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Olomouc, Czech Republic

Hruban L.,Masaryk University | Spilka J.,Czech Technical University | Chudacek V.,Czech Technical University | Janku P.,Masaryk University | And 11 more authors.
Journal of Evaluation in Clinical Practice

Rationale, aims and objectives To evaluate obstetricians' inter- and intra-observer agreement on intrapartum cardiotocogram (CTG) recordings and to examine obstetricians' evaluations with respect to umbilical artery pH and base deficit. Methods Nine experienced obstetricians annotated 634 intrapartum CTG recordings. The evaluation of each recording was divided into four steps: evaluation of two 30-minute windows in the first stage of labour, evaluation of one window in the second stage of labour and labour outcome prediction. The complete set of evaluations used for this experiment is available online. The inter- and intra-observer agreement was evaluated using proportion of agreement and kappa coefficient. Clinicians' sensitivity and specificity was computed with respect to umbilical artery pH, base deficit and to Apgar score at the fifth minute. Results The overall proportion of agreement between clinicians reached 48% with 95% confidence intervals (CI) (CI: 47-50). Regarding the different classes, proportion of agreement ranged from 57% (CI: 54-60) for normal to 41% (CI: 36-46) for pathological class. The sensitivity of clinicians' majority vote to objective outcome was 39% (CI: 16-63) for the umbilical artery base deficit and 27% (CI: 16-42) for pH. The specificity was 89% (CI: 86-92) for both types of objective outcome. Conclusions The reported inter-/intra-observer variability is large and this holds irrespective of clinicians' experience or work place. The results support the need of modernized guidelines for CTG evaluation and/or objectivization and repeatability by introduction of a computerized approach that could standardize the process of CTG evaluation within the delivery ward. © 2015 John Wiley & Sons, Ltd. Source

Vokurka S.,University Hospital in Pilsen | Bystricka E.,University Hospital in Pilsen | Svoboda T.,University Hospital in Pilsen | Gorican I.K.S.,University of Ljubljana | And 12 more authors.
Journal of Clinical Nursing

Aims and objectives: To establish the availability of High Efficiency Particulate Air (HEPA)- and nonHEPA-filtered rooms in eastern European transplant centres and to investigate the impact on incidence of pneumonia and mortality after haematopoietic stem cell transplantation (HSCT). Background: Barrier nursing in HEPA-filtered rooms is generally recommended for patients undergoing HSCT. There are only limited data on the availability of HEPA-filtered rooms and the impact on incidence of pneumonia and mortality. Design: A prospective, observational, international study. Methods: Monitoring cards were distributed within the East Forum EBMT-Nurses Group cooperating centres, and 689 consecutive patients were registered in 1/2010-6/2012. Patients were monitored for 100 days post-transplant. Results: In patients undergoing autologous HSCT, pneumonia developed in 14/400 (3·5%) and was the cause of death in 2/14 (14%) of patients. There was no significant difference in mortality between HEPA-filtered and nonHEPA-filtered groups (4·5% vs. 4·9%, respectively). 239/400 (59%) transplantations were performed in single-bed rooms [190/239 (79%) HEPA-filtered] and 161 (41%) in two-bed rooms [28/161 (17%) HEPA-filtered]. In allogeneic transplantation, pneumonia developed in 24/289 (8·3%) and was the cause of death in 11/24 (45%) of patients. There was no significant difference in mortality between HEPA-filtered and non-HEPA-filtered groups (14% vs. 17%, respectively). 281/289 (97%) of allogeneic transplantations were performed in single-bed rooms [254/281 (90%) HEPA-filtered], and pneumonia was more frequent in patients on corticosteroids and in rooms without HEPA. Conclusion: The incidence of pneumonia in the autologous transplantation setting is low. More pneumonia was observed in the allogeneic HSCT group, especially in patients on corticosteroids. There was a trend towards a lower incidence of pneumonia in allogeneic HSCT patients treated in HEPA-filtered rooms. Relevance to clinical practice: Autologous HSCT transplantation may safely be performed without HEPA filtration. HEPA filtration might be preferable in patients undergoing allogeneic transplantation. © 2013 John Wiley & Sons Ltd. Source

Hrabakova R.,Academy of Sciences of the Czech Republic | Kollareddy M.,University Hospital in Olomouc | Tyleckova J.,Academy of Sciences of the Czech Republic | Halada P.,Academy of Sciences of the Czech Republic | And 3 more authors.
Journal of Proteome Research

Drug resistance is the major obstacle to successful cancer therapy. Our study focuses on resistance to Aurora kinase inhibitors tested as anti-cancer drugs in clinical trials. We have used 2D electrophoresis in the pH ranges of 4-7 and 6-11 followed by protein identification using MALDITOF/TOF to compare the protein composition of HCT116 colon cancer cells either sensitive to CYC116 and ZM447439 inhibitors or resistant toward these drugs. The analysis also included p53+/+ and p53-/-phenotypes of HCT116 cells. Our findings demonstrate that platelet-activating factor acetylhydrolase and GTP-binding nuclear protein Ran contribute to the development of resistance to ZM447439 only where resistance is related to p53. On the other hand, serine hydroxymethyltransferase was found to promote the tumor growth in cells resistant to CYC116 without the influence of p53. Computer modeling of interaction networks highlighted a direct link of the p53-independent mechanism of resistance to CYC116 with autophagy. Importantly, serine hydroxymethyltransferase, serpin B5, and calretinin represent the target proteins that may help overcome resistance in combination therapies. In addition, serpin B5 and calretinin appear to be candidate biomarkers that may be accessible in patients for monitoring of cancer therapy with ease. © 2012 American Chemical Society. Source

Surinova S.,ETH Zurich | Surinova S.,University College London | Choi M.,Purdue University | Tao S.,German Cancer Research Center | And 18 more authors.
EMBO Molecular Medicine

Non-invasive detection of colorectal cancer with blood-based markers is a critical clinical need. Here we describe a phased mass spectrometry-based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88-plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five-protein biomarker signature for colorectal cancer detection. © 2015 EMBO. Source

Snasel J.,Czech Institute of Organic Chemistry And Biochemistry | Naus P.,Czech Institute of Organic Chemistry And Biochemistry | Dostal J.,Czech Institute of Organic Chemistry And Biochemistry | Hnizda A.,Czech Institute of Organic Chemistry And Biochemistry | And 16 more authors.
Journal of Medicinal Chemistry

Adenosine kinase (ADK) from Mycobacterium tuberculosis (Mtb) was selected as a target for design of antimycobacterial nucleosides. Screening of 7-(het)aryl-7-deazaadenine ribonucleosides with Mtb and human (h) ADKs and testing with wild-type and drug-resistant Mtb strains identified specific inhibitors of Mtb ADK with micromolar antimycobacterial activity and low cytotoxicity. X-ray structures of complexes of Mtb and hADKs with 7-ethynyl-7-deazaadenosine showed differences in inhibitor interactions in the adenosine binding sites. 1D 1H STD NMR experiments revealed that these inhibitors are readily accommodated into the ATP and adenosine binding sites of Mtb ADK, whereas they bind preferentially into the adenosine site of hADK. Occupation of the Mtb ADK ATP site with inhibitors and formation of catalytically less competent semiopen conformation of MtbADK after inhibitor binding in the adenosine site explain the lack of phosphorylation of 7-substituted-7-deazaadenosines. Semiempirical quantum mechanical analysis confirmed different affinity of nucleosides for the Mtb ADK adenosine and ATP sites. © 2014 American Chemical Society. Source

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