97 research outputs found

    Microbes, histology, blood analysis, enterotoxins, and cytokines: Findings from the ASERF Systemic Symptoms in Women-Biospecimen Analysis Study: Part 3

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    BACKGROUND: There has been an increasing need to acquire rigorous scientific data to answer the concerns of physicians, patients, and the FDA regarding the self-reported illness identified as breast implant illness (BII). There are no diagnostic tests or specific laboratory values to explain the reported systemic symptoms described by these patients. OBJECTIVES: The aim of this study was to determine if there are quantifiable laboratory findings that can be identified in blood, capsule tissue pathology, or microbes that differentiate women with systemic symptoms they attribute to their implants from 2 control groups. METHODS: A prospective blinded study enrolled 150 subjects into 3 cohorts: (A) women with systemic symptoms they attribute to implants who requested implant removal; (B) women with breast implants requesting removal or exchange who did not have symptoms attributed to implants; and (C) women undergoing cosmetic mastopexy who have never had any implanted medical device. Capsule tissue underwent detailed analysis and blood was sent from all 3 cohorts to evaluate for markers of inflammation. RESULTS: No significant histologic differences were identified between the cohorts, except there were more capsules with synovial metaplasia in the non-BII cohort. There was no statistical difference in thyroid-stimulating hormone, vitamin D levels, or complete blood count with differential between the cohorts. Next-generation sequencing revealed no statistically significant difference in positivity between Cohort A and B. Of the 12 cytokines measured, 3 cytokines, interleukin (IL)-17A, IL-13, and IL-22, were found to be significantly more often elevated in sera of subjects in Cohort A than in Cohorts B or C. The enterotoxin data demonstrated an elevation in immunoglobulin G (IgG) anti-Staphylococcus aureus enterotoxin A in Cohort A. There was no correlation between the presence of IgE or IgG anti-Staphylococcal antibody and a positive next-generation sequencing result. CONCLUSIONS: This study adds to the current literature by demonstrating few identifiable biomedical markers to explain the systemic symptoms self-reported by patients with BII

    PERCIVAL mission to Mars

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    With the downturn of the world economy, the priority of unmanned exploration of the solar system has been lowered. Instead of foregoing all missions to our neighbors in the solar system, a new philosophy of exploration mission design has evolved to insure the continued exploration of the solar system. The 'Discovery-class' design philosophy uses a low cost, limited mission, available technology spacecraft instead of the previous 'Voyager-class' design philosophy that uses a 'do-everything at any cost' spacecraft. The Percival Mission to Mars was proposed by Ares Industries as one of the new 'Discovery-class' of exploration missions. The spacecraft will be christened Percival in honor of American astronomer Percival Lowell who proposed the existence of life on Mars in the early twentieth century. The main purpose of the Percival mission to Mars is to collect and relay scientific data to Earth suitable for designing future manned and unmanned missions to Mars. The measurements and observations made by Percival will help future mission designers to choose among landing sites based on the feasibility and scientific interest of the sites. The primary measurements conducted by the Percival mission include gravity field determination, surface and atmospheric composition, sub-surface soil composition, sub-surface seismic activity, surface weather patterns, and surface imaging. These measurements will be taken from the orbiting Percival spacecraft and from surface penetrators deployed from Mars orbit. The design work for the Percival Mission to Mars was divided among four technical areas: Orbits and Propulsion System, Surface Penetrators, Gravity and Science Instruments, and Spacecraft Structure and Systems. The results for each of the technical areas is summarized and followed by a design cost analysis and recommendations for future analyses

    Patterns of bruising in preschool children with inherited bleeding disorders: a longitudinal study

