German S3-guidelines on the treatment of psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance (Richards et al. in J Am Acad Dermatol 41(4):581-583, 1999). To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis first published in 2006 and now updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. This short version of the guidelines presents the resulting series of therapeutic recommendations, which were based on a systematic literature search and discussed and approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs, as well as detailed information on how best to apply the treatments described (for full version please see Nast et al. in JDDG Suppl 2:S1-S104, 2011 or http://www.psoriasis-leitlinie.de ).

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

A subpopulation of nervus terminalis neurons projects to the olfactory mucosa in Xenopus laevis.

Biocytin application to the normal or zinc sulfate-treated nasal cavity of Xenopus laevis was used to trace retrogradely neurons associated with the terminal nerve (TN). Immunocytochemistry was conducted to identify the relationship of gonadotropin-releasing hormone-immunoreactive (GnRH-ir) TN neurons with biocytin-labeled neurons. Neurons that accumulated biocytin were located in olfactory nerve fascicles close to the olfactory mucosa lining the caudal, medial, and rostral walls of the principal cavity. GnRH-ir fibers were observed only in the olfactory nerve fascicle projecting to the rostral edge of the principal cavity. In addition, GnRH-ir fibers did not contact biocytin-labeled TN neurons. We hypothesize that these two classes of neurons represent separate components of the TN.

Reverse engineering of metabolic pathways from observed data using genetic programming.

Recent work has demonstrated that genetic programming is capable of automatically creating complex networks (such as analog electrical circuits and controllers) whose behavior is modeled by linear and non-linear continuous-time differential equations and whose behavior matches prespecified output values. The concentrations of substances participating in networks of chemical reactions are also modeled by non-linear continuous-time differential equations. This paper demonstrates that it is possible to automatically create (reverse engineer) a network of chemical reactions from observed time-domain data. Genetic programming starts with observed time-domain concentrations of input substances and automatically creates both the topology of the network of chemical reactions and the rates of each reaction within the network such that the concentration of the final product of the automatically created network matches the observed time-domain data. Specifically, genetic programming automatically created metabolic pathways involved in the phospholipid cycle and the synthesis and degradation of ketone bodies.

Effects of the T-type calcium channel blockade with oral mibefradil on the electrophysiologic properties of the human heart.

BACKGROUND: As the calcium T-channel blockade is a new pharmacological category with presumably unique electrophysiological effects, the influence of its only representative yet mibefradil was tested after the single oral dose. MATERIAL AND METHODS: 10 patients underwent the electrophysiologic examination. Normal baseline values in sinus node cycle length (SNCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), PA interval, atrial effective refractory period, AH interval, Wenckebach point (WP), atrioventricular nodal refractory period, and HV interval were measured using standard techniques. After that a single dose of 100 mg mibefradil was given and the testing repeated in 90 minutes. RESULTS: Though non-significantly in a study-group limited in size due to global withdrawal of mibefradil, sinus node automaticity was suppressed (prolongation of SNRT by 5.1% and CSNRT by 11.5%) and heart rate lowered (SNCL prolonged by 2.8%) comparatively more than was the negative dromotropic effect on the atrioventricular node (negligible prolongation of AH interval by 1.1% and WP cycle by 0.4%). CONCLUSIONS: Demonstrated electrophysiological effects of oral mibefradil with more pronounced influence on the automaticity of the sinus node seem to be in agreement with the preclinical data on the predominant role of T-channels in the pacemaker activity of the sinus node. According to the Framingham data on the risk of heart rate for the cardiovascular as well as all-cause mortality, calcium T-channel blockade offers a desirable profile for antihypertensive treatment. From this point of view development of new representatives of calcium T-channel blockers could be a useful contribution to clinical practice.

[Efforts to eradicate poliomyelitis in the Czech Republic]. / Snaha o eradikaci poliomyelitidy v Ceské republice.

The Czech Republic is one of the first countries where the paralytic form of poliomyelitis was eradicated by vaccination with the live attenuated vaccine. The effectiveness of vaccination was monitored every year up to 1992 by assessment of the immunity against polioviruses in a large group of sera from volunteers (cca 1500 subjects). This made it possible to improve occasional drops of immunity of the population, in particular in type 3. However, the absence of the paralytic form of poliomyelitis does not imply eradication of poliomyelitis which means elimination of wild polioviruses from the circulation in the population of a country. The circulation of wild polioviruses is monitored in the Czech Republic in cases of acute mild pareses, in particular, however, in waste waters of some large towns. A wild poliovirus was not detected so far. These investigations must started and be conducted up to the time when the Czech Republic will be granted the status of "country with eradicated poliomyelitis".

