Tenofovir alafenamide compared to tenofovir disoproxil fumarate, induces dysglycemia, and dyslipidemia in Wistar rats.

OBJECTIVES: To determine the metabolic effects of tenofovir alafenamide (TAF) compared to tenofovir disoproxil fumarate (TDF) in vivo. DESIGN AND METHODS: Male Wistar rats (Rattus novergicus, 250-300 g body weight) were divided into 3 groups (n = 8) and orally treated daily with 1.0 ml distilled water (group 1), TAF (0.42 mg/kg) (group 2), or TDF (5.0 mg/kg) (group 3), respectively, for 56 days. Glucose tolerance tests were done before the animals were sacrificed by halothane overdose, and blood was collected by cardiac puncture for the analysis of plasma lipids, electrolytes, and insulin. The kidney and pancreatic tissues were excised and homogenized to measure oxidative stress. Compartmentation of TAF and TDF was determined in NRK-52 and Peripheral Blood Mononuclear Cells (PBMC). RESULTS: There were no significant differences in weight gain among controls, TAF- or TDF-treated rats. TAF-treated rats had significantly increased fasting blood glucose (FBG), fasting plasma insulin (FPI), insulin resistance, impaired glucose tolerance, and dyslipidemia compared to control or TDF-treated rats, respectively. There was increased lipid peroxidation in the pancreas of TAF-treated compared to TDF-treated or control animals, respectively. TDF- treated rats presented with symptoms of Fanconi syndrome compared to TAF-treated or control animals, respectively. Kidney homogenates from TDF-treated animals had significantly reduced antioxidant enzyme activity compared to TAF-treated animals or controls, respectively. Intracellular concentrations of TAF were significantly higher than TDF in both NRK-52E cells and PBMC, respectively. CONCLUSIONS: TAF treatment is weight-neutral and causes dysglycemia, and dyslipidemia but not Fanconi syndrome compared to TDF.

Temporal variation in the structure, abundance, and composition of Laminaria hyperborea forests and their associated understorey assemblages over an intense storm season.

Kelp species function as important foundation organisms in coastal marine ecosystems where they provide biogenic habitat and ameliorate environmental conditions, often facilitating the development of diverse understorey assemblages. The structure of kelp forests is influenced by a variety of environmental factors, changes in which can result in profound shifts in ecological structure and functioning. Intense storm-induced wave action in particular, can severely impact kelp forest ecosystems. Given that storms are anticipated to increase in frequency and intensity in response to anthropogenic climate change, it is critical to understand their potential impacts on kelp forest ecosystems. During the 2021/22 northeast Atlantic storm season, the United Kingdom (UK) was subject to several intense storms, of which the first and most severe was Storm Arwen. Due to the unusual northerly wind direction, the greatest impacts of Storm Arwen were felt along the northeast coast of the UK where wind gusts exceeded 90 km/h, and inshore significant wave heights of 7.2 m and wave periods of 9.3 s were recorded. Here, we investigated temporal and spatial variation in the structure of L. hyperborea forests and associated understorey assemblages along the northeast coast of the UK over the 2021/22 storm season. We found significant changes in the cover, density, length, biomass, and age structure of L. hyperborea populations and the composition of understorey assemblages following the storm season, particularly at our most north facing site. We suggest continuous monitoring of these systems to further our understanding of temporal variation and potential recovery trajectories, alongside enhanced management to promote resilience to future perturbations.

Hypoxanthine in the microenvironment can enable thiopurine resistance in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, with relapse being a major obstacle to successful treatment. Our understanding of the mechanisms driving chemotherapy resistance and ultimately relapse in leukemia remains incomplete. Herein, we investigate the impact of the tumor microenvironment on leukemia cell drug responses using human plasma-like media (HPLM), designed to mimic physiological conditions more accurately ex vivo. We demonstrate that while most chemotherapeutics maintain an efficacy in HPLM comparable to standard tissue culture media, the thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) exhibit significantly reduced potency and efficacy against both B- and T- leukemia cells in HPLM. By merging our understanding of thiopurines' mechanism of action with the metabolites supplemented in HPLM compared to standard media, we proposed and subsequently validated the hypothesis that hypoxanthine, a purine derivative, is responsible for conferring resistance to the thiopurines. Importantly, the concentration of hypoxanthine required for resistance is comparable to physiological levels found in vivo, supporting clinical relevance. Our findings demonstrate the utility of a more physiologic media in identifying and characterizing mechanisms by which the microenvironment can enable resistance. Understanding such interactions may inform strategies to overcome drug resistance and improve therapeutic outcomes in pediatric leukemia.

