In Vivo Neural Tract Tracing Procedures: Unravelling Neural Hodology Using Fluorescent and Non-fluorescent Neural Tract Tracers, Optogenetic Approach, and Diffusion Tensor Neurotractography Protocols.

Fluorescent and non-fluorescent neural tract tracers enable the investigation of neural pathways in both peripheral and central nervous systems in laboratory animals demonstrating images with high resolution and great anatomic precision. Anterograde and retrograde viral tracers are important cutting-edge tools for neuroanatomical mapping. The optogenetic consists of an advanced alternative for in vivo neural tract tracing procedures, fundamentally considering the possibility to dissect and modulate pathways either exciting or inhibiting neural circuits in laboratory animals. The neurotractography by diffusion tensor imaging in vivo procedures enables the study of neural pathways in humans with reasonable accuracy. Here we describe the procedure of classical anatomic neural tract tracing and modern optogenetic technique performed in anima vili in addition to different diffusion tensor neurotractography performed in anima nobili.

Association of Overweight and Obesity with Impaired Executive Functioning in Mexican Adolescents: The Importance of Inhibitory Control.

Overweight and obesity are major public health issues worldwide, including in Mexico, particularly among adolescents. This study aimed to analyze the associations between nutritional status and impaired executive function (EF) in Mexican adolescents. A case-control study was conducted with 98 male and female adolescents, categorized into normal weight and overweight/obese groups based on body mass index. EF was assessed using the BANFE-2 test. The prevalence of overweight and obesity was 54.3%. The EF assessment revealed that 82.45% of the overweight/obese group exhibited mild-to-severe impairment, compared to only 36.58% in the normal weight group (X2 = 21.69, p < 0.0001). In the inhibitory control assessment, adolescents with overweight and obesity performed worse than their normal-weight counterparts. Specifically, females with overweight/obesity scored lower than females with normal weight on the risk-benefit processing test. The risk of severe EF impairment significantly increased with the presence of overweight/obesity (OR = 7.8, p < 0.0001). These findings indicate that EF, particularly inhibitory control and risk-benefit processing, is impaired in adolescents with overweight or obesity.

Antifungal Activity of Morinda citrifolia Methanolic Extract against Candida albicans: An In Vitro Study.

Aim: Natural medicine used as an alternative and/or complementary treatment to counteract diseases is of great importance in public health. Therefore, the purpose of the present study was to assess the in vitro antifungal activity of Morinda citrifolia methanolic extract of peel, pulp, and seed against Candida albicans. Materials and Methods: The present study was experimental in vitro and cross-sectional. Eight replicates were prepared in Sabouraud dextrose agar with five wells each, where 0.12% chlorhexidine, distilled water, and methanolic extract of seed, peel, and pulp of Morinda citrifolia fruit were placed at concentrations of 10,690, 8,270, and 6,430 mg/mL, respectively, to evaluate sensitivity according to Duraffourd's scale. In addition, the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined by dilution and agar seeding method. Statistical analysis was performed by analysis of variance (ANOVA) and Tukey's post hoc test, considering a significance level of P < 0.05. Results: The inhibition halos of Morinda citrifolia methanolic extract of seed, peel, and pulp against Candida albicans measured on average 15.94, 11.94, and 11.56 mm, respectively. The MIC of seed, peel, and pulp extract were 1366.25, 2067.5, and 1607.5 mg/mL respectively, whereas the MFC for seed, peel, and pulp extract were 2672.50, 2067.5, and 3215 mg/mL, respectively. Moreover, seed extract presented significantly higher antifungal activity than peel and pulp (P < 0.001). Conclusions: Morinda citrifolia methanolic extract of peel, pulp, and seed showed fungistatic and fungicidal effect against Candida albicans, being this very sensitive to seed extract with a MIC of 1366.25 mg/mL and a MFC of 2672.5 mg/mL, which allows recommending the development of effective pharmacological formulations for the control of candidiasis.

Group A streptococcus isolated in Guyana with reduced susceptibility to ß-lactam antibiotics.

