Meta-analysis of the population and phenotypic expression of CYP2C9/2C19 polymorphism on drug metabolism in different ethnicities

The term "pharmacogenetics" has been defined as the scientific study of inherited factors that affect the human drug response. Many pharmacogenetie studies have been published since 1995 and have focussed on the principal enzyme family involved in drug metabolism, the cytochrome P450 family, particularly cytochrome P4502C9 and 2C19. In order to investigate the pharmacogenetic aspect of pharmacotherapy, the relevant studies describing the association of pharmacogenetic factor(s) in drug responses must be retrieved from existing literature using a systematic review approach. In addition, the estimation of variant allele prevalence for the gene under study between different ethnic populations is important for pharmacogenetic studies. In this thesis, the prevalence of CYP2C9/2C19 alleles between different ethnicities has been estimated through meta-analysis and the population genetic principle. The clinical outcome of CYP2C9/2C19 allelic variation on the pharmacotherapy of epilepsy has been investigated; although many new antiepileptic drugs have been launched into the market, carbamazepine, phenobarbital and phenytoin are still the major agents in the pharmacotherapy of epilepsy. Therefore, phenytoin was chosen as a model AED and the effect of CYP2C9/2C19 genetic polymorphism on phenytoin metabolism was further examined.An estimation of the allele prevalence was undertaken for three CYP2C9/2C19 alleles respectively using a meta-analysis of studies that fit the Hardy-Weinberg equilibrium. The prevalence of CYP2C9*1 is approximately 81%, 96%, 97% and 94% in Caucasian, Chinese, Japanese, African populations respectively; the pooled prevalence of CYP2C19*1 is about 86%, 57%, 58% and 85% in these ethnic populations respectively. However, the studies of association between CYP2C9/2C19 polymorphism and phenytoin metabolism failed to achieve any qualitative or quantitative conclusion. Therefore, mephenytoin metabolism was examined as a probe drug for association between CYP2C19 polymorphism and mephenytoin metabolic ratio. Similarly, analysis of association between CYP2C9 polymorphism and warfarin dose requirement was undertaken.It was confirmed that subjects carrying two mutated CYP2C19 alleles have higher S/R mephenytoin ratio due to deficient CYP2C19 enzyme activity. The studies of warfarin and CYP2C9 polymorphism did not provide a conclusive result due to poor comparability between studies.The genetic polymorphism of drug metabolism enzymes has been studied extensively, however other genetic factors, such as multiple drug resistance genes (MDR) and genes encoding ion channels, which may contribute to variability in function of drug transporters and targets, require more attention in future pharmacogenetic studies of antiepileptic drugs.

Dioon Lindl. (Zamiaceae): Perspectives from phylogeny and a population genetic study of Dioon edule

Dioon Lindl. (Zamiaceae) is a small genus restricted to Mexico (12 species) and Honduras (one species). Previous systematic studies have been unable to fully resolve species relationships within the genus. Phylogenetic analyses were conducted with data from several sources, including Restriction Fragment Length Polymorphisms from the chloroplast genome, morphology, two introns of the low copy nuclear gene S-adenosyl-L-homocysteine hydrolase (SAHH) and the 5.8S/ITS2 regions of the nuclear ribosomal DNA. The goals of the study were to construct a total evidence species level phylogeny and to explore current biogeographical hypotheses. None of the analyses performed produced a fully resolved topology. Dioon is comprised of two main lineages (the Edule and Spinulosum Clades), which represents an ancient divergence within the genus. The two introns of the nuclear gene SAHH offer additional evidence for the split into two lineages. Intron 2 contains a 18 bp deletion in the Spinulosum Clade, providing a synapomorphy for that group. The 5.8S/ITS2 regions were highly polymorphic and subsequently omitted from the combined analyses. In order to visualize congruence between morphology and molecular data, morphological characters were mapped onto the combined molecular tree. Current biogeographical hypotheses of a general northward pattern of migration and speciation are supported here. However, sister relationships within the Edule Clade are not fully resolved. Seven DNA microsatellite markers were developed to investigate patterns of genetic variation of seven populations of D. edule, a species restricted to Eastern Mexico. We found that most of the genetic variation lies within populations (Ho = 0.2166–0.3657) and that levels of population differentiation are low (Fst = 0.088); this finding is congruent with the breeding system of this species, dioicy. Four of the populations deviate from Hardy Weinberg Equilibrium and have a high number of identical genotypes, we suggest that this unexpected pattern is due to the life-history strategy of the species coupled with the few number of polymorphic loci detected in these populations. Our results are not congruent with earlier evidence from morphology and allozyme markers that suggest that the two northernmost populations represent a distinct entity that is recognized by some taxonomists as D. angustifolium.

