Vitamin D Toxicity from an Unusual and Unexpected Source: A Report of 2 Cases.

Introduction: Hypervitaminosis D is a relatively uncommon etiology of hypercalcemia. Toxicity is usually caused by very high doses, mostly secondary to erroneous prescription or administration of vitamin D, and less commonly, contaminated foods or manufacturing errors of vitamin D-containing supplements.

Case Presentation: A 16-year-old male, previously healthy, presented with 2-week history of nonspecific symptoms (fatigue, gastrointestinal complaints).

REEP5 depletion causes sarco-endoplasmic reticulum vacuolization and cardiac functional defects.

The sarco-endoplasmic reticulum (SR/ER) plays an important role in the development and progression of many heart diseases. However, many aspects of its structural organization remain largely unknown, particularly in cells with a highly differentiated SR/ER network. Here, we report a cardiac enriched, SR/ER membrane protein, REEP5 that is centrally involved in regulating SR/ER organization and cellular stress responses in cardiac myocytes.

A novel Sigma metric encompasses global multi-site performance of 18 assays on the Abbott Alinity system.

Objectives: The Abbott Alinity family of chemistry and immunoassay systems recently launched with early adopters contributing imprecision and bias data, which was consolidated to assess the performance of Alinity assays across multiple sites using the Sigma metric. Multi-site Sigma metrics were determined for 3 ion-selective electrodes, 12 photometric assays, and 3 immunoassays across 11 independent laboratory sites in 9 countries.

Methods: Total allowable error (TEa) goals followed a previously defined hierarchy that used CLIA as the primary goal.

Hypoxia-Induced Changes in the Fibroblast Secretome, Exosome, and Whole-Cell Proteome Using Cultured, Cardiac-Derived Cells Isolated from Neonatal Mice.

Cardiac fibroblasts (CFs) represent a major subpopulation of cells in the developing and adult heart. Cardiomyocyte (CM) and CF intercellular communication occurs through paracrine interactions and modulate myocyte development and stress response. Detailed proteomic analysis of the CF secretome in normal and stressed conditions may offer insights into the role of CF in heart development and disease.

Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.

Phospholamban (PLN) plays a central role in Ca homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca-ATPase 2A (SERCA2A) Ca pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates.

Self-renewing resident arterial macrophages arise from embryonic CX3CR1(+) precursors and circulating monocytes immediately after birth.

Resident macrophages densely populate the normal arterial wall, yet their origins and the mechanisms that sustain them are poorly understood. Here we use gene-expression profiling to show that arterial macrophages constitute a distinct population among macrophages. Using multiple fate-mapping approaches, we show that arterial macrophages arise embryonically from CX3CR1(+) precursors and postnatally from bone marrow-derived monocytes that colonize the tissue immediately after birth.

Large-scale characterization of the murine cardiac proteome.

Cardiomyopathies are diseases of the heart that result in impaired cardiac muscle function. This dysfunction can progress to an inability to supply blood to the body. Cardiovascular diseases play a large role in overall global morbidity.

The cardiovascular exosome: current perspectives and potential.

The exosome is a secreted microvesicle that has been shown to contain genetic material and proteins and is involved in multiple levels of cellular communication. The cardiovascular exosome proteome is a promising subproteome that warrants investigation since a detailed understanding of its role in the heart should improve our comprehension of intercellular communication in the heart, and may even assist in biomarker discovery. Indeed, uncovering the role of the exosome in cardiovascular physiology could be accomplished with the application of scientific approaches and insights gained from studies of exosomes in other fields, such as cancer biology and immunology, where much of the established knowledge of the exosome has been generated.

Recent advances in cardiovascular proteomics.

Cardiovascular diseases (CVDs) are the major source of global morbidity and death and more people die annually from CVDs than from any other cause. These diseases can occur quickly, as seen in acute myocardial infarction (AMI), or progress slowly over years as with chronic heart failure. Advances in mass spectrometry detection and analysis, together with improved isolation and enrichment techniques allowing for the separation of organelles and membrane proteins, now allow for the indepth analysis of the cardiac proteome.