The molecular basis of pH sensing by the human fungal pathogen TOK potassium channel.

Two-pore domain, outwardly rectifying potassium (TOK) channels are exclusively expressed in fungi. Human fungal pathogen TOK channels are potential antifungal targets, but TOK channel modulation in general is poorly understood. Here, we discovered that TOK (CaTOK) is regulated by extracellular pH, in contrast to TOK channels from other fungal species tested.

Isolated Aneurysms of the Great Saphenous Vein: A Case Series and Review of the Literature.

Great saphenous vein aneurysms (GSVA) represent a rare yet clinically significant condition, often misdiagnosed due to their infrequent presentation and resemblance to more common inguinal pathologies. This case series examines five instances of GSVA, emphasizing the diagnostic challenges, surgical interventions, and postoperative outcomes. Patients presented with varying symptoms, including groin masses and lower extremity pain, which were initially misattributed to other conditions.

Avoiding Complications with Transcarotid Artery Revascularization.

Background: Transcarotid artery revascularization (TCAR) for carotid artery stenting offers an innovative method for treating carotid artery occlusive disease. This technique utilizes the ENROUTE Transcarotid Neuroprotection System (Silk Road Medical, Sunnyvale, CA) to temporarily reverse flow in the carotid artery prior to crossing or treating the carotid lesion, reducing the perioperative risk of stroke. This review aims to summarize possible complications associated with the procedure and offer suggestions to address or avoid these issues in practice.

Describing the development and implementation of a novel collaborative multidisciplinary approach to deliver foot health supports for individuals experiencing homelessness and its outcomes.

Basic foot care is a real need of people experiencing homelessness. To improve access to foot health for this group, three services structured to provide healthcare support for people experiencing homelessness collaborated in metropolitan Melbourne, Australia: an established nurse-led Homeless Persons Program (HPP), a specialty community health podiatry clinic servicing people experiencing homelessness, and a charity supporting disadvantaged communities providing free socks, foot first aid kits and second-hand footwear for distribution by nurses and podiatrists of participating services. This paper outlines the implementation and evaluation of this collaboration.

Predictive and protective factors for failing first pass intubation in prehospital rapid sequence intubation: an aetiology and risk systematic review with meta-analysis.

Background: Prehospital rapid sequence intubation first pass success rates vary between 59% and 98%. Patient morbidity is associated with repeat intubation attempts. Understanding what influences first pass success can guide improvements in practice.

Outcomes of Aortobifemoral Bypass Based on Configuration of the Proximal Anastomosis.

Background: Aortobifemoral bypass (ABF) remains an important treatment modality in the revascularization of aortoiliac occlusive disease. Despite ABF being performed for decades, questions remain regarding the preferred technique for the proximal anastomosis, specifically whether an end-to-end (EE) or an end-to-side (ES) configuration is superior. The goal of this study was to compare the outcomes of ABF based on proximal configuration.

The Use of Paclitaxel-Coated Devices in the Treatment of Peripheral Arterial Disease is Not Associated With Increased Mortality or Amputations.

Background: Strategies for the most effective treatment for peripheral arterial disease (PAD) remain controversial among clinicians. Several trials have shown improved primary patency of femoropopliteal interventions with the utilization of paclitaxel-coated balloons or stents compared to conventional balloons or stents. However, a 2018 meta-analysis suggested an increased mortality risk for patients receiving drug-coated balloons or stents (DCBS), resulting in an international pause in the use of DCBS.

Outcomes of operative and nonoperative management of blunt thoracic aortic injury.

Objective: Although the current guidelines for the management of blunt traumatic aortic injury (BTAI) have recommended intervention for grade 2 injuries or higher, a national trend has occurred for aggressive endovascular treatment of low-grade BTAIs. Little is known about the natural history of grade 1 and 2 injuries treated nonoperatively. We hypothesized that most of these low-grade injuries would remain stable with nonoperative management.

Ozone for SARS-CoV-2 inactivation on surfaces and in liquid cell culture media.

This study evaluated the inactivation of SARS-CoV-2, the virus responsible for COVID-19, by ozone using virus grown in cell culture media either dried on surfaces (plastic, glass, stainless steel, copper, and coupons of ambulance seat and floor) or suspended in liquid. Treatment in liquid reduced SARS-CoV-2 at a rate of 0.92 ± 0.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Human Lung Microvascular Endothelial Cells Controls Oxidative Stress, Reactive Oxygen-Mediated Cell Signaling and Inflammatory Responses.

