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Background Total serum 25-hydroxyvitamin D [25(OH)D] is considered the best marker of vitamin D status and used routinely in clinical practice. However, 25(OH)D is predominantly bound to vitamin D-binding protein (VDBP), and it has been reported that the free-25(OH)D and 25(OH)D loosely bound to albumin fraction correlates better with clinical outcomes. Methods We assessed total-25(OH)D, measured free-25(OH)D, and calculated free-25(OH)D and their relationship with VDBP and biomarkers of mineral metabolism in 61 children (22 CKD 2–3, 18 dialysis, and 21 post-transplant). Results Total-25(OH)D concentrations were comparable across the three groups (p = 0.09), but free- and bioavailable-25(OH)D (free- and albumin-25(OH)D) were significantly lower in the transplant group (both: p = 0.01). Compared to CKD and dialysis patients, the transplant group had significantly higher VDBP concentrations (p = 0.03). In all three groups, total-25(OH)D concentrations were positively associated with measured free-, calculated free-, and bioavailable-25(OH)D. Multivariable regression analysis showed that total-25(OH)D was the only predictor of measured free-25(OH)D concentrations in the dialysis group (β = 0.9; R2 = 90%). In the transplant group, measured free-25(OH)D concentrations were predicted by both total-25(OH)D and VDBP concentrations (β = 0.6, − 0.6, respectively; R2 = 80%). Correlations between parathyroid hormone with total-25(OH)D and measured and calculated free-25(OH)D were only observed in the transplant group (all: p Conclusions In transplanted patients, VDBP concentrations were significantly higher compared to CKD and dialysis patients, and consequently, free-25(OH)D concentrations were lower, despite a comparable total-25(OH)D concentration. We suggest that free-25(OH)D measures may be required in children with CKD, dialysis, and transplant, with further research required to understand its association with markers of mineral metabolism.

The octanol–water partition coefficients (Kow) of the aristolochic acids, AA I and AA II, were determined using the traditional shake-flask method as a function of pH and ionic strength. These compounds have been implicated in the etiology of Balkan endemic nephropathy, but evidence of a plausible exposure pathway remains elusive, and research is constrained by the absence of critical physical–chemical parameters on these compounds. Apparent Kow values were determined across a range of pH and ionic strength conditions. The results show that the apparent Kow decreased by approximately four orders of magnitude as pH increased from 2 to 9. The pH dependence was well described by a simple model that calculated the apparent Kow based on the ionization fractions and intrinsic Kow values for the neutral and ionized species. Higher ionic strength solutions resulted in higher Kow values at high pH, but had no effect at low pH. These results suggest that transport of aristolochic acids will be highly dependent on pH and ionic strength, with significant aqueous-phase transport at neutral to slightly alkaline conditions, with the highest mobility occurring under low ionic strength conditions, and the possibility of significant partitioning to nonpolar phases, such as soil organic matter or plant material, at low pH. Much of the region where BEN is prevalent is a karst environment, and pH values are generally above 8, thus leaching and groundwater transport are favored, which can suggest possible exposure routes.

The kidney contains a network of lymphatic vessels that clear fluid, small molecules, and cells from the renal interstitium. Through modulating immune responses and via crosstalk with surrounding renal cells, lymphatic vessels have been implicated in the progression and maintenance of kidney disease. In this Review, we provide an overview of the development, structure, and function of lymphatic vessels in the healthy adult kidney. We then highlight the contributions of lymphatic vessels to multiple forms of renal pathology, emphasizing CKD, transplant rejection, and polycystic kidney disease and discuss strategies to target renal lymphatics using genetic and pharmacologic approaches. Overall, we argue the case for lymphatics playing a fundamental role in renal physiology and pathology and treatments modulating these vessels having therapeutic potential across the spectrum of kidney disease.

Gaining insight into different cell behaviors is key to better understanding different pathologies. These behaviors may be explained in part through close observation of 3D cell morphology. Therefore, the objective of this research was to develop a machine learning (ML) framework that can predict 3D subcellular morphological variation of endothelial cells (ECs) to generate digital twins. ECs were cultured and their membrane, nucleus, and focal adhesion (FA) sites were stained and imaged with confocal microscopy. The multicellular confocal z stacks were segmented resulting in a total of 60 single-cell stacks. Fifty randomly picked cells were augmented 20-fold to train the ML framework, and the remaining 10 were used for an independent test of prediction accuracy. The ML framework was based on an open-source conditional generative adversarial network (cGAN), which was expanded to make 3D predictions using membrane only as input to predict nucleus and FA morphology. After training the framework, the results on the independent test showed an average prediction accuracy of ~87% for nucleus and ~70% for FA sites. The predictions were used to build a digital twin of each EC and compared to their respective ground truth, showing an average ~79% global accuracy and ~84% accuracy in FA-Nucleus distribution. The results presented show the effectiveness of the developed ML framework to generate digital twins of ECs using limited amount of data. These digital twins can be used to couple EC morphology with different behaviors. The ML framework can be potentially expanded to predict morphology of other subcellular structures as well as to study other types of cells.

