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Endovascular Thrombectomy Peri-Procedural Recall: A Mixed Methods Study
No full textPurpose: This study aimed to explore patient characteristics and recollection of the peri-procedural endovascular thrombectomy (EVT) phase for individuals diagnosed with large vessel occlusion (LVO) stroke. Methods: A convergent mixed methods study was conducted to understand the lived experience of individuals receiving EVT intervention for LVO stroke. The relationship between patient recollection of the peri-procedural EVT period and LVO characteristics was explored. Stroke survivors participated in semi-structured interviews during acute hospitalization and completed the PHQ-9 and PSS-I-5 to assess potential psychological consequences of their life-threatening event and neurointerventional treatment. Results: A total of 20 patients participated in the study; 45% recalled the peri-procedural EVT period despite receiving conscious sedation; and a body mass index (BMI) \u3e 30 (obesity) was significantly associated with recollection (p = 0.025). Recall of EVT was not associated with either depression or post-traumatic stress disorder (PTSD) symptoms. Higher National Institutes of Health Stroke Scale (NIHSS) scores were associated with increased odds of depressive symptoms 24-hour post-EVT (OR = 8.33; 95% CI = 1.034-67.142) and at discharge or day 7 (OR = 13.55; 95% CI = 1.197-152.211). Patients with higher NIHSS scores also had increased odds of PTSD symptoms 24-hour post-EVT (OR = 21; 95% CI = 1.777-248.103) and at discharge or day 7 (OR = 16; 95% CI = 1.788-143.150). Qualitative data revealed three key themes regarding survivor experiences, converging with quantitative findings to show that obese patients were more likely to have procedural memory and those with persistent neurologic disability were more likely to experience depression and PTSD. Conclusion: Peri-procedural EVT recall is a multifactorial phenomenon influenced by patient BMI despite sedation, but is not associated with depression or PTSD. Patients with higher NIHSS disability have increased odds of early depression and PTSD. Tailored BMI-driven conscious sedation protocols should be evaluated to determine their impact on EVT recall. Future observational research is needed to confirm these findings in larger cohorts using objective recall measures to better understand this population\u27s needs and inform targeted interventions
Neurotransmitter Modulation of Alcohol-Induced GABAergic Signaling in the Central Amygdala
No full textAlcohol use disorder (AUD) is a chronic and relapsing condition characterized by compulsive alcohol seeking and consumption, loss of control over intake, and the emergence of negative affective states during withdrawal. The central amygdala (CeA), a predominantly GABAergic structure that integrates stress and reward signals, plays a critical role in the emotional and motivational processes that sustain alcohol dependence. Although pharmacotherapies targeting stress-related neuropeptide systems have shown promise, their efficacy remains limited. Neurotransmitter systems such as oxytocin (OXT), corticotropin-releasing factor (CRF), and serotonin (5-HT) have demonstrated therapeutic potential in reducing alcohol-related behaviors. However, how these neuromodulators alter GABAergic transmission in the CeA and interact with alcohol, particularly at the circuit level, remains poorly understood. This dissertation investigated how OXT, CRF, and 5-HT modulate GABAergic inhibitory transmission in the CeA under alcohol-naïve and chronic alcohol–dependent conditions in male and female Wistar rats. Using whole-cell patch-clamp electrophysiology in acute brain slices, inhibitory postsynaptic currents (IPSCs) were recorded to assess presynaptic and postsynaptic mechanisms of neuromodulation. Immunocytochemistry was used to quantify hypothalamic OXT-expressing neurons, and in situ hybridization was used to measure mRNA expression levels of oxytocin receptor (OXTR), CRF, and serotonin receptors (5-HT1A, 5-HT1B, and 5-HT2C) within the CeA. Electrophysiological findings revealed distinct sex-dependent and subregion-specific mechanisms of modulation. In males, both naïve and dependent, acute alcohol increased GABAergic transmission in the medial CeA (CeM) and lateral CeA (CeL). OXT suppressed presynaptic GABA release in the CeL of naïve males and blocked alcohol-induced facilitation of GABA transmission in both CeL and CeM of naïve and dependent males. In contrast, in females, OXT increased GABAergic tone in the CeM, and co-application of alcohol further potentiated this effect. Exogenous CRF produced modest postsynaptic effects selectively in alcohol-dependent males within the CeL, whereas CRF1 receptor antagonism decreased presynaptic GABA release in naïve males and blocked alcohol-induced facilitation regardless of alcohol history. Serotonin increased presynaptic GABA release in females (independent