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Effects of Genetics and Sex on Hippocampal Gene Expression and Adolescent Behaviors Following Neonatal Ethanol Exposure in BXD Recombinant Inbred Mice
Get PDFFetal alcohol spectrum disorders (FASD) are the leading preventable neurodevelopmental disorders in the western world. A hallmark symptom of FASD is cognitive and learning deficits that present in early childhood and continue throughout adulthood. Teratogenic effects of alcohol include increased cell death in the hippocampus, a brain region critically important in learning and memory. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effect on the developing brain. Previous work in our lab identified differential vulnerability to ethanol-induced call death in the hippocampus using fourteen BXD strains and the two parental strains. The goal of the present study was to examine the effect of genetics and sex on differential gene expression changes and behavioral responses in animals exposed to postnatal ethanol.
To test this, we examined multiple BXD strains that showed increased susceptibility to ethanol-induced cell death in the hippocampus, multiple BXD strains that were resistant to ethanol’s effect on hippocampal cell death, and the parental B6 and D2 strains which showed moderate levels of cell death in the hippocampus after ethanol exposure. Neonatal mice were treated on postnatal day 7 (third trimester equivalent in humans). Animals received a subcutaneous injection of either 5.0g/kg ethanol in saline solution or isovolumetric saline given in two equal doses two hours apart. Animals were sacrificed 7 hours after initial ethanol exposure. Differential gene expression was examined using the Affymetrix Microarray platform across the strains. In another subset of animals exposed to the same alcohol paradigm, we investigated the long-term effects of developmental alcohol exposure on cognition and behavior in select BXD strains and parental strains. Adolescent animals exposed to postnatal ethanol were tested across the following behavioral tests: elevated plus maze, open field, Y-maze, and T-maze.
We identified gene expression changes after postnatal ethanol exposure in all BXD and parental strains with little overlap between males and females in the same strain. However, there were limited gene expression changes that showed a sex x treatment interaction. Sex-specific ethanol-induced gene expression changes were limited within each strain and these changes were not carried over across strains. Multiple genes showed a significant interaction between strain x treatment and/or strain x sex x treatment. Enrichment analysis of these genes revealed a number of significant over-represented biological categories involved in cell death and apoptosis. Genes that met our criteria and were also highly correlated with a number of apoptosis and learning and memory behaviors included Bcl2l11, Jun, Txnip, Chka, and Tgfb3. Interestingly, Tgfb3 has been previously linked to a significant QTL mediating strain-specific differences in hippocampal cell death after exposure to postnatal ethanol in BXD mice.
When comparing ethanol-induced gene expression changes in high cell death strains (HCD) and low cell death strains (LCD), we observed almost double the number of differentially ethanol-induced gene expression changes in the HCD strains compared to the LCD strains. Enrichment analysis revealed some overlap in significant over-represented categories between the HCD and LCD strains, though HCD showed more cell death and apoptosis categories. Significant ethanol-induced gene expression changes in the HCD and LCD strains were always regulated in the same direction suggesting 1) more perturbed effects of ethanol-induced gene expression changes in the HCD strains compared to LCD strains and 2) limited gene expression changes that confer resistance to ethanol-induced cell death in the hippocampus in the LCD strains.
In our behavioral study, our results demonstrate that the effects of developmental alcohol exposure on adolescent behavioral responses are highly dependent on strain, though the strains that showed the most behavioral alterations after exposure to postnatal alcohol were the B6 and D2 parental strains and the BXD100 and BXD48a HCD strains. In these four strains, we observed many anxiety-like and activity-related behaviors that were significantly affected by postnatal ethanol exposure and in many of these measures there were sex-specific differences within the strain. The LCD strains, BXD60 and BXD71, showed minimal effect of treatment in all behavioral tests. Interestingly, the HCD strains, BXD100 and BXD48a, were the only strains that showed significant effect of postnatal ethanol exposure in hippocampal-dependent spatial learning and memory assessment. These results suggest that there are long-term effects of developmental alcohol exposure on adolescent behavior and that these effects are highly strain specific.
