Medical Physiology Commons^™

Reply To: S. N. Katkuri Et Al. And H. Liu Et Al. On Early And Sustained Improvements In Sense Of Smell With Tezepelumab Treatment In Patients With Chronic Rhinosinusitis With Nasal Polyps (Waypoint), Joaquim Mullol, Joseph K. Han, Tanya M. Laidlaw, Claire Hopkins, Anju T. Peters, Oliver Pfaar, Martin Desrosiers, Stella E. Lee, Andrew P. Lane, Claudia Chen, Yun Chon, Sandhia S. Ponnarambil, Andrew Foster, Andrew W. Lindsley, Christopher S. Ambrose

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] We thank Dr. S. N. Katkuri, Dr. H. Liu, and their coauthors [1, 2] for their interest in our recent publication describing the improvements in loss of smell symptoms with tezepelumab versus placebo in patients with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) in the WAYPOINT trial (NCT04851964) [3]. We are grateful for the authors' feedback on the clinical significance of the data presented and their appreciation of the consistency observed across a range of baseline clinical characteristic and demographic subgroups.

Single Intratympanic Injection Of Proprietary Brain-Derived Neurotrophic Factor (Oto-413) In Subjects With Speech-In-Noise Hearing Impairment: A Randomized, Dose Escalating, Double-Blind, Placebo-Controlled Phase 1/2 Study, Alan C. Foster, Jeffery J. Anderson, David R. Moore, Morgan Oktela Fuentes, Yiwei Wang, Peter G. Volsky, K. Paul Boyev, Victoria A. Sanchez

Department of Otolaryngology (ENT) Faculty Publications

Purpose

To evaluate the safety and tolerability and exploratory efficacy of OTO-413, an intratympanic-administered, sustained release formulation of brain-derived neurotrophic factor (BDNF) in a thermoreversible gel, in participants with speech-in-noise hearing difficulties.

Methods

This was a single dose, dose-ascending, randomized, double-blind, Placebo-controlled Phase 1/2 study conducted at 7 enrolling clinical sites in the U.S. 110 participants (56% female) enrolled had self-reported speech-in-noise (SIN) difficulties that were confirmed by a SIN test and were randomized to OTO-413 or Placebo. OTO-413 dose range was escalated from 0.01 mg to 1.5 mg within 7 Cohorts. Safety evaluations included monitoring for treatment-emergent adverse events, …

Yk-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure Of A Stabilized Free Radical Containing An Angiotensin At₁ Receptor Inhibitor, Simon Friedrich, Yali Kong, Faik N. Musayev, Milton L. Brown, B. Frank Gupton

Department of Biomedical and Translational Sciences Faculty Publications

We report the first crystal structure of the telmisartan-tempol conjugate 2,2,6,6-tetramethyl-1-(λ'-oxidaneyl)piperidin-4-yl 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl]-[1,1'-biphenyl]-2-carboxylate free radical (YK-4-250, C₄₂H₄₆N₅O₃), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT₁R) and reactive oxygen species (ROS). Structural analysis reveals a unique crystal architecture in which the nitroxide radical is stabilized within a sterically protected environment while preserving the telmisartan pharmacophore essential for high-affinity receptor antagonism. YK-4-250 is a novel small-molecule conjugate of telmisartan and tempol that incorporates a catalytic stabilized nitroxide radical and was rationally designed to mitigate gastrointestinal acute radiation syndrome (GI-ARS).

Pilot Study On The Use Of Multimorbidity Index In Patients Receiving Home Parenteral Nutrition, Michael M. Rothkopf, Mohan Pant, Zachary Rothkopf, Rebecca Brown Rdn, Jaime Haselhorst Rdn, Debbie L. Stevenson Rdn, Andrew Depalma Mba, Michael Saracco

Epidemiology, Biostatistics, & Environmental Health Faculty Publications

Background

Home parenteral nutrition (HPN) patients often have multiple comorbidities. A validated multimorbidity index (MMI) could help determine resource needs and risks with HPN. We evaluated MMI scoring to determine if it predicted HPN resource use and outcomes.