The utility of an Integrated Qualitative /Quantitative Data Analytic Strategy (IQ -DAS) to evaluate the impact of youth development interventions to positive qualitative change in the life course

This study reports one of the first controlled studies to examine the impact of a school based positive youth development program (Lerner, Fisher, & Weinberg, 2000) on promoting qualitative change in life course experiences as a positive intervention outcome. The study built on a recently proposed relational developmental methodological metanarrative (Overton, 1998) and advances in use of qualitative research methods (Denzin & Lincoln, 2000). The study investigated the use the Life Course Interview (Clausen, 1998) and an integrated qualitative and quantitative data analytic strategy (IQ-DAS) to provide empirical documentation of the impact the Changing Lives Program on qualitative change in positive identity in a multicultural population of troubled youth in an alternative public high school. The psychosocial life course intervention approach used in this study draws its developmental framework from both psychosocial developmental theory (Erikson, 1968) and life course theory (Elder, 1998) and its intervention strategies from the transformative pedagogy of Freire's (1983/1970). ^ Using the 22 participants in the Intervention Condition and the 10 participants in the Control Condition, RMANOVAs found significantly more positive qualitative change in personal identity for program participants relative to the non-intervention control condition. In addition, the 2X2X2X3 mixed design RMANOVA in which Time (pre, post) was the repeated factor and Condition (Intervention versus Control), Gender, and Ethnicity the between group factors, also found significant interactions for the Time by Gender and Time by Ethnicity. ^ Moreover, the directionality of the basic pattern of change was positive for participants of both genders and all three ethnic groups. The pattern of the moderation effects also indicated a marked tendency for participants in the intervention group to characterize their sense of self as more secure and less negative at the end of the their first semester in the intervention, that was stable across both genders and all three ethnicities. The basic differential pattern of an increase in the intervention condition of a positive characterization of sense of self relative to both pre test and relative to the directionality of the movement of the non-intervention controls, was stable across both genders and all three ethnic groups. ^

Substructuring in four populations of African descent

When a suspect's DNA profile is admitted into court as a match to evidence the probability of the perpetrator being another individual must be calculated from database allele frequencies. The two methods used for this calculation are phenotypic frequency and likelihood ratio. Neither of these calculations takes into account substructuring within populations. In these substructured populations the frequency of homozygotes increases and that of heterozygotes usually decreases. The departure from Hardy- Weinberg expectation in a sample population can be estimated using Sewall Wright's Fst statistic. Fst values were calculated in four populations of African descent by comparing allele frequencies at three short tandem repeat loci. This was done by amplifying the three loci in each sample using the Polymerase Chain Reaction and separating these fragments using polyacrylamide gel electrophoresis. The gels were then silver stained and autoradiograms taken, from which allele frequencies were estimated. Fst values averaged 0.007+- 0.005 within populations of African descent and 0.02+- 0.01 between white and black populations.

D1S80 DNA profiling in five African populations

The highly polymorphic DlS80 locus has no known genetic function. This variable number of tandem repeat (VNTR) has been valuable in forensic identification. We have obtained allelic and genotypic frequencies for five African populations (Benin, Cameroon, Egypt, Kenya and Rwanda), which could be employed as databases to identify individuals. The polymerase chain reaction, followed by vertical polyacrylamide gel electrophoresis and silver staining was our method of analysis. Allele frequencies were used to infer genetic associations using Phylip 3.5, Principal Component and G-test statistical programs. Tests for Hardy-Weinberg equilibrium were employed. Fst estimates and power of discrimination values were also determined for each of our populations. Our analyses of 28 additional populations demonstrated that the D1 S80 locus alone provided for the discrimination of major racial groups. Genetic homogeneity between the African groups was observed. We have generated a database useful for human differentiation and phylogenetic studies.

