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THE ROLE OF MYOCARDIN IN THE PROGRESSION OF NON-SMALL CELL LUNG CANCER
Get PDFLung cancer is the leading cause of cancer-related mortality in the world and NSCLC accounts for 85% of all lung cancer cases. The mainstay of treatment for patients with stage I, II and IIIA NSCLC is surgery, followed by post-operative cisplatin-based chemotherapy. Additional adjuvant therapy involving targeted tyrosine kinase inhibitors has been in use, however even for the targeted therapy, resistance eventually develops. Therefore, there is a need for identifying novel targets for this life-threatening disease. Given that preliminary studies in Ikebe lab revealed that myocardin knockdown significantly promoted caspase-3 degradation, in this study, using myocardin siRNA, we investigated the effect of the knockdown (KD) of myocardin gene on important apoptotic biomarkers such as PARP, caspase-3, and Bax; and on mitochondrial dysfunction involving respiration, and ROS formation. Our results indicated changes in the expression of multiple important apoptotic markers by myocardin knockdown in A549 NSCLC cells and myocardin knockdown was found to significantly decrease cell viability in A549 cells. Myocardin KD also showed a large, significant decrease in the maximal respiration of the cells and was found to significantly induce higher levels of ROS formation compared to the control. In summary, this study highlights myocardin as an important target in NSCLC progression and presents an interesting insight on the potential role of myocardin as a druggable target in lung adenocarcinoma. It also provides the basis for further investigation on its mechanism of apoptosis induction
EFFECTS OF INTERLEUKIN-22 (IL-22) ON NECROPTOSIS, INFLAMMATORY RESPONSES, AND METABOLISM OF MYCOBACTERIUM TUBERCULOSIS STIMULATED TYPE 2 DIABETES MELLITUS MOUSE MACROPHAGES
Get PDFMycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes nearly 1.3 million deaths per year. Limited information is available about the immune responses during Mtb infection in type 2 diabetic hosts. Our laboratory developed an experimentally induced type 2 diabetes (T2DM) model in wild-type C57BL/6 mice and found that IL-22 and type 3 innate lymphoid cells (ILC3s) reduce inflammation and mortality of Mtb-infected T2DM mice. Our laboratory also found that Mtb-infected alveolar macrophages (AMs) from T2DM mice undergo necroptosis compared to Mtb-infected AMs of non-T2DM mice. In the current study, we determined whether recombinant IL-22 treatment of γMtb-stimulated macrophages of T2DM mice inhibits the expression of necroptosis, reduces inflammatory cytokine production, and regulates the metabolism of the macrophages. We found that γMtb stimulation of T2DM mice lung macrophages significantly enhanced the expression of necroptotic markers such as pMLKL (phosphorylated pseudokinase mixed lineage kinase domain-like protein) compared to γMtb-stimulated lung macrophages of non-diabetic mice. Recombinant IL-22 treatment significantly inhibited the expression of pMLKL by γMtb stimulated lung macrophages of T2DM mice. The treatment marginally reduced the glycolytic parameters of these macrophages. However, the treatment had no effect on pro-inflammatory cytokines (IL-6 and TNF-α) production by γMtb-stimulated macrophages of T2DM mice. In future studies, live Mtb H37Rv will be used to infect macrophages to determine cell viability and necroptosis. Further understanding of the mechanisms involved in IL-22-mediated inhibition of pMLKL will help to develop therapies to prevent excess inflammation in T2DM individuals with active and latent tuberculosis infection
Average or Outlier? Introductory Statistics Adjunct Instructors’ Beliefs, Practices, and Experiences
Get PDFIn recent years, the adjunct faculty phenomenon has grown steadily. This research focused on adjunct instructors teaching introductory statistics courses. The purpose of the study was to give a voice to adjunct instructors by allowing them to describe their experiences teaching statistics. We conducted a qualitative study with 15 adjunct instructors of introductory statistics through semi-structured interviews. The participants came from several fields: psychology, nursing, and business, among others. Thematic analysis was used to find themes of statistical anxiety, use of technology in the classroom, lack of curriculum flexibility, and connection to the host institution. Our findings can inform institutions and interdisciplinary departments hosting introductory statistics courses. Similarly, educational statisticians can gain knowledge on the practices and barriers of adjunct instructors
Factors of Teacher Retention
Get PDFThe steady decline in teacher retention within the teaching profession remains a pressing issue for our education system, as it significantly impacts student success. This study investigated the crucial factors influencing teacher retention through a design-based implementation mixed-method research methodology. The research includes gathering current teacher retention data from a large suburban school district, analyzing human resource department field notes, conducting teacher interviews, and administering exit and stay surveys. The findings from the literature review and collected data highlight campus culture, sense of belonging, and teacher participation in shared decision-making as influential factors affecting teacher retention. By examining these factors, this study aims to shed light on the complex dynamics of teacher retention and provide insights for improving the overall educational environment
THE EFFECTS OF SCHOOL BOARD BEHAVIORS ON STUDENT OUTCOMES: AN EVALUATIVE STUDY OF LONE STAR GOVERNANCE
Get PDFEnhancing student outcomes is fundamentally attributed to classroom teachers, yet Rice et al. (2000) highlight the influential role of school boards in shaping these outcomes. This study delves into the efficacy of Lone Star Governance (LSG) as a facilitative instrument for promoting optimal governance practices across diverse schools. It also investigates the influence of governance coaching on student performance.
