671 research outputs found

    Pre-amplification methods for tracking low-grade Plasmodium falciparum populations during scaled-up interventions in Southern Zambia

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    Background: Malaria is receding in many endemic countries with intervention scale -up against the disease. However, this resilient scourge may persist in low-grade submicroscopic infections among semi-immune members of the population, and be poised for possible resurgence, creating challenges for detection and assessment of intervention impact. Parasite genotyping methods, such as the molecular barcode, can identify specific malaria parasite types being transmitted and allow tracking and evaluation of parasite population structure changes as interventions are applied. This current study demonstrates application of pre-amplification methods for successful detection and genotyping of residual Plasmodium falciparum infections during a dramatic malarial decline. Methods: The study was a prospective cross-sectional design and based on a 2,000 sq km vicinity of Macha Mission Hospital in southern Zambia. Willing and predominantly asymptomatic residents of all ages were screened for malaria by microscopy during the 2005 and 2008 transmission seasons, with simultaneous collection of dried blood spots (DBS) on filter paper, and extraction of Plasmodium falciparum DNA was performed. Plasmodium falciparum infections were genotyped using a 24 SNP-based molecular barcode assay using real-time PCR. Submicroscopic parasitaemia samples were subjected to pre-amplification using TaqMan PreAmp Master Mix following the manufacturer’s instructions before SNP barcode analysis. Results: There was a dramatic decline of malaria between 2005 and 2008, and the geometric mean parasite density (95% CI) fell from 704/μL (390–1,271) in 2005 to 39/μL (23–68) in 2008, culminating in a large proportion of submicroscopic infections of which 90% failed to yield ample DNA for standard molecular characterization among 2008 samples. Pre-amplification enabled successful detection and genotyping of 74% of these low-grade reservoir infections, overall, compared to 54% that were detectable before pre-amplification (p <0.0005, n = 84). Furthermore, nine samples negative for parasites by microscopy and standard quantitative PCR amplification were positive after pre-amplification. Conclusions: Pre-amplification allows analysis of an otherwise undetectable parasite population and may be instrumental for parasites identification, tracking and assessing the impact of interventions on parasite populations during malaria control and elimination programmes when parasitaemia is expected to decline to submicroscopic levels

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    Iatrogenic Spinal Cord Injury Resulting From Cervical Spine Surgery.

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    STUDY DESIGN: Retrospective cohort study of prospectively collected data. OBJECTIVE: To examine the incidence of iatrogenic spinal cord injury following elective cervical spine surgery. METHODS: A retrospective multicenter case series study involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network was conducted. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, were reviewed to identify occurrence of iatrogenic spinal cord injury. RESULTS: In total, 3 cases of iatrogenic spinal cord injury following cervical spine surgery were identified. Institutional incidence rates ranged from 0.0% to 0.24%. Of the 3 patients with quadriplegia, one underwent anterior-only surgery with 2-level cervical corpectomy, one underwent anterior surgery with corpectomy in addition to posterior surgery, and one underwent posterior decompression and fusion surgery alone. One patient had complete neurologic recovery, one partially recovered, and one did not recover motor function. CONCLUSION: Iatrogenic spinal cord injury following cervical spine surgery is a rare and devastating adverse event. No standard protocol exists that can guarantee prevention of this complication, and there is a lack of consensus regarding evaluation and treatment when it does occur. Emergent imaging with magnetic resonance imaging or computed tomography myelography to evaluate for compressive etiology or malpositioned instrumentation and avoidance of hypotension should be performed in cases of intraoperative and postoperative spinal cord injury

    Molecular and Cellular Biology Animations: Development and Impact on Student Learning

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    Educators often struggle when teaching cellular and molecular processes because typically they have only two-dimensional tools to teach something that plays out in four dimensions. Learning research has demonstrated that visualizing processes in three dimensions aids learning, and animations are effective visualization tools for novice learners and aid with long-term memory retention. The World Wide Web Instructional Committee at North Dakota State University has used these research results as an inspiration to develop a suite of high-quality animations of molecular and cellular processes. Currently, these animations represent transcription, translation, bacterial gene expression, messenger RNA (mRNA) processing, mRNA splicing, protein transport into an organelle, the electron transport chain, and the use of a biological gradient to drive adenosine triphosphate synthesis. These animations are integrated with an educational module that consists of First Look and Advanced Look components that feature captioned stills from the animation representing the key steps in the processes at varying levels of complexity. These animation-based educational modules are available via the World Wide Web at http://vcell.ndsu.edu/animations. An in-class research experiment demonstrated that student retention of content material was significantly better when students received a lecture coupled with the animations and then used the animation as an individual study activity