Return on Investment of Three-Year Accelerated Programs for Students, Medical Schools, Departments, and Community.

Building on the initial accelerated pathway programs in the 1970s to increase workforce, nearly 30 schools have launched accelerated 3-year pathways (A3YP) during the past decade. The authors based on their educational roles, experiences, and scholarship with A3YP provide this perspective of the argument for A3YP and potential disadvantages for each group-students, schools, residencies, departments, and community. When schools consider innovations, they might consider A3YPs for multiple reasons; this perspective helps provide justification for the program and broadly considers return on investment (ROI). The ROI for students includes decreased debt, reduced costs and stress associated with the fourth-year residency applications, and a directed pathway with facilitated transition into a residency program with accompanying professional identity development. Disadvantages for students include early specialty commitment, risk of deceleration, and condensed curriculum. The ROI for schools includes recruiting and retaining students, who will then transition more easily into residency and stimulating innovation. Residency programs gain residents with known skills, who have been a part of the department for 3 years. In addition, fewer residency slots for interviewing leads to saving recruitment administrative costs and time. Finally, many programs are intended to increase the workforce, since students who come to the region for medical school and transition directly into residency are likely to stay in the region. Disadvantages include increased curricular complexity for the medical school, increased administrative support, and advising resources. Finally, several of the accelerated programs attract matriculants from diverse backgrounds contributing to the diversity of the medical school, residency program, and community workforce.

The genome sequence of common knotgrass, Polygonum aviculare L. (Polygonaceae).

We present a genome assembly from an individual Polygonum aviculare (common knotgrass; Eudicot; Magnoliopsida; Caryophyllales; Polygonaceae). The genome sequence is 351.6 megabases in span. Most of the assembly is scaffolded into 10 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 333.39 kilobases and 163.28 kilobases in length, respectively.

Malignant Epithelioid Mesenchymal Neoplasm with FUS::CREM Gene Fusion Arising in the Tongue: A Case Report Detailing Clinicopathological, Imaging, and Molecular Features.

FUS::CREM fusion is a distinct primary driver in rare neoplasms of the head and neck and other anatomic sites. Herein, we describe the clinicopathological, imaging, and molecular features of a malignant epithelioid mesenchymal neoplasm harboring FUS::CREM fusion, arising in the tongue of a 46-year-old male. Clinically, the patient presented with a left upper neck mass. Imaging revealed a 4.0 cm mass at the left base of tongue. Histologically, the tumor consisted of sheets of loosely cohesive, small round to ovoid cells with moderate cytoplasm, small nuclei with coarse chromatin, frequent nuclear pseudoinclusions, and dense peripheral lymphoplasmacytic and histiocytic infiltrates. Malignant features, including tumor necrosis, perineural invasion, and increased mitotic activity were observed; however, lymphovascular invasion was absent with no evidence metastatic disease in the examined lymph nodes. A comprehensive panel of immunohistochemical stains showed positivity for synaptophysin and ALK, with negative results for all other markers. RNA-based next-generation sequencing using anchored multiplex polymerase chain reaction (PCR) was performed and detected FUS::CREM fusion gene. The patient was treated by excision and postsurgical chemoradiation with no evidence of recurrence after four months. Additional cases supported by comprehensive clinical data collected over an extended period are necessary to precisely characterize epithelioid mesenchymal neoplasms harboring FUS::CREM fusion in the head and neck.

A comparison of respiratory oscillometry and spirometry in idiopathic pulmonary fibrosis: performance time, symptom burden and test-retest reliability.

