Targeting the bacterial-host interaction: leveling the playing field.
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ABSTRACT:
SUBMITTER: Mosher D
PROVIDER: S-EPMC3478237 | biostudies-literature | 2012 Jul
REPOSITORIES: biostudies-literature
Publications
Targeting the bacterial-host interaction: leveling the playing field.
Virulence 20120701 4
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Project description:Among the many race-based health disparities that have persistently plagued the US population,1 the disproportionate burden of adverse neurodevelopmental outcomes to Black children affected by autism spectrum disorder (ASD) is particularly devastating given its major lifelong consequences. Recently, in 3 successive reports from the Autism and Developmental Disabilities Monitoring (ADDM) program of the US Centers for Disease Control and Prevention (CDC) (birth cohort years 2014, 2016, and 2018), we and our collaborators reported that although the prevalence of community-diagnosed ASD had equalized for Black and non-Hispanic White (NHW) children in the United States, there has persisted a pronounced racial disparity in the proportion of ASD-affected children with comorbid intellectual disability (ID), on the order of 50% for Black children with ASD vs 20% for White children with ASD.2 Here, we provide data to support the following: much earlier diagnosis is possible; early diagnosis alone is not likely to close the ID comorbidity disparity; and judicious efforts over care as usual are necessary to ensure that Black children have access to timely implementation of developmental therapy, for which we observed promising associations with improved cognitive and adaptive outcomes in our sample.
| S-EPMC10948275 | biostudies-literature
Project description:Although desktop simulations can be useful in representing scientific phenomena during inquiry activities, they do not allow students to embody or contextualize the spatial aspects of those phenomena. One learning technology that does attempt to combine embodiment and grounded experience to support learning in science is Embedded Phenomena. The objective of this research was to investigate the effectiveness of a classroom-based Embedded Phenomena activity for learning in geoscience, and to investigate whether individual differences in spatial skills had an impact on the effectiveness. The simulated scientific phenomenon was earthquakes, and 44 fifth grade (10-year old) students learned from a unit containing both content instruction and simulations. In the embedded condition, 15 earthquake events were simulated within the classroom space and students enacted the computation of epicenters with strings and their bodies. Students in the non-embedded condition received the same content instruction and did the same activities, but the epicenter computations were done with maps instead of with students' bodies. Students in the embedded condition showed greater learning gains overall. Further, the Embedded Phenomena activity attenuated the effect of individual differences in spatial skills on learning in science such that low spatial individuals performed as well as high spatial individuals in the embedded condition.
| S-EPMC5256455 | biostudies-literature
Project description:IntroductionSmoking rates differ by insurance type; rates are often double for Medicaid and uninsured compared with that for Medicare or privately insured. State-funded tobacco quitlines' provision of free nicotine replacement therapy varies. In some states, Medicaid beneficiaries must obtain nicotine replacement therapy from a physician, whereas others get nicotine replacement therapy mailed to them.MethodsThis secondary analysis examined the differences in the source and use of cessation treatment by insurance type and their impacts on cessation. The parent trial excluded people who were pregnant, had private insurance, or were not ready to quit. From June 1, 2017 to November 15, 2020, a total of 1,944 low-income people who smoke daily completed a baseline survey and were enrolled in a quitline program; 1,380 (71%) completed a 3-month follow-up. Analyses were completed in August 2022. Participants were classified as Medicaid/dual (55%), Medicare/Veterans Affairs (14%), or uninsured (31%). Nine months into the trial, owing to a system error, the quitline provided nicotine replacement therapy to all study participants regardless of insurance type.ResultsBefore error versus after error, Medicaid participants reported lower nicotine replacement therapy receipt (3.2% vs 50.8%) and use (32.4% vs 52.6%). The odds of quitting (7-day point prevalence) by 3 months increased for people who smoke who completed more quitline calls and used any (36% quit) versus used no (20% quit) pharmacotherapy, but quitting did not differ by insurance classifications (27%-29%). Getting and using nicotine replacement therapy from the quitline produced the highest quit rates (38%).ConclusionsResults illustrate the benefit of receiving nicotine replacement therapy from the quitline on cessation. Mailing nicotine replacement therapy to all people who smoke should be standard practice to reduce smoking disparities.
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Project description:Molecular diagnostics are becoming increasingly important in clinical research to stratify or identify molecularly profiled patient cohorts for targeted therapies, to modify the dose of a therapeutic, and to assess early response to therapy or monitor patients. Molecular diagnostics can also be used to identify the pharmacogenetic risk of adverse drug reactions. The articles in this CCR Focus section on molecular diagnosis describe the development and use of markers to guide medical decisions regarding cancer patients. They define sources of preanalytic variability that need to be minimized, as well as the regulatory and financial challenges involved in developing diagnostics and integrating them into clinical practice. They also outline a National Cancer Institute program to assist diagnostic development. Molecular diagnostic clinical tests require rigor in their development and clinical validation, with sensitivity, specificity, and validity comparable to those required for the development of therapeutics. These diagnostics must be offered at a realistic cost that reflects both their clinical value and the costs associated with their development. When genome-sequencing technologies move into the clinic, they must be integrated with and traceable to current technology because they may identify more efficient and accurate approaches to drug development. In addition, regulators may define progressive drug approval for companion diagnostics that requires further evidence regarding efficacy and safety before full approval can be achieved. One way to accomplish this is to emphasize phase IV postmarketing, hypothesis-driven clinical trials with biological characterization that would permit an accurate definition of the association of low-prevalence gene alterations with toxicity or response in large cohorts.
