Introduction: The processes of atherosclerosis, inflammation, and carbamylation are closely linked in cardiovascular (CV) disease, but the potential of carbamylation burden as a CV mortality predictor is unclear, especially in patients with no or mild chronic kidney disease (CKD). This study aimed to investigate whether elevated carbamylated albumin (C-Alb), as a surrogate marker for carbamylation burden, is associated with mortality and arterial stiffness/atherosclerotic burden in patients with no or mild CKD, using pulse pressure (PP) as a marker for arterial stiffness.
Methods: We measured C-Alb in 3,193 participants of the Ludwigshafen Risk and Cardiovascular Health study who had been referred for coronary angiography and followed up for 10 years.
Rationale & Objective: Hemoglobin A (HbA) is widely used to estimate glycemia, yet it is less reliable in patients with chronic kidney disease (CKD). There is growing interest in the complementary use of glycated albumin (GA) to improve glycemic monitoring and risk stratification. However, whether GA associates with clinical outcomes in a non-dialysis-dependent CKD population remains unknown.
View Article and Find Full Text PDFMushroom (amatoxin) poisoning from ingestion is a rare but life-threatening medical emergency characterized by gastrointestinal symptoms before progression to multisystem organ failure in severe cases. Many therapies of amatoxin intoxication have been described, including supportive care, medical therapies, detoxification strategies, and liver transplant. The evidence supporting these therapies remains limited due to the rarity of amatoxin poisoning and challenge of a timely diagnosis.
View Article and Find Full Text PDFThyroid hormone (3,5,3'-triiodothyronine, T3) is a key regulator of pituitary gland function. The response to T3 is thought to hinge crucially on interactions of nuclear T3 receptors with enhancers but these sites in pituitary chromatin remain surprisingly obscure. Here, we investigate genome-wide receptor binding in mice using tagged endogenous thyroid hormone receptor β (TRβ) and analyze T3-regulated open chromatin using an anterior pituitary-specific Cre driver (Thrb).
View Article and Find Full Text PDFObjectives: This study aims to quantify the degree to which an underserved, Hispanic population in Los Angeles is impacted by SARS-CoV-2, and determine factors associated with paediatric seropositivity.
Design: Cross-sectional.
Setting: AltaMed, a Federally Qualified Health Center in Los Angeles.
Significance Statement: Protein carbamylation, a nonenzymatic post-translational protein modification partially driven by elevated blood urea levels, associates with mortality and adverse outcomes in patients with ESKD on dialysis. However, little is known about carbamylation's relationship to clinical outcomes in the much larger population of patients with earlier stages of CKD. In this prospective observational cohort study of 3111 individuals with CKD stages 2-4, higher levels of carbamylated albumin (a marker of protein carbamylation burden) were associated with a greater risk of developing ESKD and other significant adverse clinical outcomes.
View Article and Find Full Text PDFObjective: Glycated hemoglobin (HbA1c) can predict risk for microvascular complications in patients with diabetes. However, HbA1c's reliability in chronic kidney disease (CKD) has been questioned, with concerns including competition from another posttranslational protein modification, carbamylation, acting on the same amino groups as glycation, and anemia with reduced erythrocyte lifespans leading to altered glycation accumulation. We investigated whether carbamylation and anemia modify the impact of HbA1c on renal outcomes in patients with diabetes and CKD.
View Article and Find Full Text PDFObjectives: Manufacturer recalls and altered supply chains during the coronavirus disease 2019 (COVID-19) pandemic caused a nationwide shortage of blue-top tubes (BTTs). Most non-point-of-care coagulation tests use these tubes, leaving laboratories and health care facilities in short supply. The Department of Pathology and Laboratory Medicine at Cedars-Sinai Medical Center implemented interventions to conserve supply without sacrificing patient safety.
View Article and Find Full Text PDFTo understand how kidney donation leads to an increased risk of preeclampsia, we studied pregnant outbred mice with prior uninephrectomy and compared them with sham-operated littermates carrying both kidneys. During pregnancy, uninephrectomized (UNx) mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms-like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia. Maternal hypertension in UNx mice was associated with low plasma volumes, an increased rate of fetal resorption, impaired spiral artery remodeling, and placental ischemia.
View Article and Find Full Text PDFBackground: The objective of this analysis was to compare the performance sensitivity and specificity of manufacturer-recommended signal-to-cutoff (S/Co) thresholds with modified S/Co values to estimate the prevalence of SARS-CoV-2-specific antibodies in a cohort of firefighters with a known infection history.
Methods: Plasma venipuncture samples were used for serologic analysis of firefighters in Los Angeles, CA, USA, in October 2020. Seropositivity was assessed using the manufacturer's recommended S/Co (≥1.
Background: The multiple mutations comprising the epsilon variant demonstrate the independent convergent evolution of severe acute respiratory syndrome coronavirus (SARS-CoV-2), with its spike protein mutation L452R present in the delta (L452R), kappa (L452R), and lambda (L452Q) variants.
Methods: Coronavirus disease 2019 (COVID-19) variants were detected in 1017 patients using whole-genome sequencing and were assessed for outcome and severity. The mechanistic effects of the epsilon versus non-epsilon variants were investigated using a multiomic approach including cellular response assays and paired cell and host transcriptomic and proteomic profiling.
Objective: We estimate the seroprevalence of SARS-CoV-2 antibodies among a sample of firefighters in the Los Angeles (LA), California fire department in October 2020 and compare demographic and contextual factors for seropositivity.
Methods: We conducted a serological survey of firefighters in LA, California, USA, in October 2020. Individuals were classified as seropositive for SARS-CoV-2 if they tested positive for IgG, IgM or both.
Patients with end-stage kidney disease (ESKD) have increased vascular disease. While protein-bound molecules that escape hemodialysis may contribute to uremic toxicity, specific contributing toxins remain ambiguous. In this issue of the JCI, Arinze et al.
View Article and Find Full Text PDFBackground: Protein carbamylation is a post-translational protein modification caused, in part, by exposure to urea's dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis-dependent end-stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established.
Methods: We conducted two nested case-control studies within the Chronic Renal Insufficiency Cohort Study.
Objective: We sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers.
Design: Observational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionnaires.
Settings: A multisite healthcare delivery system located in Los Angeles County.
J Womens Health (Larchmt)
January 2021
Depression is a common complication of pregnancy and vitamin D deficiency is one biological risk factor for postpartum depression (PPD). We evaluated the ratio of 24,25(OH)D and 25(OH)D serum concentrations referred to as the Vitamin D Metabolite Ratio (VMR), a new candidate biomarker during pregnancyand its relationship with PPD. Women were enrolled in the first trimester of pregnancy and followed through four timepoints.
View Article and Find Full Text PDFImportance: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.
Objective: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection.
Design: Retrospective observational study.
Neurogastroenterol Motil
September 2020