Overall, our study aimed to better understand genetic variation in ethanol-induced susceptibility to ethanol’s teratogenic effects. Our results accomplish this by identifying differential gene expression changes and behavioral responses in animals exposed to postnatal ethanol using the BXD RI mice and parental strains. Additionally, our study identified sex differences in both ethanol-induced gene expression changes and adolescent behaviors in mice exposed to postnatal ethanol, though sex-specific effects were highly dependent on strain. To our knowledge, this is the first study using the BXD RI strains to examine the effects of genetics and sex on 1) ethanol-induced gene expression changes during development, and 2) adolescent behaviors in mice exposed to postnatal ethanol
Long-Term Outcomes in Children with Acute Flaccid Myelitis
Get PDFThe purpose of our critically appraised topic is to combine the best evidence regarding the long-term outcomes in children with acute flaccid myelitis (AFM) regarding posture and movement, gross and fine motor control, and activities of daily living (ADL) performance. The final portfolio contains eight articles. The study designs of these articles include a retrospective cohort study, two retrospective non-randomized studies without a control group, a retrospective review, a nationwide follow-up questionnaire analysis study, a case report, a case series, and a multiple quantitative case study. All studies related directly to our evidence-based PICO question and were used to determine the best evidence of the long-term outcomes in children with AFM. Overall, our findings showed that functional improvements were seen in most individuals, however, this varied from complete to incomplete recovery along with some persistent motor and functional deficits. Every case is different depending on when they were diagnosed, and how quickly they were able to implement a rehabilitation program into their everyday routine
Going Remote: Marketing Library Resources and Services
Get PDFObjectives
• Describe the library’s efforts in restructuring marketing strategies strategies to reach out and engage library patrons in a virtual environment
• Examine the impact of the efforts on library services and resource acces
New Beginnings: Starting a Career as a Medical Librarian during a Global Pandemic
Get PDFObjective This poster aims to discuss experiential reflections of starting a new career as a medical library professional during the global pandemic and the respective supervisorial perspective. The reflections convey some of the challenges faced while beginning a career where traditional on-the-job experience was unavailable and the issues of providing training and mentoring remotely to subordinates.
Methods Written narratives from two library professionals who received their degrees during the global pandemic and their supervisors. It presents subjective pros and cons in a ‘new normal’ workplace from the reflections written by four medical library professionals. As well, it lists some of the methods they utilized to combat burnout during the COVID-19 pandemic.
Results We found some of the changes resulted in quality-of-life improvements in the workplace, while other adjustments placed limitations on services provided. Collectively, we were able to scrutinize how we traditionally utilized workspace and staffing to see if there is a better approach as we go forward. The burden of the pandemic still affects the library with staff shortages as we begin to recover and move to full reopening in preparation for the new academic year.
Conclusions Some of the traditional aspects of learning through on-the-job experiences were, unfortunately, limited. Alternatives for professional development were implemented, and some provided great opportunities. There have been obvious challenges to everyone’s personal and professional life since the start of the pandemic. Library professionals, traditionally, have had to adapt and evolve their job as patron needs shift which may make them more resilient. Some have found ways to thrive, and others find ways to get through the bumps
Developing Deep-Learning Methods for Diagnosis and Prognosis of Pediatric Progressive Diseases Using Modern Imaging Techniques
Get PDFPurpose and Rationale. Central nervous system manifestations form a significant burden of disease in young children. There have been efforts to correlate the neurological disease state in tuberous sclerosis complex (TSC) neurological disease state with imaging findings is a standard part of patient care. However, such analysis of neuroimaging is time- and labor-intensive. Automated approaches to these tasks are needed to improve speed, accuracy, and availability. Automated medical image analysis tools based on 3D/2D deep learning algorithms can help improve the quality and consistency of image diagnosis and interpretation for cognitive disorders in infants. We propose to automate neuroimaging analysis with artificial intelligence algorithms. This novel approach can be used to improve the accuracy of TSC diagnosis and treatment. Deep learning (DL) is among the most successful types of machine learning and utilizes deep artificial neural networks (ANNs), which can determine efficient feature representations of input data. DL algorithms have created new opportunities in medical image analysis. Applications of DL, specifically convolutional neural networks (CNNs), in medical image analysis, cover a broad spectrum of tasks, including risk prediction/estimation with a machine learning system trained on these classification tasks.
