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Association Of Circulating Ceramides With Cardiac Structure And Function In The Community: The Framingham Heart Study, Chike C Nwabuo, Meredith Duncan, Vanessa Xanthakis, Linda R Peterson, Gary F Mitchell, David Mcmanus, Susan Cheng, Ramachandran S. Vasan
Association Of Circulating Ceramides With Cardiac Structure And Function In The Community: The Framingham Heart Study, Chike C Nwabuo, Meredith Duncan, Vanessa Xanthakis, Linda R Peterson, Gary F Mitchell, David Mcmanus, Susan Cheng, Ramachandran S. Vasan
Open Access Publications
Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography-tandem mass spectrometry-based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate …
Practice Variability In Pediatric Heart Transplantation: Opportunities For Collaboration, Aecha Marion Ybarra, Chesney Castleberry
Practice Variability In Pediatric Heart Transplantation: Opportunities For Collaboration, Aecha Marion Ybarra, Chesney Castleberry
Open Access Publications
The pediatric heart transplant population continues to grow and more centers are now providing advanced heart failure and transplant services. Though more patients are surviving after transplant, pediatric center protocols have remained relatively unchanged with limited research to guide protocol optimization. The authors explore recent literature reviewing the impact of the different approaches to pre and post-transplant care and as well as the impact these variations have on the field and future directions.
Transcriptional And Epigenetic Regulation Of Cardiac Electrophysiology, Jesus Jimenez, Stacey L Rentschler
Transcriptional And Epigenetic Regulation Of Cardiac Electrophysiology, Jesus Jimenez, Stacey L Rentschler
Open Access Publications
Spatiotemporal gene expression during cardiac development is a highly regulated process. Activation of key signaling pathways involved in electrophysiological programming, such as Notch and Wnt signaling, occurs in early cardiovascular development and these pathways are reactivated during pathologic remodeling. Direct targets of these signaling pathways have also been associated with inherited arrhythmias such as Brugada syndrome and arrhythmogenic cardiomyopathy. In addition, evidence is emerging from animal models that reactivation of Notch and Wnt signaling during cardiac pathology may predispose to acquired arrhythmias, underscoring the importance of elucidating the transcriptional and epigenetic effects on cardiac gene regulation. Here, we highlight specific …
Current Landscape Of Treatments For Wolfram Syndrome, Damien Abreu, Fumihiko Urano
Current Landscape Of Treatments For Wolfram Syndrome, Damien Abreu, Fumihiko Urano
Open Access Publications
Wolfram syndrome is a rare genetic spectrum disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration, and ranges from mild to severe clinical symptoms. There is currently no treatment to delay, halt, or reverse the progression of Wolfram syndrome, raising the urgency for innovative therapeutics for this disease. Here, we summarize our vision for developing novel treatment strategies and achieving a cure for Wolfram-syndrome-spectrum disorder.
Patient-Reported Outcomes Measurement Information System Physical Function Correlates With Toronto Extremity Salvage Score In An Orthopaedic Oncology Population, Kristen L Ploetze, Jay F Dalton, Ryan P Calfee, Douglas J Mcdonald, Regis J O'Keefe, Cara A Cipriano
Patient-Reported Outcomes Measurement Information System Physical Function Correlates With Toronto Extremity Salvage Score In An Orthopaedic Oncology Population, Kristen L Ploetze, Jay F Dalton, Ryan P Calfee, Douglas J Mcdonald, Regis J O'Keefe, Cara A Cipriano
Open Access Publications
Background: The National Institute of Health's Patient-Reported Outcomes Measurement Information System (PROMIS) uses computerised-adaptive testing to reduce survey burden and improve sensitivity. PROMIS is being used across medical and surgical disciplines but has not been studied in orthopaedic oncology.
Questions/purposes: The aim of the study was to compare PROMIS measures with upper extremity (UE) and lower extremity (LE) Toronto Extremity Salvage Score (TESS) by assessing the following: (1) responder burden, (2) correlation between scores and (3) floor/ceiling effects.
