Digital Commons Network^™

Bone Quality Response To Lifestyle Intervention In Older Adults With Obesity (Limb-Q Trial): A Randomised Controlled Trial, Giulia Gregori, Sanjay Mediwala, Michael Liebschner, Daeseung Kim, Mon S Bryant, Nina Klonis, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Background: Lifestyle interventions for weight loss might exacerbate age-related bone loss and osteoporosis. However, there is limited knowledge about their effects on bone quality. We examined whether lifestyle intervention can preserve or enhance bone quality, despite reductions in bone mineral density.

Methods: The Lifestyle Intervention to Improve Bone Quality (LIMB-Q) study was a randomised controlled trial conducted at Baylor College of Medicine and the Michael E DeBakey VA Medical Center (Houston, TX, USA) including older adults (aged 65-85 years) with obesity (BMI ≥30 kg/m2). Participants were randomly assigned to receive either an intensive lifestyle intervention (intensive lifestyle group, consisting of …

Acute Loss Of Tactile Input Leads To General Compensatory Changes In Eye-Hand Coordination During Object Manipulation, Kevin Ung, John F Magnotti, Brandon Kim, Jeffrey M Yau, Per F Nordmark

Faculty, Staff and Students Publications

Current models of motor control emphasize the critical role of sensory feedback, as demonstrated by movement coordination deficits following sensory impairment. When both vision and touch are available for object-oriented manual behaviors, they serve distinct roles; vision guides the execution of planned movements, while touch provides more direct feedback on hand-object interactions. The impact of losing somatosensory feedback on eye-hand coordination during dexterous object manipulation tasks has not been thoroughly studied. Conceivably, vision is recruited to compensate for the feedback lost when touch is abolished based on the dexterity demands of the behavior. To investigate this, we tested healthy participants …

2d Speckle Tracking Strain Echocardiography In Multisystem Inflammatory Syndrome In Children: A Multicenter Analysis From The Music Study, Francesca Sperotto, Valiantsina Kazlova, Felicia L Trachtenberg, Dongngan T Truong, Sanjeev Aggarwal, Joseph R Block, Tamara T Bradford, Sujatha Buddhe, Audrey Dionne, Andreea Dragulescu, Kanwal M Farooqi, Daniel E Forsha, Therese M Giglia, Ian F Golding, Keren Hasbani, Pei-Ni Jone, Anita Krishnan, Sean M Lang, Carol A Mcfarland, Elizabeth C Mitchell, Elias Moussi Saad, Todd T Nowlen, Ricardo H Pignatelli, Scott Pletzer, Ryan Serrano, Divya Shakti, Shubhika Srivastava, Thor Thorsson, Jodie K Votava-Smith, Hunter C Wilson, Jane W Newburger, Kevin G Friedman

Faculty, Staff and Students Publications

Background: 2D-speckle tracking echocardiography may help detect subclinical ventricular dysfunction, but data in multisystem inflammatory syndrome in children (MIS-C) are scarce. We investigated left ventricular (LV) strain parameters in MIS-C and their association with outcomes.

Methods: We performed an ambi-directional, 32-center cohort study on hospitalized patients with MIS-C (March 2020-November 2021) with at least 1 echocardiogram read by the Core Lab. Generalized estimating equation modeling was used to test associations between LV strain and a composite in-hospital adverse cardiovascular outcome (vasoactive support, arrhythmias, cardiac arrest, extracorporeal support, death, or heart transplant).

Results: Of 349 patients (median age, 8.7 years [interquartile …

De Novo Pathogenic Csf1r Variant Implicates Microglial Dysfunction In Pathogenesis Of Febrile Infection-Related Epilepsy Syndrome, Kristen S Fisher, Jesse M Levine, Alexander Ankar, Ruizhi Duan, Yi Chen Lai, Eyal Muscal, Sarah R Risen, James J Riviello, Pei-Chien Tsai, Daniel G Calame

