Digital Commons Network^™

Green Synthesis Of Zinc Oxide Nanoparticles From Althaea Officinalis Flower Extract Coated With Chitosan For Potential Healing Effects On Diabetic Wounds By Inhibiting Tnf-Α And Il-6/Il-1Β Signaling Pathways, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed Abdul Kareem Saeed Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Ahmed Mohsen Elsaid Hamdan, Mohamed Mansour Khalifa, Sandra Hababeh, Mohammad Ahmad Khasawneh, Gehad M Khamis, Jakline Nelson, Passant M Mohie, Rania A Gad, Amira Rizk, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Tayseer Elnawawy, Fatma E Hassan, Mohamed A El-Nabarawi

Faculty, Staff and Students Publications

BACKGROUND: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia.

METHOD AND RESULTS: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean …

Revolutionizing Psoriasis Topical Treatment: Enhanced Efficacy Through Ceramide/Phospholipid Composite Cerosomes Co-Delivery Of Cyclosporine And Dithranol: In-Vitro, Ex-Vivo, And In-Vivo Studies, Sammar Fathy Elhabal, Nashwa Abdelaal, Saeed A S Al-Zuhairy, Mohamed Fathi Mohamed Elrefai, Mohamed Mansour Khalifa, Mohammad Ahmad Khasawneh, Ahmed Mohsen Elsaid Hamdan, Passant M Mohie, Rania A Gad, Soad L Kabil, Mohamed Kandeel El-Ashery, Bhaskara R Jasti, Nahla A Elzohairy, Nehal Elfar, Tayseer Elnawawy, Fatma E Hassan, Mohamed Ahmed El-Nabarawi

Faculty, Staff and Students Publications

PURPOSE: Improving the treatment of psoriasis is a serious challenge today. Psoriasis is an immune-mediated skin condition affecting 125 million people worldwide. It is commonly treated with cyclosporine-A (CsA) and dithranol (DTH). CsA suppresses the activation of T-cells, immune cells involved in forming psoriatic lesions. Meanwhile, DTH is a potent anti-inflammatory and anti-proliferative drug that effectively reduces the severity of psoriasis symptoms such as redness, scaling, and skin thickness. CsA and DTH belong to BCS class II with limited oral bioavailability. We aim to develop a drug delivery system for topical co-delivery of CsA and DTH, exploring its therapeutic potential. …

Traf4-Mediated Nonproteolytic Ubiquitination Of Androgen Receptor Promotes Castration-Resistant Prostate Cancer, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Steroid Receptor Coactivators In Treg And Th17 Cell Biology And Function, Yosi Gilad, Ortal Shimon, Sang Jun Han, David M Lonard, Bert W O'Malley

Faculty, Staff and Students Publications

Steroid receptor coactivators (SRCs) are master regulators of transcription that play key roles in human physiology and pathology. SRCs are particularly important for the regulation of the immune system with major roles in lymphocyte fate determination and function, macrophage activity, regulation of nuclear factor κB (NF-κB) transcriptional activity and other immune system biology. The three members of the p160 SRC family comprise a network of immune-regulatory proteins that can function independently or act in synergy with each other, and compensate for - or moderate - the activity of other SRCs. Recent evidence indicates that the SRCs are key participants in …

Mir-142: A Master Regulator In Hematological Malignancies And Therapeutic Opportunities, Wilson Huang, Doru Paul, George A Calin, Recep Bayraktar

Faculty, Staff and Student Publications

MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias. This review elucidates the multifaceted role of miR-142 in human physiology, its influence on hematopoiesis and hematopoietic cells, and its intriguing involvement in exosome-mediated miR-142 transport. Moreover, we offer a comprehensive …

Benefits Of Sharing Neurophysiology Data From The Brain Initiative Research Opportunities In Humans Consortium, Vasiliki Rahimzadeh, Kathryn Maxson Jones, Mary A Majumder, Michael J Kahana, Ueli Rutishauser, Ziv M Williams, Sydney S Cash, Angelique C Paulk, Jie Zheng, Michael S Beauchamp, Jennifer L Collinger, Nader Pouratian, Amy L Mcguire, Sameer A Sheth

Center for Medical Ethics and Health Policy Staff Publications

Sharing human brain data can yield scientific benefits, but because of various disincentives, only a fraction of these data is currently shared. We profile three successful data-sharing experiences from the NIH BRAIN Initiative Research Opportunities in Humans (ROH) Consortium and demonstrate benefits to data producers and to users.

