Large interindividual variations of Plasmodium falciparum growth in in-vitro cultures : investigation of underlying factors especially related to red blood cells

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2021Fundamento: Plasmodium falciparum (P.f.) cresce a uma taxa variável entre indivíduos, resultando em diferentes parasitemias, cargas parasitárias e graus de gravidade da doença. Além da imunidade, outros fatores parecem influenciar a taxa de crescimento do parasita e o prognóstico da doença, como o grupo sanguíneo ou as hemoglobinopatias, embora os mecanismos ainda não estejam esclarecidos. As culturas in vitro são uma ferramenta essencial para estudar o P.f. e investigar melhores intervenções. É fundamental entender como estas variações afetam o crescimento do parasita em cultura e quais os fatores envolvidos. Objetivos: Este trabalho tem como objetivo investigar possíveis diferenças no crescimento de P.f. em indivíduos não imunes à malária num sistema de cultura in vitro e estudar possíveis associações para as variações observadas. Métodos: Realizaram-se culturas in vitro de P.f. com sangue de 69 indivíduos não imunes à malária. Numa segunda fase, 24 voluntários foram novamente chamados para dar outra amostra de sangue para repetir culturas de P.f. e realizar uma avaliação analítica. Em 14 voluntários, a suplementação a cultura com soro bovino foi substituída por soro humano. Resultados: A média da razão do crescimento do P.f. após 96 horas foi de 10.0, com uma grande variabilidade entre indivíduos (intervalo:3.0–19.3, DP:3.8). Três grupos foram criados. O grupo de “baixo crescimento” é definido por uma razão 1DP abaixo da média (n=12, média:4.7, SD:1.2, intervalo:3.0–6.1). O grupo de “elevado crescimento” é definido por uma razão 1DP acima da média (n=13, média:16.0, DP:1.8, intervalo:13.8–19.3). Os dados sugerem que os indivíduos que apresentam menor crescimento do P.f. estão ligados a países onde a malária é endémica (p=0.03). Além disso, um menor crescimento parece estar relacionado à anemia (p=0.01), apontando para algum problema nos eritrócitos, embora este estudo não tenha permitido encontrar o mecanismo subjacente. A suplementação com soro humano não alterou este padrão de crescimento. Além dos níveis de hemoglobina (p=0.03), nenhum outro parâmetro analítico apresentou diferença significativa.Conclusão: Existem indivíduos cujo sangue permite um crescimento do P.f. consistentemente alto ou baixo. A grande variabilidade do crescimento não é influenciada pelo soro, sugerindo que os eritrócitos parecem ser responsáveis por este padrão. Esta ideia é reforçada pelo facto de que indivíduos com uma história clínica de anemia ou níveis de hemoglobina baixos apresentam menores taxas de crescimento. Assim, a variabilidade no crescimento do parasita pode ser explicada por pequenas variações genéticas ao nível da hemoglobina.Background: Plasmodium falciparum (P.f.) grows at a variable rate between individuals, resulting in different parasitaemia, total body parasite burden and degrees of disease severity. In addition to immunity, other factors appear to influence the parasite growth rate and disease prognoses, such as blood group or haemoglobinopathies, although the mechanisms are not yet clear. In-vitro culture is an essential tool for studying P.f. and for research into better interventions. It is critical to understand how these variations affect parasite growth in culture and what factors may influence it. Objectives: This work aims to investigate possible interindividual differences in the P.f. growth in malaria-naïve individuals in an in-vitro culture system and to study possible associations for the observed variation. Methods: In-vitro P.f. cultures were performed with blood from 69 malaria-naïve individuals. In the second phase, 24 volunteers were called back to give another blood sample to repeat P.f. cultures and perform blood tests. In 14 volunteers, the culture supplementation with bovine serum was replaced by human serum. Results: The mean fold-change of P.f. growth after 96 hours was 10.0, with a large inter-individual variability (range:3.0–19.3, SD:3.8). Three groups were created. The “lower growers” group is defined by a fold-change below 1SD from the mean (n=12, mean:4.7, SD:1.2, range:3.0–6.1). The “higher growers” group is defined by a fold-change above 1SD from the mean (n=13, mean:16.0, SD:1.8, range:13.8–19.3). Data suggest that inidviduals presenting with a lower parasite growth are connected to malaria-endemic countries (p=0.03). Furthermore it appeared to be related to anaemia (p=0.01), pointing to some problem in the RBC, although this study did not allow to find the underlying mechanism. Supplementation with human serum did not change the growth pattern. Besides haemoglobin levels (p=0.03), no other haematology-biochemical parameter showed a statistically significant difference. Conclusion: There are individuals whose blood allows a growth of P.f. consistently high or low. The large variability of parasite growth is not changed by serum, suggesting that the RBC are responsible for this pattern. This idea is reinforced by the fact that individuals with a clinical history of anaemia or low haemoglobin levels have the lowest growth rates. Thus, differences in the parasite growth could be explained by some minor genetic variations in haemoglobin

