Two-Photon Na+ Imaging Reports Somatically Evoked Action Potentials in Rat Olfactory Bulb Mitral and Granule Cell Neurites

Dendrodendritic synaptic interactions are a hallmark of neuronal processing in the vertebrate olfactory bulb. Many classes of olfactory bulb neurons including the principal mitral cells (MCs) and the axonless granule cells (GCs) dispose of highly efficient propagation of action potentials (AP) within their dendrites, from where they can release transmitter onto each other. So far, backpropagation in GC dendrites has been investigated indirectly via Ca2+ imaging. Here, we used two-photon Na+ imaging to directly report opening of voltage-gated sodium channels due to AP propagation in both cell types. To this end, neurons in acute slices from juvenile rat bulbs were filled with 1 mM SBFI via whole-cell patch-clamp. Calibration of SBFI signals revealed that a change in fluorescence Delta F/F by 10% corresponded to a Delta[Na+](i) of similar to 22 mM. We then imaged proximal axon segments of MCs during somatically evoked APs (sAP). While single sAPs were detectable in similar to 50% of axons, trains of 20 sAPs at 50 Hz always resulted in substantial Delta F/F of similar to 15% (similar to 33 mM Delta[Na+](i)). Delta F/F was significantly larger for 80 Hz vs. 50 Hz trains, and decayed with half-durations tau(1/2) similar to 0.6 s for both frequencies. In MC lateral dendrites, AP trains yielded small Delta F/F of similar to 3% (similar to 7 mM Delta[Na+](i)). In GC apical dendrites and adjacent spines, single sAPs were not detectable. Trains resulted in an average dendritic Delta F/F of 7% (16 mM Delta[Na+](i)) with tau(1/2) similar to 1 s, similar for 50 and 80 Hz. Na+ transients were indistinguishable between large GC spines and their adjacent dendrites. Cell-wise analysis revealed two classes of GCs with the first showing a decrease in Delta F/F along the dendrite with distance from the soma and the second an increase. These classes clustered with morphological parameters. Simulations of Delta[Na+](i) replicated these behaviors via negative and positive gradients in Na+ current density, assuming faithful AP backpropagation. Such specializations of dendritic excitability might confer specific temporal processing capabilities to bulbar principal cell-GC subnetworks. In conclusion, we show that Na+ imaging provides a valuable tool for characterizing AP invasion of MC axons and GC dendrites and spines

How can we improve stroke thrombolysis rates? : a review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care

Background: Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke. Methods: Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted. Results: Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio=2.1, p=0.05). Conclusions: In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients

A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women

Aims To assess the joint influence of inflammatory biomarkers on the risk of incident atrial fibrillation (AF) in women. Methods and results We performed a prospective cohort study among women participating in the Women's Health Study. All women were free of AF at study entry and provided a baseline blood sample assayed for high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and fibrinogen. To evaluate the joint effect of these three biomarkers, an inflammation score was created that ranged from 0 to 3 and reflected the number of biomarkers in the highest tertile per individual. During a median follow-up of 14.4 years, 747 of 24 734 women (3.0%) experienced a first AF event. Assessed individually, all three biomarkers were associated with incident AF, even after adjustment for traditional risk factors. When combined into an inflammation score, a strong and independent relationship between inflammation and incident AF emerged. Across increasing inflammation score categories, there were 1.66, 2.22, 2.73, and 3.25 AF events per 1000 person-years of follow-up. The corresponding hazard ratios (95% confidence intervals) across inflammation score categories were 1.0, 1.22 (1.00-1.49), 1.32 (1.06-1.65), and 1.59 (1.22-2.06) (P for linear trend 0.0006) after multivariable adjustment. Conclusion In this large-scale prospective study among women without a history of cardiovascular disease, markers of systemic inflammation were significantly related to AF even after controlling for traditional risk factor

Parental Involvement and Academic Performance of High School Students: A Correlational Study

The main purpose of this study was to examine the correlation between parental involvement (PI) and academic performance (AP) among junior high school (JHS) students in selected schools in Cebu. This study employed a quantitative correlational design. There were thirty (30) JHS students who participated in this research who were identified using a simple random sampling method. Descriptive statistical tools, particularly mean and standard deviation were used to describe the level of PI and AP of the students. Consequently, the Pearson product-moment coefficient of correlation test was run to assess the correlation between PI and AP among JHS students. Based on the findings, it showed that there is a very low negative correlation between the two variables. Thus, there is no significant correlation between PI and AP among JHS students, r (30) = - .06, p = .74. With these results, the null hypothesis was not rejected since the p-value is greater than the significance level, p > .05. Therefore, PI does not affect the AP of the students. Findings suggest that educational staff and administrators be able to identify other factors that influence the AP of the students. Because the scope of this study is restricted within the perception of students towards PI, it would be better for the future studies to let the parents of the students be involved, and their side will be taken into consideration; new variables in the inquiry – motivation and self-competence among students; and to conduct a qualitative or a mixed-method study for future studies about the topic

Novel algorithms for improved detection and analysis of fluorescent signal fluctuations

Fluorescent dyes and genetically encoded fuorescence indicators (GEFI) are common tools for visualizing concentration changes of specifc ions and messenger molecules during intra- as well as intercellular communication. Using advanced imaging technologies, fuorescence indicators are a prerequisite for the analysis of physiological molecular signaling. Automated detection and analysis of fuorescence signals require to overcome several challenges, including correct estimation of fuorescence fuctuations at basal concentrations of messenger molecules, detection, and extraction of events themselves as well as proper segmentation of neighboring events. Moreover, event detection algorithms need to be sensitive enough to accurately capture localized and low amplitude events exhibiting a limited spatial extent. Here, we present two algorithms (PBasE and CoRoDe) for accurate baseline estimation and automated detection and segmentation of fuorescence fuctuations