Person:

Conrad, Claudius Horst Oskar

Chest compressions have saved the lives of countless patients in cardiac arrest as they generate a small but critical amount of blood flow to the heart and brain. This is achieved by direct cardiac massage as well as a thoracic pump mechanism. In order to optimize blood flow excellent chest compression technique is critical. Thus, the quality of the delivered chest compressions is a pivotal determinant of successful resuscitation. If a patient is found unresponsive without a definite pulse or normal breathing then the responder should assume that this patient is in cardiac arrest, activate the emergency response system and immediately start chest compressions. Contra-indications to starting chest compressions include a valid Do Not Attempt Resuscitation Order. Optimal technique for adult chest compressions includes positioning the patient supine, and pushing hard and fast over the center of the chest with the outstretched arms perpendicular to the patient's chest. The rate should be at least 100 compressions per minute and any interruptions should be minimized to achieve a minimum of 60 actually delivered compressions per minute. Aggressive rotation of compressors prevents decline of chest compression quality due to fatigue. Chest compressions are terminated following return of spontaneous circulation. Unconscious patients with normal breathing are placed in the recovery position. If there is no return of spontaneous circulation, then the decision to terminate chest compressions is based on the clinical judgment that the patient's cardiac arrest is unresponsive to treatment. Finally, it is important that family and patients' loved ones who witness chest compressions be treated with consideration and sensitivity.

Hippo-Lats-Yorkie signaling regulates tissue overgrowth and tumorigenesis in Drosophila. We show that the Mst1 and Mst2 protein kinases, the mammalian Hippo orthologs, are cleaved and constitutively activated in the mouse liver. Combined Mst1/2 deficiency in the liver results in loss of inhibitory Ser127 phosphorylation of the Yorkie ortholog, Yap1, massive overgrowth, and hepatocellular carcinoma (HCC). Reexpression of Mst1 in HCC-derived cell lines promotes Yap1 Ser127 phosphorylation and inactivation and abrogates their tumorigenicity. Notably, Mst1/2 inactivates Yap1 in liver through an intermediary kinase distinct from Lats1/2. Approximately 30% of human HCCs show low Yap1(Ser127) phosphorylation and a majority exhibit loss of cleaved, activated Mst1. Mst1/2 inhibition of Yap1 is an important pathway for tumor suppression in liver relevant to human HCC.