Effect of equine assisted therapy on respiratory function and scoliosis in children with spinal muscular atrophy: observed intervention study

Respiratory function is one of the key pillars of health in children/patients with neuromuscular diseases such as spinal muscular atrophy. Impaired respiratory function is closely linkedtothe development of scoliotic posture andthe subsequent onset of scoliosis.For this reason, I have chosen these two health parameters to assess the effect of hippotherapy as a therapeutic method for children with neuromuscular diseases such as spinal muscular atrophy. Therefore, respiratory functions and scoliosis status were examined. The aim of this study was to measure the impact of hippotherapy on these functions and compare their values across three measurements conducted during a hippotherapy rehabilitation stay for children with spinal muscular atrophy. The study includedparticipants aged3 to9 years with a diagnosedspinal muscular atrophy, all of whom attended a hipporehabilitation stay at the Mirákl Hipporehabilitation Center. All children received gene therapy, and more than half of them presented with respiratory problems and scoliosis of varying degrees. During these six-day stays, the participants underwent intensive hippotherapy sessions lasting 15 minutes twice a day, along with additional complementary therapies (physiotherapy, canine therapy, art therapy, etc.) and the total duration of the study...Dechová funkce je jedna z hlavních pilířů zdravotního stavu dětí/pacientů s neuromuskulárními onemocněními jako je spinální svalová atrofie. Současně se zhoršenou dechovou funkcí se pojí vznik a rychlejší progrese skoliózykvůli nedostatečné aktivitě dechových a posturálníchsvalů. (41) Z tohoto důvodu jsem si zvolil tyto dva zdravotní parametrypro zjištění efektu hipoterapie, jakožto jednu z léčebných metod pro děti s neuromuskulárním onemocněním. Testovány tedy byly dechové funkce a stav skoliózy. Cílem této práce bylo změřit vliv hiporehabilitace - hipoterapie na tyto funkce a porovnat jejichhodnoty mezi trěmi měřeními vrámci hiporehabilitačníhopobytuu dětí se spinální svalovou atrofií. Využita byla certifikovaná metodika Hipoterapie u dětské mozkové obrny a její principy léčby aplikované na onemocnění SMA. Do studie byli zapojeni probandi, účastnící se hiporehabilitačního pobytu v Centrum hiporehabilitace Mirákl, ve věku 3-9 let s diagnostikovaným onemocněním spinální svalové atrofie, u všech dětí byla aplikována genová terapie, přičemž u více než poloviny byly přítomné dechové obtíže a skolióza různého stupně. V rámci těchto dvanácti hiporehabilitačních jednotek probandi podstoupili intenzivní hipoterapii v délce 15 minut dvakrát za den a další doplňující sociální terapie, která má spíše...Department of Rehabilitation Medicine 3FM CU and UHKVKlinika rehabilitačního lékařství 3. LF UK a FNKV3. lékařská fakultaThird Faculty of Medicin

Regional undo/redo techniques for large interactive surfaces

When multiple users are simultaneously sharing a work-space, it is not always clear what should happen when a user invokes an undo action. In this paper we explore dif-ferent user interfaces for undo/redo for co-located collabo-rative workspaces, such as large interactive whiteboards. A preliminary study revealed that users expect neither a global nor personal undo, but rather a regional undo. We propose and evaluate three automatic regional undo/redo techniques (clustering, workspace, field of view) designed for a large interactive whiteboard. The results of the evaluation showed that an undo technique based on users ’ field of view was most preferred, while the content-based clustering technique produced most errors. We conclude with poten-tial improvements to the developed techniques, and propose a set of design recommendations for implementing regional undo/redo on large interactive surfaces. Author Keywords Undo; co-located collaboration; interactive surfaces; inter

Autophagy in the Thymic Epithelium Is Dispensable for the Development of Self-Tolerance in a Novel Mouse Model

