotype or non-informative cytogenetics, and always in isolated del(17p).

A UniChem and electron momentum spectroscopy investigations into the valence electronic structure of trans 1,3 butadiene

Energy Technology Data Exchange (ETDEWEB)

Michalewicz, M.T. [CSIRO, Supercomputing Support Group, Carlton, VIC (Australia). Division of Information Technology; Winkler, D.A. [Commonwealth Scientific and Industrial Research Organisation (CSIRO), Clayton, VIC (Australia). Div. of Chemical Physics; Brunger, M.J.; McCarthy, L.E. [Flinders Univ. of South Australia, Bedford Park, SA (Australia). School of Physical Sciences; Von Niessen, W. [Flinders Univ. of South Australia, Bedford Park, SA (Australia). School of Physical Sciences

1996-09-01

The experimental (e,2e) coincidence spectroscopy, known as electron momentum spectroscopy (EMS) was applied to the trans 1,3 butadiene (C{sub 4}H{sub 6}) molecule with detailed binding energy spectra and orbital momentum distributions (MDs) being measured. A small selection of this data is presented. The usage of UniChem computational chemistry codes for the Flinders-developed AMOLD program allows to calculate theoretical MDs for each orbital, to help elucidate the valence electronic structure of butadiene. The results of the many-body Green`s function calculation is also presented, to the ADC(3) level, for the binding energies and spectroscopic factors of the respective orbitals of C{sub 4}H{sub 6}. A critical comparison between the experimental and theoretical MDs allows to determine the optimum wavefunction from the basis sets studied. The determination of the wavefunction then allows to make further use of the UniChem package to derive butadiene`s chemically interesting molecular properties. A summary of these results and comparison of them with the previous results of other workers is presented. 23 refs., 2 tabs., 2 figs.

A UniChem and electron momentum spectroscopy investigations into the valence electronic structure of trans 1,3 butadiene

International Nuclear Information System (INIS)

Michalewicz, M.T.; Winkler, D.A.; Brunger, M.J.; McCarthy, L.E.; Von Niessen, W.

1996-09-01

The experimental (e,2e) coincidence spectroscopy, known as electron momentum spectroscopy (EMS) was applied to the trans 1,3 butadiene (C 4 H 6 ) molecule with detailed binding energy spectra and orbital momentum distributions (MDs) being measured. A small selection of this data is presented. The usage of UniChem computational chemistry codes for the Flinders-developed AMOLD program allows to calculate theoretical MDs for each orbital, to help elucidate the valence electronic structure of butadiene. The results of the many-body Green's function calculation is also presented, to the ADC(3) level, for the binding energies and spectroscopic factors of the respective orbitals of C 4 H 6 . A critical comparison between the experimental and theoretical MDs allows to determine the optimum wavefunction from the basis sets studied. The determination of the wavefunction then allows to make further use of the UniChem package to derive butadiene's chemically interesting molecular properties. A summary of these results and comparison of them with the previous results of other workers is presented. 23 refs., 2 tabs., 2 figs

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

Science.gov (United States)

Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

2015-01-01

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

Limited numbers of apoptotic cells in fresh paraffin embedded bone marrow samples of patients with myelodysplastic syndrome

NARCIS (Netherlands)

Brada, SJL; van de Loosdrecht, AA; Koudstaal, J; de Wolf, JTM; Vellenga, E

In myelodysplasia (MDS) the precise mechanism of ineffective erythropoiesis is not fully elucidated, but it is suggested that apoptosis may contribute to this process. We performed TdT-mediated dUTP-nick end labelling (TUNEL) staining of paraffin embedded bone marrow specimens to assess the amount

MRI of the femoral bone marrow in the assessment of aplastic anemia

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Osamu; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun; Takagi, Shojiro [Jichi Medical School, Saitama (Japan) Omiya Medical Center

1995-11-01

MR imaging of the femoral bone marrow was performed in 12 patients with untreated aplastic anemia and six patients with hypoplastic myelodysplastic syndrome (MDS). The MRI appearance was classified into four patterns; fatty marrow faint signal, nodular pattern and heterogeneous infiltration. The MRI patterns of aplastic anemia were evaluated and compared with those of hypoplastic MDS. In spite of hypocellular biopsies, MRI of the femoral marrow showed unexpected abnormal signal intensities in aplastic anemia; nodular pattern in five and heterogeneous infiltration pattern in two patients. Completely fatty marrow was depicted in four patients mainly with severe aplastic anemia. The nodular pattern with a background of fatty marrow was commonly seen in moderate or severe cases, while the heterogeneous infiltration pattern was noted in mild cases of the disease. Compared with hypoplastic MDS, asymmetrical nodular pattern suggesting patchy hematopoiesis was thought to be a characteristic finding of aplastic anemia. One patient clinically diagnosed as aplastic anemia, who had shown heterogeneous infiltration pattern, evolved to acute myeloid leukemia. We concluded that MRI of the femoral marrow could be useful in the assessment of aplastic anemia and detection of myelodysplastic or leukemic transformation. (author).

Genes that bias Mendelian segregation.

Directory of Open Access Journals (Sweden)

Pierre Grognet

Full Text Available Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs, complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

MRI of the femoral bone marrow in the assessment of aplastic anemia

International Nuclear Information System (INIS)

Tanaka, Osamu; Matsuura, Katsuhiko; Ichikawa, Tamaki; Kobayashi, Yasuyuki; Nagai, Jun; Takagi, Shojiro

1995-01-01

MR imaging of the femoral bone marrow was performed in 12 patients with untreated aplastic anemia and six patients with hypoplastic myelodysplastic syndrome (MDS). The MRI appearance was classified into four patterns; fatty marrow faint signal, nodular pattern and heterogeneous infiltration. The MRI patterns of aplastic anemia were evaluated and compared with those of hypoplastic MDS. In spite of hypocellular biopsies, MRI of the femoral marrow showed unexpected abnormal signal intensities in aplastic anemia; nodular pattern in five and heterogeneous infiltration pattern in two patients. Completely fatty marrow was depicted in four patients mainly with severe aplastic anemia. The nodular pattern with a background of fatty marrow was commonly seen in moderate or severe cases, while the heterogeneous infiltration pattern was noted in mild cases of the disease. Compared with hypoplastic MDS, asymmetrical nodular pattern suggesting patchy hematopoiesis was thought to be a characteristic finding of aplastic anemia. One patient clinically diagnosed as aplastic anemia, who had shown heterogeneous infiltration pattern, evolved to acute myeloid leukemia. We concluded that MRI of the femoral marrow could be useful in the assessment of aplastic anemia and detection of myelodysplastic or leukemic transformation. (author)

Outcomes for Patients with Chronic Lymphocytic Leukemia (CLL) and Acute Leukemia or Myelodysplastic Syndrome

Science.gov (United States)

Tambaro, Francesco Paolo; Garcia-Manero, Guillermo; O’Brien, Susan M.; Faderl, Stefan H.; Ferrajoli, Alessandra; Burger, Jan A.; Pierce, Sherry; Wang, Xuemei; Do, Kim-Anh; Kantarjian, Hagop M.; Keating, Michael J.; Wierda, William G.

2016-01-01

Acute leukemia (AL) and myelodysplastic syndrome (MDS) are uncommon in CLL. We retrospectively identified 95 patients with CLL also diagnosed with AL (n=38) or MDS (n=57), either concurrently (n=5) or subsequent (n=90) to CLL diagnosis and report their outcomes. Median number of CLL treatments prior to AL and MDS was 2(0–9) and 1(0–8), respectively; the most common regimen was purine analogue combined with alkylating agent±CD20 mAb. Twelve had no prior CLL treatment. Among 38 with AL, 33 had AML, 3 had ALL (1Ph+), 1 had biphenotypic, and 1 had extramedullary (bladder) AML. Unfavorable AML karyotype was noted in 26, intermediate-risk in 7. There was no association between survival from AL and number of prior CLL regimens or karyotype. Expression of CD7 on blasts was associated with shorter survival. Among MDS cases, all IPSS were represented; karyotype was unfavorable in 36, intermediate in 6, and favorable in 12 patients; 10 experienced transformation to AML. Shorter survival from MDS correlated with higher-risk IPSS, poor-risk karyotype, and increased number of prior CLL treatments. Overall, outcomes for patients with CLL subsequently diagnosed with AL or MDS were poor; AL/MDS occurred without prior CLL treatment. Effective therapies for these patients are desperately needed. PMID:26290497

Re-thinking the role of the dorsal striatum in egocentric/response strategy.

Science.gov (United States)

Botreau, Fanny; Gisquet-Verrier, Pascale

2010-01-01

Rats trained in a dual-solution cross-maze task, which can be solved by place and response strategies, predominantly used a response strategy after extensive training. This paper examines the involvement of the medial and lateral dorsal striatum (mDS and lDS) in the choice of these strategies after partial and extensive training. Our results show that rats with lDS and mDS lesions used mainly a response strategy from the early phase of training. We replicated these unexpected data in rats with lDS lesions and confirmed their tendency to use the response strategy in a modified cross-maze task. When trained in a dual-solution water-maze task, however, control and lesioned rats consistently used a place strategy, demonstrating that lDS and mDS lesioned rats can use a place strategy and that the shift towards a response strategy did not systematically result from extensive training. The present data did not show any clear dissociation between the mDS and lDS in dual solution tasks. They further indicate that the dorsal striatum seems to determine the strategies adopted in a particular context but cannot be considered as a neural support for the response memory system. Accordingly, the role of the lateral and medial part of the dorsal striatum in egocentric/response memory should be reconsidered.

Maternal depressive symptoms, mother-child interactions, and children's executive function.

