BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses

Exerting its actions pre-, post- and peri-synaptically, brain-derived neurotrophic factor (BDNF) is one of the most potent modulators of hippocampal synaptic function. Here, we examined the effects of BDNF on a rapidly recycling pool (RRP) of vesicles within excitatory synapses. First, we estimated vesicular release in hippocampal cultures by performing FM4-64 imaging in terminals impinging on enhanced green fluorescent protein (eGFP)-labelled dendritic spines – a hallmark of excitatory synapses. Consistent with a modulation of the RRP, BDNF increased the evoked destaining rate of FM4-64 only during the initial phase of field stimulation. Multiphoton microscopy in acute hippocampal slices confirmed these observations by selectively imaging the RRP, which was loaded with FM1-43 by hyperosmotic shock. Slices exposed to BDNF showed an increase in the evoked and spontaneous rates of FM1-43 destaining from terminals in CA1 stratum radiatum, mostly representing excitatory terminals of Schaffer collaterals. Variance-mean analysis of evoked EPSCs in CA1 pyramidal neurons further confirmed that release probability is increased in BDNF-treated slices, without changes in the number of independent release sites or average postsynaptic quantal amplitude. Because BDNF was absent during dye loading, imaging, destaining and whole-cell recordings, these results demonstrate that BDNF induces a long-lasting enhancement in the probability of transmitter release at hippocampal excitatory synapses by modulating the RRP. Since the endogenous BDNF scavenger TrkB-IgG prevented the enhancement of FM1-43 destaining rate caused by induction of long-term potentiation in acute hippocampal slices, the modulation of a rapidly recycling vesicle pool may underlie the role of BDNF in hippocampal long-term synaptic plasticity.     

A photoetched cell relocation matrix for long-term, quantitative observations of selected individual neurons in culture

A photoetched matrix of indium tin oxide (ITO) on glass has been developed and tested as a tool to assist in the relocation and identification of individual neuronal cells in culture. The matrix is formed by 10-15 micron wide and 300 A thick ITO lines which subdivide a 1-cm2 area into 625 smaller squares. Each of the smaller squares measures 400 micron on a side and contains a photoetched two-letter "address". The address code allows precise relocation of specific regions of a culture as well as verification of the identities of individual neurons selected for repeated observation. Marks at 50 micron intervals along the sides of the address squares permit quantitative analysis of morphological changes, cell migration, reaggregation, etc. The ITO is transparent and does not interfere with visualization of even fine details of cells with high power microscopy.     

Clinical pharmacology of oral and intravenous 4-demethoxydaunorubicin

Summary The clinical pharmacology of 4-demethoxydaunorubicin (4-DMDNR) was studied in 28 patients with advanced breast cancer, using a sensitive reverse-phase HPLC technique. All patients had normal renal and hepatic function. The serum levels of 4-DMDNR after a single i.v. bolus injection followed a triple exponential decay curve (T1/2=9.6 min, T1/2=3.2 h and T1/2=34.7 h) and conformed to a three-compartment model. Comparison of the area under the curve (AUC) and urinary excretion for the oral and i.v routes suggests an oral bioavailability of approximately 24%. In patients treated with a schedule of weekly oral administration for periods of up to 12 months there was no significant alteration in either AUC or elimination half-life for the parent drug or its principal metabolite 13-OH4DMDNR. Moreover, there was no evidence of accumulation of the metabolite although measurable amounts were present 7 days after administration of 4-DMDNR.This work was supported by the Cancer Research Campaign and Farmitalia Carlo Erba Ltd     

Barriers and Facilitators to Participation in Health Screening: an Umbrella Review Across Conditions

Prevention Science - Screening is an essential prevention practice for a number of health conditions. However, screening coverage remains generally low. Studies that investigate determinants of...     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Ureteral reconstruction for complex strictures: a review of the current literature

International Urology and Nephrology - Frequently employed procedures for ureteral reconstruction include balloon dilation, pyeloplasty and ureteral re-implants. However, these procedures do not...     

Extent of resection in diffuse low-grade gliomas and the role of tumor molecular signature—a systematic review of the literature

Neurosurgical Review - There is a lack of class I evidence concerning the impact of surgery in the treatment of diffuse low-grade glioma; the early maximal resection with preservation of eloquent...     

High Rates of Spacer Fracture in the Setting of Extended Trochanteric Osteotomy With a Specific Thin-Core Articulating Antibiotic Hip Spacer

BackgroundTwo-stage revision remains the standard of care for prosthetic joint infection after total hip arthroplasty. However, there are substantial complications associated with articulating antibiotic hip spacers. Handmade and molded spacers have been shown to have higher rates of spacer fracture than antibiotic-coated prostheses (ACPs). The aim of this study is to review outcomes with an implant that is often categorized as an ACP spacer, the Zimmer-Biomet StageOne Select Femoral Spacer (ZBSO).MethodsA retrospective review was performed of 63 patients who underwent placement of a ZBSO. Patients were compared based on whether or not an extended trochanteric osteotomy (ETO) was performed using Fisher’s exact and t-tests.ResultsFive patients were excluded due to lack of follow-up or death shortly after stage 1 surgery, leaving 58 patients. Spacer fracture was noted in 5 of 58 patients (8.6%). Sixteen patients underwent ETO and 25.0% suffered a spacer fracture compared to 2.3% without ETO (odds ratio 13.7, P = .0248). There was no association between patient demographics or ETO length and spacer fracture. Two patients had periprosthetic fractures (3.4%) and 4 had dislocations (6.9%). Forty-nine patients (84.4%) went on to second-stage revision; of those 26.5% failed to clear the infection and required an average of 2.2 additional surgeries.ConclusionThe ZBSO spacer has overall complication rates similar to previously reported spacer series. Although the ZBSO looks like an ACP spacer, in the setting of ETO, it behaves like a molded or handmade spacer with a high rate of spacer fracture (25%) due to the small diameter of the core. This implant should be used with caution in combination with an ETO.