Identification of novel expressed sequences, up-regulated in the leucocytes of chronic fatigue syndrome patients

BACKGROUND: Chronic fatigue syndrome (CFS) is an increasing medical phenomenon of unknown aetiology leading to high levels of chronic morbidity. Of the many hypotheses that purport to explain this disease, immune system activation, as a central feature, has remained prominent but unsubstantiated. Supporting this, a number of important cytokines have previously been shown to be over-expressed in disease subjects. The diagnosis of CFS is highly problematic since no biological markers specific to this disease have been identified. The discovery of genes relating to this condition is an important goal in seeking to correctly categorize and understand this complex syndrome. OBJECTIVE: The aim of this study was to screen for changes in gene expression in the lymphocytes of CFS patients. METHODS: 'Differential Display' is a method for comparing mRNA populations for the induction or suppression of genes. In this technique, mRNA populations from control and test subjects can be 'displayed' by gel electrophoresis and screened for differing banding patterns. These differences are indicative of altered gene expression between samples, and the genes that correspond to these bands can be cloned and identified. Differential display has been used to compare expression levels between four control subjects and seven CFS patients. RESULTS: Twelve short expressed sequence tags have been identified that were over-expressed in lymphocytes from CFS patients. Two of these correspond to cathepsin C and MAIL1 - genes known to be upregulated in activated lymphocytes. The expression level of seven of the differentially displayed sequences have been verified by quantifying relative level of these transcripts using TAQman quantitative PCR. CONCLUSION: Taken as a whole, the identification of novel gene tags up-regulated in CFS patients adds weight to the idea that CFS is a disease characterized by subtle changes in the immune system.

The role of animal nutrition in improving the nutritive value of animal-derived foods in relation to chronic disease

Foods derived from animals are an important source of nutrients in the diet; for example, milk and meat together provide about 60 and 55% of the dietary intake of Ca and protein respectively in the UK. However, certain aspects of some animal-derived foods, particularly their fat and saturated fatty acid (SFA) contents, have led to concerns that these foods substantially contribute to the risk of CVD, the metabolic syndrome and other chronic diseases. In most parts of Europe dairy products are the greatest single dietary source of SFA. The fatty acid composition of various animal-derived foods is, however, not constant and can, in many cases, be enhanced by animal nutrition. In particular, milk fat with reduced concentrations of the C12-16 SFA and an increased concentration of 18:1 MUFA is achievable, although enrichment with very-long-chain n-3 PUFA is much less efficient. However, there is now evidence that some animal-derived foods (notably milk products) contain compounds that may actively promote long-term health, and research is urgently required to fully characterise the benefits associated with the consumption of these compounds and to understand how the levels in natural foods can be enhanced. It is also vital that the beneficial effects are not inadvertently destroyed in the process of reducing the concentrations of SFA. In the future the role of animal nutrition in creating foods closer to the optimum composition for long-term human health is likely to become increasingly important, but production of such foods on a scale that will substantially affect national diets will require political and financial incentives and great changes in the animal production industry.

Williams Syndrome: the extent of agreement between parent and self report of psychological difficulties

Background and Objectives: People with Williams syndrome (WS) have been reported by their carers to have problems with attention, anxiety and social relationships. People with WS have been shown to report their anxieties. This study extends our knowledge of how people with WS see themselves in terms of behaviour and social relationships. Methods: A survey using self and parent report forms of the Strengths and Difficulties Questionnaire. Results: Both parents and individuals with WS (N = 31) reported difficulties in emotional disorder and hyperactivity symptoms and strengths in prosocial behaviours such as altruism and empathy. They disagreed about peer problems. Conclusions: People with WS understand some but not all of their difficulties. In particular they fail to recognize their social difficulties which may lead them to be vulnerable to exploitation.

