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Articles 14971 - 15000 of 18687
Full-Text Articles in Medical Specialties
14-3-3Τ Drives Estrogen Receptor Loss Via Erα36 Induction And Gata3 Inhibition In Breast Cancer, Lidija A Wilhelms Garan, Yang Xiao, Weei-Chin Lin
14-3-3Τ Drives Estrogen Receptor Loss Via Erα36 Induction And Gata3 Inhibition In Breast Cancer, Lidija A Wilhelms Garan, Yang Xiao, Weei-Chin Lin
Faculty, Staff and Students Publications
About one-fourth of recurrent estrogen receptor-positive (ER+) breast cancers lose ER expression, leading to endocrine therapy failure. However, the mechanisms underlying ER loss remain to be fully explored. We now show that 14-3-3τ, up-regulated in ∼60% of breast cancer, drives the conversion of ER+ to ER- and epithelial-to-mesenchymal transition (EMT). We identify ERα36, an isoform of ERα66, as a downstream effector of 14-3-3τ. Overexpression of 14-3-3τ induces ERα36 in xenografts and tumor spheroids. The regulation is further supported by a positive correlation between ERα36 and 14-3-3τ expression in human breast cancers. ERα36 can antagonize ERα66 and inhibit ERα66 expression. Isoform-specific …
Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han
Interferon Signaling In The Endometrium And In Endometriosis, Yuri Park, Sang Jun Han
Faculty, Staff and Students Publications
Endometriosis is an estrogen-dependent inflammatory disease that develops in reproductive-aged women who experience pelvic pain and infertility. Even though endometriosis is not a new disease, its molecular etiology has not been clearly elucidated. Defects in the immune system might be one of the factors that promote endometriosis progression. For example, elevated levels of proinflammatory cytokines are associated with endometriosis. Interferon is one of the cytokines that is elevated in endometriotic tissues compared with normal endometrium. Therefore, high interferon levels play a crucial role in endometriosis progression. In addition to endometriosis, however, interferon has a critical role in endometrial function, particularly …
Loss Of Non-Motor Kinesin Kif26a Causes Congenital Brain Malformations Via Dysregulated Neuronal Migration And Axonal Growth As Well As Apoptosis, Xuyu Qian, Ellen M Degennaro, Maya Talukdar, Shyam K Akula, Abbe Lai, Diane D Shao, Dilenny Gonzalez, Jack H Marciano, Richard S Smith, Norma K Hylton, Edward Yang, J Fernando Bazan, Lee Barrett, Rebecca C Yeh, R Sean Hill, Samantha G Beck, Aoi Otani, Jolly Angad, Tadahiro Mitani, Jennifer E Posey, Davut Pehlivan, Daniel Calame, Hatip Aydin, Osman Yesilbas, Kendall C Parks, Emanuela Argilli, Eleina England, Kiho Im, Ajay Taranath, Hamish S Scott, Christopher P Barnett, Peer Arts, Elliott H Sherr, James R Lupski, Christopher A Walsh
Loss Of Non-Motor Kinesin Kif26a Causes Congenital Brain Malformations Via Dysregulated Neuronal Migration And Axonal Growth As Well As Apoptosis, Xuyu Qian, Ellen M Degennaro, Maya Talukdar, Shyam K Akula, Abbe Lai, Diane D Shao, Dilenny Gonzalez, Jack H Marciano, Richard S Smith, Norma K Hylton, Edward Yang, J Fernando Bazan, Lee Barrett, Rebecca C Yeh, R Sean Hill, Samantha G Beck, Aoi Otani, Jolly Angad, Tadahiro Mitani, Jennifer E Posey, Davut Pehlivan, Daniel Calame, Hatip Aydin, Osman Yesilbas, Kendall C Parks, Emanuela Argilli, Eleina England, Kiho Im, Ajay Taranath, Hamish S Scott, Christopher P Barnett, Peer Arts, Elliott H Sherr, James R Lupski, Christopher A Walsh
Faculty, Staff and Students Publications
Kinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth-factor-receptor-bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early- and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and …
Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon
Prevalence Of Prediabetes And Diabetes Vary By Ethnicity Among Us Asian Adults At Healthy Weight, Overweight, And Obesity Ranges: An Electronic Health Record Study, William S Vicks, Joan C Lo, Lynn Guo, Jamal S Rana, Sherry Zhang, Nirmala D Ramalingam, Nancy P Gordon
Faculty, Staff and Student Publications
BACKGROUND: Asian adults develop Type 2 diabetes at a lower body mass index (BMI) compared to other racial/ethnic groups. We examined the variation in prevalence of prediabetes and diabetes among Asian ethnic groups within weight strata by comparing middle-aged Chinese, Filipino, South Asian, and White adults receiving care in the same integrated healthcare delivery system.
