Hexasodium fytate exposure-response correlations in a randomized, placebo-controlled study of patients on dialysis with cardiovascular calcification.

Background: Patients receiving dialysis have high cardiovascular risk in part due to extensive vascular calcification. In the CaLIPSO study, infusion of hexasodium fytate (SNF472), the hexasodium salt of inositol hexaphosphate, for 52 weeks thrice weekly during hemodialysis significantly reduced progression of coronary artery calcification (CAC). This report examines pharmacokinetic/pharmacodynamic (PK/PD) and exposure-efficacy in CaLIPSO. Methods: We measured hexasodium fytate plasma concentrations (PK) by validated liquid chromatography-mass spectroscopy, and hydroxyapatite crystallization in plasma (PD) by validated spectrophotometry. Analyses included patients evaluable for PK, PD, and CAC change (per-protocol analysis). We developed a simple Emax model for maximum concentration (Cmax) and PD effect, and linear and non-linear Emax models for exposure-efficacy among individual average Cmax and absolute and percent changes in CAC score from baseline to week 52. Results: Among evaluable patients receiving placebo (n = 15), 300 mg (n = 20), or 600 mg (n = 20), average Cmax across visits was not quantifiable (<0.76 µM), 15 µM, and 46 µM, respectively. These results suggest a more-than-proportional increase, without accumulation, with a Cmax ratio of approximately 3 for the doses administered. Average inhibition of hydroxyapatite crystallization was 15%, 61%, and 75%, respectively, and similar across visits. Simple Emax models described 80% maximal effect at exposures >21.9 µM and a plateau in exposure-efficacy above the third quartile of Cmax (≥32 µM). Conclusion: Hexasodium fytate has exposure-dependent effects on hydroxyapatite crystallization and progression of cardiovascular calcification. Simple Emax models show robust relations among exposure, inhibition of hydroxyapatite crystallization, and change in CAC volume. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier NCT02966028.

Psychometric Properties, Factor Structure, and Gender and Educational Level Invariance of the Abbreviated Math Anxiety Scale (AMAS) in Spanish Children and Adolescents.

The present study aimed to investigate the factor structure and degree of measurement invariance of a Spanish adaptation of the Abbreviated Math Anxiety Scale (AMAS) in primary and secondary school students (N = 1,504 students, 46.08% males, 7-19 years of age). The results of confirmatory factor analysis corroborated the original two-factor structure, although a modified two-factor model with one item loading simultaneously on both factors was better supported. Full measurement invariance was observed across gender, and partial measurement invariance was achieved across educational levels (primary and secondary education). The AMAS showed reasonable internal consistency, test-retest reliability, and convergent validity. These results highlight the utility of the AMAS as a measure of math anxiety in primary and secondary school students whose scores can be compared by gender and educational level.

A novel assay to measure calcification propensity: from laboratory to humans.

Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N = 38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and ~ 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r = 0.628, P = 0.005). In patients with calciphylaxis (N = 14), infusion of SNF472 (~ 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N = 274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r = 0.401, P = 0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors.

Wisconsin Card Sorting Test-Learning Potential: Usefulness for Assessing Children with Autism Spectrum Disorder.

This study analyzes the Wisconsin Card Sorting Test-Learning Potential (WCST-LP) in children with Autism Spectrum Disorder (ASD) versus children with typical development (TD). Its main aim was to assess: the test's construct validity; the effect of IQ on its pretest and LP scores; and whether the WCST-LP held any relationship to cognitive/EF and social abilities. Participants were 105 children (43 with ASD/62 with TD). Results showed evidence of construct validity in an ASD population (improvements from pretest to posttest), that full IQ influenced pretest performance but did not affect LP, and that a relationship between LP and verbal and social abilities existed only in children with ASD. Conclusions indicate the appropriateness of the WCST-LP in ASD prognosis assessment.

Discrepancies When Assessing Interpersonal Problem-Solving Skills in Autism Spectrum Disorder: A Diagnostic Indicator.

