Executive functions in 5- to 8-year olds: Developmental changes and relationship to academic achievement

Pronounced improvements in executive functions (EF) during preschool years have been documented in cross-sectional studies. However, longitudinal evidence on EF development during the transition to school and predictive associations between early EF and later school achievement are still scarce. This study examined developmental changes in EF across three time-points, the predictive value of EF for mathematical, reading and spelling skills and explored children's specific academic attainment as a function of early EF. Participants were 323 children following regular education; 160 children were enrolled in prekindergarten (younger cohort: 69 months) and 163 children in kindergarten (older cohort: 78.4 months) at the first assessment. Various tasks of EF were administered three times with an interval of one year each. Mathematical, reading and spelling skills were measured at the last assessment. Individual background characteristics such as vocabulary, non-verbal intelligence and socioeconomic status were included as control variables. In both cohorts, changes in EF were substantial; improvements in EF, however, were larger in preschoolers than school-aged children. EF assessed in preschool accounted for substantial variability in mathematical, reading and spelling achievement two years later, with low EF being especially associated with significant academic disadvantages in early school years. Given that EF continue to develop from preschool into primary school years and that starting with low EF is associated with lower school achievement, EF may be considered as a marker or risk for academic disabilities.

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.

Declining transition rates to psychosis: The role of diagnostic spectra and symptom overlaps in individuals with attenuated psychosis syndrome

Transition to psychosis in at-risk individuals has markedly declined in recent years. So far it has never been discussed in detail that with the growing awareness and increasing availability of early psychosis services, a much broader diagnostic spectrum is now being seen in these services. Subsequently, subjects present with symptoms that meet psychosis risk on a purely psychometric basis but may be the phenotypical expression of another underlying mental disorder. Here we critically review four groups of symptoms and clinical features that are frequently reported by individuals with suspected psychosis risk states, yet share strong commonalities with other mental disorders and conditions: isolated hallucinations; unusual bodily perceptions, hypochondriatic fears and cenesthetic psychotic symptoms; depersonalization; obsessive–compulsive, overvalued and delusional ideas. Of the 616 individuals so far assessed in the Bruderholz Early Psychosis Outpatient Service for Adolescents and Young Adults, 218 (30.5%) met ultra-high risk (UHR) criteria, 188 (86.2%) of whom suffered from one of the four above-mentioned symptom groups. The appraisal of the diagnostic spectra and their overlapping symptoms constitute a tremendous challenge in the clinical assessment of each referred individual. The final conclusion of a clinical assessment should not end with the mere assignment – or non-assignment – to a presumed psychosis risk group, but needs to take into account the ‘Gestalt’ of these particular symptoms and clinical features and thus be based on many more facets than solely a psychometric or nosological approach. Such an approach may break down the heterogeneous psychosis risk group and enable appropriate treatment regimes.

Development of meta-representations: Procedural metacognition and the relationship to Theory of Mind

In several studies it was shown that metacognitive ability is crucial for children and their success in school. Much less is known about the emergence of that ability and its relationship to other meta-representations like Theory of Mind competencies. In the past years, a growing literature has suggested that metacognition and Theory of Mind could theoretically be assumed to belong to the same developmental concept. Since then only a few studies showed empirically evidence that metacognition and Theory of Mind are related. But these studies focused on declarative metacognitive knowledge rather than on procedural metacognitive monitoring like in the present study: N = 159 children were first tested shortly before making the transition to school (aged between 5 1/2 and 7 1/2 years) and one year later at the end of their first grade. Analyses suggest that there is in fact a significant relation between early metacognitive monitoring skills (procedural metacognition) and later Theory of Mind competencies. Notably, language seems to play a crucial role in this relationship. Thus our results bring new insights in the research field of the development of meta-representation and support the view that metacognition and Theory of Mind are indeed interrelated, but the precise mechanisms yet remain unclear.

