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Background and Objective: In acute kidney injury (AKI), a strong inflammatory component is activated in response to the renal damage, and one of the main mediators behind this process is the pro-inflammatory interleukin 6 or IL-6. Beside to this phenomenon, there are also alterations in different components of mineral metabolism, such as those dependent on fibroblast growth factor (FGF)23 and the anti-ageing cofactor klotho. The aim of this work was to explore the association between renal function and systemic levels of IL-6, as well as FGF23 and klotho in the early stages of AKI, analysing the predictive capacity of IL-6 in early mortality associated with AKI., Material and Methods: Plasma levels of IL-6, klotho and FGF23 were analysed in samples from 28 patients with AKI and related to renal function on hospital admission, and after 24 and 72 h. In addition, the predictive capacity of IL-6 on AKI-associated mortality was analysed at the three study time points. In an experimental nephrotoxic -AKI mouse model, systemic IL-6 and FGF23 values were also analysed 24 and 72 h after induction of kidney damage, as well as in mice overexpressing the anti-ageing protein, klotho., Results: Systemic IL-6 levels increased in AKI patients, especially in hospital admission time, and decreased in parallel with improving renal function. At the same time as IL-6 values increased, there was an increase in FGF23 and a decrease in klotho levels, with a significant and positive correlation between IL-6 and FGF23 levels. In addition, we obtained that systemic IL-6 levels were a good predictor of mortality in these patients, with an area under the curve equal to one at 72 h after AKI. In the experimental mouse AKI model, we also observed an increase in plasma levels in both IL-6 and FGF23 after 24 h of kidney damage. Nevertheless, in transgenic mice overexpressing klotho, there was no such increase in any of them., Conclusions: There is an association between renal damage and increased levels of IL-6 and FGF23 in patients with AKI, especially on hospital admission time. Moreover, IL-6 levels are able to predict mortality in these patients, being a promising prognostic biomarker at any study time with a strong prediction at 72 h after patient admission. Maintaining adequate klotho levels could prevent the IL-6 mediated inflammatory response and therefore also reduce the degree and severity of renal damage after AKI., Competing Interests: Declaration of competing interest The authors of this paper have no conflicts of interest to declare., (Copyright © 2024 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1-326.5) per 10,000 person-years. In the nested case-control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73-0.99 and AOR = 0.89; 95%CI: 0.74-1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56-0.94 and AOR = 0.64; 95%CI: 0.46-0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.

Background: Current definition of chronic kidney disease (CKD) identifies only advanced stages, but effective management demands early detection. Urinary albumin-to-creatinine ratio (ACR) 30 mg/g is a cut-off point for CKD clinical diagnosis. Patients with lower values (normoalbuminuria) and eGFR > 60 mL/min/1.73 m 2 are considered at no increased cardiorenal risk. However, higher incidence of renal function decline and cardiovascular events have been shown within the normoalbuminuria range. Novel subclinical indicators may help to identify higher-risk patients. Urinary extracellular vesicles (uEVs) are sentinels of renal function non-invasively. Here we aimed to approach the early assessment of cardiorenal risk by investigating the protein cargo of uEVs., Methods: Hypertensive patients were classified in control group (C) with ACR < 10 mg/g, and high-normal group (HN) with ACR 10-30 mg/g. Isolated uEVs were characterized by western blotting and electron microscopy and the protein cargo was analyzed by untargeted proteomics (LC-MS/MS) in a first discovery cohort. Protein confirmation was performed in a different cohort by ExoView. Immunohistochemistry of human kidney biopsies was also performed to evaluate the potential of uEVs to reflect renal damage., Results: HN albuminuria does not affect the uEVs concentration, size, or tetraspanin profile. Among >6200 uEVs proteins identified, 43 define a panel significantly altered in HN patients without variation in urine, mostly annotated in the tubule (39 out of 43). The tubular transporter long-chain fatty acid transport protein 2 (SLC27A2) and the apical membrane protein amnionless (AMN) confirmed their alteration in HN patients evidencing impaired tubular reabsorption. SLC27A2 showed tubular expression and significantly reduced levels in patients with diagnostic criteria for CKD., Conclusions: Alterations in the EV-mediated molecular profile are evident before pathological ACR levels are reached. Direct quantitation of SLC27A2 and AMN in uEVs helps identifying normoalbuminuric subjects with higher cardiorenal risk in early monitoring of CKD., Competing Interests: All the authors declared no competing interests., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Water soaking is a commercially important disorder of field-grown strawberries that is exacerbated by surface wetness and high humidity. The objective was to establish the effect of genotype on susceptibility to water soaking. Three greenhouse-grown model 'collections' were used comprising a total of 172 different genotypes: (1) a segregating F2 population, (2) a collection of strawberry cultivars and breeding clones, and (3) a collection of wild Fragaria species. A standardized immersion assay was used to induce water soaking. Potential relationships between water soaking and water uptake characteristics, depth of the achene depressions, fruit firmness, cuticle mass and strain relaxation and microcracking were investigated. Further, the effect of downregulating the polygalacturonase genes ( FaPG1 and FaPG2 ) on the susceptibility to water soaking was investigated. The collection of wild species was most susceptible to water soaking. This was followed by the collection of cultivars and breeding clones, and by the F2 population. Susceptibility to water soaking was strongly correlated with water uptake rate (mass of water, per fruit, per time). For the pooled dataset of 172 genotypes, 46% of the variability in water soaking was accounted for by the permeance of the skin to osmotic water uptake. Susceptibility to water soaking was not, or was only poorly correlated with measurements of fruit surface area or of the osmotic potential of the expressed fruit juice. The only exceptions were the wild Fragaria species which were highly variable in fruit size and also in fruit osmotic potential. For genotypes from the F2 and the wild species collections, firmer fruit were less susceptible to water soaking than softer fruit. There were no relationships between fruit firmness and susceptibility to water soaking in transgenic plants in which FaPG1 and FaPG2 were down-regulated. Susceptibility to water soaking was not related to cuticle mass per unit fruit surface area, nor to strain relaxation of the cuticle upon isolation, nor to achene position. In summary, strawberry's susceptibility to water soaking has a significant genetic component and is closely and consistently related to the skin's permeance to osmotic water uptake., Competing Interests: The authors declare that they have no competing interests. Klaus Olbricht is employed by Hansabred GmbH & Co. KG., (© 2024 Hurtado et al.)

