Implications of environmental nanoparticles on neurodegeneration.

The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications-especially in enhancing drug transport across the blood-brain barrier-these particles also introduce possible hazards due to inadvertent exposure. This concise review explores the paradoxical nature of nanoparticles, emphasizing their promising applications in healthcare juxtaposed with their potential neurotoxic consequences. Through a detailed examination, we delineate the pathways through which nanoparticles can reach the brain and the subsequent health implications. There is growing evidence of a disturbing association between nanoparticle exposure and the onset of neurodegenerative conditions, highlighting the imperative for comprehensive research and strategic interventions. Gaining a deep understanding of these mechanisms and enacting protective policies are crucial steps toward reducing the health threats of nanoparticles, thereby maximizing their therapeutic advantages.

Support Networks for Exclusive Breastfeeding (SNEB). A conceptual approach and characterization in Mexico.

BACKGROUND: This study focuses on the conceptualization and graphical characterization of Exclusive Breastfeeding Support Networks (EBSN) in Mexico. METHODS: Through a sample design stratified by federal entity with state significance at 95%, a questionnaire was administered online via Microsoft Forms to a representative sample of 2989 women whose primiparity occurred in Mexico. The questionnaire primarily focused on sociodemographic data of the mothers and the structure of their EBSNs during primiparity. RESULTS: In this work, EBSNs are defined as networks mainly composed of women, whose function is to share knowledge and experiences about breastfeeding, as well as to provide emotional and physical support to breastfeeding mothers, contributing to strengthening the emotional and caregiving bonds between mothers and their newborns. CONCLUSIONS: Sankey diagrams were employed for the characterization of EBSNs, revealing that the mother of the primipara is generally the main node, resulting in a network with greater flow and reach. Conversely, when the first node is not related to the primipara, the networks tend to be smaller and with less flow.

INTRODUCCIÓN: Este estudio se centra en la conceptualización y la caracterización gráfica de las Redes de Apoyo a la Lactancia Materna Exclusiva (RALME) en México. MÉTODOS: Mediante un diseño muestral estratificado por entidad federativa con significancia estatal al 95%, se aplicó un cuestionario en línea, a través de Microsoft Forms, a una muestra representativa de 2989 mujeres cuya primiparidad fue en México. El cuestionario se enfocó principalmente en datos sociodemográficos de las madres y en la estructura de sus RALME durante la primiparidad. RESULTADOS: En este trabajo se definen las RALME como redes compuestas mayormente por mujeres, cuya función es compartir conocimientos y experiencias sobre la lactancia, así como ofrecer apoyo emocional y físico a madres lactantes, contribuyendo a fortalecer los lazos afectivos y de cuidado entre las madres y sus recién nacidos. CONCLUSIONES: Para la caracterización de las RALME se utilizó el diagrama de Sankey, revelando que la madre de la primípara es generalmente el nodo principal, lo que resulta en una red con mayor flujo y alcance. Por el contrario, cuando el primer nodo no tiene parentesco con la primípara, las redes tienden a ser más reducidas y con menor flujo.

Single-Cell Analyses Offer Insights into the Different Remodeling Programs of Arteries and Veins.

Arteries and veins develop different types of occlusive diseases and respond differently to injury. The biological reasons for this discrepancy are not well understood, which is a limiting factor for the development of vein-targeted therapies. This study contrasts human peripheral arteries and veins at the single-cell level, with a focus on cell populations with remodeling potential. Upper arm arteries (brachial) and veins (basilic/cephalic) from 30 organ donors were compared using a combination of bulk and single-cell RNA sequencing, proteomics, flow cytometry, and histology. The cellular atlases of six arteries and veins demonstrated a 7.8× higher proportion of contractile smooth muscle cells (SMCs) in arteries and a trend toward more modulated SMCs. In contrast, veins showed a higher abundance of endothelial cells, pericytes, and macrophages, as well as an increasing trend in fibroblasts. Activated fibroblasts had similar proportions in both types of vessels but with significant differences in gene expression. Modulated SMCs and activated fibroblasts were characterized by the upregulation of MYH10, FN1, COL8A1, and ITGA10. Activated fibroblasts also expressed F2R, POSTN, and COMP and were confirmed by F2R/CD90 flow cytometry. Activated fibroblasts from veins were the top producers of collagens among all fibroblast populations from both types of vessels. Venous fibroblasts were also highly angiogenic, proinflammatory, and hyper-responders to reactive oxygen species. Differences in wall structure further explain the significant contribution of fibroblast populations to remodeling in veins. Fibroblasts are almost exclusively located outside the external elastic lamina in arteries, while widely distributed throughout the venous wall. In line with the above, ECM-targeted proteomics confirmed a higher abundance of fibrillar collagens in veins vs. more basement ECM components in arteries. The distinct cellular compositions and transcriptional programs of reparative populations in arteries and veins may explain differences in acute and chronic wall remodeling between vessels. This information may be relevant for the development of antistenotic therapies.

