Now showing items 41-60 of 2221

    • Nurses’ Well-being and the Work Environment During the COVID-19 Pandemic

      Baek, Hyang; Baek, Hyang; Trinkoff, Alison M. (2023)
      Problem: The Coronavirus Disease 2019 pandemic, despite the improved current situation, has lasted longer than expected and has had a severe impact on the nursing profession. Nurses continue to face heightened levels of stress, frustration, exhaustion, and overwork. As a result, many nurses have either retired or left their positions, further worsening the existing nursing shortage. This shortage poses a significant threat to the efficiency and resources of the healthcare system. Therefore, it is crucial to gain a better understanding of how work-related factors affect the well-being of nurses. Purpose: The aims of this study were to 1) Examine the relationship between work-related factors and personal well-being during the pandemic; 2) Examine the degree and severity of workplace bullying in nurses and work-related factors; and 3) Examine the relationship between well-being and intention to stay while examining the potential moderating effect of workplace support on this relationship. Methods: This cross-sectional study analyzed survey responses from 1170 registered nurses across the US. The study data are from the Nurse Worklife and Wellness Study, 2020-21 (Trinkoff et al., 2021a). Results: Nurses who were younger, less experienced, working in hospitals, a staff or charge nurse, or on the frontlines reported lower well-being than their counterparts. Factors such as sufficient staffing and enough time to complete tasks significantly influenced nurses’ well-being. In aim 2, over 40% of nurses experienced workplace bullying, with 13.4% experiencing severe bullying in the past year. Inadequate staffing, insufficient time to complete tasks, and lack of breaks away from the work area were significantly related to severe bullying. For aim 3, only 75% of the nurses expressed their intention to stay at their current job for the next year. The intention to stay significantly differed by age and work-related factors, but workplace support had a significant moderating effect. As workplace support increased, the positive relationship between well-being and intention to stay was strengthened. Conclusion: This study provides guidance for organizations and management to address adverse work-related factors and to establish a healthy work environment. By ensuring sufficient staffing, providing adequate time for tasks, and actively addressing workplace bullying, nursing management can create an improved environment, ultimately promoting nurse retention.
    • The Relationship of Resilient Factors to Chronic Orofacial and Patient Expectations of Analgesia

      Thomas, Sharon L; Colloca, Luana (2023)
      Background: Adults with chronic orofacial pain experience significantly impaired daily functioning and reduced quality of life. Patient expectations are recognized as useful in medical treatment. However, we know little about coping behaviors, beliefs, and attitudes influencing disability or expectations in adults with chronic orofacial pain. Purpose: Positive psychological factors are protective against functional impairment and are implicated in placebo and expectations of analgesia. Examining the relationships between psychological factors, pain-related disability, and patient expectations will help identify correlates of disability, and individual susceptibility to placebo effects, a useful pain management modality. Methods: Three cross-sectional studies explored the correlates of pain-related disability and determined the influence of resilience on pain-related disability and patient expectations in adults with temporomandibular disorder. This study used secondary data from a clinical trial of placebo manipulation to examine the relationships between patient expectations of analgesia and psychological factors (resilience, dispositional optimism ) and a correlational observation design to explore the relationship between personal characteristics and psychological factors and pain-related disability in adults with TMD. The Aims were to 1) determine how positive and negative psychological constructs, jaw function, and chronic overlapping pain conditions contribute to pain-related disability; 2) describe the coping strategy patterns which patients engage in and compare the differences in these patterns based on pain characteristics; and 3) determine the relationship between pain resilience, pain interference, and patients expectations. Results Study 1 found that Resilience factors, optimism, and positive affect had a positive relationship with pain-related disability. Study 2 demonstrated chronic orofacial pain patients used both wellness and illness coping strategies. High Pain interference, Pain intensity, and Pain catastrophizing were associated with higher frequency use of all coping strategies. Study 3 revealed that pain resilience had an inverse relationship with pain disability and a direct and positive relationship with patient expectations. Conclusion: Psychosocial factors are important targets for clinical management of chronic pain. The effect of pain resilience on pain interference and reinforced expectations of analgesia means that clinicians focus efforts on building pain-resilient mechanisms, which can result in improved pain outcomes, augment its effect on expectations, and directly influence placebo treatment outcomes.
    • TLR4-SNP Mice Reveal the Role of M2a Macrophages in Resolution of Chemically-Induced Colitis