Understanding and production of prosody in children with Williams syndrome: A developmental trajectory approach

This study investigated the development of three aspects of linguistic prosody in a group of children with Williams syndrome compared to typically developing children. The prosodic abilities investigated were: (1) the ability to understand and use prosody to make specific words or syllables stand out in an utterance (focus); (2) the ability to understand and use prosody to disambiguate complex noun phrases (chunking); (3) the ability to understand and use prosody to regulate conversational behaviour (turn-end). The data were analysed using a cross-sectional developmental trajectory approach. The results showed that, relative to chronological age, there was a delayed onset in the development of the ability of children with WS to use prosody to signal the most important word in an utterance (the focus function). Delayed rate of development was found for all the other aspects of expressive and receptive prosody under investigation. However, when non-verbal mental age was taken into consideration, there were no differences between the children with WS and the controls neither with the onset nor with the rate of development for any of the prosodic skills under investigation apart from the ability to use prosody in order to regulate conversational behaviour. We conclude that prosody is not a ‘preserved’ cognitive skill in WS. The genetic factors, development in other cognitive domains and environmental influences affect developmental pathways and as a result, development proceeds along an atypical trajectory.

Earworms ("stuck song syndrome"): towards a natural history of intrusive thoughts

Two studies examine the experience of “earworms”, unwanted catchy tunes that repeat. Survey data show that the experience is widespread but earworms are not generally considered problematic, although those who consider music to be important to them report earworms as longer, and harder to control, than those who consider music as less important. The tunes which produce these experiences vary considerably between individuals but are always familiar to those who experience them. A diary study confirms these findings and also indicates that, although earworm recurrence is relatively uncommon and unlikely to persist for longer than 24 hours, the length of both the earworm and the earworm experience frequently exceed standard estimates of auditory memory capacity. Active attempts to block or eliminate the earworm are less successful than passive acceptance, consistent with Wegner’s (1994) theory of ironic mental control.

Intonation abilities of children with Williams syndrome: a preliminary investigation

Purpose: The authors investigated expressive and receptive intonation abilities in children with Williams syndrome (WS) and the relation of these abilities to other linguistic abilities. Method: Fourteen children with WS, 14 typically developing children matched to the WS group for receptive language (LA), and 15 typically developing children matched to the WS group for chronological age (CA) were compared on a range of receptive and expressive intonation tasks from the Profiling Elements of Prosodic Systems-Child version (PEPS-C) battery. Results: The WS group performed similarly to the LA group on all intonation tasks apart from the long-item imitation task, on which the WS group scored significantly lower than the LA group. When compared with the CA group, the WS group was significantly poorer on all aspects of intonation. Whereas there were a number of significant correlations between the intonation and language measures in the control groups, in the WS group, there was only 1 significant correlation between a PEPS-C task and one of the language measures. Conclusion: As a result of this study, the authors concluded that children with WS have expressive and receptive intonation abilities as expected for their level of language comprehension and that intonation and other linguistic abilities in WS are not strongly related.

Linguistic heterogeneity in Williams syndrome

Williams syndrome (WS) is a rare genetic disorder resulting from a deletion on chromosome 7. A number of studies have shown that individuals with WS have a superior linguistic profile compared to their non-verbal abilities, however the evidence has been inconclusive, as many studies have disputed such a profile. The vast majority of studies on WS have assumed a single, homogeneous WS linguistic profile in order to support various theoretical viewpoints. The present study investigated the linguistic profiles of 5 individuals with WS on a number of standardized verbal measures and in conversational settings. The results indicated substantially variable performance in all aspects of the verbal domain, which supports the view that WS, linguistically, is a rather heterogeneous condition and this should be taken into consideration when referring to it in theoretical accounts of language acquisition and debates on modularity.

Conversations around homework: links to parental mental health, family characteristics and child psychological functioning

Parents are increasingly expected to supplement their children's school-based learning by providing support for children's homework. However, parents' capacities to provide such support may vary and may be limited by the experience of depression. This may have implications for child development. In the course of a prospective, longitudinal study of children of postnatally depressed and healthy mothers, we observed mothers (N = 88) and fathers (N = 78) at home during maths homework interactions with their 8-year-old children. The quality of parental communication was rated and analysed in relation to child functioning. The quality of communication of each of the parents was related to their mental state, social class and IQ. While postnatal depression was not directly related to child development, there was some evidence of the influence of maternal depression occurring in the child's school years. Different aspects of parental communication with the child showed specific associations with different child outcomes, over and above the influence of family characteristics. In particular, child school attainment and IQ were associated with parental strategies to encourage representational thinking and mastery motivation, whereas child behavioural adjustment at school and self-esteem were linked to the degree of parental emotional support and low levels of coercion. Notably, the influence of maternal homework support was more strongly related to child outcome than was paternal support, a pattern reflected in mothers' greater involvement in children's schools and school-related activities. Some parents may need guidance in how to support their children's homework if it is to be of benefit to child functioning.

