[Diagnosis of cardiac rhabdomyoma in the first trimester of pregnancy]. / Diagnóstico de un rabdomioma intracardiaco en el primer trimestre de la gestación.

BACKGROUND: Rhabdomyoma is the most common cardiac tumor detected during fetal life and childhood; despite of this, its incidence is very low. CLINICAL CASE: cardiac rhabdomyoma diagnosed at first trimester ultrasound. CONCLUSION: Early diagnosis is important for performing further studies to detect the possible presence of associated anomalies, including TS (tuberous sclerosis). Prognosis is conditioned by number, size and location. In our case, the presence of early hypoplastic right ventricle and pulmonar and tricuspid atresia (probably because of tumor size) conditioned a very bad prognosis, so the patient decided termination of pregnancy.

Effects of atmospheric pollutants (CO, O3, SO2) on the allergenicity of Betula pendula, Ostrya carpinifolia, and Carpinus betulus pollen.

Pollen of Betula pendula, Ostrya carpinifolia, and Carpinus betulus was exposed in vitro to relatively low levels of the air pollutants, namely carbon monoxide, ozone, and sulfur dioxide. The allergenicity of the exposed pollen was compared with that of non-exposed pollen samples to assess if air pollution exposition affects the allergenicity potential of pollen. The immunodetection assays indicated higher IgE recognition by all sera of allergic patients to the pollen protein extracts in all exposed samples in comparison to the non-exposed samples. These results show that the pollen exposition to low pollutants' levels induces increased allergic reaction to sensitized individuals.

Evaluation of physicians' practice patterns in France concerning fertility preservation in women with endometriosis.

OBJECTIVE: We aim to evaluate the knowledge and physicians' practices concerning fertility preservation in women with endometriosis. DESIGN: Descriptive, observational, national study using an online self-questionnaire, sent by email to French gynaecologists in October 2019 within 2 months. RESULTS: We obtained 110 analyzable responses from mainly surgeons (54 %) and reproductive clinicians (19 %) with a good experience (average 15 years of practice). Amongst these practitioners, 91 % seemed aware of latest French recommendations on endometriosis issued in December 2017. The most commonly used surgical techniques for management of endometriomas were intra-peritoneal cystectomy (51 %), vaporization by plasma energy (29 %) and destruction by bipolar coagulation (8.5 %). Preoperative AMH was systematically or often prescribed by 78 % of the practitioners against 37.3 % who did it postoperatively. Furthermore, 74 % also considered and performed fertility preservation strategy to manage endometriosis. It was offered in situations of bilateral or recurrent endometrioma, but only 33 % offered it in unilateral endometrioma cases. In the cases recorded, vitrification of mature oocytes appears to be the most common fertility preservation technique (used by 87 % of the practitioners). CONCLUSION: We observed in our population of sensitized practitioners a good and adequate knowledge concerning endometriosis physiopathology and recommendations for its management, with good information delivery to women. Operating techniques are adapted although information and education concerning fertility preservation indications seem necessary. The place of multidisciplinary concertation meeting in endometriosis appears essential both for discussion of surgical indications and for fertility preservation possibilities. Creation of dedicated structures should be encouraged.

QSAR for RNases and theoretic-experimental study of molecular diversity on peptide mass fingerprints of a new Leishmania infantum protein.

