Glomerular filtration rate (GFR) as a marker of kidney function is important in health and disease management because decreased kidney function is associated with all-cause and cardiovascular mortality, progression of kidney disease, predisposition to acute kidney injury (AKI), and for drug dosage modification. While measured glomerular filtration rate (mGFR) is acknowledged as the most accurate method for evaluating kidney function, it is at present not feasible to be applied in the clinical arena. Estimated glomerular filtration rate (eGFR) is preferred due to its convenience, cost-effectiveness, and seamless integration into standard clinical practice for kidney function evaluation.
View Article and Find Full Text PDFEnhancers play a critical role in regulating precise gene expression patterns essential for development and cellular identity; however, how gene-enhancer specificity is encoded within the genome is not clearly defined. To investigate how this specificity arises within topologically associated domains (TAD), we performed allele-specific genome editing of sequences surrounding the Lefty1 and Lefty2 paralogs in mouse embryonic stem cells. The Lefty genes arose from a tandem duplication event and these genes interact with each other in chromosome conformation capture assays which place these genes within the same TAD.
View Article and Find Full Text PDFWhile macrophage heterogeneity during metabolic dysfunction-associated steatohepatitis (MASH) has been described, the fate of these macrophages during MASH regression is poorly understood. Comparing macrophage heterogeneity during MASH progression vs regression, we identified specific macrophage subpopulations that are critical for MASH/fibrosis resolution. We elucidated the restorative pathways and gene signatures that define regression-associated macrophages and establish the importance of TREM2 macrophages during MASH regression.
View Article and Find Full Text PDFIntroduction: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse.
View Article and Find Full Text PDFThe uterine muscular layer, or myometrium, undergoes profound changes in global gene expression during its progression from a quiescent state during pregnancy to a contractile state at the onset of labor. In this study, we investigate the role of SOX family transcription factors in myometrial cells and provide evidence for the role of SOX4 in regulating labor-associated genes. We show that Sox4 has elevated expression in the murine myometrium during a term laboring process and in two mouse models of preterm labor.
View Article and Find Full Text PDFContext: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB), are presently the major infectious diseases imposing a consequential public health threat and their coinfection has a significant impact on the outcome.
Aims: To evaluate the clinical features and outcomes of COVID-19-TB coinfected cases compared to solely COVID-19-infected cases.
Settings And Design: A retrospective observational study was conducted between August 1, 2020, to February 28, 2022, at a tertiary care hospital.
While numerous cellular proteins in the HIV envelope are known to alter virus infection, methodology to rapidly phenotype the virion surface in a high throughput, single virion manner is lacking. Thus, many human proteins may exist on the virion surface that remain undescribed. Herein, we developed a novel flow virometry screening assay to discover new proteins on the surface of HIV particles.
View Article and Find Full Text PDFSpontaneous uterine contractions are initiated when smooth muscle cells (SMCs) within the uterine muscle, or myometrium, transition from a functionally dormant to an actively contractile phenotype at the end of the pregnancy period. We know that this process is accompanied by gestational time point-specific differences in the SMC transcriptome, which can be modulated by the activator protein 1 (AP-1), nuclear factor kappa beta (NF-κβ), estrogen receptor (ER), and progesterone receptor (PR) transcription factors. Less is known, however, about the additional proteins that might assist these factors in conferring the transcriptional changes observed at labor onset.
View Article and Find Full Text PDFHow distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization.
View Article and Find Full Text PDFThe onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for foetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e.
View Article and Find Full Text PDFWe present 2 cases that demonstrate the potential for vascular complications following trans-subclavian TAVR and the role of percutaneous intervention in managing such situations.
View Article and Find Full Text PDFEnhancers are -regulatory sequences located distally to target genes. These sequences consolidate developmental and environmental cues to coordinate gene expression in a tissue-specific manner. Enhancer function and tissue specificity depend on the expressed set of transcription factors, which recognize binding sites and recruit cofactors that regulate local chromatin organization and gene transcription.