Faculty, Staff and Students Publications

Febrile infection-related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus following a febrile illness with resulting refractory epilepsy. Evidence supports the presence of immune dysregulation in patients with FIRES, but a monogenic basis for FIRES has not been identified in most cases. We present a case of a previously healthy 16-year-old male with FIRES who was found to have a de novo predicted damaging missense variant in CSF1R on clinical whole genome sequencing, a gene encoding a critical regulator of microglial homeostasis in which pathogenic variants cause adult onset leukoencephalopathy. Molecular modeling demonstrates that the CSF1R variant …

Generation Of Induced Pluripotent Stem Cell Lines (Rfsci003-A, Rfsci004-A) From Monozygotic Twins Discordant For Age-Related Macular Degeneration, Naresh Rajendran, Wendy Runyon, Sam Hu, Ajeet Singh, Rinki Ratnapriya, Ritu Kumar, Karl Csaky, Srinivasa R Sripathi

Faculty, Staff and Students Publications

Age-related macular degeneration (AMD) has significant genetic component, yet monozygotic twins frequently exhibit discordance in disease status, highlighting the role of non-genetic factors. To enable comparative studies of AMD pathogenesis, we generated two induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of a monozygotic twin pair discordant for AMD. These iPSC lines offer a unique genetically matched resource to investigate molecular differences between affected and unaffected twins, as well as their responses to genetic, epigenetic, and environmental contributors to AMD development.

Steroids For Pediatric Adenotonsillectomy Pain-A Prospective Multicenter Randomized Trial, Kevin D Pereira, Wiktoria A Gocal, Anna V Borodianski, Mary E Williamson, Hengameh K Behzadpour, Sonal Saraiya, Diego A Preciado, Amal Isaiah

Faculty, Staff and Students Publications

Objective: To compare postoperative caregiver-reported pain control of two steroid regimens following pediatric adenotonsillectomy. Secondary objectives assessed differences in analgesic use, return to normal diet, caregiver calls, adverse effects, and emergency room (ER) visits.

Study design: Prospective randomized pragmatic trial.

Setting: Three academic tertiary care children's hospitals.

Methods: Healthy children aged 3 to 10 undergoing adenotonsillectomy were recruited and randomly assigned to receive either 0.6 mg/kg dexamethasone on postoperative day 3 or prednisolone 0.5 mg/kg days 1 to 3. Both groups continued standard weight-based regimens of acetaminophen and ibuprofen. A blinded research team member performed postoperative telephone surveys using the …

Optimal Head-Of-Bed Positioning Before Thrombectomy In Large Vessel Occlusion Stroke: A Randomized Clinical Trial, Anne W Alexandrov, Anne J Shearin, Pitchaiah Mandava, Gabriel Torrealba-Acosta, Cheran Elangovan, Balaji Krishnaiah, Katherine Nearing, Elizabeth Robinson, Cara Guthrie-Chu, Matthew Holzmann, Bryan Fill, Dharti R Trivedi, Alicia Richardson, Sandy Middleton, Barbara B Brewer, David S Liebeskind, Nitin Goyal, James C Grotta, Andrei V Alexandrov

Faculty, Staff and Students Publications

Importance: Small studies show that 0° head positioning of patients with large vessel occlusion (LVO) stroke improves penumbral blood flow and clinical stability. Understanding whether 0° head position maintains clinical stability would allow for optimal patient positioning before thrombectomy.

Objective: To determine superiority of 0° over 30° head positioning at maintaining clinical stability in patients with LVO before thrombectomy.

Design, setting, and participants: This was a prospective randomized clinical trial with blinding to study enrollment/end points conducted from May 2018 to November 2023. There were 3 planned interim analyses, and the study was conducted at certified thrombectomy hospitals in the …

Experiences Of Emotional Support Among Parents Of Children And Adolescents With Type 1 Diabetes: A Qualitative Study, Sahar S Eshtehardi, Marissa N Baudino, Barbara J Anderson, Deborah I Thompson, David G Marrero, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Parents of youth with type 1 diabetes (T1D) experience substantial disease-specific demands and distress, yet their perceptions about the emotional support they receive related to the challenges of caring for a child with diabetes have not been well described. This research aimed to characterize the types of emotional support parents of youth with T1D receive and how they experience emotional support.

