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Articles 4201 - 4230 of 5889
Full-Text Articles in Entire DC Network
The Arabic Version Of The Personality Inventory For The Dsm-5 (Pid-5) In A Clinical Sample Of United Arab Emirates (Uae) Nationals, Olga Coelho, Rute Pires, Ana Sousa Ferreira, Bruno Gonçalves, Samia A. Alkhoori, Mohamed A. Sayed, Amany Elrasheed, Sara Belhoul, Maryam Aljassmi, Joana Stocker
The Arabic Version Of The Personality Inventory For The Dsm-5 (Pid-5) In A Clinical Sample Of United Arab Emirates (Uae) Nationals, Olga Coelho, Rute Pires, Ana Sousa Ferreira, Bruno Gonçalves, Samia A. Alkhoori, Mohamed A. Sayed, Amany Elrasheed, Sara Belhoul, Maryam Aljassmi, Joana Stocker
All Works
Objectives: We aimed to test the potential of the Arabic version of the PID-5 to distinguish between clinical and non-clinical participants, as well as to examine its convergent validity and factor structure in an Emirati clinical sample. Methods: The Arabic version of the PID-5 was administered to a clinical sample comprised of 156 participants (Mage = 31.38, SD = 8.99, 37.8% male, 62.2% female) and a community sample also comprised of 156 participants (Mage = 31.43, SD = 9.52, 37.2% male, 62.8% female). We addressed the descriptive measures, internal consistency, mean rank scores differences, convergent validity with SCL-90-R, and PID-5's …
Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute
Genetics Of Smoking Behaviors In American Indians, Jeffrey A Henderson, Dedra S Buchwald, Barbara V Howard, Patricia Nez Henderson, Yafang Li, Rachel F Tyndale, Christopher I Amos, Olga Y Gorlova, Collaborative To Improve Native Cancer Outcomes (Cinco), A P50 Center For Population Health And Health Disparities Program Project Sponsored By The National Cancer Institute
Faculty, Staff and Students Publications
BACKGROUND: The smoking behavior of American Indians (AI) differs from that of non-Hispanic whites (NHW). Typically light smokers, cessation interventions in AIs are generally less effective. To develop more effective cessation programs for AIs, clinicians, researchers, and public health workers need a better understanding of the genetic factors involved in their smoking behavior. Our aim was to assess whether SNPs associated with smoking behavior in NHWs are also associated with smoking in AIs.
METHODS: We collected questionnaire data on smoking behaviors and analyzed blood and saliva samples from two Tribal populations with dramatically different cultures and smoking prevalence, one in …
Chronic Ulcers And Malnutrition In An African Patient\, Timothy G Singer, Monica A Bray, Audrey Chan, Saki Ikeda, Brittany Walters, Maren Y Fuller, Carla Falco
Chronic Ulcers And Malnutrition In An African Patient\, Timothy G Singer, Monica A Bray, Audrey Chan, Saki Ikeda, Brittany Walters, Maren Y Fuller, Carla Falco
Faculty, Staff and Students Publications
An 11-year-old female with a congenitally malformed left hand, sickle-cell trait, asthma, and history of appendicitis was transferred from Zambia for evaluation and treatment of widespread suppurative and ulcerative skin lesions that typically appeared following trauma to her skin. The ulcers first presented 3 years earlier but had markedly worsened in the 9 months prior to transfer, spreading circumferentially on her extremities and abdomen at the site of an appendectomy. They were painful and did not resolve with multiple courses of intravenous (IV) antibiotics and close management by a Pediatric Infectious Disease specialist working for a non-governmental organization (NGO) in …
Maternal Altitude And Risk Of Low Birthweight: A Systematic Review And Meta-Analyses, Lin Yang, Veronika Helbich-Poschacher, Chao Cao, Katrin Klebermass-Schrehof, Thomas Waldhoer
Maternal Altitude And Risk Of Low Birthweight: A Systematic Review And Meta-Analyses, Lin Yang, Veronika Helbich-Poschacher, Chao Cao, Katrin Klebermass-Schrehof, Thomas Waldhoer
2020-Current year OA Pubs
BACKGROUND: Previous studies conducted in high altitude regions showed that maternal altitude was associated with low birth weight. The effect size of birth weight reduction is inclusive with unknown effects due to preterm birth. We systematically reviewed the literature and synthesize evidence on associations between altitude elevation from sea level and birth weight.