Introduction. Streptococcus pyogenes [group A streptococci (GAS)] is the causative agent of pharyngitis and various other syndromes involving cellulitis, streptococcal toxic shock syndrome (STSS), and necrotising fasciitis. Although the prevalence of GAS infections globally remains high, necessitating the widespread use of ß-lactam antibiotics, GAS have remained largely susceptible to these agents. However, there have been several reports of GAS with reduced susceptibility harbouring mutations in genes for penicillin-binding proteins (PBPs). The objectives of this study were to examine the in vitro ß-lactam susceptibility patterns of group A streptococci, determine the prevalence of drug resistance, and ascertain whether such resistance could be attributed to mutations in specific PBP genes. Methods. In this study, we sought to use Sanger sequencing to identify mutations in PBP genes of Streptococcus pyogenes isolated from patients that required inpatient and outpatient care that could confer reduced PBP affinity for penicillin and/or cephalosporin antibiotics. All isolates were screened for susceptibility to penicillin, amoxicillin, and cefazolin using E-test strips. Results. While there were no documented cases of reduced susceptibility to penicillin or amoxicillin, 13 isolates had reduced susceptibility to cefazolin. Examination of pbp1a by Sanger sequencing revealed several isolates with single amino acid substitutions, which could potentially reduce the affinity of PBP 1A for cefazolin and possibly other first-generation cephalosporins. Conclusion. Penicillin and penicillin-derived antibiotics remain effective treatment options for GAS infections, but active surveillance is needed to monitor for changes to susceptibility patterns against these and other antibiotics and understand the genetic mechanisms contributing to them.

Antifungal Activity of Aniba canelilla (Kunth) Mez Essential Oil and Its Main Compound 1-Nitro-2-Phenylethane against Dermatophytes.

The essential oil of Aniba canelilla (Kunth) Mez (EOAC), an Amazon plant composed of a rare nitro compound, has shown scientific evidence of antifungal activity but is still unexplored against dermatophytes. The antifungal susceptibility of EOAC and its main compound, 1-nitro-2-phenylethane (NP), was evaluated against dermatophytes (Trichophyton rubrum, T. mentagrophytes and Microsporum canis), evidencing antifungal activity with an inhibitory concentration lower than 256 µg/mL. The mechanism of action was also evaluated, and it is suggested that EOAC and NP have fungicidal action in the fungal membrane, since the antifungal activity occurs through a modification of the shape of the conidial structures of the fungus, showing the permeability of the intracellular content due to the visually observed plasmolysis and cytosolic extravasation through an osmotic process. These results suggest the essential oil and its main compound are promising plant-derived alternatives for treating ungual dermatophytosis.

The Human Developing Cerebral Cortex Is Characterized by an Elevated De Novo Expression of Long Noncoding RNAs in Excitatory Neurons.

The outstanding human cognitive capacities are computed in the cerebral cortex, a mammalian-specific brain region and the place of massive biological innovation. Long noncoding RNAs have emerged as gene regulatory elements with higher evolutionary turnover than mRNAs. The many long noncoding RNAs identified in neural tissues make them candidates for molecular sources of cerebral cortex evolution and disease. Here, we characterized the genomic and cellular shifts that occurred during the evolution of the long noncoding RNA repertoire expressed in the developing cerebral cortex and explored putative roles for these long noncoding RNAs in the evolution of the human brain. Using transcriptomics and comparative genomics, we comprehensively annotated the cortical transcriptomes of humans, rhesus macaques, mice, and chickens and classified human cortical long noncoding RNAs into evolutionary groups as a function of their predicted minimal ages. Long noncoding RNA evolutionary groups showed differences in expression levels, splicing efficiencies, transposable element contents, genomic distributions, and transcription factor binding to their promoters. Furthermore, older long noncoding RNAs showed preferential expression in germinative zones, outer radial glial cells, and cortical inhibitory (GABAergic) neurons. In comparison, younger long noncoding RNAs showed preferential expression in cortical excitatory (glutamatergic) neurons, were enriched in primate and human-specific gene co-expression modules, and were dysregulated in neurodevelopmental disorders. These results suggest different evolutionary routes for older and younger cortical long noncoding RNAs, highlighting old long noncoding RNAs as a possible source of molecular evolution of conserved developmental programs; conversely, we propose that the de novo expression of primate- and human-specific young long noncoding RNAs is a putative source of molecular evolution and dysfunction of cortical excitatory neurons, warranting further investigation.

