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Articles 1 - 19 of 19
Full-Text Articles in Medicine and Health Sciences
Pum1 Mediates The Posttranscriptional Regulation Of Human Fetal Hemoglobin, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Merlin Nithya Gnanapragasam
Pum1 Mediates The Posttranscriptional Regulation Of Human Fetal Hemoglobin, Yuncheng Man, Amma Owusu-Ansah, Omar Y. Mian, Umut A. Gurkan, Anton A. Komar, Merlin Nithya Gnanapragasam
Faculty Scholarship
The fetal-to-adult hemoglobin switching at about the time of birth involves a shift in expression from γ-globin to β-globin in erythroid cells. Effective re-expression of fetal γ-globin can ameliorate sickle cell anemia and β-thalassemia. Despite the physiological and clinical relevance of this switch, its posttranscriptional regulation is poorly understood. Here, we identify Pumilo 1 (PUM1), an RNA-binding protein with no previously reported functions in erythropoiesis, as a direct posttranscriptional regulator of β-globin switching. PUM1, whose expression is regulated by the erythroid master transcription factor erythroid Krüppel-like factor (EKLF/KLF1), peaks during erythroid differentiation, binds γ-globin messenger RNA (mRNA), and reduces γ-globin …
The Relationship Between Anti-Müllerian Hormone, Body Mass Index And Weight Loss: A Review Of The Literature, Jacqueline Kloos, Rachel Weinerman
The Relationship Between Anti-Müllerian Hormone, Body Mass Index And Weight Loss: A Review Of The Literature, Jacqueline Kloos, Rachel Weinerman
Student Scholarship
Anti-Müllerian hormone (AMH) is commonly used as a proxy for ovarian reserve due to its secretion by antral follicles. It is considered a metric for prediction of ovarian response to certain assisted reproduction therapies. As obesity has a negative impact on fertility, it is important to establish whether obesity-induced hormonal changes influence AMH levels, if and how weight loss affects AMH, and if that influence represents altered reproductive function. The aim of this study was to review the existing literature on the effects of body mass index and weight loss on AMH levels. A PubMed literature keyword search with relevant …
Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan
Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan
Faculty Scholarship
Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including …
Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan
Catch Bonds In Sickle Cell Disease: Shear-Enhanced Adhesion Of Red Blood Cells To Laminin, Utku Goreke, Shamreen Iram, Gundeep Singh, Sergio Domínguez-Medina, Yuncheng Man, Allison Bode, Ran An, Jane A. Little, Christopher L. Wirth, Michael Hinczewski, Umut A. Gurkan
Faculty Scholarship
Could the phenomenon of catch bonding—force-strengthened cellular adhesion—play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant micro-scale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases …
The Impact Of Obesity And Adipokines On Breast And Gynecologic Malignancies, Surabhi Tewari, Roberto Vargas, Ofer Reizes
The Impact Of Obesity And Adipokines On Breast And Gynecologic Malignancies, Surabhi Tewari, Roberto Vargas, Ofer Reizes
Faculty Scholarship
The link between obesity and multiple disease comorbidities is well established. In 2003, Calle and colleagues presented the relationship between obesity and several cancer types, including breast, ovarian, and endometrial malignancies. Nearly, 20% of cancer-related deaths in females can be accounted for by obesity. Identifying obesity as a risk factor for cancer led to a focus on the role of fat-secreted cytokines, known as adipokines, on carcinogenesis and tumor progression. Early studies indicated that the adipokine leptin increases cell proliferation, invasion, and inhibition of apoptosis in multiple cancer types. As a greater appreciation of the obesity–cancer link has amassed, we …
Prediction Of Neonatal Growth Restriction In Fetuses With Gastroschisis By Early Third Trimester Ultrasonography Utilizing Contemporary Birth Weight Percentiles, Madeline Mckenna
Prediction Of Neonatal Growth Restriction In Fetuses With Gastroschisis By Early Third Trimester Ultrasonography Utilizing Contemporary Birth Weight Percentiles, Madeline Mckenna
Student Scholarship
Objective: To identify the estimated fetal weight (EFW) formula and threshold for the optimal prediction of fetal growth restriction (FGR) at 26–34 weeks' in fetuses with gastroschisis. Methods: Late second and third trimester ultrasound data were used to calculate the EFW utilizing eight different formulas: Hadlock I-IV, Honarvar, Shepard, Siemer, and Warsof. EFW and birth weight percentiles were assigned from US population growth curves. FGR and small for gestational age (SGA) were defined as EFW and birth weight less than the tenth percentile for gestational age; Receiver operating characteristic (ROC) curves were used to compare formula performance for FGR diagnosis …
Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta
Chronic Red Cell Exchange In Sickle Cell Patients With Iron Overload May Not Affect Mortality, Yi Yuan Zhou, Hollie M. Reeves, Robert W. Maitta
Faculty Scholarship
