ABSTRACT
Micro- and nano-plastics (NPs) are found in human milk, blood, tissues, and organs and associate with aberrant health outcomes including inflammation, genotoxicity, developmental disorders, onset of chronic diseases, and autoimmune disorders. Yet, interfacial interactions between plastics and biomolecular systems remain underexplored. Here, we have examined experimentally, in vitro, in vivo, and by computation, the impact of polystyrene (PS) NPs on a host of biomolecular systems and assemblies. Our results reveal that PS NPs essentially abolished the helix-content of the milk protein ß-lactoglobulin (BLG) in a dose-dependent manner. Helix loss is corelated with the near stoichiometric formation of ß-sheet elements in the protein. Structural alterations in BLG are also likely responsible for the nanoparticle-dependent attrition in binding affinity and weaker on-rate constant of retinol, its physiological ligand (compromising its nutritional role). PS NP-driven helix-to-sheet conversion was also observed in the amyloid-forming trajectory of hen egg-white lysozyme (accelerated fibril formation and reduced helical content in fibrils). Caenorhabditis elegans exposed to PS NPs exhibited a decrease in the fluorescence of green fluorescent protein-tagged dopaminergic neurons and locomotory deficits (akin to the neurotoxin paraquat exposure). Finally, in silico analyses revealed that the most favorable PS/BLG docking score and binding energies corresponded to a pose near the hydrophobic ligand binding pocket (calyx) of the protein where the NP fragment was found to make nonpolar contacts with side-chain residues via the hydrophobic effect and van der Waals forces, compromising side chain/retinol contacts. Binding energetics indicate that PS/BLG interactions destabilize the binding of retinol to the protein and can potentially displace retinol from the calyx region of BLG, thereby impairing its biological function. Collectively, the experimental and high-resolution in silico data provide new insights into the mechanism(s) by which PS NPs corrupt the bimolecular structure and function, induce amyloidosis and onset neuronal injury, and drive aberrant physiological and behavioral outcomes.
Subject(s)
Caenorhabditis elegans , Lactoglobulins , Muramidase , Animals , Muramidase/chemistry , Muramidase/metabolism , Lactoglobulins/chemistry , Lactoglobulins/metabolism , Caenorhabditis elegans/metabolism , Polystyrenes/chemistry , Nanoparticles/chemistry , Vitamin A/chemistry , Vitamin A/metabolism , Humans , Homeostasis/drug effects , Plastics/chemistryABSTRACT
Environmental agents such as pesticides, weedicides and herbicides (collectively referred to as pesticides) are associated with the onset and pathogenesis of neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's (AD) diseases. The development of blood-brain barrier (BBB)-penetrating therapeutic candidates to both prevent and treat the aforementioned xenotoxicant-induced neurodegenerative disorders remains an unmet need. Here, we examine whether caffeic-acid based Carbon Quantum Dots (CACQDs) can intervene in pesticide-associated onset and progress of the PD phenotype. Pulse-chase fluorescence analyses revealed that CACQDs intervene in the soluble-to-toxic transformation of the amyloid-forming protein model Hen Egg White Lysozyme (HEWL). The sp2-rich CACQDs also scavenged free radicals, a milestone along the PD trajectory. In-vitro, CACQDs introduced into a human neuroblastoma-derived cell line (SH-SY5Y) demonstrated negligible cytotoxicity up to 5 mg/mL and protected the cell line against oxidative stress-induced neuronal injury induced by the pesticide and potent neurotoxin, paraquat. Our findings suggest that the potentially BBB-penetrating CACQDs derived from caffeic acid hold promise for mitigating neurodegenerative disorders associated with environmental pesticides and xenobiotic neurotoxicants. Importantly, CACQDs sourced from coffee, coupled with their facile synthesis, represent a sustainable, green chemistry platform for generating interventional candidates in neurodegeneration.
