Recombinant antigen 5 from Polybia paulista wasp venom (Hymenoptera, Vespidae): Antigen-specific antibody production and functional profile of CD4+ T cells in the immune response.

Polybia paulista is a neotropical social wasp related to severe accidents and allergic reactions cases, including anaphylaxis, in southeastern Brazil. Antigen 5 (Poly p 5) is a major allergenic protein from its venom with potential use for component-resolved diagnostic. Therefore, the previous characterization of the immune response profile triggered by Poly p 5 should be evaluated. Recombinant Poly p 5 (rPoly p 5) was used to sensitize BALB/c mice with six weekly intradermal doses, and the specific antibody production and the functional profile of CD4+ T cells were assessed. rPoly p 5 induced the production of specific immunoglobulins (sIg) sIgE, sIgG1 and sIgG2a, which could recognize natural Poly p 5 presented in the venom of four different wasp species. rPoly p 5 stimulated in vitro the CD4+ T cells from immunized mice, which showed a significant proliferative response. These antigen-specific CD4+T cells produced IFN-γ and IL-17A cytokines and increased ROR-γT transcription factor expression. No differences between the control group and sensitized mice were found in IL-4 production and GATA-3 and T-bet expression. Interestingly, increased CD25+FoxP3+ regulatory T cells (Tregs) frequency was observed in the splenocyte cell cultures from rPoly p 5 immunized mice after the in vitro stimulation with both P. paulista venom extract and rPoly p 5. Here we showed that rPoly p 5 induces antigen-specific antibodies capable of recognizing Antigen 5 in the venom of four wasp species and modulates antigen-specific CD4+ T cells to IFN-γ production response associated with a Th17 profile in sensitized mice. These findings emphasize the potential use of rPoly p 5 as an essential source of a major wasp allergen with significant immunological properties.

Orthodontic resins loaded with niobium silicate particles: Impact of filler concentration on the physicochemical and biological properties.

OBJECTIVES: White spot lesions (WSL) are prevalent in patients using orthodontic appliances. The presence of ion-releasing compounds in the tooth-appliance interface may limit enamel demineralization to control WSL incidence. Thus, this study aims to evaluate the mineral formation on SiNb-containing experimental orthodontic resins and the influence of these fillers on the physicochemical and biological properties of developed materials. MATERIALS AND METHODS: The SiNb particles were synthesized via the sol-gel route and characterized by their molecular structure and morphology. Photopolymerizable orthodontic resins were produced with a 75 wt% Bis-GMA/25 wt% TEGDMA and 10 wt%, 20 wt%, or 30 wt% addition of SiNb. A control group was formulated without SiNb. These resins were tested for their degree of conversion, softening in solvent, cytotoxicity in fibroblasts, flexural strength, shear bond strength (SBS), and mineral deposition. RESULTS: The addition of 10 wt% of SiNb did not impair the conversion of monomers, cytotoxicity, and flexural strength. All groups with SiNb addition presented similar softening in solvent. The presence of these particles did not affect the bond strength between metallic brackets and enamel, with SBS values ranging from 16.41 to 18.66 MPa. The mineral deposition was observed for all groups. CONCLUSION: The use of niobium silicate as filler particles in resins may be a strategy for the adhesion of orthodontic appliances. The 10 wt% SiNb concentration resulted in a material with suitable physicochemical and biological properties while maintaining the bond strength to tooth enamel and promoting mineral deposition.

Interest Groups as an Alternative for Medical Education in Sleep Medicine: Experience Report at a Brazilian Medical School.