This research targeted rural school districts in the coastal bend of Texas that participated in the Texas Education Agency\u27s Lone Star Governance training. Employing a mixed-method embedded design, specifically an embedded experimental research model, the study assessed accountability score advancements. Complementing this quantitative analysis, in-depth interviews with school superintendents and surveys among school board members were conducted to unveil the impact of Lone Star Governance on board behaviors. Although the sample size was deliberately restricted to ensure training consistency, this limitation constrained the scope of statistical analysis.
The study found that a governance coaching intervention was essential in implementing the LSG model. Mean accountability scores exhibited a notable rise among LSG districts compared to their non-LSG counterparts. Statistical significance was observed through the Mann-Whitney U test (p = 0.01), indicating superior accountability scores in LSG campuses. Aligning with these findings, LSG participants acknowledged the correlation between improved student outcomes and their district\u27s adoption of LSG.
The data compiled justified the need for additional research for more detailed analysis to reinforce the study\u27s conclusion that Lone Star Governance is a continuous improvement tool that positively impacts the classroom
THE SCIENCE OF READING: INFORMING TYPICAL LITERACY PRACTICES AND IMPROVING IMPLEMENTATION OF RESEARCH-INFORMED PRACTICES
Get PDFMore than twenty years have passed since the National Reading Panel (NRP) (2000) report attempted to answer the question: Does comprehension strategy instruction improve reading? After reviewing about 200 studies on comprehension strategy instruction, the NRP divided reading instruction into the “Big Five” components. The NRP recommended explicitly teaching phonemic awareness, phonics, fluency, vocabulary, and comprehension. Despite the panel’s expertise, national reading scores (NAEP, 2022) indicate persistently poor performance of most 4th and 8th graders after more than two decades since the NRP report. At the same time, a preponderance of evidence from scientifically based research continues to pursue improved reading performance by aligning instructional practices to the science of reading. For instance, the science of reading aims to advance explicit and systematic instruction in how students decode words, including the word part analysis of syllables. Nevertheless, longstanding literacy practices of how to teach reading, such as instruction based on the three-cueing miscue analysis, endure despite scientific evidence. Admittedly, researchers recognize the limitations of interpreting scientific discoveries into effective classroom practices even with promising advances in reading instruction. Without practitioner-informed translation of scientifically aligned decoding instruction, two decades of data from typical literacy practices informed by the NRP reveal the limited likelihood of improving reading performance. Supporting a scientific change process towards a set of comprehensive practices that ensure reading proficiency for all students depends on the classroom contributions of practitioners
Bacterial Outer Membrane Vesicles Promote Lung Inflammatory Responses and Macrophage Activation via Multi-Signaling Pathways
Get PDFEmerging evidence suggests that Gram-negative bacteria release bacterial outer membrane vesicles (OMVs) and that these play an important role in the pathogenesis of bacterial infectionmediated inflammatory responses and organ damage. Despite the fact that scattered reports have shown that OMVs released from Gram-negative bacteria may function via the TLR2/4-signaling pathway or induce pyroptosis in macrophages, our study reveals a more complex role of OMVs in the development of inflammatory lung responses and macrophage pro-inflammatory activation. We first confirmed that various types of Gram-negative bacteria release similar OMVs which prompt proinflammatory activation in both bone marrow-derived macrophages and lung alveolar macrophages. We further demonstrated that mice treated with OMVs via intratracheal instillation developed significant inflammatory lung responses. Using mouse inflammation and autoimmune arrays, we identified multiple altered cytokine/chemokines in both bone marrow-derived macrophages and alveolar macrophages, suggesting that OMVs have a broader spectrum of function compared to LPS. Using TLR4 knock-out cells, we found that OMVs exert more robust effects on activating macrophages compared to LPS. We next examined multiple signaling pathways, including not only cell surface antigens, but also intracellular receptors. Our results confirmed that bacterial OMVs trigger both surface protein-mediated signaling and intracellular signaling pathways, such as the S100-A8 protein-mediated pathway. In summary, our studies confirm that bacterial OMVs strongly induced macrophage pro-inflammatory activation and inflammatory lung responses via multi-signaling pathways. Bacterial OMVs should be viewed as a repertoire of pathogen-associated molecular patterns (PAMPs), exerting more robust effects than Gram-negative bacteria-derived LPS
Comparison of Tertiary Drug Information Resources With the CDC Guideline for Oxycodone Dosing: Are Patients at Risk?
