Faculty Bibliography

The pluripotent stem cell (PSC)-derived human primordial germ cell-like cells (PGCLCs) are a cell culture-derived surrogate model of embryonic primordial germ cells. Upon differentiation of PSCs to PGCLCs, multiple loci of HML-2, the hominoid-specific human endogenous retrovirus (HERV), are strongly activated, which is necessary for PSC differentiation to PGCLCs. In PSCs, strongly activated loci of HERV-H family HERVs create chromatin contacts, which are required for the pluripotency. Chromatin contacts in the genome of human PSCs and PGCLCs were determined by Hi-C sequencing, and their locations were compared with those of HML-2 loci strongly activated in PGCLCs but silenced in the precursor naïve iPSCs. In both iPSCs and PGCLCs, the size of chromatin contacts were found to be around one megabase, which corresponds to the Topologically Associated Domains in the human genome but is slightly larger in PGCLCs than iPSCs. The number of small-sized chromatin contacts diminished while numbers of larger-sized contacts increased. The distances between chromatin contacts newly formed in PGCLCs and the degrees of activation of the closest HML-2 loci showed significant inverse correlation. Our study provides evidence that strong activation of HML-2 provirus loci may be associated with newly formed chromatin contacts in their vicinity, potentially contributing to PSC differentiation to the germ cell lineage.

BACKGROUND/UNASSIGNED:While prolonged operative time and increased levels fused have been shown to increase the risk of prolonged intensive care unit (ICU) length-of-stay (LOS), studies are limited in guiding decision-making regarding the need for intensive care postoperatively. This is especially the case among the cohort of adolescent idiopathic scoliosis (AIS) patients undergoing posterior spinal fusion (PSF); associations between comorbidities and ICU LOS are not well-delineated. METHODS/UNASSIGNED:AIS patients who underwent PSF from January 1st, 2016 to December 1st, 2016 at 101 participating centers were identified using the American College of Surgeons (ACS) National Surgical Quality Im-provement Project (NSQIP) Pediatric database. Patients were subsequently grouped by ICU LOS 0-1 day; 2-3 days; and >3 days. Multivariate regression identified predictors of increased ICU LOS. RESULTS/UNASSIGNED:2,346 AIS patients were included. The >3 days and 2-3 days groups had higher asthma rates compared to 0-1 day. The >3 days group had higher rates of structural airway abnormalities and he-matologic disorders. Cognitive impairment rates were highest for >3-day ICU LOS. Hematologic dis-orders, structural airway abnormalities, asthma and cognitive impairment were associated with prolonged ICU LOS. CONCLUSION/UNASSIGNED:.

INTRODUCTION/BACKGROUND:Early lung cancer screening (LCS) through low-dose CT (LDCT) is crucial but underused due to various barriers, including incomplete or inaccurate patient smoking data in the electronic health record and limited time for shared decision-making. The objective of this trial is to investigate a patient-centred intervention, MyLungHealth, delivered through the patient portal. The intervention is designed to improve LCS rates through increased identification of eligible patients and informed decision-making. METHODS AND ANALYSIS/METHODS:MyLungHealth is a multisite pragmatic trial, involving University of Utah Health and New York University Langone Health primary care clinics. The MyLungHealth intervention was developed using a user-centred design process, informed by patient and provider focus groups and interviews. The intervention's effectiveness will be evaluated through a patient-randomised trial, comparing the combined use of MyLungHealth and DecisionPrecision+ (a provider-focused shared decision-making intervention) against DecisionPrecision+ alone. The first study hypothesis is that among patients aged 50-79 with uncertain LCS eligibility (eg, 10-19 pack-years or unknown pack-years or unknown quit date for individuals who used to smoke), MyLungHealth eligibility questionnaires will result in increased identification of LCS-eligible patients (n~26 729 patients). The second study hypothesis is that among patients aged 50-79 with documented LCS eligibility (20+ pack-years, quit within the last 15 years if individuals who used to smoke, and no recent screening or screening discussion), MyLungHealth education will result in increased LDCT ordering (n~4574 patients). Primary outcomes will be identification of LCS-eligible patients among individuals with uncertain LCS eligibility and LDCT ordering rates among individuals with documented LCS eligibility. ETHICS AND DISSEMINATION/BACKGROUND:The protocol was approved by the University of Utah Institutional Review Board (# 00153806). The patient data collected for this study will not be shared publicly due to the sensitive nature of the patient health information and the fact that we will not be obtaining written informed consent to allow public sharing of their data. Results will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER/BACKGROUND:Clinicaltrials.gov, NCT06338592.