Does sorghum phenolic extract have antifungal effect?

This study aimed to evaluate the antifungal effect of SC319 sorghum phenolic extract (SPE) on the Aspergillus, Fusarium, Penicillium, Stenocarpella, Colletotrichum, and Macrophomina genera. SPE was extracted by 20% ethanol and used in four assays: (1) against Fusarium verticillioides in solid (PDA) and liquid (PD) potato dextrose media; (2) Minimum Inhibitory Concentration (MIC) assay with 16 fungi isolates; (3) Conidial Germination Rate (CGR) with 14 fungi isolates and (4) Growth Curve (GC) with 11 fungi isolates. There was no reduction in the mycelial growth (colony diameter and dry weight) and in the number of Fusarium verticillioides spores in assay 1 (PDA and PD). The colony's dry weight was almost six times higher in the presence than in the absence of SPE. All SPE samples presented MIC (assay 1) above the maximum concentration tested (5000 µg.mL-1) for the 16 isolates. Also, there was no inhibitory effect of SPE on conidia germination rate (CGR). Oppositely, in GC assay, the control had a higher CFU count than the samples with SPE in 24 h. This result suggests that SPE can delay the fungal growth in the first hours of incubation, which is an important finding that may help reduce the severity of fungal diseases in plants. However, further studies are needed to confirm these results, including sorghum genotypes with different profiles of phenolic compounds. Although the SC319 SPE was not effective as an antifungal agent, it may have potential as a growth promoter of beneficial fungi in the food and pharmaceutical industries.

Left OFC Activation in Functional Near-Infrared Spectroscopy during an Inhibitory Control Task in an Early Years Sample: Integrating Stress Responses with Cognitive Function and Brain Activation.

INTRODUCTION: Previous functional near-infrared spectroscopy (fNIRS) studies using Go/No-Go (GNG) tasks have focused on brain activation in relation to cognitive processes, particularly inhibitory control (IC). The results of these studies commonly describe right hemispheric engagement of the dorsolateral, ventromedial, or inferior frontal regions of the prefrontal cortex. Considering that typical healthy cognitive development is negatively correlated with higher cortisol levels (which may alter brain development), the overarching aim of the current study was to investigate how elevated stress (due to unforeseeable events such as the pandemic) impacts early cognitive development. METHOD: In this study, we examined fNIRS data collected from a sample of children (aged 2-4 years) during a GNG task relative to the response to stressors measured via hair cortisol concentrations. We acquired data in an ecological setting (Early Childhood Education and Care) during the coronavirus pandemic. RESULTS: We found that children with higher stress levels and a less efficient IC recruited more neural terrain and our group-level analysis indicated activation in the left orbitofrontal area during IC performance. CONCLUSIONS: A contextual stressor may disrupt accuracy in the executive function of IC early in development. More research efforts are needed to understand better how an orbitofrontal network subserves goal-directed behavior.

Anti-Listerial Activity of Bacteriocin-like Inhibitory Substance Produced by Enterococcus lactis LBM BT2 Using Alternative Medium with Sugarcane Molasses.