The toxicity and low success of current treatments for Leishmaniosis determines the search of new peptide drugs and/or molecular targets in Leishmania pathogen species (L. infantum and L. major). For example, Ribonucleases (RNases) are enzymes relevant to several biologic processes; then, theoretical and experimental study of the molecular diversity of Peptide Mass Fingerprints (PMFs) of RNases is useful for drug design. This study introduces a methodology that combines QSAR models, 2D-Electrophoresis (2D-E), MALDI-TOF Mass Spectroscopy (MS), BLAST alignment, and Molecular Dynamics (MD) to explore PMFs of RNases. We illustrate this approach by investigating for the first time the PMFs of a new protein of L. infantum. Here we report and compare new versus old predictive models for RNases based on Topological Indices (TIs) of Markov Pseudo-Folding Lattices. These group of indices called Pseudo-folding Lattice 2D-TIs include: Spectral moments pi ( k )(x,y), Mean Electrostatic potentials xi ( k )(x,y), and Entropy measures theta ( k )(x,y). The accuracy of the models (training/cross-validation) was as follows: xi ( k )(x,y)-model (96.0%/91.7%)>pi ( k )(x,y)-model (84.7/83.3) > theta ( k )(x,y)-model (66.0/66.7). We also carried out a 2D-E analysis of biological samples of L. infantum promastigotes focusing on a 2D-E gel spot of one unknown protein with M<20, 100 and pI <7. MASCOT search identified 20 proteins with Mowse score >30, but not one >52 (threshold value), the higher value of 42 was for a probable DNA-directed RNA polymerase. However, we determined experimentally the sequence of more than 140 peptides. We used QSAR models to predict RNase scores for these peptides and BLAST alignment to confirm some results. We also calculated 3D-folding TIs based on MD experiments and compared 2D versus 3D-TIs on molecular phylogenetic analysis of the molecular diversity of these peptides. This combined strategy may be of interest in drug development or target identification.

Vestibular rehabilitation therapy in children.

OBJECTIVES: Vestibular disturbances are underdiagnosed in children. However, balance impairment may compromise the normal development of affected children. The appropriate therapeutic approach has not been agreed on for this age group. Vestibular rehabilitation therapy has excellent results in adults, but very few data exist regarding its results in children. We evaluated through clinical assessment and computerized dynamic posturography the outcome of children with peripheral vestibular disturbances undergoing vestibular rehabilitation therapy and observed the influence of learning and of central nervous system maturation on posturography retest results. METHODS: Sixteen children (10 boys and 6 girls) with peripheral vestibular disorders (mean age, 8 yr 7 mo) constituted the cohort and were consecutively treated with vestibular rehabilitation therapy. Symptomatic children underwent pre- and posttreatment computerized dynamic posturography. Their outcome was clinically assessed. Another 16 asymptomatic children, paired by sex and age, underwent two computerized dynamic posturography procedures with the same time interval as that of the symptomatic group. RESULTS: All children completed the treatment. Total recovery of symptoms occurred in nine (56.3%) patients, whereas a dramatic partial recovery was observed in the remaining seven (43.7%) children. Posturography Conditions 5 and 6, the vestibular ratio of the sensory analysis, and the composite equilibrium score had a significant quantitative improvement after vestibular rehabilitation therapy. No adverse reactions occurred to the exercises. No statistically significant posturography changes were observed in the asymptomatic children. CONCLUSION: Vestibular rehabilitation therapy seems to be a safe and efficacious therapeutic option in children with peripheral vestibular disturbances.

[Research in primary care: 1994-2003]. / Investigación en atención primaria: 1994-2003.

OBJECTIVES: To analyse the characteristics of the original articles published in the journal Atención Primaria (Primary Care) during the last 10 years. DESIGN: Literature study. SETTING: Primary health care. PARTICIPANTS: Original articles published in Atención Primaria between 1994 and 2003. MAIN MEASUREMENTS: The professional category of the authors, whether it was a multidisciplinary or multicentred study, the autonomous community of origin, the topic, the type of study, and if it had a grant or financial assistance. RESULTS: 1229 articles have been reviewed. In 40.0% of them a family doctor is included in the authorship. 31.4% can be considered multidisciplinary and 20.5% multicentred. The Communities of Valencia, Madrid, Andalusia, and Catalonia took up 60% of the volume of publications. The most common topic is the provision and organisation of the health services (40.5%). Only 4.3% of the designs are experimental. A grant or financial aid is stated in 16.2% of the articles. CONCLUSIONS: Although the situation as regards the previous years has not varied too much, some positive findings, such as the emergence of research groups, increasing presence of multicentre and multidisciplinary studies, better access to sources of finance, etc, suggest that we are in a process of improving the quality of research in primary care.

