Identification of novel inhibitors of the transcriptional coactivator MRTF-A for HCC therapy.

Myocardin-related transcription factor A (MRTF-A) is a coactivator of serum response factor (SRF), which regulates the expression of genes involved in cell proliferation, migration, and differentiation and has been implicated in hepatocellular carcinoma (HCC) progression. We recently established inhibition of the transcriptional activity of MRTF-A by NS8593 as a novel therapeutic approach for HCC therapy. NS8593 is a negative gating modulator of the transient receptor potential cation channel TRPM7.

Multifunctional microelectronic fibers enable wireless modulation of gut and brain neural circuits.

Progress in understanding brain-viscera interoceptive signaling is hindered by a dearth of implantable devices suitable for probing both brain and peripheral organ neurophysiology during behavior. Here we describe multifunctional neural interfaces that combine the scalability and mechanical versatility of thermally drawn polymer-based fibers with the sophistication of microelectronic chips for organs as diverse as the brain and the gut. Our approach uses meters-long continuous fibers that can integrate light sources, electrodes, thermal sensors and microfluidic channels in a miniature footprint.

Multi-organ dysfunction syndrome in patients undergoing extracorporeal life support.

Background: Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable.

Methods: Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed.

Mid-Term Outcomes of a Hybrid Approach Involving Open Surgery Plus TEVAR of the Descending Aorta in the Treatment of Complex Type A Dissection.

Objectives: Type A aortic dissection with true lumen collapse and malperfusion downstream is associated with a devastating prognosis. This study compares the clinical outcomes of two operative strategies for this disease: hybrid approach of ascending aorta (and hemiarch replacement) supplemented with retrograde stenting of the descending aorta (thoracic endovascular aortic repair [TEVAR]) and standard ascending aorta (and hemiarch) replacement without stent placement.

Methods: From January 1, 2016 to December 31, 2019, 81 patients with type A aortic dissection were studied.

The preference for sugar over sweetener depends on a gut sensor cell.

Guided by gut sensory cues, humans and animals prefer nutritive sugars over non-caloric sweeteners, but how the gut steers such preferences remains unknown. In the intestine, neuropod cells synapse with vagal neurons to convey sugar stimuli to the brain within seconds. Here, we found that cholecystokinin (CCK)-labeled duodenal neuropod cells differentiate and transduce luminal stimuli from sweeteners and sugars to the vagus nerve using sweet taste receptors and sodium glucose transporters.

Evaluation of Flavor Effects on Oral Nicotine Liking and/or Disliking Using the Taste Reactivity Test in Rats.

Introduction: Tobacco product flavors may change the sensory properties of nicotine, such as taste and olfactory cues, which may alter nicotine reward and aversion and nicotine taking behavior. The hedonic or aversive value of a taste stimulus can be evaluated by examining affective orofacial movements in rodents.

Aims And Methods: We characterized taste responses to various oral nicotine concentrations using the taste reactivity test in rats.

Inner hair cell stereocilia displacement in response to focal stimulation of the basilar membrane in the ex vivo gerbil cochlea.

The inner hair cells in the mammalian cochlea transduce mechanical signals to electrical signals that provide input to the auditory nerve. The spatial-temporal displacement of the inner hair cell stereocilia (IHCsc) relative to basilar membrane (BM) displacement is central to characterizing the transduction process. This study specifically focuses on measuring displacement of the stereocilia hair bundles in the radial dimensions where they are most sensitive.

Female Patients With Sleep-Disordered Breathing Display More Frequently Heart Failure With Preserved Ejection Fraction.

Sleep-disordered breathing (SDB) is a widespread disease that is often associated with heart failure (HF) with preserved ejection fraction (HFpEF). HFpEF is more frequent in women than in men, but detailed pathomechanisms remain unclear. We investigated HFpEF in women and men in a high-risk cohort with SDB monitoring.

The nerve not taken.

Nutrients entering the gut influence our brains through uncharacterized circuits. In this issue of Cell Metabolism, Goldstein et al. (2021) show hypothalamic neurons responding, via distinct neural paths, to nutrients infused in different intestinal segments.

A decade of surgical therapy in an all-comer cohort with type A aortic dissection.

Background: We reported on a decade of aortic surgery for type A aortic dissection to assess surgical techniques employed and outcomes over time in an all-comer analysis of a mid-size university cardiosurgical center.

Methods: From 2009 to 2018, 283 patients (189 males and 94 females, mean age 62 years, range 30-85 years), who underwent surgical therapy for type A aortic dissection in our institution were included in a retrospective statistical analysis.

Results: Among all the patients, 55.

Long-Term Results of Patch Repair in Destructive Valve Endocarditis.

Objectives: Treatment of destructive endocarditis with abscess formation is a surgical challenge and associated with significant morbidity and mortality. A root replacement is often performed in case of an annular abscess. This retrospective study was designed to assess the long-term outcome of extensive debridement and patch reconstruction as an alternative approach.