View Article and Find Full Text PDFDuring gestation, uterine smooth muscle cells transition from a state of quiescence to one of contractility, but the molecular mechanisms underlying this transition at a genomic level are not well-known. To better understand these events, we evaluated the epigenetic landscape of the mouse myometrium during the pregnant, laboring, and postpartum stages. We generated gestational time point-specific enrichment profiles for histone H3 acetylation on lysine residue 27 (H3K27ac), histone H3 trimethylation of lysine residue 4 (H3K4me3), and RNA polymerase II (RNAPII) occupancy by chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq), as well as gene expression profiles by total RNA-sequencing (RNA-seq).
View Article and Find Full Text PDFBackground: The continuing increase in care, needs and costs in cardiology with the advances in percutaneous coronary intervention (PCI) techniques represent the ideal scenario for considering same-day discharge (SDD) PCI program.
Aim: The primary endpoints were to examine feasibility and safety of SDD-PCI.
Methods: We conducted a comparative observational study of a prospective cohort (April 2017 to September 2017) where patients benefited from SDD-PCI with a retrospective cohort (October 2016 to March 2017) where patients were conventionally managed.
Background: Cardiogenic shock complicating ST elevation myocardial infarction is burdened by a high mortality. There is only limited evidence for the management except for early revascularization and the relative ineffectiveness of intra-aortic balloon pump.
Aim: Our objectives were to evaluate outcome and predictors of early all-cause 30-day mortality in the setting of cardiogenic shock complicating ST elevation myocardial infarction.
Background: Unprotected left main (LM) coronary artery disease (CAD) represents a challenging lesion with a major prognostic impact.
Aim: Evaluate the clinical outcome and major adverse cardiac events (MACE) predictors of unprotected LM percutaneous coronary intervention (PCI) in an "all-comers" population.
Methods: We performed a prospective observational study of patients with unprotected LM stenosis treated by PCI.
Background: Patients with low-gradient (LG) severe aortic stenosis (AS) have worse outcome following surgical aortic valve replacement (SAVR) than patients with high-gradient AS. We hypothesized that transcatheter aortic valve replacement (TAVR) may be a better treatment option for these patients. The aim of this study was to compare outcomes of patients with LG AS referred for TAVR and SAVR.
View Article and Find Full Text PDFBackground: Aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is usually due to paravalvular leak, is more common with self-expanding valves and is associated with adverse outcomes. Treatment of AR with a second valve (valve-in-valve) has been reported, however the mechanism of benefit is unclear. We hypothesized that location of the initial valve in relation to the aortic annulus should guide positioning of the second valve.
View Article and Find Full Text PDFBackground: Outcomes of patients with acute ST-elevation myocardial infarction (STEMI) are strongly correlated to the time interval from hospital entry to primary percutaneous coronary intervention (PPCI). Current guidelines recommend a door to balloon time of < 90 minutes.
Objectives: To reduce the time from hospital admission to PPCI and to increase the proportion of patients treated within 90 minutes.
Vascular complications are common after transcatheter aortic valve replacement (TAVR) and are associated with increased morbidity and mortality. Stent graft implantation enables percutaneous treatment of access site bleeding; however, the efficacy and durability and of this approach are unknown. We studied the immediate outcome of stent graft implantation for control of access site bleeding and the need for repeat vascular interventions after stenting, in a cohort of consecutive patients with severe symptomatic aortic stenosis who underwent transfemoral TAVR.
View Article and Find Full Text PDFContext: Xerostomia and hyposalivation are associated with diabetes. Research is sparse regarding electrostimulation as a mainstream therapy for salivary gland hypofunction.
Objective: To clinically evaluate the effectiveness of transcutaneous electric nerve stimulation (TENS) therapy in stimulating whole salivary flow among patients with xerostomia and hyposalivation caused by diabetes mellitus.