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Abstract Background There has been an increase in the integration of qualitative studies in randomised controlled trials. The purpose of this article is to reflect on our experience of carrying out a rapid qualitative study during a feasibility trial of goal-directed fluid therapy (GDFT) in patients with acute pancreatitis, including our sharing of emerging findings and the use of these findings by the trial team. Methods The study was designed as a rapid feedback evaluation and combined interviews with staff and patients who took part in the trial. Findings The rapid qualitative study pointed to common problems in trial recruitment among multiple sites, where lack of engagement of clinical teams across sites might impact negatively on patient recruitment. The article describes how the use of rapid feedback loops can be used as the trial is ongoing to inform changes in implementation. It also covers the potential challenges of working rapidly and collaborative with the trial team. Conclusions Rapid feedback evaluations can be used to generate findings across all stages of trial design and delivery. Additional research is required to explore the implementation of this research design in other settings and trial designs.

Highly ordered monolayers of [epsi]-Co nanopartilces are prepared from Langmuir films and self-assembled three-dimensional (3D) arrays formed by slow precipitation of colloidal dispersions of same nanoparticles. Three-dimensional (3D) arrays of [epsi]-Co nanoparticles show stronger interactions compared to monolayers due to an increased number of nearest neighbors.

Magnetostatic interactions are studied in two types of nanoparticle assemblies. Highly ordered monolayers of [variant_greek_epsilon]-Co nanoparticles are prepared from Langmuir films and self-assembled three-dimensional (3D) arrays formed by slow precipitation of colloidal dispersions of same nanoparticles. The structure of assemblies is found from electron microscopy and small-angle x-ray scattering. The differences in magnetic behavior are interpreted in terms of the particle moment, interparticle separation, and coordination number. Preferential in-plane magnetization is observed due to interactions within a monolayer. 3D arrays show stronger interactions compared to monolayers due to an increased number of nearest neighbors. [ABSTRACT FROM AUTHOR]

The sales of fermented, roasted and boiled bamboo shoots in the market places of Arunachal Pradesh, Manipur, Meghalaya, Nagaland and Sikkim, of the North-Eastern Himalayan (NEH) region, India have been reported. The results are based on the survey of 118 markets covering 1200 primary and secondary vendors from 51 districts of NEH region. The consumption of fermented, roasted and boiled shoots was estimated to be ca. 680 tonnes; the highest occurs in Arunachal Pradesh (481 tonnes/year) and the lowest in Nagaland (19.5 tonnes/year). The bamboo shoots are consumed in the form of fermented-slice, crushed-fermented moist, crushed-fermented dry, fermented whole shoot, roasted whole shoot and boiled whole shoot in different states of the region. Cost–return analysis for sales of these bamboo products revealed a net income of 23 million rupees per annum (US$ 502 950) from the entire region with the highest (17.5 million rupees/year or US$ 38 270) in Arunachal Pradesh and the lowest in Sikkim (0.47 million rupees/year or US$ 10 280). Employment opportunities have also been worked out and ca. 1260 persons/year could earn their subsistence through selling of bamboo shoot products. [ABSTRACT FROM AUTHOR]

Solid cancers constitute a tremendous burden on global healthcare, requiring a deeper understanding of the molecular mechanisms underlying cancer development and progression. Epigenetic changes, notably N 6 -methyladenosine (m 6 A) RNA methylation, have emerged as important contributors to the biology of solid tumors in recent years. This epigenetic mark dynamically affects gene expression at the post-transcriptional level and modulates a variety of cellular processes, making it a focus of research in the context of solid tumors. m 6 A modification patterns are dysregulated in a variety of solid cancers, including ovarian, breast, lung, colorectal, pancreatic, and others. This dysregulated m 6 A landscape has been shown to induce significant changes in the expression of oncogenes, tumor suppressors, and genes involved in cancer stem cells, metastasis, and treatment resistance. In solid tumors, the interaction of m 6 A "writers" (e.g., METTL3, METTL14, and others), "erasers" (e.g., ALKBH5, FTO), and "readers" (e.g., members of YTHDF proteins and others) delicately changes the m 6 A methylome. Targeting m 6 A regulators as a potential therapeutic method to control gene expression and prevent tumor development seems a novel strategy. To enhance treatment results, advances in this area of research have led to the development of targeted treatments aiming at restoring or altering m 6 A alteration patterns in solid tumors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Diabetes leads to dysregulated macrophage immunometabolism, contributing to accelerated atherosclerosis progression. Identifying critical factors to restore metabolic alterations and promote resolution of inflammation remains an unmet goal. MicroRNAs (miRs) orchestrate multiple signaling events in macrophages, yet their therapeutic potential in diabetes-associated atherosclerosis remains unclear., Methods and Results: MiRNA profiling revealed significantly lower miR-369-3p expression in aortic intimal lesions from Ldlr-/- mice on a high-fat sucrose containing (HFSC) diet for 12 weeks. miR-369-3p was also reduced in peripheral blood mononuclear cells (PBMCs) from diabetic patients with coronary artery disease (CAD). Cell-type expression profiling showed miR-369-3p enrichment in aortic macrophages. In vitro, oxLDL treatment reduced miR-369-3p expression in mouse bone marrow-derived macrophages (BMDMs). Metabolic profiling in BMDMs revealed that miR-369-3p overexpression blocked the oxLDL-mediated increase in the cellular metabolite succinate and reduced mitochondrial respiration (OXPHOS) and inflammation (lL-1β, TNF-a, IL-6). Mechanistically, miR-369-3p targeted the succinate receptor (GPR91) and alleviated the oxLDL-induced activation of inflammasome signaling pathways. Therapeutic administration of miR-369-3p mimics in HFSC-fed Ldlr-/- mice reduced GPR91 expression in lesional macrophages and diabetes-accelerated atherosclerosis, evident by a decrease in plaque size and pro-inflammatory Ly6Chi monocytes. RNA-seq analyses showed more pro-resolving pathways in plaque macrophages from miR-369-3p treated mice, consistent with an increase in macrophage efferocytosis in lesions. Finally, a GPR91 antagonist attenuated oxLDL-induced inflammation in primary monocytes from human subjects with diabetes., Conclusion: These findings establish a therapeutic role for miR-369-3p in halting diabetes-associated atherosclerosis by regulating GPR91 and macrophage succinate metabolism., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

