Federal University of Pelotas

Water is a fundamental component of life, playing a critical role in regulating metabolic processes and facilitating the dissolution and transport of essential molecules. However, emerging contaminants, such as pharmaceuticals, pose significant challenges to water quality and safety. Nanomaterial-based technologies emerge as a promising solution for removing those contaminants from water. Nevertheless, interfacial water plays a major role in the adsorption of chemical compounds in nanomaterials—as it plays in biological processes such as protein folding, enzyme activity, and drug delivery. To understand this role, in this study, we employ molecular dynamics simulations to explore the adsorption dynamics of potassium diclofenac on single-walled carbon nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs), considering both dry and wet conditions. Our findings reveal that the structuring of water molecules around CNTs creates hydration layers that significantly influence the accessibility of active sites and the interaction strength between contaminants and adsorbents. Our analysis indicates higher energy barriers for adsorption in DWCNTs compared to SWCNTs, which is attributed to stronger water–surface interactions. This research highlights the importance of understanding nanoscale water behavior for optimizing the design and functionality of nanomaterials for water purification. These findings can guide the development of more efficient and selective nanomaterials, enhancing contaminant removal and ensuring safer water resources while contributing to a deeper understanding of fundamental biological interactions.

Procedural content generation (PCG) has significantly impacted game design by automating the creation of dynamic game environments, thereby saving time and effort while maintaining the freshness at each play which is required for games as a service. Recent advances in machine learning, particularly Generative Adversarial Networks (GANs), offer exciting possibilities for generating diverse and playable game levels that surpass traditional methods. Despite challenges such as training instability and ensuring playability, GANs present considerable potential for dynamic content generation. This paper explores the advantages of GAN-based approaches, addresses their limitations, and suggests improvement strategies, including combining algorithms or using solvers to mitigate poor generations. This paper explores the advantages and limitations of GAN-based approaches and suggests promising research directions to improve GAN-based procedural level generation, including combining algorithms or using solvers to mitigate poor generations. Future research directions are also identified, such as the need for user studies and improved GAN training techniques to fully harness the potential of GANs in game-level generation.

Objectives This study investigated the prevalence and associations of xerostomia in older adults in southern Brazil. Methods A cross‐sectional study was carried out in Pelotas, Brazil, during 2014. A representative sample of the city's older adult population (60+) was selected. The dependent variable was self‐reported feeling of dry mouth in the past 6 months. Covariates included socio‐economic status, schooling, gender, age, tobacco and alcohol consumption, polypharmacy, hypertension, diabetes, arthritis, depression, dentition status and use of removable dental prostheses. Descriptive analysis was carried out, and Poisson regression was used to obtain prevalence ratios and 95% confidence intervals. Analyses used STATA 15.1. Results Most of the 1451 participants were female (63.3%). The prevalence of xerostomia was 36.7% (95% CI 34.3–39.1). Adjusted analysis showed that xerostomia was significantly more common among females (PR 1.44, 95% CI 1.22–1.74), those with less schooling (PR 1.31, 95% CI 1.10–1.51), those exposed to polypharmacy (PR 1.22, 95% CI 1.05–1.37), people with arthritis (PR 1.42, 95% CI 1.23–1.61) and those with depression symptoms (PR 1.45, 95% CI 1.23–1.70). Conclusion Xerostomia is common among older adults. Health workers need to pay attention to its associated factors for early identification and promotion of appropriate interventions, particularly the rational use of medicines.

The Northeast region of Brazil is characterized by long periods of drought. However, the region is also frequently affected by floods. The socioeconomic characteristics of the locality make the population more vulnerable to the impacts of these disasters. Therefore, the aim of this article is to investigate the short to long‐term impacts of hydrological disasters in northeastern Brazil on morbidity and mortality rates, by age groups. For this purpose, the difference‐in‐differences method proposed by Callaway and Sant'Anna was applied to a monthly panel data spanning the period from 2000 to 2012. The results indicate that in the short term there is an increase in the mortality rate associated with drowning. In the medium term, there are effects particularly on morbidity rates, with emphasis on leptospirosis and acute respiratory diseases. For the long‐term diseases analyzed, no effects of hydrological disasters were observed.