| S-EPMC3307147 | biostudies-other
Project description:Haunted attractions are illustrative examples of recreational fear in which people voluntarily seek out frightening experiences in pursuit of enjoyment. We present findings from a field study at a haunted-house attraction where visitors between the ages of 12 and 57 years (N = 110) were equipped with heart rate monitors, video-recorded at peak scare points during the attraction, and asked to report on their experience. Our results show that enjoyment has an inverted-U-shaped relationship with fear across repeated self-reported measures. Moreover, results from physiological data demonstrate that the experience of being frightened is a linear function of large-scale heart rate fluctuations, whereas there is an inverted-U-shaped relationship between participant enjoyment and small-scale heart rate fluctuations. These results suggest that enjoyment is related to forms of arousal dynamics that are "just right." These findings shed light on how fear and enjoyment can coexist in recreational horror.
| S-EPMC7734554 | biostudies-literature
Project description:Streptococcussuis is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against S. suis infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of S. suis (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with S. suis strain 10 or an isogenic ssnA mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with S. suis strain 10 or S. suis 10ΔssnA showed the presence of NETs in CSF and developed similar clinical signs. Therefore, SsnA does not seem to be a crucial virulence factor that contributes to the development of meningitis in pigs. Importantly, DNase activity was detectable in the CSF of both infection groups, indicating that host nucleases, in contrast to bacterial nuclease SsnA, may play a major role during the onset of meningitis. The effect of DNase 1 on neutrophil functions was further analyzed in a 3D-cell culture model of the porcine blood-CSF barrier. We found that DNase 1 partially contributes to enhanced killing of S. suis by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF.
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Project description:As NHS trusts are told to give priority to employing UK and EU citizens over doctors from other countries, Surinder Sharma, the NHS's equality director, is facing tough times
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Project description:BackgroundResearch abstracts are submitted for presentation at scientific conferences; however, criteria for judging abstracts are variable. We sought to develop two rigorous abstract scoring rubrics for education research submissions reporting (1) quantitative data and (2) qualitative data and then to collect validity evidence to support score interpretation.MethodsWe used a modified Delphi method to achieve expert consensus for scoring rubric items to optimize content validity. Eight education research experts participated in two separate modified Delphi processes, one to generate quantitative research items and one for qualitative. Modifications were made between rounds based on item scores and expert feedback. Homogeneity of ratings in the Delphi process was calculated using Cronbach's alpha, with increasing homogeneity considered an indication of consensus. Rubrics were piloted by scoring abstracts from 22 quantitative publications from AEM Education and Training "Critical Appraisal of Emergency Medicine Education Research" (11 highlighted for excellent methodology and 11 that were not) and 10 qualitative publications (five highlighted for excellent methodology and five that were not). Intraclass correlation coefficient (ICC) estimates of reliability were calculated.ResultsEach rubric required three rounds of a modified Delphi process. The resulting quantitative rubric contained nine items: quality of objectives, appropriateness of methods, outcomes, data analysis, generalizability, importance to medical education, innovation, quality of writing, and strength of conclusions (Cronbach's α for the third round = 0.922, ICC for total scores during piloting = 0.893). The resulting qualitative rubric contained seven items: quality of study aims, general methods, data collection, sampling, data analysis, writing quality, and strength of conclusions (Cronbach's α for the third round = 0.913, ICC for the total scores during piloting = 0.788).ConclusionWe developed scoring rubrics to assess quality in quantitative and qualitative medical education research abstracts to aid in selection for presentation at scientific meetings. Our tools demonstrated high reliability.
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Project description:By providing useful tools to study host-pathogen interactions, next-generation omics has recently enabled the study of gene expression changes in both pathogen and infected host simultaneously. However, since great discriminative power is required to study pathogen and host simultaneously throughout the infection process, the depth of quantitative gene expression profiling has proven to be unsatisfactory when focusing on bacterial pathogens, thus preferentially requiring specific strategies or the development of novel methodologies based on complementary omics approaches. In this review, we focus on the difficulties encountered when making use of proteogenomics approaches to study bacterial pathogenesis. In addition, we review different omics strategies (i.e., transcriptomics, proteomics and secretomics) and their applications for studying interactions of pathogens with their host.
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Project description:Our incomplete knowledge of the human transcriptome impairs the detection of disease-causing variants, in particular in transcripts only expressed under certain conditions. These transcripts are often lacking from reference transcript sets, such as Ensembl/GENCODE and RefSeq, and could be relevant for establishing genetic diagnoses. We present SUsPECT (Solving Unsolved Patient Exomes/gEnomes using Custom Transcriptomes), a pipeline based on the Ensembl Variant Effect Predictor (VEP) to predict variant impact on custom transcript sets, such as those generated by long-read RNA-sequencing, for downstream prioritization. Our pipeline predicts the functional consequence and likely deleteriousness scores for missense variants in the context of novel open reading frames predicted from any transcriptome. We demonstrate the utility of SUsPECT by uncovering potential mutational mechanisms of pathogenic variants in ClinVar that are predicted to be benign using the reference transcript annotation. In further support of SUsPECT’s utility, we identified an enrichment of immune-related variants predicted to have a more severe molecular consequence when annotating with a newly generated transcriptome from stimulated immune cells instead of the reference transcriptome. Our pipeline outputs crucial information for further prioritization of potentially disease-causing variants for any disease and will become increasingly useful as more long-read RNA sequencing datasets become available.
| EGAS00001006779 | EGA