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Association Between Antiviral Prophylaxis And Cytomegalovirus And Epstein-Barr Virus Dnaemia In Pediatric Recipients Of Allogeneic Hematopoietic Stem Cell Transplant, Ndeye Soukeyna Diop, Pascal Roland Enok Bonong, Chantal Buteau, Michel Duval, Jacques Lacroix, Louise Laporte, Marisa Tucci, Nancy Robitaille, Philip C Spinella, Geoffrey Cuvelier, Suzanne M Vercauteren, Victor Lewis, Caroline Alfieri, Helen Trottier Jan 2021

Association Between Antiviral Prophylaxis And Cytomegalovirus And Epstein-Barr Virus Dnaemia In Pediatric Recipients Of Allogeneic Hematopoietic Stem Cell Transplant, Ndeye Soukeyna Diop, Pascal Roland Enok Bonong, Chantal Buteau, Michel Duval, Jacques Lacroix, Louise Laporte, Marisa Tucci, Nancy Robitaille, Philip C Spinella, Geoffrey Cuvelier, Suzanne M Vercauteren, Victor Lewis, Caroline Alfieri, Helen Trottier

Open Access Publications

BACKGROUND: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients.

METHODS: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March …


Toll-Like Receptor Signaling In The Establishment And Function Of The Immune System, Jahnavi Aluri, Megan A Cooper, Laura G Schuettpelz Jan 2021

Toll-Like Receptor Signaling In The Establishment And Function Of The Immune System, Jahnavi Aluri, Megan A Cooper, Laura G Schuettpelz

Open Access Publications

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in …


Impact Of Antibiotic Heterogeneity By Periodic Antibiotic Monitoring And Supervision Strategy At Two Units With Different Prevalences Of Multidrug-Resistant Organisms, Surachai Chaononghin, Kittiya Jantarathaneewat, David J Weber, David K Warren, Anucha Apisarnthanarak Jan 2021

Impact Of Antibiotic Heterogeneity By Periodic Antibiotic Monitoring And Supervision Strategy At Two Units With Different Prevalences Of Multidrug-Resistant Organisms, Surachai Chaononghin, Kittiya Jantarathaneewat, David J Weber, David K Warren, Anucha Apisarnthanarak

Open Access Publications

In an intensive care unit, antibiotic heterogeneity led to an increase in antibiotic heterogeneity index (P = .002) and a reduction in carbapenem-resistance Enterobacteriaceae incidence (P = .04). In a general medicine unit with low prevalence of multidrug-resistant organisms, antibiotic heterogeneity index and incidence of multidrug-resistant organisms did not improve.


Flexor Tendon Injury And Repair: The Influence Of Synovial Environment On The Early Healing Response In A Canine Mode, Hua Shen, Susumu Yoneda, Shelly E Sakiyama-Elbert, Qiang Zhang, Stavros Thomopoulos, Richard H Gelberman Jan 2021

Flexor Tendon Injury And Repair: The Influence Of Synovial Environment On The Early Healing Response In A Canine Mode, Hua Shen, Susumu Yoneda, Shelly E Sakiyama-Elbert, Qiang Zhang, Stavros Thomopoulos, Richard H Gelberman

Open Access Publications

BACKGROUND: Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair.

METHODS: Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw …


Nanoparticulate Matter Exposure Results In White Matter Damage And An Inflammatory Microglial Response In An Experimental Murine Model, Michelle Connor, Krista Lamorie-Foote, Qinghai Liu, Kristina Shkirkova, Hans Baertsch, Constantinos Sioutas, Todd E. Morgan, Caleb E. Finch, William J. Mack Jan 2021

Nanoparticulate Matter Exposure Results In White Matter Damage And An Inflammatory Microglial Response In An Experimental Murine Model, Michelle Connor, Krista Lamorie-Foote, Qinghai Liu, Kristina Shkirkova, Hans Baertsch, Constantinos Sioutas, Todd E. Morgan, Caleb E. Finch, William J. Mack

Open Access Publications

Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban …


Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer Jan 2021

Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer

Open Access Publications

Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …


Prognostic And Pathophysiologic Significance Of Il-8 (Cxcl8) In Biliary Atresia, Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Päivi Heikkilä, Antti Kyrönlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Mikko P Pakarinen Jan 2021

Prognostic And Pathophysiologic Significance Of Il-8 (Cxcl8) In Biliary Atresia, Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Päivi Heikkilä, Antti Kyrönlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Mikko P Pakarinen

Open Access Publications

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 …


Identifying The Impact Of Intimate Partner Violence In Humanitarian Settings: Using An Ecological Framework To Review 15 Years Of Evidence, Melissa Meinhart, Ilana Seff, Katrina Troy, Samantha Mcnelly, Luissa Vahedi, Catherine Poulton, Lindsay Stark Jan 2021

Identifying The Impact Of Intimate Partner Violence In Humanitarian Settings: Using An Ecological Framework To Review 15 Years Of Evidence, Melissa Meinhart, Ilana Seff, Katrina Troy, Samantha Mcnelly, Luissa Vahedi, Catherine Poulton, Lindsay Stark

Open Access Publications

Intimate partner violence (IPV) is a pervasive form of gender-based violence that exacerbates in humanitarian settings. This systematic review examined the myriad IPV impacts and the quality of existing evidence of IPV in humanitarian settings. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures, a total of 51 articles were included from the 3924 screened. We identified the impact of IPV across two levels of the ecological framework: individual and microsystem. Our findings corroborated previous evidence that indicated IPV to be associated with adverse physical and mental health for survivors. Our findings also uniquely synthesized the intergenerational …


Role Of Anesthetics And Their Adjuvants In Neurovascular Protection In Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage, Umeshkumar Athiraman, Gregory J Zipfel Jan 2021

Role Of Anesthetics And Their Adjuvants In Neurovascular Protection In Secondary Brain Injury After Aneurysmal Subarachnoid Hemorrhage, Umeshkumar Athiraman, Gregory J Zipfel

Open Access Publications

Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuroprotective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or …


Safety Of Using A Combinatorial Pharmacogenomic Test For Patients With Major Depressive Disorder In The Guided Trial, Sagar V Parikh, Gabriela K Khazanov, Michael E Thase, Anthony J Rothschild, Boadie W Dunlop, Charles Debattista, Charles R Conway, Brent P Forester, Richard C Shelton, Matthew Macaluso, James Li, Kunbo Yu, Michael R Jablonski, Stephanie Meek, John F Greden Jan 2021

Safety Of Using A Combinatorial Pharmacogenomic Test For Patients With Major Depressive Disorder In The Guided Trial, Sagar V Parikh, Gabriela K Khazanov, Michael E Thase, Anthony J Rothschild, Boadie W Dunlop, Charles Debattista, Charles R Conway, Brent P Forester, Richard C Shelton, Matthew Macaluso, James Li, Kunbo Yu, Michael R Jablonski, Stephanie Meek, John F Greden

Open Access Publications

BACKGROUND: Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).

MATERIALS AND METHODS: Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing …


Basophils Balance Healing After Myocardial Infarction Via Il-4/Il-13, Florian Sicklinger, Kory J Lavine, Et Al Jan 2021

Basophils Balance Healing After Myocardial Infarction Via Il-4/Il-13, Florian Sicklinger, Kory J Lavine, Et Al

Open Access Publications

The inflammatory response after myocardial infarction (MI) is a precisely regulated process that greatly affects subsequent remodeling. Here, we show that basophil granulocytes infiltrated infarcted murine hearts, with a peak occurring between days 3 and 7. Antibody-mediated and genetic depletion of basophils deteriorated cardiac function and resulted in enhanced scar thinning after MI. Mechanistically, we found that basophil depletion was associated with a shift from reparative Ly6Clo macrophages toward increased numbers of inflammatory Ly6Chi monocytes in the infarcted myocardium. Restoration of basophils in basophil-deficient mice by adoptive transfer reversed this proinflammatory phenotype. Cellular alterations in the absence of basophils were …


