Obesity can increase the risk of diseases such as type 2 diabetes mellitus and cardiovascular disease(1). Glucose control is critical to both preventing and managing diabetes and can be achieved by enhancing secretion of insulin, limiting absorption of glucose from the gut and by upregulating the use of glucose in the muscles(2). Abnormalities in glucose management(3) and blood pressure control(4) are known to impair cognitive function. Epidemiological studies report an inverse risk of type 2 diabetes with increased intake of polyphenols. These data are also supported by in vitro and animal studies reporting positive effects of polyphenols on insulin sensitivity, carbohydrate digestion and glucose regulation(5). Here we aimed to evaluate postprandial glucose metabolism, blood pressure and cognitive function following a high carbohydrate meal accompanied by different doses of anthocyanin containing blueberry drinks.

A double-blind, placebo-controlled, dose-response study was designed and received ethical approval and 22 participants were recruited. Each participant attended four study days in a crossover design, separated by a minimum of 5 days during which, they consumed a high carbohydrate meal consisting of two slices of toast and one of three doses of blueberry beverage or a control beverage. Memory performance was assessed using the visual verbal learning test (VVLT), measured at baseline and 90 minutes post consumption. Glucose was monitored every 15 minutes using a continuous glucose monitor which was worn across 10 days, and blood pressure was assessed every 30 minutes for a period of 4 hours in the laboratory. Glucose area under the curve (AUC) were analysed using linear mixed models. Blood pressure and VVLT data were analysed using repeated measures ANOVA.

The analysis was performed blind to condition. In total, 22 participants completed all four study visits (mean age 28 ± 5.9, mean weight 61kg ± 10.4, mean height, 1.64m ± 0.9, mean BMI 22.7 ± 2.27, N=20 female, N=2 male). There was a significant effect of treatment on total words recalled in the VVLT with best performance following condition B compared to condition C, and condition D compared to condition C (p < 0.05). Condition B also resulted in significant systolic blood pressure lowering compared to condition C (-2.47mmHg, P <0.003). There was no effect of treatment on area under the curve for glucose over 3 hours postprandial (p > 0.05).

Taken together these results suggest that condition B conferred greatest benefit for memory performance and that this was associated with anthocyanin related effects on systolic blood pressure.

This study was funded by the Wild Blueberry Association of North America (WBANA).

Diets deficient in fibre are reported globally. The associated health risks of insufficient dietary fibre are sufficiently grave to necessitate large-scale interventions to increase population intake levels. The Danish Whole Grain Partnership (DWP) is a public–private enterprise model that successfully augmented whole-grain intake in the Danish population. The potential transferability of the DWP model to Slovenia, Romania and Bosnia-Herzegovina has recently been explored. Here, we outline the feasibility of adopting the approach in the UK. Drawing on the collaborative experience of DWP partners, academics from the Healthy Soil, Healthy Food, Healthy People (H3) project and food industry representatives (Food and Drink Federation), this article examines the transferability of the DWP approach to increase whole grain and/or fibre intake in the UK. Specific consideration is given to the UK’s political, regulatory and socio-economic context. We note key political, regulatory, social and cultural challenges to transferring the success of DWP to the UK, highlighting the particular challenge of increasing fibre consumption among low socio-economic status groups – which were also most resistant to interventions in Denmark. Wholesale transfer of the DWP model to the UK is considered unlikely given the absence of the key ‘success factors’ present in Denmark. However, the DWP provides a template against which a UK-centric approach can be developed. In the absence of a clear regulatory context for whole grain in the UK, fibre should be prioritised and public–private partnerships supported to increase the availability and acceptability of fibre-rich foods.