Methods

We performed a secondary analysis of 60 HPN patients from a previous study based on Cumulative Illness Rating Scale (CIRS) scoring. We examined three variables: PN formula changes, hospitalizations, and hospital length of stay (LOS). Density plots were produced to select a CIRS score cutoff value. Spearman correlations among the three variables of interest were computed. The data were then subjected …

Differences In Biologic Clinical Trials For Chronic Rhinosinusitis With Nasal Polyps—Are We Comparing Apples With Oranges?, Marjolein Cornet, Peter W. Hellings, Martin Desrosiers, Martin Wagenmann, Richard Follows, Laura Walrave, Luz Adriana Jimenez, Lee Tombs, Dawn Edwards, Peter Howarth, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

In recent years, several biologics targeting Type 2 inflammation have been developed for treating chronic rhinosinusitis with nasal polyps (CRSwNP). These have been studied in registrational randomized controlled trials (RCTs), which vary in their patient populations, trial design, endpoints, geography, timing, or data-handling processes. While (in)direct treatment comparisons and meta-analyses have been carried out to compare efficacy results from RCTs, often these fail to properly account for these between-study differences. Here, we summarize the key between-study differences that can influence trial outcomes and highlight the resulting challenges faced when comparing outcomes from different Phase III RCTs of biologics in CRSwNP.

The Impact Of Gastric Sleeve And Roux-En-Y Gastric Bypass On Chief Cell Function And Protein Digestion In Obese Patients, Garikoitz Mikel Gainza

Honors Undergraduate Theses

Obesity has become one of the largest global health concerns of the 21^st century, correlating with numerous associated diseases. To help address the growing prevalence and burden of obesity, sleeve gastrectomy and Roux-en-Y gastric bypass have become two commonly performed surgical procedures done to promote weight loss by altering the anatomical structure of the stomach and surrounding organs of the gastrointestinal system. Although the benefits of improved metabolism linked to these surgical procedures are well studied, their impact on the physiology of gastric cells, and more specifically chief cells as they relate to protein digestion post-surgery, is yet to …

Endothelin-1 In The Failing Fontan: Pathobiology, Precision Therapeutics, And Future Trial Design, Iman Maiza

Department of Pediatrics Faculty Publications

The Fontan circulation, devised as definitive palliation for single-ventricle congenital heart disease, imposes systemic venous hypertension, loss of pulmonary arterial pulsatility, and restricted preload reserve. These hemodynamic trade-offs progressively injure the pulmonary vasculature, liver, and lymphatic system, producing late morbidities including elevated pulmonary vascular resistance, Fontan-associated liver disease (FALD), protein-losing enteropathy, and arrhythmias. Endothelin-1 (ET-1), a potent vasoconstrictor and profibrotic mediator, plausibly unifies these complications. Mechanistic studies demonstrate ET-1 upregulation in failed Fontan lungs, activating PLC–Ca²⁺, RhoA/ROCK, and MAPK/ERK cascades to drive vasoconstriction and remodeling. In cirrhotic livers, ET-1 localizes to stellate cells, promoting contraction and fibrogenesis, mechanisms biologically relevant …

The Effects Of Habitual Temperature And Diet On Crayfish Physiological Processes, Tyler D. Deramo, Sunny Rana, Victor Popoviciu

Williams Honors College, Honors Research Projects

We will use crayfish to test the individual and combined effects of temperature and diet to see how they impact physiological processes such as metabolism, growth rate, molting patterns, and behavioral analysis. A total of forty-eight crayfish will be used throughout the experiment, and they will be housed in separate containers. A plant-based diet (consisting of fresh kale) and an animal-based diet (consisting of dried bloodworms) will be tested alongside room temperature (~18 degrees Celsius) and a warmer habitual temperature (~24 degrees Celsius). Metabolism will be measured via O2 consumption, and growth will be measured by weighing and measuring the …

Gaze Transition Entropy And Automation Trust In Multitasking Workspace, Yusuke Yamani, Austin Jackson, Tetsuya Sato, Feyishola Ashimi, Michael S. Politowicz, Eric T. Chancey, Makoto Itoh

Psychology Faculty Publications

Safe flight operation requires visual scanning across multiple displays in a cockpit, which collectively represent the state of the aircraft and supporting automation. Trust is a crucial factor that drives human-automation interaction, and recent work has suggested a relationship between an operator's visual attention and automation trust. One index that captures predictability of eye movements between different areas of interest is gaze transition entropy. The current work reanalyzed data from Sato et al., which examined eye movement patterns and trust in automation associated with the system monitoring task of the Multi-Attribute Task Battery. Results showed credible positive correlations between the …

Physiologic Markers Of Mortality In Acute Valve Syndrome: An Ischemic Physiology Score Stratifies Patient Risk, Omar Saleh, Nicholas J. Valle, Israa Saleh, Raymond Benza, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background: Acute valve syndrome (AVS) represents a high-risk phenotype of advanced valvular disease with largely uncharacterized risk heterogeneity. We aimed to validate an expanded AVS definition and develop a physiology-dependent risk stratification tool using available clinical markers.