This study reports the preparation of hydrogels (HG) made with xanthan gum (XG) and ƙ-carrageenan (KC) polysaccharides containing ketoprofen (KET)-loaded nanoemulsions (NK) and their evaluation in a rheumatoid arthritis (RA) model. The nano-based HGs exhibited nanometric-sized droplets (~ 100 nm), an acidic pH (5.10–6.83), drug content above 85%, a suitable spreadability factor, and pseudoplastic flow behavior. The most promising blend (HGCX 2:1) demonstrated sustained KET release, reaching 81.44 ± 6.11% after 5 h, and superior drug concentration in the skin layers (237.91 ± 41.0 µg/g). The formulation was selected due to its enhanced bioadhesiveness, with the HG-NK formulation showing the highest bioadhesion force and occlusion factor. RA was induced by complete Freund’s adjuvant (CFA) intraplantar injection into the left hind paw of male and female Swiss mice. Treatments with HGs were applied to the animals’ dorsal region for 7 days. Notably, HG-NK demonstrated remarkable efficacy, reversing mechanical sensitivity in male mice and significantly reducing thermal sensitivity in both genders. Moreover, HG-NK provided a significant reduction in paw edema (52-fold in males, 27-fold in females) and inflammatory markers, such as myeloperoxidase activity (32-fold in males, 14-fold in females) and lipid peroxidation (2.5-fold in males, twofold in females). The formulation also promoted greater permeation of KET across the skin. These findings underscore the significant reduction in inflammatory markers by the HG-NK formulation, highlighting its potent anti-inflammatory effects and potential as a promising therapeutic strategy for managing RA.

The objective of this study was to evaluate effects caused by adverse hydric conditions associated with seed treatments and the influence these conditions have on the seeds physiological performance and early growth, antioxidant activity and metabolites accumulation in seedlings of different barley cultivars. The experimental design was entirely casualized with factorial scheme 5 × 6x2 (5 cultivars, 6 treatments and 2 water conditions). Cultivars and seed treatments were selected according to the greatest demand for them in the southern region of Brazil, where barley production is concentrated in the country, while the application of water restrictions was performed using Polyethylene glycol 6000. To evaluate the physiological performance, data about germination, first germination count and germination speed index were collected, considering early growth. Meanwhile, for seedlings initial growth, growth and dry mass of the shoots and roots were analyzed. To rate seedlings enzymatic activity, enzymatic activity of superoxide dismutase, catalase and ascorbate peroxidase, as well as the percentage of hydrogen peroxide and lipid peroxidation, were measured. Furthermore, to indicate metabolites accumulation in seedlings, data concerning total soluble sugar, proline and protein were extracted. BRS Quaranta was the cultivar that showed superior results when subjected to hydric restriction and when Triadimenol was used as seed treatment. Seeds physiological performance and seedlings initial growth were reduced when subjected to water restriction. Antioxidant enzymatic activity and metabolites accumulation were increased due to occurrence of water restriction. Triadimenol was the product that caused the greatest phytotoxic effects in barley seeds and seedlings. BRS Quaranta proved to be the least sensitive cultivar to occurrence of water restriction. Therefore, this research had as purpose to verify the behavior of different genotypes under hydric restriction conditions during barley initial establishment, but studies about other abiotic stresses are necessary, for example, high temperatures, low temperatures and flooding, as well as in different stages of barley development, such as tillering, elongation and seed filling.

Objective Despite the Global Vaccine Action Plan’s goal of at least 90% vaccine coverage for all children, Uganda has made limited progress in vaccination over the past decade. The objective of this study was to examine the subnational trends in the prevalence and inequalities in under-immunisation and zero-dose among children aged 12–23 months in Uganda. Study design A retrospective national cross-sectional study. Setting Uganda Participants Uganda Demographic and Health Survey secondary data of only children aged 12–23 months. The samples selected for analyses were 1507 in 2006, 1409 in 2011 and 2650 children in 2016. Outcome measure The primary outcomes were under-immunisation and zero-dose vaccination. Absolute and relative inequality measures were used in the analysis. Results From 2006 to 2016, the under-vaccination rate decreased by 21%, but remained high at 40.8%. The zero-dose vaccination rate dropped by 82%, affecting 1.2% of children in 2016. Subnational inequalities in under-vaccination increased over time with widening gaps between regions. While inequalities across wealth quintiles, maternal education levels and places of residence narrowed, children of mothers with lower education levels continued to have the highest under-vaccination rates. The rural–urban gap for zero-dose vaccination remained unchanged, with rural children disproportionately impacted. Conclusion While some progress was made in reducing under-vaccination rates in Uganda within the study period, no region achieved an under-vaccination rate below 20%. This indicates significant challenges in reaching the Sustainable Development Goal target of at least 80% immunisation coverage. Targeted interventions are necessary to improve healthcare access, enhance public health communication and strengthen the health system, particularly in underserved communities and among vulnerable populations.

Gold-based (Au) nanostructures are efficient catalysts for CO oxidation, hydrogen evolution (HER), and oxygen evolution (OER) reactions, but stabilizing them on graphene (Gr) is challenging due to weak affinity from delocalized $p_{z}$ carbon orbitals. This study investigates forming metal alloys to enhance stability and catalytic performance of Au-based nanocatalysts. Using ab initio density functional theory, we characterize ${\text {M}_{(n-x)}\text {Au}_{x}}$ sub-nanoclusters (M = Ni, Pd, Pt, Cu, and Ag) with atomicities $n=1-4$ , both in gas-phase and supported on Gr. We find that M atoms act as “anchors,” enhancing binding to Gr and modulating catalytic efficiency. Notably, ${\text {Pt}_{(n-x)}\text {Au}_{x}}$ /Gr shows improved stability, with segregation tendencies mitigated upon adsorption on Gr. The d -band center ( $\varepsilon _{\text {d}}$ ) model indicates catalytic potential, correlating an optimal $\varepsilon _{\text {d}}$ range of $-1 \text { to }-2$ eV for HER and OER catalysts. Incorporating Au into ${\text{M}_n}$ adjusts $\varepsilon _{\text {d}}$ closer to the Fermi level, especially for Group-10 alloys, offering designs with improved stability and efficiency comparable to pure Au nanocatalysts. Our methodology leveraged SimStack, a workflow framework enabling modeling and analysis, enhancing reproducibility, and accelerating discovery. This work demonstrates SimStack’s pivotal role in advancing the understanding of composition-dependent stability and catalytic properties of Au-alloy clusters, providing a systematic approach to optimize metal-support interactions in catalytic applications.

Background Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC). Methods MANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression. Results Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (p=0.031) and euthymic BD participants (p=0.013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all p>0.05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (p>0.05). Conclusion Individuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress.

Purinergic signaling plays a major role in aging and neurodegenerative diseases, which are associated with memory decline. Blackcurrant (BC), an anthocyanin-rich berry, is renowned for its antioxidant and neuroprotective activities. However, evidence on the effects of BC on purinergic signaling is lacking. This study investigated the effects of BC and its association with Donepezil (DNPZ) on learning and memory, on the modulation of purinergic signaling, pro-inflammatory responses, and oxidative markers in a mouse model of cognitive impairment chronically induced by scopolamine (SCO). Animals were divided into twelve groups and treated with BC (50 or 100 mg/kg), and/or DNPZ (5 mg/kg), and/or SCO (1 mg/kg). Results showed that SCO decreased spatial learning and memory as assessed by the Morris Water Maze test, and treatment with BC and/or DNPZ restored these effects. Furthermore, BC and/or DNPZ treatments also prevented changes in ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase (ADA) activities and restored the increased density of P2X7 and A2A receptors in synaptosomes of the cerebral cortex of SCO-induced mice. Moreover, the increased Nod-like receptor protein 3 (NLRP3) and interleukin-1β expression, and the oxidative stress markers levels were reduced by BC and/or DNPZ treatments, compared with the SCO group. Overall, BC and/or DNPZ treatments ameliorated SCO-induced cognitive decline, alleviated oxidative stress and pro-inflammatory responses, and improved purinergic signaling. These findings underscore the potential of BC, especially when in combination with DNPZ, as a therapeutic agent for the prevention of memory deficits associated with aging or neurological diseases. Graphical Abstract

In this work we describe the synthesis of selenium‐containing dihydrobenzofurans through the selenocyclization reaction of 2‐allylphenols. The reaction procedure uses only an I2/TBHP oxidant system at room temperature, enabling an efficient synthesis of 2‐[(organoselanyl)methyl]‐2,3‐dihydrobenzofurans. The products are formed immediately after the addition of the oxidant system in a mixture of 2‐allylphenol and diorganyl diselenide, in the absence of solvent, at mild experimental conditions. Furthermore, control experiments were carried out, including ⁷⁷Se NMR analyses to identify intermediates, which contributed to the elucidation of the reaction mechanism.

Objectives This cross-sectional study aimed to evaluate the occurrence of Streptococcus spp., Streptococcus mutans, its serotypes (c, e, f, and k), collagen-binding genes (cnm/cbm), and Candida albicans in medium deep (D2) and deep (D3) dentin carious lesions of permanent teeth. Materials and methods Carious dentin was collected from D2 (n = 23) and D3 (n = 24) lesions in posterior teeth from 31 individuals. DNA was extracted and analyzed using polymerase chain reaction (PCR). Results Streptococcus spp. exhibited a high prevalence in both D2 and D3 lesions, with a 100% occurrence rate in D3. Although S. mutans was prevalent in both lesion types, serotype distribution highlighted differences in complexity. Serotype e was the most frequently detected in D2 samples. Serotype c was absent in D2 but present in 19.0% of D3; serotype k was exclusively found in multi-serotype D3 alongside f, c, and e. The cbm gene and undetermined serotypes were detected only in D3. Candida albicans was not found in any samples, regardless of lesion depth. Conclusion Dentinal lesions exhibited a complex array of S. mutans serotypes, with a notable prevalence of the genus Streptococcus and an overall S. mutans prevalence of approximately 35%. Candida albicans was absent. In addition, a high diversity of serotypes was observed, including multiple and indeterminate serotypes, along with the presence of the collagen-binding cbm gene. Clinical relevance The identification of diverse Streptococcus mutans serotypes and the cbm gene in carious dentin from permanent teeth offers insights into microbial factors potentially linked to dentinal caries lesions. Additionally, the absence of Candida albicans suggests a limited role in this context.

