Treatment Guidelines for Rare, Early-Onset, Treatment-Resistant Epileptic Conditions:A Literature Review on Dravet Syndrome, Lennox-Gastaut Syndrome and CDKL5 Deficiency Disorder

Background: Dravet syndrome (DS), Lennox-Gastaut syndrome (LGS) and CDKL5 deficiency disorder (CDD) are rare epileptic conditions, characterised by drug-resistant seizures. Seizure management in these patients requires careful therapy selection. This targeted literature review (TLR) aimed to collate and synthesise information from country-specific and international treatment guidelines for DS, LGS and CDD.Methods: A TLR was performed between 25th January and 11th March 2021. Online rare diseases and guideline databases were manually searched in addition to websites of national health technology assessment bodies for the following countries: Australia, Canada, France, Germany, Israel, Italy, Japan, Spain, Switzerland, UK and US, as defined by pre-specified eligibility criteria. Search terms, developed for each condition, were translated into local languages where appropriate. Descriptive analyses were performed to examine the geographical distribution of included guidelines; methodologies used to develop guidelines; cross-referencing of treatment recommendations made within other guidelines; patterns of treatment recommendations. An author map was created using R version 3.5.1, to visualise the extent of collaboration between authors.Results: Forty total guidelines were included, of which 29, 34 and 0 contained recommendations for DS, LGS and CDD, respectively (some provided recommendations for ≥1 condition). Most were country-specific, with guideline authors predominantly publishing in regional groups. Five guidelines were classified as “International” and displayed connections between author groups in the US, UK, France and Italy. Reported guideline development processes were lacking [43% (17 guidelines) had unclear/absent literature review methodologies] and those reported were variable, including both systematic and targeted literature reviews. Use of expert consultation was also variable. A high degree of heterogeneity was observed in the availability of treatment recommendations across disorders, with 271 and 190 recommendations for LGS and DS, respectively, and contradictory positive and negative treatment recommendations for several drugs in each indication [35% (11/31) and 22% (6/27) in LGS and DS, respectively].Conclusions: This review highlights the need for further high-quality international consensus-based treatment guidelines for LGS, DS, and particularly for CDD (for which no treatment guidelines were identified). Supra-national consensus guidance based on findings from a wider geographical range may improve resource allocation and establish an improved world-wide standard of care

Proof-of-concept trial of the combination of lactitol with Bifidobacterium bifidum and Lactobacillus acidophilus for the eradication of intestinal OXA-48-producing Enterobacteriaceae

Background: The major reservoir of carbapenemase-producing Enterobacteriaceae (CPE) is the gastrointestinal tract of colonized patients. Colonization is silent and may last for months, but the risk of infection by CPE in colonized patients is significant. Methods: Eight long-Term intestinal carriers of OXA-48-producing Enterobacteriaceae (OXA-PE) were treated during 3 weeks with daily oral lactitol (Emportal®), Bifidobacterium bifidum and Lactobacillus acidophilus (Infloran®). Weekly stool samples were collected during the treatment period and 6 weeks later. The presence of OXA-PE was investigated by microbiological cultures and qPCR. Results: At the end of treatment (EoT, secondary endpoint 1), four of the subjects had negative OXA-PE cultures. Three weeks later (secondary endpoint 2), six subjects were negative. Six weeks after the EoT (primary endpoint), three subjects had negative OXA-PE cultures. The relative intestinal load of OXA-PE decreased in all the patients during treatment. Conclusions: The combination of prebiotics and probiotics was well tolerated. A rapid reduction on the OXA-PE intestinal loads was observed. At the EoT, decolonization was achieved in three patients

LA FIGURA DEL EDUCADOR SOCIAL

At the moment we are attending the origin of new social, cultural and demographic situations that they make sprout in the professionals of the education new concerns of attention and formative development. In this article reference is made to diverse characteristic that can characterize one of these professionals: the social educator.Actualmente estamos asistiendo al origen de nuevas situaciones sociales, culturales y demográficas que hacen brotar en los profesionales de la educación nuevas preocupaciones de atención y desarrollo formativo. En este artículo se hace referencia a diversas características que pueden caracterizar a uno de estos profesionales: el educador social

Development of secretome‑based strategies to improve cell culture protocols in tissue engineering

