Structure and function of the N-terminal extension of the formin INF2.

In INF2-a formin linked to inherited renal and neurological disease in humans-the DID is preceded by a short N-terminal extension of unknown structure and function. INF2 activation is achieved by Ca2+-dependent association of calmodulin (CaM). Here, we show that the N-terminal extension of INF2 is organized into two α-helices, the first of which is necessary to maintain the perinuclear F-actin ring and normal cytosolic F-actin content. Biochemical assays indicated that this helix interacts directly with CaM and contains the sole CaM-binding site (CaMBS) detected in INF2. The residues W11, L14 and L18 of INF2, arranged as a 1-4-8 motif, were identified as the most important residues for the binding, W11 being the most critical of the three. This motif is conserved in vertebrate INF2 and in the human population. NMR and biochemical analyses revealed that CaM interacts directly through its C-terminal lobe with the INF2 CaMBS. Unlike control cells, INF2 KO cells lacked the perinuclear F-actin ring, had little cytosolic F-actin content, did not respond to increased Ca2+ concentrations by making more F-actin, and maintained the transcriptional cofactor MRTF predominantly in the cytoplasm. Whereas expression of intact INF2 restored all these defects, INF2 with inactivated CaMBS did not. Our study reveals the structure of the N-terminal extension, its interaction with Ca2+/CaM, and its function in INF2 activation.

Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation.

Risk of recurrence of small-for-gestational-age foetus after first pregnancy.

The aim of this study was to assess the incidence of and to analyse factors related to the recurrence of small-for-gestational-age (SGA) neonates in the second pregnancy. A prospective observational study was conducted at a tertiary university hospital in Granada, Spain. A total of 7896 women who delivered their first and second singleton pregnancies at the hospital from 2003-2013 were included and evaluated all birth weights. Women whose first pregnancy was complicated by a SGA birth had a fivefold increased risk of recurrence (23.6% vs. 5.7%, p < .001). Multivariate analyses revealed that only SGA at first birth retained a statistically significant relationship, revealing that the other variables (maternal age, gestational age, interdelivery interval, maternal pre-pregnancy body mass index, occupation of the mother, smoking, hypertension, and diabetes mellitus) were confounders. Prevention of SGA in subsequent pregnancies by modification of established risk factors could be of limited utility based on the present results, supporting a genetic contribution to SGA recurrence. Impact statement The results support a genetic contribution on recurrence of SGA.

Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies.

Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the target antigen. By using an ex vivo enrichment process against freshly disaggregated tumors to purge the repertoire, in combination with in vivo biopanning at optimized phage circulation time, we have identified a human domain antibody capable of mediating selective localization of phage to human prostate cancer xenografts. Affinity chromatography followed by mass spectrometry analysis showed that the antibody recognizes the proteasome activator complex PA28. The specificity of soluble antibody was confirmed by demonstrating its binding to the active human PA28αß complex. Whereas systemically administered control phage was confined in the lumen of blood vessels of both normal tissues and tumors, the selected phage spread from tumor vessels into the perivascular tumor parenchyma. In these areas, the selected phage partially colocalized with PA28 complex. Furthermore, we found that the expression of the α subunit of PA28 [proteasome activator complex subunit 1 (PSME1)] is elevated in primary and metastatic human prostate cancer and used anti-PSME1 antibodies to show that PSME1 is an accessible marker in mouse xenograft tumors. These results support the use of PA28 as a tumor marker and a potential target for therapeutic intervention in prostate cancer.

[Educational intervention for preventing unwanted pregnancies and sexually-transmitted diseases among teenagers in the city of Toledo, Spain]. / Intervención educativa para la prevención de embarazos no deseados y enfermedades de transmisión sexual en adolescentes de la ciudad de toledo.

