MicroRNAs in aldosterone production and action.

Aldosterone is a cardiovascular hormone with a key role in blood pressure regulation, among other processes, mediated through its targeting of the mineralocorticoid receptor in the renal tubule and selected other tissues. Its secretion from the adrenal gland is a highly controlled process subject to regulatory influence from the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis. MicroRNAs are small endogenous non-coding RNA molecules capable of regulating gene expression post-transcriptionally through stimulation of mRNA degradation or suppression of translation.

Smart Buildings: Water Leakage Detection Using TinyML.

The escalating global water usage and the increasing strain on major cities due to water shortages highlights the critical need for efficient water management practices. In water-stressed regions worldwide, significant water wastage is primarily attributed to leakages, inefficient use, and aging infrastructure. Undetected water leakages in buildings' pipelines contribute to the water waste problem.

Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.

Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1.

Cluster analysis of angiotensin biomarkers to identify antihypertensive drug treatment in population studies.

Background: The recent progress in molecular biology generates an increasing interest in investigating molecular biomarkers as markers of response to treatments. The present work is motivated by a study, where the objective was to explore the potential of the molecular biomarkers of renin-angiotensin-aldosterone system (RAAS) to identify the undertaken antihypertensive treatments in the general population. Population-based studies offer an opportunity to assess the effectiveness of treatments in real-world scenarios.

New advances in endocrine hypertension: from genes to biomarkers.

Hypertension (HT) is a major cardiovascular risk factor that affects 10% to 40% of the general population in an age-dependent manner. Detection of secondary forms of HT is particularly important because it allows the targeted management of the underlying disease. Among hypertensive patients, the prevalence of endocrine HT reaches up to 10%.

Vascular and hormonal interactions in the adrenal gland.

Primary aldosteronism is the most common form of secondary arterial hypertension, due to excessive aldosterone production from the adrenal gland. Although somatic mutations have been identified in aldosterone producing adenoma, the exact mechanisms leading to increased cell proliferation and nodule formation remain to be established. One hypothesis is that changes in vascular supply to the adrenal cortex, due to phenomena of atherosclerosis or high blood pressure, may influence the morphology of the adrenal cortex, resulting in a compensatory growth and nodule formation in response to local hypoxia.

Mechanism by Which Inflammation and Oxidative Stress Induce Mineralocorticoid Receptor Gene Expression in Aging Vascular Smooth Muscle Cells.

Background: Vascular MR (mineralocorticoid receptor) expression increases with age driving aging-associated vascular stiffness and hypertension. MR has two isoforms (1α and 1β) with distinct 5'-untranslated and promoter sequences (P1 and P2), but the gene regulatory mechanisms remain unknown. We investigated mechanisms driving MR gene transcriptional regulation in aging human smooth muscle cells (SMC).

Machine learning for classification of hypertension subtypes using multi-omics: A multi-centre, retrospective, data-driven study.

Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter.

Identification of risk loci for primary aldosteronism in genome-wide association studies.

Primary aldosteronism affects up to 10% of hypertensive patients and is responsible for treatment resistance and increased cardiovascular risk. Here we perform a genome-wide association study in a discovery cohort of 562 cases and 950 controls and identify three main loci on chromosomes 1, 13 and X; associations on chromosome 1 and 13 are replicated in a second cohort and confirmed by a meta-analysis involving 1162 cases and 3296 controls. The association on chromosome 13 is specific to men and stronger in bilateral adrenal hyperplasia than aldosterone producing adenoma.

Predicting Hypertension Subtypes with Machine Learning Using Targeted Metabolites and Their Ratios.

Hypertension is a major global health problem with high prevalence and complex associated health risks. Primary hypertension (PHT) is most common and the reasons behind primary hypertension are largely unknown. Endocrine hypertension (EHT) is another complex form of hypertension with an estimated prevalence varying from 3 to 20% depending on the population studied.

Preanalytical Pitfalls in Untargeted Plasma Nuclear Magnetic Resonance Metabolomics of Endocrine Hypertension.

Despite considerable morbidity and mortality, numerous cases of endocrine hypertension (EHT) forms, including primary aldosteronism (PA), pheochromocytoma and functional paraganglioma (PPGL), and Cushing's syndrome (CS), remain undetected. We aimed to establish signatures for the different forms of EHT, investigate potentially confounding effects and establish unbiased disease biomarkers. Plasma samples were obtained from 13 biobanks across seven countries and analyzed using untargeted NMR metabolomics.

On-Device IoT-Based Predictive Maintenance Analytics Model: Comparing TinyLSTM and TinyModel from Edge Impulse.

A precise prediction of the health status of industrial equipment is of significant importance to determine its reliability and lifespan. This prediction provides users information that is useful in determining when to service, repair, or replace the unhealthy equipment's components. In the last decades, many works have been conducted on data-driven prognostic models to estimate the asset's remaining useful life.

Preanalytical Considerations and Outpatient Versus Inpatient Tests of Plasma Metanephrines to Diagnose Pheochromocytoma.

Context: Sampling of blood in the supine position for diagnosis of pheochromocytoma and paraganglioma (PPGL) results in lower rates of false positives for plasma normetanephrine than seated sampling. It is unclear how inpatient vs outpatient testing and other preanalytical factors impact false positives.

Objective: We aimed to identify preanalytical precautions to minimize false-positive results for plasma metanephrines.

Accelerating Large-Scale-Structure data analyses by emulating Boltzmann solvers and Lagrangian Perturbation Theory.

The linear matter power spectrum is an essential ingredient in all theoretical models for interpreting large-scale-structure observables. Although Boltzmann codes such as CLASS or CAMB are very efficient at computing the linear spectrum, the analysis of data usually requires 10 -10 evaluations, which means this task can be the most computationally expensive aspect of data analysis. Here, we address this problem by building a neural network emulator that provides the linear theory (total and cold) matter power spectrum in about one millisecond with ≈0.

Epilepsy in patients undergoing cardiac surgery with ExtraCorporeal Circulation: case series and description of a peculiar clinical phenotype.

Background: Extracorporeal circulation (ECC) is now being increasingly used in critical care settings. Epileptic seizures are a recognized but under reported complication in patients receiving this care. Acute symptomatic post-operative seizures have been described, as well as remote seizure, mostly in the form of convulsive seizures.

Mobility-Aware Proactive Edge Caching Optimization Scheme in Information-Centric IoV Networks.

Edge caching is a promising approach to alleviate the burden on the backhaul of network links. It has a significant role in the Internet of Vehicle (IoV) networks performance by providing cached data at the edge and reduce the burden of the core network caused by the number of participating vehicles and data volume. However, due to the limited computing and storage capabilities of edge devices, it is hard to guarantee that all contents are cached and every requirement of the device are satisfied for all users.

Identification of glucocorticoid-related molecular signature by whole blood methylome analysis.

Objective: Cushing's syndrome represents a state of excessive glucocorticoids related to glucocorticoid treatments or to endogenous hypercortisolism. Cushing's syndrome is associated with high morbidity, with significant inter-individual variability. Likewise, adrenal insufficiency is a life-threatening condition of cortisol deprivation.

Circulating microRNAs as Diagnostic Markers in Primary Aldosteronism.

Primary aldosteronism (PA) is a common and highly treatable condition, usually resulting from adrenocortical tumorous growth or hyperplasia. PA is currently underdiagnosed owing to its complex and protracted diagnostic procedures. A simplified biomarker-based test would be highly valuable in reducing cardiovascular morbidity and mortality.

Colocalization of Wnt/β-Catenin and ACTH Signaling Pathways and Paracrine Regulation in Aldosterone-producing Adenoma.

Context: Aldosterone-producing adenomas (APAs) are a common cause of primary aldosteronism (PA). Despite the discovery of somatic mutations in APA and the characterization of multiple factors regulating adrenal differentiation and function, the sequence of events leading to APA formation remains to be determined.

Objective: We investigated the role of Wnt/β-catenin and adrenocorticotropin signaling, as well as elements of paracrine regulation of aldosterone biosynthesis in adrenals with APA and their relationship to intratumoral heterogeneity and mutational status.

Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs.

Somatic mutations in adrenals from patients with primary aldosteronism not cured after adrenalectomy suggest common pathogenic mechanisms between unilateral and bilateral disease.

Objective: Primary aldosteronism (PA) is the most common form of secondary and curable hypertension. Different germline and somatic mutations are found in aldosterone-producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with APA; however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH.