Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for Chronic Daily Headache: Protocol for a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity.</p> <p>Methods</p> <p>Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks.</p> <p>Results</p> <p>Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/(NCT01157208)">(NCT01157208)</a></p

Semantic control deficits impair understanding of thematic relationships more than object identity

Recent work has suggested a potential link between the neurocognitive mechanisms supporting the retrieval of events and thematic associations (i.e., knowledge about how concepts relate in a meaningful context) and semantic control processes that support the capacity to shape retrieval to suit the circumstances. Thematic associations and events are inherently flexible: the meaning of an item changes depending on the context (for example, lamp goes with reading, bicycle and police). Control processes might stabilise weak yet currently-relevant interpretations during event understanding. In contrast, semantic retrieval for objects (to understand what items are, and the categories they belong to) is potentially constrained by sensory-motor features (e.g., bright light) that change less across contexts. Semantic control and event understanding produce overlapping patterns of activation in healthy participants in left prefrontal and temporoparietal regions, but the potential causal link between these aspects of semantic cognition has not been examined. We predict that event understanding relies on semantic control, due to associations being necessarily context-dependent and variable. We tested this hypothesis in two ways: (i) by examining thematic associations and object identity in patients with semantic aphasia, who have well-documented deficits of semantic control following left frontoparietal stroke and (ii) using the same tasks in healthy controls under dual-task conditions that depleted the capacity for cognitive control. The patients were impaired on both identity and thematic matching tasks, and they showed particular difficulty on non-dominant thematic associations which required greater control over semantic retrieval. Healthy participants showed the same pattern under conditions of divided attention. These findings support the view that semantic control is necessary for organising and constraining the retrieval of thematic associations

Semantic control deficits impair understanding of thematic relationships more than object identity

Recent work has suggested a potential link between the neurocognitive mechanisms supporting the retrieval of events and thematic associations (i.e., knowledge about how concepts relate in a meaningful context) and semantic control processes that support the capacity to shape retrieval to suit the circumstances. Thematic associations and events are inherently flexible: the meaning of an item changes depending on the context (for example, lamp goes with reading, bicycle and police). Control processes might stabilise weak yet currently-relevant interpretations during event understanding. In contrast, semantic retrieval for objects (to understand what items are, and the categories they belong to) is potentially constrained by sensory-motor features (e.g., bright light) that change less across contexts. Semantic control and event understanding produce overlapping patterns of activation in healthy participants in left prefrontal and temporoparietal regions, but the potential causal link between these aspects of semantic cognition has not been examined. We predict that event understanding relies on semantic control, due to associations being necessarily context-dependent and variable. We tested this hypothesis in two ways: (i) by examining thematic associations and object identity in patients with semantic aphasia, who have well-documented deficits of semantic control following left frontoparietal stroke and (ii) using the same tasks in healthy controls under dual-task conditions that depleted the capacity for cognitive control. The patients were impaired on both identity and thematic matching tasks, and they showed particular difficulty on non-dominant thematic associations which required greater control over semantic retrieval. Healthy participants showed the same pattern under conditions of divided attention. These findings support the view that semantic control is necessary for organising and constraining the retrieval of thematic associations

Hydroxychloroquine in the pregnancies of women with lupus: a meta-analysis of individual participant data

ObjectiveMultiple guidelines recommend continuing hydroxychloroquine (HCQ) for SLE during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to identify the potential benefits and harms of HCQ use within lupus pregnancies.MethodsEligible studies included prospectively collected pregnancies in women with lupus. After a systematic literature search, seven datasets meeting inclusion criteria were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset, and results were aggregated to provide a pooled OR.ResultsSeven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a first trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared with pregnancies without HCQ, those with HCQ had lower odds of highly active lupus, but did not have different odds of fetal loss, preterm delivery or pre-eclampsia. Among women with low lupus activity, HCQ reduced the odds of preterm delivery.ConclusionsThis large study of prospectively-collected lupus pregnancies demonstrates a decrease in lupus activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy

The effects of a novel "fluid loading" strategy on cardiovascular and haematological responses to orthostatic stress

Water drinking reduces the occurrence of syncope in healthy volunteers but the effects of hyperhydration are unknown. This study assessed the effects of combined creatine (Cr) and glycerol (Gly) induced hyperhydration on the cardiovascular and haematological responses to postural change. Subjects in all trials lay supine for 30 min before being tilted head-up to 70&#176; for a further 30 min or until the limit of their tolerance. Following 2 baseline trials, 19 subjects were matched for body mass and assigned to ingest either 20 g Cr and 2 g Gly kg-1 body mass (BM) plus 2 l of water or 2 l of water alone (Pl) each day for 6 days and once more 5 h prior to the experimental trial. Subjects ingested 500 ml of water prior to all trials to ensure euhydration. During baseline trials, 3 subjects in the Cr/Gly group and 2 in the Pl group experienced presyncope during head-up tilt. Following Cr/Gly supplementation, BM increased by (mean &#177; S.D.) 0.9 &#177; 0.3 and total body water (TBW) increased by 0.7 &#177; 0.2 l with no change in the Pl group. Cr/Gly supplementation resulted in a significant increase in systolic (11 mmHg) and diastolic (7 mmHg) blood pressure during head-up tilt with no change following Pl supplementation. Cr/Gly. Following Cr/Gly supplementation the number of subjects who became presyncopal was reduced from 3 to 1, with no change in the Pl group. These data suggest that hyperhydration mediated by Cr and Gly can enhance orthostatic tolerance in healthy individual