Doing more with less - How frugal innovations can contribute to improving healthcare systems

The dominance of an innovation discourse laden with cutting edge and expensive technologies, may be preventing us from recognizing alternative and complementary perspectives, which could help cut healthcare costs while improving worldwide access to health services. One such complementary approach is that of frugal innovation. Frugal innovation, as a way to produce efficacious and affordable products using fewer resources to reach the underserved customers, has received increasing attention in the social sciences literature. Although frugal innovation is commonly associated with emerging economies, there is now a rising interest from healthcare providers in developed countries, to find and apply effective, and lower-cost solutions. Nonetheless, knowledge on frugal innovation and its role in healthcare is dispersed across different literatures which hampers researchers and practitioners to access a fuller, and integrated picture of the phenomenon. In this study, by synthesizing extant knowledge, we tackle the fragmentation of the phenomenon. We elucidate on who the actors are, what is being done, how are such innovations being developed, and what the outcomes are, providing a framework that lays out the underlying mechanisms of frugal innovation in healthcare (FIH). The midrange theory that we develop, provides a conceptual framework for researchers to undertake empirical observation and models to guide managerial practices. Furthermore, by providing a more unified perspective of frugal innovation in healthcare, we hope to initiate conversations on the development, adequacy and adoption of these innovations in healthcare services, which could increase affordability and access for the population while maintaining quality

From fruit pulp wastes to biomethane: assessment of substrate shifts on the performance of a two-stage anaerobic system and biogas upgrading studies

Wastes with high organic content, such as food waste, are produced worldwide and can cause serious pollution problems when poorly managed. Thus, there is the need for the implementation of environmental friendly treatment systems for organic wastes. Anaerobic digestion has the potential to contribute for the sustainable treatment of these wastes while producing biogas which provides a renewable energy source, methane (CH4). In this study, a two-stage anaerobic system was operated treating three different fruit pulp wastes (peach, raspberry and white guava) in a sequential operation. The effect of substrate shifts and different operational conditions, such as hydraulic retention time (HRT), organic loading rate (OLR) and pH on the system’s performance was assessed. The shift of substrates caused no long-term instability issues. The differences observed in the acidogenic performance in terms of gas production between substrates were considerable. Conversely, only slight differences were observed in fermentation products (FP) concentration and profiles. No evident association was found between pH and HRT/OLR changes on FP concentration and profiles in the range studied. Overall, the sugar removal efficiencies obtained were between 93.8 – 97.8% and the acidification degree varied between 53.7% – 76.4%. In regard to the methanogenic reactor, biogas production (3.6 – 12.8 L d-1) increased as OLR increased up to 7.4 g COD L-1, while CH4 yield (0.30 – 0.37 L CH4 g-1 COD) and content (75.9– 80.6%) remained approximately constant. Maximal chemical oxygen demand (COD) removal efficiency (around 93%) was achieved at HRTs of 8.6 and 5 days (OLR of 1.9 – 3.7 g COD L-1 d-1). Currently, there is the need to develop effective and economical viable solutions for biogas upgrading. Thus, gas permeation studies using mixed-matrix membranes (MMMs) with two different metal organic frameworks (MOFs) - MIL-53 and MOF-5 - were carried out in other to assess the potential for CH4 and carbon dioxide (CO2) separation. Matrimid®5218 with 10% (w/w) MIL-53 membrane showed the best performance among the membranes tested

Value creation using minimal resources – A meta-synthesis of frugal innovation

The practice of frugal innovation (FI) has been garnering great research interest in recent years. Although initially focused on emerging economies, the idea is now more global, gaining adepts in developed economies. FI shows potential to effectively provide valuable products for underserved communities while sparing resources globally and contributing for social and environmental change. To reconcile a fragmented literature and provide a useful basis for evidence-based entrepreneurship and management, we conducted a meta-synthesis of 36 studies comprising 95 FI cases. We draw on our evidence-based analysis to present a phenomenological overview of FI through the sequential and interrelated relationships of the who-why-where-how-what of the practice. We then structure the evidence into a typology of archetypes, establishing the building blocks for future research to focus on the less investigated elements and explore additional interrelationships. Our conclusions contribute to the FI literature by providing a broader view of the concept, constituting a foundation for future theory and practice

