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- Neurophysiological markers of cardiac interoceptive processing in expectant parents: a study with heartbeat-evoked potentialsPublication . Braga, Patrícia Vilela; Marshall, Amanda; Lamela, Diogo; Jongenelen, Inês; Rocha, Nuno Barbosa; Costa, Raquel; Pasion, Rita; Schütz-Bosbach, Simone; Pinto, Tiago Miguel; Feldman, Ruth; Campos, Carlos; Campos, Carlos; Rocha, NunoPregnancy and parenthood are associated with functional and morphological brain changes. Specifically, the parental caregiving network encompasses key structures implicated in interoception, that is, the ability to perceive and subjectively experience inner bodily states. Interoceptive processing may be critical for successful caregiving, allowing parents to integrate perceived changes in their own bodily states with information stemming from their child. Thus, it is feasible to hypothesize that pregnancy-related neurophysiological changes can modify interoception in expectant parents. Objective: To compare neural markers of cortical interoceptive processing (heartbeat-evoked potentials; HEP) between first-time expectant parents (mothers and fathers) and matched non-parents. First-time expectant heterosexual couples at 26-34 weeks gestational age (n = 70) and matched non-parents (n = 140, 70 female) will complete a multilevel interoception assessment protocol. Neural markers of interoception will be indexed by HEP, that is, neurophysiological responses to cardiac afferent inputs which are obtained through electroencephalography recordings (EEG) time-locked to electrocardiography events (ECG). HEP will be recorded while participants complete the Baby Face Repetition Suppression Paradigm in which sad or neutral infant facial expressions are either repeated or alternated in a 500 ms interstimulus interval. This manipulation induces an emotion-specific repetition modulation on HEP amplitude (differential effects for sad vs. neutral facial expressions). A condition with adult facial expressions will be employed to examine domain-general vs. infant-specific effects. Expectant parents will display increased allocation of neural resources to interoceptive inputs (larger repetition-induced HEP modulation) in contrast to non-parents, particularly when considering infant facial expressions. Effect sizes will be larger when contrasting sad vs. neutral infant facial expressions. Findings from this pioneering study will provide further understanding of the parental brain and the role of interoception during pregnancy, contributing to the comprehension of complex processes involved in caregiving and the development of the parent-infant bond.
- Cardiac interoceptive processing across psychopathy dimensions: evidence from the heartbeat tapping task and the attentional modulation of heartbeat-evoked potentialsPublication . Campos, Carlos; Sá, Catarina; Mazer, Prune; Pasion, Rita; Garcez, Helena; Paiva, Tiago O.; Braga, Patrícia Vilela; Rocha, Nuno Barbosa; Barbosa, Fernando; Rocha, Nuno; Campos, CarlosPsychopathy is a multidimensional personality structure encompassing interpersonal, affective, and behavioral traits. Interoception (ability to perceive and subjectively experience inner bodily states) may be a putative mechanism underlying the etiological pathways of psychopathy. Individual differences in interoceptive processing across psychopathy dimensions may interfere with the ability to perceive somatic sensations that signal the emotional valence of everyday events. To examine the association between psychopathy dimensions (triarchic phenotypes - boldness, meanness, and disinhibition; classical 4-facets - interpersonal, affective, impulsive, antisocial) and cardiac interoceptive processing, namely objectively measured cardiac interoceptive attention and accuracy. Fifty community-dwelling participants (25 women) were recruited and completed: (a) self-report measures indexing psychopathy, trait-based interoceptive attention and accuracy, and alexithymia; (b) modified Heartbeat Tapping Task to index cardiac interoceptive accuracy, where subjects were required to tap after each heartbeat under rest and breath hold conditions (the latter enhanced the magnitude of cardiac signals); (c) modified Heartbeat Attention Task for producing an attentional modulation of heartbeat-evoked potentials (HEP) - neuronal markers of cardiac interoceptive processing - where subjects were required to allocate their attention on their heart vs. an exteroceptive stimulus (objective measure of interoceptive attention). Cardiac interoception was only significantly related to boldness traits. Boldness was positively associated with cardiac interoceptive accuracy after the breath hold manipulation (non-significant after controlling for heart rate), despite no significant effects being observed at rest. Boldness was also negatively correlated with the attentional modulation of HEP due to atypical neuronal responses when allocating attentional resources to the heart. The current findings implicate cardiac interoception in the boldness phenotype, as this psychopathy dimension was associated with enhanced interoceptive-specific perceptual sensitivity and atypical neuronal responses to cardiac afferent inputs when attending to heart-related sensations. Future studies should examine how other interoceptive modalities (e.g., respiratory, gastric) are implicated in psychopathy.
