The effectiveness of providing training and ongoing support to foster cultural humility in volunteers serving as mentors to youth of color: a mixed-methods study protocol.

Background: The aim of this randomized control trial is to test the impact of providing additional training and support to volunteers who are paired with youth of color in the Big Brothers Big Sisters (BBBS) community-based mentoring program. The aim of the intervention activities is to enhance the capacity of mentors to have more culturally responsive and informed interactions with their mentees of color, thereby strengthening the youth's ethnic/racial identity and abilities to both cope with experiences of racism and contribute to causes that advance social justice.

Methods: Recruitment started in June 2022, with a goal of enrolling 240 dyads (i.

Jehovah's Witnesses: Challenges in liver disease management and in liver transplantation.

Patients of Jehovah's Witnesses faith who are in need of liver transplantation pose unique challenges. These patients should be seen at transplant centers with experience in caring for Jehovah's Witnesses to formulate careful preoperative, intraoperative, and postoperative strategies on an individualized basis with multidisciplinary input to mitigate the risk of bleeding complications and to prepare for potentially catastrophic scenarios. In-depth and individualized conversations about what constitutes acceptable bloodless transfusion strategies both for the patient and for the transplant center should begin as early as possible with an experienced coordinator or church liaison.

Outcomes of High-Grade Immune Checkpoint Inhibitor Hepatitis in Hospitalized and Nonhospitalized Patients.

Background & Aims: Guidelines recommend hospitalization for severe immune checkpoint inhibitor (ICI) hepatitis. We compared patient outcomes in the inpatient versus outpatient settings.

Methods: We conducted a multicenter, retrospective cohort study of 294 ICI-treated patients who developed grade 3-4 ICI hepatitis.

A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers.

KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heterotetramers with Kv2.1 ( ) or Kv2.2 ( ).

Kill rates by immune cells: Ratio-dependent, or mass action?

We describe a cell-based fixed-lattice model to simulate immune cell and tumor cell interaction involving MHC recognition, and FasL vs perforin lysis. We are motivated by open questions about the mechanisms behind observed kill rates of tumor cells by different types of effector cells. These mechanisms play a big role in the effectiveness of many cancer immunotherapies.

Distinct cellular expression and subcellular localization of Kv2 voltage-gated K channel subtypes in dorsal root ganglion neurons conserved between mice and humans.

The distinct organization of Kv2 voltage-gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located.

Electrically silent KvS subunits associate with native Kv2 channels in brain and impact diverse properties of channel function.

Voltage-gated K channels of the Kv2 family are highly expressed in brain and play dual roles in regulating neuronal excitability and in organizing endoplasmic reticulum - plasma membrane (ER-PM) junctions. Studies in heterologous cells suggest that the two pore-forming alpha subunits Kv2.1 and Kv2.

Distinct cellular expression and subcellular localization of Kv2 voltage-gated K channel subtypes in dorsal root ganglion neurons conserved between mice and humans.

The distinct organization of Kv2 voltage-gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located.

Structural modeling of hERG channel-drug interactions using Rosetta.

The human ether-a-go-go-related gene (hERG) not only encodes a potassium-selective voltage-gated ion channel essential for normal electrical activity in the heart but is also a major drug anti-target. Genetic hERG mutations and blockage of the channel pore by drugs can cause long QT syndrome, which predisposes individuals to potentially deadly arrhythmias. However, not all hERG-blocking drugs are proarrhythmic, and their differential affinities to discrete channel conformational states have been suggested to contribute to arrhythmogenicity.

Initiatives, Concepts, and Implementation Practices of the Findable, Accessible, Interoperable, and Reusable Data Principles in Health Data Stewardship: Scoping Review.

Background: Thorough data stewardship is a key enabler of comprehensive health research. Processes such as data collection, storage, access, sharing, and analytics require researchers to follow elaborate data management strategies properly and consistently. Studies have shown that findable, accessible, interoperable, and reusable (FAIR) data leads to improved data sharing in different scientific domains.

Pancreatitis and Hyperlipasemia in the Setting of Immune Checkpoint Inhibitor Therapy.

Background: Immune checkpoint inhibitor-induced pancreatic injury (ICI-PI) ranges from asymptomatic hyperlipasemia to symptomatic acute pancreatitis (AP). The proportion of pancreatic injury while receiving ICIs that is attributable to therapy remains unclear. We evaluated the etiology of hyperlipasemia in patients receiving ICIs, and the clinical characteristics, management, and outcomes of ICI-PI.

Early Liver Specialist Consultation is Associated With Faster Biochemical Resolution of Severe Immune Checkpoint Inhibitor-Induced Hepatitis.