      Vlk, Alexandra M. ; Vogel, Stefanie N. (2023)
      Toll-like receptor 4 (TLR4) is an innate immune receptor responsive to Gram negative lipopolysaccharide (LPS). Single nucleotide polymorphisms (SNPs) in human TLR4 that encode an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I) render individuals hyporesponsive to LPS. In humans, these SNPs have also been associated with increased susceptibility to inflammatory bowel disease (IBD). IBD, including Crohn’s Disease (CD) and Ulcerative Colitis (UC), impacts millions of individuals worldwide and severely impairs quality of life for these patients. While multiple treatments are available for IBD, there are several problems: (1) not all patients respond, (2) responses may diminish over time, and (3) treatments often have undesirable side effects. Some patients with IBD express these SNPs and, using knock-in mice engineered to express the murine homologues of these human TLR4 mutations (“TLR4-SNP” mice), we have shown that TLR4-SNP mice develop significantly more severe colitis induced by dextran sodium sulfate (DSS) than wild-type (WT) mice. Previous studies have provided indirect evidence for a role of “tissue repair” M2 macrophages (Mφ) in the resolution of colitis. Signaling through the shared IL-4/IL-13 receptor, IL-4Rα, leading to activation of the transcription factor peroxisome proliferator-activated receptor (PPARγ) has been shown to be required for induction of M2a Mφ and our data provide direct evidence for the involvement of both in repair of DSS-induced colonic damage. In response to DSS, colons of TLR4-SNP mice produced reduced levels of M2a Mφ marker mRNA and protein. Additionally, PPARγ protein levels were reduced in colons from DSS-treated TLR4-SNP mice and therapeutic administration of the PPARγ agonist ligand, rosiglitazone, ameliorated colitis in TLR4-SNP mice. Together, these data indicate that the failure of TLR4-SNP mice to resolve DSS-induced colitis may be secondary to their failure to induce “tissue repair” M2a Mφ. Our findings provide insight into the potential development of novel therapies targeting Mφ signaling pathways that aim to alleviate the debilitating symptoms experienced by individuals with IBD.
    • From What to How: An Exploration of How Genetic Counseling Program Directors Learn to Teach

      Dixon, Shannan; Kulo, Violet; Cestone, Christina (2023)
      The pathway from medical practitioner to academic teacher is not-well defined, specifically, there is a lack of clarity in how clinicians learn to teach, particularly within the field of genetic counseling. While there is a defined curricular pathway for entry into clinical practice there is not a defined pathway for instruction of health professionals who want to teach. While healthcare professionals enter an academic role with a defined set of clinical skills, they often lack formal training in how to teach. This qualitative phenomenological study, using a community of practice (CoP) theoretical model, explored the pathway to teaching for genetic counseling education program directors. Thirteen study participants shared their professional journey of learning to teach. Data from this study support the three phases of CoP in genetic counseling education program director development: engagement, imagination, and alignment. Participants reported content, instructional, and pedagogical reflection as they progressed in their understanding and development of their own teaching practice. Engagement with genetic counseling education programs was reported in three different ways: planned, sequential, and unplanned. All respondents acknowledged content reflection as a part of their early practice of learning to teach. The imagination phase is demonstrated as individuals expanded their understanding of teaching, program leadership, and responsibilities required to serve as a program director – in other words they began a practice of instructional reflection. Those who reported alignment did so based on mentorship and contribution to the community of genetic counseling education program directors and shared instances of pedagogical reflection. The findings of this study support the premise that genetic counseling education program directors, although not formal scholars in education prior to entry into their educator role, practice the scholarship of teaching and learning through a CoP. They are committed to the practice of evaluating how students learn to improve their own teaching. Further, they are committed to modeling professional development and learning as a member of a CoP. What they lack is the formal understanding of educational theory as it relates to genetic counseling instruction – without this knowledge it is difficult to conduct theoretically grounded educational research and advance the profession.
    • The Effect of Medication Information Delivery Format on Cognitive Load and Knowledge Retention of Informal Caregivers

