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PGC-1α Activation to Enhance Macrophage Immune Function in Mycobacterial Infections
Get PDFNontuberculous Mycobacteria (NTM) are a heterogeneous group of environmental microorganisms with distinct human pathogenesis. Their incidence and prevalence are rising worldwide, due in part to elevated antimicrobial resistance which complicates treatment and potential successful outcomes. Although information exists on the clinical significance of NTMs, little is known about host immune response to infection. NTM infections alter macrophage mitochondrial capacity and decrease ATP production, efficient immune response, and bacterial clearance. Transcription factor peroxisome proliferator activated receptor (PPAR) γ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis, influencing metabolism, mitochondrial pathways, and antioxidant response. Mitochondrial transcription factor A (TFAM) is a protein essential for mitochondrial DNA (mtDNA) genome stability, integrity, and metabolism. Both PGC-1α and TFAM regulate mitochondrial biogenesis and activity, and their disruption is linked to inflammatory signaling and altered macrophage function. We show that NTM causes macrophage mitochondrial damage and disrupted bioenergetics. Mechanistically we show that this is related to attenuation of expression of PGC-1α and TFAM in infected macrophages. Importantly, rescuing expression of PGC-1α and TFAM using pharmacologic approaches restored macrophage immune function. Our results suggest that pharmacologic approaches to enhance mitochondrial function provide a novel approach to target macrophage immune function and means to combat NTM infections
Simulating Vascular Emergencies in Robotic Surgery: Preparing OB-GYN Residents for Surgical Complications
Get PDFObjective: To teach and prepare obstetrics and gynecology (OB-GYN) trainees for rare, vascular emergencies that can occur during robotic surgery before they encounter such a stressful intraoperative event. We sought to create, evaluate, and implement two inexpensive vascular bleeding models for robotic gynecologic surgery simulation.
Design: Using readily available materials such as plastic tubing, twisting balloons, foam, a suction container, and a small water pump, we created two vascular bleeding models. A small diameter vessel was made with 2- and 3-mm tubing and secured to a foam uterus. A larger diameter vessel using twisting balloons was then secured to a board. The models were connected to a small water pump that simulated blood flow. The tubing was punctured, and the models were placed in the training abdomen and robot docked. Trainees then worked through patient cases to control the bleed robotically.
Setting: The simulated operating room at the University of Nebraska Medical Center Davis Global Center.
Participants: Sixteen OB-GYN residents, house officer 1-4 participated in a robotic surgery simulation.
Results: The low-cost bleeding models effectively simulated vascular emergencies during robotic surgery. OB-GYN residents participated in two robotic gynecologic surgery simulated cases, first encountering a small diameter vessel bleed and then a larger diameter vessel bleed. With guidance from faculty, the residents successfully identified and managed both bleeding emergencies. The residents provided positive verbal feedback on the realism and effectiveness of the models.
Conclusions: The low-cost bleeding models successfully simulated vascular emergencies during robotic surgery, providing OB-GYN residents with valuable experience in managing such scenarios, which can be very stressful when encountered. Future goals for our models include improving anatomical realism, testing efficacy, and expanding use to multidisciplinary surgical teams. By doing so, we aim to reduce surgical complications, enhance patient outcomes, and contribute to the advancement of surgical training
Analyzing the Acceptability of HPV Self-Swabs for Cervical Cancer Screening in Hispanic Populations
Get PDFhttps://digitalcommons.unmc.edu/com_fam_pres/1016/thumbnail.jp
Multilineage Hematopoietic Function of SAM-Containing Proteins
No full textCellular differentiation which begins with the stem cell and ends with mature cells is guided by various mechanisms like extracellular signals, signal transduction, transcription factor activity, and epigenetic modifications which all influence gene expression to facilitate differentiation. Studies of hematopoietic stem and progenitor cell (HSPC) differentiation have highlighted the intricacy of this process, involving several intermediate states of progressively restricted lineage-committed cells that each require a different set of mechanisms to promote differentiation. Misregulation of differentiation resulting in blocks in differentiation or defective cells cause diseases such as blood cancers, sickle cell anemia, and myelodysplastic syndrome (MDS).
A family of related sterile alpha motif (SAM)-containing proteins have recently been found to coordinate hematopoiesis. The commonly ascribed roles for SAMs in regulating cell signaling and transcription via homo- or heterologous interactions with other SAMs suggest shared control mechanisms. However, in many cases, their function remains uncharacterized. Previously, we identified the sterile alpha motif protein-14 (Samd14) as a coordinator of receptor tyrosine kinase Kit signaling in stress erythropoiesis. Additionally, we identified that the sterile alpha motif protein-1 (SAMD1) protein is expressed highly in hematopoietic stem cells (HSCs) and the erythroid lineage and is predicted to control key hematopoietic transcription factors such as GATA2.
My dissertation research has discovered new functions of Samd14 and SAMD1 in hematopoiesis. Using a conditional Samd14 knockout mouse model, we identified that Samd14 coordinates mast cell differentiation and function through the Kit receptor. It also uncovers new functions of SAMD1 in hematopoiesis. Furthermore, we find that SAMD1 facilitates the output of mature hematopoietic cells. In erythropoiesis, SAMD1 influences the chromatin landscape through coordination of H3K4 methylation. Additionally, with the use of an exciting new human bone marrow organoid model (BMO), SAMD1’s role in HSPCs is examined.
