813 research outputs found

    The Experience of Neuropsychological Assessment, Views of Clients with Neurodegenerative Conditions

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    Background: It is estimated there are currently 2.6 million people living with a progressive neurological condition in England (Neurological Alliance, 2014). Neuropsychological assessment to detect associated cognitive changes are a primary aspect of care, yet little is known about how neuropsychological assessment is experienced. Aims: This study captures the experience of undergoing a neuropsychological assessment from the viewpoint of clients with neurodegenerative conditions. Methodology: Semi-structured interviews were conducted with eight people with neurodegenerative conditions, who had recently undergone a neuropsychological assessment. The transcripts were analysed using Interpretative Phenomenological Analysis (IPA). Results: Four interrelated superordinate themes emerged from analysis: expectations of assessment, relationship with clinician, experience during testing and outcome of assessment. Overall, the experience of neuropsychological assessment was characterised as emotional and intense experience, yet most talked about the process as a positive experience. Participants hoped the assessment would objectively measure suspected or ‘hidden’ cognitive deficits, to increase understanding and help them cope with potential impairments. Participants reported the relationship with the assessing clinician was vital in determining their experience and helping them to withstand the emotional stresses of testing. Participants described diverse experiences during testing, from enjoying a sense of retained ability, to feelings of frustration, stress and disappointment at perceived ‘failure’. Various coping strategies were utilised to cope with the evoked emotions. The assessment environment was highlighted as important, with distractors felt to negatively impact performance. There was a sense the assessment provided objective ‘proof’ of the presence or absence of cognitive deficits, with accessible and prompt written feedback empowering participants to cope, adjust to difficulties and increasing relative’s awareness. Participants described mixed responses to feedback, from a therapeutic sense of relief, to feeling forced to confront the objective description of the impact of their condition. Despite participants reporting some negative aspects to testing, most emerged with a sense of having benefited from the experience. Implications and Conclusions: The findings of the study are considered in light of existing research, with consideration given to future research opportunities. The implications for clinical practice and training are discussed, including recommendations of pre-assessment meetings to prepare clients for the process (including the emotional aspects), and testing to be conducted by a familiar clinician, with whom the client has built rapport, and who can provide reassurance to offset the inherent uncertainty over performance. Providing an optimal environment, and ensuring feedback is timely, comprehensible and meaningful were also found to be of importance

    Actin depolymerization is associated with meiotic acceleration in cycloheximide-treated ovine oocytes

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    Oocytes treated with the protein synthesis inhibitor cycloheximide (CHX) arrest at the germinal vesicle (GV) stage and undergo accelerated GV breakdown (GVBD) after CHX is removed. However, little is known about the underlying mechanism of accelerated meiotic maturation. Here, we investigated this mechanism and found that oocytes released from CHX arrest have higher amounts of cyclin B1 (CCNB1) and phosphorylated mitogen-activated protein kinase (pMAPK) proteins. Increased levels of these factors were not associated with mRNA polyadenylation or increased transcription rates of CCNB1 and MOS (Moloney murine sarcoma viral oncogene homolog) during CHX arrest. We found that treatment of CHX-arrested oocytes with the actin filament-stabilizing agent Jasplakinolide (Jasp) delayed GVBD following release from CHX arrest and that this was correlated with reduced maturation-promoting factor (MPF) activity. These results suggest that CCNB1 mRNAs released from actin filaments during CHX arrest increase CCNB1 transcripts available for translation after release from CHX arrest, leading to the precocious activation of MPF and accelerated meiotic progression

    SALL4 Expression in Gonocytes and Spermatogonial Clones of Postnatal Mouse Testes

