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Azathioprine is used frequently to treat several inflammatory conditions. However, treatment is limited by adverse events—in particular, myelotoxicity. Thiopurine‐S‐methyltransferase (TPMT) and nudix hydrolase‐15 (NUDT15) are enzymes involved in azathioprine metabolism; variants in the genes encoding these enzymes increase the risk for azathioprine myelotoxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has recommended dose adjustments based on the results of TPMT and NUDT15 genotyping. However, little is known about the importance of this genetic information in routine clinical care. We hypothesized that in patients with inflammatory diseases, TPMT and NUDT15 genotype data predict the risk of discontinuing azathioprine due to myelotoxicity. This was a retrospective cohort study in 1,403 new adult azathioprine users for the management of inflammatory conditions for whom we had genetic information and clinical data. Among patients who discontinued azathioprine, we adjudicated the reason(s). Genotyping was performed using the Illumina Infinium Expanded Multi‐Ethnic Genotyping Array plus custom content. We used CPIC guidelines to determine TPMT and NUDT15 metabolizer status; patients were grouped as either: (i) poor/intermediate, or (ii) normal/indeterminate metabolizers. We classified 110 patients as poor/intermediate, and 1,293 patients as normal/indeterminate metabolizers. Poor/intermediate status was associated with a higher risk for azathioprine discontinuation due to myelotoxicity compared to normal/indeterminate metabolizers (hazard ratio (HR) = 2.90, 95% confidence interval (CI): 1.58–5.31, P = 0.001). This association remained significant after adjustment for race, age at initiation, sex, primary indication, and initial daily dose of azathioprine (adjusted HR (aHR) = 2.67, 95% CI: 1.44–4.94, P = 0.002). In conclusion, TPMT and NUDT15 metabolizer status predicts discontinuation due to myelotoxicity for patients taking azathioprine for inflammatory conditions. [ABSTRACT FROM AUTHOR]

Best practices for urinary catheter insertion and care are well documented in the literature. However, the development of educational methods to address best practice standards has been relatively stagnant. A novel educational approach to teach practicing providers proper catheter insertion and care was developed under a blended learning model with online videos and hands-on simulations. The education was custom created for each participant role. This education also highlighted the providers' own hospitals' catheter-associated urinary tract infections (CAUTI) rates, the negative patient outcomes that have occurred as a result of CAUTIs, and the financial burdens caused by CAUTIs. Results showed a significant inverse relationship between whether the education was occurring and the number of monthly CAUTIs. The results provided evidence that engaging frontline workers in blended learning catheter care simulation education was significantly associated with a lower number of monthly CAUTIs. Other institutions can design similar educational interventions to reduce their CAUTI rates. [ABSTRACT FROM AUTHOR]

CD8+ T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8+ T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by CD8+ T cells bearing a transgenic T cell receptor specific for a parasite epitope. We report several features that have not been described by in vitro analysis of the process, chiefly the formation of large clusters of effector CD8+ T cells around infected hepatocytes. The formation of clusters requires antigen-specific CD8+ T cells and signaling by G protein-coupled receptors, although CD8+ T cells of unrelated specificity are also recruited to clusters. By combining mathematical modeling and data analysis, we suggest that formation of clusters is mainly driven by enhanced recruitment of T cells into larger clusters. We further show various death phenotypes of the parasite, which typically follow prolonged interactions between infected hepatocytes and CD8+ T cells. These findings stress the need for intravital imaging for dissecting the fine mechanisms of pathogen recognition and killing by CD8+ T cells. [ABSTRACT FROM AUTHOR]

Purpose: This article reviews the institution of mock code simulation training to improve registered nurses responder performance at a trauma 1 teaching hospital. Method: An in-situ mock code is held on random medical-surgical/telemetry units every month. Participants are asked to respond to 2 different scenarios using a 3-G Sim Man and the unit's emergency equipment. Each session is followed by debriefing, postsurveys, and evaluation. The time to cardiopulmonary resuscitation (CPR) and defibrillation is recorded for analysis. The participant's level of confidence is measured before and after simulation. Results: More than 250 nurses have participated in the Five Alive course since its initiation in March 2011. The participants have expressed more confidence in recognizing a declining patient health status after the simulation. They have also demonstrated a marked improvement in time to CPR and defibrillation. Conclusions: Initial findings reveal that in-situ medical emergency team/code simulation followed by debriefing improved the performance of responders. We are currently offering the Five Alive program monthly during four 1-hour sessions and have found this program to be an effective training tool. There is one challenge to offering the program on the off shift and weekends. That is finding a time that is not too disruptive to patient care. [ABSTRACT FROM AUTHOR]

The article discusses studies on childhood, particularly concerning play and toys. The first sociological research in the area of childhood began in the 1970s and covered such fields as child labor, institutionalized children, homeless children, the child's role within the family and his relationship with school, violence against children, child pornography and juvenile delinquency. Children's games have always been defined using the term rhetoric of progress, the idea that play prepares the child for adulthood. Children's play is more than a rehearsal for the drama of adult play, that it may also involve the resolutions of conflicts, the building of community and pure creativity. Thus, this is the sense of play as a child's game understanding social interaction permeated by symbols, beliefs, attitudes, fantasies and, above all, by fun, enjoyed by the children. These children have established a series of relationships, including social relationships with their families and infant groups, in a way special to that of children who play and create games. Moreover, they have developed gender relations while playing games. The article also studies whether mothers have transmitted their own games to their children and whether the games that children play demonstrate violence.

Vaccines that target the preerythrocytic phase of malaria hold great promise as elimination tools since they are the sole vaccines that can achieve sterile protection against a challenge. This chapter focuses on preerythrocytic stage vaccines based on live attenuated parasites. It first summarizes the main conclusions that have emerged from studies in rodents, which compared various parasite attenuation methods, and then presents the vaccination regimens that are currently being tested in humans.

Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy.

Purpose: This article reviews the institution of mock code simulation training to improve registered nurses responder performance at a trauma 1 teaching hospital., Method: An in-situ mock code is held on random medical-surgical/telemetry units every month. Participants are asked to respond to 2 different scenarios using a 3-G Sim Man and the unit's emergency equipment. Each session is followed by debriefing, postsurveys, and evaluation. The time to cardiopulmonary resuscitation (CPR) and defibrillation is recorded for analysis. The participant's level of confidence is measured before and after simulation., Results: More than 250 nurses have participated in the Five Alive course since its initiation in March 2011. The participants have expressed more confidence in recognizing a declining patient health status after the simulation. They have also demonstrated a marked improvement in time to CPR and defibrillation., Conclusions: Initial findings reveal that in-situ medical emergency team/code simulation followed by debriefing improved the performance of responders. We are currently offering the Five Alive program monthly during four 1-hour sessions and have found this program to be an effective training tool. There is one challenge to offering the program on the off shift and weekends. That is finding a time that is not too disruptive to patient care.