Get PDFBackground: Inappropriate prescribing of opioids is thought to play a central role in the ongoing opioid health crisis. Tertiary information resources are commonly used by clinicians for obtaining opioid dosing information. To assist health care providers in pain management, the Centers for Disease Control and Prevention (CDC) developed a guideline for prescribing opioids. Objective: To identify discrepancies for dosing information on oxycodone between commonly used tertiary drug information resources and the CDC Guideline. Methods: Searches of the tertiary drug information resources were conducted in the following order: Facts and Comparisons, Lexicomp, Medscape, and Micromedex. The term “oxycodone” was entered in the search box in the tertiary resources’ applications. Drug information items retrieved were organized in tabular format. In the Google Chrome version 106.0.5249.119 search box, the term “CDC guideline for opioid dosing” was entered to retrieve current information on the CDC Guideline. Results: Searches produced drug information on oxycodone for available formulations, dosing regimens, recommended dosing, and maximum daily dose (MDD). Searches revealed discrepancies in dosing recommendations for oxycodone among tertiary drug resources and between tertiary drug resources and the CDC Guideline. Conclusions: When considering maximum daily dosing information for oxycodone from the selected tertiary drug information resources, the potential exists for patients to be at risk of addiction, overdose, and perhaps death. Improving the way opioids are prescribed through the CDC Clinical Practice Guideline can ensure patients have access to safer, more effective chronic pain treatment while reducing the number of people who misuse or overdose from inappropriate dosing information
Optimization of CO2 Huff-n-Puff in Unconventional Reservoirs with a Focus on Pore Confinement Effects, Fluid Types, and Completion Parameters
Get PDFThe cyclic injection of CO2, referred to as the huff-n-puff (HnP) method, is an attractive option to improve oil recovery from unconventional reservoirs. This study evaluates the optimization of the CO2 HnP method and provides insight into the aspects of CO2 sequestration for unconventional reservoirs. Furthermore, this study also examines the impact of nanopore confinement, fluid composition, injection solvent, diffusivity parameters, and fracture properties on the long-term recovery factor. The results from over 500 independent simulations showed that the optimal recovery is obtained for the puff-to-huff ratio of around 2.73 with a soak period of fewer than 2.7 days. After numerous HnP cycles, an optimized CO2 HnP process resulted in about 970-to-1067-ton CO2 storage per fracture and over 32% recovery, compared to 22% recovery for natural depletion over the 30 years. The optimized CO2 HnP process also showed higher effectiveness compared to the N2 HnP scenario. Additionally, for reservoirs with significant pore confinement (pore size ≤ 10 nm), the oil recovery improved by over 3% compared to the unconfined bulk phase properties. We also observed over 300% improvement in recovery factor for a fluid with a significant fraction of light hydrocarbons (C1--C6), compared to just a 50% improvement in recovery for a fluid with a substantial fraction of heavy hydrocarbons (C7+). Finally, the results also showed that fracture properties are much more important for CO2 HnP than natural depletion. This study provides critical insights to optimize and improve CO2 HnP operations for different fluid phases and fracture properties encountered in unconventional reservoirs
Scoping review: Positive and negative impact of technology on clinicians
Get PDFBackground: Unnecessary electronic health record (EHRs) documentation burden and usability issues have negatively impacted clinician well-being (e.g., burnout and moral distress). Purpose: This scoping review was conducted by members from three expert panels of the American Academy of Nurses to generate consensus on the evidence of both positive and negative impact of EHRs on clinicians. Methods: The scoping review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews guidelines. Results: The scoping review captured 1,886 publications screened against title and abstract 1,431 excluded, examined 448 in a full-text review, excluded 347 with 101 studies informing the final review. Discussion: Findings suggest few studies that have explored the positive impact of EHRs and more studies that have explored the clinician\u27s satisfaction and work burden. Significant gaps were identified in associating distress to use of EHRs and minimal studies on EHRs\u27 impact on nurses. Conclusion: Examined the evidence of HIT\u27s positive and negative impacts on clinician\u27s practice, clinicians work environment, and if psychological impact differed among clinicians