In children with autism spectrum disorder (ASD), there are often discrepancies between direct assessment and third-party reports. We compared these children with groups with/without difficulties in interpersonal problem-solving skills in order to determine whether these discrepancies appear and if they could be a diagnostic indicator for ASD. There were 91 participants (ages 7-13): 28 children with ASD, 36 in a high family risk situation, and 27 typically developing children, all tested with direct measures and third-party reports. Results showed discrepancies only in the ASD group. Consequently, direct performance measures and third-party reports seem to be evaluating different constructs in children with ASD. In addition, both types of measures discriminate between groups, such that both are needed, especially in diagnostic assessments.

Resolución de problemas interpersonales en niños en exclusión social: Valoración de un programa de entrenamiento / Resolution of interpersonal problems in children in social exclusion: Assessment of a training program

Resumen La exclusión social es uno de los mayores desafíos de las sociedades modernas especialmente para una de las poblaciones más afectadas: la infancia. Crecer en ambientes desfavorecidos tiene un impacto negativo en la salud, la educación o el desarrollo cognitivo, emocional y social. Una de las áreas especialmente afectadas en estos niños es la competencia social, entendida como la habilidad del sujeto para enfrentarse a situaciones sociales problemáticas de forma exitosa. Este trabajo se centra en las habilidades de resolución de problemas interpersonales, consideradas componentes fundamentales de la competencia social. El objetivo del estudio ha consistido en determinar si la implementación de un programa de entrenamiento en habilidades de resolución de problemas interpersonales consigue mejorar dichas habilidades en niños en situación de exclusión social a través de un diseño cuasi-experimental pre-post-tratamiento. Los participantes han sido 61 niños de 7 a 12 años de los cuales 34 se sitúan en situación de exclusión. Los resultados muestran mejoras en la habilidad de generar soluciones a los conflictos y en solución de problemas interpersonales. De los resultados se concluye que el programa genera mejoras en las habilidades entrenadas en niños en situación de exclusión. No obstante, se hace necesario seguir investigando el impacto de las intervenciones breves en esta población.

Abstract Social exclusion is one of the biggest challenges of modern societies especially for one of the most affected populations: children. Growing up in disadvantaged environments has a negative impact on health, education or cognitive, emotional and social development. One area particularly affected in these children is social competence - the subject's ability to deal with problematic social situations successfully. This work focuses on interpersonal problem-solving skills, which are deemed as being quintessential components of social competence. This paper sought to determine whether the implementation of a training program for solving interpersonal problems improves these skills in children in situation of social exclusion, through a quasi-experimental pre-post-treatment design. Participants were 61 children aged 7-12, of which 34 were situation of exclusion. The results show improvements in the ability to generate solutions to conflicts and in interpersonal problem-solving skills. Based on the results, it can be concluded that the program generates improvements in the skills trained in children in situation of exclusion. Nevertheless, it is necessary to conduct further research on the impact of brief interventions in this population.

Interpersonal Problem-Solving Skills, Executive Function and Learning Potential in Preadolescents with High/Low Family Risk.

Situations generated by high family risk have a negative effect on personal development, especially during preadolescence. Growing up in the presence of risk factors can lead to negative consequences on mental health or on school performance. The objective of this study focuses on individual factors related to this phenomenon during preadolescence. Specifically, we seek to establish whether level of family risk (high vs. low risk) is related to interpersonal problem-solving skills, executive function and learning potential in a sample of preadolescents controlling age, sex, total IQ, verbal comprehension ability and the classroom influences. The participants were 40 children, 23 boys and 17 girls between the ages of 7 and 12, twenty of which had a record on file with the Social and Childhood Protection Services of Information deleted to maintain the integrity of the review process, and therefore, a high family risk situation. The other 20 participants had a low family risk situation. Results show that the preadolescents from high family risk performed worse on interpersonal solving-problem skills and executive function (p < .05, b from -119,201.81 to 132,199.43, confidence interval from -162,589.78/-75,813.8 to 84,403.05/179,995.8). Nevertheless, they showed the same ability to learn as the participants from low family risk. These results highlight the negative effects of high family risk situation in preadolescents and give value of taking into account protective factors such as learning potential when assessing preadolescents from high family risk.