This study was supported by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tec- nológica (I + D + I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III), grants FIS PI18/0331, FIS PI21/0980, FIS PI18/0332, FIS PI20/0317, ICI19/00024 and ICI21/00010, and by grants PE-0395- 2019 and PI-0442-2019 from the Consejería de Salud y Familias, Junta de Andalucía, Spain. Additional support was provided through grant B-CTS-450-UGR20 (proyectos de I + D + i en el marco del Programa Operativo FEDER Andalucía 2014–2020, University of Granada and Consejería de Transformación Económica, Industria, Conocimiento y Universidades), and cofinancing was provided from the European Regional Development Fund (ERDF) through the “Una manera de hacer Europa” program.The online version contains supplementary material available at https://doi. org/10. 1038/s41598-022-14115-yAdvances in skin tissue engineering have promoted the development of artificial skin substitutes to treat large burns and other major skin loss conditions. However, one of the main drawbacks to bioengineered skin is the need to obtain a large amount of viable epithelial cells in short periods of time, making the skin biofabrication process challenging and slow. Enhancing skin epithelial cell cultures by using mesenchymal stem cells secretome can favor the scalability of manufacturing processes for bioengineered skin. The effects of three different types of secretome derived from human mesenchymal stem cells, e.g. hADSC‑s (adipose cells), hDPSC‑s (dental pulp) and hWJSC‑s (umbilical cord), were evaluated on cultured skin epithelial cells during 24, 48, 72 and 120 h to determine the potential of this product to enhance cell proliferation and improve biofabrication strategies for tissue engineering. Then, secretomes were applied in vivo in preliminary analyses carried out on Wistar rats. Results showed that the use of secretomes derived from mesenchymal stem cells enhanced currently available cell culture protocols. Secretome was associated with increased viability, proliferation and migration of human skin epithelial cells, with hDPSC‑s and hWJSC‑s yielding greater inductive effects than hADSC‑s. Animals treated with hWJSC‑s and especially, hDPSC‑s tended to show enhanced wound healing in vivo with no detectable side effects. Mesenchymal stem cells derived secretomes could be considered as a promising approach to cell‑free therapy able to improve skin wound healing and regeneration.Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I + D + I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III) FIS PI18/0331, FIS PI21/0980, FIS PI18/0332, FIS PI20/0317, ICI19/00024, ICI21/00010Junta de Andalucia PE-0395-2019, PI-0442-2019Proyectos de I + D + i en el marco del Programa Operativo FEDER Andalucia , University of Granada and Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-CTS-450-UGR20European Commissio

Isolation, Characterization and Lipid-Binding Properties of the Recalcitrant FtsA Division Protein from Escherichia coli

We have obtained milligram amounts of highly pure Escherichia coli division protein FtsA from inclusion bodies with an optimized purification method that, by overcoming the reluctance of FtsA to be purified, surmounts a bottleneck for the analysis of the molecular basis of FtsA function. Purified FtsA is folded, mostly monomeric and interacts with lipids. The apparent affinity of FtsA binding to the inner membrane is ten-fold higher than to phospholipids, suggesting that inner membrane proteins could modulate FtsA-membrane interactions. Binding of FtsA to lipids and membranes is insensitive to ionic strength, indicating that a net contribution of hydrophobic interactions is involved in the association of FtsA to lipid/membrane structures

Soluble NgR Fusion Protein Modulates the Proliferation of Neural Progenitor Cells via the Notch Pathway

NogoA, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein are CNS myelin molecules that bind to the neuronal Nogo-66 receptor (NgR) and inhibit axon growth. The NgR antagonist, soluble NgR1-Fc protein (sNgR-Fc), facilitates axon regeneration by neutralizing the inhibitory effects of myelin proteins in experimental models of CNS injury. Here we aim to investigate the effect of sNgR-Fc on the proliferation of neural progenitor cells (NPCs). The hippocampus cells of embryonic rats were isolated and cultured in vitro. The expression of nestin, βIII-Tubulin, GFAP and Nogo-A on these cells was observed using immunocytochemistry. In order to investigate the effect on proliferation of NPCs, sNgR-Fc, MAG-Fc chimera and Notch1 blocker were added respectively. The total cell number for the proliferated NPCs was counted. BrdU was applied and the rate of proliferating cells was examined. The level of Notch1 was analyzed using Western blotting. We identified that NogoA is expressed in NPCs. sNgR-Fc significantly enhanced the proliferation of NPCs in vitro as indicated by BrdU labeling and total cell count. This proliferation effect was abolished by the administration of MAG suggesting specificity. In addition, we demonstrate that sNgR-Fc is a potent activator for Notch1 and Notch1 antagonist reversed the effect of sNgR-Fc on NPC proliferation. Our results suggest that sNgR-Fc may modulate Nogo activity to induce NPC proliferation via the Notch pathway

The Min System and Nucleoid Occlusion Are Not Required for Identifying the Division Site in Bacillus subtilis but Ensure Its Efficient Utilization

