The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015.

Dieting and food craving. A descriptive, quasi-prospective study.

Evidence linking food restriction and food craving is equivocal. This study investigated whether dieting was associated with a greater frequency of food craving. Dieting to lose weight was distinguished from watching so as not to gain weight. Participants were 129 women (mean age=41 yrs): 52 were currently dieting to lose weight, 40 were watching their weight, and 37 were non-dieters. They completed a food craving record after every food craving, a food diary, and a daily mood assessment over 7-days. Of the 393 craving incidents recorded, dieters experienced significantly more food cravings than non-dieters, with watchers intermediate. Chocolate was the most craved food (37% of cravings) but neither the types of food, the proportion of cravings leading to eating (∼70%), the situations in which cravings occurred, nor the time since the last eating episode differed between groups. Compared with non-dieters, dieters experienced stronger cravings that were more difficult to resist, and for foods they were restricting eating. Watchers showed similarities in experience both to dieters (low hunger) and non-dieters (lower craving intensity). These results support an association between dieting and food craving, the usefulness of distinguishing dieting to lose weight and watching, and suggest a need for further experimental investigation of actual food restriction on food craving experiences.

Effects of cortisol on the laterality of the neural correlates of episodic memory.

Alterations in the laterality of cortical activity have been shown in depressive illnesses. One possible pathophysiological mechanism for this is an effect of corticosteroids. We have previously demonstrated that endogenous cortisol concentrations correlate with the asymmetry of cortical activity related to episodic memory in healthy subjects and depressed patients. To further-examine whether this is due to a causal effect of cortisol on the laterality of episodic memory, we studied the effect of exogenous administration of cortisol in healthy subjects. Twenty-three right-handed healthy male volunteers were tested in a double-blind cross-over study. Event-related potentials (ERPs) were recorded during an episodic memory task following a four-day course of 160mg/day cortisol or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the neurocognitive task. Cortisol levels were measured in saliva samples. ERP and LORETA analysis following placebo demonstrated significant left parahippocampal activation associated with successful retrieval. Cortisol led to a decrease in the mean early frontal ERP voltage and an increase in the late right ERP voltage. LORETA suggested this to be due to a significant increased late activation of the right superior frontal gyrus. There was no significant effect of cortisol on episodic memory performance. This study suggests that exogenous cortisol leads to more positive-going waveforms over the right than the left hemisphere, possibly due to increased monitoring of the products of retrieval. The results support the hypothesis of causal effects of cortisol on the laterality of cortical activity occurring during an episodic memory task.

Repeated cortisol administration attenuates the EEG response to buspirone in healthy volunteers: evidence for desensitization of the 5-HT1A autoreceptor.

It has previously been postulated that the therapeutic effect of antidepressants, particularly selective serotonin re-uptake inhibitors (SSRIs), is mediated by a down-regulation of somatodendritic (presynaptic) 5-HT(1A) autoreceptors with chronic treatment. Animal studies have revealed that repeated administration of corticosteroids similarly down-regulate this receptor. However, it has previously been difficult to explore if this receptor is similarly modulated in man in vivo. The objective of this study was to explore the effect of repeated administration of cortisol to healthy volunteers utilising a novel putative index of somatodendritic 5-HT(1A) autoreceptor function. This method involves the administration of the 5-HT(1A) agonist buspirone and observing the subsequent negative shift in the frequency spectrum of the electroencephalogram (EEG). Healthy male volunteers were treated with cortisol 20 mg, or placebo, orally twice daily for 7 days in a double-blind random-order crossover study. After each treatment period volunteers were administered buspirone 30 mg orally prior to EEG recordings. Following a week's treatment with placebo, buspirone led to a negative shift in the EEG frequency spectrum as previously reported. However, following treatment with cortisol, the effect of buspirone was significantly attenuated. This is consistent with corticosteroids having a similar effect on somatodendritic 5-HT(1A) autoreceptors in man as seen in rodents.

A study of the neural correlates of episodic memory and HPA axis status in drug-free depressed patients and healthy controls.

Altered laterality of cortical activity, neuropsychological impairment and hypercortisolaemia have been shown in depression. The neural correlates of episodic memory in healthy subjects demonstrate hemispheric laterality but it is not known whether this is affected by depression and/or hypercortisolaemia. Twenty-seven drug-free depressed patients and 29 matched healthy controls were studied. Event-related potentials (ERPs) were recorded during an episodic memory test. During the study phase, subjects heard words spoken in either a male or female voice. Old and new words were presented visually during a test phase, when subjects were requested to identify words as old or new and recollect the gender of the voice for old words. Cortisol levels were measured in saliva and plasma samples. The results showed a trend for elevated salivary cortisol concentration in depressed patients. Reaction times were significantly longer in patients; however, there was no difference in memory accuracy performance between the two groups. Recollection performance was found to be negatively correlated with age, with a similar trend for cortisol concentrations. ERP activity not specifically related to episodic memory retrieval recorded 200-500ms post-stimulus from controls showed a marked laterality, with higher voltages over the right hemisphere; however, was not seen in patients. There was significant correlation between cortisol and the laterality of the neural activity specifically related to episodic memory retrieval recorded 500-1400ms post-stimulus in both depressed and healthy groups. These unique findings demonstrate that while the laterality of the neural correlates of episodic memory is sensitive to cortisol, it is not altered by the non-specific laterality effects seen in depression.

