Self-collection of biospecimens at-home, without specialized equipment or training, are increasingly being adopted in clinical practice due to convenience and patient preferences. However, sample inst Show more
Self-collection of biospecimens at-home, without specialized equipment or training, are increasingly being adopted in clinical practice due to convenience and patient preferences. However, sample instability during shipment means that remote access to common blood tests remains challenging. We hypothesized that the inaccuracy and imprecision in test results that develop because of sample instability could be modeled and controlled using knowledge of transit conditions captured by environmental sensors. We subjected 2685 blood samples from 65 participants to temperature cycles derived from real-world transit conditions. Training a model called Remote Control to predict change enabled accurate calibration of test results to approximate the time zero value at the point of collection, despite sample degradation. With calibration, unprocessed whole blood could be transported, for up to 9 days under ambient conditions and exposed to temperatures between 3.4 and 47.4 °C. Under these conditions, agreement with CLIA TEa ranged between 98.1 and 100%, with a |%bias| of 0.1-1.6%, a %CV of 2.2-4.9%, and a minimum sigma metric between 3 and 8.8σ for lipids (Cholesterol, HDL, LDL, Triglycerides, APO-A1, and APO-B). Performance was linear across measurement intervals (R Show less
Hypertriglyceridemia-associated pancreatitis (HTGP) accounts for 9% to 10% of acute pancreatitis; however, the exact cause and associated factors advancing HTGP are unclear. Clinical studies have reve Show more
Hypertriglyceridemia-associated pancreatitis (HTGP) accounts for 9% to 10% of acute pancreatitis; however, the exact cause and associated factors advancing HTGP are unclear. Clinical studies have revealed that hypophosphatemia is a common factor in many patients with pancreatitis. Phosphate depletion occurs in metabolic disorders and can lead to dyslipidemia. To determine if phosphate status is critical in HTGP, we used an APOC3 transgenic mouse model of hypertriglyceridemia. We found that hypertriglyceridemic mice exhibit mild pancreatic injury with elevated intra-acinar nonendoplasmic reticulum (non-ER) organelle calcium levels, decreased mitochondrial function, and increased levels of pancreatic tissue myeloperoxidase and proinflammatory cytokines (TNF-α, IL-6, and IL-1β) compared to mice with normal serum triglycerides. Phosphate supplementation normalized the non-ER stored calcium levels, restored mitochondrial function, and attenuated fatty acid-induced sustained intracellular calcium elevation in acini, protecting the pancreas from hypertriglyceridemia-induced injury by reducing inflammation. Furthermore, phosphate supplementation reduced the severity of caerulein-induced pancreatic injury in mice on a low-phosphate diet under hypertriglyceridemic conditions. This study highlights an important role for phosphate in protecting the pancreas during hypertriglyceridemia by reversing the dysregulated calcium homeostasis in non-ER organelles, restoring mitochondrial function in acini, and reducing the severity of hypertriglyceridemia-associated pancreatitis. Show less