METHOD: We searched MEDLINE/PubMed, Embase, Scopus, Web of Science, and Cochrane database, from inception to May 5, 2020 for studies that reported maternal altitude and birth weight. Bayesian multilevel effect models were employed to estimate the effect size on birth weight (and gestational age) associated with altitude. …
High Molecular Weight Adiponectin Levels Are Inversely Associated With Adiposity In Pediatric Brain Tumor Survivors., Rebecca Ronsley, Shahrad Rod Rassekh, Adam Fleming, Brianna Empringham, William Jennings, Carol Portwine, Sarah Burrow, Shayna Zelcer, Donna L Johnston, Lehana Thabane, M Constantine Samaan
High Molecular Weight Adiponectin Levels Are Inversely Associated With Adiposity In Pediatric Brain Tumor Survivors., Rebecca Ronsley, Shahrad Rod Rassekh, Adam Fleming, Brianna Empringham, William Jennings, Carol Portwine, Sarah Burrow, Shayna Zelcer, Donna L Johnston, Lehana Thabane, M Constantine Samaan
Paediatrics Publications
While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin's profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) …
Association Of Visceral Adipose Tissue And Subclinical Atherosclerosis In Us-Born Mexican Americans But Not First Generation Immigrants, Clarence Gill, Miryoung Lee, Kristina P Vatcheva, Nahid Rianon, Beverly Smulevitz, David D Mcpherson, Joseph B Mccormick, Susan P Fisher-Hoch, Susan T Laing
Association Of Visceral Adipose Tissue And Subclinical Atherosclerosis In Us-Born Mexican Americans But Not First Generation Immigrants, Clarence Gill, Miryoung Lee, Kristina P Vatcheva, Nahid Rianon, Beverly Smulevitz, David D Mcpherson, Joseph B Mccormick, Susan P Fisher-Hoch, Susan T Laing
Faculty, Staff and Student Publications
Background Excess visceral adipose tissue (VAT) is a primary driver for the cardiometabolic complications of obesity; VAT-associated cardiovascular disease risk varies by race, but most studies have been done on Non-Hispanics. This study aimed to evaluate the clinical and metabolic correlates of VAT, its association with subclinical atherosclerosis, and the factors affecting this association in Mexican Americans. Methods and Results Participants (n=527) were drawn from the Cameron County Hispanic Cohort (CCHC), on whom a carotid ultrasound to assess carotid intima media thickness and a dual-energy X-ray absorptiometry scan to assess for VAT were obtained. Those in the highest quartiles of …
Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett
Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett
2020-Current year OA Pubs
BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.
METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive …
The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski
The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski
Open Access Publications
The closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are …
Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis
Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis
Articles, Abstracts, and Reports
Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities …
Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins
Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins
Pathology Research and Scholarship
BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway.
METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.
RESULTS: NAb titers in …
Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M Richters, Sangappa B Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H Thaker, Malachi Griffith, Ramakrishna Kommagani
Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M Richters, Sangappa B Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H Thaker, Malachi Griffith, Ramakrishna Kommagani
2020-Current year OA Pubs
Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the United States. Here, in an attempt to identify new prognostic and therapeutic targets, we focused on a new area for this cancer-alternative mRNA splicing-and investigated whether splicing factor, SF3B1, plays an important role in endometrial cancer pathogenesis. Using a tissue microarray, we found that human endometrial tumors expressed …
Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton
Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton
Faculty, Staff and Students Publications
Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …
At Three Years, Patients With Acute Lymphoblastic Leukaemia Are Still At Risk For Relapse. Results Of The International Mrc Ukallxii/Ecog E2993 Trial, Chezi Ganzel, Xin V. Wang, Jacob M. Rowe, Susan M. Richards, Georgina Buck, David I. Marks, Mark R. Litzow, Elisabeth M. Paietta, Letizia Foroni, Selina M. Luger, Cheryl L. Willman, Charles G. Mullighan, Kathryn G. Roberts, Peter H. Wiernik, Dan Douer, Hillard M. Lazarus, Martin S. Tallman, Anthony H. Goldstone
