The impact of enriched environments on cerebral oxidative balance in rodents: a systematic review of environmental variability effects.

Introduction: The present review aimed to systematically summarize the impacts of environmental enrichment (EE) on cerebral oxidative balance in rodents exposed to normal and unfavorable environmental conditions. Methods: In this systematic review, four databases were used: PubMed (830 articles), Scopus (126 articles), Embase (127 articles), and Science Direct (794 articles). Eligibility criteria were applied based on the Population, Intervention, Comparison, Outcomes, and Study (PICOS) strategy to reduce the risk of bias. The searches were carried out by two independent researchers; in case of disagreement, a third participant was requested. After the selection and inclusion of articles, data related to sample characteristics and the EE protocol (time of exposure to EE, number of animals, and size of the environment) were extracted, as well as data related to brain tissues and biomarkers of oxidative balance, including carbonyls, malondialdehyde, nitrotyrosine, oxygen-reactive species, and glutathione (reduced/oxidized). Results: A total of 1,877 articles were found in the four databases, of which 16 studies were included in this systematic review. The results showed that different EE protocols were able to produce a global increase in antioxidant capacity, both enzymatic and non-enzymatic, which are the main factors for the neuroprotective effects in the central nervous system (CNS) subjected to unfavorable conditions. Furthermore, it was possible to notice a slowdown in neural dysfunction associated with oxidative damage, especially in the prefrontal structure in mice. Discussion: In conclusion, EE protocols were determined to be valid tools for improving oxidative balance in the CNS. The global decrease in oxidative stress biomarkers indicates refinement in reactive oxygen species detoxification, triggering an improvement in the antioxidant network.

Global Sensitivity Analysis of the Advanced ORYZA-N Model with Different Rice Types and Irrigation Regimes.

Identifying important parameters in crop models is critical for model application. This study conducted a sensitivity analysis of 23 selected parameters of the advanced rice model ORYZA-N using the Extended FAST method. The sensitivity analysis was applied for three rice types (single-season rice in cold regions and double-season rice (early rice and late rice) in subtropical regions) and two irrigation regimes (traditional flood irrigation (TFI) and shallow-wet irrigation (SWI)). This study analyzed the parameter sensitivity of six crop growth outputs at four developmental stages and yields. Furthermore, we compared the variation in parameter sensitivity on model outputs between TFI and SWI scenarios for single-season rice, early rice, and late rice. Results indicated that parameters RGRLMX, FRPAR, and FLV0.5 significantly affected all model outputs and varied over developmental stages. Water stress in paddy fields caused by water-saving irrigation had more pronounced effects on single-season rice than on double-season rice.

LGBTQIA+ vs the Brazilian Unified Health System: Basic Health Unit Use and Associated Factors.

The Brazilian Unified Health System provides universal health care access without regard to sexual orientation and gender identity. We conducted a nationwide study with a cross-sectional design and intentional sampling methods to investigate factors associated with Basic Health Unit (BHU) use by the LGBTQIA+ community. Data were collected via a questionnaire available through social networks. Statistical analysis included Poisson regression with robust variance. A total of 603 LGBTQIA+ community members participated in the study, of whom 417 (69.2%) had visited a BHU in the last year. The factors "transgender woman" and "self-rated health status as very good/good/fair" increased the probability of BHU use in the last year by 10% (PR: 1.10; 95% CI: 1.00-1.20) and 9% (PR = 1.09; 95% CI: 1.01-1.18), respectively. "Not suffering sexual orientation-related discrimination at a BHU" and "Not suffering discrimination by a receptionist or waiting room worker" increased the probability of use by 28% (PR = 1.28; 95% CI: 1.22-1.34) and 22% (PR = 1.22; 95% CI: 1.14-1.30), respectively. Our study supports evidence that access to primary health care services in Brazil can be influenced by the social determinants gender identity and sexual discrimination.

Inhibiting miR-195-5p Induces Proliferation of Human Corneal Endothelial Cells.

Transparency of the human cornea is responsible for clear vision, which is maintained by a monolayer of non-proliferative human corneal endothelial cells (HCEnCs). Dysfunction of these cells can result in irreversible corneal blindness. It is important to identify key factors that limit the proliferation of HCEnCs and thus attempt to reverse them. Extracellular vesicles contain cargo which includes microRNAs (miRNAs) that can modulate a cellular function. In non small cell lung cancer, expression of miR-195-5p has been shown to inhibit proliferation; therefore, we aimed to investigate the inhibitory effect of miR-195-5p in inducing the proliferation of HCEnCs. Human corneal endothelial cell line (HCEC-12) and primary HCEnCs were cultured with miR-195-5p scramble, mimic or inhibitor. Corneal tissues from human cadaveric and FECD donors, and from pigs, mice and rabbits, were used for RT-PCR. miR-195-5p showed an abundance value of 11,363.31 a.u. When normalized against HCEnCs from cadaveric donors, FECD tissues showed a significant upregulation of miR-195-5p (p < 0.05) but was significantly downregulated in pig (p < 0.001), mouse (p < 0.01) and rabbit (p < 0.001) CEnCs, which have known proliferative capacity. Proliferation, cell doubling, and wound healing rates were significantly higher when miR-195-5p was inhibited. Inhibiting miR-195-5p showed a significant improvement in viability (HEC staining), decreased cell apoptosis (TdT-dNTP staining) and expression of ZO-1, NA+/K+-ATPase and Ki-67 markers. Expression of miR-195-5p is found in HCEnCs and FECD cells, which restricts the proliferation of these cells. However, inhibiting miR-195-5p can induce the proliferation of HCEnCs, which opens exciting directions for future research in prolonging FECD pathogenesis by increasing the proliferative capacity of HCEnCs using anti-miR therapy in vivo.

