Medicine and Health Sciences Commons^™

Generalizability Analyses With A Partially Nested Trial Design: The Necrotizing Enterocolitis Surgery Trial, Sarah E Robertson, Matthew A Rysavy, Martin L Blakely, Jon A Steingrimsson, Issa J Dahabreh

Faculty, Staff and Student Publications

We discuss generalizability analyses under a partially nested trial design, where part of the trial is nested within a cohort of trial-eligible individuals, while the rest of the trial is not nested. This design arises, for example, when only some centers participating in a trial are able to collect data on non-randomized individuals, or when data on non-randomized individuals cannot be collected for the full duration of the trial. Our work is motivated by the Necrotizing Enterocolitis Surgery Trial (NEST), which compared initial laparotomy versus peritoneal drain for infants with necrotizing enterocolitis or spontaneous intestinal perforation. During the first phase …

Physical And Occupational Therapist Evaluations For Fall Prevention In The Emergency Department: A Geriatric Ed Guidelines 20 Systematic Review, Kristie Harper, Neha Raukar, Suzanne Ryer, Katherine M Hunold, Fabrice Mowbray, Charles L Maddow, Christopher R Carpenter, Shan W Liu

Faculty, Staff and Student Publications

Background: Older adults are at high risk for severe injuries and death from falls. Physical therapist (PT) and occupational therapist (OT) evaluations have been introduced into Emergency Department (ED) care to assist with fall risk evaluation and fall prevention care. An evaluation of current evidence was undertaken to inform the Geriatric ED Guidelines 2.0.

Methods: Systematic review of physical and/or occupational therapy evaluation for fall prevention in the ED. The intervention was evaluation by a rehabilitation therapist (PT, OT, or both) for fall prevention, fall assessment, or mitigation of fall risk factors. Studies that did not perform the evaluation during …

Urinary Cotinine Cut-Offs For Tobacco Smoke Exposure In Pregnancy And Associations With Child Intelligence Quotient: A Multi-Cohort Analysis, Qi Zhao, Thomas F Northrup, Penelope J E Quintana, Eunha Hoh, Georg Matt, Catherine J Karr

Faculty, Staff and Student Publications

Background: Prenatal exposure to tobacco smoke may impair neurodevelopment in children. However, accurately characterizing this exposure remains challenging.

Methods: We pursued two objectives in this large population study. First, in 1708 pregnant women from the Environmental Influences on Child Health Outcomes (ECHO) cohort, we constructed Receiver Operating Characteristic (ROC) curves to determine urinary cotinine cut-offs to classify firsthand (FHS), environmental (ETS), and no exposure, and further distinguished secondhand (SHS) from thirdhand smoke (THS) exposure within ETS. Second, among 1593 participants in three pregnancy cohorts nested in ECHO, we fit multivariable linear regressions to examine the association between the newly defined …

Consolidation Enfortumab Vedotin And Pembrolizumab After Cisplatin Induction In Metastatic Urothelial Cancer: Outcomes Of Complete Response And Bladder Preservation, Hui Zhao, Hajar Ayoub, Angel Blanco, Mark Amsbaugh, Nizar Tannir

Faculty, Staff and Student Publications

Bladder preservation remains a highly desirable therapeutic goal in urothelial carcinoma, particularly when durable survival can be achieved. Radical cystectomy is the standard treatment for muscle-invasive disease; however, it results in irreversible bladder loss and significant morbidity. Among patients with locally advanced or metastatic urothelial carcinoma, recurrence rates after standard therapy remain high. Consolidation therapy with enfortumab vedotin and pembrolizumab following cisplatin-based induction chemotherapy has demonstrated promising efficacy, with substantial complete response rates and improved bladder preservation. This single-center retrospective analysis evaluated the efficacy and safety of enfortumab vedotin plus pembrolizumab as consolidation therapy in 11 patients with metastatic urothelial …

Tuscan: Tumor Segmentation And Classification Analysis In Spatial Transcriptomics, Chenxuan Zang, Charles C Guo, Yaohong Wang, Peng Wei, Ziyi Li

Faculty, Staff and Student Publications

The identification of tumor cells is pivotal for understanding tumor heterogeneity and the tumor microenvironment. Recent advances in spatially resolved transcriptomics (SRT) have revolutionized the way that transcriptomic profiles are characterized and have enabled the simultaneous quantification of transcript locations in intact tissue samples. SRT is a promising alternative method to study gene expression patterns in spatial domains. Nevertheless, the precise detection of tumor regions within intact tissue remains a great challenge. A common strategy for identifying tumor cells is via tumor-specific marker gene expression signatures, which are highly dependent on marker accuracy. Another effective approach is through aneuploid copy …

Beyond Short Microhomologies: Mismatch-Compatible Pol Θ-Mediated Dna Damage Repair, Yuzhen Li, Richard D Wood

Faculty, Staff and Student Publications

DNA polymerase θ (Pol θ)-mediated end-joining (TMEJ), one of several pathways for repairing DNA double-strand breaks, is traditionally thought to initiate via anchoring at short, consecutive, and perfectly matched microhomologies (MHs). Emerging evidence indicates that Pol θ can utilize MHs containing mismatches both in vitro and in vivo. This revised definition of MH provides a mechanistic explanation for a broader spectrum of Pol θ-dependent repair outcomes. Here, we summarize recent findings on the revised definition of MHs utilized by Pol θ, assess the applicability of this concept across species, and compare TMEJ with other (micro)hom(e)ology-mediated repair pathways. We explore how …

Statistical Methods In Aging Research: Improving Current Practices And Embracing Emerging Approaches, Xi Rita Wang, Thirupathi R Mokalla, Olivia C Robertson, Wasiuddin Najam, Andrew E Teschendorff, Andrew W Brown, John R Speakman, Yisheng Peng, Bernard S Gorman, Heping Zhang, Luis-Enrique Becerra-Garcia, Colby J Vorland, David B Allison

Faculty, Staff and Students Publications

Aging research relies on varied statistical methods, and applying these methods appropriately is important for scientific rigor. However, proper use of these statistical techniques is a challenge. We discuss two categories of statistical methods in aging research: (a) emerging methods requiring further validation, including techniques to examine compression of morbidity, maximum lifespan, immortal time bias, molecular aging clocks, and treatment response heterogeneity, and (b) classic and existing methods needing reconsideration and improvement, such as stepwise regression, generalized linear models, methods for accounting for clustering and nesting effects, methods for testing for group differences, methods for mediation …

Participatory Action Research (Par) In Designing A Supplementary Animated Teaching Resource To Support Learning Cervical Assessment, Michelle Gray, Shelley Stuart, Melanie Welfare

Research outputs 2022 to 2026

Aim: To create an education resource that assists students to understand the movement of the cervix during labour from a posterior retroverted position to a central location, cervical effacement, dilatation of the cervix and descent of the fetal skull. Background: Learning about anatomy and physiology in relation to cervical effacement and dilatation are abstract concepts that are difficult to understand from reading alone. Diagrams are of little assistance however 3D animation has the potential to improve students learning experiences. Design: Participatory Action Research (PAR) using the 7 C's Feekery Framework approach was adopted. Participants became coresearchers in conceptualising the learning …

Preserving Residual Kidney Function In Haemodialysis: Current Practices, Challenges, And Perspectives From Renal Clinicians, Lijun Zhong, Ulrich Steinwandel, Hugh Davies, Sara Bayes, Jagadish Jamboti, Hemant Kulkarni, Doris Chan

Research outputs 2022 to 2026

Background: Residual kidney function in patients receiving haemodialysis is associated with improved survival, reduced cardiovascular risk and better quality of life. Yet, clinical guidelines on its preservation are limited, and local practices remain unclear. Objectives: To explore current practices, perceptions and challenges related to residual kidney function preservation among renal clinicians. Design: Descriptive cross-sectional survey. Participants: Renal physicians and nurses working in hospital-based haemodialysis units across Western Australia. Measurements: Role-specific questionnaires were administered to renal physicians and nurses. Results: Eighty-four completed responses were received (physicians n = 25; nurses n = 59). Over half of physicians (56%, n = 14) …