Methods: As part of a larger qualitative study on diabetes health-related quality of life, 23 parents (96% mothers) of youth with T1D (M age = 10.9 ± 3.8 years; 35% female) completed semi-structured interviews about various aspects of …

Cmr Findings In The Long-Term Outcomes After Multisystem Inflammatory Syndrome In Children (Music) Study, Sean M Lang, Dongngan T Truong, Andrew J Powell, Valiantsina Kazlova, Jane W Newburger, Jordan D Awerbach, Edem Binka, Tamara T Bradford, Mark Cartoski, Andrew Cheng, Michael P Dilorenzo, Audrey Dionne, Adam L Dorfman, Matthew D Elias, Olukayode Garuba, Jennifer F Gerardin, Keren Hasbani, Pei-Ni Jone, Christopher Z Lam, Nilanjana Misra, Lerraughn M Morgan, Arni Nutting, Jyoti K Patel, Joshua D Robinson, Eleanor L Schuchardt, Kristen Sexson Tejtel, Gautam K Singh, Timothy C Slesnick, Felicia Trachtenberg, Michael D Taylor, Music Study Investigators

Faculty, Staff and Students Publications

Background: Multisystem Inflammatory Syndrome in Children is characterized by high rates of acute cardiovascular involvement with rapid recovery of organ dysfunction. However, information regarding long-term sequelae is lacking. We sought to characterize the systolic function and myocardial tissue properties using cardiac magnetic resonance (CMR) imaging in a multicenter observational cohort of patients with Multisystem Inflammatory Syndrome in Children.

Methods: In this observational cohort study, comprising 32 centers in North America, CMR studies were analyzed by a core laboratory to assess ventricular volumetric data, tissue characterization, and coronary involvement.

Results: A total of 263 CMRs from 255 patients with Multisystem Inflammatory …

High-Fidelity Finite Element Modeling Technique To Improve Sensitivity To Bone Tissue Changes Of Older Adults With Obesity Undergoing Intensive Lifestyle Intervention, Michael A K Liebschner, Daeseung Kim, Nina Klonis, Giulia Gregori, Reina Armamento-Villareal, Clifford Qualls, Dennis T Villareal

Faculty, Staff and Students Publications

Introduction: Obesity presents a significant health risk for the aging population. Research shows that weight loss and regular exercise can greatly improve the functional status of older adults who are obese. However, weight loss may also result in a decrease in bone mass. To properly assess changes in fracture risk due to lifestyle interventions, a direct biomechanical evaluation of bone strength and fracture risk at metabolically active sites is essential.

Methods: Computed tomography scans taken at two different time points of ten human volunteers provided the foundation for this study. A high-fidelity segmentation and modeling approach was taken to generate …

The Ethics Of Clinical Ethics, Matthew Shea

Center for Medical Ethics and Health Policy Staff Publications

The concept ethics defines health care ethics as a professional practice. Yet the meaning of "ethics" is often unclear in the theory and practice of clinical ethics. Clarity on this matter is crucial for understanding the nature of clinical ethics and for debates about the professional identity and proper role of ethicists, the sort of training and skills they should possess, and whether they have ethics expertise. This article examines two different ways the ethics of clinical ethics can be understood: Real Ethics, which consists of objective moral norms grounded in moral truth; and Conventional Ethics, which consists of conventional …

Atherosclerotic Cardiovascular Disease In Gulf War Veterans In Relation To Deployment Exposures, Sarah T Ahmed, Ruosha Li, Lea Steele, Peter Richardson, Kellie Sims, Rachel Quaden, Kelly M Harrington, Vijay Nambi, John M Gaziano, Robert Morgan, George L Delclos, Drew A Helmer

Faculty, Staff and Students Publications

Many 1990-1991 Gulf War Veterans (GWVs) were exposed to toxicants and environmental hazards during deployment, including oil well fire smoke, chemical/biological agents, pyridostigmine bromide (PB) pills, and pesticides. Multiple constituents of smoke are associated with increased risk for atherosclerotic cardiovascular diseases (ASCVD), and other toxic exposures have been associated with autonomic and lipid dysfunction. We used data from the Gulf War Era Cohort and Biorepository Study of veterans deployed to Gulf War in 1990-1991 (n = 942). We evaluated the association of deployment exposures (no, yes (1-6 days), (7-30 days), (31 + days), and not sure) with clinical risk factors …