Patients and methods: This cross-sectional trial analysed all 97 adult patients treated surgically for a bone or soft tissue tumour at a …
Open-Sourced Civic Annotation Pipeline To Identify And Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes, Erica K Barnell, Adam Waalkes, Matt C Mosior, Kelsi Penewit, Kelsy C Cotto, Arpad M Danos, Lana M Sheta, Katie M Campbell, Kilannin Krysiak, Damian Rieke, Nicholas C Spies, Zachary L Skidmore, Colin C Pritchard, Todd A Fehniger, Ravindra Uppaluri, Ramaswamy Govindan, Malachi Griffith, Stephen J Salipante, Obi L Griffith
Open-Sourced Civic Annotation Pipeline To Identify And Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes, Erica K Barnell, Adam Waalkes, Matt C Mosior, Kelsi Penewit, Kelsy C Cotto, Arpad M Danos, Lana M Sheta, Katie M Campbell, Kilannin Krysiak, Damian Rieke, Nicholas C Spies, Zachary L Skidmore, Colin C Pritchard, Todd A Fehniger, Ravindra Uppaluri, Ramaswamy Govindan, Malachi Griffith, Stephen J Salipante, Obi L Griffith
Open Access Publications
PURPOSE: Clinical targeted sequencing panels are important for identifying actionable variants for patients with cancer; however, existing approaches do not provide transparent and rationally designed clinical panels to accommodate the rapidly growing knowledge within oncology.
MATERIALS AND METHODS: We used the Clinical Interpretations of Variants in Cancer (CIViC) database to develop an Open-Sourced CIViC Annotation Pipeline (OpenCAP). OpenCAP provides methods to identify variants within the CIViC database, build probes for variant capture, use probes on prospective samples, and link somatic variants to CIViC clinical relevance statements. OpenCAP was tested using a single-molecule molecular inversion probe (smMIP) capture design on 27 …
Intermediate-High Risk Pulmonary Embolism, Rosa Mirambeaux, Francisco León, Behnood Bikdeli, Raquel Morillo, Deisy Barrios, Edwin Mercedes, Lisa Moores, Victor Tapson, Roger D. Yusen, David Jiménez
Intermediate-High Risk Pulmonary Embolism, Rosa Mirambeaux, Francisco León, Behnood Bikdeli, Raquel Morillo, Deisy Barrios, Edwin Mercedes, Lisa Moores, Victor Tapson, Roger D. Yusen, David Jiménez
Open Access Publications
Limited information exists about the prevalence, management, and outcomes of intermediate-high risk patients with acute pulmonary embolism (PE). In a prospective cohort study, we evaluated consecutive patients with intermediate-high risk PE at a large, tertiary, academic medical center between January 1, 2015 and March 31, 2019. Adjudicated outcomes included PE-related mortality and a complicated course through 30 days after initiation of PE treatment. Repeat systolic blood pressure (SBP), heart rate (HR), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) measurements, and echocardiography were performed within 48 hours after diagnosis. Among 1,015 normotensive patients with acute PE, 97 (9.6%) had …
Incidence And Diagnostic Yield Of Repeat Urine Culture In Hospitalized Patients: An Opportunity For Diagnostic Stewardship, Kap Sum Foong, Satish Munigala, Ronald Jackups, Melanie L Yarbrough, Carey-Ann D. Burnham, David K Warren
Incidence And Diagnostic Yield Of Repeat Urine Culture In Hospitalized Patients: An Opportunity For Diagnostic Stewardship, Kap Sum Foong, Satish Munigala, Ronald Jackups, Melanie L Yarbrough, Carey-Ann D. Burnham, David K Warren
Open Access Publications
There is limited knowledge on the incidence, diagnostic yield, and cost associated with inappropriate repeat urine cultures. The factors that affect repeat urine culturing practices are not well understood. We conducted a retrospective study of adult inpatients who had ≥1 urine culture performed during their hospitalization between January 2015 and February 2018. We analyzed the proportion of inappropriate repeat urine cultures performed <48 h after the index culture. We defined an inappropriate repeat urine culture to be a repeat urine culture performed following a negative index culture or a repeat urine specimen obtained from the same urinary catheter. Overall, 28,141 urine cultures were performed on 21,306 patients. There were 2,060 (7.3%) urine cultures repeated in <48 h. Of these, 1,120 (54.4%) urine cultures were inappropriate. Predictors for inappropriate repeat urine cultures included collection of the initial urine sample for culture in the emergency department (adjusted odds ratio [aOR], 5.65; 95% confidence interval [CI], 4.70 to 6.78), male gender (aOR, 1.61; 95% CI, 1.42 to 1.84), congestive heart failure (aOR, 1.20; 95% CI, 1.03 to 1.38), and a longer hospital stay (aOR, 1.01 per day; 95% CI, 1.00 to 1.01). A patient with an index urine culture obtained from an indwelling catheter (aOR, 0.65; 95% CI, 0.53 to 0.80) was less likely to have an inappropriate repeat culture. Among 1,120 negative index urine cultures, only 4.7% of repeat cultures were positive for bacteriuria. The estimated laboratory charges for inappropriate repeat urine cultures were $16,800 over the study period. Among inpatients, over half of all urine cultures repeated in <48 h were inappropriate. This offers an opportunity for diagnostic stewardship and optimization of antimicrobial use.
