Hijacking ZIP codes: posttanscriptional regulation of CCN2 by nucleophosmin

CCN2 (connective tissue growth factor [CTGF]/hypertrophic chondrocyte-specific gene product 24 [Hcs24]) is regulated at the transcriptional and posttranscriptional level. For example, an element in the its 3′ untranslated region (3′-UTR) of the CCN2 mRNA controls message stability in chondrocytes. In a recent study, Mukudai et al. (Mol Cell Biol 28:6134-6147, 2008) purified and identified a trans-factor protein binding to the minimal repressive cis element in the 3′-UTR of ccn2 mRNA and identify this protein as the multifunctional nucleolar phosphoprotein nucleophosmin (NPM) This commentary summarizes these observations

Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG), which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients

The development and application of audit criteria for assessing knowledge exchange plans in health research grant applications.

Background: Research funders expect evidence of end user engagement and impact plans in research proposals. Drawing upon existing frameworks, we developed audit criteria to help researchers and their institutions assess the knowledge exchange plans of health research proposals. Findings: Criteria clustered around five themes: problem definition; involvement of research users; public and patient engagement; dissemination and implementation; and planning, management and evaluation of knowledge exchange. We applied these to a sample of grant applications from one research institution in the United Kingdom to demonstrate feasibility. Conclusion: Our criteria may be useful as a tool for researcher self-assessment and for research institutions to assess the quality of knowledge exchange plans and identify areas for systematic improvement

Pathogenesis of the cutaneous phenotype in inherited disorders of cholesterol metabolism: Therapeutic implications for topical treatment of these disorders

Molecular geneticists tend to conceptualize disease pathogenesis from the mutated gene outward, an approach that does not take into account the impact of barrier requirements in determining disease phenotype. An ‘outside-to-inside’ perspective has provided quite different explanations for the ichthyoses, including several of the disorders of distal cholesterol metabolism. Elucidation of responsible pathogenic mechanisms also is pointing to appropriate, pathogenesis (pathway)-based therapeutic strategies. In the case of the lipid metabolic disorders, it takes full advantage of new molecular, genetic and cellular pathogenesis information to correct or bypass the metabolic abnormality. This approach fully exploits the unique accessibility of the skin to a topical approach. Moreover, since it will utilize topical lipids and lipid-soluble, and often generic, lipid-soluble drugs, these treatments should be readily transported across the stratum corneum. If successful, this approach could initiate an entirely new departure for the therapy of the ichthyoses. Finally, because these agents are relatively safe and inexpensive, this form of treatment has the potential to be widely-deployed, even in the developing world

Relating Differently to Intrusive Images: The Impact of Mindfulness Based Cognitive Therapy (MBCT) on Intrusive Images in Patients With Severe Health Anxiety (Hypochondriasis).

Recurrent distressing intrusive images are a common experience in hypochondriasis. The aim of the current study was to assess the impact of Mindfulness-Based Cognitive Therapy (MBCT) for hypochondriasis on the occurrence and nature of distressing intrusive imagery in hypochondriasis. A semi-structured interview was used to assess intrusive imagery, and an adapted version of the Southampton Mindfulness Questionnaire (SMQ) was used to assess participants’ relationship with their intrusive images. A consecutive series of participants (N = 20) who were receiving MBCT for hypochondriasis as part of an ongoing research program were assessed prior to participating in an 8-week MBCT intervention, immediately following the intervention, and at three month follow-up. As compared to the baseline assessment, the frequency of intrusive images, the distress associated with them, and the intrusiveness of the images were all significantly reduced at the post-MBCT assessment. Participants’ adapted SMQ scores were significantly increased following the MBCT intervention, suggesting that participants’ relationship with their intrusive images had changed in that they had developed a more ‘mindful’ and compassionate response to the images when they did occur. Effect sizes from pre- to post-intervention were medium to large (Cohen’s d = 0.75 - 1.50). All treatment gains were maintained at 3 month follow-up. Results suggest that MBCT may be an effective intervention for addressing intrusive imagery in hypochondriasis

Drinking behaviour and alcohol-related harm amongst older adults: analysis of existing UK datasets.