The objective of this study is to investigate the potential mutagenic effects of the exposure of mice to aerosols produced from the component liquids of an electronic nicotine delivery system (ENDS). The use of electronic cigarettes (e-cigs) and ENDSs has increased tremendously over the past two decades. From what we know to date, ENDSs contain much lower levels of known carcinogens than tobacco smoke. While conventional tobacco smoke is a well-established mutagen, little is known about the mutagenicity of ENDS aerosols. Here, we report the mutagenic effects of a 3-month whole body exposure of C57 lacI mice (BigBlue^TM) to filtered air (AIR) or ENDS aerosols in several tissues. Aerosols were generated from a 50/50 vegetable glycerin (VG)/propylene glycol (PG) mixture with and without nicotine. The results revealed that in the lung, bladder urothelial tissue, and tongue, mutagenesis was significantly greater in the VG/PG/nicotine group than in the AIR group. In all organs except the bladder, mutagenesis in the VG/PG only group was similar to those exposed to AIR. In the bladder, mutagenesis in the VG/PG group was elevated compared to that in the AIR group. In the liver, mutagenesis was modestly elevated in the VG/PG/nicotine group, but the elevation failed to reach statistical significance. Overall, there were no consistent differences in mutagenesis between the sexes. The results of this study suggest that exposure to e-cig aerosols containing nicotine represents a risk factor for carcinogenesis in several organ systems, and exposure to VG/PG alone may be a risk factor for bladder cancer.

BACKGROUND/UNASSIGNED:Quadriceps weakness following total knee arthroplasty (TKA) delays rehabilitation and increases fall risk. The combined impact of tourniquets and adductor canal blocks (ACBs) on postoperative quadriceps strength has not been defined. This study evaluated the early effects of tourniquet and/or ACB usage on quadriceps strength following TKA. METHODS/UNASSIGNED:Primary, elective TKA patients were assigned to one of four groups based on whether they received an ACB and/or tourniquet. We prospectively measured bilateral, isometric knee extension strength preoperatively and within 36 hours postoperatively. Pre/post-change (Δ) and percent strength change were calculated and standardized to the contralateral leg. Strength, postoperative pain, mobility, knee buckling incidence, and falls were compared across groups. Measurements were collected for 203 patients: 68, 45, 45, and 45 in the tourniquet/ACB, tourniquet/ no ACB, ACB/no tourniquet, and no tourniquet/ no ACB groups, respectively. RESULTS/UNASSIGNED:Tourniquet use was associated with shorter operative time (p=0.004), while ACB use was associated with longer lengths of stay (p=0.005). Average preoperative (p=0.53), postoperative (p=0.12), pre/post-Δ (p=0.60), percent change (p=0.14), and standardized percent change (p=0.85) in strength measures were comparable across groups. Postoperative pain (p=0.67) and knee buckling events (p=0.18) were also comparable across groups. The no tourniquet/no ACB group had decreased postoperative mobility (p=0.004), though it was not clinically significant. No patients sustained inpatient falls. CONCLUSION/UNASSIGNED:.

BACKGROUND:Digital health technologies are increasingly being integrated into mental health care. However, the adoption of these technologies can be influenced by patients' digital literacy and attitudes, which may vary based on sociodemographic factors. This variability necessitates a better understanding of patient digital literacy and attitudes to prevent a digital divide, which can worsen existing health care disparities. OBJECTIVE:This study aimed to assess digital literacy and attitudes toward digital health technologies among a diverse psychiatric outpatient population. In addition, the study sought to identify clusters of patients based on their digital literacy and attitudes, and to compare sociodemographic characteristics among these clusters. METHODS:A survey was distributed to adult psychiatric patients with various diagnoses in an urban outpatient psychiatry program. The survey included a demographic questionnaire, a digital literacy questionnaire, and a digital health attitudes questionnaire. Multiple linear regression analyses were used to identify predictors of digital literacy and attitudes. Cluster analysis was performed to categorize patients based on their responses. Pairwise comparisons and one-way ANOVA were conducted to analyze differences between clusters. RESULTS:A total of 256 patients were included in the analysis. The mean age of participants was 32 (SD 12.6, range 16-70) years. The sample was racially and ethnically diverse: White (100/256, 38.9%), Black (39/256, 15.2%), Latinx (44/256, 17.2%), Asian (59/256, 23%), and other races and ethnicities (15/256, 5.7%). Digital literacy was high for technologies such as smartphones, videoconferencing, and social media (items with >75%, 193/256 of participants reporting at least some use) but lower for health apps, mental health apps, wearables, and virtual reality (items with <42%, 108/256 reporting at least some use). Attitudes toward using technology in clinical care were generally positive (9 out of 10 items received >75% positive score), particularly for communication with providers and health data sharing. Older age (P<.001) and lower educational attainment (P<.001) negatively predicted digital literacy scores, but no demographic variables predicted attitude scores. Cluster analysis identified 3 patient groups. Relative to the other clusters, cluster 1 (n=30) had lower digital literacy and intermediate acceptance of digital technology. Cluster 2 (n=50) had higher literacy and lower acceptance. Cluster 3 (n=176) displayed both higher literacy and acceptance. Significant between-cluster differences were observed in mean age and education level between clusters (P<.001), with cluster 1 participants being older and having lower levels of formal education. CONCLUSIONS:High digital literacy and acceptance of digital technologies were observed among our patients, indicating a generally positive outlook for digital health clinics. Our results also found that patients of older age and lower formal levels of educational attainment had lower digital literacy, highlighting the need for targeted interventions to support those who may struggle with adopting digital health tools.