Listeria monocytogenes is a foodborne pathogen that contaminates food-processing environments and persists within biofilms on equipment, thus reaching final products by cross-contamination. With the growing demand for clean-label products, the search for natural antimicrobials as biopreservants, such as bacteriocins, has shown promising potential. In this context, this study aimed to evaluate the anti-listerial action of bacteriocins produced by Enterococcus lactis LBM BT2 in an alternative medium containing sugarcane molasses (SCM). Molecular analyses were carried out to characterize the strain, including the presence of bacteriocin-related genes. In the kinetic study on SCM medium E. lactis, LBM BT2 showed biomass and bacteriocin productions similar to those observed on a sucrose-based medium (control), highlighting the potential of the sugarcane molasses as a low-cost substrate. Stability tests revealed that the molecule remained active in wide ranges of pH (4-10) and temperature (60-100 °C). Furthermore, the proteolytic treatment reduced the biomolecule's antimicrobial activity, highlighting its proteinaceous nature. After primary purification by salting out and tangential flow filtration, the bacteriocin-like inhibitory substance (BLIS) showed bacteriostatic activity on suspended L. monocytogenes cells and against biofilm formation at a concentration of 0.625 mg/mL. These results demonstrate the potential of the produced BLIS as a biopreservative in the food industry.

Perineuronal nets as regulators of parvalbumin interneuron function: Factors implicated in their formation and degradation.

The brain extracellular matrix (ECM) has garnered increasing attention as a fundamental component of brain function in a predominantly "neuron-centric" paradigm. Particularly, the perineuronal nets (PNNs), a specialized net-like structure formed by ECM aggregates, play significant roles in brain development and physiology. PNNs enwrap synaptic junctions in various brain regions, precisely balancing new synaptic formation and long-term stabilization, and are highly dynamic entities that change in response to environmental stimuli, especially during the neurodevelopmental period. They are found mainly surrounding parvalbumin (PV)-expressing GABAergic interneurons, being proposed to promote PV interneuron maturation and protect them against oxidative stress and neurotoxic agents. This structural and functional proximity underscores the crucial role of PNNs in modulating PV interneuron function, which is critical for the excitatory/inhibitory balance and, consequently, higher-level behaviours. This review delves into the molecular underpinnings governing PNNs formation and degradation, elucidating their functional interactions with PV interneurons. In the broader physiological context and brain-related disorders, we also explore their intricate relationship with other molecules, such as reactive oxygen species and metalloproteinases, as well as glial cells. Additionally, we discuss potential therapeutic strategies for modulating PNNs in brain disorders.

Dual role of α7 nicotinic acetylcholine receptors in the retrosplenial cortex for aversive memory acquisition and retrieval.

In the retrosplenial cortex (RSC), the role of cholinergic modulation via α7 nicotinic receptors and their involvement in memory is unknown. In recent years, the RSC has been shown to deteriorate in the early stages of Alzheimer's disease (AD). Likewise, the cholinergic system has been postulated as one of those responsible for cognitive impairment in patients with AD. Great interest has arisen in the study of α7 nicotinic receptors as more specific targets for the treatment of this disease. For this reason, we aim to study the role of α7 receptors of the RSC in memory processing. We infused a selective α7 receptor antagonist into the anterior part of the RSC (aRSC) to assess its role in different phases of aversive memory processing using an inhibitory avoidance task. We found that α7 nicotinic receptors are involved in memory acquisition and expression, but not in its consolidation. These results identify aRSC α7 nicotinic receptors as key players in aversive memory processing and highlight their significant potential as therapeutic targets for Alzheimer's disease.

Biological capacities of seven Chilean ferns.

Sticherus squamulosus, Hymenophyllum dentatum, Blechnum microphyllum, Polypodium Feuillei, Blechnum chilense, Lophosoria quadripinnata, and Lissopimpla excelsa are native fern species found in southern Chile and are often used in traditional medicine. However, their bioactive properties have not been confirmed. In this study, ethanolic extracts of ferns exhibited significant antibacterial capacity against human pathogens. H. dentatum and S. squamulosus were selected for further analysis owing to their antimicrobial and antioxidant capacities. The entire H. dentatum extract exhibited fungistatic and fungicidal capacity on Botrytis cinerea and Penicillium digitatum, with minimum inhibitory concentration values of 1.56 mg/mL and 6.25 mg/mL and minimum fungicidal concentration values of 6.25 mg/mL and 12.5 mg/mL, respectively. The S. squamulosus extract presented the highest rutin content (222.5 µg/g fern). In addition, the ethanolic extract of H. dentatum inhibited 91% of DPPH radicals. Therefore, both types of ferns can be used in the food industry.