METHODS: Our retrospective cross-sectional U.S. study examined data from 283,110 (non-Hispanic) White, 33,263 Chinese, 38,766 Filipino, and 17,959 South Asian adults aged 45-64 years who were members of a Northern California health plan in 2016 and had measured height and weight. Prediabetes and diabetes were …
Growth Differentiation Factor 15 Is Not Associated With Glycemic Control In Patients With Type 2 Diabetes Mellitus Treated With Metformin: A Post-Hoc Analysis Of Aim Study, Fei Gao, Cheng Li, Yufei Wang, Jingyi Lu, Wei Lu, Jian Zhou, Jun Yin, Xiaojing Ma
Growth Differentiation Factor 15 Is Not Associated With Glycemic Control In Patients With Type 2 Diabetes Mellitus Treated With Metformin: A Post-Hoc Analysis Of Aim Study, Fei Gao, Cheng Li, Yufei Wang, Jingyi Lu, Wei Lu, Jian Zhou, Jun Yin, Xiaojing Ma
Faculty, Staff and Student Publications
BACKGROUND: Growth differentiation factor 15 (GDF15) was newly discovered to be a promising target of metformin. The study was aimed to investigate the relationship between GDF15 and glycemic control after metformin treatment in patients with type 2 diabetes mellitus.
METHODS: The study was a post-hoc analysis of AIM (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed Insulin compared to Metformin) study. The participants were randomly assigned to 12 weeks of metformin (MET) or acarbose (ACA) treatment combined with insulin. Serum GDF15 levels of 51 subjects from MET group and 53 subjects from …
Associations Of Warfarin Use With Risks Of Ischemic Cerebrovascular Events And Major Bleeding In Patients With Hyperthyroidism-Related Atrial Fibrillation, Sian-De Liu, Shwu-Jiuan Lin, Chin-Ying Ray, Fang-Tsyr Lin, Weei-Chin Lin, Li-Hsuan Wang
Associations Of Warfarin Use With Risks Of Ischemic Cerebrovascular Events And Major Bleeding In Patients With Hyperthyroidism-Related Atrial Fibrillation, Sian-De Liu, Shwu-Jiuan Lin, Chin-Ying Ray, Fang-Tsyr Lin, Weei-Chin Lin, Li-Hsuan Wang
Faculty, Staff and Students Publications
The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and …
The Family Level Assessment Of Screen Use-Mobile Approach: Development Of An Approach To Measure Children's Mobile Device Use, Oriana Perez, Anil Kumar Vadathya, Alicia Beltran, R Matthew Barnett, Olivia Hindera, Tatyana Garza, Salma M Musaad, Tom Baranowski, Sheryl O Hughes, Jason A Mendoza, Ashutosh Sabharwal, Ashok Veeraraghavan, Teresia M O'Connor
The Family Level Assessment Of Screen Use-Mobile Approach: Development Of An Approach To Measure Children's Mobile Device Use, Oriana Perez, Anil Kumar Vadathya, Alicia Beltran, R Matthew Barnett, Olivia Hindera, Tatyana Garza, Salma M Musaad, Tom Baranowski, Sheryl O Hughes, Jason A Mendoza, Ashutosh Sabharwal, Ashok Veeraraghavan, Teresia M O'Connor
Children’s Nutrition Research Center Staff Publications
Background: There is a strong association between increased mobile device use and worse dietary habits, worse sleep outcomes, and poor academic performance in children. Self-report or parent-proxy report of children's screen time has been the most common method of measuring screen time, which may be imprecise or biased.