    Staying Strong Toolbox: co-design of a physical activity and lifestyle program for Aboriginal families with Machado-Joseph disease in the Top End of Australia

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    Physical activity has positive health implications for individuals living with neurodegenerative diseases. The success of physical activity programs, particularly in culturally and linguistically diverse populations, is typically dependent on their alignment with the culture, lifestyle and environmental context of those involved. Aboriginal families living in remote communities in the Top End of Australia invited researchers to collaborate with them to co-design a physical activity and lifestyle program to keep individuals with Machado-Joseph disease (MJD) walking and moving around. The knowledge of Aboriginal families living with MJD, combined with findings from worldwide MJD research, formed the foundation for the co-design. An experience-based co-design (EBCD) approach, drawing from Indigenous and Participatory methodologies, was used. An expert panel of individuals with lived experience of MJD participated in a series of co-design phases. Prearranged and spontaneous co-design meetings were led by local community researchers within each phase. Data was collected using a culturally responsive ethnographic approach and analysed thematically. Sixteen panel members worked to develop the 'Staying Strong Toolbox' to cater for individuals with MJD who are 'walking strong'; or 'wobbly'; or 'in a wheelchair'. Based on the 'Staying Strong Framework', the Toolbox was developed as a spiral bound A3 book designed to guide the user to select from a range of activities to keep them walking and moving around and to identify those activities most important to them to work on. The 'Staying Strong Toolbox' is a community driven, evidence based resource for a physical activity and lifestyle program for Aboriginal families with MJD. The Toolbox provides a guide for health professionals and support workers to deliver person-centred support to Aboriginal families with MJD, and that can be modified for use by other families with MJD or people with other forms of ataxia around the world

    Trends in Antibiotic Use by Birth Season and Birth Year

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    OBJECTIVES: We examined 2 birth cohort effects on antibiotic prescribing during the first year of life (henceforth, infancy) in Denmark: (1) the birth season effect on timing and overall occurrence of antibiotic prescribing, and (2) the birth year effect amid emerging nationwide pneumococcal vaccination programs and changing prescribing guidelines. METHODS: We linked data for all live births in Denmark from 2004 to 2012 (N = 561 729) across the National Health Service Prescription Database, Medical Birth Registry, and Civil Registration System. Across birth season and birth year cohorts, we estimated 1-year risk, rate, and burden of redeemed antibiotic prescriptions during infancy. We used interrupted time series methods to assess prescribing trends across birth year cohorts. Graphical displays of all birth cohort effect data are included. RESULTS: The 1-year risk of having at least 1 redeemed antibiotic prescription during infancy was 39.5% (99% confidence interval [CI]: 39.3% to 39.6%). The hazard of a first prescription increased with age throughout infancy and varied by season; subsequently, Kaplan-Meier-derived risk functions varied by birth season cohort. After rollout of a first vaccination program and new antibiotic prescribing guidelines, 1-year risk decreased by 4.4% over 14 months (99% CI: 3.4% to 5.5%); it decreased again after rollout of a second vaccination program by 6.9% over 3 years (99% CI: 4.4% to 9.3%). CONCLUSIONS: In Denmark, birth season and birth year cohort effects influenced timing and risk of antibiotic prescribing during infancy. Future studies of antibiotic stewardship, effectiveness, and safety in children should consider these cohort effects, which may render some children inherently more susceptible than others to downstream antibiotic effects

    Identifying the genetic basis of antigenic change in influenza A(H1N1)

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    Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-D structural information. We attributed variation in hemagglutination inhibition to individual amino acid substitutions and quantified their antigenic impact, validating a subset experimentally using reverse genetics. Substitutions identified as low-impact were shown to be a critical component of influenza antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype was doubled. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine techniques that predict the fitness and evolutionary success of variant viruses, leading to stronger theoretical foundations for selection of candidate vaccine viruses
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