Study population. We reviewed an NIMH Data Archive (NDA) dataset that was collected in 2010. We also reviewed imaging data from patients and normal cases from birth to 8 years of age acquired at Le Bonheur Children’s Hospital from 2014 to 2020. The University of Tennessee Health Science Center Institutional Review Board (IRB) approved this study.
Research Design and Study Procedures. Following Institutional Review Board (IRB) approval, this thesis: 1) Presents the first 2D/3D fusion CNN models to estimate the age of infants from birth to 3 years of age. 2) Presents the first work to look at whole-brain network to automatically distinguish TSC brain structural pathology from normal cases using a 3DCNN model.
Conclusions. The study findings indicate that deep neural networks tackle the problem of early prediction of cognitive and neurodevelopmental disorders and structural brain pathology based on MRI automatically in TSC children. It is the hope of the author that analysis of MRI images via methods of deep learning will have a positive impact on healthcare for infants and children at risk of rare diseases
The Effect of Maternal Traumatic Life Events and Social Support on Maternal-Child Interaction at Child Age 3 Years
Get PDFIntroduction: Becoming a parent is a very important role and responsibility in people’s lives and knowing the role traumatic life events (TLEs) may play on a mother-child relationship is a very important area to explore. TLEs are known to have adverse effect on individuals; however, little is known regarding the effect of maternal TLEs on maternal-child interaction. Social support has been known to positively affect the overall wellbeing of individuals, but little is known about the effect of social support on mothers who experienced TLEs and interaction with their children thus the need for this study. This study examines the effect of maternal TLEs and social support on maternal-child interaction. The Child Health Assessment Model and the Barnard Model will be used in this study. This study will examine the occurrence and severity of maternal TLEs and levels of social support and their relationship with sociodemographic factors of mothers and their 3-year-olds. It will examine the relationship between maternal TLEs, and maternal-child interaction measured by the NCAST Parent-Child Interaction (PCI) Teaching scale at child age 3 years; maternal social support and maternal-child interaction at child age 3 years; maternal TLEs and social support with maternal-child interaction at child age 3 years.
Method: This study was a secondary analysis of data from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, a longitudinal cohort study designed to improve the health, development, and well-being of children in Shelby County, Tennessee. Researchers recruited 1503 women in their second trimester of pregnancy. Data were collected at the 2nd and 3rd trimesters, at the child\u27s birth, and from mother-child dyads at different points through child age three years. Nine hundred and eighty-six mother-child dyads were included in this analysis. Data analysis was performed using R version 4.0.3 (2020-10-10). The CANDLE Study Publications and Presentations Committee approved a Manuscript Analysis Plan Proposal prior to conducting this study.
Results: Children and mothers were largely Black/African American (65.2%), and 34.8% were White. TLEs were associated with sociodemographic variables such as age, education, race, marital status, and child sex—with increased TLEs among Black/African American mothers, divorced/separated/widowed mothers, and mothers without college/professional degree, older mothers reported a lower number of ACEs than younger mothers. Mothers of male children reported fewer events associated with fear and helplessness than mothers of female children. Mother Total score and Contingency score were associated with several sociodemographic variables. Mothers with private health insurance for children ages 2- and 3-years had higher PCI Teaching scale scores. Mothers with at least a college degree at enrollment, child age 2, and child age 3 had higher PCI Teaching scale scores than mothers with no college degree. In the univariate analysis, we did not observe a significant association between maternal TLEs in the third trimester and maternal-child interaction at child age 3 years. When both maternal traumatic life events at the third trimester and social support are included, both were significantly associated with maternal-child interaction at child age 3 years. Although the associations between TLEs and PCI Teaching scale scores were non-significant the number of individuals providing social support was associated with PCI Teaching scale scores. More individuals providing social support was associated with increased PCI Teaching scale Mother-child Total (p \u3c 0.0001) and Mother-child Contingency scores (p \u3c 0.0001). Health insurance was associated with PCI Teaching scale scores — having private insurance was associated with increased Child Total scores at ages 2 (p = 0.037 and 3 (p = 0.004) years.