The conduct of high-quality nutrition research requires the selection of appropriate markers as outcomes, for example as indicators of food or nutrient intake, nutritional status, health status or disease risk. Such selection requires detailed knowledge of the markers, and consideration of the factors that may influence their measurement, other than the effects of nutritional change. A framework to guide selection of markers within nutrition research studies would be a valuable tool for researchers. A multidisciplinary Expert Group set out to test criteria designed to aid the evaluation of candidate markers for their usefulness in nutrition research and subsequently to develop a scoring system for markers. The proposed criteria were tested using thirteen markers selected from a broad range of nutrition research fields. The result of this testing was a modified list of criteria and a template for evaluating a potential marker against the criteria. Subsequently, a semi-quantitative system for scoring a marker and an associated template were developed. This system will enable the evaluation and comparison of different candidate markers within the same field of nutrition research in order to identify their relative usefulness. The ranking criteria of proven, strong, medium or low are likely to vary according to research setting, research field and the type of tool used to assess the marker and therefore the considerations for scoring need to be determined in a setting-, field- and tool-specific manner. A database of such markers, their interpretation and range of possible values would be valuable to nutrition researchers.

Foods and dietary patterns that enhance satiety may provide benefit to consumers. The aim of the present review was to describe, consider and evaluate research on potential benefits of enhanced satiety. The proposal that enhanced satiety could only benefit consumers by a direct effect on food intake should be rejected. Instead, it is proposed that there is a variety of routes through which enhanced satiety could (indirectly) benefit dietary control or weight-management goals. The review highlights specific potential benefits of satiety, including: providing appetite control strategies for consumers generally and for those who are highly responsive to food cues; offering pleasure and satisfaction associated with low-energy/healthier versions of foods without feeling ‘deprived’; reducing dysphoric mood associated with hunger especially during energy restriction; and improved compliance with healthy eating or weight-management efforts. There is convincing evidence of short-term satiety benefits, but only probable evidence for longer-term benefits to hunger management, possible evidence of benefits to mood and cognition, inadequate evidence that satiety enhancement can promote weight loss, and no evidence on which consumers would benefit most from satiety enhancement. The appetite-reducing effects of specific foods or diets will be much more subtle than those of pharmaceutical compounds in managing hunger; nevertheless, the experience of pharmacology in producing weight loss via effects on appetite suggests that there is potential benefit of satiety enhancement from foods incorporated into the diet to the consumer.

We have developed two brain slice preparations for studying tectofugal visual pathways in the chick: conventional, 400-μm slices (“thin slices”), and “thick slices” which encompass the rostral pole of the optic tectum and the contralateral optic nerve. Stimulation was delivered with a bipolar electrode positioned in stratum opticum in thin slices and in the contralateral optic nerve in thick slices. While the latter preparation provided a means of exclusively and unambiguously activating retinal afferents, several lines of evidence also indicated that the evoked field potentials in thin slices were chiefly consequent to retinal afferent excitation: (1) the similarity of evoked field potentials in thin slices to those in thick slice preparations; (2) their precise localization in retinorecipient layers as shown by prelabeling from retina with FITC-coupled cholera toxin; (3) transmission delays appropriate for retinal afferents as established with the thick slice preparation; (4) patterns of labeled afferents resulting from applications of Dil crystals to slices fixed after recording; and (5) the similarity in transmitter pharmacology between thin and thick slice preparations. Pharmacological manipulations carried out with bath-applied antagonists indicated that glutamate is the principal retinotectal transmitter. The broadly active glutamate receptor blocker, kynurenic acid, reversibly eliminated the postsynaptic component of the field potential as confirmed with 0 Ca2+ saline. A complete block was also effected by the non-NMDA antagonists CNQX and DNQX. The specific NMDA antagonist, APS, caused a smaller and variable reduction in response amplitude. The GABA antagonist, bicuculline, caused a prolongation of the monosynaptic field epsp in retinorecipient layers and an enhancement of the long-latency, negative wave in cellular layers below, supporting a late, excitation-limiting role for this inhibitory transmitter.

A prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72% (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17% (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73·9 % protective immunity (95 % C.I. 53·0–85·5 %) and relatively permanent MST responsiveness (recovery rate = 0·0098/year; 95% C.I. 0·000–0·020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17·9% per mm; P < 0·0001), and a mean MST recovery rate of 0·114/year (4/421 man-months), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections.