BACKGROUND: No-one doubts the need of effectively providing teenagers with information about birth control and sexually-transmitted diseases. This study is aimed at evaluating the results of an educational intervention related to these matters. METHODS: Before-and-after study of an educational intervention (based on lectures and handing out documentation) without a control group. A questionnaire was passed out before and after the intervention to assess changes in knowledge and attitudes of the 4th-year Compulsory Secondary Education students at five schools in Toledo. RESULTS: The questionnaire was answered by 238 of the 268 students. The average age was 15.59. A total of 54.66% were females. In all, 24.03% had had some sexual relation. The birth control method used most often was the condom (98.24%). The girls more refuse more unprotected relations (76.5% vs. 48.6%; p<0.001) and share the same classroom with a student having AIDS (80.47% vs. 60.38%; p<0.001). Six months following the start of the intervention, a total of 197 students answered the second questionnaire. Proper condom use rose from 62.13% to 73.46%. CONCLUSIONS: Following the intervention, an improvement has been noted in the degree of knowledge related to birth control methods and AIDS transmission and a more positive attitude regarding HIV.

Promoción de la autonomía personal y discapacidad visual: revisión bibliográfica / Promotion of personal autonomy and visual impairment: a bibliographic review

OBJETIVOS: conocer la efectividad del modelo de atención centrada en la persona en la rehabilitación visual. MÉTODO: se seleccionaron artículos publicados entre 2010 y 2019, recogidos en PUBMED y Web of Science. Se incluyeron aquellos dedicados a la terapia ocupacional y rehabilitación visual de personas con discapacidad visual desde un enfoque de atención centrado en la persona. Finalmente se incluyeron 14 artículos para esta revisión. RESULTADOS: de la búsqueda en PubMed se obtuvieron un total de 490 artículos y de Web of science 40, alcanzando un total de 530 artículos. Después de realizar la lectura del título, se seleccionaron 126 artículos. Tras la lectura de los resúmenes y/o el contenido completo, se excluyeron 112 por no cumplir los objetivos del estudio; resultando elegidos 13 artículos. Las diferentes investigaciones recopiladas justifican que la rehabilitación visual y la terapia ocupacional basadas en el modelo de atención centrada en la persona contribuyen a mejorar la calidad de vida de las personas con baja visión y su autonomía personal. CONCLUSIÓN: son necesarias más investigaciones que evidencien cómo la terapia ocupacional desde una atención centrada en la persona produce resultados positivos en la rehabilitación de personas con baja visión

OBJECTIVE: To know the effectiveness of the person-centered care model in visual rehabilitation. METHOD: Articles published between 2010 and 2019, collected in PUBMED and Web of Science, were selected. Those dedicated to occupational therapy and visual rehabilitation of people with visual disabilities from a person-centered care approach were included. Finally 14 articles were included for this review. RESULTS: A total of 490 articles were obtained from the PubMed search and 40 from Web of science, reaching a total of 530 articles. After reading the title, 126 articles were selected. After reading the abstracts and / or the full content, 112 were excluded because they did not meet the study objectives; resulting in 13 articles chosen. The different studies collected justify that visual rehabilitation and occupational therapy based on the person-centered care model contribute to improving the quality of life of people with low vision and their personal autonomy. CONCLUSION: More research is needed to show how occupational therapy from a person-centered care produces positive results in the rehabilitation of people with low vision

Quantification of sugars in wheat flours with an HPAEC-PAD method.

An HPAEC-PAD method has been developed and validated for the simultaneous determination and quantification of six sugars (glucose, isomaltose, maltose, maltotriose, maltotetraose and maltopentaose) in wheat flours, by extraction with water and precipitation of proteins with Carrez II. Analyses were carried out on a Hamilton RCX-30 column with a gradient elution of NaOH 50mM (A) and NaOH 50mM+NaAcO 500 mM (B). Total run time was 38 min. Detector conditions were as follows: E1, +100 mV; E2, +550 mV; E3, -100 mV. The method was validated, with LODs ranging between 0.03-0.21 mg L(-1) and LOQs between 0.10-0.71 mg L(-1), R(2) between 0.9941 and 0.9983; recoveries were from 74.16% to 110.86% and RSDs for intraday repeatability, interday repeatability and reproducibility between 0.35-8.34%, 2.34-6.64% and 1.90-5.68%, respectively. The method was successfully applied to quantification of these sugars in wheat flours.

[Efficacy of oral sildenafil as rescue therapy in patients with severe pulmonary arterial hypertension chronically treated with prostacyclin. Long-term results]. / Eficacia del sildenafilo por vía oral como terapia de rescate en pacientes con hipertensión arterial pulmonar severa en tratamiento crónico con prostaciclina. Resultados a largo plazo.

