Effect of changing the amount and type of fat and carbohydrate on insulin sensitivity and cardiovascular risk: the RISCK (Reading, Imperial, Surrey, Cambridge, and Kings) trial

Background: Insulin sensitivity (Si) is improved by weight loss and exercise, but the effects of the replacement of saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) or carbohydrates of high glycemic index (HGI) or low glycemic index (LGI) are uncertain. Objective: We conducted a dietary intervention trial to study these effects in participants at risk of developing metabolic syndrome. Design: We conducted a 5-center, parallel design, randomized controlled trial [RISCK (Reading, Imperial, Surrey, Cambridge, and Kings)]. The primary and secondary outcomes were changes in Si (measured by using an intravenous glucose tolerance test) and cardiovascular risk factors. Measurements were made after 4 wk of a high-SFA and HGI (HS/HGI) diet and after a 24-wk intervention with HS/HGI (reference), high-MUFA and HGI (HM/HGI), HM and LGI (HM/LGI), low-fat and HGI (LF/HGI), and LF and LGI (LF/LGI) diets. Results: We analyzed data for 548 of 720 participants who were randomly assigned to treatment. The median Si was 2.7 × 10−4 mL · μU−1 · min−1 (interquartile range: 2.0, 4.2 × 10−4 mL · μU−1 · min−1), and unadjusted mean percentage changes (95% CIs) after 24 wk treatment (P = 0.13) were as follows: for the HS/HGI group, −4% (−12.7%, 5.3%); for the HM/HGI group, 2.1% (−5.8%, 10.7%); for the HM/LGI group, −3.5% (−10.6%, 4.3%); for the LF/HGI group, −8.6% (−15.4%, −1.1%); and for the LF/LGI group, 9.9% (2.4%, 18.0%). Total cholesterol (TC), LDL cholesterol, and apolipoprotein B concentrations decreased with SFA reduction. Decreases in TC and LDL-cholesterol concentrations were greater with LGI. Fat reduction lowered HDL cholesterol and apolipoprotein A1 and B concentrations. Conclusions: This study did not support the hypothesis that isoenergetic replacement of SFAs with MUFAs or carbohydrates has a favorable effect on Si. Lowering GI enhanced reductions in TC and LDL-cholesterol concentrations in subjects, with tentative evidence of improvements in Si in the LF-treatment group. This trial was registered at clinicaltrials.gov as ISRCTN29111298.

Component processes of early reading, spelling, and narrative writing skills in Turkish: a longitudinal study

The study examined: (a) the role of phonological, grammatical, and rapid automatized naming (RAN) skills in reading and spelling development; and (b) the component processes of early narrative writing skills. Fifty-seven Turkish-speaking children were followed from Grade 1 to Grade 2. RAN was the most powerful longitudinal predictor of reading speed and its effect was evident even when previous reading skills were taken into account. Broadly, the phonological and grammatical skills made reliable contributions to spelling performance but their effects were completely mediated by previous spelling skills. Different aspects of the narrative writing skills were related to different processing skills. While handwriting speed predicted writing fluency, spelling accuracy predicted spelling error rate. Vocabulary and working memory were the only reliable longitudinal predictors of the quality of composition content. The overall model, however, failed to explain any reliable variance in the structural quality of the compositions

Epigenomic plasticity within populations: its evolutionary significance and potential

Epigenetics has progressed rapidly from an obscure quirk of heredity into a data-heavy ‘omic’ science. Our understanding of the molecular mechanisms of epigenomic regulation, and the extent of its importance in nature, are far from complete, but in spite of such drawbacks, population-level studies are extremely valuable: epigenomic regulation is involved in several processes central to evolutionary biology including phenotypic plasticity, evolvability and the mediation of intragenomic conflicts. The first studies of epigenomic variation within populations suggest high levels of phenotypically relevant variation, with the patterns of epigenetic regulation varying between individuals and genome regions as well as with environment. Epigenetic mechanisms appear to function primarily as genome defences, but result in the maintenance of plasticity together with a degree of buffering of developmental programmes; periodic breakdown of epigenetic buffering could potentially cause variation in rates of phenotypic evolution.