A short treatment with resveratrol after a renal ischaemia-reperfusion injury prevents maladaptive repair and long-term chronic kidney disease in rats.

Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30 min (IR) or IR+RSV. The RSV treatment commenced 24 h after IRI and continued for 10 days. The rats were studied for either 10 days or 5 months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10 days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury-related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5 months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI. KEY POINTS: Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. In this study, we found that histological tubular injury persists 10 days after ischaemia-reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells. Short-term RSV intervention influenced the post-ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes. Resveratrol effectively prevented AKI-to-CKD transition even 5 months after the intervention. The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI-to-CKD transition.

Dissecting the complex genetic basis of pre- and post-harvest traits in Vitis vinifera L. using genome-wide association studies.

Addressing the pressing challenges in agriculture necessitates swift advancements in breeding programs, particularly for perennial crops like grapevines. Moving beyond the traditional biparental quantitative trait loci (QTL) mapping, we conducted a genome-wide association study (GWAS) encompassing 588 Vitis vinifera L. cultivars from a Chilean breeding program, spanning three seasons and testing 13 key yield-related traits. A strong candidate gene, Vitvi11g000454, located on chromosome 11 and related to plant response to biotic and abiotic stresses through jasmonic acid signaling, was associated with berry width and holds potential for enhancing berry size in grape breeding. We also mapped novel QTL associated with post-harvest traits across chromosomes 2, 4, 9, 11, 15, 18, and 19, broadening our grasp on the genetic intricacies dictating fruit post-harvest behavior, including decay, shriveling, and weight loss. Leveraging gene ontology annotations, we drew parallels between traits and scrutinized candidate genes, laying a robust groundwork for future trait-feature identification endeavors in plant breeding. We also highlighted the importance of carefully considering the choice of the response variable in GWAS analyses, as the use of best linear unbiased estimators (BLUEs) corrections in our study may have led to the suppression of some common QTL in grapevine traits. Our results underscore the imperative of pioneering non-destructive evaluation techniques for long-term conservation traits, offering grape breeders and cultivators insights to improve post-harvest table grape quality and minimize waste.

Transient inhibition of sodium-glucose cotransporter 2 after ischemia/reperfusion injury ameliorates chronic kidney disease.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin (Dapa), exhibited nephroprotective effects in patients with chronic kidney disease (CKD). We assessed the efficacy of short-term Dapa administration following acute kidney injury (AKI) in preventing CKD. Male Wistar rats were randomly assigned to Sham surgery, bilateral ischemia for 30 minutes (abbreviated as IR), and IR + Dapa groups. Daily treatment with Dapa was initiated just 24 hours after IR and maintained for only 10 days. Initially, rats were euthanized at this point to study early renal repair. After severe AKI, Dapa promptly restored creatinine clearance (CrCl) and significantly reduced renal vascular resistance compared with the IR group. Furthermore, Dapa effectively reversed the mitochondrial abnormalities, including increased fission, altered mitophagy, metabolic dysfunction, and proapoptotic signaling. To study this earlier, another set of rats was studied just 5 days after AKI. Despite persistent renal dysfunction, our data reveal a degree of mitochondrial protection. Remarkably, a 10-day treatment with Dapa demonstrated effectiveness in preventing CKD transition in an independent cohort monitored for 5 months after AKI. This was evidenced by improvements in proteinuria, CrCl, glomerulosclerosis, and fibrosis. Our findings underscore the potential of Dapa in preventing maladaptive repair following AKI, emphasizing the crucial role of early intervention in mitigating AKI long-term consequences.

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Artificial intelligence: ChatGPT as a disruptive didactic strategy in dental education.