      McPherson, Mary Lynn M.; Kulo, Violet A; Cestone, Christina (2023)
      Informal caregivers (IFCs) are tasked with many responsibilities in patient care, including medication management. Many IFCs feel ill-prepared for this responsibility, and it is incumbent on health care professionals to provide education and ensure IFCs competence in medication management. One common strategy is to provide a medication information leaflet to the IFC to prepare them for this role. Designing medication information leaflets using sound educational principles, such as an infographic designed according to the cognitive theory of multimedia learning (CTML), may optimize knowledge retention and decrease cognitive load for IFCs. The purpose of this randomized, experimental study was to investigate the impact of medication information delivery format on immediate retention of medication information and cognitive load of IFCs of patients with a serious illness. Using purposive sampling, 120 IFCs who have provided some element of medication management for patients diagnosed with a serious illness, including patients who may have been receiving hospice or palliative care services were recruited. Study participants were randomly assigned in either the experimental group or the control group. The experimental group viewed an infographic on the medication hydromorphone, followed by a knowledge quiz, and a self-assessment of cognitive load. This was followed by a second infographic on hydroxyzine, the quiz, and cognitive load assessment. The control group went through the same steps but viewed a text-only medication leaflet. Statistical analyses included descriptive statistics, independent samples t-test, one-way analysis of variance, and one-way multivariate analysis of variance. Statistically significantly higher quiz scores were observed among those who viewed the infographics than those who viewed text-only medication leaflets, indicating better immediate knowledge retention of medication information. Those who viewed the infographic also had statistically significantly lower intrinsic and extraneous cognitive load, and higher germane cognitive load. These findings are consistent with the hypothesis that infographics prepared using the CTML result in better and more efficient learning. Limitations of this research include use of nonprobability sampling, examining only two medications that are commonly used in serious illness, and lack of systematic randomization. Additional research is needed to continue determining best practices for instructing and supporting IFCs in medication management. 
    • Evaluation of Salmonella enterica serovar Typhimurium Vaccines in the Context of Immunosenescence

      Allen, Jessica; Tennant, Sharon M. (2023)
      Non-typhoidal Salmonella (NTS) is responsible for a high burden of foodborne infections and deaths worldwide. In the United States, NTS infections are the leading cause of hospitalizations and deaths due to foodborne illnesses, and older adults (≥65 years) are disproportionately affected by Salmonella infections. Due to this public health concern, we have developed a live attenuated vaccine, CVD 1926 (I77 ΔguaBA ΔclpP ΔpipA ΔhtrA), against Salmonella enterica serovar Typhimurium, a common serovar of NTS. The effects of age on parenteral vaccination are well documented, however, how advanced age impacts oral vaccine responses is less understood. In this dissertation, systemic and mucosal immune responses to CVD 1926 were evaluated in adult (six-to-eight-week-old) and aged (18-month-old) mice. We demonstrated that aged mice immunized with CVD 1926 failed to reduce bacterial burden upon challenge with wild-type S. Typhimurium, which was associated with lower vaccine-induced antibody titers and weaker T cell responses. Notably, characteristics of a successful mucosal vaccine response were weak in aged mice, suggesting that mucosal responses to oral vaccines decrease with advanced age. In efforts to develop a NTS vaccine that is effective for older adults, two vaccine approaches were evaluated: (i) a novel live-attenuated vaccine strain, CVD 1926 ΔsteD and (ii) heterologous prime boost strategy involving a mucosal prime with CVD 1926 that was followed by a parenteral boost with a conjugate S. Typhimurium vaccine. SteD is a Salmonella effector that suppresses CD4+ T cell responses during infection with wild-type S. Typhimurium. Using in vitro and in vivo assays, we demonstrated that CVD 1926 ΔsteD immunization elicits enhanced MHC-II expression, increased flagellin-specific CD4+ T cells, robust serum IgG and fecal IgA responses, and protection against S. Typhimurium colonization of the spleen, cecum, and small intestine upon challenge in aged mice. While the heterologous prime boost strategy induced robust Salmonella-specific antibody responses in aged mice, only modest protection against S. Typhimurium colonization was observed, suggesting that this vaccination approach cannot overcome immunosenescence. Taken together, these studies identify the age-associated deficits in mucosal vaccine responses and presents a promising prototype vaccine strain that may be effective for older adults.
    • The Effects of Graded Versus Ungraded Individual Readiness Assurance Tests on Pharmacy Students’ Assessment Performance and Achievement Goals in a Team-Based Learning Classroom

