Proteomics science & society : the role of knowledge translation in moving towards clinical applications

Background: Outside the mass-spectrometer, proteomics research does not take place in a vacuum. It is affected by policies on funding and research infrastructure. Proteomics research both impacts and is impacted by potential clinical applications. It provides new techniques & clinically relevant findings, but the possibilities for such innovations (and thus the perception of the potential for the field by funders) are also impacted by regulatory practices and the readiness of the health sector to incorporate proteomics-related tools & findings. Key to this process is how knowledge is translated. Methods: We present preliminary results from a multi-year social science project, funded by the Canadian Institutes of Health Research, on the processes and motivations for knowledge translation in the health sciences. The proteomics case within this wider study uses qualitative methods to examine the interplay between proteomics science and regulatory and policy makers regarding clinical applications of proteomics. Results: Adopting an interactive format to encourage conference attendees’ feedback, our poster focuses on deficits in effective knowledge translation strategies from the laboratory to policy, clinical, & regulatory arenas. An analysis of the interviews conducted to date suggests five significant choke points: the changing priorities of funding agencies; the complexity of proteomics research; the organisation of proteomics research; the relationship of proteomics to genomics and other omics sciences; and conflict over the appropriate role of standardisation. Conclusion: We suggest that engagement with aspects of knowledge translation, such as those mentioned above, is crucially important for the eventual clinical application ofproteomics science on any meaningful scale.

An analytical tool that quantifies cellular morphology changes from three-dimensional fluorescence images

The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology(1) even in complex tissue sections(2). Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells(3), however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine : involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.

Varenicline decreases alcohol consumption in heavy-drinking smokers

Rationale Emerging evidence suggests that the α4β2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR α4β2 subunit partial agonist varenicline (Chantix™), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518–12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655–663, 2011; McKee et al., Biol Psychiatry 66:185–190 2009). Objectives We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n = 64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens. Results Varenicline significantly decreases alcohol consumption (χ 2 = 35.32, p < 0.0001) in smokers. Although varenicline has previously been associated with suicidality and depression, side effects were low in this study and declined over time in the varenicline treatment group. Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.

Weight bias on psychological and physical health

It is a round table discussion article. "Weight bias refers to negative weight-related attitudes and beliefs, expressed in a range of forms towards individuals who are overweight or obese. Consequences of weight bias could be very significant to the individuals which may predispose them to additional weight gain. This brief literature review discusses the concept of weight bias and its impact on psychological and physical health on overweight and obese individuals..."

Pregnancy losses in young Australian women : findings from the Australian Longitudinal Study on Women's Health

INTRODUCTION: Little research has examined recognized pregnancy losses in a general population. Data from an Australian cohort study provide an opportunity to quantify this aspect of fecundity at a population level. METHOD: Participants in the Australian Longitudinal Study on Women's Health who were aged 28-33 years in 2006 (n = 9,145) completed up to 4 mailed surveys over 10 years. Participants were categorized according to the recognized outcome of their pregnancies, including live birth, miscarriage/stillbirth, termination/ectopic, or no pregnancy. RESULTS: At age 18-23, more women reported terminations (7%) than miscarriages (4%). By 28-33 years, the cumulative frequency of miscarriage (15%) was as common as termination (16%). For women aged 28-33 years who had ever been pregnant (n = 5,343), pregnancy outcomes were as follows: birth only (50%); loss only (18%); and birth and loss (32%), of which half (16%) were birth and miscarriage. A comparison between first miscarriage and first birth (no miscarriage) showed that most first miscarriages occurred in women aged 18-23 years who also reported a first birth at the same survey (15%). Half (51%) of all first births and first miscarriages in women aged 18-19 ended in miscarriage. Early childbearers (<28 years) often had miscarriages around the same time period as their first live birth, suggesting proactive family formation. Delayed childbearers (32-33 years) had more first births than first miscarriages. CONCLUSION: Recognized pregnancy losses are an important measure of fecundity in the general population because they indicate successful conception and maintenance of pregnancy to varying reproductive endpoints.

The psychometric properties of the Spanish version of the Foot Health Status Questionnaire

Purpose: Clinical studies suggest that foot pain may be problematic in one-third of patients in early disease. The Foot Health Status Questionnaire (FHSQ) was developed and validated to evaluate the effectiveness of conservative (orthoses, taping, stretching) and surgery interventions. Despite this fact, there are few validated instruments that measure foot health status in Spanish. Thus, the primary aim of the current study was to translate and evaluate psychometrically a Spanish version of FHSQ. Methods: A cross-sectional study was designed in a university community-based podiatric clinic located in south of Spain. All participants (n = 107) recruited consecutively completed a Spanish version of FHSQ and EuroQoL Health Questionnaire 5 dimensions, and 29 participants repeated these same measures 48 h later. Data analysis included test–retest reliability, construct and criterion-related validity and factor analyses. Results: Construct validity was appropriate with moderate-to-high corrected item–subscale correlations (α = ≥0.739) for all subscales. Test–retest reliability was satisfactory (ICC > 0.932). Factor analysis revealed four dimensions with 86.6 % of the common variance explained. The confirmatory factor analysis findings demonstrated that the proposed structure was well supported (comparative fit index = 0.92, standardized root mean square = 0.09). The Spanish EuroQoL 5D score negatively correlated with the FHSQ pain (r = −0.445) and positively with general foot health and function (r = 0.261 − 0.579), confirming criterion-related validity. Conclusion: The clinimetric properties of the Spanish version of FHSQ were satisfactory.

Health Assessment and Physical Examination

"This first Australia and New Zealand edition of the comprehensive Estes’ Health Assessment and Physical Examination is designed to teach students to assess a patient’s physical, psychological, cultural and emotional dimensions of health as a foundation of nursing care. The skills of interviewing, inspection, percussion, palpation, auscultation, and documentation are defined to help students to make clinical assessments and promote healthy patient outcomes. A strong emphasis on science encompasses all the technical aspects of anatomy, physiology and assessment, while highlighting clinically relevant information. Emphasis on caring is displayed through themes of assessment of the whole person, which also encourages nurses to think about care for themselves as well as patients."--publisher website

Multicultural mental health awareness scale

Australia is one of the most culturally and linguistically diverse (CALD) society in the world. There are individuals from all over the globe settled in Australia. They enter Australia as migrants or refugees. Although, the process of migration differs from individual to individual, it can be an uprooting experience and can bring with it many mental health challenges which need professional attention. Mainstream allied and mental health professionals need to be prepared for this diverse population and their mental health issues and concerns. These professionals may have to offer multicultural counselling to clients from an ethnic and cultural background, which is very different from their own. It is therefore essential for them to demonstrate multicultural counselling competencies (MCC)...

Using staffing ratios for workforce planning : evidence on nine allied health professions - a narrative review

Background: Modern healthcare managers are faced with pressure to deliver effective, efficient services within the context of fixed budget constraints. This requires decisions regarding the skill mix of the workforce particularly when staffing new services. One measure used to identify numbers and mix of staff in healthcare settings is workforce ratio. The aim of this study was to identify workforce ratios in nine allied health professions and to identify whether these measures are useful for planning allied health workforce requirements. Method: A systematic literature search using relevant MeSH headings of business, medical and allied health databases and relevant grey literature for the period 2000-2008 was undertaken. Results: Twelve articles were identified which described the use of workforce ratios in allied health services. Only one of these was a staffing ratio linked to clinical outcomes. The most comprehensive measures were identified in rehabilitation medicine. Conclusions: The evidence for use of staffing ratios for allied health practitioners is scarce and lags behind the fields of nursing and medicine.