Macronutrient Intake in Pregnancy and Child Cognitive and Behavioural Outcomes.

Prenatal nutrient exposures can impact on brain development and disease susceptibility across the lifespan. It is well established that maternal macronutrient intake during pregnancy influences foetal and infant development. Therefore, we hypothesise that macronutrient intakes during pregnancy are correlated with cognitive development during early childhood. The current study aimed to investigate the relationship between maternal macronutrient intake during pregnancy and child cognitive and behavioural outcomes at age 4 years. We analysed prospective data from a cohort of 64 Australian mother-child dyads. Maternal macronutrient intake was assessed using a validated 74-item food frequency questionnaire at 2 timepoints during pregnancy. Child cognition and behaviour were measured at age 4 years using the validated Wechsler Preschool and Primary Scale of Intelligence, 3rd version (WPPSI-III) and the Child Behaviour Checklist (CBC). Linear regression models were used to quantify statistical relationships and were adjusted for maternal age, education, pre-pregnancy BMI, breastfeeding duration and birthweight. Child Performance IQ was inversely associated with maternal starch intake (b = -11.02, p = 0.03). However, no other associations were found. Further research is needed to explore the association between different types of starch consumed during pregnancy and child cognitive development.

Global DNA methylation and cognitive and behavioral outcomes at 4 years of age: A cross-sectional study.

BACKGROUND: Accumulating evidence suggests that breastfeeding exclusivity and duration are positively associated with child cognition. This study investigated whether DNA methylation, an epigenetic mechanism modified by nutrient intake, may contribute to the link between breastfeeding and child cognition. The aim was to quantify the relationship between global DNA methylation and cognition and behavior at 4 years of age. METHODS: Child behavior and cognition were measured at age 4 years using the Wechsler Preschool and Primary Scale of Intelligence, third version (WPPSI-III), and Child Behavior Checklist (CBC). Global DNA methylation (%5-methylcytosines (%5mC)) was measured in buccal cells at age 4 years, using an enzyme-linked immunosorbent assay (ELISA) commercial kit. Linear regression models were used to quantify the statistical relationships. RESULTS: Data were collected from 73 children recruited from the Women and Their Children's Health (WATCH) study. No statistically significant associations were found between global DNA methylation levels and child cognition or behavior (p > .05), though the estimates of effect were consistently negative. Global DNA methylation levels in males were significantly higher than in females (median %5mC: 1.82 vs. 1.03, males and females, respectively, (p < .05)). CONCLUSION: No association was found between global DNA methylation and child cognition and behavior; however given the small sample, this study should be pooled with other cohorts in future meta-analyses.

Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age.

The Children's Memory Questionnaire-Revised.

The aim of the current study was to conduct a factor analysis of the Children's Memory Questionnaire-Revised (CMQ-R) and evaluate it as a reliable and effective measurement of memory functioning in children. The CMQ-R is a 36-item questionnaire designed to assess parents' perceptions of their children's memory. Three hundred and seventy-one children aged 5 to 12 years old participated in this study. Three hundred and forty-two children were recruited from schools and 29 were recruited from Kaleidoscope outpatient medical and allied health clinics. Parents of all 371 children completed the CMQ-R, and the parents of 6-, 8-, 10-, and 12-year-olds in the school group completed a 2nd CMQ-R approximately 1 month later. In the school group, children at these ages also participated in a formal assessment of memory. In the clinical group, all 29 children were tested. The results indicated that correlations between the CMQ-R and formal memory testing were low; however, these results improved slightly when age groups were separated with the highest correlation occurring for the 12-year-olds. The school and clinical groups were compared on measures of the CMQ-R, and results indicated that there was a significant difference in the CMQ-R total between the school and clinical groups. A factor analysis of the CMQ-R revealed three factors with moderate to strong loadings, and these reflected, although were not limited to, episodic memory, visual memory, and working memory/attention. The possibility is discussed that the CMQ-R was assessing different aspects of memory than formal testing and that these are likely to be everyday memory abilities.