      Noel, Zachary; Cestone, Christina; Gordes, Karen L. (2023)
      Individual readiness assurance tests (iRATs) are frequently graded in team-based learning (TBL) classrooms, with the goal of incentivizing individual pre-class preparation. The purpose of this study was to determine whether shifting to an ungraded iRAT process affects student preparation and learning, as measured using assessment scores, and whether this is accompanied by a change in achievement goals. Using a crossover design in a required second-year Doctor of Pharmacy pharmacotherapy course, students were assigned to one of two iRAT grading sequences: graded/ungraded (G/UG) or ungraded/graded (UG/G). In the G condition iRATs were graded based on correctness and in the UG condition based on completion. Each period consisted of four iRATs and one examination. Students completed the Achievement Goal Questionnaire at the conclusion of each period. A one-way repeated measures multivariate analysis of variance (MANOVA) was used to test within-subject differences of mean iRAT and examination scores across grading conditions. A separate one-way repeated measures MANOVA was used to analyze differences in achievement goal scores. A total of 91 doctor of pharmacy students were included in the study. There was a statistically significant main effect for iRAT grading condition on assessment scores, F(2,88) = 3.851, Wilks’ Λ = .992, p = .025. Univariate testing using one-way analysis of variance with Bonferroni correction demonstrated a significant difference only in iRAT scores, with the mean score higher in the G condition (72.51% versus 67.99%; p = .011). Examination scores were similar in the G and UG conditions (81.07% versus 80.32%, p = .397). There was not a statistically significant difference in achievement goals based on iRAT grading condition, F(4,85) = 1.109, η2 =.050, p = .358. In conclusion, a modest reduction in iRAT performance was observed when shifting from a graded to ungraded iRAT; however, this had no effect on examination performance. Achievement goals were unaffected by the change in iRAT grading condition.
    • The quality of information on oral hygiene instructions for orthodontic patients in TikTok videos

      Dorfmann, Sabrina; Schneider, Monica, D.D.S., M.S. (2023)
      Objective: The study aimed to assess the reliability, content, quality, and overall usefulness of orthodontic oral hygiene instructions in TikTok videos. Methods: The final videos were evaluated for content, reliability, quality, and usefulness by using a content domain checklist, DISCERN questionnaire, and Global Quality Scale (GQS). Descriptive video characteristics were also recorded. Results: Dental professionals uploaded 70.00% of the TikTok videos, with orthodontists responsible for 39%. The videos had average scores of 2.19 for DISCERN, 3.96 for content, 2.14 for GQS, and 6.10 for usefulness. Video length was significantly associated with content scores (r = 0.3553, P = 0.0003), usefulness (r=0.3553, P = 0.0003), and quality (GQS) (r=0.2620, P=0.0085). Conclusion: Most TikTok videos on orthodontic oral hygiene were uploaded by dental professionals. Reliability, content, and quality of the videos were all poor. Videos were considered slightly useful. Longer videos were significantly correlated with higher content, higher quality, and increased usefulness.
    • Predictors of Traumatic Stress in Hospital Nurses in the Third Year of COVID-19 and Their Lived Experiences: A Mixed Methods Study

      Storm, Asha; Friedmann, Erika (2023)
      Background: Research on nurses early in the COVID-19 pandemic shows elevated severity of trauma-related stress, depression, anxiety, and poorer well-being than before the pandemic. Fewer studies examined nurses’ experiences three years into the pandemic and the relationships of the experiences that predict increased post-traumatic stress severity. Objectives: This study evaluates the relationships among peritraumatic distress, moral distress, resilience, and post-traumatic stress severity as its primary objective. The study also examined the relationships of depression, anxiety, sleep quality, and nurses’ perceived work environment to post-traumatic stress as its secondary objective. The overall goal is to understand targets for intervention on the path to the development of post-traumatic stress that could potentially reduce the impact of crises on nurses. Methods: This study evaluates the interrelationships of these variables using a concurrent triangulation mixed methods framework. Nurses participated in multiple surveys, and a subset of these nurses participated in semi-structured interviews. A structural equation model (SEM) examined the relationships of the primary outcomes, and multiple regression analyses investigate the independent predictive ability of the variables on post-traumatic stress. The interviews utilized a descriptive phenomenological methodology to describe the lived experiences of traumatic stress during the pandemic for these nurses. Results: In the SEM, moral distress partially complementarily mediated the direct positive effect of peritraumatic distress on post-traumatic stress and negatively moderated the direct negative effect of resilience on post-traumatic stress. A multiple regression with all variables excluding resilience and sleep quality (not significant at p < .20) accounted for 62.6% of the variability in post-traumatic stress symptom severity. The interviews revealed that nurses exist in three interrelated worlds: their “Internal World” (emotions and personal well-being), their ‘Hospital World” (coworkers, leadership, environment, etc.) and the “Outside World” (the public, social media, current events, etc.). Conclusion: Nurses require support for their mental health at work and outside the hospital during a crisis, and hospital policies must consider all three. Reduction in peritraumatic stress and moral distress and support for nurse resilience are some of the most critical areas to focus on to reduce the post-traumatic stress severity in nurses during a long-term crisis.
    • Calcium-Dependent Mechanisms of Microtentacle Regulation in Mammary Epithelial and Breast Tumor Cells