Science.gov (United States)

Gueron-Sela, Noa; Camerota, Marie; Willoughby, Michael T; Vernon-Feagans, Lynne; Cox, Martha J

2018-01-01

This study examined the independent and mediated associations between maternal depression symptoms (MDS), mother-child interaction, and child executive function (EF) in a prospective longitudinal sample of 1,037 children (50% boys) from predominantly low-income and rural communities. When children were 6, 15 and 24 months of age, mothers reported their level of depressive symptomatology. At 24 and 36 months of age, mother-child interactions during play were rated for warmth-sensitivity and harsh-intrusiveness, and dyadic joint attention and maternal language complexity were assessed from a book sharing activity. Children's EF (i.e., inhibitory control, working memory, and set shifting) were assessed at ages 36 and 48 months using a battery of six tasks. Results indicated that MDS at ages 15 and 24 months were negatively associated with children's EF at age 48 months. Additionally, harsh-intrusive mother-child interactions partially mediated this link. Although warmth-sensitivity, dyadic joint attention and maternal language complexity were all longitudinally related to EF, they did not serve as mediating mechanisms between MDS and EF. These results were obtained while controlling for multiple demographic factors, children's earlier cognitive abilities, maternal general distress and childcare experiences. Findings from this study identify 1 mechanism through which early exposure to MDS could be related to children's EF. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Dissociative tendencies and individual differences in high hypnotic suggestibility.

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Terhune, Devin Blair; Cardeña, Etzel; Lindgren, Magnus

2011-03-01

Inconsistencies in the relationship between dissociation and hypnosis may result from heterogeneity among highly suggestible individuals, in particular the existence of distinct highly suggestible subtypes that are of relevance to models of psychopathology and the consequences of trauma. This study contrasted highly suggestible subtypes high or low in dissociation on measures of hypnotic responding, cognitive functioning, and psychopathology. Twenty-one low suggestible (LS), 19 low dissociative highly suggestible (LDHS), and 11 high dissociative highly suggestible (HDHS) participants were administered hypnotic suggestibility scales and completed measures of free recall, working memory capacity, imagery, fantasy-proneness, psychopathology, and exposure to stressful life events. HDHS participants were more responsive to positive and negative hallucination suggestions and experienced greater involuntariness during hypnotic responding. They also exhibited impaired working memory capacity, elevated pathological fantasy and dissociative symptomatology, and a greater incidence of exposure to stressful life events. In contrast, LDHS participants displayed superior object visual imagery. These results provide further evidence for two highly suggestible subtypes: a dissociative subtype characterised by deficits in executive functioning and a predisposition to psychopathology, and a subtype that exhibits superior imagery and no observable deficits in functioning.

Are Dysphoric Individuals More Suggestible or Less Suggestible Than Nondysphoric Individuals?

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MacFarland, Wendy L.; Morris, Steven J.

1998-01-01

Dysphoric individuals are shown to be susceptible to interrogative suggestion, whether in the form of leading questions or interrogative pressure. The association of a clinically relevant condition of dysphoria (depression) with relatively high levels of suggestibility was investigated in a college student population (N=139). Applicability to…

Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

International Nuclear Information System (INIS)

Tanaka, K.; Tanaka, H.; Kamada, N.

2003-01-01

It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

Placebo-suggestion modulates conflict resolution in the Stroop Task.

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Pedro A Magalhães De Saldanha da Gama

Full Text Available Here, we ask whether placebo-suggestion (without any form of hypnotic induction can modulate the resolution of cognitive conflict. Naïve participants performed a Stroop Task while wearing an EEG cap described as a "brain wave" machine. In Experiment 1, participants were made to believe that the EEG cap would either enhance or decrease their color perception and performance on the Stroop task. In Experiment 2, participants were explicitly asked to imagine that their color perception and performance would be enhanced or decreased (non-hypnotic imaginative suggestion. We observed effects of placebo-suggestion on Stroop interference on accuracy: interference was decreased with positive suggestion and increased with negative suggestion compared to baseline. Intra-individual variability was also increased under negative suggestion compared to baseline. Compliance with the instruction to imagine a modulation of performance, on the other hand, did not influence accuracy and only had a negative impact on response latencies and on intra-individual variability, especially in the congruent condition of the Stroop Task. Taken together, these results demonstrate that expectations induced by a placebo-suggestion can modulate our ability to resolve cognitive conflict, either facilitating or impairing response accuracy depending on the suggestion's contents. Our results also demonstrate a dissociation between placebo-suggestion and non-hypnotic imaginative suggestion.

Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

International Nuclear Information System (INIS)

Oda, Kenji; Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

1998-01-01

It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

Increased relative risk of myelodysplastic syndrome in atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Oda, Kenji [Hiroshima City Hospital (Japan); Kimura, Akiro; Matsuo, Tatsuki; Tomonaga, Masao; Kodama, Kazunori; Mabuchi, Kiyohiko

1998-12-01

It was investigated what blood disorders except leukemia increased the relative risk with dose dependency in atomic bomb survivors. Subjects were 217 patients of atomic bomb survivors in Hiroshima and Nagasaki, who had blood disorders except leukemia and died between 1950 and 1990. Their medical records were analyzed and their diagnoses were reevaluated. Sixteen cases were diagnosed as the aplastic anemia and 12 as the myelodysplastic syndrome (MDS). In the aplastic anemia, there was no correlation between the exposure dose and the mortality. In MDS, the excess relative risk (ERR)/bone marrow exposure dose of 1 Sv was very high (13.0). These results supports the hypothesis that MDS would be broken out by the clonal abnormality of the hematopoietic stem cell and radiation exposure could cause the appearance of the abnormal stem cell clone. (K.H.)

HEALTH TECHNOLOGY ASSESSMENT OF MEDICAL DEVICES IN EUROPE: PROCESSES, PRACTICES, AND METHODS.

Science.gov (United States)

Fuchs, Sabine; Olberg, Britta; Panteli, Dimitra; Busse, Reinhard

2016-01-01

To review and compare current Health Technology Assessment (HTA) activities for medical devices (MDs) across European HTA institutions. A comprehensive approach was adopted to identify institutions involved in HTA in European countries. We systematically searched institutional Web sites and other online sources by using a structured tool to extract information on the role and link to decision making, structure, scope, process, methodological approach, and available HTA reports for each included institution. Information was obtained from eighty-four institutions, forty-seven of which were analyzed. Fifty-four methodological documents from twenty-three agencies in eighteen countries were identified. Only five agencies had separate documents for the assessment of MDs. A few agencies made separate provisions for the assessment of MDs in their general methods. The amount of publicly available HTA reports on MDs varied by device category and agency remit. Despite growing consensus on their importance and international initiatives, such as the EUnetHTA Core Model®, specific tools for the assessment of MDs are rarely developed and implemented at the national level. Separate additional signposts incorporated in existing general methods guides may be sufficient for the evaluation of MDs.

Myelodysplastic syndromes and the role of iron overload.

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Harvey, R Donald

2010-04-01

The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

The Promise of Telemedicine for Movement Disorders: an Interdisciplinary Approach.

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Ben-Pazi, H; Browne, P; Chan, P; Cubo, E; Guttman, M; Hassan, A; Hatcher-Martin, J; Mari, Z; Moukheiber, E; Okubadejo, N U; Shalash, A

2018-04-13

Advances in technology have expanded telemedicine opportunities covering medical practice, research, and education. This is of particular importance in movement disorders (MDs), where the combination of disease progression, mobility limitations, and the sparse distribution of MD specialists increase the difficulty to access. In this review, we discuss the prospects, challenges, and strategies for telemedicine in MDs. Telemedicine for MDs has been mainly evaluated in Parkinson's disease (PD) and compared to in-office care is cost-effective with similar clinical care, despite the barriers to engagement. However, particular groups including pediatric patients, rare MDs, and the use of telemedicine in underserved areas need further research. Interdisciplinary telemedicine and tele-education for MDs are feasible, provide similar care, and reduce travel costs and travel time compared to in-person visits. These benefits have been mainly demonstrated for PD but serve as a model for further validation in other movement disorders.

IER3 Expression in Childhood Myelodysplastic Syndrome

DEFF Research Database (Denmark)

de Vries, Andrica; Zwaan, Christian M.; Danen van Ooschot, Astrid

Background: Childhood myelodysplastic syndrome (MDS) is a rare disease accounting for less than 5% of all hematological malignancies. In about 50% of the MDS cases an abnormal karyotype is found by conventional karyotyping, of which chromosome 6 is involved in 10%. The immediate-early-response 3...... (IER3) gene, which is located on chromosome 6p21, encodes for a glycoprotein that plays a role in the regulation of apoptosis and cell cycle progression. Recently, it was shown that IER3 gene aberrations frequently occur in adult MDS patients, which are not restricted to patients with chromosome 6...... aberrations and that low IER3 expression was associated with a worse outcome. Therefore, we investigated the frequency and prognostic impact of IER3 expression in childhood MDS. Methods: IER3 mRNA expression was determined by quantitative real-time PCR in 58 childhood MDS patients of which 17 carried...

Tempo of Diversification of Global Amphibians: One-Constant Rate, One-Continuous Shift or Multiple-Discrete Shifts?

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Youhua Chen

2014-01-01

Full Text Available In this brief report, alternative time-varying diversification rate models were fitted onto the phylogeny of global amphibians by considering one-constant-rate (OCR, one-continuous-shift (OCS and multiplediscrete- shifts (MDS situations. The OCS diversification model was rejected by γ statistic (γ=-5.556, p⁄ 0.001, implying the existence of shifting diversification rates for global amphibian phylogeny. Through model selection, MDS diversification model outperformed OCS and OCR models using “laser” package under R environment. Moreover, MDS models, implemented using another R package “MEDUSA”, indicated that there were sixteen shifts over the internal nodes for amphibian phylogeny. Conclusively, both OCS and MDS models are recommended to compare so as to better quantify rate-shifting trends of species diversification. MDS diversification models should be preferential for large phylogenies using “MEDUSA” package in which any arbitrary numbers of shifts are allowed to model.

Burgers vector analysis of large area misfit dislocation arrays from bend contour contrast in transmission electron microscope images

CERN Document Server

Spiecker, E

2002-01-01

A transmission electron microscopy method is described which allows us to determine the Burgers vectors (BVs) of a large number of interfacial misfit dislocations (MDs) in mismatched heterostructures. The method combines large-area plan-view thinning of the sample for creating a strongly bent electron transparent foil with the analysis of the splitting and displacement of bend contours at their crossings with the MDs. The BV analysis is demonstrated for 60 deg. MDs in a low-mismatched SiGe/Si(001) heterostructure. Crossings of various bend contours with the MDs are analysed with respect to their information content for the BV analysis. In future applications the method may be used for analysing such a large number of MDs that a quantitative comparison with x-ray diffraction experiments, especially with data on diffusely scattered x-rays originating from the strain fields around the dislocations, becomes possible.