Background The HEAD study focuses on collecting an extensive dataset from various tau‐PET tracers, aiming to establish robust anchor values, which are essential for harmonizing tau‐PET measurements. Here, we aim to showcase the capability of converting 3D tau‐PET images into a common scale using the Universal Tau‐PET Scale, Uniτ (tau), and to use these 3D images to subsequently obtain ROIs as needed. Methods We assessed 185 individuals across the aging and AD spectrum from the HEAD study, with [18F]Flortaucipir and [18F]MK‐6240 tau‐PET tracers. Tau‐PET SUVR images were standardized to a common 8mm FWHM, using the inferior cerebellar gray matter as the reference region. We generated Uniτ Tau‐PET 3D images using a single formula based on Meta‐temporal parameters in two steps: first, within‐tracer anchoring based on young (<25 years) and cognitively impaired individuals; second, between‐tracer anchoring using a piecewise transformation from [18F]Flortaucipir to [18F]MK‐6240, with smoothing at the piecewise inflection point. Subsequently, we extracted mean Uniτ values from these 3D images for key ROIs, including meta‐temporal, mesial, temporo‐parietal, frontal, and Braak stages III‐VI. Finally, we correlated Uniτ values across ROIs between the two tracers to evaluate the accuracy of estimates from the voxel‐wise transformation. Results The original SUVR images present large differences between the two tau‐PET tracers (Figure 1). However, upon applying the Uniτ piecewise transformation with smoothing to all brain voxels, we were able to reasonably harmonize these images to the Uniτ scale, substantially reducing visual variability. Notably, the mean Uniτ values for the ROIs extracted from these harmonized 3D tau‐PET brain images demonstrated a high level of association between the two tracers (Figure 2). Furthermore, estimates generated from ROIs or extracted from our 3D parametric Uniτ model yielded identical estimates (Figure 3). Conclusion The strong associations between tracers after directly harmonizing 3D images to Uniτ scale using the piecewise transformation with smoothing, underscore the effectiveness of the proposed method. This approach provides a reliable and standardized way to compare tau‐PET data across different tracers. Our results indicate the feasibility of harmonizing 3D tau‐PET images without relying on pre‐established ROIs, overcoming the limitation of restricting the analysis to only few brain regions.

Background The HEAD study aims to collect a large dataset of multiple tau‐PET tracers to provide robust anchor values for tau‐PET harmonization. Here, we tested the hypothesis that anchoring two tau tracer uptake values using head‐to‐head measurements has the potential to generate an accurate universal tau‐PET scale, named Uniτ(tau). Methods We assessed 200 individuals across the aging and AD spectrum (Training:HEAD data freeze 2.0, n=185; Testing:UPitt dataset (Gogola et al.), n=15) with [18F]Flortaucipir and [18F]MK‐6240 tau‐PET. SUVRs were processed to a common 8mm FWHM, with inferior cerebellar gray matter as the reference region (Pascoal et al.). Uniτ explored two anchoring/harmonization methods. First, we examined within‐tracer anchoring by creating anchor values based on the mean SUVR of Youngs (<25 years) and 95th percentile voxels from cognitively impaired individuals. Second, we explored within‐ plus between‐tracer anchoring, employing linear (e.g., piecewise) and non‐linear regressions. To address the inherent problem of discontinuity of piecewise transformations, we implemented two smoothing methods at the inflection point between equations, transforming them into a continuous function. Results Uniτ scale anchoring within‐tracer resulted in similar estimates for high values, but less accurate in the lower range (Figure 1,2). Anchoring within‐ plus between‐tracer improved estimate consistency, with the piecewise transformation generating the best results. The piecewise smoothing equation yielded estimates comparable to those obtained from the piecewise method without smoothing. This allowed for the use of a single formula. In addition, this leads to more robust results when the goal is to study longitudinal changes in the scale (data not shown). UPitt testing dataset showed similar results to the training set (Figure 3). Conclusion Our preliminary findings suggest that anchoring tau‐PET values both within and between tracers has the potential to harmonize tau‐PET tracers, while preserving their characteristics. Currently, piecewise smoothing is the preferred method for Uniτ, but we are continuously fine‐tuning scale parameters as we acquire more data. The final scale parameters will be determined based on extensive training and testing data from multiple tracers. This cautious methodology holds the promise of delivering reliable, robust, and reproducible results, ensuring safe usage of the scale in clinical trials, and potentially paving the way for future use in clinical practice.