Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression.

Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation

Protocol for a randomised controlled trial examining the impact of a web-based personally controlled health management system on the uptake of influenza vaccination rates

<p>Abstract</p> <p>Background</p> <p>Online social networking and personally controlled health management systems (PCHMS) offer a new opportunity for developing innovative interventions to prevent diseases of public health concern (e.g., influenza) but there are few comparative studies about patterns of use and impact of these systems.</p> <p>Methods/Design</p> <p>A 2010 CONSORT-compliant randomised controlled trial with a two-group parallel design will assess the efficacy of a web-based PCHMS called <it>Healthy.me </it>in facilitating the uptake of influenza vaccine amongst university students and staff. Eligible participants are randomised either to obtain access to <it>Healthy.me </it>or a 6-month waitlist. Participants complete pre-study, post-study and monthly surveys about their health and utilisation of health services. A post-study clinical audit will be conducted to validate self-reports about influenza vaccination and visits to the university health service due to influenza-like illness (ILI) amongst a subset of participants. 600 participants older than 18 years with monthly access to the Internet and email will be recruited. Participants who (i) discontinue the online registration process; (ii) report obtaining an influenza vaccination in 2010 before the commencement of the study; or (iii) report being influenced by other participants to undertake influenza vaccination will be excluded from analysis. The primary outcome measure is the number of participants obtaining influenza vaccination during the study. Secondary outcome measures include: number of participants (i) experiencing ILI symptoms, (ii) absent from or experiencing impairment in work or study due to ILI symptoms, (iii) using health services or medications due to ILI symptoms; (iv) expressing positive or negative attitudes or experiences towards influenza vaccination, via their reasons of receiving (or not receiving) influenza vaccine; and (v) their patterns of usage of <it>Healthy.me </it>(e.g., frequency and timing of hits, duration of access, uptake of specific functions).</p> <p>Discussion</p> <p>This study will provide new insights about the utility of online social networking and PCHMS for public health and health promotion. It will help to assess whether a web-based PCHMS, with connectivity to a health service provider, containing information and self-management tools, can improve the uptake of preventive health services amongst university students and staff.</p> <p>Trial registration</p> <p><a href="http://www.anzctr.org.au/ACTRN12610000386033.aspx">ACTRN12610000386033</a> (Australian New Zealand Clinical Trials Registry)</p

Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP

Raf-1 phosphorylates and activates MEK-1, a kinase that activates the extracellular signal regulated kinases (ERK). This kinase cascade controls the proliferation and differentiation of different cell types. Here we describe a Raf-1-interacting protein, isolated using a yeast two-hybrid screen. This protein inhibits the phosphorylation and activation of MEK by Raf-1 and is designated RKIP (Raf kinase inhibitor protein). In vitro, RKIP binds to Raf-1, MEK and ERK, but not to Ras. RKIP co-immunoprecipitates with Raf-1 and MEK from cell lysates and colocalizes with Raf-1 when examined by confocal microscopy. RKIP is not a substrate for Raf-1 or MEK, but competitively disrupts the interaction between these kinases. RKIP overexpression interferes with the activation of MEK and ERK, induction of AP-1-dependent reporter genes and transformation elicited by an oncogenically activated Raf-1 kinase. Downregulation of endogenous RKIP by expression of antisense RNA or antibody microinjection induces the activation of MEK-, ERK- and AP-1-dependent transcription. RKIP represents a new class of protein-kinase-inhibitor protein that regulates the activity of the Raf/MEK/ERK modul

Madness decolonized?: Madness as transnational identity in Gail Hornstein’s Agnes’s Jacket

The US psychologist Gail Hornstein’s monograph Agnes’s Jacket: A Psychologist’s Search for the Meanings of Madness (2009) is an important intervention in the identity politics of the mad movement. Hornstein offers a resignified vision of mad identity that embroiders the central trope of an “anti-colonial” struggle to reclaim the experiential world “colonized” by psychiatry. A series of literal and figurative appeals make recourse to the inner world and (corresponding) cultural world of the mad, as well as to the ethno-symbolic cultural materials of dormant nationhood. This rhetoric is augmented by a model in which the mad comprise a diaspora without an origin, coalescing into a single transnational community. The mad are also depicted as persons displaced from their metaphorical homeland, the “inner” world “colonized” by the psychiatric regime. There are a number of difficulties with Hornstein’s rhetoric, however. Her “ethnicity-and-rights” response to the oppression of the mad is symptomatic of Western parochialism, while her proposed transmutation of putative psychopathology from limit upon identity to parameter of successful identity is open to contestation. Moreover, unless one accepts Hornstein’s porous vision of mad identity, her self-ascribed insider status in relation to the mad community may present a problematic “re-colonization” of mad experience