ABSTRACT
Anion exchange membranes (AEM) are core components for alkaline electrochemical energy technologies, such as water electrolysis and fuel cells. They are regarded as promising alternatives for proton exchange membranes (PEM) due to the possibility of using platinum group metal (PGM)-free electrocatalysts. However, their chemical stability and conductivity are still of great concern, which is appearing to be a major challenge for developing AEM-based energy systems. Herein, we highlight an AEM with styrene-b-ethylene-b-butylene-b-styrene copolymer (SEBS) as a backbone and pyrrolidinium or piperidinium functional groups tethered on flexible ethylene oxide spacer side-chains (SEBS-Py2O6). This membrane reached 27.8 mS cm-1 hydroxide ion conductivity at room temperature, which is higher compared to previously obtained piperidinium-functionalized SEBS reaching up to 10.09 mS cm-1. The SEBS-Py206 combined with PGM-free electrodes in an AWE water electrolysis (AEMWE) cell achieves 520 mA cm-2 at 2 V in 0.1 M KOH and 171 mA cm-2 in ultra-pure water (UPW). This high performance indicates that SEBS-Py2O6 membranes are suitable for application in water electrolysis.
ABSTRACT
INTRODUCTION: The interaction of antiseizure medication with contraceptives, its potential teratogenicity and implications in pregnancy and breastfeeding are aspects to consider in the neurological care of women with epilepsy of childbearing age. To ensure the commitment in therapeutic decisions and the appropriate planning of maternity, it is essential that women are informed about the implications of their disease in these domains. The main aim of this study was to assess the knowledge of women of childbearing age with epilepsy concerning the impact of epilepsy in contraception, pregnancy and breastfeeding. As secondary aims we defined (1) the demographic, clinical and therapeutic characterization of this group of patients, (2) the identification of variables that correlated with the level of knowledge of women with epilepsy, and (3) the identification of preferential methods to acquire new knowledge about epilepsy. MATERIAL AND METHODS: The study was observational, cross-sectional and multicentric, and was carried out in five hospitals of the Lisbon metropolitan area. After identifying all women of childbearing age with epilepsy followed in the epilepsy clinic of each center, we applied an electronic questionnaire based on a non-systematic review of the literature. RESULTS: One hundred and fourteen participants were validated, with a median age of 33 years. Half of the participants were on monotherapy, and the majority had no seizures in the last six months. We identified important gaps in the participants' knowledge. Sections about complications and administration of antiseizure medication during pregnancy were the ones with the worst results. None of the clinical and demographic variables correlated with the final questionnaire score. Having had a previous pregnancy and the desire to breastfeed in a future pregnancy were positively correlated with the performance in breastfeeding section. Face-to-face discussion during medical outpatient visits was selected as the preferential method to learn about epilepsy, and the internet and social media were the least preferred ones. CONCLUSION: The knowledge of women of childbearing age with epilepsy in the Lisbon metropolitan area concerning the impact of epilepsy in contraception, pregnancy and breastfeeding seems to have significant gaps. Medical teams should consider engaging in patient education particularly during outpatient clinics.
Introdução: A interação dos fármacos anticrise epilética com os métodos contracetivos, a sua potencial teratogenicidade e as implicações na gravidez e amamentação são aspetos a considerar no acompanhamento de mulheres com epilepsia em idade fértil. Para o seu desejado envolvimento nas decisões terapêuticas e o adequado planeamento da maternidade, é essencial que as mulheres estejam corretamente informadas acerca das implicações da sua doença. O objetivo principal do presente estudo foi avaliar o conhecimento das mulheres com epilepsia em idade fértil sobre o impacto da epilepsia na contraceção, gravidez e amamentação. Como objetivos secundários definiram-se (1) a caracterização demográfica, clínica e terapêutica deste grupo de doentes, (2) a identificação de variáveis correlacionadas com o nível de conhecimento das mulheres com epilepsia, e (3) a identificação de meios e suportes preferenciais para aquisição de novos conhecimentos sobre epilepsia. Material e Métodos: O estudo foi observacional, transversal e multicêntrico, tendo decorrido em cinco centros hospitalares da região metropolitana de Lisboa. Após identificação das mulheres com epilepsia em idade fértil seguidas na Consulta de Epilepsia de cada centro, aplicou-se um questionário eletrónico construído após revisão não sistemática da literatura. Resultados: Foram validadas 114 participantes, com uma idade mediana de 33 anos. Metade das participantes apresentavam-se sob monoterapia, tendo a maioria a epilepsia controlada há pelo menos seis meses. Identificaram-se importantes lacunas no conhecimento das participantes. Conceitos sobre complicações dos fármacos anticrise epilética e a sua administração durante a gravidez motivaram piores resultados. Não houve correlação entre variáveis clinico-demográficas e o resultado no questionário. A ocorrência de gravidez prévia e o desejo de amamentar numa gravidez futura correlacionaram-se com o desempenho na secção sobre amamentação. A discussão oral na consulta foi a forma preferencial para aquisição de novos conhecimentos sobre epilepsia, tendo a internet e as redes sociais sido os meios menos escolhidos. Conclusão: O conhecimento das mulheres com epilepsia em idade fértil na área metropolitana de Lisboa sobre o impacto da sua doença na contraceção, gravidez e amamentação parece apresentar lacunas importantes. A educação para a saúde deste grupo deverá constituir uma preocupação por parte das equipas médicas, devendo privilegiar-se a consulta como local de ensino.
