Urinary Epidermal Growth Factor Reflects Distal Tubular Mass and is Associated with Hypertension, Serum Magnesium, and Kidney Outcomes.

Background: Epidermal growth factor is expressed in the distal tubule and secreted in urine (uEGF) after cleavage of membrane-bound pro-EGF. Lower uEGF is associated with kidney disease progression. EGF also plays a role in the regulation of serum magnesium and blood pressure, but whether uEGF is associated with these parameters is unknown.

The metalloproteinase PAPP-A is required for IGF-dependent chondrocyte differentiation and organization.

Insulin-like growth factor (IGF) signaling is required for proper growth and skeletal development in vertebrates. Consequently, its dysregulation may lead to abnormalities of growth or skeletal structures. IGF is involved in the regulation of cell proliferation and differentiation of chondrocytes.

Accuracy of Cranial Shape Measurements Using Smartphones: A Prospective Study.

Objective: Prospectively validate the accuracy of smartphone-based digital cranial measurements for the diagnosis and treatment of deformational plagiocephaly and/or brachycephaly (DPB), compared with calipers used in the standard of care.

Design/methods: Bird's-eye-view head photos were captured via smartphone, and their heads were measured with hand calipers by an expert user. CI/CVAI/CVA were calculated from photos and caliper measurements, and from 3D photogrammetry of the head as ground truth.

Genetic deletion of the kidney sodium/proton exchanger-3 (NHE3) does not alter calcium and phosphate balance due to compensatory responses.

The sodium/proton exchanger-3 (NHE3) plays a major role in acid-base and extracellular volume regulation and is also implicated in calcium homeostasis. As calcium and phosphate balances are closely linked, we hypothesized that there was a functional link between kidney NHE3 activity, calcium, and phosphate balance. Therefore, we examined calcium and phosphate homeostasis in kidney tubule-specific NHE3 knockout mice (NHE3 mice).

Inducible deletion of the prostaglandin EP3 receptor in kidney tubules of male and female mice has no major effect on water homeostasis.

The prostaglandin E (PGE) receptor EP3 has been detected in the thick ascending limb (TAL) and the collecting duct of the kidney, where its actions are proposed to inhibit water reabsorption. However, EP3 is also expressed in other cell types, including vascular endothelial cells. The aim here was to determine the contribution of EP3 in renal water handling in male and female adult mice by phenotyping a novel mouse model with doxycycline-dependent deletion of EP3 throughout the kidney tubule (EP3 mice).

The Effect of Thiazide Diuretics on Urinary Prostaglandin E2 Excretion and Serum Sodium in the General Population.

Context: Thiazide-induced hyponatremia is one of the most common forms of hyponatremia, but its pathogenesis is incompletely understood. Recent clinical data suggest links with prostaglandin E2 (PGE2) and a single nucleotide polymorphism (SNP) in the prostaglandin transporter gene (SLCO2A1), but it is unknown if these findings also apply to the general population.

Objective: To study the associations between serum sodium, thiazide diuretics, urinary excretions of PGE2, and its metabolite (PGEM), and the rs34550074 SNP in SLCO2A1 in the general population.

Regulation of the water channel aquaporin-2 by cullin E3 ubiquitin ligases.

Aquaporin 2 (AQP2) is a vasopressin (VP)-regulated water channel in the renal collecting duct. Phosphorylation and ubiquitylation of AQP2 play an essential role in controlling the cellular abundance of AQP2 and its accumulation on the plasma membrane in response to VP. Cullin-RING ubiquitin ligases (CRLs) are multisubunit E3 ligases involved in ubiquitylation and degradation of their target proteins, eight of which are expressed in the collecting duct.

Anaesthetic records: an evaluation of variation across England.

We collected blank non-specialist anaesthetic records from 71 National Health Service Trusts in England. A data set was established by collating all data items found in an initial tranche of 28 records. All 71 records were subsequently analysed for each data item in this data set.

Bystander Intervention in Football and Sports. A Quasi-Experimental Feasibility Study of a Bystander Violence Prevention Program in the United Kingdom.

In recent years, social campaigns and high-profile cases have brought increased attention to violence against women. Athletes can be role models, shaping both prosocial and antisocial attitudes. Their engagement in violence prevention could be an effective tool to tackle violence against women through bystander intervention.