Study question: In large multinational patient surveys, spirometry (which requires repeated, reproducible maximal efforts) can be associated with cough, breathlessness and tiredness, particularly in those with idiopathic pulmonary fibrosis (IPF). Oscillometry is an effort-independent test of airways resistance and reactance. We hypothesised that oscillometry would take less time to perform and would be associated with reduced symptom burden than spirometry. Patients and methods: Spirometry and oscillometry were performed in 66 participants with IPF and repeated 2 weeks later. We compared time taken to perform tests, symptom burden and test-retest reliability with Bland-Altman plots and intraclass correlation coefficients (ICCs). Results: Oscillometry took significantly less time to perform than spirometry (mean -4.5 (99% CI -6.0 to -3.0) min) and was associated with lower symptom burden scores for cough (-1.3, 99% CI -1.7 to -0.8), breathlessness (-1.0, 99% CI -1.4 to -0.5), and tiredness (-0.5, 99% CI -0.9 to -0.2). On Bland-Altman analysis, all measures showed good agreement, with narrow limits of agreement and the mean bias lying close to 0 in all cases. The ICCs for forced expiratory volume in 1 s and forced vital capacity were 0.94 and 0.89, respectively, and ranged between 0.70 and 0.90 for oscillometry measures. Conclusion: Oscillometry is quicker to perform and provokes less symptoms than spirometry in patients with IPF.

Next generation triplex-forming PNAs for site-specific genome editing of the F508del CFTR mutation.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein for which there is no cure. One approach to cure CF is to correct the underlying mutations in the CFTR gene. We have used triplex-forming peptide nucleic acids (PNAs) loaded into biodegradable nanoparticles (NPs) in combination with donor DNAs as reagents for correcting mutations associated with genetic diseases including CF. Previously, we demonstrated that PNAs induce recombination between a donor DNA and the CFTR gene, correcting the F508del CFTR mutation in human cystic fibrosis bronchial epithelial cells (CFBE cells) and in a CF murine model leading to improved CFTR function with low off-target effects, however the level of correction was still below the threshold for therapeutic cure. METHODS: Here, we report the use of next generation, chemically modified gamma PNAs (γPNAs) containing a diethylene glycol substitution at the gamma position for enhanced DNA binding. These modified γPNAs yield enhanced gene correction of F508del mutation in human bronchial epithelial cells (CFBE cells) and in primary nasal epithelial cells from CF mice (NECF cells). RESULTS: Treatment of CFBE cells and NECF cells grown at air-liquid interface (ALI) by NPs containing γtcPNAs and donor DNA resulted in increased CFTR function measured by short circuit current and improved gene editing (up to 32 %) on analysis of genomic DNA. CONCLUSIONS: These findings provide the basis for further development of PNA and NP technology for editing of the CFTR gene.

Exploration of Materials for Three-Dimensional NMR Microcoil Production via CNC Micromilling and Laser Etching.

The excellent versatility of 5-axis computer numerical control (CNC) micromilling has led to its application for prototyping NMR microcoils tailored to mass-limited samples (reducing development time and cost). However, vibrations during 5-axis milling can hinder the creation of complex 3D volume microcoils (i.e., solenoids and saddle coils). To address these limitations, a high-resolution NSCNC ELARA 4-axis milling machine was developed with the extra precision required for making complex 3D volume microcoils. Upon investigating the performance of resonators made with various copper-coated dielectrics, resonators with poly(methyl methacrylate) (PMMA) provided the best SNR/line shape. Thus, complex 1.7 mm microcoil designs were machined from Cu-coated PMMA. A milled 6.4 mm solenoid also provided 6.6× the total carbon signal for a 13C-labeled broccoli seed compared to a commercial inverse 5 mm NMR probe (demonstrating potential for larger coil designs). However, the manufacture of coils <1.7 mm with copper-coated PMMA rods was challenging as ∼0.5 mm of remaining PMMA was needed to retain their structural integrity. To manufacture smaller microcoils, both a solenoid and saddle coil (both with 1 mm O.D., 0.1 mm thick walls) were etched from Cu-coated glass capillaries using a UV picosecond laser that was mounted onto an NSCNC 5-axis MiRA7L. Both resonators showed excellent signal and identified a wide range of metabolites in a 13C-labeled algae extract, while the solenoid was further tested on two copepod egg sacs (∼4 µg of total sample). In summary, the flexibility to prototype complex microcoils in-house allows laboratories to tailor microcoils to specific mass-limited samples while avoiding the costs of cleanrooms.

