BrightFocus Alzheimer's Fast Track 2019.
Ontology highlight
ABSTRACT:
SUBMITTER: Whitaker KW
PROVIDER: S-EPMC6924007 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
BrightFocus Alzheimer's Fast Track 2019.
Whitaker Keith W KW LaFerla Frank M FM Steinbusch Harry W M HWM Lemere Cynthia A CA Bovenkamp Diane E DE
Molecular neurodegeneration 20191220 1
The 3 day workshop "Alzheimer's Fast Track" is a unique opportunity for graduate students, postdoctoral fellows, or other early-career scientists, focused on Alzheimer's disease research, to gain new knowledge and become an expert in where this emerging scientific field is moving. In addition, it is not only about receiving a good overview, but also learning to write and defend a successful application for securing funding for Alzheimer's disease research projects. ...[more]
Similar Datasets
Project description:Considerable technological advancements have recently been made with endovascular stent grafts for the treatment of abdominal aortic aneurysm (AAA). However, there is opportunity to further improve the efficiency of endovascular aneurysm repair (EVAR), which may yield better patient outcomes and lower perioperative treatment costs.The Least Invasive Fast-Track EVAR (LIFE) registry was developed to determine the clinical utility and cost effectiveness of the Ovation® Prime stent graft when used under least invasive conditions using a defined fast-track protocol. The LIFE study is a prospective multicenter post-market registry of the ultra-low profile (14F) Ovation Prime stent graft when used in the treatment of patients with AAA using a fast-track protocol, consisting of appropriate patient selection, bilateral percutaneous access, avoidance of general anesthesia and intensive care unit admission, and next-day discharge. The primary endpoint of the study is the proportion of subjects that experience a major adverse event within 30 days of the initial procedure. Primary endpoint data will be compared to a target performance goal. A total of 250 subjects will be enrolled at up to 40 sites in the United States. The first subject in this study was enrolled in October 2014 and enrollment is anticipated to continue through mid-2016.The recent development of ultra low-profile stent grafts enables EVAR using least invasive methods. A structured fast-track EVAR protocol may yield clinical and cost benefits versus standard EVAR.ClinicalTrials.gov Identifier: NCT02224794.
| S-EPMC4684921 | biostudies-literature
Project description:The present study examines whether the Fast Track (FT) intervention, a 10-year randomized controlled trial with children at risk for conduct problems, affects family formation in adulthood, as indexed by partnerships, parenthood, and family structure, and whether the intervention effect differs across participants' gender and race/ethnicity. Participants included 891 children (intervention n = 445; control n = 446; 69% male; 51% Black, 47% White) who were recruited in kindergarten and followed to age 32 or 34 (80% participation of still-living participants), when they reported on their romantic partnerships, parenthood, and family structure. Controlling for numerous covariates that are related to family formation, intervention participants were more likely than those in the control group to be married rather than single and to have a larger number of children; the intervention and control groups did not differ on cohabitation status, age at first marriage, whether they had ever been divorced, their likelihood of being a parent, the age at which they first became a parent, the spacing of births, family structure (partnered or not, with or without children), or in whether they were residentially independent of their parents and grandparents. Intervention effects were not moderated by gender, but race/ethnicity moderated the effect of the intervention on the probability of having any children and the number of children. These findings suggest that several elements of family formation may remain unchanged by an intervention that changes many other behavioral and psychological trajectories of participants. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
| S-EPMC9870928 | biostudies-literature
Project description:Many embryonic species are initially transcriptionally quiescent after fertilization. In this issue of Developmental Cell, Blythe et al. reveal that beta-catenin acts very early in Xenopus development to specifically modify the chromatin of organizer genes, poising them for rapid activation when transcription begins.
| S-EPMC5568668 | biostudies-other
Project description:Promoters are key components for the application of biotechnological techniques in crop plants. Reporter genes such as GUS or GFP have been used to test the activity of promoters for diverse applications. A huge number of T-DNAs carrying promoterless GUS near their right borders have been inserted into the rice genome, and 105,739 flanking sequence tags from rice lines with this T-DNA insertion have been identified, establishing potential promoter trap lines for 20,899 out of 55,986 genes in the rice genome. Anatomical meta-expression data and information on abiotic stress related to these promoter trap lines enable us to quickly identify new promoters associated with various expression patterns. In the present report, we introduce a strategy to identify new promoters in a very short period of time using a combination of meta-expression analysis and promoter trap lines.
| S-EPMC7020180 | biostudies-literature
Project description:Postoperative joint stiffness following total knee arthroplasty (TKA) may compromise the outcome and necessitate manipulation. Previous studies have not been in a fast-track setting with optimized pain treatment, early mobilization, and short length of stay (LOS), which may have influenced the prevalence of joint stiffness and subsequent manipulation. We investigated the prevalence of manipulation following fast-track TKA and identified patients at risk of needing manipulation.3,145 consecutive unselected elective primary unilateral TKA patients operated in 6 departments with well-defined fast-track settings were included in the study. Demographic data, prevalence, type and timing of manipulation, and preoperative and postoperative ROM were recorded prospectively, ensuring complete 1-year follow-up.70 manipulations were performed within 1 year (2.2%) at a mean of 4 months after index surgery. Younger age and not using walking aids preoperatively were associated with a higher risk of manipulation. LOS ? 4 days (as opposed to a longer LOS) was not associated with an increased risk of manipulation.The prevalence of manipulation was lower or comparable to that in most published studies following more conventional pathways. Inherent patient demographics were identified as risk factors for manipulation whereas LOS ? 4 days was not. Thus, fast-track TKA does not result in increased risk of manipulation-despite a shorter LOS. Optimized pain treatment and early mobilization may contribute to these favorable results that support the use of fast-track.
| S-EPMC4366662 | biostudies-literature
Project description:BackgroundRepositioning of existing drugs has been suggested as a fast track for developing new anti-malarial agents. The compound libraries of GlaxoSmithKline (GSK), Pfizer and AstraZeneca (AZ) comprising drugs that have undergone clinical studies in other therapeutic areas, but not achieved approval, and a set of US Food and Drug Administration (FDA)-approved drugs and other bio-actives were tested against Plasmodium falciparum blood stages.MethodsMolecules were tested initially against erythrocytic co-cultures of P. falciparum to measure proliferation inhibition using one of the following methods: SYBR®I dye DNA staining assay (3D7, K1 or NF54 strains); [(3)H] hypoxanthine radioisotope incorporation assay (3D7 and 3D7A strain); or 4',6-diamidino-2-phenylindole (DAPI) DNA imaging assay (3D7 and Dd2 strains). After review of the available clinical pharmacokinetic and safety data, selected compounds with low ?M activity and a suitable clinical profile were tested in vivo either in a Plasmodium berghei four-day test or in the P. falciparum Pf3D7(0087/N9) huSCID 'humanized' mouse model.ResultsOf the compounds included in the GSK and Pfizer sets, 3.8% (9/238) had relevant in vitro anti-malarial activity while 6/100 compounds from the AZ candidate drug library were active. In comparison, around 0.6% (24/3,800) of the FDA-approved drugs and other bio-actives were active. After evaluation of available clinical data, four investigational drugs, active in vitro were tested in the P. falciparum humanized mouse model: UK-112,214 (PAF-H1 inhibitor), CEP-701 (protein kinase inhibitor), CEP-1347 (protein kinase inhibitor), and PSC-833 (p-glycoprotein inhibitor). Only UK-112,214 showed significant efficacy against P. falciparum in vivo, although at high doses (ED90 131.3 mg/kg [95% CI 112.3, 156.7]), and parasitaemia was still present 96 hours after treatment commencement. Of the six actives from the AZ library, two compounds (AZ-1 and AZ-3) were marginally efficacious in vivo in a P. berghei model.ConclusionsRepositioning of existing therapeutics in malaria is an attractive proposal. Compounds active in vitro at ?M concentrations were identified. However, therapeutic concentrations may not be effectively achieved in mice or humans because of poor bio-availability and/or safety concerns. Stringent safety requirements for anti-malarial drugs, given their widespread use in children, make this a challenging area in which to reposition therapy.
| S-EPMC4021201 | biostudies-literature
Project description:Background In pediatric cardiac surgery, perioperative management has evolved from slow weaning of mechanical ventilation in the intensive care unit to "ultra-fast-track" anesthesia with early extubation (EE) in theater to promote a faster recovery. The strategy of EE has not been assessed in adults with congenital heart disease, a growing population of patients who often require surgery. Methods And Results Data were collected retrospectively on all patients >16 years of age who underwent adult congenital heart surgery in our tertiary center between December 2012 and January 2020. Coarsened exact matching was performed for relevant baseline variables. Overall, 711 procedures were performed: 133 (18.7%) patients underwent EE and 578 (81.3%) patients received conventional extubation. After matching, patients who received EE required less inotropic or vasopressor support in the early postoperative period (median Vasoactive-inotropic score 0.5 [0.0-2.0] versus 2.0 [0.0-3.5]; P<0.0001) and had a lower total net fluid balance than patients after conventional extubation (1168±723 versus 847±733 mL; P=0.0002). The overall reintubation rate was low at 0.3%. EE was associated with a significantly shorter postoperative length of stay in higher dependency care units before a "step-down" to ward-based care (48 [45-50] versus 50 [47-69] hours; P=0.004). Lower combined intensive care unit and high dependency unit costs were incurred by patients who received EE compared with patients who received conventional extubation (£3949 [3430-4222] versus £4166 [3893-5603]; P<0.0001). Conclusions In adult patients undergoing surgery for congenital heart disease, EE is associated with a reduced need for postoperative hemodynamic support, a shorter intensive care unit stay, and lower health-care-related costs.
| S-EPMC8483528 | biostudies-literature
Project description:Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder characterized by an insatiable appetite, leading to chronic overeating and obesity. Additional features include short stature, intellectual disability, behavioral problems and incomplete sexual development. Although significant progress has been made in understanding the genetic basis of PWS, the mechanisms underlying the pathogenesis of the disorder remain poorly understood. Treatment for PWS consists mainly of palliative therapies; curative therapies are sorely needed. Zebrafish, Danio rerio, represent a promising way forward for elucidating physiological problems such as obesity and identifying new pharmacotherapeutic options for PWS. Over the last decade, an increased appreciation for the highly conserved biology among vertebrates and the ability to perform high-throughput drug screening has seen an explosion in the use of zebrafish for disease modeling and drug discovery. Here, we review recent advances in developing zebrafish models of human disease. Aspects of zebrafish genetics and physiology that are relevant to PWS will be discussed, and the advantages and disadvantages of zebrafish models will be contrasted with current animal models for this syndrome. Finally, we will present a paradigm for drug screening in zebrafish that is potentially the fastest route for identifying and delivering curative pharmacotherapies to PWS patients.
| S-EPMC5110251 | biostudies-literature
Project description:Electric eels (Electrophorus electricus) are legendary for their ability to incapacitate fish, humans, and horses with hundreds of volts of electricity. The function of this output as a weapon has been obvious for centuries but its potential role for electroreception has been overlooked. Here it is shown that electric eels use high-voltage simultaneously as a weapon and for precise and rapid electrolocation of fast-moving prey and conductors. Their speed, accuracy, and high-frequency pulse rate are reminiscent of bats using a 'terminal feeding buzz' to track insects. Eel's exhibit 'sensory conflict' when mechanosensory and electrosensory cues are separated, striking first toward mechanosensory cues and later toward conductors. Strikes initiated in the absence of conductors are aborted. In addition to providing new insights into the evolution of strongly electric fish and showing electric eels to be far more sophisticated than previously described, these findings reveal a trait with markedly dichotomous functions.
| S-EPMC4667699 | biostudies-literature
Project description:Alzheimer's disease is a form of general dementia marked by amyloid plaques, neurofibrillary tangles, and neuron degeneration. The disease has no cure, and early detection is critical in improving patient outcomes. Magnetic resonance imaging (MRI) is important in measuring neurodegeneration during the disease. Computer-aided image processing tools have been used to aid medical professionals in ascertaining a diagnosis of Alzheimer's in its early stages. As characteristics of non and very-mild dementia stages overlap, tracking the progression is challenging. Our work developed an adaptive multi-thresholding algorithm based on the morphology of the smoothed histogram to define features identifying neurodegeneration and track its progression as non, very mild, mild, and moderate. Gray and white matter volume, statistical moments, multi-thresholds, shrinkage, gray-to-white matter ratio, and three distance and angle values are mathematically derived. Decision tree, discriminant analysis, Naïve Bayes, SVM, KNN, ensemble, and neural network classifiers are designed to evaluate the proposed methodology with the performance metrics accuracy, recall, specificity, precision, F1 score, Matthew's correlation coefficient, and Kappa values. Experimental results showed that the proposed features successfully label the neurodegeneration stages.
| S-EPMC10761829 | biostudies-literature