The utility of an integrated qualitative/quantitative data analytic strategy (IQ-DAS) to evaluate the impact of youth development interventions on positive qualitative change in the life course

This study reports one of the first controlled studies to examine the impact of a school based positive youth development program (Lerner, Fisher, & Weinberg, 2000) on promoting qualitative change in life course experiences as a positive intervention outcome. The study built on a recently proposed relational developmental methodological metanarrative (Overton, 1998) and advances in use of qualitative research methods (Denzin & Lincoln, 2000). The study investigated the use the Life Course Interview (Clausen, 1998) and an integrated qualitative and quantitative data analytic strategy (IQDAS) to provide empirical documentation of the impact the Changing Lives Program on qualitative change in positive identity in a multicultural population of troubled youth in an alternative public high school. The psychosocial life course intervention approach used in this study draws its developmental framework from both psychosocial developmental theory (Erikson, 1968) and life course theory (Elder, 1998) and its intervention strategies from the transformative pedagogy of Freire's (1983/1970). Using the 22 participants in the Intervention Condition and the 10 participants in the Control Condition, RMANOVAs found significantly more positive qualitative change in personal identity for program participants relative to the non-intervention control condition. In addition, the 2X2X2X3 mixed design RMANOVA in which Time (pre, post) was the repeated factor and Condition (Intervention versus Control), Gender, and Ethnicity the between group factors, also found significant interactions for the Time by Gender and Time by Ethnicity. Moreover, the directionality of the basic pattern of change was positive for participants of both genders and all three ethnic groups. The pattern of the moderation effects also indicated a marked tendency for participants in the intervention group to characterize their sense of self as more secure and less negative at the end of the their first semester in the intervention, that was stable across both genders and all three ethnicities. The basic differential pattern of an increase in the intervention condition of a positive characterization of sense of self relative to both pre test and relative to the directionality of the movement of the non-intervention controls, was stable across both genders and all three ethnic groups.

Valor prognóstico de polimorfismos nos genes de reparo do DNA XRCC3 E RAD51 em pacientes com carcinoma epidermóide oral e de orofaringe

Faults in the genes responsible for repairs to the DNA can influence the onset of cancer or affect the response to treatment. This research evaluated the frequency of three single nucleotide polymorphisms (SNPs) in two repair genes DNA RAD51 172g> T (rs1801321), RAD51 135G> C (rs1801320) and XRCC3 T241M (rs861539) in individuals without cancer (n = 130) and patients with oral squamous cell carcinoma (OSC) and carcinoma oropharyngeal squamous (ORSC) (n = 126) and investigated possible relationships of these findings with clinical and pathological data and clinical outcomes: tumor response to radiotherapy and chemotherapy, disease-free survival, and overall survival. It was found that the allele and genotype frequencies were in equilibrium Hard-Weinberg equilibrium. The presence of at least one polymorphic allele in XRCC3 (rs861539) gene is associated with histological grade (WHO) higher (p = 0.007). We observed a higher recurrence rate trend (p = 0.08) and more advanced stage (p = 0.08) in the group that had at least one polymorphic allele of RAD51 gene (rs1801321). The presence of the analyzed SNPs not proved to be a risk factor for the development of CEO or CEOR; however, when combined with smoking or drinking, increased the risk of developing cancer from three to one hundred and fifty times. The tumor response to radiotherapy and chemotherapy was similar in patients with and without SNPs. No polymorphism showed statistical significance in relation to recurrence-free survival or overall survival. We conclude that the presence of at least one polymorphic allele of the SNPs rs861539 in XRCC3 gene, rs1801320 and rs1801321 in the RAD51 gene increase the risk of development of OSC and ORSC, when associated with the habit of drinking or smoking. Polymorphisms studied in XRCC3 and RAD51 genes are not associated with response to radiation therapy, relapse-free survival or overall survival.

Effects of Altered Prenatal Sensory Stimulation on Postnatal Contingency Learning in Bobwhite Quail Neonates (Colinus Virginianus)

Preterm infants are exposed to high levels of modified early sensory experience in the Neonatal Intensive Care Unit (NICU). Reports that preterm infants show deficits in contingency detection and learning when compared to full-term infants (Gekoski, Fagen, & Pearlman, 1984; Haley, Weinberg, & Grunau, 2006) suggest that their exposure to atypical amounts or types of sensory stimulation might contribute to deficits in these critical skills. Experimental modifications of sensory experience are severely limited with human fetuses and preterm infants, and previous studies with precocial bird embryos that develop in ovo have proven useful to assess the effects of modified perinatal sensory experience on subsequent perceptual and cognitive development. In the current study, I assessed whether increasing amounts of prenatal auditory or visual stimulation can interfere with quail neonates’ contingency detection and contingency learning in the days following hatching. Results revealed that augmented prenatal visual stimulation prior to hatching does not disrupt the ability of bobwhite chicks to recognize and prefer information learned in a contingent fashion, whereas augmented prenatal auditory stimulation disrupted the ability of chicks to benefit from contingently presented information. These results suggest that specific types of augmented prenatal stimulation that embryos receive during late prenatal period can impair the ability to learn and remember contingently presented information. These results provide testable developmental hypotheses, with the goal of improving the developmental care and management of preterm neonates in the NICU setting.

The Electoral Rise of Populist Radical Right Parties in Europe: Ideological Parameters and Social Motivations

Populist radical right parties have become major political actors in Europe. This paper analyses the path and the different phases that have led them from the fringes of public debate to their present signifi cance, which is based on their capacity to attract electoral support and infl uence the political agendas in their respective countries. Besides, an analysis of the core ideological beliefs of these parties, and of the topics on which their mobilization capacity rests, is provided, as well as of the type of voters that are attracted by them. Finally, the authors discuss the meaning and impact of the growing popularity of the ideas and proposals put forward by the populist radical right parties.

Diagnóstico del rendimiento académico de estudiantes de una escuela de educación superior en México

El objetivo del artículo es realizar un diagnóstico sobre la percepción de los factores que intervienen en el rendimiento académico de los estudiantes de cinco carreras universitarias en una escuela de educación superior en México, para así reconocer las áreas de oportunidad que permitan sugerir políticas y estrategias para elevar su rendimiento. Se utilizó una muestra de 1651 estudiantes, se obtuvieron los datos a partir de un cuestionario con treinta preguntas que estudian la percepción del rendimiento académico en escala tipo Likert. Se realizó un análisis factorial exploratorio que permitiera reducir los datos, facilitar la interpretación y validar el instrumento. Se identificaron tres factores: a) el rol de los profesores, b) la evaluación y c) la motivación de los estudiantes. Se llevó a cabo un análisis comparativo por carrera. Se encontró que los estudiantes perciben que la mayoría de los maestros no se preocupan por la condición de los jóvenes en situación de reprobación. Además, casi no motivan y carecen de expresiones de sentimientos de orgullo por los logros académicos de los estudiantes. La mitad de los participantes piensa que los docentes no cubren el temario en su totalidad. Se detectó que los estudiantes poseen una alta motivación siendo esto positivo porque son alumnos dedicados y responsables. Se concluye realizando una serie de sugerencias y explicando las implicaciones que tiene este trabajo para las instituciones de educación superior.

La historia contemporánea en relación con la memoria, los museos y los espacios de memoria Internacionales - pasado, presente y futuro

El artículo examina los conceptos de Monumentos, Sitios y Museos conmemorativos a nivel internacional. Se comienza con la terminología de historia contemporánea como un término que se desarrolló y amplió desde 1950. La historia contemporánea influye también en el campo de las Bellas Artes. Los monumentos conmemorativos o sitios de la memoria en lugares auténticos son de gran importancia para la concienciación. En combinación con los museos tienen la posibilidad de recoger diversos objetos como fuentes escritas, artefactos, fotografías y registros de la historia oral como testimonios de los antiguos acontecimientos. En cuanto a los museos, esto se refleja particularmente en las concepciones de los museos para la Guerra y la Paz, los museos de la Memoria sobre el Genocidio, y los museos de Movimientos de Resistencia. Un artefacto particular del ataque terrorista del 11 de septiembre de 2001 es la Karyatide del famoso artista alemán Fritz Koenig, ahora colocado en el Battery Park al sur de Manhattan. Por último, el Memorial y Museo Nacional 11 de Septiembre se explica junto con su arquitectura, la idea de “Ausencia Reflexionada” y la Misión de la Memoria para el futuro.

Terrorismo, Yihadismo y Crimen Organizado en la Estrategia Global de Seguridad de la Unión Europea

El terrorismo es considerado en la Estrategia Global para la Política Exterior y de Seguridad de la UE como una de las principales amenazas a la seguridad de la Unión Europea. La lucha contra el terrorismo ha dado sus frutos en los últimos quince años, pero este artículo analiza la nueva Estrategia y se pregunta si será suficiente para responder con eficacia a esta amenaza y si se están empleando todos los medios necesarios para atajarla.