As one of the deadliest gynaecological cancers, ovarian cancer has been on the list. With lesser-known symptoms and lack of an accurate detection method, it is still difficult to catch it early. In terms of both the diagnosis and outlook for cancer, liquid biopsy has come a long way with significant advancements. Exosomes, extracellular components commonly shed by cancerous cells, are nucleic acid-rich particles floating in almost all body fluids and hold enormous promise, leading to minimallyinvasive molecular diagnostics. They have been shown as potential biomarkers in liquid biopsy, being implicated in tumour growth and metastasis. In order to address the drawbacks of ovarian cancer tumor heterogeneity, a liquid biopsy-based approach is being investigated by detecting cell-free nucleic acids, particularly non-coding RNAs, having the advantage of being less invasive and more prominent in nature. microRNAs are known to actively contribute to cancer development and their existence inside exosomes has also been made quite apparent which can be leveraged to diagnose and treat the disease. Extraction of miRNAs and exosomes is an arduous execution, and while other approaches have been investigated, none have produced results that are as encouraging due to limits in time commitment, yield, and, most significantly, damage to the exosomal structure resulting discrepancies in miRNA-based expression profiling for disease diagnosis. We have briefly outlined and reviewed the difficulties with exosome isolation techniques and the need for their standardization. The several widely used procedures and their drawbacks in terms of the exosomal purity they may produce have also been outlined., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Ovarian cancer, among all gynecologic malignancies, exhibits the highest incidence and mortality rate, primarily because it is often presents with non-specific or no symptoms during its early stages. For the advancement of Ovarian Cancer Diagnosis, it is crucial to identify the potential molecular signatures that could significantly differentiate between healthy and ovarian cancerous tissues and can be used further as a diagnostic biomarker for detecting ovarian cancer. In this study, we investigated the genome-wide methylation patterns in ovarian cancer patients using Methylated DNA Immunoprecipitation (MeDIP-Seq) followed by NGS. Identified differentially methylated regions (DMRs) were further validated by targeted bisulfite sequencing for CpG site-specific methylation profiles. Furthermore, expression validation of six genes by Quantitative Reverse Transcriptase-PCR was also performed. Out of total 120 differentially methylated genes (DMGs), 68 genes were hypermethylated, and 52 were hypomethylated in their promoter region. After analysis, we identified the top 6 hub genes, namely POLR3B, PLXND1, GIGYF2, STK4, BMP2 and CRKL. Interestingly we observed Non-CpG site methylation in the case of POLR3B and CRKL which was statistically significant in discriminating ovarian cancer samples from normal controls. The most significant pathways identified were focal adhesion, the MAPK signaling pathway, and the Ras signaling pathway. Expression analysis of hypermethylated genes was correlated with the downregulation of the genes. POLR3B and GIGYF2 turned out to be the novel genes associated with the carcinogenesis of EOC. Our study demonstrated that methylation profiling through MeDIP-sequencing has effectively identified six potential hub genes and pathways that might exacerbate our understanding of underlying molecular mechanisms of ovarian carcinogenesis., (© 2024. The Author(s).)

Ovarian cancer is one of the most aggressive and significant malignant tumor forms in the female reproductive system. It is the leading cause of death among gynecological cancers owing to its metastasis. Since its preliminary disease symptoms are lacking, it is imperative to develop early diagnostic biomarkers to aid in treatment optimization and personalization. In this vein, microRNAs, which are short sequence non-coding molecules, displayed great potential as highly specific and sensitive biomarker. miRNAs have been extensively advocated and proven to serve an instrumental part in the clinical management of cancer, especially ovarian cancer, by promoting the cancer cell progression, invasion, delayed apoptosis, epithelial-mesenchymal transition, metastasis of cancer cells, chemosensitivity and resistance and disease therapy. Here, we cover our present comprehension of the most up-to-date microRNA-based approaches to detect ovarian cancer, as well as current diagnostic and treatment strategies, the role of microRNAs as oncogenes or tumor suppressor genes, and their significance in ovarian cancer progression, prognosis, and therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bhadra, Sachan and Nara.)

Introduction: Oral Squamous Cell Carcinoma (OSCC), the sixth most widespread malignancy in the world, accounts for 90% of all cases of oral cancer. The primary risk factors are tobacco chewing, alcohol consumption, viral infection, and genetic modifications. OSCC has a high morbidity rate due to the lack of early diagnostic methods. Nowadays, liquid biopsy plays a vital role in the initial diagnosis of oral cancer. ctNAs extracted from saliva and serum/plasma offer meaningful insights into tumor genetics and dynamics. The interplay of these elements in saliva and serum/plasma showcases their significance in advancing noninvasive, effective OSCC detection and monitoring., Areas Covered: This review mainly focused on the role of liquid biopsy as an emerging point in the diagnosis and prognosis of OSCC and the current advancements and challenges associated with liquid biopsy., Expert Opinion: Liquid biopsy is regarded as a new, minimally invasive, real-time monitoring tool for cancer diagnosis and prognosis. Many biomolecules found in bodily fluids, including ctDNA, ctRNA, CTCs, and EVs, are significant biomarkers to identify cancer in its early stages. Despite these groundbreaking strides, challenges persist. Standardization of sample collection, isolation, processing, and detection methods is imperative for ensuring result reproducibility across diverse studies.

Epithelial ovarian cancer (EOC) is the most aggressive and frequent malignancy detected among women worldwide. The pathophysiology of OC should, therefore be better understood to identify diagnostic, prognostic, and predictive novel biomarkers necessary for early detection, management, and prognostication. In this study, we aimed to investigate transcriptomic landscape and biomarker through RNA-seq data analysis. Further analysis by Protein Protein network identified top 10 Differentially Expressed Genes (DEGs). KEGG pathway enrichment analysis revealed the significant enrichment of DEGs in basal cell carcinoma, cell cycle and FoxO signalling pathway. The RNA-seq results of 10 DEGs were validated by QRT-PCR and TCGA database. Correlation studies were also performed between gene expression and clinical characteristics followed by survival analysis. Finally, 8 DEGs (CDKN1A, BCL6, CDC45, WNT2, TLR5, AQP5) including two novel DEGs (CSN1S1 and NKILA) were identified showing significant correlations with EOC characteristics. These may serve as interesting biomarkers and novel treatment targets and warrant further investigation into the functional outcome of EOC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the treatment of choice for hemodynamically significant pulmonary stenosis (PS). Currently, the Tyshak balloon is preferred but requires multiple dilatations because of its instability across the valve leading to a watermelon seeding effect. Accura balloon (Vascular Concept, UK) offers an advantage in its self-positioning configuration, variable diameter, and rapid inflation-deflation sequence which shortens the procedural time and valve injury., Method: 43 patients with severe pulmonary valve stenosis underwent PBPV using an Accura balloon at LPS Institute of Cardiology, GSVM Medical College, Kanpur, UP, India from March 2018 to February 2022. The procedure was carried out using the standard technique but the metallic straightener was removed when the catheter reached the right atrium to facilitate its delivery across the pulmonary valve. Patients were followed up by 2D echo at 24 hours and 6 months., Result: Successful BPV was done in all 43 patients [with mean age 21.9 (range 18-41); 31 males and 12 females] among which 5 patients had dysplastic valves. The mean diameter of the annulus was 18.5 (range 15-21) mm. Immediate hemodynamic improvement was observed in 38 patients (88%) as peak systolic gradient reduced from 84±13 to 22±12 mmHg (P<0.005) while 5 patients (12%) had <50% reduction of resting gradient, though it came down significantly at 6 months. Fluoroscopy and procedural time were 5.2±1.9 min and 22.6±3.4 min respectively. Major complications (death, cardiac perforation, tamponade, tricuspid regurgitation, requirement of blood transfusion) were none. Minor complications (transient hypotension, ventricular premature contraction, transient bradycardia) were reported in all patients. Accura balloon being bulky were delivered over left atrial and super stiff Amplatz wire in 36 and 7 patients respectively., Conclusion: PBPV using Accura balloon is safe and effective for both stenosed and dysplastic valves. In a few patients, maximal effect will be observed over a period of 6 months., Competing Interests: None., (AJCD Copyright © 2023.)

Epithelial ovarian cancer (EOC) treatment strategies mainly focused on surgery combined with chemotherapy. Recent targeted therapy techniques emerge as milestone and could be used for management of ovarian cancer (OC) progression with more efficacy. The aim is to evaluate the therapeutic and diagnostic potential of microRNA (miRNA) in management of EOC using in silico and quantitative real-time PCR (qRT-PCR) expression analysis. We performed functional enrichment and miRNA-Target genes expression analysis in 48 EOC and 22 normal tissue samples using qRT-PCR and correlated with miRNA expression data in matched samples to evaluate the diagnostic and therapeutic potential of miRNA in OC management. In silico functional enrichment analysis revealed miRNA association with disease. Target genes of miRNAs participate in several biologically important pathways leading to cancer progression. Targets of miRNA-205 and miRNA-34a were significantly downregulated, and upregulated, respectively, in EOC. Moreover, significant negative correlation between relative expression of miRNA-205 and target genes (BCL2, ZEB1, E2F1, and TP53) was observed with r  = -0.813; r  = -0.755; r  = -0.559; and r  = -0.767, respectively. Similarly, miRNA-34a also showed higher negative correlation with target genes (MDM4, MAPK3, BRCA1, AREG) with r  = -0.840; r  = -0.870; r  = -0.622; and r  = -0.623, respectively. In addition, receiver operating characteristics analysis of combined miRNA panel, miRNA-205-Target gene panel, and miRNA-34a-Target gene panel exhibited higher diagnostics value with area under the curve (AUC) of 92.7 ( p  < 0.0001), 94.8 ( p  < 0.0001), and 98.3 ( p  < 0.0001), respectively. Negative Correlation between miRNA and target genes expression data in matched samples highlights therapeutic potential of miRNA in EOC management. Moreover, combined diagnostic potential of miRNA-target gene panel could predict risk of EOC with higher AUC, sensitivity, and specificity.