Interpersonal problem-solving skills, executive function and learning potential in preadolescents with high/low family risk

Situations generated by high family risk have a negative effect on personal development, especially during preadolescence. Growing up in the presence of risk factors can lead to negative consequences on mental health or on school performance. The objective of this study focuses on individual factors related to this phenomenon during preadolescence. Specifically, we seek to establish whether level of family risk (high vs. low risk) is related to interpersonal problem-solving skills, executive function and learning potential in a sample of preadolescents controlling age, sex, total IQ, verbal comprehension ability and the classroom influences. The participants were 40 children, 23 boys and 17 girls between the ages of 7 and 12, twenty of which had a record on file with the Social and Childhood Protection Services of Information deleted to maintain the integrity of the review process, and therefore, a high family risk situation. The other 20 participants had a low family risk situation. Results show that the preadolescents from high family risk performed worse on interpersonal solving-problem skills and executive function (p < .05, b from -119,201.81 to 132,199.43, confidence interval from -162,589.78/-75,813.8 to 84,403.05/179,995.8). Nevertheless, they showed the same ability to learn as the participants from low family risk. These results highlight the negative effects of high family risk situation in preadolescents and give value of taking into account protective factors such as learning potential when assessing preadolescents from high family risk (AU)

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Primer caso en México y América Latina de linfoma anaplásico de células gigantes en paciente con implantes mamarios / First case report in Mexico and Latin America of anaplastic large cell limphoma in a patient with mammary implants

El Linfoma Anaplásico de Células Gigantes (LACG) asociado a implantes mamarios es una patología poco frecuente. Desde el primer caso publicado en la década de los noventa, en los últimos años hemos observado un mayor número de casos recogidos en la literatura. Si bien se tiene información de aproximadamente 90 casos publicados en el mundo, algunos autores mencionan la posibilidad de que existan más de 100 o 200 casos, por lo que su presencia ha suscitado mucha controversia, si bien en general se sigue considerando una patología infrecuente. Hasta donde hemos podido conocer, presentamos el primer caso de LACG documentado por un cirujano plástico en México y América Latina, en una mujer de 43 años de edad portadora de implantes mamarios, con historia de asimetría mamaria unilateral por seroma tardío, y en la que tras 2 punciones sin mejoría de la sintomatología se realizó retirada del implante y capsulectomía, confirmando en líquido periprotésico la presencia del LACG (AU)

Anaplastic Large Cell Lymphoma (ALCL) associated to breast implants is a rare condition. Since the first case report in the nineties, we have seen lately an increase of the total of reported cases. In the literature, we can find around 90 cases and some authors mentioned the possibility of 100 or 200 cases around the world. Anyway it keeps on been and infrequent pathology. To our knowledge, we present the first case reported by a plastic surgeon in Mexico and Latin America in a 43-year female with history of breast augmentation, and unilateral asymmetry due late seroma. After 2 punctures without success, removal of breast implant and capsulectomy was scheduled. Diagnostic of ALCL was confirmed in the periprosthetic fluid (AU)

Reunión de consenso para recomendaciones sobre la gama de productos Restylane Skinboosters(R) / Advisory board recommendations on the products Restylane(R) Skinboosters

