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- 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.
- Potential anticancer activity from food-isolated fungi extractsPublication . Ferreira, Diogo; Rocha, Ana Catarina; Baylina, Pilar; Sieiro, Carmen; Fernandes, RúbenFungal species have demonstrated great potential to produce a wide range of metabolites, including enzymes, antibiotics, and other bioactive compounds with therapeutic interest. Prostate cancer (PCa) is one of the most frequent cancers in men. This type of tumors have high levels of heterogeneity, leading to therapeutic failures and increasing resistance against chemotherapeutic drugs. Hence, is essential to research new therapeutic agents against PCa. Exploring the rich reservoir of fungal diversity, this study aims to uncover bioactive compounds that may serve as valuable candidates for developing novel therapeutics against prostate cancer. Isolation from chestnuts, chestnut flour and sunflower seeds led to the creation of a fungal collection of 165 isolates. Fungi isolates grew in flask cultures for 15 days, and culture broths were extracted with ethyl acetate. Human prostate epithelial cells (HPepiC) and the human prostate cancer cell line (PC3) were exposed to the fungal extracts at a concentration 100 μg/mL, and cell viability was evaluated by MTT assay. Results show that several fungal extracts significantly reduce the viability of tumor cells, with some showing little to no effect on healthy human cells, however, species identification is essential to carry on our studies.
- Antimicrobial activity of food-isolated fungi extractsPublication . Ferreira, Diogo; Areal-Hermida, Lara; Baylina, Pilar; Fernandes, Rúben; Sieiro, CarmenOne major source for drug discovery are microbial metabolites. Fungi, renowned for their ability to produce an array of broad and diverse secondary metabolites, due to their extensive dispersion and diversity, offer a rich resource for drug discovery. Antibiotic resistance is a major concern. Rapid increase of resistant bacteria worldwide, dampens antibiotic efficiency, burdens healthcare services and increase morbidity and mortality. Antibiotic misuse and lack of new drug development are the main responsible for this health crisis. So, the creation of fungal libraries to find and study new compounds is essential to tackle the rising of antimicrobial resistance and continue with industrial efforts of drug discovery and production. Isolation from chestnuts, chestnut flour and sunflower seeds allowed us to obtain a collection of 165 fungal isolates. Bioactivity of fungal extracts were screened against different antibiotic resistant bacteria. Bacteria grown overnight, adjusted to 1.5 x 108 CFU/mL was exposed to fungal extracts, at a concentration of 100 μg/mL for 24 hours and inhibition rates were calculated. Several extracts showed activity against antimicrobial resistant bacteria and further studies should be made in order to find if new molecules could be responsible for our fungi antimicrobial activity.
- Combining natural bile acids with old basic drugs affords new triple stage antimalarial surface-active ionic liquidsPublication . Silva, Ana Teresa; Oliveira, Isabel; Duarte, Denise; Moita, Diana; Prudêncio, Miguel; Nogueira, Fátima; Ferraz, Ricardo; Marques, Eduardo F.; Gomes, PaulaIonic liquids (ILs) are special organic salts that have been gaining momentum in medicinal chemistry. Despite their simple and cost-effective synthesis, ILs offer an easy access to structures of biological interest by combining bioactive molecules with opposite polarities, e.g., via simple ionic pairing of an acid with a base. This makes ILs of special interest for treating malaria. Since this disease is prevalent mainly in low-to-middle income countries, novel chemotherapeutic strategies must be kept affordable. Malaria is caused by Plasmodium parasites, whose complex life cycle includes three developmental stages in the host: the blood stage, the liver stage, and the gametocyte stage. This complexity turns the development of new effective drugs quite difficult, which is aggravated by the fast emergence of drug-resistant strains. This fact has often led to the disuse of several antimalarials, driving the need to find new ones with multiple-stage action. In this context, we have been working on new antimalarial ILs by mixing antimalarial aminoquinolines—chloroquine and primaquine—with natural lipids. Two new families of salts derived from those antimalarial drugs and naturally-occurring bile acids were now produced by acid-base neutralization, and evaluated for their antiplasmodial action. The chloroquine-derived bile salts were found active against all the three stages of parasite development in the host. Their behavior as surface-active ionic liquids (SAILs), i.e. their interfacial and self-aggregation properties, were also investigated, as they may contribute critically to their delivery and therapeutic action.
- Synthesis and physicochemical characterization of antimalarial surface-active ionic liquidsPublication . Silva, Ana Teresa; Oliveira, Isabel; Ferraz, Ricardo; Marques, Eduardo F.; Gomes, PaulaIonic liquids are a particular class of compounds that attract interest in medicinal chemistry due to the simplicity of their preparation. Novel structures with biological activity can be achieved through simple, cost-effective reactions.1 Reusing old ionizable drugs and improving their characteristics can be achieved economically and simply by mixing them with molecules of opposite charge. This approach is attractive for reviving old antimalarials, not only because of the prevalence of malaria in low- to middle-income countries, but also because several of these drugs are associated with malaria parasite resistance. In this context, our work has been focusing on synthesizing ionic liquids with potential antimalarial activity by mixing antimalarial aminoquinolines, specifically chloroquine, and primaquine, with natural lipids.2, 3 More recently, using an acid-base reaction between chloroquine and bile acids (Figure 1), we synthesized surface-active ionic liquids (SAILs), which proved to possess significant antiplasmodial activity in vitro. The presence of an amphiphilic anion in the ionic pair confers surfaceactive and self-aggregation properties to the ionic liquids. The interfacial and aggregations properties of these SAILs have been characterized by surface tension, electric conductivity, dynamic light scattering, and differential scanning microcalorimetry. Moreover, the interactions of SAILs with micelles of the block copolymer F127 have been studied with the aim of designing an efficient, robust, and biocompatible nanocarrier system for the encapsulation and in vivo release of these antimalarial ionic liquids.
- In vitro evaluation of peptides with potential antioxidant, anti-inflammatory and antihypertensive activitiesPublication . Borges, Thais; Ferraz, Ricardo; Coelho, Pedro; Prudêncio, Cristina; Gomes, Ana; Gomes, PaulaHypertension develops from genetic and environmental factors, and is exacerbated by disorders that increase systemic vascular resistance, like oxidative stress, inflammation and immune system dysfunction1,2. The search for natural compounds as an alternative or a complement to the drugs used to treat hypertension and other chronic diseases has gained momentum in recent years1 . One example is that of food-derived peptides as nutraceuticals3,4,5. In this context, we are exploring the antioxidant, anti-inflammatory, and antihypertensive potential of synthetic peptides derived from proteins found in milk (lactoferrins from different species of mammals) and in other food sources (e.g., jumbo squid - Dosidicus gigas). Antioxidant activity in vitro was determined by both the DPPH radical scavenging activity and the Ferric Reducing Antioxidant Power (FRAP) assays. While none of the squid peptides was active, lactoferrin (LF) ones showed antioxidant potential: aLF-17-31, from donkey (Equus africanus asinus) LF, displayed the stronger radical scavenging activity (IC50 3.53 mol/mol DPPH), and nhLF268-284, from human (Homo sapiens) LF, showed the stronger reducing power (1.26 ± 0.86 mM Fe2+ equivalents). The ABTS radical scavenging activity of LF peptides was further assessed, with bLF-1-11 from bovine (Bos taurus) LF standing out with a Total Antioxidant Status (TAS) of 5.68 ± 9.23 mM. The peptides’ ability to inhibit the angiotensin converting enzyme 1 (ACE1) was also tested in vitro, as an indication of their antihypertensive potential; squid peptide RC7 inhibited ACE1 with an IC50 of 908.6 µM. Relevantly, none of the peptides was cytotoxic (MTT assay on macrophages), as only bLF1-11 showed some toxicity (IC50 417.6 µg/mL). In conclusion, new non-toxic food-derived peptides with ntioxidant/antihypertensive activity were found. Ongoing studies will assess their anti-inflammatory activity (Griess method) as well as their effect of on the TAS in macrophages (superoxide anion production).
- Rastreio organizado do cancro do colo do útero açores – Perspetiva de um novo paradigmaPublication . Maciel, Débora; Fernandes, Sílvia; Silva, Regina A.O cancro do colo do útero é um dos cancros mais frequentes na mulher a nível global. Em 2010, foi implementado o programa de Rastreio Organizado do Cancro do Colo do Útero dos Açores (ROCCA) usando como teste primário o método de citologia líquida para a identificação precoce de lesões precursoras. Em 2020 foi implementada uma nova metodologia de rastreio, o teste de HPV mRNA - AptimaTM HPV Assay (Hologic), seguido de genotipagem. Este trabalho tem como objetivo avaliar a eficácia da implementação do ROCCA, bem como a adequabilidade do método molecular enquanto ferramenta de rastreio.
- Epidemiologia do cancro do colo uterino e o impacto da vacinação contra o HPV: a realidade portuguesa no contexto europeuPublication . Marques, Ana; Fernandes, Sílvia; Silva, Regina A.A atual disponibilidade de vacinas e testes de rastreio molecular para o HPV aumentaram a possibilidade de eliminar globalmente o cancro cervical e outras patologias relacionadas com o vírus. No entanto, têm surgido vários obstáculos à implementação dos programas de vacinação contra o HPV a nível mundial. Este estudo tem como objetivos compilar e analisar estatisticamente a informação acerca da vacinação contra o HPV e políticas de rastreio de cancro cervical, em Portugal e em outros países europeus; e avaliar o impacto na incidência e mortalidade de cancro cervical, ao longo dos anos.
- Ictal and interictal source connectivity during gelastic seizures in a focal cortical dysplasia of the cingulate gyrusPublication . Borges, Daniel Filipe; Dias, Daniela; Cordeiro, Helena; Leal, AlbertoGelastic seizures are rare manifestations of epilepsy often associated with hypothalamic hamartomas (HH). In the absence of HH, localization of the origin is more difficult and there are several less well-established possibilities. Non-invasive assessment is often complicated by the deep localization of the epileptogenic area and the complex dynamics of spike activity. Robust neurophysiologic methods and careful validation of intrinsically epileptogenic lesions detected by RM can improve the validity of scalp EEG analysis. To analyze the dynamics of epileptic activity in gelastic seizures associated with cortical dysplasia. A 26-year-old girl with daily refractory gelastic seizures since the age of 6 underwent a neurophysiological assessment with long-term EEG recordings (24h, 31 channels) and an MRI of the brain. She had previously been rejected in an epilepsy surgery program because no structural brain lesion had been found and the EEG information was not informative enough. A recent 3T MRI showed cortical dysplasia in the cingulate gyrus, which was highly suspicious as an epileptogenic focus. We analyzed the 31-channel EEG (ictal and interictal) using source and functional connectivity methods to obtain a solid computer model of the origin and dynamics of epileptic activity and correlate it with the anatomical information of the MRI. Source analysis of interictal activity revealed multiple sources that dominated at different time points, indicating considerable dynamics that prevented clear source identification. The ictal recordings demonstrated barely late rhythmic activity over the frontal areas, but no early focalization. Connectivity analysis, which revealed the flow of information between cortical sources, showed a consistent origin of epileptic activity in the vicinity of cortical dysplasia for both interictal and ictal activity. EEG connectivity analysis significantly improves the performance of non-invasive methods for determining intracranial dynamics of epileptic activity and correlation with structural lesions.