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    Objective The extent that inherited bleeding disorders affect; number, size and location of bruises in young children <6 years. Design Prospective, longitudinal, observational study. Setting Community. Patients 105 children with bleeding disorders, were compared with 328 without a bleeding disorder and classified by mobility: premobile (non-rolling/rolling over/ sitting), early mobile (crawling/cruising) and walking and by disease severity: severe bleeding disorder factor VIII/IX/XI <1 IU/dL or type 3 von Willebrand disease. Interventions Number, size and location of bruises recorded in each child weekly for up to 12 weeks. Outcomes The interventions were compared between children with severe and mild/moderate bleeding disorders and those without bleeding disorders. Multiple collections for individual children were analysed by multilevel modelling. Results Children with bleeding disorders had more and larger bruises, especially when premobile. Compared with premobile children without a bleeding disorder; the modelled ratio of means (95% CI) for number of bruises/ collection was 31.82 (8.39 to 65.42) for severe bleeding disorders and 5.15 (1.23 to 11.17) for mild/moderate, and was 1.81 (1.13 to 2.23) for size of bruises. Children with bleeding disorders rarely had bruises on the ears, neck, cheeks, eyes or genitalia. Conclusions Children with bleeding disorder have more and larger bruises at all developmental stages. The differences were greatest in premobile children. In this age group for children with unexplained bruising, it is essential that coagulation studies are done early to avoid the erroneous diagnosis of physical abuse when the child actually has a serious bleeding disorder, however a blood test compatible with a mild/moderate bleeding disorder cannot be assumed to be the cause of bruising

    Differences in the Quality of Pediatric Resuscitative Care Across a Spectrum of Emergency Departments

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    Importance: The quality of pediatric resuscitative care delivered across the spectrum of emergency departments (EDs) in the United States is poorly described. In a recent study, more than 4000 EDs completed the Pediatric Readiness Survey (PRS); however, the correlation of PRS scores with the quality of simulated or real patient care has not been described. Objective: To measure and compare the quality of resuscitative care delivered to simulated pediatric patients across a spectrum of EDs and to examine the correlation of PRS scores with quality measures. Design, Setting, and Participants: This prospective multicenter cohort study evaluated 58 interprofessional teams in their native pediatric or general ED resuscitation bays caring for a series of 3 simulated critically ill patients (sepsis, seizure, and cardiac arrest). Main Outcomes and Measures: A composite quality score (CQS) was measured as the sum of 4 domains: (1) adherence to sepsis guidelines, (2) adherence to cardiac arrest guidelines, (3) performance on seizure resuscitation, and (4) teamwork. Pediatric Readiness Survey scores and health care professional demographics were collected as independent data. Correlations were explored between CQS and individual domain scores with PRS. Results: Overall, 58 teams from 30 hospitals participated (8 pediatric EDs [PEDs], 22 general EDs [GEDs]). The mean CQS was 71 (95% CI, 68-75); PEDs had a higher mean CQS (82; 95% CI, 79-85) vs GEDs (66; 95% CI, 63-69) and outperformed GEDs in all domains. However, when using generalized estimating equations to estimate CQS controlling for clustering of the data, PED status did not explain a higher CQS (beta = 4.28; 95% CI, -4.58 to 13.13) while the log of pediatric patient volume did explain a higher CQS (beta = 9.57; 95% CI, 2.64-16.49). The correlation of CQS to PRS was moderate (r = 0.51; P \u3c .001). The correlation was weak for cardiac arrest (r = 0.24; P = .07), weak for sepsis (rho = 0.45; P \u3c .001) and seizure (rho = 0.43; P = .001), and strong for teamwork (rho = 0.71; P \u3c .001). Conclusions and Relevance: This multicenter study noted significant differences in the quality of simulated pediatric resuscitative care across a spectrum of EDs. The CQS was higher in PEDs compared with GEDs. However, when controlling for pediatric patient volume and other variables in a multivariable model, PED status does not explain a higher CQS while pediatric patient volume does. The correlation of the PRS was moderate for simulation-based measures of quality

    Community-based in situ simulation: bringing simulation to the masses

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    Simulation-based methods are regularly used to train inter-professional groups of healthcare providers at academic medical centers (AMC). These techniques are used less frequently in community hospitals. Bringing in-situ simulation (ISS) from AMCs to community sites is an approach that holds promise for addressing this disparity. This type of programming allows academic center faculty to freely share their expertise with community site providers. By creating meaningful partnerships community-based ISS facilitates the communication of best practices, distribution of up to date policies, and education/training. It also provides an opportunity for system testing at the community sites. In this article, we illustrate the process of implementing an outreach ISS program at community sites by presenting four exemplar programs. Using these exemplars as a springboard for discussion, we outline key lessons learned discuss barriers we encountered, and provide a framework that can be used to create similar simulation programs and partnerships. It is our hope that this discussion will serve as a foundation for those wishing to implement community-based, outreach ISS

    Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

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    Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

    Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

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    Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV
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