Orthogonal supramolecular protein assembly on patterned bifunctional surfaces.

We report successful and selective dual protein assembly on patterned bifunctional ßCD-Ni(ii)NTA surfaces, using red fluorescent protein variants with hexahistidine-tags and teal fluorescent protein variants conjugated with a peptide containing three adamantyl groups. We show that dual protein patterns can only be assembled, when opposing supramolecular interactions have been optimized and nonspecific interactions have been sufficiently suppressed.

Utility of cardiac CT for evaluating delayed contrast enhancement in dilated cardiomyopathy.

BACKGROUND: The presence of myocardial fibrosis is associated with adverse outcome in dilated cardiomyopathy (DCM). Delayed contrast-enhanced cardiac magnetic resonance (DE-CMR) currently represents the gold standard in noninvasive evaluation of myocardial scarring. However, a significant number of patients are unable to undergo DE-CMR study for various reasons. We sought to determine the diagnostic accuracy of cardiac CT (CCT) compared with CMR in the investigation of the presence of delayed contrast enhancement (DCE) in subjects with DCM. METHODS: We prospectively enrolled 17 consecutive patients with DCM, who were initially referred to our institution because of recently manifested heart failure due to unexplained left ventricular systolic dysfunction. In all subjects, CCT and DE-CMR were performed within 1 week. RESULTS: CCT and DE-CMR showed satisfactory agreement in detecting DCE (agreement in 82% cases, κ = 0.56) with 50% sensitivity, 100% specificity, and a positive predictive value of 100%. CONCLUSION: CCT may be a valuable method for detecting DCE in patients with DCM. CCT thus might be considered as an alternative method to DE-CMR in the assessment of the presence and extent of myocardial fibrosis in subjects who are not suitable for DE-CMR examination.

Model-based vs hybrid iterative reconstruction technique in ultralow-dose submillisievert CT colonography.

OBJECTIVE: To compare image quality of different reconstruction techniques in submillisievert ultralow-dose CT colonography (CTC) and to correlate colonic findings with subsequent optical colonoscopy. METHODS: 58 patients underwent ultralow-dose CTC. The images were reconstructed with filtered back projection (FBP), hybrid iterative reconstruction (HIR) or model-based iterative reconstruction (MBIR) techniques. In each segment, endoluminal noise (expressed as standard deviation of endoluminal density) was measured and image quality was rated on a five-point Likert scale by two independent readers. Colonic lesions were evaluated in consensus and correlated with subsequent optical colonoscopy where possible. RESULTS: The estimated radiation dose was 0.41 ± 0.05 mSv for the supine and 0.42 ± 0.04 mSv for the prone acquisitions. In the endoluminal view, the image quality was rated better in HIR, whereas better scores were obtained in MBIR in the cross-sectional view, where the endoluminal noise was the lowest (p < 0.0001). Five (26%) polyps were not identified using both computer-aided detection and endoluminal inspection in FBP images vs only one (5%) in MBIR and none in HIR images. CONCLUSION: This study showed that in submillisievert ultralow-dose CTC, the image quality for the endoluminal view is better when HIR is used, whereas MBIR yields superior images for the cross-sectional view. The inferior quality of images reconstructed with FBP may result in decreased detection of colonic lesions. ADVANCES IN KNOWLEDGE: Radiation dose from CTC can be safely reduced <1 mSv for both positions when iterative reconstruction is used. MBIR provides better image quality in the cross-sectional view and HIR in the endoluminal view.

[Results of the Czech National Breast Cancer screening programme]. / Výsledky Národního programu screeningu karcinomu prsu v Ceské republice.

