Medicine and Health Sciences Commons^™

The Clinical And Molecular Spectrum Of The Kdm6b-Related Neurodevelopmental Disorder, Dmitrijs Rots, Taryn E Jakub, Crystal Keung, Adam Jackson, Siddharth Banka, Rolph Pfundt, Bert B A De Vries, Richard H Van Jaarsveld, Saskia M J Hopman, Ellen Van Binsbergen, Irene Valenzuela, Maja Hempel, Tatjana Bierhals, Fanny Kortüm, Francois Lecoquierre, Alice Goldenberg, Jens Michael Hertz, Charlotte Brasch Andersen, Maria Kibæk, Eloise J Prijoles, Roger E Stevenson, David B Everman, Wesley G Patterson, Linyan Meng, Charul Gijavanekar, Karl De Dios, Shenela Lakhani, Tess Levy, Matias Wagner, Dagmar Wieczorek, Paul J Benke, María Soledad Lopez Garcia, Renee Perrier, Sergio B Sousa, Pedro M Almeida, Maria José Simões, Bertrand Isidor, Wallid Deb, Andrew A Schmanski, Omar Abdul-Rahman, Christophe Philippe, Ange-Line Bruel, Laurence Faivre, Antonio Vitobello, Christel Thauvin, Jeroen J Smits, Livia Garavelli, Stefano G Caraffi, Francesca Peluso, Laura Davis-Keppen, Dylan Platt, Erin Royer, Lisette Leeuwen, Margje Sinnema, Alexander P A Stegmann, Constance T R M Stumpel, George E Tiller, Daniëlle G M Bosch, Stephanus T Potgieter, Shelagh Joss, Miranda Splitt, Simon Holden, Matina Prapa, Nicola Foulds, Sofia Douzgou, Kaija Puura, Regina Waltes, Andreas G Chiocchetti, Christine M Freitag, F Kyle Satterstrom, Silvia De Rubeis, Joseph Buxbaum, Bruce D Gelb, Aleksic Branko, Itaru Kushima, Jennifer Howe, Stephen W Scherer, Alessia Arado, Chiara Baldo, Olivier Patat, Demeer Bénédicte, Diego Lopergolo, Filippo M Santorelli, Tobias B Haack, Andreas Dufke, Miriam Bertrand, Ruth J Falb, Angelika Rieß, Peter Krieg, Stephanie Spranger, Maria Francesca Bedeschi, Maria Iascone, Sarah Josephi-Taylor, Tony Roscioli, Michael F Buckley, Jan Liebelt, Aditi I Dagli, Emmelien Aten, Anna C E Hurst, Alesha Hicks, Mohnish Suri, Ermal Aliu, Sunil Naik, Richard Sidlow, Juliette Coursimault, Gaël Nicolas, Hanna Küpper, Florence Petit, Veyan Ibrahim, Deniz Top, Francesca Di Cara, Raymond J Louie, Elliot Stolerman, Han G Brunner, Lisenka E L M Vissers, Jamie M Kramer, Tjitske Kleefstra

Faculty, Staff and Students Publications

De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause "neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities." Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is …

Frequent Questions And Responses On The 2022 Lipoprotein(A) Consensus Statement Of The European Atherosclerosis Society, Florian Kronenberg, Samia Mora, Erik S G Stroes, Brian A Ference, Benoit J Arsenault, Lars Berglund, Marc R Dweck, Marlys L Koschinsky, Gilles Lambert, François Mach, Catherine J Mcneal, Patrick M Moriarty, Pradeep Natarajan, Børge G Nordestgaard, Klaus G Parhofer, Salim S Virani, Arnold Von Eckardstein, Gerald F Watts, Jane K Stock, Kausik K Ray, Lale S Tokgözoğlu, Alberico L Catapano

