Long noncoding RNA (lncRNA) H19: An essential developmental regulator with expanding roles in cancer, stem cell differentiation, and metabolic diseases.

Recent advances in deep sequencing technologies have revealed that, while less than 2% of the human genome is transcribed into mRNA for protein synthesis, over 80% of the genome is transcribed, leading to the production of large amounts of noncoding RNAs (ncRNAs). It has been shown that ncRNAs, especially long non-coding RNAs (lncRNAs), may play crucial regulatory roles in gene expression. As one of the first isolated and reported lncRNAs, H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis, development, tumorigenesis, osteogenesis, and metabolism. Mechanistically, H19 mediates diverse regulatory functions by serving as competing endogenous RNAs (CeRNAs), Igf2/H19 imprinted tandem gene, modular scaffold, cooperating with H19 antisense, and acting directly with other mRNAs or lncRNAs. Here, we summarized the current understanding of H19 in embryogenesis and development, cancer development and progression, mesenchymal stem cell lineage-specific differentiation, and metabolic diseases. We discussed the potential regulatory mechanisms underlying H19's functions in those processes although more in-depth studies are warranted to delineate the exact molecular, cellular, epigenetic, and genomic regulatory mechanisms underlying the physiological and pathological roles of H19. Ultimately, these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

Emergent surgical interventions in noncritical traumatic long bone fractures and lactate monitoring: a retrospective cohort study.

Serum lactate levels have been recommended as a standard in guiding resuscitation and management of post-traumatic orthopedic injuries. Studies have suggested an increased incidence of postoperative complications in trauma patients with injury severity scores (ISSs) greater than 18. However, in trauma patients without an elevated ISS, the role of lactate in guiding operative timing has not been explored. This study considers the role of lactate measurement with respect to surgical timing and predicting postoperative complications in trauma patients with long bone fractures and an ISS less than 16. Materials and methods: A total of 164 patients, ages 18 and above with long bone fractures and ISS less than 16 were sampled in the last 5 years. Demographic data was ascertained. Patients were placed into two cohorts with a serum preoperative lactate greater than or equal to 2.0 mmol/l and a serum preoperative lactate less than 2.0 mmol/l. Key endpoints included hospital mortality, length of hospitalization (LOH), discharge designation, and postoperative complications. Results: A total of 148 patients had a lactate level less than 2.0 mmol/l and 16 had a lactate greater than or equal to 2.0 mmol/l. There was no significant difference in demographics between these two preoperative lactate groups. There was no statistical difference when considering mortality, discharge designation, LOH, and postoperative complications. Conclusion: Lactate levels assist providers in guide resuscitative efforts in trauma patients. However, this study finds that preoperative lactate measurements and efforts made to normalize lactate level are not correlated with mortality, LOH, and postoperative complications in trauma patients with an ISS less than 16. This study does not support preoperative lactate normalization in guiding surgical timing.

Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia.

Arginine vasopressin (AVP) made by hypothalamic neurons is released into the circulation to stimulate water resorption by the kidneys and restore water balance after blood loss. Patients who lack this antidiuretic hormone suffer from central diabetes insipidus. We observed that many of these patients were anemic and asked whether AVP might play a role in red blood cell (RBC) production. We found that all three AVP receptors are expressed in human and mouse hematopoietic stem and progenitor cells. The AVPR1B appears to play the most important role in regulating erythropoiesis in both human and mouse cells. AVP increases phosphorylation of signal transducer and activator of transcription 5, as erythropoietin (EPO) does. After sublethal irradiation, AVP-deficient Brattleboro rats showed delayed recovery of RBC numbers compared to control rats. In mouse models of anemia (induced by bleeding, irradiation, or increased destruction of circulating RBCs), AVP increased the number of circulating RBCs independently of EPO. In these models, AVP appears to jump-start peripheral blood cell replenishment until EPO can take over. We suggest that specific AVPR1B agonists might be used to induce fast RBC production after bleeding, drug toxicity, or chemotherapy.

Surgical management of pancreatic necrosis: towards lesser and later.

BACKGROUND/PURPOSE: Our aim was to determine the overall success rate and survival rate with respect to the timing of intervention in the management of pancreatic necrosis. The use of minimally invasive pancreatic necrosectomy was also examined. METHODS: This was a retrospective study carried out in a tertiary referral hospital. The subjects were all patients who suffered from acute pancreatic necrosis with emergency interventions from January 2001 to December 2007. For outcome measures, special emphasis was placed on the overall success rate and survival rate with respect to the timing of intervention. The success rate of percutaneous pancreatic necrosectomy (PCPN) was examined. RESULTS: A total of 26 patients with pancreatic necrosis were studied. The overall mortality rate was 26.9% and the rate was significantly higher in those patients who had earlier intervention (before 6 weeks). Eleven patients had PCPN. There were 2 failures due to PCPN in the early phase; 2 had partial success, while the procedure was completely successful to remove all the necrotic tissues in the other 7 patients. CONCLUSIONS: With a multidisciplinary approach, particularly with sophisticated intensive care, most patients with pancreatic necrosis can survive the initial phase. Open surgery should be limited to simple drainage and laparostomy to relieve the abdominal tension. Active intervention preferably should be delayed until the necrosis has become walled off, when a variety of minimally invasive maneuvers, notably percutaneous necrosectomy, can be offered to remove the debris. The surgical management of pancreatic necrosis should change towards a strategy of "lesser and later".