The Maple reactor project

International Nuclear Information System (INIS)

Malkoske, G.R.; Labrie, J.-P.

2003-01-01

MDS Nordion supplies the majority of the world's reactor-produced medical isotopes. These isotopes are currently produced in the NRU reactor at AECL's Chalk River Laboratories (CRL). Medical isotopes and related technology are relied upon around the world to prevent, diagnose and treat disease. The NRU reactor, which has played a key role in supplying medical isotopes to date, has been in operation for over 40 years. Replacing this aging reactor has been a priority for MDS Nordion to assure the global nuclear medicine community that Canada will continue to be a dependable supplier of medical isotopes. MDS Nordion contracted AECL to construct two MAPLE reactors dedicated to the production of medical isotopes. The MDS Nordion Medical Isotope Reactor (MMIR) project started in September 1996. This paper describes the MAPLE reactors that AECL has built at its CRL site, and will operate for MDS Nordion. (author)

Multidimensional scaling analysis of financial time series based on modified cross-sample entropy methods

Science.gov (United States)

He, Jiayi; Shang, Pengjian; Xiong, Hui

2018-06-01

Stocks, as the concrete manifestation of financial time series with plenty of potential information, are often used in the study of financial time series. In this paper, we utilize the stock data to recognize their patterns through out the dissimilarity matrix based on modified cross-sample entropy, then three-dimensional perceptual maps of the results are provided through multidimensional scaling method. Two modified multidimensional scaling methods are proposed in this paper, that is, multidimensional scaling based on Kronecker-delta cross-sample entropy (MDS-KCSE) and multidimensional scaling based on permutation cross-sample entropy (MDS-PCSE). These two methods use Kronecker-delta based cross-sample entropy and permutation based cross-sample entropy to replace the distance or dissimilarity measurement in classical multidimensional scaling (MDS). Multidimensional scaling based on Chebyshev distance (MDSC) is employed to provide a reference for comparisons. Our analysis reveals a clear clustering both in synthetic data and 18 indices from diverse stock markets. It implies that time series generated by the same model are easier to have similar irregularity than others, and the difference in the stock index, which is caused by the country or region and the different financial policies, can reflect the irregularity in the data. In the synthetic data experiments, not only the time series generated by different models can be distinguished, the one generated under different parameters of the same model can also be detected. In the financial data experiment, the stock indices are clearly divided into five groups. Through analysis, we find that they correspond to five regions, respectively, that is, Europe, North America, South America, Asian-Pacific (with the exception of mainland China), mainland China and Russia. The results also demonstrate that MDS-KCSE and MDS-PCSE provide more effective divisions in experiments than MDSC.

Development a minimum data set of the information management system for burns.

Science.gov (United States)

Ahmadi, Maryam; Alipour, Jahanpour; Mohammadi, Ali; Khorami, Farid

2015-08-01

Burns are the most common and destructive injuries in across of the world and especially in developing countries. Nevertheless, a standard tool for collecting the data of burn injury has not been developed yet. The purpose of this study was to develop a minimum data set (MDS) of the information management system for burns in Iran. This descriptive and cross-sectional study was performed in 2014. Data were collected from hospitals affiliated with Hormozgan and Iran University of Medical Sciences and medical documents centers, emergency centers and legal medicine centers located in Bandar Abbas city, in addition to internet access and library. Investigated documents were burn injury records in 2013, and documents that retrieved from the internet, and printed materials. Records were selected randomly based on T20-T29 categories from ICD-10. Data were collected using a checklist. In order to make a consensus about the data elements the decision Delphi technique was applied using a questionnaire. The content validity and reliability of questionnaire were assessed by expert's opinions and test-retest method, respectively. An MDS of burns was developed. This MDS divided into two categories: administrative and clinical with six and 17 section and 161 and 311 data elements respectively. This study showed that comprehensive and uniform data elements about burns do not exist in Iran. Therefore a MDS was developed for burns in Iran. Development of an MDS will result in standardization and effective management of the data through providing uniform and comprehensive data elements for burns. Thus, comparability of the extracted information from different analyses and researches will be possible in various levels. In addition, establishment of policies and prevention and control of burns will be possible, which results in the improvement of the quality of care and containment of costs. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Considering Bone Marrow Blasts From Nonerythroid Cellularity Improves the Prognostic Evaluation of Myelodysplastic Syndromes.

Science.gov (United States)

Arenillas, Leonor; Calvo, Xavier; Luño, Elisa; Senent, Leonor; Alonso, Esther; Ramos, Fernando; Ardanaz, María Teresa; Pedro, Carme; Tormo, Mar; Marco, Víctor; Montoro, Julia; Díez-Campelo, María; Brunet, Salut; Arrizabalaga, Beatriz; Xicoy, Blanca; Andreu, Rafael; Bonanad, Santiago; Jerez, Andrés; Nomdedeu, Benet; Ferrer, Ana; Sanz, Guillermo F; Florensa, Lourdes

2016-09-20

WHO classification of myeloid malignancies is based mainly on the percentage of bone marrow (BM) blasts. This is considered from total nucleated cells (TNCs), unless there is erythroid-hyperplasia (erythroblasts ≥ 50%), calculated from nonerythroid cells (NECs). In these instances, when BM blasts are ≥ 20%, the disorder is classified as erythroleukemia, and when BM blasts are < 20%, as myelodysplastic syndrome (MDS). In the latter, the percentage of blasts is considered from TNCs. We assessed the percentage of BM blasts from TNCs and NECs in 3,692 patients with MDS from the Grupo Español de Síndromes Mielodisplásicos, 465 patients with erythroid hyperplasia (MDS-E) and 3,227 patients without erythroid hyperplasia. We evaluated the relevance of both quantifications on classification and prognostication. By enumerating blasts systematically from NECs, 22% of patients with MDS-E and 12% with MDS from the whole series diagnosed within WHO categories with < 5% BM blasts, were reclassified into higher-risk categories and showed a poorer overall survival than did those who remained in initial categories (P = .006 and P = .001, respectively). Following WHO recommendations, refractory anemia with excess blasts (RAEB)-2 diagnosis is not possible in MDS-E, as patients with 10% to < 20% BM blasts from TNCs fulfill erythroleukemia criteria; however, by considering blasts from NECs, 72 patients were recoded as RAEB-2 and showed an inferior overall survival than did patients with RAEB-1 without erythroid hyperplasia. Recalculating the International Prognostic Scoring System by enumerating blasts from NECs in MDS-E and in the overall MDS population reclassified approximately 9% of lower-risk patients into higher-risk categories, which indicated the survival expected for higher-risk patients. Regardless of the presence of erythroid hyperplasia, calculating the percentage of BM blasts from NECs improves prognostic assessment of MDS. This fact should be considered in future

[3D printing in health care facilities: What legislation in France?].

Science.gov (United States)

Montmartin, M; Meyer, C; Euvrard, E; Pazart, L; Weber, E; Benassarou, M

2015-11-01

Health care facilities more and more use 3D printing, including making their own medical devices (MDs). However, production and marketing of MDs are regulated. The goal of our work was to clarify what is the current French regulation that should be applied concerning the production of custom-made MDs produced by 3D printing in a health care facility. MDs consist of all devices used for diagnosis, prevention, or treatment of diseases in patients. Prototypes and anatomic models are not considered as MDs and no specific laws apply to them. Cutting guides, splints, osteosynthesis plates or prosthesis are MDs. In order to become a MD manufacturer in France, a health care facility has to follow the requirements of the 93/42/CEE directive. In addition, custom-made 3D-printed MDs must follow the annex VIII of the directive. This needs the writing of a declaration of conformity and the respect of the essential requirements (proving that a MD is secure and conform to what is expected), the procedure has to be qualified, a risk analysis and a control of the biocompatibility of the material have to be fulfilled. The documents proving that these rules have been respected have to be available. Becoming a regulatory manufacturer of MD in France is possible for a health care facility but the specifications have to be respected. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The impact of hypnotic suggestibility in clinical care settings.

Science.gov (United States)

Montgomery, Guy H; Schnur, Julie B; David, Daniel

2011-07-01

Hypnotic suggestibility has been described as a powerful predictor of outcomes associated with hypnotic interventions. However, there have been no systematic approaches to quantifying this effect across the literature. This meta-analysis evaluates the magnitude of the effect of hypnotic suggestibility on hypnotic outcomes in clinical settings. PsycINFO and PubMed were searched from their inception through July 2009. Thirty-four effects from 10 studies and 283 participants are reported. Results revealed a statistically significant overall effect size in the small to medium range (r = .24; 95% Confidence Interval = -0.28 to 0.75), indicating that greater hypnotic suggestibility led to greater effects of hypnosis interventions. Hypnotic suggestibility accounted for 6% of the variance in outcomes. Smaller sample size studies, use of the SHCS, and pediatric samples tended to result in larger effect sizes. The authors question the usefulness of assessing hypnotic suggestibility in clinical contexts.

Therapy related myelodysplastic syndrome: A case report and review of literature

Directory of Open Access Journals (Sweden)

Smita Sonawane

2011-01-01

Full Text Available Therapy related myeloid neoplasm is directly related to previous cytotoxic chemotherapy or radiation therapy. We present a 47-year-old lady who developed therapy related myelodysplastic syndrome (MDS 2.5 years after she received four cycles of chemotherapy and local radiation therapy for carcinoma breast. She presented with bicytopenia with trilineage dyspoiesis in the peripheral blood, bone marrow aspirate and biopsy. Fluorescent in-situ hybridization studies did not reveal any of the common abnormalities associated with MDS. A diagnosis of therapy related MDS was rendered. Different studies have shown that patients treated with alkylating agents and ionizing radiation present as MDS with a latent period of 3-10 years. Our patient developed MDS within 2.5 years of starting chemotherapy and radiotherapy and did not reveal any of the conventional cytogenetic abnormalities. It highlights the importance of simple tests like a complete blood count and peripheral blood smear examination in follow-up of the patients treated with chemotherapy.