Association of folate metabolic pathway genes with human spina bifida meningomyelocele

Neural tube defects including spina bifida meningomyelocele (SBMM) are common malformations of the brain and spinal cord, and include all abnormalities resulting from lack of closure of the developing neural tube during embryological development.^ The specific aims of this study were to determine if single nucleotide polymorphic variants (SNPs) in the folate/homocysteine metabolic pathway genes confer a risk for NTD susceptibility within this SBMM population.^ In completion of the first specific aim, two novel SNPs were identified in the FOLR1 gene in Chromosome 11of patients including one in non-coding exon 1 with a C → T transition at nucleotide position 71578317 and another in non-coding exon 3 with a T → G transversion at nucleotide position 71579123. It will be important to determine if these variants are present in the respective parents of these individuals. If they are in fact de novo variants, then these SNPs may be more likely to contribute to the birth defect.^ The second project aim was to analyze genotypes associated with SBMM risk by transmission disequilibrium tests (TDT) and association was detected on several SNPs across the folate metabolic pathway genes in this population. SNPs with significant RC-TDT values were found within the DHFR gene (rs1650723), the MTRR gene (rs327592), the FOLR2 gene (rs13908), four tightly linked variants in the FOLR3 gene (rs7925545, rs7926875, rs7926987, rs7926360) and a variant in the SLC19A1 gene (rs1888530). The product of each of these genes performs a vital function in the folate metabolic pathway. It is conceivable, therefore, that if the individual SNP or SNPs can be proven to perturb the function in some way that they may be involved in the disruption of folate metabolism and in the resulting birth defect. Validating the results of this study in other independent populations will further strengthen the evidence that dysfunction of folate enzymes and receptors may confer SBMM risk in humans. ^

The association between parity and selected structural birth defects

BACKGROUND: Parity is a risk factor in neonatal morbidity and mortality. This dissertation examined the association between first births and selected birth defects. The first aim was to assess the risk of 66 birth defects among first births and third or greater births. The second aim was to determine if maternal race, maternal age, infant sex or infant birth weight modify the association between first births and selected birth defects. METHODS: The Texas Birth Defects Registry provided data for 1999-2009. For the first aim, odds ratios were calculated for each birth defect. For the second aim, analysis was restricted to the ten birth defects significantly associated with first births. Stratified analyses were conducted and interaction terms were added to logistic regression models to assess whether differences in the odds ratios for the effect of first birth were statistically significant across strata. RESULTS: Findings for the first aim showed that first births had significantly increased odds of having an infant with 24 of the 66 birth defects. Third or greater births had significantly increased odds of having four of the 66 birth defects. For the second aim, a number of significant effect modifiers were observed. For patent ductus arteriosis, obstructive urinary defects and gastroschisis, the effect of first births was significantly modified by black or U.S.-born Hispanic mothers. The effect of first birth was also significantly modified among mothers ≥30 years for mitral valve insufficiency, atrial septal defect and congenital hip dislocation. The effect of first births was significantly modified among infants with low birth weight for hypospadias, congenital hip dislocation and gastroschisis. CONCLUSIONS: First births were associated with an elevated risk of 24 categories of birth defects. For some of the birth defects studied, the effect of first birth is modified by maternal age, maternal race and low birth weight. Knowledge of the increased risk for birth defects among women having their first birth allows physicians and midwives to provide better patient care and spur further research into the etiology of associated birth defects. This knowledge may bring about interventions prior to conception in populations most likely to conceive.^

Changes in the foreign trade structure of the Russian Far East under the process of transition toward a market economy

Under the process of transition toward a market economy, the economic connections of the Russian Far East (RFE) with external regions changed from a division of labor among the regions of the USSR (Russia) to an international division of labor. This happened due to factors including the liberalization of the trade system away from a state monopoly, the presence of rich natural resources and of developed industries related to these resources, the advantage of geographically proximity to Asia-Pacific countries, and the political and economic division of the once unified national economic space during the process of transition. The economic connections of RFE with external economies changed radically under the transition toward the market economy. First, the value of foreign trade increased dramatically and the importance of foreign trade for the RFE economy increased enormously. Second, however, different territories of RFE traveled along different trajectories, due to factors involving their industrial structure and geographical conditions. Third, in recent years connections with China, in the areas of both exports and imports, have grown. Fourth, the share within exports of "fuel, mineral resources and metal" increased radically from the end of the 1990s, and the share of "machine, facilities and transportation means" increased from 2002 year within imports. Under this situation, especially since 2002, there has been a major change in the structure of foreign trade.

