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Mediation analysis assesses whether an exposure directly produces changes in cognitive behavior or is influenced by intermediate "mediators". Electroencephalographic (EEG) spectral measurements have been previously used as effective mediators representing diverse aspects of brain function. However, it has been necessary to collapse EEG measures onto a single scalar using standard mediation methods. In this article, we overcome this limitation and examine EEG frequency-resolved functional connectivity measures as a mediator using the full EEG cross-spectral tensor (CST). Since CST samples do not exist in Euclidean space but in the Riemannian manifold of positive-definite tensors, we transform the problem, allowing for the use of classic multivariate statistics. Toward this end, we map the data from the original manifold space to the Euclidean tangent space, eliminating redundant information to conform to a "compressed CST." The resulting object is a matrix with rows corresponding to frequencies and columns to cross spectra between channels. We have developed a novel matrix mediation approach that leverages a nuclear norm regularization to determine the matrix-valued regression parameters. Furthermore, we introduced a global test for the overall CST mediation and a test to determine specific channels and frequencies driving the mediation. We validated the method through simulations and applied it to our well-studied 50+-year Barbados Nutrition Study dataset by comparing EEGs collected in school-age children (5-11 years) who were malnourished in the first year of life with those of healthy classmate controls. We hypothesized that the CST mediates the effect of malnutrition on cognitive performance. We can now explicitly pinpoint the frequencies (delta, theta, alpha, and beta bands) and regions (frontal, central, and occipital) in which functional connectivity was altered in previously malnourished children, an improvement to prior studies. Understanding the specific networks impacted by a history of postnatal malnutrition could pave the way for developing more targeted and personalized therapeutic interventions. Our methods offer a versatile framework applicable to mediation studies encompassing matrix and Hermitian 3D tensor mediators alongside scalar exposures and outcomes, facilitating comprehensive analyses across diverse research domains.
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Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Criança , Pré-Escolar , Feminino , Masculino , Conectoma/métodos , Cognição/fisiologia , Desnutrição/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , LactenteRESUMO
This paper introduces methods and a novel toolbox that efficiently integrates high-dimensional Neural Mass Models (NMMs) specified by two essential components. The first is the set of nonlinear Random Differential Equations (RDEs) of the dynamics of each neural mass. The second is the highly sparse three-dimensional Connectome Tensor (CT) that encodes the strength of the connections and the delays of information transfer along the axons of each connection. To date, simplistic assumptions prevail about delays in the CT, often assumed to be Dirac-delta functions. In reality, delays are distributed due to heterogeneous conduction velocities of the axons connecting neural masses. These distributed-delay CTs are challenging to model. Our approach implements these models by leveraging several innovations. Semi-analytical integration of RDEs is done with the Local Linearization (LL) scheme for each neural mass, ensuring dynamical fidelity to the original continuous-time nonlinear dynamic. This semi-analytic LL integration is highly computationally-efficient. In addition, a tensor representation of the CT facilitates parallel computation. It also seamlessly allows modeling distributed delays CT with any level of complexity or realism. This ease of implementation includes models with distributed-delay CTs. Consequently, our algorithm scales linearly with the number of neural masses and the number of equations they are represented with, contrasting with more traditional methods that scale quadratically at best. To illustrate the toolbox's usefulness, we simulate a single Zetterberg-Jansen and Rit (ZJR) cortical column, a single thalmo-cortical unit, and a toy example comprising 1000 interconnected ZJR columns. These simulations demonstrate the consequences of modifying the CT, especially by introducing distributed delays. The examples illustrate the complexity of explaining EEG oscillations, e.g., split alpha peaks, since they only appear for distinct neural masses. We provide an open-source Script for the toolbox.
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Conectoma , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Simulação por Computador , Axônios , AlgoritmosRESUMO
Protein Energy Malnutrition (PEM) has lifelong consequences on brain development and cognitive function. We studied the lifelong developmental trajectories of resting-state EEG source activity in 66 individuals with histories of Protein Energy Malnutrition (PEM) limited to the first year of life and in 83 matched classmate controls (CON) who are all participants of the 49 years longitudinal Barbados Nutrition Study (BNS). qEEGt source z-spectra measured deviation from normative values of EEG rhythmic activity sources at 5-11 years of age and 40 years later at 45-51 years of age. The PEM group showed qEEGt abnormalities in childhood, including a developmental delay in alpha rhythm maturation and an insufficient decrease in beta activity. These profiles may be correlated with accelerated cognitive decline.
