Background. In renal tubules, paracellular permeability is tightly controlled to facilitate solute absorption and urinary concentration and is regulated by tight junctions, which incorporate claudin proteins. There is very limited information confirming the localization of these proteins in the human renal cortex. Most data is inferred from mouse, bovine and rabbit studies and differences exist between mouse and other species.Methods. A survey of claudin staining was performed on human kidney cortex embedded in glycolmethacrylate resin to enhance tissue morphology and facilitate the cutting of 2 µm serial sections.Results. Claudin-2, -10 and -11 antibodies labelled renal tubular epithelial cells, correlating with Lotus tetragonolobus and N-cadherin positive proximal tubules. Claudin-3, -10, -11 and -16 antibodies strongly stained a population of tubules that were positive for Tamm Horsfall protein on adjacent sections, confirming expression in the thick ascending limb of the Loop of Henle. Claudin-3, -4 and -8 antibodies reacted with tubules that correlated with the distal nephron markers, E-cadherin, epithelial membrane antigen and Dolichos biflorus and claudin-3, -4, -7 and -8 with the distal tubule marker, calbindin, and the collecting duct marker, aquaporin-2. Claudin-14 was localized in distal convoluted tubules, correlating positively with calbindin but negatively with aquaporin-2, whereas claudin-1 staining was identified in the parietal epithelium of Bowman's capsule, distal convoluted tubule and collecting duct. Cellular and tight junction localization of claudin staining in renal tubules was heterogeneous and is discussed.Conclusions. Complex variation in the expression of human claudins likely determines paracellular permeability in the kidney. Altered claudin expression may influence pathologies involving abnormalities of absorption.

Cardiac remodeling and hypertrophy are the pathological consequences of cardiovascular disease and are correlated with its associated mortality. Activity of the transcription factor NF-κB is increased in the diseased heart; however, our present understanding of how the individual subunits contribute to cardiovascular disease is limited. We assign a new role for the c-Rel subunit as a stimulator of cardiac hypertrophy and fibrosis. We discovered that c-Rel-deficient mice have smaller hearts at birth, as well as during adulthood, and are protected from developing cardiac hypertrophy and fibrosis after chronic angiotensin infusion. Results of both gene expression and cross-linked chromatin immunoprecipitation assay analyses identified transcriptional activators of hypertrophy, myocyte enhancer family, Gata4, and Tbx proteins as Rel gene targets. We suggest that the p50 subunit could limit the prohypertrophic actions of c-Rel in the normal heart, because p50 overexpression in H9c2 cells repressed c-Rel levels and the absence of cardiac p50 was associated with increases in both c-Rel levels and cardiac hypertrophy. We report for the first time that c-Rel is highly expressed and confined to the nuclei of diseased adult human hearts but is restricted to the cytoplasm of normal cardiac tissues. We conclude that c-Rel-dependent signaling is critical for both cardiac remodeling and hypertrophy. Targeting its activities could offer a novel therapeutic strategy to limit the effects of cardiac disease.

Although the population of younger drivers has decreased over recent decades, their crash rates have increased. Research has associated their higher crash rates with societal influences and youthful behavior. Research was conducted to identify the specific driving maneuvers of which unsuccessful undertaking results in specific types of crashes involving younger drivers. Four types of crashes were identified as the most prominent for young drivers: intersection, rear end, passing, and single vehicle. The analysis was performed by examining the Kentucky crash database for the 1994-1996 period by using the quasi-induced exposure method. The results showed that for all crashes, there is a general trend of decreasing involvement with increasing age, which indicates that these drivers’ inexperience is the largest single contributor to their increased crash rates. Of significance is that for all crashes, a dramatic decrease of involvement after the first year of driving between the ages of 16 and 17 is observed. This may be indicative of a steep learning curve in the first years of driving regarding the ability to control a vehicle. Therefore, little can be done to improve this phenomenon. Increasing awareness among young drivers about these issues and their likely crash involvement appears to be the only viable approach. However, preliminary efforts from the graduated license program show that some trends have been reduced, indicating a possible influence on the crash rates of young drivers.

Unmanned aerial systems (UASs) and unmanned aerial vehicles (UAVs) have become increasingly attractive for numerous surveying applications in civil engineering, agriculture, and many other fields. The unmanned systems and vehicles are capable of performing photogrammetric data acquisition with equipped digital cameras that allows for converting images to highly precise, georeferenced three-dimensional models. However, more studies are needed to demonstrate practical applications of UAS systems and UAVs on construction sites. In this project, UAS systems and UAVs and digital photogrammetry technology are introduced to estimate the earthwork volume of a highway extension project. The georeferenced images were processed by the photogrammetry software, Pix4Dmapper, which is a tool for converting images into an accurate and applicable three-dimensional point cloud model. Progress models were created over the course of several weeks. The volume of earth was computed by comparing the point cloud of the progress models after model processing. To ensure reliability, the accuracy of the UAS and UAV photogrammetry was verified by comparison with conventional ground survey methods and the results from different flights. The project presents the feasibility and effectiveness of using UAS systems and UAVs in estimating earthwork volumes on the basis of the results of an accuracy test and the efficiency of the survey.

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OBJECTIVE Finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease trial. We explored whether baseline HbA1c level and insulin treatment influenced outcomes. RESEARCH DESIGN AND METHODS Patients with T2D, urine albumin-to-creatinine ratio (UACR) of 30–5,000 mg/g, estimated glomerular filtration rate (eGFR) of 25 to <75 mL/min/1.73 m2, and treated with optimized renin–angiotensin system blockade were randomly assigned to receive finerenone or placebo. Efficacy outcomes included kidney (kidney failure, sustained decrease ≥40% in eGFR from baseline, or renal death) and cardiovascular (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) composite endpoints. Patients were analyzed by baseline insulin use and by baseline HbA1c <7.5% (58 mmol/mol) or ≥7.5%. RESULTS Of 5,674 patients, 3,637 (64.1%) received insulin at baseline. Overall, 5,663 patients were included in the analysis for HbA1c; 2,794 (49.3%) had baseline HbA1c <7.5% (58 mmol/mol). Finerenone significantly reduced risk of the kidney composite outcome independent of baseline HbA1c level and insulin use (Pinteraction = 0.41 and 0.56, respectively). Cardiovascular composite outcome incidence was reduced with finerenone irrespective of baseline HbA1c level and insulin use (Pinteraction = 0.70 and 0.33, respectively). Although baseline HbA1c level did not affect kidney event risk, cardiovascular risk increased with higher HbA1c level. UACR reduction was consistent across subgroups. Adverse events were similar between groups regardless of baseline HbA1c level and insulin use; few finerenone-treated patients discontinued treatment because of hyperkalemia. CONCLUSIONS Finerenone reduces kidney and cardiovascular outcome risk in patients with CKD and T2D, and risks appear consistent irrespective of HbA1c levels or insulin use.

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