Peptidyl arginine deiminase inhibition alleviates angiotensin II-induced fibrosis.

Objectives: The conversion of protein arginine residues to citrulline by calcium-dependent peptidyl arginine deiminases (PADs) has been implicated in the pathogenesis of several diseases, indicating that PADs are therapeutic targets. A recent study indicated that PAD4 regulates age-related organ fibrosis and dysfunction; however, the specific role of this PAD and its citrullination substrate remains unclear. We investigated whether pharmacological inhibition of PAD activity could affect the progression of fibrosis and restore heart function.

Comparative proteomic profiling of uric acid, ammonium acid urate, and calcium-based kidney stones.

Introduction: Kidney stone matrix proteins may help explain cellular mechanisms of stone genesis. However, most existing proteomic studies have focused on calcium oxalate stones. Here, we present a comparative proteomic analysis of different kidney stone types.

Apparent Risks of Postural Orthostatic Tachycardia Syndrome Diagnoses After COVID-19 Vaccination and SARS-Cov-2 Infection.

Postural orthostatic tachycardia syndrome (POTS) has been previously described after SARS-CoV-2 infection; however, limited data is available on the relation of POTS with COVID-19 vaccination. Here we show in a cohort of 284,592 COVID-19 vaccinated individuals using a sequence-symmetry analysis, that the odds of POTS are higher 90 days after vaccine exposure than 90 days prior to exposure, and that the odds for POTS are higher than referent conventional primary care diagnoses, but lower than the odds of new POTS diagnosis after SARS-CoV-2 infection. Our results identify a possible association between COVID-19 vaccination and incidence of POTS.

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum.

Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone.

Racial Disparities in Mortality Associated With Acute Myocardial Infarction and COVID-19 in the United States: A Nationwide Analysis.

This study assessed the COVID-19 pandemic's impact on racial disparities in acute myocardial infarction (AMI) management and outcomes. We reviewed AMI patient management and outcomes in the pandemic's initial nine months, comparing COVID-19 and non-COVID-19 cases using 2020's National Inpatient Sample data. Our findings revealed that patients with concurrent AMI and COVID-19 had higher in-hospital mortality (aOR 3.

Repeat Mitral Transcatheter Edge-to-Edge Repair for Recurrent Significant Mitral Regurgitation.

Background There are limited data on repeat mitral transcatheter edge-to-edge repair for recurrent significant mitral regurgitation (MR). Methods and Results We conducted a single-center, retrospective analysis of consecutive patients referred to a second mitral transcatheter edge-to-edge repair after a technically successful first procedure. Clinical, laboratory, and echocardiographic measures were assessed up to 1 year after the intervention.

Harmonization and standardization of nucleus pulposus cell extraction and culture methods.

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources.

Family History of Modifiable Risk Factors and Association With Future Cardiovascular Disease.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent-child trios in the multigenerational longitudinal Framingham Heart Study.

Implications of Extra-cardiac Disease in Patient Selection for Heart Transplantation: Considerations in Cardiac Amyloidosis.

Disease-modifying therapies in both light chain and transthyretin amyloidosis have improved patient functional status and survival. Conceivably, as heart failure may progress despite amyloid therapies, more patients may be considered for heart transplantation. In earlier eras, extra-cardiac amyloid deposits significantly reduced post-heart transplant patient survival and functional status compared to the non-amyloid population.

Linear IgA bullous dermatosis and elevated bullous interleukin-6 levels: Responsive to treatment with Anti-IL-6 receptor monoclonals.

Linear IgA bullous dermatosis (LABD) is  a rare autoimmune/inflammatory skin condition. Here, we report on a patient who developed treatment resistant LABD. At diagnosis, elevations of IL-6 and C-reactive protein in the blood and extreme elevations of IL-6 in LABD bullous fluid were seen.

Combination Sodium Nitrite and Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity in a "2-Hit" Murine Model.

Background Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a "2-hit" murine model.

