Genome-wide association studies and transcriptomics reveal mechanisms explaining the diversity of wheat root responses to nutrient availability.

Nutrient availability profoundly influences plant root system architecture, which critically determines crop productivity. While Arabidopsis has provided important insights into the genetic responses to nutrient deficiency, translating this knowledge to crops, particularly wheat, remains a subject of inquiry. Here, examining a diverse wheat population under varying nitrogen (N), phosphorus (P), potassium (K), and iron (Fe) levels, we uncover a spectrum of root responses, spanning from growth inhibition to stimulation, highlighting genotype-specific strategies. Furthermore, we reveal a nuanced interplay between macronutrient deficiency (N, P, and K) and Fe availability, emphasizing the central role of Fe in modulating root architecture. Through genome-wide association mapping, we identify 11 quantitative trait loci underlying root traits under varying nutrient availabilities, including homologous genes previously validated in Arabidopsis, supporting our findings. In addition, utilizing transcriptomics, ROS imaging, and antioxidant treatment, we uncover that wheat root growth inhibition by nutrient deficiency is attributed to ROS accumulation, akin to the role of ROS in governing Arabidopsis root responses to nutrient deficiency. Therefore, our study reveals the conservation of molecular and physiological mechanisms between Arabidopsis and wheat to adjust root growth to nutrient availability, paving the way for targeted crop improvement strategies aimed at increasing nutrient use efficiency.

Conduction system pacing: promoting the physiology to prevent heart failure.

Cardiac conduction system pacing provides physiological ventricular activation by directly stimulating the conduction system. This review describes the two types of conduction system pacing: His bundle pacing (HBP) and left bundle area pacing (LBAP). The most significant advantage of HB pacing is that it can provide a regular, narrow QRS; however, the disadvantages are challenging implantation and a high risk of re-intervention due to lead dislodgement and the development of high pacing threshold. LBAP provides optimum physiological activation of the left ventricle by engaging the left bundle/fascicular fibers. LBAP is more physiological than traditional RV apical pacing and could be an attractive alternative to conventional cardiac resynchronization therapy (CRT). The advantages of LBAP are a relatively more straightforward implantation technique than HBP, better lead stability and pacing thresholds. HBP and LBAP are more physiological than right ventricular pacing and may be used instead of conventional pacemakers. Both HBP and LBBP are being investigated as alternatives to conventional CRT.

Current status and future perspectives of proton exchange membranes for hydrogen fuel cells.

The world is on the lookout for sustainable and environmentally benign energy generating systems. Fuel cells (FCs) are regarded as environmentally friendly technology since they address a variety of environmental issues, such as hazardous levels of local pollutants, while also delivering economic advantages owing to their high efficiency. A fuel cell is a device that changes chemical energy contained in fuels (such as hydrogen and methanol) into electrical energy. A wide variety of FCs are commercially available; however, proton exchange membranes for hydrogen fuel cells (PEMFCs) have received overwhelming attention owing to their potential to significantly reduce our energy consumption, pollution emissions, and reliance on fossil fuels. The proton exchange membrane (PEM) is a critical element; it is made of semipermeable polymer and serves as a barrier between the cathode and anode during fuel cell construction. Additionally, membranes function as an insulator between the cathode and anode, facilitating proton exchange and inhibiting electron exchange between the electrodes. Due to the excellent features such as durability and proton conductivity, Nafion membranes are commercially viable and have been in use for a long time. However, Nafion membranes are costly, and their proton exchange capacities degrade over time at higher temperatures and low relative humidity. Other types of membranes have been considered in addition to Nafion membranes. This article discusses the problems connected with several types of PEMs, as well as the strategies adopted to improve their characteristics and performance.

Ten Steps in Adoption of Emerging Procedural Techniques: An Experience With Ethanol Ablation of Vein of Marshall (VOM).

Proceduralists must update their skill sets to provide patients with better care because of the addition of new and effective strategies post-training. For example, the current procedural strategy of pulmonary vein isolation for treating persistent atrial fibrillation (AF) is inadequate. However, the addition of ethanol ablation of the vein of Marshall (VOM), a relatively new procedural technique, can improve outcomes. Furthermore, the purpose of this report was to briefly explain VOM ethanol ablation, its role in atrial fibrillation and atypical flutter ablation, and to provide a template for performing a new procedural technique in the field.