INTRODUCTION AND OBJECTIVE: Prostacyclin therapy is an effective treatment for severe pulmonary hypertension. Sildenafil, a selective phosphodiesterase type 5 inhibitor, induces selective vasodilatation of the pulmonary vessels. A synergistic effect has been described for these two drugs. The aim of this study was to evaluate the efficacy and safety of sildenafil as rescue therapy in patients with severe pulmonary hypertension on chronic treatment with prostacyclin whose clinical or functional course was unsatisfactory. PATIENTS AND METHOD: Observational study of 11 patients (7 men, 4 women, mean age 42 [8] years) diagnosed as having severe idiopathic pulmonary hypertension, who were receiving chronic prostacyclin therapy. Sildenafil was started after a worsening of their clinical or functional status. Baseline, 3-month and 12-month follow-up evaluations were based on functional status (NYHA functional class and 6-minute walking test), the presence of decompensated right heart failure and echocardiogram. RESULTS: Seven of the 11 patients showed significant improvements in exercise capacity (distance walked in 6 minutes) at 3 (+25 m) and 12 months' follow-up (+36 m). Improvements in functional class were seen, and heart failure disappeared. No significant adverse effects of sildenafil were detected. The echocardiographic parameters showed a significant reduction in right ventricular end-diastolic diameter and left ventricular diastolic eccentricity index. One patient died after 4 months of follow-up from sudden cardiac death. CONCLUSIONS: The addition of oral sildenafil to chronic prostacyclin treatment in patients with severe pulmonary hypertension improved functional capacity and reduced episodes of decompensated right heart failure, with good tolerance and no significant adverse effects.

[C677T and A1298C MTHFR polymorphisms in the etiology of neural tube defects in Spanish population]. / Implicación de los polimorfismos C677T y A1298C del gen MTHFR en el desarrollo de los defectos del tubo neural en la población española.

BACKGROUND AND OBJECTIVE: The etiology of neural tube defects (NTDs) is multifactorial. The presence of mutated genotypes of C677T and A1298C polymorphisms, and their combined heterozygosity, have been considered risk factors for the occurrence and recurrence of NTDs in some populations. SUBJECTS AND METHOD: This case-control study included 159 healthy controls, 27 NTDs patients, 28 patients' mothers and 23 siblings. The polymorphism study was performed by PCR. For fragment digestion, we used the restriction enzymes Hinf I (C677T) and Mbo II (A1298C). RESULTS: There was no significant difference (p = 0.991) in C677T genotypes between controls (CC: 35%, CT: 50% and TT: 15%) and patients (37, 52 and 11%, respectively), patients' mothers (39, 50 and 11%, respectively) and siblings (35, 48 and 17%, respectively). The prevalence of A1298C genotypes in controls (AA: 49%, AC: 45% and CC: 6%) was similar (p = 0.917) to the prevalence in patients (41, 56 and 4%, respectively), patients' mothers (43, 50 and 7%, respectively) and siblings (52, 39 and 9%, respectively). CONCLUSIONS: The absence of differences in the two polymorphisms between these groups makes us conclude that there is no association with NTDs in the Spanish population.

Covalent immobilization of cyclodextrin glucosyltransferase (CGTase) in activated silica and Sepharose.

Cyclodextrin glucanotransferase is a non-Leloir glycosyltransferase that directly employs the free energy of cleavage of starch to produce cyclodextrins. In presence of appropriate acceptors, this enzyme synthesizes oligosaccharides containing alpha(1-->4) bonds. We have investigated the covalent immobilization of CGTase onto different activated supports. Silica was aminated and further activated with glutaraldehyde. The maximum amount of bound protein was about 4 mg CGTase per gram of support; however, the catalytic efficiency of the immobilized enzyme was lower than 6%. Sepharose 4B activated with cyanogen bromide (CNBr-activated Sepharose) and Sepharose 4B with a spacer arm of 1,6-diaminohexane (EAH Sepharose) were also assayed. These gels react with the amino and carboxylic groups of CGTase, respectively. With CNBr-activated Sepharose, a low percentage of enzyme was bound to the support but with a significant catalytic efficiency (29%). A higher recovery of protein was obtained with EAH Sepharose (62%), but only 2.4% of the initial activity was present in the immobilized biocatalyst. The results were discussed in terms of CGTase structure and mechanism. In addition, the solvent accessibility of amino or carboxylic groups, calculated using the NACCESS software, was considered.

pSM19035-encoded zeta toxin induces stasis followed by death in a subpopulation of cells.

The toxin-antitoxin operon of pSM19035 encodes three proteins: the omega global regulator, the epsilon labile antitoxin and the stable zeta toxin. Accumulation of zeta toxin free of epsilon antitoxin induced loss of cell proliferation in both Bacillus subtilis and Escherichia coli cells. Induction of a zeta variant (zetaY83C) triggered stasis, in which B. subtilis cells were viable but unable to proliferate, without selectively affecting protein translation. In E. coli cells, accumulation of free zeta toxin induced stasis, but this was fully reversed by expression of the epsilon antitoxin within a defined time window. The time window for reversion of zeta toxicity by expression of epsilon antitoxin was dependent on the initial cellular level of zeta. After 240 min of constitutive expression, or inducible expression of high levels of zeta toxin for 30 min, expression of epsilon failed to reverse the toxic effect exerted by zeta in cells growing in minimal medium. Under the latter conditions, zeta inhibited replication, transcription and translation and finally induced death in a fraction (approximately 50 %) of the cell population. These results support the view that zeta interacts with its specific target and reversibly inhibits cell proliferation, but accumulation of zeta might lead to cell death due to pleiotropic effects.

Síndrome de inversión duplicación del cromosoma 15 (INVDUP15) «de novo»: presentación de tres casos clínicos / Chromosome 15 inversion duplication syndrome (INVDUP15) “de novo”: presentation of three clinical cases

Introducción. El síndrome de inversión duplicación del cromosoma 15 se refiere a un conjunto de características clínicas entre las que se encuentran hipotonía central desde el nacimiento, retraso psicomotor, epilepsia o trastorno del espectro autista. Una invdup(15) resulta de la tetrasomía parcial de 15q y generalmente está implicada la región del Síndrome de Prader-Willi (SPW). Se evalúan tres casos remitidos a Genética por hipotonía y retraso psicomotor. Material y métodos. Cultivo de linfocitos de sangre periférica, cariotipo de alta resolución, FISH, extracción de ADN de linfocitos de sangre periférica, MS-MLPA de SPW y estudio de microsatélites. Resultados. El primer caso presentó un cariotipo 47,XY+der(15)(q13;p11.2)(pter->q13::p11.2->pter) y un cariotipo molecular arr 15q12.1q13(18,432,358-26,658,490)x3∼4 con ganancia de 8,23Mb implicando a genes sometidos a imprinting de la región causante de los síndromes de PWS y Angelman (SA). En el segundo caso se obtuvo una fórmula cromosómica 47, XX, + mar.ish idic (15)(q13)(Acro p-arm ++, D15Z1 ++, D15S10 ++, PML-) y cariotipo molecular arr 15q11.2q13.3(18,432,358-30,230,511)x3, con duplicación de aproximadamente 12Mb. En el tercer caso la paciente resultó ser portadora de una doble línea celular en mosaico 47,XX+ der (15) inv (15)(q11;p11.2) [40%] / 46,XX [60%]. En los tres casos se analizó mediante MLPA la región del SPW encontrándose un patrón de metilación alterado y la causa genética resultó ser un síndrome invdup(15) «de novo». Discusión. A pesar de la dificultad para establecer una correlación fenotipo-genotipo en los casos con invdup(15) las técnicas genéticas más recientes pueden aportar información para el diagnóstico clínico de estos pacientes (AU)

Introduction. The chromosome 15 inversion duplication syndrome refers to distinctive clinical findings, such as, early central hypotonia, developmental delay, epilepsy and autistic behaviour. Invdup(15) results from partial 15q tetrasomy and the Prader-Willi syndrome(PWS) region is generally involved. We have analyzed three clinical cases in a Genetics Unit diagnosed with hypotonia and developmental delay. Material and methods. Lymphocyte cultures from peripheral blood samples, high resolution karyotype, FISH, DNA isolation from peripheral blood leukocytes, PWS MS-MLPA and microsatellites study. Results. The first case showed a karyotype 47,XY+der(15)(q13;p11.2)(pter->q13::p11.2->pter) and a molecular karyotype arr 15q12.1q13(18,432,358-26,658,490)x3 ∼ 4 with an extra 8.23Mb genetic material involving imprinted genes from SPW and Angelman (SA) syndromes region. In the second case there was a karyotype 47, XX, + mar.ish idic (15)(q13)(Acro p-arm ++, D15Z1 ++, D15S10 ++, PML-) and a molecular karyotype arr 15q11.2q13.3(18,432,358-30,230,511)x3 with an approximately 12Mb duplication. The third patient was a carrier of a mosaic double line cell with karyotype 47,XX+ der (15) inv (15)(q11;p11.2) [40%] / 46,XX [60%]. In the three cases the SPW region was analysed using a modified methylation pattern and all resulted from a invdup(15) «de novo» genetic defect. Discussion. Although it is difficult to establish a phenotype-genotype correlation in invdup (15) cases, most recent genetic techniques should provide information for the clinical diagnosis in these patients (AU)

Intervención educativa para la prevención de embarazos no deseados y enfermedades de transmisión sexual en adolescentes de la ciudad de Toledo (*) / Educational intervention for preventing unwanted pregnancies and sexually-transmitted diseases among teenagers in the city of Toledo, Spain

Fundamento: Nadie duda de la necesidad de acercar de formaefectiva a los adolescentes información sobre anticoncepción yenfermedades de transmisión sexual. El objetivo de este estudio esevaluar el resultado de una intervención educativa en este ámbito.Métodos: Estudio antes-después de una intervención educativa(basada en charlas y entrega de documentación) sin grupo control. Sepasó un cuestionario antes y después de la intervención para valorarcambios en conocimientos y actitudes a los alumnos de 4º EnseñanzaSecundaria Obligatoria de cinco centros educativos de Toledo.Resultados: Contestaron 238 alumnos (de un total de 268). Laedad media fue de 15,59. El 54,66% eran mujeres. El 24,03% ya habíanmantenido alguna relación sexual. El método anticonceptivo másutilizado fue el preservativo (98,24%). Las chicas rechazan una relaciónsin protección con más frecuencia que los chicos (76,5% vs48,6%; p<0,001) y tienen más facilidad para compartir clase con unenfermo de sida (80,47% vs 60,38%; p<0,001). A los seis meses delinicio de la intervención respondieron al segundo cuestionario 197alumnos. El uso correcto del preservativo pasó del 62,13% al 73,46%.Conclusiones: Tras la intervención se aprecia una mejora en elnivel de conocimientos sobre anticonceptivos y sobre transmisióndel sida y una actitud más positiva frente al VIH

Background: No-one doubts the need of effectively providingteenagers with information about birth control and sexually-transmitteddiseases. This study is aimed at evaluating the results of aneducational intervention related to these matters.Methods: Before-and-after study of an educational intervention(based on lectures and handing out documentation) without a controlgroup. A questionnaire was passed out before and after the interventionto assess changes in knowledge and attitudes of the 4th-yearCompulsory Secondary Education students at five schools in Toledo.Results: The questionnaire was answered by 238 of the 268 students.The average age was 15.59. A total of 54.66% were females.In all, 24.03% had had some sexual relation. The birth controlmethod used most often was the condom (98.24%). The girls morerefuse more unprotected relations (76.5% vs. 48.6%; p<0.001) andshare the same classroom with a student having AIDS (80.47% vs.60.38%; p<0.001). Six months following the start of the intervention,a total of 197 students answered the second questionnaire. Propercondom use rose from 62.13% to 73.46%.Conclusions: Following the intervention, an improvement hasbeen noted in the degree of knowledge related to birth controlmethods and AIDS transmission and a more positive attitude regardingHIV

Resultados de una intervención comunitaria en Educación para la Salud frente al consumo de tabaco, alcohol y otras drogas de abuso en adolescentes / Results of a communitary actuation in the matter of tobacco, alcohol and narcotics in adolescents

