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Background: This systematic review aimed to evaluate the impact of nutrition interventions on participant reported pain severity and intensity in populations with chronic pain. Methods: Eight databases were systematically searched for studies that included adult populations with a chronic pain condition, a nutrition intervention and a measure of pain. Where possible, data were pooled using meta‐analysis. Seventy‐one studies were included, with 23 being eligible for meta‐analysis. Results: Studies were categorised into four groups: (i) altered overall diet with 12 of 16 studies finding a significant reduction in participant reported pain; (ii) altered specific nutrients with two of five studies reporting a significant reduction in participant reported pain; (iii) supplement‐based interventions with 11 of 46 studies showing a significant reduction in pain; and (iv) fasting therapy with one of four studies reporting a significant reduction in pain. The meta‐analysis found that, overall, nutrition interventions had a significant effect on pain reduction with studies testing an altered overall diet or just one nutrient having the greatest effect. Conclusions: This review highlights the importance and effectiveness of nutrition interventions for people who experience chronic pain. [ABSTRACT FROM AUTHOR]

Key points The in vivo fetal cardiovascular defence to chronic hypoxia has remained by and large an enigma because no technology has been available to induce significant and prolonged fetal hypoxia whilst recording longitudinal changes in fetal regional blood flow as the hypoxic pregnancy is developing., We introduce a new technique able to maintain chronically instrumented maternal and fetal sheep preparations under isobaric chronic hypoxia for most of gestation, beyond levels that can be achieved by high altitude and of relevance in magnitude to the human intrauterine growth-restricted fetus., This technology permits wireless recording in free-moving animals of longitudinal maternal and fetal cardiovascular function, including beat-to-beat alterations in pressure and blood flow signals in regional circulations., The relevance and utility of the technique is presented by testing the hypotheses that the fetal circulatory brain sparing response persists during chronic fetal hypoxia and that an increase in reactive oxygen species in the fetal circulation is an involved mechanism., Abstract Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l−1, P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species. [ABSTRACT FROM AUTHOR]

Objective To gain an 'in-depth' understanding of patients' concerns and their related coping strategies during the genetic risk assessment process. Methods Participants were the 'usual care' arm of a trial of a coping intervention targeted at men and women undergoing assessment of genetic risk for familial cancer. Participants completed questionnaires measuring the degree to which they experienced up to 11 concerns and which of 8 coping strategies they used to respond to each of them at entry into the programme and 1 month subsequently (before they received their risk information). Findings A majority of participants were at least 'quite worried' about all the identified concerns, although the levels of concern fell over the waiting period. Participants used several strategies in response to their varying concerns - although a primary coping strategy for each concern was identifiable. The emotion-focused strategies of acceptance and positive appraisal were generally used in response to concerns they could not change, and seeking social support was used primarily to gain information, but not emotional support from their family. Cluster analysis identified three unique clusters of coping responses. Conclusions Genetic risk assessment comprises a number of different stressors each of which is coped with using different strategies. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Purpose: The acute effects of PGE(2) on bladder smooth muscle and nerves were examined to determine the origin of PGE(2)-induced spontaneous rhythmic contractions.Experimental Approach: Contraction studies, confocal Ca(2+) imaging and electrophysiological recordings in strips of mouse urinary bladder were used to differentiate the effects of PGE(2) on bladder smooth muscle and efferent nerves.Key Results: PGE(2) (50 µM) increased the tone and caused phasic contractions of detrusor smooth muscle strips. Confocal Ca(2+) imaging showed that PGE(2) increased the frequency of whole-cell Ca(2+) transients (WCTs) (72 ± 5%) and intracellular recordings showed it increased the frequency of spontaneous depolarizations, from 0.31·s(-1) to 0.90·s(-1). Non-selective inhibition of EP receptors using SC-51322 and AH-6809 (10 µM), or the L-type Ca(2+) channel blocker nifedipine (1 µM), prevented these phasic contractions and WCTs, and reduced the tone (by 45 ± 7% and 59 ± 6%, respectively). Blocking P2X1 receptors with NF449 (10 µM) caused a small but significant reduction in the frequency of PGE(2)-induced phasic contractions (24 ± 9%) and WCTs (28 ± 17%) but had no significant effect on spontaneous depolarizations or tone. Inhibiting muscarinic receptors with cyclopentolate (1 µM) had no significant effect on these measures. Spontaneous WCTs became synchronous in PGE(2), implying enhanced functional coupling between neighbouring cells. However, the electrical input resistance was unchanged.Conclusions and Implications: It was concluded that depolarization alone is sufficient to explain a functional increase in intercellular coupling and the ability of PGE(2) to increase detrusor spontaneous rhythmic activity does not require parasympathetic nerves. [ABSTRACT FROM AUTHOR]

