The Effect of Organophosphate Exposure on Neuronal Cell Coenzyme Q10 Status.

Organophosphate (OP) compounds are widely used as pesticides and herbicides and exposure to these compounds has been associated with both chronic and acute forms of neurological dysfunction including cognitive impairment, neurophysiological problems and cerebral ataxia with evidence of mitochondrial impairment being associated with this toxicity. In view of the potential mitochondrial impairment, the present study aimed to investigate the effect of exposure to commonly used OPs, dichlorvos, methyl-parathion (parathion) and chloropyrifos (CPF) on the cellular level of the mitochondrial electron transport chain (ETC) electron carrier, coenzyme Q10 (CoQ10) in human neuroblastoma SH-SY5Y cells. The effect of a perturbation in CoQ10 status was also evaluated on mitochondrial function and cell viability. A significant decreased (P < 0.0001) in neuronal cell viability was observed following treatment with all three OPs (100 µM), with dichlorvos appearing to be the most toxic to cells and causing an 80% loss of viability. OP treatment also resulted in a significant diminution in cellular CoQ10 status, with levels of this isoprenoid being decreased by 72% (P < 0.0001), 62% (P < 0.0005) and 43% (P < 0.005) of control levels following treatment with dichlorvos, parathion and CPF (50 µM), respectively. OP exposure was also found to affect the activities of the mitochondrial enzymes, citrate synthase (CS) and mitochondrial electron transport chain (ETC) complex II+III. Dichlorvos and CPF (50 µM) treatment significantly decreased CS activity by 38% (P < 0.0001) and 35% (P < 0.0005), respectively compared to control levels in addition to causing a 54% and 57% (P < 0.0001) reduction in complex II+III activity, respectively. Interestingly, although CoQ10 supplementation (5 µM) was able to restore cellular CoQ10 status and CS activity to control levels following OP treatment, complex II+III activity was only restored to control levels in neuronal cells exposed to dichlorvos (50 µM). However, post supplementation with CoQ10, complex II+III activity significantly increased by 33% (P < 0.0005), 25% (P < 0.005) and 35% (P < 0.0001) in dichlorvos, parathion and CPF (100 µM) treated cells respectively compared to non-CoQ10 supplemented cells. In conclusion, the results of this study have indicated evidence of neuronal cell CoQ10 deficiency with associated mitochondrial dysfunction following OP exposure. Although CoQ10 supplementation was able to ameliorate OP induced deficiencies in CS activity, ETC complex II+III activity appeared partially refractory to this treatment. Accordingly, these results indicate the therapeutic potential of CoQ10 supplementation in the treatment of OP poisoning. However, higher doses may be required to engender therapeutic efficacy.

Guidelines International Network: toward international standards for clinical practice guidelines.

Guideline development processes vary substantially, and many guidelines do not meet basic quality criteria. Standards for guideline development can help organizations ensure that recommendations are evidence-based and can help users identify high-quality guidelines. Such organizations as the U.S. Institute of Medicine and the United Kingdom's National Institute for Health and Clinical Excellence have developed recommendations to define trustworthy guidelines within their locales. Many groups charged with guideline development find the lengthy list of standards developed by such organizations to be aspirational but infeasible to follow in entirety. Founded in 2002, the Guidelines International Network (G-I-N) is a network of guideline developers that includes 93 organizations and 89 individual members representing 46 countries. The G-I-N board of trustees recognized the importance of guideline development processes that are both rigorous and feasible even for modestly funded groups to implement and initiated an effort toward consensus about minimum standards for high-quality guidelines. In contrast to other existing standards for guideline development at national or local levels, the key components proposed by G-I-N will represent the consensus of an international, multidisciplinary group of active guideline developers. This article presents G-I-N's proposed set of key components for guideline development. These key components address panel composition, decision-making process, conflicts of interest, guideline objective, development methods, evidence review, basis of recommendations, ratings of evidence and recommendations, guideline review, updating processes, and funding. It is hoped that this article promotes discussion and eventual agreement on a set of international standards for guideline development.