Faculty, Staff and Students Publications

In 2022, the European Atherosclerosis Society (EAS) published a new consensus statement on lipoprotein(a) [Lp(a)], summarizing current knowledge about its causal association with atherosclerotic cardiovascular disease (ASCVD) and aortic stenosis. One of the novelties of this statement is a new risk calculator showing how Lp(a) influences lifetime risk for ASCVD and that global risk may be underestimated substantially in individuals with high or very high Lp(a) concentration. The statement also provides practical advice on how knowledge about Lp(a) concentration can be used to modulate risk factor management, given that specific and highly effective mRNA-targeted Lp(a)-lowering therapies are still in clinical …

Transcriptional Differences In Identical Twins With Different Reproductive Capacities: A Case Report, Katherine Campbell, Alexandra Dullea, Christian Ramsoomair, Kyle Schuppe, Armin Ghomeshi, Kajal Khodamoradi, Himanshu Arora, Carolina Jorgez, Ranjith Ramasamy

Faculty, Staff and Students Publications

Disorders of sperm production can be classified quantitatively as oligospermia (low sperm count) or azoospermia (no sperm during ejaculation). Numerous genes have been implicated in spermatogenesis. We describe a case of two identical twins who presented with different reproductive capabilities. One brother was infertile due to azoospermia, and the other, although oligospermic, previously naturally fathered a child. They were found to have differential gene expression based on RNA sequencing analysis. In the man with azoospermia, we found elevated E2F1 and HOXB9 gene expressions when compared with his brother, suggesting that the increased RNA expression of these genes could influence sperm …

Reworking Emergency Medicine Resident Education Post-Dobbs V Jackson Women's Health Organization, Monica Rakesh Saxena, Esther K Choo, Sara Andrabi

Faculty, Staff and Students Publications

No abstract provided.

Go With The Flow: An Experimental Analysis With Tubing Alternative With Irrigation., Scott S Hyland, Daniel T Degenova, Joseph P Scheschuk, Benjamin C Taylor

Trauma and Acute Care Articles

BACKGROUND AND AIMS: Literature regarding alternative tubing for fluid delivery in irrigation and debridement procedures is lacking. The purpose of this study was to compare three different apparatuses with varying quantities of irrigation fluid to assess efficiency of administration and evaluate overall time for fluid administration.

METHODS: This model was designed to compare available methods of gravity irrigation used in practice. Fluid flow time was measured for three types of tubing: single-lumen cystoscopy tubing, Y-type double-lumen cystoscopy tubing, and nonconductive suction tubing. Irrigation times were assessed for varying volumes of 3, 6, and 9 L to investigate the relationship between …

Interdisciplinary Simulation Training Reduces Restraint Use In The Emergency Department: A Pilot Study., Gary Duncan, Brad Gable, Megan Schabbing

Medical Education Articles

Introduction Safe and effective management of agitated patients poses multiple challenges for healthcare professionals. Patients placed in restraints because of agitated behavior are at a higher risk of complications, including death. This intervention was designed to provide emergency department staff a framework for de-escalation, improve teamwork, and reduce the use of violent physical restraints. Methods Emergency medicine nurses, patient support associates, and protective services officers underwent a 90-minute educational intervention in 2017. A 30-minute lecture focusing on communication and early use of medication for agitation was followed by a simulation using standardized participants, then a structured debriefing. A standardized return-on-learning …

Correction To: Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Black Bioethics In The Age Of Black Lives Matter, Keisha Ray, Faith E Fletcher, Daphne O Martschenko, Jennifer E James

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Patient-Reported Fatigue And Pain In Erdheim-Chester Disease: A Registry-Based, Mixed Methods Study, Anne S Reiner, Dana Bossert, Justin J Buthorn, Allison M Sigler, Selin Gonen, Deanna Fournier, Kathleen Brewer, Jessica Corkran, Gaurav Goyal, Carl E Allen, Kenneth L Mcclain, Thomas M Atkinson, Kathleen A Lynch, Jun J Mao, Katherine S Panageas, Eli L Diamond

Faculty, Staff and Students Publications

No abstract provided.