Accelerated evolution as a consequence of transitions to mutualism

Differential rates of nucleotide substitutions among taxa are a common observation in molecular phylogenetic studies, yet links between rates of DNA evolution and traits or behaviors of organisms have proved elusive. Likelihood ratio testing is used here for the first time to evaluate specific hypotheses that account for the induction of shifts in rates of DNA evolution. A molecular phylogenetic investigation of mutualist (lichen-forming fungi and fungi associated with liverworts) and nonmutualist fungi revealed four independent transitions to mutualism. We demonstrate a highly significant association between mutualism and increased rates of nucleotide substitutions in nuclear ribosomal DNA, and we demonstrate that a transition to mutualism preceded the rate acceleration of nuclear ribosomal DNA in these lineages. Our results suggest that the increased rate of evolution after the adoption of a mutualist lifestyle is generalized across the genome of these mutualist fungi.

Handoff from recombinase to replisome: Insights from transposition

Bacteriophage Mu replicates as a transposable element, exploiting host enzymes to promote initiation of DNA synthesis. The phage-encoded transposase MuA, assembled into an oligomeric transpososome, promotes transfer of Mu ends to target DNA, creating a fork at each end, and then remains tightly bound to both forks. In the transition to DNA synthesis, the molecular chaperone ClpX acts first to weaken the transpososome's interaction with DNA, apparently activating its function as a molecular matchmaker. This activated transpososome promotes formation of a new nucleoprotein complex (prereplisome) by yet unidentified host factors [Mu replication factors (MRFα2)], which displace the transpososome in an ATP-dependent reaction. Primosome assembly proteins PriA, PriB, DnaT, and the DnaB–DnaC complex then promote the binding of the replicative helicase DnaB on the lagging strand template of the Mu fork. PriA helicase plays an important role in opening the DNA duplex for DnaB binding, which leads to assembly of DNA polymerase III holoenzyme to form the replisome. The MRFα2 transition factors, assembled into a prereplisome, not only protect the fork from action by nonspecific host enzymes but also appear to aid in replisome assembly by helping to activate PriA's helicase activity. They consist of at least two separable components, one heat stable and the other heat labile. Although the MRFα2 components are apparently not encoded by currently known homologous recombination genes such as recA, recF, recO, and recR, they may fulfill an important function in assembling replisomes on arrested replication forks and products of homologous strand exchange.

The new dysmorphology: application of insights from basic developmental biology to the understanding of human birth defects.

Information obtained from studies of developmental and cellular processes in lower organisms is beginning to make significant contributions to the understanding of the pathogenesis of human birth defects, and it is now becoming possible to treat birth defects as inborn errors of development. Mutations in genes for transcription factors, receptors, cell adhesion molecules, intercellular junctions, molecules involved in signal transduction, growth factors, structural proteins, enzymes, and transporters have been identified in genetically caused human malformations and dysplasias. The identification of these mutations and the analysis of their developmental effects have been greatly facilitated by the existence of natural or engineered models in the mouse and even of related mutations in Drosophila, and in some instances a remarkable conservation of function in development has been observed, even between widely separated species.

Hemoglobina fetal mutante : um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Mortality and perinatal infectious complications following home birth in Washington State: 2003-2013

Thesis (Master's)--University of Washington, 2016-06

A comparison of the efficacy and safety of olanzapine versus haloperidol during transition from intramuscular to oral therapy

