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41. Engagement of adolescents with ADHD in a narrative-centered game-based behavior change environment to reduce alcohol use

Title Tesim:
Engagement of adolescents with ADHD in a narrative-centered game-based behavior change environment to reduce alcohol use
Creator:
Penilla C., Berna M., Barbaresi W.J., Tebb K.P., Ozer E., Kumaran V., Mott M., Lester J.C., Buckelew S., Blum N.J., Pugatch M., Giovanelli A., Rowe J., and Hennigan S.
Date of publication:
2023
Abstract Tesim:
Background: Attention deficit hyperactivity disorder (ADHD) affects about 13% of adolescents and is associated with substance use-related morbidity and mortality. While evidence on effective interventions to reduce alcohol use among adolescents with ADHD is limited, parent-teen communication about alcohol use has been found to be protective. Other approaches, such as educational interventions, hold promise to reduce alcohol-related harms in adolescents with ADHD. Digital technology offers an innovative approach to health behavior change, expanding access to services and may promote learning for neurodiverse youth, including teens with ADHD. INSPIRE, a narrative-centered game-based behavior change environment designed to promote self-regulation and self-efficacy to prevent risky alcohol use has been found to engage a general adolescent population. The goals of this pilot study are (1) to examine the engagement of youth with ADHD in INSPIRE; and (2) to examine if INSPIRE fosters parent-teen communication. Method: Adolescents diagnosed with ADHD aged 14–16 were recruited from developmental medicine clinics and invited to a focus group offered via Zoom. Participants completed a pre-survey, interacted with the INSPIRE game, and answered a post-survey as well as open-ended questions about their gaming experience during the focus group. Engagement was measured through both self-report using subscales from the User Engagement Scale and computer data; survey and qualitative data collected information on parent-teen communication. Univariate statistics described adolescent characteristics, Rank-sum and Fisher’s exact tests examined relationships among variables, and qualitative analysis identified themes in open-ended questions. Results: Of adolescent participants (N = 40), 45% identified as female, 17.5% Black, 7.5%, Hispanic, and 62.5% White. Post-survey mean engagement subscales of Usability (on a 5-point scale) was 3.67 (SD = 0.74), and Satisfaction was 3.63 (SD = 0.75). Computer data indicated that participants played the game for a median of 24 min. Adolescents shared that playing the game strengthened refusal skills and their ability to navigate social gatherings with alcohol. Post-survey, 63% planned to share information from INSPIRE with a parent. Conclusion: Findings suggest that INSPIRE may support facilitating youth with ADHD to learn the developmental competencies needed to mitigate risk and thrive. INSPIRE warrants further testing to explore its impact on alcohol use in youth with ADHD.
Resource type:
Article
Affiliation Label Tesim:
Department of Computer Science
DOI:
https://doi.org/10.17615/vnjc-fx02
Edition:
Publisher
Identifier:
https://doi.org/10.3389/feduc.2023.1183994
ISSN:
2504-284X
Journal Title:
Frontiers in Education
Journal Volume:
8
Keyword:
parenting, technology, life course, prevention, attention deficit hyperactivity disorder, ADHD, alcohol-related disorders, and adolescent
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of California, San Francisco, Boston Children’s Hospital, North Carolina State University, , and Children’s Hospital of Philadelphia
Person:
Penilla C., Berna M., Barbaresi W.J., Tebb K.P., Ozer E., Kumaran V., Mott M., Lester J.C., Buckelew S., Blum N.J., Pugatch M., Giovanelli A., Rowe J., and Hennigan S.
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
7b7f9c31-71d6-47b9-85ab-c7d4ac046c0d

