Medicine and Health Sciences Commons^™

Blinatumomab Consolidation Post-Autologous Stem Cell Transplantation In Patients With Diffuse Large B-Cell Lymphoma, Armin Ghobadi, Nicole C Foley, Jared Cohen, Michael P Rettig, Amanda F Cashen, Leah Gehrs, Stephanie Christ, Emily Street, Nicholas Wallace, Julie Ritchey, Neha Mehta-Shah, Peter Westervelt, Todd A Fehniger, Brad Kahl, Nancy L Bartlett, John F Dipersio

2020-Current year OA Pubs

Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five …

Outcomes Of Marginal Zone Lymphoma Treated With Ibrutinib In The First-Line Setting In The United States: A Real-World Analysis, Narendranath Epperla, Qiuhong Zhao, Tamara Moyo, Marcus P Watkins, Montreh Tavakkoli, Celeste Bello, Pallawi Torka, Nishitha Reddy, Colin Thomas, Kaitlin Annunzio, Beth Christian, Stefan K Barta, Geoffrey Shouse, Adam J Olszewski, Nancy L Bartlett

2020-Current year OA Pubs

No abstract provided.

A General Computational Design Strategy For Stabilizing Viral Class I Fusion Proteins, Karen J Gonzalez, Jiachen Huang, Miria F Criado, Avik Banerjee, Stephen M Tompkins, Jarrod J Mousa, Eva-Maria Strauch

2020-Current year OA Pubs

Many pathogenic viruses rely on class I fusion proteins to fuse their viral membrane with the host cell membrane. To drive the fusion process, class I fusion proteins undergo an irreversible conformational change from a metastable prefusion state to an energetically more stable postfusion state. Mounting evidence underscores that antibodies targeting the prefusion conformation are the most potent, making it a compelling vaccine candidate. Here, we establish a computational design protocol that stabilizes the prefusion state while destabilizing the postfusion conformation. With this protocol, we stabilize the fusion proteins of the RSV, hMPV, and SARS-CoV-2 viruses, testing fewer than a …

Inadequate Prophylaxis In Patients With Trauma: Anti-Xa-Guided Enoxaparin Dosing Management In Critically Ill Patients With Trauma, Grace Martin Niziolek, Lauren Mangan, Cassidi Weaver, Vanessa Prendergast, Raymond Lamore, Megan Zielke, Niels D Martin

2020-Current year OA Pubs

UNLABELLED: Venous thromboembolism (VTE) causes significant morbidity in patients with trauma despite advances in pharmacologic therapy. Prior literature suggests standard enoxaparin dosing may not achieve target prophylactic anti-Xa levels. We hypothesize that a new weight-based enoxaparin protocol with anti-Xa monitoring for dose titration in critically injured patients is safe and easily implemented.

METHODS: This prospective observational study included patients with trauma admitted to the trauma intensive care unit (ICU) from January 2021 to September 2022. Enoxaparin dosing was adjusted based on anti-Xa levels as standard of care via a performance improvement initiative. The primary outcome was the proportion of subtarget …

Connexin43 In Mesenchymal Lineage Cells Regulates Body Adiposity And Energy Metabolism In Mice, Seung-Yon Lee, Francesca Fontana, Toshifumi Sugatani, Ignacio Portales Castillo, Giulia Leanza, Ariella Coler-Reilly, Roberto Civitelli

2020-Current year OA Pubs

Connexin43 (Cx43) is the most abundant gap junction protein present in the mesenchymal lineage. In mature adipocytes, Cx43 mediates white adipose tissue (WAT) beiging in response to cold exposure and maintains the mitochondrial integrity of brown adipose tissue (BAT). We found that genetic deletion of Gja1 (Cx43 gene) in cells that give rise to chondro-osteogenic and adipogenic precursors driven by the Dermo1/Twist2 promoter led to lower body adiposity and partial protection against the weight gain and metabolic syndrome induced by a high-fat diet (HFD) in both sexes. These protective effects were related to increased locomotion, fuel utilization, energy expenditure, nonshivering …

Investigating The "Sex Paradox" In Pulmonary Arterial Hypertension: Results From The Pulmonary Hypertension Association Registry (Phar), Jacqueline T. Desjardin, Noah Kime, Nicholas A. Kolaitis, Richard A. Kronmal, Matthew R. Lammi, Stephen C. Mathai, Corey E. Ventetuolo, Teresa De Marco

