Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render ...the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.
Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which ...leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.
This study investigated the 30-days altitude training (2500 m, LHTH-live and training high) on hematological responses and aerobic-anaerobic performances parameters of high-level Paralympic athletes. ...Aerobic capacity was assessed by 3000 m run, and anaerobic variables (velocity, force and mechanical power) by a maximal 30-s semi-tethered running test (AO30). These assessments were carried out at low altitude before (PRE) and after LHTH (5-6 and 15-16 days, POST1 and POST2, respectively). During LHTH, hematological analyzes were performed on days 1, 12, 20 and 30. After LHTH, aerobic performance decreased 1.7% in POST1, but showed an amazing increase in POST2 (15.4 s reduction in the 3000 m test, 2.8%). Regarding anaerobic parameters, athletes showed a reduction in velocity, force and power in POST1, but velocity and power returned to their initial conditions in POST2. In addition, all participants had higher hemoglobin (Hb) values at the end of LHTH (30 days), but at POST2 these results were close to those of PRE. The centrality metrics obtained by complex networks (pondered degree, pagerank and betweenness) in the PRE and POST2 scenarios highlighted hemoglobin, hematocrit (Hct) and minimum force, velocity and power, suggesting these variables on the way to increasing endurance performance. The Jaccard's distance metrics showed dissimilarity between the PRE and POST2 graphs, and Hb and Hct as more prominent nodes for all centrality metrics. These results indicate that adaptive process from LHTH was highlighted by the complex networks, which can help understanding the better aerobic performance at low altitude after 16 days in Paralympic athletes.
Conventional basic electrodes varnished and basic electrodes agglomerated with polymer in underwater wet welding in a simulated depth of 10 m were compared. A hyperbaric tank was used for depth ...simulation and a gravity welding device for making the bead on plate welds. Bead on plate welds were deposited with welding currents of 100, 120, 140, 160 and 180 A with DCEN and DCEP polarities, in order to evaluate the arc stability through a non-dimensional statistical index. The welding current which showed better stability level in both polarities was chosen to evaluate weld bead morphology, weld metal porosity, weld metal oxygen and diffusible hydrogen levels. A methodology was used to correlate the heat input and short-circuit frequency with the weld bead morphology. It was observed a direct relation with the weld metal oxygen and penetration and an inverse relation of the weld metal oxygen with the diffusible hydrogen. Electrodes agglomerated with polymer showed higher penetration values than conventional electrodes in both polarities and lowest diffusible hydrogen levels in the DCEP polarity. It was observed lower levels of weld metal porosity for the electrodes agglomerated with polymer in comparison to conventional electrodes. This result was related to lower levels of porosity found in the droplets formed at the tip of the electrodes agglomerated with polymer.
The monoterpene alcohol (−)‐borneol has many biological effects such as sedative, anti‐inflammatory, analgesic, anti‐nociceptive, antithrombotic and vasorelaxant effects. Our objective in this study ...was to investigate the mechanism of action of (−)‐borneol and determine its vasorelaxant effect. (−)‐Borneol was tested on isolated aortic rings contracted with PE (10−6 m). This study was performed in the absence or in the presence of endothelium, L‐NAME (100 μm), indomethacin (10 μm), TEA (1 and 10 mm), 4‐AP (1 mm) or glibenclamide (1 mm) to assess the participation of EDRF, nitric oxide, prostanoids and potassium channels on the relaxing effect of (−)‐borneol. In this work, (−)‐borneol induced a relaxant effect in aortic rings, with and without endothelium, in a concentration‐dependent manner. The pharmacological characterization obtained using L‐NAME, indomethacin, TEA, 4‐AP and glibenclamide demonstrates that the effect of (−)‐borneol was modified in the presence of L‐NAME, indomethacin and glibenclamide showing that these signal transduction pathways are involved in the relaxing effect of the monoterpene. (−)‐Borneol has a vasorelaxant effect that depends on the presence of vascular endothelium, with the participation of nitric oxide and prostanoids. Also, (−)‐borneol displayed a direct action on the vascular smooth muscle, greatly dependent on KATP channels.
Background:
Depression is a psychiatric disorder with limited therapy options. Psychedelics are new antidepressant candidates, being the ayahuasca one of the most promising ones. A synergistic ...combination of N,N-dimethyltryptamine (DMT) and β-carbolines allows ayahuasca antidepressant properties. Another psychedelic and DMT-containing beverage is the jurema wine used religiously by indigenous people from Northeastern Brazil.
