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Common mechanistic pathways in rare congenital syndromes with primary microcephaly
Publication . Jorge, Xavier; Milagre, Inês; Ferreira, Anita; Calado, Sofia; Oliveira, Raquel; Carvalhal, Sara
Primary microcephaly is an often-seen phenotype in several rare congenital syndromes. It is characterised by a smaller brain size at birth compared to the norm. The causes of this malformation are not fully understood, but genetic testing suggests a connection with defective genes involved in mitotic regulation and proteins related to DNA repair and replication pathways. Cohesinopathies represent a group of rare syndromes, where several subtypes exhibit spontaneous railroad chromosomes and primary microcephaly. This includes Roberts Syndrome, Warsaw Breakage Syndrome and a recently characterised syndrome caused by mutations in the BUB1 gene. Currently, we are examining fibroblast cells from patients with these syndromes to identify common mechanistic pathways. In this context, we have identified a new promising candidate: Topoisomerase II alpha, a protein responsible for resolving of the DNA catenation both in the DNA replication and mitosis. Defective localisation of Topoisomerase II alpha may contribute to the observed mitotic defects in these cells. We are currently exploring the impact of these defects on brain development using reprogramming techniques to assess proper neuronal differentiation.
A 3d cell culture model of the tuberculosis granuloma that can be applied for host genetic studies in the context of a multicellular immunologic response to infection
Publication . David, Susana; Mandal, Manoj; Anes, Elsa; Pires, David
Introduction: The granuloma is an inflammatory infiltrate of mononuclear cells. Some bacterial infections are characterized by the formation of granulomas as part of the immune response to contain the infection. Granuloma models have contributed valuable insights into the genetic basis of granuloma formation during infection. For example, IFNGR1 and IFNGR2 variants have been found to disrupt the immune response, resulting in impaired granuloma formation and increased susceptibility to diseases by Mycobacterium sp. More easily implemented comprehensive models would facilitate the study of the different immune mechanisms and help identify new diseaseassociated genes. Our objective is to generate an in vitro 3D cell culture model using human primary cells and microspheres to generate a stratified granuloma model for future use in genetic, immunological and drug discovery studies. Methods: A commercial system was used to encapsulate human peripheral blood mononuclear cells (PBMC) infected with GFP-expressing M. tuberculosis and maintained in culture for several weeks. The cellular constituents of these granulomas and their organization were characterized by fluorescence microscopy and flow cytometry as well as the viability of the cells and the extent of bacterial replication in factor of time. Results: The results demonstrate a ready recruitment of cells towards infected macrophages, leading to the formation of densely populated aggregates. These aggregates maintained cell viability for several weeks and displayed an enhanced control of bacterial replication compared to the more common monolayer infection models. Moreover, the capsules can be easily disrupted when required to isolate genetic material for further analysis. Conclusion: The proposed 3D model resembles some structural and cellular characteristics of the tuberculosis granuloma and maintains its stability beyond more common 2D models of infection. These preliminary results demonstrate that this model can be used to further explore the determinants of granuloma formation and host response to infection.
Improving formulation of innovative edible insect-based crispbread containing Tenebrio molitor or Acheta domesticus through sensory profiling and liking
Publication . Rocha, C.; Ribeiro, J. C.; Barbosa, B.; Lima, R. C.; Osimani, A.; Aquilanti, L.; Cesaro, C.; Costa, A. I. A.; Roos, N.; Cunha, L. M.