Combined Machine Learning and GRID-Independent Molecular Descriptor (GRIND) Models to Probe the Activity Profiles of 5-Lipoxygenase Activating Protein Inhibitors.

Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA), and their high production has been reported in multiple allergic, autoimmune, and cardiovascular disorders. The biological synthesis of leukotrienes is instigated by transfer of AA to 5-lipoxygenase (5-LO) via the 5-lipoxygenase-activating protein (FLAP). Suppression of FLAP can inhibit LT production at the earliest level, providing relief to patients requiring anti-leukotriene therapy. Over the last 3 decades, several FLAP modulators have been synthesized and pharmacologically tested, but none of them could be able to reach the market. Therefore, it is highly desirable to unveil the structural requirement of FLAP modulators. Here, in this study, supervised machine learning techniques and molecular modeling strategies are adapted to vaticinate the important 2D and 3D anti-inflammatory properties of structurally diverse FLAP inhibitors, respectively. For this purpose, multiple machine learning classification models have been developed to reveal the most relevant 2D features. Furthermore, to probe the 3D molecular basis of interaction of diverse anti-inflammatory compounds with FLAP, molecular docking studies were executed. By using the most probable binding poses from docking studies, the GRIND model was developed, which indicated the positive contribution of four hydrophobic, two hydrogen bond acceptor, and two shape-based features at certain distances from each other towards the inhibitory potency of FLAP modulators. Collectively, this study sheds light on important two-dimensional and three-dimensional structural requirements of FLAP modulators that can potentially guide the development of more potent chemotypes for the treatment of inflammatory disorders.

Block of branching portion of bundle of His from catheter shaft during ablation of left ventricular outflow tract ventricular premature complexes.

Ventricular premature contractions are often located in the left ventricular outflow tract (LVOT). Components of the normal atrioventricular conduction apparatus are located just below the aortic valve in proximity to the membranous septum, between the noncoronary cusp and right coronary cusp. We present a case of injury to the bundle of His during an ablation of a ventricular premature contraction in the LVOT below the left coronary cusp, remote from the bundle of His, due to pressure from the proximal shaft of the catheter between the noncoronary cusp and the right coronary cusp.

Atrial tachyarrhythmia as a presenting symptom leading to the diagnosis of pulmonary sarcoidosis treated with catheter-based ablation.

A 55-year-old woman was referred for recurrent palpitations. A 48-hour ambulatory cardiac monitor revealed an atrial tachycardia rate up to 170 beats per minute. A subsequent electrophysiology study revealed atrial fibrillation and both typical and atypical atrial flutter. Computed tomography revealed multiple pulmonary nodules, and an endobronchial ultrasound-guided fine-needle aspiration confirmed the diagnosis of pulmonary sarcoidosis. The patient underwent radiofrequency ablation of the cavotricuspid isthmus and left common, right superior, and right inferior pulmonary vein isolation via cryoablation, without recurrent symptoms.

Flecainide toxicity late after liver transplantation.

Flecainide is an antiarrhythmic agent indicated for patients with supraventricular arrhythmias without ischemic or structural heart disease. Flecainide toxicity is a rare condition in which patients may present with bradycardia, widening of QRS, PR prolongation, ventricular tachycardia, syncope, malaise, dizziness, visual disturbance, nausea, vomiting, and/or lethargy. It carries an associated mortality rate of approximately 10%. Herein, we describe the course of a patient who experienced flecainide toxicity in the setting of renal and liver failure.

Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases.

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.

Cost-Effectiveness of an Antibacterial Envelope for Cardiac Implantable Electronic Device Infection Prevention in the US Healthcare System From the WRAP-IT Trial.