Mind over mood: exploring the executive function's role in downregulation.

Emotion regulation plays a key role in well adapted behaviour, however, factors influencing individual differences in ER are still under investigation. Across two studies we investigate the complex relationship between executive functions (EFs) and emotional downregulation through two complementary research designs. The focus lies on key components of EFs-working memory, inhibitory control, and switching-and their relationship with effective emotional regulation. Surprisingly, switching emerged as the sole significant predictor in two multiple linear regression models, challenging the conventional belief that all major EFs broadly contribute to emotional downregulation. The first study, involving 248 Ecuadorian adults between 18 and 60 years old, used experimental tasks to assess the association between EFs and emotional regulation, aligning with existing literature that posits a link between EFs and emotional control. The second study, involving 180 Ecuadorian adults between 18 and 43 years old, added depth by incorporating self-report measures, providing a broader, ecologically valid perspective. However, these measures did not significantly predict downregulation, highlighting a gap between self-perception and actual cognitive abilities. Additionally, demographic predictors varied between the two studies, urging future research to consider methodological design and task selection carefully. The study also raises questions about the validity of commonly used measures, emphasising the need for more nuanced tools to capture the complexity of EFs and emotional regulation. Our findings suggest a targeted research avenue focusing on EFs for both future research and clinical interventions. Attention is called to the methodological decisions that can influence the observed associations, and the need for broader demographic representation in future studies.

How do physicochemical properties contribute to inhibitory activity of promising peptides against Zika Virus NS3 protease?

CONTEXT AND RESULTS: Flavivirus diseases' cycles, especially Dengue and Yellow Fever, can be observed all over Brazilian territory, representing a great health concern. Additionally, there are no drugs available in therapy. In this scenario, in silico methodologies were applied to obtain physicochemical properties, as well as to better understand the ligand-biological target interaction mode of 20 previously reported NS2B/NS3 protease inhibitors of Dengue virus. Since catalytic site of flavivirus hold similarities, such as the same catalytic triad (His51, Asp75 e Ser135), the ability of this series of molecules to fit in Zika NS3 domains can be achieved. We performed an exploratory data analysis, using statistical methodologies, such as PCA (Principal Component Analysis) and HCA (Hierarchical Component Analysis), to assist the comprehension of how physicochemical properties impact the interaction observed by the docking studies, as well as to build a correlation between the respective ranked characteristics. Based on these previous studies, peptides were selected for the dynamics simulations, which were useful to better understand the ligand-protein interactions. Information relating to, for instance, energy, ΔG, average number of hydrogen bonds and distance from Ser135 (one of the main amino acids in the catalytic pocket) were discussed. In this sense, peptides 15 (considering ΔG value and Hbond number), 7 (ΔG and energy) and 1, 6, 7 and 15 (the proximity to Ser135 throughout the dynamics simulation) were highlighted as promising. Those interesting results could contribute to future studies regarding Zika virus drug design, since this infection represents a great concern in neglected populations. METHODS: The models were constructed in the ChemDraw software. The ligand parametrization was performed in the CHEM3D 17.0, UCSF Chimera. Docking simulations were carried out in the GOLD software, after the redocking validation. We used ASP as the function score. Additionally, for dynamics simulations we applied GROMACS software, exploring, mainly, free binding energy calculations. Exploratory analysis was carried out in Minitab 17.3.1 statistical software. Prior to the exploratory analysis, data of quantum chemical properties of the peptides were collected in Microsoft Excel spreadsheet and organized to obtain Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA).

Agreement of methods to assess antimicrobial susceptibility using Escherichia coli isolates as target models.