Investigation Of Convergent And Divergent Genetic Influences Underlying Schizophrenia And Alcohol Use Disorder, Emma C Johnson, Alexander S Hatoum, Sarah Hartz, Arpana Agrawal, Et Al Jan 2021

Investigation Of Convergent And Divergent Genetic Influences Underlying Schizophrenia And Alcohol Use Disorder, Emma C Johnson, Alexander S Hatoum, Sarah Hartz, Arpana Agrawal, Et Al

Open Access Publications

BACKGROUND: Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

METHODS: We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

RESULTS: We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. …


Bictegravir-Based Antiretroviral Therapy-Associated Accelerated Hyperglycemia And Diabetes Mellitus, Nathanial S. Nolan, Samantha Adamson, Dominic Reeds, Jane A. O'Halloran Jan 2021

Bictegravir-Based Antiretroviral Therapy-Associated Accelerated Hyperglycemia And Diabetes Mellitus, Nathanial S. Nolan, Samantha Adamson, Dominic Reeds, Jane A. O'Halloran

Open Access Publications

Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is first line for treatment of people with human immunodeficiency virus (PWH). Emerging data suggest the possibility of adverse metabolic effects of these medications. We describe 3 cases in which PWH developed hyperglycemia and ketoacidosis within months of being switched to bictegravir-based ART.


Public Preferences For Social Distancing Policy Measures To Mitigate The Spread Of Covid-19 In Missouri, Ingrid Eshun-Wilson, Aaloke Mody, Virginia Mckay, Matifadza Hlatshwayo, Cory Bradley, Vetta Thompson, David V. Glidden, Elvin H. Geng Jan 2021

Public Preferences For Social Distancing Policy Measures To Mitigate The Spread Of Covid-19 In Missouri, Ingrid Eshun-Wilson, Aaloke Mody, Virginia Mckay, Matifadza Hlatshwayo, Cory Bradley, Vetta Thompson, David V. Glidden, Elvin H. Geng

Open Access Publications

Importance: Policies to promote social distancing can minimize COVID-19 transmission but come with substantial social and economic costs. Quantifying relative preferences among the public for such practices can inform locally relevant policy prioritization and optimize uptake.

Objective: To evaluate relative utilities (ie, preferences) for COVID-19 pandemic social distancing strategies against the hypothetical risk of acquiring COVID-19 and anticipated income loss.

Design, Setting, and Participants: This survey study recruited individuals living in the Missouri area from May to June 2020 via randomly distributed unincentivized social media advertisements and local recruitment platforms for members of minority racial and ethnic groups. Participants answered …


Strategies For Disseminating And Implementing Covid-19 Vaccines In Rural Areas, Beth Prusaczyk Jan 2021

Strategies For Disseminating And Implementing Covid-19 Vaccines In Rural Areas, Beth Prusaczyk

Open Access Publications

The United States has well-documented rural-urban health disparities, and it is imperative that these are not exacerbated by an inefficient rollout of coronavirus disease 2019 (COVID-19) vaccines to rural areas. In addition to the preexisting barriers to delivering and receiving health care in rural areas, such as high patient:provider ratios and long geographic distances between patients and providers, rural residents are significantly more likely to say they have no intention of receiving a COVID-19 vaccine, compared with urban residents. To overcome these barriers and ensure that rural residents receive the vaccine, officials and communities should look to previous research on …


The Fidelity Of Dna Replication, Particularly On Gc-Rich Templates, Is Reduced By Defects Of The Fe-S Cluster In Dna Polymerase Δ, Denis A. Kiktev, Margaret Dominska, Tony Zhang, Joseph Dahl, Elena I. Stepchenkova, Piotr Mieczkowski, Peter M. Burgers, Scott Lujan, Adam Burkholder, Thomas A. Kunkel, Thomas D. Petes Jan 2021