Objectives: There is little evidence regarding the long-term psychological implications of breast cancer risk assessment for women at moderate genetic risk. A follow-up study of a trial cohort was conducted to evaluate psychological outcomes and their predictors at 6-year follow-up. A further aim was to examine threshold scores for high cancer worry. Methods: Questionnaires were sent to 384 women assessed as moderate risk during a UK trial of genetic assessment (TRACE). Measures included cancer worry, perceived risk, health behaviours, general anxiety, psychological morbidity, optimism, and background variables assessed during TRACE and at 6-year follow-up. Results: Reductions from baseline cancer worry and breast self-examination (BrSE) frequency were maintained 6 years after risk assessment, with relatively consistent levels over short- and long-term follow-up. Provision of risk information led to short-term reductions in perceived risk. During the 6-year period, 43% of women reported having made lifestyle changes and 27% had requested a mammogram. Baseline and post-risk cancer worry were the only significant predictors of long-term cancer worry. Greater worry at baseline predicted more frequent BrSE and higher perceived risk, but not lifestyle change or mammogram requests, at 6 years. Eighteen percent of women reported cancer worry above a threshold of 12.5 at long-term follow-up, compared with 30% at baseline. Conclusions: Overall reductions in cancer worry following moderate risk assessment were maintained in the long term. However, women at risk of sustained high cancer worry should be identified at an early stage in the risk assessment process for more intensive psycho-educational intervention. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: Generic measures of coping fail to capture the process of undergoing specific health processes such as cancer genetic risk assessment. The Genetic Risk Assessment Coping Evaluation (GRACE) has been developed to provide greater specificity of measurement. Method: Based upon previous research findings, the GRACE measures the degree of stress associated with 11 recognised sources of stress for individuals undergoing the early stages of cancer genetic risk assessment, and the use of up to eight coping strategies they may elicit. This paper reports preliminary data from the piloting of the GRACE within a randomised trial of a coping intervention. Results: Of the 265 participants who completed and returned their baseline questionnaire (prior to being informed of their level of genetic risk), 257 completed the GRACE. The most highly endorsed sources of stress involved concerns relating to family members, endorsed by over 60% of respondents, and concerns about how the participants would cope if found to be at increased risk (59%). Participants made use of multiple coping strategies across different sources of stress. The most frequently reported coping strategies were emotion-focused, which may reflect the stage of the assessment process. Conclusion: The completion rates for the matrix and specificity of responses provided suggest that the GRACE may be an acceptable measurement tool. Further data collection and validation is ongoing. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

AIMS: To identify how women adjusted to living at intermediate risk of breast cancer six years following risk assessment, and what factors contributed to health service usage. METHOD: Two studies are reported. Both report data from a cohort of women found at intermediate risk of breast cancer six years previously. In the first, 30 women with a range of Cancer Worry Scale (Lerman et al. Health Psychol 1991;10:259-267) scores were interviewed about how they lived with their risk of cancer and their use of health resources. The generalisability of these findings was tested in a sample of 387 women from the same cohort using psychometrically appropriate measures. FINDINGS: In study 1, women scoring above the median baseline BCWS scale score were most likely to perceive their family history as a burden, exaggerate their susceptibility to breast cancer, not be reassured by genetic counselling, be focussed on the need for mammographic screening, and have a low reliance on breast self-examination. Key findings of the second study were that over a quarter of the cohort were experiencing at least moderate levels of intrusive worries. Worries were associated with perceptions of high personal vulnerability to and severity of cancer and breast cancer being highly salient. Women aged over 50 years with high levels of worry-related distress were most likely to request a mammogram. CONCLUSION: The high levels of distress in this cohort reinforce the need to provide appropriate interventions for vulnerable women following risk assessment. [ABSTRACT FROM AUTHOR]

Determining whether ATP and noradrenaline are released from the same vesicle at mature autonomic neuroeffector junctions is challenging because of the difficulty of simultaneously detecting the packeted release of these neurotransmitters. Contraction, overflow and electrophysiology experiments all show that both ATP and noradrenaline are released following field stimulation (although the ratio might vary) from autonomic nerves in tissues including the vas deferens, rat tail artery and mesenteric artery. The occurrence of purinergic neuroeffector Ca2+ transients (NCTs) has been used to detect the packeted release of the neurotransmitter ATP acting on postjunctional P2X receptors to cause Ca2+ influx. Neuroeffector Ca2+ transients can also be used to detect the local effects of noradrenaline through its α2-adrenoceptor-mediated prejunctional autoinhibitory effects on nerve terminal Ca2+ concentration and the probability of exocytosis (measured by counting NCTs). Evidence is presented that exocytosis from sympathetic varicosities does not occur in a manner independent of the history of that varicosity, but rather that the release of a packet of ATP transiently suppresses (or predicts the transient suppression of) subsequent release. This could arise by autoinhibition (by the prejunctional action of noradrenaline or purines) or due to a transient shortage of vesicles readily available for release. In summary, two high-resolution approaches are proposed to measure the intermittent release of packets of neurotransmitter: (1) local transient suppression of nerve terminal Ca2+ transients; and (2) the local and transient inhibition of NCTs to infer local autoinhibition, hence transmitter release. Such approaches may allow the packeted corelease of ATP and noradrenaline to be investigated without the need to measure both neurotransmitters directly. [ABSTRACT FROM AUTHOR]

Objective: This longitudinal study investigated pre-screening factors that predicted breast cancer-specific distress among 1286 women who were undergoing annual mammography screening as part of a UK programme for younger women (i.e., under 50) with a family history of breast cancer. Methods: Women completed questionnaires one month prior to screening, and one and six months after receiving screening results. Factors measured were breast cancer worry, perceived risk, cognitive appraisals, coping, dispositional optimism, and background variables relating to screening history and family history. Results: Pre-screening cancer worry was the most important predictor of subsequent worry, explaining 56/61% and 54/57% of the variance at one and six months follow-up, respectively. Other salient pre-screening predictors included high perceived risk of breast cancer, appraisals of high relevance and threat associated with the family history, and low perceived ability to cope emotionally. Women who had previously been part of the screening programme and those with a relative who had recently died from breast cancer were also vulnerable to longer-term distress. A false positive screening result, pessimistic personality, and coping efforts relating to religion and substance use predicted outcomes of screening at one month follow-up, but were not predictive in the longer-term. Conclusion: Early intervention to ameliorate high levels of cancer-related distress and negative appraisals would benefit some women as they progress through the familial breast screening programme. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study identified levels of distress, and predictors of levels of distress, in women undergoing assessment for genetic risk of breast/ovarian cancer based on their family history. It comprised a cohort study following 154 women who completed questionnaires at entry into a cancer genetic assessment programme and following risk provision. Independent significant associates of anxiety following risk provision were age, neuroticism, feeling hopeless about developing cancer, a perceived lack of control over developing cancer, lack of a social confidant, and a coping response involving acceptance/resignation. Depression was associated with age, neuroticism, feeling hopeless about developing cancer, lack of social confidant, and a coping response involving acceptance/resignation. To avoid high levels of psychological morbidity in future cohorts undergoing cancer genetic risk assessment, information should be given that emphasises that some degree of control over health outcomes through behaviour change or increased surveillance is possible. [ABSTRACT FROM AUTHOR]