Class II Division 1 malocclusion treatment with extraction of maxillary first molars:Evaluation of treatment and post-treatment changes by the PAR Index

OBJECTIVE To investigate occlusal result and post-treatment changes after orthodontic extraction of maxillary first permanent molars in patients with a Class II division 1 malocclusion. SETTING AND SAMPLE Retrospective longitudinal study in a private practice, with outcome evaluation by an independent academic hospital. Ninety-six patients (53 males, 43 females) consecutively treated by one orthodontist with maxillary first permanent molar extraction were studied, divided into three facial types, based on pre-treatment cephalometric values: hypodivergent (n = 18), normodivergent (n = 21) and hyperdivergent (n = 57). METHODS Occlusal outcome was scored on dental casts at T1 (pre-treatment), T2 (post-treatment) and T3 (mean follow-up 2.5 ± 0.9 years) using the weighted Peer Assessment Rating (PAR) Index. The paired sample t test and one-way ANOVA followed by Tukey's post hoc test were used for statistical analysis. RESULTS PAR was reduced by 95.7% and 89.9% at T2 and T3, respectively, compared with the start of treatment. The largest post-treatment changes were found for overjet and buccal occlusion. Linear regression analysis did not reveal a clear effect (R-Square 0.074) of age, sex, PAR score at T1, incremental PAR score T2-T1, overjet and overbite at T1, and facial type on the changes after treatment (incremental PAR score T3-T2). CONCLUSIONS The occlusal outcome achieved after Class II division 1 treatment with maxillary first permanent molar extractions was maintained to a large extent over a mean post-treatment follow-up of 2.5 years. Limited changes after treatment were found, for which no risk factors could be discerned

Developing the content of two behavioural interventions : using theory-based interventions to promote GP management of upper respiratory tract infection without prescribing antibiotics #1

Background: Evidence shows that antibiotics have limited effectiveness in the management of upper respiratory tract infection (URTI) yet GPs continue to prescribe antibiotics. Implementation research does not currently provide a strong evidence base to guide the choice of interventions to promote the uptake of such evidence-based practice by health professionals. While systematic reviews demonstrate that interventions to change clinical practice can be effective, heterogeneity between studies hinders generalisation to routine practice. Psychological models of behaviour change that have been used successfully to predict variation in behaviour in the general population can also predict the clinical behaviour of healthcare professionals. The purpose of this study was to design two theoretically-based interventions to promote the management of upper respiratory tract infection (URTI) without prescribing antibiotics. Method: Interventions were developed using a systematic, empirically informed approach in which we: selected theoretical frameworks; identified modifiable behavioural antecedents that predicted GPs intended and actual management of URTI; mapped these target antecedents on to evidence-based behaviour change techniques; and operationalised intervention components in a format suitable for delivery by postal questionnaire. Results: We identified two psychological constructs that predicted GP management of URTI: "Self-efficacy," representing belief in one's capabilities, and "Anticipated consequences," representing beliefs about the consequences of one's actions. Behavioural techniques known to be effective in changing these beliefs were used in the design of two paper-based, interactive interventions. Intervention 1 targeted self-efficacy and required GPs to consider progressively more difficult situations in a "graded task" and to develop an "action plan" of what to do when next presented with one of these situations. Intervention 2 targeted anticipated consequences and required GPs to respond to a "persuasive communication" containing a series of pictures representing the consequences of managing URTI with and without antibiotics. Conclusion: It is feasible to systematically develop theoretically-based interventions to change professional practice. Two interventions were designed that differentially target generalisable constructs predictive of GP management of URTI. Our detailed and scientific rationale for the choice and design of our interventions will provide a basis for understanding any effects identified in their evaluation. Trial registration: Clinicaltrials.gov NCT00376142This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