Coenzyme Q Headgroup Intermediates Can Ameliorate A Mitochondrial Encephalopathy, Guangbin Shi, Claire Miller, Sota Kuno, Alejandro G Rey Hipolito, Salsabiel El Nagar, Giulietta M Riboldi, Megan Korn, Wyatt C Tran, Zixuan Wang, Lia Ficaro, Tao Lin, Quentin Spillier, Begoña Gamallo-Lana, Drew R Jones, Matija Snuderl, Soomin C Song, Adam C Mar, Alexandra L Joyner, Roy V Sillitoe, Robert S Banh, Michael E Pacold

Duncan NRI Faculty and Staff Publications

Decreased brain levels of coenzyme Q10 (CoQ10), an endogenously synthesized lipophilic antioxidant1,2, underpin encephalopathy in primary CoQ10 deficiencies3,4 and are associated with common neurodegenerative diseases and the ageing process5,6. CoQ10 supplementation does not increase CoQ10 pools in the brain or in other tissues. The recent discovery of the mammalian CoQ10 headgroup synthesis pathway, in which 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL) makes 4-hydroxymandelate (4-HMA) to synthesize the CoQ10 headgroup precursor 4-hydroxybenzoate (4-HB)7, offers an opportunity to pharmacologically restore CoQ10 synthesis and mechanistically treat CoQ10 deficiencies. To test whether 4-HMA …

The Effect Of Tert Promoter Mutation On Predicting Meningioma Outcomes: A Multi-Institutional Cohort Analysis, Karenna J Groff, Ruchit V Patel, Yang Feng, Hia S Ghosh, Miguel A Millares Chavez, Joseph O'Brien, William C Chen, Vijay Nitturi, Akshay V Save, Mark W Youngblood, Craig M Horbinski, James P Chandler, Felix Ehret, Chloe Gui, Justin Z Wang, Kristen Park, Sonia Ajmera, Marc Rosenblum, Abigail K Suwala, Catena Kresbach, Christopher W Mount, Ulrich Schüller, Sandro Santagata, Felix Sahm, Tejus A Bale, Christina Jackson, Timothy E Richardson, Chunyu Cai, Farshad Nassiri, Gelareh Zadeh, David Kaul, David Capper, Stephen T Magill, John G Golfinos, Chandra Sen, Akash J Patel, David R Raleigh, Jennifer Moliterno, Donato Pacione, Matija Snuderl, Wenya Linda Bi

Duncan NRI Faculty and Staff Publications

Background: Molecular aberrations have been incorporated into tumour classification guidelines of meningioma. TERT-promoter (TERTp) mutation is associated with worse prognosis and is designated a WHO grade 3 biomarker. However, it remains unclear whether TERTp mutation is context-dependent, with other co-occurring genetic alterations potentially driving its association with prognosis. We sought to characterise the role of TERTp mutation in meningioma and guide TERTp sequencing.

Methods: We identified 1492 patients of all ages who had previously received surgery for meningioma across 14 medical centres in the USA, Canada, and Germany. Patients were eligible if they had post-surgical clinical or radiographical assessment of …

Plasma Lipidome Dysregulation In Frontotemporal Dementia Reveals Shared, Genotype-Specific, And Severity-Linked Alterations., Yohannes A Ambaw, Peter A Ljubenkov, Shubham Singh, Abdi Hamed, Sebastian Boland, Adam L Boxer, Tobias C Walther, Robert V Farese

Duncan NRI Faculty and Staff Publications

Introduction: Biomarkers are essential for monitoring the progression of frontotemporal dementia (FTD). Although dysregulated brain lipid metabolism, particularly sphingolipids enriched in the nervous system, is a key feature of neurodegeneration, plasma lipids remain underexplored as biomarkers compared to imaging and serum proteins.