Sleep medicine classes and teachings are usually deficient and insufficient during undergraduate medical education. In order to circumvent the educational deficits in sleep medicine, students at a Brazilian Medical School created a sleep medicine interest group-an academic organization for teaching purposes whose administration is carried out by the undergraduate students themselves. This study aims to describe the establishment of a sleep medicine interest group, as well as to evaluate the results of its first edition on the knowledge about sleep medicine among undergraduate medical students. Classes were taken biweekly and consisted of lectures by invited professors, presentation of clinical cases, and discussion with the students. By the end of the course, both attendees and non-attendees were invited to fill out a questionnaire including an objective assessment of knowledge (15 multiple choice questions). The questionnaire was filled out by 32 participants, of which 18 were attendees and 14 were non-attendees. The average result on the final exam was significantly higher among the attendees (6.1 ± 1.2) in comparison with non-attendees (4.9 ± 1.3-p = 0.015). The results demonstrate that an interest group proved to be feasible as a source of complementary information to undergraduate medical students and a valid alternative to circumvent the educational deficits.

Corrigendum: An accumulation-of-evidence task using visual pulses for mice navigating in virtual reality.

[This corrects the article DOI: 10.3389/fnbeh.2018.00036.].

Genetically tagging cholinergic diversity.

In this issue of Neuron, Li et al. (2022) identify and genetically target two sub-populations of cholinergic neurons in the basal forebrain. They show that these cholinergic subtypes have distinct projection patterns, electrophysiological phenotypes, and behavioral functions.

Multiple timescales of sensory-evidence accumulation across the dorsal cortex.

Cortical areas seem to form a hierarchy of intrinsic timescales, but the relevance of this organization for cognitive behavior remains unknown. In particular, decisions requiring the gradual accrual of sensory evidence over time recruit widespread areas across this hierarchy. Here, we tested the hypothesis that this recruitment is related to the intrinsic integration timescales of these widespread areas. We trained mice to accumulate evidence over seconds while navigating in virtual reality and optogenetically silenced the activity of many cortical areas during different brief trial epochs. We found that the inactivation of all tested areas affected the evidence-accumulation computation. Specifically, we observed distinct changes in the weighting of sensory evidence occurring during and before silencing, such that frontal inactivations led to stronger deficits on long timescales than posterior cortical ones. Inactivation of a subset of frontal areas also led to moderate effects on behavioral processes beyond evidence accumulation. Moreover, large-scale cortical Ca2+ activity during task performance displayed different temporal integration windows. Our findings suggest that the intrinsic timescale hierarchy of distributed cortical areas is an important component of evidence-accumulation mechanisms.

Opponent control of behavior by dorsomedial striatal pathways depends on task demands and internal state.

A classic view of the striatum holds that activity in direct and indirect pathways oppositely modulates motor output. Whether this involves direct control of movement, or reflects a cognitive process underlying movement, remains unresolved. Here we find that strong, opponent control of behavior by the two pathways of the dorsomedial striatum depends on the cognitive requirements of a task. Furthermore, a latent state model (a hidden Markov model with generalized linear model observations) reveals that-even within a single task-the contribution of the two pathways to behavior is state dependent. Specifically, the two pathways have large contributions in one of two states associated with a strategy of evidence accumulation, compared to a state associated with a strategy of repeating previous choices. Thus, both the demands imposed by a task, as well as the internal state of mice when performing a task, determine whether dorsomedial striatum pathways provide strong and opponent control of behavior.

Biological and Inflammatory Effects of Antigen 5 from Polybia paulista (Hymenoptera, Vespidae) Venom in Mouse Intraperitoneal Macrophages.

The social wasp Polybia paulista (Hymenoptera, Vespidae) is highly aggressive, being responsible for many medical occurrences. One of the most allergenic components of this venom is Antigen 5 (Poly p 5). The possible modulation of the in vitro immune response induced by antigen 5 from P. paulista venom, expressed recombinantly (rPoly p 5), on BALB/c mice peritoneal macrophages, activated or not with LPS, was assessed. Here, we analyzed cell viability changes, expression of the phosphorylated form of p65 NF-κB subunit, nitric oxide (NO), proinflammatory cytokines production, and co-stimulatory molecules (CD80, CD86). The results suggest that rPoly p 5 does not affect NO production nor the expression of co-stimulatory molecules in mouse peritoneal macrophages. On the other hand, rPoly p 5 induced an increase in IL-1ß production in non-activated macrophages and a reduction in the production of TNF-α and MCP-1 cytokines in activated macrophages. rPoly p 5 decreased the in vitro production of the phosphorylated p65 NF-κB subunit in non-activated macrophages. These findings suggest an essential role of this allergen in the polarization of functional M2 macrophage phenotypes, when analyzed in previously activated macrophages. Further investigations, mainly in in vivo studies, should be conducted to elucidate Polybia paulista Ag5 biological role in the macrophage functional profile modulation.