      Chang, Katarina; Martin, Stuart S. (2023)
      Remodeling of cellular cytoskeletal structures in circulating tumor cells facilitates metastatic spread. Rearrangements of actin and tubulin in a nonadherent environment such as the vasculature produces microtubule-based protrusions termed microtentacles. Microtentacles are highly dynamic tubulin structures formed on free-floating cells when the physical outward force generated by the microtubule network overcomes the inward contractile force of the actin cortex. When cells enter a free-floating environment, microtentacles form within minutes, along a similar timeline to the rapid initiation of calcium signal transduction after mechanical stimulation. Historically, many studies focus on aberrant calcium-mediated oncogenic signaling pathways through receptor overactivation or overexpression to examine long-term (>24 hours) functions and phenotypes. Thus, the acute cellular response that occurs within seconds to minutes of stimulation is often overlooked in cancer biology. This study directly examines the cytoskeletal response of breast cancer cells to fluctuations in intracellular and extracellular calcium content. With the use of TetherChip technology in tandem with confocal microscopy, live cell time course imaging, and quantitative cell-based assays we have defined the rapid signaling mechanisms that mediated the cytoskeletal changes in detached and suspended breast epithelial and tumor cells. These findings reveal an induction of acute elevations of cytoplasmic calcium in tumorigenic and metastatic breast tumor cells. We observed that cells undergo rapid actomyosin contraction and rearrangement through phosphorylation on myosin light chain 2 and dephosphorylation of cofilin to suppress the microtentacle phenotype and functions. Moreover, rapid fluctuations from physiological to low intracellular and extracellular calcium conditions profoundly affect microtentacles in mammary epithelial and breast tumor cells. Although the probability of cancer cells encountering extreme environmental calcium gradient changes, these cells modulate their cytoplasmic calcium homeostasis through various calcium sensitive upstream regulators. Therefore, examining these specific channels, pumps, and receptors could have interesting implications for cancer cell behaviors in the tumor microenvironment. By understanding the acute molecular responses to calcium-mediated signal transduction, we can better develop and profile calcium modulators to target circulating tumor cells for the eventual application of rapidly profiling patient circulating tumor cells.
    • The ACE Project: A Pilot Study of an Afterschool Program for School-Aged Racial Minority Children Living in an Under-Resourced Community

      Klumpner, Susan T; Rose, Theda; Woolley, Michael E. (2023)
      Of the 91 million children living in the United States, approximately 25 million children are not able to access after school programs (ASPs). ASPs are becoming an increasingly ubiquitous feature in the U.S. public school system; however, demand outweighs the system’s ability to serve all children who want and could benefit from participation. ASPs and the promotion of youth development are considered a promising solution to closing the documented inequities and educational gaps among at-risk children. Guided by a strengths-based, developmental-ecological framework, this mixed methods study examined the influence of one after school program on positive youth development (PYD) outcomes during the coronavirus (herein referred to as COVID) pandemic. This pilot evaluation of The ACE Project, an ASP which was designed and developed by the author of this study, was implemented in Fall 2020 during the height of COVID restrictions. This forced several changes to implementation (e.g., shifting from a school- to a community-based setting, social distancing, mask wearing, increased sanitization) and evaluation (e.g., fewer measures administered, delayed timeline, and smaller sample size). These modifications were substantial and affected the study’s methods, findings, and implications. In the quantitative phase of this study, 8 youth from Chicago completed surveys that assessed individual and youth development characteristics (i.e., Competence, Character, Connection, and Caring). In the qualitative phase, 15 program staff completed semi-structured interviews addressing issues related to implementation and observable behavioral changes among youth. Results from paired samples t-tests suggest that there were no statistically significant changes between pre- and post- test; meaning, there were no PYD changes from the beginning to the end of the program. Interviews with program staff revealed anecdotal evidence of PYD changes within program participants; though, these positive effects were mitigated by aspects of the running a youth program during COVID. Furthermore, more sports-based (i.e., tennis) or physical activity components, formalized human resource policies and procedures, and supplementary staff training to address preparedness and professional development was implicated as necessary improvements to the program. Additional research must be conducted to fully understand the influence of individual-level factors and program context and its impact on PYD outcomes.
    • RTS,S/AS02A/1B induces antibodies to a novel Plasmodium falciparum circumsporozoite protein epitope with sequence similarities to the junctional region