Where immunization campaigns locally eliminate measles, it will be important to identify the vaccination policy most likely to prevent future epidemics. The optimum age for vaccination depends on the rate of decline of maternal antibody, because the presence of antibody reduces vaccine efficacy. The first part of this paper contains a quantitative reappraisal of the data on antibody decline and seroconversion rates by age. The decline in maternal antibody protection follows delayed exponentials, with delays of 2–4 months, and subsequent half-lives of 1–2 months. Using this result in an analytical mathematical model we find that the optimal age to administer a single dose of vaccine to children, which is independent of vaccine coverage, lies within the range 11–19 months. We also show that, where the optimal age cannot be met, it is better to err towards late rather than early vaccination. There are therefore two reasons why developing countries, which presently vaccinate during infancy because measles transmission rates are high should eventually switch to the second year of life. The possible gains from two-dose vaccination schedules are explored with respect to both coverage and efficacy. A two-dose schedule will be beneficial, in principle, only when there is a need to increase net vaccine efficacy, after coverage has been maximized with a one-dose schedule.

Serological tests are very frequently used in epidemiological surveys of leishmaniasis and other parasitoses. Their sensitivity and specificity are generally defined with respect to parasitism and diseases, rather than infection. The reason is that known positives are those individuals most likely to yield parasites, or who have distinctive clinical signs, and concomitantly high antibody titres. This paper investigates the performance of one serological method, the indirect fluorescent antibody test (IFAT), in detecting Leishmania infantum infection during an intensive 2-year cohort study of dogs in southern France. The results show that sensitivity and specificity with respect to infection can be simultaneously high, but maximum sensitivity is probably <80%, and lasts for a relatively short period of 2–3 months after a lengthy incubation period. The IFAT gave the incidence of infection as 18–65% in the first year, whereas the best estimate of incidence based on parasite isolation and clinical observation was 72%. But data from the second year suggest that the 72% was itself an underestimate. We argue that, during epidemiological surveys, the IFAT in particular, and serological tests for leishmania in general, will underestimate prevalence, incidence and hence the scale of the control problem. However, there is evidence that tests for canine leishmaniasis employing high threshold titres will identify the most infectious animals, allowing selective treatment or culling of those which contribute disproportionately to transmission.

The paper describes a mathematical model for canine leishmaniasis and presents formulae which can be used to estimate the basic reproduction number, R0. The primary concern has been to devise methods of estimation which make best use of those data most easily obtained by fieldwork, e.g. surveys of prevalence in dog (by age) and sandfly populations. A range of formulae are offered which are more or less demanding of data, and which consequently give more or less precise estimates of R0. They include methods for assessing the influence on R0 of heterogeneous biting rates of sandflies on dogs, in which the essence of heterogeneous transmission can be captured merely by measuring relative rather than absolute contact rates.

Until recently, almost all studies of leishmaniasis epidemiology were qualitative and descriptive. But now that the natural history of many Leishmania parasites is quite well known, there is growing interest in quantitative analysis. In this paper I use mathematical models in conjunction with field data to try to answer a wider range of questions than has previously been possible with descriptive techniques, and to sharpen some of the outstanding questions for laboratory workers. This is done with reference to the persistence and resilience of canine leishmaniasis, the maintenance of virulence poly morphisms in Leishmania populations, and the possible existence of cycles of human kala-azar. I conclude by posing a set of problems under three headings: diagnosis of infection (as distinct from disease), natural immunity to Leishmania infection in the vertebrate host, and genetic variation in the parasite population. Some solutions from the laboratory can be found in the companion paper by Black (1992).

Assessment of the resilience of canine leishmaniasis to control or, more ambitiously, the effort needed to eradicate infection, requires an estimate of the basic case reproduction number (R0). This paper applies the theoretical results of Hasibeder, Dye & Carpenter (1992) to data from a cross-sectional survey on the Maltese island of Gozo in which dogs of known age, sex and occupation (pet, guard etc) were subjected to three different serological tests for the presence of specific antibody (IFAT, DAT and ELISA). Difficulties in interpreting these test results, and hence of determining the proportion of dogs infected, present the main obstacle to estimating R0: estimates are critically dependent on the choice of threshold separating seropositives from seronegatives. The data do, however, allow a robust comparative analysis of risk which shows that the force of infection experienced by working dogs is about three times higher than that of pet dogs, a degree of non-homogeneous contact which actually has little effect on estimates of R0. We suggest a cautious point estimate of R0 ≃ 11, and comment briefly on its significance for leishmaniasis control.

