54,651 research outputs found

    Glycosaminoglycans as polyelectrolytes: implications in bioactivity and assembly of biomedical devices

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    Published online: 19 Jan 2022The innate negative charge of glycosaminoglycans (GAG) is in the origin of their bioactivity: it drives their spontaneous complexation with positively charged biomolecules and ions, regulating homeostatic functions by protein stabilization, protection and activation. Copycatting these interactions enables different supramolecular approaches towards the assembly of biofunctional devices. Such approaches allow processing under physiological conditions and thus, they are of unprecedented biocompliance for device build-up compared to conventional methods based on chemical cross-linkers, volatile and organic solvents, and high temperatures. We review different set-ups based on GAG electrostatic complexation and showcase their application towards the development of diverse therapeutic systems. We also discuss challenges associated with GAG complexation into intricate three-dimensional networks holding back the widespread use of these methods. Finally, we anticipate that conscious choice of GAG with distinct polyanionic strength and specific bioactivity will make possible the fabrication of constructs with personalized and customized properties in the nearest future.This work was supported by Fundação para a Ciência e a Tecnologia: [Grant Number CEECIND/02842/2017]; Fundação para a Ciência e a Tecnologia: [Grant Number PTDC/CTM-REF/0022/2020]; Fundação para a Ciência e a Tecnologia: [Grant Number PTDC/BTM-MAT/28327/2017]

