Nurses’ Personal and Professional Experiences of Dyslexia in Lifelong Learning: a Narrative Approach

This study investigated how dyslexia affected qualified nurses’ lifelong learning and how they engaged in professional development; a requirement of registration. It considered the educational and professional experiences of nurses and lecturers who had supported registered nurses with dyslexia. A qualitative, in-depth, narrative lifecourse approach was used with participants across Great Britain. The initial study informed the conduct of the main study and interview questions. The main study involved fourteen registered nurses and nine lecturers recruited purposefully through posters and Twitter. Semi-structured interviews were conducted either face-to-face, by telephone or using Skype. Data were analysed using template analysis and validated by the participants using asynchronous online discussion forums. The analysis of the data identified that dyslexia affected nurses in their professional capacity, as well as affecting their learning. The findings further identified how nurses developed compensatory strategies both personally and in practice seeking to overcome negative learning experiences. Transitions were particularly problematic, either between academic levels or practice areas. Disclosure of dyslexia was dependent on supportive relationships. However, patient safety was seen as paramount. Lecturers recognised that early identification of dyslexia was important to enable appropriate support and reasonable adjustments, but is dependent on recognition of dyslexia. The findings of the nurses’ and lecturers’ data were used to develop a conceptual framework to illustrate how both personal and professional development overlap but are also influenced by psychological and social factors. Recommendations from the study note that professional development is required for lecturers to ensure early recognition and support for nurses with dyslexia, along with early formative assessment of written work at university. However, education beyond initial training also needs to take account of the personal impacts of dyslexia and the effects of transitions should be factored into inclusive assessment strategies and support available

Coupled Enzyme Activity and Thermal Shift Screening of the Maybridge Rule of 3 Fragment Library Against Trypanosoma brucei Choline Kinase; A Genetically Validated Drug Target

In this study we interrogate 630 compounds of the Maybridge Rule of 3 Fragment Library for compounds that interact with, and inhibit TbCK. The Maybridge Rule of 3 Fragment Library is a small collection of quantifiable diverse, pharmacophoric rich, chemical entities that comply with the following criteria; MW ≤ 300, cLogP ≤ 3, H-Bond Acceptors ≤ 3, H-Bond Donors ≤ 3, Rotatable bonds (Flexibility Index) ≤ 3, Polar Surface Area ≤ 60 Å2 and aqueous solubility ≥ 1 mM using LogS and high purity (≥ 95%). Comparisons between two different screening methods, a coupled enzyme activity assay and differential scanning fluorimetry, has allowed identification of compounds that interact and inhibit the T. brucei choline kinase, several of which possess selective trypanocidal activity. Screening of a comparatively small fragment library by two different screening methods has allowed identification of several compounds that interact with and inhibit TbCK, a genetically validated drug target against African sleeping sickness. Some of the inhibitory fragments were also selectively trypanocidal, considering these are relatively simple molecules with no optimization, finding low μΜ inhibitors is very encouraging. Moreover some of the morphological phenotypes of these trypanocidal compounds include cell-cycle arrests similar to those observed for the TbCK conditional knockout grown under permissive conditions

‘Repeat abortion’, a phrase to be avoided? Qualitative insights into labelling and stigma

Background In recent years there has been growing international interest in identifying risk factors associated with ‘repeat abortion’, and developing public health initiatives that might reduce the rate. This article draws on a research study looking at young women's abortion experience in England and Wales. The study was commissioned with a specific focus on women who had undergone more than one abortion. We examine what may influence women's post-abortion reproductive behaviour, in addition to exploring abortion-related stigma, in the light of participants' own narratives. Study design Mixed-methods research study: a quantitative survey of 430 women aged 16–24 years, and in-depth qualitative interviews with 36 women who had undergone one or more abortions. This article focuses on the qualitative data from two subsets of young women: those we interviewed twice (n=17) and those who had experienced more than one unintended/unwanted pregnancy (n=15). Results The qualitative research findings demonstrate the complexity of women's contraceptive histories and reproductive lives, and thus the inherent difficulty of establishing causal patterns for more than one abortion, beyond the obvious observation that contraception was not used, or not used effectively. Women who had experienced more than one abortion did, however, express intensified abortion shame. Conclusions This article argues that categorising women who have an abortion in different ways depending on previous episodes is not helpful. It may also be damaging, and generate increased stigma, for women who have more than one abortion