42. Editorial: Non-invasive physiological measurements: from discovery to implementation

Title Tesim:
Editorial: Non-invasive physiological measurements: from discovery to implementation
Creator:
Stoner L., Pagan Lassalle P., Heffernan K., Bates-Fraser L.C., Paterson C., and Zieff G.
Date of publication:
2023
Abstract Tesim:
The goal of this Research Topic, developed by the American College of Sports Medicine Non-Invasive Physiology (ACSM-NIP) interest group, was to demystify and increase the accessibility of non-invasive physiological measurement tools and procedures. The nomenclature “noninvasive physiological measurement” typically conjures imagery of laboratory wizardry and blue-skies science (e.g., where real-world applications are not immediately apparent). However, compared to invasive measurements, noninvasive physiological measurements often reduce financial and time burdens, lower risk of harm, and provide greater accessibility. These benefits may extend beyond the research setting to the clinical setting. Non-invasive measurements are crucial to a myriad of study types and research questions with implications spanning the research-clinical spectrum. Broad examples of research types in which non-invasive physiological measurements are used or have important implications include: i) discovery (interpreting clinical signals to better understand systems physiology), ii) clinical and preclinical/subclinical (establishing efficacy and safety of techniques or interventions, iii) epidemiological: identifying the distribution of disease or track cohorts, and iv) implementation (medical system approaches for tracking patient health). We, via this Research Topic, were interested in all article types (e.g., original research, brief reports, etc.) including those focused on bioengineering, mathematical modelling, laboratory-studies, clinical studies, epidemiological studies, and implementation studies. We were also interested in articles with implications for diversity, equity, and inclusivity, including those addressing life-stage, sex, gender, race, ethnicity, and disabilities.
Resource type:
Article
Affiliation Label Tesim:
Department of Exercise and Sport Science
DOI:
https://doi.org/10.17615/22b2-hp04
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fphys.2023.1356664
ISSN:
1664-462X
Journal Title:
Frontiers in Physiology
Journal Volume:
14
Keyword:
clinical, non-invasive measurements, physiological measurements, discovery, and translation
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
and Columbia University
Person:
Stoner L., Pagan Lassalle P., Heffernan K., Bates-Fraser L.C., Paterson C., and Zieff G.
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
3fc2e0a5-4835-4d9c-b1d2-dc0eca74712b

43. Advancements in high-resolution 3D microscopy analysis of endosomal morphology in postmortem Alzheimer’s disease brains

Title Tesim:
Advancements in high-resolution 3D microscopy analysis of endosomal morphology in postmortem Alzheimer’s disease brains
Creator:
Mishra, Swati, Kirkland, Amanda, Garden, Gwenn A., Jayadev, Suman, Rose, Shannon E., Hailey, Dale W., Young, Jessica E., Williams, C. Andrew, and Keene, C. Dirk
Date of publication:
2024
Abstract Tesim:
Abnormal endo-lysosomal morphology is an early cytopathological feature of Alzheimer’s disease (AD) and genome-wide association studies (GWAS) have implicated genes involved in the endo-lysosomal network (ELN) as conferring increased risk for developing sporadic, late-onset AD (LOAD). Characterization of ELN pathology and the underlying pathophysiology is a promising area of translational AD research and drug development. However, rigorous study of ELN vesicles in AD and aged control brains poses a unique constellation of methodological challenges due in part to the small size of these structures and subsequent requirements for high-resolution imaging. Here we provide a detailed protocol for high-resolution 3D morphological quantification of neuronal endosomes in postmortem AD brain tissue, using immunofluorescent staining, confocal imaging with image deconvolution, and Imaris software analysis pipelines. To demonstrate these methods, we present neuronal endosome morphology data from 23 sporadic LOAD donors and one aged non-AD control donor. The techniques described here were developed across a range of AD neuropathology to best optimize these methods for future studies with large cohorts. Application of these methods in research cohorts will help advance understanding of ELN dysfunction and cytopathology in sporadic AD.
Resource type:
Article
Affiliation Label Tesim:
Department of Neurology
DOI:
https://doi.org/10.17615/m26f-4g69
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fnins.2023.1321680
ISSN:
1662-453X
Journal Title:
Frontiers in Neuroscience
Journal Volume:
17
Keyword:
neurons, endo-lysosomal network, early endosome, confocal microscopy, high-resolution imaging, Imaris, Alzheimer’s disease, and postmortem brain
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
University of Washington and
Person:
Mishra, Swati, Kirkland, Amanda, Garden, Gwenn A., Jayadev, Suman, Rose, Shannon E., Hailey, Dale W., Young, Jessica E., Williams, C. Andrew, and Keene, C. Dirk
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
199c7c55-9b1e-407b-9444-3c903fa25d74

44. Methodology and Implementation of a Randomized Controlled Trial (RCT) for Early Post-concussion Rehabilitation: The Active Rehab Study