    Celulose bacteriana como penso curativo

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    Tese de doutoramento em Biomedical EngineeringWounds, in particular traumatic (e.g. burns) and chronic ones, are a major cause of morbidity, impaired life quality and high health care costs. They often result in long hospitalization stays, taking up substantial health resources in developed countries. Conventional treatments are often painful, expensive and may increase the infection risk, compromising the treatments‚Äô time and success. In recent years, there have been efforts to develop new advanced methodologies to heal chronic wounds, including the topic use of growth factors or cell-based therapies. However, in many cases, the therapeutic efficacy is low, the therapies are expensive and require application in a clinical facility. Therefore, development of new therapeutics is absolutely necessary and important to satisfy these unmet clinical needs. So, this work comprised the development of a safe, easy-to-use and non expensive novel dressing, aimed at efficiently addressing these issues, by attaining faster and proper wound healing. The use of bacterial nanocellulose (BNC) has already demonstrated positive results in the treatment of different kinds of wounds. Additionally, BNC is considered a promising drug delivery system. In this work, BNC was conceived as a protective barrier against exogenous agents (particles, microorganisms) that can impair wound healing, and as a drug carrier for the controlled release of hydrophobic drugs, namely of vitamin D3 (Vit D3 ), an inducer of the endogenous expression of antimicrobial peptide (AMP) LL37, known for accelerating the wound healing process. In a first part of this project, the optimization of the static BNC production was performed, aiming at making it viable and economic at large scale. First, an experimental design, based on response surface methodology (RSM) - central composite design (CCD) - was used to optimize the culture medium for BNC production by Komagataeibacter xylinus BPR 2001, using a simple culture medium composition based on byproducts from the food industry. The optimal conditions for BNC production were (% (m/v)): molasses 5.38; CSL 1.91; ammonium sulphate 0.63; disodium phosphate 0.270; citric acid 0.115 and ethanol 1.38 % (v/v). The experimental and predicted maximum BNC production yields were 7.5 ¬Ī0.54 g/L and 6.64 ¬Ī0.079 g/L, respectively, after 9 days at 30 ¬ļC. Furthermore, the effect of the surface area and culture medium depth on the BNC production yield and productivity were evaluated. BNC dry mass production increased with the surface area and with the medium volume (depth) and fermentation time. Also, as long as nutrients were still available in the culture media, the BNC mass productivity was maintained overtime. The pre-inoculum preparation (PIP) step was also optimized with regards to the (a) identification of an inexpensive culture medium for pre-inoculum leading to a high cell density; (b) analysis of the effect of the initial cellular concentration on the static production of BNC and (c) kinetics of cell growth throughout the different steps of pre-inoculum preparation, including static and stirred - laboratorial and pilot-scale ‚Äď fermentations. The best composition for PIP medium was (% (m/v)): Glucose and Fructose syrup 1.5- 2.0; Corn Step Liquor (protein basis) 0.7; citric acid 0.115; Na2HPO4 0.27. The analysis of the cell growth kinetics in the different steps of PIP showed that a careful control on the culture time in each stage is advisable. The time required to reach the exponential phase was very different in each stage of PIP, reducing significantly from the static culture to the stirred culture and for large scale stirred culture, in a 75 L Bioreactor. In a second part of this work, the use of BNC as a drug carrier was addressed. Since Vit D3 is poorly water soluble, and thus not easily incorporated in the highly hydrophilic environment of the BNC membrane, Vit D3 was encapsulated in a self-assembled hyaluronic acid (HA)-based amphiphilic nanogel and then incorporated in the BNC membrane. The carrier was obtained by grafting hexadecylamine (Hexa) into the HA backbone (HA-Hexa). Vit D3 was successfully loaded into the nanogel (HA-Vit D3 ) with an encapsulation efficiency between 60-91 %. The loaded system- HA-Vit D3 - was embedded into BNC, conceived as a transdermal delivery system. The release of Vit D3 was monitored over time using a Franz cell device. Around 70 % of the initial Vit D3 available was released from BNC membranes in the first 48 h. Most importantly, we observed that the released Vit D3 still remained within the HA-Hexa nanogel carrier. Vit D3 is known to stimulate the endogenous production of human cathelicidin (LL37), which is known to accelerate wound healing. Thus, formulations of HA-Vit D3 and HA-LLKKK18 (an analogue of LL37) were tested in vivo, using excision and chronic wound in dexamethasone treated C57BL/6 and db+/db+ mice models, as to evaluate and compare their efficiency in wound repairing. However, the results did not confirm any wound healing improvement.As feridas cr√≥nicas e traum√°ticas (e.g. queimaduras) apresentam uma elevada morbilidade, afetando severamente a qualidade de vida dos pacientes. Os tratamentos convencionais implicam longos per√≠odos de interna√ß√£o hospitalar, com significativo consumo de