Expression and regulation of 80K/MARCKS, a major substrate of protein kinase C, in the developing rat heart

Objective: Protein kinase C (PKC) plays a pivotal role in modulating the growth and differentiation of many cell types including the cardiac myocyte. However, little is known about molecules that act immediately downstream of PKC in the heart. In this study we have investigated the expression of 80K/MARCKS, a major PKC substrate, in whole ventricles and in cardiac myocytes from developing rat hearts. Methods: Poly A+ RNA was prepared from neonatal (2-day) and adult (42-day) cardiac myocytes and whole ventricular tissue and mRNA expression determined by reverse transcription-polymerase chain reaction (RT-PCR) using primers designed to identify a 420 bp fragment in the 80K/MARCKS gene. Protein extracts were prepared from either 2-day and 42-day cardiac myocytes or from whole ventricular tissue at 2, 5–11, 14, 17, 21, 28 and 42 days of age. Protein expression was determined by immunoblotting with an 80K/MARCKS antipeptide antibody and PKC activity was determined by measuring the amount of γ32P-ATP transferred to a specific peptide substrate. Results: RT-PCR analysis of 80K/MARCKS mRNA in neonatal (2-day) and adult (42-day) cardiac myocytes showed the expression of this gene in both cell types. Immunoblotting revealed maximum 80K/MARCKS protein expression in whole ventricular tissue at 5 days (a 75% increase above values at 2 days), followed by a transient decrease in expression during the 6–8-day period (61% of the protein expressed at 2 days for 8-day tissue) with levels returning to 5 day levels by 11 days of age. 80K/MARCKS protein was present in cardiac myocytes at 2 days of age whereas it was not detectable in adult cells. In addition, PKC activity levels increased to 160% of levels present at 2 days in 8-day-old ventricles with PKC activity levels returning to 5-day levels by 9 days of age. This was then followed by a steady decline in both 80K/MARCKS protein expression and PKC activity through to adulthood. Conclusions: Expression of the PKC substrate, 80K/MARCKS, in cardiac myocytes changes significantly during development and the transient loss of immunoreactive protein during the 6–8-day developmental period may reflect 80K/MARCKS phosphorylation and subsequent down-regulation as a result of the concomitant up-regulation of PKC activity at this time.

Investigation of language and motor skills in Serbian speaking children with specific language impairment and in typically developing children

Specific language impairment (SLI) is usually defined as a developmental language disorder which does not result from a hearing loss, autism, neurological and emotional difficulties, severe social deprivation, low non-verbal abilities. Children affected with SLI typically have difficulties with the acquisition of different aspects of language and by definition, their impairment is specific to language and no other skills are affected. However, there has been a growing body of literature to suggest that children with SLI also have non-linguistic deficits, including impaired motor abilities. The aim of the current study is to investigate language and motor abilities of a group of thirty children with SLI (aged between 4 and 7) in comparison to a group of 30 typically developing children matched for chronological age. The results showed that the group of children with SLI had significantly more difficulties on the language and motor assessments compared to the control group. The SLI group also showed delayed onset in the development of all motor skills under investigation in comparison to the typically developing group. More interestingly, the two groups differed with respect to which language abilities were correlated with motor abilities, however Imitation of Complex Movements was the unique skill which reliably predicted expressive vocabulary in both typically developing children and in children with SLI.

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview

The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

Influence of birth weight on gene regulators of lipid metabolism and utilization in subcutaneous adipose tissue and skeletal muscle of neonatal pigs.

Epidemiological studies suggest that low-birth weight infants show poor neonatal growth and increased susceptibility to metabolic syndrome, in particular, obesity and diabetes. Adipose tissue development is regulated by many genes, including members of the peroxisome proliferator-activated receptor (PPAR) and the fatty acid-binding protein (FABP) families. The aim of this study was to determine the influence of birth weight on key adipose and skeletal muscle tissue regulating genes. Piglets from 11 litters were ranked according to birth weight and 3 from each litter assigned to small, normal, or large-birth weight groups. Tissue samples were collected on day 7 or 14. Plasma metabolite concentrations and the expression of PPARG2, PPARA, FABP3, and FABP4 genes were determined in subcutaneous adipose tissue and skeletal muscle. Adipocyte number and area were determined histologically. Expression of FABP3 and 4 was significantly reduced in small and large, compared with normal, piglets in adipose tissue on day 7 and in skeletal muscle on day 14. On day 7, PPARA and PPARG2 were significantly reduced in adipose tissue from small and large piglets. Adipose tissue from small piglets contained more adipocytes than normal or large piglets. Birth weight had no effect on adipose tissue and skeletal muscle lipid content. Low-birth weight is associated with tissue-specific and time-dependent effects on lipid-regulating genes as well as morphological changes in adipose tissue. It remains to be seen whether these developmental changes alter an individual's susceptibility to metabolic syndrome.