      Friedman-Klabanoff, DeAnna; Berry, Andrea A. (2023)
      Background: Plasmodium falciparum circumsporozoite protein (CSP) is the target of multiple vaccines in development. New promising monoclonal antibodies target the CSP junctional region, which is not contained in the RTS,S vaccine. Methods: We compared CSP antibody responses on a diversity-reflecting peptide array between adults receiving a full-length CSP (rCSP) vaccine and unprotected after controlled human malaria infection (CHMI), adults receiving RTS,S and protected after CHMI, and adults receiving RTS,S and unprotected after CHMI. Results: Overall, the rCSP group had lower anti-CSP antibody responses compared to the RTS,S-protected group. An epitope of interest in the C-terminal region was identified for both RTS,S groups that had sequence similarities to junctional region epitopes, and the RTS,S-protected group responded to more diverse peptides at this epitope than the RTS,S-unprotected group. Conclusions: Sequence similarities between the identified C-terminal epitope and junctional region epitopes warrant further investigation into whether these are cross-reactive antibodies driving protective responses.
    • Clinician Resilience after Traumatic Child Birth Exposure

      Robinson, Keisha; Ogbolu, Yolanda (2023)
      Background: Traumatic Childbirths (TCE) involving actual or threatened serious injury or death to a mother or child are documented sources of occupational stressors. Maternity care is a profession often perceived as filled with joy. However, TCEs may affect both professional practice and personal life and can contribute to burnout. Clinician resilience may play an important role in coping with TCEs. Purpose: The aims of this study were to describe and explore the frequency and severity of TCE experiences in OB clinicians, assess associations between TCEs and levels of resilience, and determine if TCE exposure and resilience are associated with OB clinician burnout. Methods: An anonymous survey was administered via a web link to obstetrical clinicians in five Maryland hospitals. The survey had four sections: demographics, TCE (frequency, severity, and influence on personal and professional practice), resilience (25-item Connor-Davidson Resilience Scale), and burnout (Maslach Burnout–Human Services Survey for Medical Personnel). Multi-level modeling explored factors influencing resilience and burnout nested within hospitals. Results: The 160 usable surveys included registered nurses (N=104), certified nurse-midwives (N=17), attending physicians (N=28), and resident physicians (N=11). Nearly all had experienced at least one TCE during their careers, with shoulder dystocia and stillbirth being the most frequent. The frequency of TCE exposure was associated with influencing the OB clinician’s professional practice (r=.415, p<.001) and personal life (r=.386, p<.001). Perception of severity strongly influenced professional practice (=.52, p<.001) and personal life (=.46, p<.001). Resilience scores were significantly lower in clinicians aged 35-54 years compared to the 55 or older group (B=-7.60, p=.011). TCE exposure was not associated with burnout. However, nearly a third (31%) of the convenience sample reported high emotional exhaustion, and 13% reported high depersonalization. Conclusion: TCE exposure can affect the professional practice and personal life of maternity care clinicians. While TCE did not have a strong relationship with resilience and burnout, a third of the respondents reported high emotional exhaustion, a dimension of burnout. Longitudinal research is needed to understand the short and long-term effects of TCEs and the role of resilience in helping clinicians cope with occupational stress.
    • Analysis of Novel Mass Spectrometry Diagnostics for Clinical Microbiology