Tic Suppression In Children With Recent-Onset Tics Predicts 1-Year Tic Outcome, Soyoung Kim, Deanna J Greene, Amy Robichaux-Viehoever, Emily C Bihun, Jonathan M Koller, Haley Acevedo, Bradley L Schlaggar, Kevin J Black
Tic Suppression In Children With Recent-Onset Tics Predicts 1-Year Tic Outcome, Soyoung Kim, Deanna J Greene, Amy Robichaux-Viehoever, Emily C Bihun, Jonathan M Koller, Haley Acevedo, Bradley L Schlaggar, Kevin J Black
Open Access Publications
Successful voluntary tic suppression is a key component of the behavioral interventions that are used to treat tic disorders. This study aimed to examine tic suppression in children with recent-onset tics and determine whether the capacity to suppress tics predicts future tic severity. We tested 45 children (30 male, mean age 7.74 years) with recent-onset tics (mean 3.47 months prior to the first study visit; baseline) and re-examined each child at the 12-month anniversary of the first recognized tic (follow-up). At the baseline visit, children performed a tic suppression task with several conditions: tic freely, inhibit tics given a verbal …
Casein Kinase 1 Family Proteins Promote Slimb-Dependent Expanded Degradation, Alexander D. Fulford, Maxine V. Holder, David Frith, Ambrosius P. Snijders, Nicolas Tapon, Paulo S. Ribeiro
Casein Kinase 1 Family Proteins Promote Slimb-Dependent Expanded Degradation, Alexander D. Fulford, Maxine V. Holder, David Frith, Ambrosius P. Snijders, Nicolas Tapon, Paulo S. Ribeiro
Open Access Publications
Hippo signalling integrates diverse stimuli related to epithelial architecture to regulate tissue growth and cell fate decisions. The Hippo kinase cascade represses the growth-promoting transcription co-activator Yorkie. The FERM protein Expanded is one of the main upstream Hippo signalling regulators in
Feasibility Of Detecting Change In Backscattered Energy Of Acoustic Harmonics In Locally Heated Tissues, Borna Maraghechi, Michael C Kolios, Jahan Tavakkoli
Feasibility Of Detecting Change In Backscattered Energy Of Acoustic Harmonics In Locally Heated Tissues, Borna Maraghechi, Michael C Kolios, Jahan Tavakkoli
Open Access Publications
No abstract provided.