Background: Perturbation of endothelial function in people with cystic fibrosis (CF) has been reported, which may be associated with endothelial cell expression of the cystic fibrosis transmembrane conductance regulator (CFTR). Previous reports indicate that CFTR activity upregulates endothelial barrier function, endothelial nitric oxide synthase (eNOS) expression and NO release, while limiting interleukin-8 (IL-8) release, in human umbilical vein endothelial cells (HUVECs) in cell culture. In view of reported microvascular dysfunction in people with CF we investigated the role of CFTR expression and activity in the regulation of oxidative stress, cell signaling and inflammation in human lung microvascular endothelial cells (HLMVECs) in cell culture.

An Evidence-Based Care Protocol Improves Outcomes and Decreases Cost in Pediatric Appendicitis.

Background: Appendicitis is a common indication for urgent abdominal surgery in the pediatric population. The postoperative management varies significantly in time to discharge and cost of care. The objective of this study was to investigate whether implementation of an evidence-based protocol after an appendectomy would lead to decreased length of stay and cost of care.

TOK channels use the two gates in classical K channels to achieve outward rectification.

TOKs are outwardly rectifying K channels in fungi with two pore-loops and eight transmembrane spans. Here, we describe the TOKs from four pathogens that cause the majority of life-threatening fungal infections in humans. These TOKs pass large currents only in the outward direction like the canonical isolate from Saccharomyces cerevisiae (ScTOK), and distinct from other K channels.

Spadin Selectively Antagonizes Arachidonic Acid Activation of TREK-1 Channels.

TREK-1 channel activity is a critical regulator of neuronal, cardiac, and smooth muscle physiology and pathology. The antidepressant peptide, spadin, has been proposed to be a TREK-1-specific blocker. Here we sought to examine the mechanism of action underlying spadin inhibition of TREK-1 channels.

A critical role for the inward rectifying potassium channel Kir7.1 in oligodendrocytes of the mouse optic nerve.

Inward rectifying potassium channels (Kir) are a large family of ion channels that play key roles in ion homeostasis in oligodendrocytes, the myelinating cells of the central nervous system (CNS). Prominent expression of Kir4.1 has been indicated in oligodendrocytes, but the extent of expression of other Kir subtypes is unclear.

Murine sepsis phenotypes and differential treatment effects in a randomized trial of prompt antibiotics and fluids.

Background: Clinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids.

Methods: We performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials.

Frontline Science: Rev-Erbα links blue light with enhanced bacterial clearance and improved survival in murine Klebsiella pneumoniae pneumonia.

The wavelength of light is a critical determinant of light's capacity to entrain adaptive biological mechanisms, such as enhanced immune surveillance, that precede and prepare us for the active circadian day, a time when the risk of encountering pathogen is highest. Light rich in the shorter wavelength visible blue spectrum maximally entrains these circadian rhythms. We hypothesized that exposure to blue light during sepsis will augment immunity and improve outcome.

Glial and neuronal expression of the Inward Rectifying Potassium Channel Kir7.1 in the adult mouse brain.

Inward Rectifying Potassium channels (Kir) are a large family of ion channels that play key roles in ion homeostasis and neuronal excitability. The most recently described Kir subtype is Kir7.1, which is known as a K transporting subtype.

Translational Sepsis Research: Spanning the Divide.

Objective: Our knowledge of the molecular mechanisms of sepsis has attained exponential growth. Yet, the pillars of its care remain antibiotics, fluid resuscitation, and physiologic support of failing organ systems. The inability to bring biologic breakthroughs to the bedside is not for lack of effort.

Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis.

Objectives: The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis.

TREK-1 Channel Expression in Smooth Muscle as a Target for Regulating Murine Intestinal Contractility: Therapeutic Implications for Motility Disorders.

Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K channels in mouse ileum and colon.

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches.

Bench-to-Bedside: A Translational Perspective on Murine Models of Sepsis.

Background: Considerable research effort has focused on the development of novel therapies for the treatment of sepsis, yet after decades of clinical trials, few significant advances have been achieved. This limitation persists despite a wealth of data yielded by basic science that has expanded our knowledge of the biology of this disease exponentially.

Method: Review of the English-language literature.