Clinical Decision Rules in the Evaluation and Management of Adult Gastrointestinal Emergencies.

Although abdominal pain is a common chief complaint in the emergency department, only 1 in 6 patients with abdominal pain are diagnosed with a gastrointestinal (GI) emergency. These patients often undergo extensive testing as well as hospitalizations to rule out an acute GI emergency and there is evidence that not all patients benefit from such management. Several clinical decision rules (CDRs) have been developed for the diagnosis and management of patients with suspected acute appendicitis and upper GI bleeding to identify those patients who may safely forgo further testing or hospital admission. Further validation studies demonstrating the superiority of these CDRs over contemporary practice are needed.

A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans.

cGMP-dependent protein kinases are key intracellular transducers of cell signaling. We identified a novel dominant mutation in the C. elegans egl-4 cGMP-dependent protein kinase (PKG) and show that this mutation causes increased normal gene activity although it is associated with a reduced EGL-4 protein level. Prior phenotypic analyses of this gain-of-function mutant demonstrated a reduced longevity and a reduced feeding behavior when the animals were left unperturbed. We characterize several additional phenotypes caused by increased gene activity of egl-4. These phenotypes include a small body size, reduced locomotion in the presence of food, a pale intestine, increased intestinal fat storage, and a decreased propensity to form dauer larvae. The multiple phenotypes of egl-4 dominant mutants are consistent with an instructive signaling role of PKG to control many aspects of animal physiology. This is among the first reported gain-of-function mutations in this enzyme of central physiological importance. In a genetic screen we have identified extragenic suppressors of this gain-of-function mutant. Thus, this mutant promises to be a useful tool for identifying downstream targets of PKG.