Clathrin-mediated endocytosis is required for compensatory regulation of GLR-1 glutamate receptors after activity blockade

Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a Caenorhabditis elegans glutamate receptor. In mutants lacking a voltage-dependent calcium channel (unc-2) or a vesicular glutamate transporter (VGLUT; eat-4), the abundance of GLR-1 in the ventral nerve cord was increased. Similarly, the amplitude of glutamate-evoked currents in ventral cord interneurons was increased in eat-4 VGLUT mutants compared with wild-type controls. The effects of eat-4 VGLUT mutations on GLR-1 abundance in the ventral cord were eliminated in double mutants lacking both the clathrin adaptin protein unc-11 AP180 and eat-4 VGLUT. In contrast, mutations that decreased ubiquitination of GLR-1 did not prevent increased ventral cord abundance of GLR-1 in eat-4 VGLUT mutants. Taken together, our results suggest that GLR-1 is regulated in a homeostatic manner and that this effect depends on clathrin-mediated endocytosis but does not require ubiquitination of GLR-1.     

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial

Objectives

The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI.

Transradial cardiac catheterization in patients with coronary bypass grafts: feasibility analysis and comparison with transfemoral approach.

The objective of this study was to analyze the feasibility and safety of transradial catheterization in patients with remote surgical cardiac revascularization. Selective catheterization of coronary bypass grafts might be more difficult and time-consuming from the radial artery as compared to the femoral route. This special patient subset has been either excluded or underrepresented in previous studies. Retrospective review was made of 304 cardiac diagnostic procedures performed from January 2001 through December 2004 in patients with coronary artery bypass grafts in a single center. Patients had to be considered eligible for both transradial and transfemoral approach to be included. Cases with double internal mammary or gastroepiploic grafts were excluded. Selection of the arterial access was individualized according to operator preferences. Among diagnostic cases, transradial access was attempted as first choice in 151 cases (left radial in 133) and transfemoral in 154. Total procedural time (41 +/- 22 vs. 40 +/- 23 min), fluoroscopy time (15 +/- 10 vs. 18 +/- 13 min), and dye volume (180 +/- 64 vs. 192 +/- 73 ml) were similar. Crossover rates were 4.0% in the transradial group and 1.3% in transfemoral (P = 0.28). Only two patients in transradial group needed transfemoral access because of failure to catheterize a bypass graft. Transradial angiography of coronary bypass grafts can be performed with similar success rates as compared with transfemoral procedures and without a significant time delay.     

Protocol driven palliative care consultation: Outcomes of the ENABLE CHF-PC pilot study

Background

Little has been reported about protocol-driven outpatient palliative care consultation (OPCC) for advanced heart failure (HF).