Acesso ao direito à saúde no cárcere: entre o prescrito e o real / Access to health´s right in prison: between the prescription and the real

Objetivo: Conhecer como ocorre o acesso à saúde das pessoas privadas de liberdade. Métodos: Pesquisa qualitativa, realizada em um presídio no interior de Minas Gerais, com 19 pessoas privadas de liberdade. Os dados foram coletados mediante entrevista aberta orientada por roteiro semiestruturado no período de agosto a dezembro de 2017. Realizou-se Análise de Conteúdo de Bardin. Projeto aprovado no Comitê de Ética e Pesquisa com Seres Humanos. Resultados: Apesar do direito à saúde ser uma prerrogativa constitucional a ser garantida a todo cidadão, inclusive aos privados de liberdade, existem barreiras no cárcere que impedem esse acesso, como: dependência do agente penitenciário por meio de comunicação mediante bilhete, ausência de profissionais de saúde em tempo integral e falta de medicações, necessitando que a família atue como rede de cuidado. Conclusão: Evidencia-se a necessidade de melhor estruturar o acesso à saúde das pessoas privadas de liberdade, a fim de assegurar esse direito.(AU)

Objective: To establish how it occurs the access to health care for people deprived of liberty. Methods: Qualitative research, carried out in a prison Minas Gerais's inland, with 19 people deprived of liberty. Data were collected through open interviews guided by semi-structured rotation from August to December 2017. Bardin's Content Analysis was performed. Project approved by the Ethics and Research with Human Beings Committee. Results: Despite being a constitutional prerogative to be guaranteed to all citizens, including people deprived of liberty, there are prision obstacles that prevent this access, such as: dependence on the prison guard through communication by ticket, absence of a health professional full-time and lack of medication, making it necessary for the family to see itself as a care network. Conclusion: The need to structure the access to health care for people deprived of their liberty, in order to ensure their rights.(AU)

Objetivo: Conocer cómo se dá el acceso a la salud de las personas privó de su libertad. Métodos: Investigación cualitativa, realizada en una prisión del interior de Minas Gerais, con 19 personas privadas de libertad. Los datos fueron coleccionados atraves de una entrevista abierta orientado por un itinerario semi-estructurado. Se realizó el Análisis de Contenido de Bardin. Proyecto aprobado por el Comité de Ética e Investigación con Seres Humanos. Resultados: A pesar de que el derecho a la salud es una prerrogativa constitucional que debe garantizarse a todos los ciudadanos, incluidos los privados de libertad, existen barreras en la prisión que impiden este acceso, tales como: dependencia del guardia penitenciario mediante comunicación vía boleta, ausencia de salud profesionales de salud a tiempo completo y falta de medicación, lo que obliga a la familia a actuar como red asistencial. Conclusión: Se evidencia la necesidad de estructurar mejor el acceso a la salud de las personas privó de su libertad, a fin de garantizar este derecho.(AU)

Geometry of abstract learned knowledge in the hippocampus.