INTRODUCTION: Breast cancer screening based on mammography is an effective tool for lowering mortality rates from this disease. The organised and nationwide Breast Cancer Screening Programme has been underway in the Czech Republic since 2002. MATERIAL AND METHODS: Monitoring of the programme is based on data from the Czech National Cancer Registry (CNCR), Breast Cancer Screening Registry, and the Czech National Reference Centre (CNRC). These data sources make it possible to evaluate early performance indicators according to international standards, and to monitor the cancer burden in the Czech population. The CNRC data allow us to document the high validity of the available data as well as to map non-organised mammography examinations (so-called opportunistic screening). RESULTS: Until the mid-1990s, breast cancer incidence and mortality rates saw a slight but continuous increase. In the last 15 years, however, incidence rates have grown more substantially; by contrast, mortality rates have stalled and even started to decline since the 2000s. In the mid-1990s, the proportion of cancers diagnosed at stage I was below 20%; this situation has dramatically improved since then, as more than 40% cases of breast cancer were diagnosed at stage I in 2011. Breast cancer screening coverage currently amounts to 50%; this value reached a plateau in the period 2007-2008, and unfortunately has not shown any further significant increase. CONCLUSION: Over the last few decades, the breast cancer burden among the Czech population has been significantly reduced - despite the growing incidence rates, mortality rates have decreased, which can be largely attributed to earlier detection of breast cancer based on the screening programme. Further improvements in the programmes effectiveness can only be achieved if the population coverage becomes higher; the programme of personalised invitations to mammography examinations, which was introduced in early 2014, should contribute to the accomplishment of this goal.

[Approach to population-based screening in the Czech Republic, methodology and first results of the personalised invitation of citizens to cancer screening programmes]. / Koncepce populacního screeningu v Ceské republice, metodika a první výsledky adresného zvaní obcanu do preventivních onkologických programu

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

[Performance indicators in screening programmes]. / Indikátory kvality screeningových programu

Breast, colorectal and cervical cancer screening programmes make it possible to decrease the population mortality rates of these diseases. How-ever, complex standards of the quality of care must be introduced and followed in order to maintain a favourable ratio between the benefits and risks arising from population-wide screening programmes. Such programmes should be organized and population-based, ensuring that quality control is performed at all levels. This review introduces the system of quality control in the Czech cancer screening programmes, and provides specific examples of performance indicators that are usable and/ or being used in these programmes. Cancer screening programmes in the Czech Republic are equipped with a comprehensive information background which involves monitoring of the cancer burden in the population, monitoring of the screening process based on clinical data, and monitoring of the screening process based on administrative data. In particular, the specific performance indicators describe the success rate of take up of the target population, ability of the screening test to reveal (sensitivity) or to exclude (specificity) the screened condition, correct employment of subsequent diagnostic methods or treatment of detected cancers or precancerous lesions where applicable. In the Czech breast cancer screening programme, these indicators are routinely used in order to monitor the individual centres; in both colorectal and cervical cancer screening programmes, these indicators are used to monitor the entire programme, whereas the system of quality control for individual centres is under continuous development. A project of personalized invitations was launched in 2014, and its results are regularly evaluated in cooperation with the Czech National Reference Centre and the Ministry of Health of the Czech Republic.

[Implementation of performance indicators in the Czech Breast Cancer Screening Programme -  results of the regular monitoring]. / Implementace indikátoru kvality v ceském programu screeningu karcinomu prsu - výsledky pravidelného monitoringu.

The Czech organised breast cancer screening programme was initiated in 2002. Collection of data on screening mammography examinations, subsequent diagnostic procedures, and final dia-gnosis is an indispensable part of the programme. Data collection is obligatory for all accredited centres, in accordance with regulations issued by the Czech Ministry of Health. This contribution aims to demonstrate the recent results of quality monitoring of the accredited centres. Quality indicators, whose definition complies with international standards, involve the women's participation, the volume of performed examinations, the accuracy of screening mammography, the use of preoperative diagnostics, and the proportion of early detected tumours. Our evaluation documents a continuous improvement in quality of the Czech mammography screening programme, which is thereby in full agreement with international recommendations on quality assurance.

Gastrointestinal complications after cardiac surgery : eight years experience in a single center.

