A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordOBJECTIVE: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. METHODS: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). RESULTS: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. CONCLUSION: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.Support by the following organisations is gratefully acknowledged, Ross Menzies Herbal Clinic, Bodyworks Therapy Centre; Wesnes Cognition Ltd, the Royal Botanic Gardens (RBG), Kew and Dilston Physic Garden. The phytochemical analysis was gratefully funded by the Sir Jeremiah Colman Gift Trust

Sensory ways to indigenous multimodal literacies : Hands and feet tell the story

This chapter reports original research that asks the question: What are the ways of knowing, being, and communicating that are valued and practiced in Indigenous communities? Literacy curricula, internationally and nationally, typically do not take into account the multi-sensorial dimensions of non-Western forms of representation that go beyond narrow conceptions of print. For example, literacies are often conceived as drawing on print, visual, spatial, gestural, and audio modes, but the role of haptics and locomotion has typically received little attention. This chapter highlights examples of the multi-sensoriality of Indigenous literacies observed in participatory community research with an Indigenous school. It extends recent theories of sensory studies in the history and cultural anthropology of the senses, applying these principles to literacy education. Sensory literacies is a theoretical perspective that gives priority to the sensorial dimensions of the body and its role in communication in literacy practice, because without a sensing body, we cannot know about or communicate with the world. The data demonstrates how the forgotten role of the hands and feet in dominant theories of communication is central to Indigenous identity and literacies. Written by a white academic with an Indigenous researcher, the chapter problematises the privileging of narrow, logocentric, and Western forms of literacy and its implications for rethinking the role of the whole body in literacy and the literacy curriculum for Indigenous students

Opportunities and challenges to improving antibiotic prescribing practices through a One Health approach: Results of a comparative survey of doctors, dentists and veterinarians in Australia

© 2018 Article author(s). Objectives To explore and compare the knowledge, attitudes and experiences of doctors, dentists and veterinarians (as prescribers) in relation to antibiotic use and antibiotic resistance (AbR), and to consider the implications of these for policy-making that support a One Health approach. Design A cross-sectional survey conducted online. Setting Doctors, dentists and veterinarians practising in primary, secondary or tertiary care in Australia. Participants 547 doctors, 380 dentists and 403 veterinarians completed the survey. Main outcome measures Prescribers' knowledge, attitudes and perceptions of AbR, the extent to which a range of factors are perceived as barriers to appropriate prescribing practices, and perceived helpfulness of potential strategies to improve antibiotic prescribing in practice. Results There was substantial agreement across prescriber groups that action on AbR is required by multiple sectors and stakeholders. However, prescribers externalised responsibility to some extent by seeing the roles of others as more important than their own in relation to AbR. There were common and context-specific barriers to optimal prescribing across the prescriber groups. Prescriber groups generally perceived restrictive policies as unhelpful to supporting appropriate prescribing in their practice. Conclusions The results have implications for implementing a One Health approach that involves doctors, dentists and veterinarians as key players to tackling the crisis of AbR. The findings are that (1) prescribers understand and are likely receptive to a One Health policy approach to AbR, (2) policy development should be sensitive to barriers that are specific to individual prescriber groups and (3) the development and introduction of interventions that might be perceived as reducing prescriber autonomy will need to be carefully designed and implemented

malariaAtlas: an R interface to global malariometric data hosted by the Malaria Atlas Project

Background The Malaria Atlas Project (MAP) has worked to assemble and maintain a global open-access database of spatial malariometric data for over a decade. This data spans various formats and topics, including: geo-located surveys of malaria parasite rate; global administrative boundary shapefiles; and global and regional rasters representing the distribution of malaria and associated illnesses, blood disorders, and intervention coverage. MAP has recently released malariaAtlas, an R package providing a direct interface to MAP’s routinely-updated malariometric databases and research outputs. Methods and results The current paper reviews the functionality available in malariaAtlas and highlights its utility for spatial epidemiological analysis of malaria. malariaAtlas enables users to freely download, visualise and analyse global malariometric data within R. Currently available data types include: malaria parasite rate and vector occurrence point data; subnational administrative boundary shapefiles; and a large suite of rasters covering a diverse range of metrics related to malaria research. malariaAtlas is here used in two mock analyses to illustrate how this data may be incorporated into a standard R workflow for spatial analysis. Conclusions malariaAtlas is the first open-access R-interface to malariometric data, providing a new and reproducible means of accessing such data within a freely available and commonly used statistical software environment. In this way, the malariaAtlas package aims to contribute to the environment of data-sharing within the malaria research community

Differential Calcium Signaling by Cone Specific Guanylate Cyclase-Activating Proteins from the Zebrafish Retina

Zebrafish express in their retina a higher number of guanylate cyclase-activating proteins (zGCAPs) than mammalians pointing to more complex guanylate cyclase signaling systems. All six zGCAP isoforms show distinct and partial overlapping expression profiles in rods and cones. We determined critical Ca2+-dependent parameters of their functional properties using purified zGCAPs after heterologous expression in E.coli. Isoforms 1–4 were strong, 5 and 7 were weak activators of membrane bound guanylate cyclase. They further displayed different Ca2+-sensitivities of guanylate cyclase activation, which is half maximal either at a free Ca2+ around 30 nM (zGCAP1, 2 and 3) or around 400 nM (zGCAP4, 5 and 7). Zebrafish GCAP isoforms showed also differences in their Ca2+/Mg2+-dependent conformational changes and in the Ca2+-dependent monomer-dimer equilibrium. Direct Ca2+-binding revealed that all zGCAPs bound at least three Ca2+. The corresponding apparent affinity constants reflect binding of Ca2+ with high (≤100 nM), medium (0.1–5 µM) and/or low (≥5 µM) affinity, but were unique for each zGCAP isoform. Our data indicate a Ca2+-sensor system in zebrafish rod and cone cells supporting a Ca2+-relay model of differential zGCAP operation in these cells

Highly structured slow solar wind emerging from an equatorial coronal hole

International audienceDuring the solar minimum, when the Sun is at its least active, the solar wind(1,2) is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvenic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind(3) of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain(4); theories and observations suggest that they may originate at the tips of helmet streamers(5,6), from interchange reconnection near coronal hole boundaries(7,8), or within coronal holes with highly diverging magnetic fields(9,10). The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfven-wave turbulence(11,12), heating by reconnection in nanoflares(13), ion cyclotron wave heating(14) and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe(15) at 36 to 54 solar radii that show evidence of slow Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities(10,16) that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind

Linking formal child care characteristics to children's socioemotional well-being: A comparative perspective

Most research on formal child care and children’s outcomes has focused on single countries. We, however, contend that policy context may moderate the association between formal child care characteristics and children’s socioemotional well-being. We examined this by comparing the Netherlands, Finland and the UK; three countries that differ regarding family policies. Of these three countries, Finland was recently ranked highest (ranked 1st) with regards to quality of child care in a recent analysis by the Economist ,followed by the UK (ranked 3rd) and then the Netherlands (ranked 7th) .We hypothesized that children who attend child - care settings in countries with higher- uality formal child- are provision would generally show better socioemotional outcomes. Data from the comparative ‘F amilies 24/7’ survey were used, including 990 parents with children aged 0–12. We distinguished between two age groups in our analysis. Results indicated that, compared to the UK, longer hours in formal care were less beneficial in the Netherlands. Furthermore, spen ding time in formal care during nonstandard hours was more harmful for children in Finland compared to the UK. Lastly, receiving care from multiple caregivers was more disruptive for British children than for Dutch children. No differences were found between Finland and the Netherlands

Interacting with Fictions:The Role of Pretend Play in Theory of Mind Acquisition

Pretend play is generally considered to be a developmental landmark in Theory of Mind acquisition. The aim of the present paper is to offer a new account of the role of pretend play in Theory of Mind development. To this end I combine Hutto and Gallagher’s account of social cognition development with Matravers’ recent argument that the cognitive processes involved in engagement with narratives are neutral regarding fictionality. The key contribution of my account is an analysis of pretend play as interaction with fictions. I argue that my account offers a better explanation of existing empirical data on the development of children’s pretend play and Theory of Mind than the competing theories from Leslie, Perner and Harris

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain