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Brain functional connectivity measured by resting-state fMRI varies over multiple time scales, and recurrent dynamic functional connectivity (dFC) states have been identified. These have been found to be associated with different cognitive and pathological states, with potential as disease biomarkers, but their neuronal underpinnings remain a matter of debate. A number of recurrent microstates have also been identified in resting-state EEG studies, which are thought to represent the quasi-simultaneous activity of large-scale functional networks reflecting time-varying brain states. Here, we hypothesized that fMRI-derived dFC states may be associated with these EEG microstates. To test this hypothesis, we quantitatively assessed the ability of EEG microstates to predict concurrent fMRI dFC states in simultaneous EEG-fMRI data collected from healthy subjects at rest. By training a random forests classifier, we found that the four canonical EEG microstates predicted fMRI dFC states with an accuracy of 90%, clearly outperforming alternative EEG features such as spectral power. Our results indicate that EEG microstates analysis yields robust signatures of fMRI dFC states, providing evidence of the electrophysiological underpinnings of dFC while also further supporting that EEG microstates reflect the dynamics of large-scale brain networks.

Recently, there has been an increasing interest for utilizing the host immune system to fight against cancer. Moreover, cancer vaccines, which can stimulate the host immune system to respond to cancer in the long term, are being investigated as a promising approach to induce tumor-specific immunity. In this work, we prepared an effective cancer vaccine (denoted as vacosome) by reconstructing the cancer cell membrane, monophosphoryl lipid A as a toll-like receptor 4 agonist, and egg phosphatidylcholine. The vacosome triggered and enhanced bone marrow dendritic cell maturation as well as stimulated the antitumor response against breast cancer 4T1 cells in vitro. Furthermore, an immune memory was established in BALB/c mice after three-time preimmunization with the vacosome. After that, the immunized mice showed inhibited tumor growth and prolonged survival period (longer than 50 days). Overall, our results demonstrate that the vacosome can be a potential candidate for clinical translation as a cancer vaccine.

Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is an age-related, epileptic syndrome, which associates cognitive/behavioral disturbances with a peculiar pattern of spike activity. One promising line of research is the study of ESES in cases of early thalamic lesions. We studied 7 ESES patients with unilateral thalamic lesions using magnetic resonance imaging to assess regional white matter (WM) and thalamic nuclei volume differences, and long-term electroencephalogram recordings to localize the epileptogenic cortex. N170 event-related potentials were used to demonstrate the dysfunctional character of the WM abnormalities. Diffusion-weighted images in a subset of 4 patients were used to parcellate the thalamus and evaluate volume asymmetries, based on cortical connectivity. Large WM regional atrophy in the hemisphere with the thalamic lesion was associated with both cortical dysfunction and epileptic activity. A correlation was demonstrated between lesions in the pulvinar and the mediodorsal thalamic nuclei and WM atrophy of the corresponding cortical projection areas. We propose that these abnormalities are due to the widespread structural disconnection produced by the thalamic lesions associated to a yet unknown age-dependent factor. Further exploration of WM regional atrophy association with the spike activity in other etiologies could lend support to the cortical disconnection role in ESES genesis. info:eu-repo/semantics/publishedVersion

Electroencephalogram microstates are recurrent scalp potential configurations that remain stable for around 90 ms. The dynamics of two of the four canonical classes of microstates, commonly labeled as C and D, have been suggested as a potential endophenotype for schizophrenia. For endophenotypes, unaffected relatives of patients must show abnormalities compared to controls. Here, we examined microstate dynamics in resting-state recordings of unaffected siblings of patients with schizophrenia, patients with schizophrenia, healthy controls, and patients with first episodes of psychosis (FEP). Patients with schizophrenia and their siblings showed increased presence of microstate class C and decreased presence of microstate class D compared to controls. No difference was found between FEP and chronic patients. Our findings suggest that the dynamics of microstate classes C and D are a candidate endophenotype for schizophrenia., EEG microstate abnormalities have been reported in patients with schizophrenia. Here the authors demonstrate that patients and their siblings show similar microstate abnormalities compared to healthy controls.

Introduction. Diabetic neuropathy (DN) is one of the most devastating complications of diabetes mellitus; however, in contrast to other countries, there are no scientific studies in Portugal evaluating the impact of demographic and clinical characteristics of this pathological entity. The aim of this study was to evaluate the impact of gender, metabolic control, age of diabetic patients, as well as time of disease progression, the appearance of complaints related to neuropathic pain. Material and methods. A multicentre study with a non-probabilistic, convenience sample of 359 patients was performed employing the quantitative method, using the Statistical Package for Social Science 24 software. The p-value of p < 0.05 was defined to consider a result statistically significant. The Spearman correlation coefficient (r) was determined to determine the relationship between categorical variables. Results. There was no statistically significant difference in the prevalence of DN between genders (p = 0.633 and r = 0.025). There was a statistically significant relationship between the value of HbA1c and DN, with p = 0.010 and r = 0.136. There is a relationship between age and complaints of neuropathic pain, with p = 0.034 and r = 0.112. The variable, time of disease progression, is also correlated with the appearance of complaints of neuropathic pain with p = 0.020 and r = 0.112. Conclusion. The prevalence of neuropathic pain in subjects with diabetes is not negligible and is associated with modifiable risk factors that can be identified, possibly modified and prevented. The correct approach for these patients, which involves screening and early treatment, is decisive improving functionality and quality of life.

Visual backward masking (VBM) deficits are candidate endophenotypes of schizophrenia indexing genetic liability of the disorder. In VBM, a target is followed by a mask that deteriorates target perception. Schizophrenia patients and, to a lesser extent, their unaffected relatives show strong and reproducible VBM deficits. In patients, VBM deficits are associated with strongly decreased amplitudes in the evoked-related potentials (ERPs). Here, to unveil the neural mechanisms of VBM in schizophrenia, circumventing illness-specific confounds, we investigated the electroencephalogram correlates of VBM in unaffected siblings of schizophrenia patients. We tested 110 schizophrenia patients, 60 siblings, and 83 healthy controls. As in previous studies, patients showed strong behavioral deficits and decreased ERP amplitudes compared to controls. Surprisingly, the ERP amplitudes of siblings were even higher than the ones of controls, while their performances were similar. ERP amplitudes in siblings were found to correlate with performance. These results suggest that VBM is deteriorated in patients and siblings. However, siblings, unlike patients, can partially compensate for the deficits by over-activating a network of brain regions.

Ethionamide (ETH) is a commercial drug, used as a second-line resource to neutralize Mycobacterium tuberculosis infections. It is proven that its metabolization in the organism leads to the formation of the active form of the drug, but some metabolic pathways may lead to the loss of its activity. Our work proved that the presence of oxidized methionine in cells could influence ETH's degradation, leading to the appearance of an inactive metabolite that is detectable by HPLC and mass spectrometry. In addition, it was found this process increases with the degree of methionine oxidation. This study contributes to a better understanding of ethionamide's metabolism in living organisms, and can help in the design of new drugs or ethionamide boosters for the combat of multidrug resistant tuberculosis.

Polyoxometalates are an emerging class of molecular clusters, with well-defined structures and chemical compositions that are produced through simple, low-cost, and highly reproducible methods. In particular, the wheel-shaped cluster {Mo154} is a promising photothermal agent due to its intervalence charge transfer transitions. However, its toxicity hinders its systemic administration, being the development of a localized delivery system still incipient. Herein, an injectable and self-healing hydrogel of easy preparation and administration is developed, incorporating both {Mo154} and doxorubicin for synergistic photothermal and chemotherapy applications. The hydrogel is composed of benzylaldehyde functionalized polyethylene glycol, poly(N-isopropylacrylamide) functionalized chitosan and {Mo154}. The gelation occurs within 60 s at room temperature, and the dual crosslinking by Schiff base and electrostatic interactions generates a dynamic network, which enables self-healing after injection. Moreover, the hydrogel delivers chemotherapeutic drugs, with a release triggered by dual near infra-red (NIR) radiation and pH changes. This stimuli-responsive release system along with the photothermal conversion ability of the hydrogel allows the simultaneous combination of photothermal and chemotherapy. This synergic system efficiently ablates the cancer tumor in vivo with no systemic toxicity. Overall, this work paves the way for the development of novel {Mo154}-based systems, incorporated in self-healing and injectable hydrogels for dual chemo-photothermal therapy.

Social dominance, the main organizing principle of social hierarchies, facilitates priority access to resources by dominant individuals. Throughout taxa, individuals are more likely to become dominant if they act first in social situations and acting fast may provide evolutionary advantage; yet whether fast decision-making is a behavioral predisposition of dominant persons outside of social contexts is not known. Following characterization of participants for social dominance motivation, we found that, indeed, men high in social dominance respond faster–without loss of accuracy–than those low in dominance across a variety of decision-making tasks. Both groups did not differ in a simple reaction task. Then, we selected a decision-making task and applied high-density electroencephalography (EEG) to assess temporal dynamics of brain activation through event related potentials. We found that promptness to respond in the choice task in dominant individuals is related to a strikingly amplified brain signal at approximately 240 ms post-stimulus presentation. Source imaging analyses identified higher activity in the left insula and in the cingulate, right inferior temporal and right angular gyri in high than in low dominance participants. Our findings suggest that promptness to respond in choice situations, regardless of social context, is a biomarker for social disposition.

Objective: to discuss in the scientific literature the strategies used to prevent hypothermia in newborns undergoing surgical procedures. Methods this is an integrative literature review, with structured search in April and May 2020 in 08 databases, using the descriptors: Hypothermia; Surgical Procedures, Operative; Infant, Newborn; Protocols. Four primary studies were selected and analyzed using three instruments to assess the methodological quality of the Joanna Briggs Institute and content analysis. Results: Among the strategies used, the following stand out: room temperature control; establishment of humidification and quality of air conditioning cleanliness; use of a heated incubator or cradle; use of thermal mattress; use of caps and blanket; heated fluids; temperature monitoring and abdominal organ coverage. Conclusion good hypothermia prevention strategies were identified, despite the small number of publications on this topic; thus, it points out the need for research with strong evidence. RESUMEN Objetivo: discutir, en la literatura científica, las estrategias utilizadas para prevenir la hipotermia en recién nacidos sometidos a procedimientos quirúrgicos. Métodos: revisión integrativa de la literatura, con búsqueda estructurada en abril y mayo de 2020 en 08 bases de datos, utilizando los descriptores: Hypothermia; Surgical Procedures, Operative; Infant, Newborn; Protocols. Se seleccionaron y analizaron cuatro estudios primarios utilizando tres instrumentos para evaluar la calidad metodológica del Instituto Joanna Briggs y el análisis de contenido. Resultados: entre las estrategias empleadas destacan: control de la temperatura ambiente; establecimiento de humidificación y calidad de aire acondicionado limpio; uso de una incubadora o cuna con calefacción; uso de colchón térmico; uso de gorros y mantas; fluidos calentados; monitoreo de temperatura; cobertura de órganos abdominales. Conclusión: se identificaron buenas estrategias de prevención de la hipotermia, a pesar del escaso número de publicaciones sobre este tema; por lo tanto, señala la necesidad de realizar investigaciones con evidencia sólida. RESUMO Objetivo: discutir, na literatura científica, as estratégias utilizadas para prevenção de hipotermia em recém-nascido submetido a procedimentos cirúrgicos. Métodos: revisão integrativa de literatura, com busca estruturada em abril e maio de 2020 em 08 bases de dados, utilizando os descritores: Hypothermia; Surgical Procedures, Operative; Infant, Newborn; Protocols. Foram selecionados e analisados 04 estudos primários por meio de três instrumentos para avaliação da qualidade metodológica da Joanna Briggs Institute e da análise de conteúdo. Resultados: dentre as estratégias utilizadas destaca-se: controle da temperatura ambiente; estabelecimento de umidificação e qualidade de limpeza do ar condicionado; utilização de incubadora ou berço aquecido; uso de colchão térmico; uso de toucas e cobertor; fluidos aquecidos; monitoramento da temperatura; cobertura de órgãos abdominais. Conclusão: identificaram-se boas estratégias de prevenção de hipotermia, apesar de haver um número reduzido de publicações nesta temática; dessa forma, aponta-se a necessidade de pesquisas com evidências fortes.

© The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2022, Objective: Histogram-based metrics extracted from diffusion-tensor imaging (DTI) have been suggested as potential biomarkers for cerebral small vessel disease (SVD), but methods and results have varied across studies. This work aims to assess the impact of mask selection for extracting histogram-based metrics of fractional anisotropy (FA) and mean diffusivity (MD) on their sensitivity as SVD biomarkers. Methods: DTI data were collected from 17 SVD patients and 12 healthy controls. FA and MD maps were estimated; from these, histograms were computed on two whole-brain white-matter masks: normal-appearing white-matter (NAWM) and mean FA tract skeleton (TBSS). Histogram-based metrics (median, peak height, peak width, peak value) were extracted from the FA and MD maps. These were compared between groups and correlated with the patients' cognitive scores (executive function and processing speed). Results: White-matter mask selection significantly impacted FA and MD histogram metrics. In particular, significant interactions were found between Mask and Group for FA peak height (p = 0.027), MD Median (p = 0.035) and MD peak width (p = 0.047); indicating that the mask used affected their ability to discriminate between groups. In fact, MD peak width showed a significant 8.8% increase in patients when using TBSS (p = 0.037), but not when using NAWM (p = 0.69). Moreover, the mask may have an effect on the correlations with cognitive measures. Nevertheless, MD peak width (TBSS: r = - 0.75, NAWM: r = - 0.71) and MD peak height (TBSS: r = 0.65, NAWM: r = 0.62) remained significantly correlated with executive function, regardless of the mask. Conclusion: The impact of the processing methodology, in particular the choice of white-matter mask, highlights the need for standardized MRI data-processing pipelines., We acknowledge the Portuguese Foundation for Science and Technology (FCT) for financial support through Grants SFRH/BD/139561/2018, PTDC/BBB-IMG/2137/2012, LISBOA-01-0145-FEDER-029675 and UIDB/50009/2020.