Title Tesim:
Methodology and Implementation of a Randomized Controlled Trial (RCT) for Early Post-concussion Rehabilitation: The Active Rehab Study
Creator:
Marshall, S.W., McCrea, M., McCulloch, K.L., Ranapurwala, S.I., Active Rehab Study Consortium Investigators, Mrazik, M., Schneider, K., Register-Mihalik, J.K., Mihalik, J.P., Guskiewicz, K.M., Murphy, I., Naidu, D., and Gildner, P.
Date of publication:
2019
Abstract Tesim:
Background: Sports-related concussion (SRC) is a complex injury with heterogeneous presentation and management. There are few studies that provide guidance on the most effective and feasible strategies for recovery and return to sports participation. Furthermore, there have been no randomized studies of the feasibility, safety, and efficacy of early rehabilitation strategies across multiple sports and age groups. This international cluster-randomized pragmatic trial evaluates the effectiveness of early multi-dimensional rehabilitation integrated with the current return to sport strategy vs. the current return to sport strategy alone. Methods: The study is a cluster-randomized pragmatic trial enrolling male and female athletes from 28 sites. The sites span three countries, and include multiple sports, levels of play (high school, college, and professional), and levels of contact. The two study arms are Enhanced Graded Exertion (EGE) and Multidimensional Rehabilitation (MDR). The EGE arm follows the current return to sport strategy and the MDR arm integrates early, MDR strategies in the context of the current return to sport strategy. Each arm employs a post-injury protocol that applies to all athletes from that site in the event they sustain a concussion during their study enrollment. Participants are enrolled at pre-season baseline. Assessment timepoints include pre-season baseline, time of injury (concussion), 24–48 h post-injury, asymptomatic, and 1-month post-injury. Symptoms and activity levels are tracked post injury through the return to play process and beyond. Injury and recovery characteristics are obtained for all participants. Primary endpoints include time to medical clearance for full return to sport and time to become asymptomatic. Secondary endpoints include symptom, neurocognitive, mental status, balance, convergence insufficiency, psychological distress, and quality of life trajectories post-injury. Discussion: Outputs from the trial are expected to inform both research and clinical practice in post-concussion rehabilitation across all levels of sport and extend beyond civilian medicine to care for military personnel. Ethics and Dissemination: The study is approved by the data coordinating center Institutional Review Board and registered at clinicaltrials.gov. Dissemination will include peer-reviewed publications, presentation to patients and public groups, as well as dissemination in other healthcare and public venues of interest. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02988596 Trial Funding: National Football League.
Resource type:
Article
Affiliation Label Tesim:
Department of Exercise and Sport Science, School of Medicine, Department of Epidemiology, and Injury Prevention Research Center
DOI:
https://doi.org/10.17615/3qfb-y797
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fneur.2019.01176
ISSN:
1664-2295
Journal Title:
Frontiers in Neurology
Journal Volume:
10
Keyword:
return to play, exercise, post-concussion activity, clinical intervention, and traumatic brain injury
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
, Medical College of Wisconsin, University of Alberta, University of Calgary, and New Zealand Rugby
Person:
Marshall, S.W., McCrea, M., McCulloch, K.L., Ranapurwala, S.I., Active Rehab Study Consortium Investigators, Mrazik, M., Schneider, K., Register-Mihalik, J.K., Mihalik, J.P., Guskiewicz, K.M., Murphy, I., Naidu, D., and Gildner, P.
Publisher:
Frontiers Media S.A.
Source:
de758b76-433b-49a7-b8b5-68995bfcba9e

45. Antimicrobial Resistance in Enterobacterales and Its Contribution to Sepsis in Sub-saharan Africa

Title Tesim:
Antimicrobial Resistance in Enterobacterales and Its Contribution to Sepsis in Sub-saharan Africa
Creator:
Juliano J.J., van Duin D., and Tompkins K.
Date of publication:
2021
Abstract Tesim:
Antibiotic resistant Enterobacterales (formerly Enterobactereaceae) are a growing threat to Sub-Saharan Africa. Genes causing antibiotic resistance are easily spread between the environment and humans and infections due to drug resistant organisms contribute to sepsis mortality via delayed time to appropriate antimicrobial therapy. Additionally, second or third-line antibiotics are often not available or are prohibitively expensive in resource-constrained settings leading to limited treatment options. Lack of access to water and sanitation facilities, unregulated use of antibiotics, and malnutrition are contributors to high rates of antibiotic resistance in the region. Improvements in the monitoring of drug resistant infections and antibiotic stewardship are needed to preserve the efficacy of antibiotics for the future.
Resource type:
Article
Affiliation Label Tesim:
Department of Epidemiology and Division of Infectious Diseases
DOI:
https://doi.org/10.17615/vma1-vr39
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fmed.2021.615649
ISSN:
2296-858X
Journal Title:
Frontiers in Medicine
Journal Volume:
8
Keyword:
Sub-Sahara Africa, sepsis, resistance, Klebsiella pneumoniae, and E. coli
Language Label:
English
License Label:
Attribution 4.0 International
ORCID:
Other Affiliation:
Person:
Juliano J.J., van Duin D., and Tompkins K.
Publisher:
Frontiers Media S.A.
Source:
b89e4db2-eebb-4556-b021-20a2b82bd313

46. Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques

Title Tesim:
Sutterella and its metabolic pathways positively correlate with vaccine-elicited antibody responses in infant rhesus macaques
Creator:
Heimsath H., Dennis M., Permar S.R., Van Rompay K.K.A., De Paris K., Jiang D., Goswami R., Ardeshir A., Kozlowski P.A., and Surana N.K.
Date of publication:
2023
Abstract Tesim:
Introduction: It is becoming clearer that the microbiota helps drive responses to vaccines; however, little is known about the underlying mechanism. In this study, we aimed to identify microbial features that are associated with vaccine immunogenicity in infant rhesus macaques. Methods: We analyzed 16S rRNA gene sequencing data of 215 fecal samples collected at multiple timepoints from 64 nursery-reared infant macaques that received various HIV vaccine regimens. PERMANOVA tests were performed to determine factors affecting composition of the gut microbiota throughout the first eight months of life in these monkeys. We used DESeq2 to identify differentially abundant bacterial taxa, PICRUSt2 to impute metagenomic information, and mass spectrophotometry to determine levels of fecal short-chain fatty acids and bile acids. Results: Composition of the early-life gut microbial communities in nursery-reared rhesus macaques from the same animal care facility was driven by age, birth year, and vaccination status. We identified a Sutterella and a Rodentibacter species that positively correlated with vaccine-elicited antibody responses, with the Sutterella species exhibiting more robust findings. Analysis of Sutterella-related metagenomic data revealed five metabolic pathways that significantly correlated with improved antibody responses following HIV vaccination. Given these pathways have been associated with short-chain fatty acids and bile acids, we quantified the fecal concentration of these metabolites and found several that correlated with higher levels of HIV immunogen-elicited plasma IgG. Discussion: Our findings highlight an intricate bidirectional relationship between the microbiota and vaccines, where multiple aspects of the vaccination regimen modulate the microbiota and specific microbial features facilitate vaccine responses. An improved understanding of this microbiota–vaccine interplay will help develop more effective vaccines, particularly those that are tailored for early life.
Resource type:
Article
Affiliation Label Tesim:
Department of Microbiology and Immunology
DOI:
https://doi.org/10.17615/ztqf-8x04
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fimmu.2023.1283343
ISSN:
1664-3224
Journal Title:
Frontiers in Immunology
Journal Volume:
14
Keyword:
Sutterella, macaque, metabolites, vaccine responses, infants, and gut microbiota
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Duke University School of Medicine, Weill Cornell Medicine, University of California, Davis, , and Louisiana State University Health Sciences Center
Person:
Heimsath H., Dennis M., Permar S.R., Van Rompay K.K.A., De Paris K., Jiang D., Goswami R., Ardeshir A., Kozlowski P.A., and Surana N.K.
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
89eda17f-3724-4071-b50f-d71ada3bbd9c

