Respecting the circle of life: one year outcomes from a randomized controlled comparison of an HIV risk reduction intervention for American Indian adolescents

Potential for widespread transmission of HIV/AIDS among American Indian (AI) adolescents exists, yet no evidence-based interventions (EBIs) have been adapted and evaluated with this population. Intensive psychoeducation may improve knowledge and decision-making which could potentially translate to reductions in HIV risk behaviors. A peer group randomized controlled comparison of an adapted EBI vs. control was delivered over an eight-day summer basketball camp in one reservation-based tribal community to adolescents ages 13–19. Outcome data were gathered immediately post-camp and at 6 and 12 months follow-up. Self-selected peer groups were randomized to intervention (n = 138) or control (n = 129) conditions for a total sample of 267 participants (56.2% female), mean age 15.1 years (SD = 1.7). Intervention participants had better condom use self-efficacy post-camp (Adjusted Mean Difference [AMD] = ?0.75, p < 0.005) and at 6 (AMD = ?0.44, p < 0.005) and 12 months (AMD = ?0.23, p < 0.05) follow-up. Intervention participants also had higher HIV prevention and transmission knowledge (post-camp: AMD = 0.07, p < 0.01; 6 months: AMD = 0.06, p < 0.01) were more likely to believe condoms prevent sexually transmitted infections (post-camp: RR = 1.41, p < 0.005; 6 months: RR = 1.34, p < 0.05), to talk with an adult about HIV/AIDS (post-camp: RR=1.78, p < 0.005; 6 months: RR = 1.14, p < 0.005), had higher partner negotiation efficacy related to substance use during sex (post-camp: AMD = 0.37, p < 0.01), and were more likely to intend to use a condom (post-camp: RR = 1.39, p < 0.01). The adapted intervention had short- and medium-term impacts on AI adolescent risk for HIV/AIDS, but attenuated at 12 months. Intervention delivery through a community-based camp is feasible and acceptable with strong retention. Additional study is needed to evaluate the adapted intervention's impact on sexual risk behaviors and if booster sessions and parent involvement translate to long-term impacts.     

Doppler echocardiography of 119 normal-functioning St Jude Medical mitral valve prostheses: a comprehensive assessment including time-velocity integral ratio and prosthesis performance index.

The purpose of this study was to provide, in a large number of patients, comprehensive Doppler echocardiographic assessment of normal St Jude Medical mitral valve prosthesis function using Doppler-derived hemodynamic variables, including the mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio and prosthesis performance index. The pressure half-time was less than 130 milliseconds in all patients, and all but one patient had either a peak early mitral diastolic velocity of 2 m/s or less or a mitral valve prosthesis-to-left ventricular outflow tract time-velocity integral ratio of less than 2.2. There was a significant (P < .001) negative correlation between the prosthesis performance index and prosthesis size. This negative correlation suggests that there is more efficient use of the in vitro geometric orifice area with smaller prostheses.     

Activation of tyrosine receptor kinase plays a role in expression of long-term potentiation in the rat dentate gyrus

Long-term potentiation (LTP) in perforant path-granule cell synapses has been shown to be accompanied by an increase in glutamate release. The objective of this study was to examine the possibility that nerve growth factor (NGF), by activating tyrosine kinase, modulates glutamate release and, therefore, contributes to expression of LTP in dentate gyrus. The data indicate that NGF, in the presence of trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD), enhanced KCI-stimulated release and KCI-stimulated calcium influx in vitro and that these effects were blocked by the tyrosine receptor kinase (trk) inhibitor tyrphostin AG879. The data also indicate that NGF increased phosphorylation of trkA and the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) in dentate gyrus in vitro. In addition to its effects in vitro, tyrphostin AG879 inhibited the expression of LTP in perforant path-granule cell synapses and the accompanying increase in transmitter release. Analysis of phosphorylation of the two tyrosine kinase substrates trkA and ERK in synaptosomes prepared from untetanized and tetanized dentate gyrus revealed that LTP was associated with increased phosphorylation of both proteins; no evidence of such a change was observed in either tetanized or untetanized tissue prepared from tyrphostin-pretreated rats. These findings are consistent with the hypothesis that NGF, by interacting with trkA, triggers a sequence of tyrosine kinase-dependent phosphorylation steps that modulate glutamate release and calcium influx and impact on expression of LTP in dentate gyrus.     