Investigating The Effects Of Subchronic Dietary Zinc Supplementation On Diet-Induced Metabolic Dysfunction-Associated Steatotic Liver Disease., Oluwanifemi Esther Bolatimi

Electronic Theses and Dissertations

Zinc deficiency is associated with metabolic dysfunction-associated steatotic liver disease (MASLD). Previous studies show zinc supplementation improves steatosis, but its therapeutic effects in established MASLD remain unclear. We developed a model to characterize the effects of zinc supplementation on high-fat diet (HFD) induced MASLD and hypothesized established MASLD would be attenuated. Mice were fed control diet or HFD for 12 weeks and then grouped into normal or zinc-supplemented diets for 8 additional weeks. At euthanasia, plasma and liver tissues were collected for phenotypic analysis. Twelve weeks of HFD altered glucose clearance and body composition. Eight weeks of subsequent zinc supplementation …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Biomedical Engineering: Graduate Reports and Projects

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Development Of Thermosensitive Hydrogel Of Amphotericin-B And Lactoferrin Combination-Loaded Plga-Peg-Pei Nanoparticles For Potential Eradication Of Ocular Fungal Infections, Sammar Fathy Elhabal, Shrouk A Ghaffar, Raghda Hager, Nahla A Elzohairy, Mohamed Mansour Khalifa, Passant M Mohie, Rania A Gad, Nasreen N Omar, Mohammed H Elkomy, Mohammad Ahmad Khasawneh, Nashwa Abdelaal

Faculty, Staff and Students Publications

The most prevalent conditions among ocular surgery and COVID−19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, …

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Dominant Negative Variants In Ikzf2 Cause Ichad Syndrome, A New Disorder Characterized By Immunodysregulation, Craniofacial Anomalies, Hearing Impairment, Athelia, And Developmental Delay, Arezoo Mohajeri, Maryam Vaseghi-Shanjani, Jill A Rosenfeld, Gui Xiang Yang, Henry Lu, Mehul Sharma, Susan Lin, Areesha Salman, Meriam Waqas, Mahshid Sababi Azamian, Kim C Worley, Kate L Del Bel, Frederick K Kozak, Ronak Rahmanian, Catherine M Biggs, Kyla J Hildebrand, Seema R Lalani, Sarah K Nicholas, Daryl A Scott, Sara Mostafavi, Clara Van Karnebeek, Erika Henkelman, Jessica Halparin, Connie L Yang, Linlea Armstrong, Undiagnosed Diseases Network, Anna Lehman Care 4 Rare Canada Consortium, Stuart E Turvey

Faculty, Staff and Students Publications

Background:

Helios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognized for its role in the development and function of T lymphocytes, particularly the CD4⁺ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.

Methods:

We performed detailed phenotypic, genomic, and functional investigations on …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …

Seminar: Extracellular Vesicles As Mediators Of Environmental Stress In Human Disease, Vrinda Kalia, Andrea A Baccarelli, Christine Happel, Jonathan A Hollander, Anne Marie Jukic, Kimberly A Mcallister, Ramkumar Menon, Bruce A Merrick, Aleksander Milosavljevic, Lingamanaidu V Ravichandran, Matthew E Roth, Anita Subramanian, Frederick L Tyson, Leroy Worth, Daniel T Shaughnessy

Faculty, Staff and Students Publications

Background: Extracellular vesicles (EVs), membrane-bound particles containing a variety of RNA types, DNA, proteins, and other macromolecules, are now appreciated as an important means of communication between cells and tissues, both in normal cellular physiology and as a potential indicator of cellular stress, environmental exposures, and early disease pathogenesis. Extracellular signaling through EVs is a growing field of research for understanding fundamental mechanisms of health and disease and for the potential for biomarker discovery and therapy development. EVs are also known to play important roles in mediating the effects of exposure to environmental stress.

