Prevalence of Childhood Obesity in Portugal: A Narrative Review of the Literature

Background: The number of childhood obesity cases has been increasing in several countries around the world. In view of all the associated complications at an early stage of child development, it becomes urgent to understand this problem in depth. Objective: The aim of this work was to describe the prevalence of childhood obesity in Portugal and analyze the trend of its evolution in recent years. Materials and Methods: This is a narrative review of the literature in the databases on the following platforms: Academic Google, Scientific Electronic Library Online (SciELO), EBSCO Host, and Biblioteca Virtual em Saúde (BVS). The keywords used were: Prevalence, Pediatric Obesity, Child Overweight, and Portugal. Results and Discussion: Data on the prevalence of childhood obesity in Portugal are presented, describing the results of studies conducted at national and district level, in the different age groups and by sex. Conclusions: The data reveal that the prevalence of overweight in Portugal ranges between 20 and 40%, and of obesity between 10 and 15%, which reinforces the urgent need for monitoring and implementing preventive measures.info:eu-repo/semantics/publishedVersio

Inhibition of HDACs reduces Ewing sarcoma tumor growth through EWS-FLI1 protein destabilization

Oncogenic transcription factors lacking enzymatic activity or targetable binding pockets are typically considered "undruggable". An example is provided by the EWS-FLI1 oncoprotein, whose continuous expression and activity as transcription factor are critically required for Ewing sarcoma tumor formation, maintenance, and proliferation. Because neither upstream nor downstream targets have so far disabled its oncogenic potential, we performed a high-throughput drug screen (HTS), enriched for FDA-approved drugs, coupled to a Global Protein Stability (GPS) approach to identify novel compounds capable to destabilize EWS-FLI1 protein by enhancing its degradation through the ubiquitin-proteasome system. The protein stability screen revealed the dual histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K) inhibitor called fimepinostat (CUDC-907) as top candidate to modulate EWS-FLI1 stability. Fimepinostat strongly reduced EWS-FLI1 protein abundance, reduced viability of several Ewing sarcoma cell lines and PDX-derived primary cells and delayed tumor growth in a xenograft mouse model, whereas it did not significantly affect healthy cells. Mechanistically, we demonstrated that EWS-FLI1 protein levels were mainly regulated by fimepinostat's HDAC activity. Our study demonstrates that HTS combined to GPS is a reliable approach to identify drug candidates able to modulate stability of EWS-FLI1 and lays new ground for the development of novel therapeutic strategies aimed to reduce Ewing sarcoma tumor progression. Keywords: EWS-FLI1; Ewing sarcoma; Fimepinostat; HDACi; Protein stabilit

Corrigendum to "Inhibition of HDACs reduces Ewing sarcoma tumor growth through EWS-FLI1 protein destabilization" [Neoplasia volume 27 (2022) pp. 100784/Number C]

Oncogenic transcription factors lacking enzymatic activity or targetable binding pockets are typically considered “undruggable”. An example is provided by the EWS-FLI1 oncoprotein, whose continuous expression and activity as transcription factor are critically required for Ewing sarcoma tumor formation, maintenance, and proliferation. Because neither upstream nor downstream targets have so far disabled its oncogenic potential, we performed a high-throughput drug screen (HTS), enriched for FDA-approved drugs, coupled to a Global Protein Stability (GPS) approach to identify novel compounds capable to destabilize EWS-FLI1 protein by enhancing its degradation through the ubiquitin-proteasome system. The protein stability screen revealed the dual histone deacetylase (HDAC) and phosphatidylinositol-3-kinase (PI3K) inhibitor called fimepinostat (CUDC-907) as top candidate to modulate EWS-FLI1 stability. Fimepinostat strongly reduced EWS-FLI1 protein abundance, reduced viability of several Ewing sarcoma cell lines and PDX-derived primary cells and delayed tumor growth in a xenograft mouse model, whereas it did not significantly affect healthy cells. Mechanistically, we demonstrated that EWS-FLI1 protein levels were mainly regulated by fimepinostat's HDAC activity. Our study demonstrates that HTS combined to GPS is a reliable approach to identify drug candidates able to modulate stability of EWS-FLI1 and lays new ground for the development of novel therapeutic strategies aimed to reduce Ewing sarcoma tumor progression

Human and companion animal proteus mirabilis sharing

Research Areas: MicrobiologyProteus mirabilis is an important pathogen that is associated with urinary tract infections. This study aims to determine the colonization and sharing of P. mirabilis between healthy companion animals and humans that are living together and to evaluate the clonal relatedness of the fecal and clinical stains. Eighteen households (24 humans, 18 dogs, 8 cats) with at least one human–animal pair were studied. Fecal samples were plated onto MacConkey and Hektoen agar and P. mirabilis PFGE analysis (NotI; Dice/UPGMA; 1.5% tolerance) was conducted for the households with multiple positive participants. Antimicrobial-resistance was tested according to CLSI. The fecal P. mirabilis pulse-types were compared with uropathogenic clinical strains (n = 183). Forty-nine P. mirabilis were isolated from eight households. The percentage of colonization in the dogs (44.4%, n = 8/18) was significantly higher (p = 0.0329) than in the humans (12.5%, n = 3/24). Three households had multiple colonized participants. One human–dog pair shared related P. mirabilis strains, which clustered with a clinical strain of animal origin (82.5%). One fecal P. mirabilis strain, from a dog, clustered with two human community-acquired clinical strains (80.9%, 88.9%). To our knowledge, this is the first report of dogs and humans living in close contact and sharing related P. mirabilis strains. The high frequency of colonization in the dogs underlines their possible role as P. mirabilis reservoirs for humans and other dogs.info:eu-repo/semantics/publishedVersio