Precise temporal and spatial control of cell division is essential for progeny survival. The current general view is that precise positioning of the division site at midcell in rod-shaped bacteria is a result of the combined action of the Min system and nucleoid (chromosome) occlusion. Both systems prevent assembly of the cytokinetic Z ring at inappropriate places in the cell, restricting Z rings to the correct site at midcell. Here we show that in the bacterium Bacillus subtilis Z rings are positioned precisely at midcell in the complete absence of both these systems, revealing the existence of a mechanism independent of Min and nucleoid occlusion that identifies midcell in this organism. We further show that Z ring assembly at midcell is delayed in the absence of Min and Noc proteins, while at the same time FtsZ accumulates at other potential division sites. This suggests that a major role for Min and Noc is to ensure efficient utilization of the midcell division site by preventing Z ring assembly at potential division sites, including the cell poles. Our data lead us to propose a model in which spatial regulation of division in B. subtilis involves identification of the division site at midcell that requires Min and nucleoid occlusion to ensure efficient Z ring assembly there and only there, at the right time in the cell cycle

Developmental expression of orphan g protein-coupled receptor 50 in the mouse brain

[Image: see text] Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a specific function has not been identified. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identified novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis

Role of the Cellular Prion Protein in Oligodendrocyte Precursor Cell Proliferation and Differentiation in the Developing and Adult Mouse CNS

There are numerous studies describing the signaling mechanisms that mediate oligodendrocyte precursor cell (OPC) proliferation and differentiation, although the contribution of the cellular prion protein (PrPc) to this process remains unclear. PrPc is a glycosyl-phosphatidylinositol (GPI)-anchored glycoprotein involved in diverse cellular processes during the development and maturation of the mammalian central nervous system (CNS). Here we describe how PrPc influences oligodendrocyte proliferation in the developing and adult CNS. OPCs that lack PrPc proliferate more vigorously at the expense of a delay in differentiation, which correlates with changes in the expression of oligodendrocyte lineage markers. In addition, numerous NG2-positive cells were observed in cortical regions of adult PrPc knockout mice, although no significant changes in myelination can be seen, probably due to the death of surplus cells

Psoríase e o impacto na sexualidade

Psoriasis is a skin disease, not contagious, chronic, serious and considered limiting, resulting prejudice, stigma and social exclusion providing loss in quality of life.Mostly affects self-image of affected people, as well as self-esteem and self-concept.These disease characteristics bring great losses in occupational areas, damaging interpersonal relationships of individuals, which may cause impact on various occupational areas, including sexuality, which translates not only as sex itself, but also as identity, social roles, pleasure, reproduction and other. The aim of this study was to investigate the self-image of individuals with psoriasis and their influence on sexuality. This is a qualitative study of a case study with seven patients in the Reference Center, Support and Treatment Paraíba State Psoriasis installed in the clinic of the University Hospital LauroWanderley – Universidade Federal da Paraíba. Data were collected through semi-structured interview, categorized and treated according to the Content Analysis. The results show that psoriasis affects the sexuality of individuals, more significantly in women's fashion, as attribute different meanings to the body, for reasons of aesthetics and beauty.Men also feel affected, but in view of the achievement, caring companionship, and seek to clarify their partners or future partners and their relationships, about the disease. We note here the influence of culture to gender conditions.A Psoríase é uma doença dermatológica, não contagiosa, crônica, considerada grave e limitante, acarretando preconceito, estigma e exclusão social proporcionando prejuízos na qualidade de vida. Na sua grande maioria, afeta a autoimagem das pessoas acometidas, assim como a autoestima e autoconceito. Estas características da doença trazem grandes prejuízos nas áreas ocupacionais, prejudicando as relações interpessoais dos indivíduos, podendo ocasionar impacto em várias áreas ocupacionais, incluindo a sexualidade, que se traduz não só como o sexo em si, mas também como identidade, papéis sociais, prazer, reprodução entre outros. O objetivo deste estudo foi investigar sobre a autoimagem dos indivíduos com psoríase e sua influência na sexualidade. Trata-se de um estudo qualitativo do tipo estudo de caso, com sete pacientes do Centro de Referência, Apoio e Tratamento em Psoríase do Estado da Paraíba instalado no ambulatório do Hospital Universitário Lauro Wanderley – Universidade Federal da Paraíba. Os dados foram coletados por meio de entrevista semiestruturada, categorizados e tratados de acordo com a Análise de Conteúdo. Os resultados encontrados mostram que a psoríase afeta a sexualidade dos indivíduos, de forma mais significativa nas mulheres, pois atribuem significados diferentes ao corpo, por razões de estética e beleza. Os homens também se sentem afetados, mas na perspectiva da conquista, se importando com o companheirismo, e procuram esclarecer para suas companheiras ou futuras companheiras e em seus relacionamentos, sobre a doença. Observamos aqui a influência da cultura às condições de gêner