Background and purpose:The antidysrhythmic bretylium is useful experimentally because it selectively abolishes neurotransmitter release from sympathetic peripheral nerve terminals. Its mechanism of action seemed settled, but recent results from optical monitoring of single terminals now suggests a new interpretation.Experimental approach:Orthograde transport of a dextran-conjugated Ca2+ indicator to monitor Ca2+ in nerve terminals of mouse isolated vas deferens with a confocal microscope. In some experiments, local neurotransmitter release was detected by monitoring neuroeffector Ca2+ transients (NCTs) in adjacent smooth muscles, a local measure of purinergic transmission. Sympathetic terminals were identified with catecholamine fluorescence (UV excitation) or post-experiment immunohistochemistry.Key results:Bretylium (10 μM) abolished NCTs at 60/61 junctions over the course of 2 h, indicating effective abolition of neurotransmitter release. However, bretylium did not abolish the field stimulus-induced Ca2+ transient in most nerve terminals, but did increase both action potential delay (by 2±0.4 ms) and absolute refractory period (by 4±2 ms). Immunohistochemistry demonstrated that 85–96% of terminals orthogradely filled with a dextran-conjugated fluorescent probe contained Neuropeptide Y (NPY). A formaldehyde–glutaraldehyde-induced catecholamine fluorescence (FAGLU) technique was modified to allow sympathetic terminals to be identified with a Ca2+ indicator present. Most terminals contained catecholamines (based on FAGLU) or secrete ATP (as NCTs in adjacent smooth muscle cells are abolished).Conclusions and implications:Bretylium can inhibit neurotransmitter release downstream of Ca2+ influx without abolishing the nerve terminal action potential. Bretylium-induced increases in the absolute refractory period permit living sympathetic terminals to be identified.British Journal of Pharmacology (2008) 153, 831–839; doi:10.1038/sj.bjp.0707623; published online 10 December 2007 [ABSTRACT FROM AUTHOR]

This multi-centre study examined factors associated with breast cancer-specific distress in 2321 women under 50 who are on a mammographic screening programme on account of their family history. Women were recruited from 21 UK centres, and completed a questionnaire one month before their screening appointment. The transactional theory of stress, appraisal, and coping provided the theoretical framework for the study. Factors measured included screening history, family history, perceived risk, cognitive appraisals, coping, optimism, and cancer worry. The findings indicate that the majority of women appraise their family history as being relevant and somewhat threatening to personal well-being, but something they can deal with emotionally. Acceptance was the most commonly used coping strategy. Hierarchical regression analysis identified that the factors most significantly associated with distress were an appraisal of high relevance and threat, increased risk perception, low dispositional optimism, and the use of both avoidant and task-orientated coping strategies. Women with children and those with relatives who have died from breast cancer were also more distressed. To conclude, most women appraised their situation positively but there is a potential profile of risk factors which may help clinicians identify those women who need extra psychological support as they progress through screening. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Individuals undergoing cancer genetic risk assessment have been found to have a poor understanding of the process, which may affect how well they cope with learning their risk. This paper reports free-text data from questionnaires completed by women undergoing a randomised controlled trial of a psychological intervention. Of the 268 women undergoing genetic assessment for familial breast/ovarian cancer risk who were invited to take part in the trial, 157 women returned research questionnaires. Of these, 97 women provided free-text comments upon referral to a cancer genetics clinic, 62 provided comments whilst waiting for risk information (average, moderate or high), and 36 women provided comments following notification of risk. This paper reports a thematic analysis of the free-text data. Themes reflected individuals' poor knowledge and uncertainty about genetic risk assessment. How well individuals responded to learning their risk depended upon whether expectations had been met. Regardless of risk, individuals undergoing cancer genetic risk assessment are likely to benefit from increased information about its process and timescales, and access to increased psychological support. Free-text comments can provide valuable data about individuals' expectations and knowledge of genetics services. [ABSTRACT FROM AUTHOR]

