Enhancer switching in cell lineage priming is linked to eRNA, Brg1's AT-hook, and SWI/SNF recruitment.

RNA transcribed from enhancers, i.e., eRNA, has been suggested to directly activate transcription by recruiting transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find that the AT-hook of SWI/SNF preferentially binds RNA and, as part of the esBAF complex, associates with eRNA transcribed from intronic and intergenic regions. Our data suggest that SWI/SNF is globally recruited in cis by eRNA to cell-type-specific enhancers, representative of two distinct stages that mimic early mammalian development, and not at enhancers that are shared between the two stages. In this manner, SWI/SNF facilitates recruitment and/or activation of MLL3/4, p300/CBP, and Mediator to stage-specific enhancers and super-enhancers that regulate the transcription of metabolic and cell lineage priming-related genes. These findings highlight a connection between ATP-dependent chromatin remodeling and eRNA in cell identity and typical- and super-enhancer activation.

Association between synovial tissue damage and pain in late-stage knee osteoarthritis: A cross-sectional study.

OBJECTIVE: To identify the presence and distribution of histopathological features of synovial inflammation and tissue damage, and to test their associations with ultrasound (US) imaging measures of synovitis and patient-reported measures of pain in knee osteoarthritis (OA). DESIGN: In the cross-sectional study of 122 patients undergoing surgery for painful late-stage (Kellgren-Lawrence Grade 3 or 4) knee OA, we compared US measures of synovitis (n = 118) and pain (Knee Injury and Osteoarthritis Outcome Score) to histopathological measures of inflammation vs. synovial tissue damage in synovial tissue biopsies. Associations of histopathological features with US measures of inflammation or pain were assessed using linear or logistic regression while controlling for covariates. RESULTS: Histopathological features of inflammation were associated with higher odds of moderate/severe US synovitis (odds ratio [OR] = 1.34 [95%CI 1.04, 1.74), whereas features of synovial tissue damage were associated with lower odds of moderate/severe US synovitis (OR = 0.77 [95%CI 0.57, 1.03]). Worse histopathological scores for synovial tissue damage were associated with more pain (-1.47 [95%CI -2.88, -0.05]), even while adjusting for synovial inflammation (-1.61 [95%CI -3.12, -0.10]). CONCLUSIONS: Synovial tissue damage is associated with pain in late-stage knee OA, independent from inflammation and radiographic damage. These novel findings suggest that preventing synovial tissue damage may be an important goal of disease-modifying OA therapy.

Outcomes of Impella 5.0 and 5.5 for cardiogenic shock: A single-center 137 patient experience.

BACKGROUND: This study evaluated the outcomes of patients with cardiogenic shock (CS) supported with Impella 5.0 or 5.5 and identified risk factors for in-hospital mortality. METHODS: Adults with CS who were supported with Impella 5.0 or 5.5 at a single institution were included. Patients were stratified into three groups according to their CS etiology: (1) acute myocardial infarction (AMI), (2) acute decompensated heart failure (ADHF), and (3) postcardiotomy (PC). The primary outcome was survival, and secondary outcomes included adverse events during Impella support and length of stay. Multivariable logistic regression was performed to identify risk factors for in-hospital mortality. RESULTS: One hundred and thirty-seven patients with CS secondary to AMI (n = 47), ADHF (n = 86), and PC (n = 4) were included. The ADHF group had the highest survival rates at all time points. Acute kidney injury (AKI) was the most common complication during Impella support in all 3 groups. Increased rates of AKI and de novo renal replacement therapy were observed in the PC group, and the AMI group experienced a higher incidence of bleeding requiring transfusion. Multivariable analysis demonstrated diabetes mellitus, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine were independent predictors of in-hospital mortality, but the etiology of CS did not impact mortality. CONCLUSIONS: This study demonstrates that Impella 5.0 and 5.5 provide effective mechanical support for patients with CS with favorable outcomes, with nearly two-thirds of patients alive at 180 days. Diabetes, elevated pre-insertion serum lactate, and elevated pre-insertion serum creatinine are strong risk factors for in-hospital mortality.

Patient engagement study to identify and improve surgical experience.