Commentary: Myocardial Relaxation Matters, Paige E Brlecic, Todd K Rosengart

Faculty, Staff and Students Publications

No abstract provided.

Evolution Of Cisplatin Resistance Through Coordinated Metabolic Reprogramming Of The Cellular Reductive State, Wangie Yu, Yunyun Chen, Nagireddy Putluri, Abdullah Osman, Cristian Coarfa, Vasanta Putluri, Abu H M Kamal, Jennifer Kay Asmussen, Panagiotis Katsonis, Jeffrey N Myers, Stephen Y Lai, Wuhao Lu, Clifford C Stephan, Reid T Powell, Faye M Johnson, Heath D Skinner, Jawad Kazi, Kazi Mokim Ahmed, Linghao Hu, Addison Threet, Matthew D Meyer, James A Bankson, Tony Wang, Jack Davis, Kirby R Parker, Madison A Harris, Mokryun L Baek, Gloria V Echeverria, Xiaoli Qi, Jin Wang, Andy I Frederick, Alex J Walsh, Olivier Lichtarge, Mitchell J Frederick, Vlad C Sandulache

Faculty, Staff and Student Publications

BACKGROUND: Cisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring.

METHODS: To validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics.

RESULTS: Inactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to …

Reviewing Internal Medicine Clerkship Grading Through A Proequity Lens: Results Of A National Survey, Cindy J Lai, Irene Alexandraki, Nadia Ismail, Diane Levine, Chavon Onumah, Amber T Pincavage, Jackcy Jacob, Melissa Osborn Jenkins, Amulya Nagarur, Michael Kisielewski, Nora Y Osman

Faculty and Staff Publications

Purpose: Equity in assessment and grading has become imperative across medical education. Although strategies to promote equity exist, there may be variable penetrance across institutions. The objectives of this study were to identify strategies internal medicine (IM) clerkship directors (CDs) use to reduce inequities in assessment and grading and explore IM CDs' perceptions of factors that impede or facilitate the implementation of these strategies.

Method: From October to December 2021, the Clerkship Directors in Internal Medicine of the Alliance for Academic Internal Medicine conducted its annual survey of IM core CDs at 137 U.S. and U.S. territory-based medical schools. This …

Sex Education In American Public Schools: Policy And Outcomes, Alexandra Mattingly

University Honors Theses

Sexual Education in American public schools is the subject of a long-standing debate between educators, parents, and policy makers. From the beginning of public schooling in the United States, the role that public schools ought to serve in educating students about sexual health has been unclear. This remains a topic of debate despite the fact that since the 1980s studies have shown consistently that comprehensive sexual education unequivocally leads to lower rates of pregnancy and sexually transmitted infection spread among students. Comprehensive sexual education is sexual education that includes information on safer sexual activity practices as well as information about …

Connection Between Migraine Physiology And Modifiable Lifestyle Factors And Behaviors: A Literature Review, Sophia A. Kogan

University Honors Theses

Migraine headache is a physiologically complex disorder that presents as an intense headache with other symptoms. Globally, more than one billion people suffer from migraine, and it is the second leading cause of disability worldwide. At present, migraines are targeted with many pharmaceutical interventions; however, there are no well-studied ways to combat migraines through lifestyle modifications alone. One of the molecules involved in migraine physiology is the calcitonin gene-related peptide (CGRP), which causes vasodilation and the sensation of pain. The focus of this thesis is to find connections between CGRP physiology and modifiable factors that individuals have the power and …

Neural Correlates Of Comorbidity Of Anxiety Disorders And Eating Disorders, Karsen Coelho

University Honors Theses

The presence of eating disorder and anxiety disorder comorbidity has raised the question of whether or not there is a causal relationship between them. Previous studies have found that this comorbidity has been present in various patients with anxiety disorders and eating disorders, going further to try and determine which diagnosis came first. By conducting a literature review, studies were examined to determine neurobiological regions impacted by both disorders. Prefrontal cortex abnormalities are consistent among both disorders, contributing to differences in behavior and reward systems. With the irregular structure and activation of the amygdala, emotion and fear regulation are disrupted …