Con motivo del 10º aniversario de Restylane Skinboosters(R) se llevó a cabo una reunión de consenso entre un grupo de médicos españoles con el objetivo de aumentar el estándar de seguridad, mejorar y dar coherencia a los tratamientos, favorecer la buena praxis, posibilitar mejores resultados y aumentar la seguridad con esta gama de productos. Se realizó una revisión exhaustiva de los estudios clínicos publicados que demuestran cómo Restylane Skinboosters(R) mejora la calidad de la piel, disminuyendo la rugosidad, aumentando la firmeza e hidratación a largo plazo y reduciendo las cicatrices de acné, así como estimulando la creación de colágeno tipo I. Por último, los participantes pusieron en común su experiencia clínica para realizar un resumen de las indicaciones y los protocolos más empleados con esta gama de tratamientos (AU)

Related to the 10th anniversary of Restylane Skinboosters(TM) an advisory board was carried out. It gathered a group of Spanish physicians with the aim of increasing the safety standards, improve treatments, encourage good practice, increase safety and enable better results using this product range. An exhaustive review of published clinical studies demonstrates that Restylane Skinboosters(TM) improve firmness and quality of the skin, reduce roughness, provide long-term hydration and reduce acne scars. It also stimulates creation of collagen type I. Finally, doctors summarized main indications and the most appropriate protocols with these products based on their clinical experience (AU)

Discrepancies between direct and indirect measures of interpersonal and neurocognitive skills in autism spectrum disorder children.

BACKGROUND: Subjects with autistic spectrum disorders (ASD) show persistent deficits in social interaction. In order to explore the scope of their deficits, it is of great interest to compare the different interpersonal skills and executive functions of ASD subjects to those of children with typical development. Assessing these skills usually involves a large variety of informants (parents, teachers, other family members) and of measures, with frequent discrepancies between direct performance measures and indirect measures (third-party report). Different explanations of this mismatch between measures have been addressed in previous studies. OBJECTIVES: We wish to analyze whether there are differences between children with ASD and children with typical development on several direct performance measures of interpersonal and neurocognitive skills and one third-party report on real-life performance of interpersonal skills; we also want to look at whether discrepancies appear between the two types of measurements in the two groups of participants. METHOD: A total of 68 Spanish children between the ages of 7 and 12 years participated; 34 were children with ASD, and 34 showed typical development. All participants were tested for recognition of emotions, solving interpersonal conflicts, and executive function. RESULTS: Significant differences between the two groups were not found on most of the direct performance measures, but they did appear in the report by third parties, in favor of the group with typical development. There was also a significant association between neurocognitive and social variables in the latter group. CONCLUSIONS: There were intergroup differences and discrepancies between the direct performance and indirect measures in children with ASD, and these must be explained. For this reason, future studies could seek to explain the cause of these discrepancies with a greater number of measures for each of the skills.

Estudio normativo del “test de 60 caras de Ekman” para adolescentes españoles / A normative study of the Ekman 60-faces test in Spanish adolescents

El "Test de 60 caras de Ekman" es ampliamente utilizado para medir la capacidad de reconocer emociones a través de expresiones faciales. Su uso extendido, también en España, contrasta con la ausencia de criterios normativos para población española. Este estudio evalúa las características psicométricas del test y genera baremos para adolescentes españoles. Los participantes han sido 1039 hombres y mujeres de entre 11 y 18 años de edad, de distintas comunidades autónomas del país. Los resultados muestran diferencias significativas en las puntuaciones del test (tanto totales como en cada una de las seis emociones) relacionadas con el sexo y la edad (dividida en dos rangos: 11-14 años y 15-18 años). Se presentan los análisis descriptivos de las puntuaciones, puntuaciones criterio para determinar la dificultad en la ejecución y percentiles, tanto para la puntuación total como para cada emoción, agrupados según sexo y edad. Los índices de fiabilidad encontrados son adecuados en la puntuación total del test y para cada una de las emociones. Estos resultados respaldan la utilización de esta prueba en esta población

