QSAR-derived affinity fingerprints (part 1): fingerprint construction and modeling performance for similarity searching, bioactivity classification and scaffold hopping.

An affinity fingerprint is the vector consisting of compound's affinity or potency against the reference panel of protein targets. Here, we present the QAFFP fingerprint, 440 elements long in silico QSAR-based affinity fingerprint, components of which are predicted by Random Forest regression models trained on bioactivity data from the ChEMBL database. Both real-valued (rv-QAFFP) and binary (b-QAFFP) versions of the QAFFP fingerprint were implemented and their performance in similarity searching, biological activity classification and scaffold hopping was assessed and compared to that of the 1024 bits long Morgan2 fingerprint (the RDKit implementation of the ECFP4 fingerprint). In both similarity searching and biological activity classification, the QAFFP fingerprint yields retrieval rates, measured by AUC (~ 0.65 and ~ 0.70 for similarity searching depending on data sets, and ~ 0.85 for classification) and EF5 (~ 4.67 and ~ 5.82 for similarity searching depending on data sets, and ~ 2.10 for classification), comparable to that of the Morgan2 fingerprint (similarity searching AUC of ~ 0.57 and ~ 0.66, and EF5 of ~ 4.09 and ~ 6.41, depending on data sets, classification AUC of ~ 0.87, and EF5 of ~ 2.16). However, the QAFFP fingerprint outperforms the Morgan2 fingerprint in scaffold hopping as it is able to retrieve 1146 out of existing 1749 scaffolds, while the Morgan2 fingerprint reveals only 864 scaffolds.

A case-control pilot study of stress fracture in adolescent girls: the discriminative ability of two imaging technologies to classify at-risk athletes.

Since stress fractures are common among adolescent athletes, it is important to identify bone assessment tools that accurately identify risk. We investigated the discriminative ability of two imaging technologies to classify at-risk athletes. Findings suggested that peripheral quantitative computed tomography (pQCT) has the ability to distinguish differences in bone structure in injured vs. uninjured limbs. INTRODUCTION: Given the high stress fracture (SFX) prevalence among adolescent girls, an understanding of the most informative assessment tools to identify SFX risks are required. We investigated the discriminative ability of pQCT vs. dual-energy X-ray absorptiometry (DXA) to classify athletes with or without SFX. METHODS: Twelve adolescent athletes diagnosed with a lower-extremity SFX were compared with 12 matched controls. DXA measured areal bone mineral density (aBMD) and content of the total body, and lumbar spine. Bilateral tibiae were assessed with pQCT. At the metaphysis (3%), total density (ToD), trabecular density (TrD), trabecular area (TrA), and estimated bone strength in compression (BSIc), and at the diaphysis (38% and 66%), total bone area (ToA), cortical density (CoD), cortical area (CoA), estimated bone strength in torsion (SSIp), and peri- and endocortical and muscle area (MuA) were obtained. Cortical bone mass/density around the center of mass and marrow density (estimate of adiposity) were calculated using ImageJ software. General estimated equations adjusting for multiple comparisons (Holm-Bonferroni method) were used to compare means between (1) injured limb of the case athletes vs. uninjured limb of the control athletes and (2) uninjured limb of the case athletes vs. uninjured limbs of the controls and injured vs. uninjured limb of case athletes with a SFX. RESULTS: aBMD and content showed no significant differences between cases and controls. When comparing the injured vs. uninjured leg in the case athletes by pQCT at the 3% tibia, unadjusted TrD, total density, and BSIc were significantly lower (p < 0.05) in the injured vs. uninjured leg. Marrow density at the 66% site was 1% (p < 0.05) lower in the injured vs. uninjured leg. CONCLUSIONS: These preliminary data in athletes with SFX suggest that pQCT has the ability to distinguish differences in bone structure in injured vs. uninjured limbs. No discriminative bone parameter classifications were identified between adolescent athletes with or without SFX.

Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience.