Objectives: This seminar addresses the application …

Multiancestry Analysis Of The Hla Locus In Alzheimer’S And Parkinson’S Diseases Uncovers A Shared Adaptive Immune Response Mediated By Hla-Drb1*04 Subtypes, Yann Le Guen, Guo Luo, Aditya Ambati, Vincent Damotte, Iris Jansen, Eric Yu, Aude Nicolas, Itziar De Rojas, Thiago Peixoto Leal, Akinori Miyashita, Céline Bellenguez, Michelle Mulan Lian, Kayenat Parveen, Takashi Morizono, Hyeonseul Park, Benjamin Grenier-Boley, Tatsuhiko Naito, Fahri Küçükali, Seth D Talyansky, Selina Maria Yogeshwar, Vicente Sempere, Wataru Satake, Victoria Alvarez, Beatrice Arosio, Michael E Belloy, Luisa Benussi, Anne Boland, Barbara Borroni, María J Bullido, Paolo Caffarra, Jordi Clarimon, Antonio Daniele, Daniel Darling, Stéphanie Debette, Jean-François Deleuze, Martin Dichgans, Carole Dufouil, Emmanuel During, Emrah Düzel, Daniela Galimberti, Guillermo Garcia-Ribas, José María García-Alberca, Pablo García-González, Vilmantas Giedraitis, Oliver Goldhardt, Caroline Graff, Edna Grünblatt, Olivier Hanon, Lucrezia Hausner, Stefanie Heilmann-Heimbach, Henne Holstege, Jakub Hort, Yoo Jin Jung, Deckert Jürgen, Silke Kern, Teemu Kuulasmaa, Kun Ho Lee, Ling Lin, Carlo Masullo, Patrizia Mecocci, Shima Mehrabian, Alexandre De Mendonça, Mercè Boada, Pablo Mir, Susanne Moebus, Fermin Moreno, Benedetta Nacmias, Gael Nicolas, Shumpei Niida, Børge G Nordestgaard, Goran Papenberg, Janne Papma, Lucilla Parnetti, Florence Pasquier, Pau Pastor, Oliver Peters, Yolande A L Pijnenburg, Gerard Piñol-Ripoll, Julius Popp, Laura Molina Porcel, Raquel Puerta, Jordi Pérez-Tur, Innocenzo Rainero, Inez Ramakers, Luis M Real, Steffi Riedel-Heller, Eloy Rodriguez-Rodriguez, Owen A Ross, Luis Jose Royo, Dan Rujescu, Nikolaos Scarmeas, Philip Scheltens, Norbert Scherbaum, Anja Schneider, Davide Seripa, Ingmar Skoog, Vincenzo Solfrizzi, Gianfranco Spalletta, Alessio Squassina, John Van Swieten, Raquel Sánchez-Valle, Eng-King Tan, Thomas Tegos, Charlotte Teunissen, Jesper Qvist Thomassen, Lucio Tremolizzo, Martin Vyhnalek, Frans Verhey, Margda Waern, Jens Wiltfang, Jing Zhang, Eadb, Gr@Ace Study Group, Degesco Consortium, Demgene, Eadi, Gerad, Asian Parkinson’S Disease Genetics Consortium, Henrik Zetterberg, Kaj Blennow, Zihuai He, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick G Kehoe, Ole A Andreassen, Cornelia Van Duin, Magda Tsolaki, Pascual Sánchez-Juan, Ruth Frikke-Schmidt, Kristel Sleegers, Tatsushi Toda, Anna Zettergren, Martin Ingelsson, Yukinori Okada, Giacomina Rossi, Mikko Hiltunen, Jungsoo Gim, Kouichi Ozaki, Rebecca Sims, Jia Nee Foo, Wiesje Van Der Flier, Takeshi Ikeuchi, Alfredo Ramirez, Ignacio Mata, Agustín Ruiz, Ziv Gan-Or, Jean-Charles Lambert, Michael D Greicius, Emmanuel Mignot

Faculty, Staff and Students Publications

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. …

Integrating Social Determinants Of Health Into Ethical Digital Simulations, Kristin Kostick-Quenet, Vasiliki Rahimzadeh, Sharmila Anandasabapathy, Meghan Hurley, Anika Sonig, Amy Mcguire

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

The Case For Expanding Visual Assessments During Spaceflight, Ethan Waisberg, Joshua Ong, Mouayad Masalkhi, Nasif Zaman, Sharif Amit Kamran, Prithul Sarker, Alireza Tavakkoli, Andrew G Lee

