384 research outputs found

    Perinatal mental ill health - the experiences of women from ethnic minority groups

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    This study aimed to investigate ethnic minority women’s experiences and opinions of perinatal mental health problems and the provision of perinatal mental health support services. An exploratory survey was undertaken using a questionnaire. Quantitative data were analysed using descriptive statistics and a simple thematic analysis was used for the qualitative data. A total of 51 responses from women of 14 different ethnic minority backgrounds were analysed. Women from minority ethnic groups face barriers to seeking help for perinatal mental ill health as a result of ongoing stigma and the poor attitudes and behaviours of health professionals and inappropriately designed services. Future interventions should focus on providing adequate cultural competency for health care professionals and ensure that all women are able to access culturally appropriate spaces to talk and be listened to within community settings and wider services

    Virtual Screening of Bioassay Data

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    Background: There are three main problems associated with the virtual screening of bioassay data. The first is access to freely-available curated data, the second is the number of false positives that occur in the physical primary screening process, and finally the data is highly-imbalanced with a low ratio of Active compounds to Inactive compounds. This paper first discusses these three problems and then a selection of Weka cost-sensitive classifiers (Naive Bayes, SVM, C4.5 and Random Forest) are applied to a variety of bioassay datasets. Results: Pharmaceutical bioassay data is not readily available to the academic community. The data held at PubChem is not curated and there is a lack of detailed cross-referencing between Primary and Confirmatory screening assays. With regard to the number of false positives that occur in the primary screening process, the analysis carried out has been shallow due to the lack of crossreferencing mentioned above. In six cases found, the average percentage of false positives from the High-Throughput Primary screen is quite high at 64%. For the cost-sensitive classification, Weka's implementations of the Support Vector Machine and C4.5 decision tree learner have performed relatively well. It was also found, that the setting of the Weka cost matrix is dependent on the base classifier used and not solely on the ratio of class imbalance. Conclusions: Understandably, pharmaceutical data is hard to obtain. However, it would be beneficial to both the pharmaceutical industry and to academics for curated primary screening and corresponding confirmatory data to be provided. Two benefits could be gained by employing virtual screening techniques to bioassay data. First, by reducing the search space of compounds to be screened and secondly, by analysing the false positives that occur in the primary screening process, the technology may be improved. The number of false positives arising from primary screening leads to the issue of whether this type of data should be used for virtual screening. Care when using Weka's cost-sensitive classifiers is needed - across the board misclassification costs based on class ratios should not be used when comparing differing classifiers for the same dataset

    Nutritional upgrading for omnivorous carpenter ants by the endosymbiont Blochmannia

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    <p>Abstract</p> <p>Background</p> <p>Carpenter ants (genus <it>Camponotus</it>) are considered to be omnivores. Nonetheless, the genome sequence of <it>Blochmannia floridanus</it>, the obligate intracellular endosymbiont of <it>Camponotus floridanus</it>, suggests a function in nutritional upgrading of host resources by the bacterium. Thus, the strongly reduced genome of the endosymbiont retains genes for all subunits of a functional urease, as well as those for biosynthetic pathways for all but one (arginine) of the amino acids essential to the host.</p> <p>Results</p> <p>Nutritional upgrading by <it>Blochmannia </it>was tested in 90-day feeding experiments with brood-raising in worker-groups on chemically defined diets with and without essential amino acids and treated or not with antibiotics. Control groups were fed with cockroaches, honey water and Bhatkar agar. Worker-groups were provided with brood collected from the queenright mother-colonies (45 eggs and 45 first instar larvae each). Brood production did not differ significantly between groups of symbiotic workers on diets with and without essential amino acids. However, aposymbiotic worker groups raised significantly less brood on a diet lacking essential amino acids. Reduced brood production by aposymbiotic workers was compensated when those groups were provided with essential amino acids in their diet. Decrease of endosymbionts due to treatment with antibiotic was monitored by qRT-PCR and FISH after the 90-day experimental period. Urease function was confirmed by feeding experiments using <sup>15</sup>N-labelled urea. GC-MS analysis of <sup>15</sup>N-enrichment of free amino acids in workers revealed significant labelling of the non-essential amino acids alanine, glycine, aspartic acid, and glutamic acid, as well as of the essential amino acids methionine and phenylalanine.</p> <p>Conclusion</p> <p>Our results show that endosymbiotic <it>Blochmannia </it>nutritionally upgrade the diet of <it>C. floridanus </it>hosts to provide essential amino acids, and that it may also play a role in nitrogen recycling via its functional urease. <it>Blochmannia </it>may confer a significant fitness advantage via nutritional upgrading by enhancing competitive ability of <it>Camponotus </it>with other ant species lacking such an endosymbiont. Domestication of the endosymbiont may have facilitated the evolutionary success of the genus <it>Camponotus</it>.</p

    Becoming the best mom that I can: women's experiences of managing depression during pregnancy – a qualitative study