The Ekman 60 Faces Test is widely used to assess emotion recognition ability from facial expressions. Its extended use in Spain contrasts with the absence of normative criteria for Spanish population. This study evaluates the psychometric characteristics of the test and generates adjusted normative scores for Spanish adolescents. Participants were 1039 men and women aged between 11 and 18 years of age from different autonomous communities in Spain. Results showed significant differences in test scores (total score and individual emotion scores) according to sex and age. Distinction among two ranges of age was made: 11-14 years of age and 15-18 years of age. The article includes descriptive analyses of the scores, percentiles and performance cut-off score to determine impairment, for the total score as well as for each emotion score, divided by sex and age. Reliability indexes were satisfactory for the total score and for each emotion score. These results allow the utilization of this test in Spanish adolescent population

Valoración de un programa de habilidades interpersonales en niños superdotados / Evaluation of an interpersonal skills program in gifted children

Algunos trabajos de investigación informan que cierto número de niños superdotados muestran problemas de adaptación social y habilidades sociales e interpersonales, mientras que otros consideran que esto no ocurre. Partiendo de lo anterior, Neihart, Reis, Robinson y Moon (2002) hablan de enfoque de resiliencia versus enfoque de riesgo. En este trabajo se considera el beneficio de aplicar programas de entrenamiento en habilidades interpersonales en niños superdotados para prevenir posibles problemas. Por ello, se pretende valorar la eficacia de un programa de entrenamiento en resolución de problemas interpersonales en esta población. En esta investigación participaron 40 niños superdotados de edades comprendidas entre 7 y 13 años, divididos en un grupo tratamiento y un grupo control de lista de espera. Los resultados mostraron diferencias significativas en las medidas de valoración directa en el grupo tratamiento tras la aplicación del programa. También se detectaron diferencias significativas entre el grupo tratamiento y el grupo control en las medidas postratamiento a favor del primero, y se confirmó la relación del potencial de aprendizaje de los niños con los beneficios obtenidos. En definitiva, el programa de entrenamiento se muestra eficaz en la mejora de las habilidades de solución de problemas interpersonales evaluadas en niños superdotados.

Certain research studies report that a number of gifted children show social adaptation issues, as well as problems with social and interpersonal skills, while others consider that this does not occur. In this regard, Neihart, Reis, Robinson and Moon (2002) speaks of a resilience approach versus a risk approach. From the risk viewpoint, this paper presents the benefits of applying training programs in interpersonal skills as to prevent potential problems in gifted children. For this reason, we aim to evaluate the effectiveness of a training program for solving interpersonal problems in this population. Participants include 40 gifted children aged 7 to 13, divided into a treatment group and a control - waitlisted - group. Program application results show significant differences in direct assessment measurements in the treatment group. An increase in effect sizes between the treatment group and the control group is also detected, in favor of the former, and a relationship between the children's learning potential and the benefits obtained is also confirmed. In short, the training program proves effective in interpersonal problem-solving skill improvement in children with high intellectual capacity.

Bioremediation of 2,4,6-trinitrotoluene under field conditions.

In situ bioremediation of the nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) provides a cost-effective alternative for cleaning up contaminated sites. Here we compare the effectiveness of several bioremediation techniques: natural attenuation, bioaugmentation with TNT-degrading Pseudomonas putida JLR11, phytoremediation with maize (Zea mays L.) and broad beans (Vicia faba L.), and rhizoremediation with maize and broad beans inoculated with P. putida JLR11. Experiments in spiked hydroponic medium demonstrated that inoculation with bacteria did not affect TNT levels. On the other hand, axenic plants were able to remove 32% to 38% of the TNT from the medium. However, when plants were inoculated with bacteria,TNT disappeared to an even greater extent (80% to 88%), a result that advocates a role for P. putida JLR11 in rhizoremediation. In field experiments neither natural attenuation nor bioaugmentation with P. putida JLR11 affected TNT levels to a significant degree. However, the extractable TNT content in rhizosphere soil associated to maize roots decreased by more than 96% in 60 days regardless of inoculation. This indicates that under these field conditions, the effect of phytoremediation by maize overshadowed any effect of rhizoremediation by P. putida JLR11.