47. Seasonal SIMS δ18O record in Astarte borealis from the Baltic Sea tracks a modern regime shift in the NAO

Title Tesim:
Seasonal SIMS δ18O record in Astarte borealis from the Baltic Sea tracks a modern regime shift in the NAO
Creator:
Hughes H.P., Moss D.K., Orland I.J., Zettler M.L., and Surge D.
Date of publication:
2023
Abstract Tesim:
Introduction: Astarte borealis holds great potential as an archive of seasonal paleoclimate, especially due to its long lifespan (several decades to more than a century) and ubiquitous distribution across high northern latitudes. Furthermore, recent work demonstrates that the isotope geochemistry of the aragonite shell is a faithful proxy of environmental conditions. However, the exceedingly slow growth rates of A. borealis in some locations (<0.2mm/year) make it difficult to achieve seasonal resolution using standard micromilling techniques for conventional stable isotope analysis. Moreover, oxygen isotope (δ18O) records from species inhabiting brackish environments are notoriously difficult to use as paleoclimate archives because of the simultaneous variation in temperature and δ18Owater values. Methods: Here we use secondary ion mass spectrometry (SIMS) to microsample an A. borealis specimen from the southern Baltic Sea, yielding 451 SIMS δ18Oshell values at sub-monthly resolution. Results: SIMS δ18Oshell values exhibit a quasi-sinusoidal pattern with 24 local maxima and minima coinciding with 24 annual growth increments between March 1977 and the month before specimen collection in May 2001. Discussion: Age-modeled SIMS δ18Oshell values correlate significantly with both in situ temperature measured from shipborne CTD casts (r2 = 0.52, p<0.001) and sea surface temperature from the ORAS5-SST global reanalysis product for the Baltic Sea region (r2 = 0.42, p<0.001). We observe the strongest correlation between SIMS δ18Oshell values and salinity when both datasets are run through a 36-month LOWESS function (r2 = 0.71, p < 0.001). Similarly, we find that LOWESS-smoothed SIMS δ18Oshell values exhibit a moderate correlation with the LOWESS-smoothed North Atlantic Oscillation (NAO) Index (r2 = 0.46, p<0.001). Change point analysis supports that SIMS δ18Oshell values capture a well-documented regime shift in the NAO circa 1989. We hypothesize that the correlation between the SIMS δ18Oshell time series and the NAO is enhanced by the latter’s influence on the regional covariance of water temperature and δ18Owater values on interannual and longer timescales in the Baltic Sea. These results showcase the potential for SIMS δ18Oshell values in A. borealis shells to provide robust paleoclimate information regarding hydroclimate variability from seasonal to decadal timescales.
Resource type:
Article
Affiliation Label Tesim:
Department of Earth, Marine and Environmental Sciences
DOI:
https://doi.org/10.17615/7s6q-tq28
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fmars.2023.1293823
ISSN:
2296-7745
Journal Title:
Frontiers in Marine Science
Journal Volume:
10
Keyword:
paleoclimate, North Atlantic oscillation, oxygen isotope ratios, Bivalvia, and secondary ion mass spectrometry
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
, Sam Houston State University, University of Wisconsin-Madison, and Leibniz-Institute for Baltic Sea Research
Person:
Hughes H.P., Moss D.K., Orland I.J., Zettler M.L., and Surge D.
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
0623e2b1-afab-43d6-a869-ce9daf5d6f25

48. Neurosteroid [3α,5α]-3-hydroxy-pregnan-20-one enhances IL-10 production via endosomal TRIF-dependent TLR4 signaling pathway