Mechanisms of improvement in generalized anxiety disorder: A mediation and moderated mediation analysis from a randomized controlled trial.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments. AIM: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD. DESIGN: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks. METHOD: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators. RESULTS: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations. CONCLUSION: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD.

Specific decellularized extracellular matrix promotes the plasticity of human ocular surface epithelial cells.

The ocular surface is composed of two phenotypically and functionally different epithelial cell types: corneal and the conjunctival epithelium. Upon injury or disease, ocular surface homeostasis is impaired resulting in migration of conjunctival epithelium on to the corneal surface. This can lead to incomplete transdifferentiation toward corneal epithelial-like cells in response to corneal basement membrane cues. We show that corneal extracellular matrix (ECM) proteins induce conjunctival epithelial cells to express corneal associated markers losing their conjunctival associated phenotype at both, mRNA and protein level. Corneal epithelial cells behave the same in the presence of conjunctival ECM proteins, expressing markers associated with conjunctival epithelium. This process of differentiation is accompanied by an intermediate step of cell de-differentiation as an up-regulation in the expression of epithelial stem cell markers is observed. In addition, analysis of ECM proteins by laminin screening assays showed that epithelial cell response is laminin-type dependent, and cells cultured on laminin-511 showed lower levels of lineage commitment. The phosphorylation and proteolysis levels of proteins mainly involved in cell growth and differentiation showed lower modifications in cells with lower lineage commitment. These observations showed that the ECM proteins may serve as tools to induce cell differentiation, which may have potential applications for the treatment of ocular surface injuries.

Synthesis of Fentanyl under Continuous Photoflow Conditions.

An advantageous and original synthesis of fentanyl is described. This new approach includes two efficient continuous flow reductive aminations achieved via photoredox catalysis and a final batch acylation. A telescoped protocol for the two photocatalyzed steps is also presented, and overall, this protocol provides improved sustainability, significant efficiency, reduced temperatures and reaction times, and is functional for scaling up this relevant active pharmaceutical ingredient (API).

Interspecies comparative morphological evaluation of the corneal epithelial stem cell niche: a pilot observational study.

BACKGROUND: The corneal and limbal morphology relevant to corneal epithelial maintenance in ten different species was examined using histological methods. OBJECTIVES: The presence of a Bowman's layer, limbal epithelial cell, and superficial stromal morphology was examined in the following species to evaluate the differences in corneal thickness and epithelium: Java sparrows, frogs, macaws, spoonbills, red pandas, penguins, horses, Dobermans, orangutans, and humans. METHODS: Corneal sections (4 µm) were obtained from ten ocular globes from three different animal classes: Aves, Amphibia, and Mammalia. All sections were stained with hematoxylin and eosin and periodic acid-Schiff reaction. After microscopy, all stained slides were photographed and analyzed. RESULTS: Significant morphological differences in the corneal and limbal epithelia and their underlying stroma between species were observed. The number of corneal epithelial cell layers and the overall corneal epithelial thickness varied significantly among the species. The presence of a Bowman's layer was only observed in primates (orangutans and humans). Presumed supranuclear melanin caps were noted in four species (orangutans, macaws, red pandas, and horses) in the limbal basal epithelial layer (putative site of corneal epithelial stem cells). The melanin granules covered the apex of the cell nucleus. CONCLUSIONS: Supranuclear melanin capping has been described as a process within the epidermis to reduce the concentration of ultraviolet-induced DNA photoproducts. Similarly, there may be a relationship between limbal stem cell melanin capping as a protective mechanism against ultra-violet radiation.

Multi-modal characterization of kesterite thin-film solar cells: experimental results and numerical interpretation.

We report a multi-modal study of the electrical, chemical and structural properties of a kesterite thin-film solar cell by combining the spatially-resolved X-ray beam induced current and fluorescence imaging techniques for the evaluation of a fully functional device on a cross-section. The data allowed the correlation of the chemical composition, defects at interfaces and inhomogeneous deposition of the layers with the local charge-collection efficiency of the device. We support our observations with Monte Carlo simulations of high-energy X-ray interactions with the semiconductor device, and finite-volume modeling of the charge-collection efficiency.

Epithelial Cell-Derived Extracellular Vesicles Trigger the Differentiation of Two Epithelial Cell Lines.