Work-based learning in health and social care.

This article examines some of the issues encountered in helping to develop and facilitate work-based learning (WBL) in clinical areas from the author's perspective of APEL/WBL co-ordinator. The advantages of work-based learning to both organisations and practitioners are discussed, together with possible drawbacks. The article concludes by identifying the positive aspects, including that of practice development, but suggests caution in attempting to use work-based learning in all circumstances.

Heavy and light beer: a carbon isotope approach to detect C(4) carbon in beers of different origins, styles, and prices.

The carbon isotope ratios (delta(13)C) of 160 beers from around the world ranged from -27.3 to -14.9 per thousand, primarily due to variation in the percentage of C(3) or C(4) plant carbon in the final product. Thirty-one percent of beers had a carbon signature of C(3) plants (barley, rice, etc.), whereas the remaining 69% contained some C(3)-C(4) mixture (mean of mixtures, 39 +/- 11% C(4) carbon). Use of C(4) carbon (corn, cane sugar, etc.) was not confined to beers from any particular region (Pacific Rim, Mexico, Brazil, Europe, Canada, and the United States). However, the delta(13)C of European beers indicated mostly C(3) plant carbon. In contrast, U.S. and Canadian beers contained either only C(3) or C(3)-C(4) mixtures; Brazilian, Mexican, and Pacific Rim beers were mostly C(3)-C(4) mixtures. Among different lagers, U.S.-style lagers generally contained more C(4) carbon than did imported pilsners. Among different ales, those brewed by large high-production breweries contained significant proportions of C(4) carbon, while C(4) carbon was not detected in microbrewery or home-brew ales. Furthermore, inexpensive beers generally contained more C(4) carbon than expensive beers.

Cochlear implant candidacy and performance trends in children.

Data from Clarion cochlear implant pediatric clinical trials were examined retrospectively to uncover trends in candidacy and postimplant benefit over time. In particular, age at implantation, educational setting, and communication mode were examined with respect to speech perception performance after implantation. The results showed that 1) age at implantation is decreasing, 2) children in oral education programs obtain more benefit from a cochlear implant than children in total communication programs, 3) children who undergo implantation before 2 years of age show greater benefit than children who undergo implantation between 2 and 3 years of age, 4) more younger children are using oral communication than older children, and 5) more children with good auditory skills before implantation and more residual hearing are undergoing implantation. In sum, in the 11 years since implants have been available to children in the United States, candidacy criteria have evolved and benefit has increased as cochlear implant technology has advanced.

Understanding dementia amongst people in minority ethnic and cultural groups.

AIM: This paper is a report of a study to explore perceptions of ageing, dementia and ageing-associated mental health difficulties amongst British people of Punjabi Indian origin. BACKGROUND: People from ethnic minorities are often under-represented in mental health services. Contributing factors may include lack of knowledge of dementia in these communities, lack of detection in primary care, expectations of family care and lack of appropriate services. For this to change, greater knowledge is needed about awareness and conceptualization of dementia in minority ethnic communities. METHOD: A focus-group study was conducted between 2001 and 2003 with 49 English-, Hindi- and Punjabi-speaking British South Asians, aged 17-61 years. Views of ageing and ageing-associated difficulties were explored in initial groups. In a second set of groups, vignettes were used for more specific exploration of awareness and understanding of dementia. Data were subjected to thematic analysis. FINDINGS: Ageing was seen as a time of withdrawal and isolation, and problems as physical or emotional; cognitive impairment was seldom mentioned. There was an implication that symptoms of dementia partly resulted from lack of effort by the person themselves and possibly from lack of family care. Therefore people should overcome their own problems and family action might be part of the solution. There was a sense of stigma and a lack of knowledge about mental illness and services, alongside disillusionment with doctors and exclusion from services. CONCLUSION: Health promotion and health interventions delivered with respect for the cultural context are needed, as well as education of healthcare professionals about South Asian conceptualizations of dementia.