Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study

A major challenge in biomonitoring studies with members of the general public is ensuring their continued involvement throughout the necessary length of the research. The paper presents evidence on the use of community researchers, recruited from local study areas, as a mechanism for ensuring effective recruitment and retention of farmer and resident participants for a pesticides biomonitoring study. The evidence presented suggests that community researchers' abilities to build and sustain trusting relationships with participants enhanced the rigour of the study as a result of their on-the-ground responsiveness and flexibility resulting in data collection beyond targets expected

Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation

<p>Abstract</p> <p>Background</p> <p>To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS).</p> <p>Methods</p> <p>Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus.</p> <p>Results</p> <p>The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51). The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully.</p> <p>The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis.</p> <p>Conclusions</p> <p>There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.</p

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

The Evolution of Bat Vestibular Systems in the Face of Potential Antagonistic Selection Pressures for Flight and Echolocation

PMCID: PMC3634842This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Helping someone with problem drug use: a delphi consensus study of consumers, carers, and clinicians

<p>Abstract</p> <p>Background</p> <p>Problem use of illicit drugs (i.e. drug abuse or dependence) is associated with considerable health and social harms, highlighting the need for early intervention and engagement with health services. Family members, friends and colleagues play an important role in supporting and assisting individuals with problem drug use to seek professional help, however there are conflicting views about how and when such support should be offered. This paper reports on the development of mental health first aid guidelines for problem drug use in adults, to help inform community members on how to assist someone developing problem drug use or experiencing a drug-related crisis.</p> <p>Methods</p> <p>A systematic review of the scientific and lay literature was conducted to develop a 228-item survey containing potential first-aid strategies to help someone developing a drug problem or experiencing a drug-related crisis. Three panels of experts (29 consumers, 31 carers and 27 clinicians) were recruited from Australia, Canada, New Zealand, the United Kingdom, and the United States. Panel members independently rated the items over three rounds, with strategies reaching consensus on importance written into the guidelines.</p> <p>Results</p> <p>The overall response rate across three rounds was 80% (86% consumers, 81% carers, 74% clinicians). 140 first aid strategies were endorsed as essential or important by 80% or more of panel members. The endorsed strategies provide information and advice on what is problem drug use and its consequences, how to approach a person about their problem drug use, tips for effective communication, what to do if the person is unwilling to change their drug use, what to do if the person does (or does not) want professional help, what are drug-affected states and how to deal with them, how to deal with adverse reactions leading to a medical emergency, and what to do if the person is aggressive.</p> <p>Conclusions</p> <p>The guidelines provide a consensus-based resource for community members who want to help someone with a drug problem. It is hoped that the guidelines will lead to better support and understanding for those with problem drug use and facilitate engagement with professional help.</p

Origin of the Diversity in DNA Recognition Domains in Phasevarion Associated modA Genes of Pathogenic Neisseria and Haemophilus influenzae

Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles

Measuring patient-perceived continuity of care for patients with long-term conditions in primary care

Background: Continuity of care is widely acknowledged as important for patients with multi-morbidity but simple, service-orientated indices cannot capture the full impact of continuity in complex care delivery systems. The patient's perspective is important to assess outcomes fully and this is challenging because generic measures of patient-perceived continuity are lacking. We investigate the Chao Perception of Continuity (Chao PC) scale to determine its suitability as a measure of continuity of care for patients with a long-term condition (stroke), and co-morbidity, in a primary care setting. Methods: Design and Setting: A questionnaire study embedded in a prospective observational cohort study of outcomes for patients following acute stroke. Participants: 168 community dwelling patients (58% male) mean age 68 years a minimum one year post-stroke. Functional status: Barthel Index mean =16. Intervention: A 23-item questionnaire, the Chao Perception of Continuity (Chao PC) scale, sent by post to their place of residence or administered face to face as part of the final cohort study assessment. Results: 310 patients were invited to participate; 168 (54%) completed a questionnaire. All 23 questionnaire items were entered into a Principal Component Analysis. Emergent factors from the exploratory analysis were (1) inter-personal trust (relational continuity); (2) interpersonal knowledge and information (informational and relational continuity) and (3) the process of care (managerial continuity). The strongest of these was inter-personal trust. Conclusion: The context-specific items in the Chao PC scale are difficult for respondents to interpret in a United Kingdom Primary Care setting resulting in missing data and low response rates. The Chao-PC therefore cannot be recommended for wider application as a general measure of continuity of care without significant modification. Our findings reflect the acknowledged dimensions of continuity and support the concept of continuity of care as a multi-dimensional construct. We demonstrate the overlapping boundaries across the dimensions in the factor structure derived. Trust and interpersonal knowledge are clearly identified as valuable components of any patient-perceived measure of continuity of care

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

NeuN/Rbfox3 Nuclear and Cytoplasmic Isoforms Differentially Regulate Alternative Splicing and Nonsense-Mediated Decay of Rbfox2

Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45–50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45–50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism

Mitochondrial complex 1 activity measured by spectrophotometry is reduced across all brain regions in ageing and more specifically in neurodegeneration

Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions