Chronobiological factors for compassion satisfaction and fatigue among ambulatory oncology caregivers

Primary caregivers for victims of chronic illness and or trauma experience both positive and negative emotional consequences. These are broadly classified as compassion satisfaction (CS) and compassion fatigue (CF). Because one of the components of CF, burnout, varies with chronotype and sleep quality, we assessed the influence of chronobiological features on the broader constructs of CS and CF. Responses from primary ambulatory care oncology staff working dayshifts were assessed for potential relationships of chronotype and sleep quality with CS and CF using the professional quality of life scale. These were analyzed further in a multivariate model that included personality and job satisfaction as cofactors. We found that sleep quality was a key contributor to CS development and CF reduction. Morningness was positively linked to CS, but the univariate association was masked in the multivariate model. Job satisfaction (contingent rewards, nature of work and operating procedures) heavily influenced CS and CF development. Agreeableness and openness showed positive correlations with CS and negative with burnout, while emotional stability was linked to reduced CF. While job satisfaction and personality predictably played roles in the development of CS and CF, sleep quality and chronotype contributed significantly to benefits and negative consequences of providing care.     

What it Takes to Get Passed On: Message Content,Style, and Structure as Predictors of Retransmission in the Boston Marathon Bombing Response

Message retransmission is a central aspect of information diffusion. In a disaster context, the passing on of official warning messages by members of the public also serves as a behavioral indicator of message salience, suggesting that particular messages are (or are not) perceived by the public to be both noteworthy and valuable enough to share with others. This study provides the first examination of terse message retransmission of official warning messages in response to a domestic terrorist attack, the Boston Marathon Bombing in 2013. Using messages posted from public officials’ Twitter accounts that were active during the period of the Boston Marathon bombing and manhunt, we examine the features of messages that are associated with their retransmission. We focus on message content, style, and structure, as well as the networked relationships of message senders to answer the question: what characteristics of a terse message sent under conditions of imminent threat predict its retransmission among members of the public? We employ a negative binomial model to examine how message characteristics affect message retransmission. We find that, rather than any single effect dominating the process, retransmission of official Tweets during the Boston bombing response was jointly influenced by various message content, style, and sender characteristics. These findings suggest the need for more work that investigates impact of multiple factors on the allocation of attention and on message retransmission during hazard events.     

Activation of phospholipase C in rabbit brain membranes by carbachol in the presence of GTP gamma S; effects of biological detergents

Rabbit brain cortical membranes incubated with carbachol in the presence of GTP gamma S show a marked increase in the degradation of exogenous phosphatidylinositol 4,5-bisphosphate. This activation of phospholipase C is dependent on the presence of deoxycholate and maximal at 0.8-1 mM deoxycholate. There is negligible activation by carbachol alone but in the presence of GTP gamma S a carbachol effect can be readily demonstrated. Optimal activation of phospholipase C by carbachol was seen at 10 to 100 nM free Ca2+. Washing cortical membranes with hypertonic buffer extracted 60% of the membrane protein yet the carbachol and GTP gamma S coupling remained intact. Incubation of the membranes with lysophosphatidylcholine, Nonidet P-40, sodium deoxycholate or digitonin at concentrations considerably less than those frequently used to solubilize membrane proteins abolished the carbachol response. Octyl glucoside and sodium cholate also uncoupled receptor regulation of phospholipase C but only at concentrations where solubilization of membrane proteins occurred. Prior exposure of membranes to carbachol did not prevent the uncoupling observed as a result of detergent treatment. Incubation of the membranes with carbachol and GTP gamma S did not appear to be accompanied by specific release of either active phospholipase C or inhibitors of phospholipase C activity.     

Phosphatidylinositol 3-kinase is activated by nerve growth factor and epidermal growth factor in PC12 cells.

The effects of nerve growth factor (NGF) and epidermal growth factor (EGF) on the regulation of phosphatidylinositol 3-kinase (PtdIns 3-kinase) activity were assessed in rat pheochromocytoma (PC12) cells. Both NGF and EGF induced a rapid activation of PtdIns 3-kinase as assessed by a dramatic rise in growth factor-induced PtdIns 3-kinase activity found in antiphosphotyrosine immunoprecipitates. The intracellular levels of two of the lipid products of PtdIns 3-kinase, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2), also rose dramatically, exhibiting time courses very similar to the appearance of PtdIns 3-kinase in immunoprecipitates. The activation of PtdIns 3-kinase is, therefore, a common event in the signal transduction processes elicited by growth factors stimulating distinct cellular end points in PC12 cells, namely the NGF-induced neuronal differentiation and EGF-stimulated mitogenesis. Thus the intracellular products of this enzyme may function in early biochemical events that are common components of the pathways controlling both differentiation and proliferation.     