Methods: This retrospective study analyzed 2380 patients undergoing aortic valve replacement for severe aortic stenosis and classified them as AVS (n = 1556) or progressive valvular disease (n = 824). The primary outcome was 1-year all-cause mortality. An L2-regularized logistic regression model was developed to predict 1-year mortality using admission laboratory markers and comorbidity burden. Model performance was assessed using nested cross-validation with …

The Postsynaptic Scaffolding Protein Sapap3 Shapes Mitochondrial Activity: The Case Of Huntington's Disease, Patrícia Coelho, Ildete Luísa Ferreira, Ana Sofia Lourenço, Daniela Marinho, Sandra Isabel Anjo, Zongwei Fang, Lígia Fão, Sandra I. Mota, Philippe J. Mas, Mário Carvalho, Rui Jorge Nobre, Carina Henriques, Joana Fraga, Dongqing Wang, Sandra Macedo Ribeiro, Luís Pereira De Almeida, Patrícia Monteiro, Isaura Simões, Darren J. Hart, Bruno Manadas, João Peça, Pedro Castanheira, A. Cristina Rego

Biological Sciences Faculty Publications

Postsynaptic scaffolding protein SAP90/PSD95-associated protein 3 (SAPAP3) modulates cortico-striatal signalling and regulates the maintenance of synaptic structure. Notably, SAPAP3 defects have been reported in several human psychiatric disorders that share pathophysiological features with Huntington’s disease (HD), a neurodegenerative disorder characterized by the expression of mutant huntingtin (mHTT) and marked dysfunction of cortico-striatal synapses and mitochondria. However, the role of SAPAP3 in mitochondrial function and HD pathophysiology remains unexplored. SAPAP3 was extracted from striatal synaptoneurosomes and analyzed by SWATH-MS proteomics to identify potential interactors, revealing SAPAP3 association with several mitochondrial proteins, particularly Mic60. These data were further complemented with proximity ligation …

Micrornas Regulated By Pregnancy Target Antiviral And Cancer Immunity Overlapping With The Hiv Interactome, Paula F. T. Cezar-De-Mello, Jonathan M. Dreyfuss, Pai-Lien Chen, Hidemi Yamamoto, Xiaoming Gao, Hui Pan, Charles Morrison, Gustavo F. Doncel, Robert L. Barbieri, Raina N. Fichorova

CONRAD Publications

Innate immunity predictors of HIV-1 risk and pathogenesis vary with reproductive hormones, pregnancy, and lactation, yet the underlying mechanisms remain unclear. We hypothesized that pregnancy-associated physiological adaptations alter systemic microRNA (miRNA) expression, thereby regulating immunity, pathogenesis and susceptibility to infection. We analyzed 174 serum samples from 88 participants in a longitudinal cohort from Uganda and Zimbabwe across pre-pregnancy (PP), pregnancy (P), and postpartum breastfeeding (BF). Cell-free peripheral blood miRNAs (n = 2083) were profiled using HTG EdgeSeq. Pregnancy-specific miRNAs were identified by intersecting differentially expressed (DE) miRNAs from P vs. PP and P vs. BF comparisons. miRNA targets and pathways …

When Clotting And Bleeding Collide: A Case Of Bilateral Pe And Concurrent Upper Gi Hemorrhage, Tabitha D. Baca, David Rayburn, Daniel Castro, Jessica Aird

Florida Journal of Emergency Medicine (FJEM)

Introduction

Concurrent episodes of pulmonary emboli and gastrointestinal bleeding in one patient are not commonly seen. When a patient presents with both, it presents a challenge to manage as they are opposite ends of the same disease spectrum associated with the coagulation system.

Case Report

We present the case of a 65-year-old male who presented to our hospital via EMS with unknown prior history after a witnessed cardiac arrest, who on evaluation also had a concurrent bilateral pulmonary emboli with right heart strain.