The Fidelity Of Dna Replication, Particularly On Gc-Rich Templates, Is Reduced By Defects Of The Fe-S Cluster In Dna Polymerase Δ, Denis A. Kiktev, Margaret Dominska, Tony Zhang, Joseph Dahl, Elena I. Stepchenkova, Piotr Mieczkowski, Peter M. Burgers, Scott Lujan, Adam Burkholder, Thomas A. Kunkel, Thomas D. Petes

Open Access Publications

Iron-sulfur clusters (4Fe-4S) exist in many enzymes concerned with DNA replication and repair. The contribution of these clusters to enzymatic activity is not fully understood. We identified the MET18 (MMS19) gene of Saccharomyces cerevisiae as a strong mutator on GC-rich genes. Met18p is required for the efficient insertion of iron-sulfur clusters into various proteins. met18 mutants have an elevated rate of deletions between short flanking repeats, consistent with increased DNA polymerase slippage. This phenotype is very similar to that observed in mutants of POL3 (encoding the catalytic subunit of Pol δ) that weaken binding of the iron-sulfur cluster. Comparable mutants …


Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony, Ceazar Nave, Logan Roberts, Patrick Hwu, Jerson D. Estrella, Thanh C. Vo, Thanh H. Nguyen, Tony Thai Bui, Daniel J. Rindner, Nicholas Pervolarakis, Paul J. Shaw, Tanya L. Leise, Todd C. Holmes Jan 2021

Weekend Light Shifts Evoke Persistent Drosophila Circadian Neural Network Desynchrony, Ceazar Nave, Logan Roberts, Patrick Hwu, Jerson D. Estrella, Thanh C. Vo, Thanh H. Nguyen, Tony Thai Bui, Daniel J. Rindner, Nicholas Pervolarakis, Paul J. Shaw, Tanya L. Leise, Todd C. Holmes

Open Access Publications

We developed a method for single-cell resolution longitudinal bioluminescence imaging of PERIOD (PER) protein and TIMELESS (TIM) oscillations in cultured male adult


Chronic Nerve Injuries And Delays In Surgical Treatment Negatively Impact Patient-Reported Quality Of Life, John M. Felder, Ivica Ducic Jan 2021

Chronic Nerve Injuries And Delays In Surgical Treatment Negatively Impact Patient-Reported Quality Of Life, John M. Felder, Ivica Ducic

Open Access Publications

No abstract provided.


Effects Of Gynura Bicolor On Glycemic Control And Antioxidant Ability In Prediabetes, Chu-Hsuan Hsia, Yu-Tang Tung, Yu-Sheng Yeh, Yi-Wen Chien Jan 2021

Effects Of Gynura Bicolor On Glycemic Control And Antioxidant Ability In Prediabetes, Chu-Hsuan Hsia, Yu-Tang Tung, Yu-Sheng Yeh, Yi-Wen Chien

Open Access Publications

No abstract provided.


Early Aberrant Angiogenesis Due To Elastic Fiber Fragmentation In Aortic Valve Disease, Robert B Hinton, Amy L Juraszek, Amy M Opoka, Benjamin J Landis, J Michael Smith, Robert P Mecham, Kevin E Bove Jan 2021

Early Aberrant Angiogenesis Due To Elastic Fiber Fragmentation In Aortic Valve Disease, Robert B Hinton, Amy L Juraszek, Amy M Opoka, Benjamin J Landis, J Michael Smith, Robert P Mecham, Kevin E Bove