Treatment of cutaneous leishmaniasis with localized current field (radio frequency) in Tabasco, Mexico.

In Mexico cutaneous leishmaniasis (CL) occurs in 17 of 32 States, and is a serious public health problem. This is a report of treatment of CL patients in the State of Tabasco, Mexico with a localized current field-radio frequency (LCF-RF) device to generate precisely controlled heat as an alternative to prohibitively expensive drug treatment. It was not a controlled clinical trial, but rather an evaluation of the feasibility of this form of treatment for all CL patients encountered in the endemic area. A total of 201 previously diagnosed patients with CL caused by Leishmania mexicana were treated with a portable Thermosurgery LCF-RF generator powered by rechargeable batteries. The ages of the patients ranged from two to 75 years; the sex distribution was 63% males and 37% females. A single device was used in five different municipalities. Lesions were first anesthetized with 1% lidocaine HCl and moistened with normal saline solution. Treatment consisted of a single application that produced 50 degrees C for 30 sec. After four weeks, 122 patients were available for evaluation, of which 95% were totally cured; (even those involving ear cartilage, which respond poorly to antimonials). At eight weeks post-treatment, 191 patients were evaluated, with a total cure rate of 90%. This form of treatment proved to be effective and convenient for use in primary health care facilities in Mexico and has many advantages over traditional forms of therapy.

[Validity of the protocol for evaluating the inappropriate use of hospitalization]. / Validez del protocolo de evaluación del uso inapropiado de la hospitalización.

BACKGROUND: The study was carried out in order to assess the inter-observer reliability and validity in respect of clinical appraisal given by the Appropriateness Evaluation Protocol (AEP), in the context of the Spanish Public Hospital System. MATERIAL AND METHOD: In order to assess the reliability a total of 614 hospital stays chosen at random from 56 hospital admissions were independently analysed by three reviewers (two doctors and one nurse). In order to assess the validity, the findings obtained by the nurse were compared with the majority opinion given by the 7 hospital specialists in respect of each of hospital stays under evaluation. As part of the analytical procedure, indices for observed agreement, and specific agreement were calculated, as well as the Kappa statistic, all forming of various random samples of 614 hospital stays. In order to assess the predictive validity of the AEP, its sensitivity, specificity and predictive values were all measured against the majority clinical judgement. RESULTS: The study exhibited a high degree of inter-observer reliability (specific agreement > 64%, kappa > 0.75) and a reasonable validity in comparison with the consensus of opinions formed by a least 4 or 5 of its 7 clinical reviewers (specific agreement > 61%, kappa > 0.64), these values decreasing notably when the consensus of 6 or 7 of the reviewers was required. The AEP revealed a high degree of sensitivity and a low degree of specificity in comparison with the majority clinical assessment, thus minimising the occurrence of false results when the stay was regarded as appropriate, and producing false negatives (appropriate hospital stays regarded as inappropriate) varying in degree from moderate to very high. CONCLUSIONS: The results showing high reliability and moderate validity regarding clinical assessment shows the AEP to be a useful instrument in the sifting-out of inappropriate use of hospitalisation, although they do not allow a definitive judgement to be made concerning the efficiency of hospital services nor judgements regarding individual cases.

[Importance of portal hypertension in the release of tissue plasminogen activator (t-PA): experimental study in the rat]. / Importancia de la hipertensión portal en la liberación de activador tisular del plasminógeno (t-PA): estudio experimental en la rata.

Tissue plasminogen activator (t-PA) activity was studied in three different experimental models of male Wistar rats; hepatic lesion without portal hypertension, portal hypertension without hepatic lesion and portal hypertension plus function liver suppression by ligation of both portal vein and hepatic artery. t-PA activity was higher in animals with portal hypertension alone than in animals with only hepatic lesion (146%). Maximal values were present in animals with functional liver suppression (1.774% vs. controls, 248% vs. hepatic lesion and 169% vs. portal hypertension only). These results suggest that both reduced hepatic t-PA clearance and portal hypertension could be involved in the increased t-PA activity normally appearing in chronic liver disease.