PURPOSE: To evaluate the influence of ChatGPT on academic tasks performed by undergraduate dental students. METHOD: Fifty-five participants completed scientific writing assignments. First, ChatGPT was utilized; subsequently, a conventional method involving the search of scientific articles was employed. Each task was preceded by a 30-min training session. The assignments were reviewed by professors, and an anonymous questionnaire was administered to the students regarding the usefulness of ChatGPT. Data were analyzed by Mann-Whitney U-test. RESULTS: Final scores and scores for the criteria of utilization of evidence, evaluation of arguments, and generation of alternatives achieved higher values through the traditional method than with ChatGPT (p = 0.019, 0.042, 0.017, and <0.001, respectively). No differences were found between the two methods for the remaining criteria (p > 0.05). A total of 64.29% of the students found ChatGPT useful, 33.33% found it very useful, and 3.38% not very useful. Regarding its application in further academic activities, 54.76% considered it useful, 40.48% found it very useful, and 4.76% not very useful. A total of 61.90% of the participants indicated that ChatGPT contributed to over 25% of their productivity, while 11.9% perceived it contributed to less than 15%. Concerning the relevance of having known ChatGPT for academic tasks, 50% found it opportune, 45.24% found it very opportune, 2.38% were unsure, and the same percentage thought it is inopportune. All students provided positive feedback. CONCLUSION: Dental students highly valued the experience of using ChatGPT for academic tasks. Nonetheless, the traditional method of searching for scientific articles yield higher scores.

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis.

The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking.

Erythrocyte Vulnerability to Airborne Nanopollutants.

The toxicological impact of airborne polluting ultrafine particles (UFPs, also classified as nanoparticles with average sizes of less than 100 nm) is an emerging area of research pursuing a better understanding of the health hazards they pose to humans and other organisms. Hemolytic activity is a toxicity parameter that can be assessed quickly and easily to establish part of a nanoparticle's behavior once it reaches our circulatory system. However, it is exceedingly difficult to determine to what extent each of the nanoparticles present in the air is responsible for the detrimental effects exhibited. At the same time, current hemolytic assessment methodologies pose a series of limitations for the interpretation of results. An alternative is to synthesize nanoparticles that model selected typical types of UFPs in air pollution and evaluate their individual contributions to adverse health effects under a clinical assay of osmotic fragility. Here, we discuss evidence pointing out that the absence of hemolysis is not always a synonym for safety; exposure to model nanopollutants, even at low concentrations, is enough to increase erythrocyte susceptibility and dysfunction. A modified osmotic fragility assay in combination with a morphological inspection of the nanopollutant-erythrocyte interaction allows a richer interpretation of the exposure outcomes. Membrane-nanoparticle interplay has a leading role in the vulnerability observed. Therefore, future research in this line of work should pay special attention to the evaluation of the mechanisms that cause membrane damage.

Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria.

BACKGROUND: Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. MAIN BODY: Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. CONCLUSION: Universal screening could be an option to address the problem of underdiagnosis.

Co-Circulation of Multiple Coronavirus Genera and Subgenera during an Epizootic of Lethal Respiratory Disease in Newborn Alpacas (Vicugna pacos) in Peru: First Report of Bat-like Coronaviruses in Alpacas.

Coronaviruses (CoVs) infect a wide range of hosts, including humans, domestic animals, and wildlife, typically causing mild-to-severe respiratory or enteric disease. The main objective of this study was to identify CoV genera and subgenera detected in Peruvian alpacas. Lung lavage specimens were collected from 32 animals aged 1 to 6 weeks. CoVs were identified by using RT-PCR to amplify a pan-CoV conserved region of the RNA-dependent RNA polymerase-encoding gene. A nested PCR was performed to identify ß-CoVs. Then, ß-CoV-positive samples were subjected to RT-PCR using specific primers to identify the Embecovirus subgenus. Out of 32 analyzed samples, 30 (93.8%) tested positive for at least one CoV genus. ß-, α-, or unclassified CoVs were identified in 24 (80%), 1 (3.3%), and 1 (3.3%) of the positive samples, respectively. A CoV genus could not be identified in two (6.7%) samples. A mixture of different CoV genera was detected in two (6.7%) samples: one was co-infected with ß- and α-CoVs, and the other contained a ß- and an unclassified CoV. A sequence analysis of the amplicons generated by the PCR identified 17 ß-CoV strains belonging to the subgenus Embecovirus and two α-CoV strains belonging to Decacovirus. A phylogenetic analysis of two strains revealed a relationship with an unclassified Megaderma BatCoV strain. A subgenus could not be identified in nine ß-CoV samples. Our data show a high prevalence and a high genetic diversity of CoV genera and subgenera that infect alpacas, in which the ß-CoV subgenus Embecovirus predominated. Our data also suggest a new role for bats in the dissemination and transmission of uncommon CoVs to alpacas raised in rural Peru.

Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1ß, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.

Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria.

INTRODUCTION: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. METHODS: We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. RESULTS: A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)). CONCLUSIONS: The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Delimitation and species discovery in the Profundulidae fish family: Using genetic, environmental and morphologic data to address taxonomic uncertainty.

The family Profundulidae includes some one of the most enigmatic freshwater fishes of Mesoamerica: despite many attempts, a robust phylogenetic framework to delimit species is lacking, mainly due to limited morphological variation within the group. The accumulation of molecular data of profundulid fishes has led to advances in the description of new taxa, but relatively less progress has been made estimating evolutionary and phylogenetic relationships for this fish family. Here, we adopt an integrative taxonomy approach including the use of nuclear and mitochondrial DNA sequences, morphometric and ecological data, to test species boundaries in profundulid fishes in the westernmost area of their known distribution range in the states of Guerrero and Oaxaca, Mexico. Using a combination of methods for species discovery and validation based on Bayesian gene tree topologies, our analyses support the delimitation of 15 valid species of profundulid fishes - a combination of previously described species validated by this study, the synonymy of unsupported taxa, and the description of two new species. Using species delimitation methods, examination of phenotypic variation, and ecological niche characterization, we also identify five potentially new lineages which require further evidence to be erected as new species. We demonstrate that the use of an integrative taxonomy approach provides a robust methodology to delimit species in a taxonomically complex group like Profundulidae. Accurate taxonomic and ecological information is crucial for the conservation of these microendemic fishes, as several species are endangered.

SerpinA3K Deficiency Reduces Oxidative Stress in Acute Kidney Injury.

We previously showed that SerpinA3K is present in urine from rats and humans with acute kidney injury (AKI) and chronic kidney disease (CKD). However, the specific role of SerpinA3K during renal pathophysiology is unknown. To begin to understand the role of SerpinA3K on AKI, SerpinA3K-deficient (KOSA3) mice were studied 24 h after inducing ischemia/reperfusion (I/R) and compared to wild type (WT) mice. Four groups were studied: WT+S, WT+IR, KOSA3+S, and KOSA3+IR. As expected, I/R increased serum creatinine and BUN, with a GFR reduction in both genotypes; however, renal dysfunction was ameliorated in the KOSA3+IR group. Interestingly, the increase in UH2O2 induced by I/R was not equally seen in the KOSA3+IR group, an effect that was associated with the preservation of antioxidant enzymes' mRNA levels. Additionally, FOXO3 expression was initially greater in the KOSA3 than in the WT group. Moreover, the increase in BAX protein level and the decrease in Hif1a and Vegfa induced by I/R were not observed in the KOSA3+IR group, suggesting that these animals have better cellular responses to hypoxic injury. Our findings suggest that SerpinA3K is involved in the renal oxidant response, HIF1α/VEGF pathway, and cell apoptosis.

Would Climate Change Influence the Potential Distribution and Ecological Niche of Bluetongue Virus and Its Main Vector in Peru?

Bluetongue virus (BTV) is an arbovirus that is transmitted between domestic and wild ruminants by Culicoides spp. Its worldwide distribution depends on competent vectors and suitable environmental ecosystems that are becoming affected by climate change. Therefore, we evaluated whether climate change would influence the potential distribution and ecological niche of BTV and Culicoides insignis in Peru. Here, we analyzed BTV (n = 145) and C. insignis (n = 22) occurrence records under two shared socioeconomic pathway scenarios (SSP126 and SSP585) with five primary general circulation models (GCMs) using the kuenm R package v.1.1.9. Then, we obtained binary presence-absence maps and represented the risk of transmission of BTV and niche overlapping. The niche model approach showed that north and east Peru presented suitability in the current climate scenario and they would have a decreased risk of BTV, whilst its vector would be stable and expand with high agreement for the five GCMs. In addition, its niche overlap showed that the two niches almost overlap at present and would completely overlap with one another in future climate scenarios. These findings might be used to determine the areas of highest priority for entomological and virological investigations and surveillance in order to control and prevent bluetongue infections in Peru.