BACKGROUND: The aim of this study was to evaluate the frequency of gastrointestinal complications (GICs) and associated risk factors in patients after cardiac surgery, and to stratify them according to the risk of developing GICs in order to improve our diagnostic protocols. METHODS: A total of 5959 patients who underwent cardiac surgery within a period of 97 months were retrospectively evaluated. Surgical procedures included coronary artery bypass grafting, heart valve surgery, aortic surgery, surgical correction of adult congenital heart defects, or combined procedures. RESULTS: The frequency of GICs was 1.3% (75 patients). Intestinal ischemia and upper or lower gastrointestinal bleeding were the most common GICs. From 27 patients affected by intestinal ischemia, 21 patients were previously treated with intra-aortic balloon pump (p < 0.001). Low cardiac output, renal failure or dysfunction, renal risk, peripheral arterial disease, history of myocardial infarction, male gender, intra-aortic balloon pump, cardiopulmonary bypass time, aortic cross-clamp time, duration of intubation, SIRS, and MODS were associated with significantly increased risk of GICs. CONCLUSIONS: To decrease the occurrence of intestinal ischemia, we suggest that placement of intra-aortic balloon pump should be preceded by examination of the descending aorta to rule out severe atherosclerotic changes, in which case -alternative cardiac support should be attempted.

Ultrasound guided cryoablation of fibroadenomas.

PURPOSE: Fibroadenoma (FA) of the breast is the most common disorders in young women. The aim of the study was to evaluate cryoablation (CA) under ultrasound guidance in the office setting for patients with FA. MATERIALS AND METHODS: For this prospective multicenter trial an office-based cryosurgical system was used to treat histological confirmed benign FA with a maximum dimension of 3 cm. 23 CA procedures were performed under ultrasound guidance. The cryoprobe was inserted into the center of the FA guided by real-time ultrasound. A freeze-thaw-freeze treatment cycle was performed according to the size of the FA. During the CA procedure continuous ultrasound monitoring of the ice ball was performed, verifying engulfment of the FA. Patients attended 4 follow-up visits at 1 week, 3 months, 6 months and 1 year and underwent ultrasound and physical examinations. RESULTS: Data was collected from 23 procedures. The ice ball engulfed the treated FA in 91.3 %. A sharp reduction in volume was observed at 6-month follow-up and continued more moderately up to 1 year. No serious but four minor adverse events occurred. At 1 year follow-up, lumps that were assessed pre-treatment as hard were assessed as soft or not palpable. 7 patients complained of pain caused by the lump prior to cryotherapy, while 5 of these patients felt transient pain during the follow up period. It is reasonable to assume that the pain was not related to the CA procedure as it was not consistent. In 96 % of the cases patients and physicians rated the cosmetic results of the procedure as excellent or good. CONCLUSION: The cryodestruction proved functional and safe, while showing reduction in palpability and pain caused by the FA in the treated patients.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes.

OBJECTIVE: To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. METHODS: A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). RESULTS: The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. CONCLUSION: The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Mammographic screening programmes in Europe: organization, coverage and participation.

OBJECTIVES: To summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe. METHODS: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries. RESULTS: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively. CONCLUSIONS: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

Czech National Cancer Screening Programmes in 2010.