BACKGROUND: Patient engagement is the establishment of active partnerships between patients, families, and health professionals to improve healthcare delivery. The objective of this project was to conduct a series of patient engagement workshops to identify areas to improve the surgical experience and develop strategies to address areas identified as high priority. METHODS: Faculty surgeons and patients were invited to participate in three in-person meetings. Evaluation included identifying and developing strategies for three priority areas to improve the surgical experience and level of engagement achieved at each meeting. RESULTS: Sixteen faculty surgeons and 32 patients participated. Some 63 themes to improve the surgical experience were identified; the three highest-priority themes were physician communication, discharge process, and expectations at home after discharge. Individual improvement strategies for these three prioritized themes (12, 36 and 6 respectively) were used to develop a formal strategic plan, and included a physician communication survey, discharge process worksheet and video, and guideline regarding what to expect at home after discharge. Overall, the level of engagement achieved was considered high by over 85 per cent of the participants. CONCLUSION: A high level of patient engagement was achieved. Priorities were identified with patients and surgeons to improve surgical experience, and strategies were developed to address these areas.

Who Is to Blame? Framing HPV to Influence Vaccination Intentions among College Students.

Human papillomavirus (HPV) is a prevalent sexually transmitted infection (STI) among college students. Although previous research has studied HPV-related health communication strategies using various framing techniques, the goal of this study is to test how two unique message frames-whether mentioning HPV as an STI and whether to attribute the cause of infection as external or internal-would influence young adults' intentions to receive the recommended HPV vaccine. Results indicate that gender and causal attribution framing influenced participants' intentions to receive the HPV vaccine.

The Silver Lining of Shame: Framing HPV to Influence Vaccination Intentions.

College students suffer disproportionately from human papillomavirus (HPV), a sexually transmitted infection (STI) that could result in genital warts or cancers in both males and females. Research contends that stigma and shame may serve as barriers to disclosure intentions, as well as vaccination intentions. The goal of this study was to examine whether two framing strategies-whether to mention that HPV is sexually transmitted and whether to highlight the cause of infection as internal or external-would influence young adults' intentions to disclose a potential diagnosis and their intentions to get the recommended HPV vaccine. Results indicate that STI framing and gender had consistent impacts on disclosure and vaccination intentions. Further, causal attribution framing also influenced participants' intention to get the vaccine at no cost immediately and their intention to get the vaccine at the retail price of $375 in the future. Theoretical and practical implications of these results are discussed.

Two-Mechanism Model for the Interaction of Etoposide Quinone with Topoisomerase IIα.

Topoisomerase II is an essential nuclear enzyme involved in regulating DNA topology to facilitate replication and cell division. Disruption of topoisomerase II function by chemotherapeutic agents is in use as an effective strategy to fight cancer. Etoposide is an anticancer therapeutic that disrupts the catalytic cycle of topoisomerase II and stabilizes enzyme-bound DNA strand breaks. Etoposide is metabolized into several species including active quinone and catechol metabolites. Our previous studies have explored some of the details of how these compounds act against topoisomerase II. In our present study, we extend those analyses by examining several effects of etoposide quinone on topoisomerase IIα including whether the quinone impacts ATP hydrolysis, DNA ligation, cleavage complex persistence, and enzyme/DNA binding. Our results demonstrate that the quinone inhibits relaxation at 100-fold lower levels of drug when compared to that of etoposide. Further, the quinone inhibits ATP hydrolysis by topoisomerase IIα. The quinone does appear to stabilize single-strand breaks similar to etoposide suggesting a traditional poisoning mechanism. However, there is minimal difference in cleavage complex persistence in the presence of etoposide or etoposide quinone. In contrast to etoposide, we find that etoposide quinone blocks enzyme/DNA binding, which provides an explanation for previous data showing the ability of the quinone to inactivate the enzyme over time. Finally, etoposide quinone is able to stabilize the N-terminal protein clamp implying an interaction between the compound and this portion of the enzyme. Taken together, the evidence supports a two-mechanism model for the effect of the quinone on topoisomerase II: (1) interfacial poison and (2) covalent poison that interacts with the N-terminal clamp and impacts the binding of DNA.

The discoloration of the Taj Mahal due to particulate carbon and dust deposition.

The white marble domes of the Taj Mahal are iconic images of India that attract millions of visitors every year. Over the past several decades the outer marble surfaces of the Taj Mahal have begun to discolor with time and must be painstakingly cleaned every several years. Although it has been generally believed that the discoloration is in some way linked with poor air quality in the Agra region, the specific components of air pollution responsible have yet to be identified. With this in mind, ambient particulate matter (PM) samples were collected over a one-year period and found to contain relatively high concentrations of light absorbing particles that could potentially discolor the Taj Mahal marble surfaces, that include black carbon (BC), light absorbing organic carbon (brown carbon, BrC), and dust. Analyses of particles deposited to marble surrogate surfaces at the Taj Mahal indicate that a large fraction of the outer Taj Mahal surfaces are covered with particles that contain both carbonaceous components and dust. We have developed a novel approach that estimates the impact of these deposited particles on the visible light surface reflectance, which is in turn used to estimate the perceived color by the human eye. Results indicate that deposited light absorbing dust and carbonaceous particles (both BC and BrC from the combustion of fossil fuels and biomass) are responsible for the surface discoloration of the Taj Mahal. Overall, the results suggest that the deposition of light absorbing particulate matter in regions of high aerosol loading are not only influencing cultural heritage but also the aesthetics of both natural and urban surfaces.

Oxidative stress and inflammation response following aerobic exercise: role of ethnicity.

African-Americans are at a significantly greater risk for developing several diseases and conditions. These conditions often have underlying oxidative stress mechanisms. Therefore the purpose of this investigation was to ascertain the post-exercise oxidative response to a single bout of aerobic exercise in African-American and Caucasian college-age females. A total of 10 African-American and 10 Caucasian females completed the study. Each subject had her VO2 max measured while exercising on a treadmill. A week later, each subject returned to the laboratory and performed a 30-min run at 70% of her VO2max. Blood samples were taken immediately prior to and following exercise for analysis. Lipid hydroperoxides, protein carbonyls, malondialdehyde, xanthine oxidase, glutathione in the reduced (GSH) and oxidized (GSSG) forms, TNFα and interleukin 6 were measured from blood taken before and after exercise. Significance was set at p≤0.05 a priori. Xanthine oxidase was the only measure that did not significantly increase following exercise. All other markers showed a significant elevation in response to the exercise bout with no difference between groups except that the Caucasian group had significantly higher malondialdehyde post-exercise compared to the African-American group. This cohort of college-age African-American and Caucasian females showed little difference in their response to a single 30-min run at 70% of their max in the markers of oxidative stress within the blood.

The recovery of semen from bathwater using the Evidence Recovery System (ERS).

Sexual offences are under-reported and ascertaining accurate offence numbers is difficult. Any methods which could increase the ability to obtain biological evidence or reduce the additional distress associated with reporting a sexual offence may result in an increase in reporting this crime type. The Evidence Recovery System (ERS) is designed to collect trace evidence, including hairs, fibres and biological evidence, from bath or shower water in a non-invasive manner. Initially, samples of semen were placed in baths filled with water, and washing was simulated using a range of body wash products. The water was then drained through the ERS before its filters were subjected to acid phosphatase testing and haematoxylin and eosin staining of spermatozoa. Recovered spermatozoa were then graded accordingly. Following this, the experiment was repeated with the addition of dirt/dust particulates during the washing stage, to simulate recovery of biological evidence in a more realistic environment. The results showed that spermatozoa considered 'easy to find' could regularly be obtained from bathwater using the ERS. It appeared that this recovery was not affected by the presence of different body wash products. When dust/dirt particles were added, the number of spermatozoa recovered increased at two of the evidence collection stages. The difference in recovery was considered to be statistically significant. This study provides evidence to suggest the feasibility of use of the ERS as a method to collect semen evidence from individuals subjected to sexual offences. The recovery of spermatozoa does not appear to be affected by the presence of a body wash, but does appear to be improved when skin cells, hair and other debris are transferred into the water, as would be likely during a bath/shower. Further to this, the possibility of obtaining spermatozoa from the home bath or shower of a victim following a post-offence bathing experience is implied.

Cerumen impaction: Prevalence and associated factors in the United States population.

