Discordance and shortcomings of aldosterone suppression tests in primary aldosteronism.

Background: The saline suppression test (SST) and the captopril challenge test (CCT) have traditionally been used to confirm or exclude primary aldosteronism (PA). New guidelines recommend using these tests to predict the likelihood of unilateral PA. This study evaluated the diagnostic accuracy, consistency, and clinical implications of these tests.

Warming Alaskan rivers affect first-year growth in critical northern food fishes.

Arctic and subarctic rivers are warming rapidly, with unknown consequences for migratory fishes and the human communities dependent on them. To date, few studies have provided a comprehensive assessment of possible climate change impacts on the hydrology and temperature of Arctic rivers at the regional scale, and even fewer have connected those changes to multiple fish species with input and guidance from Indigenous communities. We used climate, hydrologic, and fish-growth simulations of historical (1990-2021) and future (2034-2065) young-of-year (YOY) growth potential of Chinook salmon (Oncorhynchus tshawytscha) and Dolly Varden (Salvelinus malma) for seven river basins in the Arctic-Yukon-Kuskokwim (AYK) region of Alaska, USA and Yukon Territory, Canada.

Integrating 12 Spatial and Single Cell Technologies to Characterise Tumour Neighbourhoods and Cellular Interactions in three Skin Cancer Types.

Cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and melanoma, the three major types of skin cancer, account for over 70% of all cancer cases. Despite their prevalence, the skin cancer microenvironment remains poorly characterized, both in the outer skin layer where the cancer originates and at the deeper junctional and dermal layers into which it progresses. To address this, we integrated 12 complementary spatial single-cell technologies to construct orthogonally-validated cell signatures, spatial maps, and interactomes for cSCC, BCC, and melanoma.

Identifying county-level effect modifiers of the association between heat waves and preterm birth using a Bayesian spatial meta regression approach.

High temperature is associated with adverse health outcomes, particularly for vulnerable subpopulations including pregnant individuals and their unborn babies. Several recent studies have investigated the association between temperature and preterm birth at different geographic scales and across different spatial locations. However, there has been less focus on characterizing spatial heterogeneity in risks and identifying modifiable factors that contribute to the observed variation.

TCR activation stimulates regulated intramembrane proteolysis of L-selectin by presenilin 1 and localized proteasomal degradation of the cytoplasmic tail.

Leucocyte (L)-selectin is essential for mounting protective immunity to pathogens. As well as regulating leucocyte recruitment, it also regulates their activation and differentiation inside tissues thereby shaping local immune responses. The biochemical signals that regulate these diverse functions of L-selectin are poorly understood.

Optimizing Costs in Plastic Surgery: A Systematic Review of Time-driven Activity-based Costing Applications.

Background: The rising complexity and cost of healthcare in plastic surgery, particularly in resource-intensive procedures like free flap and breast reconstruction, pose significant financial challenges. Time-driven activity-based costing (TDABC) offers a method to accurately assess these costs by mapping each step of the care cycle based on time and resources consumed. Although TDABC has been utilized in high-cost fields such as neurosurgery and spine surgery, its application in plastic surgery remains underexplored.

The Evolution of Primary Aldosteronism and the Role of Norrin.

Primary aldosteronism (PA) is renin-independent aldosterone production that causes hypertension and cardiovascular disease. We investigated the proteomic evolution of PA from normotensive people with renin-independent aldosteronism to those with overt PA. The PA plasma proteome was characterized by pathways related to cardiovascular disease (inflammation, energy/redox, vascular remodeling).

Preterm and early-term delivery after heat waves in eight US states: A case-crossover study using the High-resolution Urban Meteorology for Impacts Dataset (HUMID).

Background: Heat wave frequency and intensity is increasing and this trend is more pronounced in urban areas. Heat waves may be acutely associated with early birth.

Objectives: To examine the acute relationship between heat waves and preterm (<37 weeks) and early-term (37-38 weeks) birth in eight states: California, Florida, Georgia, Kansas, Nevada, New Jersey, North Carolina, and Oregon.

The Impact Of Modern Industrialized Dietary Sodium Intake On The Plasma Proteome.

Background: High dietary sodium intake is associated with cardiovascular disease. We investigated the influence of sodium intake on the plasma proteome.

Methods: Prospectively recruited normotensive participants underwent 2 controlled dietary sodium interventions to evaluate hormonal and proteomic (1,512 proteins) changes: sodium-restriction resembling ancestral hunter-gatherer intake (~10 mEq/day, ~230mg/day) and sodium-loading resembling modern industrialized intake (~200 mEq/day, ~4600mg/day).

ACE Inhibition to Distinguish Low-Renin Hypertension From Primary Aldosteronism.

Background: Primary aldosteronism (PA) is a distinct cause of low-renin hypertension (LRH), characterized by inappropriate aldosterone production. We investigated the distinction between LRH and PA by leveraging the physiological effects of angiotensin-converting enzyme inhibition.

Methods: We conducted a retrospective cohort study including 756 patients with LRH who underwent a captopril challenge test (CCT) for evaluation of PA.