Methods: We examined plasma lipidomes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from individuals carrying pathogenic variants linked to autosomal dominant FTD (GRN, C9orf72, MAPT) and non-carriers.

Results: FTD subjects exhibited increased plasma levels of gangliosides (GM3(d18:1_16:0), GM3(d18:1_24:1)), ceramide Cer(d18:1_23:0), and select polyunsaturated triacylglycerols. In contrast, phosphatidylethanolamine (PE(18:0_24:0) and sphingomyelin (SM(38:0) were reduced. Subtype-specific changes included elevated glucosylsphingosine (GlcSph(d18:1) …

Heightened Risk: Childhood Trauma And Anticipatory Grief Exacerbate The Impact Of Loneliness On Depressive Symptoms And Lps-Stimulated Cytokines In Dementia Caregivers, Kelly N Brice, Jensine Paoletti-Hatcher, E Lydia Wu-Chung, Vincent D Lai, Daniel L Argueta, Michelle A Chen, Itee Mahant, Bryan T Denny, Charles Green, Luis D Medina, Paul Schulz, Jennifer Stinson, Samantha K Henry, Cobi Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Dementia spousal caregivers are at a disproportionate risk for adverse mental and physical health outcomes. Loneliness is associated with depressive symptoms and proinflammatory cytokine production among caregivers. Additionally, childhood trauma, anticipatory grief, and poor sleep quality are all associated with enhanced stress reactivity. This study used a cross-sectional design to investigate whether loneliness is associated with proinflammatory cytokine production and depressive symptoms in caregivers, and whether these relationships are strongest among caregivers who report high levels of childhood trauma, high amounts of anticipatory grief, or poor sleep quality. A sample of 111 dementia spousal caregivers provided blood samples and completed …

A Metabolomics Study Of Cardiac Dysfunction In Hyperglycemia: Findings From The Atherosclerosis Risk In Communities (Aric) Study And The Hispanic Community Health Study/Study Of Latinos (Hchs/Sol), Yilin Yoshida, Ngoc Quynh Nguyen, Eun Hye Moon, Casey Rebholz, Hicham Skali, Victoria Arthur, Justin B Echouffo-Tcheugui, Christie Ballantyne, Elizabeth Selvin, Amil Shah, Robert Kaplan, Carlos J Rodriguez, Qibin Qi, Susan Cheng, Bing Yu

Faculty, Staff and Student Publications

Objective: Hyperglycemic states (prediabetes and diabetes) are associated with heart failure (HF) risk. We aimed to identify distinct metabolites for subclinical cardiac dysfunction, a precursor of HF, in hyperglycemic or euglycemic individuals.

Research design and methods: We conducted cross-sectional and prospective analyses of 2,492 HF-free participants from the Atherosclerosis Risk in Communities (ARIC) study visit 5, 2011-2013. A total of 1,297 participants were hyperglycemic (assessed on the basis of hemoglobin A1c >5.7%, fasting glucose >100 mg/dL, use of diabetes medication, or diagnosis), and 1,195 were euglycemic. We used logistic regression for analysis of association between 790 metabolites and cardiac dysfunction, …

The Group Interview As A Method Of Efficient Hiring: The Experience Of A Regional Medical School Campus, Matthew Mcmillin, Peter Boedeker, Kammy Contreras, Stephen Charles

Faculty and Staff Publications

Problem: In 2020, Baylor College of Medicine (BCM) established a regional campus in Temple, Texas (BCM-T), that required recruitment of multiple foundational sciences faculty members in a limited time frame. Group in-person interviews were used to fill these roles efficiently while promoting interaction between candidates and BCM faculty. This study assesses whether interviewing foundational sciences medical educators in a group setting can efficiently fill faculty positions, reducing time and financial costs while being perceived as fair and acceptable to the candidates.