Objective: To examine the prevalence of cerumen impaction in a nationally representative sample of the US population and the association of cerumen impaction with sociodemographic factors, hearing loss, and tinnitus. Methods: The cohort included 14,230 individuals aged ≥12 years who completed otoscopy and audiometry in NHANES (2005-2016). Cerumen impaction (partial/complete) was determined by otoscopy. Hearing level was defined by speech-frequency pure-tone average (PTA). Multivariable regression analysis was performed to identify factors associated with cerumen impaction. Results: The prevalence of any cerumen impaction was 18.6% [95% CI: 17.3%-19.9%] among individuals ≥12 years and 32.4% [29.9%-35.1%] among those ≥70 years. The prevalence of bilateral partial and complete cerumen impaction was 6.3% [5.6%-7.1%] and 1.2% [1.0%-1.9%], respectively. Any cerumen impaction was associated with male sex (OR 1.77 [1.5-2.1]), identifying as Black race (vs. Caucasian, OR: 1.78 [1.5-2.9]), lower level of education (OR: 0.84 [0.71-0.98]), and older age (OR: 1.02 [1.01-1.03]). After adjusting for sociodemographic and clinical factors, complete impaction was associated with increased PTA (right ear: ß = 4.1 dB [2.4-5.8 dB], left ear: ß = 1.9 dB [0.46-3.4 dB]), but not with tinnitus. Conclusions: Cerumen impaction is highly prevalent in the US population, especially among older adults, and has disproportionate sociodemographic impacts. Complete impaction is associated with a small, statistically significant elevation in PTA, but there is no association with tinnitus. These findings emphasize the need to implement and disseminate best practices for ear hygiene and cerumen management broadly and equitably. Level of Evidence: 2B.

Reliability and Validity of Muscle Size and Quality Analysis Techniques.

OBJECTIVE: This study investigated reliability and validity of muscle cross-sectional area and echo intensity using an automatic image analysis program. METHODS: Twenty-two participants completed two data collection trials consisting of ultrasound imaging of the vastus lateralis (VL) at 10 and 12 MHz. Images were analyzed manually and with Deep Anatomical Cross-Sectional Area (DeepACSA). Reliability statistics (i.e., intraclass correlation coefficient [ICC] model 2,1, standard error of measure expressed as a percentage of the mean [SEM%], minimal differences [MD] values needed to be considered real) and validity statistics (i.e., constant error [CE], total error [TE], standard error of the estimate [SEE]) were calculated. RESULTS: Automatic analyses of ACSA and EI demonstrated good reliability (10 MHz: ICC2,1 = 0.83 - 0.90; 12 MHz: ICC2,1 = 0.87-0.88), while manual analyses demonstrated moderate to excellent reliability (10 MHz: ICC2,1 = 0.82-0.99; 12 MHz: ICC2,1 = 0.73-0.99). Automatic analyses of ACSA presented greater error at 10 (CE = -0.76 cm2, TE = 4.94 cm2, SEE = 3.65 cm2) than 12 MHz (CE = 0.17 cm2, TE = 3.44 cm2, SEE = 3.11 cm2). Analyses of EI presented greater error at 10 (CE = 3.35 a.u., TE = 2.70 a.u., SEE = 2.58 a.u.) than at 12 MHz (CE = 3.21 a.u., TE = 2.61 a.u., SEE = 2.34 a.u.). CONCLUSION: The results suggest the DeepACSA program may be less reliable compared to manual analysis for VL ACSA but displayed similar reliability for EI. In addition, the results demonstrated the automatic program had low error for 10 and 12 MHz.

Navigating the Landscape of Precision Education: Insights From On-the-Ground Initiatives.

ABSTRACT: A central goal of precision education (PE) is efficiently delivering the right educational intervention to the right learner at the right time. This can be achieved through a PE cycle that involves gathering inputs, using analytics to generate insights, planning and implementing interventions, learning and assessing outcomes, and then using lessons learned to inform modifications to the cycle. In this paper, the authors describe 3 PE initiatives utilizing this cycle. The Graduate Medical Education Laboratory (GEL) uses longitudinal data on graduate trainee behavior, clinical skills, and wellness to improve clinical performance and professional fulfillment. The Transition to Residency Advantage (TRA) program uses learner data from medical school coupled with individualized coaching to improve the transition to residency. The Anesthesia Research Group for Educational Technology (TARGET) is developing an automated tool to deliver individualized education to anesthesia residents based on a longitudinal digital representation of the learner. The authors discuss strengths of the PE cycle and transferrable learnings for future PE innovations. Common challenges are identified, including related to data (e.g., volume, variety, sharing across institutions, using the electronic health record), analytics (e.g., validating augmented intelligence models), and interventions (e.g., scaling up learner assessments with limited resources). PE developers need to share their experiences in order to overcome these challenges, develop best practices, and ensure ethical development of future systems. Adapting a common framework to develop and assess PE initiatives will lead to a clearer understanding of their impact, help to mitigate potential risks, and allow deployment of successful practices on a larger scale.

Can segmental bioelectrical impedance be used as a measure of muscle quality?