This work identifies new functions of SAM proteins in hematopoiesis. These studies provide a deeper understanding of SAM protein functions in cell biology and identify SAM proteins as coordinators of fundamental differentiation processes
Integration of the Science of Team Science (SciTS) with Applied Healthcare Frameworks: Interprofessional Education through a University-based Head Injury Clinic, Part I: Theory
No full textBackground: Wicked problems in healthcare, such as the complex health condition of head injury, demand interprofessional collaboration that transcends traditional disciplinary boundaries. These complex clinical challenges call for theoretical frameworks that integrate both disciplinary expertise and interdisciplinary processes.
Definitions and Concepts: Grounded in Repko and Szostak’s (2017) framework of interdisciplinary studies, this paper integrates the Science of Team Science (SciTS), the Interprofessional Education Collaborative (IPEC) competencies, and TeamSTEPPS® to construct a novel heuristic that informs the design of an interprofessional education (IPE) and practice model.
Relationships Between Concepts: We align SciTS’ four phases with IPEC and TeamSTEPPS® to enhance team-based learning. This integration provides a scaffolded theoretical and practical foundation for interdisciplinary clinical education.
How Change Occurs: Ten steps from interdisciplinary research theory guided the design of a Head Injury Clinic. These steps facilitated epistemological alignment, role clarity, shared communication, and mutual accountability among faculty and students.
Evaluation and Intervention Strategies: Evaluation included the Interprofessional Collaborator Assessment Rubric (ICAR), TeamSTEPPS® tools, and joint displays integrating qualitative and quantitative data to explore team performance and collaborative behaviors.
Application: The heuristic model was applied in the development of a team-based clinic. Faculty operationalized the framework in student training and practice design, embedding team theory into the learning environment.
Discussion: Our model supports interdisciplinary curriculum design through an epistemologically grounded approach. By embedding theory into faculty development and student learning, we support a more sustainable and scalable pathway from interprofessional education to interprofessional practice
Interventions to Enhance Care Partner Performance and Participation in Alzheimer\u27s and Neurocognitive Disorders: A Systematized Review
No full textPurpose: Care partners of people with Alzheimer’s disease (AD) and related neurocognitive disorders (NCDs) often experience disrupted routines, reduced self-care, and limited participation in meaningful occupations. Occupational therapy (OT) supports care partners’ engagement in health-promoting activities and sustainable caregiving (Rhodus et al., 2023). This systematized review examined interventions that enhance care partner performance and participation.
Design: Peer-reviewed, English-language articles were included if they involved adult care partners of individuals with AD or NCDs, implemented an intervention within the scope of OT, and used quantitate research designs.
Method: A total of 319 articles from MEDLINE, CINAHL, and Scopus were screened; 61 underwent full-text review, and 14 met inclusion criteria. Levels of evidence followed the Oxford Centre for Evidence-Based Medicine (2009), and strength of evidence and recommendations were based on the U.S. Preventive Services Task Force (2018).
Results: Five themes emerged: technology-based, multicomponent, education and psychoeducation, skills training, and yoga with mind-body exercises. Six level IB, one level IIA, and one level IIB studies provide strong evidence for technology-based and multicomponent interventions. Two level IB, one level IIB, and two level IIIB studies provide moderate evidence for education, psychoeducation and skills training. One level IIB study provides low evidence for yoga with mind-body exercises.
Conclusion: Evidence supports routinely implementing multicomponent, technology-based, skills training, and education and psychoeducation interventions to improve care partner performance and participation. Yoga and mind-body approaches may be beneficial but should only be used on a case-by-case basis.https://digitalcommons.unmc.edu/cahp_ot_sysrev/1023/thumbnail.jp
Occupational Therapy Interventions Supporting Transition to Adulthood for Individuals with IDD: A Systematized Review
No full textPurpose: Individuals with intellectual and developmental disabilities (IDD) transitioning to adulthood often receive minimal support, resulting in challenges with education, employment, and independent living. This systematized review aimed to identify interventions within the scope of occupational therapy to aid a smoother transition to adulthood for individuals with IDD. By analyzing existing research, this study identified evidence-based OT strategies to promote independence, self-determination, and community participation.
Design: A systematized review of synthesized results from peer-reviewed studies that examined transition-related interventions for individuals with IDD. Articles were included if they address programs, skills, or approaches within the scope of OT.
Method: A medical librarian performed searches in Medline, CINAHL, and Scopus, yielding 299 articles. Articles were screened by two reviewers, and consensus meetings were held to check for agreement. Data from articles were extracted into an evidence table to summarize population characteristics, intervention details, outcomes, and levels of evidence. The research team developed themes, appraised evidence quality, and identified gaps for OT practice and further research as well as used the US Preventive Services Task force definitions to characterize the strength of evidence and provide clinical recommendations.