Sickle cell disease (SCD) is an inherited blood disorder that affects ~100,000 Americans (1, 2). In SCD, red blood cells (RBC) containing aberrant sickle hemoglobin (HgbS) become sickle-shaped at low oxygen tension and stick together leading to obstructed blood flow. The resulting decrease in tissue oxygenation causes chronic complications such as vasculo-occlusive pain crises among others that require frequent hospitalizations (3). Chronic RBC transfusions play a prominent role in the treatment of this disease by improving oxygenation through addition of normal RBC and dilution of RBC containing HgbS (4, 5). However, the major disadvantage of management with simple transfusion is …
Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan
Occlusionchip: A Functional Microcapillary Occlusion Assay Complementary To Ektacytometry For Detection Of Small-Fraction Red Blood Cells With Abnormal Deformability, Yuncheng Man, Ran An, Karamoja Monchamp, Zoe Sekyonda, Erdem Kucukal, Chiara Federici, William J. Wulftange, Utku Goreke, Allison Bode, Umut A. Gurkan
Faculty Scholarship
Red blood cell (RBC) deformability is a valuable hemorheological biomarker that can be used to assess the clinical status and response to therapy of individuals with sickle cell disease (SCD). RBC deformability has been measured by ektacytometry for decades, which uses shear or osmolar stress. However, ektacytometry is a population based measurement that does not detect small-fractions of abnormal RBCs. A single cell-based, functional RBC deformability assay would complement ektacytometry and provide additional information. Here, we tested the relative merits of the OcclusionChip, which measures RBC deformability by microcapillary occlusion, and ektacytometry. We tested samples containing glutaraldehyde-stiffened RBCs for up …
Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan
Antithrombin-Iii Mitigates Thrombin-Mediated Endothelial Cell Contraction And Sickle Red Blood Cell Adhesion In Microscale Flow, William J. Wulftange, Erdem Kucukal, Yuncheng Man, Ran An, Karamoja Monchamp, Charlotte D. Sevrain, Himanshu R. Dashora, Allison Bode, Jane A. Little, Umut A. Gurkan
Faculty Scholarship
Individuals with sickle cell disease (SCD) have persistently elevated thrombin generation that results in a state of systemic hypercoagulability. Antithrombin-III (ATIII), an endogenous serine protease inhibitor, inhibits several enzymes in the coagulation cascade, including thrombin. Here, we utilize a biomimetic microfluidic device to model the morphology and adhesive properties of endothelial cells (ECs) activated by thrombin and examine the efficacy of ATIII in mitigating the adhesion of SCD patient-derived red blood cells (RBCs) and EC retraction. Microfluidic devices were fabricated, seeded with ECs, and incubated under physiological shear stress. Cells were then activated with thrombin with or without an ATIII …
Increased Cytokine Gene Expression And Cognition Risk Associated With Androgen Deprivation Therapy, Shiv Verma, Prem Prakash Kushwaha, Eswar Shankar, Lee E. Ponsky, Sanjay Gupta
Increased Cytokine Gene Expression And Cognition Risk Associated With Androgen Deprivation Therapy, Shiv Verma, Prem Prakash Kushwaha, Eswar Shankar, Lee E. Ponsky, Sanjay Gupta
Faculty Scholarship
Background: Androgen deprivation therapy (ADT) is a standard treatment modality for locally advanced, high-risk, and metastatic hormone-sensitive prostate cancer. Long-term ADT treatment likely develops side-effects that include changes in cognition or onset of dementia. However, the molecular understanding of this effect remains elusive. We attempt to establish a link between ADT and changes in cognitive function using patient databases and bioinformatics analyses. Methods: Gene expression profiling was performed using RNA sequencing data from Alzheimer patient cohort and compared with the data from advanced-stage prostate cancer patients receiving neoadjuvant antiandrogen therapy. Differentially expressed genes (DEGs) were analyzed using the Ingenuity knowledge …
Palliative Stenting Of The Venous Duct In A Premature Neonate With Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Connection, John S. Lozier, Martin L. Bocks
Palliative Stenting Of The Venous Duct In A Premature Neonate With Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Connection, John S. Lozier, Martin L. Bocks
Faculty Scholarship
In infracardiac, infradiaphragmatic total anomalous pulmonary venous connection, all four pulmonary veins connect to a descending vertical vein that usually drains to the portal vein or one of its tributaries. Obstruction is common, and definitive treatment is surgical repair. We present a case of late-diagnosed infradiaphragmatic total anomalous pulmonary venous connection in a premature neonate who was too high risk for surgery and underwent palliative stenting of the venous duct. We demonstrate the feasibility of a transhepatic approach when umbilical access is no longer available.
Respiratory Morbidity And Neurodevelopmental Outcomes In Infants Born Preterm: A Complex Web, Anna Maria Hibbs
Respiratory Morbidity And Neurodevelopmental Outcomes In Infants Born Preterm: A Complex Web, Anna Maria Hibbs
Faculty Scholarship
This commentary is on the original article by Yu et al. on pages 1246–1253 of this issue.
Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse
Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse
Faculty Scholarship
U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.
