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Inherited kidney diseases (IKDs) are a large group of disorders affecting different nephron segments, many of which progress towards kidney failure due to the absence of curative therapies. With the current advances in genetic testing, the understanding of the molecular basis and pathophysiology of these disorders is increasing and reveals new potential therapeutic targets. RNA has revolutionized the world of molecular therapy and RNA-based therapeutics have started to emerge in the kidney field. To apply these therapies for inherited kidney disorders, several aspects require attention. First, the mRNA must be combined with a delivery vehicle that protects the oligonucleotides from degradation in the blood stream. Several types of delivery vehicles have been investigated, including lipid-based, peptide-based, and polymer-based ones. Currently, lipid nanoparticles are the most frequently used formulation for systemic siRNA and mRNA delivery. Second, while the glomerulus and tubules can be reached by charge- and/or size-selectivity, delivery vehicles can also be equipped with antibodies, antibody fragments, targeting peptides, carbohydrates or small molecules to actively target receptors on the proximal tubule epithelial cells, podocytes, mesangial cells or the glomerular endothelium. Furthermore, local injection strategies can circumvent the sequestration of RNA formulations in the liver and physical triggers can also enhance kidney-specific uptake. In this review, we provide an overview of current and potential future RNA-based therapies and targeting strategies that are in development for kidney diseases, with particular interest in inherited kidney disorders.
We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics.
Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF.
Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7ylic acids that associated with hyperfiltration and hyperperfusion.
ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.
ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.
Children with chronic kidney disease (CKD) and their families deal with challenging circumstances. While numerous studies have shown that both patients and parents in these families can experience a variety of challenges and concerns, the experience of siblings is less well understood. The focus of this scoping review was on research addressing the experiences and well-being of siblings of children with CKD.
Following scoping review methodology, five databases were searched for peer-reviewed research or graduate theses published in English that addressed the experience or well-being of siblings aged 25years or younger (biological, step or foster) of children with CKD; studies from any year or location were included. Two independent coders identified relevant studies. Findings were summarized and synthesized.
Of the 2990 studies identified, 19 were chosen for full text review and eight fit the inclusion criteria. Five of the selected studies were qualitative, two were quantitative and one used mixed-meth A higher resolution version of the Graphical abstract is available as Supplementary information.
Acute kidney injury (AKI) definitions incorporate baseline creatinine (Cr
) values, but Cr
are frequently unknown in pediatrics. Our primary aim was to derive and validate a novel AKI Baseline Creatinine (ABC) estimation equation and compare it to existing methods of estimating Cr
values.
We conducted a single-center retrospective analysis of pediatric patients (0-25years) admitted from 2012 to 2019. Included patients required at least one outpatient Cr
prior to hospitalization (gold standard). Novel equations were developed with demographic and initial creatinine data. Existing methods included back-calculating Cr
based on Schwartz, Full Age Spectrum (FAS), and CKiD-under-25 (U25) equations. To determine an optimal equation, we compared novel and existing equations to the gold standard.
The optimal simplified equation (ABC) included only age and had R
= 59.9% and 73.2% of values within 30% of true Cr
. The precision increased significantly when the equation included age and minimum creatini and improved standardization of pediatric AKI definitions, enhancing health services research. A higher resolution version of the Graphical abstract is available as Supplementary information.
Glucose 6 phosphate dehydrogenase deficiency (G6PDd) is the most common enzyme deficiency in humans. Randomized clinical trials comparing the efficacy of different types of fluid therapy for prevention of acute kidney injury (AKI) following hemolysis in patients with G6PDd are lacking. The present study aimed to compare the efficacy of three different types of fluid administration, isotonic saline with or without acetazolamide versus bicarbonate solution in prevention of AKI among children with acute hemolysis due to G6PDd.
In this double-blind randomized controlled clinical trial, 120 infants and children with acute hemolysis due to G6PDd were randomly divided into three groups consisting of 40 participants in each group. Group A received normal saline. Group B received normal saline plus oral acetazolamide at a dose of 5mg/kg/day, and group C received half saline plus 75mEq/L sodium bicarbonate. The primary outcome of this study was the frequency of AKI among the different types of fluid administration.
