Complex interactions of rare earth elements in aquatic systems: Comparing observed and predicted cellular responses on Mytilus galloprovincialis.

Recent societal and technological developments have led to new sources of contamination, particularly from electronic waste (e-waste). The rapid increase in e-waste, combined with inadequate disposal and recycling practices has resulted in rising levels of hazardous substances in aquatic systems, including rare-earth elements (REEs). However, the effects of REEs on aquatic organisms remain poorly understood. This lack of understanding is concerning since REEs can simultaneously appear in aquatic systems. Thus, this study aimed to evaluate the impacts of Y, La, and Gd, individually and as mixtures on the mussel species Mytilus galloprovincialis. Biomarkers related to metabolism, energy reserves, defence enzymes, redox balance, cellular damage and neurotoxicity were analyzed. The results obtained showed that yttrium alone caused minimal stress, while gadolinium, lanthanum, and their mixtures induced moderate to severe stress, increased metabolic activity, and enzyme responses. This study highlights the ecological impacts of rare earth element (REE) mixtures on aquatic organisms. The complex interactions and additive effects, especially with gadolinium, underline the need for further research on contaminant mixtures.

Comparison Between the Veillon and the Symons-Fanning CT Classification Systems for Otosclerosis.

OBJECTIVE: To analyze the correlation between outcomes of stapes surgery and preoperative and postoperative audiometric results with different radiological staging classifications such as the Veillon classification (VC) and the Symons-Fanning classification (SFC). STUDY DESIGN: Retrospective observational study. SETTING: One tertiary hospital center. PATIENTS: Adult patients submitted to stapes surgery due to otosclerosis from January 2017 to December 2022. INTERVENTION: Evaluation of different radiological classifications such as the VC and SFC. MAIN OUTCOME MEASURES: Preoperative and postoperative pure-tone audiometric data, outcomes of stapes surgery success (closure of the ABG, rates of AC threshold less than or equal to 30 dB), and postoperative sensorineural hearing loss. RESULTS: A total of 87 patients and 97 operated ears were included. The SFC was associated with preoperative BC (p = 0.041) and AC (p = 0.018) and postoperative BC (p = 0.026) with an increase in thresholds with higher radiological stages. The VC was associated with postoperative AC (p = 0.045) with an increase in AC thresholds with increasing radiological stages. Lastly, both the VC (p = 0.032) and the SFC (p = 0.023) were associated with a decrease in rates of postoperative AC thresholds ≤30 dB with higher radiological stages. CONCLUSIONS: The SFC seems to be more useful to predict preoperative AC and BC and postoperative BC. On the contrary, the VC was more useful to predict postoperative AC. Both scales were similarly associated with the rate of AC thresholds ≤30 dB.

Factors Associated to the Presence of Isthmocele Diagnosed by Pelvic Ultrasound, Magnetic Resonance Imaging or Diagnostic Hysteroscopy: A Cross-Sectional Study.

We aimed to analyze the prevalence of isthmocele and factors associated with its onset within a cohort of women with previous history of cesarean section. A cross-sectional study with 90 women assessed from 2020 to 2022. Isthmocele was a composite variable diagnosed by transvaginal ultrasound (TVUS), magnetic resonance imaging (MRI) and/or diagnostic hysteroscopy (DxHys) and were asked about clinical symptoms, sociodemographic and obstetrical history and quality of life by the WHO-QOL questionnaire. Univariate and multivariate analysis (odds ratio (OR) plus 95% confidence intervals-CI) were performed to seek factors associated with the presence of isthmocele (5% significance level).The prevalence of isthmocele after combining MRI, TVUS and DxHys was 63.3% (n = 57). Women with isthmocele presented a higher body mass index (BMI) measured during delivery (32.70 ± 6.07 vs. 28.28 ± 9.86 kg/m2;p < 0.05) than women without isthmocele. Other sociodemographic variables, obstetrical history and WHO-QOL subdomains did not differ between groups. Within women with isthmocele, the residual myometrial mantle had an average of 4.97 ± 1.57 cm. Uterine volume was higher in the isthmocele group (103.95 vs. 81.34 cm3; p = 0.08), but with no statistical difference. Multivariate analysis (logistic regression) has reported that the factors associated with isthmocele were: higher BMI during delivery (aOR = 1.26[1.07-1.49];p < 0.05); longer interpartum interval (aOR = 1.22[1.03-1.46];p = 0.02) and presence of more than two cesarean sections (aOR = 2.16[1.16-4.01];p = 0.02). We concluded that a high prevalence of isthmocele was found. Women with previous cesarean section, with higher BMI during delivery and longer interdelivery interval were risk factors for the presence of isthmocele.