Aims:
To evaluate the antidepressant-like effect of standardized extract of Mimosa tenuiflora (SEMT), associated or not with harmine (β-carboline), in behavioral models of depression.
Methods:
The SEMT was submitted to (+) ESI-IT-LC/MS analysis for DMT quantification. To assess the antidepressant-like effect of SEMT, the open field (OFT), tail suspension (TST), and forced swim (FST) tests were performed. To verify the participation of serotonergic systems, the 5-hydroxytryptophan (5-HTP)-induced head twitch test was performed.
Results:
The content of DMT found in SEMT was 24.74 ± 0.8 mg/g. Yuremamine was also identified. SEMT presented an antidepressant-like effect in mice submitted to the TST and FST, independent from harmine, with no significant alterations on the OFT. The sub-dose interaction between SEMT and ketamine also produced an anti-immobility effect in the TST, with no changes in the OFT. SEMT potentiated the head twitch behavior induced by 5-HTP and ketanserin prevented its antidepressant-like effect in the TST (p < 0.05).
Conclusions:
SEMT presented a harmine-independent antidepressant-like effect in mice submitted to the TST and FST. This effect occurs possibly via activation of serotonergic systems, particularly the 5-HT2A/2C receptors.
Inspiratory muscles pre-activation (IM
) has been studied to improve subsequent performance in swimming. However, the effects of IM
on various parameters in swimmers are still unknown. Therefore, ...this study aimed to investigate the effects of IM
on the mechanical parameters, physiological responses, and their possible correlations with swimming performance. A total of 14 young swimmers (aged 16 ± 0 years) underwent a 30-s all-out tethered swimming test, preceded or not by IM
a load of 40% of the maximal inspiratory pressure (MIP), and with a volume of 2 sets of 15 repetitions. The mechanical (strength, impulse, and fatigue index) and physiological parameters (skin temperature and lactatemia) and the assessment of perceived exertion and dyspnea were monitored in both protocols. The IM
used did not increase the swimming force, and skin temperature, decrease blood lactate concentration, or subjective perception of exertion and dyspnea after the high-intensity tethered swimming exercises. Positive correlations were found between mean force and blood lactate (without IM
: r = 0.62, P = 0.02; with IM
: r = 0.65, P = 0.01). The impulse was positively correlated with blood lactate (without IM
: r = 0.71, P < 0.01; with IM
: r = 0.56, P = 0.03). Our results suggest that new IM
protocols, possibly with increased volume, should be developed in order to improve the performance of young swimmers.
In this article we present LLSR, an R package for the characterization of aqueous two-phase systems (ATPS). The scope of existing mathematical descriptions is ported to R and expanded with the ...implementation of a database of phase diagram parameters. The package applies nonlinear regression analysis to calculate the fitting parameters of well-known empirical equationssuch as the ones described by Merchuk and Murugesanusing data obtained from articles published in high quality journals. The database is based on empirical data obtained from published manuscripts and provides a software package with the potential to reduce experimental effort and save resources throughout the development of an ATPS-based process or product. The package requires only minimal knowledge of R and can be installed directly from its console, and the results are easily exported for subsequent analyses. Detailed examples of usage and descriptions of the package capabilities, including built-in database search functions, are demonstrated by characterizing a poly(ethylene glycol) 2000/ammonium sulfate ATPS, the data of which is provided with the package. Additional online resources for the package are also described, including the procedure to allow users to contribute to LLSR in order to expand its database and capabilities.
Studies have identified the interference of contextual factors that inhibit the effective implementation of Competency-based Management (CM) under the National Personnel Development Policy (NPDP) in ...the Brazilian public sector, though organizations have overcome these factors through various initiatives. This article proposes an integrated model that relates the factors that interfere with CM implementation with the initiatives adopted by public organizations to circumvent and overcome them. This qualitative study through documental research and interviews with those responsible for implementing CM in six organizations within the Brazilian public sector. Pre and post-categorical analysis have enabled the establishment of a relationship between the 20 categories identified and divided into four kinds of interfering factors and the 20 adopted initiatives identified in seven categories. It was identified that the organizational and departmental factors are the ones that most interfere with the implementation of CM in the public sector. The strategic role of the HR unit, capable of carrying out structural changes, was identified as the most important initiative to induce the implementation of CM. This study provides a model that integrates strategic, political, and instrumental thematics, showing how these aspects impact the effective implementation of CM, which helps HR managers to recognize the factors that are under their control and how to face them.