Extracts of tropical African spices are active against Plutella xylostella

Extracts from Piper guineense, Aframomum melegueta, Aframomum citratum and Afrostyrax kamerunensis were investigated for their antifeedant, lethal and developmental effects against Plutella xylostella larvae through laboratory dual-choice tests and topical application. Water and ethanol extracts of P. guineense were dose-dependent antifeedants at concentrations ≥300 and 500 ppm, respectively, whilst methanol extracts required ≥1,000 ppm. Methanol and hexane extracts of A. melegueta acted at ≥100 ppm and water extracts at ≥300 ppm, but ethanol extracts were deterring feeding only slightly at ≥1,000 ppm. Hexane and methanol extracts of A. citratum inhibited feeding at ≥300 ppm and water extracts did so at ≥500 ppm. None of the Afrostyrax kamerunensis extracts deterred feeding at any of the concentrations tested. No mortality was observed at any of the concentrations after topical application of the extracts on the larvae. However, the effects on larval development varied with extract concentration and larval age. Ingestion of the water and ethanol extracts of P. guineense caused 100% mortality of second instars at ≥100 ppm two to three days after infestation (DAI). Methanol and water extracts of A. melegueta and A. citratum, respectively, achieved ≥80% mortality of larvae at concentrations of ≥500 ppm and ≥1,000 ppm, respectively. With third instars, the mortalities were significantly lower; however, the P. guineense water or ethanol extracts caused 100% mortality two to four DAI. Larvae that survived till pupation had significantly longer larval periods compared with the control after application of A. melegueta extracts. We concluded that potent extracts from Aframomum melegueta, Aframomum citratum and especially P. guineense could be used as complementary measures in the management of P. xylostella by subsistence farmers.

Special issue of Reading medieval studies: first crusade historiography

Collected papers of the University of Reading Stenton Symposium, 2008.

Longitudinal investigation of the faecal microbiota of healthy full-term infants using fluorescence in situ hybridization and denaturing gradient gel electrophoresis.

From birth onwards, the gastrointestinal (GI) tract of infants progressively acquires a complex range of micro-organisms. It is thought that by 2 years of age the GI microbial population has stabilized. Within the developmental period of the infant GI microbiota, weaning is considered to be most critical, as the infant switches from a milk-based diet (breast and/or formula) to a variety of food components. Longitudinal analysis of the biological succession of the infant GI/faecal microbiota is lacking. In this study, faecal samples were obtained regularly from 14 infants from 1 month to 18 months of age. Seven of the infants (including a set of twins) were exclusively breast-fed and seven were exclusively formula-fed prior to weaning, with 175 and 154 faecal samples, respectively, obtained from each group. Diversity and dynamics of the infant faecal microbiota were analysed by using fluorescence in situ hybridization and denaturing gradient gel electrophoresis. Overall, the data demonstrated large inter- and intra-individual differences in the faecal microbiological profiles during the study period. However, the infant faecal microbiota merged with time towards a climax community within and between feeding groups. Data from the twins showed the highest degree of similarity both quantitatively and qualitatively. Inter-individual variation was evident within the infant faecal microbiota and its development, even within exclusively formula-fed infants receiving the same diet. These data can be of help to future clinical trials (e.g. targeted weaning products) to organize protocols and obtain a more accurate outline of the changes and dynamics of the infant GI microbiota.

Are you thinking what I’m thinking? Peer group similarities in adolescent hostile attribution tendencies

A bias towards attributing hostile intent to others has been linked to aggression. In an adolescent sample, we investigated whether peer group homophily exists in the tendency towards attributing hostile intent. We assessed hostile attribution tendencies and self-reported aggressive behaviours in a normative sample of 910 adolescents, and computed average peer group scores based on nominated friend scores. Results indicated that adolescents showed significant correlations between their own level of hostile attributions and that of their peer group. Further analyses indicated that this effect occurred specifically in reciprocal friendships, and was retained even once own and peer group level of aggression were controlled.

Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine158methionine (Val158Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3′ variable number of tandem repeats polymorphism; the COMT effect was present only in infants who did not have two copies of the DAT1 10-repeat allele. These findings indicate that dopaminergic polymorphisms affect selective aspects of attention as early as infancy and further validate the Freeze-Frame task as a frontal cortex task.

Interpretation of ambiguity in children: a prospective study of associations with anxiety and parental interpretations

Interpretation of ambiguity is consistently associated with anxiety in children, however, the temporal relationship between interpretation and anxiety remains unclear as do the developmental origins of interpretative biases. This study set out to test a model of the development of interpretative biases in a prospective study of 110 children aged 5–9 years of age. Children and their parents were assessed three times, annually, on measures of anxiety and interpretation of ambiguous scenarios (including, for parents, both their own interpretations and their expectations regarding their child). Three models were constructed to assess associations between parent and child anxiety and threat and distress cognitions and expectancies. The three models were all a reasonable fit of the data, and supported conclusions that: (i) children’s threat and distress cognitions were stable over time and were significantly associated with anxiety, (ii) parents’ threat and distress cognitions and expectancies significantly predicted child threat cognitions at some time points, and (iii) parental anxiety significantly predicted parents cognitions, which predicted parental expectancies at some time points. Parental expectancies were also significantly predicted by child cognitions. The findings varied depending on assessment time point and whether threat or distress cognitions were being considered. The findings support the notion that child and parent cognitive processes, in particular parental expectations, may be a useful target in the treatment or prevention of anxiety disorders in children.