Objective: The objective of this study was to assess the feasibility of measuring the screen time of children on mobile devices using the Family Level Assessment of Screen Use (FLASH)-mobile approach, an innovative method that leverages the existing features of the Android platform.
Methods: This pilot study consisted of 2 laboratory-based observational …
Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen
Cgas-Sting Activation Contributes To Podocyte Injury In Diabetic Kidney Disease, Nan Zang, Chen Cui, Xinghong Guo, Jia Song, Huiqing Hu, Mengmeng Yang, Mingyue Xu, Lingshu Wang, Xinguo Hou, Qin He, Zheng Sun, Chuan Wang, Li Chen
Faculty, Staff and Students Publications
Diabetic kidney disease (DKD) is the leading cause of end-stage renal diseases. DKD does not have efficacious treatment. The cGAS-STING pathway is activated in podocytes at the early stage of kidney dysfunction, which is associated with the activation of STING downstream effectors TBK1 and NF-κB but not IRF3. Lipotoxicity induces mitochondrial damage and mtDNA leakage to the cytosol through Bcl-2 associated X protein (BAX) in podocytes. BAX-mediated mtDNA cytosolic leakage can activate the cGAS-STING pathway in the absence of lipotoxicity and is sufficient to cause podocyte injury. Depletion of cytosolic mtDNA, genetic STING knockdown, or pharmacological inhibition of STING or …
Sensitive Image-Based Chromatin Binding Assays Using Inducible Erα To Rapidly Characterize Estrogenic Chemicals And Mixtures, Adam T Szafran, Maureen G Mancini, Fabio Stossi, Michael A Mancini
Sensitive Image-Based Chromatin Binding Assays Using Inducible Erα To Rapidly Characterize Estrogenic Chemicals And Mixtures, Adam T Szafran, Maureen G Mancini, Fabio Stossi, Michael A Mancini
Faculty, Staff and Students Publications
The United States Environmental Protection Agency (EPA) has been pursuing new high throughput in vitro assays to characterize endocrine disrupting chemicals (EDCs) that interact with estrogen receptor signaling. We characterize two new PRL-HeLa cell models expressing either inducible C-terminal (iGFP-ER) or N-terminal (iER-GFP) tagged estrogen receptor-α (ERα) that allows direct visualization of chromatin binding. These models are an order of magnitude more sensitive, detecting 87 - 93% of very weak estrogens tested compared to only 27% by a previous PRL-HeLa variant and compares favorably to the 73% detected by an EPA-developed computational model using in vitro data. Importantly, the chromatin …
Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens
Genetic Inhibition Of Nuclear Factor Of Activated T-Cell C2 Prevents Atrial Fibrillation In Crem Transgenic Mice, Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens
Faculty, Staff and Students Publications
AIMS: Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models.
METHODS AND RESULTS: Expression levels of NFATc1-c4 isoforms were assessed by quantitative reverse transcription-polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus …
Interactions Between Environmental Factors And Glutathione S-Transferase (Gst) Genes With Respect To Detectable Blood Aluminum Concentrations In Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland
Interactions Between Environmental Factors And Glutathione S-Transferase (Gst) Genes With Respect To Detectable Blood Aluminum Concentrations In Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland
Faculty, Staff and Student Publications
Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2−8 years) who participated as controls in an age- and sex-matched case−control study in Jamaica. We investigated additive and interactive associations among environmental factors and children’s genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 μg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having …
Lenalidomide Promotes The Development Of Tp53-Mutated Therapy-Related Myeloid Neoplasms, Adam S Sperling, Veronica A Guerra, James A Kennedy, Yuanqing Yan, Joanne I Hsu, Feng Wang, Andrew T Nguyen, Peter G Miller, Marie E Mcconkey, Vanessa A Quevedo Barrios, Ken Furudate, Linda Zhang, Rashmi Kanagal-Shamanna, Jianhua Zhang, Latasha Little, Curtis Gumbs, Naval Daver, Courtney D Dinardo, Tapan Kadia, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, P Andrew Futreal, Benjamin L Ebert, Koichi Takahashi
