THE CONSEQUENCES OF DISRUPTING THE MDM2-P53 BALANCE IN HEMATOPOIESIS

The bone marrow accommodates hematopoietic stem cells and progenitors. These cells provide an indispensible resource for replenishing the blood constituents throughout an organism’s life. A tissue with such a high turn-over rate mandates intact cycling checkpoint and apoptotic pathways to avoid inappropriate cell proliferation and ultimately the development of leukemias. p53, a major tumor suppressor, is a transcription factor that regulates cell cycle, and induces apoptosis and senescence. Mice inheriting a hypomorphic p53 allele in the absence of Mdm2, a p53 inhibitor, have elevated p53 cell cycle activity and die by postnatal day 13 due to hematopoietic failure. Hematopoiesis progresses normally during embryogenesis until it moves to the bone marrow in late development. Increased oxidative stress in the bone marrow compartment postnatally is the impediment for normal hematopoiesis via activation of p53. p53 in turn stimulates the generation of more reactive oxygen species and depletes bone marrow cellularity. Also, p53 exerts various defects on the hematopoietic niche by increasing mesenchymal lineage populations and their differentiation. Hematopoietic defects are rescued with antioxidants or when cells are cultured at low oxygen levels. Deletion of p16 partially rescues bone marrow cellularity and progenitors via a p53-independent pathway. Thus, although p53 is required to inhibit tumorigenesis, Mdm2 is required to control ROS-induced p53 levels for sustainable hematopoiesis and survival during homeostasis.

Comparison of hand hygiene evaluations: A literature review

Background. Because our hands are the most common mode of transmission for bacteria causing hospital acquired infections, hand hygiene practices are the most effective method of preventing the spread of these pathogens, limiting the occurrence of healthcare-associated infections and reducing transmission of multi-drug resistant organisms. Yet, compliance rates are below 40% on the average. ^ Objective. This culminating experience project is primarily a literature review on hand hygiene to help determine the barriers to hand hygiene compliance and offer solutions on improving these rates and to build on a hand hygiene evaluation performed during my infection control internship completed at Memorial Hermann Hospital during the fall semester of 2005. ^ Method. A review of peer-reviewed literature using Ovid Medline, Ebsco Medline and PubMed databases using keywords: hand hygiene, hand hygiene compliance, alcohol based handrub, healthcare-associated infections, hospital-acquired infections, and infection control. ^ Results. A total of eight hand hygiene studies are highlighted. At a children's hospital in Seattle, hand hygiene compliance rates increases from 62% to 81% after five periods of interventions. In Thailand, 26 nurses dramatically increased compliance from 6.3% to 81.2% after just 7 months of training. Automated alcohol based handrub dispensers improved compliance rates in Chicago from 36.3% to 70.1%. Using education and increased distribution of alcohol based handrubs increased hand hygiene rates from 59% to 79% for Ebnother, from 54% to 85% for Hussein and from 32% to 63% for Randle. Spartanburg Regional Medical Center increased their rates from 72.5% to 90.3%. A level III NICU achieved 100% compliance after a month long educational campaign but fell back down to its baseline rate of 89% after 3 months. ^ Discussion. The interventions used to promote hand hygiene in the highlighted studies varied from low tech approaches such as printed materials to advanced electronic gadgets that alerted individuals automatically to perform hand hygiene. All approaches were effective and increased compliance rates. Overcoming hand hygiene barriers, receiving and accepting feedback is the key to maintaining consistently high hand hygiene adherence. ^