Why should an emergency physician be aware of this?

While there is extensive research on the management …

Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner

School of Graduate Studies Faculty Publications

No abstract provided.

The Frontal Assessment Battery In Older Multilingual Kenyan Adults, Anne Njoki Gitere, Anne Nyambura, Karen Blackmon, Levi Muyela, Rachel Maina, Olivera Nesic Taylor,, Jasmit Shah, Dilraj Sokhi, Sylvia Mbugua, Samuel Gitau, Sheila Waa, Juzar Hooker, Zul Merali, Chinedu Momoh, Karen Blackmon

Brain and Mind Institute

Background: The Frontal Assessment Battery (FAB) was developed as a short (6-item) bedside assessment of executive dysfunction in older adults with suspected neurodegeneration. This study describes psychometric features of the FAB in multilingual Kenyan adults with and without clinical diagnosis of dementia.

Method: The FAB consists of six items assessing verbal abstract reasoning, lexical fluency, motor learning, and inhibitory control. The score on each item ranges from 0-3, with higher scores indicating better performance. Bilingual English-Swahili study personnel translated, blind back-translated, and applied consensus-driven cultural adaptations. FAB was then administered to 95 participants [71 cognitively unimpaired (CU) controls; 24 people …

Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi

School of Graduate Studies Faculty Publications

Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …

Introducing Patient-Centered Outcomes To Preceptors In Caate-Approved Athletic Training Programs, K. Judge

Clinical Practice in Athletic Training

The 2020 standards set by the Commission on Accreditation of Athletic Training Education (CAATE) now require the incorporation of the International Classification of Function and Patient-Centered Outcomes into professional practice. These standards can be introduced initially through simulation, but to develop a competent and culturally aware professional, outcome measures should be completed during clinical experiences under the guidance of approved preceptors. As this is a relatively new standard, many preceptors did not receive this as part of their education and may be uncomfortable integrating outcomes into their practice. This lack of integration can negatively affect the learning opportunities of athletic …

Incorporating Balance Training Into Ankle Sprain Injury Prevention Programs: An Evidence-To-Practice Review, David Tomchuk, Jacob Meyer, Kyle Schneider, Ben Fox

Clinical Practice in Athletic Training

Ankle sprains are among the most common injuries in sports and non-sporting activities. For patients, ankle sprains can result in multiple short and long-term hardships, such as financial burdens of evaluation and treatment, absenteeism from sport and physical activity, and diminished ankle and lower extremity function. However, athletic trainers and other stakeholders are also impacted by administrative and time burdens in caring for ankle sprains and how ankle sprains affect team dynamics and performance. The 2022 guiding systematic review evaluated the effectiveness of incorporating preventive balance training exercises on the incidence of ankle sprains in soccer athletes. The search performed …

Psychological And Psychosocial Effects Of Contemplative Practices In The Athletic Population: A Systematic Review, Victoria Baker, Emily Duckett, Alison Gardiner-Shires, Lindsey Keenan

Clinical Practice in Athletic Training

Mental health concerns in athletes are becoming a primary focus for institutions, companies, coaches, and more. An athlete carries an abundant load of stressors due to their lifestyle. The stressors can negatively impact an athlete by producing anxiety, depression, insomnia, and other mental health concerns. Previous studies have found a connection between the use of contemplative practices on psychological and psychosocial effects in athletes, creating an opportunity to evaluate the research of contemplative practices in the athletic population. 5, 7, 8, 13-16 A systematic review was conducted using nine electronic databases. Seven studies were included in this review, each assessing …

Use Of An Electronic Dynamometer Following Pitching To Identify Fatigue In Softball Pitchers, Bethany L. Hansberger, Peter Lisman

Clinical Practice in Athletic Training

This study used a case-series design to collect in-game fatigue measures for collegiate softball pitchers immediately after pitching during the competitive season. Five softball pitchers (age = 19.8 ± 1.5 years; height = 169.9±6.1 cm; body mass = 79.1±22.6 kg) from one Division I program were recruited. Isometric internal and external rotation, scaption, and grip strength measures were collected using an electronic dynamometer at the beginning and conclusion of the fall non-traditional season, and at the beginning of preseason in January. Strength measures were also obtained during the competitive season at the conclusion of pitching in a game and compared …