© 2021 AlphaMed Press., Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with cancer show worse outcomes compared with patients without cancer. The humoral immune response (HIR) of patients with cancer against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized patients with cancer infected with SARS-CoV-2. Materials and methods: This was a unicentric, retrospective study enrolling adult patients with SARS-CoV-2 admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptor-binding domain or spike protein IgM, IgG, and IgA antibodies. The aims of the study were to assess the HIR to SARS-CoV-2; correlate it with different cancer types, stages, and treatments; clarify the interplay between the HIR and clinical outcomes of patients with cancer; and compare the HIR of SARS-CoV-2-infected patients with and without cancer. Results: We included 72 SARS-CoV-2-positive subjects (19 with cancer, 53 controls). About 90% of controls revealed a robust serological response. Among patients with cancer, a strong response was verified in 57.9%, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among patients with cancer. No significant differences in outcomes were observed between patients with strong and weak responses. All IgG, IgM, IgA, and total Ig antibody titers were significantly lower in patients with cancer compared with those without. Conclusion: A significant portion of patients with cancer develop a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among patients with cancer. Patients with cancer have a weaker SARS-CoV-2 antibody response compared with those without cancer. Implications for practice: These results place the spotlight on patients with cancer, particularly those actively treated with chemotherapy. These patients may potentially be more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, so it is important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining, or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected patients with cancer in accordance with cancer type, stage and prognosis, treatment agents, treatment setting, and SARS-CoV-2 infection risks., LtoINNOV), the Fundação para a Ciência e a Tecnologia (SFRH/BD/131605/2017), and research4COVID19 (231_596873172, generating SARS-CoV-2 seroconversion assay), with additional support by Sociedade Francisco Manuel dos Santos.

Objetivo: descrever o processo de implantação de Planos de Alta na Clínica Cirúrgica de um hospital de grande porte de Salvador (BA). Método: relato de experiência que descreve aspectos relacionados a elaboração, atualização e implantação de cinco planos de alta hospitalar de enfermagem para pacientes atendidos nessa clínica cirúrgica. Foram direcionados aos seguintes procedimentos cirúrgicos: hernioplastias, colecistectomia, histerectomia, amputação e prostatectomia. Resultados: foram atualizados cinco planos de alta, os quais foram analisados pela coordenadora de enfermagem, médico cirurgião geral e supervisora do componente obrigatório; após sugestões e alterações realizadas, foram encaminhados para a Comissão de Padronização desse Hospital para serem implantados nas Unidades de Clínica Cirúrgica. Conclusão: a experiência possibilitou a afirmação dos instrumentos como um importante material didático para os pacientes sobre as condutas pós-cirúrgicas e para o enfermeiro, que através desse material consegue direcionar as orientações necessárias.

Extracellular matrix‐mimicking hydrogels with antioxidant, hemostasis, and antibacterial properties offer translating avenues towards wound repair through the promotion of fibroblast proliferation. In article number 2001122 by Helder A. Santos, Mohammad‐Ali Shahbazi, and co‐workers, hydrogen bonding among the functional groups of gelatin and tannic acid creates a biocompatible hydrogel, where the improvement of re‐epithelialization and collagen deposition are its main features to treat full‐thickness wounds.

Sexting has been defined as sending, receiving, or forwarding sexually explicit messages, images, or photos to others through digital platforms, and can assume more consensual or more abusive and violent forms. This study aims to explore the prevalence of abusive sexting in Portuguese adolescents and the psychological characteristics of sexting abusers in terms of emotional and behavioral problems, potential markers of psychopathy, childhood trauma and maltreatment, and different forms of aggression. A cross-sectional study was conducted with 4,281 participants, aged 12–20 years (2,264 girls and 2,017 boys), of whom 204 (4.8%) engaged in abusive sexting behaviors and 182 (4.3%) self-identified as being a non-consensual sexting victim. Abusive sexting was more common among boys and middle adolescents, and abusive sexting victims were more likely to be children of single-parent families. Engaging in abusive sexting and being a victim of abusive sexting were also related to behavioral and emotional problems, callousness, experiences of neglect and abuse in childhood, and various forms of aggression. Implications for future research and intervention are discussed.

Cerebrovascular reactivity (CVR) is defined as the ability of vessels to alter their caliber in response to vasoactive factors, by means of dilating or constricting, in order to increase or decrease regional cerebral blood flow (CBF). Importantly, CVR may provide a sensitive biomarker for pathologies where vasculature is compromised. Furthermore, the spatiotemporal dynamics of CVR observed in healthy subjects, reflecting regional differences in cerebral vascular tone and response, may also be important in functional MRI studies based on neurovascular coupling mechanisms. Assessment of CVR is usually based on the use of a vasoactive stimulus combined with a CBF measurement technique. Although transcranial Doppler ultrasound has been frequently used to obtain global flow velocity measurements, MRI techniques are being increasingly employed for obtaining CBF maps. For the vasoactive stimulus, vasodilatory hypercapnia is usually induced through the manipulation of respiratory gases, including the inhalation of increased concentrations of carbon dioxide. However, most of these methods require an additional apparatus and complex setups, which not only may not be well-tolerated by some populations but are also not widely available. For these reasons, strategies based on voluntary breathing fluctuations without the need for external gas challenges have been proposed. These include the task-based methodologies of breath holding and paced deep breathing, as well as a new generation of methods based on spontaneous breathing fluctuations during resting-state. Despite the multitude of alternatives to gas challenges, existing literature lacks definitive conclusions regarding the best practices for the vasoactive modulation and associated analysis protocols. In this work, we perform an extensive review of CVR mapping techniques based on MRI and CO2 variations without gas challenges, focusing on the methodological aspects of the breathing protocols and corresponding data analysis. Finally, we outline a set of practical guidelines based on generally accepted practices and available data, extending previous reports and encouraging the wider application of CVR mapping methodologies in both clinical and academic MRI settings.

Pain is an under-reported but prevalent symptom in Parkinson’s Disease (PD), impacting patients’ quality of life. Both pain and PD conditions cause cortical excitability reduction and non-invasive brain stimulation. Mental representation techniques are thought to be able to counteract it, also resulting effectively in chronic pain conditions. We aim to conduct two independent studies in order to evaluate the efficacy of transcranial direct current stimulation (tDCS) and mental representation protocol in the management of pain in PD patients during the ON state: (1) tDCS over the Primary Motor Cortex (M1); and (2) Action Observation (AO) and Motor Imagery (MI) training through a Brain-Computer Interface (BCI) using Virtual Reality (AO + MI-BCI). Both studies will include 32 subjects in a longitudinal prospective parallel randomized controlled trial design under different blinding conditions. The main outcomes will be score changes in King’s Parkinson’s Disease Pain Scale, Brief Pain Inventory, Temporal Summation, Conditioned Pain Modulation, and Pain Pressure Threshold. Assessment will be performed pre-intervention, post-intervention, and 15 days post-intervention, in both ON and OFF states., This research received no external funding, neither has an external sponsor.

In recent years, increasing evidence of the positive impact of Virtual Reality (VR) on neurofeedback training has emerged. The immersive properties of VR training scenarios have been shown to facilitate neurofeedback learning while leading to cognitive enhancements such as increased working memory performance. However, in the design of an immersive VR environment, there are several covariates that can influence the level of immersion. To date, the specific factors which contribute to the improvement of neurofeedback performance have not yet been clarified. This research aims to investigate the effects of vividness in a Cave automatic virtual environment (CAVE-VR) on neurofeedback training outcome, and to assess the effect on working memory performance. To achieve this, we recruited 21 participants, exposed to neurofeedback training inside a CAVE-VR environment. Participants were divided into three experimental groups, each of which received feedback in a different neurofeedback training scenario with increasing level of vividness (i.e., low, medium, high) while also assessing the effect of neurofeedback on working memory performance. Current findings show that highly vivid feedback in CAVE-VR results in increased neurofeedback performance. In addition, highly vivid training scenarios had a positive effect on user’s motivation, concentration, and reduced boredom. Finally, current results corroborate the efficacy of the neurofeedback enhancement protocol in CAVE-VR for improving working memory performance.

Research on schizophrenia typically focuses on one paradigm, for which clear-cut abnormalities between patients and controls are established. Great care is taken to understand the underlying genetical, neurophysiological, and cognitive mechanisms, which eventually may explain the clinical outcome. This approach has led to many important hypotheses about the causes of schizophrenia. One tacit assumption of these deep rooting approaches is that paradigms tap into common and representative characteristics of the disease. Here, we analyzed resting-state electroencephalogram (EEG) of 121 schizophrenia patients and 75 age-matched controls, from which we extracted 194 features. Sixty-nine of these features showed significant group differences with medium to large effect sizes, indicating important abnormalities. To understand to what extent these features tap into the same aspects of the disorder, we computed both Pearson and partial least squares correlations. Surprisingly, correlations were very low, except for very similar features, where correlations were high, suggesting that most features are sensitive to different abnormalities. Using partial least squares regression, we show that combining the 69 features increases predictability of clinical outcomes by more than a factor of 5. We propose that complementing deep with shallow rooting approaches, where many roughly independent features are extracted from one paradigm (or several paradigms), will strongly improve diagnosis and potential treatment of schizophrenia.

© 2020 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., SARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of 6 months following COVID-19 onset. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff, and 198 post-COVID-19 volunteers. Anti-SARS-CoV-2 antibody responses follow a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce subsequently, the ability to detect anti-SARS-CoV-2 IgG antibodies remained robust with confirmed neutralization activity for up to 6 months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Importantly, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2., We like to acknowledge the funding from the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV) and the Fundação para a Ciência e a Tecnologia (FCT) to P.F‐C. (SFRH/BD/131605/2017), PTDC/MED‐IMU/28003/2017, and research4COVID19 (no. 231_596873172, Generating SARS‐CoV2 seroconversion assay and no. 729, High‐throughput SARS‐CoV2 neutralizing antibodies assessment), with additional support by Sociedade Francisco Manuel dos Santos.

SARS-CoV-2 has emerged as a novel human pathogen, causing clinical signs, from fever to pneumonia – COVID-19 – but may remain mild or even asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed and have been setup around the world. We quantified immunoglobulin M (IgM), IgG and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of five months following COVID-19 disease onset or in previously SARS-CoV-2 PCR-positive volunteers. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff and 187 post-COVID19 volunteers, and assessing titres for IgM, IgG and IgA. Anti-SARS-CoV-2 antibody responses followed a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce from approximately four weeks, the ability to detect SARS-CoV-2 antibodies remained robust for five months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Moreover, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2, at least up to five months after infection.

UIDB/50006/2020 PD/BD/142880/2018 UID/DTP/04138/2020 Here, a continuous two-step glass-capillary microfluidic technique to produce a multistage oral delivery system is reported. Insulin is successfully encapsulated into liposomes, which are coated with chitosan to improve their mucoadhesion. The encapsulation in an enteric polymer offers protection from the harsh gastric conditions. Insulin permeability is enhanced across an intestinal monolayer. publishersversion published

In this study, a rationally designed nanocomposite (BUDPDA@MAP) composed of polydopamine (PDA) nanoparticle and anti‐inflammatory drug budesonide (BUD) encapsulated in a pH‐responsive endosomolytic polymer (poly(butyl methacrylate‐co‐methacrylic acid) grafted acetalated dextran, denoted by MAP), is proposed. The uniform nanocomposite is prepared using a microfluidic device. At low endosomal pH (5.5), MAP destabilizes the endosomal membranes for the cytoplasmic delivery of PDA, and releases BUD simultaneously, resulting in a greater reactive oxygen species scavenging capability than both the free drug and PDA alone. The combined therapeutic efficacy from PDA and BUD also leads to a successful macrophage phenotype switch from pro‐inflammatory M1 to anti‐inflammatory M2.

Objective With the advent of high-density EEG and studies of large numbers of participants, yielding increasingly greater amounts of data, supervised methods for artifact rejection have become excessively time consuming. Here, we propose a novel automatic pipeline (APP) for pre-processing and artifact rejection of EEG data, which innovates relative to existing methods by not only following state-of-the-art guidelines but also further employing robust statistics. Methods APP was tested on event-related potential (ERP) data from healthy participants and schizophrenia patients, and resting-state (RS) data from healthy participants. Its performance was compared with that of existing automatic methods (FASTER for ERP data, TAPEEG and Prep pipeline for RS data) and supervised pre-processing by experts. Results APP rejected fewer bad channels and bad epochs than the other methods. In the ERP study, it produced significantly higher amplitudes than FASTER, which were consistent with the supervised scheme. In the RS study, it produced spectral measures that correlated well with the automatic alternatives and the supervised scheme. Conclusion APP effectively removed EEG artifacts, performing similarly to the supervised scheme and outperforming existing automatic alternatives. Significance The proposed automatic pipeline provides a reliable and efficient tool for pre-processing large datasets of both evoked and resting-state EEG.

External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI.

N1-unsubstituted imidazolidin-4-ones of primaquine (PQ) can be stabilized by N1-alkylation under basic conditions. Here we report the development, with our conditions, of peptidomimetic derivatives of PQ with l -amino acid and alkyl derivatives. The new derivatives represent potential new therapeutics for use against protozoan parasites, through enzymatic protection of aminopeptidases.