School of Medicine Faculty Publications

BACKGROUND: Female sex is a significant risk factor for pulmonary arterial hypertension (PAH), yet males with PAH have worse survival - a phenomenon referred to as the "sex paradox" in PAH. METHODS: All adult PAH patients in the Pulmonary Hypertension Association Registry (PHAR) with congruent sex and gender were included. Baseline differences in demographics, hemodynamics, functional parameters, and quality of life were assessed by sex. Kaplan-Meier survival analysis was used to evaluate survival by sex. Mediation analysis was conducted with Cox proportional hazards regression by comparing the unadjusted hazard ratios for sex before and after adjustment for covariates. The plausibility …

The Effect Of A Single Cycle Of Ischemia On Bar Velocity During Bench Press Exercise, Marta Bichowska-Pawęska, Dawid Gaweł, Robert Trybulski, Jakub Jarosz, Kinga Łosińska, Krzysztof Fostiak, Joao Guilherme Vieira

Baltic Journal of Health and Physical Activity

Introduction: The main goal of this study was to investigate the effects of a single cycle of ischemia applied before the bench press exercise on acute bar velocity changes. Materials and Methods: Twelve physically active males participated in the study. The experiment followed a rando-mized, cross-over design under two testing conditions. The experimental condition involved the application of a single cycle of ischemia (5 minutes; 80% arterial occlusion pressure [AOP]) before the first set of bench press exercise (2 sets at 60% 1RM). The control condition did not use ischemia. The peak and mean bar velocities were measured using a …

Correlation Enhanced Distribution Adaptation For Prediction Of Fall Risk, Ziqi Guo, Teresa Wu, Thurmon Lockhart, Rahul Soangra, Hyunsoo Yoon

Physical Therapy Faculty Articles and Research

With technological advancements in diagnostic imaging, smart sensing, and wearables, a multitude of heterogeneous sources or modalities are available to proactively monitor the health of the elderly. Due to the increasing risks of falls among older adults, an early diagnosis tool is crucial to prevent future falls. However, during the early stage of diagnosis, there is often limited or no labeled data (expert-confirmed diagnostic information) available in the target domain (new cohort) to determine the proper treatment for older adults. Instead, there are multiple related but non-identical domain data with labels from the existing cohort or different institutions. Integrating different …

How To Respond To Racist Patients: Recommendations From A Literature Review, Benjamin Caplan, Jocelyn Mitchell-Williams

Cooper Rowan Medical Journal

Introduction: Dealing with racist patients is not uncommon, and these interactions can sever the therapeutic alliance, as well as leave providers feeling isolated, dehumanized, and ashamed. Investigation of published recommendations for handling these situations can give victims, peers, and institutions the tools necessary to prepare, protect, and support providers through these challenging encounters.

Methods: This paper is a literature review. For inclusion in this review, studies must have met the criteria of providing recommendations for healthcare providers or institutions on how to deal with racist patients. Excluded articles did not include recommendations on how to handle such situations or did …

Flow Cytometry Of Dnmt1 As A Biomarker Of Hypomethylating Therapies, Philip G. Woost, Basem M. William, Brenda W. Cooper, Masumi Ueda Oshima, Folashade Otegbeye, Marcos J. De Lima, David Wald, Reda Z. Mahfouz, Yogen Saunthararajah, Tammy Stefan, James W. Jacobberger

Faculty Scholarship

The 5-azacytidine (AZA) and decitabine (DEC) are noncytotoxic, differentiation-inducing therapies approved for treatment of myelodysplastic syndrome, acute myeloid leukemias (AML), and under evaluation as maintenance therapy for AML postallogeneic hematopoietic stem cell transplant and to treat hemoglobinapathies. Malignant cell cytoreduction is thought to occur by S-phase specific depletion of the key epigenetic regulator, DNA methyltransferase 1 (DNMT1) that, in the case of cancers, thereby releases terminal-differentiation programs. DNMT1-targeting can also elevate expression of immune function genes (HLA-DR, MICA, MICB) to stimulate graft versus leukemia effects. In vivo, there is a large inter-individual variability in DEC and 5-AZA activity because of …

The Lived Experience Of Nursing Faculty At Rural Community Colleges In East Texas During The Covid-19 Pandemic, Mary N. Isichei

Walden Dissertations and Doctoral Studies

The COVID-19 pandemic highlighted the need for public health (PH) emergency preparedness and for the formal training of frontline workers, primarily nurses, on how to manage PH emergencies. The need for the latter was especially evident at U.S. rural community colleges (RCC), a subset of institutions of higher education (IHEs), which, due to a lack of resources, lacked PH-trained nursing faculty members (NFMs). The purpose of this qualitative study was to discover the lived experience of NFMs in RCC in East Texas during the COVID-19 pandemic. The phenomenological theoretical (PT) framework assisted in understanding the lived experience of the NFMs …