Lenalidomide Promotes The Development Of Tp53-Mutated Therapy-Related Myeloid Neoplasms, Adam S Sperling, Veronica A Guerra, James A Kennedy, Yuanqing Yan, Joanne I Hsu, Feng Wang, Andrew T Nguyen, Peter G Miller, Marie E Mcconkey, Vanessa A Quevedo Barrios, Ken Furudate, Linda Zhang, Rashmi Kanagal-Shamanna, Jianhua Zhang, Latasha Little, Curtis Gumbs, Naval Daver, Courtney D Dinardo, Tapan Kadia, Farhad Ravandi, Hagop Kantarjian, Guillermo Garcia-Manero, P Andrew Futreal, Benjamin L Ebert, Koichi Takahashi
Faculty, Staff and Student Publications
There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem …
Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar
Control Of Ribosomal Rna Synthesis By Hematopoietic Transcription Factors, Charles Antony, Subin S George, Justin Blum, Patrick Somers, Chelsea L Thorsheim, Dexter J Wu-Corts, Yuxi Ai, Long Gao, Kaosheng Lv, Michel G Tremblay, Tom Moss, Kai Tan, Jeremy E Wilusz, Austen R D Ganley, Maxim Pimkin, Vikram R Paralkar
Faculty, Staff and Students Publications
Ribosomal RNAs (rRNAs) are the most abundant cellular RNAs, and their synthesis from rDNA repeats by RNA polymerase I accounts for the bulk of all transcription. Despite substantial variation in rRNA transcription rates across cell types, little is known about cell-type-specific factors that bind rDNA and regulate rRNA transcription to meet tissue-specific needs. Using hematopoiesis as a model system, we mapped about 2,200 ChIP-seq datasets for 250 transcription factors (TFs) and chromatin proteins to human and mouse rDNA and identified robust binding of multiple TF families to canonical TF motifs on rDNA. Using a 47S-FISH-Flow assay developed for nascent rRNA …
Objective Assessment Of Upper-Extremity Motor Functions In Spinocerebellar Ataxia Using Wearable Sensors, Reza Mohammadi-Ghazi, Hung Nguyen, Ram Kinker Mishra, Ana Enriquez, Bijan Najafi, Christopher D Stephen, Anoopum S Gupta, Jeremy D Schmahmann, Ashkan Vaziri
Objective Assessment Of Upper-Extremity Motor Functions In Spinocerebellar Ataxia Using Wearable Sensors, Reza Mohammadi-Ghazi, Hung Nguyen, Ram Kinker Mishra, Ana Enriquez, Bijan Najafi, Christopher D Stephen, Anoopum S Gupta, Jeremy D Schmahmann, Ashkan Vaziri
Center on Aging Staff Publications
The study presents a novel approach to objectively assessing the upper-extremity motor symptoms in spinocerebellar ataxia (SCA) using data collected via a wearable sensor worn on the patient’s wrist during upper-extremity tasks associated with the Assessment and Rating of Ataxia (SARA). First, we developed an algorithm for detecting/extracting the cycles of the finger-to-nose test (FNT). We extracted multiple features from the detected cycles and identified features and parameters correlated with the SARA scores. Additionally, we developed models to predict the severity of symptoms based on the FNT. The proposed technique was validated on a dataset comprising the seventeen (n …
Detection Of Fibular Rotational Changes In Cone Beam Ct: Experimental Study In A Specimen Model, Nils Beisemann, Antonella M Tilk, Jula Gierse, Paul A Grützner, Jochen Franke, Jeffrey H Siewerdsen, Sven Y Vetter
Detection Of Fibular Rotational Changes In Cone Beam Ct: Experimental Study In A Specimen Model, Nils Beisemann, Antonella M Tilk, Jula Gierse, Paul A Grützner, Jochen Franke, Jeffrey H Siewerdsen, Sven Y Vetter
Faculty, Staff and Student Publications
BACKGROUND: In syndesmotic injuries, incorrect reduction leads to early arthrosis of the ankle joint. Being able to analyze the reduction result is therefore crucial for obtaining an anatomical reduction. Several studies that assess fibular rotation in the incisura have already been published. The aim of the study was to validate measurement methods that use cone beam computed tomography imaging to detect rotational malpositions of the fibula in a standardized specimen model.