Assessing Liver And Iron Markers In Steady State Pediatric Scd Patients To Ascertain The Hepatic Consequences Of Hemotransfusion: A Case-Control Study In Ghana, John Agyemang Sah, Stephen Twumasi, Allwell Adofo Ayirebi, Benedict Sackey, Enoch Odame Anto, Richard Vikpebah Duneeh, Ebenezer Senu, Veronica Barnor, David Boakye, Daniel Nii Martey Antonio, Wina Ivy Ofori Boadu

Research outputs 2022 to 2026

Background and Aims: Between 200,000 and 300,000 children with sickle cell disease (SCD) are born in Africa every year, with 75%–80% of these children living in sub-Saharan Africa. In newborns with SCD, significant iron accumulations may develop because of their increased risk of requiring multiple blood transfusions. This study aimed to assess the hepatic effects of hemotransfusion in pediatric SCD patients in steady state by measuring liver and iron markers. Methods: This case-control research enrolled 120 children with SCD and 60 children without SCD from the Asokwa Children's Hospital Sickle Cell Clinic and Child Welfare Clinic. Participants’ sociodemographic information, history …

Physical Activity And Exercise Patterns Of Submariners In Land And Sea Environments, Benjamin Kirk, Georgios Mavropalias, Anthony Blazevich, Jodie Cochrane Wilkie, Aus Molan, Kazunori Nosaka

Research outputs 2022 to 2026

Introduction: Submarine environments pose unique challenges to maintaining physical activity and exercise routines due to confined spaces, demanding schedules, and limited resources. This study investigated submariners’ physical activity patterns, sleep quality, and perceived exercise barriers in both land- and sea-based settings, with the goal of informing targeted health interventions. Materials and Methods: Ethics approval was granted by the Defence Science and Technology Group and Edith Cowan University review panels. This cross-sectional study surveyed 21 Royal Australian Navy submariners (25-48 years; 18 male) using a modified version of the International Physical Activity Questionnaire. Participants reported weekly engagement in general physical activity …

Seeing Voices: A Dynamic, Interprofessional Approach To Teaching Performing Arts And Speech-Language Pathology Students About Vocal Anatomy And Physiology, Deborah Hersh, Luzita Fereday, Fiona Palmer, David Hall, Pedro Amarante Andrade, Priscilla Cornelius, Charn Nang, Jane White

Research outputs 2022 to 2026

Objectives: Seeing Voices was an interprofessional, technology-enabled, large-scale, teaching and learning event developed to address the need to improve voice students’ knowledge of laryngeal anatomy and physiology toward understanding and maintaining vocal health. Seeing Voices trialed a novel interprofessional educational approach, collected both quantitative and qualitative data about student experiences of laryngostroboscopic examination, and built a databank of laryngeal recordings for future student learning. Methods: Seeing Voices involved two 3-hour seminars in a large, university lecture space, run by an interprofessional team (speech-language pathologists, vocal coach, Ear Nose and Throat consultant) with quality equipment projecting laryngeal images to large screens …

A Joint Effort: Stakeholders' Perspectives Of Medication Management Reviews In Australian Residential Aged Care, Rajendra Gyawali, Marea O'Donnell, Rachel Jenkins, Amy D. Nguyen, Lalit Yadav, Rosemary Saunders, Fiona J. Clay, Johanna I. Westbrook, Karla Seaman, Magdalena Z. Raban

Research outputs 2022 to 2026

Objective: Residential Medication Management Review (RMMR) is a government-funded pharmacist-led service to address medication-related problems, such as polypharmacy, which are prevalent in aged care. Despite known benefits, concerns remain about the service's effective implementation to benefit residents. We aimed to explore stakeholders' perspectives of the service and identify challenges and improvement opportunities. Method: A qualitative study was conducted using individual interviews and focus groups with 21 stakeholders, including general practitioners (GPs), a nurse practitioner, registered nurses, pharmacists and consumers. Audio transcripts of the discussions were thematically analysed using inductive coding. Results: Seven interconnected themes were identified, highlighting complexities in RMMR …