Conclusion: The association between the number of individuals providing social support and mother-child interaction reinforces the need to provide resources such as home visitation programs to mothers and their young children. Each additional person providing social support in the third trimester was associated with increased PCI Teaching scale scores on both the Mother Total scores and Mother-child Total scores. This points to the relationship between support during the third trimester and the long-term outcome related to maternal-child interaction. The lack of association between TLEs and PCI Teaching scale scores before and after controlling for sociodemographic variables may reflect mothers\u27 resilience. The interaction effect between TLEs and social support on maternal child interaction is notable and shows the need for an upstream approach to prevent TLEs since its interaction with social support diminishes the effect of support on maternal-child interaction
Characterizing and Overcoming Resistance to Aminomethylspectinomycins in Gram-negative Bacteria
Get PDFSpectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3 )(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to modify and inactivate amSPCs has been examined by two unique biochemical assays, including an agar-based enzyme assay. Binding of APH (9)-Ia and ANT (3 )(9) to spectinomycin and amSPCs has been studied using Thermal Denaturation assay and MicroScale Thermophoresis (MST).
The microbiological role of these enzymes has been examined by minimum inhibitory concentration (MIC) shifts using an arabinose inducible expression of APH (9)-Ia and ANT (3 )(9) in E.coli K12 and JW ΔtolC strains. Our agar-based enzyme assay shows the inactivation of spectinomycin by APH(9)-Ia. Phosphorylated spectinomycin and adenylated spectinomycin products upon incubation with APH(9)-Ia and ANT(3 ,9), respectively, have been identified using MALDI-MS. APH(9)-Ia induction studies in E. coli tolC knock-out strains reveal a MIC increase against spectinomycin in the presence of 2% arabinose compared to no shift with amSPCs. ANT (3 )(9) showed an increase in MIC against spectinomycin as well as amSPCs. In conclusion, amSPCs are not inactivated by APH (9)-Ia in vivo but are inactivated by ANT (3 )(9). Most Gram-negative bacteria isolated in clinics possess one or more AMEs. By overcoming modification by AMEs, amSPCs can be a valuable tool in overcoming resistance in Gram-negative bacterial infections. We also conducted a high throughput screen of a polar small molecule library against two multi-drug resistant clinical isolates of Escherichia coli that encode aminoglycoside modifying enzyme for small molecule potentiators of amSPCs to yield 12 possible potentiating molecules that have been confirmed by dose-response analysis.
Future work as a continuation of this project will involve further analysis of any existing synergy between the potentiating molecules and amSPCs and target validation of these potentiators
Impact of Central Line Bundle Care on Reduction of Central Line Associated-Infections: A Scoping Review
Get PDFPurpose/Background Central venous catheters (CVC) are typical for critically ill patients in the intensive care unit (ICU). Due to the invasiveness of this procedure, there is a high risk for central line-associated bloodstream infection (CLABSI). These infections have been known to increase mortality and morbidity, medical costs, and reduce hospital reimbursements. Evidenced-based interventions were grouped to assemble a central line bundle to decrease the number of CLABSIs and improve patient outcomes. This scoping review will evaluate the literature and examine the association between reduced CLABSI rates and central line bundle care implementation or current use.
Methods A literature review was completed of nine critically appraised articles from the years 2010-2021. The association of the use of central line bundles and CLABSI rates was examined. These relationships were investigated to determine if the adherence to a central line bundle directly reduced the number of CLABSI rates in critically ill adult patients. A summary evaluation table was composed to determine the associations related to the implementation or current central line bundle care use.