At Three Years, Patients With Acute Lymphoblastic Leukaemia Are Still At Risk For Relapse. Results Of The International Mrc Ukallxii/Ecog E2993 Trial, Chezi Ganzel, Xin V. Wang, Jacob M. Rowe, Susan M. Richards, Georgina Buck, David I. Marks, Mark R. Litzow, Elisabeth M. Paietta, Letizia Foroni, Selina M. Luger, Cheryl L. Willman, Charles G. Mullighan, Kathryn G. Roberts, Peter H. Wiernik, Dan Douer, Hillard M. Lazarus, Martin S. Tallman, Anthony H. Goldstone
Pathology Research and Scholarship
Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. …
Evidence For Craniofacial Enhancer Variation Underlying Nonsyndromic Cleft Lip And Palate, Vershanna E Morris, S Shahrukh Hashmi, Lisha Zhu, Lorena Maili, Christian Urbina, Steven Blackwell, Matthew R Greives, Edward P Buchanan, John B Mulliken, Susan H Blanton, W Jim Zheng, Jacqueline T Hecht, Ariadne Letra
Evidence For Craniofacial Enhancer Variation Underlying Nonsyndromic Cleft Lip And Palate, Vershanna E Morris, S Shahrukh Hashmi, Lisha Zhu, Lorena Maili, Christian Urbina, Steven Blackwell, Matthew R Greives, Edward P Buchanan, John B Mulliken, Susan H Blanton, W Jim Zheng, Jacqueline T Hecht, Ariadne Letra
Faculty, Staff and Student Publications
Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect for which only ~ 20% of the underlying genetic variation has been identified. Variants in noncoding regions have been increasingly suggested to contribute to the missing heritability. In this study, we investigated whether variation in craniofacial enhancers contributes to NSCLP. Candidate enhancers were identified using VISTA Enhancer Browser and previous publications. Prioritization was based on patterning defects in knockout mice, deletion/duplication of craniofacial genes in animal models and results of whole exome/whole genome sequencing studies. This resulted in 20 craniofacial enhancers to be investigated. Custom amplicon-based …
Serially Assessed Bisphenol A And Phthalate Exposure And Association With Kidney Function In Children With Chronic Kidney Disease In The Us And Canada: A Longitudinal Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Teresa M. Attina, Mrudula Naidu, Rajendiran Karthikraj, Kurunthachalam Kannan, Bradley A. Warady, Susan Furth, Suzanne Vento, Howard Trachtman, Leonardo Trasande
Serially Assessed Bisphenol A And Phthalate Exposure And Association With Kidney Function In Children With Chronic Kidney Disease In The Us And Canada: A Longitudinal Cohort Study., Melanie H. Jacobson, Yinxiang Wu, Mengling Liu, Teresa M. Attina, Mrudula Naidu, Rajendiran Karthikraj, Kurunthachalam Kannan, Bradley A. Warady, Susan Furth, Suzanne Vento, Howard Trachtman, Leonardo Trasande
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.
METHODS AND FINDINGS: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) …
Neurofibromatosis 1 - Mutant Microglia Exhibit Sexually-Dimorphic Cyclic Amp-Dependent Purinergic Defects, Nirmeen Elmadany, Francesca Logiacco, Alice Buonfiglioli, Verena C Haage, Elizabeth C Wright-Jin, Alexander Schattenberg, Roxane M Papawassiliou, Helmut Kettenmann, Marcus Semtner, David H Gutmann
Neurofibromatosis 1 - Mutant Microglia Exhibit Sexually-Dimorphic Cyclic Amp-Dependent Purinergic Defects, Nirmeen Elmadany, Francesca Logiacco, Alice Buonfiglioli, Verena C Haage, Elizabeth C Wright-Jin, Alexander Schattenberg, Roxane M Papawassiliou, Helmut Kettenmann, Marcus Semtner, David H Gutmann
Open Access Publications
As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted …
Low-Shot Deep Learning Of Diabetic Retinopathy With Potential Applications To Address Artificial Intelligence Bias In Retinal Diagnostics And Rare Ophthalmic Diseases, Philippe Burlina, William Paul, Philip Mathew, Neil Joshi, Katia D Pacheco, Neil M Bressler
Low-Shot Deep Learning Of Diabetic Retinopathy With Potential Applications To Address Artificial Intelligence Bias In Retinal Diagnostics And Rare Ophthalmic Diseases, Philippe Burlina, William Paul, Philip Mathew, Neil Joshi, Katia D Pacheco, Neil M Bressler
Faculty, Staff and Students Publications
IMPORTANCE: Recent studies have demonstrated the successful application of artificial intelligence (AI) for automated retinal disease diagnostics but have not addressed a fundamental challenge for deep learning systems: the current need for large, criterion standard-annotated retinal data sets for training. Low-shot learning algorithms, aiming to learn from a relatively low number of training data, may be beneficial for clinical situations involving rare retinal diseases or when addressing potential bias resulting from data that may not adequately represent certain groups for training, such as individuals older than 85 years.