recursos dos sistemas de sa√ļde nos pa√≠ses desenvolvidos. Al√©m disso, s√£o dolorosos, caros e podem aumentar o risco de infe√ß√£o, comprometendo a dura√ß√£o e o sucesso dos tratamentos. Recentemente, t√™m sido desenvolvidos esfor√ßos para o desenvolvimento de novas metodologias avan√ßadas para o tratamento de feridas cr√≥nicas, incluindo a aplica√ß√£o t√≥pica de fatores de crescimento ou terapias baseadas em c√©lulas. Em muitos casos, estas novas abordagens s√£o caras, devendo ser realizadas numa unidade hospitalar, e a sua efic√°cia terap√™utica √© baixa. Assim, o desenvolvimento de novas solu√ß√Ķes para satisfazer esta necessidade cl√≠nica ainda n√£o satisfeita √© absolutamente necess√°rio. Com este trabalho pretende se desenvolver um penso curativo eficiente, inovador, f√°cil de usar e n√£o dispendioso, atrav√©s de uma abordagem segura, visando uma cicatriza√ß√£o mais r√°pida e adequada da ferida. A nanocelulose bacteriana (BNC) demonstrou j√° resultados positivos no tratamento de diferentes tipos de feridas, assim como foi j√° demonstrado tamb√©m o seu potencial como sistema de entrega de f√°rmacos. Neste trabalho, a BNC foi utilizada como ve√≠culo para a liberta√ß√£o controlada de mol√©culas hidrof√≥bicas, nomeadamente a vitamina D3 (Vit D3 ), que √© um indutor da express√£o end√≥gena do pept√≠do antimicrobiano LL37, conhecido por acelerar o processo de cicatriza√ß√£o de feridas. Al√©m disso, a BNC funciona como uma barreira protetora contra agentes ex√≥genos (poeiras, microorganismos) que podem prejudicar a cicatriza√ß√£o de feridas. Numa primeira parte, foram desenvolvidos trabalhos visando tornar a produ√ß√£o em grande escala de BNC em cultura est√°tica econ√≥mica e vi√°vel. Nesse sentido, foi usado um desenho experimental, baseado na metodologia de superf√≠cie de resposta (RSM) - planeamento composto central (CCD) - para otimizar o meio de cultura, usando subprodutos da ind√ļstria alimentar. Foi utilizada a estirpe Komagataeibacter xylinus BPR 2001, a 30 ¬ļC. Foram identificadas as seguintes condi√ß√Ķes √≥timas para a produ√ß√£o de BNC (% (m/v)): mela√ßo 5,38, xarope de milho (CSL) 1,91; sulfato de am√≥nio 0,63; fosfato diss√≥dico 0,270; √°cido c√≠trico 0,115 e etanol 1,38 % (v/v). Os rendimentos m√°ximos experimentais e previstos de produ√ß√£o de BNC foram 7,5 ¬Ī0,54 g/L e 6,64 ¬Ī0,079 g/L, respetivamente, ap√≥s 9 dias. Adicionalmente, foram avaliados o efeito da √°rea superficial e da profundidade/altura do meio de cultura no rendimento e produtividade em BNC. Verificou-se que a produ√ß√£o de BNC aumenta com a √°rea superficial, com o volume de meio de cultura (profundidade) e com o tempo de fermenta√ß√£o. Al√©m disso, observou-se que a produtividade de BNC se mant√©m constante at√© se esgotarem os nutrientes no meio de cultura. Para a etapa de prepara√ß√£o pr√©-in√≥culo (PIP), a otimiza√ß√£o consistiu em diferentes estudos, especificamente: (a) otimiza√ß√£o dum meio de cultura de custos reduzidos, que permita a obten√ß√£o de uma elevada densidade celular; (b) avalia√ß√£o do efeito da concentra√ß√£o celular inicial na produ√ß√£o est√°tica de BNC e (c) estudo da cin√©tica de crescimento celular ao longo das diferentes etapas de PIP. A melhor composi√ß√£o para o PIP foi (% (m/v)): xarope de glucose e frutose 1,5- 2,0; CSL 0,7; √°cido c√≠trico 0,115 e Na2HPO4 0,27. Os estudos de cin√©tica de crescimento celular para as diferentes etapas do PIP evidenciam a necessidade dum controle cuidadoso do tempo de cultura em cada etapa do PIP. O tempo necess√°rio para atingir a fase exponencial foi muito diferente em cada fase do PIP, reduzindo significativamente da cultura est√°tica, para a cultura agitada, e para cultura agitada em larga escala num bioreator de 75 L. A segunda parte do trabalho relaciona-se com o desenvolvimento da BNC como sistema de entrega de f√°rmacos. A Vit D3 √© pouco sol√ļvel em √°gua e, portanto, n√£o √© facilmente incorporada no ambiente altamente hidrof√≠lico como o da membrana de BNC. Para esse efeito foi usado um nanogel anfif√≠lico auto-organizado obtido pela liga√ß√£o de hexadecilamina (Hexa) na cadeia do √°cido hialur√≥nico (HA). A Vit D3 foi ent√£o encapsulada no nanogel de (HA-Hexa) e em seguida impregnada na membrana de BNC, com uma efici√™ncia de encapsula√ß√£o entre 60-91 %. A liberta√ß√£o da Vit D3 foi monitorizada ao longo do tempo, usando uma c√©lula de Franz e realizando estudos de permea√ß√£o. Observou-se a liberta√ß√£o de cerca de 70 % da Vit D3 , ainda dentro do nanogel de HA-Hexa, das membranas de BNC em 48h. Finalmente, foi testada a utiliza√ß√£o de HA-Vit D3 e de HA-LLKKK18 (um p√©ptido an√°logo √† LL37) em modelos de feridas de excis√£o e cr√≥nicas em ratinhos tratados com dexametasona e diab√©ticos tipo II (db + / db +) C57BL/6. No entanto, os resultados n√£o revelaram uma maior efici√™ncia na cicatriza√ß√£o de feridas na presen√ßa das referidas formula√ß√Ķes.Ao Projeto BioTecNorte (NORTE-01-0145-FEDER-000004), n¬ļ 003435: ‚ÄúBUILD ‚Äď Bacterial cellulose Leather‚ÄĚ, financiado pelo Fundo Europeu de Desenvolvimento Regional (FEDER) atrav√©s do Programa Operacional do Regional do Norte (NORTE 2020) e ao projeto SkinChip: Disruptive cellulose-based microfluidic device for 3D skin modelling, PTDC/BBB-BIO/1889/2014 e ainda √† Funda√ß√£o para a Ci√™ncia e Tecnologia no √Ęmbito do financiamento estrat√©gico da unidade UID / BIO / 04469/2019 e pela atribui√ß√£o da bolsa de doutoramento SFRH/BD/89547/2012