Faculty, Staff and Student Publications

Spaceflight associated neuro-ocular syndrome (SANS) is one of the potential barriers to human long-duration spaceflight (LDSF), including a manned mission to Mars. While a large barrier, the pathophysiology of SANS is not well understood, and functional and structural findings from SANS continue to be further characterized. Currently on the International Space Station (ISS), scheduled visual assessments are static visual acuity, Amsler grid, and a self-reported survey. Additional visual assessments may help the understanding of this neuro-ophthalmic phenomenon, as well as the effects of spaceflight of overall ocular health. In this paper, a case is made for expanding scheduled visual assessments …

Why Animal Experiments Are Still Indispensable In Bone Research: A Statement By The European Calcified Tissue Society, Merle Stein, Florent Elefteriou, Björn Busse, Imke Ak Fiedler, Ronald Young Kwon, Eric Farrell, Mubashir Ahmad, Anita Ignatius, Liam Grover, Liesbet Geris, Jan Tuckermann

Faculty, Staff and Students Publications

Major achievements in bone research have always relied on animal models and in vitro systems derived from patient and animal material. However, the use of animals in research has drawn intense ethical debate and the complete abolition of animal experimentation is demanded by fractions of the population. This phenomenon is enhanced by the reproducibility crisis in science and the advance of in vitro and in silico techniques. 3D culture, organ-on-a-chip, and computer models have improved enormously over the last years. Nevertheless, the overall complexity of bone tissue-cross talk and the systemic and local regulation of bone physiology can often only …

Noncanonical Binding Of Transcription Factors: Time To Revisit Specificity?, Md Abul Hassan Samee

Faculty, Staff and Students Publications

Transcription factors (TFs) are one of the most studied classes of DNA-binding proteins that have a direct functional impact on gene transcription and thus, on human physiology and disease. The mechanisms that TFs use for recognizing target DNA binding sites have been studied for nearly five decades, yet they remain poorly understood. It is classically assumed that a TF recognizes a specific sequence pattern, or motif, as its binding sites. However, recent studies are consistently finding examples of noncanonical binding, that is, TFs binding at sites that do not resemble their sequence motifs. Here we review the current literature on …

Bicc1 Drives Pancreatic Cancer Progression By Inducing Vegf-Independent Angiogenesis, Chongbiao Huang, Hui Li, Yang Xu, Chao Xu, Huizhi Sun, Zengxun Li, Yi Ge, Hongwei Wang, Tiansuo Zhao, Song Gao, Xiuchao Wang, Shengyu Yang, Peiqing Sun, Zhe Liu, Jing Liu, Antao Chang, Jihui Hao

Faculty, Staff and Student Publications

VEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors. Nevertheless, pancreatic adenocarcinoma (PAAD) cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways, thereby conferring resistance to VEGF inhibitors. Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD. The analysis of our own cohort confirmed that BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth, and worse prognosis. In cells and mice with xenograft tumors, BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent …

When A Calorie Is Not Just A Calorie: Diet Quality And Timing As Mediators Of Metabolism And Healthy Aging, Maria M Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, Zheng Chen, William W Ja, Michele Shirasu-Hiza, Mary N Latimer, Julie A Mattison, Anna E Thalacker-Mercer, Vishwa Deep Dixit, Satchidananda Panda, Dudley W Lamming

Faculty, Staff and Student Publications

An epidemic of obesity has affected large portions of the world, increasing the risk of developing many different age-associated diseases, including cancer, cardiovascular disease, and diabetes. In contrast with the prevailing notion that "a calorie is just a calorie," there are clear differences, within and between individuals, in the metabolic response to different macronutrient sources. Recent findings challenge this oversimplification; calories from different macronutrient sources or consumed at different times of day have metabolic effects beyond their value as fuel. Here, we summarize discussions conducted at a recent NIH workshop that brought together experts in calorie restriction, macronutrient composition, and …

The Genetics Of Primary Ciliary Dyskinesia In Puerto Rico, Paolo Zanoni, Katharina Steindl, Heinrich Sticht, Beatrice Oneda, Pascal Joset, Ivan Ivanovski, Anselm H C Horn, Elena M Cabello, Julia Laube, Markus Zweier, Alessandra Baumer, Anita Rauch, Nadia Khan