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Disfunção Cognitiva , Desnutrição Proteico-Calórica , Eletroencefalografia , Humanos , Estudos Longitudinais , Estado NutricionalRESUMO
This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.
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Encefalopatias , COVID-19 , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Eletroencefalografia/métodos , HumanosRESUMO
Cyclin-dependent kinase-like 5 disorder is a severe neurodevelopmental disorder caused by mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene. It predominantly affects females who typically present with severe early epileptic encephalopathy, global developmental delay, motor dysfunction, autistic features and sleep disturbances. To develop a gene replacement therapy, we initially characterized the human CDKL5 transcript isoforms expressed in the brain, neuroblastoma cell lines, primary astrocytes and embryonic stem cell-derived cortical interneurons. We found that the isoform 1 and to a lesser extent the isoform 2 were expressed in human brain, and both neuronal and glial cell types. These isoforms were subsequently cloned into recombinant adeno-associated viral (AAV) vector genome and high-titre viral vectors were produced. Intrajugular delivery of green fluorescence protein via AAV vector serotype PHP.B in adult wild-type male mice transduced neurons and astrocytes throughout the brain more efficiently than serotype 9. Cdkl5 knockout male mice treated with isoform 1 via intrajugular injection at age 28-30 days exhibited significant behavioural improvements compared to green fluorescence protein-treated controls (1012 vg per animal, n = 10 per group) with PHP.B vectors. Brain expression of the isoform 1 transgene was more abundant in hindbrain than forebrain and midbrain. Transgene brain expression was sporadic at the cellular level and most prominent in hippocampal neurons and cerebellar Purkinje cells. Correction of postsynaptic density protein 95 cerebellar misexpression, a major fine cerebellar structural abnormality in Cdkl5 knockout mice, was found in regions of high transgene expression within the cerebellum. AAV vector serotype DJ efficiently transduced CDKL5-mutant human induced pluripotent stem cell-derived neural progenitors, which were subsequently differentiated into mature neurons. When treating CDKL5-mutant neurons, isoform 1 expression led to an increased density of synaptic puncta, while isoform 2 ameliorated the calcium signalling defect compared to green fluorescence protein control, implying distinct functions of these isoforms in neurons. This study provides the first evidence that gene therapy mediated by AAV vectors can be used for treating CDKL5 disorder.
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Terapia Genética , Isoformas de Proteínas/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Adenoviridae , Animais , Encéfalo/metabolismo , Cálcio/metabolismo , Células Cultivadas , Proteína 4 Homóloga a Disks-Large/biossíntese , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Isoformas de Proteínas/genética , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/genética , Sinapses/metabolismo , TransfecçãoRESUMO
BACKGROUND: Hybridization and polyploidy are central processes in evolution and speciation. These mechanisms often lead to complex patterns of genetic variation and the creation of novel genotypes, which may establish if they become isolated from gene flow. However, in the absence of reproductive isolation, species boundaries might easily be disrupted. Here, we used a combination of AFLPs, chloroplast DNA markers and flow cytometry to investigate the evolutionary outcomes of hybridization between two endemic Ecuadorian species of Epidendrum (E. madsenii and E. rhopalostele) in three hybrid zones. Postmating isolation was also quantified to determine the role of this barrier in restraining gene flow between hybrids and the parental species. In addition, future ecological niche models were constructed to predict the outcomes of hybridization between these species. RESULTS: Our results confirmed the presence of hybrids in all hybrid zones, but revealed that a third parental species (E. falcisepalum) has contributed to one of the hybrid zones studied. Backcross genotypes were frequent in all hybrid zones, which was in accordance with the absence of strong reproductive barriers. The process of hybridization was highly asymmetric and followed in some cases by polyploidy. The projection of future niche models predicted a severe reduction in the area suitable for the occurrence of these species, although favorable conditions will still occur for the existence of the current hybrid zones. CONCLUSIONS: The recurrent process of hybridization has compromised the genetic integrity of the parental species. Most individuals of the parental species can no longer be considered as pure-bred individuals because most were classified as backcrossed hybrids. Novel genetic lineages occur in all hybrid zones implying that hybrids are fertile and can compete with the parental species. These results, together with the prediction of suitable conditions for the future occurrence of these hybrid zones, highlight the importance of conserving these geographic areas as sources of novel taxonomic entities.