BACKGROUNDS: All three cancer screening programmes recommended by the Council of the EU are available to defined target age groups in the Czech Republic. Organized programmes for screening of breast, colorectal and cervical cancer have been initiated in the last decade. MATERIALS AND METHODS: A system for information support, as an essential component of organized screening programmes, has been implemented in all screening programmes. It comprises the Czech National Cancer Registry to monitor the cancer burden and population impact of the programmes, the National Reference Centre as a provider of nationwide insurance claims data, and the specialised databases of all three programmes, which collect information on screening, diagnostics and final diagnoses. RESULTS: Early diagnostics of malignant neoplasms and progress in therapy have helped to stabilize mortality, even in diagnoses with increasing incidence. The coverage of the Czech screening programmes has constantly been rising; however, it is still insufficient: 51.2%, 17.9% and 48.4% of the target population was covered at the end of 2008 in breast, colorectal and cervical screening programmes, respectively. In 2008, a total of 468,419 women underwent screening mammography and 2,128 tumours were detected (4.5 per 1,000 screened). According to the screening colonoscopy registry, more than 13,000 men and women underwent preventive colonoscopy in 2009, 4,085 patients were diagnosed with adenoma and 619 with colorectal cancer, mostly in the early stages. The information system for cervical screening was implemented in 2009 and has been running in pilot mode; the first results are expected at the end of 2010. CONCLUSION: The system for information support within organised cancer screening programmes enables monitoring of the performance of screening and diagnostic centres and thus helps to maintain continuous quality improvements, which are a necessary presumption for replicating the promising results of clinical trials. To achieve a substantial impact on population incidence and mortality, a large increase in test coverage in target populations will be necessary. The programmes should be transformed to a population-based form, which involves inviting all people in the target population to be screened.

Asymmetry of basal ganglia in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatry disorder with several key symptoms, such as inattentiveness, impulsivity and hyperactivity. Neuropsychiatry studies have implicated the frontostriatal circuit in the pathological physiology of the disorder. Using magnetic resonance imaging (MRI), we examined the basal ganglia in 13 ADHD patients and eight unaffected comparison children. The volume of caudate, putamen and globus pallidus was measured. In the ADHD patients, we detected an increased left > right asymmetry of the basal ganglia. This reversal of asymmetry in the globus pallidus and caudate nucleus were statistically significant. These finding provide further evidence of morphological brain abnormalities in ADHD.

[Acute situation in the National Program of Breast Cancer Screening in the Czech Republic]. / Akutní stav národního programu skríninku rakoviny prsu v Ceské republice.

Czech National Breast Cancer Screening Program started in September 2002. Currently, a total of 59 accredited screening centres are involved in the program. Central data management and statistical processing of the data is performed. During the period of July 2003-December 2005 a total of 646,056 women were screened and 2,926 breast cancer cases were detected. A total of 2666 (91.1 %) cancer cases were invasive. Of these, 855 (32.1 %) were < or = 10 mm in size and 1624 (60.9 %) were node negative. A high rate of detection of early stages of the disease is the main objective of the screening process and a good indicator of long-term decrease in mortality rates. The central system of data management is based on annual data analysis. This system is in line with international standards for such systems.

[Multiple sclerosis and magnetic resonance]. / Roztrousená skleróza mozkomísní a magnetická rezonance.

Multiple sclerosis is a demyelinating process presently referred to autoimmune diseases. Its diagnostics is based on clinical examination and paraclinical tests (magnetic resonance, examination of CSF and evoked potentials recording). Magnetic resonance (MR) has the highest significance, both for the diagnostics and for the monitoring of the course of disease and results of treatment. Results of magnetic resonance are not specific for the multiple sclerosis and therefore for the reliable diagnosis the McDonadl's criteria have to be fulfilled. It appears that magnetic resonance is more sensitive to progression of disease than the clinical examination. Monitoring of the course of disease requires new techniques of MR imaging. Automatic, software assisted determination of plaque volumes in T2 and T1 weighted images--so called "lesion load", is checked during the patient's treatment. Assessment of brain volume determines progression of atrophy. The aim of all the new methods of MR imaging is to search for a reliable technique of the disease monitoring and namely for the prediction of disease progression.

Large expansion of morphologically heterogeneous mammary epithelial cells, including the luminal phenotype, from human breast tumours.