The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple Negative Breast Cancer by Attenuating TGFß Signaling.

The pogo transposable element derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFß pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Whereas POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade.

Heart rate variability during sleep onset in patients with insomnia with or without comorbid sleep apnea.

OBJECTIVES: Pre-sleep stress or hyperarousal is a known key etiological component in insomnia disorder. Despite this, physiological alterations during the sleep onset are not well-understood. In particular, insomnia and obstructive sleep apnea (OSA) are highly prevalent co-morbid conditions, where autonomic regulation may be altered. We aimed to characterize heart rate variability (HRV) during sleep onset as a potential measure of pre-sleep hyperarousal. METHODS: We described the profile of pre-sleep HRV measures and explore autonomic differences in participants with self-reported insomnia disorder (with no OSA, n = 69; with mild OSA, n = 70; with moderate or severe OSA, n = 66), compared to normal sleep controls (n = 123). Heart rate data during the sleep onset process were extracted for HRV analyses. RESULTS: During the sleep onset process, compared to normal sleep controls, participants with insomnia had altered HRV, indicated by higher heart rate (p = 0.004), lower SDNN (p = 0.003), reduced pNN20 (p < 0.001) and pNN50 (p = 0.010) and lower powers (p < 0.001). Participants with insomnia and moderate/severe OSA may have further deteriorated HRV outcomes compared to no/mild OSA patients with insomnia but differences were not significant. Insomnia itself was associated with significantly higher heart rate, lower pNN20, and lower high frequency power even after adjustment for age, gender, BMI and OSA severity. CONCLUSIONS: Participants with insomnia had lower vagal activity during the sleep onset period, which may be compounded by OSA, reflected in higher heart rates and lower HRV. These altered heart rate dynamics may serve as a physiological biomarker for insomnia during bedtime wakefulness, or as a potential tool to evaluate the efficacy of behavioral interventions which target bedtime stress.

Tunable Isometric Donor-Acceptor Wurster-Type Covalent Organic Framework Photocathodes.

Covalent organic frameworks (COFs) offer remarkable versatility, combining ordered structures, high porosity, and tailorable functionalities in nanoscale reaction spaces. Herein, we report the synthesis of a series of isostructural, photoactive Wurster-type COFs achieved by manipulating the chemical and electronic nature of the Wurster aromatic amine building blocks. A series of donor-acceptor-donor (D-A-D) Wurster building block molecules was synthesized by incorporating heteroaromatic acceptors with varying strengths between triphenylamine donor groups. These tailored building blocks were integrated into a 2D COF scaffold, resulting in highly crystalline structures and similar morphologies across all COFs. Remarkably, this structural uniformity was also achieved in the synthesis of homogeneous and oriented thin films. Steady-state photoluminescence revealed a tunable red-shift in film emission exceeding 100 nm, demonstrating effective manipulation of their optical properties. Furthermore, photoelectrochemical studies exhibited a doubled current density (8.1 µA cm-2 at 0.2 VRHE) for the COF with the strongest acceptor unit. These findings highlight the potential of these D-A-D COFs in photoelectrochemical water splitting devices and pave the way for further exploration of structure-property relationships in this promising class of photoactive materials.

Impact of aspirin dose according to race in secondary prevention of atherosclerotic cardiovascular disease: a secondary analysis of the ADAPTABLE randomised controlled trial.