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    <p>Abstract</p> <p>Background</p> <p>The purpose of this constructivist grounded theory study was to develop a theoretical model that explains women's processes of managing diagnosed depression when pregnant.</p> <p>Methods</p> <p>We explored the experiences of 19 women in Ontario who were diagnosed with depression during their pregnancy.</p> <p>Results</p> <p>The model that emerged from the analysis was becoming the best mom that I can. Becoming the best mom that I can explains the complex process of the women's journey as they travel from the depths of despair, where the depression is perceived to threaten their pregnancy and their ability to care for the coming baby, to arrive at knowing the self and being in a better place. In order to reground the self and regain control of their lives, the women had to recognize the problem, overcome shame and embarrassment, identify an understanding healthcare provider, and consider the consequences of the depression and its management. When confronting and confining the threat of depression, the women employed strategies of overcoming barriers, gaining knowledge, and taking control. As a result of counseling, medication, or a combination of both, women felt that they had arrived at a better place.</p> <p>Conclusion</p> <p>For many women, the idea that depression could occur during pregnancy was antithetical to their vision of the pregnant self. The challenge for a pregnant woman who is diagnosed with depression, is that effective care for her may jeopardize her baby's future health. This provides a dilemma for about-to-be parents and their healthcare providers. Improved awareness of depression during pregnancy on the part of healthcare professionals is needed to improve the women's understanding of this disorder and their ability to recognize and seek help with depression should it occur during the prenatal period. Further qualitative research is needed to determine the specific aspects that need to be addressed in such classes.</p

    Risk factors for antenatal depression, postnatal depression and parenting stress

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    <p>Abstract</p> <p>Background</p> <p>Given that the prevalence of antenatal and postnatal depression is high, with estimates around 13%, and the consequences serious, efforts have been made to identify risk factors to assist in prevention, identification and treatment. Most risk factors associated with postnatal depression have been well researched, whereas predictors of antenatal depression have been less researched. Risk factors associated with early parenting stress have not been widely researched, despite the strong link with depression. The aim of this study was to further elucidate which of some previously identified risk factors are most predictive of three outcome measures: antenatal depression, postnatal depression and parenting stress and to examine the relationship between them.</p> <p>Methods</p> <p>Primipara and multiparae women were recruited antenatally from two major hoitals as part of the <it>beyondblue </it>National Postnatal Depression Program <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. In this subsidiary study, 367 women completed an additional large battery of validated questionnaires to identify risk factors in the antenatal period at 26–32 weeks gestation. A subsample of these women (N = 161) also completed questionnaires at 10–12 weeks postnatally. Depression level was measured by the Beck Depression Inventory (BDI).</p> <p>Results</p> <p>Regression analyses identified significant risk factors for the three outcome measures. (1). Significant predictors for antenatal depression: low self-esteem, antenatal anxiety, low social support, negative cognitive style, major life events, low income and history of abuse. (2). Significant predictors for postnatal depression: antenatal depression and a history of depression while also controlling for concurrent parenting stress, which was a significant variable. Antenatal depression was identified as a mediator between seven of the risk factors and postnatal depression. (3). Postnatal depression was the only significant predictor for parenting stress and also acted as a mediator for other risk factors.</p> <p>Conclusion</p> <p>Risk factor profiles for antenatal depression, postnatal depression and parenting stress differ but are interrelated. Antenatal depression was the strongest predictor of postnatal depression, and in turn postnatal depression was the strongest predictor for parenting stress. These results provide clinical direction suggesting that early identification and treatment of perinatal depression is important.</p

    Expressed sequence tags from Atta laevigata and identification of candidate genes for the control of pest leaf-cutting ants

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    <p>Abstract</p> <p>Background</p> <p>Leafcutters are the highest evolved within Neotropical ants in the tribe Attini and model systems for studying caste formation, labor division and symbiosis with microorganisms. Some species of leafcutters are agricultural pests controlled by chemicals which affect other animals and accumulate in the environment. Aiming to provide genetic basis for the study of leafcutters and for the development of more specific and environmentally friendly methods for the control of pest leafcutters, we generated expressed sequence tag data from <it>Atta laevigata</it>, one of the pest ants with broad geographic distribution in South America.</p> <p>Results</p> <p>The analysis of the expressed sequence tags allowed us to characterize 2,006 unique sequences in <it>Atta laevigata</it>. Sixteen of these genes had a high number of transcripts and are likely positively selected for high level of gene expression, being responsible for three basic biological functions: energy conservation through redox reactions in mitochondria; cytoskeleton and muscle structuring; regulation of gene expression and metabolism. Based on leafcutters lifestyle and reports of genes involved in key processes of other social insects, we identified 146 sequences potential targets for controlling pest leafcutters. The targets are responsible for antixenobiosis, development and longevity, immunity, resistance to pathogens, pheromone function, cell signaling, behavior, polysaccharide metabolism and arginine kynase activity.</p> <p>Conclusion</p> <p>The generation and analysis of expressed sequence tags from <it>Atta laevigata </it>have provided important genetic basis for future studies on the biology of leaf-cutting ants and may contribute to the development of a more specific and environmentally friendly method for the control of agricultural pest leafcutters.</p