Objetivo: Conocer el grado de conocimientos y la prevalencia del consumo de sustancias de abusoen adolescentes. Valorar los cambios antes y después de una intervención comunitaria.Diseño: Estudio descriptivo transversal (fase 1). Estudio «antes-después» (fase 2).Emplazamiento: Intervención comunitaria en el núcleo urbano de Toledo.Participantes: 357 alumnos de 2º de E.S.O. pre-intervención y 259 postintervención.Intervención: Educación para la salud mediante charlas educativas y entrega de material informativoen el contexto de un concurso de mensajes publicitarios durante un curso escolar.Resultados: Edad media 13,35 años (DE 0,65). 50,83% varones.Han fumado alguna vez el 37,22% (IC95% 32,1-42,3), sin diferencias por sexos. El 30,19% (IC95%25,5-35,2) ha consumido alguna vez alcohol, mientras el 30,81% (IC95% 26,1-35,9) afirma haber probado alguna droga. Tras la intervención se observa una mejoría general de los conocimientos sobre las consecuencias del consumo de tabaco, alcohol y drogas. La consideración de gravedad del consumo aumenta en el tabaco (6,95 a 7,21), el alcohol (6,77 a 7,10) y las drogas (9,22 a 9,49). El porcentaje de los que han probado el tabaco aumenta hasta el 45,17% (p<0,05); el de los que han consumido alcohol llega hasta el 50% (p<0,001). El consumo de marihuana en el último mes pasó del8,14% al 9,41% (p>0,05).Conclusiones: Alto grado de consumo de sustancias de abuso entre alumnos de 2º de E.S.O. Tras la intervención observamos un ligero aumento del grado de conocimientos y una mayor conciencia de la gravedad del consumo, no acompañada de una reducción del mismo, posiblemente por incidir en una etapa «de prueba» de su vida

Objective: To know the level of knowledge and the prevalence of abuse of substances in adolescents.To measure changes before and after intervention.Design: Transversal (phase 1) and descriptive study. Study before and after (phase 2) the intervention.Setting: Communitary actuation in the city of Toledo.Subjects: 357, 2 ESO students before actuation and 259 after actuation.Actuation: Health education throw public lectures and delivery of information matherial in the contextof a quiz of publicity messages during the school term.Results: Average age 13,25 (SD 0,65), 50,83 male. 37,22 % (CI 95 %: 32, 1-42,3) smoked any time,without differences by sex. 30,19 % (CI 95 %: 25,5 – 35,2) had consumed alcohol one time or moore,while 30,81 % (CI 95 %: 26,1 – 35,9) confirm consumption of another adictive substance after actuationit is possible to detect general improvement in knowledge about consequence involved in tobacco,alcohol and narcotics consumption. Perception of serious ill efects about the adiction increase in tobacco(6,95 – 7,21), alcohol (6,77 – 7,10) and narcotics (9,22 – 9,49). The percentage of patients who hadtaken tobacco increased to 45,17 % (p<0,05), alcohol 50 % (p<0,001). Consumption of marihuana inlast month increased from 8,14 % to 9,41 % (p<0,05)Conclusions: High level of adictive substances consumption in 2 ESO scholars. After intervention weobserv a slight increase of knowledhe, moore awareness about the depth of the problem but it is notacompaned with a reduction of the same possibly by effect of “the trial” stage of their life

Tumor estromal gastrointestinal: diagnóstico y pronóstico / Gastrointestinal stromal tumor: diagnosis and prognosis

Los tumores estromales gastrointestinales (GIST) son tumores mesenquimatosos derivados de una célula precursora. Tiene capacidad de diferenciación miogénica o neurogénica y se caracterizan por la expresión de proteína KIT (factor de crecimiento de la tirosincinasa). Clínicamente presentan un comportamiento biológico variable. Presentamos ocho casos de GIST, describiendo su presentación radiológica en tomografía computarizada (TC) así como los criterios de benignidad y malignidad más aceptados en la bibliografía. Además, presentamos la respuesta de uno de ellos con metástasis al diagnóstico, tras tratamiento con inhibidor de la tirosincinasa. (AU)