Examining Benefits Of Early Intervention In Cases Of Pediatric Chronic Hypoxia, Kendra Stefan

University Honors Theses

There is a strong foundation of evidence and consensus in the literature that hypoxia has adverse impacts on brain function. Recent research has broadened the field in two directions. One is the treatment for acute hypoxic injuries, and the second is regarding the accumulative impact of intermittent or chronic hypoxia. Historically, in cases of acute hypoxia, action is taken to remedy the source of hypoxia. Physical and cognitive rehabilitation has typically been provided as needed depending on the severity of the injury. While cases of intermittent or chronic hypoxia may not demonstrate an acute urgency for treatment and rehabilitation, current …

Understanding Ubiquitin-Like Signaling At The Host-Pathogen Interface, Danna Eloisa Guzman Gonzalez

University Honors Theses

Research on pathogen intervention and ubiquitin modification has increased over the last few years but a lot is still unknown about ubiquitin-like modifiers (Ubl) and how or if they are modified by pathogens in the same way as Ubiquitin. In this work, two different studies conducted over the course of 2 years are highlighted. The first study focused on purifying and synthesizing four activity based probes in order to study enzymatic activity in the Ubl-modification systems. These probes were reacted with virulence factors isolated from different bacteria and it was concluded that there were unexpected bands formed between some of …

International Comparison Of Literature On Home Health: Taiwan And The United States, Jaden Gloden

University Honors Theses

Taiwan is one of the world's fastest-aging societies and in 1994 implemented its universal National Health Insurance program which would later include a comprehensive long-term care system. The United States is also an aging society and a growing number of Americans are in need of long-term care services that the government has yet to provide or finance. Aging in place, the desire of older adults to stay in their homes as they age has consistently remained popular among Americans 50+ resulting in the popularity of home-based medical care. Taiwan society also values aging in place and an emphasis on Confucian …

The Influence Of Microorganisms On Human Health, Tiffany Bui

University Honors Theses

The purpose of this thesis is to explore the interplay between the environment, lifestyle, and composition of human microbiomes across different communities, with a specific focus on immune and digestive health. This literature review investigates three distinct types of communities: isolated/traditional, transitional, and urban/industrialized communities, each characterized by unique environments, societal structures, and interactions. These factors contribute to the distinct microbial populations and compositions within each community. It is impossible to avoid contact with microorganisms as they are present in every aspect of our lives, from the air we breathe, the water we drink, the soil we walk on, the …

Model Minority Myth And Oral Health Disparities In Asian Americans Of Multnomah County In Oregon, Taylor Kang

University Honors Theses

This thesis explores the concept of the Model Minority Myth (MMM) and its impact on minority groups such as Asian American communities. It discusses how the MMM is one of the many reasons why health disparities such as oral health disparities, may exist for these groups, particularly in the context of White-majority places like the city of Portland and Multnomah County in Oregon. These disparities, as a result, prevent communities from achieving racial equity in areas such as employment, education, occupation, and income, to name a few. At first glance, the MMM seems to shed an optimistic light with its …

The Sanitary Lens: A Study Of 19th Century Public Health In British Colonial India And Australia, Josephine Cannistra

University Honors Theses

Specific colonial processes informed highly distinct policies of public health and sanitation in colonial India and Australia. Their distinctions and lasting legacies are obscured when they are uncritically lumped together within the British Empire. The 19th century was a period of great change throughout India and Australia. It was also a period of dramatic change in general understandings of sanitation and health. This paper examines colonial India and Australia through the lens of sanitation and medicine as it was understood and practiced in British spheres of influence. A comparative approach to these histories and this past sheds light on how …

Investigating The Mammillary Bodies As An Early Target Of Alzheimer's Disease, Cole Martinson