Inhibition Of 4-Aminobutyrate Aminotransferase Protects Against Injury-Induced Osteoarthritis In Mice, Jie Shen, Cuicui Wang, Jun Ying, Taotao Xu, Audrey Mcalinden, Regis J. O'Keefe
Inhibition Of 4-Aminobutyrate Aminotransferase Protects Against Injury-Induced Osteoarthritis In Mice, Jie Shen, Cuicui Wang, Jun Ying, Taotao Xu, Audrey Mcalinden, Regis J. O'Keefe
Open Access Publications
Recently we demonstrated that ablation of the DNA methyltransferase enzyme, Dnmt3b, resulted in catabolism and progression of osteoarthritis (OA) in murine articular cartilage through a mechanism involving increased mitochondrial respiration. In this study, we identify 4-aminobutyrate aminotransferase (Abat) as a downstream target of Dnmt3b. Abat is an enzyme that metabolizes γ-aminobutyric acid to succinate, a key intermediate in the tricarboxylic acid cycle. We show that Dnmt3b binds to the Abat promoter, increases methylation of a conserved CpG sequence just upstream of the transcriptional start site, and inhibits Abat expression. Dnmt3b deletion in articular chondrocytes results in reduced methylation of the …
Identifying Reproducible Individual Differences In Childhood Functional Brain Networks: An Abcd Study, Scott Marek, Muriah D Wheelock, Ryland L Miller, Timothy O Laumann, Adam T Eggebrecht, Deanna J Greene, Deanna M Barch, Nico U F Dosenbach, Et Al
Identifying Reproducible Individual Differences In Childhood Functional Brain Networks: An Abcd Study, Scott Marek, Muriah D Wheelock, Ryland L Miller, Timothy O Laumann, Adam T Eggebrecht, Deanna J Greene, Deanna M Barch, Nico U F Dosenbach, Et Al
Open Access Publications
The 21-site Adolescent Brain Cognitive Development (ABCD) study provides an unparalleled opportunity to characterize functional brain development via resting-state functional connectivity (RSFC) and to quantify relationships between RSFC and behavior. This multi-site data set includes potentially confounding sources of variance, such as differences between data collection sites and/or scanner manufacturers, in addition to those inherent to RSFC (e.g., head motion). The ABCD project provides a framework for characterizing and reproducing RSFC and RSFC-behavior associations, while quantifying the extent to which sources of variability bias RSFC estimates. We quantified RSFC and functional network architecture in 2,188 9-10-year old children from the …
Noninvasive Mapping Of The Electrophysiological Substrate In Cardiac Amyloidosis And Its Relationship To Structural Abnormalities, Michele Orini, Adam J Graham, Ana Martinez-Naharro, Christopher M Andrews, Antonio De Marvao, Ben Statton, Stuart A Cook, Declan P O'Regan, Philip N Hawkins, Yoram Rudy, Marianna Fontana, Pier D Lambiase
Noninvasive Mapping Of The Electrophysiological Substrate In Cardiac Amyloidosis And Its Relationship To Structural Abnormalities, Michele Orini, Adam J Graham, Ana Martinez-Naharro, Christopher M Andrews, Antonio De Marvao, Ben Statton, Stuart A Cook, Declan P O'Regan, Philip N Hawkins, Yoram Rudy, Marianna Fontana, Pier D Lambiase
Open Access Publications
Background The relationship between structural pathology and electrophysiological substrate in cardiac amyloidosis is unclear. Differences between light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis may have prognostic implications. Methods and Results ECG imaging and cardiac magnetic resonance studies were conducted in 21 cardiac amyloidosis patients (11 AL and 10 ATTR). Healthy volunteers were included as controls. With respect to ATTR, AL patients had lower amyloid volume (51.0/37.7 versus 73.7/16.4 mL, P=0.04), lower myocardial cell volume (42.6/19.1 versus 58.5/17.2 mL, P=0.021), and higher T1 (1172/64 versus 1109/80 ms, P=0.022) and T2 (53.4/2.9 versus 50.0/3.1 ms, P=0.003). ECG imaging revealed differences between cardiac …
Race And Risk Of Subsequent Aggressive Breast Cancer Following Ductal Carcinoma In Situ, Ying Liu, Robert West, Jason D Weber, Graham A Colditz
Race And Risk Of Subsequent Aggressive Breast Cancer Following Ductal Carcinoma In Situ, Ying Liu, Robert West, Jason D Weber, Graham A Colditz
Open Access Publications
BACKGROUND: General populations of black women have a higher risk of developing breast cancer negative for both estrogen receptor (ER) and progesterone receptor (PR) in comparison with white counterparts. Racial differences remain unknown in the risk of developing aggressive invasive breast cancer (IBC) that is characterized by negativity for both ER and PR (ER-PR-) or higher 21-gene recurrence scores after ductal carcinoma in situ (DCIS).