Relações de dor, incapacidade e força muscular podem estar assoicadas na lombalgia crônica. Objetivo: Avaliar a associação entre força muscular do músculo glúteo médio e força de preensão palmar, limiar de tolerância de dor à pressão (LTDP) e nível de incapacidade, em pacientes com lombalgia crônica. Métodos: Trata-se de um estudo transversal observacional do qual participaram 50 indivíduos de ambos os sexos. O nível de incapacidade foi avaliado pelo questionário Roland-Morris (QRM). O LTDP foi avaliado por algometria no músculo glúteo médio. A avaliação da força muscular foi feita através do teste de força manual (TFM) no glúteo médio. A força de preensão palmar foi avaliada por um dinamômetro portátil. As correlações foram estabelecidas por meio dos coeficientes de correlação de Pearson ou Spearman. Resultados: Houve associação moderada entre a força do glúteo médio e a preensão palmar (r=0,44), entre a força de preensão palmar e o LTDP do glúteo médio (r=0,45), e entre a força do glúteo médio e a incapacidade (r=-0,44). As demais correlações foram fracas ou muito fracas. Conclusão: Os dados do estudo mostram que em indivíduos com lombalgia crônica, quanto maior a força de preensão palmar, maior a força e o limiar de tolerância de dor à pressão do glúteo médio. Ainda, que quanto maior a força do glúteo médio, menor a incapacidade destes pacientes.

Electroencephalography (EEG) neurofeedback (NF) training has been shown to produce long-lasting effects on the improvement of cognitive function as well as the normalization of aberrant brain activity in disease. However, the impact of the sensory modality used as the NF reinforcement signal on training effectiveness has not been systematically investigated. In this work, an EEG-based NF-training system was developed targeting the individual upper-alpha (UA) band and using either a visual or an auditory reinforcement signal, so as to compare the effects of the two sensory modalities. Sixteen healthy volunteers were randomly assigned to the Visual or Auditory group, where a radius-varying sphere or a volume-varying sound, respectively, reflected the relative amplitude of UA measured at EEG electrode Cz. Each participant underwent a total of four NF sessions, of approximately 40 min each, on consecutive days. Both groups showed significant increases in UA at Cz within sessions, and also across sessions. Effects subsequent to NF training were also found beyond the target frequency UA and scalp location Cz, namely in the lower-alpha and theta bands and in posterior brain regions, respectively. Only small differences were found on the EEG between the Visual and Auditory groups, suggesting that auditory reinforcement signals may be as effective as the more commonly used visual signals. The use of auditory NF may potentiate training protocols conducted under mobile conditions, which are now possible due to the increasing availability of wireless EEG systems.

Continuous spike-wave of sleep (CSWS) is an age-related epileptic syndrome with an unknown mechanism of action, that affects mainly children. Nevertheless, thalamic lesions have been demonstrated to be the most common etiology. Recently, a model was proposed for the genesis of CSWS in patients with thalamic lesions that consists of a thalamo-cortical disconnection producing a pathological sleep-stage-dependent synaptic plasticity, named augmenting response during the non-rapid eye movement (non-REM) sleep stages, which leads to CSWS. Diffusion-weighted imaging (DWI) is a technique sensitive to the microstructural organization of the tissues, that has been widely used to map the white matter pathways of the brain. It also enables to parcellate brain structures according to its connectivity profile, in a method known as connectivity-based parcellation. Parcellation of the thalamus was carried out in four infants with CSWS associated with strictly unilateral thalamic lesions; the aim was to infer on the structural connectivity of the different thalamic nuclei with the cortex and identify asymmetries between the healthy and lesioned hemispheres. Electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) data were also used to support the interpretations made. The asymmetries in thalamocortical connectivity were consistent with the distribution of epileptic events observed on the EEG, supporting the hypothesis of a partial disruption of thalamic inputs to the cortex being responsible for the genesis of epileptic activity, in CSWS patients with thalamic lesions.

To maximize brain plasticity after stroke, a plethora of rehabilitation strategies have been explored. These include the use of intensive motor training, motor-imagery (MI), and action-observation (AO). Growing evidence of the positive impact of virtual reality (VR) techniques on recovery following stroke has been shown. However, most VR tools are designed to exploit active movement, and hence patients with low level of motor control cannot fully benefit from them. Consequently, the idea of directly training the central nervous system has been promoted by utilizing MI with electroencephalography (EEG)-based brain-computer interfaces (BCIs). To date, detailed information on which VR strategies lead to successful functional recovery is still largely missing and very little is known on how to optimally integrate EEG-based BCIs and VR paradigms for stroke rehabilitation. The purpose of this study was to examine the efficacy of an EEG-based BCI-VR system using a MI paradigm for post-stroke upper limb rehabilitation on functional assessments, and related changes in MI ability and brain imaging. To achieve this, a 60 years old male chronic stroke patient was recruited. The patient underwent a 3-week intervention in a clinical environment, resulting in 10 BCI-VR training sessions. The patient was assessed before and after intervention, as well as on a one-month follow-up, in terms of clinical scales and brain imaging using functional MRI (fMRI). Consistent with prior research, we found important improvements in upper extremity scores (Fugl-Meyer) and identified increases in brain activation measured by fMRI that suggest neuroplastic changes in brain motor networks. This study expands on the current body of evidence, as more data are needed on the effect of this type of interventions not only on functional improvement but also on the effect of the intervention on plasticity through brain imaging. info:eu-repo/semantics/publishedVersion

Breast cancer, with around 2 million new cases in 2019, is the second most common cancer worldwide and the second leading cause of cancer death among females. The aim of this work is to prepare a targeting nanoparticle through the conjugation of LinTT1 peptide, a specific molecule targeting p32 protein overexpressed by breast cancer and cancer associated cells, on liposomes' surface. This approach increases the cytotoxic effects of doxorubicin (DOX) and sorafenib (SRF) co-loaded in therapeutic liposomes on both 2D and 3D breast cancer cellular models. The liposome functionalization leads to a higher interaction with 3D breast cancer spheroids than bare ones. Moreover, interaction studies between LinTT1-functionalized liposomes and M2 primary human macrophages show an internalization of 50% of the total nanovesicles that interact with these cells, while the other 50% results only associated to cell surface. This finding suggests the possibility to use the amount of associated liposomes to enrich the hypoxic tumor area, exploiting the ability of M2 macrophages to accumulate in the central core of tumor mass. These promising results highlight the potential use of DOX and SRF co-loaded LinTT1-functionalized liposomes as nanomedicines for the treatment of breast cancer, especially in triple negative cancer cells.

A targeted drug delivery nanosystem for glioblastoma multiforme (GBM) based on polymersomes (Ps) made of poly(dimethylsiloxane)-poly(2-methyloxazoline) (PDMS-PMOXA) diblock copolymers was developed to evaluate their potential to actively target brain cancer cells and deliver anticancer drugs. Angiopep2 was conjugated to the surface of preformed Ps to target the low density lipoprotein receptor-related protein 1 that are overexpressed in blood brain barrier (BBB) and glioma cells. The conjugation efficiency yield for angiopep2 was estimated to be 24%. The angiopep2-functionalized Ps showed no cellular toxicity after 24h and enhanced the cellular uptake around 5 times more in U87MG glioblastoma cells compared to the non-targeted Ps. The encapsulation efficiency of doxorubicin (DOX) in Ps was 13% by co-solvent method, compared to a film rehydration method (4%). The release profiles of the DOX from Ps showed a release of 42% at pH 5.5 and 40% at pH 7.4 after 24h, indicating that Ps can efficiently retain the DOX with a slow release rate. Furthermore, the in vitro antiproliferative activity of DOX-loaded Ps-Angiopep2 showed enhanced toxicity to U87MG glioblastoma cells, compared to non-targeted Ps. Overall, our in vitro results suggested that angiopep2-conjugated Ps can be used as nanocarriers for efficient targeted DOX delivery to glioblastoma cells.

Cerebrovascular reactivity (CVR) reflects the capacity of blood vessels to adjust their caliber in order to maintain a steady supply of brain perfusion, and it may provide a sensitive disease biomarker. Measurement of the blood oxygen level dependent (BOLD) response to a hypercapnia-inducing breath-hold (BH) task has been frequently used to map CVR noninvasively using functional magnetic resonance imaging (fMRI). However, the best modeling approach for the accurate quantification of CVR maps remains an open issue. Here, we compare and optimize Fourier models of the BOLD response to a BH task with a preparatory inspiration, and assess the test-retest reproducibility of the associated CVR measurements, in a group of 10 healthy volunteers studied over two fMRI sessions. Linear combinations of sine-cosine pairs at the BH task frequency and its successive harmonics were added sequentially in a nested models approach, and were compared in terms of the adjusted coefficient of determination and corresponding variance explained (VE) of the BOLD signal, as well as the number of voxels exhibiting significant BOLD responses, the estimated CVR values, and their test-retest reproducibility. The brain average VE increased significantly with the Fourier model order, up to the 3rd order. However, the number of responsive voxels increased significantly only up to the 2nd order, and started to decrease from the 3rd order onwards. Moreover, no significant relative underestimation of CVR values was observed beyond the 2nd order. Hence, the 2nd order model was concluded to be the optimal choice for the studied paradigm. This model also yielded the best test-retest reproducibility results, with intra-subject coefficients of variation of 12 and 16% and an intra-class correlation coefficient of 0.74. In conclusion, our results indicate that a Fourier series set consisting of a sine-cosine pair at the BH task frequency and its two harmonics is a suitable model for BOLD-fMRI CVR measurements based on a BH task with preparatory inspiration, yielding robust estimates of this important physiological parameter.

Purpose To verify sociodemographic factors associated with the occurrence of abortion in women of reproductive age, in areas covered by the Family Health Strategy (FHS), a program from the Brazilian Ministry of Health. Methods A cross-sectional study using household surveys of 350 women aged 15 to 49. The report of abortion was a variable indicator, and sociodemographic aspects were covariables. Prevalence ratio (PR) and respective 95% confidence intervals were used to estimate the magnitude of the associations. Results There were associations among age, civil status, race/color, and religion; an increase in the prevalence of lower levels of education, age less than 20, and student status were protective factors. Conclusion The association between sociodemographic characteristics and the report of abortion is attributed to the fact that there is a lack at the FHS in the availability of fundamental healthcare services for young women; these findings call for action to guarantee the access to information about contraceptives and guidance to decrease the risk of unplanned pregnancies and abortions. Resumo Objetivo Verificar fatores sociodemográficos associados à ocorrência de aborto em mulheres em idade reprodutiva, em área de cobertura de Estratégia Saúde da Família ( ESF ). Métodos Estudo de corte transversal, por inquérito domiciliar com 350 mulheres de 15 a 49 anos de idade. Relato de aborto constituiu variável indicadora e aspectos sociodemográficos covariáveis. Utilizou-se a razão de prevalência (RP) e respectivos intervalos de confiança a 95% para estimar a magnitude das associações. Resultados Houve associação entre idade, estado civil, raça/cor e religião. Aumento da prevalência na menor escolaridade e ser menor de 20 anos e estudante constituíram fator de proteção. Conclusão A associação entre características sociodemográficas e relato de aborto remete a uma atenção à saúde na ESF sem cumprimento dos fundamentos das políticas para mulheres, e suscita ações que garantam às jovens acesso a informações, contraceptivos e a orientações que diminuam os riscos de gravidez não planejada e de abortos.

Tuberculosis remains as the deadliest bacterial infection in developing countries, a situation that is particularly aggravated by the increasing spread of multidrug resistant mycobacteria (MDR-TB). In this view, not only new anti-tubercular drugs are urgently needed, but also a better understanding of the existing ones may aid in the future design of more efficient derivatives or surrogates. Ethionamide (ETA) is an anti-tubercular pro-drug used as second-line therapy against MDR-TB, being bio-activated by the mycobacterial monooxygenase EtA. ETA has been the focus of several research works, devoted either to the identification of ETA's metabolites or to the development of novel derivatives potentially useful to fight against tuberculosis. In either case, structural analysis of ETA and related structures is of undeniable relevance, while the presence of sulfur in ETA's structure brings about the possibility of including 33 S-NMR in the toolbox of structural analysis techniques. In this work, we have engaged into a multinuclear NMR characterization of ETA, through the study of the drug's solubility in seven deuterated solvents, and of the chemical shifts for different nuclei in ETA. Results showed which are the best conditions to study ETA by NMR and provided some important evidence on the low reactivity of the drug's thioamide group, which may be of relevance for future drug derivatization approaches.

Background Independent Component Analysis (ICA) is commonly used for the identification of sources of interest in electroencephalographic (EEG) data, but the selection of the relevant components remains an open issue depending on the specific application. New Method We propose a novel approach for the objective selection of epilepsy-related independent components (ICs) from EEG data collected during functional Magnetic Resonance Imaging (fMRI) acquisitions, called PROJection onto Independent Components (PROJIC). Inter-ictal epileptiform discharges (IEDs) are identified on a reference EEG dataset collected outside the MRI scanner by an expert neurophysiologist, and the resulting average IED is projected onto the IC space of the EEG data collected simultaneously with fMRI. The power of the IED projection is then used to inform a k-means clustering algorithm of the ICs, allowing for the classification of epilepsy-related ICs. Comparison with existing methods The performance of PROJIC was compared with two methods previously proposed for the objective selection of EEG ICs of interest, which are based on the explicit similarity of the ICs with spatio-temporal templates of the events of interest, instead of the projection power. Results The proposed PROJIC method outperformed the others for both artificial and real data (19 datasets collected from 6 patients with drug-refractory focal epilepsy), with an average accuracy of 98.6%. Conclusions The ability of our method to accurately and objectively select epilepsy-related ICs makes it an important contribution for simultaneous EEG–fMRI epilepsy studies, with potential applications in the analysis of event-related EEG activity more generally, and also in EEG artefact correction.

