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DNA methylation can occur naturally or be induced by various environmental and chemotherapeutic agents. The regioisomeric N1- and N6-methyldeoxyadenosine (1mdA and 6mdA, respectively) represent an important class of methylated DNA adducts. In this study, we developed a shuttle vector- and next-generation sequencing-based assay to quantitatively assess the effects of 1mdA and 6mdA on the accuracy and efficiency of DNA transcription. Our results revealed that 1mdA can induce multiple types of mutant transcripts and strongly inhibit DNA transcription, whereas 6mdA is a nonmutagenic DNA adduct that can exhibit a subtle but significant inhibitory effect on DNA transcription in vitro and in human cells. Moreover, our results demonstrated that the transcription-coupled nucleotide excision repair pathway is dispensable for the removal of 1mdA and 6mdA from the template DNA strand in human cells. These findings provided new important insights into the functional interplay between DNA methylation modifications and transcription in mammalian cells.Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are the primary catabolic enzymes for endocannabinoids, anandamide (AEA), and 2-arachidonoyl glycerol. Numerous studies have shown that FAAH and MAGL play an important role in modulating various central nervous system activities; hence, the development of small molecule FAAH/MAGL inhibitors is an active area of research. Several small molecules possessing the carbamate scaffold are documented as potential FAAH/MAGL inhibitors. Here, we designed and synthesized a series of open chain and cyclic carbamates and evaluated their dual FAAH-MAGL inhibition properties. Phenyl [4-(piperidin-1-ylmethyl)phenyl]carbamate (2e) emerged as the most potent MAGL inhibitor (IC50  = 19 nM), benzyl (1H-benzo[d]imidazol-2-yl)carbamate (3h) was the most potent FAAH inhibitor (IC50  = 55 nM), and phenyl (6-fluorobenzo[d]thiazol-2-yl)carbamate (2i) egressed as a nonselective dual FAAH-MAGL inhibitor (FAAH 82 nM, MAGL 72 nM). The enzyme kinetics experiments revealed that the compounds inhibit FAAH/MAGL in a covalent-reversible manner, with a mixed binding mode of action. Moreover, the lead compounds were found suitable for blood-brain permeation in the parallel artificial membrane permeation assay. Furthermore, docking simulation experiments suggested that the potency of the lead compounds was governed by hydrogen bonds and hydrophobic interactions with the enzyme active sites. In silico drug-likeness and ADMETox prediction studies provided useful information on the compounds’ oral absorption, metabolism, and toxicity profiles. In summary, this study afforded potent multifunctional carbamates with appreciable pharmacokinetic profiles meriting further investigation.

Despite the lack of supporting data, many clinics perform sheath removal 4-6 hours after femoral percutaneous coronary intervention to reduce the risk of possible access site complications. This study aims to examine the effects of sheath removal immediately after the procedure on access site complications and patient comfort.

This prospective study included 349 patients who underwent percutaneous coronary intervention via the femoral site and 6 French guiding catheters. The sheath in the early group was removed immediately after the procedure without checking the activated clotting time levels but after 4 hours in the late group. Access site complications were recorded and patient comfort was evaluated using the Visual Analog Scale.

Patients were divided into 2 groups patients in the early removal group (n=171) and in the late removal group (n= 178). There was no statistically significant difference between the 2 groups in terms of access site complications. Three patients in the early removal group and 4 patients in the late removal group developed a hematoma. Six patients in the early removal group and 10 patients in the late removal group showed ecchymosis.TheVisualAnalogScalescorewas statistically significantly lower intheearly removal group compared with that in the late removal group [2 (1-3) vs. 3 (2-4), P < .001].

This study shows that immediate sheath removal is safe and more comfortable for patients with percutaneous coronary intervention who received weightadjusted dose of heparin, regardless of the percutaneous coronary intervention levels after the procedure.

This study shows that immediate sheath removal is safe and more comfortable for patients with percutaneous coronary intervention who received weightadjusted dose of heparin, regardless of the percutaneous coronary intervention levels after the procedure.

The aim of this study was to evaluate the contractile function of the left ventricular muscles in subjects with normal coronary artery and normal variations of coronary dominance.

This study was performed on 90 adult subjects with normal results of coronary arteries angiography, echocardiography, and electrocardiography. The participants were categorized into 3 groups of 30 with right-dominant, left-dominant, and codominant variations. Two-dimensional transthoracic echocardiography was performed with apical 2-, 3-, and 4-chamber views and parasternal basal, mid, and apical short-axis views. Then, images were analyzed offline using the velocity vector imaging method. In all studied groups, the mean and standard deviation of left ventricle coronary territorial longitudinal, circumferential, radial strains, and left ventricle global strains were determined. click here They were compared in 3 layers of sub-endocardial, myocardium, and sub-epicardial.

In terms of longitudinal and circumferential strains, there were significant differences in the most coronary territories and global strain among the right-dominant, left-dominant and codominant groups (P < .05). No significant differences in terms of territorial and global radial strains were observed among the study groups (P > .05).