Negative birth experiences are common. It is yet unclear which women may be most at risk already before pregnancy. Childhood trauma and non-autonoumous/unresolved attachment state of mind may affect how women experience giving birth. This study used longitudinal data to test childhood trauma and attachment state of mind as predictors of birth experience in at-risk sample of primipara women (N = 193). The Adverse Childhood Experiences questionnaire and the Adult Attachment interview were administered during pregnancy, and women reported about their birth experience three months postpartum. Partial Least Square Structural Equation Modelling was applied to answer the research questions. Childhood physical neglect and parental substance abuse were predictive of a more negative birth experience, while attachment state of mind was not associated with how women experienced giving birth. Cross-validation suggests that these findings may be considered externally valid. Further research using validated measures on birth experience are needed.

Increasing healthcare costs, limited healthcare resources, an aging population, and lifestyle-related diseases make wound management a growing clinical, social, and economic burden. This case series investigated the use of a novel, biocompatible, polymer-based transforming powder dressing (TPD) that transforms in situ to a shape-retentive wound matrix upon hydration for treating wounds of various etiologies.In this institutional review board-approved single-center retrospective case series, the researchers evaluated various acute and chronic wounds treated with TPD over a period of 2 years. Wounds were followed from the first TPD application up to 1 month after the last TPD application or until the wound healed or the patient was lost to follow-up, whichever came first. The researchers evaluated wound etiology, location, number of applications, change in wound surface area, and comorbidities.The researchers identified 50 patients who were treated with TPD and had at least one follow-up visit during the retrospective study period. The majority of wounds treated with TPD were venous leg ulcers (n = 27) followed by traumatic wounds (n = 11) and skin tears (n = 7). Normal rates of wound healing (>10% per week) were observed in the majority of patients (36/50, 72%) over their duration of treatment. Complete healing during the study period was observed in 43% of venous leg ulcers, 55% of traumatic wounds, 71% of skin tears, and 80% of other wound types. No adverse effects of TPD administration were observed. Treatment with TPD resulted in significant reductions in wound area of nearly all wounds, regardless of etiology.

BACKGROUND/UNASSIGNED:Optimal management of post-operative pain is a critical component of orthopedic surgical care. There is a heightened awareness of narcotic prescribing habits given the current "opioid epidemic." The lack of standardized protocols has led to increased errors, delayed access to prescribed medications, and excessive narcotic prescribing.The purpose of this study is to assess the current trends in opioid use and document the prescribing patterns in the pediatric population before and after the implementation of a standardized protocol at our Institution. METHODS/UNASSIGNED:A multimodal postoperative pain pathway was developed and implemented throughout a large, academic, pediatric orthopedic division. The pathway utilized opioid and non-opioid pain medications and educational handouts with descriptions of the different classes of pain medication and specific dosing regimens.A query of electronic medical records was completed to identify all patients under the age of 18 that underwent inpatient orthopedic surgery from January 2016 to June 2018. Based on surgical dissection and anticipated postoperative pain, procedures were grouped into low complexity and high complexity. The average amount of opioids administered to the patients during their stay in the hospital was converted to morphine milligram equivalents (MME). The average MME was plotted, and the trends were analyzed. RESULTS/UNASSIGNED:455 inpatients met the inclusion criteria. Opioid pain medication administration was significantly higher in the high-complexity group compared to the low-complexity group. Implementing the multimodal pain pathway significantly reduces opioid administration in both groups without an increase in length of stay. CONCLUSION/UNASSIGNED:.