Clinical Insights Into The Management Of Sleep Disturbances Within Cancer Care: A Qualitative Analysis, Sam Adams, Timothy D. Clay, Mitchell Turner, Christopher Kueh, Kelly Moes, Travis Cruickshank

Research outputs 2022 to 2026

Purpose: The present study aimed to gain a deeper understanding of how oncology healthcare professionals’ (HCPs) manage sleep disturbances. Methods: Semi-structured interviews were conducted with 10 oncology HCPs (medical oncologists, oncology nurse practitioners, clinical nurse consultants) working in metropolitan Perth, Western Australia. Reflexive thematic analysis was used to understand oncology HCPs’ perspectives on treating sleep disturbances, explore challenges and barriers to their management, as well as opportunities for improvement. Results: Four main themes were developed: (1) sleep disturbances are underreported and underassessed, (2) poor sleep can be difficult to manage, (3) limited capacity to address sleep issues, and (4) opportunities …

Dietary Flavonoid Intake And Psychological Well-Being – A Bidirectional Relationship, Alysha S. Thompson, Nicola P. Bondonno, Yan Lydia Liu, Farah Qureshi, Laura D. Kubzansky, Claudia Trudel-Fitzgerald, Julia K. Boehm, Eric B. Rimm, Aedín Cassidy

Research outputs 2022 to 2026

Background and aim: Higher dietary flavonoid intake has been associated with lower risks of mortality and major chronic disease, yet its relationship with psychological well-being (PWB), a key contributor to health and quality of life, remains unclear. This study aimed to investigate bidirectional associations between dietary flavonoid intake and two PWB facets: happiness (positive emotional state) and optimism (generalized expectation of positive outcomes). Specifically, we examined whether (1) overall flavonoid-rich dietary patterns (flavodiet score), (2) intake of specific flavonoid-rich foods, and (3) total flavonoid and subclass intakes were each associated with happiness and optimism over time. Methods: Data were drawn …

Mass Cytometry Workflow To Achieve High-Dimensional Immunophenotyping In Resource-Limited Or Decentralized Environments, Natalie Smith, Michael Cohen, Lauren Tracey, Julie Alipaz, Christina Loh, David King, Neha Pulyani, Rebecca Auzins, Elin Gray, Sandra Taylor, Rajat Rai, Steven Kao, Barbara Fazekas De St Groth, Helen Mcguire

Research outputs 2022 to 2026

Globally, regional and remote communities are burdened by both an increased prevalence and worse prognosis of many infectious and chronic diseases. However, largely owing to logistical challenges, these communities are under-represented in clinical trials and research studies. As individuals from rural communities experience unique environmental exposures and risk factors for disease, immune phenotyping data collected from metropolitan populations may not be broadly generalizable. To address this, we present a workflow that enables the inclusion of resource-limited sites in high-parameter mass cytometry studies. In this approach, whole blood (WB) or peripheral blood mononuclear cells (PBMCs) are collected, stained fresh for surface …

Neutrophil Gelatinase-Associated Lipocalin And Neutrophil-To-Lymphocyte Ratio As Indicators Of Nephropathy In Type 2 Diabetic Mellitus Patients In Ghana: A Case-Control Study, Allwell Adofo Ayirebi, Wina Ivy Ofori Boadu, Stephen Twumasi, Samuel Kwarteng, Benedict Sackey, Lilian Antwi Boateng, Joseph Boachie, Samuel Essien-Baidoo, Daniel Nii Martey Antonio, John Agyemang Sah, Afua Marfowaa, Mayfair Adwapa Mpiani, Joachim Baba Domosie, Abiba Khalifah, Emmanuel Ekow Korsah, Ebenezer Senu, Eugene Arele Ansah, Joseph Yorke, Enoch Odame Anto

