Semiótica da cegueira: alteritas na academia

Dois fenómenos básicos servem como pontos de partida para esta comunicação: por um lado, a cegueira branca, que se propaga de forma espectacular, afectando, em pouco tempo, muitas pessoas que são, depois, recolhidas para a quarentena colectiva e obrigatória; por outro, a metáfora que o texto de José Saramago nos leva a descortinar e as suas virtualidades atemporais, permitindo compreender os estereótipos e alteridades que caracterizam a humanidade de hoje. O texto estabelece relações de interpretação contextualizada com a realidade e com as vivências em todas as áreas político-filosóficas e sócio-culturais. Importa por isso, compreender as figurações e a semântica discursiva do romance, bem como o encadeamento dos significados textuais com a vida actual, a mudança de comportamento humano, as questões da ética, do saber ser e saber estar

The value of cell-free circulating tumour DNA profiling in advanced non-small cell lung cancer (NSCLC) management

Liquid biopsy (LB) has boosted a remarkable change in the management of cancer patients by contributing to tumour genomic profiling. Plasma circulating cell-free tumour DNA (ctDNA) is the most widely searched tumour-related element for clinical application. Specifically, for patients with lung cancer, LB has revealed valuable to detect the diversity of targetable genomic alterations and to detect and monitor the emergence of resistance mechanisms. Furthermore, its non-invasive nature helps to overcome the difficulty in obtaining tissue samples, offering a comprehensive view about tumour diversity. However, the use of the LB to support diagnostic and therapeutic decisions still needs further clarification. In this sense, this review aims to provide a critical view of the clinical importance of plasma ctDNA analysis, the most widely applied LB, and its limitations while anticipating concepts that will intersect the present and future of LB in non-small cell lung cancer patients

Upper Airway Video Endoscopy: Assessment of the response to positive pressure ventilation and mechanical in-exsufflation

Upper airways (UA) include the nasal cavities, pharynx, and larynx, and its main function is to warm and filter the inspired air. UA dysfunction is in the pathogenesis of various disorders, such as obstructive sleep apnea syndrome (OSAS) and vocal cord dysfunction. In addition, in some neurodegenerative diseases (e.g. Amyotrophic Lateral Sclerosis – ALS), UA dysfunction may also compromise the effective use of ventilatory support (VS). In this context, the endoscopic evaluation of UA may be useful in understanding the OSAS mechanisms, in determining the causes for treatment-induced airway obstruction and even in helping to titrate noninvasive ventilation (NIV) in ALS patients with bulbar or pseudo-bulbar (spastic) dysfunction. Specifically, in OSAS patients, when residual obstructive events persist, although an optimal ventilatory mode has been apparently achieved, along with interface and equipment, the endoscopic evaluation of UA seems to be a valuable tool in understanding its mechanisms, even assisting adjustments to NIV parameters. In addition, it has also been described as being useful in laryngeal response to mechanical in-exsufflation (MI-E) and Exercise-Induced Laryngeal Obstruction (EILO). However, no protocol has yet been published or validated for this. For this reason, a literature review was conducted on UA function and its response to positive pressure and MI-E. Special emphasis has also been given to the current indication for video endoscopy in chronically ventilated patients.Martins N. would like to thank the Portuguese Foundation for Science and Technology (FCT – Portugal) for the Strategic project ref. UID/BIM/04293/2013 and “ NORTE2020—Programa Operacional Regional do Norte ” ( NORTE-01-0145-FEDER-000012 )

Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational study

BACKGROUND: B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. METHODS: In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. RESULTS: Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). CONCLUSION: According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection

Molecular Responses of Mussel Mytilus galloprovincialis Associated to Accumulation and Depuration of Marine Biotoxins Okadaic Acid and Dinophysistoxin-1 Revealed by Shotgun Proteomics