Approach: Study participants were prospective foundational sciences faculty members who interviewed for a faculty position at BCM-T in a …

Cognitive Performance In Early Neuronal Synuclein Disease With Hyposmia But Without Motor Disability: Association With Dopamine Deficiency And Isolated Rapid Eye Movement Sleep Behavior Disorder, Daniel Weintraub, Anuprita R Nair, Ryan Kurth, Michael C Brumm, Christine Kohnen, Michele K York, Roseanne D Dobkin, Kenneth Marek, Caroline Tanner, Tanya Simuni, Andrew Siderowf, Douglas Galasko, Lana M Chahine, Christopher Coffey, Kalpana Merchant, Kathleen L Poston, Tatiana Foroud, Brit Mollenhauer, Ethan G Brown, Karl Kieburtz, Mark Frasier, Sohini Chowdhury, Roy N Alcalay, Aleksandar Videnovic, Parkinson's Progression Markers Initiative

Faculty, Staff and Students Publications

Objective: To determine the impact of dopamine deficiency and isolated rapid eye movement (REM) sleep behavior disorder (iRBD) on cognitive performance in early neuronal α-synuclein disease (NSD) with hyposmia but without motor disability.

Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) derived from robust healthy control (HC) norms. Performance was examined for participants with hyposmia in early NSD-Integrated Staging System (NSD-ISS), either stage 2A (cerebrospinal fluid α-synuclein seed amplification assay [SAA]+, dopamine transporter scan [DaTscan]-) or 2B (SAA+, DaTscan+).

Results: Participants were stage 2A (n = 101), stage 2B (N …

Eugenics And Polygenic Embryo Screening: Public, Clinician, And Patient Perceptions Of Conditions Versus Traits, Dorit Barlevy, Rémy A Furrer, Asha Kalapatapu, Abigail Martinez, Todd Lencz, Shai Carmi, Gabriel Lázaro-Muñoz, Stacey Pereira

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Polygenic embryo screening (PES) estimates an embryo's genetic chances of developing complex conditions (eg, cancer) and traits (eg, height). Stakeholders have raised concerns that PES promotes eugenic practices and ideology.

Methods: We surveyed a nationally representative sample of the US public on approval of screening embryos for 12 conditions and 12 traits and examined the association between disapproval and concern about eugenics. We also conducted semistructured interviews with US-based reproductive endocrinology and infertility specialists and patients undergoing in vitro fertilization on their perspectives toward PES.

Results: Among the US public (n = 1423), disapproval of screening embryos for traits …

Comparative Effectiveness Of Less Vs More Frequent Hydrocortisone Dosing In Septic Shock, Alan Hao, Tianshi David Wu, Keegan Collins, Danielle Guffey, Rebecca Kessinger, Meghna Vallabh, Ali Omranian

Faculty, Staff and Students Publications

Objectives: Guidelines recommend hydrocortisone as an adjunctive treatment in septic shock, but the optimal dosing regimen is unknown. A national shortage of hydrocortisone in 2023 prompted a change in institutional practice for hydrocortisone administration from 50 mg every 6 hours to 100 mg every 12 hours in an effort to reduce waste and conserve vials, creating an opportunity to evaluate the comparative effectiveness of these two regimens. The primary efficacy outcome was time to shock resolution, and secondary outcomes evaluated in this study were mortality, renal replacement therapy (RRT), medication costs, and maximum vasopressor dose attained.

Design: Single-center, retrospective cohort …

A Prospective, Randomized, Controlled Clinical Trial Of High-Frequency Electromagnetic Coupling Powered Permanent Peripheral Nerve Stimulator For The Treatment Of Chronic Craniofacial Pain, Salim M Hayek, Nameer Haider, Ashwin Viswanathan, Mehul Desai, Jeffrey Rosenberg, Niek E Vanquathem

Faculty, Staff and Students Publications

than one-fifth of the US population. While various medications and conservative treatment modalities are available for this condition, many patients have refractory symptoms. These patients suffer from social impairment, reduced quality of life, and increased financial burdens.

Objective: The objective of this study was to examine the clinical outcomes of patients receiving a permanent, high-frequency electromagnetic coupling (HF-EMC) powered peripheral nerve stimulator (PNS) system for the treatment of chronic craniofacial neuropathic pain.

Study design: This study was a multicenter, randomized, controlled clinical trial conducted under an investigational device exemption (IDE).