Subject(s)
Breast Feeding , Epilepsy , Female , Pregnancy , Humans , Adult , Cross-Sectional Studies , Anticonvulsants/adverse effects , Contraception , Epilepsy/drug therapy , Health Knowledge, Attitudes, Practice , Multicenter Studies as TopicABSTRACT
BACKGROUND: Persistent headache attributed to past stroke (PHAPS) is a controversial entity, recently included in the third edition of the International Classification of Headache Disorders (ICHD-3) despite being described only in retrospective studies. OBJECTIVE: To determine the frequency and characteristics of PHAPS in patients admitted with acute stroke. METHODS: We selected all patients with headache associated with acute stroke (HAAS) from a prospective, single-center registry of patients with acute stroke admitted to a Neurology ward between November 2018 and December 2019. We analyzed demographic, clinical, and neuroimaging data. We assessed the follow-up with a phone call questionnaire at 6 to 12 months. RESULTS: Among 121 patients with acute stroke, only 29 (24.0%) had HAAS. From these, 6 (5.0%) were lost to follow-up. In total, 23 (20.0%) patients answered the 6- to 12-month follow-up questionnaire and were included in this study. The median age of the sample was 53 years (interquartile range [IQR]: 38-78 years), and there was no sex predominance. Of the 10 patients (8,3%) that had persistent headache, 8 (6.6%) suffered from previous chronic headaches; however, they all mentioned a different kind of headache, and 1 (0,8%) probably had headache secondary to medication. CONCLUSIONS: In the present study, only 10 out of 121 stroke patients (8.3%) referred persistent headache at the 6- to 12-month follow-up, but the majority already suffered from previous chronic headache, which raises the question that the actual prevalence of PHAPS may be lower than previously reported.
ANTECEDENTES: A cefaleia persistente atribuída a acidente vascular cerebral (AVC) prévio é uma entidade controversa, recentemente incluída na terceira edição da Classificação Internacional de Transtornos da Cefaleia (International Classification of Headache Disorders, ICHD-3), apesar de descrita apenas em estudos restrospectivos. OBJETIVO: Determinar a frequência e as características do acidente vascular cerebral prèvio em doentes admitidos com AVC agudo. MéTODOS: Selecionamos todos os doentes com cefaleia associada a AVC agudo de um registro unicêntrico e prospectivo de doentes admitidos no serviço de Neurologia entre novembro de 2018 e dezembro de 2019. Analisamos dados demográficos, clínicos e imagiológicos. Reavaliamos aos 6 a 12 meses por questionário telefónico. RESULTADOS: Entre os 121 doentes admitidos com AVC agudo, apenas 29 (24,0%) tinham cefaleia associada a AVC agudo. Destes, 6 (5,0%) perderam-se no seguimento. Ao todo, 23 (20,0%) responderam ao questionário e foram incluídos. A idade mediana foi de 53 anos (intervalo interquartílico [IIQ]: 3878 anos), e não houve predominância de gênero. Dos 10 doentes (8,3%) que apresentam cefaleia persistente, 8 (6,6%) tinham histórico de cefaleia; no entanto todos mencionaram um tipo diferente de cefaleia, e 1 (0,8%) provavelmente tinha cefaleia secundária a medicação. CONCLUSõES: Neste estudo, apenas 10 em 121 doentes (8,3%) mencionaram cefaleia persistente aos 6 a 12 meses de seguimento, mas a maioria sofria de cefaleia prévia, pelo que a real prevalência de acidente vascular cerebral prèvio pode ser inferior à descrita nos estudos realizados até a data.