Empowering patients in the healthcare process : an analysis about patients’ perception

Personal Health Records (PHR) are becoming an important tool for patients to become active participants of their health care and help providers to improve health outcomes and systems performance. However, for PHR to be fully used by individuals it is necessary to understand the value they place on this tool and how can it be designed to improve its usage among patients. Therefore, this study deepens about Portuguese patients’ perception of PHR and which are the motivations for healthy and ill individuals to track their personal health status. A cross-sectional online survey of patients’ perception on PHR conducted to Portuguese citizens showed that although there is a lack of awareness of the concept of personal health records and use of online tools to perform health related activities, there is a positive perception about PHR and willingness to start using it in a near futureO Registo Clínico Electrónico Pessoal tem vindo a tornar-se numa ferramenta importante para transformar os utentes em participantes activos dos seus cuidados de saúde e ajudar os profissionais de saúde na melhoria de diagnósticos e desempenho dos serviços de saúde. No entanto, para que esta ferramenta seja plenamente utilizada pelos cidadãos é necessário compreender o valor acrescentado que os mesmos identificam no Registo Clínico Electrónico Pessoal e como é que o mesmo deve ser desenhado por forma a incrementar o seu uso por parte dos pacientes. Nesse sentido, este estudo centra-se na percepção dos pacientes portugueses quanto ao Registo Clínico Electrónico Pessoal e quais são as motivações para indivíduos saudáveis ou com alguma doença acompanharem o seu estado de saúde. Através de um questionário online sobre a percepção dos portugueses quanto ao Registo Clínico Electrónico Pessoal, concluiu-se que, embora haja uma falta de conhecimento deste conceito e uso de ferramentas online para realizar atividades relacionadas com a saúde, há uma percepção positiva sobre o Registo Clínico Electrónico Pessoal e os inquiridos estão dispostos a começar a utilizá-lo num futuro próximo

Environmental LCA database for conventional portuguese building technologies

Nowadays there is an increasing concern with the high emissions of polluting gases, the high use of natural resources and energy related to construction sector. There are several environmental impacts in this sector that can be moderated. This paper presents a study that allows the designers to quickly and easily apply the Life-Cycle Assessment (LCA) method to projects and therefore to understand which solutions are the best in what regards to sustainable construction. To fulfill the abovementioned goals this work studies the environmental per-formance of building technologies covered by the ITE50 manual coefficients of heat transfer of the building envelope elements . This manual covers the majority of building technologies used in Portugal

Utilização do método LCA no projeto de edifícios sustentáveis

As emissões excessivas de poluentes e a elevada utilização de recursos naturais e de energia, associados ao sector da construção, são cada vez mais preocupantes. Por conseguinte, os impactes ambientais associados a este sector são elevados, mas apresentam elevado potencial em serem minorados. É o Projetista que, na fase de execução do projeto, determina quais os materiais a aplicar numa determinada obra. Dada a necessidade atual em se minimizar os impactes ambientais, o projetista terá de demonstrar, sob um ponto de vista da construção sustentável, alguma sensibilidade na escolha dos materiais a colocar em obra. Atualmente existem no mercado ferramentas que permitem comparar os materiais e as tecnologias construtivas existentes, classificando-as como soluções “melhores” ou “piores” para cada projeto. No entanto, a complexidade e morosidade do processo restringe o seu uso a especialistas. Este estudo pretende simplificar o processo de avaliação do ciclo de vida de uma construção, permitindo, aos projetistas a aplicação, mais rápida e simples, da metodologia LCA normalizada, de forma a suportar as decisões na hora de escolher a “melhor” solução a adotar numa construção. Para o efeito foi estudado o impacte ambiental de todas as soluções construtivas que constam no manual ITE 50 "Coeficientes de transmissão térmica de elementos da envolvente dos edifícios". Este manual apresenta os processos construtivos mais correntes em Portugal. Desta forma os projetista passarão a poder cruzar o desempenho térmico das soluções construtivas com os seus potenciais impactes ambientais, permitindo optar por soluções equivalentes do ponto de vista funcional, mas que apresentam melhor desempenho ambiental

The effect of a physical literacy and differential learning program in motor, technical and tactical basketball skills

