Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons

Dopamine is believed to contribute to the degeneration of dopamine-containing neurons in the brain. However, whether dopamine affects the survival of other neuronal populations has remained unclear. Here we document that mice with persistently elevated extracellular dopamine, resulting from inactivation of the dopamine transporter gene, sporadically develop severe symptoms of dyskinesia concomitant with apoptotic death of striatal dopamine-responsive gamma-aminobutyric acidergic neurons. Chronic inhibition of dopamine synthesis prevents the appearance of motor dysfunction. The neuronal death is associated with overactivation of dopaminergic signaling as evidenced by the robust up-regulation of striatal DeltaFosB, cyclin-dependent kinase 5, and p35. Moreover, hyperphosphorylation of the tau protein, a phenomenon associated with the activation of cyclin-dependent kinase 5 in several neurodegenerative disorders, is observed in symptomatic mice. These findings provide in vivo evidence that, in addition to its proposed role in the degeneration of dopamine neurons, dopamine can also contribute to the selective death of its target neurons via a previously unappreciated mechanism.     

In vitro characterization of the human recombinant soluble granulocyte- macrophage colony-stimulating factor receptor

We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic domains that are presumably removed from the intact receptor cDNA by a mechanism of alternative splicing. The resulting soluble 55- to 60-kD glycosylated receptor species binds GM-CSF with a dissociation constant (kd) of 3.8 nmol/L. The soluble GM-CSF receptor successfully competes for GM-CSF binding not only with the transmembrane-anchored GM-CSF receptor alpha subunit but also with the native oligomeric high-affinity receptor complex. In addition, in human bone marrow colony-forming assays, the soluble GM-CSF receptor species can antagonize the activity of GM-CSF. Our data suggest that the soluble GM-CSF receptor may be capable of acting in vivo as a modulator of the biologic activity of GM-CSF.     

Effects of Question Framing on Self-Reported Memory Concerns across the Lifespan

Background/Study Context: Evidence regarding whether there is an age-related increase in subjective memory concerns is mixed. The goal of this study was to investigate whether calling to mind specific instances of memory failures affects the likelihood that individuals report being concerned about their memory.

Methods: Young, middle-aged, and older individuals responded to statements that probed general memory concerns (e.g., I am concerned about my memory) before or after probing the frequency of memory difficulties in specific everyday situations (e.g., I forget appointments).

Results: We found no relationship between age and memory concern, and older compared to younger adults reported having fewer everyday memory failures. Furthermore, individuals of all ages were more likely to report being concerned about their memory if asked before relative to after rating the frequency of specific everyday memory failures.

Conclusion: Increasing age is associated with fewer reported difficulties with specific everyday memory situations, but people of all ages display anchoring effects on memory concern based on realistic occurrences of remembering. Our findings have implications for the measurement of self-reported memory as they show that the order of questions can influence responding.     

The factor structure of the HSCL-58 in binge eaters

The present study examines the factor composition of the HSCL-58 and the item content agreement with the five postulated dimensions based on a sample of 158 female undergraduates with various degrees of binging patterns. Although the results indicated good factor congruence for five dimensions, only one of the original five dimensions postulated (Somatization) was represented. It is recommended that the HSCL-58 be used as a measure of general distress rather than as a measure of five independent symptom dimensions.     

Fast Track: urgent care within a teaching hospital emergency department: can it work?

We performed a ten-week study to understand the feasibility of a fast track system within a teaching hospital setting. Our results show that 50% or fewer of patients entering an emergency department during evening and weekend day hours can be seen in Fast Track. Average turnaround time for all patients in the ED was 161 minutes. The average for all Fast Track patients was 94.5 minutes; if laboratory and/or radiographs were ordered the average was 121.5 minutes; with no laboratory/radiographs, 79.1 minutes. Urinalysis, strep screen, and complete blood count accounted for 80% of all laboratory work. Roentgenograms of the ankle, foot, and knee accounted for 80% of all radiographs. An evaluation questionnaire showed enhanced satisfaction with a reduction in the number of complaints from 79% to 22%. The Fast Track system failed when there was a predominance of acutely ill patients in the ED, as house officers were pulled to care for the acutely ill patients.     

Calcium-independent phospholipase A(2) influences AMPA-mediated toxicity of hippocampal slices by regulating the GluR1 subunit in synaptic membranes

We have recently documented that phosphorylation of the GluR1 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) glutamate receptors is influenced by calcium-independent forms of phospholipase A(2) (iPLA(2)) activity in the brain. Given the importance of GluR1 subunit phosphorylation in the control of AMPA receptor delivery to synaptic membranes, we tested the influence of iPLA(2) activity on AMPA receptor distribution between neuronal compartments, using organotypic cultured hippocampal slices. In agreement with earlier reports, the iPLA(2) inhibitor bromoenol lactone (BEL) markedly enhanced the phosphorylation of the GluR1 subunit at both Ser831 and Ser845 residues. GluR1 subunit phosphorylation levels were selectively increased by (R)-BEL, an enantio-selective inhibitor of iPLA(2)gamma, but not by (S)-BEL, an iPLA(2)beta inhibitor. The iPLA(2)gamma inhibitor R-BEL also promoted the insertion of new GluR1 subunits into synaptic membranes and exacerbated AMPA-mediated cell death in the CA1 region of the hippocampus. The latter effect was selectively abolished by IEM 1460 and philanthotoxin-433, two antagonists specific for AMPA receptors lacking GluR2 subunits. These results provide evidence that iPLA(2)gamma-related regulation of AMPA receptor GluR1 subunit phosphorylation could represent an important mechanism modulating hippocampal cell death induced by AMPA receptor overstimulation.     

Health care professionals' grief after the death of a child

OBJECTIVES:

To evaluate the intensity of grief experienced by health care professionals (HPs) after the death of a child, to explore factors associated with a memorable death (defined as an unforgettable child’s death that has touched them in their career) and to identify the needs of HPs.

METHODS:

A cross-sectional study was performed to assess emotional reactions, coping strategies and perceived needs of paediatric HPs in a general hospital.

RESULTS:

One hundred one HPs (46 nurses, 22 paediatric physicians, 11 paediatric residents, 13 respiratory therapists and nine ‘others’) completed the questionnaire. The level of grief experienced by HPs after a memorable death was intense. Respiratory therapists showed the highest mean (± SD) intensity of grief after a memorable death versus other HPs, as measured by the Texas Revised Inventory of Grief (TRIG) (29±15 versus 16±14; P=0.002). Younger HPs (20 to 25 years of age) reported higher early grief intensity than older ones (older than 50 years of age) (22±16 versus 10±8; P=0.01). There was no significant association between the TRIG score and an HP being a parent, having received palliative care training or the length of his/her relationship with the child and family. Seventy per cent of HPs spoke with their colleagues after the death of a child and 48% with family and friends. Many participants (37%) believed that this social support helped them the most.

CONCLUSION:

Grief after a child’s death is intense for HPs. This emotional intensity and difference between professions raises issues about the emotional support received following the death of a patient.