Antimicrobial susceptibility tests (AST) conducted in vitro offer a range of methods to assess the antimicrobial resistance (AMR) of microorganisms. Escherichia coli, a widely distributed bacterium, is closely linked to the issue of AMR. In this way, the present study aimed to assess the agreement among different in vitro AST methods, including disk diffusion in agar, broth dilution, and agar dilution method. A total of 100 E. coli isolates were analyzed for their resistance levels against six antibiotics: amoxicillin, ceftiofur, ciprofloxacin, chloramphenicol, tetracycline, and sulfamethoxazole + trimethoprim, using the aforementioned AST methods. Standard breakpoint values were employed to classify isolates as resistant, intermediate, or susceptible, and comparisons among the AST methods were conducted by McNemar's test (P < .05). The obtained data demonstrated equivalence among the AST methods, highlighting the reliability of these standardized classical methodologies. This standardization aids in preventing the inappropriate use of antimicrobials and the dissemination of antimicrobial-resistant microorganisms.

A Naturalistic Intervention to Promote Executive Functions in Primary School Children: A Pilot Study.

Executive functions are related to the control of cognition, emotion, and behavior. They are essential to lifelong outcomes, including school performance. Naturalistic interventions embedded in children's daily activities and environments have greater effects. Therefore, this pilot study aimed to develop a naturalistic program suitable for schools, based on Goal Management Training (GMT), and to analyze its effects on executive functions and behavior. The participants consisted of 35 students from 2nd to 5th grade with executive dysfunction complaints. They underwent neuropsychological assessments of working memory, inhibition, cognitive flexibility, and intellectual capacity. Teachers and parents answered questionnaires on executive functions and behavior. Students were randomly assigned to an active control group, who participated in sessions on citizenship, and an experimental group (EG), stimulated through the executive function program, both with 16 sessions conducted by psychologists. After the intervention, all participants were reevaluated. The two-way Wald-type statistic (WTS) revealed greater improvement in executive functions for the EG, including working memory and inhibition. Additionally, parents and teachers, blind to the experimental conditions, reported improvements in some measures of executive functions and behavior. The results are encouraging, but further studies should test the intervention when implemented with larger samples and by teachers.

Development and evaluation of ciprofloxacin local controlled release materials based on molecularly imprinted polymers.

The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.

Are there associations between sedentary time inside and outside preschools with preschoolers' executive function?

Preschool children spend a large part of their day at school, and a large part of that time they spend in sedentary time. Although sedentary time negatively affects regions of the brain responsible for cognition, it is believed that the type of sedentary time performed can favor executive functions' performance. The present study explored the associations between sedentary time inside and outside preschools with executive function (EF) tasks in preschoolers. Seventy-three preschool children (60% girls; 55.0 ± 9.1 months of age) were objectively assessed for sedentary time and physical activity (PA) using accelerometers (wGT3X). EF was evaluated using the Go/No-Go paradigm through the Early Years Toolbox - YET. Go's inverse efficiency (IE) and the No-Go accuracy were analyzed. To establish possible associations between EF and sedentary time, a structural equation model was conducted after adjustments for sex, age, body mass index, and moderate-to-vigorous PA. A significant and positive association between sedentary time on weekend days and IE (b = 0.61; p < .001) was observed. The general model explained 52% of the variation in IE and 2.1% in the accuracy of No-Go. The sedentary time on weekend days seems to be related to worse EI. This result emphasizes a context-dependent association between time being sedentary and preschoolers' EF. Further investigations should focus on exploring the type of sedentary behavior children are engaged in different contexts.

CAR-T cell therapy: a game-changer in cancer treatment and beyond.

In recent years, cancer has become one of the primary causes of mortality, approximately 10 million deaths worldwide each year. The most advanced, chimeric antigen receptor (CAR) T cell immunotherapy has turned out as a promising treatment for cancer. CAR-T cell therapy involves the genetic modification of T cells obtained from the patient's blood, and infusion back to the patients. CAR-T cell immunotherapy has led to a significant improvement in the remission rates of hematological cancers. CAR-T cell therapy presently limited to hematological cancers, there are ongoing efforts to develop additional CAR constructs such as bispecific CAR, tandem CAR, inhibitory CAR, combined antigens, CRISPR gene-editing, and nanoparticle delivery. With these advancements, CAR-T cell therapy holds promise concerning potential to improve upon traditional cancer treatments such as chemotherapy and radiation while reducing associated toxicities. This review covers recent advances and advantages of CAR-T cell immunotherapy.