[Executive functions in children with type 1 diabetes using the neuropsychology test]. / Estudio de las funciones ejecutivas en diabetes tipo 1 mediante el test de evaluación neuropsicológica de las funciones ejecutivas en niños (ENFEN).

INTRODUCTION: Neurocognitive executive function in the paediatric diabetic population is a rarely studied field. To investigate and improve this aspect could help these patients to reach their full academic potential. This led us to study the impact that variables such as age at diagnosis and adequacy of metabolic control of diabetes may have on the executive cognitive functions of this population. PATIENTS AND METHODS: We studied 74 children: 37 with type 1 diabetes (group A) and 37 without diabetes (group B). Group A was divided into two subgroups, depending on age at diagnosis: early, before 5 years, (group A(1)) and late, after 5 years, (group A(2)). We compared group A and B and A(1) and A(2) groups using the test Neuropsychological assessment of executive functions in children (NAEFC). Diabetes metabolic control was performed by measuring HbA(1c) and capillary blood glucose before the test. Previous severe hypoglycaemic episodes were recorded. RESULTS: Differences were found among groups A and B in the test of interference. Among the A(1) and A(2) groups only differences in the scales of phonological fluency and grey trail trace were found. The scores were higher in both cases in the early diabetic group. We did not found any correlation between HbA(1c) and blood glucose with the different tests of ENFEN results. None of the patients had previous severe hypoglycaemic episodes. CONCLUSIONS: 1) Children with diabetes performed better in activities that require resistance to interference, sustained attention and attentional control. 2) Diabetic children with early diagnoses achieved high scores in phonological fluency tasks, and cognitive flexibility. 3) Response to ENFEN was not influenced by HbA(1c) and blood glucose levels before the test.

Characterization of the porcine transferrin gene (TF) and its association with disease severity following an experimental Actinobacillus pleuropneumoniae infection.

Transferrin (TF)-mediated provision of iron is essential for a productive infection by many bacterial pathogens, and iron-depletion of TF is a first line defence against bacterial infections. Therefore, the transferrin (TF) gene can be considered a candidate gene for disease resistance. We obtained the complete DNA sequence of the porcine TF gene, which spans 40 kb and contains 17 exons. We identified polymorphisms on a panel of 10 different pig breeds. Comparative intra- and interbreed sequence analysis revealed 62 polymorphisms in the TF gene including one microsatellite. Ten polymorphisms were located in the coding sequence of the TF gene. Four SNPs (c.902A>T, c.980G>A, c.1417A>G, c.1810A>C) were predicted to cause amino acid exchanges (p.Lys301Ile, p.Arg327Lys, p.Lys473Glu, p.Asn604His). We performed association analyses using six selected TF markers and 116 pigs experimentally infected with Actinobacillus pleuropneumoniae serotype 7. The analysis showed breed-specific TF allele frequencies. In German Landrace, we found evidence for a possible association of the severity of A. pleuropneumoniae infection with TF genotypes.

[Neuropsychological impairment in human immunodeficiency virus-positive children]. / Alteraciones neuropsicologicas en ninos infectados por el virus de inmunodeficiencia humana.

INTRODUCTION: From human immunodeficiency virus (HIV)/AIDS epidemic onset in 1981 through 2003, 580,000 infants, children and adolescents died worldwide. Currently, between 2.1 and 2.9 million are estimated to live with HIV/AIDS. Here we review the main features of HIV/AIDS in infants, children and adolescents from a neuropsychological stance. Also, we review current neuropsychological tests for assessment of HIV/AIDS-associated neuropsychological impairment in infants, children and adolescents. DEVELOPMENT: Most HIV-positive infants and children will die before adolescence. These children present both neurological and neuropsychological derangements with a variety of cognitive and motor deficits and important differences in their course. The main neurological condition related to HIV infection in childhood is HIV-associated progressive encephalopathy, which may be the initial presenting condition for AIDS in 18% of cases, affecting 30-60% of seropositive infants, children and adolescents at any time point of their disease. HIV-associated progressive encephalopathy causes neuropsychological deficits involving a wide variety of domains, such as speed and language, memory, learning, information processing and motor functioning. They may affect negatively children's normal development and school achievement. CONCLUSIONS: It is crucial to determine how infection affects HIV-positive children and adolescents' development and to establish which interventions are more efficient to help them to be successful at school. Also, it is necessary to determine confounding variable role in HIV-positive infants, children and adolescents' cognitive development to determine direct and indirect HIV-infection effects on neuropsychological development.