The aim of this study was to evaluate the safety of irreversible electroporation (IRE) and the outcome of patients undergoing IRE of locally advanced pancreatic cancer (PC). Twenty-one patients with unresectable PC underwent open (n=19) or percutaneous (n=2) IRE of the tumor using the Nanoknife system with two electrodes that were repositioned several times to affect the whole mass. The size of the tumor was 39±10mm with a range from 21 to 65mm. Five patients underwent neoadjuvant chemotherapy and seven patients were treated with chemotherapy after IRE. Complications occurred in five patients, which resulted in prolongation of the average hospital stay from 10 to 34 days. There was no mortality in the first postoperative month. Median survival after IRE was 10.2 months compared to 9.3 months in a matched cohort (hazard ratio = .54, p = .053). The quality of life was declining slowly. 81% of time after IRE the Karnofsky performance status was ≥70 and sharp decline occurred approximately 8 weeks before death.In conclusion, IRE is a safe palliative treatment option for a percentage of patients with locally advanced pancreatic carcinoma. The patients treated with open IRE lived a decent life until 8 weeks before their death. We believe that IRE of pancreatic carcinoma can be regarded as an option, if imaging or explorative laparotomy show that R0 resection in not possible.

[Difficult Diagnosis of Non-strabismic Binocular and Accommodative Disorders]. / Obtízná diagnostika nestrabických binokulárních a akomodacních poruch.

The aim of the paper is to inform about the current approach to the diagnosis of non-strabismic binocular and accommodative disorders. A large number of studies quote high occurrence of them in both clinical and nonclinical populations. They also point out the presence of a diagnosis deficiency or insufficient diagnosis within the optometric and ophthalmological practice. The representation in population depends not only on race and age, but also on the methodology of diagnostic tests, and the chosen diagnostic criteria in particular. For the purpose of division of binocular and accommodative disorders there are several classification systems. The widespread classification facilitates a better understanding of a great spectrum of symptoms, assignment of the characteristic signs, and decision about appropriateness and choice of treatment types.Key words: heteroforie, binocular disorders, accommodative disorders, fusional vergence, convergence insufficiency, convergence excess.

A low prevalence of mycobacteria in freshwater fish from water reservoirs, ponds and farms.

A survey of the occurrence of mycobacteria was conducted from 717 freshwater fish (25 species) in two water reservoirs, five ponds and two farms in the Czech Republic. A total of 2182 tissue samples from these fish were examined using the conventional culture method. Thirteen mycobacterial isolates were obtained from 12 (1.7%) fish belonging to nine species. Isolates were identified using sequence analysis of the 16SrRNA gene as: Mycobacterium algericum, M. fortuitum, M. gordonae, M. insubricum, M. kumamotonense, M. nonchromogenicum, two isolates of M. peregrinum, M. terrae and M. triplex. Mycobacteria were isolated more frequently from fish skin and gills than from internal organs or muscles.

First isolation of a newly described Mycobacterium insubricum from freshwater fish.

Non-tuberculous or potentially pathogenic mycobacteria are ubiquitous in a water environment and are responsible for several diseases in animals and humans known as mycobacterioses. This report describes the first isolation of the novel species Mycobacterium insubricum in clinically healthy freshwater fish (Tinca tinca) in the Czech Republic which is the first to be derived from non-human sources reported in the literature.

Voice-supported electronic health record for temporomandibular joint disorders.

OBJECTIVES: To identify support of structured data entry for an electronic health record application in temporomandibular joint disorders. METHODS: The methods of structuring information in dentistry are described and the interactive DentCross component is introduced. A system of structured voice-supported data entry in electronic health record on several real cases in the field of dentistry is performed. The connection of this component to the MUDRLite electronic health record is described. RESULTS: The use of DentVoice, an application which consists of the electronic health record MUDRLite and the voice-controlled interactive component DentCross, to collect dental information required by temporomandibular joint disorders is shown. CONCLUSIONS: The DentVoice application with the DentCross component showed the practical ability of the temporomandibular joint disorder treatment support.

Incidence of invasive pneumococcal disease in the Czech Republic and serotype coverage by vaccines, 1997-2006.