Generalization of cognitive training in an Australian sample of schizophrenia patients.

OBJECTIVE: The present study was undertaken to evaluate the effect of cognitive training in improving trained and untrained cognitive processes in schizophrenia. METHODS: A simple pre- and post experimental study with a three month follow-up was conducted to determine the efficacy of cognitive training in speed of processing and executive functions improving cognition in 22 schizophrenia patients. RESULTS: Significant improvement was found in those cognitive domains specifically targeted in the training protocol, but also to a limited extent on verbal memory and social cognition. There was also evidence of improvements in symptoms and social functioning. The training effects failed to transfer to community functioning skills however. Except for social cognition, these improvements were maintained at 3month follow-up. CONCLUSION: The study highlights the importance of understanding the mechanisms that contribute to the transfer of skills as well as the maintenance of cognitive changes in individuals with schizophrenia.

Platelet factor 4 and Duffy antigen required for platelet killing of Plasmodium falciparum.

Platelets restrict the growth of intraerythrocytic malaria parasites by binding to parasitized cells and killing the parasite within. Here, we show that the platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PF4 is released by platelets on contact with parasitized red cells, and the protein directly kills intraerythrocytic parasites. This function for PF4 is critically dependent on Fy, which binds PF4. Genetic disruption of Fy expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4. The protective function afforded by platelets during a malarial infection may therefore be compromised in Duffy-negative individuals, who do not express Fy.

A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.

The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC) disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU) mutagenesis screen and have identified a novel dominant (haploinsufficient) mutation in the Ank-1 gene (Ank1(MRI23420)) of mice displaying hereditary spherocytosis (HS). Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt). A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05). We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.

Neuropsychological correlates of auditory perceptual inference: a mismatch negativity (MMN) study.

The mismatch negativity (MMN) component of the auditory event-related potential can be used to study automatic perceptual inference. This study was designed to explore "Conditional Inference" in the MMN system-the capacity of the auditory system to use current input to switch between inference models in memory. We presented a "Random" sequence comprising a standard repeating sound occasionally interrupted by a change in frequency, duration or intensity (louder or softer). We also presented the same sequence with a conditional linkage between deviants--that is, frequency and duration deviants always followed an intensity change. We explored whether the auditory system could use intensity deviance to change the inference from "expect the standard to repeat" to "expect a frequency or duration violation" and quantified this as the proportion decline in the MMN elicited to duration and frequency deviant sounds in the linked versus random sequence. We report three main outcomes on a sample of 25 healthy young adults: (1) there was a significant conditional inference effect (a reduction in MMN amplitude in linked versus random sequences) to duration but not frequency deviants; (2) larger simple MMN and larger conditional inference effect on duration MMN were correlated with higher Digit Span; and (3) the conditional inference effect but not simple MMN to duration deviants was strongly correlated with working memory ability (r(s)=0.78, p<0.001). The results are discussed with respect to the differential cognitive demands of simple MMN and conditional inference, and the possible involvement of prefrontal cortex in implementing conditional inference in the MMN system.

Platelets kill intraerythrocytic malarial parasites and mediate survival to infection.

Platelets play a critical role in the pathogenesis of malarial infections by encouraging the sequestration of infected red blood cells within the cerebral vasculature. But platelets also have well-established roles in innate protection against microbial infections. We found that purified human platelets killed Plasmodium falciparum parasites cultured in red blood cells. Inhibition of platelet function by aspirin and other platelet inhibitors abrogated the lethal effect human platelets exert on P. falciparum parasites. Likewise, platelet-deficient and aspirin-treated mice were more susceptible to death during erythrocytic infection with Plasmodium chabaudi. Both mouse and human platelets bind malarial-infected red cells and kill the parasite within. These results indicate a protective function for platelets in the early stages of erythrocytic infection distinct from their role in cerebral malaria.