Nuances of Morphology in Myelodysplastic Diseases in the Age of Molecular Diagnostics.

Science.gov (United States)

Shaver, Aaron C; Seegmiller, Adam C

2017-10-01

Morphologic dysplasia is an important factor in diagnosis of myelodysplastic syndrome (MDS). However, the role of dysplasia is changing as new molecular genetic and genomic technologies take a more prominent place in diagnosis. This review discusses the role of morphology in the diagnosis of MDS and its interactions with cytogenetic and molecular testing. Recent changes in diagnostic criteria have attempted to standardize approaches to morphologic diagnosis of MDS, recognizing significant inter-observer variability in assessment of dysplasia. Definitive correlates between cytogenetic/molecular and morphologic findings have been described in only a small set of cases. However, these genetic and morphologic tools do play a complementary role in the diagnosis of both MDS and other myeloid neoplasms. Diagnosis of MDS requires a multi-factorial approach, utilizing both traditional morphologic as well as newer molecular genetic techniques. Understanding these tools, and the interplay between them, is crucial in the modern diagnosis of myeloid neoplasms.

A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

Science.gov (United States)

Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

2009-12-01

Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors. 2009 Wiley-Liss, Inc.

Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

Directory of Open Access Journals (Sweden)

Andrea Farini

2014-01-01

Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

Investigation of 305 patients with myelodysplastic syndromes and 20q deletion for associated cytogenetic and molecular genetic lesions and their prognostic impact.

Science.gov (United States)

Bacher, Ulrike; Haferlach, Torsten; Schnittger, Susanne; Zenger, Melanie; Meggendorfer, Manja; Jeromin, Sabine; Roller, Andreas; Grossmann, Vera; Krauth, Maria-Theresa; Alpermann, Tamara; Kern, Wolfgang; Haferlach, Claudia

2014-03-01

In patients with myelodysplastic syndromes (MDS), sole 20q deletion [del(20q)] is a recurrent favourable abnormality. We studied additional molecular and cytogenetic lesions and their prognostic impact in 305 MDS patients with del(20q) (229 males/76 females; 29-90 years). All patients were investigated by cytomorphology and chromosome banding analysis (CBA), subsets by fluorescence in situ hybridization, molecular mutation screening, and array comparative genomic hybridization (aCGH). By aCGH (n = 30), the minimal common deleted region (CDR) was flanked by PTPRT (20q13·11) and EYA2 (20q13·12). 210 (68·9%) patients had 'early MDS' without blast increase, 95 (31·1%) 'advanced' MDS with blast increase (5-19%). Additional chromosomal abnormalities (ACAs) were detected in 88/305 (28·9%) patients. Patients with advanced MDS more frequently had ACAs (P = 0·003) and had a higher mean number of ACAs (P = 0·020) and of molecular mutations (P = 0·060). Spliceosome mutations were frequent (U2AF1: n = 31/155; 20·0%; SRSF2: n = 31/159; 19·5%; SF3B1mut: n = 8/159; 5·0%). ASXL1mut (25/153; 16·3%) were associated with advanced MDS (P = 0·001). Presence of ≥3 ACAs (P = 0·003) and ASXL1mut (P = 0·002) were associated with worse 2-year survival. In conclusion, the cytogenetic subgroup of MDS with del(20q) has a good prognosis but may be further subclassified by additional cytogenetic and molecular lesions. U2AF1mut is overrepresented in MDS with del(20q), and ASXL1mut is prognostically adverse. © 2013 John Wiley & Sons Ltd.

Radiation protection at radioisotope processing facilities

International Nuclear Information System (INIS)

Hillier, L.R.; Decaire, R.

2002-01-01

MDS Inc. is Canada's largest diversified health and life sciences company and provides health care services and products to prevent, diagnose and treat disease. MDS Nordion Inc. is a subsidiary of MDS Inc. and is located in Ottawa, Ontario. It provides much of the world's supply of radioisotopes used in nuclear medicine primarily to diagnose, but also to treat disease. MDS Nordion is composed of three major production divisions at its Ottawa location and serves customers in three major markets. These are primarily: radioisotopes used in nuclear medicine (Nuclear Medicine Division), radiation processing for sterilization of medical equipment and supplies, and food (Ion Technologies Division), and teletherapy equipment used in cancer treatment (Therapy Systems Division). MDS Nordion supplies customers in over 100 countries, exporting more than 95 percent of its product processed in Canada. Every year, 15 to 20 million diagnostic imaging tests are carried out in hospitals around the world, using radioisotopes supplied by MDS Nordion. In addition, 150 to 200 million cubic feet (that's enough to cover an entire CFL field - including the end zones - stacked over half a kilometer high) of single use medical products are sterilized using MDS Nordion supplied equipment. MDS Nordion receives medical isotopes from AECL, Chalk River Laboratories and processes the material to purify and quantify the radioisotope product. Sealed sources, comprised of cobalt 60, are supplied from CANDU reactors. Production processes include ventilated shielded cells with remote manipulators, gloveboxes and fumehoods, to effectively control the safety of the workplace and the environment, and to prevent contamination of the products. The facilities are highly regulated by the Canadian Nuclear Safety Commission (CNSC) for safety and environmental protection. Products are also regulated by Health Canada and the US-Food and Drug Administration (FDA). (author)

Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

Science.gov (United States)

Komrokji, Rami; Swern, Arlene S; Grinblatt, David; Lyons, Roger M; Tobiasson, Magnus; Silverman, Lewis R; Sayar, Hamid; Vij, Ravi; Fliss, Albert; Tu, Nora; Sugrue, Mary M

2018-02-01

After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS. We searched English-language articles for prospective phase II and III azacitidine clinical trials and patient registries published between 2000 and 2015, and Embase abstracts from 2015 conferences. Patient-level data from identified relevant studies were provided by investigators. Meta-analyses followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Efficacy endpoints were RBC transfusion independence (TI) and Clinical Benefit (RBC-TI, erythroid response, and complete or partial remission, per International Working Group 2006 criteria for MDS). Data for 233 patients from 6 clinical studies and 1 registry study met criteria for inclusion in analyses. Overall, 90.3% of patients had non-del(5q) LR-MDS. Pooled estimates from random-effects models of RBC-TI and Clinical Benefit were 38.9% and 81.1%, respectively; for the ESA-refractory subgroup, they were 40.5% and 77.3%; and for patients with isolated anemia, they were 41.9% and 82.5%. In multivariate analyses, planned use of ≥6 azacitidine treatment cycles was significantly predictive of response. Azacitidine effects in these patients, most with non-del(5q) LR-MDS, were promising and generally similar to those reported for lenalidomide in similar patients. The choice of initial therapy is important because most patients eventually stop responding to front-line therapy and alternatives are limited. Lower-risk myelodysplastic syndromes (LR-MDS) are primarily characterized by

A Randomized Controlled Trial to Improve the Success of Women Assistant Professors

Science.gov (United States)

Grisso, Jeane Ann; Sammel, Mary Dupuis; Rubenstein, Arthur H.; Speck, Rebecca M.; Conant, Emily F.; Scott, Patricia; Tuton, Lucy Wolf; Westring, Alyssa Friede; Friedman, Stewart

2017-01-01

Abstract Background: Given the persistent disparity in the advancement of women compared with men faculty in academic medicine, it is critical to develop effective interventions to enhance women's careers. We carried out a cluster-randomized, multifaceted intervention to improve the success of women assistant professors at a research-intensive medical school. Materials and Methods: Twenty-seven departments/divisions were randomly assigned to intervention or control groups. The three-tiered intervention included components that were aimed at (1) the professional development of women assistant professors, (2) changes at the department/division level through faculty-led task forces, and (3) engagement of institutional leaders. Generalized linear models were used to test associations between assignment and outcomes, adjusting for correlations induced by the clustered design. Results: Academic productivity and work self-efficacy improved significantly over the 3-year trial in both intervention and control groups, but the improvements did not differ between the groups. Average hours worked per week declined significantly more for faculty in the intervention group as compared with the control group (−3.82 vs. −1.39 hours, respectively, p = 0.006). The PhD faculty in the intervention group published significantly more than PhD controls; however, no differences were observed between MDs in the intervention group and MDs in the control group. Conclusions: Significant improvements in academic productivity and work self-efficacy occurred in both intervention and control groups, potentially due to school-wide intervention effects. A greater decline in work hours in the intervention group despite similar increases in academic productivity may reflect learning to “work smarter” or reveal efficiencies brought about as a result of the multifaceted intervention. The intervention appeared to benefit the academic productivity of faculty with PhDs, but not MDs, suggesting

Population data of 19 autosomal STR loci in the Li population from Hainan Province in southernmost China.

Science.gov (United States)

Fan, Haoliang; Wang, Xiao; Ren, Zheng; He, Guanglin; Long, Ren; Liang, Anwen; Song, Tao; Deng, Jianqiang

2018-03-20

In the present study, population data of 19 autosomal STR loci included in the Goldeneye™ DNA ID System 20A in 653 Li individuals was obtained and population genetic relationships among 13 populations were investigated. MDS and phylogenetic analysis suggested that the Hainan Li population kept a close genetic relationship with the Chinese Han populations, especially for Southern Han populations (Guangdong Han, Sichuan Han, and Hunan Han). Our results indicated that the 19 autosomal STRs are highly discriminative and polymorphic in the Hainan Li population suitable for personal forensic identification and paternity testing.