TDO2-augmented fibroblasts secrete EVs enriched in immunomodulatory Y-derived small RNA.

Mounting evidence implicates extracellular vesicles (EVs) factors as mediators of cell therapy. Cardiosphere-derived cells are cardiac-derived cells with tissue reparative capacity. Activation of a downstream target of wnt/β-catenin signalling, tryptophan 2,3 dioxygenase (TDO2) renders therapeutically inert skin fibroblasts cardioprotective.

Patient-Centered Insights and Biases Regarding Cardiologists Via Online Review Platform Analysis.

Background Online cardiologist reviews, such as those on the Yelp website, are a frequently used method for patients to find a cardiologist. It remains unknown how bias may influence such reviews. Our objectives for this study were to (1) determine which cardiologist- or practice-related factors influence the overall rating of cardiologists and patient satisfaction and (2) discover any associations between sex and race with the overall rating of cardiologists or with cardiologist- or practice-related factors.

Activation of ONECUT2 by RB1 loss in castration-resistant prostate cancer.

Functional loss of the two major tumor repressors, TP53 and RB1, is frequently involved in the emergence and progression of castration-resistant prostate cancer (CRPC). Inactivating mutations in and promote lineage variants that suppress the androgen receptor axis and enhance therapy resistance. The present study provides the first evidence that RB1 loss, and not TP53 loss, is sufficient to activate the master regulator transcription factor ONECUT2 (OC2) in mCRPC.

The reversible impairment of behavioral variant frontotemporal brain sagging syndrome: Challenges and opportunities.

Introduction: Due to loss of brain buoyancy, spontaneous spinal cerebrospinal fluid (CSF) leaks cause orthostatic headaches but also can cause symptoms indistinguishable from behavioral variant frontotemporal dementia (bvFTD) due to severe brain sagging (including the frontal and temporal lobes), as visualized on brain magnetic resonance imaging. However, the detection of these CSF leaks may require specialized spinal imaging techniques, such as digital subtraction myelography (DSM).

Methods: We performed DSM in the lateral decubitus position under general anesthesia in 21 consecutive patients with frontotemporal dementia brain sagging syndrome (4 women and 17 men; mean age 56.

Supplementing a widely available weight loss program with gamified inhibitory control training: A randomized pilot study.

Background: Increasing evidence suggests that targeting self-regulatory processes may improve obesity treatment outcomes. Incorporating gamification principles in inhibitory control training may promote sustained training adherence and resulting benefits. This pilot study evaluated the preliminary efficacy of supplementing an evidence-based weight management program (WW) with sustained gamified inhibitory control training (PolyRules!) on change in Body Mass Index (BMI) among adults with overweight/obesity.

Differences in the gut microbiome by physical activity and BMI among colorectal cancer patients.

Associations of energy balance components, including physical activity and obesity, with colorectal cancer risk and mortality are well established. However, the gut microbiome has not been investigated as underlying mechanism. We investigated associations of physical activity, BMI, and combinations of physical activity/BMI with gut microbiome diversity and differential abundances among colorectal cancer patients.

Metastatic skull base chordoma: A systematic review.

Objective/hypothesis: To investigate the clinical features, management strategies and outcomes for patients with metastatic primary skull base chordomas.

Study Design: Systematic review.

Methods: A systematic search through Pubmed/Medline, Web of Science, and EBSCOhost (CINAHL) was conducted without restriction on dates.

Differential modulation of cancer-related genes by mitochondrial DNA haplogroups and the STING DNA sensing system.

Activation of the Simulator of Interferon Genes (STING) system by mitochondrial (mt) DNA can upregulate type 1 interferon genes and enhance immune responses to combat bacterial and viral infections. In cancers, the tumor-derived DNA activates STING leading to upregulation of IFN-beta and induction of antitumor T cells. The entire mtDNA from the cell lines was sequenced using next-generation sequencing (NGS) technology with independent sequencing of both strands in both directions, allowing identification of low-frequency heteroplasmy SNPs.