We studied the incidence of invasive pneumococcal disease (IPD) in the Czech Republic by analysing two sources of data. The incidence of pneumococcal meningitis based on routine notification data varied between 0.4 and 0.6/100 000 population between 1997 and 2006. The incidence of IPD based on laboratory surveillance varied between 2.3 and 4.3/100 000 population between 2000 and 2006. The annual IPD incidence remained stable during the study period. Estimates of absolute IPD case-load in the entire country varied from 235 to 437 per year. The age-specific incidence was highest in the <1 year age group, reaching 4.3/100 000 for pneumococcal meningitis in routine notification and 15.7/100 000 for IPD in laboratory-based surveillance data, respectively. A total of 1236 Streptococcus pneumoniae isolates from cerebrospinal fluid and sterile body sites were investigated. The most frequent serotypes causing IPD in all ages were 3, 4, 14, 8 and 19F, accounting for 41.5% of all isolates. The most frequent serotypes by age group were: <1 year (6B and 19F); 1-4 years (14, 6B and 23F); 40-64 years (3, 8 and 4), and > or = 65 years (3, 4, 9N and 14). The coverage of serotypes in all age groups by pneumococcal vaccines ranged from 41.5% for 7-valent conjugate vaccine to 67.9% for 13-valent conjugate vaccine. The coverage of serotypes causing IPD is significantly different between infants/children and adults/elderly. PCV-7 coverage by age group was: <1 year (66.0%), 1-4 years (65.1%), 40-64 years (34.4%) and > or = 65 years (39.3%). Similar age differences between infants/children and adults/elderly were found in coverage by PCV-9, PCV-11 and PCV-13. The distribution of serotypes in the total population and individual age groups was stable during the period 2000-2006.

Influence of hydroxyapatite crystallinity on the growth of keratinocytes.

Dental implantology is a field, which has made a great progression recently. The main task nowadays is to shorten the healing period and so improve the comfort for the patients. One possibility how to full fil this task is to coat the surface of the implant. Very promising material seems to be hydroxyapatite, which is a natural component of human body and suitable method is the pulsed laser deposition. In our study we tried to evaluate difference between crystalline and amorphous hydroxyapatite coated dental implants from the biological point of view. We found that the cells were able to adhere to all of our studied samples. The worst proliferation of fibroblasts was found on the amorphous coating, whereas the adhesion was fully comparable with other surfaces. The level of keratinocyte differentiation was the same on both of the studied surfaces.

[The use of thrombelastography in evaluation of coagulation in females with physiological or pathological gravidity]. / Uzití trombelastografie pri hodnocení koagulace u zen s fyziologicky a patologicky probíhajícím tehotenstvím.

BACKGROUND: During gravidity changes in coagulation develop, however different norms for pregnant women and prevailing population are rarely used. Pathological gravidity can be accompanied with more significant coagulopathies. Thrombelastography is more and more frequently used for evaluation of coagulation parameters of pregnant women. The aim of the study was to compare thrombelastographic coagulation parameters in females with physiological or pathological gravidity and with norms for prevailing population. METHODS AND RESULTS: 60 women in the 3rd trimester of physiological gravidity (group ZDRAVE) and 50 women with pathological gravidity (women with preeclampsia or with a dead fetus, group PATOL) were examined. Both groups were of the comparable age. Average values of studied parameters in the group ZDRAVE were found at the level of "procoagulation" limits for prevailing population. In the group PATOL, average values were even more "procoagulative", however, differences to the ZDRAVE group were nor significant: time r 4.7 (SD 1.7) vs. 4.4 (SD 2.0) p = 0.461 (norm for prevailing population 4-8 min), time to 1.5 (0.5) vs. 1.3 (0.4) p = 0.030 (norm 1-4 min), angle alpha 69.6 (5.5) vs. 71.0 (7.7) p = 0.324 (norm 47-74 degrees), maximal amplitude 71.3 (4.5) vs. 73.1 (4.7) p = 0.079 (norm 55-73 mm), coagulation index 2.7 (1.8) vs. 3.2 (1.8) p = 0.219 (norm (-3)-(+3)). In the group PATOL higher variability than in the group ZDRAVE was found. On the basis of the group ZDRAVE selection percentiles, new norms of thrombelastographic coagulation parameters for pregnant women were elaborated. CONCLUSIONS: Coagulation during pregnancy differs significantly from that of prevailing population. That is why the new thrombelastographic norms for pregnant women are submitted. Coagulation changes in pathological pregnancies are more difficult to anticipate than in healthy gestations.