Tumor- And Circulating-Free Dna Methylation Identifies Clinically Relevant Small Cell Lung Cancer Subtypes, Simon Heeke, Carl M Gay, Marcos R Estecio, Hai Tran, Benjamin B Morris, Bingnan Zhang, Ximing Tang, Maria Gabriela Raso, Pedro Rocha, Siqi Lai, Edurne Arriola, Paul Hofman, Veronique Hofman, Prasad Kopparapu, Christine M Lovly, Kyle Concannon, Luana Guimaraes De Sousa, Whitney Elisabeth Lewis, Kimie Kondo, Xin Hu, Azusa Tanimoto, Natalie I Vokes, Monique B Nilsson, Allison Stewart, Maarten Jansen, Ildikó Horváth, Mina Gaga, Vasileios Panagoulias, Yael Raviv, Danny Frumkin, Adam Wasserstrom, Aharona Shuali, Catherine A Schnabel, Yuanxin Xi, Lixia Diao, Qi Wang, Jianjun Zhang, Peter Van Loo, Jing Wang, Ignacio I Wistuba, Lauren A Byers, John V Heymach

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given the known epigenetic regulation of critical SCLC transcriptional programs, we hypothesized that subtype-specific patterns of DNA methylation could be detected in tumor or blood from SCLC patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) in two cohorts totaling 179 SCLC patients and using machine learning approaches, we report a highly accurate DNA methylation-based classifier (SCLC-DMC) that can distinguish SCLC subtypes. We further adjust the classifier for circulating-free DNA (cfDNA) to subtype …

Understanding The Role Of Palliative Care Within Routine Care Of Advanced Liver Disease, Simone A. Jarrett, Edward Bley, Richard S. Kalman

Einstein Health Papers

Purpose of Review

This paper aims to investigate the crucial role of palliative care in the management of chronic liver disease (CLD) and cirrhosis. Faced with a global surge in liver-related morbidity and mortality, our goal is to understand the impact of early engagement with palliative care specialists on symptom management, quality of life, and the overall trajectory of advanced liver disease.

Recent Findings

While strides have been made in preventing and treating specific etiologies of CLD, such as viral infections, the escalating rates of alcohol use and obesity present new challenges for physicians. Despite advancements, liver transplantation unfortunately remains …

Phase I Study Of Mtorc1/2 Inhibitor Sapanisertib (Cb-228/Tak-228) In Combination With Metformin In Patients With Mtor/Akt/Pi3k Pathway Alterations And Advanced Solid Malignancies, Vivek Subbiah, Niamh Coleman, Sarina A Piha-Paul, Apostolia M Tsimberidou, Filip Janku, Jordi Rodon, Shubham Pant, Ecaterina E Ileana Dumbrava, Siqing Fu, David S Hong, Shizhen Zhang, Ming Sun, Yunfang Jiang, Jason Roszik, Juhee Song, Ying Yuan, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

BACKGROUND: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5'-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors.

METHODS: Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day …

Intouch Week Of February 12, 2024, New York Medical College

InTouch

• NYMC Celebrated the Grand Re-Opening of Doc’s Café
• NYMC and Regeneron Debut Neighborhood Science Seminar Series
• NYMC Alums Share Marriage, Memories, and a Lifetime Together
• LCME Element of the Week
• SIGN Hosts “Ask a Neurologist” Podcast Series
• Student Spotlight: SOM Student Ariel Yusupov Secures Spot in Westchester County Biosciences Accelerator Program

Variations In Duration Of Clinical Follow-Up After Spinal Fusion For Adolescent Idiopathic Scoliosis: A Survey Of Posna And Srs Membership, Taylor R Johnson, Nicole A Segovia, Xochitl Bryson, Meghan N Imrie, John S Vorhies

Faculty, Staff and Student Publications

Background: There are currently no evidence-based guidelines addressing the optimal duration of follow-up after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Despite the safety and efficacy of PSF for AIS, long-term complications exist, including infection, pseudoarthrosis, adjacent segment disease, deformity progression, persistent pain, and junctional deformities. In this study, we describe practice variation existing among surgeons regarding duration and intervals of patient follow-up after surgical treatment of AIS in addition to factors influencing provider recommendations for duration of radiographic and clinical follow-up. This investigation of practice variation is important, as opportunities exist for both limiting unnecessary radiation exposure, …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Efficacy Of Supplemental Ultrasound-Guided Pericapsular Nerve Group (Peng) Block Combined With Lateral Femoral Cutaneous Nerve Block In Patients Receiving Local Infiltration Analgesia After Hip Fracture Surgery: A Prospective Randomized Controlled Trial, Seung-Hee Yoo, Min-Jin Lee, Min-Hyouk Beak, Won-Joong Kim

Faculty, Staff and Student Publications

No abstract provided.