[Evoked potentials in a population of children below 1,500 grams at birth: a description and probabilities]. / Potenciales evocados en una población de niños menores de 1.500 gramos: descripción y probabilidades.

INTRODUCTION: Bioelectrical behaviour was studied in a group of low birth weight children. AIM: To evaluate whether the characteristics of the waves of the brain potentials in these children, who weighed less than 1500 g at birth and experienced anomalous circumstances and events during their perinatal period, would help reach an early diagnosis of the possible developmental disorders they might suffer later on in life. SUBJECTS AND METHODS: Both visual and auditory cerebral evoked potentials were recorded in a group of children born underweight and the results were compared with the findings from another group of healthy children who were born in normal physiological conditions and were apparently free of any kind of pathology. RESULTS: In the waves and locations that were examined, the problem group displayed latencies that were longer than those of the control group; in contrast, no statistically significant differences were found in the amplitude, regardless of the location. Low gestational age and lower weight made latencies longer, but no relationship was found between latencies and the other perinatal features that were studied. CONCLUSIONS: Children with low weight at birth have slower wave latencies than normal children. This slowing, which is inversely proportional to the weight and weeks of gestation, is considered to be an anomalous sign that could be related to brain immaturity, delayed development or to disorders affecting myelination. Moreover, the amplitude, which has received far less attention from researchers, is usually shorter in these processes, although in our study we found no differences with the group of healthy children--only very slightly in the P300, in the weeks and the weight, and the N100 only in one location with respect to weight. Since these children usually have developmental disorders, the use of evoked potentials could be a very useful tool in their detection and ensuing therapy.

[Cognitive performance of right-handed and left-handed persons on the Wechsler Adult Intelligence Scale (WAIS-III)]. / Rendimiento cognitivo de diestros y zurdos en la escala de inteligencia de Wechsler para adultos (WAIS-III).

AIM: To contribute to the knowledge of the cognitive differences existent between right-handed and left-handed evaluating the cognitive outcome in a group of adults right-handed and another group of left-handed of similar characteristic (age, gender, cultural level) by means of the Wechsler Adult Intelligence Scale (WAIS-III). SUBJECTS AND METHODS: Two groups were studied: one formed by 25 right-handed (RHG) and another formed by 25 left-handed (LHG). None of those subject of the study presented mental deficiency neither neurological dysfunctions. The age stocking was of 24.28 years, with a range between 20 and 28 years. RESULTS: There are not differences in the intellectual quotient (verbal and performance), among the two groups. The LHG obtains worse results that the right-handed in speed of prosecution and in the subtests of arithmetic and key, while the RHG has obtained better results in the subtest of incomplete figures. CONCLUSIONS: The LHG has a cognitive yield similar to that of the RHG, with slight deficiencies in activities of visoperceptual component. It becomes necessary to continue deepening in the neuropsychological and cognitive differences between right-handed and left-handed, since the cognitive outcome of the left-handed ones continues being a topic in discussion.

[A study of evoked potentials in the brains of very low birth weight infants]. / Estudio de potenciales evocados cerebrales en niños de muy bajo peso al nacimiento.