University Honors Theses

Alzheimer's disease (AD) is the most common form of dementia. With minimal treatment options and no cure, developing a deeper understanding of the pathology of the disease is crucial. For nearly four decades, the accumulation of beta-amyloid (Aβ) plaques has been correlated with the disease and its progression. Previous studies mapping this accumulation show that the mammillary bodies (MB) are an early target of the disease. Glutamatergic neurons are of key interest due to their prevalence in the central nervous system, specifically the MB. To understand the effects of AD on the glutamatergic system, we used vesicular glutamate transporter 2 …

Cortical Adaptation Of The Night Monkey To A Nocturnal Niche Environment: A Comparative Non-Invasive T1w/T2w Myelin Study, Takuro Ikeda, Joonas A Autio, Akihiro Kawasaki, Chiho Takeda, Takayuki Ose, Masahiko Takada, David C Van Essen, Matthew F Glasser, Takuya Hayashi

2020-Current year OA Pubs

Night monkeys (Aotus) are the only genus of monkeys within the Simian lineage that successfully occupy a nocturnal environmental niche. Their behavior is supported by their sensory organs' distinctive morphological features; however, little is known about their evolutionary adaptations in sensory regions of the cerebral cortex. Here, we investigate this question by exploring the cortical organization of night monkeys using high-resolution in-vivo brain MRI and comparative cortical-surface T1w/T2w myeloarchitectonic mapping. Our results show that the night monkey cerebral cortex has a qualitatively similar but quantitatively different pattern of cortical myelin compared to the diurnal macaque and marmoset monkeys. T1w/T2w myelin …

Technology-Guided Assessment Of Vocalisations And Their Diagnostic Value As Pain Indicators For People Living With Dementia, Kreshnik Hoti, Mustafa Atee, Paola Chivers, Ipsit Vahia, Jeffrey Hughes

Research outputs 2022 to 2026

BACKGROUND: during pain assessment in persons unable to self-report, such as people living with dementia, vocalisations are commonly used as pain indicators. However, there is a lack of evidence from clinical practice regarding their diagnostic value and relationship with pain. We aimed to explore vocalisations and pain in people with dementia undergoing pain assessments in clinical practice settings. METHODS: a total of 22,194 pain assessments were reviewed in people with dementia (n = 3,144) from 34 different Australian aged care homes and two dementia specific programs. Pain assessments were conducted by 389 purposely trained health care professionals and cares using …

Assessment And Management Of Older Adults Undergoing Pci, Part 1: A Jacc: Advances Expert Panel, Michael G Nanna, Michael W Rich, Et Al.

2020-Current year OA Pubs

As the population ages, older adults represent an increasing proportion of patients referred to the cardiac catheterization laboratory. Older adults are the highest-risk group for morbidity and mortality, particularly after complex, high-risk percutaneous coronary interventions. Structured risk assessment plays a key role in differentiating patients who are likely to derive net benefit vs those who have disproportionate risks for harm. Conventional risk assessment tools from national cardiovascular societies typically rely on 3 pillars: 1) cardiovascular risk; 2) physiologic and hemodynamic risk; and 3) anatomic and procedural risks. We propose adding a fourth pillar: geriatric syndromes, as geriatric domains can supersede …

Kinetics Of Wound Development And Healing Suggests A Skin-Stabilizing Effect Of Allogeneic Abcb5+ Mesenchymal Stromal Cell Treatment In Recessive Dystrophic Epidermolysis Bullosa, Elke Niebergall-Roth, Kathrin Dieter, Cristina Daniele, Silvia Fluhr, Maria Khokhrina, Ines Silva, Christoph Ganss, Markus H. Frank, Mark A. Kluth

Research outputs 2022 to 2026

Recessive dystrophic epidermolysis (RDEB) is a rare, inherited, and currently incurable skin blistering disorder characterized by cyclically recurring wounds coexisting with chronic non-healing wounds. In a recent clinical trial, three intravenous infusions of skin-derived ABCB5+ mesenchymal stromal cells (MSCs) to 14 patients with RDEB improved the healing of wounds that were present at baseline. Since in RDEB even minor mechanical forces perpetually provoke the development of new or recurrent wounds, a post-hoc analysis of patient photographs was performed to specifically assess the effects of ABCB5+ MSCs on new or recurrent wounds by evaluating 174 wounds that occurred after baseline. During …

Interleukin-18 Signaling Promotes Activation Of Hepatic Stellate Cells In Mouse Liver Fibrosis, Jana Knorr, Joel D. Schilling, Et Al.