Results: There were 9 articles ranging from randomized clinical trials, feasibility and intervention evaluation studies, practice guidelines, tool development studies, and review articles. One IB and one IIIB study found moderate evidence for self-determination and self-advocacy interventions. A level IB, IIIB, V study provided moderate evidence for life skills and daily living training . A, IIIB article found low evidence for technology-based and e-health interventions. One IIB and one IV study found low evidence for community and social participation. One IV article found low evidence for systems-level and programmatic models.
Conclusion: To support individuals with IDD transitioning to adulthood, OTs can consider providing self-determination and self-advocation skills education and life skills and daily living training routinely and technology-based or e-health supports, community participation programs, and systems level or programmatic models on a case-by-case basis.
Impact Statement: This review can guide practice by providing evidence about interventions to promote independence, self-determination, and participation in individuals with IDD during their transition to adulthood.https://digitalcommons.unmc.edu/cahp_ot_sysrev/1026/thumbnail.jp
Biological Response of Abaloparatide and Alendronate on the Osteochondral Tissue of TMJ-OA
No full textTemporomandibular joint osteoarthritis (TMJ-OA) is a degenerative condition marked by synovial inflammation, cartilage loss, and subchondral bone sclerosis, leading to chronic jaw pain. Current treatments are largely palliative, and regenerative options remain unavailable. Abaloparatide and alendronate have shown anabolic effects in healthy mice TMJs, but their therapeutic potential in TMJ-OA has not been well studied. This study aimed to evaluate the individual effects of abaloparatide and alendronate on cartilage and subchondral bone in a mouse model of TMJ-OA. Eighty 2-month-old C57BL/6J mice (40 male, 40 female) were subjected to unilateral mechanical loading via a bonded anterior crossbite device to induce TMJ-OA. Mice received subcutaneous injections of alendronate (50 μg/kg), abaloparatide (80 μg/kg), or saline. Mandibular condylar cartilage and subchondral bone were harvested for analysis. Samples were examined using micro-computed tomography and histological staining, including toluidine blue, Safranin O, TRAP, alkaline phosphatase, and immunohistochemistry for MMP13 and ADAMTS5. Imaging was performed with a ZEISS Axioscan 7. Data were analyzed using one-way ANOVA with Tukey’s post-hoc test. Alendronate treatment partially rescued cartilage integrity and preserved subchondral bone structure. Abaloparatide showed early signs of anabolic activity but will require dose optimization for conclusive outcomes. Our findings suggest that alendronate and may reverse damage to the cartilage and subchondral bone from mechanically induced TMJ-OA and warrant further studies on optimized dosing, local delivery, and age-specific responses
Efficacy and Safety of Thrombolysis for Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis
No full textWe conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen nonrandomized studies were included and no randomized clinical trials addressed these questions. Thrombolysis might be associated with a higher risk of major bleeding, clinically relevant nonmajor bleeding, or unspecified bleeding with risk differences of 0.09 (95% CI, -0.06 to 0.23), 0.06 (95% CI, -0.11 to 0.22), and 0.09 (95% CI, -0.04 to 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in submassive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of postthrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very-low-certainty evidence because of confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE
Interventions to Improve Functional Use of Hemiplegic Upper Extremity Post-stroke: A Systematized Review
No full textPurpose: Stroke is a leading cause of long-term disability with upper limb hemiplegia, significantly limiting participation in daily life (Lee & Howe, 2024; Long et al., 2020). This systematized review was conducted to address interventions within the scope of OT used to improve functional use of hemiplegic UE for adults post-stroke. Design: A systematized review protocol was used with inclusion criteria of full-text, English-language articles addressing rehabilitation interventions for hemiplegic UEs post-stroke containing participants ranging from ages 18-85. A medical librarian at the McGoogan Health Sciences library conducted a search across multiple databases for articles meeting the criteria for the clinical question. Method: Data were collected using a structured review process and synthesis of findings. The U.S. Preventive Services Task Force (USPSTF) definitions were used to characterize the strength of evidence and guide clinical recommendations. The procedure was a thematic analysis with findings categorized into 5 emergent themes based on primary intervention type. Results: A total of 21 articles were included, representing Level 1A, 1B, 2B, 3B, and 4 studies. Four themes emerged: (1) Movement Therapy/TOT; (2) Electrical Stimulation; (3) Robotics/Technology; and (4) Non-Invasive Brain Stimulation. Various strengths of evidence (SOE) emerged from synthesizing the findings; strong SOE supports NIBS from two Level 1A studies; moderate to strong SOE supports movement therapy and TOT from one Level 1A and 3 Level 1B studies; moderate to low SOE supports the use of e-stim from 4 Level 1B, one Level 2B and one Level 4 studies; and moderate to low SOE supports robotics and technology from seven Level 1B, one Level 2B, and one Level 3B studies. Conclusion: This study found that movement Therapy/TOT should be used routinely. All other interventions should be used on a case-by-case basis due to the variability of interventions, patient context, and technological supports of the other themes. Impact Statement: This systematized review will guide practitioners in choosing effective interventions for improving UE functional use in adults post-stroke.https://digitalcommons.unmc.edu/cahp_ot_sysrev/1029/thumbnail.jp