Background: Acutely agitated patients with schizophrenia who receive intramuscular (IM) medications typically are switched to oral (PO) antipsychotic maintenance therapy Objective: The goal of this study was to assess the efficacy and safety of olanzapine versus those of haloperidol during transition from IM to PO therapy We used additional data from a previously reported trial to test the hypothesis that the reduction in agitation achieved by IM olanzapine 10 mg or IM haloperidol 7.5 mg would be maintained following transition to 4 days of PO olanzapine or PO haloperidol (5-20 mg/d for both). We also hypothesized that olanzapine would maintain its more favorable extrapyramidal symptom (EPS) safety profile. Methods: This was a multinational (hospitals in 13 countries), double-blind, randomized, controlled trial. Acutely agitated inpatients with schizophrenia were treated with 1 to 3 IM injections of olanzapine 10 mg or haloperidol 7.5 mg over 24 hours and were entered into a 4-day PO treatment period with the same medication (5-20 mg/d for both). The primary efficacy measurement was reduction in agitation, as measured by the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score. Adverse events and scores on EPS rating scales were assessed. Results: A total of 311 patients (204 men, 107 women; mean [SD] age, 38.2 [11.6] years) were enrolled (131, 126, and 54 patients in the olanzapine, haloperidol, and placebo groups, respectively). In all, 93.1% (122/131) of olanzapine-treated patients and 92.1% (116/126) of haloperidol-treated patients completed the IM period and entered the PO period; 85.5% (112/131) of olanzapine-treated patients and 84.1% (106/126) of haloperidol-treated patients completed the PO period. IM olanzapine and IM haloperidol effectively reduced agitation over 24 hours (mean [SD] PANSS-EC change, -7.1 [4.8] vs -6.7 [4.3], respectively). Reductions in agitation were sustained throughout the PO period with both study drugs (mean [SD] change from PO period baseline, -0.6 [4.8] vs -1.3 [4.4], respectively). During PO treatment, haloperidol-treated patients spontaneously reported significantly more acute dystonia than olanzapine-treated patients (4.3% [5/116] vs 0% [0/122], respectively; P = 0.026) and akathisia (5.2% [6/116] vs 0% [0/122], respectively; P = 0.013). Significantly more haloperidol-treated patients than olanzapine-treated patients met categorical criteria for treatment-emergent akathisia (18.5% [17/92] vs 6.5% [7/107], respectively; P = 0.015). Conclusions: In the acutely agitated patients with schizophrenia in this study, both IM olanzapine 10 mg and IM haloperidol 7.5 mg effectively reduced agitation over 24 hours. This alleviation of agitation was sustained following transition from IM therapy to 4 days of PO treatment (5-20 mg/d for both). During the 4 days of PO treatment, olanzapine-treated patients did not spontaneously report any incidences of acute dystonia, and olanzapine had a superior EPS safety profile to that of haloperidol. The combination of IM and PO olanzapine may help improve the treatment of acutely agitated patients with schizophrenia. Copyright (C) 2003 Excerpta Medica, Inc.

Timing, magnitude, and location of initial soluble aluminum injuries to mungbean roots

Despite a century's knowledge that soluble aluminum (Al) is associated with acid soils and poor plant growth, it is still uncertain how Al exerts its deleterious effects. Hypotheses include reactions of Al with components of the cell wall, plasmalemma, or cytoplasm of cells close to the root tip, thereby reducing cell expansion and root growth. Digital microscopy was used to determine the initial injuries of soluble Al to mungbean (Vigna radiata L.) roots. Roots of young seedlings were marked with activated carbon particles and grown in 1 mm CaCl2 solution at pH 6 for ca. 100 min (control period), and AlCl3 solution was added to ensure a final concentration of 50 muM Al (pH 4). Further studies were conducted on the effects of pH 4 with and without 50 muM Al. Four distinct, but possibly related, initial detrimental effects of soluble Al were noted. First, there was a 56-75% reduction in the root elongation rate, first evident 18-52 min after the addition of Al, root elongation continuing at a decreased rate for ca. 20 It. Decreasing solution pH from 6 to 4 increased the root elongation rate 4-fold after 5 min, which decreased to close to the original rate after 130 min. The addition of Al during the period of rapid growth at pH 4 reduced the root elongation rate by 71% 14 min after the addition of Al. The activated carbon marks on the roots showed that, during the control period, the zone of maximum root growth occurred at 2,200-5,100 mum from the root tip (i.e. the cell elongation zone). It was there that Al first exerted its detrimental effect and low pH increased root elongation. Second, soluble Al prevented the progress of cells from the transition to the elongation phase, resulting in a considerable reduction of root growth over the longer term. The third type of soluble Al injury occurred after exposure for ca. 4 h to 50 mum Al when a kink developed at 2,370 mum from the root tip. Fourth, ruptures of the root epidermal and cortical cells at 1,900-2,300 mum from the tip occurred greater than or equal to4.3 h after exposure to soluble Al. The timing and location of Al injuries support the contention that Al initially reduces cell elongation, thus decreasing root growth and causing damage to epidermal and cortical cells.

Stress associated with the transition from high school to university: The effect of social support and self-efficacy

The present study aimed to evaluate the role of social support and self-efficacy on the level of stress associated with the transition from high school to university. One hundred and eight-five university students who had completed high school in the previous year completed a three-part questionnaire designed to gather information on their levels of self-efficacy, social support, and stress associated with their transition. The results showed that self-efficacy was a significant predictor of stress associated with the transition to university in that higher levels of self-efficacy were associated with lower levels of stress while social support was a non-significant predictor of stress. [Author abstract]