METHODS: This study identified 163,892 women (10.5% black, 9.8% Asian, and 8.6% Hispanic) with incident DCIS between 1990 and 2015 from the Surveillance, Epidemiology, and End Results data sets. Cox proportional hazards regression was used …
Neural Correlates Of Early Deliberate Emotion Regulation: Young Children's Responses To Interpersonal Scaffolding., Adam S Grabell, Theodore J Huppert, Frank A Fishburn, Yanwei Li, Christina O Hlutkowsky, Hannah M Jones, Lauren S Wakschlag, Susan B Perlman
Neural Correlates Of Early Deliberate Emotion Regulation: Young Children's Responses To Interpersonal Scaffolding., Adam S Grabell, Theodore J Huppert, Frank A Fishburn, Yanwei Li, Christina O Hlutkowsky, Hannah M Jones, Lauren S Wakschlag, Susan B Perlman
Open Access Publications
Deliberate emotion regulation, the ability to willfully modulate emotional experiences, is shaped through interpersonal scaffolding and forecasts later functioning in multiple domains. However, nascent deliberate emotion regulation in early childhood is poorly understood due to a paucity of studies that simulate interpersonal scaffolding of this skill and measure its occurrence in multiple modalities. Our goal was to identify neural and behavioral components of early deliberate emotion regulation to identify patterns of competent and deficient responses. A novel probe was developed to assess deliberate emotion regulation in young children. Sixty children (age 4-6 years) were randomly assigned to deliberate emotion regulation …
Identification Of 4-Amino-Thieno[2,3-D]Pyrimidines As Qcrb Inhibitors In Mycobacterium Tuberculosis, Gregory A Harrison, Anne E Mayer Bridwell, Megh Singh, Keshav Jayaraman, Leslie A Weiss, Rachel L Kinsella, Janessa S Aneke, Kelly Flentie, Miranda E Schene, Margaret Gaggioli, Samantha D Solomon, Scott A Wildman, Marvin J Meyers, Christina L Stallings
Identification Of 4-Amino-Thieno[2,3-D]Pyrimidines As Qcrb Inhibitors In Mycobacterium Tuberculosis, Gregory A Harrison, Anne E Mayer Bridwell, Megh Singh, Keshav Jayaraman, Leslie A Weiss, Rachel L Kinsella, Janessa S Aneke, Kelly Flentie, Miranda E Schene, Margaret Gaggioli, Samantha D Solomon, Scott A Wildman, Marvin J Meyers, Christina L Stallings
Open Access Publications
Antibiotic resistance is a global crisis that threatens our ability to treat bacterial infections, such as tuberculosis, caused by
The Complete Mitochondrial Genome Of The New Zealand Parasitic Roundworm Teladorsagia Circumcincta (Trichostrongyloidea: Haemonchidae) Field Strain Nz_Teci_Np, Nikola Palevich, Paul H Maclean, Makedonka Mitreva, Richard Scott, David Leathwick
The Complete Mitochondrial Genome Of The New Zealand Parasitic Roundworm Teladorsagia Circumcincta (Trichostrongyloidea: Haemonchidae) Field Strain Nz_Teci_Np, Nikola Palevich, Paul H Maclean, Makedonka Mitreva, Richard Scott, David Leathwick
Open Access Publications
The complete mitochondrial genome of the New Zealand parasitic nematode
Virus-Induced Cochlear Inflammation In Newborn Mice Alters Auditory Function, Cathy Yea Won Sung, Maria C. Seleme, Shelby Payne, Stipan Jonjic, Keiko Hirose, William Britt
Virus-Induced Cochlear Inflammation In Newborn Mice Alters Auditory Function, Cathy Yea Won Sung, Maria C. Seleme, Shelby Payne, Stipan Jonjic, Keiko Hirose, William Britt
Open Access Publications
Although human cytomegalovirus (HCMV) is a known cause of sensorineural hearing loss in infants with congenital HCMV (cCMV) infections, mechanisms that contribute to sensorineural hearing loss (SNHL) in infants with cCMV infection are not well defined. Using a murine model of CMV infection during auditory development, we have shown that peripheral infection of newborn mice with murine CMV (MCMV) results in focal infection of the cochlea and virus-induced cochlear inflammation. Approximately 50%-60% of infected mice exhibited increased auditory brainstem response (ABR) thresholds across a range of sound frequencies. Histological analyses of the cochlea in MCMV-infected mice with elevated ABR thresholds …