Setting: This study was conducted in 7 clinical sites in …

Acad10 And Acad11 Enable Mammalian 4-Hydroxy Acid Lipid Catabolism, Edrees H Rashan, Abigail K Bartlett, Jingying Zhang, Andrew J Smith, Zakery N Baker, Patrick Forny, Peng Yuan, David J Pagliarini, Et Al.

2020-Current year OA Pubs

Fatty acid β-oxidation is a central catabolic pathway with broad health implications. However, various fatty acids, including 4-hydroxy acids (4-HAs), are largely incompatible with β-oxidation machinery before being modified. Here we reveal that two atypical acyl-CoA dehydrogenases, ACAD10 and ACAD11, drive 4-HA catabolism in mice. Unlike other ACADs, ACAD10 and ACAD11 feature kinase domains that phosphorylate the 4-hydroxy position as a requisite step in converting 4-hydroxyacyl-CoAs into conventional 2-enoyl-CoAs. Through cryo-electron microscopy and molecular modeling, we identified an atypical dehydrogenase binding pocket capable of accommodating this phosphorylated intermediate. We further show that ACAD10 is mitochondrial and necessary for catabolizing shorter-chain …

Variation In Recommended Treatment Strategies Among American Surgeons For Actual Adult Traumatic Brachial Plexus Injury Cases, Michele N Christy, Christopher J Dy, R Glenn Gaston, Bryan J Loeffler, Mihir J Desai, Steve K Lee, Harvey Chim, Jeffrey B Friedrich, Sameer K Puri, Jason H Ko, Planet Study Group

2020-Current year OA Pubs

PURPOSE: The surgical management of adult traumatic brachial plexus injuries (BPI) is challenging, with no consensus on optimal strategies. This study aimed to gather preferred reconstructive strategies from BPI surgeons for actual cases from a multicenter cohort to identify areas of agreement.

METHODS: Four case files (history, physical examination, and imaging and electrodiagnostic testing results) were distributed to eight self-designated Level IV expert BPI surgeons in the United States. Each surgeon independently reviewed the cases and provided a preferred reconstructive plan via free text response.

RESULTS: For a pan-plexus case after blunt trauma (67 years old; 3 months from injury): …

Inflammatory Pain In Mice Induces Light Cycle-Dependent Effects On Sleep Architecture, Dominika J Burek, Khairunisa Mohamad Ibrahim, Andrew G Hall, Ashish Sharma, Jessica A Cucinello-Ragland, Erik S Musiek, Jose A Morón, William A Carlezon Jr

2020-Current year OA Pubs

Pain syndromes include physical, sensory, emotional, and cognitive symptoms such as disability, negative affect, feelings of stress, and fatigue. Experimental induction of long-term inflammatory pain in rodents by hindpaw injection of complete Freund's adjuvant (CFA) produces anhedonia and dysregulated naturalistic behaviors, similar to the effects of unregulated stress. We examined whether these similarities extend to changes in sleep and rhythms, such as those induced by chronic social defeat stress, using actigraphy and wireless EEG in mice. Comparisons were made between groups that received injections at the onset of the light or dark phase. We found that CFA-induced inflammatory pain alters …

Associations Of Biomarkers Of Systemic Inflammation, Angiogenesis, And Cell-To-Cell Adhesion With Tumor Budding Among Early-Onset And Later-Onset Colorectal Cancer Patients, Oda Hausmann, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: High tumor budding and elevated systemic inflammation are adverse prognostic indicators in colorectal cancer. Its underlying mechanisms remain poorly understood. It is unclear whether systemic inflammation, angiogenesis, and cell-to-cell adhesion influence tumor budding.

METHODS: We investigated n = 132 stage I-III colorectal cancer patients recruited at Huntsman Cancer Institute enrolled in the ColoCare Study. Tumor budding was evaluated using an evidence-based scoring system, and patient sera were analyzed for nine circulating biomarkers using the Meso Scale Discovery platform. We examined associations between biomarkers and tumor budding using multivariable linear regression models adjusted for age, sex, neoadjuvant treatment, stage, and …

Nerve-Associated Macrophages Control Adipose Homeostasis Across Lifespan And Restrain Age-Related Inflammation, Elsie Gonzalez-Hurtado, Maxim N Artyomov, Et Al.