- Modulation of brain structure and motor function by safinamide multimodal actions in a pre-clinical model of Parkinson’s DiseasePublication . Araújo, Bruna; Campos, Jonas; Silva, Rita Caridade; Pinheiro, Bárbara Mendes; Marques, Raquel; Barata, Sandra; Lima, Rui; Macedo, Joana Martins; Gomes, Eduardo; Larrat, Benoit; Salgado, António; Mériaux, Sébastien; Domingues, Sofia; Teixeira, Fábio; Gomes, EduardoTo date, no neuroprotective/disease-modifying strategy has been approved as a Parkinson’s Disease (PD) therapy, because of the‘one-disease-one-target’ view that has been followed. New drug-based therapeutic routes, namely Safinamide, have been introduced as a promising multimodal drug combining dopaminergic and non-dopaminergic (neuroprotective) actions, representing a new potential alternative therapy to prevent or delay PD progression. Thus, the present work addressed Safinamide's impact on PD, relying on the possibility of potentiating dopaminergic neurons (DAn) survival by tackling cellular/molecular impairments responsible for its failure. Safinamide (10mg/kg) was given by oral gavage to a 6-OHDA pre-clinical rat model. DAn survival, neuroinflammation, and redox system homeostasis were assessed by histological and molecular analysis. Additionally, to overpass the selective blood-brain barrier (BBB) permeability, which reduces drug bioavailability reaching PD brain regions, we conducted magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) to transiently open the BBB to precisely deliver Safinamide in PD-affected areas. Results revealed that Safinamide monotherapy was able to potentiate the densities of DAn and fibers, revealing a protective effect when compared to the untreated group. To understand possible pathways associated with this improvement, we found that Safinamide appears to be a modulator of the antioxidant and autophagy systems since an increase in the expression levels of DJ-1, SOD-1, and LC3B was observed when compared to the non-treated group. Furthermore, Safinamide presents a potential modulatory activity on neuroinflammation and astrogliosis, as a decrease in microglia (CD11b+) and astrocytic (GFAP+) cells number was observed when compared to 6-OHDA group. Additionally, the anatomical and functional MRI analysis exhibited connectivity and metabolite alterations. Collectively, these data demonstrate the promising therapeutic potential of Safinamide as a neuroprotection strategy for PD, which may open new therapeutic opportunities for individuals in prodromal stages, potentially delaying clinical manifestation in high-risk patients.
- P-588 The impact of display screen use on visual function at an early agePublication . Mateus, Catarina; Dias, Libânia; Rodrigues, Matilde; Magalhães, Rúben; Ferreira, Simão; Rocha, Nuno; Mateus, Catarina; Dias, Libânia; Rodrigues, Matilde; Ferreira, Simão; Rocha, NunoAs the use of smartphones and other digital devices becomes an integral part of modern life, it is increasingly common to witness children engaging with these devices at younger ages and for extended periods. The outbreak of the COVID-19 pandemic further exacerbated this trend, significantly impacting the way children interact with technology. This study aims to evaluate visual function and lacrimal volume in preschool-aged children and explore possible correlations with the age of screen usage initiation and daily screen time.
- Development of a stable melanoma dual reporter cell line expressing Luciferase and GFPPublication . Aguiar, Gonçalo; Torres, Sílvia; Prudêncio, Cristina; Soares, Raquel; Coelho, Pedro; Prudêncio, Cristina; Coelho, PedroMelanoma is the most aggressive and lethal form of skin cancer, with a high risk of metastatic spread. Obesity is recognized as a risk factor for various types of cancer. However, regarding melanoma, this association remains controversial. Obesity might act as a double-edged sword in melanoma, promoting primary tumour growth but at the same time limiting metastatic spread - the "obesity paradox”. Herein, we aimed to create a stable murine B16F10 melanoma cell line expressing both firefly luciferase (Luc) and green fluorescent protein (GFP), which will later be engrafted into diet induced-obesity animal model for future in vivo studies. B16F10-Luc-GFP cells were generated by transfection with premade lentiviral particles, featuring a construct with Luc and GFP under a cytomegalovirus promoter and mediated by a F2A element. The antibiotic selection marker (puromycin) is expressed under a Rous sarcoma virus promoter. Afterwards, the transfected cells were selected with 1 μg/ml of puromycin. The clones with the highest levels of GFP-positive cells and GFP fluorescence were purified by two rounds of cell sorting and submitted to fluorescence and bioluminescence quantification, morphology, injury, BrdU incorporation, 7-AAD, and PI cell cycle assays and compared to the parental cell line. B16F10-Luc-GFP were successfully generated, and both GFP fluorescence and D-luciferin bioluminescence are present and proportional to cell density. As expected, the parental cell line didn’t display GFP or Luc activities. Moreover, transduced cells exhibit similar morphology, motility, proliferation, viability, and cell cycle progression as B16F10 cells. Conclusions: Altogether, the future engraftment of B16F10-LucGFP in obese mice, will improve melanoma research models, enabling the in vivo and ex vivo visualization of primary tumours and metastasis, providing a better understanding of the underlying molecular mechanisms, to clarify the “obesity paradox” in melanoma.