Extracellular vesicles (EVs), specifically exosomes, carry a cell-type dependent cargo that is transported to the recipient cell and translated in the presence of a required machinery. Differences in the cargo carried by the corneal and conjunctival-derived EVs could be the agent that triggers the transdifferentiation of these two cell populations. Therefore, this study investigates the role of EVs in triggering the plasticity of corneal and conjunctival epithelial cells and identifies prospective miRNA and genes responsible for maintaining ocular surface homeostasis. The EVs were extracted from the conditioned media (after starving) of corneal epithelial (hTCEpi) and conjunctival (HCjE-Gi) cell lines using ultracentrifugation. HCjE-Gi cells were cultured with hTCEpi-derived EVs and vice-versa. The EVs were characterized as exosomes using Nanosight and Flow cytometry. KRT3 and KRT12 were used as associated corneal markers, whereas KRT7 and KRT13 were used as associated conjunctival markers with ΔNp63 as a differentiation marker. Shift of these markers was an indication of transdifferentiation. The cargo of the extracted exosomes from both the cell types was explored using next-generation sequencing. The hTCEpi-derived EVs induced conjunctival epithelial cells to express the corneal-associated markers KRT3 and KRT12, losing their conjunctival phenotype at both the mRNA and protein level. Simultaneously, HCjE-Gi-derived EVs induced corneal epithelial cells to express the conjunctival associated markers KRT7 and KRT13, losing their corneal phenotype. This process of differentiation was accompanied by an intermediate step of cell de-differentiation showed by up-regulation in the expression of epithelial stem cell marker ΔNp63, also shown on the ex vivo human cadaveric donor corneas. miRNA molecules (total of 11 including precursor and mature) with significant differences in their relative abundance between the two populations (p < 0.05) were found and investigated. miR-9-5p expression was higher in HCjE-Gi cells and HCjE-Gi-derived EVs when compared to hTCEpi cells and hTCEPi-derived EVs (p < 0.001). The results suggest that EVs released by the two cell types have the ability to influence the transdifferentiation of human conjunctival and corneal epithelial cells. miR-9-5p could have a role in stem cell homeostasis and cell differentiation via HES-1 gene.

PEOT/PBT Polymeric Pastes to Fabricate Additive Manufactured Scaffolds for Tissue Engineering.

The advantages of additive manufactured scaffolds, as custom-shaped structures with a completely interconnected and accessible pore network from the micro- to the macroscale, are nowadays well established in tissue engineering. Pore volume and architecture can be designed in a controlled fashion, resulting in a modulation of scaffold's mechanical properties and in an optimal nutrient perfusion determinant for cell survival. However, the success of an engineered tissue architecture is often linked to its surface properties as well. The aim of this study was to create a family of polymeric pastes comprised of poly(ethylene oxide therephthalate)/poly(butylene terephthalate) (PEOT/PBT) microspheres and of a second biocompatible polymeric phase acting as a binder. By combining microspheres with additive manufacturing technologies, we produced 3D scaffolds possessing a tailorable surface roughness, which resulted in improved cell adhesion and increased metabolic activity. Furthermore, these scaffolds may offer the potential to act as drug delivery systems to steer tissue regeneration.

A Three-Arm Randomized Clinical Trial Comparing the Efficacy of a Mindfulness-Based Intervention with an Active Comparison Group and Fluoxetine Treatment for Adults with Generalized Anxiety Disorder.

INTRODUCTION: Mindfulness-based interventions have been studied as an alternative treatment for anxiety disorders, but there are only a few studies comparing these with established treatments. OBJECTIVE: To evaluate the efficacy of a Body in Mind Training (BMT) program for adults with generalized anxiety disorder (GAD), an active comparison protocol called Quality of Life and Psychoeducation (QoL), and treatment with fluoxetine (FLX). METHODS: This study comprises a 3-arm parallel-group, randomized clinical trial (ClinicalTrials.gov ID: NCT03072264). Adults with a primary diagnosis of GAD and no current treatment were recruited from the community and randomized in a ratio 1:1:1. The primary outcomes were assessed by means of the Hamilton Anxiety Rating Scale (HAM-A) and the Penn State Worry Questionnaire (PSWQ) at week 8. Data were analyzed using a superiority analysis (BMT vs. QoL) and a noninferiority analysis (BMT vs. FLX). RESULTS: A total of 249 participants were included and 223 were analyzed (76 BMT, 79 FLX, and 68 QoL). All groups improved after intervention. However, BMT was not superior to QoL at week 8 (mean difference = -1.36; p = 0.47), nor was it noninferior to FLX as assessed with theHAM-A (mean difference = 3.5; 95% CI -0.06 to 7.06; noninferiority margin = -2.43; p = 0.054). QoL (mean difference = 3.54; p = 0.04) and FLX (mean difference = -7.72; 95% CI -10.89 to -4.56; noninferiority margin = -2.09; p < 0.001) were superior to BMT in reducing PSWQ score. CONCLUSION: Our data suggest that BMT, in its current format, cannot be considered an effective mindfulness protocol to improve GAD.