Escherichia coli has multiple enzymes that attack TNT and release nitrogen for growth.

There has been a growing interest in the degradation of 2,4,6-trinitrotoluene (TNT) over the last decade, ever since its removal from polluted sites was declared an international environmental priority. Certain aerobic and anaerobic microorganisms are capable of using TNT as an N source, although very few studies have proven the mineralization of this compound. An unexpected observation in our laboratory led us to discover that certain Escherichia coli bench laboratory strains have multiple enzymes that attack TNT. One of the NemA products is responsible for the release of nitrite from the nitroaromatic ring: among the metabolites observed in vitro include Meisenheimer dihydride complexes of TNT from which 2-hydroxylamino-6-nitrotoluene is slowly formed during their rearomatization under concomitant release of nitrite. Furthermore, NemA, together with NfsA and NfsB reduce the nitro groups on the aromatic ring to the corresponding hydroxylamino derivatives, which probably results in the release of ammonium ions which can, in turn be used as a nitrogen source by E. coli for growth.

Bioremediation of polynitrated aromatic compounds: plants and microbes put up a fight.

Industrialization and the quest for a more comfortable lifestyle have led to increasing amounts of pollution in the environment. To address this problem, several biotechnological applications aimed at removing this pollution have been investigated. Among these pollutants are xenobiotic compounds such as polynitroaromatic compounds--recalcitrant chemicals that are degraded slowly. Whereas 2,4,6-trinitrophenol (TNP) can be mineralized and converted into carbon dioxide, nitrite and water, 2,4,6-trinitrotoluene (TNT) is more recalcitrant--although several microbes can use it as a nitrogen source. The most effective in situ biotreatments for TNT are the use of bioslurry (which can be preceded by an abiotic step) and phytoremediation. Phytoremediation can be enhanced by using transgenic plants alone or together with microbes.

Cellular XylS levels are a function of transcription of xylS from two independent promoters and the differential efficiency of translation of the two mRNAs.

XylS controls the expression of the meta-cleavage pathway for the metabolism of benzoates in Pseudomonas putida KT2440. The xylS gene is expressed from two promoters, Ps1 and Ps2. Transcription from Ps2 is low and constitutive, whereas transcription from Ps1 is induced in the presence of toluene. In this study, we also show that translation of mRNA generated from Ps1 is 10 times more efficient than that generated from Ps2. This pattern of transcription and translation of xylS gives rise to two modes of activation of the promoter of the meta pathway operon (Pm) according to the concentration of XylS in the cell. In cells growing with benzoate, with small amounts of XylS, the activated XylS regulator binds the effector and stimulates transcription from Pm, whereas in cells growing with toluene, the high levels of XylS suffice to stimulate transcription from Pm even in the absence of XylS effectors.

XylS activator and RNA polymerase binding sites at the Pm promoter overlap.

Transcription from the TOL plasmid meta-cleavage pathway operon, Pm, depends on the XylS protein being activated by a benzoate effector. The XylS binding sites are two imperfect 5'-TGCAN(6)GGNTA-3' direct repeats located between positions -70/-56 and -49/-35 [González-Pérez et al. (1999) J. Biol. Chem. 274, 2286-2290]. An intrinsic bending of 40 degrees, which is not essential for transcription, is centered at position -43. We have determined the potential overlap between the XylS and RNA polymerase binding sites. The insertion of 2 or more bp between C and T at positions -37 and -36 abolished transcription activation by the wild-type XylS and by XylSS229I, a mutant with increased affinity for the XylS binding sites. In contrast, a 1-bp insertion at -37 was permissible, although when in addition to the 1-bp insertion at -37 the mutant promoter had a point mutation at the XylS binding site (C-47-->T), transcription was abolished with the wild-type XylS protein, but not with XylSS229I. The overlap between the proximal XylS binding site and the -35 region recognized by RNA polymerase at positions -35 and -36 appears to be critical for transcription.