METHODS: An artificial Maisonneuve injury was created on 16 pairs of fresh-frozen lower legs. Using a stable instrument, rotational malpositions of 5, 10, and 15° internal and external rotation …
Diabetes-Related Worries And Coping Among Youth And Young Adults With Type 1 Diabetes, Lindsay Taraban, Rachel Wasserman, Viena T Cao, Sahar S Eshtehardi, Barbara J Anderson, Debbe Thompson, David G Marrero, Marisa E Hilliard
Diabetes-Related Worries And Coping Among Youth And Young Adults With Type 1 Diabetes, Lindsay Taraban, Rachel Wasserman, Viena T Cao, Sahar S Eshtehardi, Barbara J Anderson, Debbe Thompson, David G Marrero, Marisa E Hilliard
Children’s Nutrition Research Center Staff Publications
Objective: Although mood and anxiety symptoms are common in youth with type 1 diabetes (T1D), little research has described their worries across developmental stages or the strategies they use to cope with these worries. This secondary data analysis aimed to describe and characterize common T1D-related worries and coping strategies from middle childhood through young adulthood.
Methods: Twenty-three youth (9 children, 7 adolescents, and 7 young adults) completed semistructured qualitative interviews about health-related quality of life. We coded interview transcripts using thematic analysis to generate common themes of diabetes-related worries and coping strategies.
Results: Participants' worries fell into four major themes: …
Recent Advances In Rapid Detection Techniques For Pesticide Residue: A Review, Lingyuan Xu, A M Abd El-Aty, Jong-Bang Eun, Jae-Han Shim, Jing Zhao, Xingmei Lei, Song Gao, Yongxin She, Fen Jin, Jing Wang, Maojun Jin, Bruce D Hammock
Recent Advances In Rapid Detection Techniques For Pesticide Residue: A Review, Lingyuan Xu, A M Abd El-Aty, Jong-Bang Eun, Jae-Han Shim, Jing Zhao, Xingmei Lei, Song Gao, Yongxin She, Fen Jin, Jing Wang, Maojun Jin, Bruce D Hammock
Faculty, Staff and Student Publications
As an important chemical pollutant affecting the safety of agricultural products, the on-site and efficient detection of pesticide residues has become a global trend and hotspot in research. These methodologies were developed for simplicity, high sensitivity, and multiresidue detection. This review introduces the currently available technologies based on electrochemistry, optical analysis, biotechnology, and some innovative and novel technologies for the rapid detection of pesticide residues, focusing on the characteristics, research status, and application of the most innovative and novel technologies in the past 10 years, and analyzes challenges and future development prospects. The current review could be a good reference …
Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace
Hdac6 Inhibition Reverses Cisplatin-Induced Mechanical Hypersensitivity Via Tonic Delta Opioid Receptor Signaling, Jixiang Zhang, Jazzmine M Junigan, Ronnie Trinh, Annemieke Kavelaars, Cobi J Heijnen, Peter M Grace
Faculty, Staff and Student Publications
Peripheral neuropathic pain induced by the chemotherapeutic cisplatin can persist for months to years after treatment. Histone deacetylase 6 (HDAC6) inhibitors have therapeutic potential for cisplatin-induced neuropathic pain since they persistently reverse mechanical hypersensitivity and spontaneous pain in rodent models. Here, we investigated the mechanisms underlying reversal of mechanical hypersensitivity in male and female mice by a 2 week treatment with an HDAC6 inhibitor, administered 3 d after the last dose of cisplatin. Mechanical hypersensitivity in animals of both sexes treated with the HDAC6 inhibitor was temporarily reinstated by a single injection of the neutral opioid receptor antagonist 6β-naltrexol or …
Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur
Anterior Connectivity Critical For Recovery Of Connected Speech After Stroke, Junhua Ding, Tatiana T Schnur
Faculty, Staff and Student Publications
Connected speech recovers to different degrees across people after left hemisphere stroke, but white matter predictors of differential recovery from the acute stage of stroke are unknown. We assessed changes in lexical-syntactic aspects of connected speech in a longitudinal analysis of 40 individuals (18 females) from the acute stage of left hemisphere stroke (within an average of 4 days post-stroke) to subacute (within 2 months) and chronic stages (early: 6 months, late: 1 year) while measuring the extent of acute lesions on white matter tracts to identify tracts predictive of recovery. We found that acute damage to the frontal aslant …