25 Years' Experience with Redo Operations in Cardiac Surgery-Third-Time Sternotomy Procedures.

Background: Over the years, open heart surgery has become more complex, and especially reoperative surgery, more demanding. The risk of third-time or more sternotomy procedures is unclear.

Methods: We reviewed our institutional experience of 25 years based on two generations of cardiac surgeons in a German university medical center to document frequency, outcome, and complications of the various types of open heart procedures.

Diagnostic value of FDG PET/CT imaging in patients with surgically managed infective endocarditis: results of a retrospective analysis at a tertiary center.

Background: We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE).

Methods: We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT.

Results: Final analysis included 29 patients, whereof 28 patients had surgically proven IE.

The oral Ca/calmodulin-dependent kinase II inhibitor RA608 improves contractile function and prevents arrhythmias in heart failure.

Aims: Excessive activation of Ca/calmodulin-dependent kinase II (CaMKII) is of critical importance in heart failure (HF) and atrial fibrillation. Unfortunately, lack of selectivity, specificity, and bioavailability have slowed down development of inhibitors for clinical use. We investigated a novel CaMKIIδ/CaMKIIɣ-selective, ATP-competitive, orally available CaMKII inhibitor (RA608) on right atrial biopsies of 119 patients undergoing heart surgery.

Dantrolene reduces CaMKIIδC-mediated atrial arrhythmias.

Aims: In atrial fibrillation (AF), an increased diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) mediated by calcium/calmodulin-dependent-protein-kinaseIIδC (CaMKII) can serve as a substrate for arrhythmia induction and persistence. Dantrolene has been shown to stabilize the cardiac ryanodine-receptor. This study investigated the effects of dantrolene on arrhythmogenesis in human and mouse atria with enhanced CaMKII activity.

Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats.

Acetylcholine is implicated in mood disorders including depression and anxiety. Increased cholinergic tone in humans and rodents produces pro-depressive and anxiogenic-like effects. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate these responses in male rats, as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and the forced swim test (FST).

Neuropod Cells: The Emerging Biology of Gut-Brain Sensory Transduction.

Guided by sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior.

The impact of interleukin serum levels on the prognosis of patients undergoing venoarterial extracorporeal membrane oxygenation.

Extracorporeal life support is increasingly used in the treatment of patients presenting with cardiogenic shock or in need of cardiopulmonary resuscitation. Identifying therapeutic targets and factors associated with the prognosis are highly desirable. The present study analyzed the impact of interleukin 6 and 8 on the outcome of patients undergoing venoarterial extracorporeal membrane oxygenation (VA ECMO).

Enhanced CaMKII-Dependent Late I Induces Atrial Proarrhythmic Activity in Patients With Sleep-Disordered Breathing.

Rationale: Sleep-disordered breathing (SDB) is frequently associated with atrial arrhythmias. Increased CaMKII (Ca/calmodulin-dependent protein kinase II) activity has been previously implicated in atrial arrhythmogenesis.

Objective: We hypothesized that CaMKII-dependent dysregulation of Na current (I) may contribute to atrial proarrhythmic activity in patients with SDB.

Cholinergic Receptor Blockade in the VTA Attenuates Cue-Induced Cocaine-Seeking and Reverses the Anxiogenic Effects of Forced Abstinence.

Drug relapse after periods of abstinence is a common feature of substance abuse. Moreover, anxiety and other mood disorders are often co-morbid with substance abuse. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate drug-seeking and anxiety-related behavior in rodent models.

Remote programming of cochlear implants in users of all ages.

Background: Remote programming for adult cochlear implant (CI) users is feasible, safe, and effective. Limited evidence, however, exists on if remote CI programming can also be productively done with paediatric CI users.

Aims/objectives: To assess the safety and feasibility of remote CI programming in CI users for all ages.

Ischemia-related vascular complications of percutaneously initiated venoarterial extracorporeal membrane oxygenation: Indication setting, risk factors, manifestation and outcome.

Purpose: Venoarterial (VA) ECMO is widely accepted as salvage therapy for cardio-respiratory or cardiac failure. Vascular complications from cannulation are common and potentially life-threatening. Here, we retrospectively analyzed vascular complications following VA ECMO therapy.

Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia.

Introduction: Patients with schizophrenia (SCZ) smoke at a rate of 4-5 times higher than the general population, contributing to negative health consequences in this group. One possible explanation for this increased smoking is that individuals with SCZ find nicotine (NIC) more reinforcing. However, data supporting this possibility are limited.

Impact of coronary angiography early after CABG for suspected postoperative myocardial ischemia.

Background: The incidence of perioperative myocardial infarction is reported to 2-8%. The aim of the study (retrospectively registered) was to evaluate whether control coronary angiography after surgery is useful in case of suspected postoperative myocardial ischemia.

Methods: All patients who demonstrated signs of myocardial ischemia post CABG and underwent coronary angiography from 6/2008 to 06/2015 were retrospectively analyzed.