Older adults experience age-related physiological changes that increase sensitivity and decrease tolerance to alcohol and there are a number of age-related harms such as falls, social isolation and elder abuse, which are compounded by alcohol misuse. Despite this unique vulnerability and the fact that the number of older adults is increasing, the literature on drinking behaviour and alcohol-related harm in older adults is sparse. This article describes a secondary analysis of UK data to address this knowledge gap

Closely related Lak megaphages replicate in the microbiomes of diverse animals

Lak phages with alternatively coded ∼540 kbp genomes were recently reported to replicate in Prevotella in microbiomes of humans that consume a non-western diet, baboons and pigs. Here, we explore Lak phage diversity and broader distribution using diagnostic PCR and genome-resolved metagenomics. Lak phages were detected in 13 animal types, including reptiles, and are particularly prevalent in pigs. Tracking Lak through the pig gastrointestinal tract revealed significant enrichment in the hindgut compared to the foregut. We reconstructed 34 new Lak genomes, including six curated complete genomes, all of which are alternatively coded. An anomalously large (∼660 kbp) complete genome reconstructed for the most deeply branched Lak from a horse microbiome is also alternatively coded. From the Lak genomes, we identified proteins associated with specific animal species; notably, most have no functional predictions. The presence of closely related Lak phages in diverse animals indicates facile distribution coupled to host-specific adaptation

Exposure to revised drinking guidelines and 'COM-B' determinants of behaviour change: descriptive analysis of a monthly cross-sectional survey in England

BACKGROUND: January 2016 saw the publication of proposed revisions to the UK's lower risk drinking guidelines but no sustained promotional activity. This paper aims to explore the impact of publishing guidelines without sustained promotional activity on reported guideline exposure and determinants of behaviour (capability, opportunity and motivation) proposed by the COM-B model. METHODS: Data were collected by a monthly repeat cross-sectional survey of adults (18+) resident in England over 15 months between November 2015 and January 2017 from a total of 16,779 drinkers, as part of the Alcohol Toolkit Study. Trends and associated 95% confidence intervals were described in the proportion of reported exposure to guidelines in the past month and measures of the capability, opportunity and motivation to consume alcohol within drinking guidelines. RESULTS: There was a rise in reported exposure to drinking guidelines in January 2016 (57.6-80.6%) which did not reoccur in January 2017. Following the increase in January 2016, reported exposure reduced slowly but remained significantly higher than in December 2015. In February 2016, there was an increase in measures of capability (31.1% reported tracking units of alcohol consumption and 87.8% considered it easier to drink safely) and opportunity (84.0% perceived their lifestyle as conducive to drinking within guidelines). This change was not maintained in subsequent months. Other measures showed marginal changes between January and February 2016 with no evidence of change in subsequent months. CONCLUSIONS: Following the publication of revised drinking guideline in January 2016, there was a transient increase in exposure to guidelines, and capability and opportunity to drink within the guidelines that diminished over time. The transience and size of the changes indicate that behaviour change is unlikely. Well-designed, theory-based promotional campaigns may be required for drinking guidelines to be an effective public health intervention

Comparison of embedded and added motor imagery training in patients after stroke: Study protocol of a randomised controlled pilot trial using a mixed methods approach

Copyright @ 2009 Schuster et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Two different approaches have been adopted when applying motor imagery (MI) to stroke patients. MI can be conducted either added to conventional physiotherapy or integrated within therapy sessions. The proposed study aims to compare the efficacy of embedded MI to an added MI intervention. Evidence from pilot studies reported in the literature suggests that both approaches can improve performance of a complex motor skill involving whole body movements, however, it remains to be demonstrated, which is the more effective one.Methods/Design: A single blinded, randomised controlled trial (RCT) with a pre-post intervention design will be carried out. The study design includes two experimental groups and a control group (CG). Both experimental groups (EG1, EG2) will receive physical practice of a clinical relevant motor task ('Going down, laying on the floor, and getting up again') over a two week intervention period: EG1 with embedded MI training, EG2 with MI training added after physiotherapy. The CG will receive standard physiotherapy intervention and an additional control intervention not related to MI.The primary study outcome is the time difference to perform the task from pre to post-intervention. Secondary outcomes include level of help needed, stages of motor task completion, degree of motor impairment, balance ability, fear of falling measure, motivation score, and motor imagery ability score. Four data collection points are proposed: twice during baseline phase, once following the intervention period, and once after a two week follow up. A nested qualitative part should add an important insight into patients' experience and attitudes towards MI. Semi-structured interviews of six to ten patients, who participate in the RCT, will be conducted to investigate patients' previous experience with MI and their expectations towards the MI intervention in the study. Patients will be interviewed prior and after the intervention period.Discussion: Results will determine whether embedded MI is superior to added MI. Findings of the semi-structured interviews will help to integrate patient's expectations of MI interventions in the design of research studies to improve practical applicability using MI as an adjunct therapy technique