Psychotherapeutic practice in paediatric oncology: four examples

Psychotherapy, often used with children treated for a solid tumour, is seldom described. We present four examples of such therapies: a mother who refused enucleation for her 7-month-old boy; a boy's jealousy towards his sister who was being treated for a brain tumour; a teenager troubled by his scar; a 7-year-old boy embarrassed by the unconscious memory of his treatment when he was 5 months old. All names have been changed, for reasons of privacy. Psychotherapies aim to help children and parents to cope with the violent experience of having cancer, to recover their freedom of thought and decision-making concerning their life, their place in the family, their body image, their self-esteem, their identity. These descriptions of brief psychotherapy could help paediatricians to gain a more thorough understanding of the child's experience, to improve collaboration with psychotherapists and to confront clinical skills of psychotherapists. © 2000 Cancer Research Campaig

The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

Definitive radiotherapy and Single-Agent radiosensitizing Ifosfamide in Patients with localized, irresectable Soft Tissue Sarcoma: A retrospective analysis

<p>Abstract</p> <p>Background and Purpose</p> <p>Standard therapy for soft-tissue sarcomas remains complete resection. For primary radiotherapy local control rates of 30-45% have been reported. We analyzed retrospectively 11 cases of radiochemotherapy with single-agent ifosfamide in patients with macroscopic soft-tissue sarcomas.</p> <p>Patients and Methods</p> <p>The patients were treated in irresectable high risk situations. Radiation therapy was performed with median 60 Gy. During the first and fifth week the concomitant chemotherapy with ifosfamide was added. Two patients received trimodal therapy with additional regional hyperthermia.</p> <p>Results</p> <p>The therapy was completed in 73% of the patients. Average local control time was 91 months, median disease-free-survival/overall-survival was 8/26 months. Five-year rates for local control/disease free survival/overall survival were 70%/34%/34%. The limited prognosis is mainly caused by systemic treatment failure.</p> <p>Conclusions</p> <p>The data strongly suggest a better outcome of radiochemotherapy with ifosfamide compared to radiotherapy alone and radiotherapy in combination with other radiosensitizers.</p

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

New Alzheimer Amyloid β Responsive Genes Identified in Human Neuroblastoma Cells by Hierarchical Clustering

Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. Aβ42, in contrast to Aβ40, is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased Aβ40 and Aβ42 levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on Aβ40 and Aβ42 levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased Aβ42/Aβ40 ratio. Importantly however, an increased Aβ42/Aβ40 ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased Aβ42/Aβ40 ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased Aβ42/Aβ40 ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes

Functional characterization of the trans-membrane domain interactions of the Sec61 protein translocation complex beta-subunit

<p>Abstract</p> <p>Background</p> <p>In eukaryotic cells co- and post-translational protein translocation is mediated by the trimeric Sec61 complex. Currently, the role of the Sec61 complex β-subunit in protein translocation is poorly understood. We have shown previously that in <it>Saccharomyces cerevisiae </it>the trans-membrane domain alone is sufficient for the function of the β-subunit Sbh1p in co-translational protein translocation. In addition, Sbh1p co-purifies not only with the protein translocation channel subunits Sec61p and Sss1p, but also with the reticulon family protein Rtn1p.</p> <p>Results</p> <p>We used random mutagenesis to generate novel Sbh1p mutants in order to functionally map the Sbh1p trans-membrane domain. These mutants were analyzed for their interactions with Sec61p and how they support co-translational protein translocation. The distribution of mutations identifies one side of the Sbh1p trans-membrane domain α-helix that is involved in interactions with Sec61p and that is important for Sbh1p function in protein translocation. At the same time, these mutations do not affect Sbh1p interaction with Rtn1p. Furthermore we show that Sbh1p is found in protein complexes containing not only Rtn1p, but also the two other reticulon-like proteins Rtn2p and Yop1p.</p> <p>Conclusion</p> <p>Our results identify functionally important amino acids in the Sbh1p trans-membrane domain. In addition, our results provide additional support for the involvement of Sec61β in processes unlinked to protein translocation.</p