- Creation of a fungal library and screening of antimicrobial and anticancer activityPublication . Ferreira, Diogo; Hermida, Lara Areal; Rocha, Ana Catarina; Baylina, Pilar; Sieiro, Carmen; Fernandes, Rúben; BAYLINA MACHADO, PILARAccording to the World Health Organization, cancer and infectious diseases are two of the most problematic diseases nowadays. Cancer kills 10 million people every year and the emergence of resistance to antitumoral drugs is an important medical challenge. At the same time, antimicrobial resistance (AMR) is also a serious threat to human and environmental health. Besides mortality, AMR burdens healthcare services and dampens medical procedures such as surgeries, cancer treatments and other invasive procedures. The development of new drug therapies to fight drug resistance is essential to contest the rising of resistant bacteria and reduction of the effectiveness of antitumoral drugs. Microorganisms have been a major source for natural compounds throughout the years. Fungi, renowned for their ability to produce an array of broad and diverse secondary metabolites, offer a rich resource for drug discovery. We built a collection of fungal species, isolated from chestnuts, sunflower seeds, and chestnut flour, and explored their extracts for potential antimicrobial and anticancer activity. Fungi cultures for secondary metabolite biosynthesis were done in submerged fermentation in Malt Extract broth for 15 days at 26 °C. Liquid-liquid extraction techniques, with ethyl acetate as a solvent, were applied to obtain crude secondary metabolite extracts. Clinical resistant bacteria, yeasts, and prostate cell lines (human prostate epithelial cells – HpepiC; human caucasian prostate adenocarcinoma cells - PC3) were exposed to fungal extracts at a single concentration of 100 µg/mL. Our results so far show several extracts with antimicrobial and/or anticancer activity without decreasing cell viability of non-tumoral cells, showing their potential as therapeutic drugs without possible secondary effects. Although, more studies should be done, and pending fungal identification will allow us to select which extracts will be further investigated to find if the displayed bioactivity could be happening due to unknown natural compounds
- Avaliação do potencial antimicrobiano de fungos filamentosos: Um estudo promissor na abordagem do pé diabético e da resistência bacterianaPublication . Ferreira, D.; BAYLINA MACHADO, PILAR; Sá, S.; Areal Hermida, L.; Rocha, A. C.; Baylina, Pilar; Fernandes, R.; Sieiro, C.Prevê-se que até 2045, cerca de 700 milhões de pessoas possam ser afetadas pela Diabetes Mellitus (DM). Uma complicação frequente em indivíduos com DM é o pé diabético, que se manifesta por feridas nos pés causadas por danos nos nervos e vasos sanguíneos, resultando frequentemente na amputação dos membros inferiores. Esta situação é agravada por infeções bacterianas, causadas por estirpes resistentes, como Staphylococcus aureus resistente à meticilina (MRSA), Pseudomonas aeruginosa e Klebsiella spp. produtoras de beta-lactamases de espectro estendido (ESBL), dificultando o tratamento destas lesões. A resistência antibiótica, impulsionada pelo uso excessivo e indiscriminado de antibióticos, destaca a necessidade urgente de novos fármacos e terapias mais eficazes. Neste contexto, os fungos apresentam-se como uma fonte promissora de novos agentes antimicrobianos, devido à vasta gama e diversidade de compostos bioativos que conseguem sintetizar.