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    The spermatogenic lineage is established after birth when gonocytes migrate to the basement membrane of seminiferous tubules and give rise to spermatogonial stem cells (SSC). In adults, SSCs reside within the population of undifferentiated spermatogonia (Aundiff) that expands clonally from single cells (Asingle) to form pairs (Apaired) and chains of 4, 8 and 16 Aaligned spermatogonia. Although stem cell activity is thought to reside in the population of Asingle spermatogonia, new research suggests that clone size alone does not define the stem cell pool. The mechanisms that regulate self-renewal and differentiation fate decisions are poorly understood due to limited availability of experimental tools that distinguish the products of those fate decisions. The pluripotency factor SALL4 (sal-like protein 4) is implicated in stem cell maintenance and patterning in many organs during embryonic development, but expression becomes restricted to the gonads after birth. We analyzed the expression of SALL4 in the mouse testis during the first weeks after birth and in adult seminiferous tubules. In newborn mice, the isoform SALL4B is expressed in quiescent gonocytes at postnatal day 0 (PND0) and SALL4A is upregulated at PND7 when gonocytes have colonized the basement membrane and given rise to spermatogonia. During steady-state spermatogenesis in adult testes, SALL4 expression overlapped substantially with PLZF and LIN28 in Asingle, Apaired and Aaligned spermatogonia and therefore appears to be a marker of undifferentiated spermatogonia in mice. In contrast, co-expression of SALL4 with GFRα1 and cKIT identified distinct subpopulations of Aundiff in all clone sizes that might provide clues about SSC regulation. Collectively, these results indicate that 1) SALL4 isoforms are differentially expressed at the initiation of spermatogenesis, 2) SALL4 is expressed in undifferentiated spermatogonia in adult testes and 3) SALL4 co-staining with GFRα1 and cKIT reveals distinct subpopulations of Aundiff spermatogonia that merit further investigation. © 2013 Gassei, Orwig

    A database of microRNA expression patterns in Xenopus laevis

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    MicroRNAs (miRNAs) are short, non-coding RNAs around 22 nucleotides long. They inhibit gene expression either by translational repression or by causing the degradation of the mRNAs they bind to. Many are highly conserved amongst diverse organisms and have restricted spatio-temporal expression patterns during embryonic development where they are thought to be involved in generating accuracy of developmental timing and in supporting cell fate decisions and tissue identity. We determined the expression patterns of 180 miRNAs in Xenopus laevis embryos using LNA oligonucleotides. In addition we carried out small RNA-seq on different stages of early Xenopus development, identified 44 miRNAs belonging to 29 new families and characterized the expression of 5 of these. Our analyses identified miRNA expression in many organs of the developing embryo. In particular a large number were expressed in neural tissue and in the somites. Surprisingly none of the miRNAs we have looked at show expression in the heart. Our results have been made freely available as a resource in both XenMARK and Xenbase

    Exploring interdisciplinarity studies: a reconstructed curricular approach to the development of a humanities course emphasizing conceptual intergration and synthesis of disciplinary concepts

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    This project explores the question, how does the design of a humanities course emerge from previously published research and my own practical experience. The process takes into account the complex nature of interdisciplinarity studies. The identification and examination of Social Studies and English curricula are central to the entire project, as all the other decisions, pedagogically and in assessment are built on the understanding of those curricula. Through a reconstructed curricula focused on conceptual integration and synthesis of disciplinary concepts a curricular framework is created. From this framework, an humanities 10 curriculum map is developed as a living document to be shared with other teachers. The document focuses on curriculum, pedagogy and assessment practice. This project will demonstrate the benefits and the challenges that educators encounter when constructing interdisciplinarity studies

    Sprouty2 mediated tuning of signalling is essential for somite myogenesis

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    Background: Negative regulators of signal transduction cascades play critical roles in controlling different aspects of normal embryonic development. Sprouty2 (Spry2) negatively regulates receptor tyrosine kinases (RTK) and FGF signalling and is important in differentiation, cell migration and proliferation. In vertebrate embryos, Spry2 is expressed in paraxial mesoderm and in forming somites. Expression is maintained in the myotome until late stages of somite differentiation. However, its role and mode of action during somite myogenesis is still unclear. Results: Here, we analysed chick Spry2 expression and showed that it overlaps with that of myogenic regulatory factors MyoD and Mgn. Targeted mis-expression of Spry2 led to inhibition of myogenesis, whilst its C-terminal domain led to an increased number of myogenic cells by stimulating cell proliferation. Conclusions: Spry2 is expressed in somite myotomes and its expression overlaps with myogenic regulatory factors. Overexpression and dominant-negative interference showed that Spry2 plays a crucial role in regulating chick myogenesis by fine tuning of FGF signaling through a negative feedback loop. We also propose that mir-23, mir-27 and mir-128 could be part of the negative feedback loop mechanism. Our analysis is the first to shed some light on in vivo Spry2 function during chick somite myogenesis