Assessing cortisol and dehydroepiandrosterone (DHEA) in saliva: effects of collection method.

An increasing number of studies are utilizing saliva sampling as a method of assessing adrenal steroid secretion. Saliva samples have certain advantages over plasma, being non-invasive and easily collected. However, some methods of collection may compromise the accuracy of the assay, particularly those which employ aids to stimulate saliva production. We sought to compare the accuracy of cortisol and dehydroepiandrosterone (DHEA) measurement by examining the association between plasma levels, saliva and saliva collected using a citric acid-treated salivette device. Twenty six healthy male volunteers were recruited for the study. To increase the range of steroid levels in the samples collected, half the subjects were pre-treated with hydrocortisone (20mg, twice a day for 7 days) and half with placebo. Saliva samples were then collected from each subject using both a 'passive drool' method and a citric acid-treated salivette. A plasma sample was also collected. Cortisol and DHEA levels were measured by radioimmunoassay. For cortisol levels, both methods of saliva collection correlated highly with plasma levels and with each other (r 0.85; R(2) 0.72 for all). For DHEA levels, only saliva samples collected using the unstimulated collection method correlated with plasma levels. DHEA collected using the salivette device did not correlate significantly with either plasma or the unstimulated saliva (r 0.2;R(2) 0.04). It is crucial that future studies are aware of these issues and are cognizant of the effects of the method of collection when examining steroid levels in saliva.

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study.

RATIONALE: Dehydroepiandrosterone (DHEA) has been reported to enhance cognition in rodents, although there are inconsistent findings in humans. OBJECTIVES: The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential (ERP) technique. METHODS: Twenty-four healthy young men were treated with a 7-day course of oral DHEA (150 mg b.d.) or placebo in a double blind, random, crossover and balanced order design. Subjective mood and memory were measured using visual analogue scales (VASs). Cortisol concentrations were measured in saliva samples. ERPs were recorded during retrieval in an episodic memory test. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the cognitive task. RESULTS: DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration. LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo. DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex (ACC). CONCLUSIONS: DHEA treatment improved memory recollection and mood and decreased trough cortisol levels. The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing. These findings are distinctive, being the first to show such beneficial effects of DHEA on memory in healthy young men.

Development and validation of NEWSQOL, the Newcastle Stroke-Specific Quality of Life Measure.

BACKGROUND: A review of stroke-specific quality of life (QOL) measures indicated little evidence of their validity/reliability. PURPOSE: To describe the development/validation of a new measure - the Newcastle Stroke-Specific Quality of Life Measure (NEWSQOL). METHODS: Phase I: qualitative interviews (28 stroke patients) determined QOL issues for inclusion in the measure. Initial items/response categories were pre-tested (30 patients). Administration of the NEWSQOL in the item reduction stage (100 patients) identified poorly performing items and factor analysis showed likely domains. Internal consistency was examined. Phase II: NEWSQOL and comparator measures were administered (106 patients) to examine validity/test-retest reliability. RESULTS: Phase I: 140 items were identified for initial inclusion. Qualitative pre-testing led to an extensive revision. Item reduction resulted in a final measure of 56 items in 11 domains (feelings, activities of daily living/self-care, cognition, mobility, emotion, sleep, interpersonal relationships, communication, pain/sensation, vision, fatigue; Cronbach's alpha = 0.71-0.90). Phase II: NEWSQOL domain scores, except cognition, were moderately/highly correlated (0.45-0.76) with relevant comparator measures. NEWSQOL domains feelings, communication and cognition low/moderately correlated with Barthel Index scores (-0.49 to -0.28), as predicted. Test-retest reliability was high (intraclass correlation coefficient range 0.78-0.92). CONCLUSIONS: NEWSQOL is an acceptable, patient-derived, interviewer-administered, stroke-specific QOL measure with evidence of reliability and validity, making it a promising instrument for assessing QOL after stroke. Involvement of relevant patients in determining the content and format considerably enhances confidence in its validity.

Effects of acute tryptophan depletion on executive function in healthy male volunteers.

BACKGROUND: Neurocognitive impairment is frequently described in a number of psychiatric disorders and may be a direct consequence of serotonergic dysfunction. As impairments in executive functions are some of the most frequently described, the purpose of this study was to examine the performance of normal volunteers on a range of executive tasks following a transient reduction of central serotonin (5-HT) levels using the method of acute tryptophan depletion (ATD). METHODS: Fifteen healthy male subjects participated in a within-subject, double-blind, counterbalanced crossover study. ATD was induced by ingestion of a 100 g amino-acid drink. Executive function was evaluated using the Wisconsin Card Sorting Test, Stroop, Verbal Fluency and Trail Making. Visual analogue scales were administered to assess mood. RESULTS: Plasma free and total tryptophan concentrations were significantly reduced by the depleting drink (P < 0.001). ATD selectively improved motor speed/ attention on the Trails A test (P = 0.027), with no effect on subjective ratings of mood. Interaction effects between drink and the order of drink administration were observed on most neurocognitive tests. CONCLUSIONS: The improvement in simple motor speed/ attention following ATD is in keeping with the ascribed role of 5-HT in the cortex, however performance on tests of executive function is not robustly altered. The presence of interaction effects on most tasks suggests that subtle changes may occur but are masked, possibly by simple learning effects, in the context of a crossover design. This has implications for the design of future studies, particularly those examining executive functions.