    A multidimensional concept for mercury neuronal and sensory toxicity in fish - From toxicokinetics and biochemistry to morphometry and behavior

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    Neuronal and sensory toxicity of mercury (Hg) compounds has been largely investigated in humans/mammals with a focus on public health, while research in fish is less prolific and dispersed by different species. Well-established premises for mammals have been governing fish research, but some contradictory findings suggest that knowledge translation between these animal groups needs prudence [e.g. the relative higher neurotoxicity of methylmercury (MeHg) vs. inorganic Hg (iHg)]. Biochemical/physiological differences between the groups (e.g. higher brain regeneration in fish) may determine distinct patterns. This review undertakes the challenge of identifying sensitive cellular targets, Hg-driven biochemical/physiological vulnerabilities in fish, while discriminating specificities for Hg forms.Thanks are due for the financial support to CESAM (UID/AMB/50017/2019), to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. Patr√≠cia Pereira acknowledges the support of FCT through the post-doctoral research grants (SFRH/BPD/69563/2010 and SFRH/BPD/107718/2015). Currently, Patr√≠cia Pereira is funded by national funds (OE), through FCT ‚Äď Funda√ß√£o para a Ci√™ncia e a Tecnologia, I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. The authors are also grateful to the Co-Editors Professor Cristina Carvalho and Professor Michael Aschner for the opportunity to publish this article in a special issue of BBAGEN organized under their supervision

    Mangroves of Maputo. Towards urban resilience through green infrastructure

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    Doutoramento em Arquitetura Paisagista e Ecologia Urbana - Instituto Superior de Agronomia. Universidade de Lisboa / Faculdade de Ciências. Universidade do Porto / Faculdade de Ciências e Tecnologia. Universidade de CoimbraCities in Africa, where the most remarkable forthcoming developments in the global pattern of urbanization are expected, and quite notably in Sub-Saharan cities such as Maputo, are experiencing accelerating population increases. As a consequence of this growth urban infrastructures are being stressed beyond capacity and there is increased pressure on the existent valuable ecosystems. In recent times, and mostly due to foreign intervention, investments have been welcomed into Maputo’s grey urban infrastructure network whereas little attention has been given to green infrastructure. In the city’s coastal plains, the recently constructed Maputo ring road and the Katembe bridge are drawing urban development towards the last stretch of vacant land of the Municipality, compromising the mangrove ecosystems and flood plains of this territory. Based on the hypothesis that mangroves have the potential to become a structuring element for the improvement of resilience in self-produced neighbourhoods on the coastal plains, the aim of this research is to contribute towards the outline of an urban green infrastructure for the coastal areas of Maputo, as a strategy to accommodate current and future urban development challenges, not only as biophysical networks that can create urban socio-ecological networks that improve urban resilience through a stewardship of ecosystems, but also as an ecosystem-based approach for adaptation to climate change. Considering the specific dynamics of Sub-Southern African cities, where research and planning around environmental issues is in very early stages, it is urgent to promote research and design strategies to tackle the problematics of urban development in ecologically sensitive and landscape valuable areas. This research thus expects to anticipate the sustainable development of Maputo, exploring the potential of its coastal landscape for the establishment of an urban green infrastructureN/

    Treatment of saline wastewater amended with endocrine disruptors by aerobic granular sludge: assessing performance and microbial community dynamics