Regular expansion of heterogeneous populations of epithelial cells, including the luminal phenotype, was achieved from small biopsies of human breast tumours and cutaneous metastases by optimized feeder layer technique based on irradiated NIH 3T3 cells. Forty-one out of 47 primary tumour specimens and all three cutaneous metastases grew successfully for two to 10 passages in vitro. The main phenotypes of cultured cells and their changes in subcultures were characterized using immunocytochemistry and phase contrast microscopy (in few cases also time-lapse recording). In the majority of cultured cell populations a fraction of cells positive for keratin 19 (K19+), typical for the luminal phenotype, was detected. This is the cell type from which breast carcinoma is supposed to arise. While in cultures derived from benign lesions only basic phenotypes of luminal and myoepithelial cells were found, in cultures derived from malignant tumours unusual phenotypes of epithelial cells, in their majority K19+, were detected. The growth properties of cells from six benign and seven malignant samples were analyzed in detail. In the analyzed cell populations the culture lifetime - related to the number of colony-forming cells varied for cells from malignant tumours between 21 and 51 and from benign tumours between 22 and 40 cell generations. The total number of passages achieved was three to seven for malignant or four to nine for benign cultures. In spite of negative results of tumourigenicity testing in immunologically compromised Nu/nu mice the potential to culture apparently neoplastic cells was indicated by positive immunostaining for the p53 oncoprotein (seven of 23 tested malignant cases), the src oncoprotein (five of eight), and overexpression of the c-erbB-2 protein (five of 26). This was further confirmed by successful cultivation of malignant cells from cutaneous metastases. Two of the three metastasis-derived cultures were nearly homogeneously positive for K19 while the third was almost negative. The results proved the optimized feeder layer technique to be useful for regular yielding of large amounts of epithelial cells from small tumour biopsies and for supporting the majority of cell phenotypes present in the original tumour. Therefore, it appeared to be a promising tool for further analysis of interactions between luminal and myoepithelial cells in the development of human breast carcinoma and for the study of individual tumours.

Relevance of sonographic B-mode criteria and computer-aided ultrasonic tissue characterization in differential/diagnosis of solid breast masses.

We aimed to evaluate the differential diagnostic value of a method of computer-assisted texture analysis in comparison to established ultrasonographic B-mode characteristics in the examination of solid breast masses. At two centers, 77 patients presenting with a solid mass on B-mode scan were studied at 7.5 MHz. Description of B-mode appearance included assessment of tumor shape, borders, presence of an echogenic rim, tissue architecture, internal echo structure, absorption and elasticity. For statistical pattern recognition, the following parameters were used: form factor, mean grey level, signal-to-noise ratio, mean gradient and correlation from the co-occurrence matrix. At center 1, the most decisive parameter for differential diagnosis was distortion of tissue architecture (sensitivity, SN, 83%; specificity, SP, 92%) and, at center 2, relation to the adjacent tissue (SN 93%, SP 92%). Among texture parameters, best discrimination was achieved for correlation from the co-occurrence matrix at center 1 (SN 58%, SP 73%) and for form factor at center 2 (SN 93%, SP 77%). Among sonographic criteria, the highest contribution to the diagnosis was found for an unsharp border (odds ratio, OR, 12.2), architectural distortion (OR, 8.6), fixation to skin or chest wall (OR, 9.0) and fixation to adjacent breast parenchyma (OR, 8.8), according to texture analysis for parameters form factor (OR 4.0) and correlation from the co-occurrence matrix (OR 4.7). Ultrasonographic texture analysis can be helpful as an additional parameter in differential diagnosis of breast tumors, but did not reach differential diagnostic accuracy of sonomorphologic features.

[EEG findings in patients with systemic lupus erythematosus]. / EEG nálezy u nemocných se systemovým lupus erythematosus.

We have examined electroencephalography (EEG) and Mini-Mental State Examination (MMSE) in 38 patients with verified diagnosis of systemic lupus erythematosus (SLE). In the clinical neurological finding there were epileptic attacks in 9 patients, 10 patients suffered from stroke, 15 patients from lupus headache, 4 patients from psychosis, in 15 patients cranial neuropathy was present, in one person extrapyramidal syndrome. EEG findings were in 12 patients normal (32%), in 26 patients abnormal (66%). In 3 cases there were focal abnormalities (8%), in 19 cases episodic ones (48%), four times abnormalities were diffuse (10%). Diffuse abnormalities correlated in EEG findings with case history of GM attacks.