Potassium-Switch Signaling Pathway Dictates Acute Blood Pressure Response to Dietary Potassium.

Background: Potassium (K)-deficient diets, typical of modern processed foods, increase blood pressure (BP) and NaCl sensitivity. A K-dependent signaling pathway in the kidney distal convoluted tubule, coined the K switch, that couples extracellular K sensing to activation of the thiazide-sensitive NaCl cotransporter (NCC) and NaCl retention has been implicated, but causality has not been established.

Methods: To test the hypothesis that small, physiological changes in plasma K (P) are translated to BP through the switch pathway, a genetic approach was used to activate the downstream switch kinase, SPAK (SPS1-related proline/alanine-rich kinase), within the distal convoluted tubule.

SAM68 directs STING signaling to apoptosis in macrophages.

DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription.

The role of the specialist nurse in comprehensive care for bleeding disorders in Europe: An integrative review.

Introduction: Managing bleeding disorders (BDs) is complex, requiring a comprehensive approach coordinated by a multidisciplinary team (MDT). Haemophilia nurses (HNs) play a central role in the MDT, frequently coordinating care. As novel treatments bring change to the treatment landscape, ongoing education and development is key.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

Background: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production.

Methods And Results: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study.

Guidelines on antibody use in physiology research.

Antibodies are one of the most used reagents in scientific laboratories and are critical components for a multitude of experiments in physiology research. Over the past decade, concerns about many biological methods, including those that use antibodies, have arisen as several laboratories were unable to reproduce the scientific data obtained in other laboratories. The lack of reproducibility could be largely attributed to inadequate reporting of detailed methods, no or limited verification by authors, and the production and use of unvalidated antibodies.

Metabolic Communication by SGLT2 Inhibition.

Background: SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood.

Methods: To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SGLT2i treatment of nondiabetic as well as diabetic mice with early and uncomplicated hyperglycemia.

Results: Kidneys of nondiabetic mice reacted most strongly to SGLT2i in terms of proteomic reconfiguration, including evidence for less early proximal tubule glucotoxicity and a broad downregulation of the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acids), supported by mouse and human SGLT2 interactome studies.

Pediatric Residency Graduates' Characteristics, Career Choice, and Satisfaction by Race and Ethnicity, 2011-2022.

Objective: Learning more about resident characteristics, career choices, job search experiences, and satisfaction for different racial and ethnic backgrounds can inform needs and approaches to diversifying the physician workforce.

Methods: We analyzed survey data collected from national random samples of pediatric residents graduating from 2011 to 2022. We used chi-square linear association to examine trends in reported race and ethnicity and multivariable logistic regression to estimate associations of race and ethnicity with graduates' characteristics including debt, career choice, job search experience, and satisfaction with specialty choice and report predicted percentage values (PV).

Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure.

Consumption of low dietary potassium, common with ultraprocessed foods, activates the thiazide-sensitive sodium chloride cotransporter (NCC) via the with no (K) lysine kinase/STE20/SPS1-related proline-alanine-rich protein kinase (WNK/SPAK) pathway to induce salt retention and elevate blood pressure (BP). However, it remains unclear how high-potassium "DASH-like" diets (dietary approaches to stop hypertension) inactivate the cotransporter and whether this decreases BP. A transcriptomics screen identified Ppp1Ca, encoding PP1A, as a potassium-upregulated gene, and its negative regulator Ppp1r1a, as a potassium-suppressed gene in the kidney.

Prostaglandin E2, Osmoregulation, and Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

Background: Prostaglandin E2 (PGE2) plays a physiological role in osmoregulation, a process that is affected early in autosomal dominant polycystic kidney disease (ADPKD). PGE2 has also been implicated in the pathogenesis of ADPKD in preclinical models, but human data are limited. Here, we hypothesized that urinary PGE2 excretion is associated with impaired osmoregulation, disease severity, and disease progression in human ADPKD.

Accommodation in Children after 4.7 Years of Multifocal Contact Lens Wear in the BLINK Study Randomized Clinical Trial.

Significance: When worn for myopia control in children, soft multifocal contact lenses with a +2.50 D add reduced the accommodative response over a 3-year period, but wearing them for more than 4 years did not affect accommodative amplitudes, lag, or facility.

Purpose: This study aimed to compare the accommodative response to a 3D stimulus between single-vision, +1.