- Avaliação do potenicial antimicrobiano do extrato de Gnomoniopsis sp. contra agentes infeciosos do pé diabéticoPublication . Rocha, A. C.; Areal Hermida, L.; Baylina, Pilar; Fernandes, R.; Sieiro, C.; BAYLINA MACHADO, PILAREstima-se que até ao ano de 2045, aproximadamente 700 milhões de pessoas sofram de Diabetes mellitus (DM). O pé diabético é uma complicação comum em pacientes com DM e caracteriza-se por lesões nos pés devido a danos nos nervos e vasos sanguíneos, levando muitas vezes à amputação dos membros inferiores. A infeção causada por bactérias resistentes, como Staphyloccus aureus resistente a meticilina (MRSA), Pseudomonas aeruginosa e espécies de Klebsiella beta-lactamases de espetro estendido (ESBL), acentuam a gravidade destas lesões, tornando o seu tratamento mais complexo. A resistência a antibióticos resulta do uso exagerado e indiscriminado de antibióticos e o desenvolvimento de medicamentos inovadores e de terapias mais eficazes é urgente. Assim, os fungos, nomeadamente fungos filamentosos, surgem como um potencial reservatório para novos compostos antimicrobianos, devido à grande quantidade e diversidade de compostos bioativos produzidos por estes organismos.
- The effects of 24-hour sleep deprivation on the human brain: a multimodal neurophysiological approachPublication . Gonçalves, Alice; Pinto, Sara; Ferreira, Simão; Borges, Daniel FilipeIntroduction: Sleep is an important aspect of human health and well-being and influences various physiological and cognitive functions such as learning and attention. On the other hand, sleep deprivation activates the sympathetic nervous system, negatively impacting blood pressure, heart rate, glucose metabolism, cortisol, and hormones. It alters mood, behaviour, and reduces awareness leading to a poor performance, hence the importance of studying the neurophysiological and neurocognitive effects of 24h sleep deprivation. Objective: Our main goal is to investigate the effects of acute sleep deprivation on the cerebral cortex in healthy university students using a multimodal approach and neurocognitive scales. Methods: This study will use a magnetic stimulator to assess neurophysiological changes, while actigraphy will verify sleep deprivation in the intervention group. Neuropsychological assessments include the Trail Making Test (TMT), measuring visual processing speed and cognitive flexibility, the Psychomotor Vigilance Task (PVT), assessing sustained attention through reaction times to unpredictable stimuli and N-Back test measuring working memory by requiring participants to recall objects presented a few steps earlier. EEG data will be recorded using a cap with 32 channels during. This integrated approach provides a comprehensive analysis of the effects of sleep deprivation on cognitive and neurophysiological functions. Expected Results: Hypothetically, there will be a significant decline in cognitive performance, with impairments in key areas such as visual attention, processing speed and cognitive flexibility. These results will likely manifest in longer reaction times, more frequent errors and overall lower task execution.
- Wearable sleep staging technology as an alternative to polysomnography: a systematic review and meta-analysisPublication . Borges, Maria; Pereira, Telmo; Borges, Daniel Filipe; Soares, Joana IsabelIntroduction:Sleep is vital for health as it has regenerative and protective functions. During sleep, there is a cyclicity of different phases that are analysed and classified for clinical purposes using polysomnography (PSG), a costly and technically demanding method. The tremendous growth of sleep medicine, where demand for studies far outstrips supply, opens a window for the development of accurate, low-threshold sleep monitoring solutions that can be self-administered at home and could help avoid these issues of convenience, accessibility and reproducibility. Objective:This study aims to analyse the existing literature on the feasibility of wearable devices as an alternative to PSG for the classification of sleep stages. Methods: The literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). All studies published in English or Portuguese with healthy adults who used wearables to record sleep were included. A meta-analysis was also performed to assess the mean values of the sleep metrics: total sleep time (TST), sleep latency (SL) and wake after sleep onset (WASO), all in minutes and time per stage (in minutes and as relative frequency of TST), as well as sleep efficiency (SE) (in %) and the corresponding statistics between the wearables used and the PSG. Results: Given the high variability of wearables, the analysed metrics whose values were closest to the PSG came from different devices. Nevertheless, the meta-analysis revealed that most wearables tend to overestimate these variables Conclusions: The performance of wearables demonstrates remarkable accuracy in sleep staging, rivalling the gold standard PSG in some variables while providing a more convenient and unobtrusive alternative. This review enriches our global knowledge of sleep measurement and summarizes the limitations that need to be overcome, as informed decision making depends on understanding the different device options, validation contexts and cost implications.