Abstract One of the critical factors in increasing consumer acceptance of edible insects is the development of appropriate products that lead to satisfactory sensory experiences. This way, the negative associations with entomophagy can be hampered, and developed products can be more successfully integrated into consumers' diets. This research aimed to integrate consumers into the food product development process, achieving crispbread formulations with increased acceptance and liking. Crispbread was developed with different formulations and sensory profiles, incorporating house cricket Acheta domesticus or yellow mealworm Tenebrio molitor. Two panels of 50 and 100 untrained consumers evaluated the crispbreads incorporating A. domesticus and T. molitor, respectively. The panels rated overall liking (9-point hedonic scale) and profiled the crispbreads using a Check-All-That-Apply ballot. Regardless of insect species and formulation, all the samples were accepted by consumers with hedonic scores above 5.5. Significant differences were observed between formulations for both insect species, with the chives-based crispbread having the highest liking scores and the incorporation of fennel seeds leading to the lowest liking scores. It was also possible to observe an effect of species, as crispbreads incorporating A. domesticus presented lower hedonic scores and higher association with negative attributes related to odour/flavour ('Earthy', 'Pet Food', 'Bitter) and texture ('Floury'). The results from this study highlight the importance of assessing consumers' opinions while developing insect-based food products, demonstrating that Portuguese consumers present higher liking scores of products incorporating T. molitor and chives.
Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021
Publication . GBD 2021 Tuberculosis Collaborators; Ledesma, Jorge R.; Ma, Jianing; Zhang, Meixin; Basting, Ann V.L.; Chu, Huong Thi; Vongpradith, Avina; Novotney, Amanda; LeGrand, Kate E.; Xu, Yvonne Yiru; Dai, Xiaochen; Nicholson, Sneha Ingle; Stafford, Lauryn K.; Carter, Austin; Ross, Jennifer M.; Abbastabar, Hedayat; Abdoun, Meriem; Abdulah, Deldar Morad; Aboagye, Richard Gyan; Abolhassani, Hassan; Abrha, Woldu Aberhe; Abubaker Ali, Hiwa; Abu-Gharbieh, Eman; Aburuz, Salahdein; Addo, Isaac Yeboah; Adepoju, Abiola Victor; Adhikari, Kishor; Adnani, Qorinah Estiningtyas Sakilah; Adra, Saryia; Afework, Abel; Aghamiri, Shahin; Agyemang-Duah, Williams; Ahinkorah, Bright Opoku; Ahmad, Danish; Ahmad, Sajjad; Ahmadzade, Amir Mahmoud; Ahmed, Haroon; Ahmed, Mohammed; Ahmed, Ayman; Akinosoglou, Karolina; AL-Ahdal, Tareq Mohammed Ali; Alam, Nazmul; Albashtawy, Mohammed; AlBataineh, Mohammad T.; Al-Gheethi, Adel Ali Saeed; Ali, Abid; Ali, Endale Alemayehu; Ali, Liaqat; Ali, Zahid; Ali, Syed Shujait Shujait; Bettencourt, Paulo J. G.
Background: Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. Methods: We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. Findings: We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths. Interpretation: Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups. Funding: Bill & Melinda Gates Foundation.
Histórias de vida cruzadas nos balneários de Lisboa
Publication . Figueiredo, Amélia; Mineiro, Ana; Vidal Mendes, Maria Teresa; Castro-Caldas, Alexandre
Histórias de vidas cruzadas nos Balneários de Lisboa é um livro que é, ao mesmo tempo, uma inspiração e um ato de serviço à humanidade. Os autores do projeto, e dos textos que aqui nos deixam, participaram num programa de enorme importância que a Universidade Católica Portuguesa apoiou, consciente da responsabilidade que tem, como instituição católica de ensino superior, de promover ações que contribuam para combater as desigualdades e fomentar a vida digna. in Nota de abertura, Isabel Capeloa Gil, Reitora da Universidade Católica Portuguesa. As vidas que passam pelo Balneário de Alcântara são marcadas por uma vulnerabilidade, que é a um tempo existencial, e por isso nos interpela a todos, e contextual, fruto da contingência social e económica que transforma o próprio coletivo social em estado precário. As histórias aqui contadas são testemunho da vulnerabilidade humana que se interliga num gesto dedicado com o cuidador responsável, que serve o outro, e que faz muitas vezes a ponte entre o mundo real dos utilizadores dos balneários e a vida sonhada, que alguns ainda têm esperança de conseguir alcançar.