[Remarks on embolization of uterine fibroids]. / Praktické poznámky k embolizaci delozních myomú.

OBJECTIVE: To give a systematic comment on uterine artery embolization for the treatment of uterine fibroids. DESIGN: Expert comment. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and General Faculty Hospital, Charles University, Prague. METHODS: The analysis of results of the group of patients treated with uterine fibroid embolization in our facility in the years 2001-2005. RESULTS: Opinions of the multidisciplinary team, specialized in complex therapy of uterine fibroids were summarized. On the base of experience with more than 110 patients treated with uterine fibroid embolization we worked up practical comments on indications, cover and implementation of the procedure, and on suggested studies pre and post-procedurally with regard to expected effect and possible complications. CONCLUSION: Uterine artery embolization is a minimally invasive procedure with large symptomatic potential in therapy of post-fertile females with leiomyomas. The indication of such therapy for pregnancy planning women is controversial and needs thorough individual consideration about benefits and risks of embolization and its comparison with standard therapy (myomectomy). Organizing of the whole procedure (preoperative studies, equipment and experience of interventional radiologist, pain management, handling with complications) is challenging and should be performed by specialized teams and centers.

Emergence of a novel macrolide-resistant Streptococcus pyogenes emm53 strain.

An unusual emm53, T-28/T-non-typeable, iMLS(B) phenotype clone represented a substantial proportion (28.6%) of invasive erythromycin-resistant group A streptococcus (GAS) isolates in the Czech Republic during 2003. Clonal analysis of emm53 isolates between 2001 and 2004 revealed four pulsed-field gel electrophoresis (PFGE) patterns and two emm subtypes. Isolates produced identical PFGE patterns regardless of their invasiveness and/or tetracycline resistance. Multilocus sequence typing classified all isolates as ST340. An ST5 (emm83) isolate, a potential ancestor of ST340, was isolated in the Czech Republic from an impetigo patient in 1988. The Czech emm53/ST340 isolates shared only three of seven alleles with the original Lancefield emm53/ST11 isolate.

[Enucleation of intramural uterine fibroids in women at fertile age: midterm results of prospective clinical trials]. / Enukleace intramurálnch delozních myomu u zen ve fertilním veku: strednedobé výsledky prospektivní klinické studie.

OBJECTIVE: To analyze clinical and reproductive outcomes of patients after laparoscopic (LM) or open (OM) myomectomy. DESIGN: Prospective clinical trial. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine and General Faculty Hospital, Charles University, Prague. METHODS: Women under the age of 40 with intramural fibroid larger than 4 cm were indicated for myomectomy. LM was performed when laparoscopy revealed solitary or 2 fibroids smaller than 8 cm; otherwise the OM was carried out. The patients were followed at 6 months intervals. RESULTS: 80 myomectomies with extirpation of 121 myomas was performed from January 2002 to April 2005. The average age was 33.5 years, average size of dominant fibroid 56 mm. 38% of women suffered from infertility; the mean follow-up was 15.6 months. We performed LM in 56 cases (70%). From 24 open procedures 18 were elective and 6 converted from laparoscopy. In 18 patients some of the fibroid--ischemization procedures (uterine arteries embolization or laparoscopic dissection, or laparoscopic myolysis) preceded myomectomy. In the group with LM there was significantly lower peri-procedural blood loss, lower count of leucocytes and CRP concentration the 2nd day after surgery, shorter stay in the hospital, shorter interval between surgery and conception, and lower incidence of early complications than in women with OM. Fibroid related symptoms fully disappeared in 76% of patients. 20 women from 38 that have already tried to conceive have achieved 22 gestations so far: 9 deliveries (2 preterm; 3 vaginal, 6 Cesarean), 6 miscarriages, 1 ectopic and 6 ongoing pregnancies at the moment. CONCLUSION: In the hands of surgeons experienced in operative laparoscopy the enucleation of intramural uterine fibroids is safe, symptomatically effective, mostly low invasive procedure with good reproductive prognosis.