Title Tesim:
Neurosteroid [3α,5α]-3-hydroxy-pregnan-20-one enhances IL-10 production via endosomal TRIF-dependent TLR4 signaling pathway
Creator:
Balan, Irina, Morrow, A. Leslie, O’Buckley, Todd K., and Grusca, Adelina
Date of publication:
2023
Abstract Tesim:
Background Previous studies demonstrated the inhibitory effect of allopregnanolone (3α,5α-THP) on the activation of inflammatory toll-like receptor 4 (TLR4) signals in RAW264.7 macrophages and the brains of selectively bred alcohol-preferring (P) rats. In the current study, we investigated the impact of 3α,5α-THP on the levels of IL-10 and activation of the TRIF-dependent endosomal TLR4 pathway. Methods The amygdala and nucleus accumbens (NAc) of P rats, which exhibit innately activated TLR4 pathways as well as RAW264.7 cells, were used. Enzyme-linked immunosorbent assays (ELISA) and immunoblotting assays were used to ascertain the effects of 3α,5α-THP on the TRIF-dependent endosomal TLR4 pathway and endosomes were isolated to examine translocation of TLR4 and TRIF. Additionally, we investigated the effects of 3α,5α-THP and 3α,5α-THDOC (0.1, 0.3, and 1.0 µM) on the levels of IL-10 in RAW264.7 macrophages. Finally, we examined whether inhibiting TRIF (using TRIF siRNA) in RAW264.7 cells altered the levels of IL-10. Results 3α,5α-THP administration facilitated activation of the endosomal TRIF-dependent TLR4 pathway in males, but not female P rats. 3α,5α-THP increased IL-10 levels (+13.2 ± 6.5%) and BDNF levels (+21.1 ± 11.5%) in the male amygdala. These effects were associated with increases in pTRAM (+86.4 ± 28.4%), SP1 (+122.2 ± 74.9%), and PI(3)K-p110δ (+61.6 ± 21.6%), and a reduction of TIRAP (−13.7 ± 6.0%), indicating the activation of the endosomal TRIF-dependent TLR4 signaling pathway. Comparable effects were observed in NAc of these animals. Furthermore, 3α,5α-THP enhanced the accumulation of TLR4 (+43.9 ± 11.3%) and TRIF (+64.8 ± 32.8%) in endosomes, with no significant effect on TLR3 accumulation. Additionally, 3α,5α-THP facilitated the transition from early endosomes to late endosomes (increasing Rab7 levels: +35.8 ± 18.4%). In RAW264.7 cells, imiquimod (30 µg/mL) reduced IL-10 while 3α,5α-THP and 3α,5α-THDOC (0.1, 0.3, and 1.0 µM) restored IL-10 levels. To determine the role of the TRIF-dependent TLR4 signaling pathway in IL-10 production, the downregulation of TRIF (−62.9 ± 28.2%) in RAW264.7 cells led to a reduction in IL-10 levels (−42.3 ± 8.4%). TRIF (−62.9 ± 28.2%) in RAW264.7 cells led to a reduction in IL-10 levels (−42.3 ± 8.4%) and 3α,5α-THP (1.0 µM) no longer restored the reduced IL-10 levels. Conclusion The results demonstrate 3α,5α-THP enhancement of the endosomal TLR4-TRIF anti-inflammatory signals and elevations of IL-10 in male P rat brain that were not detected in female P rat brain. These effects hold significant implications for controlling inflammatory responses in both the brain and peripheral immune cells.
Resource type:
Article
Affiliation Label Tesim:
Bowles Center for Alcohol Studies
DOI:
https://doi.org/10.17615/5gz4-v408
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fendo.2023.1299420
ISSN:
1664-2392
Journal Title:
Frontiers in Endocrinology
Journal Volume:
14
Keyword:
toll-like receptor 4, neuroinflammation, toll/interleukin-1 receptor domain-containing adapter-inducing interferon-b (TRIF), [3a,5a]-3,21-dihydroxypregnan-20-one (3a,5a-THDOC), and [3a,5a]-3-hydroxy-pregnan-20-one (3a,5a-THP)
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Person:
Balan, Irina, Morrow, A. Leslie, O’Buckley, Todd K., and Grusca, Adelina
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
0ff6a456-8f2a-4476-9bd0-20305a4746c3

49. Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure

Title Tesim:
Metabolic status differentiates Trp53inp2 function in pressure-overload induced heart failure
Creator:
Liu, Jianfang, Bouso, Eyad, Wang, Yibin, Liu, Tian, Gao, Chen, Mamlouk, Samir, Ren, Shuxun (Vincent), Rau, Christoph D., and Zhu, Cansheng
Date of publication:
2023
Abstract Tesim:
Cardiometabolic disorders encompass a broad range of cardiovascular complications associated with metabolic dysfunction. These conditions have an increasing share in the health burden worldwide due to worsening endemic of hypertension, obesity, and diabetes. Previous studies have identified Tumor Protein p53-inducible Nuclear Protein 2 (Trp53inp2) as a molecular link between hyperglycemia and cardiac hypertrophy. However, its role in cardiac pathology has never been determined in vivo. In this study, we generated a cardiac specific knockout model of Trp53inp2 (Trp53inp2-cKO) and investigated the impact of Trp53inp2 inactivation on the pathogenesis of heart failure under mechanic or/and metabolic stresses. Based on echocardiography assessment, inactivation of Trp53inp2 in heart led to accelerated onset of HFrEF in response to pressure-overload, with significantly reduced ejection fraction and elevated heart failure marker genes comparing to the control mice. In contrast, inactivation of Trp53inp2 ameliorated cardiac dysfunction induced by combined stresses of high fat diet and moderate pressure overload (Cardiometabolic Disorder Model). Moreover, Trp53inp2 inactivation led to reduced expression of glucose metabolism genes in lean, pressure-overloaded hearts. However, the same set of genes were significantly induced in the Trp53inp2-cKO hearts under both mechanical and metabolic stresses. In summary, we have demonstrated for the first time that cardiomyocyte Trp53inp2 has diametrically differential roles in the pathogenesis of heart failure and glucose regulation under mechanical vs. mechanical plus metabolic stresses. This insight suggests that Trp53inp2 may exacerbate the cardiac dysfunction during pressure overload injury but have a protective effect in cardiac diastolic function in cardiometabolic disease.
Resource type:
Article
Affiliation Label Tesim:
Department of Genetics
DOI:
https://doi.org/10.17615/ckq2-8z79
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fcvm.2023.1226586
ISSN:
2297-055X
Journal Title:
Frontiers in Cardiovascular Medicine
Journal Volume:
10
Keyword:
Trp53inp2, transcription factor, heart failure, glucose metabolism, and cardiometabolic syndrome
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Renmin Hospital of Wuhan University, University of Cincinnati, DukeNUS Medical School, and
Person:
Liu, Jianfang, Bouso, Eyad, Wang, Yibin, Liu, Tian, Gao, Chen, Mamlouk, Samir, Ren, Shuxun (Vincent), Rau, Christoph D., and Zhu, Cansheng
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
ae689b4d-04a0-493f-9350-49dac00ad4e6