Subject(s)
Headache Disorders , Stroke , Humans , Adult , Middle Aged , Aged , Retrospective Studies , Prospective Studies , Headache/complications , Stroke/complicationsABSTRACT
Abstract Background Persistent headache attributed to past stroke (PHAPS) is a controversial entity, recently included in the third edition of the International Classification of Headache Disorders (ICHD-3) despite being described only in retrospective studies. Objective To determine the frequency and characteristics of PHAPS in patients admitted with acute stroke. Methods We selected all patients with headache associated with acute stroke (HAAS) from a prospective, single-center registry of patients with acute stroke admitted to a Neurology ward between November 2018 and December 2019. We analyzed demographic, clinical, and neuroimaging data. We assessed the follow-up with a phone call questionnaire at 6 to 12 months. Results Among 121 patients with acute stroke, only 29 (24.0%) had HAAS. From these, 6 (5.0%) were lost to follow-up. In total, 23 (20.0%) patients answered the 6- to 12-month follow-up questionnaire and were included in this study. The median age of the sample was 53 years (interquartile range [IQR]: 38-78 years), and there was no sex predominance. Of the 10 patients (8,3%) that had persistent headache, 8 (6.6%) suffered from previous chronic headaches; however, they all mentioned a different kind of headache, and 1 (0,8%) probably had headache secondary to medication. Conclusions In the present study, only 10 out of 121 stroke patients (8.3%) referred persistent headache at the 6- to 12-month follow-up, but the majority already suffered from previous chronic headache, which raises the question that the actual prevalence of PHAPS may be lower than previously reported.
Resumo Antecedentes A cefaleia persistente atribuída a acidente vascular cerebral (AVC) prévio é uma entidade controversa, recentemente incluída na terceira edição da Classificação Internacional de Transtornos da Cefaleia (International Classification of Headache Disorders, ICHD-3), apesar de descrita apenas em estudos restrospectivos. Objetivo Determinar a frequência e as características do acidente vascular cerebral prèvio em doentes admitidos com AVC agudo. Métodos Selecionamos todos os doentes com cefaleia associada a AVC agudo de um registro unicêntrico e prospectivo de doentes admitidos no serviço de Neurologia entre novembro de 2018 e dezembro de 2019. Analisamos dados demográficos, clínicos e imagiológicos. Reavaliamos aos 6 a 12 meses por questionário telefónico. Resultados Entre os 121 doentes admitidos com AVC agudo, apenas 29 (24,0%) tinham cefaleia associada a AVC agudo. Destes, 6 (5,0%) perderam-se no seguimento. Ao todo, 23 (20,0%) responderam ao questionário e foram incluídos. A idade mediana foi de 53 anos (intervalo interquartílico [IIQ]: 38-78 anos), e não houve predominância de gênero. Dos 10 doentes (8,3%) que apresentam cefaleia persistente, 8 (6,6%) tinham histórico de cefaleia; no entanto todos mencionaram um tipo diferente de cefaleia, e 1 (0,8%) provavelmente tinha cefaleia secundária a medicação. Conclusões Neste estudo, apenas 10 em 121 doentes (8,3%) mencionaram cefaleia persistente aos 6 a 12 meses de seguimento, mas a maioria sofria de cefaleia prévia, pelo que a real prevalência de acidente vascular cerebral prèvio pode ser inferior à descrita nos estudos realizados até a data.
ABSTRACT
BACKGROUND: Considering the potential COVID-19 impact on pwMS health and the importance of vaccination for this population, we decided to assess: (a) pwMS' beliefs and knowledge on COVID-19 pandemic; (b) their acceptance towards COVID-19 vaccination and (c) pwMS' opinions on general vaccination. METHODS: Observational study, based on a cross-sectional (10-20th September 2020) online survey, conducted in a cohort of pwMS' followed at two Portuguese hospitals. The survey included measures to characterize the sample and a questionnaire designed to assess the topics defined for this study. RESULTS: 270 respondents completed the full survey (response rate 58.2%). pwMS greatest concern during the pandemic was an aggravation of MS, especially by patients older than 50 years old. Almost 40% of the patients older than 50 felt that the pandemic negatively affected their MS related medical assistance. Most patients believed they would recover from COVID-19 infection. More than half of the responders feared a MS aggravation if they got COVID-19; this was more pronounced in patients with progressive MS. About 12% of the participants did not want to be vaccinated and almost 40% was unsure. Regarding vaccines in general, almost a third of the participants feared their side effects or MS related complications. CONCLUSION: Having knowledge of pwMS' opinions on COVID-19 pandemic impact and vaccination is useful to better address these issues. Fears and expectations towards vaccination must be discussed with pwMS.