Urban settlements are rapidly growing outward and upward, with consequences for resource use, greenhouse gas emissions, and ecosystem and public health, but rates of change are uneven around the world. Understanding trajectories and predicting consequences of global urban expansion requires quantifying rates of change with consistent, well-calibrated data. Microwave backscatter data provides important information on upward urban growth – essentially the vertical built-up area. We developed a multi-sensor, multi-decadal, gridded (0.05° lat/lon) data set of global urban microwave backscatter, 1993–2020. Comparison of backscatter from two C-band sensors (ERS and ASCAT) and one Ku-band sensor (QuikSCAT) are made at four invariant non-urban sites (~3500 km2) to evaluate instrument stability and multi-decadal pattern. For urban areas, there was a strong linear correlation (overall R2 = 0.69) between 2015 ASCAT urban backscatter and a continental-scale gridded product of building volume, across 8450 urban grid cells (0.05° × 0.05°) in Europe, China, and the USA. This urban backscatter data set provides a time series characterizing global urban change over the past three decades.

Basement membranes (BMs) are complex macromolecular networks underlying all continuous layers of cells. Essential components include collagen IV and laminins, which are affected by human genetic variants leading to a range of debilitating conditions including kidney, muscle, and cerebrovascular phenotypes. We investigated the dynamics of BM assembly in human pluripotent stem cell-derived kidney organoids. We resolved their global BM composition and discovered a conserved temporal sequence in BM assembly that paralleled mammalian fetal kidneys. We identified the emergence of key BM isoforms, which were altered by a pathogenic variant in COL4A5. Integrating organoid, fetal, and adult kidney proteomes, we found dynamic regulation of BM composition through development to adulthood, and with single-cell transcriptomic analysis we mapped the cellular origins of BM components. Overall, we define the complex and dynamic nature of kidney organoid BM assembly and provide a platform for understanding its wider relevance in human development and disease.

Riccardia fuscovirens Lindb. is lectotypified and the lectotype is described. It is morphologically very similar to Aneura pinguis and provisionally regarded as synonym to it.

Here, we present a study of the phenomena of decayless kink oscillations in a system of active-region (AR) coronal loops. Using high-resolution observations from two different instruments, namely the Extreme Ultraviolet Imager (EUI) on board Solar Orbiter and the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory, we follow these AR loops for an hour each on three consecutive days. Our results show significantly more resolved decayless waves in the higher resolution EUI data compared with the AIA data. Furthermore, the same system of loops exhibits many of these decayless oscillations on Day 2, while we detect very few oscillations on Day 3 , and find none at all on Day 1. Analysis of photospheric magnetic field data reveals that, most of the time, these loops were rooted in sunspots, where supergranular flows are generally absent. This suggests that supergranular flows, which are often invoked as drivers of decayless waves, are not necessarily driving such oscillations in our observations. Similarly, our findings also cast doubt on other possible drivers of these waves, such as a transient driver or mode conversion of longitudinal waves near the loop footpoints. In conclusion, our analysis suggests that none of the commonly suspected sources proposed to drive decayless oscillations in active-region loops seem to be operating in this event, and therefore the search for that elusive wave driver needs to continue., Astronomy & Astrophysics, 666, ISSN:0004-6361, ISSN:1432-0746

Background: Greater trochanteric pain syndrome (GTPS) is a debilitating chronic condition, most prevalent in postmenopausal women. A positive association between high estrogen levels and tendon health may exist, and postmenopausal women have reduced estrogen. Menopausal hormone therapy (MHT) may reduce the incidence of tendon abnormality, particularly when combined with exercise. Purpose: To determine the effect of MHT and exercise on tendon pain and function in postmenopausal women with GTPS. Study Design: Randomized controlled clinical trial; Level of evidence, 1. Methods: Postmenopausal women (N = 132; n = 12, lost to follow-up) with GTPS were randomized into MHT and placebo transdermal cream groups combined with tendon-specific or sham exercise. All groups received education about avoiding gluteal tendon compression and load management throughout 12 weeks of intervention. The primary outcome was the Victorian Institute of Sport Assessment for gluteal tendinopathy (VISA-G), and secondary outcomes were measured at baseline and at 12 and 52 weeks. The Global Rating of Change was assessed at 12 and 52 weeks. A linear mixed-effects model was used to assess differences. Body mass index (BMI) was included as a covariate. Results: All participant groups improved over time (baseline vs 12 weeks, P < .001; baseline vs 52 weeks, P < .001). There was no difference among exercise groups measured by all outcomes (VISA-G: baseline, P = .97, mean difference [MD] = 0.10; 12 weeks, P = .49, MD = 2.15; 52 weeks, P = .32, MD = −3.08). There was a significant interaction effect between cream and BMI; therefore, the population was stratified by BMI levels (Conclusion: MHT or placebo combined with tendon-specific or sham exercise plus education reduced pain and increased function for this population. For women with a BMI Registration: ACTRN12614001157662 (Australian New Zealand Clinical Trials Registry).