Research outputs 2022 to 2026

Introduction: Serum neutrophil gelatinase-associated lipocalin (sNGAL), a renal tubular marker, and neutrophil-to-lymphocyte ratio (NLR), a hematological inflammatory marker are two biomarkers that have recently received attention, because of their association with kidney disease. This study examined the diagnostic value sNGAL and NLR in type 2 diabetes mellitus (T2DM) patients with nephropathy. Materials and Methods: In this hospital-based case-control research, 97 T2DM participants and 70 healthy subjects were included. Participants' information was documented using a structured questionnaire and patient case records. Venous blood was drawn from each participant and early morning midstream urine samples were collected for blood and urine measurements …

Optimizing Agility Training In Team Sport Players—The Role Of Perception-Action Coupling: A Systematic Review With Multi-Level Meta-Analysis, Zhiwei Zhao, Yuhang Liu, Kai Xu

Research outputs 2022 to 2026

Agility, characterized by rapid whole-body movement in response to external stimuli, is a key performance determinant in team sports owing to its reliance on perception-action coupling. Despite its importance, existing evidence on training effects is disproportionately focused on change-of-direction ability, overlooking the perceptual-cognitive demands of true agility. This systematic review therefore sought to quantify the effects of agility-specific training, examine moderators and establish dose-response model in team-sport players, while accounting for perception-action coupling. Following PRISMA 2020 guidelines, systematic searches were conducted in Web of Science, Scopus and PubMed for peer-reviewed English-language studies. Risk of bias was appraised using a modified …

Pleural Metastases From Acral Lentiginous Melanoma Diagnosed By Medical Thoracoscopy, Ad Rian Chong, Khai Lip Ng, Nai-Chien Huan, Nur Husna Mohd Aminudin, Fazilah Hassan, Kasuma Mohamed Nordin

Research outputs 2022 to 2026

Acral lentiginous melanoma (ALM) with pleural metastases is rare and under-recognised. We report an 86-year-old woman with progressive dyspnoea and pleuritic chest pain. 18 months ago, she was diagnosed with stage IIC ALM of the right heel, and was treated with wide local excision, but she declined adjuvant therapy. Imaging demonstrated a large left pleural effusion with diffuse pleural thickening, pulmonary mass, and hepatic metastases. Brownish pleural fluid, along with thoracoscopic identification of multiple pigmented nodules, led to a histologically confirmed diagnosis. Talc pleurodesis was performed for symptom control, and best supportive care was pursued. This case highlights the diagnostic …

Work Challenges And Cancer-Related Cognitive Impairment: Level Of Education Accounts For Unmet Needs Beyond Cognitive Impairment Severity, Darren Haywood, Susan L. Rossell, Ashley Henneghan, Frank D. Baughman, Jennifer Haywood, Evan Dauer, Annika Hegde, Ahmed A. Moustafa, Nicolas H. Hart

Research outputs 2022 to 2026

Purpose: Cancer-related cognitive impairment (CRCI) can impact cancer survivors’ return to work and occupational functioning for many years following the completion of cancer treatment. Understanding the characteristics of CRCI-related occupational difficulties and unmet supportive care needs is critical for the development of effective interventions. Within occupational roles, a higher level of education is typically associated with greater cognitive load and different demands. The objective of this study was to examine whether the level of education accounted for CRCI-related (a) occupational difficulties and (b) occupational unmet supportive care needs, beyond the contributions of perceived cognitive functioning and employment level. Methods: A …

Does Genetic Testing Influence Outcomes: Early Experience In Melanoma Case Series, Ryan Reyes, George Skenteris, Stella Coker Watson Self Ph.D., Ms, Christine Marie-Gilligan Schammel, Steven D. Trocha

Faculty Publications

Background:

The treatment and prognosis of melanoma have historically been based on histologic stage and Breslow depth; however, due to the increase in surveillance, melanomas are being identified at an earlier stage and lower Breslow depth. Advances in genetic testing, such as Decision Dx®, mean that melanoma diagnostic decisions and prognosis can now be directed by genetics. The purpose of this project was to assess the influence of a Decision Dx® high-grade (Class 2A/B) classification on the treatment of melanoma patients at a regional medical center, particularly those not deemed high risk by conventional classification methods, including Breslow depth and …

