Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients

Background: The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10) in brain tissue of multiple system atrophy (MSA) patients differ from those in elderly controls and in patients with other neurodegenerative diseases. Methods: Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA) type, 6 striatonigral degeneration (SND) type, and 5 mixed type] was used for this study. Elderly controls (n = 37) as well as idiopathic Parkinson's disease (n = 7), dementia with Lewy bodies (n = 20), corticobasal degeneration (n = 15) and cerebellar ataxia (n = 18) patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography. Results: We detected a statistically significant decrease (by 3–5%) in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001), specifically in OPCA (P = 0.001) and mixed cases (P = 0.005), when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001), idiopathic Parkinson's disease (P<0.001), corticobasal degeneration (P<0.001), and cerebellar ataxia (P = 0.001)]. Conclusion: Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated

Developing a matrix to identify and prioritise research recommendations in HIV Prevention

BACKGROUND: HIV prevention continues to be problematic in the UK, as it does globally. The UK Department of Health has a strategic direction with greater focus on prevention as part of its World Class Commissioning Programme. There is a need for targeted evidence-based prevention initiatives. This is an exploratory study to develop an evidence mapping tool in the form of a matrix: this will be used to identify important gaps in contemporary HIV prevention evidence relevant to the UK. It has the potential to aid prioritisation in future research.METHODS: Categories for prevention and risk groups were developed for HIV prevention in consultation with external experts. These were used as axes on a matrix tool to map evidence. Systematic searches for publications on HIV prevention were undertaken using electronic databases for primary and secondary research undertaken mainly in UK, USA, Canada, Australia and New Zealand, 2006-9. Each publication was screened for inclusion then coded. The risk groups and prevention areas in each paper were counted: several publications addressed multiple risk groups. The counts were exported to the matrix and clearly illustrate the concentrations and gaps of literature in HIV prevention.RESULTS: 716 systematic reviews, randomised control trials and other primary research met the inclusion criteria for HIV prevention. The matrix identified several under researched areas in HIV prevention.CONCLUSIONS: This is the first categorisation system for HIV prevention and the matrix is a novel tool for evidence mapping. Some important yet under-researched areas have been identified in HIV prevention evidence: identifying the undiagnosed population; international adaptation; education; intervention combinations; transgender; sex-workers; heterosexuals and older age groups.<br/

Dietary Supplements and Sports Performance: Amino Acids

This is the third in a series of six articles to discuss the major classes of dietary supplements (vitamins; minerals; amino acids; herbs or botanicals; metabolites, constituents/extracts, or combinations). The major focus is on efficacy of such dietary supplements to enhance exercise or sport performance

The Effects of Age, Exposure History and Malaria Infection on the Susceptibility of Anopheles Mosquitoes to Low Concentrations of Pyrethroid

Chemical insecticides are critical components of malaria control programs. Their ability to eliminate huge numbers of mosquitoes allows them to swiftly interrupt disease transmission, but that lethality also imposes immense selection for insecticide resistance. Targeting control at the small portion of the mosquito population actually responsible for transmitting malaria parasites to humans would reduce selection for resistance, yet maintain effective malaria control. Here, we ask whether simply lowering the concentration of the active ingredient in insecticide formulations could preferentially kill mosquitoes infected with malaria and/or those that are potentially infectious, namely, old mosquitoes. Using modified WHO resistance-monitoring assays, we exposed uninfected Anopheles stephensi females to low concentrations of the pyrethroid permethrin at days 4, 8, 12, and 16 days post-emergence and monitored survival for at least 30 days to evaluate the immediate and long-term effects of repeated exposure as mosquitoes aged. We also exposed Plasmodium chabaudi- and P. yoelii-infected An. stephensi females. Permethrin exposure did not consistently increase mosquito susceptibility to subsequent insecticide exposure, though older mosquitoes were more susceptible. A blood meal slightly improved survival after insecticide exposure; malaria infection did not detectably increase insecticide susceptibility. Exposure to low concentrations over successive feeding cycles substantially altered cohort age-structure. Our data suggest the possibility that, where high insecticide coverage can be achieved, low concentration formulations have the capacity to reduce disease transmission without the massive selection for resistance imposed by current practice

Ethical considerations in prehospital ambulance based research : qualitative interview study of expert informants