The Transcriptomics of the Human Vein Transformation After Arteriovenous Fistula Anastomosis Uncovers Layer-Specific Remodeling and Hallmarks of Maturation Failure.

Introduction: The molecular transformation of the human preaccess vein after arteriovenous fistula (AVF) creation is poorly understood. This limits our ability to design efficacious therapies to improve maturation outcomes. Methods: Bulk RNA sequencing (RNA-seq) followed by paired bioinformatic analyses and validation assays were performed in 76 longitudinal vascular biopsies (veins and AVFs) from 38 patients with stage 5 chronic kidney disease or end-stage kidney disease undergoing surgeries for 2-stage AVF creation (19 matured, 19 failed). Results: A total of 3637 transcripts were differentially expressed between veins and AVFs independent of maturation outcomes, with 80% upregulated in fistulas. The postoperative transcriptome demonstrated transcriptional activation of basement membrane and interstitial extracellular matrix (ECM) components, including preexisting and novel collagens, proteoglycans, hemostasis factors, and angiogenesis regulators. A postoperative intramural cytokine storm involved >80 chemokines, interleukins, and growth factors. Postoperative changes in ECM expression were differentially distributed in the AVF wall, with proteoglycans and fibrillar collagens predominantly found in the intima and media, respectively. Interestingly, upregulated matrisome genes were enough to make a crude separation of AVFs that failed from those with successful maturation. We identified 102 differentially expressed genes (DEGs) in association with AVF maturation failure, including upregulation of network collagen VIII in medial smooth muscle cells (SMCs) and downregulation of endothelial-predominant transcripts and ECM regulators. Conclusion: This work delineates the molecular changes that characterize venous remodeling after AVF creation and those relevant to maturation failure. We provide an essential framework to streamline translational models and our search for antistenotic therapies.

Periadventitial ß-aminopropionitrile-loaded nanofibers reduce fibrosis and improve arteriovenous fistula remodeling in rats.

Background: Arteriovenous fistula (AVF) postoperative stenosis is a persistent healthcare problem for hemodialysis patients. We have previously demonstrated that fibrotic remodeling contributes to AVF non-maturation and lysyl oxidase (LOX) is upregulated in failed AVFs compared to matured. Herein, we developed a nanofiber scaffold for the periadventitial delivery of ß-aminopropionitrile (BAPN) to determine whether unidirectional periadventitial LOX inhibition is a suitable strategy to promote adaptive AVF remodeling in a rat model of AVF remodeling. Methods: Bilayer poly (lactic acid) ([PLA)-]- poly (lactic-co-glycolic acid) ([PLGA)] scaffolds were fabricated with using a two-step electrospinning process to confer directionality. BAPN-loaded and vehicle control scaffolds were wrapped around the venous limb of a rat femoral-epigastric AVF during surgery. AVF patency and lumen diameter were followed monitored using Doppler ultrasound surveillance and flow was measured before euthanasia. AVFs were harvested after 21 days for histomorphometry and immunohistochemistry. AVF compliance was measured using pressure myography. RNA from AVF veins was sequenced to analyze changes in gene expression due to LOX inhibition. Results: Bilayer periadventitial nanofiber scaffolds extended BAPN release compared to the monolayer design (p < 0.005) and only released BAPN in one direction. Periadventitial LOX inhibition led to significant increases in AVF dilation and flow after 21 days. Histologically, BAPN trended toward increased lumen and significantly reduced fibrosis compared to control scaffolds (p < 0.01). Periadventitial BAPN reduced downregulated markers associated with myofibroblast differentiation including SMA, FSP-1, LOX, and TGF-ß while increasing the contractile marker MYH11. RNA sequencing revealed differential expression of matrisome genes. Conclusion: Periadventitial BAPN treatment reduces fibrosis and promotes AVF compliance. Interestingly, the inhibition of LOX leads to increased accumulation of contractile VSMC while reducing myofibroblast-like cells. Periadventitial LOX inhibition alters the matrisome to improve AVF vascular remodeling.