APPRAISAL KEBERLANJUTAN MULTIDIMENSI PENGGUNAAN LAHAN UNTUK SAWAH DI KARAWANG - JAWA BARAT

Directory of Open Access Journals (Sweden)

Widiatmaka Widiatmaka

2015-10-01

Full Text Available Indonesian national food sovereignty is very dependent on the supply of rice from paddy fields in Java Island. Various factors influence the farmer’s decision to continue using his farm. This study aims to analyze the sustainable use of paddy field, determinant factors and strategies for improving sustainability. The study was conducted in Karawang Regency, one of the centers of rice production in West Java. The methodology used is a multi-dimensional scaling (MDS using 43 attributes of 5 dimensions (ecological, social, economical, technological and legal and institutional dimension. Against the sensitive attribute analysis resulting from MDS, a prospective analysis was conducted to determine the key factors of sustainability. Priority policies for improving sustainability are developed based on the location of the key factors in the prospective diagram. The research results showed that the land utilization for paddy field in Karawang is actually less sustainable. Increasing the sustainability can be done through intervention and improving performance, preferably on sensitive attributes resulting from leverage analysis, covering 16 attributes. Priority policies is directed in the 5 key factors resulting from prospective analysis. Policies suggested are the tightening of new permits for building, strict implementation of the official spatial land use planning and delineation of agricultural land for sustainable food crops, counseling the community, revitalizing the role of BULOG, provision of subsidies as well as capital assistance to farmers.

Characterization and prognostic implication of 17 chromosome abnormalities in myelodysplastic syndrome.

Science.gov (United States)

Sánchez-Castro, Judit; Marco-Betés, Víctor; Gómez-Arbonés, Xavier; Arenillas, Leonor; Valcarcel, David; Vallespí, Teresa; Costa, Dolors; Nomdedeu, Benet; Jimenez, María José; Granada, Isabel; Grau, Javier; Ardanaz, María T; de la Serna, Javier; Carbonell, Félix; Cervera, José; Sierra, Adriana; Luño, Elisa; Cervero, Carlos J; Falantes, José; Calasanz, María J; González-Porrás, José R; Bailén, Alicia; Amigo, M Luz; Sanz, Guillermo; Solé, Francesc

2013-07-01

The prognosis of chromosome 17 (chr17) abnormalities in patients with primary myelodysplastic syndrome (MDS) remains unclear. The revised International Prognostic Scoring System (IPSS-R) includes these abnormalities within the intermediate cytogenetic risk group. This study assessed the impact on overall survival (OS) and risk of acute myeloid leukemia transformation (AMLt) of chr17 abnormalities in 88 patients with primary MDS. We have compared this group with 1346 patients with primary MDS and abnormal karyotype without chr17 involved. The alterations of chr17 should be considered within group of poor prognosis. The different types of alterations of chromosome 17 behave different prognosis. The study confirms the intermediate prognostic impact of the i(17q), as stated in IPSS-R. The results of the study, however, provide valuable new information on the prognostic impact of alterations of chromosome 17 in complex karyotypes. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Results of immunosupressive therapy in children with severe aplastic anaemia. Report of the Polish Paediatric Haematology Group].

Science.gov (United States)

Pawelec, Katarzyna; Matysiak, Michał; Niewiadomska, Edyta; Rokicka-Milewska, Roma; Kowalczyk, Jerzy; Stefaniak, Jolanta; Balwierz, Walentyna; Załecka-Czerpko, Ewa; Chybicka, Alicja; Szmyd, Krzysztof; Sońta-Jakimczyk, Danuta; Bubała, Halina; Krauze, Agnieszka; Wysocki, Mariusz; Kurylak, Andrzej; Wachowiak, Jacek; Grund, Grzegorz; Młynarski, Wojciech; Bulas, Monika; Krawczuk-Rybak, Maryna; Leszczyńska, Elzbieta; Urasiński, Tomasz; Peregud-Pogorzelski, Jarosław; Balcerska, Anna; Włazłowski, Marek

2008-01-01

Bone marrow transplantation from HLA identical family donors is the treatment of choice for children with severe aplastic anaemia (SAA). When there is no donor available, combined immunosuppressive therapy is given. evaluation of results of immunosupressive therapy in children with severe aplastic anaemia. SAA was diagnosed in 105 children (42 girls, 73 boys), aged 2-18 years, in the eleven haematological centres in Poland, between 1993-2007. All patients received the Severe Aplastic Anaemia Working Party of the EBMT protocol which included: antilymphocyte globulin or antithymocyte globulin, cyclosporin A, prednisolone. Granulocyto- or granulocytomacrophagic-cell stimulation factor was additionally administered during deep neutropenia. Haematological response was evaluated on day 84 or 112 and 180 of the therapy. complete remission occurred in 53 patients (51.5%), partial remission in 27 (24.7%), no response was obtained in 25 children (23.8%) on day 180, of the therapy. Period of observation was from 12 months to 12.5 years. During this time relapse occurred in 10 patients (9.5%). We observed 22 deaths: 8 early, during the first 3 months of IS and 14 after the first 3 months of immunosuppresive therapy (IS). At present 70 children (66.6%) are in first remission with lasts from 12 months to 12.5 years. The survival at 12.5-years is 78.6%. During the 12.5 years of follow-up we had two cases with a late clonal complication (PNH and MDS). Transformation to acute nonlymphoblastic leukaemia was observed in two of our patients. 1. Immunosuppresive therapy (IS) in children with SAA, without bone marrow family donors, is more effective after introduction of combined IS (12.5 years survival in this study was 80% for children with very severe aplastic anaemia (v SAA). 2. In our studies among the children followed up after IS therapy, there were: 1 case of periodic nocturnal haemoglobinuria (PNH), 1 case of myelodysplastic syndrome (MDS) and 2 cases of myeloid leukaemia

Pesticide exposure as a risk factor for myelodysplastic syndromes: a meta-analysis based on 1,942 cases and 5,359 controls.

Directory of Open Access Journals (Sweden)

Jie Jin

Full Text Available Pesticide exposure has been linked to increased risk of cancer at several sites, but its association with risk of myelodysplastic syndromes (MDS is still unclear. A meta-analysis of studies published through April, 2014 was performed to investigate the association of pesticide exposure with the risk of MDS.Studies were identified by searching the Web of Science, Cochrane Library and PubMed databases. Summary odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated using random- or fixed-effect models.This meta-analysis included 11 case-control studies, all of which demonstrated a correlation between pesticide exposure and a statistically significant increased risk of MDS (OR=1.95, 95% CI 1.23-3.09. In subgroup analyses, patients with pesticide exposure had increased risk of developing MDS if they were living in the Europe or Asia and had refractory anemia (RA or RA with ringed sideroblasts (RARS. Moreover, in the analysis by specific pesticides, increased risk was associated with exposure to insecticides (OR=1.71, 95% CI 1.22-2.40 but not exposure to herbicides or fungicides.This meta-analysis supports the hypothesis that exposure to pesticides increases the risk of developing MDS. Further prospective cohort studies are warranted to verify the association and guide clinical practice in MDS prevention.

Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

Science.gov (United States)

Shammo, Jamile M; Komrokji, Rami S

2018-06-14

Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

Enhancing business intelligence by means of suggestive reviews.

Science.gov (United States)

Qazi, Atika; Raj, Ram Gopal; Tahir, Muhammad; Cambria, Erik; Syed, Karim Bux Shah

2014-01-01

Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers' choices and designers' understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1) classify comparative and suggestive sentences; (2) categorize suggestive sentences into different types, either explicit or implicit locutions; (3) perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons.

Supportive care organisation in France: an in depth study by the French speaking association for supportive care in cancer (AFSOS).

Science.gov (United States)

Scotté, F; Hervé, C; Oudard, S; Bugat, M E; Bugat, R; Farsi, F; Namer, M; Tourani, J M; Tournigand, C; Yazbek, G; Richard, S; Krakowski, I

2013-03-01

Supportive care in cancer (SCC) was further enhanced in the Second National Cancer Act decreed in December 2009. The aim of our study was to assess current SCC efficacy. The French speaking association for supportive care in cancer (AFSOS) conducted an observational study to evaluate practices, organisations and information given to patients. A specific 32 point questionnaire was sent to 1621 French physicians (MDs) caring for cancer patients. Three different organisations were evaluated: the individual MDs, the transversal team and its particular structure specialised in global patient care specifically developed at comprehensive cancer centres - CCC. During their disease, 68% of patients received SCC, which was more available during the palliative period (90%) than at the diagnosis (44%). Our results found that 71% of cancer departments had a specific interdisciplinary cross-team to provide SCC, particularly in CCC (62%; p=0.01) while 37% had specific inpatient units. A specific organisation dedicated to home care was greater in CCC than in public or private centres (69%, 45%, 20% respectively; p=0.01). Adverse event information was performed more by an oncologist than other specialists (p=0.01). Our results suggest that the specific SCC organisation could be a useful management tool to improve supportive care for cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vitro study on chromosomal abnormality, proliferation and differentiation of hemopoietic stem cells from atomic bomb exposures and patients with acute leukemia and related disorders

Energy Technology Data Exchange (ETDEWEB)

Amenomori, Tatsuhiko

1988-12-01

By using in vitro cloning method and cytogenetic analysis from single hemopoietic colonies, the kinetics of differentiation and proliferation, and chromosomal abnormalities of hemopoietic stem cells (CFU-GM, BFU-E) from atomic bomb exposures and patients with acute leukemia and myelodysplastic syndrome (MDS) were investigated. High incidence (24 colonies/ 206 total colonies; 11.7%) of irradiation-induced chromosomal abnormalities was observed in circulating hemopoietic stem cells from 21 high dose exposures. In two individuals, karyotypic abnormalities closely resembling those observed in the peripheral T lymphocytes were also seen in the myeloid stem cells (BFU-E). This finding suggests that totipotential stem cells common to myeloid and lymphoid lineages exist in healthy human adults and atomic bomb irradiation produced chromosomal aberrations in them. In each of 5 MDS cases with both GM colony and erythroid burst formation, identical marker chromosomes were seen in CFU-GM and BFU-E. This finding demonstrates that MDS is a clonal hemopathy that originates in a pluripotential stem cell. Whether acute leukemia is also a clonal hemopathy originating in a pluripotential stem cell remains to be determined. But there was a considerable heterogeneity in kinetics of proliferation and in responsiveness to colony stimulating factors among these cases. (author) 54 refs.