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    An aerobic granular sludge (AGS) sequencing batch reactor (SBR) adapted to salinity (12gL-1 NaCl) was operated under alternating anaerobic-aerobic conditions for the treatment of synthetic saline wastewater containing endocrine-disrupting chemicals (EDCs), namely 17estradiol (E2), 17ethinylestradiol (EE2) and bisphenol-A (BPA). The SBR was intermittently fed with the EDCs at 2mgL-1 of each compound. E2 was completely biodegraded, with 60% to 80% removal attained anaerobically and the remaining quickly consumed under aeration. EE2 was sorbed onto the granular sludge biomass in the anaerobic period, but it was desorbed in subsequent cycles even when the compound was not supplied to the reactor. BPA removal was poor but improved after bioaugmentation with an EDCs degrading bacteria. EDCs shock loads did not significantly affect the COD removal nor the activity of ammonium- and nitrite-oxidizing bacteria (AOB and NOB, respectively). In contrast, the activity of phosphate-accumulating organisms (PAOs) was affected, implying a decrease in P removal within the aerobic phase. AGS core microbiome grouped most bacteria belonging to the phylum Proteobacteria, followed by Bacteroidetes. The microbial profile showed that the introduction of the EDCs mixture increased the relative abundance of Chryseobacterium and Flavobacterium. AOB and NOB species were detected in the AGS biomass, with the latter showing lower relative abundance. Different PAOs, such as Rhodocyclus, Tetrasphaera and Gemmatimonas, were also part of the microbial community, but the addition of EDCs decreased significantly the relative abundance of Rhodocyclus. High microbial diversity was sustained over reactor operation, with the main bacterial groups responsible for nutrients and EDCs removal preserved in the AGS system. The results pointed to the maintenance of a core microbiome over reactor operation that may be related to the stability of the AGS process during EDCs loading.This study was supported in part by the Coordena√ß√£o de Aperfei√ßoamento de Pessoal de N√≠vel Superior (CAPES/Brasil) ‚Äď Finance Code 001 and the other part was financed by National Funds from Funda√ß√£o para a Ci√™ncia e a Tecnologia (FCT/Portugal) - through the project AGeNT - PTDC/BTA-BTA/31264/2017 (POCI-01-0145-FEDER 031264)and the project CBQF - UID/Multi/50016/2019info:eu-repo/semantics/publishedVersio

    Política nacional de ciencia y tecnología 2000-2002

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    "Este documento somete a consideraci√≥n del CONPES, la pol√≠tica nacional de ciencia y tecnolog√≠a que tiene como objetivo central el desarrollo de las estrategias necesarias para la articulaci√≥n y el fortalecimiento del Sistema Nacional de Ciencia y Tecnolog√≠a ‚Äď SNCyT"Departamento Administrativo de Ciencia, Tecnologia e Innovaci√≥n Colciencia

    Anxiety and depressive symptoms effects on cortisol trajectories from pregnancy to postpartum: Differences and similarities between women and men

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    Anxiety and depressive symptoms may influence cortisol trajectories in women and men during pregnancy and the postpartum period. Using a multilevel approach, anxiety and depressive symptoms effects on 24-hour urinary free cortisol trajectories from the 2nd trimester to 3-months postpartum were examined in a sample of 66 women and 65 men with no known psychosocial or medical risk (N¬†=¬†131; 33 (50%) of them were couples that participated in the same assessment waves). Results showed that both anxiety and depressive symptoms influence women's and men's cortisol trajectories from mid-pregnancy to 3-months postpartum. Women with high depressive symptoms and men with high anxiety or high depressive symptoms exhibited less accentuated variations in the 24-hour urinary free cortisol trajectories compared with women with low depressive symptoms and men with low anxiety or depressive symptoms, respectively. These effects were significant for women's cortisol trajectories from the 2nd to the 3rd pregnancy trimester and for men's cortisol trajectories throughout the entire period. The effect of anxiety and depressive symptoms on HPA axis functioning and cortisol production during pregnancy and postpartum, seems to be sex-specific. Reproductive-related alterations (associated with gestation, parturition and lactation) in women's HPA axis functioning may explain these sex-specific effects.This research was funded under a doctoral grant for Science in Measure IV.3 and co-funded under the 2010 Science and Innovation Operational Program (POCI 2010) from Foundation for Science and Technology, Government of the Portuguese Republic (Ref. SFRH/BD/13768/2003). This research was also supported by FEDER Funds through the Programa Operacional Factores de Competitividade ‚Äď COMPETE and by National Funds through FCT ‚Äď Funda√ß√£o para a Ci√™ncia e a Tecnologia under the project: PTDC/SAU/SAP/116738/2010 (PI: Barbara ¬ī Figueiredo) and by FSE and FCT under the PostDoctoral Grant SFRH/BPD/117597/2016. EPIUnit is funded by FCT ‚Äď Funda√ß√£o para a Ci√™ncia e a Tecnologia, I.P. (UIDB/04750/2020). The sponsors had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