Mapping The Universe Of Eph Receptor And Ephrin Ligand Transcripts In Epithelial And Fiber Cells Of The Eye Lens, Michael P Vu, Catherine Cheng
Mapping The Universe Of Eph Receptor And Ephrin Ligand Transcripts In Epithelial And Fiber Cells Of The Eye Lens, Michael P Vu, Catherine Cheng
Faculty, Staff and Student Publications
The eye lens is a transparent, ellipsoid organ in the anterior chamber of the eye that is required for fine focusing of light onto the retina to transmit a clear image. Cataracts, defined as any opacity in the lens, remains the leading cause of blindness in the world. Recent studies in humans and mice indicate that Eph-ephrin bidirectional signaling is important for maintaining lens transparency. Specifically, mutations and polymorphisms in the EphA2 receptor and the ephrin-A5 ligand have been linked to congenital and age-related cataracts. It is unclear what other variants of Ephs and ephrins are expressed in the lens …
Estimating The Optimal Linear Combination Of Predictors Using Spherically Constrained Optimization, Priyam Das, Debsurya De, Raju Maiti, Mona Kamal, Katherine A Hutcheson, Clifton D Fuller, Bibhas Chakraborty, Christine B Peterson
Estimating The Optimal Linear Combination Of Predictors Using Spherically Constrained Optimization, Priyam Das, Debsurya De, Raju Maiti, Mona Kamal, Katherine A Hutcheson, Clifton D Fuller, Bibhas Chakraborty, Christine B Peterson
Faculty, Staff and Student Publications
Background: In the context of a binary classification problem, the optimal linear combination of continuous predictors can be estimated by maximizing the area under the receiver operating characteristic curve. For ordinal responses, the optimal predictor combination can similarly be obtained by maximization of the hypervolume under the manifold (HUM). Since the empirical HUM is discontinuous, non-differentiable, and possibly multi-modal, solving this maximization problem requires a global optimization technique. Estimation of the optimal coefficient vector using existing global optimization techniques is computationally expensive, becoming prohibitive as the number of predictors and the number of outcome categories increases.
Results: We propose an …
Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson
Therapeutic Efficacy Of The Humanized Jaa-F11 Anti-Thomsen-Friedenreich Antibody Constructs H2al2a And H3l3 In Human Breast And Lung Cancer Xenograft Models, Diala Ghazal, Fatma Zalzala, John C Fisk, Swetha Tati, Loukia G Karacosta, Susan Morey, James R Olson, Sally Quataert, Grace K Dy, Kate Rittenhouse-Olson
Faculty, Staff and Student Publications
The Thomsen-Friedenreich antigen (TF-Ag-α) is found on ~85% of human carcinomas but is cryptic on normal tissue. The humanized highly specific hJAA-F11-H2aL2a and -H3L3 antibodies target TF-Ag-α without binding to TF-Ag-beta (found on surface glycolipids of some normal cells). The relative affinity of H3L3 is 17 times that of H2aL2a, which would seem to favor superior efficacy, however, increased affinity can result in less tumor penetration. To assess the potential therapeutic efficacy of these antibodies, four human cancer- mouse xenograft models were treated with H2aL2a and H3L3. The tumor xenograft models used were human non-small cell lung cancer, H520, and …
The Modifying Effect Of The Serum-To-Dialysate Potassium Gradient On The Cardiovascular Safety Of Ssris In The Hemodialysis Population: A Pharmacoepidemiologic Study, Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, Maurice Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe
The Modifying Effect Of The Serum-To-Dialysate Potassium Gradient On The Cardiovascular Safety Of Ssris In The Hemodialysis Population: A Pharmacoepidemiologic Study, Magdalene M Assimon, Patrick H Pun, Sana M Al-Khatib, Maurice Alan Brookhart, Bradley N Gaynes, Wolfgang C Winkelmayer, Jennifer E Flythe
Faculty, Staff and Students Publications
Background: Hypokalemia is a risk factor for drug-induced QT prolongation. Larger serum-to-dialysate potassium gradients during hemodialysis (HD) may augment the proarrhythmic risks of selective serotonin reuptake inhibitors (SSRIs).