50. Day one postoperative MRI findings following electrode placement for deep brain stimulation: analysis of a large case series

Title Tesim:
Day one postoperative MRI findings following electrode placement for deep brain stimulation: analysis of a large case series
Creator:
Kessler, Brice, Hadar, Eldad, Quinsey, Carolyn, Succop, Benjamin S., Roque, Daniel Alberto, and Zamora, Carlos
Date of publication:
2023
Abstract Tesim:
Objective This study sought to characterize postoperative day one MRI findings in deep brain stimulation (DBS) patients.MethodsDBS patients were identified by CPT and had their reviewed by a trained neuroradiologist and neurosurgeon blinded to MR sequence and patient information. The radiographic abnormalities of interest were track microhemorrhage, pneumocephalus, hematomas, and edema, and the occurrence of these findings in compare the detection of these complications between T1/T2 gradient-echo (GRE) and T1/T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance (MR) sequences was compared. The presence, size, and association of susceptibility artifact with other radiographic abnormalities was also described. Lastly, the association of multiple microelectrode cannula passes with each radiographic finding was evaluated. Ad-hoc investigation evaluated hemisphere-specific associations. Multiple logistic regression with Bonferroni correction (corrected p = 0.006) was used for all analysis. Results Out of 198 DBS patients reviewed, 115 (58%) patients showed entry microhemorrhage; 77 (39%) track microhemorrhage; 44 (22%) edema; 69 (35%) pneumocephalus; and 12 (6%) intracranial hematoma. T2 GRE was better for detecting microhemorrhage (OR = 14.82, p < 0.0001 for entry site and OR = 4.03, p < 0.0001 for track) and pneumocephalus (OR = 11.86, p < 0.0001), while T2 FLAIR was better at detecting edema (OR = 123.6, p < 0.0001). The relatively common findings of microhemorrhage and edema were best visualized by T2 GRE and T2 FLAIR sequences, respectively. More passes intraoperatively was associated with detection of ipsilateral track microhemorrhage (OR = 7.151, p < 0.0001 left; OR = 8.953, p < 0.0001 right). Susceptibility artifact surrounding electrodes possibly interfered with further detection of ipsilateral edema (OR = 4.323, p = 0.0025 left hemisphere only). Discussion Day one postoperative magnetic resonance imaging (MRI) for DBS patients can be used to detect numerous radiographic abnormalities not identifiable on a computed tomographic (CT) scan. For this cohort, multiple stimulating cannula passes intraoperatively was associated with increased microhemorrhage along the electrode track. Further studies should be performed to evaluate the clinical relevance of these observations.
Resource type:
Article
Affiliation Label Tesim:
Department of Neurosurgery, School of Medicine, and Department of Neurology
DOI:
https://doi.org/10.17615/pns3-m736
Edition:
Publisher
Identifier:
https://doi.org/10.3389/fneur.2023.1253241
ISSN:
1664-2295
Journal Title:
Frontiers in Neurology
Journal Volume:
14
Keyword:
essential tremor, stereotactic neurosurgery, functional neurosurgery, Parkinson’s disease, deep brain stimulation, and postoperative MRI
Language Label:
English
License Label:
Attribution 4.0 International
Other Affiliation:
Person:
Kessler, Brice, Hadar, Eldad, Quinsey, Carolyn, Succop, Benjamin S., Roque, Daniel Alberto, and Zamora, Carlos
Publisher:
Frontiers Media SA
Rights Statement Label:
In Copyright
Source:
f83b9c54-c925-4d7e-ac2e-4848e97d9beb