Epithelial apoptotic pattern emerges from global and local regulation by cell apical area.

Geometry is a fundamental attribute of biological systems, and it underlies cell and tissue dynamics. Cell geometry controls cell-cycle progression and mitosis and thus modulates tissue development and homeostasis. In sharp contrast and despite the extensive characterization of the genetic mechanisms of caspase activation, we know little about whether and how cell geometry controls apoptosis commitment in developing tissues.

White blood cell population dynamics for risk stratification of acute coronary syndrome.

The complete blood count (CBC) provides a high-level assessment of a patient's immunologic state and guides the diagnosis and treatment of almost all diseases. Hematology analyzers evaluate CBCs by making high-dimensional single-cell measurements of size and cytoplasmic and nuclear morphology in high throughput, but only the final cell counts are commonly used for clinical decisions. Here, we utilize the underlying single-cell measurements from conventional clinical instruments to develop a mathematical model guided by cellular mechanisms that quantifies the population dynamics of neutrophil, lymphocyte, and monocyte characteristics.

Determinants of red blood cell alloantibody detection duration: analysis of multiply alloimmunized patients supports peritransfusion factors.

Background: Alloimmunization to red blood cells (RBCs) can cause serious transfusion reactions and complicate the search for compatible blood products. Alloantibodies can be detected for periods ranging from a few days to several years, yet the mechanisms controlling the duration of detectability remain unknown. We studied the detection durations in patients forming multiple antibodies to investigate whether the duration is more strongly determined by conditions present at the time of each transfusion (peritransfusion factors) or by more stable patient-specific factors likely to persist across transfusions.

Mathematical Model of Ammonia Handling in the Rat Renal Medulla.

The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney.

Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis.

Sepsis is a frequently fatal condition characterized by an uncontrolled and harmful host reaction to microbial infection. Despite the prevalence and severity of sepsis, we lack a fundamental grasp of its pathophysiology. Here we report that the cytokine interleukin-3 (IL-3) potentiates inflammation in sepsis.

Albumin infusion improves renal blood flow autoregulation in patients with acute decompensation of cirrhosis and acute kidney injury.

Background & Aims: In cirrhotic patients with renal failure, renal blood flow autoregulation curve is shifted to the right, which is consequent upon sympathetic nervous system activation and endothelial dysfunction. Albumin infusion improves renal function in cirrhosis by mechanisms that are incompletely understood. We aimed to determine the effect of albumin infusion on systemic haemodynamics, renal blood flow, renal function and endothelial function in patients with acute decompensation of cirrhosis and acute kidney injury.

Arterial ammonia levels in cirrhosis are determined by systemic and hepatic hemodynamics, and by organ function: a quantitative modelling study.

Background & Aims: Hyperammonaemia is a common complication of chronic liver failure. Two main factors are thought to underlie this complication: a loss of hepatic detoxification function and the development of portosystemic shunting. However, few studies have tried to quantify the importance of portosystemic shunting.

Ornithine phenylacetate revisited.

In patients with liver failure hyperammonemia is associated with the development of hepatic encephalopathy (HE) and immune impairment. Treatment of hyperammonemia is an unmet clinical need. Ornithine phenylacetate (OP) is a novel drug that is targeted at reducing ammonia concentration in patients with liver disease and therefore a potential treatment for HE.

Interorgan ammonia metabolism in liver failure: the basis of current and future therapies.

Hepatic encephalopathy complicates the course of both acute and chronic liver disease and its treatment remains an unmet clinical need. Ammonia is thought to be central in its pathogenesis and remains an important target of current and future therapeutic approaches. In liver failure, the main detoxification pathway of ammonia metabolism is compromised leading to hyperammonaemia.