The thymic epithelium plays critical roles in the positive and negative selection of T cells. Recently, it was proposed that autophagy in thymic epithelial cells is essential for the induction of T cell tolerance to self antigens and thus for the prevention of autoimmune diseases. Here we have tested this hypothesis using mouse models in which autophagy was blocked specifically in epithelial cells expressing keratin 14 (K14), including the precursor of thymic epithelial cells. While the thymic epithelial cells of mice carrying the floxed Atg7 gene (ATG7 f/f) showed a high level of autophagy, as determined by LC3 Western blot analysis and fluorescence detection of the recombinant green fluorescent protein (GFP)-LC3 reporter protein on autophagosomes, autophagy in the thymic epithelium was efficiently suppressed by deletion of the Atg7 gene using the Cre-loxP system (ATG7 f/f K14-Cre). Suppression of autophagy led to the massive accumulation of p62/sequestosome 1 (SQSTM1) in thymic epithelial cells. However, the structure of the thymic epithelium as well as the organization and the size of the thymus were not altered in mutant mice. The ratio of CD4 to CD8-positive T cells, as well as the frequency of activated (CD69+) CD4 T cells in lymphoid organs, did not differ between mice with autophagy-competent and autophagy-deficient thymic epithelium. Inflammatory infiltrating cells, potentially indicative of autoimmune reactions, were present in the liver, lung, and colon of a similar fraction of ATG7 f/f and ATG7 f/f K14-Cre mice. In contrast to previously reported mice, that had received an autophagy-deficient thymus transplant, ATG7 f/f K14-Cre mice did not suffer from autoimmunity-induced weight loss. In summary, the results of this study suggest that autophagy in the thymic epithelium is dispensable for negative selection of autoreactive T cells

Molecular Dissection of Mesenchymal–Epithelial Interactions in the Hair Follicle

De novo hair follicle formation in embryonic skin and new hair growth in adult skin are initiated when specialized mesenchymal dermal papilla (DP) cells send cues to multipotent epithelial stem cells. Subsequently, DP cells are enveloped by epithelial stem cell progeny and other cell types to form a niche orchestrating hair growth. Understanding the general biological principles that govern the mesenchymal–epithelial interactions within the DP niche, however, has been hampered so far by the lack of systematic approaches to dissect the complete molecular make-up of this complex tissue. Here, we take a novel multicolor labeling approach, using cell type–specific transgenic expression of red and green fluorescent proteins in combination with immunolabeling of specific antigens, to isolate pure populations of DP and four of its surrounding cell types: dermal fibroblasts, melanocytes, and two different populations of epithelial progenitors (matrix and outer root sheath cells). By defining their transcriptional profiles, we develop molecular signatures characteristic for the DP and its niche. Validating the functional importance of these signatures is a group of genes linked to hair disorders that have been largely unexplored. Additionally, the DP signature reveals novel signaling and transcription regulators that distinguish them from other cell types. The mesenchymal–epithelial signatures include key factors previously implicated in ectodermal-neural fate determination, as well as a myriad of regulators of bone morphogenetic protein signaling. These findings establish a foundation for future functional analyses of the roles of these genes in hair development. Overall, our strategy illustrates how knowledge of the genes uniquely expressed by each cell type residing in a complex niche can reveal important new insights into the biology of the tissue and its associated disease states

Caspase-8 deficiency in epidermal keratinocytes triggers an inflammatory skin disease

Expression of enzymatically inactive caspase-8, or deletion of caspase-8 from basal epidermal keratinocytes, triggers chronic skin inflammation in mice. Unlike similar inflammation resulting from arrest of nuclear factor κB activation in the epidermal cells, the effect induced by caspase-8 deficiency did not depend on TNF, IL-1, dermal macrophage function, or expression of the toll-like receptor adapter proteins MyD88 or TRIF. Both interferon regulatory factor (IRF) 3 and TANK-binding kinase were constitutively phosphorylated in the caspase-8–deficient epidermis, and knockdown of IRF3 in the epidermis-derived cells from these mice abolished the expression of up-regulated genes. Temporal and spatial analyses of the alterations in gene expression that result from caspase-8 deficiency reveal that the changes are initiated before birth, around the time that cornification develops, and occur mainly in the suprabasal layer. Finally, we found that caspase-8–deficient keratinocytes display an enhanced response to gene activation by transfected DNA. Our findings suggest that an enhanced response to endogenous activators of IRF3 in the epidermis, presumably generated in association with keratinocyte differentiation, contributes to the skin inflammatory process triggered by caspase-8 deficiency