Hippocampal neurons encode physical variables1-7 such as space1 or auditory frequency6 in cognitive maps8. In addition, functional magnetic resonance imaging studies in humans have shown that the hippocampus can also encode more abstract, learned variables9-11. However, their integration into existing neural representations of physical variables12,13 is unknown. Here, using two-photon calcium imaging, we show that individual neurons in the dorsal hippocampus jointly encode accumulated evidence with spatial position in mice performing a decision-making task in virtual reality14-16. Nonlinear dimensionality reduction13 showed that population activity was well-described by approximately four to six latent variables, which suggests that neural activity is constrained to a low-dimensional manifold. Within this low-dimensional space, both physical and abstract variables were jointly mapped in an orderly manner, creating a geometric representation that we show is similar across mice. The existence of conjoined cognitive maps suggests that the hippocampus performs a general computation-the creation of task-specific low-dimensional manifolds that contain a geometric representation of learned knowledge.

Au@Ag bimetallic nanoparticles deposited on palygorskite in the presence of TiO2 for enhanced photodegradation activity through synergistic effect.

Herbicides are hazardous organic pollutants that contribute to the risk of environmental contamination. The aim of this work was to investigate the synergistic effect of silver (Ag) and gold (Au) bimetallic nanoparticles deposited on palygorskite (PAL) in the presence of TiO2 for photodegradation of bentazone (BTZ) herbicide under UV light. Ag and Au@Ag nanoparticles exhibited an average size below 75 nm and surface charge values less than - 30 mV. UV-Vis spectroscopy indicates the formation of core@shell bimetallic nanoparticles. XRD results showed the interactions between the NPs and the palygorskite structure. SEM images clearly illustrate the presence of small spherical particles distributed in the clay fibers. The control of the size and distribution of the nanoparticles played an important role in the properties of the composites. The degradation of the herbicide BTZ showed that nanoparticles, clay, and only TiO2 did not produce satisfactory results; however, when Ag-Pal and Au@Ag-Pal were in the presence of the TiO2, the degradation was efficient. The best photodegradative system was Au@Ag-Pal+TiO2, which was maintained after the third cycle. The bentazone photodegradation using Au@Ag-PAL+TiO2 exhibited toxicity against Artemia salina. Therefore, Au@Ag-PAL+TiO2 photocatalyst showed that the synergy of bimetallic nanoparticles deposited on clay for enhanced photodegradation activity of bentazone herbicide.

Task-Dependent Changes in the Large-Scale Dynamics and Necessity of Cortical Regions.

Neural activity throughout the cortex is correlated with perceptual decisions, but inactivation studies suggest that only a small number of areas are necessary for these behaviors. Here we show that the number of required cortical areas and their dynamics vary across related tasks with different cognitive computations. In a visually guided virtual T-maze task, bilateral inactivation of only a few dorsal cortical regions impaired performance. In contrast, in tasks requiring evidence accumulation and/or post-stimulus memory, performance was impaired by inactivation of widespread cortical areas with diverse patterns of behavioral deficits across areas and tasks. Wide-field imaging revealed widespread ramps of Ca2+ activity during the accumulation and visually guided tasks. Additionally, during accumulation, different regions had more diverse activity profiles, leading to reduced inter-area correlations. Using a modular recurrent neural network model trained to perform analogous tasks, we argue that differences in computational strategies alone could explain these findings.

Perfil térmico de rutina proveniente da fava d’anta (Dimorphandra gardneriana Tulasne) / Thermal profile of rutina from fava d'anta (Dimorphandra gardneriana Tulasne)

Dimorphandra gardneriana Tulasne é conhecida como fava d’anta, é uma árvore brasileira, naturalmente do Cerrado e Caatinga, têm uma importância ecológica e funcional, seus frutos são ricos em flavonoides (rutina, quercetina, isoquercitrina). O objetivo deste trabalho foi estudar a estabilidade térmica da fava d’anta e da rutina purifica através da termogravimetria. As amostras foram analisadas no Termogravimétrico Shimadzu, TGA-51, no Laboratório de Materiais do IFPI, onde foram acondicionadas em porta-amostras de platina, com atmosfera de nitrogênio e com fluxo de 50 mL/min. A temperatura foi elevada a 600°C, com taxa de aquecimento de 2 °C/min. Obteve-se sucesso com a purificação da fava d’anta, pois a rutina obtida teve maior uniformidade nos eventos térmicos e maior estabilidade térmica em relação a fava.

