Barriers to adopting a Mediterranean diet in Northern European adults at high risk of developing cardiovascular disease.

BACKGROUND: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations. METHODS: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis. RESULTS: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences. CONCLUSIONS: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations.

Adding dynamics to the Human Connectome Project with MEG.

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

Morning-evening variation in human brain metabolism and memory circuits.

It has been posited that a critical function of sleep is synaptic renormalization following a net increase in synaptic strength during wake. We hypothesized that wake would alter the resting-state functional organization of the brain and increase its metabolic cost. To test these hypotheses, two experiments were performed. In one, we obtained morning and evening resting-state functional MRI scans to assess changes in functional brain organization. In the second experiment, we obtained quantitative positron emission tomography measures of glucose and oxygen consumption to assess the cost of wake. We found selective changes in brain organization. Most prominently, bilateral medial temporal regions were locally connected in the morning but in the evening exhibited strong correlations with frontal and parietal brain regions involved in memory retrieval. We speculate that these changes may reflect aspects of memory consolidation recurring on a daily basis. Surprisingly, these changes in brain organization occurred without increases in brain metabolism.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Undernutrition during suckling in rats elevates plasma adiponectin and its receptor in skeletal muscle regardless of diet composition: a protective effect?

OBJECTIVE: Nutrition during critical periods in early life may increase the subsequent risk of obesity, hypertension and metabolic diseases in adulthood. Few studies have focused on the long-term consequences of poor nutrition during the suckling period on the susceptibility to developing obesity when exposed to a palatable cafeteria-style high-fat diet (CD) after weaning. DESIGN: This study examined the impact of early undernutrition, followed by CD exposure, on blood pressure, hormones and genes important for insulin sensitivity and metabolism and skeletal muscle mRNA expression of adiponectin receptor 1 (AdipoR1), carnitine palmitoyl-transferase I (CPT-1), cytochrome c oxidase 4 (COX4) and peroxisome proliferator-activated receptor alpha (PPARalpha). Following normal gestation, Sprague-Dawley rat litters were adjusted to 18 (undernourished) or 12 (control) pups. Rats were weaned (day 21) onto either palatable CD or standard chow. RESULTS: Early undernourished rats were significantly lighter than control by 17 days, persisting into adulthood only when animals were fed chow after weaning. Regardless of litter size, rats fed CD had doubled fat mass at 15 weeks of age, and significant elevations in plasma leptin, insulin and adiponectin. Importantly, undernutrition confined to the suckling period, elevated circulating adiponectin regardless of post-weaning diet. Blood pressure was reduced in early undernourished rats fed chow, and increased by CD. Early undernutrition was associated with long-term elevations in the expression of AdipoR1, CPT-1, COX4 and PPARalpha in skeletal muscle. CONCLUSION: This study demonstrates the important role of early nutrition on body weight and metabolism, suggesting early undernourishment enhances insulin sensitivity and fatty-acid oxidation. The long-term potential benefit of limiting nutrition in the early postnatal period warrants further investigation.

An unusual case of basal cell carcinoma of the vulva with lung metastases.

Basal cell carcinoma (BCC) is the most common non-melanomatous skin cancer, typically arising in sun-exposed areas such as the head and neck. Defective signaling through the Hedgehog (HH) signaling pathway forms the molecular basis for BCC. Surgery remains the mainstay of treatment. Basal cell carcinoma of the genital tract is rare as is metastatic BCC. We report a case of metastatic BCC in a young woman with previously resected vulval BCC presenting six years later with inguinal nodal recurrence and multiple lung metastases.

Repositioning the patient: the implications of being 'at risk'.

In the modern era of biomedical practice, genetic knowledge has redefined the idea of 'the patient' to include those who are 'at risk' of disease alongside those who are already sick. For such individuals, it is risk itself that constitutes the raison d'être of medical intervention. Using data from interviews with 58 users of a UK cancer genetics service together with data derived from clinical consultations, we consider the way such patients or clients make sense of a cancer genetic risk estimate and how they integrate genetic risk information into their lifeworld. In particular, we note that patient-clients who are 'at risk' tend to see themselves in a liminal position betwixt the healthy and the sick, and that such individuals consequently seek recourse to systems of medical surveillance that can continuously monitor their state of health. Our analysis also revealed the fact that many of those deemed by professionals to be at low risk of inheriting cancer-related mutations subsequently strove to be re-categorised as being at moderate or high risk of an adverse outcome. A number of explanations concerning lay health beliefs, lay 'representations' of health and the nature of the patient-client's lifeworld are examined and assessed in order to account for this apparent paradox.

A pilot study of sexual lifestyle in a random sample of the population of Great Britain.

