Astrocytes are critical participants in synapse development and function, but their role in synaptic plasticity is unclear. Eph receptors and their ephrin ligands have been suggested to regulate neuron-glia interactions and EphA4-mediated ephrin reverse signaling is required for synaptic plasticity in the hippocampus. Here we show that long-term potentiation (LTP) at the CA3-CA1 synapse is modulated by EphA4 in the postsynaptic CA1 cell and by ephrinA3, a ligand of EphA4 that is found in astrocytes. Lack of EphA4 increases the levels of glial glutamate transporters and ephrinA3 modulates transporter currents in astrocytes. Pharmacological inhibition of glial glutamate transporters rescues the LTP defects in EphA4 and ephrinA3 mutant mice. Transgenic overexpression of ephrinA3 in astrocytes reduces glutamate transporter levels and produces focal dendritic swellings possibly caused by glutamate excitotoxicity. These results suggest that EphA4/ephrinA3 signaling is a critical mechanism for astrocytes to regulate synaptic function and plasticity.
The involvement of an SOPC team leads to a significant improvement in the quality of life of patients and caregivers and can lower the burden of home care for the caregivers of severely ill patients.
BackgroundCancer care including aggressive treatment procedures during the last phase of life in patients with incurable cancer has increasingly come under scrutiny, while integrating specialist palliative care at an early stage is regarded as indication for high quality end-of-life patient care.AimTo describe the demographic and clinical characteristics and the medical care provided at the end of life of cancer patients who died in a German university hospital.MethodsRetrospective cross-sectional study on the basis of anonymized hospital data for cancer patients who died in the Munich University Hospital in 2014. Descriptive analysis and multivariate logistic regression analyses for factors influencing the administration of aggressive treatment procedures at the end of life.ResultsOverall, 532 cancer patients died. Mean age was 66.8 years, 58.5% were men. 110/532 (20.7%) decedents had hematologic malignancies and 422/532 (79.3%) a solid tumor. Patients underwent the following medical interventions in the last 7/30 days: chemotherapy (7.7%/38.3%), radiotherapy (2.6%/6.4%), resuscitation (8.5%/10.5%), surgery (15.2%/31.0%), renal replacement therapy (12.0%/16.9%), blood transfusions (21.2%/39.5%), CT scan (33.8%/60.9%). In comparison to patients with solid tumors, patients with hematologic malignancies were more likely to die in intensive care (25.4% vs. 49.1%; p = 0.001), and were also more likely to receive blood transfusions (OR 2.21; 95% CI, 1.36 to 3.58; p = 0.001) and renal replacement therapy (OR 2.65; 95% CI, 1.49 to 4.70; p = 0.001) in the last 7 days of life. Contact with the hospital palliative care team had been initiated in 161/532 patients (30.3%). In 87/161 cases (54.0%), the contact was initiated within the last week of the patient’s life.ConclusionsOverambitious treatments are still reality at the end of life in cancer patients in hospital but patients with solid tumors and hematologic malignancies have to be differentiated. More efforts are necessary for the timely inclusion of specialist palliative care.
Objective: To compare the provision of specialized home palliative care (SHPC) by the adult and pediatric SHPC teams at the Munich University Hospital. Methods: All patients treated by one of the SHPC teams and their primary caregivers were eligible for the prospective nonrandomized survey. We analyzed the demographics, the underlying diseases, duration and impact of SHPC on symptom control and quality of life (QOL) as well as the caregivers' burden and QOL. Results: Between April 2011 and June 2012, 100 adult and 43 pediatric patients were treated consecutively; 60 adults (median age, 67.5 years; 55% male) and 40 children (median age, 6 years, 57% male) were included in the study. Oncologic diseases were dominant only in the adult cohort (87 versus 25%, p < 0.001). The median period of care was higher in the pediatric sample (11.8 versus 4.3 weeks; NS). Ninety-five percent of adult and 45% of pediatric patients died by the end of the study ( p < 0.001), 75% and 90% of them at home, respectively. The numbers of significant others directly affected by the patient's disease was higher in children (mean 3.4 versus 1.2; p < 0.001). The QOL of adult patients and children ( p < 0.05 for both), as well as of their primary caregivers ( p < 0.001 for both) improved during SHPC, while the caregivers' burden was lowered ( p < 0.001 for both). Conclusions: Our results show important differences in several clinically relevant parameters between adults and children receiving SHPC. This should assist in the development of age-group specific SHPC concepts that effectively address the specific needs of each patient population.
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