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M Taylor, Kang Ho Kim, J Marc Rhoads, Yuying Liu

Faculty, Staff and Student Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Molecular-Guided Therapy For The Treatment Of Patients With Relapsed And Refractory Childhood Cancers: A Beat Childhood Cancer Research Consortium Trial., Giselle L Saulnier Sholler, Genevieve Bergendahl, Elizabeth C. Lewis, Jacqueline Kraveka, William Ferguson, Abhinav B. Nagulapally, Karl Dykema, Valerie I Brown, Michael S. Isakoff, Joseph Junewick, Deanna Mitchell, Jawhar Rawwas, William Roberts, Don Eslin, Javier Oesterheld, Randal K. Wada, Devang Pastakia, Virginia Harrod, Kevin Ginn, Raya Saab, Kevin Bielamowicz, Jason Glover, Eugenia Chang, Gina K. Hanna, Daniel Enriquez, Tyler Izatt, Rebecca F Halperin, Abigail Moore, Sara A. Byron, William P D Hendricks, Jeffrey M. Trent

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children with relapsed central nervous system (CNS tumors), neuroblastoma, sarcomas, and other rare solid tumors face poor outcomes. This prospective clinical trial examined the feasibility of combining genomic and transcriptomic profiling of tumor samples with a molecular tumor board (MTB) approach to make real‑time treatment decisions for children with relapsed/refractory solid tumors.

METHODS: Subjects were divided into three strata: stratum 1-relapsed/refractory neuroblastoma; stratum 2-relapsed/refractory CNS tumors; and stratum 3-relapsed/refractory rare solid tumors. Tumor samples were sent for tumor/normal whole-exome (WES) and tumor whole-transcriptome (WTS) sequencing, and the genomic data were used in a multi-institutional MTB to make real‑time treatment …

Insights From The Histopathologic Analysis Of Acquired And Genetic Thoracic Aortic Aneurysms And Dissections, L Maximilian Buja, Bihong Zhao, Humaira Sadaf, Michelle Mcdonald, Ana M Segura, Li Li, Alana Cecchi, Siddharth K Prakash, Rana O Afifi, Charles C Miller, Anthony L Estrera, Dianna M Milewicz

Faculty, Staff and Student Publications

OBJECTIVE: The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases.

METHODS: A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74).

RESULTS: The various types …

Belzutifan, Hif-2Α Inhibitor, And Clear Cell Renal Cell Carcinoma With Somatic Von-Hippel-Lindau Loss-Of-Function Mutation, Kok Hoe Chan, Ningjing Li, Ran Lador, Mark Amsbaugh, Anneliese Gonzalez, Putao Cen

Faculty, Staff and Student Publications

The Von-Hippel-Lindau (VHL) gene, acting as a tumor suppressor, plays a crucial role in the tumorigenesis of clear cell renal cell carcinoma (ccRCC). Approximately 90% of individuals with advanced ccRCC exhibit somatic mutations in the VHL gene. Belzutifan, orally administered small-molecule inhibitor of hypoxia-induced factor-2α, has demonstrated promising efficacy in solid tumors associated with germline loss-of-function mutations in VHL, including ccRCC. However, its impact on cases with somatic or sporadic VHL mutations remains unclear. Here, we present 2 cases where belzutifan monotherapy was employed in patients with advanced ccRCC and somatic loss-of-function mutations in VHL. Both patients exhibited a swift …

Ic3d Classification Of Corneal Dystrophies-Edition 3, Jayne S. Weiss, Christopher J. Rapuano, Berthold Seitz, Massimo Busin, Tero T. Kivelä, Nacim Bouheraoua, Cecilie Bredrup, Ken K. Nischal, Harshvardhan Chawla, Vincent Borderie, Kenneth R. Kenyon, Eung Kweon Kim, Hans Ulrik Møller, Francis L. Munier, Tim Berger, Walter Lisch

School of Medicine Faculty Publications

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( …

Cannula Placement For Cerebral Protection Without Circulatory Arrest In Patients Undergoing Hemiarch Aortic Aneurysm Repair, Joseph C Sweeney, Jaimin R Trivedi, Toyokazu Endo, Akhila Ankem, Siddharth V Pahwa, Mark S Slaughter, Brian L Ganzel

The Texas Heart Institute Journal

BACKGROUND: Aortic aneurysms involving the proximal aortic arch, which require hemiarch-type repair, typically require circulatory arrest with antegrade cerebral perfusion. Left carotid antegrade cerebral perfusion (LCP) via distal arch cannulation without circulatory arrest was used in this study's patient population. The goal was to assess the operative efficiency and clinical outcomes of using a distal arch cannulation technique that would not require any hypothermic circulatory arrest (HCA) time compared with more traditional brachiocephalic artery cannulation with right-sided unilateral antegrade cerebral perfusion (RCP) and HCA.

METHODS: A single-center retrospective review of patients with replacement of the distal ascending aorta involving the …

Specifying Cross-System Collaboration Strategies For Implementation: A Multi-Site Qualitative Study With Child Welfare And Behavioral Health Organizations, Alicia C Bunger, Emmeline Chuang, Amanda M Girth, Kathryn E Lancaster, Rebecca Smith, Rebecca J Phillips, Jared Martin, Fawn Gadel, Tina Willauer, Marla J Himmeger, Jennifer Millisor, Jen Mcclellan, Byron J Powell, Lisa Saldana, Gregory A Aarons

2020-Current year OA Pubs

BACKGROUND: Cross-system interventions that integrate health, behavioral health, and social services can improve client outcomes and expand community impact. Successful implementation of these interventions depends on the extent to which service partners can align frontline services and organizational operations. However, collaboration strategies linking multiple implementation contexts have received limited empirical attention. This study identifies, describes, and specifies multi-level collaboration strategies used during the implementation of Ohio Sobriety Treatment and Reducing Trauma (Ohio START), a cross-system intervention that integrates services across two systems (child welfare and evidence-based behavioral health services) for families that are affected by co-occurring child maltreatment and parental …

Predicting Proximal Tubule Failed Repair Drivers Through Regularized Regression Analysis Of Single Cell Multiomic Sequencing, Nicolas Ledru, Parker C Wilson, Yoshiharu Muto, Yasuhiro Yoshimura, Haojia Wu, Dian Li, Amish Asthana, Stefan G Tullius, Sushrut S Waikar, Giuseppe Orlando, Benjamin D Humphreys

2020-Current year OA Pubs

Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes. Single nucleus joint RNA- and ATAC-seq sequencing offers an opportunity to study the gene regulatory networks underpinning these changes in order to identify key regulatory drivers. We develop a regularized regression approach to construct genome-wide parametric gene regulatory networks using multiomic datasets. We generate a …

Circuit-Based Intervention Corrects Excessive Dentate Gyrus Output In The Fragile X Mouse Model, Pan-Yue Deng, Ajeet Kumar, Valeria Cavalli, Vitaly A Klyachko

2020-Current year OA Pubs

Abnormal cellular and circuit excitability is believed to drive many core phenotypes in fragile X syndrome (FXS). The dentate gyrus is a brain area performing critical computations essential for learning and memory. However, little is known about dentate circuit defects and their mechanisms in FXS. Understanding dentate circuit dysfunction in FXS has been complicated by the presence of two types of excitatory neurons, the granule cells and mossy cells. Here we report that loss of FMRP markedly decreased excitability of dentate mossy cells, a change opposite to all other known excitability defects in excitatory neurons in FXS. This mossy cell …

Effects Of Metformin On Glucose Metabolism And Mitochondrial Function In Patients With Obstructive Sleep Apnea: A Pilot Randomized Trial, Elizabeth R.M. Zunica, Elizabeth C. Heintz, Wagner S. Dantas, R. Caitlin Hebert, Ma Kayla Tanksley, Robbie A. Beyl, Edward C. Mader, John P. Kirwan, Christopher L. Axelrod, Prachi Singh

School of Medicine Faculty Publications

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = …

Probiotic Limosilactobacillus Reuteri Dsm 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia And Chronic Hepatitis In Mice, Erini Nessim Kostandy, Ji Ho Suh, Xiangjun Tian, Beanna Okeugo, Erin Rubin, Sara Shirai, Meng Luo, Christopher M. Taylor, Kang Ho Kim, J. Marc Rhoads, Yuying Liu

School of Medicine Faculty Publications

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids …

Impact Of Smoking And Drinking Habits On Lipid Profiles In Diabetic And Non-Diabetic Individuals & Their Oral Implications, Dinraj Kulkarni

Annual Research Symposium

The rising prevalence of lifestyle-related diseases, notably diabetes mellitus and cardiovascular diseases (CVD), underscores the importance of investigating modifiable risk factors such as smoking and alcohol consumption. These habits are known to influence lipid profiles, crucial indicators of cardiovascular health. Main aim of this study To investigate & evaluate the effect of smoking and drinking habits on lipid profiles of diabetic and non-diabetic individuals and their oral implications.