alpha-Synuclein promotes dilation of the exocytotic fusion pore

The protein α-synuclein has a central role in the pathogenesis of Parkinson's disease. Like that of other proteins that accumulate in neurodegenerative disease, however, the function of α-synuclein remains unknown. Localization to the nerve terminal suggests a role in neurotransmitter release, and overexpression inhibits regulated exocytosis, but previous work has failed to identify a clear physiological defect in mice lacking all three synuclein isoforms. Using adrenal chromaffin cells and neurons, we now find that both overexpressed and endogenous synuclein accelerate the kinetics of individual exocytotic events, promoting cargo discharge and reducing pore closure ('kiss-and-run'). Thus, synuclein exerts dose-dependent effects on dilation of the exocytotic fusion pore. Remarkably, mutations that cause Parkinson's disease abrogate this property of α-synuclein without impairing its ability to inhibit exocytosis when overexpressed, indicating a selective defect in normal function

Economic and environmental analysis of extrusion processing of grains into foods and feeds

One of the major problems facing our planet with such a rapidly growing population is a need for cheap and healthy food in developing countries. Although there have already been many valiant attempts at helping this crisis, a cure-all solution is still not likely. A common nutrient lacking from many people\u27s diets in developing countries is protein. One way in which this problem can be mitigated is through the use of Textured Vegetable Protein (TVP). This product is produced from the grain extrusion process, is lightweight, and carries high-protein content. It is important to analyze if this product can act as a suitable, sustainable option for protein in developing countries. In order to examine this we have focused on Brazil and Bolivia specifically. In this project, we have five scenarios and we will conduct techno-economic analysis and life cycle assessment to compare all scenarios

Pragmatic characteristics of patient-reported outcome measures are important for use in clinical practice

OBJECTIVES: Measures for assessing patient-reported outcomes (PROs) that may have initially been developed for research are increasingly being recommended for use in clinical practice as well. Although psychometric rigor is essential, this article focuses on pragmatic characteristics of PROs that may enhance uptake into clinical practice. STUDY DESIGN AND SETTING: Three sources were drawn on in identifying pragmatic criteria for PROs: (1) selected literature review including recommendations by other expert groups; (2) key features of several model public domain PROs; and (3) the authors' experience in developing practical PROs. RESULTS: Eight characteristics of a practical PRO include: (1) actionability (i.e., scores guide diagnostic or therapeutic actions/decision making); (2) appropriateness for the relevant clinical setting; (3) universality (i.e., for screening, severity assessment, and monitoring across multiple conditions); (4) self-administration; (5) item features (number of items and bundling issues); (6) response options (option number and dimensions, uniform vs. varying options, time frame, intervals between options); (7) scoring (simplicity and interpretability); and (8) accessibility (nonproprietary, downloadable, available in different languages and for vulnerable groups, and incorporated into electronic health records). CONCLUSION: Balancing psychometric and pragmatic factors in the development of PROs is important for accelerating the incorporation of PROs into clinical practice

Characteristics of Successful Nursing Students

In an attempt to look into ways to reduce attrition rates in nursing programs, we did a study to look into what non-academic factors can be looked at in addition to the current standard admission data. The research question of interest was “What non-academic characteristics of students can lead to best chance of success in nursing school?” Our sample included 115 students at Georgia Southern University School of Nursing, who have already completed at least one semester of nursing school. Instrument of collection was an IRB approved 20-item self-reported questionnaire with anonymous and passive content. Data was analyzed using SPSS version 21 software, and the data comparisons were made using appropriate statistical analysis methods such as: cross tab tables, Pearson correlation coefficient, and chi-square. Alpha was set at 0.05 for all analyses. Results indicated a strong positive correlation between students who cope with program stress, assume leadership roles, and adapt to change. Advanced degree was the highest motivation for students \u3e3.5 GPA. Additionally, these students also reported the most utilized weekend study time. However, due to a low sample size and lack of time and resources, we were unable to make full concrete conclusions from our study. Additionally, P-values did not meet our 0.05 goal therefore we were unable to reject the null hypotheses. Further testing using more credible survey, larger sample size, which includes those students who drop or fail out, and data that is not self-reported is needed to make stronger conclusions regarding expanding the nursing selection process

Field surveys of capercaillie ( Tetrao urogallus ) in the Swiss Alps underestimated local abundance of the species as revealed by genetic analyses of non-invasive samples

An increasing number of species are becoming threatened by habitat loss and fragmentation. Therefore, solid estimates of the species' abundance in the remaining populations are required to develop suitable conservation measures and to monitor their effectiveness. The capercaillie (Tetrao urogallus L.) has experienced a dramatic decline in central Europe and has disappeared from large areas of its former natural range. In Switzerland, the species' distribution, habitat requirements and demographic status were studied and evaluated in an attempt to support appropriate management decisions to conserve the species. National surveys of the capercaillie in Switzerland have traditionally been obtained from male counts at leks. However, individual attendance to the lek is sex- and age-specific. Thus, male counts at leks may provide a biased estimate of local population sizes. In the present study, we compared two alternative indirect methods to estimate the sizes of local populations at eight study sites situated in the Alps and Prealps of Switzerland. We first assessed the sizes of local populations from the observed density and distribution of direct and indirect evidence of the species' presence during field surveys. Feather and faeces samples collected during field surveys were genotyped at twelve nuclear microsatellite loci and a sex-specific nuclear gene fragment. Individual genotypes were used as genetic tags to estimate the sizes of the eight local populations using an urn model developed for small populations. The index of local population sizes assessed from field surveys was lower than the number of unique genotypes at each study site, which itself underestimated the abundances of populations in most cases. Based on our results, the genetic tagging method appeared to be less biased than the field survey method. However, an alternative faeces sampling scheme, resulting in 2-3genotypings per individual, could further improve the accuracy of the size estimates of local populations. Our study confirms that genetic tagging methods are a valuable tool to estimate the sizes of local populations and to monitor the response of rare and elusive species to management action

The SPADE Symptom Cluster in Primary Care Patients with Chronic Pain

Objectives: Sleep disturbance, pain, anxiety, depression, and low energy/fatigue, the SPADE pentad, are the most prevalent and co-occurring symptoms in the general population and clinical practice. Co-occurrence of SPADE symptoms may produce additive impairment and negatively affect treatment response, potentially undermining patients’ health and functioning. The purpose of this paper is to determine: (1) prevalence and comorbidity (ie, clustering) of SPADE symptoms; (2) internal reliability and construct validity of a composite SPADE symptom score derived from the Patient-Reported Outcomes Measurement Information System (PROMIS) measures; and (3) whether improvement in somatic symptom burden represented by a composite score predicted subsequent measures of functional status at 3 and 12 months follow-up. Methods: Secondary analysis of data from the Stepped Care to Optimize Pain care Effectiveness study, a randomized trial of a collaborative care intervention for Veterans with chronic pain. Results: Most patients had multiple SPADE symptoms; only 9.6% of patients were monosymptomatic. The composite PROMIS symptom score had good internal reliability (Cronbach’s alpha=0.86) and construct validity and strongly correlated with multiple measures of functional status; improvement in the composite score significantly correlated with higher scores for 5 of 6 functional status outcomes. The standardized error of measurement (SEM) for the composite T-score was 2.84, suggesting a 3-point difference in an individual’s composite score may be clinically meaningful. Discussion: Brief PROMIS measures may be useful in evaluating SPADE symptoms and overall symptom burden. Because symptom burden may predict functional status outcomes, better identification and management of comorbid symptoms may be warranted

A new rotational thrombectomy catheter: System design and first clinical experiences

Purpose: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy and safety in vitro and in vivo. Methods: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy of the device was tested in arterial models and fresh bovine carotid arteries (n=72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 ±10.1 years) with occlusions of the superficial femoral artery (2-12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter. Results: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher consistency was cut into particles of 100-500 μm and transported outside. Thrombectomy was successful and vessel patency restored in all 10 patients. The ankle/brachial pressure index significantly (p<0.0005) increased from 0.41±0.18 before intervention to 0.88±0.15 after 48 hr and to 0.84±0.20 after 3 months. Two reocclusions occurred within 14 days after the intervention. Conclusion: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal arter

Visualization Component of Vehicle Health Decision Support System

The visualization front-end of a Decision Support System (DSS) also includes an analysis engine linked to vehicle telemetry, and a database of learned models for known behaviors. Because the display is graphical rather than text-based, the summarization it provides has a greater information density on one screen for evaluation by a flight controller.This tool provides a system-level visualization of the state of a vehicle, and drill-down capability for more details and interfaces to separate analysis algorithms and sensor data streams. The system-level view is a 3D rendering of the vehicle, with sensors represented as icons, tied to appropriate positions within the vehicle body and colored to indicate sensor state (e.g., normal, warning, anomalous state, etc.). The sensor data is received via an Information Sharing Protocol (ISP) client that connects to an external server for real-time telemetry. Users can interactively pan, zoom, and rotate this 3D view, as well as select sensors for a detail plot of the associated time series data. Subsets of the plotted data can be selected and sent to an external analysis engine to either search for a similar time series in an historical database, or to detect anomalous events. The system overview and plotting capabilities are completely general in that they can be applied to any vehicle instrumented with a collection of sensors. This visualization component can interface with the ISP for data streams used by NASA s Mission Control Center at Johnson Space Center. In addition, it can connect to, and display results from, separate analysis engine components that identify anomalies or that search for past instances of similar behavior. This software supports NASA's Software, Intelligent Systems, and Modeling element in the Exploration Systems Research and Technology Program by augmenting the capability of human flight controllers to make correct decisions, thus increasing safety and reliability. It was designed specifically as a tool for NASA's flight controllers to monitor the International Space Station and a future Crew Exploration Vehicle