Objectives Childhood absence epilepsy (CAE) is a syndrome with well-defined electroclinical features but unknown pathological basis. An increased thalamic tonic GABA inhibition has recently been discovered on animal models (Cope et al., 2009), but its relevance for human CAE is unproven. Methods We studied an 11-year-old boy, presenting the typical clinical features of CAE, but spike–wave discharges (SWD) restricted to one hemisphere. Results High-resolution EEG failed to demonstrate independent contralateral hemisphere epileptic activity. Consistently, simultaneous EEG–fMRI revealed the typical thalamic BOLD activation, associated with caudate and default mode network deactivation, but restricted to the hemisphere with SWD. Cortical BOLD activations were localized on the ipsilateral pars transverse. Magnetic resonance spectroscopy, using MEGA-PRESS, showed that the GABA/creatine ratio was 2.6 times higher in the hemisphere with SWD than in the unaffected one, reflecting a higher GABA concentration. Similar comparisons for the patient's occipital cortex and thalamus of a healthy volunteer yielded asymmetries below 25%. Significance In a clinical case of CAE with EEG and fMRI-BOLD manifestations restricted to one hemisphere, we found an associated increase in thalamic GABA concentration consistent with a role for this abnormality in human CAE., Highlights • A childhood absence epilepsy case with single hemispheric involvement is described. • Thalamic GABA/Cr ratio of affected versus reference hemisphere was increased to 2.57. • A similar ratio between occipital cortex ROIs was 1.09, which was within normal range. • We propose a role for increased thalamic GABA in childhood absence epilepsy.

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.

REVIEW QUESTION/OBJECTIVE The objective of this review is to synthesize qualitative evidence on the experiences of women undergoing an induced abortion resulting from an unplanned pregnancy.More specifically, the review question is: how do women experience induced abortions resulting from an unplanned pregnancy?

Depression and schizophrenia are two psychiatric diseases with high co-morbidity. For this reason, it is important to find sensitive endophenotypes, which may disentangle the two disorders. The Shine-Through paradigm, a visual backward masking task, is a potential endophenotype for schizophrenia. Masking is strongly deteriorated in schizophrenia patients, which is reflected in reduced EEG amplitudes. Here, we tested whether masking deficits and associated EEG changes are also found in patients with major depressive disorder. First, we replicated previous findings showing that depressive patients exhibit, at most, only weak masking deficits. Second, we found that the EEG amplitudes of depressive patients were reduced compared to controls and slightly increased compared to schizophrenia patients. As a secondary analysis, we compared the performance in the masking paradigm with three cognitive tasks, namely: the Wisconsin card sorting test, a verbal fluency test and a degraded continuous performance test. Performance in all but the verbal fluency test could discriminate schizophrenia from depression.

The aim of the present study was to prepare niosome formulations for the simultaneous encapsulation, dual drug therapy, of two anticancer drugs by the ecological probe sonication method. Poloxamer and sorbitan monostearate were used as surface active agents in niosomes, and the water soluble doxorubicin and poorly-water soluble paclitaxel were used as anticancer drugs. Thorough physicochemical analysis were performed for the niosomes, and their cytotoxicity and activity were evaluated on MCF-7 and PC3-MM2 cancer cell lines. Prepared niosomes were small in size with sizes ranging from 137 nm to 893 nm, and entrapment efficiencies were high, ranging from 91.24% to 99.99%. During the four weeks stability testing, the particle size remained stable. The niosomal formulations showed in vitro sustained drug release profiles for doxorubicin and clearly increased the dissolution rate of poorly water soluble paclitaxel. The incorporation of both the drugs into niosomes improved cell penetration and antiproliferative activity of the drugs PC3-MM2 cell lines. As a conclusion, doxorubicin and paclitaxel loaded niosome formulations resulted in relatively stable, small sized niosomes with improved drug release profiles, low toxicity, better cell penetration and antiproliferative activity. The niosomes showed synergistic effect due to the presence of both drugs, which can overcome multidrug resistance.

The simultaneous acquisition of electroencephalography (EEG) with functional magnetic resonance imaging (fMRI) is a very promising non-invasive technique for the study of human brain function. Despite continuous improvements, it remains a challenging technique, and a standard methodology for data analysis is yet to be established. Here we review the methodologies that are currently available to address the challenges at each step of the data analysis pipeline. We start by surveying methods for pre-processing both EEG and fMRI data. On the EEG side, we focus on the correction for several MR-induced artifacts, particularly the gradient and pulse artifacts, as well as other sources of EEG artifacts. On the fMRI side, we consider image artifacts induced by the presence of EEG hardware inside the MR scanner, and the contamination of the fMRI signal by physiological noise of non-neuronal origin, including a review of several approaches to model and remove it. We then provide an overview of the approaches specifically employed for the integration of EEG and fMRI when using EEG to predict the blood oxygenation level dependent (BOLD) fMRI signal, the so-called EEG-informed fMRI integration strategy, the most commonly used strategy in EEG-fMRI research. Finally, we systematically review methods used for the extraction of EEG features reflecting neuronal phenomena of interest.

Copyright © 2018 The Authors; exclusive licensee Bio-protocol LLC., Eimeria vermiformis is a tissue specific, intracellular protozoan that infects the murine small intestinal epithelia, which has been widely used as a coccidian model to study mucosal immunology. This mouse infection model is valuable to investigate the mechanisms of host protection against primary and secondary infection in the small intestine. Here, we describe the generation of an E. vermiformis stock solution, preparation of sporulated E. vermiformis to infect mice and determination of oocysts burden. This protocol should help to establish a highly reproducible natural infection challenge model to study immunity in the small intestine. The information obtained from using this mouse model can reveal fundamental mechanisms of interaction between the pathogen and the immune response, e.g., provided by intraepithelial lymphocytes (IEL) at the basolateral site of epithelial cells but also a variety of other immune cell populations present in the gut., This work was supported by the European Union H2020 ERA project (No. 667824– EXCELLtoINNOV) for work in the Veldhoen laboratory and Fundação para a Ciência e a Tecnologia (FCT) Studentship SFRH/BD/131605/2017 to P.F-C.

