Combined mirror visual and auditory feedback therapy for upper limb phantom pain: a case report

<p>Abstract</p> <p>Introduction</p> <p>Phantom limb sensation and phantom limb pain is a very common issue after amputations. In recent years there has been accumulating data implicating 'mirror visual feedback' or 'mirror therapy' as helpful in the treatment of phantom limb sensation and phantom limb pain.</p> <p>Case presentation</p> <p>We present the case of a 24-year-old Caucasian man, a left upper limb amputee, treated with mirror visual feedback combined with auditory feedback with improved pain relief.</p> <p>Conclusion</p> <p>This case may suggest that auditory feedback might enhance the effectiveness of mirror visual feedback and serve as a valuable addition to the complex multi-sensory processing of body perception in patients who are amputees.</p

Neuronal Plasticity and Multisensory Integration in Filial Imprinting

Many organisms sample their environment through multiple sensory systems and the integration of multisensory information enhances learning. However, the mechanisms underlying multisensory memory formation and their similarity to unisensory mechanisms remain unclear. Filial imprinting is one example in which experience is multisensory, and the mechanisms of unisensory neuronal plasticity are well established. We investigated the storage of audiovisual information through experience by comparing the activity of neurons in the intermediate and medial mesopallium of imprinted and naïve domestic chicks (Gallus gallus domesticus) in response to an audiovisual imprinting stimulus and novel object and their auditory and visual components. We find that imprinting enhanced the mean response magnitude of neurons to unisensory but not multisensory stimuli. Furthermore, imprinting enhanced responses to incongruent audiovisual stimuli comprised of mismatched auditory and visual components. Our results suggest that the effects of imprinting on the unisensory and multisensory responsiveness of IMM neurons differ and that IMM neurons may function to detect unexpected deviations from the audiovisual imprinting stimulus

The projection score - an evaluation criterion for variable subset selection in PCA visualization

<p>Abstract</p> <p>Background</p> <p>In many scientific domains, it is becoming increasingly common to collect high-dimensional data sets, often with an exploratory aim, to generate new and relevant hypotheses. The exploratory perspective often makes statistically guided visualization methods, such as Principal Component Analysis (PCA), the methods of choice. However, the clarity of the obtained visualizations, and thereby the potential to use them to formulate relevant hypotheses, may be confounded by the presence of the many non-informative variables. For microarray data, more easily interpretable visualizations are often obtained by filtering the variable set, for example by removing the variables with the smallest variances or by only including the variables most highly related to a specific response. The resulting visualization may depend heavily on the inclusion criterion, that is, effectively the number of retained variables. To our knowledge, there exists no objective method for determining the optimal inclusion criterion in the context of visualization.</p> <p>Results</p> <p>We present the projection score, which is a straightforward, intuitively appealing measure of the informativeness of a variable subset with respect to PCA visualization. This measure can be universally applied to find suitable inclusion criteria for any type of variable filtering. We apply the presented measure to find optimal variable subsets for different filtering methods in both microarray data sets and synthetic data sets. We note also that the projection score can be applied in general contexts, to compare the informativeness of any variable subsets with respect to visualization by PCA.</p> <p>Conclusions</p> <p>We conclude that the projection score provides an easily interpretable and universally applicable measure of the informativeness of a variable subset with respect to visualization by PCA, that can be used to systematically find the most interpretable PCA visualization in practical exploratory analysis.</p

The Alcohol Intervention Training Program (AITP): A response to alcohol misuse in the farming community

Background Farm men and women in Australia have higher levels of problematic alcohol use than their urban counterparts and experience elevated health risks associated with excessive alcohol consumption. The Sustainable Farm Families (SFF) program has worked successfully with farm men and women to address health, well- being and safety and has identified that further research and training is required to understand and address alcohol misuse behaviours. This project will add an innovative component to the program by training health professionals working with farm men and women to discuss and respond to alcohol-related physical and mental health problems. Methods/Design A mixed method design with multi-level evaluation will be implemented following the development and delivery of a training program (The Alcohol Intervention Training Program {AITP}) for Sustainable Farm Families health professionals. Pre-, post- and follow-up surveys will be used to assess both the impact of the training on the knowledge, confidence and skills of the health professionals to work with alcohol misuse and associated problems, and the impact of the training on the attitudes, behaviour and mental health of farm men and women who participate in the SFF project. Evaluations will take a range of forms including self-rated outcome measures and interviews. Discussion The success of this project will enhance the health and well-being of a critical population, the farm men and women of Australia, by producing an evidence-based strategy to assist them to adopt more positive alcohol-related behaviours that will lead to better physical and mental health

Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells.</p> <p>Methods</p> <p>Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA.</p> <p>Results</p> <p>We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment.</p> <p>Conclusions</p> <p>We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade.</p

Immune function biomarkers in children exposed to lead and organochlorine compounds: a cross-sectional study

BACKGROUND: Different organochlorines and lead (Pb) have been shown to have immunomodulating properties. Children are at greater risk for exposure to these environmental toxicants, but very little data exist on simultaneous exposures to these substances. METHODS: We investigated whether the organochlorine compounds (OC) dichlorodiphenylethylene (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (γ-HCH), the sum of polychlorinated biphenyls (ΣPCBs) and Pb were associated with immune markers such as immunoglobulin (Ig) levels, white blood cell (WBC), counts of lymphocytes; eosinophils and their eosinophilic granula as well as IgE count on basophils. The investigation was part of a cross-sectional environmental study in Hesse, Germany. In 1995, exposure to OC and Pb were determined, questionnaire data collected and immune markers quantified in 331 children. For the analyses, exposure (OC and Pb) concentrations were grouped in quartiles (γ-HCH into tertiles). Using linear regression, controlling for age, gender, passive smoking, serum lipids, and infections in the previous 12 months, we assessed the association between exposures and immune markers. Adjusted geometric means are provided for the different exposure levels. RESULTS: Geometric means were: DDE 0.32 μg/L, ΣPCBs 0.50 μg/L, HCB 0.22 μg/L, γ-HCH 0.02 μg/L and Pb 26.8 μg/L. The ΣPCBs was significantly associated with increased IgM levels, whereas HCB was inversely related to IgM. There was a higher number of NK cells (CD56+) with increased γ-HCH concentrations. At higher lead concentrations we saw increased IgE levels. DDE showed the most associations with significant increases in WBC count, in IgE count on basophils, IgE, IgG, and IgA levels. DDE was also found to significantly decrease eosinophilic granula content. CONCLUSION: Low-level exposures to OC and lead (Pb) in children may have immunomodulating effects. The increased IgE levels, IgE count on basophils, and the reduction of eosinophilic granula at higher DDE concentrations showed a most consistent pattern, which could be of clinical importance in the etiology of allergic diseases

Interview investigation of insecure attachment styles as mediators between poor childhood care and schizophrenia-spectrum phenomenology

Background Insecure attachment styles have received theoretical attention and some initial empirical support as mediators between childhood adverse experiences and psychotic phenomena; however, further specificity needs investigating. The present interview study aimed to examine (i) whether two forms of poor childhood care, namely parental antipathy and role reversal, were associated with subclinical positive and negative symptoms and schizophrenia-spectrum personality disorder (PD) traits, and (ii) whether such associations were mediated by specific insecure attachment styles. Method A total of 214 nonclinical young adults were interviewed for subclinical symptoms (Comprehensive Assessment of At-Risk Mental States), schizophrenia-spectrum PDs (Structured Clinical Interview for DSM-IV Axis II Disorders), poor childhood care (Childhood Experience of Care and Abuse Interview), and attachment style (Attachment Style Interview). Participants also completed the Beck Depression Inventory-II and all the analyses were conducted partialling out the effects of depressive symptoms. Results Both parental antipathy and role reversal were associated with subclinical positive symptoms and with paranoid and schizotypal PD traits. Role reversal was also associated with subclinical negative symptoms. Angry-dismissive attachment mediated associations between antipathy and subclinical positive symptoms and both angry-dismissive and enmeshed attachment mediated associations of antipathy with paranoid and schizotypal PD traits. Enmeshed attachment mediated associations of role reversal with paranoid and schizotypal PD traits. Conclusions Attachment theory can inform lifespan models of how adverse developmental environments may increase the risk for psychosis. Insecure attachment provides a promising mechanism for understanding the development of schizophrenia-spectrum phenomenology and may offer a useful target for prophylactic intervention

Comparison of the Safety and Pharmacokinetics of ST-246® after IV Infusion or Oral Administration in Mice, Rabbits and Monkeys