Results Of the study sample (N=9), all but one demonstrated a significant decrease in CLABSI rates when a central line bundle was in place. A trend towards reducing CLABSI was noted in the remaining article, a randomized controlled study, but the results were not significantly different. In all the other studies, a meta-analysis, randomized controlled trial, control trial, cohort or case-control studies, and quality improvement project, there was a significant improvement in CLABSI rates when utilizing a central line bundle. The extensive use of different levels of evidence provided an excellent synopsis that implementing a central line bundle care would directly affect decreasing CLABSI rates.
Implications for Nursing Practice Results provided in this scoping review afforded the authors a diverse level of evidence that using a central line bundle has a direct outcome on reducing CLABSI rates. This practice can be implemented within the hospital setting as suggested by the literature review to prevent or reduce CLABSI rates. Implementing a standard central line bundle care hospital-wide helps avoid this hospital-acquired infection
Building Responsive Research Capacity: A Survey of Academic Health Faculty
Get PDFThe objective of this study was to evaluate the use of and satisfaction with the University of South Florida Health Libraries (USFHL) research support services (RSS). A secondary objective was to understand the research skills of academic health faculty. The data will help inform future service offerings.
The mixed methods study is comprised of two phases: a survey followed by focus groups. The survey assessed 1) knowledge of and satisfaction with specific RSS, 2) faculty confidence in performing 10 specific research tasks, and 3) preference for potential class topics. Open-ended fields allowed for additional comments and suggestions. Respondents self-identified if they were willing to participate in subsequent focus groups. The survey was emailed to all Health faculty, with two reminders. Basic demographics broke out respondents by their college, department, or school; years of conducting and publishing research, and writing grants.
Preliminary analyses of the 105 respondents indicated most were extremely/satisfied with USFHL RSS, which were defined as consultations with the librarians, library classes/workshops, LibGuides, and research databases. Less than half of faculty reported confidence in using qualitative research methods and applying for research funding. Potential class topics identified were the 1) scholarly publishing topics, 2) conduct of types of literature reviews, 3) research metrics, 4) research tool recommendations, and 5) effective search strategies. A third of participants volunteered to participate in future focus groups. The qualitative data centered around issues with access and tools; requests for additional trainings, and praise for librarians, resources, & services.
Based on initial findings, we plan to add more grants workshops and develop a series on finding, critically reviewing, and writing qualitative studies
A Longitudinal Examination of Mobile App Usage in Medical Students
Get PDFObjective: The objective of this study is to determine both the usefulness of librarian instruction on mobile apps and student preference for mobile apps during 3rd and 4th year clinical rotations.
Methods: An electronic RedCap survey was administered to students for the purpose of gathering baseline information on library-provided mobile apps and instruction. This brief survey was given to 3rd year medical students at the beginning of this school year (2021-2022) with a second follow-up survey scheduled for later in the academic year. (spring 22) The students were asked questions about their mobile app usage and preferences as well as how often they reach out to librarians for assistance. The follow-up survey will assess any changes in preferences for or comfort with apps and will monitor any changes to the number of self-reported interactions with library staff.
Results: Results of the initial survey confirmed that students are largely comfortable with the technical aspects of mobile app use both in and outside of the medical sphere; however, they may require more guidance on app content to determine which apps are most useful for researching different topics or different styles of questions. DynaMed was chosen by students as their favorite medical mobile app so far likely due to its wide coverage of topics and content. While the library instruction session increased student confidence with using medical mobile apps, students showed a lack of history of contacting librarians for assistance.
Conclusions: This survey confirms librarian suspicions that students may require guidance not on how to use apps, but on which apps are recommended for use in which scenarios. Although students report that library instruction is beneficial for their understanding of app use, they also report that they do not frequently ask librarians for assistance. This may be due to various reasons such as student insecurity, lack of perceived time, or lack of understanding about which questions may be asked or what apps to ask questions about. The follow-up survey will gather information on these topics and will seek to address student knowledge of which apps to use in different clinical scenarios as well as whether contact with librarians has increased or whether faculty recommendations in clinical settings change student app preferences