of alcohol history) and in naïve males within the CeL. Pharmacological activation or inhibition of serotonergic receptors, along with chemogenetic suppression of 5-HT signaling, attenuated or prevented alcohol-induced increases in GABA transmission in males. Neurohistochemical analysis revealed that chronic alcohol exposure reduced hypothalamic OXT neuron numbers, while RNAscope analyses demonstrated that chronic alcohol altered OXTR and CRF receptor expression in the CeA. Females expressed higher levels of OXTR and CRF mRNA regardless of alcohol history, whereas males, especially dependent males, exhibited greater expression of serotonin receptor subtypes. Together, these findings demonstrate that alcohol, OXT, CRF, and 5-HT interact to shape CeA inhibitory microcircuits through sex- and subregion-specific mechanisms. By elucidating how these neuromodulatory systems regulate inhibitory tone within the CeM and CeL, this dissertation identifies neurobiological substrates that may inform the development of targeted, sex-specific pharmacotherapies for alcohol use disorder
Colorectal Cancer Screening and Correlating Gender Disparities
Full text linkPurpose/Background
In 2023, colorectal cancer (CRC) was the second leading cause of cancer-related deaths in the US, equating to approximately 50,000 total deaths (National Cancer Institute, 2024). Further, it is estimated that an additional 1.4 million Americans are living with CRC (National Cancer Institute, 2024). Early detection screening modalities remain imperative since the NIH has released a combined survival rate of 70% when utilized (National Cancer Institute, 2024). Different derivatives of CRC develop from pre-cancerous polyps and are often without signs or symptoms of disease progression; this asymptomatic period emphasizes the importance of early detection and prevention of colorectal cancer (Gupta, 2022). Current guidelines set by the U.S. Preventative Services Task Force (2021) recommend that all adults ages 45-75 receive CRC screening.
Methods
A 6-month chart review was performed identifying adult patients, ages 45-75 years presenting to an outpatient family medicine clinic in need of CRC screening. The charts were reviewed for gender and whether or not a CRC screening was ordered.
Results
Of the thirty patients identified, over half received an order for CRC screening. Although males made up only 20% of the total chart review population, they had a 100% rate of screenings being ordered. Females, on the other hand, comprised the remaining 80% of the chart review population; however, only had a 54% rate of screenings being ordered.
Implications for Nursing Practice
Overall, this chart review indicates a large gap in CRC screening specifically for the female demographic. A further study identifying the clinical significance of this could help identify and resolve this care disparity
Pulmonary Embolism Response Team in Acute Care Settings: A scoping Review of the Evidence
Full text linkPurpose/Background
Pulmonary embolism (PE) is a critical cardiovascular emergency associated with high morbidity and mortality. Despite its prevalence, traditional PE management often lacks cohesion, leading to suboptimal outcomes. Pulmonary Embolism Response Teams (PERTs) offer a multidisciplinary approach aimed at improving patient outcomes by streamlining diagnosis, facilitating timely interventions, and promoting evidence-based treatment. This scoping review evaluates the evidence supporting PERT efficacy across various clinical and resource-related outcomes with the aim to decrease mortality rates, shorten inpatient length of stay, improve cost efficacy, and minimize adverse events from treatment modalities.
Methods
A comprehensive literature search was conducted using PRISMA guidelines across databases, including PubMed, Cochrane Library, and CINAHL. Search terms included “pulmonary embolism,” “PERT,” “clinical protocols,” and “time to intervention.” Inclusion criteria encompassed studies on adult inpatients managed by PERTs, published within the last eight years. Of 38 articles initially identified, 13 met inclusion criteria. Data were charted and synthesized to evaluate PERT outcomes. A levels of evidence table was created to classify the strength of the studies, and an outcomes synthesis table was used to organize and display key findings for analysis.
Results
PERT implementation reduced hospital stays by up to two days and ICU stays by 1.5 days. Studies reported a 15% decrease in 30-day mortality rates for patients managed by PERT compared to traditional care pathways. PERT facilitated faster diagnostic and therapeutic 3 interventions, with time to intervention reduced by 30–40% in critically ill patients. Additionally, advanced treatment modalities, such as catheter-directed thrombolysis (CDT) and extracorporeal membrane oxygenation (ECMO), were more frequently utilized. Cost efficacy was achieved through shorter hospitalizations and optimized resource allocation.