Trypanosoma brucei bloodstream forms depend upon uptake of myo-inositol for Golgi phosphatidylinositol synthesis and normal cell growth

myo-Inositol is a building block for all inositol-containing phospholipids in eukaryotes. It can be synthesized de novo from glucose-6-phosphate in the cytosol and endoplasmic reticulum. Alternatively, it can be taken up from the environment via Na+- or H+-linked myo-inositol transporters. While Na+-coupled myo-inositol transporters are found exclusively in the plasma membrane, H+-linked myo-inositol transporters are detected in intracellular organelles. In Trypanosoma brucei, the causative agent of human African sleeping sickness, myo-inositol metabolism is compartmentalized. De novo synthesized myo-inositol is used for glycosylphosphatidylinositol production in the endoplasmic reticulum, whereas the myo-inositol taken up from the environment is used for bulk phosphatidylinositol synthesis in the Golgi. We now provide evidence that the Golgi localized T. brucei H+-linked myo-inositol transporter (TbHMIT) is essential in bloodstream forms. Down-regulation of TbHMIT expression by RNA interference blocked phosphatidylinositol production and inhibited growth of parasites in culture. Characterization of the transporter in a heterologous expression system demonstrated a remarkable selectivity of TbHMIT for myo-inositol. It only tolerates a single modification on the inositol ring, such as the removal of a hydroxyl group, or the inversion of stereochemistry at a single hydroxyl group relative to myo-inositol.PostprintPeer reviewe

Comparison of characteristics and function of translation termination signals between and within prokaryotic and eukaryotic organisms

Six diverse prokaryotic and five eukaryotic genomes were compared to deduce whether the protein synthesis termination signal has common determinants within and across both kingdoms. Four of the six prokaryotic and all of the eukaryotic genomes investigated demonstrated a similar pattern of nucleotide bias both 5′ and 3′ of the stop codon. A preferred core signal of 4 nt was evident, encompassing the stop codon and the following nucleotide. Codons decoded by hyper-modified tRNAs were over-represented in the region 5′ to the stop codon in genes from both kingdoms. The origin of the 3′ bias was more variable particularly among the prokaryotic organisms. In both kingdoms, genes with the highest expression index exhibited a strong bias but genes with the lowest expression showed none. Absence of bias in parasitic prokaryotes may reflect an absence of pressure to evolve more efficient translation. Experiments were undertaken to determine if a correlation existed between bias in signal abundance and termination efficiency. In Escherichia coli signal abundance correlated with termination efficiency for UAA and UGA stop codons, but not in mammalian cells. Termination signals that were highly inefficient could be made more efficient by increasing the concentration of the cognate decoding release factor

Postinfective bowel dysfunction following Campylobacter enteritis is characterised by reduced microbiota diversity and impaired microbiota recovery

Objectives Persistent bowel dysfunction following gastroenteritis (postinfectious (PI)-BD) is well recognised, but the associated changes in microbiota remain unclear. Our aim was to define these changes after gastroenteritis caused by a single organism, Campylobacter jejuni, examining the dynamic changes in the microbiota and the impact of antibiotics. Design A single-centre cohort study of 155 patients infected with Campylobacter jejuni. Features of the initial illness as well as current bowel symptoms and the intestinal microbiota composition were recorded soon after infection (visit 1, 80 days later (visits 2 and 3). Microbiota were assessed using 16S rRNA sequencing. Results PI-BD was found in 22 of the 99 patients who completed the trial. The cases reported significantly looser stools, with more somatic and gastrointestinal symptoms. Microbiota were assessed in 22 cases who had significantly lower diversity and altered microbiota composition compared with the 44 age-matched and sex-matched controls. Moreover 60 days after infection, cases showed a significantly lower abundance of 23 taxa including phylum Firmicutes, particularly in the order Clostridiales and the family Ruminoccocaceae, increased Proteobacteria abundance and increased levels of Fusobacteria and Gammaproteobacteria. The microbiota changes were linked with diet; higher fibre consumption being associated with lower levels of Gammaproteobacteria. Conclusion The microbiota of PI-BD patients appeared more disturbed by the initial infection compared with the microbiota of those who recovered. The prebiotic effect of high fibre diets may inhibit some of the disturbances seen in PI-BD.Peer reviewe

Patients\u27 Willingness to Accept Social Needs Navigation After In-Person Versus Remote Screening

Social needs screening and referral interventions are increasingly common in health care settings. Although remote screening offers a potentially more practical alternative to traditional in-person screening, there is concern that screening patients remotely could adversely affect patient engagement, including interest in accepting social needs navigation

Towards chemical validation of Leishmania infantum ribose 5-phosphate isomerase as a drug target