Methods: We conducted a cohort study using 2007-2017 data from the United States Renal Data System and a large dialysis provider to examine if the serum-to-dialysate potassium gradient modifies SSRI cardiac safety. Using a new-user design, we compared 1-year sudden cardiac death (SCD) risk among HD patients newly treated with higher (citalopram, escitalopram) versus lower (fluoxetine, fluvoxamine, paroxetine, sertraline) QT-prolonging potential SSRIs, overall and stratified by baseline potassium gradient (≥4 versus < 4 mEq/l). We used inverse probability of treatment-weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) and conducted a confirmatory nested case-control study.
Results: …
Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong
Loss Of Activity-Induced Mitochondrial Atp Production Underlies The Synaptic Defects In A Drosophila Model Of Als, Nicholas E Karagas, Richa Gupta, Elham Rastegari, Kai Li Tan, Ho Hang Leung, Hugo J Bellen, Kartik Venkatachalam, Ching-On Wong
Faculty, Staff and Students Publications
Mutations in the gene encoding vesicle-associated membrane protein B (VAPB) cause a familial form of amyotrophic lateral sclerosis (ALS). Expression of an ALS-related variant of vapb (vapbP58S) in Drosophila motor neurons results in morphologic changes at the larval neuromuscular junction (NMJ) characterized by the appearance of fewer, but larger, presynaptic boutons. Although diminished microtubule stability is known to underlie these morphologic changes, a mechanism for the loss of presynaptic microtubules has been lacking. By studying flies of both sexes, we demonstrate the suppression of vapbP58S-induced changes in NMJ morphology by either a loss of endoplasmic …
The Development And Implementation Of Evidence-Based Preanesthesia Assessment Tools For Lvad Patients Undergoing Non-Cardiac Procedures, Tracey Rooney, Casey Weimer, Eileen Giardino, Kerry Shanklin, Pete Pelletier, Audrey Rosenblatt
The Development And Implementation Of Evidence-Based Preanesthesia Assessment Tools For Lvad Patients Undergoing Non-Cardiac Procedures, Tracey Rooney, Casey Weimer, Eileen Giardino, Kerry Shanklin, Pete Pelletier, Audrey Rosenblatt
Journal of Nursing & Interprofessional Leadership in Quality & Safety
Abstract
A university-affiliated tertiary medical center with a newly developed Advanced Heart Failure and Mechanical Circulatory Support program identified the need to implement a more systematic approach to the preanesthesia assessment process for patients with a Left Ventricular Assist Device (LVAD) undergoing noncardiac procedures and standardized guidelines to determine the best blood pressure monitoring system for patients with an LVAD during these noncardiac procedures. A multidisciplinary panel of clinical experts developed an LVAD Preanesthesia Toolkit using standard recommendations identified via evidence-based literature and expert opinion. The Toolkit included an LVAD Preanesthesia Assessment (VaPA) tool and an LVAD Blood Pressure Monitoring …
Highlights Of The 2021 Brano Heart Failure Forum, Rajko Radovancevic, Bojan Vrtovec, Igor D. Gregoric
Highlights Of The 2021 Brano Heart Failure Forum, Rajko Radovancevic, Bojan Vrtovec, Igor D. Gregoric
The VAD Journal
Since 2007, the Branislav “Brano” Radovancevic Heart Failure Forum has been held annually to provide a venue for experts to present and discuss “Innovations and New Treatment Strategies in Heart Failure.” Clinicians and researchers gather yearly in a different Eastern European city to discuss the latest in heart failure diagnostics and therapeutics. The forum was postponed in 2020 due to the COVID-19 pandemic and then resumed in September of 2021 in Graz, Austria. It was attended by over 75 faculty from 13 countries. Due to the ongoing pandemic, 13 presentations were given virtually. Throughout the forum, 17 separate sessions focused …
Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini
Daphnia As A Sentinel Species For Environmental Health Protection: A Perspective On Biomonitoring And Bioremediation Of Chemical Pollution, Muhammad Abdullahi, Xiaojing Li, Mohamed Abou-Elwafa Abdallah, William Stubbings, Norman Yan, Marianne Barnard, Liang-Hong Guo, John K Colbourne, Luisa Orsini
