Preventing falls in patients with alcohol problems.

A ward implemented the Productive Ward programme to reduce falls. The importance of staff engagement is highlighted.

Cardioprotective stress response in the human fetal heart.

OBJECTIVE: We propose that the fetal heart is highly resilient to hypoxic stress. Our objective was to elucidate the human fetal gene expression profile in response to simulated ischemia and reperfusion to identify molecular targets that account for the innate cardioprotection exhibited by the fetal phenotype. METHODS: Primary cultures of human fetal cardiac myocytes (gestational age, 15-20 weeks) were exposed to simulated ischemia and reperfusion in vitro by using a simulated ischemic buffer under anoxic conditions. Total RNA from treated and baseline cells were isolated, reverse transcribed, and labeled with Cy3 or Cy5 and hybridized to a human cDNA microarray for expression analysis. This analysis revealed a highly significant (false discovery rate, <3%) suppression of interleukin 6 transcript levels during the reperfusion phase confirmed by means of quantitative polymerase chain reaction (0.25 +/- 0.11-fold). Interleukin 6 signaling during ischemia and reperfusion was assessed at the protein expression level by means of Western measurements of interleukin 6 receptor, the signaling subunit of the interleukin 6 receptor complex (gp130), and signal transducer of activated transcription 3. Posttranslational changes in the protein kinase B signaling pathway were determined on the basis of the phosphorylation status of protein kinase B, mitogen-activated protein kinase, and glycogen synthase kinase 3beta. The effect of suppression of a prohypertrophic kinase, integrin-linked kinase, with short-interfering RNA was determined in an ischemia and reperfusion-stressed neonatal rat cardiac myocyte model. Endogenous secretion of interleukin 6 protein in culture supernatants was measured by enzyme-linked immunosorbent assay. RESULTS: Human fetal cardiac myocytes exhibited a significantly lower rate of apoptosis induction during ischemia and reperfusion and after exposure to staurosporine and recombinant interleukin 6 compared with that observed in neonatal rat cardiac myocytes ( P < .05 for all comparisons, analysis of variance). Exposure to exogenously added recombinant interleukin 6 increased the apoptotic rate in both rat and human fetal cardiac myocytes ( P < .05). Short-interfering RNA-mediated suppression of integrin-linked kinase, a prohypertrophy upstream kinase regulating protein kinase B and glycogen synthase kinase 3beta phosphorylation, was cytoprotective against ischemia and reperfusion-induced apoptosis in neonatal rat cardiac myocytes ( P < .05). CONCLUSIONS: Human fetal cardiac myocytes exhibit a uniquely adaptive transcriptional response to ischemia and reperfusion that is associated with an apoptosis-resistant phenotype. The stress-inducible fetal cardiac myocyte gene repertoire is a useful platform for identification of targets relevant to the mitigation of cardiac ischemic injury and highlights a novel avenue involving interleukin 6 modulation for preventing the cardiac myocyte injury associated with ischemia and reperfusion.

Mood changes following exercise.

26 participants completed a mood measure to assess anger, confusion, depression, fatigue, tension, and vigor immediately before and immediately after two exercise sessions. Analysis showed significant mood enhancement for each exercise session. Follow-up univariate results indicated that Depressed mood scores were reduced significantly and Fatigue scores increased significantly following the first exercise session. Scores after the second exercise session indicated that Depressed mood decreased significantly. There was no interaction. Results lend support for the notion that exercise reduces depressed mood scores. It is suggested that researchers should consider the mechanisms that produce changes in mood following exercise.

Composition and function of AP-1 transcription complexes during muscle cell differentiation.

The role of activating protein-1 (AP-1) in muscle cells is currently equivocal. While some studies propose that AP-1 is inhibitory for myogenesis, others implicate a positive role in this process. We tested whether this variation may be due to different properties of the AP-1 subunit composition in differentiating cells. Using Western analysis we show that c-Jun, Fra-2, and JunD are expressed throughout the time course of differentiation. Phosphatase assays indicate that JunD and Fra-2 are phosphorylated in muscle cells and that at least two isoforms of each are expressed in muscle cells. Electrophoretic mobility shift assays combined with antibody supershifts indicate the appearance of Fra-2 as a major component of the AP-1 DNA binding complex in differentiating cells. In this context it appears that Fra-2 heterodimerizes with c-Jun and JunD. Studying the c-jun enhancer in reporter gene assays we observed that the muscle transcription factors MEF2A and MyoD can contribute to robust transcriptional activation of the c-jun enhancer. In differentiating muscle cells mutation of the MEF2 site reduces transactivation of the c-jun enhancer and MEF2A is the predominant MEF2 isoform binding to this cis element. Transcriptional activation of an AP-1 site containing reporter gene (TRE-Luc) is enhanced under differentiation conditions compared with growth conditions in C2C12 muscle cells. Further studies indicate that Fra-2 containing AP-1 complexes can transactivate the MyoD enhancer/promoter. Thus, an AP-1 complex containing Fra-2 and c-Jun or JunD is consistent with muscle differentiation, indicating that AP-1 function during myogenesis is dependent on its subunit composition.