Transposition of the great arteries (TGA) is a congenital heart defect successfully corrected through arterial switch operation (ASO). Although this technique had significant impact in improving survival, little is known about the functional capacity of the operated patients long-term after surgery. Objective The aim of this study was to compare the functional capacity of children with TGA long-term after ASO with that of healthy children. Design Retrospective study. Patients. All patients that performed cardiopulmonary exercise test (CPET) were included in the study. As a control group, healthy children in evaluation for physical activity that performed CPET during the same period were also enrolled. Results Thirty-one TGA patients (19 male) were compared with 29 age-matched controls (21 male). Maximum oxygen consumption was higher in the control group (45.47 ± 8.05 vs. 40.52 ± 7.19, P = .017), although within normal limits in both groups (above 90% of predicted value). The heart rate behavior during exercise was different in both groups, with a mean chronotropic index significantly lower in the TGA group (63% ± 14 vs. 81% ± 12, P

The neural substrates of associative and item priming and recognition were investigated in a functional magnetic resonance imaging study over two separate sessions. In the priming session, participants decided which object of a pair was bigger during both study and test phases. In the recognition session, participants saw different object pairs and performed the same size-judgement task followed by an associative recognition memory task. Associative priming was accompanied by reduced activity in the right middle occipital gyrus as well as in bilateral hippocampus. Object item priming was accompanied by reduced activity in extensive priming-related areas in the bilateral occipitotemporofrontal cortex, as well as in the perirhinal cortex, but not in the hippocampus. Associative recognition was characterized by activity increases in regions linked to recollection, such as the hippocampus, posterior cingulate cortex, anterior medial frontal gyrus and posterior parahippocampal cortex. Item object priming and recognition recruited broadly overlapping regions (e.g., bilateral middle occipital and prefrontal cortices, left fusiform gyrus), even though the BOLD response was in opposite directions. These regions along with the precuneus, where both item priming and recognition were accompanied by activation, have been found to respond to object familiarity. The minimal structural overlap between object associative priming and recollection-based associative recognition suggests that they depend on largely different stimulus-related information and that the different directions of the effects indicate distinct retrieval mechanisms. In contrast, item priming and familiarity-based recognition seemed mainly based on common memory information, although the extent of common processing between priming and familiarity remains unclear. Further implications of these findings are discussed.

The enhanced functional sensitivity offered by ultra-high field imaging may significantly benefit simultaneous EEG-fMRI studies, but the concurrent increases in artifact contamination can strongly compromise EEG data quality. In the present study, we focus on EEG artifacts created by head motion in the static B0 field. A novel approach for motion artifact detection is proposed, based on a simple modification of a commercial EEG cap, in which four electrodes are non-permanently adapted to record only magnetic induction effects. Simultaneous EEG-fMRI data were acquired with this setup, at 7 T, from healthy volunteers undergoing a reversing-checkerboard visual stimulation paradigm. Data analysis assisted by the motion sensors revealed that, after gradient artifact correction, EEG signal variance was largely dominated by pulse artifacts (81-93%), but contributions from spontaneous motion (4-13%) were still comparable to or even larger than those of actual neuronal activity (3-9%). Multiple approaches were tested to determine the most effective procedure for denoising EEG data incorporating motion sensor information. Optimal results were obtained by applying an initial pulse artifact correction step (AAS-based), followed by motion artifact correction (based on the motion sensors) and ICA denoising. On average, motion artifact correction (after AAS) yielded a 61% reduction in signal power and a 62% increase in VEP trial-by-trial consistency. Combined with ICA, these improvements rose to a 74% power reduction and an 86% increase in trial consistency. Overall, the improvements achieved were well appreciable at single-subject and single-trial levels, and set an encouraging quality mark for simultaneous EEG-fMRI at ultra-high field.

SummaryIntroduction: This article is part of the Focus Theme of Methods of Information in Medicine on “Biosignal Interpretation: Advanced Methods for Neural Signals and Images”.Background: Dynamic Causal Modelling (DCM) is a generic formalism to study effective brain connectivity based on neuroimaging data, particularly functional Magnetic Resonance Imaging (fMRI). Recently, there have been attempts at modifying this model to allow for stochastic disturbances in the states of the model.Objectives: This paper proposes the Multiple- Model Kalman Filtering (MMKF) technique as a stochastic identification model discriminating among different hypothetical connectivity structures in the DCM framework; moreover, the performance compared to a similar de terministic identification model is assessed.Methods: The integration of the stochastic DCM equations is first presented, and a MMKF algorithm is then developed to perform model selection based on these equations. Monte Carlo simulations are performed in order to investigate the ability of MMKF to distinguish between different connectivity structures and to estimate hidden states under both deterministic and stochastic DCM.Results: The simulations show that the proposed MMKF algorithm was able to successfully select the correct connectivity model structure from a set of pre-specified plausible alternatives. Moreover, the stochastic approach by MMKF was more effective compared to its deterministic counterpart, both in the selection of the correct connectivity structure and in the estimation of the hidden states.Conclusions: These results demonstrate the applicability of a MMKF approach to the study of effective brain connectivity using DCM, particularly when a stochastic formulation is desirable.

Background: Studies of brain perfusion during migraine without aura attacks have inconsistent results. Methods: Arterial Spin Labeling (ASL) MRI, a non-invasive quantitative perfusion technique, was used to prospectively study a spontaneous untreated migraine without aura attack and a headache-free period. Image analysis used FSL and MATLAB software; Group analysis used permutation methods for perfusion differences between sessions. Results: Thirteen women (age 35.7) were scanned during an attack of an average intensity of 6.8 (on 0-10 Visual Analogue Scale, VAS) and 16 hours duration. No global or regional perfusion differences were identified comparing migraine and migraine-free sessions. Discussion: Our findings suggest that the painful phase of migraine without aura attacks is not associated with brain perfusion abnormalities

Objective We hypothesize that the hypersynchronization associated with epileptic activity is best described by EEG synchronization measures, and propose to use these as predictors of epilepsy-related BOLD fluctuations. Methods We computed the phase synchronization index (PSI) and global field synchronization (GFS), within two frequency bands, a broadband (1–45 Hz) and a narrower band focused on the presence of epileptic activity (3–10 Hz). The associated epileptic networks were compared with those obtained using conventional unitary regressors and two power-weighted metrics (total power and root mean square frequency), on nine simultaneous EEG-fMRI datasets from four epilepsy patients, exhibiting inter-ictal epileptiform discharges (IEDs). Results The average PSI within 3–10 Hz achieved the best performance across several measures reflecting reliability in all datasets. The results were cross-validated through electrical source imaging of the IEDs. The applicability of PSI when no IEDs are recorded on the EEG was evaluated on three additional patients, yielding partially plausible networks in all cases. Conclusions Epileptic networks can be mapped based on the EEG PSI metric within an IED-specific frequency band, performing better than commonly used EEG metrics. Significance This is the first study to investigate EEG synchronization measures as potential predictors of epilepsy-related BOLD fluctuations.

Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB). (C) 2016 Elsevier Ltd. All rights reserved., Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (European Union) for funding through UID/MULTI/04378/2013, project grant IF/00092/2014 and IF2014 position. Thanks are also due to “Comissão de Coordenação e Desenvolvimento Regional do Norte (CCDR-N)/NORTE2020/Portugal 2020” for funding through project DESignBIOtechHealth (ref. Norte-01-0145-FEDER-000024). H.A.S. acknowledges financial support from the Academy of Finland (decision nos. 252215 and 281300), the University of Helsinki Research Funds, the Biocentrum Helsinki, and the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013, Grant No. 310892). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FCT or CCDR-N, info:eu-repo/semantics/publishedVersion