Open Access Publications

Elastic fiber fragmentation (EFF) is a hallmark of aortic valve disease (AVD), and neovascularization has been identified as a late finding related to inflammation. We sought to characterize the relationship between early EFF and aberrant angiogenesis. To examine disease progression, regional anatomy and pathology of aortic valve tissue were assessed using histochemistry, immunohistochemistry, and electron microscopy from early-onset (<40 yo) and late-onset (≥40 yo) non-syndromic AVD specimens. To assess the effects of EFF on early AVD processes, valve tissue from Williams and Marfan syndrome patients was also analyzed. Bicuspid aortic valve was more common in early-onset AVD, and cardiovascular comorbidities were more common in late-onset AVD. Early-onset AVD specimens demonstrated angiogenesis without inflammation or atherosclerosis. A distinct pattern of elastic fiber components surrounded early-onset AVD neovessels, including increased emilin-1 and decreased fibulin-5. Different types of EFF were present in Williams syndrome (WS) and Marfan syndrome (MFS) aortic valves; WS but not MFS aortic valves demonstrated angiogenesis. Aberrant angiogenesis occurs in early-onset AVD in the absence of inflammation, implicating EFF. Elucidation of underlying mechanisms may inform the development of new pharmacologic treatments.


Models Of Distal Arthrogryposis And Lethal Congenital Contracture Syndrome, Julia Whittle, Aaron Johnson, Matthew B Dobbs, Christina A Gurnett Jan 2021

Models Of Distal Arthrogryposis And Lethal Congenital Contracture Syndrome, Julia Whittle, Aaron Johnson, Matthew B Dobbs, Christina A Gurnett

Open Access Publications

Distal arthrogryposis and lethal congenital contracture syndromes describe a broad group of disorders that share congenital limb contractures in common. While skeletal muscle sarcomeric genes comprise many of the first genes identified for Distal Arthrogyposis, other mechanisms of disease have been demonstrated, including key effects on peripheral nerve function. While Distal Arthrogryposis and Lethal Congenital Contracture Syndromes display superficial similarities in phenotype, the underlying mechanisms for these conditions are diverse but overlapping. In this review, we discuss the important insights gained into these human genetic diseases resulting from in vitro molecular studies and in vivo models in fruit fly, zebrafish, …


Promoting Coronavirus Disease 2019 (Covid-19) Vaccination Among Healthcare Personnel: A Multifaceted Intervention At A Tertiary-Care Center In Japan, Akane Takamatsu, Hitoshi Honda, Tomoya Kojima, Kengo Murata, Hilary M Babcock Jan 2021

Promoting Coronavirus Disease 2019 (Covid-19) Vaccination Among Healthcare Personnel: A Multifaceted Intervention At A Tertiary-Care Center In Japan, Akane Takamatsu, Hitoshi Honda, Tomoya Kojima, Kengo Murata, Hilary M Babcock

Open Access Publications

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccine may hold the key to ending the pandemic, but vaccine hesitancy is hindering the vaccination of healthcare personnel (HCP). We examined their perceptions of the COVID-19 vaccine and implemented an intervention to increase vaccination uptake.

DESIGN: Before-and-after trial.

PARTICIPANTS AND SETTING: Healthcare personnel at a 790-bed tertiary-care center in Tokyo, Japan.

INTERVENTIONS: A prevaccination questionnaire was administered to HCP to examine their perceptions of the COVID-19 vaccine. A multifaceted intervention was then implemented involving (1) distribution of informational leaflets to all HCP, (2) hospital-wide announcements encouraging vaccination, (3) a mandatory lecture, (4) an …


Developmental Variation In Testosterone: Cortisol Ratio Alters Cortical- And Amygdala-Based Cognitive Processes, Jimin Lew, Sherri Lee Jones, Christina Caccese, Isobel Orfi, Charlotte Little, Kelly N Botteron, James T Mccracken, Tuong-Vi Nguyen Jan 2021

Developmental Variation In Testosterone: Cortisol Ratio Alters Cortical- And Amygdala-Based Cognitive Processes, Jimin Lew, Sherri Lee Jones, Christina Caccese, Isobel Orfi, Charlotte Little, Kelly N Botteron, James T Mccracken, Tuong-Vi Nguyen