A programming course in bioinformatics for computer and information science students.

We have created a course entitled "Representations and Algorithms for Computational Molecular Biology" with three specific goals in mind. First, we want to provide a technical introduction for computer science and medical information science students to the challenges of computing with molecular biology data, particularly the advantages of having easy access to real-world data sets. Second, we want to equip the students with the skills required of productive research assistants in molecular biology computing research projects. Finally, we want to provide a showcase for local investigators to describe their work in the context of a course that provide adequate background information. In order to achieve these goals, we have created a programming course, in which three major projects and six smaller assignments are assigned during the quarter. We stress fundamental representations and algorithms during the first part of the course in lectures given by the core faculty, and then have more focused lectures in which faculty research interests are highlighted. The course stressed issues of structural molecular biology, in order to better motivate the critical issues in sequence analysis. The culmination of the course was a challenge to the students to use a version of protein threading to predict which members of a set of unknown sequences were globins. The course was well received, and has been made a core requirement in the Medical Information Sciences program.

A case study where biology inspired a solution to a computer science problem.

This paper describes how the biological theory of gene duplication described in Susumu Ohno's provocative book, Evolution by Means of Gene Duplication, was brought to bear on a vexatious problem from the domain of automated machine learning, namely the problem of architecture discovery. Six new architecture-altering operations for genetic programming were motivated by the way that new biological structures, functions, and behaviors arise in nature using gene duplication. Genetic programming with the new architecture-altering operations was then applied to the transmembrane protein segment identification problem. The out-of-sample error rate for the best genetically-evolved program achieved was slightly better than that of previously-reported human-written algorithms for this problem.

Evolution of a computer program for classifying protein segments as transmembrane domains using genetic programming.

The recently-developed genetic programming paradigm is used to evolve a computer program to classify a given protein segment as being a transmembrane domain or non-transmembrane area of the protein. Genetic programming starts with a primordial ooze of randomly generated computer programs composed of available programmatic ingredients and then genetically breeds the population of programs using the Darwinian principle of survival of the fittest and an analog of the naturally occurring genetic operation of crossover (sexual recombination). Automatic function definition enables genetic programming to dynamically create subroutines dynamically during the run. Genetic programming is given a training set of differently-sized protein segments and their correct classification (but no biochemical knowledge, such as hydrophobicity values). Correlation is used as the fitness measure to drive the evolutionary process. The best genetically-evolved program achieves an out-of-sample correlation of 0.968 and an out-of-sample error rate of 1.6%. This error rate is better than that reported for four other algorithms reported at the First International Conference on Intelligent Systems for Molecular Biology. Our genetically evolved program is an instance of an algorithm discovered by an automated learning paradigm that is superior to that written by human investigators.

[Virologic and morphologic study in sudden and unexpected death in children]. / Virologická a morfologická studie u náhle a neocekávane zemrelých detí.

The authors examined a group of 47 children who died at the age of 1-9 months, incl. 19 female and 28 male children. In 23 the death was described as sudden and in 24 as unexpected. From 19 dead children a virus was isolated: in 14 one or two serotypes of enterovirus were found, in two the virus of parainfluenza 3 in two adenoviruses (type 2, 7). A total of 46 viral strains were isolated. By immunofluorescence in tissues antigens of the parainfluenza virus 3 and adenovirus were detected. Immune complexes were not detected in tissues. The distribution of vaccination polioviruses in organs and tissues after a known interval following vaccination was recognized. In some of the infants a possible causal relationship between the virological and morphological findings was found and the authors discuss the possible pathogenetic role of the revealed changes in sudden death.

[Selected cases of prosthetic treatment in patients with lowered height of the occlusion]. / Wybrane przypadki leczenia protetycznego pacjentów z obnizona wysokoscia zwarcia.

In the paper three selected cases that illustrate comprehensive prosthetic treatment in which modern methods and prosthetic materials have been used non-conventional composed bridges with partial crowns on abutment teeth sealed with composites in patients with deep bite are reported. For facing the crowns and bridges such materials as Izosit, porcelain, acryl-derived material--Colorstat which is superior to acrylate considering its physicochemical properties have been used. For the reconstruction of the patients, own teeth Izofil adhesive material has been used for capping the teeth partly or totally establishing a new occlusal situation in anterior and lateral segments.

Transplacental antibodies. Part III: Maternal antibodies against polioviruses, M. parotitidis and M. parainfluenzae.