Implicación de los polimorfismos C677T y A1298C del gen MTHFR en el desarrollo de los defectos del tubo neural en la población española / C677T and A1298C MTHFR polymorphisms in the etiology of neural tube defects in Spanish population

FUNDAMENTO Y OBJETIVO: La etiología de los defectos de tubo neural (DTN) es multifactorial. La presencia del genotipo mutado para los polimorfismos C677T y A1298C y su heterocigosidad combinada se han considerado factores de riesgo en determinadas poblaciones. SUJETOS Y MÉTODO: El estudio de casos y controles estuvo formado por 159 controles sanos, 27 pacientes afectados de espina bífida, 28 madres y 23 hermanos de pacientes con espina bífida. El estudio de los polimorfismos se realizó mediante reacción en cadena de la polimerasa (PCR) y digestión de los fragmentos obtenidos con las enzimas de restricción Hind I (C677T) y MboII (A1298C). RESULTADOS: No se han encontrado diferencias estadísticamente significativas (p = 0,991) entre la prevalencia de los genotipos C677T del grupo control (CC: 35 por ciento; CT: 50 por ciento, y TT: 15 por ciento) y los obtenidos en el grupo de pacientes (37, 52 y 11 por ciento, respectivamente), grupo de madres de pacientes (39, 50 y 11 por ciento, respectivamente) y grupo de hermanos de pacientes (35, 48 y 17 por ciento, respectivamente). Asimismo, la prevalencia de los genotipos A1298C dentro del grupo control (AA: 49 por ciento; AC: 45 por ciento, y CC: 6 por ciento) fue similar (p = 0,917) a la encontrada en el grupo de pacientes (41, 56 y 4 por ciento, respectivamente), grupo de madres de pacientes (43, 50 y 7 por ciento, respectivamente) y grupo de hermanos de pacientes (52, 39 y 9 por ciento, respectivamente). CONCLUSIONES: La ausencia de diferencias estadísticamente significativas de los dos polimorfismos estudiados en los distintos grupos hace concluir que éstos no participan en la etiología de los DTN en la población española (AU)

Guías de práctica clínica de la Sociedad Española de Cardiología en tromboembolismo e hipertensión pulmonar / Guidelines of the Spanish Society of Cardiology for Pulmonary Thromboembolism and Hypertension

La hipertensión pulmonar primaria es una enfermedad de carácter progresivo, más frecuente en mujeres jóvenes y de mediana edad. Su etiología se desconoce, aunque existe una predisposición familiar hasta en un 6 por ciento de los casos. Las teorías patogénicas actuales se centran en la existencia de disfunción endotelial y fallos en los canales iónicos de las fibras musculares lisas del vaso. Las pruebas diagnósticas se dirigen a descartar las causas secundarias y a evaluar la gravedad de la enfermedad. El test vasodilatador agudo es imprescindible para la elección del tratamiento más adecuado. La anticoagulación oral está indicada en todos los pacientes. El trasplante de pulmón queda reservado a aquellos casos en los que fracasa el tratamiento médico. La septostomía auricular es un procedimiento paliativo útil en casos seleccionados. La hipertensión pulmonar tromboembólica crónica es una forma especial de hipertensión pulmonar secundaria; aunque indistinguible clínicamente de la hipertensión pulmonar primaria, su diagnóstico resulta crucial, ya que es posible su curación mediante la realización de tromboendarterectomía pulmonar. El tromboembolismo pulmonar es frecuente en pacientes hospitalizados, presentando elevadas tasas de mortalidad (el 30 por ciento en pacientes no tratados). El diagnóstico es difícil, ya que puede acompañar o simular otras enfermedades cardiopulmonares. Las pruebas diagnósticas no invasivas tienen una baja sensibilidad y especificidad. Nuevas alternativas como la determinación de dímero D o la TAC helicoidal incrementan la precisión diagnóstica. El tratamiento estándar consiste en la administración de heparina durante 5-10 días y posteriormente anticoagulantes orales durante 3-6 meses. La prevención con heparinas o dextranos en los pacientes de alto riesgo ha demostrado claros beneficios (AU)