    A Novel Mutation in the HSD17B10 Gene of a 10-Year-Old Boy with Refractory Epilepsy, Choreoathetosis and Learning Disability

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    Hydroxysteroid (17beta) dehydrogenase 10 (HSD10) is a mitochondrial multifunctional enzyme encoded by the HSD17B10 gene. Missense mutations in this gene result in HSD10 deficiency, whereas a silent mutation results in mental retardation, X-linked, syndromic 10 (MRXS10). Here we report a novel missense mutation found in the HSD17B10 gene, namely c.194T\u3eC transition (rs104886492), brought about by the loss of two forked methyl groups of valine 65 in the HSD10 active site. The affected boy, who possesses mutant HSD10 (p.V65A), has a neurological syndrome with metabolic derangements, choreoathetosis, refractory epilepsy and learning disability. He has no history of acute decompensation or metabolic acidosis whereas his urine organic acid profile, showing elevated levels of 2-methyl-3-hydroxybutyrate and tiglylglycine, is characteristic of HSD10 deficiency. His HSD10 activity was much lower than the normal control level, with normal β-ketothiolase activity. The c.194T\u3eC mutation in HSD17B10 can be identified by the restriction fragment polymorphism analysis, thereby facilitating the screening of this novel mutation in individuals with intellectual disability of unknown etiology and their family members much easier. The patient\u27s mother is an asymptomatic carrier, and has a mixed ancestry (Hawaiian, Japanese and Chinese). This demonstrates that HSD10 deficiency patients are not confined to a particular ethnicity although previously reported cases were either Spanish or German descendants

    Exposure of polychlorinated naphthalenes (PCNs) to Pakistani populations via non-dietary sources from neglected e-waste hubs:A problem of high health concern

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    To date limited information's are available concerning unintentional productions, screening, profiling, and health risks of polychlorinated naphthalenes (PCNs) in ambient environment and occupational environment. Literature reveals that dust is a neglected environmental matrix never measured for PCNs. To our knowledge, this is the first study to investigate the concentrations and health risks of PCNs in indoor dust, air, and blood of major e-waste recycling hubs in Pakistan. Indoor air (n = 125), dust (n = 250), and serum (n = 250) samples were collected from five major e-waste hubs and their vicinity to measure 39 PCN congeners using GC-ECNI-MS. ∑ 39PCN concentrations in indoor air, dust, and serum (worker > resident > children) samples ranged from 7.0 to 9583 pg/m 3, from 0.25 to 697 ng/g, and from 0.15 to 401 pg/g lipid weight, respectively. Predominant PCN congeners in indoor air and dust were tri- and tetra-CNs, while tetra- and penta-CNs were dominant in human serum samples. The higher PCNs contribution was recorded at the recycling units, while the lower was observed at the shops of the major e-waste hubs. Higher contribution of combustion origin CNs in air, dust and human samples showed combustion sources at the major e-waste hubs, while Halowax and Aroclor based technical mixture showed minor contribution in these samples. Mean toxic equivalent (TEQ) concentrations of PCNs were 2.79E +00 pg-TEQ/m 3, 1.60E −02 ng-TEQ/g, 8.11E −01 pg-TEQ/g, 7.14E −01 pg-TEQ/g, and 6.37E −01 pg-TEQ/g for indoor air, dust, and serum samples from workers, residents, and children, respectively. In our study, CNs- 66/67 and −73 in indoor air, dust, and human serum were the great contributors to total TEQ concentrations of PCNs. This first base line data directs government and agencies to implement rules, regulation to avoid negative health outcomes and suggests further awareness in regard of provision of proper knowledge to the target population. Due to lack of data on production, screening, and profiling of PCNs, this is the first study to investigate concentrations of PCNs in indoor dust, air, and blood serum at the major e-waste recycling hubs in Pakistan where crude recycling methods were common and the potential health risks to human via its non-dietary pathways exposure would experience. This study results identified that Tri-to penta-CNs were dominant in the environmental samples and showed that higher PCNs contribution in the environmental samples was recorded by Combustion based activities as compared to technical mixture based CNs
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