Open Access Publications

Testosterone (T) and cortisol (C) are the end products of neuroendocrine axes that interact with the process of shaping brain structure and function. Relative levels of T:C (TC ratio) may alter prefrontal-amygdala functional connectivity in adulthood. What remains unclear is whether TC-related effects are rooted to childhood and adolescence. We used a healthy cohort of 4-22-year-olds to test for associations between TC ratios, brain structure (amygdala volume, cortical thickness (CTh), and their coordinated growth), as well as cognitive and behavioral development. We found greater TC ratios to be associated with the growth of specific brain structures: 1) parietal CTh; 2) …


Effectiveness Of A Vancomycin Dosing Protocol Guided By Area Under The Concentration-Time Curve To Minimal Inhibitory Concentration (Auc/Mic) With Multidisciplinary Team Support To Improve Hospital-Wide Adherence To A Vancomycin Dosing Protocol: A Pilot Study, Panipak Katawethiwong, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, David J Weber, David K Warren, Nuntra Suwantarat Jan 2021

Effectiveness Of A Vancomycin Dosing Protocol Guided By Area Under The Concentration-Time Curve To Minimal Inhibitory Concentration (Auc/Mic) With Multidisciplinary Team Support To Improve Hospital-Wide Adherence To A Vancomycin Dosing Protocol: A Pilot Study, Panipak Katawethiwong, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, David J Weber, David K Warren, Nuntra Suwantarat

Open Access Publications

BACKGROUND: Limited data are available on the implementation of an area under the concentration-time curve (AUC)-based dosing protocol with multidisciplinary team (MT) support to improve adherence with vancomycin dosing protocol.

OBJECTIVE: To evaluate the effectiveness of an AUC-based dosing protocol with MT support intervention with adherence to a hospital-wide vancomycin dosing protocol at Thammasat University Hospital.

METHOD: We conducted a quasi-experimental study in patients who were prescribed intravenous vancomycin. The study was divided into 2 periods; (1) the preintervention period when the vancomycin dosing protocol was already applied in routine practice and (2) the post-intervention period when the implementation of …


Genomic Risk Prediction For Breast Cancer In Older Women, Paul Lacaze, Yin Cao, Et Al Jan 2021

Genomic Risk Prediction For Breast Cancer In Older Women, Paul Lacaze, Yin Cao, Et Al

Open Access Publications

Genomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40-69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was …


Bioactivation Of Isoxazole-Containing Bromodomain And Extra-Terminal Domain (Bet) Inhibitors, Noah R Flynn, Michael D Ward, Mary A Schleiff, Corentine M C Laurin, Rohit Farmer, Stuart J Conway, Gunnar Boysen, S Joshua Swamidass, Grover P Miller Jan 2021

Bioactivation Of Isoxazole-Containing Bromodomain And Extra-Terminal Domain (Bet) Inhibitors, Noah R Flynn, Michael D Ward, Mary A Schleiff, Corentine M C Laurin, Rohit Farmer, Stuart J Conway, Gunnar Boysen, S Joshua Swamidass, Grover P Miller

Open Access Publications

The 3,5-dimethylisoxazole motif has become a useful and popular acetyl-lysine mimic employed in isoxazole-containing bromodomain and extra-terminal (BET) inhibitors but may introduce the potential for bioactivations into toxic reactive metabolites. As a test, we coupled deep neural models for quinone formation, metabolite structures, and biomolecule reactivity to predict bioactivation pathways for 32 BET inhibitors and validate the bioactivation of select inhibitors experimentally. Based on model predictions, inhibitors were more likely to undergo bioactivation than reported non-bioactivated molecules containing isoxazoles. The model outputs varied with substituents indicating the ability to scale their impact on bioactivation. We selected OXFBD02, OXFBD04, and I-BET151 …


Rp11-362k2.2:Rp11-767i20.1 Genetic Variation Is Associated With Post-Reperfusion Therapy Parenchymal Hematoma. A Gwas Meta-Analysis, Elena Muiño, Laura Heitsch, Laura Ibañez, Carlos Cruchaga, Rajat Dhar, Jin-Moo Lee, Et Al Jan 2021

Rp11-362k2.2:Rp11-767i20.1 Genetic Variation Is Associated With Post-Reperfusion Therapy Parenchymal Hematoma. A Gwas Meta-Analysis, Elena Muiño, Laura Heitsch, Laura Ibañez, Carlos Cruchaga, Rajat Dhar, Jin-Moo Lee, Et Al

Open Access Publications

Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing …


Ser 71 Phosphorylation Inhibits Actin-Binding Of Profilin-1 And Its Apoptosis-Sensitizing Activity, Faliang Wang, Cuige Zhu, Shirong Cai, Aaron Boudreau, Sun-Joong Kim, Mina Bissell, Jieya Shao Jan 2021

Ser 71 Phosphorylation Inhibits Actin-Binding Of Profilin-1 And Its Apoptosis-Sensitizing Activity, Faliang Wang, Cuige Zhu, Shirong Cai, Aaron Boudreau, Sun-Joong Kim, Mina Bissell, Jieya Shao

Open Access Publications

The essential actin-binding factor profilin-1 (Pfn1) is a non-classical tumor suppressor with the abilities toboth inhibit cellular proliferation and augment chemotherapy-induced apoptosis. Besides actin, Pfn1 interacts with proteins harboring the poly-L-proline (PLP) motifs. Our recent work demonstrated that both nuclear localization and PLP-binding are required for tumor growth inhibition by Pfn1, and this is at least partially due to Pfn1 association with the PLP-containing ENL protein in the Super Elongation Complex (SEC) and the transcriptional inhibition of pro-cancer genes. In this paper, by identifying a phosphorylation event of Pfn1 at Ser


Using Monozygotic Twins To Dissect Common Genes In Posttraumatic Stress Disorder And Migraine, Charlotte K Bainomugisa, Heidi G Sutherland, Richard Parker, Allan F Mcrae, Larisa M Haupt, Lyn R Griffiths, Andrew Heath, Elliot C Nelson, Margaret J Wright, Ian B Hickie, Nicholas G Martin, Dale R Nyholt, Divya Mehta Jan 2021

Using Monozygotic Twins To Dissect Common Genes In Posttraumatic Stress Disorder And Migraine, Charlotte K Bainomugisa, Heidi G Sutherland, Richard Parker, Allan F Mcrae, Larisa M Haupt, Lyn R Griffiths, Andrew Heath, Elliot C Nelson, Margaret J Wright, Ian B Hickie, Nicholas G Martin, Dale R Nyholt, Divya Mehta

Open Access Publications

Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC …


The Stroke Neuro-Imaging Phenotype Repository: An Open Data Science Platform For Stroke Research, Hossein Mohammadian Foroushani, Rajat Dhar, Yasheng Chen, Jenny Gurney, Ali Hamzehloo, Jin-Moo Lee, Daniel S Marcus Jan 2021

The Stroke Neuro-Imaging Phenotype Repository: An Open Data Science Platform For Stroke Research, Hossein Mohammadian Foroushani, Rajat Dhar, Yasheng Chen, Jenny Gurney, Ali Hamzehloo, Jin-Moo Lee, Daniel S Marcus

Open Access Publications

Stroke is one of the leading causes of death and disability worldwide. Reducing this disease burden through drug discovery and evaluation of stroke patient outcomes requires broader characterization of stroke pathophysiology, yet the underlying biologic and genetic factors contributing to outcomes are largely unknown. Remedying this critical knowledge gap requires deeper phenotyping, including large-scale integration of demographic, clinical, genomic, and imaging features. Such big data approaches will be facilitated by developing and running processing pipelines to extract stroke-related phenotypes at large scale. Millions of stroke patients undergo routine brain imaging each year, capturing a rich set of data on stroke-related …