A Continuum of Cell States Spans Pluripotency and Lineage Commitment in Human Embryonic Stem Cells

Background: Commitment in embryonic stem cells is often depicted as a binary choice between alternate cell states, pluripotency and specification to a particular germ layer or extraembryonic lineage. However, close examination of human ES cell cultures has revealed significant heterogeneity in the stem cell compartment. Methodology/Principal Findings: We isolated subpopulations of embryonic stem cells using surface markers, then examined their expression of pluripotency genes and lineage specific transcription factors at the single cell level, and tested their ability to regenerate colonies of stem cells. Transcript analysis of single embryonic stem cells showed that there is a gradient and a hierarchy of expression of pluripotency genes in the population. Even cells at the top of the hierarchy generally express only a subset of the stem cell genes studied. Many cells co-express pluripotency and lineage specific genes. Cells along the continuum show a progressively decreasing likelihood of self renewal as their expression of stem cell surface markers and pluripotency genes wanes. Most cells that are positive for stem cell surface markers express Oct-4, but only those towards the top of the hierarchy express the nodal receptor TDGF-1 and the growth factor GDF3. Significance: These findings on gene expression in single embryonic stem cells are in concert with recent studies of early mammalian development, which reveal molecular heterogeneity and a stochasticity of gene expression in blastomeres. Our work indicates that only a small fraction of the population resides at the top of the hierarchy, that lineage priming (co-expression of stem cell and lineage specific genes) characterizes pluripotent stem cell populations, and that extrinsic signaling pathways are upstream of transcription factor networks that control pluripotency

Abeta42-Induced Neurodegeneration via an Age-Dependent Autophagic-Lysosomal Injury in Drosophila

The mechanism of widespread neuronal death occurring in Alzheimer's disease (AD) remains enigmatic even after extensive investigation during the last two decades. Amyloid beta 42 peptide (Aβ1–42) is believed to play a causative role in the development of AD. Here we expressed human Aβ1–42 and amyloid beta 40 (Aβ1–40) in Drosophila neurons. Aβ1–42 but not Aβ1–40 causes an extensive accumulation of autophagic vesicles that become increasingly dysfunctional with age. Aβ1–42-induced impairment of the degradative function, as well as the structural integrity, of post-lysosomal autophagic vesicles triggers a neurodegenerative cascade that can be enhanced by autophagy activation or partially rescued by autophagy inhibition. Compromise and leakage from post-lysosomal vesicles result in cytosolic acidification, additional damage to membranes and organelles, and erosive destruction of cytoplasm leading to eventual neuron death. Neuronal autophagy initially appears to play a pro-survival role that changes in an age-dependent way to a pro-death role in the context of Aβ1–42 expression. Our in vivo observations provide a mechanistic understanding for the differential neurotoxicity of Aβ1–42 and Aβ1–40, and reveal an Aβ1–42-induced death execution pathway mediated by an age-dependent autophagic-lysosomal injury

Global Gene Expression Analysis of Murine Limb Development

Detailed information about stage-specific changes in gene expression is crucial for understanding the gene regulatory networks underlying development and the various signal transduction pathways contributing to morphogenesis. Here we describe the global gene expression dynamics during early murine limb development, when cartilage, tendons, muscle, joints, vasculature and nerves are specified and the musculoskeletal system of limbs is established. We used whole-genome microarrays to identify genes with differential expression at 5 stages of limb development (E9.5 to 13.5), during fore- and hind-limb patterning. We found that the onset of limb formation is characterized by an up-regulation of transcription factors, which is followed by a massive activation of genes during E10.5 and E11.5 which levels off at later time points. Among the 3520 genes identified as significantly up-regulated in the limb, we find ∼30% to be novel, dramatically expanding the repertoire of candidate genes likely to function in the limb. Hierarchical and stage-specific clustering identified expression profiles that are likely to correlate with functional programs during limb development and further characterization of these transcripts will provide new insights into specific tissue patterning processes. Here, we provide for the first time a comprehensive analysis of developmentally regulated genes during murine limb development, and provide some novel insights into the expression dynamics governing limb morphogenesis