The SARS-CoV-2 virus causes COVID-19, and it is responsible for the largest pandemic since the 1918 H1N1 influenza outbreak. The classic symptoms of the disease have been well defined by the World ...Health Organization; however, olfactory/gustatory disorders have been reported in some studies, but there are still several missing points in the understanding and in the consensus about the clinical management of these cases.
To identify evidence in the scientific literature about olfactory/gustatory disorders, their clinical presentation, prevalence and possible specific treatments associated with COVID-19.
A systematic review of articles published up to April 25, 2020 was performed in Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus and Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine and Reasearch Gate. Inclusion criteria: (1) Studies on patients with COVID-19; (2) Records of COVID-19 signs/symptoms, and olfactory/gustatory functions. Exclusion criteria: (1) Studies on non-human coronavirus; (2) Review articles; (3) Experimental studies (in animals or in vitro); (4) Olfactory/gustatory disorders initiated prior to SARS-CoV-2 infection. The risk assessment of bias of the selected studies was performed using the Newcastle-Ottawa scale.
Six articles from the 1788 records met the inclusion criteria and were analyzed. A total of 1457 patients of different ethnicities were assessed; of them, 885 (60.7%) and 822 (56.4%) had smell and taste disorders, respectively, with women being most often affected. There were olfactory/gustatory disorders even without nasal obstruction/rhinorrhea and beginning even before the signs/symptoms of COVID-19; the recovery of smell/taste, when it occurs, usually happened in the first two weeks after COVID-19 resolution. There is evidence that olfactory/gustatory disorders are strong predictors of infection by SARS-CoV-2, and it is possible to recommend patient isolation, as early as of the medical consultation, preventing the spread of the virus. No scientific evidence has been identified for effective treatments for any of the disorders.
Olfactory/gustatory disorders may occur at varying intensities and prior to the general symptoms of COVID-19 and should be considered as part of the clinical features of COVID-19, even in mild cases. There is still no scientific evidence of specific treatments for such disorders in COVID-19 disease.
O vírus SARS-CoV-2 causa a COVID-19 e é responsável pela maior pandemia desde o surto de influenza H1N1 de 1918. Os sintomas clássicos da doença já foram bem definidos pela Organização Mundial da Saúde; entretanto, distúrbios olfativo-gustativos têm sido relatados em alguns estudos, mas ainda com várias lacunas no entendimento e no consenso sobre a condução clínica desses casos.
Identificar evidências na literatura científica sobre os distúrbios olfativo-gustativos acerca da apresentação clínica, prevalência e possíveis tratamentos específicos associados à COVID-19.
Revisão sistemática de artigos publicados até 25 de abril de 2020 nas bases de dados: Medline, Cochrane Clinical Trials, ScienceDirect, Lilacs, Scopus e Google Schoolar, OpenGrey.eu, DissOnline, The New York Academy of Medicine e Reasearch Gate. Foram critérios de inclusão: 1) Estudos com indivíduos com COVID-19; 2) Registro dos sinais/sintomas da COVID-19 e das funções olfativo-gustativa. Foram critérios de exclusão: 1) Estudos sobre coronavírus não humano; 2) Artigos de revisão; 3) Estudos experimentais (em animais ou in vitro); 4) Distúrbios olfativos-gustativos iniciados previamente à infecção pelo SARS-CoV-2. A avaliação de risco de viés dos estudos selecionados foi feita por meio da escala de Newcastle-Ottawa.
Seis artigos dos 1.788 registros foram selecionados. Um total de 1.457 pacientes de diversas etnias foi avaliado; desses, 885 (60,7%) apresentaram perda do olfato e 822 (56,4%) perda do paladar, sendo as mulheres as mais afetadas. Os distúrbios olfativo-gustativos estiveram presentes mesmo sem obstrução nasal/rinorreia e com início mesmo antes dos sinais/sintomas clínicos da COVID-19; a recuperação do olfato/paladar, quando ocorre, geralmente se dá nas duas primeiras semanas após a resolução da doença. Há evidências que os distúrbios olfativo-gustativos sejam fortes preditores de infecção pelo SARS-CoV-2, podendo-se recomendar o isolamento do paciente, já a partir da consulta médica, para evitar a disseminação do vírus. Não foram identificadas evidências científicas para tratamentos eficazes para nenhum dos distúrbios.
Podem ocorrer distúrbios olfativo-gustativos em intensidades variáveis e prévios aos sintomas gerais da COVID-19, devem ser considerados como parte dos sintomas da doença, mesmo em quadros leves. Não há ainda evidências científicas de tratamentos específicos para tais distúrbios na COVID-19.
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