The molecular pathways behind the toxicity of diarrheic shellfish toxins (DSTs) in bivalves have been scarcely studied. Thus, a shotgun proteomics approach was applied in this work to understand bivalves’ molecular responses to the dinoflagellate Prorocentrum lima (1.0 × 106 cells/L). Protein expression along with toxins levels were analyzed in the gills and digestive gland of the mussel Mytilus galloprovincialis during and after exposure to this toxic strain. Results revealed an accumulation of OA and DTX1 only in the digestive gland with maximum amounts attained at the end of uptake phase (day 5; 2819.2 ± 522.2 µg OA/kg and 1107.1 ± 267.9 µg DTX1/kg). At the end of the depuration phase (day 20), 16% and 47% of total OA and DTX1 concentrations remained in the digestive gland tissues, respectively. The shotgun proteomic analyses yielded 3051 proteins in both organs. A total of 56 and 54 differentially expressed proteins (DEPs) were revealed in the digestive gland and gills, respectively. Both organs presented the same response dynamics along the experiment, although with tissue-specific features. The early response (3 days uptake) was characterized by a high number of DEPs, being more marked in gills, in relation to the latter time points (5 days uptake and depuration). Functional enrichment analysis revealed the up-regulation of carboxylic (GO:0046943) and organic acid transmembrane transporter activity (GO:0005342) pathways after 3 days uptake for digestive gland. Matching to these pathways are a group of proteins related to transmembrane transport and response to toxic substances and xenobiotics, namely P-glycoprotein (ABCB11), Sodium-dependent proline transporter (SLC6A7), and Sideroflexin-1 (SFXN1). According to Clusters of Orthologous Groups (GOs) categories, most of the DEPs found for digestive gland in all time-points were related with “cellular processes and signaling” and involving signal transduction mechanisms, cytoskeleton and post-translational modification, protein turnover, chaperone functions. In gills, the early uptake phase was marked by a balance between DEPs related with “cellular processes and signaling” and “metabolism.” Depuration is clearly marked by processes related with “metabolism,” mainly involving secondary metabolites biosynthesis, transport, and catabolism. Proteomic data are available via ProteomeXchange with identifier PXD022293.This work was funded by Portuguese Science Foundation (Fundação para a Ciência e a Tecnologia, FCT) and under the Projects MOREBIVALVES (PTDC/ASP-PES/31762/2017) and by the Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 through national funds provided by FCT and European Regional Development Fund (ERDF), in the framework of the program PT2020. This work had also support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013 and LISBOA-01-0145-FEDER-022125)

Issue 2 - “Update on adverse respiratory effects of indoor air pollution” Part 1): Indoor air pollution and respiratory diseases: A general update and a Portuguese perspective

Objective To quantify the impact of different air pollutants on respiratory health based on robust estimates based on international data and to summarise the evidence of associations between indoor exposure to those pollutants and respiratory morbidity in the Portuguese population. Results Several systematic reviews and meta-analyses (MA) at the world level demonstrate the impact of indoor air quality on respiratory health, with indoor particulate matter and gasses exerting a significant effect on the airways. Volatile organic compounds (VOC) have been related to asthma and lung cancer. However, only meta-analyses on biomass use allowed documentation of long-term respiratory effects. While early publications concerning Portuguese-based populations mainly focused on indoor exposure to environmental tobacco smoke, later studies relocated the attention to relevant exposure environments, such as day care buildings, schools, residences and nursing homes. Looking at the pooled effects from the reviewed studies, high levels of carbon dioxide and particulate matter in Portuguese buildings were significantly associated with asthma and wheezing, with VOC and fungi showing a similar effect in some instances. Conclusions Despite the significant reduction of indoor air pollution effects after the 2008 indoor smoking prohibition in public buildings, studies show that several indoor air parameters are still significantly associated with respiratory health in Portugal. The country shares the worldwide necessity of standardisation of methods and contextual data to increase the reach of epidemiological studies on household air pollution, allowing a weighted evaluation of interventions and policies focused on reducing the associated respiratory morbidity

Characterization of mycobacteria and mycobacteriophages isolated from compost at the São Paulo Zoo Park Foundation in Brazil and creation of the new mycobacteriophage Cluster U

Background: A large collection of sequenced mycobacteriophages capable of infecting a single host strain of Mycobacterium smegmatis shows considerable genomic diversity with dozens of distinctive types (clusters) and extensive variation within those sharing evident nucleotide sequence similarity. Here we profiled the mycobacterial components of a large composting system at the São Paulo zoo. Results: We isolated and sequenced eight mycobacteriophages using Mycobacterium smegmatis mc2155 as a host. None of these eight phages infected any of mycobacterial strains isolated from the same materials. The phage isolates span considerable genomic diversity, including two phages (Barriga, Nhonho) related to Subcluster A1 phages, two Cluster B phages (Pops, Subcluster B1; Godines, Subcluster B2), three Subcluster F1 phages (Florinda, Girafales, and Quico), and Madruga, a relative of phage Patience with which it constitutes the new Cluster U. Interestingly, the two Subcluster A1 phages and the three Subcluster F1 phages have genomic relationships indicating relatively recent evolution within a geographically isolated niche in the composting system. Conclusions: We predict that composting systems such as those used to obtain these mycobacteriophages will be a rich source for the isolation of additional phages that will expand our view of bacteriophage diversity and evolution

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science