Remote sensing tree classification with a multilayer perceptron.

To accelerate scientific progress on remote tree classification-as well as biodiversity and ecology sampling-The National Institute of Science and Technology created a community-based competition where scientists were invited to contribute informatics methods for classifying tree species and genus using crown-level images of trees. We classified tree species and genus at the pixel level using hyperspectral and LiDAR observations. We compared three algorithms that have been implemented extensively across a broad range of research applications: support vector machines, random forests, and multilayer perceptron. At the pixel level, the multilayer perceptron algorithm classified species or genus with high accuracy (92.7% and 95.9%, respectively) on the training data and performed better than the other two algorithms (85.8-93.5%). This indicates promise for the use of the multilayer perceptron (MLP) algorithm for tree-species classification based on hyperspectral and LiDAR observations and coincides with a growing body of research in which neural network-based algorithms outperform other types of classification algorithm for machine vision. To aggregate patterns across the images, we used an ensemble approach that averages the pixel-level outputs of the MLP algorithm to classify species at the crown level. The average accuracy of these classifications on the test set was 68.8% for the nine species.

Eficácia e segurança da toxina botulínica no tratamento da paraparesia espástica: revisão sistemática / Efficacy and safety of botulinum toxin in the treatment of spastic paraparesis: systematic review

A paraparesia espástica é caracterizada pela perda de função total ou parcial dos membros inferiores associado ao aumento do tônus muscular velocidade-dependente. A toxina botulínica é utilizada no tratamento de diversos padrões de espasticidade, sejam em flexão, extensão ou adução. Objetivo: determinar a eficácia e segurança do bloqueio químico com toxina botulínica em pacientes com paraparesia espástica. Método: foi realizada uma revisão sistemática com busca nas bases de dados do PUBMED, MEDLINE, LILACS e SCIELO. Os critérios de inclusão foram: ensaios clínicos que utilizaram a toxina botulínica para o tratamento de pacientes com paraparesia espástica e publicados em inglês a partir da década de 1980. Os desfechos considerados foram: a pontuação na Escala de Ashworth Modificada, a amplitude de movimento passiva e ativa e os efeitos adversos da toxina botulínica. Resultados: foram incluídos cinco artigos. Todos mostraram melhora da espasticidade nos pacientes estudados. Quatro artigos mostraram aumento da amplitude de movimento passivo e três relataram aumento da amplitude de movimento ativo. Três artigos trouxeram relatos de efeitos adversos após o uso da toxina botulínica, mas a maioria deles não eram graves e cessaram espontaneamente. Conclusão: os estudos analisados mostraram que a toxina botulínica é eficaz e segura em pacientes com paraparesia espástica.(AU)

Spastic paraparesis is the loss of total or partial lower limb function associated with increased speed-dependent muscle tone. Botulinum toxin is used in the treatment of several spasticity presentations that include flexion, extension and adduction. Objective: To determine both safety and efficacy of botulinum toxin as a blocking agent in the treatment of spastic paraparesis. Method:A systematic review was carried out with a search on PUBMED, MEDLINE, LILACS and SCIELO databases. The inclusion criteria were: clinical trials that used botulinum toxin for the treatment of patients with spastic paraparesis and published in English from the 1980s. The following outcomes were assessed by the studies: the Ashworth Modified scale score, the range of passive and active motion and botulinum toxin adverse effects. Results:Five articles were included. All of them showed spasticity improvements in the patients. Four studies showed increases in passive range of motion and three articles showed increase in active range of motion. Three papers reported adverse effects after botulinum toxin use but they were mostly mild and ceased spontaneously. Conclusion: Most analyzed studies indicated that botulinum toxin is safe and efficient inthe treatment of spastic paraparesis. (AU)

An Accumulation-of-Evidence Task Using Visual Pulses for Mice Navigating in Virtual Reality.