Vincristine And Bortezomib Use Distinct Upstream Mechanisms To Activate A Common Sarm1-Dependent Axon Degeneration Program, Stefanie Geisler, Ryan A Doan, Galen C Cheng, Aysel Cetinkaya-Fisgin, Shay X Huang, Ahmet Höke, Jeffrey Milbrandt, Aaron Diantonio
Vincristine And Bortezomib Use Distinct Upstream Mechanisms To Activate A Common Sarm1-Dependent Axon Degeneration Program, Stefanie Geisler, Ryan A Doan, Galen C Cheng, Aysel Cetinkaya-Fisgin, Shay X Huang, Ahmet Höke, Jeffrey Milbrandt, Aaron Diantonio
Open Access Publications
Chemotherapy-induced peripheral neuropathy is one of the most prevalent dose-limiting toxicities of anticancer therapy. Development of effective therapies to prevent chemotherapy-induced neuropathies could be enabled by a mechanistic understanding of axonal breakdown following exposure to neuropathy-causing agents. Here, we reveal the molecular mechanisms underlying axon degeneration induced by 2 widely used chemotherapeutic agents with distinct mechanisms of action: vincristine and bortezomib. We showed previously that genetic deletion of SARM1 blocks vincristine-induced neuropathy and demonstrate here that it also prevents axon destruction following administration of bortezomib in vitro and in vivo. Using cultured neurons, we found that vincristine and bortezomib converge …
Association Of Timing Of Adverse Childhood Experiences And Caregiver Support With Regionally Specific Brain Development In Adolescents, Joan L. Luby, Rebecca Tillman, Deanna M. Barch
Association Of Timing Of Adverse Childhood Experiences And Caregiver Support With Regionally Specific Brain Development In Adolescents, Joan L. Luby, Rebecca Tillman, Deanna M. Barch
Open Access Publications
Importance: Few data are available to inform the associations and timing of the associations between adversity, caregiver support, and brain outcomes. Consideration of timing has important public health implications to inform more precise prevention strategies.
Objective: To evaluate the timing and regional specificity of the association between adverse childhood experiences (ACEs) and caregiver support to structural development of limbic and striatal brain regions in middle childhood and adolescence.
Design, Setting, and Participants: This 15-year developmental, neuroimaging cohort study included 211 children and their caregivers screened from day care centers and preschools in the St Louis, Missouri, metropolitan area during the …
A Gorilla Adenovirus-Based Vaccine Against Zika Virus Induces Durable Immunity And Confers Protection In Pregnancy, Ahmed O Hassan, Igor P Dmitriev, Elena A Kashentseva, Haiyan Zhao, Douglas E Brough, Daved H Fremont, David T Curiel, Michael S Diamond
A Gorilla Adenovirus-Based Vaccine Against Zika Virus Induces Durable Immunity And Confers Protection In Pregnancy, Ahmed O Hassan, Igor P Dmitriev, Elena A Kashentseva, Haiyan Zhao, Douglas E Brough, Daved H Fremont, David T Curiel, Michael S Diamond
Open Access Publications
The teratogenic potential of Zika virus (ZIKV) has made the development of an effective vaccine a global health priority. Here, we generate two gorilla adenovirus-based ZIKV vaccines that encode for pre-membrane (prM) and envelope (E) proteins (GAd-Zvp) or prM and the ectodomain of E protein (GAd-Eecto). Both vaccines induce humoral and cell-mediated immune responses and prevent lethality after ZIKV challenge in mice. Protection is antibody dependent, CD8
Wnd/Dlk Is A Critical Target Of Fmrp Responsible For Neurodevelopmental And Behavior Defects In The Drosophila Model Of Fragile X Syndrome, Alexandra Russo, Aaron Diantonio
Wnd/Dlk Is A Critical Target Of Fmrp Responsible For Neurodevelopmental And Behavior Defects In The Drosophila Model Of Fragile X Syndrome, Alexandra Russo, Aaron Diantonio
Open Access Publications
Fragile X syndrome (FXS) is the leading heritable cause of intellectual disability and commonly co-occurs with autism spectrum disorder. Silencing of the Fmr1 gene leads to the absence of the protein product, fragile X mental retardation protein (FMRP), which represses translation of many target mRNAs. Excess translation of these targets is one cause of neuronal dysfunction in FXS. Utilizing the Drosophila model of FXS, we identified the mitogen-activated protein kinase kinase kinase (MAP3K) Wallenda/dual leucine zipper kinase (DLK) as a critical target of FMRP. dFMRP binds Wallenda mRNA and is required to limit Wallenda protein levels. In dFmr1 mutants, Wallenda …