Variable Structure Controller for Energy Savings in an Underwater Sensor Platform.

This paper introduces a new variable structure controller designed for depth control of an autonomous underwater sensor platform equipped with a variable buoyancy module. To that end, the prototype linear model is presented, and a finite element-based method is used to estimate one of its parameters, the hull deformation due to pressure. To manage potential internal disturbances like hull deformation or external disturbances like weight changes, a disturbance observer is developed. An analysis of the observer steady-state estimation error in relation to input disturbances and system parameter uncertainties is developed. The locations of the observer poles according to its parameters are also identified. The variable structure controller is developed, keeping energy savings in mind. The proposed controller engages when system dynamics are unfavorable, causing the vehicle to deviate from the desired reference, and disengages when dynamics are favorable, guiding the vehicle toward the target reference. A detailed analysis determines the necessary switching control actions to ensure the system reaches the desired reference. Finally, simulations are run to compare the proposed controller's performance with that of PID-based controllers recently developed in the literature, assessing dynamic response and energy consumption under various operating conditions. Both the VBM- and propeller-actuated vehicles were evaluated. The results demonstrate that the proposed controller achieves an average energy consumption reduction of 22% compared to the next most efficient PID-based controller for the VBM-actuated vehicle, though with some impact on control performance.

Image analysis for bright-field HER2 in situ hybridization: validation for clinical use.

The aim of the present study was to develop and validate a quantitative image analysis (IA) algorithm to aid pathologists in assessing bright-field HER2 in situ hybridization (ISH) tests in solid cancers. A cohort of 80 sequential cases (40 HER2-negative and 40 HER2-positive) were evaluated for HER2 gene amplification with bright-field ISH. We developed an IA algorithm using the ISH Module from HALO software to automatically quantify HER2 and CEP17 copy numbers per cell as well as the HER2/CEP17 ratio. We observed a high correlation of HER2/CEP17 ratio, an average of HER2 and CEP17 copy number per cell between visual and IA quantification (Pearson's correlation coefficient of 0.842, 0.916, and 0.765, respectively). IA was able to count from 124 cells to 47,044 cells (median of 5565 cells). The margin of error for the visual quantification of the HER2/CEP17 ratio and of the average of HER2 copy number per cell decreased from a median of 0.23 to 0.02 and from a median of 0.49 to 0.04, respectively, in IA. Curve estimation regression models showed that a minimum of 469 or 953 invasive cancer cells per case is needed to reach an average margin of error below 0.1 for the HER2/CEP17 ratio or for the average of HER2 copy number per cell, respectively. Lastly, on average, a case took 212.1 s to execute the IA, which means that it evaluates about 130 cells/s and requires 6.7 s/mm2. The concordance of the IA software with the visual scoring was 95%, with a sensitivity of 90% and a specificity of 100%. All four discordant cases were able to achieve concordant results after the region of interest adjustment. In conclusion, this validation study underscores the usefulness of IA in HER2 ISH testing, displaying excellent concordance with visual scoring and significantly reducing margins of error.

Rare earth elements and warming: Implications for adult mussel health and sperm quality.

The present study aimed to investigate the effects of europium (Eu) exposure (10 µg/L), warming (a 4 °C increase), and their combination on Mytilus galloprovincialis. Biochemical and histopathological changes in adult mussels were evaluated after a 28-day exposure period. Additionally, biochemical and physiological alterations in sperm were measured following a 30-min exposure period. The overall responses to each treatment were assessed using the Integrated Biological Response index version 2 (IBRv2). In adult mussels, warming elevated metabolism and activated glutathione S-transferases (GSTs), leading to redox imbalance and cellular damage. Europium exposure alone slightly enhanced metabolism and GSTs activity, resulting in cellular damage and histopathological injuries in digestive tubules. The combined exposure to Eu and warming was the most detrimental treatment for adults, as indicated by the highest IBRv2 value. This treatment slightly increased metabolism and uniquely elevated the activity of antioxidant enzymes, as well as GSTs and carboxylesterases. Despite these responses, they were inadequate to prevent redox imbalance, cellular damage, and histopathological injuries in digestive tubules and gills. Regarding sperm, warming reduced reactive oxygen species (ROS) production but raised lipid peroxidation levels. Sperm exposed to this treatment also increased their oxygen consumption and exhibited reduced velocity. The IBRv2 indicated that Eu was the most harmful treatment for sperm, significantly increasing ROS production and notably decreasing sperm velocity. When combined with warming, Eu elevated superoxide anion (O2-) production, lowered sperm velocity, and increased oxygen consumption. This study underscores the importance of investigating the effects of rare earth elements and their interaction with climate change-related factors.