The gradual accumulation of sensory evidence is a crucial component of perceptual decision making, but its neural mechanisms are still poorly understood. Given the wide availability of genetic and optical tools for mice, they can be useful model organisms for the study of these phenomena; however, behavioral tools are largely lacking. Here, we describe a new evidence-accumulation task for head-fixed mice navigating in a virtual reality (VR) environment. As they navigate down the stem of a virtual T-maze, they see brief pulses of visual evidence on either side, and retrieve a reward on the arm with the highest number of pulses. The pulses occur randomly with Poisson statistics, yielding a diverse yet well-controlled stimulus set, making the data conducive to a variety of computational approaches. A large number of mice of different genotypes were able to learn and consistently perform the task, at levels similar to rats in analogous tasks. They are sensitive to side differences of a single pulse, and their memory of the cues is stable over time. Moreover, using non-parametric as well as modeling approaches, we show that the mice indeed accumulate evidence: they use multiple pulses of evidence from throughout the cue region of the maze to make their decision, albeit with a small overweighting of earlier cues, and their performance is affected by the magnitude but not the duration of evidence. Additionally, analysis of the mice's running patterns revealed that trajectories are fairly stereotyped yet modulated by the amount of sensory evidence, suggesting that the navigational component of this task may provide a continuous readout correlated to the underlying cognitive variables. Our task, which can be readily integrated with state-of-the-art techniques, is thus a valuable tool to study the circuit mechanisms and dynamics underlying perceptual decision making, particularly under more complex behavioral contexts.

Cholinergic shaping of neural correlations.

A primary function of the brain is to form representations of the sensory world. Its capacity to do so depends on the relationship between signal correlations, associated with neuronal receptive fields, and noise correlations, associated with neuronal response variability. It was recently shown that the behavioral relevance of sensory stimuli can modify the relationship between signal and noise correlations, presumably increasing the encoding capacity of the brain. In this work, we use data from the visual cortex of the awake mouse watching naturalistic stimuli and show that a similar modification is observed under heightened cholinergic modulation. Increasing cholinergic levels in the cortex through optogenetic stimulation of basal forebrain cholinergic neurons decreases the dependency that is commonly observed between signal and noise correlations. Simulations of correlated neural networks with realistic firing statistics indicate that this change in the correlation structure increases the encoding capacity of the network.

Calcium Imaging of Basal Forebrain Activity during Innate and Learned Behaviors.

The basal forebrain (BF) plays crucial roles in arousal, attention, and memory, and its impairment is associated with a variety of cognitive deficits. The BF consists of cholinergic, GABAergic, and glutamatergic neurons. Electrical or optogenetic stimulation of BF cholinergic neurons enhances cortical processing and behavioral performance, but the natural activity of these cells during behavior is only beginning to be characterized. Even less is known about GABAergic and glutamatergic neurons. Here, we performed microendoscopic calcium imaging of BF neurons as mice engaged in spontaneous behaviors in their home cages (innate) or performed a go/no-go auditory discrimination task (learned). Cholinergic neurons were consistently excited during movement, including running and licking, but GABAergic and glutamatergic neurons exhibited diverse responses. All cell types were activated by overt punishment, either inside or outside of the discrimination task. These findings reveal functional similarities and distinctions between BF cell types during both spontaneous and task-related behaviors.

Calcium imaging of sleep-wake related neuronal activity in the dorsal pons.

The dorsal pons has long been implicated in the generation of rapid eye movement (REM) sleep, but the underlying circuit mechanisms remain poorly understood. Using cell-type-specific microendoscopic Ca(2+) imaging in and near the laterodorsal tegmental nucleus, we found that many glutamatergic neurons are maximally active during REM sleep (REM-max), while the majority of GABAergic neurons are maximally active during wakefulness (wake-max). Furthermore, the activity of glutamatergic neurons exhibits a medio-lateral spatial gradient, with medially located neurons more selectively active during REM sleep.