2020-Current year OA Pubs

BACKGROUND AND AIMS: Nucleotide-binding oligomerization domain-like receptor-family pyrin domain-containing 3 (NLRP3) inflammasome activation has been shown to result in liver fibrosis. Mechanisms and downstream signaling remain incompletely understood. Here, we studied the role of IL-18 in hepatic stellate cells (HSCs), and its impact on liver fibrosis.

APPROACH AND RESULTS: We observed significantly increased serum levels of IL-18 (128.4 pg/ml vs. 74.9 pg/ml) and IL-18 binding protein (BP; 46.50 ng/ml vs. 15.35 ng/ml) in patients with liver cirrhosis compared with healthy controls. Single cell RNA sequencing data showed that an immunoregulatory subset of murine HSCs highly expresses Il18 and Il18r1 . …

Clinical Programs For Cardiometabolic Health For South Asian Patients In The United States: A Review Of Key Program Components, Reeti K Gulati, Mustafa Husaini, Rajesh Dash, Jaideep Patel, Nilay S Shah

2020-Current year OA Pubs

Medical literature shows that South Asians have approximately a 2-fold higher risk of atherosclerotic cardiovascular disease (CVD) compared with other populations. Given this high prevalence, clinical programs to promote cardiovascular health have emerged in the United States that are dedicated to clinical care for South Asian individuals. In this review, we have summarized the key characteristics of clinical programs in the U.S. dedicated to preventing and managing CVD in South Asian American patients. These clinical centers have many unique components in common that are catered to South Asian patient populations including ethnicity concordance of clinical providers, intensive cardiovascular screening protocols …

Neurosteroid Enantiomers As Potentially Novel Neurotherapeutics, Douglas F Covey, Alex S Evers, Yukitoshi Izumi, Jamie L Maguire, Steven J Mennerick, Charles F Zorumski

2020-Current year OA Pubs

Endogenous neurosteroids and synthetic neuroactive steroids (NAS) are important targets for therapeutic development in neuropsychiatric disorders. These steroids modulate major signaling systems in the brain and intracellular processes including inflammation, cellular stress and autophagy. In this review, we describe studies performed using unnatural enantiomers of key neurosteroids, which are physiochemically identical to their natural counterparts except for rotation of polarized light. These studies led to insights in how NAS interact with receptors, ion channels and intracellular sites of action. Certain effects of NAS show high enantioselectivity, consistent with actions in chiral environments and likely direct interactions with signaling proteins. Other …

Rare Dysfunctional Complement Factor I Genetic Variants And Progression To Advanced Age-Related Macular Degeneration, Johanna M Seddon, Bernard Rosner, Dikha De, Tianxiao Huan, Anuja Java, John Atkinson

2020-Current year OA Pubs

PURPOSE: To evaluate associations between rare dysfunctional

DESIGN: Prospective, longitudinal study.

PARTICIPANTS: Patients aged 55 to 80 years at baseline identifying as White with non-AAMD in 1 or both eyes at baseline were included. Follow-up grades were assigned as early, intermediate, or AAMD (GA or NV).

METHODS: Analyses were performed using the Seddon Longitudinal Cohort Study (N = 2116 subjects, 3901 eyes, and mean follow-up of 8.3 years) and the Age-Related Eye Disease Study (N = 2837 subjects, 5200 eyes, and mean follow-up of 9.2 years).

MAIN OUTCOME MEASURES: Progression to AAMD, GA, or NV.

RESULTS: In the prospective cohort …