2020-Current year OA Pubs

Age-related inflammation or 'inflammaging' increases disease burden and controls lifespan. Adipose tissue macrophages (ATMs) are critical regulators of inflammaging; however, the mechanisms involved are not well understood in part because the molecular identities of niche-specific ATMs are unknown. Using intravascular labeling to exclude circulating myeloid cells followed by single-cell sequencing with orthogonal validation via multiparametric flow cytometry, we define sex-specific changes and diverse populations of resident ATMs through lifespan in mice. Aging led to depletion of vessel-associated macrophages, expansion of lipid-associated macrophages and emergence of a unique subset of CD38

Aberrant Expression Of Nuclear Prothymosin Α Contributes To Epithelial-Mesenchymal Transition In Lung Cancer, Liyun Chen, Chung-Teng Wang, Jia-Ming Chang, Ai-Li Shiau, Gia-Shing Shieh, Yau-Lin Tseng, Yi-Ting Yen, Tang-Hsiu Huang, Li-Hsin Cheng, Yu-Chih Wu, Chao-Liang Wu, Bing-Hua Su, Pensee Wu

2020-Current year OA Pubs

Elevated expression of prothymosin α (ProT) is frequently observed in cancers, but the underlying molecular mechanism remains poorly understood. Here, we report the clinical relevance of ProT expression and its correlation with lung cancer progression. We have shown that ProT was highly expressed in early-stage lung cancer, exhibiting nuclear localization; on the contrary, a loss of nuclear ProT expression was detected in late-stage tumor specimens. Furthermore, the expression of nuclear ProT impaired lung cancer cell migration, suppressed TGF-β-induced epithelial-to-mesenchymal transition (EMT)-associated transcription factor expression, and inhibited in vivo tumor metastasis. The suppressive effect of ProT was further found to trigger …

Walking Interventions And Cognitive Health In Older Adults: A Systematic Review Of Randomized Controlled Trials, Jongwon Lee, Delia West, Christine Pellegrini, Jingkai Wei, Sara Wilcox, Jean Neils-Strunjas, A Caroline Rudisill, Daniela B Friedman, David X Marquez, Jenna Dzwierzynski, Joyce Balls-Berry, Rachelle Gajadhar, Chih-Hsiang Yang

2020-Current year OA Pubs

ObjectiveThis systematic review summarizes the effectiveness and the dose of walking interventions on specific cognition domains in older adults, including executive function, memory, attention, processing speed, and global cognition.Data sourcePublished randomized controlled trials in PubMed, Embase, and Web of Science until 10 May 2023.Study Inclusion and Exclusion CriteriaStudies include older adults without Alzheimer's or related dementias, involving a walking intervention and performance-based neuropsychological assessments for executive function, memory, processing speed, attention, or global cognition.Data ExtractionTwo independent research assistants reviewed 8424 studies and included 17 studies.Data SynthesisParticipant demographics, intervention features (type, intensity, time, frequency, duration, format, and context), cognitive assessment tools, …

Dual-Vector Raavrh8 Gene Therapy For Gm2 Gangliosidosis: A Phase 1/2 Trial, Florian Eichler, Xuntian Jiang, Et Al.

2020-Current year OA Pubs

The dual rAAVrh8-HEXA and rAAVrh8-HEXB vector can restore central nervous system hexosaminidase (Hex) enzyme activity, decrease GM2 levels in cerebrospinal fluid and rescue phenotypic consequences of GM2 gangliosidosis, Tay-Sachs and Sandhoff diseases in animal models following simultaneous bi-thalamic (BiT) injections. Following up on an n = 2 expanded access trial, we initiated a phase 1/2, single-dose, dose-escalation of combined BiT, intra-cisterna magna and intrathecal infusion in children with Tay-Sachs and Sandhoff diseases (six infantile, three juvenile). The BiT injection volume and vector dose were doubled between four cohorts, with the lowest dose matching the earlier expanded access trial. Cerebrospinal fluid …