62021 research outputs found
Sort by
Implementation of an Evidence-Based Tool to Evaluate the Impact on the Consistency of Pressure Injury Identification and Staging
No full textThe purpose of this DNP initiative was to evaluate the implementation of an evidence-based tool on pressure injury staging and identification. This initiative was conducted at a National Cancer Institute (NCI) designated hospital that is a part of a large academic medical center in the Midwestern region of the United States. The initiative was developed and implemented to evaluate the use of the NE1 Wound Assessment Tool (WAT) on pressure injury identification and staging among a certified Wound, Ostomy, and Continence Nursing (WOCN) team. A total of 191 records were reviewed for adoption and fidelity. During the observation period, the tool was completed in 136 of the 191 observations, representing a 71% adoption rate. The 136 records were then evaluated for fidelity. A total of 121 records (89%) reflected 100% fidelity. Sixty-five patient records were sent to the WOCN team to determine the degree of agreement across the team. With the use of the NE1 WAT, the team saw an improvement in the overall degree of agreement. Percent agreement ranged from 76.92- 83.08%, with the initiative goal being 80%. However, while the overall percentage agreement with the use of the NE1 WAT, the Kappa Statistic ranged from 0.4902-0.6261, indicating moderate agreement across the team for each assessment. The implications of this initiative indicate that the use of the NE1 WAT can have a positive impact on the overall identification and staging of pressure injuries in an acute care setting.A five-year embargo was granted for this item
High Throughput Method for Analyzing β-sheet Protein Stability
Full text linkProteins are responsible for a vast array of biological processes, and their stability ensures proper folding, activity, and interaction with other biomolecules. Instability can lead to misfolding or aggregation that can trigger a cascade of biological consequences including loss of protein function or disease development. While general principles of folding are understood and computational models can be used to predict protein structures, the correlation between specific structural features and thermodynamic stability is not fully defined. Previous literature presents disagreements on the contribution of β-sheet side-chain interactions to overall protein stability. A deeper understanding of the factors that influence protein stability can facilitate the development of novel therapeutic strategies and drug discovery. In this study, we refine a high-throughput method using a β-sheet protein model to establish a framework for investigating factors that influence protein stability.
We use the B1 domain of protein G as a four beta-sheet containing model protein that binds with strong affinity to IgG. The small nature, well-understood structure, and high stability make GB1 an ideal candidate for study. More specifically, we establish a method to examine mutations in four surface-exposed interstrand residues on the beta-sheets and four residues in the hairpin loops. These residues were chosen for the inconsistent conclusions of previous research regarding the significance of amino acid properties versus side-chain interactions in relation to stability. Importantly, these selected residues are distinct from those identified in previous studies as being involved in IgG binding.
We utilize phage display to express GB1 on the pIII protein of M13 filamentous phage. This enables the scalable creation of libraries, efficient screening and selection processes, and establishes a direct connection between genotype and phenotype. Stability is assessed using a plate-based IgG-binding competition assay, which selects for properly folded variants with enhanced stability. Preliminary studies using analytical digest gels and Sanger sequencing have demonstrated enrichment of wild-type GB1 over engineered destabilized variants. Building on this foundation, the assay will be applied to two libraries, one focusing on beta-sheets and the other on hairpin loops. High-throughput next-generation sequencing will identify more stable variants and correlate their stability with intrinsic physical properties.
This project contributes to a broader understanding of protein stability by investigating structural and biochemical factors that drive thermodynamic resilience. By addressing longstanding questions about how specific residues and their interactions impact stability, this research holds significant potential to inform the development of engineered proteins and therapeutic interventions.No embargoAcademic Major: Biochemistr
Examining Decision-Making and Effect on Depression Scores Among Parents of Seriously Ill Infants Admitted to the Neonatal Intensive Care Unit
No full textBackground: Over 500,000 infants are admitted to neonatal intensive care units (NICUs) annually in the United States. NICU admissions are stressful for families, making decision-making about infant care challenging.
Methods: Parents of infants in a large Midwestern NICU were enrolled in a prospective, longitudinal study within the first week of hospitalization and followed for up to 12 weeks. Weekly surveys assessed whether parents felt they had made medical decisions, factors considered in decision-making, treatment goals, agreement levels with partners and healthcare teams, and distress levels.
Results: 76 mothers and 53 fathers of 79 infants participated. Mothers reported higher decision-making levels than fathers. Initially, about 50% of parents felt they had decided on their infant's care, decreasing to 35% of mothers and 12% of fathers over time. Most parents reported high agreement with partners and healthcare teams, but over 10% showed significant discrepancies. Key decision-making factors included doing what was best for the infant and considering future quality of life. During weeks when decisions were made, parents’ scores increased with a subset reporting moderate to severe depressive symptoms.
Conclusion: Understanding parental decision-making patterns in NICUs is crucial, as it relates to increased parental distress. In September 2024, the U.S. Surgeon General emphasized parent mental health as a national priority. Interventions supporting parental decision-making are needed to mitigate negative effects on parent distress. This study highlights the complexities of parental decision-making in NICUs and underscores the need for targeted support to improve outcomes for both infants and parents during this challenging time.A three-year embargo was granted for this item.Academic Major: Nursin
A Catecholamine-Induced AKAP1/PKA /JNK2 Stress Kinase Signaling Pathway Mediating Cardiac Calcium Triggered Arrhythmic Activity
No full textEmotional stress is as an independent risk factor for the onset of cardiac arrhythmias. Takotsubo Syndrome is a form of stress-induced cardiomyopathy with catecholamine surge-linked electrical and mechanical dysfunction in the heart, often associated with life-threatening ventricular arrhythmias. Catecholamines activate β-adrenergic signalling via PKA and A-Kinase Anchoring Protein-1 (AKAP1)-mediated complexes to effect subcellular trafficking. However, mechanisms of catecholamine-linked arrhythmias remain unclear. Here, we report a mechanistic link between AKAP1, PKA, and JNK2 in isoproterenol (ISO)-evoked ER Ca2+ mishandling using a heterologous HEK-RyR2 cell model. We found that enhanced JNK2 activation in ISO-treated HEK-RyR2 cells vs controls (n=3,3). Next, we fractionated FLAG-AKAP1/tGFP-JNK2 co-transfected HEK-RyR2 cells and saw that AKAP1 increased JNK2 localization to the membrane (p<0.01, n=7,6), implicating AKAP1 in subcellular trafficking of JNK2. Moreover, tGFP-JNK2 was found co-immunoprecipitated (IP) with anti-FLAG antibody pulldown of FLAG-AKAP1 proteins. Functionally, ISO-evoked JNK2 activation increased ER Ca2+ leak and AKAP1-mediated JNK2 membrane localization further enhanced this JNK2-driven ER Ca2+ leak vs sham controls (p<0.01, n=34,45), while cells co-transfected with AKAP1 and inactive JNK2-APF (T/183/A & Y/185/F dominant negative mutations) had no effect either, suggesting a critical role for active JNK2 in ISO-evoked ER Ca2+ leak, with AKAP1 augmenting this action. Disrupting AKAP1-PKA binding via AKAP1-A328P mutation or PKA activity inhibition by PKI (1 μM, 24 h) normalized ISO-evoked ER Ca2+ leak to sham control levels (p<0.05; n=34,24,14), implicating a key role of AKAP1-PKA complex in augmented JNK2-driven ER Ca2+ mishandling in response to ISO-stimulation. Moreover, we found that activated-JNK2 in the heart reduced mitochondrial complex functionality and ATP-generation efficiency, whilst taking over mitochondrial homeostasis by promoting dephosphorylation of Drp1 at Serine 616 (p<0.05, n=3,3), which was further evidenced by recovery of Drp1-S616-P when assessing JNK2-APF compared to mock (p<0.05, n=3,3) Overall, our findings reveal a novel role for AKAP1 in ISO-evoked membrane translocation of active-JNK2, and its critical contribution to ER Ca2+ mishandling and arrhythmogenicity, with a subsequent discovery of activated-JNK2 driving mitochondrial dysfunctionality. The AKAP1-PKA-JNK2 link is likely involved in catecholamine-evoked cardiac arrhythmogenesis.(Dr. Xun Ai) National Institute of HealthA five-year embargo was granted for this item.Academic Major: Microbiolog
Dysfluent in Fiction: Vocal Disability and Nineteenth-Century Literature
No full textIntroduction: The stammering century -- Lisping lovers : plotting dysfluent union in Thackeray and Brontë -- Refusing to grow up and speak right : prosthetic authorship and dysfluent choice in Dodgson -- "The dumb detec(k)tive" : Braddon's professionalization of the mute role -- Our American cousin, our dysfluent nation : celebrity speech disorder on the transatlantic stage -- "I have cut loose your stammering tongue" : enslavement, dysfluency, and the vocal metaphors of freedom -- Coda: "Th-th-th-that's all, folks!
Interview of Kim Sinkhorn by Alice Duncanson
No full textRemote interview.Kim Sinkhorn, who participated in athletic activities from an early age, was a student-athlete at Ohio State in the late 1970s. Sinkhorn discusses how the enactment in 1972 of Title IX – requiring equal opportunities for women in educational programs, such as in organized sports – affected her participation in sports both in high school and at Ohio State. She also discusses how the law influenced her career after her Ohio State graduation. She describes what it was like to play a women's sport at that time, particularly on a close-knit team like field hockey. Sinkhorn also talks about the impact of the team's coach – Harriet Reynolds – on her participation in the sport and on the trajectory of her career in secondary education after earning her degree. In addition, Sinkhorn discusses the relationships she built with OSU teammates, coaches, and the students whom she taught as a high school Physical Education teacher. Finally, she discusses her retirement activities, and her overall relationship with Ohio State over the years
Arabidopsis mutants deficient for ethylene-signaling are hypersensitive to geminivirus infection
No full textGeminiviruses are agriculturally important pathogens that are responsible for damaging billions of dollars of crops annually. These viruses package circular single-stranded DNA (ssDNA) in virus particles (virions) and replicate in the host cell nucleus via double-stranded DNA (dsDNA) intermediates that associate with host histones. Because of their small genomes, geminivirus proteins must be multifunctional, including the AL2 and L2 proteins, which are pathogenicity factors encoded by different but related geminiviruses. Critically, AL2/L2 inactivate adenosine kinase (ADK), which, among other roles, is responsible for phosphorylating adenosine to produce adenosine monophosphate (AMP) in the methyl cycle. The methyl cycle generates S-adenosyl methionine (SAM), a methyl group donor and required cofactor for methyltransferases responsible for RNA-directed DNA methylation (RdDM), a key epigenetic defense against geminiviruses. RdDM causes compaction of chromatin, including viral chromatin, which results in transcriptional gene silencing (TGS). When AL2/L2 inactivate ADK, flux through the methyl cycle is inhibited, thereby decreasing SAM synthesis and hindering RdDM. RdDM mutants demonstrate increased susceptibility to geminivirus infection, and AL2/L2 suppression underscores the importance of RdDM as an anti-geminivirus defense. Importantly, SAM is also a biochemical precursor to the gaseous hormone ethylene (Et). Thus, by inhibiting ADK, AL2/L2 might also reduce Et biosynthesis, suggesting Et-signaling may be involved in anti-geminivirus defense. Based on the role SAM plays in RdDM and ethylene biosynthesis, a novel geminivirus mechanism is proposed: the inhibition of the methyl cycle by AL2/L2 hinders multiple antiviral defenses, namely the established RdDM and proposed Et-signaling defenses. In support, we show that AL2/L2 do in fact reduce ethylene biosynthesis. Further, we show that ethylene-insensitive (ein) and ethylene-deficient (acs) Arabidopsis thaliana mutants are hypersensitive to Cabbage leaf curl virus 3 (CaLCuV) and Beet curly top virus (BCTV) infection, with the ethylene-deficient mutant symptoms being especially pronounced. Conversely, ethylene-overproduction mutants demonstrate increased tolerance to geminivirus infection. Moreover, RdDM mutants do not show reduced ethylene production, suggesting that the RdDM and Et-signaling pathways are independent. These findings support RdDM and Et-signaling as distinct anti-geminivirus defense pathways, both of which are inhibited by the inactivation of ADK by AL2/L2.President’s Research Excellence Accelerator Award (via The Ohio State University)National Science FoundationA one-year embargo was granted for this item.Academic Major: Molecular Genetic
Examining Phasic Variations in Hormonal and Metabolic Changes in Women Over Two Consecutive Menstrual Cycles
Full text linkThe menstrual cycle’s hormonal fluctuations significantly impact women’s physiology, influencing metabolism, body composition, and physical performance. Resting energy expenditure (REE), accounting for 60–75% of daily energy expenditure, tends to increase during the luteal phase compared to the follicular phase. However, inconsistent methods for identifying menstrual phases have limited the validation of these findings. Respiratory Quotient (RQ) is a measure of carbohydrate and fat oxidation, and provides further insight into metabolic changes across the cycle. Research suggests that body composition and substrate oxidation vary, particularly during the luteal phase, though individual responses differ. Fluid retention, a common menstrual symptom, peaks on the first day of menses when estradiol and progesterone levels are lowest, highlighting the dynamic relationship between hormones and physiological changes.
The Strategic Hormonal Evaluation and Instrument-Reliability Study (SHE IS) examines these relationships by analyzing hormonal blood markers (follicle stimulating hormone, Luteinizing Hormone, estrogen, progesterone) and their effects on body composition, REE, RQ, fluid retention (via InBody), and muscle strength/endurance (using Biodex). The study integrates femtech devices (Mira, OvuSense, Femometer) for precise cycle tracking. Eleven women (27.4 ± 7 years) are enrolled, with most completing at least two monitored cycles. A one-way repeated-measures ANOVA was conducted to evaluate changes across menstrual phases (α=0.05).
Analysis revealed trends toward significance for total body water weight (p=0.065) and REE (p=0.052). Total fat mass changes were not significant (p=0.191), but RQ showed significant variation across phases (p=0.041). No post hoc significance was found, though the luteal phase exhibited the greatest variation. These findings suggest promising trends, emphasizing the need for more participants to enhance statistical power.
Preliminary SHE IS data aligns with prior research, indicating increased REE and body composition changes during the luteal phase. This study highlights the scarcity of longitudinal, high-quality research in this field and underscores the value of femtech for precise cycle tracking. Continued funding and innovation are crucial to advancing menstrual health research and improving personalized health solutions for women.Undergraduate Research Scholarship (URS)No embargoAcademic Major: Public Healt
Prevalence of Cefazolin Inoculum Effect in Methicillin-Susceptible Staphylococcus aureus Isolates from Healthcare Systems
Full text linkIntroduction: The principal treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections comprises of first-generation cephalosporins, specifically Cefazolin (CFZ). Despite advantages such as better tolerability, convenient dosing, and reduced nephrotoxicity, treatment with cefazolin poses a significant concern due to the existence of the cefazolin inoculum effect (CzIE). CzIE is defined as reduced effectiveness of cefazolin against bacterial isolates when the bacterial inoculum is large, leading to a decrease in the antibiotic’s ability to inhibit bacterial growth. The general criteria for CzIE is defined as cefazolin minimum inhibitory concentration (MIC) values of ≥ 16 µg/mL at the high inoculum and ≤ 8µg/mL at the standard inoculum. The presence of the CzIE in MSSA isolates is linked to the beta-lactamase gene (BlaZ) expression and is associated with clinical treatment failure.
Methods: In this investigation, we evaluated the CzIE on a cohort of S. aureus isolates derived from cystic fibrosis, pediatric, and bone and joint infections. MIC tests were performed using micro-broth dilution assays based on CLSI (Clinical & Laboratory Standards Institute) guidelines. Briefly, antibiotic was serially diluted in a broth medium across a 96-well microtiter plate, and bacterial inoculum was added to each sample well. After incubating the plates at 37°C for 24 hours, the MIC was determined as the lowest concentration of antibiotic that completely inhibited visible bacterial growth.
Results: A cohort of 97 isolates were tested with cefoxitin to identify potential MSSA isolates. Isolates exhibiting MIC values ≤ 4µg/mL were classified as MSSA and were taken further for CFZ antibiotic susceptibility testing at low (10^4) and high (10^8) inoculum concentrations. We identified 32 MSSA isolates, among which only 3 demonstrated the CzIE (high inoculum MIC ≥ 16 µg/mL; low inoculum MIC ≤ 8 µg/mL). The MSSA isolates that did not exhibit CzIE were characterized as CzIE-negative. The CzIE-positive isolates will undergo further testing for the β-lactamase enzyme (BlaZ) expression evaluation via the Nitrocefin chromogenic assay. Additionally, the BlaZ gene cascade will be identified through genome sequencing.
Conclusion: This study highlights the need for a more extensive collection of MSSA isolates, given the considerable variation in CzIE frequency across different geographical regions.No embargoAcademic Major: Pharmaceutical Science
Regulation of goblet cells by diet and microbiota derived metabolites
Full text linkTrillions of commensal microbes, collectively called microbiota, reside in the mammalian intestine. Microbiota break down dietary components to produce metabolites that regulate the symbiotic relationship between the host and microbiota. Intestinal epithelial cells (IECs) reside at the direct interface between the host and microbiota and respond to metabolites from the diet and microbiota. We hypothesize that diet and microbiota-derived metabolites regulate goblet cells within the Intestine.
We found mice fed rice bran exhibited decreased numbers of goblet cells, which are the specialized IEC that maintains mucosal barrier function through secretion of the compound mucin. Furthermore, rice bran feeding resulted in reduced epithelial expression of the gene Mucin 2 (Muc2).
Rice bran is known to contain high amounts of both fiber and phytate. Microbial fermentation of dietary fiber produces the short chain fatty acid (SCFA) butyrate. In addition, dietary phytate is digested by distinct microbial enzymes to produce phosphorous and inositol phosphate metabolites. Interestingly, utilizing in vitro culture systems employing a human colonic epithelial cell line, we found that butyrate inhibited goblet cell gene expression. On the other hand, phytate metabolites promoted the goblet cell gene Muc2 expression. When treated with both butyrate and phytate, the phytate effect was overridden by the butyrate effect. Thus, our results suggest that rice bran can decrease goblet cells in the colon through microbial metabolism of fiber, despite opposing effects by phytateNo embargoAcademic Major: Animal Science