Rates of sexual-partner change and patterns of high-risk behaviour are important determinants of the spread of HIV. We carried out a survey to assess the feasibility of studying sexual lifestyle in a random sample of the British population, aged 16-64 years, in November 1987. Two thousand and seventy-seven households were selected using a multi-stage probability sampling procedure. Seven hundred and eight-five adults participated in a structured interview. The schedule included demographic details, attitudes to AIDS, numbers of sexual partners in different time periods, history of homosexuality and contact with prostitutes. An interview was obtained in 61% of households where contact was made, but the overall response rate was low (48%). There was marked variability between individuals in numbers of sexual partners in given time intervals. Men and women in younger cohorts had experienced first sexual intercourse earlier and had higher numbers of sexual partners than people in older cohorts. Surprisingly few reported high-risk behaviour such as homosexuality and use of prostitution. The methodological problems in trying to obtain unbiased and valid data on sexual behaviour are discussed. Further work is necessary to improve the response rate and questionnaire design.

The Drosophila melanogaster genome contains a member of the Rh/T2/S-glycoprotein family of ribonuclease-encoding genes.

Members of the Rh/T2/S-glycoprotein family of ribonuclease(RNase)-encoding genes have been found predominantly in fungi, plants and bacteria, where they have been implicated in functions as diverse as the phosphate-starvation response and self-incompatibility. We report the isolation and sequence of DmRNase-66B, the first member of this family to be found in an insect genome. This gene was identified by the analysis of a cDNA clone derived from cytological region 66B1-2 of the genome of Drosophila melanogaster. In a search of sequence databases for homologs of this gene, two animal viral proteins, gp53 of the bovine viral diarrhea virus (BVDV) and gp44/48 of the hog cholera virus (HCV), were also found to exhibit the characteristic features of this class of RNases. In all cases, the proteins contain two conserved pentameric amino-acid regions that have been shown to lie in the active site of these RNases. A series of Cys residues are also conserved in all members of this gene family. The discovery of members of this family of genes in an insect genome indicates that these RNases are widely conserved and play important roles in the animal, as well as the plant and prokaryotic kingdoms.

Frequency dependent activation of a slow N-methyl-D-aspartate-dependent excitatory postsynaptic potential in turtle cerebellum by mossy fibre afferents.

The synaptic responses of turtle cerebellar Purkinje cells to stimulation of localized mossy fibre systems have been studied by use of intrasomatic and intradendritic recordings in a brainstem-cerebellum preparation in vitro. Activation of mossy fibre inputs from the spinocerebellar pathway evoked fast, disynaptic postsynaptic potentials which were graded in amplitude with stimulus intensity and elicited at latencies consistent with those reported for peripheral nerve stimulation. Repetitive activation (50-100 Hz, 2-10 stimuli) of both spinocerebellar and trigeminocerebellar pathways evoked a slow, long-lasting excitatory postsynaptic potential regardless of whether single stimuli resulted in excitatory, inhibitory, or no postsynaptic responses. This slow potential was capable of triggering dendritic pacemaker discharges in recorded Purkinje cells in addition to volleys of simple spikes when activated at or near resting membrane potential. The fast excitatory synaptic potentials evoked by spinocerebellar stimulation were blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione, consistent with the hypothesis that they are mediated by activation of ionotropic glutamate receptors of the alpha-amino-3-hydroxy-5-methylisox-azole-4-proprionic acid subtype at the mossy fibre-granule cell synapse and the subsequent parallel fibre-Purkinje cell synapse. The slow excitatory synaptic potential evoked by repetitive stimulation of either the spinocerebellar tract or trigeminal nerve was blocked by DL-2-amino-5-phosphonvalerate, indicating that this potential is primarily dependent upon N-methyl-D-aspartate receptors at the mossy fibre-granule cell synapse for its expression. This slow potential was reversibly potentiated by L-2-amino-4-phosphonobutyrate and bicuculline; the metabotropic glutamate antagonist (+)-alpha-methyl-4-carboxyphenylglycine did not block this potentiation. The ability of mossy fibre inputs to drive long, slow excitatory events in Purkinje cells adds another dimension to the mechanisms by which various sensory modalities can be processed interactively in the cerebellar cortex. The ability of incoming systems to access a second, longer duration response of the cerebellar output neuron may be of significant consequence to our understanding of the manner in which this neural centre integrates sensory information from multiple sources.

The 56/58 kDa androgen-binding protein in male genital skin fibroblasts with a deleted androgen receptor gene.