The aim of this study was to examine the effect of a physical literacy and differential learning program in motor, technical and tactical basketball skills. Seventy-six college students (age 20.4 ± 1.9) were randomly allocated into control and experimental (BasketCAL) groups. The motor skills were assessed using Illinois Agility Test, technical abilities were evaluated through Taco Bell skills challenge and tactical variables were examined during a 4-on-4 full-court basketball game. Globally, the learning program and respective classes could be characterized by attentional breadth, large unpredictability and adaptation demands. The results indicated that BasketCAL group had a significant improvement in agility comparatively to the control group. Also, was noted that BasketCAL students decreased the unsuccessful actions performed during the game. Overall, this program prepares the players to attune the relevant stimulus through the development of adaptive behaviors to overcome environment constraints, leading to better game decisions.El objetivo de este estudio fue examinar el efecto de un programa de alfabetización motora y aprendizaje diferenciado en el desempeño motor, habilidades técnicas y tácticas de baloncesto. Setenta y seis estudiantes universitarios (20.4 ± 1.9 años de edad) fueron asignados de modo aleatorio en grupos experimental (BasketCAL) y de control. Las habilidades motoras se evaluaron a través de la prueba la agilidad de Illinois, la habilidad técnica se evaluó a través de concurso Taco Bell y se examinaron las variables tácticas durante un juego de baloncesto 4 contra 4 en toda la cancha. En general, el programa BasketCAL y las respectivas clases podrían caracterizarse por la amplitud atencional, gran imprevisibilidad y demandas de adaptación. Los resultados indicaron que el grupo BasketCAL tuvo una mejora significativa en la agilidad comparativamente con el grupo control. Además, se observó que los estudiantes BasketCAL disminuyeron las acciones sin suceso durante el juego. En conclusión, este programa prepara a los jugadores para sintonizar el estímulo relevante a través del desarrollo de conductas adaptables para superar las limitaciones del entorno, lo que lleva a mejores decisiones en el juego

Forgiveness as a need of the survivors of the Colombian armed conflict: dialogues between Hannah Arendt and the women of the documentary "Desde diversas orillas"

Este artículo analiza el perdón como una “necesidad” de las víctimas del conflicto armado colombiano, a partir de la voz de las mujeres contenida en el video documental “Desde diversas orillas” (2012). Adicionalmente, se tendrá en cuenta el pensamiento filosófico y político de Hannah Arendt (1906-1975), quien concibe el perdón como una “necesidad” propia de la interacción en comunidad, que posibilita el respeto y la confianza entre los seres humanos y que permite remediar los actos que causaron un daño. Este artículo utilizó variados textos académicos y relatos de las mujeres que aparecen en el documental referido. Este ejercicio investigativo tiene como paradigma y método la hermenéutica, buscando comprender el concepto de perdón desde diferentes enfoques y relaciones con términos análogos, tales como promesa, olvido, reconocimiento de la culpa, libertad, pensamiento y la reconciliación. Este trabajo concluye advirtiendo que el perdón no se puede generalizar (no todas las víctimas del documental aceptan esta posibilidad), ni obviar en los procesos de justicia transicional, los debates académicos y las experiencias socio-políticas.This article analyzes forgiveness as a “need” of the victims of the Colombian armed conflict, based on the voice of women contained in the documentary video “From various shores” (2012). In addition, the philosophical and political thought of Hannah Arendt (1906-1975) will be considered, who conceives forgiveness as a "need" proper to interaction in community, which enables respect and trust between human beings and allows remedy the acts that caused harm. This article used academic texts and stories from the women that appear in the aforementioned documentary. This investigative exercise has hermeneutics as its paradigm and method, seeking to understand the concept of forgiveness from different approaches and relationships with analogous terms, such as promise, forgetfulness, recognition of guilt, freedom, thought and reconciliation. This paper concludes by noting that forgiveness cannot be generalized (not all victims of the documentary accept this possibility), nor can it be ignored in transitional justice processes, academic debates and socio-political experiences

Attitudes and Perceptions of Young Men towards Gender Equality and Violence in Timor-Leste

This article examines attitudes and perceptions of young men toward gender relations and gender-based violence in post-conflict Timor-Leste. A high level of domestic violence is reported and a law against domestic violence has been passed in recent years. In 2013, a research team surveyed almost 500 young men using the Gender-Equitable Men (GEM) Scale in both rural and urban contexts. It was found that young men become less gender equitable as they get older, and the environment they grow up in influences their gender attitudes. Existing contradictions and tensions between national government policy and local customary practices are well-known, and these are reflected in young men’s acceptance of general principles of gender equality, which is unmatched by their willingness to accept more equitable gender relations in their own lives. Of concern was the level of young men’s acceptance of sexual harassment and forced sex. Mechanisms are required to influence young men’s attitudes to gender equality and intimate partner relations in school programs and other arenas as a priority