The psychological, neurochemical and functional neuroanatomical mediators of the effects of positive and negative mood on executive functions

In this review we evaluate the cognitive and neural effects of positive and negative mood on executive function. Mild manipulations of negative mood appear to have little effect on cognitive control processes, whereas positive mood impairs aspects of updating, planning and switching. These cognitive effects may be linked to neurochemistry: with positive mood effects mediated by dopamine while negative mood effects may be mediated by serotonin levels. Current evidence on the effects of mood on regional brain activity during executive functions, indicates that the prefrontal cortex is a recurrent site of integration between mood and cognition. We conclude that there is a disparity between the importance of this topic and awareness of how mood affects, executive functions in the brain. Most behavioural and neuroimaging studies of executive function in normal samples do not explore the potential role of variations in mood, yet the evidence we outline indicates that even mild fluctuations in mood can have a significant influence on neural activation and cognition. (c) 2006 Elsevier Ltd. All rights reserved.

Texture segmentation in Williams syndrome

Williams syndrome (WS) is a developmental disorder in which visuo-spatial cognition is poor relative to verbal ability. At the level of visuo-spatial perception, individuals with WS can perceive both the local and global aspects of an image. However, the manner in which local elements are integrated into a global whole is atypical, with relative strengths in integration by luminance, closure, and alignment compared to shape, orientation and proximity. The present study investigated the manner in which global images are segmented into local parts. Segmentation by seven gestalt principles was investigated: proximity, shape, luminance, orientation, closure, size (and alignment: Experiment I only). Participants were presented with uniform texture squares and asked to detect the presence of a discrepant patch (Experiment 1) or to identify the form of a discrepant patch as a capital E or H (Experiment 2). In Experiment 1, the pattern and level of performance of the WS group did not differ from that of typically developing controls, and was commensurate with the general level of non-verbal ability observed in WS. These results were replicated in Experiment 2, with the exception of segmentation by proximity, where individuals with WS demonstrated superior performance relative to the remaining segmentation types. Overall, the results suggest that, despite some atypical aspects of visuo-spatial perception in WS, the ability to segment a global form into parts is broadly typical in this population. In turn, this informs predictions of brain function in WS, particularly areas V1 and V4. (c) 2006 Elsevier Ltd. All rights reserved.

Perceptual grouping ability in Williams syndrome: evidence for deviant patterns of performance

Williams syndrome (WS) is a rare genetic disorder. At a cognitive level, this population display poor visuo-spatial cognition when compared to verbal ability. Within the visuo-spatial domain, it is now accepted that individuals with WS are able to perceive both local and global aspects of an image, albeit at a low level. The present study examines the manner in which local elements are grouped into a global whole in WS. Fifteen individuals with WS and 15 typically developing controls, matched for non-verbal ability, were presented with a matrix of local elements and asked whether these elements were perceptually grouped horizontally or vertically. The WS group was at the same level as the control group when grouping by luminance, closure, and alignment. However, their ability to group by shape, orientation and proximity was significantly poorer than controls. This unusual profile of grouping abilities in WS suggests that these individuals do not form a global percept in a typical manner. (c) 2004 Published by Elsevier Ltd.

Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome

Objective: In the metabolic syndrome (MetS), increased fat storage in ‘nonadipose’ tissues such as skeletal muscle may be related to insulin resistance (‘lipid overflow’ hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). Subjects and Methods: In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn−3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [2H2]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-13C]-palmitate to label chylomicron-TAG. Results: Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn−3 group compared to the HSFA group (ΔiAUC −139±67 vs 167±70 μmol l−1 min−1, P=0.009), together with decreased concentrations of [U-13C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Conclusion: Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn−3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.

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.