Translating clinicians' beliefs into implementation interventions (TRACII) : a protocol for an intervention modeling experiment to change clinicians' intentions to implement evidence-based practice

Background: Biomedical research constantly produces new findings, but these are not routinely incorporated into health care practice. Currently, a range of interventions to promote the uptake of emerging evidence are available. While their effectiveness has been tested in pragmatic trials, these do not form a basis from which to generalise to routine care settings. Implementation research is the scientific study of methods to promote the uptake of research findings, and hence to reduce inappropriate care. As clinical practice is a form of human behaviour, theories of human behaviour that have proved to be useful in other settings offer a basis for developing a scientific rationale for the choice of interventions. Aims: The aims of this protocol are 1) to develop interventions to change beliefs that have already been identified as antecedents to antibiotic prescribing for sore throats, and 2) to experimentally evaluate these interventions to identify those that have the largest impact on behavioural intention and behavioural simulation. Design: The clinical focus for this work will be the management of uncomplicated sore throat in general practice. Symptoms of upper respiratory tract infections are common presenting features in primary care. They are frequently treated with antibiotics, and research evidence is clear that antibiotic treatment offers little or no benefit to otherwise healthy adult patients. Reducing antibiotic prescribing in the community by the "prudent" use of antibiotics is seen as one way to slow the rise in antibiotic resistance, and appears safe, at least in children. However, our understanding of how to do this is limited. Participants will be general medical practitioners. Two theory-based interventions will be designed to address the discriminant beliefs in the prescribing of antibiotics for sore throat, using empirically derived resources. The interventions will be evaluated in a 2 × 2 factorial randomised controlled trial delivered in a postal questionnaire survey. Two outcome measures will be assessed: behavioural intention and behavioural simulation.This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

Scaling of cardiac morphology is interrupted by birth in the developing sheep Ovis aries.

Scaling of the heart across development can reveal the degree to which variation in cardiac morphology depends on body mass. In this study, we assessed the scaling of heart mass, left and right ventricular masses, and ventricular mass ratio, as a function of eviscerated body mass across fetal and postnatal development in Horro sheep Ovis aries (~50-fold body mass range; N = 21). Whole hearts were extracted from carcasses, cleaned, dissected into chambers and weighed. We found a biphasic relationship when heart mass was scaled against body mass, with a conspicuous 'breakpoint' around the time of birth, manifest not by a change in the scaling exponent (slope), but rather a jump in the elevation. Fetal heart mass (g) increased with eviscerated body mass (Mb , kg) according to the power equation 4.90 Mb0.88 ± 0.26 (± 95%CI) , whereas postnatal heart mass increased according to 10.0 Mb0.88 ± 0.10 . While the fetal and postnatal scaling exponents are identical (0.88) and reveal a clear dependence of heart mass on body mass, only the postnatal exponent is significantly less than 1.0, indicating the postnatal heart becomes a smaller component of body mass as the body grows, which is a pattern found frequently with postnatal cardiac development among mammals. The rapid doubling in heart mass around the time of birth is independent of any increase in body mass and is consistent with the normalization of wall stress in response to abrupt changes in volume loading and pressure loading at parturition. We discuss variation in scaling patterns of heart mass across development among mammals, and suggest that the variation results from a complex interplay between hard-wired genetics and epigenetic influences

Real-time registration of adverse events in Dutch hospitalized children in general pediatric units: first experiences

The objectives of this study are to describe the number and nature of adverse events occurring in general pediatric practice, to describe factors contributing to the occurrence of these adverse events, and to report on the experience of pediatricians with reporting adverse events. It is a prospective study on 11 pediatric units in a 3-month period; adverse events were registered for all newly admitted patients. Ninety-four adverse events were registered in 88 of 5,669 patients, amounting to a 1.6 per 100 admissions rate and a 0.4 per 100 patient days rate. Ninety percent of the adverse events did not cause serious harm. Failed diagnostic procedures were most common. Conclusion: Adverse event registration in general pediatric practice is a first step in assessing quality and safety of care. It yields a considerable number of adverse events. Compliance to adverse event registration in daily practice is difficult but also key to optimal monitoring of quality of care