Gene expression in splenic CD4 and CD8 cells from BALB/c mice immunized with Porphyromonas gingivalis.

BACKGROUND: T cells are fundamental in the pathogenesis of periodontal disease. Suppression of cell-mediated responses is associated with disease progression together with the concomitant increase in plaque pathogens including Porphyromonas gingivalis. The aim of the present study was to examine gene expression in T cells in response to P. gingivalis in mice. METHODS: BALB/c mice were given weekly intraperitoneal injections of P. gingivalis outer-membrane antigens with Freund's incomplete adjuvant for 3 weeks, whereas control mice received phosphate buffered saline (PBS) and adjuvant only. Splenic CD4 and CD8 subpopulations were isolated by magnetic cell separation and their responses investigated using microarray analysis. RESULTS: Most genes coded for enzymes concerned with metabolic pathways. Only five and 28 genes, respectively, were upregulated in CD4 and CD8 cells extracted from P. gingivalis-immunized mice, including immunoglobulin (Ig) heavy-chain genes for IgG1 and IgG2a in CD4 cells. In contrast, 1,141 and 1,175 genes, respectively, were downregulated. A total of 60 and 65 genes, respectively, coded for immune response proteins or those relevant to periodontal disease pathogenesis. The overlap of genes in the two subsets was 21%. One of the major effects, apart from T-cell function suppression, was the shift away from Th1 responses, although there was also a downregulation of two genes and upregulation of one Th2-response gene. Genes downregulated included those encoding cytokines, proteins involved in Ig binding, antigen presentation, innate immunity, extracellular matrix, and cell adhesion molecules that could result in dysregulation in the progressive periodontal lesion. CONCLUSIONS: Early findings in humans demonstrated that periodontopathic bacteria induce immunosuppressive effects on T cells. The present study has shown that P. gingivalis had a predominant downregulatory effect on gene expression in CD4 and CD8 T cells in mice.

Use of the everyday memory questionnaire with children.

The Everyday Memory Questionnaire (EMQ; Sunderland, Harris, & Baddeley, 1983) was examined for its suitability to assess children's memory. The parents of 226 school children (6-12 years) completed the EMQ in relation to their own children. A subset of these children (N = 101), in 6, 8 and 10 years age groups, completed subtests of the Wide Range Assessment of Memory and Learning (WRAML; Sheslow & Adams, 1990). Comparison of EMQ and WRAML data found aspects of verbal memory correlated moderately with the EMQ in the 10 years age group. There were no meaningful correlations in the 8 years age group. In the 6 years age group aspects of visual memory correlated moderately with the EMQ. The diagnostic utility of the EMQ for children was assessed by comparing the school group to children diagnosed with ADHD and/or learning disorders. Diagnostic indicators revealed the EMQ to have high sensitivity (89%) but poor positive predictive power, identifying 40% of the school group as having memory deficits. Negative predictive power (confirming a negative diagnosis) was high. Validity data suggested that the EMQ could be useful with children at least as young as 10 years and further research needs to be conducted to establish the utility of the EMQ in clinical groups with primary memory deficits.

Role of complement C5 and T lymphocytes in pathogenesis of disseminated and mucosal candidiasis in susceptible DBA/2 mice.

The aims of the study were to compare the pathogenesis of Candida albicans infection in various organs and anatomical regions of C5-deficient (DBA/2) and C5-sufficient (BALB/c) mice, and to evaluate the importance of complement C5 and T lymphocytes as factors that determine host susceptibility or resistance. The kidneys of DBA/2 mice showed higher colonisation and more severe tissue damage than those of BALB/c, but infection at other sites, including oral and vaginal mucosa, was generally similar in the two strains. Passive transfer of C5-sufficient serum into DBA/2 mice decreased the fungal burden in the kidney, and prolonged survival of the reconstituted animals. Depletion of CD4(+) and/or CD8(+) cells did not exacerbate either systemic or mucosal infection when compared to controls, and passive transfer of splenocytes from infected donors caused only a small and transient reduction in numbers of yeasts recovered from the kidney of sub-lethally infected recipients. It is concluded that the acute susceptibility of the kidneys in this mouse strain is due to C5 deficiency expressed on a susceptible genetic background. T lymphocytes, however, appear to have minimal influence on recovery from systemic infection with this isolate of C. albicans.

Event-related potentials to Stroop and reverse Stroop stimuli.

In the Stroop task, the latency of response to a colour is either faster or slower in the presence of a congruent or incongruent colour-word (J. Exp. Psychol. 18 (1935) 643). Debate remains as to whether this effect occurs during early stimulus processing or late response competition. The present study examined the task using reaction time (RT) and event-related potentials to determine temporal differences in this processing. The 'reverse Stroop' effect (where colour interferes with processing of a colour-word) which is much less well established, was also examined. Standard Stroop interference was found as well as reverse Stroop interference. A late lateralised negativity at frontal sites was greater for Incongruent trials and also for the word-response (reverse Stroop) task, and was interpreted as semantic selection and word-rechecking effects. Late positive component latency effects generally mirrored the speed of processing of the different conditions found in RT data. Stroop effects were also found in early temporal N100 and parietal P100 components, which differentiated Congruent from Incongruent trials in the reverse Stroop but not the standard Stroop, and were interpreted as early perception of physical mismatch between the colour and word. It was concluded that Stroop stimuli are processed in parallel in a network of brain areas rather than a particular structure and that Stroop interference arises at the output stage.

First-trimester pregnancy scanning as a screening tool for high-risk and abnormal pregnancies in a district general hospital setting.

This study set out to evaluate the feasibility and acceptability of routine early ultrasound (12-14 weeks) within a district general hospital (DGH) for identifying high-risk and abnormal pregnancies. This was a pilot study for screening by ultrasound examination all women who presented to their community midwife before 12 weeks' gestation. The study involved 991 women who presented clinically pregnant before 12 weeks' gestation between May 1998 and May 1999. Women were offered routinely two ultrasound examinations during their pregnancy, the first at 12-14 weeks' gestation and the second at 20-21 weeks' gestation. The main outcome measures were: range and number of abnormal/high-risk pregnancies identified during an ultrasound scan at 12-14 weeks' gestation; range and number of abnormalities diagnosed during scans at later gestations; outcomes of the pregnancies; questionnaires assessing how the women viewed early pregnancy ultrasound as a method of screening. Nine hundred and eighty-four (99%) women accepted the offer of an early ultrasound scan at 12-14 weeks' gestation; of these 840(85%) women accepted screening for trisomy 21 (T21) by fetal nuchal translucency thickness (NT) and maternal age (fetal medicine foundation risk assessment programme) and this was completed successfully in 797(80%) of cases. Twenty-four women (2%) had a failed pregnancy and where necessary an ERPC was performed following a planned admission. Thirty pregnancies (3%) were diagnosed as abnormal or having high risk of abnormality at the early scan. A major abnormality was confirmed before the expected anomaly scan at 20 weeks in five (17%) pregnancies; all of these patients opted for an elective termination. Twenty-six (3%) pregnancies had a diagnosis of abnormality at their anomaly scan. Of these, three pregnancies were diagnosed as major abnormalities with two resulting in termination of the affected pregnancy before 24 weeks' gestation. Eight hundred and thirty-seven women (85%) completed questionnaires, 833 women (84.5%) were satisfied with the counselling they received before the ultrasound scan and 827 women (84%) answered that they would accept an early pregnancy scan if offered during their next pregnancy. Early pregnancy ultrasound at 12-14 weeks' gestation can be used as an effective method of identifying and screening for major abnormalities of pregnancy within a DGH setting, but it is appropriate to use this in conjunction with an anomaly scan at around 20 weeks' gestation. Women found this method of screening acceptable.