Faculty, Staff and Student Publications
Despite available technology and the knowledge that chemical pollution damages human and ecosystem health, chemical pollution remains rampant, ineffectively monitored, rarely prevented, and only occasionally mitigated. We present a framework that helps address current major challenges in the monitoring and assessment of chemical pollution by broadening the use of the sentinel species Daphnia as a diagnostic agent of water pollution. And where prevention has failed, we propose the application of Daphnia as a bioremediation agent to help reduce hazards from chemical mixtures in the environment. By applying “omics” technologies to Daphnia exposed to real-world ambient chemical mixtures, we show improvements …
Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner
Association Of Mrna Vaccination With Clinical And Virologic Features Of Covid-19 Among Us Essential And Frontline Workers, The Heroes-Recover Network, Mark G Thompson, Sarang K Yoon, Allison L Naleway, Jennifer Meece, Thomas P Fabrizio, Alberto J Caban-Martinez, Jefferey L Burgess, Manjusha Gaglani, Lauren E W Olsho, Allen Bateman, Jessica Lundgren, Lauren Grant, Andrew L Phillips, Holly C Groom, Elisha Stefanski, Natasha Schaefer Solle, Katherine Ellingson, Karen Lutrick, Kayan Dunnigan, Meredith G Wesley, Kyley Guenther, Angela Hunt, Josephine Mak, Kurt T Hegmann, Jennifer L Kuntz, Adam Bissonnette, James Hollister, Spencer Rose, Tyler C Morrill, Karley Respet, Ashley L Fowlkes, Matthew S Thiese, Patrick Rivers, Meghan K Herring, Marilyn J Odean, Young M Yoo, Matthew Brunner, Edward J Bedrick, Deanna E Fleary, John T Jones, Jenna Praggastis, James Romine, Monica Dickerson, Sana M Khan, Julie Mayo Lamberte, Shawn Beitel, Richard J Webby, Harmony L Tyner
Faculty, Staff and Student Publications
IMPORTANCE: Data on the epidemiology of mild to moderately severe COVID-19 are needed to inform public health guidance.
OBJECTIVE: To evaluate associations between 2 or 3 doses of mRNA COVID-19 vaccine and attenuation of symptoms and viral RNA load across SARS-CoV-2 viral lineages.
DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of essential and frontline workers in Arizona, Florida, Minnesota, Oregon, Texas, and Utah with COVID-19 infection confirmed by reverse transcriptase-polymerase chain reaction testing and lineage classified by whole genome sequencing of specimens self-collected weekly and at COVID-19 illness symptom onset. This analysis was conducted among 1199 participants with SARS-CoV-2 …
Hospital Change To Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion For Parenteral Nutrition In Hospitalized And Critically Ill Adults Improves Outcomes: A Pre–Post-Comparative Study, Krista L Haines, Tetsu Ohnuma, Charles Trujillo, Obanor Osamudiamen, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E Wischmeyer
Hospital Change To Mixed Lipid Emulsion From Soybean Oil-Based Lipid Emulsion For Parenteral Nutrition In Hospitalized And Critically Ill Adults Improves Outcomes: A Pre–Post-Comparative Study, Krista L Haines, Tetsu Ohnuma, Charles Trujillo, Obanor Osamudiamen, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E Wischmeyer
Faculty, Staff and Student Publications
INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.
METHODS: We conducted a single-center retrospective …
Intensive Blood Pressure Lowering In Patients With Malignant Left Ventricular Hypertrophy, Simon B Ascher, James A De Lemos, Minjae Lee, Elaine Wu, Elsayed Z Soliman, Ian J Neeland, Dalane W Kitzman, Christie M Ballantyne, Vijay Nambi, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry
Intensive Blood Pressure Lowering In Patients With Malignant Left Ventricular Hypertrophy, Simon B Ascher, James A De Lemos, Minjae Lee, Elaine Wu, Elsayed Z Soliman, Ian J Neeland, Dalane W Kitzman, Christie M Ballantyne, Vijay Nambi, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry
Faculty, Staff and Students Publications
Background: Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart failure and death.
Objectives: The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.
Methods: A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type …