INTRODUCTION: This work studies the behaviour of the N200 and P300 waves of the brain evoked potentials (BEP) in a group of very low birth weight infants and results are compared with a second group of children whose weight was normal at birth. AIMS: The objective of this study was to determine whether the N200 and, more especially, the P300 waves in children under the age of 3 could be used to assess the development and prognosis of their disorders. PATIENTS AND METHODS: BEP were performed in very low birth weight infants (taken as the test group) and in others whose weight at birth was normal (control group); the difference in ages when the potentials were recorded was not statistically significant. RESULTS: The EEG index was evaluated for both the test and the control group, and a difference was found with a significance of p < 0.001. Latency, in milliseconds, of the N200 wave and the P300 wave was recorded at the same sites for the test and control groups and showed differences with a significance of p < 0.001. CONCLUSIONS: The findings from the EEG and the latencies of the N200 and P300 waves in the BEP of very low birth weight infants are pathological and are linked to immaturity of the brain, which is characteristic of this population. This tool could help to detect developmental disorders and to facilitate a better approach to attending these children.

Profiles of accepted mutation: from neutrality in a pseudogene to disease-causing mutation on its homologous gene.

We have compared the substitution pattern of the glucocerebrosidase gene (GBA) and the glucocerebrosidase pseudogene (psGBA), two highly homologous regions under different selective pressures and within the same genomic background. Mutations in GBA may lead to Gaucher disease, an inborn metabolic disorder. Disease-causing mutations and neutral variation in the gene have been compared to neutral variation in the pseudogene. This comparison offers a unique opportunity to better understand the action of purifying selection, since the differences between mutational patterns can be attributed to different selective pressures. A similar frequency of CpG dinucleotides was observed in GBA and in psGBA, and CpG pairs were mutated with the same high frequency in both regions. However, nucleotides not in CpG pairs were more likely to contribute to disease-causing mutation than to accepted polymorphisms. This pattern, which resulted in a lower transition to transversion ratio in the gene, may be due to CpG avoidance on critical regions within exons.

Sequence variability of a human pseudogene.

We have obtained haplotypes from the autosomal glucocerebrosidase pseudogene (psGBA) for 100 human chromosomes from worldwide populations, as well as for four chimpanzee and four gorilla chromosomes. In humans, in a 5420-nucleotide stretch analyzed, variation comprises 17 substitutions, a 3-bp deletion, and a length polymorphism at a polyadenine tract. The substitution rate on the pseudogene (1.23 +/- 0.22 x 10(-9) per nucleotide and year) is within the range of previous estimates considering phylogenetic estimations. Recombination within the pseudogene was recognized, although the low variability of this locus prevented an accurate measure of recombination rates. At least 13% of the psGBA sequence could be attributed to gene conversion from the contiguous GBA gene, whereas the reciprocal event has been shown to lead to Gaucher disease. Human psGBA sequences showed a recent coalescence time (approximately 200,000 yr ago), and the most ancestral haplotype was found only in Africans; both observations are compatible with the replacement hypothesis of human origins. In a deeper timeframe, phylogenetic analysis showed that the duplication event that created psGBA could be dated at approximately 27 million years ago, in agreement with previous estimates.

Glucocerebrosidase pseudogene variation and Gaucher disease: Recognizing pseudogene tracts in GBA alleles.

We surveyed the genetic variability of the glucocerebrosidase pseudogene (psGBA) in a worldwide sample of 100 human chromosomes. psGBA is the non-functional duplicate of the gene responsible for Gaucher disease (GBA), the most common lipid storage disorder. The existence of only one psGBA allele described until now, together with the high homology between GBA and psGBA, often prevented recognition of the complex alleles formed by the combination of GBA and psGBA, because psGBA variants could be confused with GBA mutations. In order to determine the variability existent in psGBA, the whole psGBA DNA segment was PCR-amplified and sequenced, and the genotype for all samples was obtained. The ascertainment of the phase among the heterozygous sites was possible through cloning and sequencing a single allele. Eighteen variable sites were detected along psGBA. Two of the variants already have been reported as Gaucher-causing mutations when present in GBA alleles. The other variants were unknown. The knowledge of the psGBA variants described in this report will allow identification of psGBA-GBA complex alleles that may aid in understanding the intricate phenotype-genotype relationship in Gaucher disease.