PF1 (SDPNFLRFamide) is a FMRFamide-like peptide extracted from the free-living nematode Panagrellus redivivus. Here we show that this peptide causes a hyperpolarization of somatic muscle cells of the parasitic nematode Ascaris suum and a relaxation of the somatic muscle strip preparation. We have assessed whether or not the relaxation of Ascaris dorsal muscle strip by PF1 is due to (i) inhibition of the release of the excitatory neuromuscular junction transmitter acetylcholine (ACh), (ii) potentiation of the release of the inhibitory neuromuscular junction transmitter γ-aminobutyric acid (GABA) or (iii) a direct inhibitory action of the peptide on the muscle cells. Under the experimental conditions described here, tonic ACh release does not seem to be involved in determining the resting membrane potential or resting tone of the Ascaris dorsal muscle strip and thus inhibition of tonic ACh release is unlikely to explain the relaxation elicited by the peptide. Furthermore, PF1 (100 nM–1 μM) inhibited the contraction of the muscle strip elicited by bath application of ACh, suggesting either a direct inhibitory action of the peptide on the muscle cells or a potentiation of GABA release. In electrophysiological experiments, the reversal potential for the PF1 hyperpolarization was not the same as that for GABA. Thus, PF1 hyperpolarizes Ascaris muscle by a mechanism that does not involve stimulation of GABA release from inhibitory pre-synaptic terminals.

A great deal of published experimental evidence shows that parasite-induced changes in host choice, and biting and survival rates of bloodsucking insects are an important source of bias in estimates of Vectorial Capacity. I argue here that, because of the difficulties of handling these and other biases in practice, indices (based on the Vectorial Capacity) which purport to measure transmission rate are best used in a comparative rather than an absolute way. They should attempt to measure, not transmission rate, but changes in transmission rate. In this case, the less restrictive assumption that parasites are responsible for constant bias (rather than no bias) leads to relatively small errors. The results encourage a more optimistic view of the performance of classical entomological indices such as the parous rate. They should also help to redirect the principal epidemiological question about vector–parasite interactions: future studies should be concerned with the impact of parasites, not directly on Vectorial Capacity, but on the comparative measures which are actually used to evaluate transmission rate.

Peptides belonging to the FMRFamide family are widely distributed amongst invertebrates. We report here on the isolation of the FMRFamide neuropeptide AF2 (Lys-His-Glu-Tyr-Leu-Arg-Phe-NH2) from the parasitic nematode Haemonchus contortus. Immunocytochemical techniques showed that FMRFamide-like material was distributed in several regions of these organisms including nerve cords and cell bodies of the central nervous system. AF2 was isolated using a method that employed 6 steps of reverse-phase HPLC. The concentration of AF2 in this organism was approximately 30 pmol/g of nematode.

The histochemical marker for nitric oxide synthase, NADPH diaphorase, is known to co-localize in mammalian neurones with various classical neurotransmitters and neuropeptides. The nervous system of the parasitic nematode Ascaris suum has previously been shown to contain both NADPH diaphorase activity and neuropeptide immunoreactivity. This study examined the possibility that NADPH diaphorase and neuropeptide immunoreactivity may co-exist in the same neurones. Two antisera were used, one raised to KYSALMFamide, a C-terminal synthetic analogue of SALMFamide 1 (GFNSALMFamide), and another that recognizes calcitonin-gene-related peptide (CGRP). We provide evidence that in a distinct subset of neurones in the ventral, dorsal and lateral ganglia NADPH diaphorase staining and SALMFamide- like immunoreactivity are co-localized, suggesting a possible role for nitric oxide in modulating neuropeptide activity in these regions. CGRP-like immunoreactivity was less widely distributed, and was not consistently co-localized with NADPH diaphorase.

Whether and how microparasites such as rabies persist in their host populations are among the fundamental questions of infectious disease epidemiology. Rabies is a fatal disease of all mammalian species, but not all mammalian species can maintain the infection as reservoirs. The approach to control depends on which of the affected species do act as reservoirs. Bringing together old and new data, we examine here the role of wild and domestic animals in maintaining rabies in the Serengeti region of Tanzania, presenting our findings in two parts. In Part I, we argue that domestic dogs are the likely reservoirs because: (1) rabies has been continuously present in the dog population since its (re)introduction in 1977, whilst (2) wildlife cases have been very rare over this period, despite intensive study of Serengeti carnivores; (3) outbreaks of rabies in wild canids (jackals) elsewhere in Africa (Zimbabwe) have followed, rather than preceded, outbreaks in the dog population; (4) all viruses isolated from wild carnivores in the Serengeti ecosystem (including the Kenyan Masai Mara) are antigenically and genetically indistinguishable from the typical domestic dog Strain; (5) dog rabies control in the Serengeti between 1958–77 apparently eliminated the disease from both dogs and wildlife. Having identified dogs as reservoirs, Part II explores some possible mechanisms of maintenance in dog populations. In theory, infection is more likely to be maintained at higher dog densities, and we provide evidence that rabies is maintained in one district with a dog density > 5/km2, but not in two other districts with densities < 1/km2. Because 5 dogs/km2 is much lower than the expected density required for persistence, we go on to investigate the role of atypical infections, showing: (1) from serology, that a substantial proportion of healthy dogs in the Serengeti have detectable serum levels of rabies-specific antibody; (2) from mathematical models that, whilst we cannot be sure what seropositivity means, persistence in low-density dog populations is more likely if seropositives are infectious carriers, rather than slow-incubators or immunes.

This study had 2 objectives: first, to investigate how the processes of slender form replication, of differentiation from dividing slender to non-dividing stumpy forms, and of stumpy mortality, combine to determine the initial (acute-phase) growth rate of Trypanosoma brucei populations; second, to determine how acute-phase growth rates influence parasite densities during the subsequent, chronic phase of infection. During the acute phase, slender and stumpy populations both grew approximately exponentially, the latter more slowly than the former. Mathematical models showed how this difference in slender and stumpy growth rates can be explained in terms of heterogeneous replication and differentiation rates. Stumpy life-expectancy was determined for one stock and found to be age-dependent with a half-life of 48–72 h, much larger than observed population doubling times of 5–10 h. A comparison of cloned stocks showed that the highest parasite densities during the chronic phase were associated with the highest acute-phase growth rates of both the whole parasite population and of the subpopulation of slender forms. By contrast, high chronic-phase parasitaemias artificially produced following rapid syringe passage were associated with low acute-phase growth rates of slender forms. Syringe-passaging is a laboratory procedure which selects for virulent parasites, but these parasites behave differently from naturally virulent stocks.

The paper describes a longitudinal field study of canine leishmaniasis in sympatric domestic dog and crab-eating fox (Cerdocyon thous) populations. Dogs were studied in house-to-house surveys, and foxes were studied by live-trapping and radio-telemetry. Because serological tests (IFAT in this case) for leishmaniasis are often of uncertain sensitivity and specificity, we draw conclusions comparatively. Both cross-sectional (age–prevalence) and longitudinal analyses indicate that incidence in dogs was highest in the dry season. Seasonal changes in the age–prevalence relationship for dogs suggest that serological conversion and recovery rates decline with prior exposure to infection, where ‘recovery’ may be due to loss of a positive antibody titre or death from leishmaniasis. The mean incidence in dogs was higher in the rural than in the urban population and higher in hunting dogs than pet dogs. Cross-sectional and longitudinal analyses of fox serological data suggest that foxes remain positive for longer than dogs on average, either because detectable antibody is more persistent or because they experience a lower mortality rate due to leishmaniasis.