Mining Biosynthetic Gene Clusters In Virgibacillus Genomes, Ghofran Othoum, Salim Bougouffa, Ameerah Bokhari, Feras F Lafi, Takashi Gojobori, Heribert Hirt, Ivan Mijakovic, Vladimir B Bajic, Magbubah Essack
Mining Biosynthetic Gene Clusters In Virgibacillus Genomes, Ghofran Othoum, Salim Bougouffa, Ameerah Bokhari, Feras F Lafi, Takashi Gojobori, Heribert Hirt, Ivan Mijakovic, Vladimir B Bajic, Magbubah Essack
Open Access Publications
BACKGROUND: Biosynthetic gene clusters produce a wide range of metabolites with activities that are of interest to the pharmaceutical industry. Specific interest is shown towards those metabolites that exhibit antimicrobial activities against multidrug-resistant bacteria that have become a global health threat. Genera of the phylum Firmicutes are frequently identified as sources of such metabolites, but the biosynthetic potential of its Virgibacillus genus is not known. Here, we used comparative genomic analysis to determine whether Virgibacillus strains isolated from the Red Sea mangrove mud in Rabigh Harbor Lagoon, Saudi Arabia, may be an attractive source of such novel antimicrobial agents.
RESULTS: …
Expression Of The Mxra8 Receptor Promotes Alphavirus Infection And Pathogenesis In Mice And Drosophila, Rong Zhang, James T Earnest, Arthur S Kim, Emma S Winkler, Pritesh Desai, Lucas J Adams, Gaowei Hu, Christopher Bullock, Beth Gold, Sara Cherry, Michael S Diamond
Expression Of The Mxra8 Receptor Promotes Alphavirus Infection And Pathogenesis In Mice And Drosophila, Rong Zhang, James T Earnest, Arthur S Kim, Emma S Winkler, Pritesh Desai, Lucas J Adams, Gaowei Hu, Christopher Bullock, Beth Gold, Sara Cherry, Michael S Diamond
Open Access Publications
Mxra8 is a recently described receptor for multiple alphaviruses, including Chikungunya (CHIKV), Mayaro (MAYV), Ross River (RRV), and O'nyong nyong (ONNV) viruses. To determine its role in pathogenesis, we generated mice with mutant Mxra8 alleles: an 8-nucleotide deletion that produces a truncated, soluble form (Mxra8
Structural Disconnections Explain Brain Network Dysfunction After Stroke, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman
Structural Disconnections Explain Brain Network Dysfunction After Stroke, Joseph C Griffis, Nicholas V Metcalf, Maurizio Corbetta, Gordon L Shulman
Open Access Publications
Stroke causes focal brain lesions that disrupt functional connectivity (FC), a measure of activity synchronization, throughout distributed brain networks. It is often assumed that FC disruptions reflect damage to specific cortical regions. However, an alternative explanation is that they reflect the structural disconnection (SDC) of white matter pathways. Here, we compare these explanations using data from 114 stroke patients. Across multiple analyses, we find that SDC measures outperform focal damage measures, including damage to putative critical cortical regions, for explaining FC disruptions associated with stroke. We also identify a core mode of structure-function covariation that links the severity of interhemispheric …
Videofluoroscopic Swallow Study Features Of Lower Esophageal Sphincter Achalasia-Like Syndrome In Dogs, Megan E Grobman, James Schachtel, C Prakash Gyawali, Teresa E Lever, Carol R Reinero
Videofluoroscopic Swallow Study Features Of Lower Esophageal Sphincter Achalasia-Like Syndrome In Dogs, Megan E Grobman, James Schachtel, C Prakash Gyawali, Teresa E Lever, Carol R Reinero
Open Access Publications
BACKGROUND: Megaesophagus (ME) carries a poor long-term prognosis in dogs. In people, lower esophageal sphincter (LES) disorders causing functional obstruction are rare causes of ME that may respond to targeted treatment. Functional LES disorders are reported rarely in dogs because of challenges in diagnostic methodologies.