Recent works have shown bioelectrical impedance spectroscopy (BIS) may assess tissue quality. The purpose of this project was to examine associations between ultrasound echo intensity (EI) of quadriceps muscles (vastus lateralis [VL], vastus medialis [VM], vastus intermedius [VI], rectus femoris [RF]) and BIS parameters (R0, R1, C, α, fp), and if the associations are specific to individual muscles or associated with a representation of the entire quadriceps. Twenty-two participants (age: 22 ± 4 years; BMI: 25.47 ± 3.26 kg/m2) participated in all study activities. Participants had transverse ultrasound scans of each individual quadriceps muscle taken at 25, 50, and 75 % of the muscle length to generate an average EI for the VL, VM, VI, and RF, which were further averaged to generate an EI for the entire quadriceps. For BIS, participants were seated with electrodes placed on the thigh to measure the segmental quadriceps. The Cole-impedance model parameters that best fit the BIS data for each participant was used for all analyses. Pearson's correlation coefficient (r) were calculated to determine associations between muscles' EI and BIS parameters. The results suggest averaged EI of individual VL, VM, VI, RF muscles and the average EI of the segmental quadriceps were significantly related to the R0, C, α metrics of the Cole-impedance model representing quadriceps segmental tissues. This supports that segmental BIS may be an appropriate technique for rapid evaluation of segmental muscle quality.

Climbing the Ranks: A Study of Firefighter Health Disparities.

The fire service command structure encompasses recruit, incumbent firefighter, and officer positions. The purpose of this study was to quantify the effect of rank (recruits, incumbent firefighters, and officers) on health and physical ability characteristics within the fire service. Retrospective data from thirty-seven recruits (age = 29 ± 5 yrs, BMI = 26.5 ± 2.3 kg/m2); eighty-two incumbent firefighters (age = 30 ± 7 yrs, BMI = 28.8 ± 4.3 kg/m2); and forty-one officers (age = 41 ± 6 yrs, BMI = 28.6 ± 4.3 kg/m2) from a single department were used. Participants completed body composition tests (i.e., body fat percentage [%BF] and body mass index [BMI]), an air consumption test (ACT), and cardiopulmonary exercise testing. The ACT consisted of 10 standardized tasks. Five separate one-way analyses of co-variance (ANCOVA) were calculated, accounting for age. Partial eta squared statistics were calculated and Bonferroni-corrected post-hoc analyses were employed. The results demonstrated a significant effect of rank on %BF (F = 9.61, p < 0.001, η2 = 0.10); BMI (F = 3.45, p = 0.02, η2 = 0.05); relative VO2MAX (F = 12.52, p < 0.001; η2 = 0.11); and HRMAX (F = 18.89, p < 0.001, η2 = 0.03), but not on ACT time (F = 0.71, p = 0.55, η2 = 0.01). These outcomes suggest there are variations in anthropometric and physiological metrics of health across firefighter ranks. Administrators should be aware how these markers of health may vary across firefighter ranks.

Concomitant use of extracorporeal membrane oxygenation and percutaneous microaxial assist device support for cardiogenic shock.

Objectives: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) with concomitant percutaneous microaxial left ventricular assist device support is an emerging treatment modality for cardiogenic shock (CS). Survival outcomes by CS etiology with this support strategy have not been well described. Methods: This study was a retrospective, single-center analysis of patients with CS due to acute myocardial infarction (AMI-CS) or decompensated heart failure (ADHF-CS) supported with VA-ECMO with concomitant percutaneous microaxial left ventricular assist device support from December 2020 to January 2023. Results: A total of 44 patients were included (AMI-CS, n = 20, and ADHF-CS, n = 24). Patients with AMI-CS and ADHF-CS had similar survival at 90 days postdischarge (P = .267) with similar destinations after support (P = .220). Patients with AMI-CS initially supported with VA-ECMO were less likely to survive 90 days postdischarge (P = .038) when compared with other cohorts. Limb ischemia and acute kidney injury occurred more frequently in patients presenting with AMI-CS (P =.013; P = .030). Subanalysis of ADHF-CS patients into acute-on-chronic decompensated HF and de novo HF demonstrated no difference in survival or destination. Conclusions: VA-ECMO with concomitant percutaneous microaxial left ventricular assist device support can be used to successfully manage patients with CS. There is no difference in survival or destination for AMI-CS and ADHF-CS with this support strategy. AMI-CS patients with initial VA-ECMO support have increased mortality in comparison to other cohorts. Future multicenter studies are required to fully analyze the differences between AMI-CS and ADHF-CS with this support strategy.