The effect of posthypnotic suggestion, hypnotic suggestibility, and goal intentions on adherence to medical instructions.

Science.gov (United States)

Carvalho, Claudia; Mazzoni, Giuliana; Kirsch, Irving; Meo, Maria; Santandrea, Maura

2008-04-01

The effects of implementation intentions and posthypnotic suggestion were investigated in 2 studies. In Experiment 1, participants with high levels of hypnotic suggestibility were instructed to take placebo pills as part of an investigation of how to best enhance compliance with medical instruction. In Experiment 2, participants with high, medium, and low levels of hypnotic suggestibility were asked to run in place, take their pulse rate before, and send an e-mail report to the experimenter each day. Experiment 1 revealed enhanced adherence as a function of both implementation intentions and posthypnotic suggestion. Experiment 2 failed to find any significant main effects but found a significant interaction between suggestibility and the effects of posthypnotic suggestion. Posthypnotic suggestion enhanced adherence among high suggestible participants but lowered it among low suggestibles.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder

Directory of Open Access Journals (Sweden)

Cristy Phillips

2017-01-01

Full Text Available Mood disorders (MDs are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA has shown clear and consistent promise. Accordingly, the aims of this review are to (1 explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2 explore the putative mechanisms by which PA mitigates these features; (3 review protocols used to induce the positive effects of PA in MDs; and (4 highlight implications for clinicians and researchers.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder

Science.gov (United States)

2017-01-01

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers. PMID:28529805

Suggestibility under Pressure: Theory of Mind, Executive Function, and Suggestibility in Preschoolers

Science.gov (United States)

Karpinski, Aryn C.; Scullin, Matthew H.

2009-01-01

Eighty preschoolers, ages 3 to 5 years old, completed a 4-phase study in which they experienced a live event and received a pressured, suggestive interview about the event a week later. Children were also administered batteries of theory of mind and executive function tasks, as well as the Video Suggestibility Scale for Children (VSSC), which…

Structural and functional correlates of hypnotic depth and suggestibility.

Science.gov (United States)

McGeown, William Jonathan; Mazzoni, Giuliana; Vannucci, Manila; Venneri, Annalena

2015-02-28

This study explores whether self-reported depth of hypnosis and hypnotic suggestibility are associated with individual differences in neuroanatomy and/or levels of functional connectivity. Twenty-nine people varying in suggestibility were recruited and underwent structural, and after a hypnotic induction, functional magnetic resonance imaging at rest. We used voxel-based morphometry to assess the correlation of grey matter (GM) and white matter (WM) against the independent variables: depth of hypnosis, level of relaxation and hypnotic suggestibility. Functional networks identified with independent components analysis were regressed with the independent variables. Hypnotic depth ratings were positively correlated with GM volume in the frontal cortex and the anterior cingulate cortex (ACC). Hypnotic suggestibility was positively correlated with GM volume in the left temporal-occipital cortex. Relaxation ratings did not correlate significantly with GM volume and none of the independent variables correlated with regional WM volume measures. Self-reported deeper levels of hypnosis were associated with less connectivity within the anterior default mode network. Taken together, the results suggest that the greater GM volume in the medial frontal cortex and ACC, and lower connectivity in the DMN during hypnosis facilitate experiences of greater hypnotic depth. The patterns of results suggest that hypnotic depth and hypnotic suggestibility should not be considered synonyms. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Enhancing Business Intelligence by Means of Suggestive Reviews

Science.gov (United States)

Qazi, Atika

2014-01-01

Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers' choices and designers' understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1) classify comparative and suggestive sentences; (2) categorize suggestive sentences into different types, either explicit or implicit locutions; (3) perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons. PMID:25054188

Enhancing Business Intelligence by Means of Suggestive Reviews

Directory of Open Access Journals (Sweden)

Atika Qazi

2014-01-01

Full Text Available Appropriate identification and classification of online reviews to satisfy the needs of current and potential users pose a critical challenge for the business environment. This paper focuses on a specific kind of reviews: the suggestive type. Suggestions have a significant influence on both consumers’ choices and designers’ understanding and, hence, they are key for tasks such as brand positioning and social media marketing. The proposed approach consists of three main steps: (1 classify comparative and suggestive sentences; (2 categorize suggestive sentences into different types, either explicit or implicit locutions; (3 perform sentiment analysis on the classified reviews. A range of supervised machine learning approaches and feature sets are evaluated to tackle the problem of suggestive opinion mining. Experimental results for all three tasks are obtained on a dataset of mobile phone reviews and demonstrate that extending a bag-of-words representation with suggestive and comparative patterns is ideal for distinguishing suggestive sentences. In particular, it is observed that classifying suggestive sentences into implicit and explicit locutions works best when using a mixed sequential rule feature representation. Sentiment analysis achieves maximum performance when employing additional preprocessing in the form of negation handling and target masking, combined with sentiment lexicons.

Outcome of patients treated for myelodysplastic syndromes without deletion 5q after failure of lenalidomide therapy

OpenAIRE

Prebet, Thomas; Toma, Andrea; Cluzeau, Thomas; Sekeres, Mikkael A.; Vey, Norbert; Park, Sophie; Al Ali, Najla; Sugrue, Marie M.; Komrokji, Rami; Fenaux, Pierre; Gore, Steven D.

2017-01-01

Anemia is a key survival prognostic factor in lower-risk myelodysplastic syndromes (MDS). Lenalidomide (LEN) can correct anemia in 25% of MDS patients without deletion 5q (del5q). As this therapy will inevitably fail, understanding the outcome of these patients will facilitate development of subsequent treatment strategies. To answer this question, an international retrospective study focused on LEN-treated lower-risk, non-del5q, MDS patients was performed. We analyzed the overall survival af...

Nature of the last contact with a medical doctor before suicide

OpenAIRE

Mars, Urša; Pirc, Lara; Mesec Rodi, Petra; Poštuvan, Vita; De Leo, Diego

2018-01-01

A relevant number of suicide decedents visit medical doctors (MDs) in a short period before death. This study aimed to learn about MDs’ attitudes towards suicide prevention, their previous education on suicide, the experience with suicide, and eventually the nature of the last visit with a patient that died by suicide. 159 Slovenian MDs participated in an online survey covering previously mentioned topics. More than a third of MDs have never been trained on suicide prevention and reported lac...

Green House Adoption and Nursing Home Quality.

Science.gov (United States)

Afendulis, Christopher C; Caudry, Daryl J; O'Malley, A James; Kemper, Peter; Grabowski, David C

2016-02-01

To evaluate the impact of the Green House (GH) model on nursing home resident-level quality of care measures. Resident-level minimum data set (MDS) assessments merged with Medicare inpatient claims for the period 2005 through 2010. Using a difference-in-differences framework, we compared changes in care quality and outcomes in 15 nursing homes that adopted the GH model relative to changes over the same time period in 223 matched nursing homes that had not adopted the GH model. For individuals residing in GH homes, adoption of the model lowered readmissions and several MDS measures of poor quality, including bedfast residents, catheter use, and pressure ulcers, but these results were not present across the entire GH organization, suggesting possible offsetting effects for residents of non-GH "legacy" units within the GH organization. GH adoption led to improvement in rehospitalizations and certain nursing home quality measures for individuals residing in a GH home. The absence of evidence of a decline in other clinical quality measures in GH nursing homes should reassure anyone concerned that GH might have sacrificed clinical quality for improved quality of life. © Health Research and Educational Trust.

Racial and ethnic comparisons of nursing home residents at admission.

Science.gov (United States)

Buchanan, Robert J; Rosenthal, Mark; Graber, David R; Wang, Suojin; Kim, Myung Suk

2008-10-01

To present racial/ethnic comparisons of comprehensive profiles of nursing home residents at admission, including whites, African Americans, Hispanics, Asians/Pacific Islanders, and American Indians/Alaska Natives. More than 885,000 admission assessments recorded in the national Minimum Data Set (MDS) were analyzed. Racial and ethnic analyses of the MDS admission assessments were conducted using the software package SAS. There were significant racial/ethnic differences in gender and age, with minority residents more likely to be male and younger. African American, Hispanic, and Asian/Pacific Islanders were significantly more likely than white residents to exhibit total dependence in the self-performance of the ADLs and to have greater cognitive impairments, with Asian/Pacific Islanders the most physically dependent and cognitively impaired. The results illustrate significant and substantive differences among the racial/ethnic groups for many demographic characteristics, as well as health-related indicators and conditions. This analysis suggests that the general perspective that economically disadvantaged minorities enter nursing homes in worse condition than whites is too simplistic. More research, particularly qualitative studies of specific minority groups, will advance our understanding of why members of some racial/ethnic groups require nursing home placement sooner than other groups.

Distinct neutrophil subpopulations phenotype by flow cytometry in myelodysplastic syndromes.

Science.gov (United States)

Vikentiou, Myrofora; Psarra, Katerina; Kapsimali, Violetta; Liapis, Konstantinos; Michael, Michalis; Tsionos, Konstantinos; Lianidou, Evi; Papasteriades, Chryssa

2009-03-01

The cardinal feature of myelodysplastic syndromes (MDS) is dysplasia involving one or more myeloid cell lineages. In the present study, we used 4-color flow cytometric analysis to investigate dysgranulopoiesis in bone marrow specimens from 65 patients with MDS. The antigen expression patterns of total neutrophil granulocytes (TNG) and of the two distinct neutrophil granulocytic subpopulations (NGSs), NGS-1 (dimmer CD45 expression) and NGS-2 (stronger CD45 expression) identified on the side scatter (SS) vs. CD45-intensity plot, were studied. The neutrophil granulocytes from patients with MDS showed characteristic antigen expression aberrancies which were more pronounced in NGS-2 subpopulation. Studying separately the NGS-2 subpopulation with the CD16/MPO/LF combination, the low CD16(+)/MPO(+) and low CD16(+)/LF(+) percentages seemed to discriminate between lower-risk and higher-risk patients with MDS in most occasions. Furthermore, a detailed assessment of the NGS-1 and NGS-2 immunophenotypic patterns revealed early dysplastic changes, not otherwise observed by standard TNG analysis, especially in cases of lower-risk MDS.