Genetic structure of north-west Africa revealed by STR analysis.

We have analysed a large set of autosomal short tandem repeat (STR) loci in several Arabic and Berber-speaking groups from north-west Africa (ie Moroccan Arabs, northern-central and southern Moroccan Berbers, Saharawis, and Mozabites). Two levels of analysis have been devised using two sets of 12STR loci, (D3S1358, vWA, FGA, THO1, TPOX, CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820) and 21 (the former set plus D9S926, D11S2010, D13S767, D14S306, D18S848, D2S1328, D4S243, F13A1, and FES/FPS). For each set, data for a number of external reference populations were gathered from the literature. Several methods of analysis based on genetic distances (neighbour-joining trees, principal coordinate analysis, boundary detection), as well as AMOVA, showed that genetic differentiation among NW African populations was very low and devoid of any spatial pattern. When the NW African populations were grouped according to cultural or linguistic differences, the partition was not associated with genetic differentiation. Thus, it is likely that Arabisation was mainly a cultural process. A clear genetic difference was found between NW African populations and Iberians, which underscores the Gilbraltar Straits as a strong barrier to genetic exchange; nonetheless, some degree of gene flow into Southern Iberia may have existed. NW Africans were genetically closer to Iberians and to other Europeans than to African Americans.

The tyrosinase gene in gorillas and the albinism of 'Snowflake'.

The sequence of the tyrosinase (Tyr) gene coding tracts has been obtained for the gorilla (Gorilla gorilla gorilla). The five exons of the gene were sequenced in three gorillas and in a normally pigmented human. The tyrosinase gene has been found to be a very conserved locus with a very low substitution rate. Some nucleotide and amino acid differences were found between the gorilla and human tyrosinase coding sequences. One of the gorillas included in the study is the only known case of albinism in a gorilla ('Snowflake'). Mutations of the TYR gene lead to Oculocutaneous Albinism type 1 (OCA1), the most common type of albinism in humans (OMIM accession number 203100). The TYR gene encodes the tyrosinase enzyme (E.C. 1.14.18.1), whose activity was found to be completely lacking in 'Snowflake', indicating that a mutation in the Tyr gene is the likely cause of his albinism. Nonetheless, no nucleotide changes were detected that could account for the lack of Tyr product or tyrosinase activity in Snowflake, and explanations of these findings are discussed.

[Psychometric validation of the telephone memory test]. / Validación psicométrica del Autotest Telefónico de Memoria.

INTRODUCTION: Several pathologies (i.e. Alzheimer's disease) that courses with memory alterations, appears in a context of impaired cognitive status and mobility. In recent years, several investigations were carried out in order to design short batteries that detect those subjects under risk of dementia. Some of this batteries were also design to be administrated over the telephone, trying to overcome the accessibility limitations of this patients. METHODOLOGY: In this paper we present a battery (called Autotest de Memoria) essentially composed by episodic and semantic memory tests, administered both over the telephone and face to face. This battery was employed in the cognitive assessment of healthy controls and subjects diagnosed as probable Alzheimer's disease patients. RESULTS: Results show the capability of this battery in order to discriminate patients and healthy controls, a great sensibility and specificity, and a nearly absolute parallelism of telephone and face to face administrations. CONCLUSION: These data led us to claim the usefulness and practicality of our so called <>.

Sex-specific migration patterns in Central Asian populations, revealed by analysis of Y-chromosome short tandem repeats and mtDNA.