      Smith, Richard Daniel; Johnson, J Kristie; Ernst, Robert K. (2023)
      To optimally manage bloodstream infections, quick and appropriate antimicrobial treatment is critical. Rapid diagnostic testing (RDT) can help guide antimicrobial therapy in a timely and reliable fashion. Use of RDT in clinical microbiology is associated with improved patient outcomes including decreased mortality, morbidity, time of hospital stay, and patient costs. The ideal RDT is accurate, rapid, identifies antimicrobial resistance, is easy to use, and low cost. For septic patients, time to appropriate antimicrobial therapy is inversely related to the patient’s survival; therefore, fast, and accurate RDT is especially important. Several different types of RDT assays exist, including polymerase chain reaction, nanoparticle probe technology, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). MALDI-TOF MS is a mainstay diagnostic technology that has revolutionized the world of clinical microbiology. MALDI-TOF MS methods are high-throughput and have extensive pathogen panels. Microorganisms can be identified by MALDI-TOF MS once growth in culture is visible, thereby providing a decrease in both pathogen identification and time to effective antimicrobial therapy. Limitations of current MALDI-TOF MS diagnostics include limited ability in the identification of antimicrobial resistance and time to identification of organism, typically requiring 24-48 hours of additional ex vivo culture after positive blood culture. Recently, novel MALDI-TOF MS based technologies have been developed to identify pathogens direct from positive blood culture bottles, eliminating the need for further culture; however, novel technologies need to be evaluated and compared to current methods to provide valuable insight about the use of these diagnostics in clinical microbiology laboratory settings. This study addresses current limitations of MALDI-TOF MS diagnostics. In Specific Aim 1, a novel lipid-based technique termed Fast Lipid Analysis Technique (FLAT) was evaluated for its clinical utility in identifying colistin resistant Enterobacter species and Klebsiella aerogenes utilizing MALDI-TOF MS. For Specific Aim 2, positive patient blood cultures were prospectively collected from the University of Maryland Medical Center (UMMC) clinical microbiology laboratory to evaluate and compare the FDA-approved Bruker MBT Sepsityper® to other FDA-approved direct-from-blood culture RDTs. Finally, Specific Aim 3 compared the use of FLAT for direct-from-blood culture identification to the other previously compared RDTs using the novel Benefit-risk Evaluation for Diagnostics Framework (BED-FRAME).
    • The Role of Parabrachial in Nociception and Pain in Awake Mice

      Smith, Jesse; Keller, Asaf (2023)
      The parabrachial nuclear complex is a nexus for aversion, and for the sensory and affective components of pain perception. It has been previously shown that, during chronic pain, parabrachial neurons have increased activity and respond to noxious stimuli with prolonged after-discharges – responses that far outlast the stimulus. This phenomenon—like most of what we know about the electrophysiology of pain—has only been observed in anesthetized animals. Anesthesia profoundly alters neuronal responses to nociceptive stimuli and masks their responses to the affective component of pain. I have developed a method to investigate parabrachial neurons in awake, behaving animals by recording single units in vivo from head restrained mice, and applying reproducible noxious stimuli. This offered opportunities to study the time course of changes in parabrachial activity by recording repeatedly from the same animals. It also allows me to correlate parabrachial activity with the animal's behavioral state, by using pupil changes as a proxy for internal states. I report that, in parabrachial neurons from both male and female mice, anesthesia leads to decreased activity, including a decrease in spontaneous activity and reduced magnitude of responses to noxious stimuli. I also demonstrate that, in awake mice, evoked response after chronic pain results in a lasting amplification of parabrachial activity. Finally, I show that changes in parabrachial activity are related to changes in arousal, measured as increases in pupil diameter states.
    • The Impact of Genetic Ancestry on Mutation Frequency and Histopathologic Characteristics in High-Grade Endometrial Cancer

      Bremseth-Vining, Ryan; O'Connor, Timothy D. (2023)
      Endometrial cancer, like numerous other cancer types, exhibits clear racial disparities in the United States for both the incidence and outcomes of the disease. This study seeks to interrogate the role that germline genetic influences, specifically genetic ancestry, may play in contributing to endometrial cancer disparities. This is accomplished by examining the relationship between local ancestry inferences and somatic mutation frequency as well as histologic subtypes. This study highlights three regions along the genome wherein African local ancestry segments were found to significantly correlate with higher tumor mutation burden. A relationship between heterozygous ancestry combinations and increased mutation frequency is also described. Finally, this study identified a single region wherein African local ancestry was found to significantly correlate with a higher incidence of the serous histologic subtype. These findings help to uncover the complex relationships between genetic ancestry and multiple factors underlying the incidence and outcomes of endometrial cancer.
    • The claustrum: A novel cortical network hub

      Qadir, Houman; Mathur, Brian N. (Brian Neil) (2023)
      The human brain is an exceedingly complex biological system with billions of neurons that allows us to process and respond to a constant changing physical environment. Examining the interconnectivity of each of these regions at a circuit level provides insight to brain functions that dictate cognition and action. The work from this dissertation stands to expand our current knowledge of cerebral cortical systems and introduces a heavily understudied cortical-subcortical loop network that bridges cortical network components critical for performing cognitive functions. Using viral tract-tracing and ex vivo electrophysiology methods, I found that a subcortical structure, called the claustrum, connects specific cortical network components. In doing so, I revealed the bulk of the input-to-output circuit map of the murine claustrum. These findings support a model wherein the claustrum supports cortical networks for cognitive control. Understanding the neural circuit mechanisms underlying cortical networks is critical for treating cortical network dysfunction, and resultant cognitive impairment, across a multitude of neuropsychiatric diseases.
    • Perception of lip attractiveness: a survey of orthodontists, general dentists, and laypersons