Background: We evaluated the impact of gastroenterology/hepatology consultation, as recommended by guidelines, on the management of severe immune checkpoint inhibitor (ICI)-induced hepatitis.

Methods: We conducted a multicenter, retrospective cohort study of 294 patients who developed grade ≥3 (alanine aminotransferase [ALT] >200 U/L) ICI-induced hepatitis, with early gastroenterology/hepatology consultation defined as occurring within 7 days of diagnosis. The primary outcome was time to ALT normalization (≤40 U/L), and the secondary outcome was time to ALT improvement to ≤100 U/L.

Molecular determinants of μ-conotoxin KIIIA interaction with the human voltage-gated sodium channel Na1.7.

The voltage-gated sodium (Na) channel subtype Na1.7 plays a critical role in pain signaling, making it an important drug target. Here we studied the molecular interactions between μ-Conotoxin KIIIA (KIIIA) and the human Na1.

Reconversion of Parahydrogen Gas in Surfactant-Coated Glass NMR Tubes.

The application of parahydrogen gas to enhance the magnetic resonance signals of a diversity of chemical species has increased substantially in the last decade. Parahydrogen is prepared by lowering the temperature of hydrogen gas in the presence of a catalyst; this enriches the para spin isomer beyond its normal abundance of 25% at thermal equilibrium. Indeed, parahydrogen fractions that approach unity can be attained at sufficiently low temperatures.

Computational design of peptides to target Na1.7 channel with high potency and selectivity for the treatment of pain.

The voltage-gated sodium Na1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy. ProTx-II is a potent and moderately selective peptide toxin from tarantula venom that inhibits human Na1.

Immune checkpoint inhibitor gastritis is often associated with concomitant enterocolitis, which impacts the clinical course.

Background: Gastrointestinal immune-related adverse events are frequently caused by immune checkpoint inhibitors (ICIs) and often require interruption of cancer treatment. Compared with ICI colitis and enteritis, limited information exists about ICI gastritis. This study characterized clinical features and treatment outcomes of ICI gastritis.

Quantitative Analysis of Liver Disease Using MRI-Based Radiomic Features of the Liver and Spleen.

Background: Radiomics extracts quantitative image features to identify biomarkers for characterizing disease. Our aim was to characterize the ability of radiomic features extracted from magnetic resonance (MR) imaging of the liver and spleen to detect cirrhosis by comparing features from patients with cirrhosis to those without cirrhosis.

Methods: This retrospective study compared MR-derived radiomic features between patients with cirrhosis undergoing hepatocellular carcinoma screening and patients without cirrhosis undergoing intraductal papillary mucinous neoplasm surveillance between 2015 and 2018 using the same imaging protocol.

Structural modeling of the hERG potassium channel and associated drug interactions.

The voltage-gated potassium channel, K11.1, encoded by the human -Related Gene (hERG), is expressed in cardiac myocytes, where it is crucial for the membrane repolarization of the action potential. Gating of the hERG channel is characterized by rapid, voltage-dependent, C-type inactivation, which blocks ion conduction and is suggested to involve constriction of the selectivity filter.

Pore opening, not voltage sensor movement, underpins the voltage-dependence of facilitation by a hERG blocker.

A drug that blocks the cardiac myocyte voltage-gated K channels encoded by the human Ether-à-go-go-Related Gene (hERG) carries a potential risk of long QT syndrome and life-threatening cardiac arrhythmia, including Interestingly, certain hERG blockers can also facilitate hERG activation to increase hERG currents, which may reduce proarrhythmic potential. However, the molecular mechanism involved in the facilitation effect of hERG blockers remains unclear. The hallmark feature of the facilitation effect by hERG blockers is that a depolarizing preconditioning pulse shifts voltage-dependence of hERG activation to more negative voltages.

Mechanism of use-dependent Kv2 channel inhibition by RY785.

Understanding the mechanism by which ion channel modulators act is critical for interpretation of their physiological effects and can provide insight into mechanisms of ion channel gating. The small molecule RY785 is a potent and selective inhibitor of Kv2 voltage-gated K+ channels that has a use-dependent onset of inhibition. Here, we investigate the mechanism of RY785 inhibition of rat Kv2.

The AMIGO1 adhesion protein activates Kv2.1 voltage sensors.

Kv2 voltage-gated potassium channels are modulated by amphoterin-induced gene and open reading frame (AMIGO) neuronal adhesion proteins. Here, we identify steps in the conductance activation pathway of Kv2.1 channels that are modulated by AMIGO1 using voltage-clamp recordings and spectroscopy of heterologously expressed Kv2.