Corrosion deterioration of materials is a major problem affecting economic, safety, and logistical issues, especially in the aeronautical sector. Detecting the correct corrosion type in metal alloys is very important to know how to mitigate the corrosion problem. Electrochemical noise (EN) is a corrosion technique used to characterize the behavior of different alloys and determine the type of corrosion in a system. The objective of this research is to characterize by EN technique different aeronautical alloys (Al, Ti, steels, and superalloys) using different analysis methods such as time domain (visual analysis, statistical), frequency domain (power spectral density (PSD)), and frequency-time domain (wavelet decomposition, Hilbert Huang analysis, and recurrence plots (RP)) related to the corrosion process. Optical microscopy (OM) is used to observe the surface of the tested samples. The alloys were exposed to 3.5 wt.% NaCl and H 2 SO 4 solutions at room temperature. The results indicate that HHT and recurrence plots are the best options for determining the corrosion type compared with the other methods due to their ability to analyze dynamic and chaotic systems, such as corrosion. Corrosion processes such as passivation and localized corrosion can be differentiated when analyzed using HHT and RP methods when a passive system presents values of determinism between 0.5 and 0.8. Also, to differentiate the passive system from the localized system, it is necessary to see the recurrence plot due to the similarity of the determinism value. Noise impedance (Z n ) is one of the best options for determining the corrosion kinetics of one system, showing that Ti CP2 and Ti-6Al-4V presented 742,824 and 939,575 Ω·cm 2 , while R n presented 271,851 and 325,751 Ω·cm 2 , being the highest when exposed to H 2 SO 4 .

Objective: Research suggests that antiimmigrant policies enacted in the United States, magnified during the 2016-2020 period, propagate widespread trauma across communities of immigrants (von Werthern et al., 2018). While these policies harm all groups of immigrants, structural conditions (e.g., lack of documentation status, race, ethnicity, country of origin, and other social and legal determinants) shape how they are experienced. To address the widespread traumatic harm inflicted by racist and xenophobic policies, a group of leaders from eight Divisions of the American Psychological Association (APA) and the National Latinx Psychological Association (NLPA) launched an Interdivisional Immigration Project (IIP)., Method: The IIP served to develop a model for collaborative advocacy, bringing together mental health providers (i.e., psychologists, social workers), allied professionals, and immigration activists from community organizations across the country. This model was developed over the course of 1 year, coinciding with the global coronavirus disease 2019 (COVID-19) pandemic and the amplified movement for racial justice., Results: This article describes the key components of the IIP collaborative advocacy model: (a) structuring leadership in a democratic and egalitarian manner, (b) centering and uplifting immigrant voices, (c) forming teams across five U.S. regions, (d) facilitating critical dialogues grounded in liberatory practices, (e) centering trauma and empowerment, and (f) developing advocacy strategies. The IIP collaborative advocacy model is informing advocacy to protect immigrants from harm., Discussion: This model may be used as the basis for ongoing humane immigration policy activism that centers the voices of community activists, and that pushes psychologists and allied professionals to use their positionality to support community-based efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Ideally, the barrier properties of a fruit's cuticle persist throughout its development. This presents a challenge for strawberry fruit, with their rapid development and thin cuticles. The objective was to establish the developmental time course of cuticle deposition in strawberry fruit., Results: Fruit mass and surface area increase rapidly, with peak growth rate coinciding with the onset of ripening. On a whole-fruit basis, the masses of cutin and wax increase but on a unit surface-area basis, they decrease. The decrease is associated with marked increases in elastic strain. The expressions of cuticle-associated genes involved in transcriptional regulation (FaSHN1, FaSHN2, FaSHN3), synthesis of cutin (FaLACS2, FaGPAT3) and wax (FaCER1, FaKCS10, FaKCR1), and those involved in transport of cutin monomers and wax constituents (FaABCG11, FaABCG32) decreased until maturity. The only exceptions were FaLACS6 and FaGPAT6 that are presumably involved in cutin synthesis, and FaCER1 involved in wax synthesis. This result was consistent across five strawberry cultivars. Strawberry cutin consists mainly of C16 and C18 monomers, plus minor amounts of C19, C20, C22 and C24 monomers, ω-hydroxy acids, dihydroxy acids, epoxy acids, primary alcohols, carboxylic acids and dicarboxylic acids. The most abundant monomer is 10,16-dihydroxyhexadecanoic acid. Waxes comprise mainly long-chain fatty acids C29 to C46, with smaller amounts of C16 to C28. Wax constituents are carboxylic acids, primary alcohols, alkanes, aldehydes, sterols and esters., Conclusion: The downregulation of cuticle deposition during development accounts for the marked cuticular strain, for the associated microcracking, and for their high susceptibility to the disorders of water soaking and cracking., (© 2024. The Author(s).)

