Mechanisms of ligand-mediated modulation of mineralocorticoid receptor signaling.

The mineralocorticoid receptor plays a central role in homeostasis, mediating the regulation by aldosterone of epithelial sodium transport. In addition, it regulates a range of responses in other tissues where it is likely responding to both mineralocorticoids and glucocorticoids. Structural, functional and evolutionary studies have provided insights into the mechanisms of receptor activation by agonist ligands and how interactions within the domains of the mineralocorticoid receptor may modulate the response to individual ligands including the mechanisms of antagonism.

Endovascular thrombectomy for large vessel occlusion stroke patients with baseline disability: Long-term outcomes and end-of-life care.

Background: One third of all patients with acute ischemic strokes have a pre-existing disability. Patients with pre-existing disabilities have historically been excluded from landmark clinical trials of acute stroke interventions, leading to ongoing controversy about the risks and benefits of acute stroke interventions such as endovascular thrombectomy (EVT). To address this controversy, we compared long-term outcomes and end-of-life care in large vessel occlusion (LVO) patients with moderate-to-severe baseline disability treated with EVT versus medical management alone.

Circadian disruption and its impact on the cardiovascular system.

Circadian rhythms are highly conserved biorhythms of ~24 h that govern many fundamental biological processes, including cardiovascular (CV) homeostasis. Disrupting the timing of cellular oscillators promotes cellular stress, and induction of pathogenic pathways underpins the pathogenesis of many CV diseases (CVDs). Thus, shift work, late eating, sleep disturbances, and other disruptors can result in an elevated risk of heart disease and increased incidence of adverse CV events.

Ethically Translating Advanced Neurotechnologies for Disorders of Consciousness: A Survey of Clinicians' Perspectives.

Although evaluation of disorders of consciousness (DoC) following brain injury has traditionally relied on bedside behavioral examination, advances in neurotechnology have elucidated novel approaches to detecting and predicting recovery of consciousness. Professional society guidelines now recommend that clinicians integrate these neurotechnologies into clinical practice as part of multimodal evaluations for some patients with DoC but have not crafted concrete protocols for this translation. Little is known about the experiences and ethical perspectives held by key stakeholder groups around the clinical implementation of advanced neurotechnologies to detect and predict recovery of consciousness.

Doctors as Device Manufacturers? Regulation of Clinician-Generated Innovation in the ICU.

Critical care physicians are rich sources of innovation, developing new diagnostic, prognostic, and treatment tools they deploy in clinical practice, including novel software-based tools. Many of these tools are validated and promise to actively help patients, but physicians may be unlikely to distribute, implement, or share them with other centers noncommercially because of unsettled ethical, regulatory, or medicolegal concerns. This Viewpoint explores the potential barriers and risks critical care physicians face in disseminating device-related innovations for noncommercial purposes and proposes a framework for risk-based evaluation to foster clear pathways to safeguard equitable patient access and responsible implementation of clinician-generated technological innovations in critical care.

Novel Post-Neurointensive Care Recovery Clinic: Design, Utilization, and Clinician Perspectives.

Background And Objectives: Despite increasing interest in post-intensive care unit (ICU) clinical care and management, there have been limited descriptions focused on the post-neurologic (neuro)-ICU population. Here, we describe the design of a post-neuro-ICU Neurorecovery Clinic (NRC) and present data collected regarding the clinic's population, referrals, visits, and clinician satisfaction.

Methods: This is a single-institution experience with a NRC designed to provide an infrastructure for post-ICU care to patients recovering from acute neurologic disorders or systemic conditions with neurologic sequelae.

Update on Low-Renin Hypertension: Current Understanding and Future Direction.

Low-renin hypertension is common and affects 1 in 4 people with hypertension. Understanding the different causes and management of low-renin hypertension is becoming increasingly relevant as renin measurements are more widely ordered in clinical practice. Importantly, many people with low-renin hypertension do not fit traditional definitions of known causes, and the approach to management of these people is not unclear.