Human genital skin fibroblasts (GSF) make a relatively abundant 56/58 kDa protein that binds androgens. The protein shares many properties with the approximately 100 kDa androgen receptor that is encoded by a locus in the q12 region of the X chromosome. It does not appear to be androgen-induced, yet is absent in GSF of most patients with complete androgen insensitivity (CAI). A precursor-product relation with the androgen receptor (AR) protein has been largely excluded; that it may be an unorthodox product of the AR gene has not. The 56/58 kDa protein is made by the GSF of a mentally retarded subject who has CAI because of a complete deletion of the coding portion of the AR gene. Hence, the strong constitutional and statistical correlations that have been demonstrated between the two proteins cannot arise because they share the same gene. The subject's genomic DNA hybridizes normally with 11 single-copy probes from Xq11-Xq13. Therefore, we cannot attribute her mental retardation to a contiguous gene syndrome.

GABAergic inhibition and epileptiform discharges in the turtle hippocampus in vitro.

The effects of excitatory amino acid (EAA) receptor antagonists were examined on intracellularly recorded epileptiform discharges in turtle hippocampal (ventromedial cortical) pyramidal neurons in vitro. Afferent synaptic activation of turtle hippocampal neurons evoked monophasic or biphasic GABAergic inhibitory postsynaptic potentials (IPSPs). In the presence of bicuculline (5 microM) or picrotoxin (100 microM) IPSPs were reduced, and long-lasting ictal-like discharges were transiently observed prior to the establishment of a regular rhythm of discharge of spontaneous paroxysmal depolarization shifts (PDSs). Bicuculline-induced PDSs were reversibly reduced in amplitude and duration, but not abolished by the EAA receptor antagonists kynurenic acid (1 mM), cis-2,3-piperidine dicarboxylic acid (cis-2,3-PDA) (1 mM), or DL-2-amino-5-phosphonovalerate (DL-AP-5) (100 microM), revealing a long-lasting hyperpolarizing afterpotential. These results indicate that the blockade of GABAergic inhibition leads to the genesis of epileptiform discharges, and EAA receptor antagonists (particularly those of the N-methyl-D-aspartate (NMDA) receptor subtype) block the maintained depolarization underlying PDSs, but do not prevent their spontaneous discharge in turtle hippocampus.

Localization of 2-[125I]iodomelatonin binding sites in visual areas of the turtle brain.

The hormone melatonin is believed to play an important role in the regulation of both circadian and circannual rhythms. In mammalian vertebrates melatonin receptors are discretely localized, with broader distributions reported in avians and reptiles. To examine the sites at which melatonin may act in the turtle brain, 2-[125I]iodomelatonin binding sites were assessed using quantitative autoradiography. Specific binding sites were primarily restricted to forebrain structures with a wide distribution in visual recipient areas. The distribution of melatonin sensitive sites within the turtle visual system suggests that the ability to transduce received photoperiodic signals in the reptilian brain is broadly distributed within the central nervous system.

Excitatory amino acid receptors mediate slow synaptic transmission in turtle cerebellum.

In the isolated turtle cerebellum intracellular recordings from Purkinje cell dendrites and somata reveal novel slow excitatory synaptic potentials evoked by activation of climbing fiber (CF) or parallel fiber (PF) inputs. Classical fast excitatory synaptic responses to CF and PF stimulation are followed by large, slow excitatory postsynaptic potentials (sEPSPs) which are associated with an increase in conductance and are enhanced by hyperpolarization. Both sEPSPs are blocked by the excitatory amino acid (EAA) antagonist kynurenate, but not by DL-2-amino-5-phosphonovalerate (AP-5). The EAA receptor antagonist L-amino-4-phosphonobutyric acid (L-AP-4) reversibly blocked the PF-sEPSP without affecting the CF-sEPSP. Two novel slow synaptic potentials mediated by excitatory amino acid receptors can therefore be observed in turtle cerebellum which may play an important role in synaptic integration.

Identification of central 5-HT and 5-HT1A receptors in the turtle brain (Chrysemys picta).

Radiologand binding studies were undertaken in the turtle whole brain, cerebellum and raphe using the selective radioligands [3H]5-hydroxytryptamine trifluoroacetate ([3H]5-HT) amd [3H]+/-8-hydroxy-2-(di-N-propylamino) tetralin hydrobromide ([3H]DPAT) to identify serotonin (5-HT) receptors and the specific 5-HT1A receptor subtype. Scatchard analysis identified a nanomolar affinity binding site for [3H]5-HT (12 nM) in turtle whole brain assays. A low affinity 5-HT1A site (102 nM) was also identified in turtle whole brain assays, with a higher affinity site noted in binding studies performed with tissue from the inferior raphe (20 nM). The difference in affinity for 5-HT receptors in reptilian versus mammalian brain may prove characteristic of lower vertebrate brains with implications for the physiologic effects of this neurotransmitter in the central nervous system.

Community versus hospital care: the crisis in psychiatric provision.

The movement away from hospital-based schemes of care for those with a psychiatric disability in favour of community-based schemes of care constitutes a turning point in the history of psychiatric provision in most Western European societies. The origins and rationale of this movement have sometimes been explained by reference to extra-discursive (economic) interests, and sometimes by reference to a form of technological or scientific determinism in which the discovery of such things as the neuroleptic drugs during the 1950s is said to have played a major role. This paper argues that the impetus for community as against hospital-based care can only be understood in terms of a changing discourse of psychiatry and psychiatric nursing, and especially those forms of thought which have tended to place 'illness' in the wings and set its primary sights on behavioural and social 'deficits'. There is a sense, therefore, in which hospital-based practices of psychiatrists and nurses have constituted the source and origin of their own transformation--a transformation in which the rationale of the psychiatric hospital has been eroded. The arguments in this paper are substantiated by reference to a current study of the forms of knowledge and daily practice which are drawn upon by nurses and psychiatrists in the psychiatric wards of a large Northern Irish hospital.

Doing things with illness. The micro politics of the CFS clinic.

This paper focuses on lay and professional ideas about the nature of chronic fatigue syndrome (CFS), and in particular, the ways in which understandings of the disorder are developed in a clinical setting. Our data are drawn from observations of consultations between sufferers and physicians in a UK medical out-patients clinic. We treat the clinic as a political field. That is to say, as an arena in which 'problems' (about the management of illness) are constituted, and alternative approaches and solutions to such problems are pressed. We note that in the realms of symptoms, aetiology and treatment evaluation, lay people in the CFS clinic have quite distinct ideas about what their problems are and how they might be analysed and managed--ideas that are often in conflict with those of medical professionals. Thus, lay sufferers, for example, operate within a different conceptual terrain from that of many professional experts. They are more likely to refer to a disease (myalgic encephalomyelitis or ME), rather than a syndrome. They call upon different kinds of hypotheses to explain their symptoms. They hold to conflicting ideas about the order of causal sequences, and they give emphasis to different kinds of phenomena in their accounts of illness. As a consequence, clinical consultations can often take on the form of a political contest between physician and patient to define the true and real nature of the patient's disorder--a micro political struggle in which neurological symptoms can be re-framed as psychiatric symptoms, and psychiatric symptoms as neurological. In short, a contest in which the demarcation lines between mind and body are continually assessed and re-defined, and the tenets of 'biomedicine' are constantly challenged.

Communication about risk--dilemmas for general practitioners. The Department of General Practice Working Group, University of Wales College of Medicine.

Measures of risk frequently contribute to our understanding, prevention, or treatment of disease, but it is important that general practitioners (GPs) explain clinical risks effectively to patients to ensure they are not misunderstood, as risk information can assist in decision-making processes and encourage behavioural change. However, the interpretation of risks by patients and doctors varies. It is argued that problems arise because communication about risk is usually framed in terms of the language of chance or probability. In this paper, we describe how probability theory developed, and suggest that attempts to communicate empirical risk processes in probabilistic language are bound to produce dilemmas. We explore how the theory relates to clinical practice and identify key issues that doctors must address in discussing risk with individual patients.

Exploring lay views on physical activity and their implications for public health policy. A case study from East Belfast.

It is now recognised that inactive lifestyles underpin much of the disease burden evident in the richer nations of the world. Indeed, the WHO has identified physical inactivity as a 'global public health problem' and has established minimum physical activity (PA) targets for people at different stages of the life-course. Yet, according to WHO, just under 1/3 of working age adults across the globe meet those targets and it is not at all clear how the disjunction between the recommendations of policy makers and the behaviour of ordinary people might be surmounted. Using an opportunity to examine the impact of an urban regeneration project on community residents in East Belfast (Northern Ireland) this paper examines the views of some 113 people on how to increase rates of PA in an area of multiple deprivation. The results of the analysis suggest that lay people rarely consider PA as a discrete issue, or one that centres on individuals and their motivation, but rather as one component in a complex web of concerns, processes and events that include such things as the actions of neighbours and relatives, material and political environments, vandalism, violence, and the weather. We explore and unravel the nature of those concerns using novel methods of content analysis that generate 'issue webs'. Particular attention is paid to the ways in which lay people conceptualize 'activity' and to the manner in which they point to ways of encouraging activity that are rooted in everyday life rather than in the corpocentric, agent-centred and often sport dominated strategies favoured by local policy makers. Our results support those who argue that interventions to increase rates of PA need to move beyond behavioural approaches that focus on individuals and consider the social, political and material contexts in which 'activity' occurs.