    Análise do processo de certificação dos clientes do setor agroalimentar

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    Disserta√ß√£o de mestrado em Tecnologia e Ci√™ncia AlimentarCom o aumento da conscientiza√ß√£o dos consumidores com rela√ß√£o √† seguran√ßa alimentar, no decorrer dos anos houve um aumento quanto √† press√£o junto aos organismos reguladores e √†s ind√ļstrias alimentares, de forma a garantir a produ√ß√£o de alimentos com qualidade e seguran√ßa para o consumidor. Nesse contexto, surgem os Sistemas de Gest√£o de Seguran√ßa Alimentar, essenciais para a avalia√ß√£o e a gest√£o dos perigos, dos riscos e de suas consequ√™ncias para o consumidor e tamb√©m para as rela√ß√Ķes comerciais. O presente trabalho tem, como objetivo, contribuir com sugest√Ķes de melhorias da Gest√£o de Processos de Certifica√ß√£o do setor agroalimentar, nos referenciais BRC e IFS, do organismo de certifica√ß√£o. Quanto √† metodologia adotada no trabalho, foi a IA (Investiga√ß√£o A√ß√£o), que √© essencialmente pr√°tica e tem o prop√≥sito de resolver problemas organizacionais, atrav√©s do contato com a equipa de colaboradores imersos na rotina e nos problemas da empresa, de forma a realizar diagn√≥stico, planeamento, implementa√ß√Ķes de a√ß√Ķes e avalia√ß√£o. No estudo, pode-se observar uma necessidade de ajustes relacionados ao fluxograma de processos, aos sistemas de inform√°tica do organismo de certifica√ß√£o e organismo parceiro, √† aten√ß√£o aos inqu√©ritos de satisfa√ß√£o do cliente, metodologia de avalia√ß√£o do desempenho dos servi√ßos prestados pela empresa e auditores e aten√ß√£o ao comprometimento da empresa com a qualidade dos servi√ßos ofertados com o quadro atual de colaboradores. As oportunidades de melhoria identificadas ao longo deste trabalho s√£o sugest√Ķes para uma avalia√ß√£o da gest√£o de topo com o intuito de aumento na qualidade dos servi√ßos prestados, assim como satisfa√ß√£o dos clientes e melhores condi√ß√Ķes para os colaboradores realizarem suas atividades conforme preconizado pela empresa.The increase of customers‚Äô awareness concerning food safety caused, over the years, an increase about the pressure on regular organizations and food industries, to ensure the food production of quality and safety for consumers. In this context, the food Safety Management Systems appeared, and they are essential to do evaluation and management of the risks and their consequences for both consumers and trade relations. This work aims to contribute with suggestions for improvements on the Certification Process Management agri-food sector, the references BRC and IFS, the Organization of Certification. The methodology used in this work was the Action Research (IA - Investiga√ß√£o A√ß√£o), that is essentially practical and has the purpose to solve organizational problems, through contact with the group of collaborators immersed in the routine and company problems, to they be able to do diagnosis, planning, implementations of actions and evaluation. In this study, it is observed the necessity of adjusts on the processes flowchart, the certification body and partner body computing systems, the attention for the inquiries of customer‚Äôs satisfaction, evaluation methodology of the accomplishment on services provided by the company, auditors and attention to the company commitment with the quality of the services offered with the collaborators‚Äô current group. The opportunities of improvement identified along this work are suggestions to evaluation of the top management, in order to increase the quality of the services provided, as customers‚Äô satisfaction and better conditions for the collaborators do their activities as recommended by the company

    Encapsulated bacteriophages for pre-slaughter interventions to reduce Shiga toxin-producing E. coli (STEC) in ruminants

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    Fundação para a Ciência e Tecnologia (FCT), COMPETE 2020, NORTE 2020info:eu-repo/semantics/publishedVersio