HYPOTHESIS/OBJECTIVES: To identify dogs with videofluoroscopic swallow study (VFSS) features of LES achalasia-like syndrome (LES-AS). We hypothesized that dogs with LES-AS could be distinguished from normal dogs using standardized VFSS criteria.
ANIMALS: Dogs with LES-AS by VFSS (n = 19), healthy normal dogs (n = 20).
METHODS: Retrospective study. One-hundred thirty dogs presented to the …
Distribution Of Cardiovascular Health By Individual- And Neighborhood-Level Socioeconomic Status: Findings From The Jackson Heart Study, Randi E Foraker, Christopher Bush, Melissa A Greiner, Mario Sims, Kamal Henderson, Sakima Smith, Aurelian Bidulescu, Abigail B Shoben, N Chantelle Hardy, Emily O'Brien
Distribution Of Cardiovascular Health By Individual- And Neighborhood-Level Socioeconomic Status: Findings From The Jackson Heart Study, Randi E Foraker, Christopher Bush, Melissa A Greiner, Mario Sims, Kamal Henderson, Sakima Smith, Aurelian Bidulescu, Abigail B Shoben, N Chantelle Hardy, Emily O'Brien
Open Access Publications
BACKGROUND: Data demonstrate a positive relationship between socioeconomic status (SES) and cardiovascular health (CVH).
OBJECTIVE: To assess the association between individual- and neighborhood-level SES and CVH among participants of the JHS (Jackson Heart Study), a community-based cohort of African Americans in Jackson, Mississippi.
METHODS: We included all JHS participants with complete SES and CVH information at the baseline study visit (n = 3,667). We characterized individual- and neighborhood-level SES according to income (primary analysis) and education (secondary analysis), respectively. The outcome of interest for these analyses was a CVH score, based on 7 modifiable behaviors and factors, summed to a …
Hiv And Tuberculosis Co-Infection In East Asia And The Pacific From 1990 To 2017: Results From The Global Burden Of Disease Study 2017, Jianrong Zhang, Stephanie Kern-Allely, Tiange Yu, Rumi Kato Price
Hiv And Tuberculosis Co-Infection In East Asia And The Pacific From 1990 To 2017: Results From The Global Burden Of Disease Study 2017, Jianrong Zhang, Stephanie Kern-Allely, Tiange Yu, Rumi Kato Price
Open Access Publications
Background: Periodic surveillance is crucial to provide information for resource allocation to control HIV/AIDS, tuberculosis (TB), and their co-infection, especially in areas with high morbidity and mortality like East Asia and the Pacific. Therefore, we examined the morbidity and mortality of HIV/AIDS and TB co-infection in this region from 1990 to 2017.
Methods: Utilizing the Global Burden of Disease (GBD) Study 2017, we obtained incidence, prevalence, and mortality numbers and rates of HIV/AIDS and TB co-infection, including HIV and drug-susceptible TB (DS-TB), multidrug-resistant TB without extensive drug resistance (MDR-TB without XDR), and extensive drug-resistant TB (XDR-TB). The trends in incidence, …
Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy (Ebus-Ifb)-Technical Review, George Cheng, Amit Mahajan, Scott Oh, Sadia Benzaquen, Alexander Chen
Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy (Ebus-Ifb)-Technical Review, George Cheng, Amit Mahajan, Scott Oh, Sadia Benzaquen, Alexander Chen
Open Access Publications
Endobronchial ultrasound (EBUS) and transbronchial needle aspiration (TBNA) have changed the landscape of pulmonology. Mediastinal structures beyond the confines of airway walls are visualized in real-time with EBUS, leading to improved accuracy of tissue sampling and diagnostic yield. With the development of various needle sizes ranging from 25-G to 19-G, the sampling of lymph nodes is becoming easier and more commonplace. Yet, certain conditions such as sarcoidosis and lymphoma may still be difficult to diagnose via EBUS-TBNA. Furthermore, in the age of targeted therapy, there are more demands on EBUS-TBNA samples for molecular marker testing and next-generation sequencing. Here, we …