Extracellular vesicles shed by trypanosoma brucei brucei manipulate host mononuclear cells

Funding Information: Funding: This study was supported by FCT—Foundation for Science and Technology, I.P., through research grant PTDC/CVT-CVT/28908/2017 and by national funds within the scope of Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA, UIDB/00276/2020) and Global Health and Tropical Medicine (GHTM, UID/04413/2020). Funding Information: This study was supported by FCT?Foundation for Science and Technology, I.P., through research grant PTDC/CVT-CVT/28908/2017 and by national funds within the scope of Centro de Investiga??o Interdisciplinar em Sanidade Animal (CIISA, UIDB/00276/2020) and Global Health and Tropical Medicine (GHTM, UID/04413/2020). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.African trypanosomiasis or sleeping sickness is a zoonotic disease caused by Trypanosoma brucei, a protozoan parasite transmitted by Glossina spp. (tsetse fly). Parasite introduction into mammal hosts triggers a succession of events, involving both innate and adaptive immunity. Macrophages (MΦ) have a key role in innate defence since they are antigen-presenting cells and have a micro-bicidal function essential for trypanosome clearance. Adaptive immune defence is carried out by lymphocytes, especially by T cells that promote an integrated immune response. Like mammal cells, T. b. brucei parasites release extracellular vesicles (TbEVs), which carry macromolecules that can be transferred to host cells, transmitting biological information able to manipulate cell immune response. However, the exact role of TbEVs in host immune response remains poorly understood. Thus, the current study examined the effect elicited by TbEVs on MΦ and T lymphocytes. A combined approach of microscopy, nanoparticle tracking analysis, multiparametric flow cytometry, colourimetric assays and detailed statistical analyses were used to evaluate the influence of TbEVs in mouse mononuclear cells. It was shown that TbEVs can establish direct communication with cells of innate and adaptative immunity. TbEVs induce the differentiation of both M1-and M2-MΦ and elicit the expansion of MHCI+, MHCII+ and MHCI+ MHCII+ MΦ subpopulations. In T lymphocytes, TbEVs drive the overexpression of cell-surface CD3 and the nuclear factor FoxP3, which lead to the differentiation of regulatory CD4+ and CD8+ T cells. Moreover, this study indicates that T. b. brucei and TbEVs seem to display opposite but complementary effects in the host, establishing a balance between parasite growth and controlled immune response, at least during the early phase of infection.publishersversionpublishe

Finely tuned fiber-based porous structures for bone tissue engineering applications

info:eu-repo/semantics/publishedVersio

Referenciação aos cuidados de saúde secundários

Introdução: O processo de referenciação dos Cuidados de Saúde Primários (CSP) para os Cuidados de Saúde Secundários (CSS) é de grande interesse, sobretudo devido a aspectos relacionados com a qualidade dos cuidados prestados e de ordem económica. O Estudo Europeu sobre Referenciação revelou, em Portugal, uma taxa de referenciação de 5,56%. Em Portugal, não existem estudos sobre a qualidade da referenciação. A Unidade Local de Saúde (ULS) de Matosinhos pretende prestar cuidados globais aos utentes colocando em rede os CSP e CSS. Em termos de referenciação, esta ligação necessita de ser aperfeiçoada. Objectivos: Determinar a taxa de referenciação, caracterizar a população referenciada, avaliar as características das referenciações, descrever e analisar a resposta dos CSS. Metodologia: Estudo transversal analítico. Recolha do número de referenciações do CS Senhora da Hora (CSSH) no ano de 2003. Amostra aleatória de 400 referenciações efectuadas para o Hospital Pedro Hispano (HPH). Determinação das estatísticas descritivas da amostra e uso do teste de 2 para comparação de proporções (a = 0,05). Resultados: A taxa de referenciação foi de 10,1%. A idade média da população referenciada foi 45,3 anos; 61,8% do sexo feminino. As especialidades mais referenciadas foram ORL, Ginecologia e Cirurgia. As cartas de referenciação contêm, na sua maioria, o nome do doente (98,9%), objectivo de referenciação (92,8%) e data (94,8%). Contudo, grande parte não referia medicação habitual (71,3%), descrição do exame físico (51,5%) ou identificação do médico (52,3%). Em 50,8% dos casos, a efectivação da consulta verificou-se 1 a 6 meses após a referenciação. Obteve-se informação de retorno em 26,3% das referenciações. Conclusão: Este estudo revelou lacunas na articulação dos cuidados de saúde. O médico deve ter em conta que as cartas de referenciação/retorno são um veículo primordial de comunicação, devendo ser aperfeiçoadas, pois delas depende a qualidade dos cuidados prestados. Sistemas de informação em rede e regras de referenciação protocoladas podem melhorar a articulação dos cuidados

Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment

Research Areas: Veterinary SciencesCanine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-alpha, TGF-beta, and IFN-gamma by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-gamma and downregulation of IL-2, IL-4, and TGF-beta, while gene expression of IL-12, TNF-alpha, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-gamma gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.info:eu-repo/semantics/publishedVersio