Removal of Rare Earth Elements from complex mixtures by using manganese ferrite nanoparticles: Optimization through surface response methodology.

The crucial role of Rare Earth Elements (REEs) in the development of hi-tech in addition to their limited availability have urged countries to develop sustainable alternatives to their conventional primary sources (ore mining). Sorption technologies using magnetic materials such as spinel ferrite nanoparticles provide efficient removal of REEs from contaminated solutions and ease of separation through application of an external magnetic field. However, there is still limited knowledge available regarding the optimal operational conditions in which to use these materials, especially in complex aqueous mixtures with different REEs. In this study, we have used Surface Response Methodology (SRM) applied to MnFe2O4 nanosorbents to identify their ideal sorption conditions of pH (4-8), REEs concentration (1-5 µM) and sorbent mass (20-180 mg L-1) in a mixture of nine REEs in water samples of distinct salinity (NaCl: 0-30 g L-1). Our results indicated that high pH favored REEs sorption because of the material's surface charge, which promoted interactions with REEs ions at pH 6-8. Yttrium was the least removed element, but total removal was achieved for lowest REEs concentration using 151 mg L-1 of sorbent. High removals were also obtained for the concentration of 5 µM (100 % removal, except for Y and La). Salinity did not impair sorption significantly (<10 %), which was owed to the high sorbent mass used in those assays. An increase in sorbent mass and initial REEs concentration also promoted faster kinetics. The spinel type MnFe2O4 nanoparticles showed great promise in a realistic application, which is the next proposed step in this line of research.

New and emerging oral therapies for psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Effect of processing and formulation factors on Catalase activity in tablets.

The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity. Saccharides often act as stabilizers of proteins in formulations, yet their stabilizing ability throughout solid oral dosage processing, such as tableting, has been barely studied. This work aimed to investigate the effects of formulation and process (tableting and spray-drying) variables on catalase tablets containing dextran, mannitol, and trehalose as potential stabilizers. Non-spray-dried and spray-dried formulations were prepared and tableted (100, 200, and 400 MPa). The enzymatic activity, number of aggregates, reflecting protein aggregation and structure modifications were studied. A principal component analysis was performed to reveal underlying correlations. It was found that tableting and spray-drying had a notable negative effect on the activity and number of aggregates formed in catalase formulations. Overall, dextran and mannitol failed to preserve the catalase activity in any unit operation studied. On the other hand, trehalose was found to preserve the activity during spray-drying but not necessarily during tableting. The study demonstrated that formulation and process variables must be considered and optimized together to preserve the characteristics of catalase throughout processing.

Which dimensions of nature contact in Urban Green Spaces most significantly contribute to mental wellbeing? A multidimensional analysis in Brazilian metropolitan cities.

BACKGROUND: Urban environments pose challenges to mental health, an issue that Urban Green Spaces (UGS) can potentially mitigate. While the benefits of nature contact for mental wellbeing are recognized, a multidimensional analysis remains unexplored. PURPOSE: This study aims to fill this gap by examining the association between nature contact within UGS and mental health. It underscores the importance of considering multiple dimensions of nature engagement-such as naturalness, intensity, duration, frequency, and infrastructure-in enhancing psychological wellbeing. METHOD: A comprehensive analysis, including canonical correlation, multivariate analyses of variance, and Fisher discriminant analysis, was applied to survey data from several Brazilian metropolitan cities to assess how different aspects of nature contact influence mental health. RESULTS AND CONCLUSIONS: Findings reveal association between these dimensions and mental wellbeing indicators, highlighting the importance of a multidimensional perspective. PRACTICAL IMPLICATIONS: Results advocate for incorporating diverse aspects of nature contact in UGS design and policy-making to enhance urban dwellers' mental health. FUTURE DIRECTIONS: Further research should focus on longitudinal studies and explore the mediating effects of socio-demographic factors. Additionally, expanding research to include other developing countries will provide valuable comparative insights.