ST-246® is an antiviral, orally bioavailable small molecule in clinical development for treatment of orthopoxvirus infections. An intravenous (IV) formulation may be required for some hospitalized patients who are unable to take oral medication. An IV formulation has been evaluated in three species previously used in evaluation of both efficacy and toxicology of the oral formulation. plasma concentrations. These effects were eliminated using slower IV infusions. associated toxicity. Shorter infusions at higher doses in NHP resulted in decreased clearance, suggesting saturated distribution or elimination. Elimination half-lives in all species were similar between oral and IV administration. The administration of ST-246 was well tolerated as a slow IV infusion

Valuing health states: is the MACBETH approach useful for valuing EQ-5D-3L health states?

Background Quality Adjusted Life Years (QALYs) are a key outcome measure widely used within health technology assessment and health service research studies. QALYs combine quantity and quality of life, with quality of life calculations relying on the value of distinct health states. Such health states’ values capture the preferences of a population and have been typically built through numerical elicitation methods. Evidence points to these value scores being influenced by methods in use and individuals reporting cognitive difficulties in eliciting their preferences. Evidence from other areas has further suggested that individuals may prefer using distinct elicitation techniques and that this preference can be influenced by their numeracy. In this study we explore the use of the MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) non-numerical preference elicitation approach for health states’ evaluation. Methods A new protocol for preference elicitation based on MACBETH (only requiring qualitative judgments) was developed and tested within a web survey format. A sample of the Portuguese general population (n=243) valued 25 EQ-5D-3L health states with the MACBETH protocol and with a variant of the time trade-off (TTO) protocol, for comparison purposes and for understanding respondents’ preference for distinct protocols and differences in inconsistent evaluations. Respondents answered to a short numeracy test, and basic socio-economic information collected. Results Results show that the mean values derived from MACBETH and the TTO variant are strongly correlated; however, there are substantial differences for several health states’ values. Large and similar numbers of logical inconsistencies were found in respondents’ answers with both methods. Participants with higher levels of numeracy according to the test preferred expressing value judgments with MACBETH, while participants with lower levels were mostly indifferent to both methods. Higher correlations between MACBETH and TTO variant evaluations were observed for individuals with higher numeracy. Conclusion Results suggest that it is worth researching the use of non-numerical preference elicitation methods. Numeracy tests more appropriate for preference elicitation when no explicit considerations of uncertainty are made need to be explored and used. Further behavioural research is needed to fully understand the potential for using these methods in distinct settings (e.g. in different evaluation contexts and in face-to-face and non-face-to-face environments), as well as to explore the effect of literacy on assessments and on respondents’ preferences.UID/MULTI/4066/2016info:eu-repo/semantics/publishedVersio

Identification of a Classical Bipartite Nuclear Localization Signal in the Drosophila TEA/ATTS Protein Scalloped

Drosophila melanogaster wing development has been shown to rely on the activity of a complex of two proteins, Scalloped (Sd) and Vestigial (Vg). Within this complex, Sd is known to provide DNA binding though its TEA/ATTS domain, while Vg modulates this binding and provides transcriptional activation through N- and C-terminal activation domains. There is also evidence that Sd is required for the nuclear translocation of Vg. Indeed, a candidate sequence which shows consensus to the bipartite family of nuclear localization signals (NLSs) has been identified within Sd previously, though it is not known if it is functional, or if additional unpredicted signals that mediate nuclear transport exist within the protein. By expressing various enhanced green fluorescent protein (eGFP) tagged constructs within Drosophila S2 cells, we demonstrate that this NLS is indeed functional and necessary for the proper nuclear localization of Sd. Additionally, the region containing the NLS is critical for the wildtype function of ectopically expressed Sd, in the context of wing development. Using site-directed mutagenesis, we have identified a group of five amino acids within this NLS which is critical for its function, as well as another group of two which is of lesser importance. Together with data that suggests that this sequence mediates interactions with Importin-α3, we conclude that the identified NLS is likely a classical bipartite signal. Further dissection of Sd has also revealed that a large portion of the C-terminal domain of the protein is required its proper nuclear localization. Finally, a Leptomycin B (LB) sensitive signal which appears to facilitate nuclear export is identified, raising the possibility that Sd also contains a nuclear export signal (NES)