Implications for Nursing Practice
PERTs improve clinical outcomes and enhance resource efficiency in acute care settings. For advanced practice providers, PERT offers a collaborative framework that supports rapid, evidence-based decision-making and facilitates improved outcomes for patients with pulmonary embolism. The findings underscore the need for widespread adoption of PERT in acute care settings to standardize treatment approaches and enhance patient care. Standardization of PERT protocols and further research on long-term outcomes are recommended to solidify its role in PE management
Cholesterol Modulation of BK Currents and Cerebral Artery Diameter Via Channel-Forming Alpha-Subunit
No full textVoltage- and calcium-gated, large conductance potassium channels (BK; MaxiK) are ubiquitously expressed and subsequently mediate numerous physiological processes. Cholesterol is consumed in high amounts with the diet and accumulates in cellular membranes when plasma levels become elevated. Cholesterol is a known inhibitor of BK channels and is suspected of contribution to many pathophysiological issues via its interaction with these channels. However, the molecular mechanisms that drive cholesterol inhibition of BK channels remain largely unexplored. This dissertation hypothesized that cholesterol inhibits BK currents via binding to specific amino acid(s) of the channel-forming alpha subunit, and involving distinct modifications of channel gating. This project determines that cholesterol binds to the protein at physiologically relevant levels. A single amino acid, Y450, is required for this interaction between cholesterol and the BK channel-forming alpha subunit, as the conservative mutation of this residue is sufficient to prevent cholesterol binding. While other amino acid residues within the large BK channel-forming protein could interact with cholesterol, determination of their role, if any, requires a separate study. By applying an analytical approach in the form of Horrigan-Aldrich model, this project also identified specific gating parameters that are altered by cholesterol and result in BK channel inhibition. These parameters belong to all three known modes of BK channel gating: intrinsic, calcium-, and voltage-gating. The second major hypothesis of this thesis stated that cholesterol interaction with the BK channel alpha subunit results in cerebral artery diameter physiological responses. Specifically, we addressed the physiological and pharmacological consequences of cholesterol-BK channels protein interaction via Y450. While results demonstrate a lack of change in mouse middle cerebral artery diameter upon cholesterol enrichment, this does not conflict with the hypothesis that cholesterol induces a BK channel-mediated physiological response. Rather, the multimeric nature of BK channel complex and other protein receptors within smooth muscle tissue likely compensates for any alteration of normal cerebral artery physiological action, which is essential to maintaining consistent blood supply to the brain. This study, for the first time, developed a unifying scheme that explains the actions of cholesterol on BK channel alpha subunit function due to direct sterol-protein binding
Synthesis and Design of ClpP Activators as Novel Antibiotics
No full textPurpose. Design and synthesize novel compounds to treat Staphylococcus aureus infections by targeting the dysregulation of the Casein Protease P, ClpP. Methods. Utilize established chemical methods to synthesize ureadepsipeptides, small-molecule ClpP activators, and ureadepsipeptide hybrids. Assess their effectiveness by using minimum inhibitory concentration assays and in vitro biochemical assays for ClpP activation. Explore their potential as antibiotics through mitochondrial toxicity tests, glucose/galactose assays, and biophysical measurements related to metabolism and clearance, including thermal shift and surface plasmon resonance assays. Results. Synthesized and tested 33 novel compounds, comprising a total of 80 synthetic steps. Conclusion. The three-part conclusion from the dissertation is that: Heterocycles and bulky side chains are not well tolerated in the ureadepsipeptide structure at the phenylurea position, and a LogD of approximately 2 serves as a good marker for whole-cell activity. Small-molecule ClpP activators can achieve MIC activity but require further optimization for specificity against S. aureus. Biasing the pucker state of the southern proline on the UDEP macrocycle increases MIC activity, but attaching siderophore sidechains to the southern proline via a short linker does not confer broad-spectrum activity to UDEPs
GATA1 Occupancy Site Regulates Erythroid Cell Fitness through Pleiotropic Functions