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Evolução Molecular , Hibridização Genética , Orchidaceae/genética , Poliploidia , Isolamento Reprodutivo , Fluxo Gênico , Marcadores Genéticos , Variação Genética , Endogamia , Dados de Sequência MolecularRESUMO
Hybridization and introgression are complex evolutionary mechanisms that can increase species diversity and lead to speciation, but may also lead to species extinction. In this study, we tested the presence and genetic consequences of hybridization between the rare and Ecuadorian endemic O. loxensis van der Werff and the widespread O. infrafoveolata van der Werff (Lauraceae). Phenotypically, some trees are difficult to identify, and we expect that some might in fact be cryptic hybrids. Thus, we developed nuclear microsatellites to assess the existence of hybrids, as well as the patterns of genetic diversity and population structure in allopatric and sympatric populations. The results revealed high levels of genetic diversity, even in the rare O. loxensis, being usually significantly higher in sympatric than in allopatric populations. The Bayesian assignment of individuals into different genetic classes revealed a complex scenario with different hybrid generations occurring in all sympatric populations, but also in allopatric ones. The absence of some backcrossed hybrids suggests the existence of asymmetric gene flow, and that some hybrids might be more fitted than others might. The existence of current and past interspecific gene flow also explains the blurring of species boundaries in these species and could be linked to the high rates of species found in Ocotea.
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Layered oxides constitute one of the most promising cathode materials classes for large-scale sodium-ion batteries because of their high specific capacity, scalable synthesis, and low cost. However, their practical use is limited by their low energy density, physicochemical instability, and poor cycling stability. Aiming to mitigate these shortcomings, in this work, we synthesized polycrystalline (PC) and single-crystal (SC) P2-type Na0.67-δMn0.67Ni0.33O2 (NMNO) cathode materials through a solid-state route and evaluated their physicochemical and electrochemical performance. The SC-NMNO cathode with a large mean primary particle size (D50) of 12.7 µm was found to exhibit high cycling stability leading to 47% higher capacity retention than PC-NMNO after 175 cycles at 1C rate in the potential window 4.2-1.5 V. This could be attributed to the effective mitigation of parasitic side reactions at the electrode-electrolyte interface and suppressed intergranular cracking induced by anisotropic volume changes. This is confirmed by the lower volume variation of SC-NMNO (ΔV â¼ 1.0%) compared to PC-NMNO (ΔV â¼ 1.4%) upon charging to 4.2 V. Additionally, the SC-NMNO cathode displayed slightly higher thermal stability compared to PC-NMNO. Both cathodes exhibited good chemical stability against air and water exposure, thus enabling material storage/handling in the ambient atmosphere as well as making them suitable for aqueous processing. In this regard, PC-NMNO was investigated with two low-cost aqueous binders, carboxymethyl cellulose, and sodium trimetaphosphate, which exhibited higher binding strength and displayed excellent electrochemical performance compared to PVDF, which could potentially lead to significant cost reduction in electrode manufacturing.
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Ecuador has a high diversity of orchids, but little is known about levels of genetic diversity for the great majority of species. Understanding how orchids might adapt to changes is crucial as deforestation and fragmentation of forest ecosystems threaten the survival of many epiphytic orchids that depend on other species, such as fungi and their host trees, for germination, growth, and establishment. Overcollection and the illegal trade are also major concerns for the survival of wild populations of orchids. Despite increasing awareness, effective interventions are often limited by a lack of data concerning the impacts that overexploitation might have. To fill this gap, we tested the effects of overcollection in the genetic diversity and structure of Masdevallia rosea, a narrow distributed epiphytic orchid historically collected in Ecuador, in comparison with the widely distributed Pleurothallis lilijae. Genotyping based on AFLPs showed reduced levels of diversity in wild populations but most especially in the overcollected, M. rosea. Overall, genetic admixture was high in P. lilijae segregating populations by altitude levels while fewer genetic groups were found in M. rosea. Genetic differentiation was low in both species. A spatial genetic structure was found in P. lilijae depending on altitude levels, while no spatial genetic structure was found in M. rosea. These results suggest different scenarios for the two species: while gene flow over long distance is possible in P. lilijae, the same seems to be unlikely in M. rosea possibly due to the low levels of individuals in the known populations. In situ and ex situ conservation strategies should be applied to protect the genetic pool in these epiphytic orchid species, and to promote the connectivity between wild populations. Adopting measures to reduce overexploitation and to understand the impacts of harvesting in wild populations are necessary to strengthen the legal trade of orchids.