In 1981 we examined 247 sera for the presence of antibodies against all three types of poliovirus and 253 sera for antibodies against M. parotitidis and three types of M. parainfluenzae viruses. The sera were obtained from the cord blood of mothers between 15 and 34 years of age. All mothers were divided into four age groups, each with primipara and multipara subgroups. The rate of seropositivity for type 1 and type 2 poliovirus-specific antibody was in all age groups higher than 90%, the overall seropositivity rate for type 3 poliovirus antibody was 83.6%, with 73.1% as the lowest rate for age group of youngest mothers. Significant seropositivity variations between the primipara and multipara subgroups were recorded only for type 3 antibody in the two age groups of oldest mothers (25-29 and 30-34 years). This is consistent with the assumed booster effect of Sabin vaccine strains on mothers of families with more than one child. Antibodies specific to mumps virus were present in the cord blood of 78.6% of all mothers and the rates of seropositivity were found to rise with the increasing age. Seropositivity for M. parainfluenzae type 1-specific antibody was demonstrated in 95.8%, for type 2-specific antibody in 98.9% and for type 3-specific antibody in 100% of mothers, which is suggestive of high herd immunity levels in the population.

Properties of poliovirus strains isolated from waste waters of nurseries in Prague in 1969-1982.

The rct marker and antigenic marker were studied in poliovirus strains of all the three types isolated from waste waters of selected communities of children in Prague in 1969-1982. Only three isolated strains (two of type 2 and one of type 3) i.e. 1.38% of strains from nursery waste waters and 0.99% of strains from the total Prague municipal sewerage system, differed in both markers from prototype vaccine strains. The rct marker was most frequently altered in strains of type 1; antigenic marker varied most often in strains of type 3, less conspicuously in strains of type 2 and minimum changes were found in type 1 strains. The dependence of changes in both studied markers of isolated strains on the interval between vaccination and isolation from waste waters was reflected in the dynamics of changes. The highest dynamics of changes in rct marker and antigenic marker was recorded in type 3 and type 2 strains, minimal dynamics being found in type 1 strains. Study of type 2 strains isolated for a long time in some years showed that the longer the interval between vaccination and isolation, the higher the similarity between the isolated strain and the prototype vaccine strain.

Polio antibody outfit of newborns and infants born after 20 years of mass vaccination with live poliovaccine.

Antibodies against type 1 and 2 poliovirus were tested in 250 infants and against type 3 poliovirus in 341 infants aged 0-13 months to compare the polio antibody outfit of newborns and infants born to three groups of mothers: (a) nonvaccinated, above 35 years of age; (b) vaccinated with attenuated poliovirus but having had chance of contact with wild poliovirus during childhood, age 22-35 years, and (c) vaccinated but not having had contact with wild poliovirus, below 22 years of age. Over 90% of newborns had specific neutralizing antibodies against all three poliovirus types. With increasing infant age the percentage of antibody-positive infants decreased: by age 9-11 months only 46%, 27% and 14% of infants displayed antibodies to polio-virus types 1, 2 and 3, respectively. Geometric mean titres decreased accordingly. Differences between infants born to mothers of the above three groups were nonsignificant: the results obtained suggest that future newborns will also possess satisfactory levels of antibodies acquired from mothers who have only had contact with attenuated vaccine poliovirus.

Properties of poliovirus strains isolated over the period 1969-1978 from the main municipal sewerage system of the city of Prague.

Biological properties (rct marker and antigenic relatedness) were compared in vaccine prototype strains and in 62 poliovirus strains isolated during a period 1969-1978 from the main municipal sewerage system of the City of Prague. None of the strains isolated from the municipal sewerage showed biologic properties that would fully differ from those observed in vaccine-derived strains. The strains detected very late postvaccination (after about a year) showed a lesser extent of changes than strains isolated earlier after vaccination. The most frequent changes were recorded in type 2 strains, less frequent in type 3 strains and the least frequency of changes was found in type 1 strains. To facilitate comparisons of these changes in dependence on time of postvaccination virus excretion a supporting evaluation criterion has been developed to help express the dynamics of changes in the isolated poliovirus strains. The recorded degree of the dynamics of changes was highest in type 2 strains, lower in type 3 strains and lowest in type 1 strains. The dynamics of changes detected in strains of various types was not always constant in the course of years: in a given year (or in a period of several years) changes occurred always in strains of the same serologic type, whereas strains of the other two types changed only insignificantly during the respective period.