How to: assess patient suitability for unlicensed phage therapy in the United Kingdom.

Background: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach that has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licensed phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis.

A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design.

Low-renin hypertension affects 1 in 4 people with hypertension, but the optimal management of this condition is not known. We hypothesize that a large proportion of people with low-renin hypertension is mediated by excess mineralocorticoid receptor (MR) activation and that targeted treatment with an MR antagonist (MRA) will be beneficial. This randomized, single-blinded, titration-to-effect aims to investigate whether targeted treatment in low-renin hypertension with MRA is better compared to standard antihypertensives in terms of blood pressure control and end-organ protection.

Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.

Endometrial cancer (EC) is a devastating and common disease affecting women's health. The NCI Surveillance, Epidemiology, and End Results Program predicted that there would be >66,000 new cases in the United States and >13,000 deaths from EC in 2023, and EC is the sixth most common cancer among women worldwide. Regulation of mitochondrial metabolism plays a role in tumorigenesis.

Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population.

Introduction: Low-renin hypertension is an underrecognized subtype of hypertension with specific treatment options. This study aims to identify the prevalence in primary care and to compare patient characteristics to those with normal-renin hypertension and primary aldosteronism (PA).

Methods: In a cohort study, patients with treatment-naïve hypertension were screened for PA with plasma aldosterone and direct renin concentrations.

Equity in Clinical Care and Research Involving Persons with Disorders of Consciousness.

People with disorders of consciousness (DoC) are characteristically unable to synchronously participate in decision-making about clinical care or research. The inability to self-advocate exacerbates preexisting socioeconomic and geographic disparities, which include the wide variability observed across individuals, hospitals, and countries in access to acute care, expertise, and sophisticated diagnostic, prognostic, and therapeutic interventions. Concerns about equity for people with DoC are particularly notable when they lack a surrogate decision-maker (legally referred to as "unrepresented" or "unbefriended").

Nonequilibrium Anion Detection in Solid-Contact Ion-Selective Electrodes.

Low-cost and portable nitrate and phosphate sensors are needed to improve farming efficiency and reduce environmental and economic impact arising from the release of these nutrients into waterways. Ion selective electrodes (ISEs) could provide a convenient platform for detecting nitrate and phosphate, but existing ionophore-based nitrate and phosphate selective membrane layers used in ISEs are high cost, and ISEs using these membrane layers suffer from long equilibration time, reference potential drift, and poor selectivity. In this work, we demonstrate that constant current operation overcomes these shortcomings for ionophore-based anion-selective ISEs through a qualitatively different response mechanism arising from differences in ion mobility rather than differences in ion binding thermodynamics.

Applying the IEEE BRAIN neuroethics framework to intra-cortical brain-computer interfaces.

. Brain-computer interfaces (BCIs) are neuroprosthetic devices that allow for direct interaction between brains and machines. These types of neurotechnologies have recently experienced a strong drive in research and development, given, in part, that they promise to restore motor and communication abilities in individuals experiencing severe paralysis.

USP24-i-101 targeting of USP24 activates autophagy to inhibit drug resistance acquired during cancer therapy.

Drug resistance in cancer therapy is the major reason for poor prognosis. Addressing this clinically unmet issue is important and urgent. In this study, we found that targeting USP24 by the specific USP24 inhibitors, USP24-i and its analogues, dramatically activated autophagy in the interphase and mitotic periods of lung cancer cells by inhibiting E2F4 and TRAF6, respectively.

Role of Surface Chemistry in Pyrrole Autoxidation.

Chemical compounds in liquid hydrocarbon fuels that contain five-membered pyrrole (Py) rings readily react with oxygen from air and polymerize through a process known as autoxidation. Autoxidation degrades the quality of fuel and leads to the formation of unwanted gum deposits in fuel storage vessels and engine components. Recent work has found that the rate of formation of these gum deposits is affected by material surfaces exposed to the fuel, but the origins of these effects are not yet understood.