Faculty, Staff and Student Publications

Pediatric Moyamoya Angiopathy (MMA) is a progressive intracranial occlusive arteriopathy that represents a leading cause of transient ischemic attacks and strokes in childhood. Despite this, up to now no large, exclusively pediatric MMA cohort has been subjected to systematic genetic investigation. In this study, we performed molecular karyotyping, exome sequencing and automated structural assessment of missense variants on a series of 88 pediatric MMA patients and correlated genetic, angiographic and clinical (stroke burden) findings. The two largest subgroups in our cohort consisted of RNF213 and neurofibromatosis type 1 (NF1) patients. While deleterious RNF213 variants were associated with a severe MMA …

Lateral Septum As A Melanocortin Downstream Site In Obesity Development, Yuanzhong Xu, Zhiying Jiang, Hongli Li, Jing Cai, Yanyan Jiang, Joshua Otiz-Guzman, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons …

Toxicological Evaluation Of A Polyherbal Formulation On Testicular Function And Gonadal Histomorphology In Exposed Wistar Rats, Godswill James Udom, Uduak Peter Ise, Omoirri Moses Aziakpono, Ayodeji Aturamu, Mba Ogbonnaya, Israel Kevin Umana, Jude Efiom Okokon

BioMedicine

Introduction: Dr Iguedo Goko Cleanser® is a herbal formulation (HF) widely marketed in southern Nigeria and purported to be very efficacious for the management of various diseases including giardiasis, toilet infections, hypertension, diabetes, ulcer, impotence, low libido, low sperm count amongst others. Medicinal plants reportedly produce an array of adverse reactions capable of inducing harmful conditions, including death. Aim: This study evaluated the subchronic toxicity concern of HF on testicular function and gonadal histoarchitecture in Wistar rats. Methods: Thirty Wistar rats of both sexes were randomly divided into six groups (5/group) and were orally administered HF for 60 days. The …

Evaluating The Impact Of Routine Enteral Iron Fortification On Gastrointestinal Dysbiosis In Premature Infants, Matthew Van Ormer

Theses & Dissertations

The gastrointestinal microbiome in preterm infants bears significant influence on optimal outcomes – dysbiosis is shown to substantially increase the risk of the life-threatening necrotizing enterocolitis, whereas optimal microbiome composition improves nutrient digestion and immune function. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurological development. However, excess colonic iron exhibits potent oxidation capacity and alters the competitive environment of microbes – potentially facilitating the proliferation of pathological bacterial strains in the gut. Of note, breastfed preterm infants routinely receive iron fortification starting at 14 days of life and are …

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

The Association Between Caffeine Intake And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Annie Dai, Kristi Hoffman, Anthony A Xu, Shawn Gurwara, Donna L White, Fasiha Kanwal, Albert Jang, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

We examined the association between caffeine and coffee intake and the community composition and structure of colonic microbiota. A total of 34 polyp-free adults donated 97 colonic biopsies. Microbial DNA was sequenced for the 16S rRNA gene V4 region. The amplicon sequence variant was assigned using DADA2 and SILVA. Food consumption was ascertained using a food frequency questionnaire. We compared the relative abundance of taxonomies by low (<82.9 mg) vs. high (≥82.9 mg) caffeine intake and by never or <2 cups vs. 2 cups vs. ≥3 cups coffee intake. False discovery rate-adjusted p values (q values) <0.05 indicated statistical significance. Multivariable negative binomial regression models were used to estimate the incidence rate ratio and its 95% confidence interval of having a non-zero count of certain bacteria by intake level. Higher caffeine and coffee intake was related to higher alpha diversity (Shannon index p < 0.001), higher relative abundance of Faecalibacterium and Alistipes, and lower relative abundance of Erysipelatoclostridium (q values < 0.05). After adjustment of vitamin B2 in multivariate analysis, the significant inverse association between Erysipelatoclostridium count and caffeine intake remained statistically significant. Our preliminary study could not …

Health Consequences Of Low Energy Availability In Females And Their Underlying Physiological Mechanisms, Grace Parry

Senior Honors Theses

Low energy availability (LEA) is a state in which energy intake is insufficient to support energy expenditure while maintaining energy balance, which has been shown to result in gastrointestinal distress, immunosuppression, reduced metabolic rate, menstrual dysfunction, diminished bone health, and impaired cardiovascular function in females. Alterations to the microbiome and mucosal lining may propagate gastrointestinal complaints and compromised immune function associated with LEA. The pathophysiology of LEA is otherwise largely driven by hormonal adaptations. Diminished production of thyroid hormones is known to contribute to reduced metabolic rate. Decreases in leptin and insulin and increases in ghrelin disrupt reproductive function through …