In this study, 72 (60%) patients were boys with the mean age and length of hospital stay of 3.9 ± 2.2years and 54.4 ± 29.9h, respectively. AKI as the primary outcome of this study occurred only in one patient in group C and the rate of AKI did not differ significantly among patients receiving different types of fluid resuscitation (P > 0.05).
Normal saline was equivalent to fluids containing alkalinizing agents in preventing heme-induced nephropathy in patients with G6PDd. A higher resolution version of the Graphical abstract is available as Supplementary information.
Normal saline was equivalent to fluids containing alkalinizing agents in preventing heme-induced nephropathy in patients with G6PDd. A higher resolution version of the Graphical abstract is available as Supplementary information.The predictive capabilities of some existing theoretical models to quantify thermodiffusion have been investigated in this work. To do so, the tests have been performed on two model fluids, the hard-sphere and the Lennard-Jones (including spheres and dimers) ones, exploring different mixtures and thermodynamic conditions thanks to extensive molecular simulations. It has been confirmed that the thermal diffusion factor should be expressed as the sum of one term related to the isotope effect and one term related to the "chemical" effects and that a kinetic term is required to quantify thermodiffusion from the gas state to the liquid state. In addition, regarding the isotope effects, it has been obtained that none of the available theoretical models are able to yield a reasonable prediction relatively to the molecular simulations results and that the moment of inertia contribution is one order of magnitude smaller than the mass contribution in the liquid state. Finally, concerning the chemical effects, it has been shown the Shukla and Firoozabadi model, complemented with a kinetic term, is probably the most reasonable option to estimate the chemical contribution to the thermal diffusion factor, even if it fails in capturing the effect of the asymmetry in size and in shape between the species. Overall, this works confirms that there is still a lack of a generic model able to predict accurately thermal diffusion factors, or equivalently Soret coefficient, in simple binary mixtures from the gas state to the liquid state.
To evaluate the potential of intravoxel incoherent motion (IVIM) and apparent diffusion coefficient (ADC) in the prediction of tumor grade, lymph node metastasis and pleural invasion of non-small cell lung cancer (NSCLC) before surgery.
65 patients diagnosed with NSCLC by surgery were enrolled. IVIM-DWI (10 b-values, 0-1000s/mm
) was performed before surgery. The mean and minimum ADC (ADC
, ADC
) and IVIM parameters D, D* and f were independently measured and calculated by 2 radiologists by drawing regions of interest (ROIs) including the solid component of the whole tumor. Intraclass correlation coefficients (ICCs) were analysed. Spearman analysis was used to determine the correlation between IVIM parameters and tumor differentiation. Independent sample t-tests (normal distribution) or Mann-Whitney U tests (non-normal distribution) were used to compare the differences between the parameters in moderately-well and poorly differentiated groups, with and without lymph node metastasis and pleural invasionon in NSCLC patients before surgery.The traceability of different cultivation modes is critical for ensuring the commercial viability of high-value Dendrobium officinale. In this study, by means of polarizing microscopy, SEM-EDX, ICP-MS and ICP-AES, the possibility of combining microscopic characteristics, multielemental analysis and multivariate statistical authenticity analysis was realized to determine the origins of the fresh stem and dried stem powder of D. officinale derived from three different cultivation modes from six provinces of China. The microscopic structure, chemical elements on the surface of the main microstructures and concentrations of Ca, K, Ba, Cs, As and Cu varied among specimens derived from different cultivation modes. The fresh stems of D. Mito-TEMPO ic50 officinale derived from different cultivation modes can be effectively and quickly identified by various microscopic characteristics and different contents of Ca on the surface of the parenchyma, phloem and xylem. Meanwhile, linear discriminant analysis showed that 98.1% of the dried stem powder samples were correctly classified, and the accuracy of cross-validation was 95.3%. This study facilitated an effective integrated method for determining the traceability of the fresh stem and dried stem powder of D. officinale derived from three different cultivation modes. This approach offers a potential method for identifying the origins of medicinal plants derived from different cultivation modes.
Website: https://www.selleckchem.com/products/mito-tempo.html
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