Compensation for fear and worry‐induced psychiatric illness: The Australian position

New species of claims for psychiatric injury will cause courts to reassess the principles governing the way the common law has compensated those compromised by careless exposure to trauma. Pleas are emerging in an increasing variety of scenarios far removed from those which gave rise to the earliest suits for damages for nervous conditions. Recent litigation highlights the inadequacies of the traditional limitations on liability for the negligent infliction of psychiatric disorder, their conflict with contemporary medical and psychological opinion, and the impossibility of analysing many modem allegations by reference to them. The shortcomings of the orthodox approach are no better exposed than by the claims of those who suffer psychiatric damage through the fear or worry of future consequences following their actual or perceived exposure to disease‐causing agents.     

Gene expression in colon cancer: A focus on tumor site and molecular phenotype

Hundreds to thousands of genes are differentially expressed in tumors when compared to nontumor colonic tissue samples. We evaluated gene expression patterns to better understand differences in colon cancer by tumor site and tumor molecular phenotype. We analyzed RNA‐seq data from tumor/normal paired samples from 175 colon cancer patients. We implemented a cross validation strategy with nonparametric tests to identify genes which displayed varying expression characteristics related to paired tumor/nontumor tissue across proximal and distal colon sites and by tumor molecular phenotypes, that is, TP53, KRAS, CpG Island Methylator Phenotype (CIMP), and microsatellite instability (MSI). We used Ingenuity Pathway Analysis (IPA) to determine networks associated with deregulated genes in our data. Genes showed significant differences in expression characteristics at the 0.01 level in both validation groups between tumor subsite (116 genes), CIMP high versus CIMP low (79 genes), MSI versus microsatellite stable (MSS) (49 genes), TP53‐mutated versus not mutated (17genes), and KRAS‐mutated versus not mutated (1 gene). Deregulated genes for CIMP high and MSI tumors were often down‐regulated. In contrast to CIMP high and MSI tumors, genes that were deregulated in TP53 were likely to be up‐regulated. ERK1, WNT, growth factors and inflammation‐related factors were focal points of both CIMP and MSI IPA networks. The MUC family of genes was up‐regulated MSI networks. Numerous genes showed differences in expression between proximal and distal tumors, nontumor proximal and distal tissue, and tumor molecular phenotype. Deregulated mucin genes appear to play an important role in MSI tumors. © 2015 Wiley Periodixzcals, Inc.     

Are pressure injuries related to skin failure in critically ill patients?

Background

Pressure injuries contribute significantly to patient morbidity and healthcare costs. Critically ill patients are a high risk group for pressure injury development and may suffer from skin failure secondary to hypoperfusion. The aim of this study was to report hospital acquired pressure injury incidence in intensive care and non-intensive care patients; and assess the clinical characteristics and outcomes of ICU patients reported as having a hospital acquired pressure injury to better understand patient factors associated with their development in comparison to ward patients.

Wild-type tumor repressor protein 53 (Trp53) promotes ovarian cancer cell survival

Loss of Pten in the Kras(G12D);Amhr2-Cre mutant mice leads to the transformation of ovarian surface epithelial (OSE) cells and rapid development of low-grade, invasive serous adenocarcinomas. Tumors occur with 100% penetrance and express elevated levels of wild-type tumor repressor protein 53 (TRP53). To test the functions of TRP53 in the Pten;Kras (Trp53+) mice, we disrupted the Trp53 gene yielding Pten;Kras(Trp53-) mice. By comparing morphology and gene expression profiles in the Trp53+ and Trp53- OSE cells from these mice, we document that wild-type TRP53 acts as a major promoter of OSE cell survival and differentiation: cells lacking Trp53 are transformed yet are less adherent, migratory, and invasive and exhibit a gene expression profile more like normal OSE cells. These results provide a new paradigm: wild-type TRP53 does not preferentially induce apoptotic or senescent related genes in the Pten;Kras(Trp53+) cancer cells but rather increases genes regulating DNA repair, cell cycle progression, and proliferation and decreases putative tumor suppressor genes. However, if TRP53 activity is forced higher by exposure to nutlin-3a (a mouse double minute-2 antagonist), TRP53 suppresses DNA repair genes and induces the expression of genes that control cell cycle arrest and apoptosis. Thus, in the Pten;Kras(Trp53+) mutant mouse OSE cells and likely in human TP53+ low-grade ovarian cancer cells, wild-type TRP53 controls global molecular changes that are dependent on its activation status. These results suggest that activation of TP53 may provide a promising new therapy for managing low-grade ovarian cancer and other cancers in humans in which wild-type TP53 is expressed.