Emerging Options And Future Strategies In Immunotherapy For Advanced Lung Squamous-Cell Carcinoma, Y Wang, R Rosell, F R Hirsch, S Lu, R Govindan, K Park, S Peters, J J Zhang

2020-Current year OA Pubs

Advanced-stage lung squamous-cell carcinoma (LUSC) remains a therapeutic challenge. Although immune checkpoint inhibitors (ICIs) have revolutionized LUSC treatment, only a small subset of LUSC patients can achieve durable clinical benefits, underscoring the need for novel strategies. Emerging immunotherapy strategies have demonstrated early evidence of promise for LUSC patients, particularly multi-specific antibodies and fusion proteins, antibody-drug conjugates, adoptive cell therapies, and cancer vaccines. Additionally, advances in multi-omics and artificial intelligence offer potential for precise immunotherapy by deciphering the complex tumor-immune microenvironment and predicting therapeutic responses. The future of LUSC treatment lies in rational multi-target and biological therapies to boost immune cytotoxicity, …

Single-Cell Multi-Omic Techniques Highlight The Diverse Composition And Intercellular Interactions Of The Vestibular Schwannoma Tumor Microenvironment, Shree S Pari, Sangami Pugazenthi, Albert H Kim, Bhuvic Patel

2020-Current year OA Pubs

Vestibular schwannomas (VS) are tumors arising from Schwann cells of the vestibulocochlear nerve, often leading to hearing loss, gait imbalance, and other neurological complications. Recently, molecular profiling of VS using bulk and single-cell transcriptional and epigenetic approaches has reshaped our understanding of VS pathogenesis and challenged the long-standing view of VS being molecularly homogeneous. These integrative, multi-omic approaches reveal significant differences within VS and highlight diverse Schwann cell subpopulations and their interactions with the tumor microenvironment. Interestingly, these analyses also uncover 2 molecularly distinct groups of VS, one containing Schwann cells with an "Injury-like" phenotype that drives VS progression through …

Finding Significant Hits In Networks: A Network-Based Tool For Analyzing Gene-Level P-Values To Identify Significant Genes Missed By Standard Methods, Sandeep Acharya, Vaha Akbary Moghaddam, Wooseok J Jung, Yu S Kang, Shu Liao, Michael A Province, Michael R Brent

2020-Current year OA Pubs

Finding Significant Hits in Networks (FISHNET) uses prior biological knowledge, represented as gene interaction networks and gene function annotations, to identify genes that do not meet the genome-wide significance threshold but replicate, nonetheless. Its input is gene-level P-values from any source, including omicsWAS, aggregation of genome-wide association studies P-values, CRISPR screens, or differential expression analysis. It is based on the idea that genes whose P-values are low purely by chance are distributed randomly across networks and functions, so genes with suggestive P-values that cluster in densely connected subnetworks and share common functions are less likely to reflect chance and more …

Bacterial Immune Activation Via Supramolecular Assembly With Phage Triggers, Tong Zhang, Yifei Lyu, Christina R Beck, Naseer Iqbal, Renee Barbosa, Alireza Ghanbarpour, Michael T Laub

2020-Current year OA Pubs

Bacteria use diverse mechanisms to protect themselves against phages

Comparison Of Variant Callers Using 60 532 Multi-Ancestry Whole Genome Sequences, Hufeng Zhou, Nathan O Stitziel, Et Al.

2020-Current year OA Pubs

Whole genome sequencing (WGS) studies play a pivotal role in studying the genetic underpinnings of human diseases and traits. High quality and reproducible variant calling is the cornerstone for the success of downstream analyses, including WGS association studies and polygenic risk prediction. This paper compares the data quality, performance, and concordance of two widely used WGS variant callers, the Genome Analysis Toolkit (GATK) and Variant Tool set that discovers short variants (VT), using 60 532 multi-ancestry whole genomes sequenced by the Centers for Common Disease Genomics (CCDGs) of the NHGRI Genome Sequencing Program. Our findings show that both QCed GATK …