      McCormack, Katie; Copello, Flavio (2023)
      We aim to investigate the proposed standards of ideal lip proportions and compare those standards to what different people view as most attractive. A 16-question survey was distributed via Qualtrics to orthodontists, general dentists, and laypersons asking demographics as well as opinion-based questions regarding a series of facial photographs. Photographs were digitally altered using Adobe Photoshop to produce different dimensions of the lips from both profile and frontal views. Participants were asked to rate the perceived attractiveness of the lips shown. Regardless of occupation, individuals preferred the appearance of slightly protrusive or thicker lips. Retrusive and thin lip varieties had the lowest median attractiveness scores. Average values for lip projection and thickness were not found to be mutually agreed upon across occupation types (p<0.05) and average lip thickness was not mutually agreed upon between age groups of orthodontists (p=0.004). Based on the results of this study, care should be taken not to produce retrusive or thin lips during orthodontic treatment. Acceptance of a slightly thick or protrusive lip profile may be a more esthetic or well-accepted patient outcome.
    • Three-Dimensional Assessment of Virtual Clear Aligner Attachment Removal: A Prospective Clinical Study

      Dock, Jeremy; Bosio, Jose A. (2023)
      Virtual attachment removal (VAR) is a process used in digital dentistry to prefabricate retainers by removing attachments from a digital scan before the removal of clear aligner attachments. This study aims to evaluate the accuracy of VAR in the maxillary arch. 110 teeth were analyzed from a sample of 54 maxillary scans from 25 subjects. Models with attachments were virtually debonded using Meshmixer® and superimposed over the control group in MeshLab. Vector Analysis Module was used to calculate 3D distances on the buccal surfaces between the superimposed models. The VAR protocol showed no statistical differences in the root mean square between different tooth segments with an overall tendency for inadequate attachment removal. No difference between the groups were found when regarding the number of attachments was used as a main factor. The VAR technique is precise enough for the fabrication of retainers from printed dental models in a clinical setting.
    • Under-ascertainment and underreporting of adverse events in clinical trials

      Hong, Kyungwan; Doshi, Peter (2023)
      Introduction: Clinical trials are widely regarded as the “gold standard” for evaluating different interventions’ adverse events (AEs). However, numerous cases have suggested that AEs are underreported in clinical trials due to inadequate data collection methodology and inconsistent reporting criteria. This study examined 1) the AE ascertainment methodologies used for the marketing approval of new drugs and 2) the diversity and consistency of AE reporting criteria used in trial reports. Methods: We screened drugs approved by the US Food and Drug Administration (FDA) in 2018-2019 and collected publicly available trial documents for all pivotal trials. From these documents, we examined ascertainment methods of adverse events of special interest (AESIs) and newly signaled post-marketing AEs. We also assessed the association between trial characteristics and the AE ascertainment approach using binary logistic regression. Additionally, from the obtained reports, we examined the characteristics of reported AEs and the usage of AE reporting criteria. Then, we assessed the consistency of the number of reported AE types and reporting criteria used across trial publications and other important sources of trial results. Results: 322 AESIs were identified from trial documents for 64 trials reporting 31 drugs approved in 2018-2019. 71% were systematically ascertained, mainly using diagnostic measurement tools and laboratory assessments. 10% were non-systematically ascertained. The ascertainment method of 19% was unclear. The regression analysis did not reveal statistically significant associations between trial characteristics and the use of a systematic ascertainment approach for AESIs. Of the six examined newly signaled post-marketing AEs, one was systematically ascertained. The examined sources utilized various criteria to report both serious and non-serious AEs. Frequency criteria were the most commonly used AE reporting criteria. Furthermore, the examined sources inconsistently reported serious AEs and inconsistently utilized reporting criteria. Conclusions: We were unable to identify the ascertainment methodology for some AEs, even with access to underlying trial documents. Additionally, trial reports applied various criteria that potentially resulted in only a subset of AEs recorded during the trial being reported. The study suggests room for improvement in AE data collection and reporting to aid unbiased harm-benefit assessments of study interventions and informed treatment decisions.