Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: A meta-analysis

Background: We present a systematic review and meta-analysis of the available clinical trials concerning the usefulness of aripiprazole in the treatment of the psychotic symptoms in bipolar disorder.Methods: A systematic MEDLINE and repository search concerning clinical trials for aripiprazole in bipolar disorder was conducted.Results: The meta-analysis of four randomised controlled trials (RCTs) on acute mania suggests that the effect size of aripiprazole versus placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for the total Positive and Negative Syndrome Scale (PANSS) score. The effect was higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24) and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale (0.12). No data on the depressive phase of bipolar illness exist, while there are some data in favour of aripiprazole concerning the maintenance phase, where at week 26 all except the total PANSS score showed a significant superiority of aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and d = 0.71 for the hostility subscales) and at week 100 the results were similar (d = 0.42, 0.63 and 0.48, respectively).Conclusion: The data analysed for the current study support the usefulness of aripiprazole against psychotic symptoms during the acute manic and maintenance phases of bipolar illness. © 2009 Fountoulakis et al; licensee BioMed Central Ltd

Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.

Lipids modulate the conformational dynamics of a secondary multidrug transporter

Direct interactions with lipids have emerged as key determinants of the folding, structure and function of membrane proteins, but an understanding of how lipids modulate protein dynamics is still lacking. Here, we systematically explored the effects of lipids on the conformational dynamics of the proton-powered multidrug transporter LmrP from Lactococcus lactis, using the pattern of distances between spin-label pairs previously shown to report on alternating access of the protein. We uncovered, at the molecular level, how the lipid headgroups shape the conformational-energy landscape of the transporter. The model emerging from our data suggests a direct interaction between lipid headgroups and a conserved motif of charged residues that control the conformational equilibrium through an interplay of electrostatic interactions within the protein. Together, our data lay the foundation for a comprehensive model of secondary multidrug transport in lipid bilayers

Sources of stakeholder salience in the responsible investment movement: why do investors sign the Principles for Responsible Investment?

Since its inception in 2006, the United Nations-backed Principles for Responsible Investment (PRI) have grown to over 1300 signatories representing over $45 trillion. This growth is not slowing down. In this paper, we argue that there is a set of attributes which make the PRI salient as a stakeholder and its claim to sign the six PRI important to institutional investors. We use Mitchell et al.’s (Acad Manag Rev 22:853–886, 1997) theoretical framework of stakeholder salience, as extended by Gifford (J Bus Eth 92:79–97, 2010). We use as evidence confidential data from the annual survey of signatories carried out by the PRI in a 5-year period between 2007 and 2011. The findings highlight pragmatic and organizational legitimacy, normative and utilitarian power, and management values as the attributes that contribute most to the salience of the PRI as a stakeholder

Predation success by a plant-ant indirectly favours the growth and fitness of its host myrmecophyte

Mutualisms, or interactions between species that lead to net fitness benefits for each species involved, are stable and ubiquitous in nature mostly due to "byproduct benefits" stemming from the intrinsic traits of one partner that generate an indirect and positive outcome for the other. Here we verify if myrmecotrophy (where plants obtain nutrients from the refuse of their associated ants) can explain the stability of the tripartite association between the myrmecophyte Hirtella physophora, the ant Allomerus decemarticulatus and an Ascomycota fungus. The plant shelters and provides the ants with extrafloral nectar. The ants protect the plant from herbivores and integrate the fungus into the construction of a trap that they use to capture prey; they also provide the fungus and their host plant with nutrients. During a 9-month field study, we over-provisioned experimental ant colonies with insects, enhancing colony fitness (i.e., more winged females were produced). The rate of partial castration of the host plant, previously demonstrated, was not influenced by the experiment. Experimental plants showed higher δ¹⁵N values (confirming myrmecotrophy), plus enhanced vegetative growth (e.g., more leaves produced increased the possibility of lodging ants in leaf pouches) and fitness (i.e., more fruits produced and more flowers that matured into fruit). This study highlights the importance of myrmecotrophy on host plant fitness and the stability of ant-myrmecophyte mutualisms