Background: Provisional stenting is preferred for bifurcation lesion; however, certain anatomical substrate does require two stents as a part of dedicated stent technique. Here, the present study evaluated outcomes of ultra-thin (60 µm) Supra family sirolimus-eluting stent (SES) (Sahajanand Medical Technologies Limited, Surat, India) for dedicated bifurcation lesions using nano-crush technique at 12 months angiographic follow-up., Methods: This was prospective, single-center observational study which enrolled patients with de novo bifurcation lesion and underwent angioplasty with Supra family SES using nano-crush technique at a tertiary care center in India, between March-2017 and February-2019. Primary endpoint at 12 months was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included patient-oriented composite endpoint (POCE), all-cause death, any revascularization, clinically driven target vessel revascularization, stent thrombosis, periprocedural and spontaneous MI, and device failure., Results: The study enrolled total 63 patients with a mean age of 62.5±4.9 years and had male dominance (89%). Left main (LM) bifurcation and non-LM bifurcation were observed in 21 (33%) and 42 (67%) patients, respectively. Total 50 (80%) patients had Medina class- 1,1,1. At 12 months, TLF occurred in 4 (6%) patients which included one cardiac death (1.5%), two (3.0%) TV-MI, and one CD-TLR (1.5%). POCE was observed in 6 (9.6%) patients. Stent failure was seen in 2 (3.1%) patient and one patient (1.5%) developed late stent thrombosis. Twelve months angiographic follow-up indicated intact stent patency in all other patients. On multivariate analysis, LM bifurcation, renal dysfunction, LM bifurcation with renal dysfunction, ejection fraction (<35%) and calcified lesion were found as predictors of TLF., Conclusions: Dedicated stenting with ultra-thin Supra family SES for complex bifurcation lesion using nano-crush technique reported acceptable clinical outcomes among real-world patients and can be performed safely with ease without any procedural complications.

MicroRNAs (miRNAs), a class of small noncoding RNAs, are critical to gene regulation in eukaryotes. They are involved in modulating a variety of physiological processes, including the host response to intracellular infections. Little is known about miRNA functions during infection by Coxiella burnetii, the causative agent of human Q fever. This bacterial pathogen establishes a large replicative vacuole within macrophages by manipulating host processes such as apoptosis and autophagy. We investigated miRNA expression in C. burnetii-infected macrophages and identified several miRNAs that were down- or upregulated during infection. We further explored the functions of miR-143-3p, an miRNA whose expression is downregulated in macrophages infected with C. burnetii, and show that increasing the abundance of this miRNA in human cells results in increased apoptosis and reduced autophagy-conditions that are unfavorable to C. burnetii intracellular growth. In sum, this study demonstrates that C. burnetii infection elicits a robust miRNA-based host response, and because miR-143-3p promotes apoptosis and inhibits autophagy, downregulation of miR-143-3p expression during C. burnetii infection likely benefits the pathogen.

Ovarian cancer remains the most eminent silent killer, with high morbidity and mortality among all gynaecological cancers. The advanced-stage patient's diagnosis has a low survival rate caused by its asymptomatic progression and diverse histopathological sub-types, wherefore in poor prognosis and highly recurring malignancy with multidrug resistance towards chemotherapy. Epigenetic biomarkers open promising avenues of intriguing research to combat OC malignancy, furthermore a tool for its early diagnosis. 5-hydroxymethycytosine (5-hmC), alias the sixth base of the genome, is an intermediate formed during the recently established DNA demethylation process and catalysed via ten-eleven translocation (TET) family of enzymes. It plays a significant role in regulating gene expression and has sparked interest in various cancer types. This review summarizes the role of active DNA demethylation process, its enzymes and intermediate 5-hmC in epigenetic landscape of ovarian cancer as a potent biomarker for clinical translation in identification of therapeutic targets, diagnostic and prognostic evaluation., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background and Aims: Accumulating evidence supports a critical role for CD4 + T cells as drivers and modifiers of the chronic inflammatory response in atherosclerosis. Effector T cells have pro-atherogenic properties, whereas CD4 + regulatory T cells (Tregs) exert suppressive activity in atherosclerosis through increased secretion of inhibitory cytokines such as transforming growth factor-β or interleukin-10. In addition, Tregs have been shown to suppress inflammatory macrophages and promote the resolution of atherosclerosis plaques. Impaired Treg numbers and function have been associated with atherosclerosis plaque development. However, the underlying mechanisms remain unclear., Methods and Results: Here, we investigated a cell-autonomous role of a transcription factor, Krüppel-like factor 10 (KLF10), in CD4 + T cells in regulating atherosclerosis progression. Using CD4 + T-cell-specific KLF10 knockout (TKO) mice, we identified exaggerated plaque progression due to defects in immunosuppressive functions of Tregs on macrophages. TKO mice exhibited increased lesion size as well as higher CD4 + T cells and macrophage content compared to WT mice. TKO plaques also showed increased necrotic cores along with defective macrophage efferocytosis. In contrast, adoptive cellular therapy using WT Tregs abrogated the accelerated lesion progression and deleterious effects in TKO mice. Intriguingly, RNA-seq analyses of TKO lesions revealed increased chemotaxis and cell proliferation, and reduced phagocytosis compared to WT lesions. Mechanistically, TKO-Tregs impaired the efferocytosis capacity of macrophages in vitro and promoted a pro-inflammatory macrophage phenotype via increased IFN-γ and decreased TGF-β secretion., Conclusions: Taken together, these findings establish a critical role for KLF10 in regulating CD4 + Treg-macrophage interactions and atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Atrial septal defect (ASD) is one of the common congenital heart defects. Its management has transformed dramatically in the last 4 decades with the transition from surgical to percutaneous transcatheter closure for most secundum-type ASDs. Various devices are available for transcatheter closure of ASD with Amplatzer atrial septal occluder being most commonly used worldwide. Cocoon septal occlude has a nanocoating of platinum using nano-fusion technology over nitinol framework that imparts better radiopacity and excellent biocompatibility and prevents leaching of nickel into circulation, and by smoothening nitinol wire makes this device very soft and smooth. The aim of this study was to evaluate feasibility, effectiveness, safety, and long-term outcome of transcatheter closure of ASD using Cocoon septal occluder (Vascular Innovation, Thailand)., Results: All patients undergoing transcatheter closure of hemodynamically significant ASD between September 2012 and July 2019 in our institute were included into this single-center, prospective study. Exclusion criteria were defect > 40 mm, unsuitable anatomy, Eisenmenger syndrome, and anomalous pulmonary venous return. Three hundred and twenty patients underwent device closure, of which 238 (74%) were female. The mean age was 14.6 years (range 6-29), and the median weight was 30.2 kg (range 10-53 kg). Procedure was performed under fluoroscopy using transthoracic and transesophageal echocardiography in 298 (93.1%) and 22(6.9%) patients, respectively. Balloon-assisted technique was used, when septal defect was ≥ 34 mm, in 9 (2.8%) patients. The mean diameter of defect and device was 21.4 mm (range 12-36 mm) and 26.9 mm (range 14-40 mm), respectively. Aortic rim was absent in 11 (3.4%) patients. Primary success was achieved in 312 (97.5%) patients. Early embolization to right ventricle was noted in 2 (0.6%) patients. In both cases, 40-mm device was attempted for defect of 36 mm with inadequate aortic rim using balloon-assisted technique. One (0.3%) patient developed perforation of right atrium. All were surgically repaired. Three (0.9%) patients developed complete heart block following device deployment requiring device retrieval. Two patients had had moderate residual shunt at 6 months of follow-up. After mean follow-up of 50.92 months (range 12.5-89 months), no erosion, allergic reactions to nickel, or other major complications were reported., Conclusions: Percutaneous transcatheter closure of ASD by Cocoon septal occluder (up to 36 mm) is safe and feasible with high success rate and without any significant device-related major complications over long-term follow-up. With unique device design and excellent long-term safety, it could be preferred dual-disk occluder for transcatheter closure of atrial septal defect. In most of the patients, ASD device can be safely deployed under transthoracic echocardiographic guidance., (© 2022. The Author(s).)

Objective: To correlate the genome-wide methylation signature of microRNA genes with dysregulated expression of selected candidate microRNA in tissue and serum samples of epithelial ovarian cancer (EOC) and control using quantitative reverse transcription polymerase chain reaction (qRT-PCR), and evaluation of EOC predictive value of candidate microRNA at an early stage., Methods: We performed Methylated DNA Immunoprecipitation coupled with NGS (MeDIP-NGS) sequencing of 6 EOC and 2 normal tissue samples of the ovary. Expression of selected microRNA from tissue (EOC=85, normal=30) and serum (EOC=50, normal=15) samples was evaluated using qRT-PCR. We conducted bioinformatics analysis to identify the candidate miRNA's potential target and functional role., Results: MeDIP-NGS sequencing revealed hypermethylation of several microRNAs gene promoters. Three candidate microRNAs were selected (microRNA-34a, let-7f, and microRNA-31) from MeDIP-NGS data analysis based on log2FC and P-value. The relative expression level of microRNA-34a, let-7f, and microRNA-31 was found to be significantly reduced in early-stage EOC tissues and serum samples (p<0.0001). The receiver operating characteristic analysis of microRNA-34a, let-7f and miR-31 showed improved diagnostic value with area under curve(AUC) of 92.0 (p<0.0001), 87.9 (p<0.0001), and 85.6 (p<0.0001) and AUC of 82.7 (p<0.0001), 82.0 (p<0.0001), and 81.0 (p<0.0001) in stage III-IV and stage I-II EOC serum samples respectively. The integrated diagnostic performance of microRNA panel (microRNA-34a+let-7f+microRNA-31) in late-stage and early-stage serum samples was 95.5 and 96.9 respectively., Conclusion: Our data correlated hypermethylation-associated downregulation of microRNA in EOC. In addition, a combined microRNA panel from serum could predict the risk of EOC with greater AUC, sensitivity, and specificity., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: The aim of the study is to compare intubating conditions and hemodynamic changes during awake fiber-optic intubation (AFOI) using midazolam and fentanyl versus dexmedetomidine in cases of difficult airway., Materials and Methods: A randomized prospective study was conducted in the department of oral and maxillofacial surgery, with a total of 60 patients, 18-55 years of age, ASA class I-II, of either sex with anticipated difficult airway planned for elective surgery. They were divided into two groups; group I patients received 1 μg/kg of dexmedetomidine and then an infusion of 0.5 to 0.7 μg/kg/hr of dexmedetomidine, whereas group II patients received 1 μg/kg of intra-venous (iv) fentanyl and 0.05 mg/kg of iv midazolam with additional doses of 0.02 mg/kg to achieve a Ramsay Sedation Scale score of ≥2. The ease of placement of the fiber-optic scope and the endotracheal tube and the patient's reaction to placement of the fiber-optic scope were assessed on a scale of 1-4 and were recorded as endoscopist satisfaction score and patient discomfort score, respectively., Results: The endoscopy time ranged from 2.66 ± 1.00 (group I) to 3.90 ± 0.96 (group II) minutes and was found to be statistically significant (p < 0.05). Also, the patient discomfort score was recorded during endoscopy (1-4) and ranged from 1.3 ± 0.53 (group I) and 2.33 ± 0.66 (group II) and was found to be statistically significant (p value < 0.05). Patients undergoing the procedure who received dexmedetomidine were thus more comfortable than those who received fentanyl and midazolam combination., Conclusion: Dexmedetomidine provided better intubating conditions, patient tolerance, higher endoscopist satisfaction, and reduced hemodynamic responses compared to fentanyl and midazolam combinations. Also, the major advantage of dexmeditomidine for preservation of airway with a lesser degree of respiratory depression allows for safer use of AFOI in cases of difficult airway., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 National Journal of Maxillofacial Surgery.)

Background: Temporary pacing is usually performed by cardiologists under fluoroscopic, echocardiographic, or ECG guidance. However, in the developing world, there are inadequate number of cardiologists, and C-arm, catheterization laboratories, or echocardiography are not available at primary or secondary healthcare facilities. In addition, in emergencies option of fluoroscopy and echocardiography is limited. So these patients are transferred to a facility where cardiologists and these facilities are available. Crucial time is lost in transit, which leads to increased mortality. In this study, we aimed to evaluate the safety, efficacy, and practicability of unguided temporary pacemaker insertion., Results: A total of 1093 patients were enrolled in this study. After cannulating the internal jugular vein or subclavian vein, the pacing lead attached to the pulse generator was advanced blindly till ventricular pacing was achieved. Procedural success was taken as the primary endpoint. Secondary endpoints included the number of attempts taken for successful central venous puncture and procedural time. Complications and mortality were assessed for safety outcomes. Finally, the position of the pacing lead was assessed after the procedure on X-ray or fluoroscopy. The procedure was successful in all but one patient in whom a femoral vein approach was required because of brachiocephalic vein obstruction. Right internal jugular access was achieved in 981 (89.75%) patients. The mean number of attempts taken for achieving successful venous accesses was 1.54 ± 0.85; however, in 726 (66.42%) patients it was achieved in the first attempt. The mean procedural time was 11.5 ± 2.1 min. Overall, 117 (10.70%) patients developed complications; however, most of them were minor. Pneumothorax developed in 12 (1.1%) patients, of whom 2 needed an intercostal tube. Pericardial effusion was seen in 21 (1.92%) patients. Pacing lead tip was located in the right ventricular cavity abutting interventricular septum or free wall in 843 (77.20%) patients. No mortality attributable to procedure occurred., Conclusions: Unguided temporary pacing via jugular or subclavian venous approach in an emergency setting is possible with high success and a low complication rate. Thus, it is a safe and effective procedure, and clinicians working at primary and secondary healthcare levels should be encouraged to perform this procedure. Trial registration UMIN Clinical Trials Registry, UMIN000046771. Registered 28 January 2022-Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000053348., (© 2022. The Author(s).)

Cellular reprogramming through targeting microRNAs (miRNAs) holds promise for regenerative therapy due to their profound regulatory effects in proliferation, differentiation, and function. We hypothesized that transdifferentiation of vascular smooth muscle cells (SMCs) into endothelial cells (ECs) using a miRNA cassette may provide a novel approach for use in vascular disease states associated with endothelial injury or dysfunction. miRNA profiling of SMCs and ECs and iterative combinatorial miRNA transfections of human coronary SMCs revealed a 4-miRNA cassette consisting of miR-143-3p and miR-145-5p inhibitors and miR-146a-5p and miR-181b-5p mimics that efficiently produced induced endothelial cells (iECs). Transcriptome profiling, protein expression, and functional studies demonstrated that iECs exhibit high similarity to ECs. Injected iECs restored blood flow recovery even faster than conventional ECs in a murine hindlimb ischemia model. This study demonstrates that a 4-miRNA cassette is sufficient to reprogram SMCs into ECs and shows promise as a novel regenerative strategy for endothelial repair., (© 2022 Federation of American Societies for Experimental Biology.)

Objective To evaluate the impact of successful percutaneous balloon mitral valvuloplasty (BMV) on left atrial (LA) reservoir function and LA volume in patients with severe mitral stenosis (MS) using peak atrial longitudinal strain (PALS). Method This was a prospective, non-randomized observational study conducted at the Laxmipat Singhania (LPS) Institute of Cardiology, Kanpur from August 2018 to February 2020 among patients with severe rheumatic MS undergoing BMV to assess LA reservoir function and its volume after BMV using PALS. Inclusion criteria were symptomatic severe rheumatic MS (NYHA ≥II), normal ventricular systolic function, and suitable valve morphology. Exclusion criteria were the coexistence of aortic valve involvement, left atrial appendage clot, mitral leak more than mild, pregnancy, hypertension, diabetes, and coronary artery disease. To assess LA reservoir function and its volume after BMV, PALS was used. LA was divided into six regions of interest and longitudinal strain curves of individual segments together with global strain were recorded. PALS was calculated at baseline 24 hours following the intervention, and at three months of follow-up. Result Successful BMV was performed in 260 patients (109 or 41.9% males and 151 or 58.1% females), resulting in significant improvement in mitral valve area (MVA) (0.89±0.11 cm 2 vs. 1.83±0.3 cm 2 ; p<0.001). The mean age of patients was 26.7±4.7 years; 214 (82.3%) patients were in normal sinus rhythm (NSR) while 46 (17.7%) had atrial fibrillation (AF). Significant improvement in PALS was noted immediately following the procedure (6.5±11.6% vs. 7.7±10.5%; p< 0.001) and it continued to improve at three months of follow-up (6.5±11.6% vs. 11.3±12.5%; p<0.001), which was 24% and 74% improvement from baseline respectively. Significant reduction in indexed left atrial (LA) volume was observed immediately following the procedure (56.8±14.3 ml/m 2 vs 48.4±12.5 ml/m 2 ; p=0.003), and at three months of follow-up (56.8±14.3 ml/m 2 vs. 45.4±13.3 ml/m 2 ; p=0.002). Those with AF had lesser improvement in PALS in comparison to those with NSR (60% vs. 84%; p=0.044) at three months of follow-up. At three months, the increase in PALS was also lower in patients with a history of stroke as compared to those without it (55% vs 80%; p=0.039). Both LA volume and indexed LA volume reduced significantly immediately at 24 hours and during follow-up. Conclusion LA reservoir function, as assessed by PALS, is reduced in patients with severe MS. It improved significantly within 24 hours following BMV and continued to improve at three months of follow-up. It is an underutilized modality among patients of MS for decision-making prior to intervention and to assess the effect of the intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Samrat et al.)

Canine parvovirus-2 (CPV-2) is ubiquitously distributed in dog population worldwide causing a severe and often fatal gastroenteritis. Owing to its highly contagious nature, rapid detection of CPV is crucial in effective control of the disease. Aptamers have emerged as potential alternative to antibodies as affinity reagents in diagnostic field. Present study was aimed to select and validate ssDNA aptamers specific to CPV. Systematic evolution of ligands through exponential enrichment (SELEX) method was employed for selection of CPV structural protein (VP2) specific DNA aptamers. SELEX was performed using a pool of ssDNA library comprising 30 random nucleotide region. A total of seven rounds of SELEX were performed using VP2 protein as target antigen which yielded ten aptamers (1A-10A) with distinct sequences. Target binding of all ten aptamers was assessed by dot blot and enzyme-linked oligonucleotide assay (ELONA) which revealed that 5A, 6A, 9A, and 10A were superior binders. In silico analysis of the aptamers revealed the existence of binding site on VP2 protein, and binding pattern was similar to in vitro findings. The affinity (K D ) of all these four binders against CPV was evaluated by ELONA indicating relatively higher affinity of 6A and 10A than remaining two DNA sequences. Out of which, aptamer 6A displayed cross-reactivity with canine distemper virus and canine corona virus. Hence, aptamer 10A was considered as better binding sequence having high specificity and affinity for CPV. The study confirms the future utility of selected aptamers in development of a reliable diagnostic for rapid detection of CPV. KEY POINTS: • Canine parvovirus-specific ssDNA aptamers were identified with nanomolar affinity (100-150 nM). • Three aptamers displayed negligible cross-reactivity with other related viruses. • Aptamer 10A displayed high binding affinity and specificity to CPV., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: During ongoing coronavirus disease 2019 (COVID-19) pandemic, social isolation and lockdown measures were implemented to prevent spread of virus which created enormous challenges to patient healthcare. In order to overcome these challenges, teleconsultation (telecardiology) was initiated. Objective of this study was to assess outcome of telecardiology using audio/visual/audio-visual consultation among patients with implantable cardiac devices., Methods: Telecardiology was performed (either physician-initiated or patient-initiated) among 1200 patients over a five-month period (July 13 to December 13, 2020) to review health status of patients to decide further course of treatment and to access their satisfaction level with telecardiology., Results: Teleconsultation was cardiologist- and patient-initiated in 1042 (86.8%) and 158 (13.2%) cases, respectively. 1117 (93.2%) patients were stable, while scheduled admission, urgent hospitalization, and death were noted in 20 (1.8%), 45 (3.9%), and 18 (1.5%) patients, respectively. Next visit was rescheduled in 986 (82.2%), while 127 (10.6%) were called earlier because of battery depletion. Majority (n = 1077, 89.8%) were satisfied., Conclusion: Telecardiolgy is an effective option during COVID-19 to minimize interpersonal contact, spread of disease, psychological stress, and burden on already stretched healthcare., (© 2021 Isfahan Cardiovascular Research Center & Isfahan University of Medical Sciences.)

Objective: Aim of study was to evaluate safety and efficacy of abluminal Mitigator DES + Sirolimus Eluting Stent (Envision Scientific, Surat, India) incorporating novel technology of fusion coating of bioresorbable polymer on both abluminal surface of stent and exposed parts of balloon among real world patients specially focusing younger patients (<35 years)., Method: 1293 patients received Mitigator DES + at LPS Institute of Cardiology, Kanpur, India. Primary outcome was target lesion failure (TLF)- composite of cardiovascular death, target vessel myocardial infarction (TVMI), and target lesion revascularization (TLR) and secondary end points including peri-procedural device failure (failure of stent delivery, change of stent, stent fracture), target vessel failure (TVF), and patient oriented composite end point (POCE)-composite of all deaths, MI, and revascularization and stent thrombosis (ST) at 1-year follow-up., Result: Younger population comprised of 374 (29%) patients. Various indications of interventions were STEMI (n = 614; 47.4%), NSTEMI (n = 416; 32.2%), UA (n = 161; 12.5%), and CCS (n = 102; 7.9%). TLF at 1 year in young and overall population were 3.4% and 3.5% respectively which was driven by TVMI and TLR in 1.3% and 1.1% patients respectively. POCE was observed in 9.5% in each group mainly contributed by any revascularization (3.9%). Device failure was significantly lower in young group than overall population (1.3% vs. 2.2%; p = 0.04) which was mainly driven by stent delivery (1.1%) and edge dissection (0.5%). Definite and probable ST was 1.3% and 1.7% respectively which was not significant. Young patients showed insignificantly lower TLF, TVF, ST and POCE and significantly lower device failure (1.3% vs. 2.6%; p = 0.04) when compared to patients >35 years. On multivariate regression analysis, complex lesion, in-stent restenosis, failure of stent delivery and edge dissection were independent predictors of events or device success rate., Conclusion: Mitigator DES+™ is safe among real world patients, including young population., Competing Interests: Conflict of interest The authors certify that there is no conflict of interest with any financial organization regarding material discussed in the manuscript., (© 2021 Saudi Heart Association.)

Most ovarian cancers, despite improvement in management of cancer, are still diagnosed at an advanced stage. Early detection plays an essential role in reducing ovarian cancer mortality and, therefore, is critically needed. Liquid biopsies-based approaches hold significant promise for cancer detection. The present study investigates a panel of epigenetic biomarkers for the detection of epithelial ovarian cancer. A qPCR assay has been developed based on the assessment of DNA methylation markers in circulating cell-free DNA as a minimally invasive tool. Herein, the promoter methylation of seven ovarian cancer-specific genes (RASSF1A, DAPK1, SOX1, HOXA9, HIC1, SPARC, and SFRP1) was analyzed quantitatively in 120 tissue samples by MethyLight assay. The best-performing genes were further evaluated for their methylation status in 70 matched serum cell-free DNA of cancerous and non-cancerous samples. Additionally, DNA methylation patterns of these best-performing genes were validated by clonal bisulfite sequencing. The ROC (Receiver-operator characteristic) curves were constructed to evaluate the diagnostic performances of both individual and combined gene panels. The seven candidate genes displayed a methylation frequency of 61.0-88.0% in tissue samples. The promoter methylation frequencies for all the seven candidate genes were significantly higher in cancer samples than in normal matched controls. In tissue samples, the multiplex MethyLight assay for HOXA9, HIC1, and SOX1 were the best performing gene panels in terms of sensitivity and specificity. The three best-performing genes exhibited individual frequencies of 53.0-71.0% in serum CFDNA, and the multiplex assay for these genes were identified to discriminate serum from cancer patients and healthy individuals (area under the curve: HOXA9+HIC1 = 0.95, HIC1+SOX1 = 0.93 and HOXA9+SOX1 = 0.85). The results of MethyLight showed high concordance with clonal bisulfite sequencing results. Individual genes and combined panel exhibited better discriminatory efficiencies to identify ovarian cancer at various stages of disease when analyzed in tissue and serum cell-free DNA. We report a qPCR-based non-invasive epigenetic biomarker assay with high sensitivity and specificity for OC screening. Our findings also reveal the potential utility of methylation-based detection of circulating cell-free tumor DNA in the clinical management of ovarian cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Singh, Gupta and Sachan.)

Background: Coronary no-reflow (NRF) following percutaneous coronary intervention (PCI) is infrequent but one of the most dreaded complication which results from impaired flow of microvascular bed. It is associated with adverse outcome if flow is not restored. Objective of this study was to find safety, effectiveness and outcome of intracoronary nikorandil (IC) administered using perforated balloon technique (PBT) to reverse NRF., Method: 2-4 mg of nicorandil was diluted with 5 ml of normal saline and administered using PBT over 5-minute. Its effectiveness was evaluated after 10 minute qualitatively using TIMI flow and quantitatively corrected TIMI frame count (cTFC) method., Result: Study comprised of 84 patients (out of 1789 patients undergoing PCI between January 2019 and February 2020). Their mean age was 57.8±17.9 years. Following PBT, TIMI III flow was successfully normalized in 71 subjects (84.5%), ten (12%) patients had TIMI II flow and it was not successful in three (3.5%) patients. TIMI flow grade got bettered from 1.03 to 2.58 and cTIMI frame count regressed from 52.9±11 to 16.5±5 (P < 0.001). PBT was well tolerated except short lived drop in blood pressure (n=10; 11.9%)., Conclusion: This study, for the first time to the best our knowledge, demonstrated that PBT mediated intracoronary administration of nikorandil distally was rapid, safe, and efficacious method to deal with NRF., Competing Interests: None., (AJCD Copyright © 2021.)