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

Science.gov (United States)

Remacha, A F; Arrizabalaga, B; Villegas, A; Manteiga, R; Calvo, T; Julià, A; Fernández Fuertes, I; González, F A; Font, L; Juncà, J; del Arco, A; Malcorra, J J; Equiza, E P; de Mendiguren, B P; Romero, M

1999-12-01

Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

An effective suggestion method for keyword search of databases

KAUST Repository

Huang, Hai

2016-09-09

This paper solves the problem of providing high-quality suggestions for user keyword queries over databases. With the assumption that the returned suggestions are independent, existing query suggestion methods over databases score candidate suggestions individually and return the top-k best of them. However, the top-k suggestions have high redundancy with respect to the topics. To provide informative suggestions, the returned k suggestions are expected to be diverse, i.e., maximizing the relevance to the user query and the diversity with respect to topics that the user might be interested in simultaneously. In this paper, an objective function considering both factors is defined for evaluating a suggestion set. We show that maximizing the objective function is a submodular function maximization problem subject to n matroid constraints, which is an NP-hard problem. An greedy approximate algorithm with an approximation ratio O((Formula presented.)) is also proposed. Experimental results show that our suggestion outperforms other methods on providing relevant and diverse suggestions. © 2016 Springer Science+Business Media New York

Minimum Data Set Active Resident Information Report

Data.gov (United States)

U.S. Department of Health & Human Services — The MDS Active Resident Report summarizes information for residents currently in nursing homes. The source of these counts is the residents MDS assessment record....

c-Src activation through a TrkA and c-Src interaction is essential for cell proliferation and hematological malignancies

International Nuclear Information System (INIS)

Kim, Min Soo; Kim, Gyoung Mi; Choi, Yun-Jeong; Kim, Hye Joung; Kim, Yoo-Jin; Jin, Wook

2013-01-01

Highlights: •TrkA was mainly present in other types of leukemia including AML. •TrkA enhances the survival of leukemia by activation of PI3K/Akt pathway. •TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1. •TrkA acted as a key regulator of leukemogenesis and survival through c-Src activation. -- Abstract: Although the kinase receptor TrkA may play an important role in acute myeloid leukemia (AML), its involvement in other types of leukemia has not been reported. Furthermore, how it contributes to leukemogenesis is unknown. Here, we describe a molecular network that is important for TrkA function in leukemogenesis. We found that TrkA is frequently overexpressed in other types of leukemia such as acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) including AML. In addition, TrkA was overexpressed in patients with MDS or secondary AML evolving from MDS. TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1, and enhanced survival and proliferation of leukemia, which was correlated with activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway. Moreover, endogenous TrkA associated with c-Src complexes was detected in leukemia. Suppression of c-Src activation by TrkA resulted in markedly decreased expression of PLK-1 and Twist-1 via suppressed activation of Akt/mTOR cascades. These data suggest that TrkA plays a key role in leukemogenesis and reveal an unexpected physiological role for TrkA in the pathogenesis of leukemia. These data have important implications for understanding various hematological malignancies

Investigation of the Binding Site of CCR2 using 4-Azetidinyl-1-aryl-cyclohexane Derivatives: A Membrane Modeling and Molecular Dynamics Study

Energy Technology Data Exchange (ETDEWEB)

Kothandan, Gugan; Gadhe, Changdev G.; Cho, Seung Joo [Chosun Univ., Gwangju (Korea, Republic of)

2013-11-15

Chemokine receptor (CCR2) is a G protein-coupled receptor that contains seven transmembrane helices. Recent pharmaceutical research has focused on the antagonism of CCR2 and candidate drugs are currently undergoing clinical studies for the treatment of diseases like arthritis, multiple sclerosis, and type 2 diabetes. In this study, we analyzed the time dependent behavior of CCR2 docked with a potent 4-azetidinyl-1-aryl-cyclohexane (4AAC) derivative using molecular dynamics simulations (MDS) for 20 nanoseconds (ns). Homology modeling of CCR2 was performed and the 4AAC derivative was docked into this binding site. The docked model of selected conformations was then utilized to study the dynamic behavior of the 4AAC enzyme complexes inside lipid membrane. MDS of CCR2-16b of 4AAC complexes allowed us to refine the system since binding of an inhibitor to a receptor is a dynamic process and identify stable structures and better binding modes. Structure activity relationships (SAR) for 4AAC derivatives were investigated and reasons for the activities were determined. Probable binding pose for some CCR2 antagonists were determined from the perspectives of binding site. Initial modeling showed that Tyr49, Trp98, Ser101, Glu291, and additional residues are crucial for 4AAC binding, but MDS analysis showed that Ser101 may not be vital. 4AAC moved away from Ser101 and the hydrogen bonding between 4AAC and Ser101 vanished. The results of this study provide useful information regarding the structure-based drug design of CCR2 antagonists and additionally suggest key residues for further study by mutagenesis.

c-Src activation through a TrkA and c-Src interaction is essential for cell proliferation and hematological malignancies

Energy Technology Data Exchange (ETDEWEB)

Kim, Min Soo; Kim, Gyoung Mi; Choi, Yun-Jeong [Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840 (Korea, Republic of); Kim, Hye Joung [Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Kim, Yoo-Jin, E-mail: yoojink@catholic.ac.kr [Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Jin, Wook, E-mail: jinwo@gachon.ac.kr [Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Medical Center, Incheon 405-760 (Korea, Republic of)

2013-11-15

Highlights: •TrkA was mainly present in other types of leukemia including AML. •TrkA enhances the survival of leukemia by activation of PI3K/Akt pathway. •TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1. •TrkA acted as a key regulator of leukemogenesis and survival through c-Src activation. -- Abstract: Although the kinase receptor TrkA may play an important role in acute myeloid leukemia (AML), its involvement in other types of leukemia has not been reported. Furthermore, how it contributes to leukemogenesis is unknown. Here, we describe a molecular network that is important for TrkA function in leukemogenesis. We found that TrkA is frequently overexpressed in other types of leukemia such as acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) including AML. In addition, TrkA was overexpressed in patients with MDS or secondary AML evolving from MDS. TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1, and enhanced survival and proliferation of leukemia, which was correlated with activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway. Moreover, endogenous TrkA associated with c-Src complexes was detected in leukemia. Suppression of c-Src activation by TrkA resulted in markedly decreased expression of PLK-1 and Twist-1 via suppressed activation of Akt/mTOR cascades. These data suggest that TrkA plays a key role in leukemogenesis and reveal an unexpected physiological role for TrkA in the pathogenesis of leukemia. These data have important implications for understanding various hematological malignancies.

Underreporting of nursing home utilization on the CMS-2728 in older incident dialysis patients and implications for assessing mortality risk.

Science.gov (United States)

Bowling, C Barrett; Zhang, Rebecca; Franch, Harold; Huang, Yijian; Mirk, Anna; McClellan, William M; Johnson, Theodore M; Kutner, Nancy G

2015-03-21

The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported. There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement. The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46 - 1.64) for MDS/2728, 1.48 (1.42 - 1.54) for MDS/No 2728, and 1.38 (1.25 - 1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model. The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.

Faecal analysis suggests generalist diets in three species of ...

African Journals Online (AJOL)

The overlap in other arthropod taxa ingested was low across species and seasons, suggesting an opportunistic component to their foraging behaviour. We distinguished plant matter in faecal samples of all species in all seasons, reflecting either voluntary or accidental ingestion. The results of this study suggest that the ...

High Frequency of AML1/RUNX1 Point Mutations in Radiation-Associated Myelodysplastic Syndrome Around Semipalatinsk Nuclear Test Site

OpenAIRE

Dinara, ZHARLYGANOVA; Hironori, HARADA; Yuka, HARADA; Sergey, SHINKAREV; Zhaxybay, ZHUMADILOV; Aigul, ZHUNUSOVA; Naylya J., TCHAIZHUNUSOVA; Kazbek N., APSALIKOV; Vadim, KEMAIKIN; Kassym, ZHUMADILOV; Noriyuki, KAWANO; Akiro, KIMURA; Masaharu, HOSHI; Department of Radiation Biophysics, Research Institute for Radiation Biology and Medicine, Hiroshima University; Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University

2008-01-01

It is known that bone marrow is a sensitive organ to ionizing radiation, and many patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) have been diagnosed in radiation-treated cases and atomic bomb survivors in Hiroshima and Nagasaki. The AML1/RUNX1 gene has been known to be frequently mutated in MDS/AML patients among atomic bomb survivors and radiation therapy-related MDS/AML patients. In this study, we investigated the AML1 mutations in radiation-exposed patients wi...

[Suggestions to improve dentist-endodontist collaboration].

Science.gov (United States)

Zabalegui, B; Zabalegui, I; Flores, L

1989-01-01

Referrals from the general dentist to the endodontist are in some occasions complicated with lack of proper communication among dentist-patient-specialist, resulting in the loss of confidence or even the patient. Suggestions to improve this communication are discussed, which will provide the patient a higher confidence in the indicated endodontic treatment and a better dental service. It will also enhance the prestige of the general dentists' and specialists' practice.

Belief in the paranormal and suggestion in the seance room.

Science.gov (United States)

Wiseman, Richard; Greening, Emma; Smith, Matthew

2003-08-01

In Experiment 1, participants took part in a fake seance. An actor suggested that a table was levitating when, in fact, it remained stationary. After the seance, approximately one third of participants incorrectly reported that the table had moved. Results also showed a significant relationship between the reported movement of the table and belief in the paranormal, with a greater percentage of believers than disbelievers, reporting that the table had moved. Experiment 2 varied whether the suggestion was consistent, or inconsistent, with participants' belief in the paranormal. Results again showed that believers were more susceptible to suggestion than disbelievers, but only when the suggestion was consistent with their belief in the paranormal. Approximately one fifth of participants believed that the fake seances contained genuine paranormal phenomena.

MECP2 Duplication Syndrome

DEFF Research Database (Denmark)

Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

2016-01-01

Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... similar to those observed in RTT patients except for higher plasma F2-isoprostanes levels (P work shows unique data in patients affected by MDS. For the first...

Hearing loss in a patient with the myopathic form of mitochondrial DNA depletion syndrome and a novel mutation in the TK2 gene.

Science.gov (United States)

Martí, Ramon; Nascimento, Andrés; Colomer, Jaume; Lara, Mari C; López-Gallardo, Ester; Ruiz-Pesini, Eduardo; Montoya, Julio; Andreu, Antoni L; Briones, Paz; Pineda, Mercè

2010-08-01

Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a devastating disorder of infancy caused by a significant reduction of the number of copies of mitochondrial DNA in one or more tissues. We report a Spanish patient with the myopathic form of MDS, harboring two mutations in the thymidine kinase 2 gene (TK2): a previously reported deletion (p.K244del) and a novel nucleotide duplication in the exon 2, generating a frameshift and premature stop codon. Sensorineural hearing loss was a predominant symptom in the patient and a novel feature of MDS due to TK2 mutations. The patient survived up to the age of 8.5 y, which confirms that survival above the age of 5 y is not infrequent in patients with MDS due to TK2 deficiency.

Metacognition of agency is reduced in high hypnotic suggestibility.

Science.gov (United States)

Terhune, Devin B; Hedman, Love R A

2017-11-01

A disruption in the sense of agency is the primary phenomenological feature of response to hypnotic suggestions but its cognitive basis remains elusive. Here we tested the proposal that distorted volition during response to suggestions arises from poor metacognition pertaining to the sources of one's control. Highly suggestible and control participants completed a motor task in which performance was reduced through surreptitious manipulations of cursor lag and stimuli speed. Highly suggestible participants did not differ from controls in performance or metacognition of performance, but their sense of agency was less sensitive to cursor lag manipulations, suggesting reduced awareness that their control was being manipulated. These results indicate that highly suggestible individuals have aberrant metacognition of agency and may be a valuable population for studying distortions in the sense of agency. Copyright © 2017 Elsevier B.V. All rights reserved.

Object Detection and Tracking using Modified Diamond Search Block Matching Motion Estimation Algorithm

Directory of Open Access Journals (Sweden)

Apurva Samdurkar

2018-06-01

Full Text Available Object tracking is one of the main fields within computer vision. Amongst various methods/ approaches for object detection and tracking, the background subtraction approach makes the detection of object easier. To the detected object, apply the proposed block matching algorithm for generating the motion vectors. The existing diamond search (DS and cross diamond search algorithms (CDS are studied and experiments are carried out on various standard video data sets and user defined data sets. Based on the study and analysis of these two existing algorithms a modified diamond search pattern (MDS algorithm is proposed using small diamond shape search pattern in initial step and large diamond shape (LDS in further steps for motion estimation. The initial search pattern consists of five points in small diamond shape pattern and gradually grows into a large diamond shape pattern, based on the point with minimum cost function. The algorithm ends with the small shape pattern at last. The proposed MDS algorithm finds the smaller motion vectors and fewer searching points than the existing DS and CDS algorithms. Further, object detection is carried out by using background subtraction approach and finally, MDS motion estimation algorithm is used for tracking the object in color video sequences. The experiments are carried out by using different video data sets containing a single object. The results are evaluated and compared by using the evaluation parameters like average searching points per frame and average computational time per frame. The experimental results show that the MDS performs better than DS and CDS on average search point and average computation time.

Dietary pattern analysis: a comparison between matched vegetarian and omnivorous subjects.

Science.gov (United States)

Clarys, Peter; Deriemaeker, Peter; Huybrechts, Inge; Hebbelinck, Marcel; Mullie, Patrick

2013-06-13

Dietary pattern analysis, based on the concept that foods eaten together are as important as a reductive methodology characterized by a single food or nutrient analysis, has emerged as an alternative approach to study the relation between nutrition and disease. The aim of the present study was to compare nutritional intake and the results of dietary pattern analysis in properly matched vegetarian and omnivorous subjects. Vegetarians (n = 69) were recruited via purposeful sampling and matched non-vegetarians (n = 69) with same age, gender, health and lifestyle characteristics were searched for via convenience sampling. Two dietary pattern analysis methods, the Healthy Eating Index-2010 (HEI-2010) and the Mediterranean Diet Score (MDS) were calculated and analysed in function of the nutrient intake. Mean total energy intake was comparable between vegetarians and omnivorous subjects (p > 0.05). Macronutrient analysis revealed significant differences between the mean values for vegetarians and omnivorous subjects (absolute and relative protein and total fat intake were significantly lower in vegetarians, while carbohydrate and fibre intakes were significantly higher in vegetarians than in omnivorous subjects). The HEI and MDS were significantly higher for the vegetarians (HEI = 53.8.1 ± 11.2; MDS = 4.3 ± 1.3) compared to the omnivorous subjects (HEI = 46.4 ± 15.3; MDS = 3.8 ± 1.4). Our results indicate a more nutrient dense pattern, closer to the current dietary recommendations for the vegetarians compared to the omnivorous subjects. Both indexing systems were able to discriminate between the vegetarians and the non-vegetarians with higher scores for the vegetarian subjects.

Hotel Employees' Japanese Language Experiences: Implications and Suggestions.

Science.gov (United States)

Makita-Discekici, Yasuko

1998-01-01

Analyzes the Japanese language learning experiences of 13 hotel employees in Guam. Results of the study present implications and suggestions for a Japanese language program for the hotel industry. The project began as a result of hotel employees frustrations when they were unable to communicate effectively with their Japanese guests. (Auth/JL)

German Translation and Validation of the “Freezing of Gait Questionnaire” in Patients with Parkinson’s Disease

Directory of Open Access Journals (Sweden)

Anina Vogler

2015-01-01

Full Text Available Background. Freezing of Gait (FOG is a disabling parkinsonian symptom. The Freezing of Gait Questionnaire (FOG-Q reliably detects FOG in patients with Parkinson’s disease (PD. Objectives. The aim of this study was to develop a German translated version of the FOG-Q and to assess its validity. Methods. The translation was accomplished using forward-backward-translation. The construct validity of the FOG-Q was examined in twenty-seven German native speaking PD patients. Convergent validity was assessed by correlating the FOG-Q with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS II-III, the Parkinson Disease Questionnaire 39 (PDQ-39, and the Timed Up and Go Test (TUG. Divergent validity was assessed by correlating the FOG-Q with the MDS-UPDRS I. The internal consistency was measured using Cronbach’s alpha (Cα. Results. A good internal structure of the FOG-Q was found (Cα=0.83. Significant moderate correlations between the FOG-Q and the MDS-UPDRS item 2.13 (freezing (rs=0.568, P=0.002 and between the FOG-Q and the PDQ-39 subscale mobility (rs=0.516, P=0.006 were found. The lack of correlation with the MDS-UPDRS I demonstrated good divergent validity. Conclusion. The German FOG-Q is a valid tool to assess FOG in German native speaking PD patients.

Designing minimum data sets of health smart card system

Directory of Open Access Journals (Sweden)

Mohtaram Nematollahi

2014-10-01

Full Text Available Introduction: Nowadays different countries benefit from health system based on health cards and projects related to smart cards. Lack of facilities which cover this technology is obvious in our society. This paper aims to design Minimum Data Sets of Health Smart Card System for Iran. Method: This research was an applied descriptive study. At first, we reviewed the same projects and guidelines of selected countries and the proposed model was designed in accordance to the country’s needs, taking people’s attitude about it by Delphi technique. A data analysis in study stage of MDS(Minimum Data Sets of Health Smart Card in the selective countries was done by comparative tables and determination of similarities and differences of the MDS. In the stage of gaining credit for model, it was accomplished with descriptive statistics to the extent of absolute and relative frequency through SPSS (version 16. Results: MDS of Health Smart Card for Iran is presented in the patient’s card and health provider’s card on basisof studiesin America, Australia, Turkey and Belgium and needs of our country and after doing Delphi technique with 94 percent agreement confirmed. Conclusion: Minimum Data Sets of Health Smart Card provides continuous care for patients and communication among providers. So, it causes a decrease in the complications of threatening diseases. Collection of MDS of diseases increases the quality of care assessment

Thermal properties of methane hydrate by experiment and modeling and impacts upon technology

Energy Technology Data Exchange (ETDEWEB)

Warzinski, R.P.; Gamwo, I.K.; Rosenbaum, E.J. [United States Dept. of Energy, Pittsburgh, PA (United States). National Energy Technology Laboratory; Myshakin, E.M. [NETL Support Contractor, South Park, PA (United States); Jiang, H.; Jordan, K.D. [Pittsburgh Univ., Pittsburgh, PA (United States). Dept. of Chemistry; English, N.J. [Dublin University College, Dublin (Ireland). Conway Inst. of Biomolecular and Biomedical Research, Centre for Synthesis and Chemical Biology; Shaw, D.W. [Geneva College, Beaver Falls, PA (United States). Dept. of Engineering

2008-07-01

The current hydrate research at the National Energy Technology Laboratory (NETL) involves both experimental and theoretical work on developing models and methods for predicting the behaviour of gas hydrates in their natural environment under production of climate change scenarios. The modeling efforts include both fundamental and reservoir scale simulations and economic modeling. The thermal properties of methane hydrate are important for hydrate production, seafloor stability and climate change scenarios. A new experimental technique and advanced molecular dynamics simulation (MDS) have determined the thermal properties of pure methane hydrate under conditions similar to naturally occurring hydrate-bearing sediments. The thermal conductivity and thermal diffusivity values of low-porosity methane hydrate formed in the laboratory were measured using an innovative single-sided, Transient Plane Source (TPS) technique. The results were in good agreement with results from an equilibrium MDS method using in-plane polarization of the water molecules. MDS was also performed using a non-equilibrium model with a fully polarizable force field for water. The Tough+Hydrate reservoir simulator was also used to evaluate the impact of thermal conductivity on gas production from a hydrate-bearing reservoir. 42 refs., 1 tab., 5 figs.

Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

Science.gov (United States)