Astrocyte-Specific Deletion Of Lrrc8a Causes Neurological Dysfunction But Not Chronic White Matter Edema, Sven Kerst, Leoni Hoogterp, Marjolein Breur, Gemma M Van Rooijen-Van Leeuwen, Marianna Bugiani, Rajan Sah, Huibert D Mansvelder, Marjo S Van Der Knaap, Rogier Min

2020-Current year OA Pubs

Volume-regulated anion channels (VRACs) are central to cell volume homeostasis. They mediate swelling-induced efflux of chloride and organic osmolytes to drive regulatory volume decrease. In the brain, VRACs have been proposed to play a key role in astrocytic volume regulation. Genetic defects in astrocytic VRAC modulating proteins (MLC1, GlialCAM, Aquaporin-4, GPRC5B) cause the leukodystrophy Megalencephalic leukoencephalopathy with subcortical cysts (MLC), characterized by chronic white matter edema and myelin vacuolization. Disrupted VRAC activity in MLC-patient-derived lymphoblasts and primary astrocytes from MLC mice further supports a pathogenic link between defective VRAC activity and MLC. Here, we studied the physiological and pathological consequences …

Longitudinal Analysis Of Rotator Cuff Repair: Joint Kinematics And Clinical Outcomes, Sujata Khandare, Rebekah L Lawrence, Alena Jalics, Roger Zauel, Vasilios Moutzouros, Eric C Makhni, Stephanie Muh, Michael J Bey

2020-Current year OA Pubs

BACKGROUND: Rotator cuff repair is a common surgical procedure, but postoperative outcomes can be highly variable, and postoperative repair tissue healing remains a significant clinical challenge. Furthermore, the biomechanical effects of rotator cuff repair are not fully understood.

METHODS: Twenty-two participants scheduled for arthroscopic rotator cuff repair were evaluated preoperatively and at 3, 12, and 24 months postsurgery. The following data were recorded at each time point: glenohumeral and scapulothoracic kinematics, shoulder strength, and patient-reported measures of pain and function. Postoperative repair integrity was assessed via magnetic resonance imaging at 3 months and 24 months postsurgery.

RESULTS: At 3 months …

Piezo Mechanosensitivity In Chondrocytes Is Differentially Modulated By L-Type And T-Type Voltage-Sensitive Ion Channels, Alireza Savadipour, Gabrielle K Marushack, Robert J Nims, Jaquelin M Garcia-Castorena, Wolfgang Liedtke, Farshid Guilak

2020-Current year OA Pubs

OBJECTIVE: One of the primary factors contributing to OA development is altered or excessive mechanical stress on the joint, which chondrocytes sense in part through the PIEZO mechanosensitive ion channels. These channels activate signaling pathways that result in joint inflammation and cartilage degeneration. In addition to PIEZO channels, voltage-gated calcium (Ca

DESIGN: To better understand the relationship between PIEZO1 and VGCCs, we quantified porcine chondrocytes' intracellular Ca

RESULTS: In primary chondrocytes, nifedipine, an L-type VGCC blocker, reduced PIEZO1 sensitivity to both mechanical compression and pharmacological agonism, while NNC-55, a T-type VGCC blocker, increased PIEZO1 activation in response to both stimuli. …

From Damage Signals To Immune Modulators: Oxidized Lipids In Immunometabolic Inflammation, Neetu Srivastava, Xiaoxiao Wan

2020-Current year OA Pubs

Oxidized lipids, once viewed as byproducts of oxidative stress, are now recognized as critical mediators linking metabolism, redox imbalance, and immunity. Generated through enzymatic and nonenzymatic oxidation of polyunsaturated fatty acids, oxidized phospholipids, lipid aldehydes, and oxidized lipoproteins act as context-dependent signals regulating immune activation, resolution, and metabolic adaptation. In metabolic inflammation, these lipids engage scavenger and Toll-like receptors to influence macrophage polarization, dendritic-cell function, and T-cell differentiation. Their context and concentration determine whether oxidized lipids amplify inflammation or promote immune tolerance. Accumulation of these species connects oxidative stress to immune dysfunction, contributing to diseases, such as atherosclerosis, obesity, diabetes, …