Abstract: Background: Prehospital ambulance based research has unique ethical considerations due to urgency, time limitations and the locations involved. We sought to explore these issues through interviews with experts in this research field. Methods: We undertook semi-structured interviews with expert informants, primarily based in the UK, seeking their views and experiences of ethics in ambulance based clinical research. Participants were questioned regarding their experiences of ambulance based research, their opinions on current regulations and guidelines, and views about their general ethical considerations. Participants were chosen because they were actively involved in, or in their expert capacity (e.g. law) expressed an interest in, ambulance based research. Results: Fourteen participants were interviewed including principal investigators, researchers, ethicists and medical lawyers. Five major themes were identified: Capacity, Consent, Clinical Considerations, Consultation and Regulation. Questions regarding consent and capacity were foremost in the discussions as all participants highlighted these as areas for concern. The challenges and use of multiple consent models reflected the complexity of research in this environment. The clinical theme referred to the role of paramedics in research and how research involving ambulance services is increasingly informing improvements to patient care and outcomes and reducing the burden on hospital services. Most felt that, although current regulations were fit for purpose, more specific guidance on implementing these in the ambulance setting would be beneficial. This related closely to the theme of consultation, which examined the key role of ethics committees and other regulatory bodies, as well as public engagement. Conclusions: By interviewing experts in research or ethics in this setting we were able to identify key concerns and highlight areas for future development such as improved guidance

Pore-scale numerical investigation of pressure drop behaviour across open-cell metal foams

The development and validation of a grid-based pore-scale numerical modelling methodology applied to five different commercial metal foam samples is described. The 3-D digital representation of the foam geometry was obtained by the use of X-ray microcomputer tomography scans, and macroscopic properties such as porosity, specific surface and pore size distribution are directly calculated from tomographic data. Pressure drop measurements were performed on all the samples under a wide range of flow velocities, with focus on the turbulent flow regime. Airflow pore-scale simulations were carried out solving the continuity and Navier–Stokes equations using a commercial finite volume code. The feasibility of using Reynolds-averaged Navier–Stokes models to account for the turbulence within the pore space was evaluated. Macroscopic transport quantities are calculated from the pore-scale simulations by averaging. Permeability and Forchheimer coefficient values are obtained from the pressure gradient data for both experiments and simulations and used for validation. Results have shown that viscous losses are practically negligible under the conditions investigated and pressure losses are dominated by inertial effects. Simulations performed on samples with varying thickness in the flow direction showed the pressure gradient to be affected by the sample thickness. However, as the thickness increased, the pressure gradient tended towards an asymptotic value

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Aging partially restores the efficacy of malaria vector control in insecticide-resistant populations of Anopheles gambiae s.l. from Burkina Faso

&lt;br&gt;Background: The operational impact of insecticide resistance on the effectiveness of long-lasting insecticide nets (LLINs) and indoor residual spraying (IRS) is poorly understood. One factor which may prolong the effectiveness of these tools in the field is the increase in insecticide susceptibility with mosquito age. In this study, LLINs and IRS were tested against young (three to five days) and old (17-19 days) pyrethroid resistant Anopheles gambiae s.l. from Burkina Faso.&lt;/br&gt; &lt;br&gt;Methods: Blood-fed adult Anopheles gambiae s.l. were collected from south-west Burkina Faso and identified to species/form level. Cohorts of the F1 progeny of An. gambiae s.s. S-forms were exposed to deltamethrin (0.05%) at three to five or 17-19 days post-emergence and tested for the frequency of the resistance allele 1014F. Isofemale lines of the M, S- form of An. gambiae s.s. and Anopheles arabiensis were exposed in WHO cone tests to either a) LLINs deployed in households for two years or (b) bendiocarb sprayed walls.&lt;/br&gt; &lt;br&gt;Results: Mortality rates in response to deltamethrin (0.05%) increased from levels indicative of strong resistance in three to five day old F1 mosquitoes, to near full susceptibility in the 17-19 day old cohort. On exposure to LLINs sampled from the field, the mortality rate in isofemale lines was higher in older mosquitoes than young (OR = 5.28, CI 95% = 2.81-9.92), although the mortality estimates were affected by the LLIN tested. In general, the LLINs sampled from the field performed poorly in WHO cone bioassays using either laboratory susceptible or field caught mosquito populations. Finally, there was a clear relationship between mortality and age on exposure to bendiocarb-sprayed walls, with older mosquitoes again proving more susceptible (OR = 3.39, CI 95% = 2.35-4.90).&lt;/br&gt; &lt;br&gt;Conclusions: Age is a key factor determining the susceptibility of mosquitoes to insecticides, not only in laboratory studies, but in response to field-based vector control interventions. This has important implications for understanding the epidemiological impact of resistance. If mosquitoes old enough to transmit malaria are still being suppressed with available insecticides, is resistance potentially having less of an impact than often assumed? However, the poor performance of LLINs used in this study in Burkina Faso, is a cause for concern and requires urgent investigation.&lt;/br&gt