BACKGROUND: In the WRAP-IT trial (Worldwide Randomized Antibiotic Envelope Infection Prevention), adjunctive use of an absorbable antibacterial envelope resulted in a 40% reduction of major cardiac implantable electronic device infection without increased risk of complication in 6983 patients undergoing cardiac implantable electronic device revision, replacement, upgrade, or initial cardiac resynchronization therapy defibrillator implant. There is limited information on the cost-effectiveness of this strategy. As a prespecified objective, we evaluated antibacterial envelope cost-effectiveness compared with standard-of-care infection prevention strategies in the US healthcare system. METHODS: A decision tree model was used to compare costs and outcomes of antibacterial envelope (TYRX) use adjunctive to standard-of-care infection prevention versus standard-of-care alone over a lifelong time horizon. The analysis was performed from an integrated payer-provider network perspective. Infection rates, antibacterial envelope effectiveness, infection treatment costs and patterns, infection-related mortality, and utility estimates were obtained from the WRAP-IT trial. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality-adjusted life years were discounted at 3%. An upper willingness-to-pay threshold of $150 000 per quality-adjusted life year was used to determine cost-effectiveness, in alignment with the American College of Cardiology/American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. RESULTS: The base case incremental cost-effectiveness ratio of the antibacterial envelope compared with standard-of-care was $112 603/quality-adjusted life year. The incremental cost-effectiveness ratio remained lower than the willingness-to-pay threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. CONCLUSIONS: The absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of cardiac implantable electronic device infection. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02277990.

Convergent epicardial-endocardial ablation for treatment of long-standing persistent atrial fibrillation: A review of literature.

BACKGROUND AND AIM OF STUDY: The convergent procedure (CVP) is a hybrid ablation technique via a subxiphoid incision that has recently emerged as a treatment option for non-paroxysmal atrial fibrillation (npAF). By combining endocardial and epicardial ablation into a simultaneous or staged procedure, the pulmonary vein and posterior left atrium can be isolated with transmural lesion sets while minimizing the risk of proarrhythmic gaps that are a known limitation with endocardial linear lesion sets. We reviewed the 12-month outcomes in patients who underwent CVP compared to those who underwent endocardial catheter ablation (CA) and surgical ablation (SA). METHODS: A literature search was conducted using the PubMed database for publications related to CVP. Selected studies included detailed 12-month follow-up of patients, patient characteristics, periprocedural complications, use of antiarrhythmic drugs (AADs), and monitoring method. RESULTS: Five studies with 340 patients who underwent CVP between January 2009 and March 2017 were selected for this review. A total of 8.5% of patients had paroxysmal AF (pAF), 42.2% had persistent AF (peAF), and 49.1% had long-standing persistent AF (lspAF). At 12 months, 81.9% of patients were in sinus rhythm, while 54.1% of patients were in sinus rhythm while not taking AADs. The overall complication rate was 10%. CONCLUSION: CVP had better 1-year efficacy in eliminating AF when compared to CA. However, SA, specifically the Cox Maze IV, had lower rates of AF recurrence in the npAF patient population. Despite its promising 1-year efficacy rates, the periprocedural complication rate for CVP was significantly higher than both CA and SA.

Antibacterial Envelope to Prevent Cardiac Implantable Device Infection.

BACKGROUND: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

Effect of radiofrequency catheter ablation of ventricular tachycardia on left ventricular function in patients with prior myocardial infarction.

INTRODUCTION: Successful RF ablation of VT late after MI can involve multiple applications and long lines of RF lesions. The impact on left ventricular function is potentially important, but not well defined. Quantitative echocardiography was used to determine the effect of radiofrequency (RF) ablation on left ventricular function in patients with ventricular tachycardia (VT) after myocardial infarction (MI). METHODS AND RESULTS: In 62 patients (55 men; age 67 +/- 1.1 yr.) who underwent RF ablation for VT late after MI, left ventricular ejection fraction (LVEF) was quantified from digitized echocardiograms performed 25 RF lesions (Pre-LVEF 28.5 +/- 11.1% vs. Post-LVEF 28.1 +/- 10.8%, p = 0.74) or for the 7 patients who received >40 RF lesions (Pre-LVEF 29.9 +/- 12.7% vs. Post-LVEF 29.2 +/- 6.2%, p = 0.84). Although LVEF did not change for the group, LVEF increased >5% in 12/62 (19.4%) pts and decreased >/=5% in 14/62 (22.5%) pts. Patients with a decrease in EF did not differ from the remaining patients with respect to age, gender, number of RF lesions, or use of a cooled RF catheter, but did have a better initial EF (38.8 +/- 12.2% versus 27.2 +/- 10.6%, p = 0.001). CONCLUSION: Multiple RF ablation lesions confined to infarct regions do not measurably affect LV function, but a cautious approach, confining ablation lesions to areas of scar, as was attempted in this study, seems prudent.