No full textUnderstanding how non-coding variants influence cellular function remains a significant challenge in genetics, largely due to limited knowledge about regulatory sequence grammar, complex chromatin environments, and the transcriptional regulatory networks that link genotype to phenotype. In this study, we combined base editor-mediated perturbations of regulatory elements, CRISPR-mediated gene disruptions, epigenetic profiling, and chromatin organization data with hybrid deep learning models to quantitatively predict the functional consequences of mutations disrupting transcription factor GATA1 binding sites. Our models achieve high predictive accuracy and reveal key regulatory features underlying these effects. However, we observed that a small subset of GATA1 binding sites with the most substantial functional effects are consistently underestimated by the model. To investigate this discrepancy, we focused on a critical GATA1 binding site located within the PRPF19 gene. Notably, disruption of this site decreased PRPF19 expression but elevated the expression of its downstream gene, PTGDR2. Further analysis revealed that this GATA1 binding site serves dual roles as an enhancer of PRPF19 and as a regulator of proper RNA Polymerase II elongation. Its disruption impaired transcription termination, causing readthrough transcription that aberrantly activated PTGDR2. Our findings uncover novel pleiotropic functions of GATA1 binding sites and illustrate the current limitations of deep learning models in predicting rare yet critical regulatory events
On the Role of Solvation in Ligand Binding: Structural and Thermodynamic Studies
No full textWater is known to be the matrix of life. Liquid water, which is present in every living organism, is indispensable for all biological processes. Doubtlessly, water molecules play a critical role in ligand binding. In spite of its fundamental thermodynamic impact, solvent energetics is often bypassed in virtual screening. On the one hand, the determination of water energetics is generally hampered by the cooperative nature of these interactions. On the other hand, accounting for the correct energetic cost for water displacement by the ligand is thought to be one of the factors that limits the accuracy of docking. In addition, despite this critical role of water, experimental techniques that specifically provide information about solvation energetics are very limited. The first part of this dissertation discusses structural evidence for cases where water can play a favorable role in ligand binding. In the second part, the fact that the solvent can compete with ligand binding is discussed. Accounting for such effects allowed the development of strategies that enabled the determination of ligand affinity based on structural data. Finally, we developed a density-based solvation method that deduces solvent energetics directly from crystallographic electron density maps. To illustrate its feasibility, the method was applied to idealized electron density maps that were calculated from Molecular Dynamics trajectories. Unlike idealized electron density maps computed from atomic coordinates, the application of our solvation method to experimental density maps faced several challenges. These challenges were addressed, allowing the method to become applicable to experimental electron density maps
Written Reminders for Mammogram Compliance
Full text linkPurpose/Background
Breast cancer remains the second leading cause of cancer death among women in the United States, with a median age of mortality at 68 years old. Mammography has been shown to improve early detection and reduce mortality rates. Current United States Preventive Services Task Force (USPSTF) recommends biennial mammograms for women aged 50-74. However, compliance with biennial mammogram screenings remains inconsistent. This project aims to evaluate the effectiveness of written reminder letters in improving mammogram compliance among women aged 50-74 years old. The study focuses on comparing mammogram adherence rates among patients who received reminder letters compared to those who did not.
Methods
A retrospective chart review of 30 women aged 50-74 years who visited the University Clinical Health Family Medicine between January 1, 2024 and June 30, 2024, was conducted. Data collection included mammogram compliance and whether patients received a written reminder letter. Descriptive statistics were used to analyze the effectiveness of written reminders in promoting adherence to mammogram screening guidelines.
Results
The analysis revealed that 40% of women who received a reminder letter completed a mammogram, compared to only 16.67% of women who did not receive a letter. Additionally, 23.33% of women received a reminder letter but did not complete their mammogram. Overall, 57% of participants underwent a mammogram during the study period, and 63% received reminder letters. These findings identify the role of written reminders in improving mammogram compliance, while also identifying a subset of patients for whom additional interventions may be necessary.
Implications for Nursing Practice
This project highlights the potential for written reminder letters as a targeted, evidence- based intervention to improve biennial mammogram adherence. Advanced practice nurses are uniquely positioned to implement, evaluate, and refine patient-centered strategies to enhance screening compliance. Future initiatives should address barriers to adherence and explore the integration of a multimodal reminder system to optimize outcomes in breast cancer prevention and early detection