[Effects of blood volume expansion on atrial natriuretic factor and the renin-aldosterone axis in experimental cirrhosis]. / Efectos de la expansión de la volemia sobre el factor auricular natriurético y el eje renina-aldosterona en la cirrosis experimental.

Serum concentrations of ANF, Renin and Aldosterone were measured in animals with experimental cirrhosis and volume overload. We studied 75 Wistar rats divided in five groups. Group I: rats with hepatic cirrhosis induced by CCl4; Group II: Control rats; Group III: rats with hepatic cirrhosis and continuous infusion of saline serum; Group IV: control rats with continuous infusion and Group V: cirrhotic rats and bolus infusion of saline. There were no statistical differences in serum concentrations of ANF (232 +/- 75 vs 195 +/- 42 pg/ml) and Renin concentration (182 +/- 24 vs 171 +/- 34 ng/ml/hour) between controls and rats with cirrhosis. However, Aldosterone levels were elevated in cirrhotic rats in basal conditions as compared to controls (1197 +/- 287 vs 475 +/- 88 pg/ml; p < 0.001). The volume overload caused a paradoxical decrease of ANF in cirrhotic rats (124 +/- 15 and 122 +/- 17; p < 0.001). On the other hand, no changes were observed in Renin and Aldosterone after volume expansion. These results suggest the existence of a hemodynamic response to compensate the volume overload. Other studies are necessary to confirm this hypothesis.

[Evaluation of the treatment of vestibular disorders in children with computerized dynamic posturography: preliminary results]. / Avaliação do tratamento dos distúrbios vestibulares na criança através da posturografia dinâmica computadorizada: resultados preliminares.

OBJECTIVE: This study aimed at evaluating dynamic posturography as an evaluation method in children with balance problems due to peripheral vestibulopathy, before and after treatment with vestibular rehabilitation, establishing its correlation with classical clinical evaluation. METHOD: Ten children (six boys and four girls) with vestibular symptoms of peripheral origin were evaluated through a complete clinical history and with dynamic computerized posturography after being treated by vestibular rehabilitation therapy. Posturographic data were analyzed and compared to standard clinical evaluation parameters. RESULTS: Dynamic posturography showed a significant improvement of condition 1 (orthostatic position, fixed support and open eyes) and 5 (orthostatic position, sway-referenced support and closed eyes) of the vestibular function and of the composite balance score. The data showed significant correlation with the clinical improvement observed. A significant reduction of proprioceptive influence was also observed. CONCLUSIONS: Data showed that the dynamic posturography adds important quantitative information to the conventional clinical evaluation of vestibular symptoms, especially in children.

Model for vaccine design by prediction of B-epitopes of IEDB given perturbations in peptide sequence, in vivo process, experimental techniques, and source or host organisms.

Perturbation methods add variation terms to a known experimental solution of one problem to approach a solution for a related problem without known exact solution. One problem of this type in immunology is the prediction of the possible action of epitope of one peptide after a perturbation or variation in the structure of a known peptide and/or other boundary conditions (host organism, biological process, and experimental assay). However, to the best of our knowledge, there are no reports of general-purpose perturbation models to solve this problem. In a recent work, we introduced a new quantitative structure-property relationship theory for the study of perturbations in complex biomolecular systems. In this work, we developed the first model able to classify more than 200,000 cases of perturbations with accuracy, sensitivity, and specificity >90% both in training and validation series. The perturbations include structural changes in >50000 peptides determined in experimental assays with boundary conditions involving >500 source organisms, >50 host organisms, >10 biological process, and >30 experimental techniques. The model may be useful for the prediction of new epitopes or the optimization of known peptides towards computational vaccine design.

In vitro exposure of Ostrya carpinifolia and Carpinus betulus pollen to atmospheric levels of CO, O3 and SO 2.