OBJECTIVE: To evaluate whether low-shot deep learning methods are beneficial when using …
An Autism-Linked Missense Mutation In Shank3 Reveals The Modularity Of Shank3 Function, Li Wang, Kaifang Pang, Kihoon Han, Carolyn J Adamski, Wei Wang, Lingjie He, Jason K Lai, Vitaliy V Bondar, Joseph G Duman, Ronald Richman, Kimberley F Tolias, Patrick Barth, Timothy Palzkill, Zhandong Liu, J Lloyd Holder, Huda Y Zoghbi
An Autism-Linked Missense Mutation In Shank3 Reveals The Modularity Of Shank3 Function, Li Wang, Kaifang Pang, Kihoon Han, Carolyn J Adamski, Wei Wang, Lingjie He, Jason K Lai, Vitaliy V Bondar, Joseph G Duman, Ronald Richman, Kimberley F Tolias, Patrick Barth, Timothy Palzkill, Zhandong Liu, J Lloyd Holder, Huda Y Zoghbi
Faculty, Staff and Students Publications
Genome sequencing has revealed an increasing number of genetic variations that are associated with neuropsychiatric disorders. Frequently, studies limit their focus to likely gene-disrupting mutations because they are relatively easy to interpret. Missense variants, instead, have often been undervalued. However, some missense variants can be informative for developing a more profound understanding of disease pathogenesis and ultimately targeted therapies. Here we present an example of this by studying a missense variant in a well-known autism spectrum disorder (ASD) causing gene SHANK3. We analyzed Shank3's in vivo phosphorylation profile and identified S685 as one phosphorylation site where one ASD-linked variant has …
Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee
Phase 1 Study Of The Mdm2 Antagonist Ro6839921 In Patients With Acute Myeloid Leukemia, Geoffrey L Uy, Sarit Assouline, Anne-Marie Young, Steven Blotner, Brian Higgins, Lin-Chi Chen, Karen Yee
2020-Current year OA Pubs
In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) …
Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev
Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev
Faculty, Staff and Students Publications
RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.
OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.
METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca
CONCLUSIONS: Preexisting Ca
Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze
Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze
Pathology Research and Scholarship
Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We …
Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, Hannah M Campbell, Ann P Quick, Issam Abu-Taha, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens
Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, Hannah M Campbell, Ann P Quick, Issam Abu-Taha, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens
Faculty, Staff and Students Publications
BACKGROUND: Enhanced diastolic calcium (Ca
METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca
RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca
CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca
Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt
Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt
Faculty, Staff and Students Publications
Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …
Swell1 Regulates Skeletal Muscle Cell Size, Intracellular Signaling, Adiposity And Glucose Metabolism, Ashutosh Kumar, Litao Xie, Chau My Ta, Antentor O Hinton, Susheel K Gunasekar, Rachel A Minerath, Karen Shen, Joshua M Maurer, Chad E Grueter, E Dale Abel, Gretchen Meyer, Rajan Sah
Swell1 Regulates Skeletal Muscle Cell Size, Intracellular Signaling, Adiposity And Glucose Metabolism, Ashutosh Kumar, Litao Xie, Chau My Ta, Antentor O Hinton, Susheel K Gunasekar, Rachel A Minerath, Karen Shen, Joshua M Maurer, Chad E Grueter, E Dale Abel, Gretchen Meyer, Rajan Sah
2020-Current year OA Pubs
Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism; however, the molecular mechanosensor remains unknown. Here, we show that SWELL1 (
Inherited Risk For Autism Through Maternal And Paternal Lineage, Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John N Constantino, Sven Sandin
Inherited Risk For Autism Through Maternal And Paternal Lineage, Dan Bai, Natasha Marrus, Benjamin Hon Kei Yip, Abraham Reichenberg, John N Constantino, Sven Sandin
2020-Current year OA Pubs
BACKGROUND: Autism spectrum disorder (ASD) is highly familial, with a positively skewed male-to-female ratio that is purported to arise from the so-called female protective effect. A serious implication of a female protective effect is that familial ASD liability would be expected to aggregate asymptomatically in sisters of affected probands, who would incur elevated rates of ASD among their offspring. Currently, there exist no data on second-generation recurrence rates among families affected by ASD.
METHODS: We analyzed data from the Swedish National Patient Register and the Multi-Generation Register for a cohort of children born between 2003 and 2012. ASD was ascertained …
Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss
Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss
Open Access Publications
COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …
Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva
Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva
Pediatrics Research and Scholarship
BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.
METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of …
Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox
Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox
Pathology Research and Scholarship
The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of …
Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn
Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn
Pathology Research and Scholarship
Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …
Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley
Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley
Pathology Research and Scholarship
As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have …