OBJECTIVES: To evaluate whether the effectiveness and safety of low (81 mg daily) versus high-dose (325 mg daily) aspirin is consistent across races among patients with established atherosclerotic cardiovascular disease (ASCVD). DESIGN: A secondary analysis of the randomised controlled trial ADAPTABLE was performed. SETTING: The study was conducted in 40 centres and one health plan participating in the National Patient-Centred Clinical Research Network (PCORnet) in the USA. PARTICIPANTS: Among 15 076 participants with established ASCVD, 14 096 had self-reported race available and were included in the analysis. Participants were divided according to self-reported race as Black (n=1311, 9.3%), White (n=11 990, 85.1%) or other race (n=795, 5.6%). INTERVENTIONS: Participants were randomised to open-label daily aspirin doses of 81 mg versus 325 mg in a 1:1 ratio for a median of 26.2 months. PRIMARY AND SECONDARY OUTCOMES MEASURES: The primary effectiveness endpoint was a composite of death from any cause, hospitalisation for myocardial infarction or hospitalisation for stroke. The primary safety endpoint was hospitalisation for bleeding requiring blood product transfusion. RESULTS: Estimated cumulative incidence of the primary effectiveness endpoint at median follow-up with the 81 mg and the 325 mg daily doses were 6.70% and 7.12% in White participants (adjusted HR: 1.00 [95% CI: 0.88 to 1.15]); 12.27% and 10.69% in Black participants (adjusted HR: 1.40 [95% CI: 1.02 to 1.93]); and 6.88% and 7.69% in other participants (adjusted HR: 0.86 [95% CI: 0.54 to 1.39]) (p-interaction=0.12), respectively. There was no significant interaction between self-reported race and assigned aspirin dose regarding the secondary effectiveness and the primary safety endpoints. CONCLUSION: Race is not an effect modifier on the impact of aspirin dosing on effectiveness and safety in patients with established ASCVD. In clinical practice, treatment decisions regarding aspirin dose in secondary prevention of ASCVD should not be influenced by race. TRIAL REGISTRATION NUMBER: NCT02697916.

Quantitative plasma proteomic analysis in children after superior cavopulmonary anastomosis with pulmonary arteriovenous malformations.

Approximately 1000 children are born every year in the United States with one effective cardiac pumping chamber, or single ventricle heart disease. One of the early causes of mortality in this population is pulmonary arteriovenous malformations (PAVMs), which allow blood to bypass gas exchange in the lungs. PAVMs most frequently occur in children after superior cavopulmonary anastomosis (SCPA), a procedure that redirects venous blood from the upper body to the lungs. Because plasma proteins are in part responsible for directing angiogenesis, we hypothesized that differential protein concentrations would be observed in superior caval blood among children after SCPA according to PAVM status. We performed quantitative plasma proteomics from 11 children with PAVMs and in seven children without PAVMs; an additional 11 children with Fontan circulation were included as a reference. Among children with SCPA, there were no significant differences in the plasma proteomes for those with and without PAVMs. When comparing children with Fontan circulation to those with SCPA and PAVMs, 18 proteins exhibited differential expression (10 downregulated and eight upregulated) in superior caval plasma. These results suggest that factors other than, or in addition to, plasma proteins may be responsible for single ventricle patients' susceptibility to PAVMs after SCPA. IMPACT: What is the key message of your article? We did not identify significant differences in plasma proteins when comparing those children with and without pulmonary arteriovenous malformations (PAVMs) after superior cavopulmonary anastomosis (SCPA). What does it add to the existing literature? The etiology of PAVMs in this population is likely due to factors other than, or in addition to, differences in plasma proteins. What is the impact? Further studies are needed to identify causes of PAVMs among children after SCPA.

Cyto- and genotoxicity evaluation of water samples collected from two rivers in the Kosovo.

River water in Kosovo is exposed to various discharges from industrial and agricultural activities as well as to urban wastewater. Rivers Sitnica and Drenica are among the most affected ones and water samples drawn from these rivers show the presence of various toxic substances. Genotoxic effects are seen in fish living in these rivers indicating a cytotoxic and mutagenic potential of the river water. Aiming at substantiating these observations, we assessed cyto- and genotoxic effects of water samples collected at different locations from Drenica and Sitnica river. Samples drawn from Lake Badovc served for comparison. To address seasonal effects, samples were collected at different seasons/time points during the period summer 2016 - spring 2018. The water samples were analyzed employing primary rat hepatocytes as reliable in vitro cell model for the assessment of cytotoxic effects (mitotic arrest and cell death) and DNA damage/genotoxicity (micronucleus assay, Comet assay). The results do not account for significant effects associated with specific locations but demonstrate seasonal differences of the genotoxic potential of the water samples collected along both rivers, which are accompanied by a limited cytotoxic potential. Our data provide substantial support to earlier observations and strongly warrant the need for continuous chemical as well as biological monitoring of the river water in Kosovo, focusing on an improved toxicant profiling of the river water and investigations addressing the observed seasonal variations.

The Job Demands and Accommodation Planning Tool (JDAPT): A Nine-Month Evaluation of Use, Changes in Self-efficacy, Presenteeism, and Absenteeism in Workers with Chronic and Episodic Disabilities.