Obesity Accelerates Acute Promyelocytic Leukemia In Mice And Reduces Sex Differences In Latency And Penetrance, John W. R. Kincaid, Gretchen Weiss, Anne E. Hill-Baskin, Heidi M. Schmidt, Ovwoioise Omoijuanfo, Cheryl L. Thompson, Rose C. Beck, Nathan A. Berger
Obesity Accelerates Acute Promyelocytic Leukemia In Mice And Reduces Sex Differences In Latency And Penetrance, John W. R. Kincaid, Gretchen Weiss, Anne E. Hill-Baskin, Heidi M. Schmidt, Ovwoioise Omoijuanfo, Cheryl L. Thompson, Rose C. Beck, Nathan A. Berger
Faculty Scholarship
Objective: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). Methods: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. …
Extrusion: A New Method For Rapid Formulation Of High-Yield, Monodisperse Nanobubbles, Claire Counil, Eric Abenojar, Reshani Perera, Agata A. Exner
Extrusion: A New Method For Rapid Formulation Of High-Yield, Monodisperse Nanobubbles, Claire Counil, Eric Abenojar, Reshani Perera, Agata A. Exner
Faculty Scholarship
Shell-stabilized gas microbubbles (MB) and nanobubbles (NB) are frequently used for biomedical ultrasound imaging and therapeutic applications. While it is widely recognized that monodisperse bubbles can be more effective in these applications, the efficient formulation of uniform bubbles at high concentrations is difficult to achieve. Here, it is demonstrated that a standard mini-extruder setup, commonly used to make vesicles or liposomes, can be used to quickly and efficiently generate monodisperse NBs with high yield. In this highly reproducible technique, the NBs obtained have an average diameter of 0.16 ± 0.05 µm and concentration of 6.2 ± 1.8 × 1010 NBs …
Urate-Lowering Therapy For Patients With Gout On Hemodialysis, Reem Alkilany, Douglas Einstadter, Maria Antonelli
Urate-Lowering Therapy For Patients With Gout On Hemodialysis, Reem Alkilany, Douglas Einstadter, Maria Antonelli
Faculty Scholarship
Objective: Gout is the most common form of inflammatory arthritis and is caused by deposition of monosodium urate crystals resulting from a high burden of uric acid (UA). High UA burden also has been associated with increased morbidity and mortality in the general population and progression to chronic kidney disease. In persons with gout and end-stage renal disease (ESRD), prior studies suggest that UA levels decrease after initiation of hemodialysis (HD). We evaluated UA level and the use of urate-lowering therapies (ULTs) in patients with gout and ESRD on HD. Methods: We performed a retrospective review of patients with gout …
The Time-Varying Cardiovascular Benefits Of Glucagon-Like Peptide-1 Receptor Agonist Therapy In Patients With Type 2 Diabetes Mellitus: Evidence From Large Multinational Trials, Salil V. Deo, Yakov Elgudin
The Time-Varying Cardiovascular Benefits Of Glucagon-Like Peptide-1 Receptor Agonist Therapy In Patients With Type 2 Diabetes Mellitus: Evidence From Large Multinational Trials, Salil V. Deo, Yakov Elgudin
Faculty Scholarship
Aims: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. Material and Methods: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran's Q statistic. …
Anti‐Cd20 Therapeutic Options In Immune‐Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta
Anti‐Cd20 Therapeutic Options In Immune‐Mediated Thrombotic Thrombocytopenic Purpura, Robert W. Maitta
Faculty Scholarship
Immunosuppression with rituximab in immune-mediated thrombotic thrombocytopenic purpura helps decrease production of autoantibody mediating ADAMTS13 clearance from circulation. Failure to respond to rituximab in a satisfactory way or made difficult by adverse events to the medication does not represent a reason to stop considering anti-CD20 therapies to control antibody production. Therefore, both of atumumab and obinutuzumab with specificity to CD20, represent potentially valuable therapeutic tools in patients who are not candidates for rituximab. Commentary on: Doyle et al. The use of obinutuzumab and ofatumumab in the treatment of immune thrombotic thrombocytopenic purpura. Br J Haematol. 2022;198:391-396.1.
Low Voltage-Guided Ablation Of Posterior Wall Improves 5-Year Arrhythmia-Free Survival In Persistent Atrial Fibrillation, Ahmad Jabri, Soufian T. Almahameed, Ohad Ziv
Low Voltage-Guided Ablation Of Posterior Wall Improves 5-Year Arrhythmia-Free Survival In Persistent Atrial Fibrillation, Ahmad Jabri, Soufian T. Almahameed, Ohad Ziv
Faculty Scholarship
Introduction: The posterior wall (PW) has been proposed as a standard target for ablation beyond pulmonary vein antral isolation (PVI) in patients with persistent atrial fibrillation (AF). However, studies have shown inconsistent outcomes with the addition of PW ablation. The presence or absence of low voltage on the PW may explain these inconsistencies. We evaluated whether PW ablation based on the presence or absence of low voltage improves long-term arrhythmia-free outcomes. Methods: We retrospectively reviewed 5-year follow-up in 152 consecutive patients who received either standard ablation (SA) with PVI alone or PVI + PW ablation (PWA) based on physician discretion …