    Polycomb-mediated silencing in neuroendocrine prostate cancer

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    BACKGROUND: Neuroendocrine prostate cancer (NEPC) is a highly aggressive subtype of prostate cancer (PCa) for which the median survival remains less than a year. Current treatments are only palliative in nature, and the lack of suitable pre-clinical models has hampered previous efforts to develop novel therapeutic strategies. Addressing this need, we have recently established the first in vivo model of complete neuroendocrine transdifferentiation using patient-derived xenografts. Few genetic differences were observed between parental PCa and relapsed NEPC, suggesting that NEPC likely results from alterations that are epigenetic in nature. Thus, we sought to identify targetable epigenetic regulators whose expression was elevated in NEPC using genome-wide profiling of patient-derived xenografts and clinical samples. RESULTS: Our data indicate that multiple members of the polycomb group (PcG) family of transcriptional repressors were selectively upregulated in NEPC. Notably, CBX2 and EZH2 were consistently the most highly overexpressed epigenetic regulators across multiple datasets from clinical and xenograft tumor tissues. Given the striking upregulation of PcG genes and other transcriptional repressors, we derived a 185-gene list termed 'neuroendocrine-associated repression signature' (NEARS) by overlapping transcripts downregulated across multiple in vivo NEPC models. In line with the striking upregulation of PcG family members, NEARS was preferentially enriched with PcG target genes, suggesting a driving role for PcG silencing in NEPC. Importantly, NEARS was significantly associated with high-grade tumors, metastatic progression, and poor outcome in multiple clinical datasets, consistent with extensive literature linking PcG genes and aggressive disease progression. CONCLUSIONS: We have explored the epigenetic landscape of NEPC and provided evidence of increased PcG-mediated silencing associated with aberrant transcriptional regulation of key differentiation genes. Our results position CBX2 and EZH2 as potential therapeutic targets in NEPC, providing opportunities to explore novel strategies aimed at reversing epigenetic alterations driving this lethal disease

    Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge

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    <p>Abstract</p> <p>Background</p> <p>Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV) model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control) and then cats were vaginally challenged with cell-associated or cell-free FIV.</p> <p>Results</p> <p>Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN) expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls.</p> <p>Conclusions</p> <p>The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus) can be modulated by mucosal exposure to uninfected heterologous cells.</p

    Altering the trajectory of early postnatal cortical development can lead to structural and behavioural features of autism

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    <p>Abstract</p> <p>Background</p> <p>Autism is a behaviourally defined neurodevelopmental disorder with unknown etiology. Recent studies in autistic children consistently point to neuropathological and functional abnormalities in the temporal association cortex (TeA) and its associated structures. It has been proposed that the trajectory of postnatal development in these regions may undergo accelerated maturational alterations that predominantly affect sensory recognition and social interaction. Indeed, the temporal association regions that are important for sensory recognition and social interaction are one of the last regions to mature suggesting a potential vulnerability to early maturation. However, direct evaluation of the emerging hypothesis that an altered time course of early postnatal development can lead to an ASD phenotype remains lacking.</p> <p>Results</p> <p>We used electrophysiological, histological, and behavioural techniques to investigate if the known neuronal maturational promoter valproate, similar to that in culture systems, can influence the normal developmental trajectory of TeA <it>in vivo</it>. Brain sections obtained from postnatal rat pups treated with VPA <it>in vivo </it>revealed that almost 40% of cortical cells in TeA prematurely exhibited adult-like intrinsic electrophysiological properties and that this was often associated with gross cortical hypertrophy and a reduced predisposition for social play behaviour.</p> <p>Conclusions</p> <p>The co-manifestation of these functional, structural and behavioural features suggests that alteration of the developmental time course in certain high-order cortical networks may play an important role in the neurophysiological basis of autism.</p

    Predicting Decisions in Human Social Interactions Using Real-Time fMRI and Pattern Classification

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    Negotiation and trade typically require a mutual interaction while simultaneously resting in uncertainty which decision the partner ultimately will make at the end of the process. Assessing already during the negotiation in which direction one's counterpart tends would provide a tremendous advantage. Recently, neuroimaging techniques combined with multivariate pattern classification of the acquired data have made it possible to discriminate subjective states of mind on the basis of their neuronal activation signature. However, to enable an online-assessment of the participant's mind state both approaches need to be extended to a real-time technique. By combining real-time functional magnetic resonance imaging (fMRI) and online pattern classification techniques, we show that it is possible to predict human behavior during social interaction before the interacting partner communicates a specific decision. Average accuracy reached approximately 70% when we predicted online the decisions of volunteers playing the ultimatum game, a well-known paradigm in economic game theory. Our results demonstrate the successful online analysis of complex emotional and cognitive states using real-time fMRI, which will enable a major breakthrough for social fMRI by providing information about mental states of partners already during the mutual interaction. Interestingly, an additional whole brain classification across subjects confirmed the online results: anterior insula, ventral striatum, and lateral orbitofrontal cortex, known to act in emotional self-regulation and reward processing for adjustment of behavior, appeared to be strong determinants of later overt behavior in the ultimatum game. Using whole brain classification we were also able to discriminate between brain processes related to subjective emotional and motivational states and brain processes related to the evaluation of objective financial incentives
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