Ostrya spp. and Carpinus spp. pollen was in vitro exposed to three atmospheric pollutants: CO, O3 and SO2. Two levels of each pollutant were used, and the first level corresponds to a concentration about the atmospheric hour-limit value acceptable for human health protection in Europe and the second level to about the triple of the first level. Experiments were done under artificial solar light with temperature and relative humidity controlled. The viability of the exposed pollen samples showed a significant decrease. Also, the germination percentage showed a significant decrease in both exposed pollens, and the effect was most pronounced for SO2, followed by O3 and CO. A general decreasing trend in the total soluble protein content of the exposed pollen samples when compared with the control was observed, but it was only statistically significant for the Ostrya spp pollen. The results showed marked effects were observed on the Ostrya spp. and Carpinus spp. pollen when exposed to air pollutant levels that can be considered safe for human health protection.

Effect of air pollutant NO2 on Betula pendula, Ostrya carpinifolia and Carpinus betulus pollen fertility and human allergenicity.

Pollen of Betula pendula, Ostrya carpinifolia and Carpinus betulus was exposed in vitro to two levels of NO2 (about 0.034 and 0.067 ppm) - both below current atmospheric hour-limit value acceptable for human health protection in Europe (0.11 ppm for NO2). Experiments were performed under artificial solar light with temperature and relative humidity continuously monitored. The viability, germination and total soluble proteins of all the pollen samples exposed to NO2 decreased significantly when compared with the non-exposed. The polypeptide profiles of all the pollen samples showed bands between 15 and 70 kDa and the exposure to NO2 did not produce any detectable changes in these profiles. However, the immunodetection assays indicated higher IgE recognition by patient sera sensitized to the pollen extracts from all exposed samples in comparison to the non-exposed samples. The common reactive bands to the three pollen samples correspond to 58 and 17 kDa proteins.

LECTINPred: web Server that Uses Complex Networks of Protein Structure for Prediction of Lectins with Potential Use as Cancer Biomarkers or in Parasite Vaccine Design.

Lectins (Ls) play an important role in many diseases such as different types of cancer, parasitic infections and other diseases. Interestingly, the Protein Data Bank (PDB) contains +3000 protein 3D structures with unknown function. Thus, we can in principle, discover new Ls mining non-annotated structures from PDB or other sources. However, there are no general models to predict new biologically relevant Ls based on 3D chemical structures. We used the MARCH-INSIDE software to calculate the Markov-Shannon 3D electrostatic entropy parameters for the complex networks of protein structure of 2200 different protein 3D structures, including 1200 Ls. We have performed a Linear Discriminant Analysis (LDA) using these parameters as inputs in order to seek a new Quantitative Structure-Activity Relationship (QSAR) model, which is able to discriminate 3D structure of Ls from other proteins. We implemented this predictor in the web server named LECTINPred, freely available at http://bio-aims.udc.es/LECTINPred.php. This web server showed the following goodness-of-fit statistics: Sensitivity=96.7 % (for Ls), Specificity=87.6 % (non-active proteins), and Accuracy=92.5 % (for all proteins), considering altogether both the training and external prediction series. In mode 2, users can carry out an automatic retrieval of protein structures from PDB. We illustrated the use of this server, in operation mode 1, performing a data mining of PDB. We predicted Ls scores for +2000 proteins with unknown function and selected the top-scored ones as possible lectins. In operation mode 2, LECTINPred can also upload 3D structural models generated with structure-prediction tools like LOMETS or PHYRE2. The new Ls are expected to be of relevance as cancer biomarkers or useful in parasite vaccine design.

Naïve Bayes QSDR classification based on spiral-graph Shannon entropies for protein biomarkers in human colon cancer.

Fast cancer diagnosis represents a real necessity in applied medicine due to the importance of this disease. Thus, theoretical models can help as prediction tools. Graph theory representation is one option because it permits us to numerically describe any real system such as the protein macromolecules by transforming real properties into molecular graph topological indices. This study proposes a new classification model for proteins linked with human colon cancer by using spiral graph topological indices of protein amino acid sequences. The best quantitative structure-disease relationship model is based on eleven Shannon entropy indices. It was obtained with the Naïve Bayes method and shows excellent predictive ability (90.92%) for new proteins linked with this type of cancer. The statistical analysis confirms that this model allows diagnosing the absence of human colon cancer obtaining an area under receiver operating characteristic of 0.91. The methodology presented can be used for any type of sequential information such as any protein and nucleic acid sequence.

Predicting drugs and proteins in parasite infections with topological indices of complex networks: theoretical backgrounds, applications, and legal issues.

Quantitative Structure-Activity Relationship (QSAR) models have been used in Pharmaceutical design and Medicinal Chemistry for the discovery of anti-parasite drugs. QSAR models predict biological activity using as input different types of structural parameters of molecules. Topological Indices (TIs) are a very interesting class of these parameters. We can derive TIs from graph representations based on only nodes (atoms) and edges (chemical bonds). TIs are not time-consuming in terms of computational resources because they depend only on atom-atom connectivity information. This information expressed in the molecular graphs can be tabulated in the form of adjacency matrices easy to manipulate with computers. Consequently, TIs allow the rapid collection, annotation, retrieval, comparison and mining of molecular structures within large databases. The interest in TIs has exploded because we can use them to describe also macromolecular and macroscopic systems represented by complex networks of interactions (links) between the different parts of a system (nodes) such as: drug-target, protein-protein, metabolic, host-parasite, brain cortex, parasite disease spreading, Internet, or social networks. In this work, we review and comment on the following topics related to the use of TIs in anti-parasite drugs and target discovery. The first topic reviewed was: Topological Indices and QSAR for antiparasitic drugs. This topic included: Theoretical Background, QSAR for anti-malaria drugs, QSAR for anti-Toxoplasma drugs. The second topic was: TOMO-COMD approach to QSAR of antiparasitic drugs. We included in this topic: TOMO-COMD theoretical background and TOMO-COMD models for antihelmintic activity, Trichomonas, anti-malarials, anti-trypanosome compounds. The third section was inserted to discuss Topological Indices in the context of Complex Networks. The last section is devoted to the MARCH-INSIDE approach to QSAR of antiparasitic drugs and targets. This begins with a theoretical background for drugs and parameters for proteins. Next, we reviewed MARCH-INSIDE models for Pharmaceutical Design of antiparasitic drugs including: flukicidal drugs and anti-coccidial drugs. We close MARCH-NSIDE topic with a review of multi-target QSAR of antiparasitic drugs, MARCH-INSIDE assembly of complex networks of antiparasitic drugs. We closed the MARCH-INSIDE section discussing the prediction of proteins in parasites and MARCH-INSIDE web-servers for Protein-Protein interactions in parasites: Plasmod-PPI and Trypano-PPI web-servers. We closed this revision with an important section devoted to review some legal issues related to QSAR models.

Review of MARCH-INSIDE & complex networks prediction of drugs: ADMET, anti-parasite activity, metabolizing enzymes and cardiotoxicity proteome biomarkers.

In this communication we carry out an in-depth review of a very versatile QSPR-like method. The method name is MARCH-INSIDE (MARkov CHains Ivariants for Network Selection and DEsign) and is a simple but efficient computational approach to the study of QSPR-like problems in biomedical sciences. The method uses the theory of Markov Chains to generate parameters that numerically describe the structure of a system. This approach generates two principal types of parameters Stochastic Topological Indices (sto-TIs). The use of these parameters allows the rapid collection, annotation, retrieval, comparison and mining structures of molecular, macromolecular, supramolecular, and non-molecular systems within large databases. Here, we review and comment by the first time on the several applications of MARCH-INSIDE to predict drugs ADMET, Activity, Metabolizing Enzymes, and Toxico-Proteomics biomarkers discovery. The MARCH-INSIDE models reviewed are: a) drug-tissue distribution profiles, b) assembling drug-tissue complex networks, c) multi-target models for anti-parasite/anti-microbial activity, c) assembling drug-target networks, d) drug toxicity and side effects, e) web-server for drug metabolizing enzymes, f) models in drugs toxico-proteomics. We close the review with some legal remarks related to the use of this class of QSPR-like models.