Dynamics of PCR-based diagnosis in patients with invasive meningococcal disease.

Invasive meningococcal disease continues to be a life-threatening condition and rapid diagnosis is important for the administration of appropriate treatment. This study focused on the use of PCR for the diagnosis of meningococcal aetiology and the dynamics of PCR-based diagnosis over time in various biological samples. Sixty cerebrospinal fluid (CSF) and 144 serum samples collected during the first week of hospitalisation from 37 patients with laboratory-confirmed invasive meningococcal disease were investigated. Overall, 91.9% of CSF samples and 45.9% of serum samples were PCR-positive, while culture of CSF and blood was positive for only 35% and 39% samples, respectively. Positive PCR results were obtained until day 7 with CSF and until day 5 with serum. It is therefore recommended that samples for molecular diagnosis should be collected early in the course of suspected invasive meningococcal disease.

The influence of mutation, recombination, population history, and selection on patterns of genetic diversity in Neisseria meningitidis.

Patterns of genetic diversity within populations of human pathogens, shaped by the ecology of host-microbe interactions, contain important information about the epidemiological history of infectious disease. Exploiting this information, however, requires a systematic approach that distinguishes the genetic signal generated by epidemiological processes from the effects of other forces, such as recombination, mutation, and population history. Here, a variety of quantitative techniques were employed to investigate multilocus sequence information from isolate collections of Neisseria meningitidis, a major cause of meningitis and septicemia world wide. This allowed quantitative evaluation of alternative explanations for the observed population structure. A coalescent-based approach was employed to estimate the rate of mutation, the rate of recombination, and the size distribution of recombination fragments from samples from disease-associated and carried meningococci obtained in the Czech Republic in 1993 and a global collection of disease-associated isolates collected globally from 1937 to 1996. The parameter estimates were used to reject a model in which genetic structure arose by chance in small populations, and analysis of molecular variation showed that geographically restricted gene flow was unlikely to be the cause of the genetic structure. The genetic differentiation between disease and carriage isolate collections indicated that, whereas certain genotypes were overrepresented among the disease-isolate collections (the "hyperinvasive" lineages), disease-associated and carried meningococci exhibited remarkably little differentiation at the level of individual nucleotide polymorphisms. In combination, these results indicated the repeated action of natural selection on meningococcal populations, possibly arising from the coevolutionary dynamic of host-pathogen interactions.

Surveillance of invasive meningococcal disease in the Czech Republic.

Routine notification of invasive meningococcal disease has a long tradition in the Czech Republic: mortality data are available from 1921 and morbidity data from 1943. The collection of Neisseria meningitidis strains kept in the NRL for Meningococcal Infections in Prague dates from 1970 onwards, and represents more than 3500 strains isolated from invasive disease and their contacts, from healthy carriers and from respiratory infection. Analysis of these strains showed that the Czech meningococcal population is different from that seen in western Europe. In 1993, the incidence serogroup C meningococcal disease increased and was associated with the emergence of the hypervirulent complex Neisseria meningitidis C, ST-11, ET-15/37, and caused an increase in the incidence of invasive meningococcal disease which peaked in 1995 (2.2/100,000). A vaccination strategy targeting the part of the population at highest risk of invasive meningococcal disease was adopted in the country.

Comparison of Streptococcus pneumoniae serotypes causing acute otitis media & invasive disease in young children in the Czech Republic.