A Bioengineered Implant for a Predetermined Bone Cellular Response to Loading Forces. A Literature Review and Case Report

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142048/1/jper1276.pd

Toward a Theory of Collective Resource Distribution: A Study of a Dynamic Morphogenesis Controller

Distribution of resources can be a collective decision making process in both natural and artificial systems. The division of a colony into subtasks, the ant trails exploring the environment and connecting the nest to the food sources, and the growth and spread of branches in a tree to optimize the access to light, are different examples of collective distribution processes. In this paper, collective decision on distribution of resource is investigated via an algorithm inspired by plants morphogenesis. The algorithm, called Vascular Morphogenesis Controller (VMC), acts based on the competition of branches in a plant for limited shared resources - water, minerals, etc. The VMC algorithm decides on the changes in the shape of an artificial structure. The structure is a collective entity consisting of several nodes. The nodes act as agents running the algorithm and deciding collectively on the distribution of a shared resource. A change in the distribution of the resource may lead to addition or deletion of nodes and change the morphology of the structure. The system is dynamic and adaptive to variations in the environmental conditions (e.g. light). In this paper, the effects of different parameterizations of the algorithm on the morphology aspects of the collective structure (e.g. asymmetry and dynamicity) are studied analytically and numerically. A set of experiments are presented with the VMC embodied in a physical structure. The structure is made out of modules that hold VMC nodes and can be manually attached or detached following the suggestions of the algorithm. The experiments are performed with various parameters and environmental conditions (e.g. different lighting). The results support the findings of the theoretical study. The paper provides a deeper understanding of the functionalities of VMC and a basis for parameter selection according to desired behaviors. It also indicates similarities in some of the properties of this system and other collective systems suggesting potential benefits of viewing various types of collective systems from the perspective of resource distribution.<br/

Climate for evidence-informed health systems: A print media analysis in 44 low- and middle-income countries that host knowledge-translation platforms

<p>Abstract</p> <p>Background</p> <p>We conducted a print media analysis in 44 countries in Africa, the Americas, Asia, and the Eastern Mediterranean in order to understand one dimension of the climate for evidence-informed health systems and to provide a baseline for an evaluation of knowledge-translation platforms. Our focus was whether and how policymakers, stakeholders, and researchers talk in the media about three topics: policy priorities in the health sector, health research evidence, and policy dialogues regarding health issues.</p> <p>Methods</p> <p>We developed a search strategy consisting of three progressively more delimited phases. For each jurisdiction, we searched <it>Major World Publications </it>in LexisNexis Academic <it>News </it>for articles published in 2007, selected relevant articles using one set of general criteria and three sets of concept-specific criteria, and coded the selected articles to identify common themes. Second raters took part in the analysis of Lebanon and Malaysia to assess inter-rater reliability for article selection and coding.</p> <p>Results</p> <p>We identified approximately 5.5 and 5 times more articles describing health research evidence compared to the number of articles describing policy priorities and policy dialogues, respectively. Few articles describing health research evidence discussed systematic reviews (2%) or health systems research (2%), and few of the policy dialogue articles discussed researcher involvement (9%). News coverage of these concepts was highly concentrated in several countries like China and Uganda, while few articles were found for many other jurisdictions. Kappa scores were acceptable and consistently greater than 0.60.</p> <p>Conclusions</p> <p>In many countries the print media, at least as captured in a global database, are largely silent about three topics central to evidence-informed health systems. These findings suggest the need for proactive-media engagement strategies.</p

The Bankart repair versus the Putti-Platt procedure: A randomized study with WOSI score at 10-year follow-up in 62 patients

Background and purpose This randomized study compared clinical results after surgery for posttraumatic shoulder instability with either an anatomical repair or an older, less anatomical but commonly used method. The less anatomical procedure has been considered quicker and less demanding, but it has been questioned regarding the clinical result. We therefore wanted to compare the clinical outcome of the two different procedures. Our hypothesis was that the anatomical repair would give less residual impairment postoperatively