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Abstract: Hyponatremia at time of inpatient admission is associated with increased severity of illness and mortality in patients hospitalized for treatment of medical conditions. This study was conducted to determine the clinical outcome of psychiatric inpatients with admission hyponatremia. The cohort comprised 1000 adults consecutively admitted to a free-standing psychiatric hospital in 2010. Emergency transfer to a general hospital was used as a proxy marker for poor medical outcome. The point prevalence of hyponatremia (sodium level <136mEq/l) at admission was 6.49%. Older age and a diagnosis of arterial hypertension were independent correlates of admission hyponatremia. Medical deteriorations occurred in 26.7% of hyponatremic patients and 13.1% of those with normal sodium levels. Admission hyponatremia is associated with an increased rate of significant medical deteriorations of psychiatric inpatients and should trigger enhanced clinical monitoring to identify and treat somatic disorders. [Copyright &y& Elsevier]

Background & Aims: Heparin-binding epidermal growth factor–like growth factor (HB-EGF) is produced as a type-I, single-pass transmembrane protein that can be cleaved to release a diffusible peptide. HB-EGF, often overexpressed in damaged or diseased epithelium, is normally expressed in pancreatic islets, but its function is not understood. Methods: To understand the function of each isoform of HB-EGF, we made transgenes expressing either a constitutively transmembrane or a constitutively secreted protein. Results: The transmembrane isoform was not an inert precursor protein, but a functional molecule, downregulating the glucose-sensing apparatus of pancreatic islets. Conversely, the secreted form of HB-EGF improved islet function, but had severe fibrotic and neoplastic effects on surrounding tissues. Each isoform had a more severe phenotype than that of full-length HB-EGF, even though the full-length protein was efficiently cleaved, thus producing both isoforms, suggesting that a level of regulation was lost by separating the isoforms. Conclusions: This work demonstrates that islet function depends on the ratio of cleaved to uncleaved HB-EGF and that the transmembrane intermediate, while deleterious to islet function, is necessary to restrict action of soluble HB-EGF away from surrounding tissue. [Copyright &y& Elsevier]

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury. [ABSTRACT FROM AUTHOR]