BACKGROUND & OBJECTIVES: The availability of a type-specific pneumococcal vaccine for children is a worldwide problem. It is necessary to study the serotypes prevalent in a country before introducing a type-specific vaccine. The objective of the present study was to analyse the prevalence of Streptococcus pneumoniae serotypes in children suffering from acute otitis media or invasive pneumococcal disease and to compare a coverage of serotypes by individual pneumococcal vaccines. METHODS: Children suffering from acute otitis media and invasive pneumococcal disease were analysed in the Czech Republic from October 1999 to November 2000. Serotyping was performed by the quellung technique using antisera from Statens Serum Institute (Denmark). RESULTS: The most frequent serotypes in patients with acute otitis media were 3, 19F, 23F, 14, 9V, 1, 6B, 11A and 28F. Vaccine coverage for the identified serotypes in acute otitis media patients was 52.1 per cent for the 7-valent vaccine, 57.8 per cent for the 9-valent vaccine and 75.7 per cent for the 11-valent form of the vaccine. In 108 patients with invasive pneumococcal disease, the most frequent serotypes were 6B, 9V, 14, 19F, 3 and 23F. Vaccine coverage for the identified serotypes in patients with invasive pneumococcal disease was 62 per cent for the 7-valent vaccine, 66.4 per cent for the 9-valent vaccine and 77.5 per cent for the 11-valent form of the vaccine. INTERPRETATION & CONCLUSION: Vaccine coverage for the identified serotypes for the 11-valent pneumococcal vaccine was better than the other two vaccines.

[Combined treatment of uterine myoma (uterine arteries embolization followed by laparoscopic myomectomy)]. / Kombinovaná lécba delozního myomu (embolizace uterinních arterií s následnou laparoskopickou myomektomii).

OBJECTIVE: The treatment of uterine myoma with pretreatment of uterine arteries embolization followed by laparoscopic myomectomy is presented. DESIGN: Case report. SETTING: Department of Obstetrics and Gynaecology 1st Medical Faculty of Charles University and General Faculty Hospital in Prague. SUBJECT AND METHOD: Forty two years old woman with uterine myoma was "pretreated" with uterine arteries embolization followed by laparoscopic myomectomy next day. The reason for this procedure was to improve in short period conditions for surgery and definitively solve uterine pathology. CONCLUSION: The "pretreatment" with uterine arteries embolization improves basically conditions and effect of uterine myoma surgery. This "two step procedure" could be recommended mainly for cases of large and vascularizated myomas.

Multilocus sequence typing of Neisseria meningitidis directly from cerebrospinal fluid.

MLST typing of Neisseria meningitidis directly from clinical material was introduced in the National Reference Laboratory for Meningococcal Infections in Prague. Four cerebrospinal fluid samples were obtained from patients with suspected meningococcal invasive disease. In all samples, all classical laboratory methods gave negative results and the only positive method was PCR, which revealed Neisseria meningitidis group C (two specimens) and group B (two specimens), respectively. MLST performed directly from cerebrospinal fluid revealed that the strains causing the two group C infections were of sequence type (ST) 11, while the two group B infections were characterized as ST-32 and ST-33 respectively. Multi-locus sequence typing of meningococci directly from clinical material offers the opportunity to improve further the surveillance of meningococcal disease and has now been introduced into the routine portfolio of tests employed at the national reference laboratory of the Czech Republic.

Phenotypic and genotypic approaches to characterization of isolates of Neisseria meningitidis from patients and their close family contacts.

Characterization of isolates of Neisseria meningitidis obtained from patients with meningococcal disease or from pharyngeal swabs of asymptomatic carriers can be achieved by several approaches which provide different levels of discrimination. A total of 45 gram negative, oxidase-positive diplococcus strains isolated from 15 individuals with meningococcal disease and 30 of their family contacts were examined by three approaches: serological typing, multilocus enzyme electrophoresis (MLEE), and multilocus sequence typing (MLST). For 10 of the 15 patient and contact groups, all of the isolates were confirmed as meningococci, and the bacteria obtained from the patients and contacts, including their mother or principal caregiver in the case of children, were indistinguishable by all three methods. In the remaining five groups the isolates from the patients were distinct from those recovered from the contacts, and in three examples, in two separate groups, the contacts were shown by MLST to be carrying strains of Neisseria lactamica. The data obtained from the three techniques were consistent, although complete serological typing was possible for only a minority of isolates. Both MLEE and MLST established the genetic relationships of the isolates and identified members of known hypervirulent lineages, but MLST was faster than MLEE and had the additional advantages that it could be performed on noninfective material distributed by mail and that the results from different laboratories could be compared via the internet (http://mlst.zoo.ox.ac.uk).