    Impacto da diversidade genética do VIH-1 na interação com o hospedeiro

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    Tese de doutoramento em Envelhecimento e Doen√ßas Cr√≥nicasEm 2019, estima-se que 38 milh√Ķes de pessoas viveriam infetadas pelo v√≠rus da imunodefici√™ncia humana (VIH). Atualmente, n√£o existe uma cura para a infe√ß√£o por VIH e a extensa variabilidade gen√©tica do v√≠rus representa um dos maiores obst√°culos para acabar com a prolifera√ß√£o da pandemia e desenvolver uma terapia eficiente. O Brasil √© o pa√≠s com o maior n√ļmero de pessoas infetadas por VIH na Am√©rica Latina, apresentando uma distribui√ß√£o heterog√©nea de subtipos e recombinantes virais pelas suas diferentes regi√Ķes geogr√°ficas. Perceber a epidemia do VIH-1 no Brasil poder√° dar-nos informa√ß√Ķes valiosas sobre a diversidade gen√©tica do v√≠rus e da sua rela√ß√£o com as caracter√≠sticas gen√©ticas e sociodemogr√°ficas da popula√ß√£o. Assim, primeiramente, neste estudo, tentamos perceber a din√Ęmica das muta√ß√Ķes de resist√™ncia em pacientes em fal√™ncia terap√™utica no Brasil, entre 2008 e 2017, e, posteriormente, tentamos investigar a epidemiologia molecular e a evolu√ß√£o dos subtipos de VIH neste pa√≠s. Os nossos resultados revelaram uma preval√™ncia de muta√ß√Ķes de resist√™ncia elevada na popula√ß√£o estudada, apesar de um decr√©scimo ter sido observado ao longo dos anos. Contrariamente, um aumento significativo foi observado na preval√™ncia da muta√ß√£o de resist√™ncia a inibidores da transcriptase reversa K65R, seguindo as altera√ß√Ķes efetuadas a n√≠vel dos f√°rmacos recomendados para tratamento. Foi, tamb√©m, encontrada evidencia de transmiss√£o da muta√ß√£o e os nossos resultados sugeriram que a mesma poderia aumentar o reconhecimento viral pelo HLA-B27, que tem uma preval√™ncia relativamente reduzida na popula√ß√£o braseira. Mais ainda, foi verificado um aumento na preval√™ncia do subtipo C, especialmente no Sul, onde √© dominante. Encontramos, tamb√©m, evidencia de transmiss√£o do subtipo C entre o Sul e outras regi√Ķes do Brasil, apesar de a sua propor√ß√£o ser pequena nestas √°reas. Adicionalmente, este subtipo foi mais associado a baixos n√≠veis de imunossupress√£o e a transmiss√£o de mulher para homem e m√£e para filho, do que o subtipo B, sustentando a hip√≥tese que alguns subtipos podem tirar partido de per√≠odos assintom√°ticos mais longos e das caracter√≠sticas sociodemogr√°ficas da popula√ß√£o para proliferar. No geral, estes resultados refor√ßam a import√Ęncia de se perceber a din√Ęmica da expans√£o do VIH e da monitoriza√ß√£o das muta√ß√Ķes de resist√™ncia, de modo a serem criadas diretrizes de controlo e tratamento mais espec√≠ficas, para se reduzir o fardo da epidemia do VIH.In 2019, 38 million people were estimated to be living with Human Immunodeficiency Virus (HIV) infection. Currently, there is still no cure for HIV infection and the extensive viral genetic diversity represents the one of the biggest obstacles to end the spread of the pandemics and to develop an effective therapy. Brazil represents the country with the largest number of people living with HIV in Latin America, presenting a heterogeneous distribution of HIV-1 subtypes and recombinant forms across different geographic regions. Understanding HIV-1 epidemics in a country as vast as Brazil, could give valuable insights about the viral genetic diversity and its relationship with genetic and sociodemographic characteristics of the host population. Thus, in this study, we firstly aimed at understanding the dynamics of the drug resistance mutations (DRMs) in HIV-1 infected individuals failing antiretroviral treatment (ART) in Brazil, between the years 2008 and 2017, and, posteriorly, at investigating the molecular epidemiology and evolution of HIV-1 subtypes, in the same country. Our results revealed a high prevalence of DRMs in the studied population, although a mild decline was observed over the years. Contrastingly, a significant increase on the prevalence of the K65R reverse transcriptase mutation was noticed, following a shift on the used ART regimens. Evidence of K65R transmission was also verified and our results suggested that this mutation could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Moreover, our results indicated an increase on subtype C prevalence over the years, especially in the South of Brazil, where it dominates. We also observed evidence for subtype C transmission events between the South and other Brazilian regions, although this subtype was only present in small proportions in these areas. Additionally, subtype C was significantly associated with lower levels of immunodepression infection of women and women-to-child transmission, when compared with subtype B, sustaining the hypothesis that some subtypes might take advantage of longer asymptomatic periods and the sociodemographic characteristics of the population to proliferate. Overall, our results reinforce the importance of understanding the dynamics of HIV-1 subtype expansion and monitoring DRMs prevalence to establish specific guidelines for prevention and treatment, aiming at decreasing the epidemic burden of the HIV-1 infection.O estudo foi financiado pela bolsa PD/BD/127827/2016 e por fundos nacionais, atrav√©s da Funda√ß√£o para a Ci√™ncia e Tecnologia - projetos UIDB/50026/2020 e UIDP/50026/2020
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