PURPOSE: Enhancing workplace communication and support processes to enable individuals living with disabilities to sustain employment and return to work is a priority for workers, employers, and community stakeholders. The objective of this study was to evaluate a new resource that addresses support challenges, the Job Demands and Accommodation Planning Tool (JDAPT), and assess its use, relevance, and outcomes over a nine-month follow-up period. METHODS: Workers with physical and mental health/cognitive conditions causing limitations at work were recruited using purposive sampling. Online surveys were administered at baseline (prior to using the JDAPT), and at three and nine months post-baseline. Information was collected on demographics (e.g., age, gender) and work characteristics (e.g., job sector, organization size). Outcomes included assessing JDAPT use and relevance, and changes in self-efficacy, work productivity difficulties, employment concerns, difficulties with job demands, and absenteeism. RESULTS: Baseline participants were 269 workers (66% women; mean age 41 years) of whom 188 (69.9%) completed all three waves of data collection. Many workers reported using JDAPT strategies at and outside of work, and held positive perceptions of the tool's usability, relevance, and helpfulness. There were significant improvements (Time 1-2; Time 1-3) in self-efficacy, perceived work productivity, and absenteeism with moderate to large effect sizes in self-efficacy and productivity (0.46 to 0.78). Findings were consistent across gender, age, health condition, and work context variables. CONCLUSIONS: The JDAPT can enhance support provision and provide greater transparency and consistency to workplace disability practices, which is critical to creating more inclusive and accessible employment opportunities.

Polarized Raman Study of First-Order Phonons in Self-Flux Grown Single-Crystalline WTe2.

Bulk single crystals of WTe2 were grown by the self-flux method and characterized by X-ray diffraction, polarized micro-Raman spectroscopy, and optical microscopy. All methods revealed a high crystalline quality, thus demonstrating the advantages of the growth method used as a starting base for the synthesis of high-quality 2D materials. In each main scattering configuration, we recorded a series of Raman spectra in different sample orientations achieved by rotating the sample around the incident laser beam. In addition to the well-established case of excitation along the c crystal axis, we also applied laser excitation along the a and b axes. Thus, scattering configurations were also realized in the XZ and YZ polarization planes, for which no comparative literature data have yet been established. In these experiments, two new Raman-active phonons with B2 symmetry and frequencies of 89 cm-1 and 122 cm-1 were identified. The obtained experimental data enabled us to derive the magnitude ratios of all three tensor elements of the A1 modes and to find their phase differences.

ZEBRA study: The Z stitch Early Bed Rest Assessment study.

Background: Safe and effective management of venous vascular access is a key component of electrophysiology (EP) procedures. Recently, the Z-stitch method has been developed for effective venous hemostasis. However, the standard postprocedure protocol often includes prolonged bed rest, which may affect patient satisfaction. The ZEBRA (Z stitch Early Bed Rest Assessment) study aims to systematically investigate and quantify patient satisfaction metrics and safety parameters associated with the early mobilization after Z-stitch placement. Objective: This study primarily investigates whether early mobilization following Z-stitch placement in venous vascular access management during EP procedures enhances patient satisfaction without compromising safety. Methods: In this prospective, multicenter, randomized clinical trial, approximately 200 patients undergoing various EP procedures at Oregon Health and Science University and Veterans Affairs Portland Health Care System will be randomly assigned to either a 1- or 4-hour bed rest regimen post-Z stitch. Patient satisfaction will be assessed through survey, alongside monitoring for hematomas, bleeding complications, and other safety endpoints. The study includes stratification based on heparin administration and sheath size to ensure robust and nuanced data analysis. Results: We anticipate that early mobilization will lead to higher patient satisfaction scores. We also expect to closely monitor and report the incidence of hematomas, pain medication use, healthcare costs, patient outcomes at 30 days, time to ambulation, and hospital readmissions or emergency visits related to groin complications. Conclusion: The ZEBRA study is poised to fill a critical knowledge gap in postprocedure care in EP labs. By rigorously evaluating the impact of early mobilization on patient satisfaction and safety, this study could significantly influence future guidelines and improve patient experiences in EP procedures.