Background and Purpose: Nicotinic agonists increase sympathetic field-stimulus-evoked contraction of the rodent vas deferens, presumably by increasing evoked neurotransmitter release. This presumption was tested in two species.Experimental Approach: The effect of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine on neurotransmitter release in mouse and guinea pig isolated vas deferens was investigated using contraction studies and conventional intracellular recording techniques.Key Results: In 12 of 14 mouse vasa deferentia, slow bath application of epibatidine (100 nM) had no significant effect on excitatory junction potential (EJP) amplitude and spontaneous EJP (SEJP) frequency. However, rapid application of epibatidine to the mouse vas deferens caused an increase in SEJP frequency (by 530%), with no effect on EJP amplitude. Despite the absence of an effect on EJPs, electrically-evoked contractions of the mouse vas deferens were significantly increased in the presence of epibatidine (by 50%). A transient contraction was reliably induced by a higher epibatidine concentration (1 microM). This contraction was significantly reduced in the presence of prazosin, tetrodotoxin, or alpha,beta-methyleneATP. Epibatidine did not induce a contraction in the presence of a combination of prazosin, alpha,beta-methyleneATP and cyclopentolate. In guinea pig vasa deferentia, bath-applied epibatidine potentiated EJP amplitude in a biphasic pattern, lasting for at least 30 minutes.Conclusion and Implications: The nAChR-mediated augmentation of neurogenic contraction is indeed prejunctional, but in the mouse arises from an increase in spontaneous neurotransmitter release that primes smooth muscle for subsequent contraction, while in the guinea pig there is a direct augmentation of evoked neurotransmitter (ATP) release. [ABSTRACT FROM AUTHOR]

Brain K, Sivell S, Bennert K, Howell L, France L, Jordan S, Rogers MT, Gray J, Sampson J. An exploratory comparison of genetic counselling protocols for HNPCC predictive testing. Most UK genetics centres offering predictive testing for hereditary non-polyposis colorectal cancer (HNPCC) use an extended counselling protocol originally developed for Huntington's disease. Shortened counselling may be more appropriate in the context of treatable genetic conditions such as HNPCC. Twenty-six high-risk individuals were randomized to extended genetic counselling (two sessions of education and reflection held 1 month apart) or shortened genetic counselling (a single educational session) prior to HNPCC testing. Prospective questionnaires, interviews and transcripts of counselling sessions were analysed. Participants were unsure what to expect prior to genetic counselling and had already decided to undergo genetic testing. There was no evidence of psychological harm caused by shortened genetic counselling, with a high level of satisfaction with the counselling received in both groups. Reflective counselling occurred in both groups but was framed in terms of practical action and information. Participants expressed differing preferences for the level of information received. This exploratory study indicates that shortened genetic counselling may be an appropriate means of supporting decisions already made by individuals about HNPCC testing. However, participants would benefit from preparatory information to help them reflect on issues not previously considered, which can then be explored more fully as part of a tailored counselling approach. [ABSTRACT FROM AUTHOR]

Predictive testing for hereditary non-polyposis colorectal cancer (HNPCC) is typically offered within an extended genetic counselling protocol, originally developed in the context of Huntington's Disease. We conducted a questionnaire survey of 20 UK regional genetics centres to obtain evidence regarding current approaches to HNPCC pre-test counselling. Centres were asked to describe the structure and content of pre-test counselling and their views on shortening the protocol. Sixteen centres responded to the survey. Four centres were considering shortening the protocol or had already done so. The remaining centres followed an extended protocol of two sessions separated by a 1-month period for reflection, although two centres conceded that the protocol had been reduced in certain cases. Different centres used different terminology to describe the content of pre-test counselling. Although content areas relating to education or impact of test results were covered more frequently than those relating to reflection, there was a marked tendency to consider all three areas as essential and to use both educational and reflective counselling, even in those centres that favoured a shortened protocol. This apparent dilemma highlights both the practical difficulty of how to shorten HNPCC pre-test counselling protocols and the need for controlled trials of different approaches. [ABSTRACT FROM AUTHOR]

Genetic testing is now feasible for a growing number of cancers. Although the implications for unaffected relatives have been widely described, the impact of the tests on affected individuals are often not recognized. We present and discuss four cases that highlight some of the issues-for example, feelings of guilt and anxiety; intrafamilial conflict, and support needs-that may arise in testing affected individuals. We offer some suggestions to aid in the approach to such testing. [ABSTRACT FROM AUTHOR]