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Ecossistema , Orchidaceae , Humanos , Equador , Florestas , Orchidaceae/genética , Variação GenéticaRESUMO
Oxidative stress is a common characteristic of psychiatric, neurological, and neurodegenerative disorders. Therefore, compounds that are neuroprotective and reduce oxidative stress may be of interest as novel therapeutics. Phenolic, flavonoid and anthocyanin content, ORAC and DPPH free radical scavenging, and Cu2+ and Fe2+ chelating capacities were examined in variations (fresh/capsule) of Queen Garnet plum (QGP, Prunus salicina), black pepper (Piper nigrum) clove (Syzygium aromaticum), elderberry (Sambucus nigra), lemon balm (Melissa officinalis) and sage (Salvia officinalis), plus two blends (Astralagus membranaceus-lemon balm-rich, WC and R8). The ability of samples to prevent and treat H2O2-induced oxidative stress in SH-SY5Y cells was investigated. Pre-treatment with WC, elderberry, QGP, and clove prevented the oxidative stress-induced reduction in cell viability, demonstrating a neuroprotective effect. Elderberry increased cell viability following oxidative stress induction, demonstrating treatment effects. Clove had the highest phenolic and flavonoid content, DPPH, and Cu2+ chelating capacities, whereas QGP and elderberry were highest in anthocyanins. Black pepper had the highest ORAC and Fe2+ chelating capacity. These findings demonstrate that plant extracts can prevent and treat oxidative stress-induced apoptosis of neuron-like cells in vitro. Further research into phytochemicals as novel therapeutics for oxidative stress in the brain is needed.
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Melissa , Neuroblastoma , Fármacos Neuroprotetores , Sambucus , Humanos , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Antocianinas , Peróxido de Hidrogênio , Flavonoides/farmacologiaRESUMO
We report on the quantitative electroencephalogram (qEEG) and cognitive effects of Neuroepo in Parkinson's disease (PD) from a double-blind safety trial (https://clinicaltrials.gov/, number NCT04110678). Neuroepo is a new erythropoietin (EPO) formulation with a low sialic acid content with satisfactory results in animal models and tolerance in healthy participants and PD patients. In this study, 26 PD patients were assigned randomly to Neuroepo (n = 15) or placebo (n = 11) groups to test the tolerance of the drug. Outcome variables were neuropsychological tests and resting-state source qEEG at baseline and 6 months after administering the drug. Probabilistic Canonical Correlation Analysis was used to extract latent variables for the cognitive and for qEEG variables that shared a common source of variance. We obtained canonical variates for Cognition and qEEG with a correlation of 0.97. Linear Mixed Model analysis showed significant positive dependence of the canonical variate cognition on the dose and the confounder educational level (p = 0.003 and p = 0.02, respectively). Additionally, in the mediation equation, we found a positive dependence of Cognition with qEEG for (p = < 0.0001) and with dose (p = 0.006). Despite the small sample, both tests were powered over 89%. A combined mediation model showed that 66% of the total effect of the cognitive improvement was mediated by qEEG (p = 0.0001), with the remaining direct effect between dose and Cognition (p = 0.002), due to other causes. These results suggest that Neuroepo has a positive influence on Cognition in PD patients and that a large portion of this effect is mediated by brain mechanisms reflected in qEEG.
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"Medicinal cannabis" is defined as the use of cannabis-based products for the treatment of an illness. Investigations of cannabis compounds in psychiatric and neurological illnesses primarily focus on the major cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), which are hypothesised to benefit multiple illnesses manifesting cognitive impairment, neurodegeneration and neuro-inflammation, as well as chronic pain, epilepsy and post-traumatic stress disorder, respectively. The cannabis plant contains >500 compounds, including terpenes responsible for the flavour and fragrance profiles of plants. Recently, research has begun providing evidence on the potential use of certain plant-derived terpenes in modern medicine, demonstrating anti-oxidant, anti-inflammatory, and neuroprotective effects of these compounds. This review examined the effects of two key terpenes, pinene and linalool, on parameters relevant to neurological and psychiatric disorders, highlighting gaps in the literature and recommendations for future research into terpene therapeutics. Overall, evidence is mostly limited to preclinical studies and well-designed clinical trials are lacking. Nevertheless, existing data suggests that pinene and linalool are relevant candidates for further investigation as novel medicines for illnesses, including stroke, ischemia, inflammatory and neuropathic pain (including migraine), cognitive impairment (relevant to Alzheimer's disease and ageing), insomnia, anxiety, and depression. Linalool and pinene influence multiple neurotransmitter, inflammatory and neurotrophic signals as well as behaviour, demonstrating psycho-activity (albeit non-intoxicating). Optimising the phytochemical profile of cannabis chemovars to yield therapeutic levels of beneficial terpenes and cannabinoids, such as linalool, pinene and CBD, could present a unique opportunity to discover novel medicines to treat psychiatric and neurological illnesses; however, further research is needed.
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OBJECTIVE: To evaluate the aspirin resistance prevalence in patients with previous ischemic cerebrovascular disease undergoing aspirin therapy for secondary prevention. MATERIALS AND METHODS: Three hundred fifty patients presenting ischemic strokes and 100 healthy controls under aspirin treatment were evaluated using the optic platelet aggregation test. RESULTS: Aspirin resistance was found in 7.4% of the patients with ischemic stroke and 4% of controls. Aspirin resistance was associated with stroke recurrence in univariate analysis (p = 0.004). Aspirin resistance was not associated with smoking, diabetes, or hypercholesterolemia. CONCLUSION: Aspirin resistance is present in Colombian patients with ischemic stroke as well as in healthy controls.
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Heteroptera is a worldwide distributed group of insects inhabiting both terrestrial and aquatic habitats and has an important ecological role. A survey of aquatic and semiaquatic Heteroptera from Cuba is provided based on literature reports and field collections. General data on species geographical distribution are given, along with altitude and collection season. Representatives of 86 species and morphospecies of the infraorders Dipsocoromorpha, Leptopodomorpha, Gerromorpha and Nepomorpha are listed, distributed in 35 genera and 16 families were found. Based on distributional data, a preference for habitats of stagnant water or slow current and lower altitudes is inferred. Fifteen species are distributed throughout the entire island. A higher species diversity was found in the Eastern sector, with 53 species (61.63%), 16 of which (18.60%) are confined to this area. The strongest biological similarity was found between Eastern and Western sectors (25%), and the weakest between Western and Central sectors (14%).
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Ecossistema , Heterópteros/classificação , Animais , Cuba , Água Doce , GeografiaRESUMO
Bromus setifolius var. pictus (Hook) Skottsb., B. setifolius var. setifolius Presl. and B.setifolius var. brevifolius Ness are three native Patagonian taxa in the section Pnigma Dumort of the genus Bromus L. AFLP and RAPD analysis, in conjunction with genetic distance measurements and statistical techniques, revealed variation within this group and indicated that B. setifolius var. brevifolius was closely related to B. setifolius var. pictus, with both taxa being more distantly related to B. setifolius var. setifolius. Cytogenetic analysis confirmed the chromosomal number of B. setifolius var. pictus (2n = 70) and B. setifolius var. setifolius (2n = 28) and showed for the first time that B. setifolius var. brevifolius had 2n = 70. The combination of molecular genetic and cytogenetic evidence supported a species status for two of the three taxa and suggested hypotheses for the evolutionary origin of these complex taxa. Species status was also indicated for B. setifolius var. setifolius. Based on these findings, we suggest that B. setifolius var. pictus be referred to as B. pictus Hook var. pictus, and B. setifolius var brevifolius as B. pictus Hook var brevifolius. The correlation between AFLP diversity and variation in ecological parameters suggested that this marker system could be used to assess breeding progress and to monitor the domestication of Patagonian Bromus species for agronomic use.
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Cognitive impairment is a core symptom of schizophrenia; however, current antipsychotic drugs have limited efficacy to treat these symptoms and can cause serious side-effects, highlighting a need for novel therapeutics. Cannabidiol (CBD) is a non-intoxicating phytocannabinoid that has demonstrated pro-cognitive effects in multiple disease states, including a maternal immune activation (poly I:C) model of schizophrenia, but the mechanisms underlying the efficacy of CBD require investigation. Muscarinic neurotransmission is highly implicated in the cognitive impairments of schizophrenia; however, the effect of CBD on this system is unknown. We examined alterations in markers of muscarinic neurotransmission in the pre-frontal cortex (PFC) and hippocampus (HPC) following CBD treatment. Pregnant Sprague-Dawley rats (nâ¯=â¯16) were administered poly I:C (4â¯mg/kg) or saline. Adult offspring were treated (3-weeks) with CBD (10â¯mg/kg) or vehicle. Receptor autoradiography (using [3H]pirenzepine) was used to examine changes in muscarinic M1/M4 receptor (M1/M4R) binding density. Levels of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) protein expression were examined using Western blot. M1/M4R binding density was downregulated in the PFC and CA1/CA2 and CA3 subregions in male poly I:C offspring. M1/M4R deficits were normalised after CBD treatment. ChAT protein expression was reduced in the HPC of male poly I:C offspring, while CBD treated poly I:C offspring exhibited control-like ChAT levels. AChE levels were unaltered in any of the groups. There were also no changes in muscarinic signalling in female offspring. These findings demonstrate that CBD can normalise muscarinic neurotransmission imbalances in male poly I:C offspring in regions of the brain implicated in cognition.
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Canabidiol/farmacologia , Hipocampo/efeitos dos fármacos , Poli I-C , Córtex Pré-Frontal/efeitos dos fármacos , Receptor Muscarínico M1/metabolismo , Receptor Muscarínico M4/metabolismo , Esquizofrenia/induzido quimicamente , Transmissão Sináptica/efeitos dos fármacos , Acetilcolinesterase/biossíntese , Animais , Colina O-Acetiltransferase/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Hipocampo/metabolismo , Masculino , Córtex Pré-Frontal/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ratos , Caracteres SexuaisRESUMO
Epiphytic vascular plants comprise an essential part of the tropical flora and are a key component for ecosystem functioning. Some recent studies have used a network approach to investigate the interaction of epiphytes with host phorophytes at the community level. However, knowledge on commensalistic epiphyte-phorophyte network structure still lags behind with regard to other biotic interaction networks. Our goal was to provide a more complete overall perspective on commensalistic epiphyte-phorophyte interaction and its placement with respect to other better studied mutualistic interactions. We hypothesized that the intensity of the fitness effect of the different types of biotic interactions would determine the degree of specialization of the interacting organisms. Thus, commensalistic epiphyte-phorophyte interactions would have lower specialization than mutualistic interactions. We compiled and analysed the structural properties (nestedness, network specialization and modularity) of 12 commensalistic epiphyte-phorophyte networks and compared them with the same metrics to 11 ant-myrmecophyte, 86 pollination and 13 seed dispersal mutualistic networks. Epiphyte-phorophyte networks were nested and modular with regard to the corresponding null models and had greater nestedness than mutualistic networks, whereas specialization and modularity were significantly lower. Commensalistic epiphyte-phorophyte networks of interactions are both nested and modular, and hence, are structured in a similar way to most other types of networks that involve co-evolutionary interactions. Nevertheless, the nature and intensity of the ecological processes involved in the generation of these patterns is likely to differ. The lower values of modularity in commensalistic epiphyte-phorophyte networks are probably due to the low levels of specialization and the lack of co-evolutionary processes between the interacting partners.
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OBJECTIVE: The present study was undertaken to assess the impact, effectiveness and safety of a monophasic hormone replacement treatment (HRT) for continuous use with regards to the clinical effects, bleeding patterns and lipid profile of menopausal women in four Latin American countries. DESIGN: Three hundred and six postmenopausal women with natural menopause and uterus present were recruited. This was a multicentre prospective, clinical trial; the participating countries were Brazil (BR), Colombia (CO), Mexico (MX) and Argentina (AR). The study period was 12 months. The HRT regime was formulated in tablets containing 2 mg estradiol E2 and 1mg norethisterone acetate (NETA); one visit every 3 months was solicited. METHODS: HRT was given as one tablet every day without interruption for 1 year. Climacteric complaints, side-effects, reason for discontinuation, bleeding patterns, lipid profile at baseline and 12 months of treatment were documented. RESULTS: There were no significant differences between the four populations on clinical measurements. Thirty-four women discontinued, 13 for bleeding problems. The five most common side-effects were mastalgia, bleeding problems, headache, pelvic pain and nausea. 44.8% of women experienced scanty vaginal bleeding during the first 3 months of therapy. Ninety seven percent of women had amenorrhea at the end of the study in MX, BR and AR, and 100% in CO. Body weight was constant during the study, and no correlation was found between body weight and total days with bleeding. The Kupperman index score was used to evaluate the climacteric complaints, and the score decreased from a mean of 25.4 to 5.1 at 12-months visit. Total cholesterol levels were significantly reduced in BR and CO (P < 0.05) between baseline and the final sample; serum triglycerides remained unchanged, HDL-cholesterol was significantly increased in MX (P < 0.05), and LDL-cholesterol was significantly reduced in CO (P < 0.05). The results of this 1-year study emphasize that a continuous combined HRT regimen with 2 mg E2/1 mg NETA is an attractive alternative for postmenopausal women who are at least 1 year after their menopause and optimally 2 years after their menopause. Although the combination of 2 mg E2 with 1 mg NETA in a continuous combined therapy scheme has been in use in the Nordic countries for over a decade and in Latin America for the last 6 years, there have been no previous published reports on its effectivity in Latin American women. This publication reports the experience in a group of 306 Latin American women, and it is the first Latin American publication with this formulation.
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Anticoncepcionais Orais Sintéticos/uso terapêutico , Estradiol/uso terapêutico , Terapia de Reposição de Estrogênios , Menopausa , Noretindrona/análogos & derivados , Noretindrona/uso terapêutico , Administração Oral , Adulto , Ansiedade/tratamento farmacológico , Anticoncepcionais Orais Sintéticos/efeitos adversos , Depressão/tratamento farmacológico , Tontura/tratamento farmacológico , Estradiol/efeitos adversos , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Cefaleia/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Fogachos/tratamento farmacológico , Humanos , América Latina , Lipídeos/sangue , Pessoa de Meia-Idade , Debilidade Muscular/tratamento farmacológico , Noretindrona/efeitos adversos , Acetato de Noretindrona , Parestesia/tratamento farmacológico , Estudos ProspectivosRESUMO
RESUMEN El envejecimiento en general, y el cutáneo, en particular, es un proceso deletéreo y universal. El envejecimiento cutáneo se puede dividir en envejecimiento cronológico y fotoenvejecimiento, este último se activa a través del daño en la piel humana, atribuible a la exposición repetida a los rayos ultravioleta (UV) de la luz solar. Se ha considerado que los ácidos grasos derivados del aceite de pescado (omega 3) están asociados con la fotoprotección de la piel. El objetivo de este trabajo es describir los efectos del omega 3 como medicamento antienvejecimiento en la población de adultos mayores. Para ello, se realizó una revisión bibliográfica de artículos publicados entre enero de 2010 y junio de 2020, en Pubmed y Google Scholar. La literatura disponible evidencia el efecto y beneficio de estos ácidos grasos en el proceso de envejecimiento, los cuales constituyen terapias clínicas a nivel dermatológico y en áreas de cirugía plástica. Su uso ejerce un efecto positivo sobre el proceso de envejecimiento en diferentes órganos, mediante la acción frente al estrés oxidativo.
ABSTRACT Aging in general, and skin aging in particular, is a deleterious and universal process. Skin aging can be divided into chronological aging and photoaging, the latter being activated through damage to human skin, attributable to repeated exposure to ultraviolet (UV) rays from sunlight. Fatty acids derived from fish oil (omega 3) have been considered to be associated with photoprotection of the skin. The objective of this work is to describe the effects of omega 3 as an anti-aging drug in the elderly population. A bibliographic review of articles published between January 2010 and June 2020, in Pubmed and Google Scholar, was carried out. The available literature shows the effect and benefit of these fatty acids in the aging process, which constitute clinical therapies at the dermatological level and in areas of plastic surgery. Its use has a positive effect on the aging process in different organs, through action against oxidative stress.
RESUMO
INTRODUCTION: Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. OBJECTIVES: To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. METHODS AND MATERIALS: 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. RESULTS: Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. CONCLUSION: Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.