Early diagnosis and treatment of chronic kidney disease (CKD) is a worldwide challenge. Subjects with albumin-to-creatinine ratio (ACR) ≥ 30 mg/g and preserved renal function are considered to be at no cardiorenal risk in clinical practice, but prospective clinical studies evidence increased risk, even at the high-normal (HN) ACR range (10-30 mg/g), supporting the need to identify other molecular indicators for early assessment of patients at higher risk. Following our previous studies, here we aim to stratify the normoalbuminuria range according to cardiorenal risk and identify the glycoproteins and N-glycosylation sites associated with kidney damage in subclinical CKD. Glycoproteins were analyzed in urine from hypertensive patients within the HN ACR range compared to control group (C; ACR < 10 mg/g) by mass spectrometry. A different cohort was analyzed for confirmation (ELISA) and sex perspective was evaluated. Patients' follow-up for 8 years since basal urine collection revealed higher renal function decline and ACR progression for HN patients. Differential N-glycopeptides and their N -glycosylation sites were also identified, together with their pathogenicity. N-glycosylation may condition pathological protein deregulation, and a panel of 62 glycoproteins evidenced alteration in normoalbuminuric subjects within the HN range. Haptoglobin-related protein, haptoglobin, afamin, transferrin, and immunoglobulin heavy constant gamma 1 (IGHG1) and 2 (IGHG2) showed increased levels in HN patients, pointing to disturbed iron metabolism and tubular reabsorption and supporting the tubule as a target of interest in the early progression of CKD. When analyzed separately, haptoglobin, afamin, transferrin, and IGHG2 remained significant in HN, in both women and men. At the peptide level, 172 N-glycopeptides showed differential abundance in HN patients, and 26 showed high pathogenicity, 10 of them belonging to glycoproteins that do not show variation between HN and C groups. This study highlights the value of glycosylation in subjects not meeting KDIGO criteria for CKD. The identified N-glycopeptides and glycosylation sites showed novel targets, for both the early assessment of individual cardiorenal risk and for intervention aimed at anticipating CKD progression.

Background: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning-derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP)., Methods: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used., Results: For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865; P =3.61×10 - 28 ), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited., Conclusions: The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics.

Calcific aortic valve disease (CAVD) and coronary artery disease (CAD) are related cardiovascular diseases in which common mechanisms lead to tissue calcification. Oxidative stress plays a key role in these diseases and there is also evidence that the redox state of serum albumin exerts a significant influence on these conditions. To further explore this issue, we used multimarker scores (OxyScore and AntioxyScore) to assess the global oxidative status in patients with CAVD, with and without CAD, also evaluating their plasma thiol levels. In addition, valvular interstitial cells were treated with reduced, oxidized, and native albumin to study how this protein and its modifications affect cell calcification. The differences we found suggest that oxidative status is distinct in CAVD and CAD, with differences in redox markers and thiol levels. Importantly, the in vitro interstitial cell model revealed that modified albumin affects cell calcification, accelerating this process. Hence, we show here the importance of the redox system in the development of CAVD, emphasizing the relevance of multimarker scores, while also offering evidence of how the redox state of albumin influences vascular calcification. These data highlight the relevance of understanding the overall redox processes involved in these diseases, opening the door to new studies on antioxidants as potential therapies for these patients.

Introduction: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear., Methods: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%])., Results: There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients., Conclusion: DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients., (© 2024 S. Karger AG, Basel.)