Strain level decreased from endocardium to epicardium in all studied groups. Territorial and global contractile functions (longitudinal and circumferential strains) of the left ventricle vary depending on the variations of coronary arteries.

Strain level decreased from endocardium to epicardium in all studied groups. Territorial and global contractile functions (longitudinal and circumferential strains) of the left ventricle vary depending on the variations of coronary arteries.

To determine the accuracy of global longitudinal strain and territorial longitudinal strain in determining myocardial viability in comparison to single-photon emission computed tomography in out of window period anterior wall myocardial infarction patients.

This was a single-center, prospective study carried out in a tertiary care center in northern India. All patients presenting with anterior wall myocardial infarction-out of window period without ongoing chest pain and akinetic left-anterior descending territory on echocardiography were recruited. All patients underwent strain echocardiography and the determination of both global longitudinal strain and territorial longitudinal strain within 12-48 hours of anterior wall myocardial infarction. In addition, all underwent single-photon emission computed tomography to determine the viability status of the anterior myocardium.

Fifty-one patients of anterior wall myocardial infarction-out of window period were enrolled and underwent strain imaging with specafely and quickly in high-risk group of patients.

Treatment strategies in patients presenting with anterior wall myocardial infarction, outside the window period is largely guided by the hemodynamic status and influenced by the viability status of the myocardium. Strain echocardiography using speckle tracking provides gobal longitudinal strain and territorial longitudinal strain, both of which have good sensitivity and specificity in predicting viability and can be performed safely and quickly in high-risk group of patients.

Cardioneuroablation is one of the emerging therapies in vasovagal syncope. In this study, we present a simple method of cardioneuroablation performed via a rightsided approach, targeting anterior-right and right-inferior ganglionated plexi, along with procedural and follow-up data.

Patients who had underwent cardioneuroablation between March 2018 and September 2019 with vasovagal syncope in 2 clinics were enrolled in the study. All patients underwent radio-anatomically guided radiofrequency ablation targeting anterior-right ganglionated plexi and right-inferior ganglionated plexi. Syncope and symptom burden, 24-hour ambulatory electrocardiogram data at presentation, and at follow-up were assessed along with procedural data.

A total of 23 patients underwent modified right-sided cardioneuroablation. Mean basal cycle length decreased significantly from 862.3 ± 174.5 ms at the beginning of the procedure 695.8 ± 152.1 ms following the final radiofrequency ablation (P < .001). Mean 24-hour ambulatory heart rate increased significantly from 66.4 ± 10.7 bpm at baseline to 80 ± 7.6 bpm at follow-up (P < .001). Only 1 patient had 1 episode of syncope following the procedure at the mean follow-up period of 10 ± 2.9 months. The same patient had recurrent presyncope.

The right-sided cardioneuroablation approach was found to be an effective treatment for vasovagal syncope and may be regarded as a default initial cardioneuroablation technique.

The right-sided cardioneuroablation approach was found to be an effective treatment for vasovagal syncope and may be regarded as a default initial cardioneuroablation technique.

Tetrilimus (Sahajanand Medical Technologies Limited, Surat, India) is a biodegradable polymer-coated everolimus-eluting stent with cobalt-chromium stent platform and ultra-thin (60 µm) strut thickness. We aimed to report 1-year safety and clinical performance of Tetrilimus everolimus-eluting stent in patients with coronary artery disease in “real-world” clinical practice.

The PERFORMance of biodegradable polymer-coated ultra-thin EVERolimuseluting stents was an observational, multicenter, single-arm, and investigator-initiated retrospective registry. All “real-world” patients who had received Tetrilimus everolimuseluting stent between July-2015 and October-2016 at four study centers were analyzed. The data were collected retrospectively either by extraction from existing databases in consecutive fashion where index and follow-up data existed or the follow-up was obtained by telephonic contact. Primary endpoint was 1-year incidence of target lesion failure, which was defined as a composite endpoint of cardncluding those with high-risk characteristics and complex lesions.

Low incidences of target lesion failure and stent thrombosis at 1-year followup indicates that biodegradable polymer-coated ultra-thin Tetrilimus everolimus-eluting stents may have encouraging safety and efficacy in unselected real-world patients with coronary artery disease, including those with high-risk characteristics and complex lesions.

Coronary artery perforations are one of the most feared, rare, and catastrophic complication of percutaneous coronary intervention. Despite the remarkable increase in coronary angiography and percutaneous coronary intervention, there is no large database that collects coronary artery perforation for the Turkish population. Our study aimed to report our experience over a 10-year period for clinical and angiographic characteristics, management strategies, and outcomes of coronary artery perforation during the percutaneous coronary intervention at different cardiology departments in Turkey.

The study data came from a retrospective analysis of 48 360 percutaneous coronary intervention procedures between January 2010 and June 2020. A total of 110 cases who had coronary artery perforation during the percutaneous coronary intervention were found by angiographic review. Analysis has been performed for the basic clinical, angiographic, procedural characteristics, the management of coronary artery perforation, and outcome of all patients.