The insecticide resistance status of malaria vectors in the Mekong region

<p>Abstract</p> <p>Background</p> <p>Knowledge on insecticide resistance in target species is a basic requirement to guide insecticide use in malaria control programmes. Malaria transmission in the Mekong region is mainly concentrated in forested areas along the country borders, so that decisions on insecticide use should ideally be made at regional level. Consequently, cross-country monitoring of insecticide resistance is indispensable to acquire comparable baseline data on insecticide resistance.</p> <p>Methods</p> <p>A network for the monitoring of insecticide resistance, MALVECASIA, was set up in the Mekong region in order to assess the insecticide resistance status of the major malaria vectors in Cambodia, Laos, Thailand, and Vietnam. From 2003 till 2005, bioassays were performed on adult mosquitoes using the standard WHO susceptibility test with diagnostic concentrations of permethrin 0.75% and DDT 4%. Additional tests were done with pyrethroid insecticides applied by the different national malaria control programmes.</p> <p>Results</p> <p><it>Anopheles dirus s.s</it>., the main vector in forested malaria foci, was susceptible to permethrin. However, in central Vietnam, it showed possible resistance to type II pyrethroids. In the Mekong delta, <it>Anopheles epiroticus </it>was highly resistant to all pyrethroid insecticides tested. It was susceptible to DDT, except near Ho Chi Minh City where it showed possible DDT resistance. In Vietnam, pyrethroid susceptible and tolerant <it>Anopheles minimus s.l</it>. populations were found, whereas <it>An. minimus s.l</it>. from Cambodia, Laos and Thailand were susceptible. Only two <it>An. minimus s.l</it>. populations showed DDT tolerance. <it>Anopheles vagus </it>was found resistant to DDT and to several pyrethroids in Vietnam and Cambodia.</p> <p>Conclusion</p> <p>This is the first large scale, cross-country survey of insecticide resistance in <it>Anopheles </it>species in the Mekong Region. A unique baseline data on insecticide resistance for the Mekong region is now available, which enables the follow-up of trends in susceptibility status in the region and which will serve as the basis for further resistance management. Large differences in insecticide resistance status were observed among species and countries. In Vietnam, insecticide resistance was mainly observed in low or transmission-free areas, hence an immediate change of malaria vector control strategy is not required. Though, resistance management is important because the risk of migration of mosquitoes carrying resistance genes from non-endemic to endemic areas. Moreover, trends in resistance status should be carefully monitored and the impact of existing vector control tools on resistant populations should be assessed.</p

The trauma of ongoing conflict and displacement in Chechnya: quantitative assessment of living conditions, and psychosocial and general health status among war displaced in Chechnya and Ingushetia

BACKGROUND: Conflict in Chechnya has resulted in over a decade of violence, human rights abuses, criminality and poverty, and a steady flow of displaced seeking refuge throughout the region. At the beginning of 2004 MSF undertook quantitative surveys among the displaced populations in Chechnya and neighbouring Ingushetia. METHODS: Surveys were carried out in Ingushetia (January 2004) and Chechnya (February 2004) through systematic sampling. Various conflict-related factors contributing to ill health were researched to obtain information on displacement history, living conditions, and psychosocial and general health status. RESULTS: The average length of displacement was five years. Conditions in both locations were poor, and people in both locations indicated food shortages (Chechnya (C): 13.3%, Ingushetia (I): 11.3%), and there was a high degree of dependency on outside help (C: 95.4%, I: 94.3%). Most people (C: 94%, I: 98%) were confronted with violence in the past. Many respondents had witnessed the killing of people (C: 22.7%, I: 24.1%) and nearly half of people interviewed witnessed arrests (C: 53.1%, I: 48.4%) and maltreatment (C: 56.2%, I: 44.5%). Approximately one third of those interviewed had directly experienced war-related violence. A substantial number of people interviewed – one third in Ingushetia (37.5%) and two-thirds in Chechnya (66.8%) – rarely felt safe. The violence was ongoing, with respondents reporting violence in the month before the survey (C: 12.5%, I: 4.6%). Results of the general health questionnaire (GHQ 28) showed that nearly all internally displaced persons interviewed were suffering from health complaints such as somatic complaints, anxiety/insomnia, depressive feelings or social dysfunction (C: 201, 78.5%, CI: 73.0% – 83.4%; I: 230, 81.3%, CI: 76.2% – 85.6%). Poor health status was reflected in other survey questions, but health services were difficult to access for around half the population (C: 54.3%, I: 46.6%). DISCUSSION: The study demonstrates that the health needs of internally displaced in both locations are similarly high and equally unaddressed. The high levels of past confrontation with violence and ongoing exposure in both locations is likely to contribute to a further deterioration of the health status of internally displaced. As of March 2007, concerns remain about how the return process is being managed by the authorities