S-adenosylmethionine decarboxylase from Leishmania donovani. Molecular, genetic, and biochemical characterization of null mutants and overproducers.

The polyamine biosynthetic enzyme, S-adenosylmethionine decarboxylase (ADOMETDC) has been advanced as a potential target for antiparasitic chemotherapy. To investigate the importance of this protein in a model parasite, the gene encoding ADOMETDC has been cloned and sequenced from Leishmania donovani. The Delta adometdc null mutants were created in the insect vector form of the parasite by double targeted gene replacement. The Delta adometdc strains were incapable of growth in medium without polyamines; however, auxotrophy could be rescued by spermidine but not by putrescine, spermine, or methylthioadenosine. Incubation of Delta adometdc parasites in medium lacking polyamines resulted in a drastic increase of putrescine and glutathione levels with a concomitant decrease in the amounts of spermidine and the spermidine-containing thiol trypanothione. Parasites transfected with an episomal ADOMETDC construct were created in both wild type and Delta adometdc parasites. ADOMETDC overexpression abrogated polyamine auxotrophy in the Delta adometdc L. donovani. In addition, ADOMETDC overproduction in wild type parasites alleviated the toxic effects of 5'-(((Z)-4-amino-2-butenyl)methylamino)-5'-deoxyadenosine (MDL 73811), but not pentamidine, berenil, or methylglyoxyl bis(guanylhydrazone), all inhibitors of ADOMETDC activities in vitro. The molecular, biochemical, and genetic characterization of ADOMETDC establishes that it is essential in L. donovani promastigotes and a potential target for therapeutic validation.     

Comparison of the biochemical and kinetic properties of the type 1 receptor tyrosine kinase intracellular domains. Demonstration of differential sensitivity to kinase inhibitors.

Epidermal growth factor receptor (EGFR), ErbB-2, and ErbB-4 are members of the type 1 receptor tyrosine kinase family. Overexpression of these receptors, especially ErbB-2 and EGFR, has been implicated in multiple forms of cancer. Inhibitors of EGFR tyrosine kinase activity are being evaluated clinically for cancer therapy. The potency and selectivity of these inhibitors may affect the efficacy and toxicity of therapy. Here we describe the expression, purification, and biochemical comparison of EGFR, ErbB-2, and ErbB-4 intracellular domains. Despite their high degree of sequence homology, the three enzymes have significantly different catalytic properties and substrate kinetics. For example, the catalytic activity of ErbB-2 is less stable than that of EGFR. ErbB-2 uses ATP-Mg as a substrate inefficiently compared with EGFR and ErbB-4. The three enzymes have very similar substrate preferences for three optimized peptide substrates, but differences in substrate synergies were observed. We have used the biochemical and kinetic parameters determined from these studies to develop an assay system that accurately measures inhibitor potency and selectivity between the type 1 receptor family. We report that the selectivity profile of molecules in the 4-anilinoquinazoline series can be modified through specific aniline substitutions. Moreover, these compounds have activity in whole cells that reflect the potency and selectivity of target inhibition determined with this assay system.     

Nitrate retention in a sand plains stream and the importance of groundwater discharge

We measured net nitrate retention by mass balance in a 700-m upwelling reach of a third-order sand plains stream, Emmons Creek, from January 2007 to November 2008. Surface water and groundwater fluxes of nitrate were determined from continuous records of discharge and from nitrate concentrations based on weekly and biweekly sampling at three surface water stations and in 23 in-stream piezometers, respectively. Surface water nitrate concentration in Emmons Creek was relatively high (mean of 2.25 mg NO₃?CN l^?1) and exhibited strong seasonal variation. Net nitrate retention averaged 429 mg NO₃?CN m^?2 d^?1 and about 2% of nitrate inputs to the reach. Net nitrate retention was highest during the spring and autumn when groundwater discharge was elevated. Groundwater discharge explained 57?C65% of the variation in areal net nitrate retention. Specific discharge and groundwater nitrate concentration varied spatially. Weighting groundwater solute concentrations by specific discharge improved the water balance and resulted in higher estimates of nitrate retention. Our results suggest that groundwater inputs of nitrate can drive nitrate retention in streams with high groundwater discharge.