Funding from the European Community's Seventh Framework Programme under grant agreements No. 602773 (Project KINDRED) was received for all partners in this work. This work also received funds from FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior through the Research Unit No. 4293 and project POCI-01-0145-FEDER-031013 (PTDC/SAUPAR/31013/2017 to NS); Individual funding from FCT through SFRH/BD/133485/2017 (to MS) and CEECIND/02362/2017 (to JT).Neglected tropical diseases caused by kinetoplastid parasites (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) place a significant health and economic burden on developing nations worldwide. Current therapies are largely out-dated, inadequate and facing mounting drug resistance from the causative parasites. Thus, there is an urgent need for drug discovery and development. Target-led drug discovery approaches have focused on the identification of parasite enzymes catalysing essential biochemical processes, which significantly differ from equivalent proteins found in humans, thereby providing potentially exploitable therapeutic windows. One such target is ribose 5-phosphate isomerase B (RpiB), an enzyme involved in the non-oxidative branch of the pentose phosphate pathway, which catalyses the inter-conversion of D-ribose 5-phosphate and D-ribulose 5-phosphate. Although protozoan RpiB has been the focus of numerous targeted studies, compounds capable of selectively inhibiting this parasite enzyme have not been identified. Here, we present the results of a fragment library screening against Leishmania infantum RpiB, performed using thermal shift analysis. Hit fragments were shown to be effective inhibitors of LiRpiB in activity assays, and several were capable of selectively inhibiting parasite growth in vitro. These results support the identification of LiRpiB as a validated therapeutic target. The X-ray crystal structure of apo LiRpiB was also solved, permitting docking studies to assess how hit fragments might interact with LiRpiB to inhibit its activity. Overall, this work will guide structure-based development of LiRpiB inhibitors as anti-leishmanial agents.PostprintPeer reviewe

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants

Sarah: historiografkinja prošlosti i sadašnjosti žene francuskog poručnika

The article argues that Sarah, the title character of Fowles’ novel The French Lieutenant’s Woman (1969), resists the oppressive ideology of her time by writing her own historiography. In the process, not only does she emplot a tragic past for herself but she also insists on being identified as a depraved woman in the present. The analysis attempts to highlight the fact that Sarah, like a historiographer, selects the referents for her historiography—Mrs. Poulteney and Charles—and imposes her emplotment and prefiguration on her historiography of both her past and present. Employing Hayden White’s theories of postmodern historiography and Linda Hutcheon’s concept of historiographic metafiction, the paper illustrates ways in which Sarah historicizes her own past through tragic emplotment and metaphoric prefiguration of her narrative in order to convey her anarchist ideology, at the same time portraying herself as the “Woman” who has been abandoned by the French Lieutenant. Furthermore, by means of her historiography of the present, she imposes her liberal ideology through satiric emplotment of her fictional construct and ironic prefiguration of the referents of textualized oppression in society. She ironically puts Mrs. Poulteney and Charles in the situations in which their oppressive ideology is unraveled; in this way, she satirizes the codes of behavior of her present time.U članku se tvrdi da se Sarah, naslovni lik Fowlesova romana Ženska francuskog poručnika (1969), opire opresivnoj ideologiji svojega vremena pišući vlastitu historiografiju. Na taj način ona fabulira tragičnu prošlost za sebe i inzistira na tome da ju se percipira kao izopačenu ženu u sadašnjosti. Analiza pokušava istaknuti činjenicu da Sarah, poput povjesničara, odabire referente za svoju historiografiju – gđu Poulteney i Charlesa – i nameće svoju fabulaciju i prefiguraciju historiografije vlastite prošlosti i sadašnjosti. Koristeći se teorijom postmoderne historiografije Haydena Whitea i konceptom historiografske metafikcije Linde Hutcheon, rad prikazuje načine na koje Sarah historizira vlastitu prošlost kroz tragičnu fabulaciju i metaforičku prefiguraciju svoje pripovijesti kako bi istaknula svoju anarhističku ideologiju i istodobno sebe prikazala kao „žensku“ koju je napustio francuski poručnik. Nadalje, pomoću svoje historiografije sadašnjosti ona nameće svoju liberalnu ideologiju satiričkom fabulacijom svog fikcionalnog konstrukta i ironičnom prefiguracijom referenata tekstualiziranog društvenog ugnjetavanja. Na ironičan način, ona gospođu Poulteney i Charlesa stavlja u situacije u kojima se njihova represivna ideologija razotkriva; na taj način satirizira kodove ponašanja u svojoj sadašnjosti