Eight Y-linked short-tandem-repeat polymorphisms (DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393) were analyzed in four populations of Central Asia, comprising two lowland samples-Uighurs and lowland Kirghiz-and two highland samples-namely, the Kazakhs (altitude 2,500 m above sea level) and highland Kirghiz (altitude 3,200 m above sea level). The results were compared with mtDNA sequence data on the same individuals, to study possible differences in male versus female genetic-variation patterns in these Central Asian populations. Analysis of molecular variance (AMOVA) showed a very high degree of genetic differentiation among the populations tested, in discordance with the results obtained with mtDNA sequences, which showed high homogeneity. Moreover, a dramatic reduction of the haplotype genetic diversity was observed in the villages at high altitude, especially in the highland Kirghiz, when compared with the villages at low altitude, which suggests a male founder effect in the settlement of high-altitude lands. Nonetheless, mtDNA genetic diversity in these highland populations is equivalent to that in the lowland populations. The present results suggest a very different migration pattern in males versus females, in an extended historical frame, with a higher migration rate for females.

Trading genes along the silk road: mtDNA sequences and the origin of central Asian populations.

Central Asia is a vast region at the crossroads of different habitats, cultures, and trade routes. Little is known about the genetics and the history of the population of this region. We present the analysis of mtDNA control-region sequences in samples of the Kazakh, the Uighurs, the lowland Kirghiz, and the highland Kirghiz, which we have used to address both the population history of the region and the possible selective pressures that high altitude has on mtDNA genes. Central Asian mtDNA sequences present features intermediate between European and eastern Asian sequences, in several parameters-such as the frequencies of certain nucleotides, the levels of nucleotide diversity, mean pairwise differences, and genetic distances. Several hypotheses could explain the intermediate position of central Asia between Europe and eastern Asia, but the most plausible would involve extensive levels of admixture between Europeans and eastern Asians in central Asia, possibly enhanced during the Silk Road trade and clearly after the eastern and western Eurasian human groups had diverged. Lowland and highland Kirghiz mtDNA sequences are very similar, and the analysis of molecular variance has revealed that the fraction of mitochondrial genetic variance due to altitude is not significantly different from zero. Thus, it seems unlikely that altitude has exerted a major selective pressure on mitochondrial genes in central Asian populations.

HLA class I and class II DNA typing and the origin of Basques.

Seven HLA class I and class II loci (HLA-A, B, C, DRB1, DQA1, DPA1 and DPB1) were typed at the DNA level in two populations of the Iberian Peninsula (100 Basque and 88 Catalan individuals) in order to unravel their genetic relationship and to compare these results with other European and Mediterranean populations. For the first time, the frequencies of alleles and haplotypes for the class I HLA loci at the DNA level in these populations are presented. The most frequent haplotype in both populations is A*29-Cw*1601-B*44-DRB1*0701-DQA1*0201-DPA1*0103-DPB 1*0401. Neither population differed markedly from the highly homogeneous European and Mediterranean genetic landscape. The Basques, a European outlier population according to classical genetic markers, appear to lie within the genetic European variation with a slight uniqueness and show no clear relationship to North African populations, as has been postulated in some previous HLA studies. Here, the range of possibilities provided by the highly polymorphic HLA system is stressed by using genetic distances, phylogenetic trees and principal component analyses in order to reconstruct population history.

[Epidemiological study of the symptomatology of childhood depression in Madrid school-age population]. / Estudio epidemiológico de la sintomatología depresiva infantil en la población escolar madrileña de ciclo medio.

OBJECTIVES: This study shows the results of an incidental analysis of the prevalence rate of childhood depression (dysthymia and major depression) obtained in an epidemiological cross-study. MATERIAL AND METHODS: This study was carried out among Madrid's school-aged population from primary schools (3 degrees, 4 degrees and 5 degrees EGB). The sample included a total of 1,275 children, both boys and girls, between 8 and 11 years old. They were chosen at random from different school systems (public, semi-public and private) and educational levels (3 degrees, 4 degrees and 5 degrees EGB). The definition of "case" is based on Poznanski's semi-structured clinical interview (Children's Depression Rating Scale-Revised, 1984) depending on DSM-III-R's operational criterion for dysthymia and major depression symptomatology. RESULTS: The prevalence rates obtained in the general school-aged population were 6.1% for dysthymia and 4% with major depression. The total rate of depressive disorders was 10.1%.