Subclinical Primary Aldosteronism is Characterized by Maladaptive Natriuretic Peptide and Adrenal Hormonal Physiology.

Background: A continuum of non-suppressible aldosterone production has been demonstrated in normotensive individuals, termed subclinical primary aldosteronism (PA), and is consistently associated with increased risk for developing hypertension and cardiovascular disease. The hormonal mechanisms accounting for subclinical PA are not well understood.

Method: To quantify the magnitude of subclinical PA, prospectively recruited normotensive participants (n=75) had their maximally suppressed plasma aldosterone assessed after maintaining supine posture following an oral sodium loading protocol.

The influence of atmospheric drivers, environmental factors, and urban land use on extreme hourly precipitation trends over the CONtiguous United States for 40 years at 4-km resolution (CONUS404).

High-resolution datasets provide unique insights into extreme precipitation dynamics, capturing atmospheric, environmental, and anthropogenic influences missed by coarser data. Here, we use the 4 km CONUS404 dataset (1980-2021) to analyze trends in extreme hourly precipitation across the contiguous USA and adjacent regions. Using the 42 highest hourly precipitation values (HP42) from the 42-year dataset, we estimate regression slopes for their annual occurrence and intensity.

Nationwide, Pragmatic, Direct-to-Patient Primary Aldosteronism Testing Program.

Background: Primary aldosteronism, an endocrinopathy present in ≥10% to 25% of patients with hypertension, confers excess cardiovascular risk that can be mitigated with aldosterone-directed therapy. However, only 2% of eligible patients undergo guideline-recommended screening. This study aimed to bypass clinical inertia and identify people with primary aldosteronism using pragmatic, direct-to-patient testing.

GARD-LENS: A downscaled large ensemble dataset for understanding future climate and its uncertainties.

This article introduces the Generalized Analog Regression Downscaling method Large Ensemble (GARD-LENS) dataset, comprised of daily precipitation, mean temperature, and temperature range over the Contiguous U.S., Alaska, and Hawaii at 12-km, 4-km, and 1-km resolutions, respectively.

Characterizing the Origins of Primary Aldosteronism.

Background: Renin-independent aldosterone production in normotensive people increases risk for developing hypertension. In parallel, normotensive adrenal glands frequently harbor aldosterone-producing micronodules with pathogenic somatic mutations known to induce primary aldosteronism (PA). A deeper understanding of these phenomena would inform the origins of PA and its role in hypertension pathogenesis.

The High-resolution Urban Meteorology for Impacts Dataset (HUMID) daily for the Conterminous United States.

Many current gridded surface meteorological datasets are inadequate for quantifying near-surface spatiotemporal variability because they do not fully represent the impacts of land surface heterogeneity. Of note, explicit representation of the spatial structure and magnitude of local urban warming are usually lacking. Here we enhance the representation of spatial meteorological variability over urban areas in the conterminous United States (CONUS) by employing the High-Resolution Land Data Assimilation System (HRLDAS), which accounts for the fine-scale impacts of spatiotemporally varying land surfaces on weather.

Progressive 11β-Hydroxysteroid Dehydrogenase Type 2 Insufficiency as Kidney Function Declines.

Background: It has been postulated that chronic kidney disease (CKD) is a state of relative 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11βHSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range.

Methods: Adult participants were recruited at 2 academic centers.

Semaphorin heterodimerization in cis regulates membrane targeting and neocortical wiring.

Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving epilepsy, intellectual disability, speech delay, and craniofacial defects.

Saline suppression testing-induced hypocalcemia and implications for clinical interpretations.

Background: Extracellular calcium critically regulates physiologic aldosterone production. Moreover, abnormal calcium flux and signaling are involved in the pathogenesis of the majority of primary aldosteronism cases.

Methods: We investigated the influence of the saline suppression test (SST) on calcium homeostasis in prospectively recruited participants (n = 86).

Protein translation rate determines neocortical neuron fate.

The mammalian neocortex comprises an enormous diversity regarding cell types, morphology, and connectivity. In this work, we discover a post-transcriptional mechanism of gene expression regulation, protein translation, as a determinant of cortical neuron identity. We find specific upregulation of protein synthesis in the progenitors of later-born neurons and show that translation rates and concomitantly protein half-lives are inherent features of cortical neuron subtypes.

De novo assembly and annotation of the Patagonian toothfish (Dissostichus eleginoides) genome.

Background: Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae. Juveniles occupy progressively deeper waters as they mature and grow, and adults have been caught as deep as 2500 m, living on or in just above the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. As apex predators, they are a key part of the food web, feeding on a variety of prey, including krill, squid, and other fish.

A Novel N-Ethyl-N-nitrosourea-Induced Mouse Mutant with Audiogenic Epilepsy.

Epilepsy is one of the common neurological diseases that affects not only adults but also infants and children. Because epilepsy has been studied for a long time, there are several pharmacologically effective anticonvulsants, which, however, are not suitable as therapy for all patients. The genesis of epilepsy has been extensively investigated in terms of its occurrence after injury and as a concomitant disease with various brain diseases, such as tumors, ischemic events, etc.