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This research study investigates the effects of library instruction tutorial format (written versus video) on student preference and performance in chemistry education. The authors assessed the format of tutorials used to provide library instruction in an introductory chemistry course by observing 27 student participants as they took in instructions in either a video or a written format and then completed two chemistry information tasks. While participants expressed strong preferences for particular formats, neither the video tutorials nor the written instructions significantly improved task completion speed or performance. Rather, the authors determined that student preference alone is enough to justify the continued production of multiple versions of instructions for the same assignment.

Lung transplantation is the only definitive therapy for end-stage pulmonary disease. Less than 20 % of offered lungs are successfully transplanted due to a limited ischemic time window and poor donor lung quality manifested by pulmonary edema, hypoxia, or trauma. Therefore, poor donor organ recovery and utilization are significant barriers to wider implementation of the life-saving therapy of transplantation. While ischemia reperfusion injury (IRI) is often identified as the underlying molecular insult leading to immediate poor lung function in the post-operative period, this injury encompasses several pathways of cellular injury in addition to the recruitment of the innate immune system to the site of injury to propagate this inflammatory cascade. Pyroptosis is a central molecular inflammatory pathway that is the most significant contributor to injury in this early post-operative phase. Pyroptosis is another form of programmed cell death and is often associated with IRI. The mitigation of pyroptosis in the early post-operative period following lung transplantation is a potential novel way to prevent poor allograft function and improve outcomes for all recipients. Here we detail the pyroptotic pathway, its importance in lung transplantation, and several therapeutic modalities that can mitigate this harmful inflammatory pathway.

Abstract Low Earth Orbit (LEO) has emerged as a unique environment for evaluating altered stem cell properties in microgravity. LEO has become increasingly accessible for research and development due to progress in private spaceflight. Axiom Mission 2 (Ax-2) was launched as the second all-private astronaut mission to the International Space Station (ISS). Frozen human induced pluripotent stem cells (hiPSCs) expressing green fluorescent protein (GFP) under the SOX2 promoter, as well as fibroblasts differentiated from SOX2-GFP hiPSCs, were sent to the ISS. Astronauts then thawed and seeded both cell types into commercially available 96-well plates, which provided surface tension that reduced fluid movement out of individual wells and showed that hiPSCs or hiPSC-derived fibroblasts could survive either in suspension or attached to a Matrigel substrate. Furthermore, both cell types could be transfected with red fluorescent protein (RFP)-expressing plasmid. We demonstrate that hiPSCs and hiPSC-fibroblasts can be thawed in microgravity in off-the-shelf, commercially-available cell culture hardware, can associate into 3D spheroids or grow adherently in Matrigel, and can be transfected with DNA. This lays the groundwork for future biomanufacturing experiments in space.

Background: Patients with pulmonary arterial hypertension (PAH) and additional cardiac or pulmonary comorbidities have a poor prognosis and are frequently excluded from clinical trials. The purpose of this study was to evaluate outcomes of patients with pulmonary hypertension (PH) secondary to a range of World Symposium on PH (WSPH) groups treated with inhaled treprostinil (iTRE) in a real-world setting. Methods: Patients with PH who were started on treatment with iTRE at Duke University were classified by WSPH Group and included patients with Groups 1, 2, 3, combined Groups 2 and 3 (PH in the setting of left heart failure and chronic lung disease), Group 4, and Group 5 PH. Time to disease worsening, a composite of death, lung transplantation, or transition to intravenous prostacyclin was compared by WSPH Group, and iTRE treatment status using a multivariable Cox proportional hazards model adjusted for age, sex, and Registry to Evaluate Early and Long-Term PAH Disease Management Lite 2 risk score. Treatment with iTRE was defined as a time-varying covariate. Results: The cohort included 270 patients with PH: 30.6% Group 1; 10% Group 2; 32.2% Group 3; 11.1% combined Groups 2 and 3; and 15.9% with either Group 4 or 5 PH. At 3 and 6 months of follow-up, 24.8% and 38.9% of patients, respectively, were no longer treated with iTRE. Patients who discontinued treatment with iTRE had a significantly higher risk of disease worsening (adjusted hazard ratio: 5.02, 95% confidence interval: 3.44-7.31). There was no significant difference in disease worsening among WSPH Groups. Conclusions: In a real-world setting, many patients with PH secondary to a range of WSPH Groups tolerated treatment with iTRE. Future studies should phenotype patients with PH based on both comorbidities and therapeutic responsiveness.

Abstract Alzheimer’s disease (AD) prevalence is twice as high in non-Hispanic Blacks (NHBs) as in non-Hispanic Whites (NHWs). The objective of this study was to determine whether aberrant methylation at imprint control regions (ICRs) is associated with AD. Differentially methylated regions (DMRs) were bioinformatically identified from whole-genome bisulfite sequenced DNA derived from brain tissue of 9 AD (5 NHBs and 4 NHWs) and 8 controls (4 NHBs and 4 NHWs). We identified DMRs located within 120 regions defined as candidate ICRs in the human imprintome ( https://genome.ucsc.edu/s/imprintome/hg38.AD.Brain_track ). Eighty-one ICRs were differentially methylated in NHB-AD, and 27 ICRs were differentially methylated in NHW-AD, with two regions common to both populations that are proximal to the inflammasome gene, NLRP1, and a known imprinted gene, MEST/MESTIT1. These findings indicate that early developmental alterations in DNA methylation of regions regulating genomic imprinting may contribute to AD risk and that this epigenetic risk differs between NHBs and NHWs.

Background: As lung transplant candidates are older with increased comorbidities, we sought to examine the prevalence and outcomes of lung transplant recipients after prior cardiac surgery. Methods: Lung transplants were identified from the United Network for Organ Sharing/Organ Procurement and Transplantation Network Database. Patients were stratified based on prior cardiac surgery (no surgery [NS], prior coronary artery bypass grafting [CABG], prior valve [Valve]). Unadjusted comparisons were performed among all groups, and propensity matching was utilized for adjusted comparisons. Survival was examined with Kaplan-Meier methods. Results: A total of 28,710 patients were identified, 467 (1.6%) had prior CABG and 84 (0.3%) had prior valvular surgery. Before matching, the NS group was significantly younger, less commonly male, and had lower lung allocation scores. There were significantly fewer bilateral lung transplants in the CABG and Valve groups. Length of stay was shortest in the CABG group, but there were no significant differences in postoperative stroke, dialysis, or in-hospital mortality. There was an increased incidence of cardiac/cerebrovascular cause of death in CABG recipients (18.3%) and malignancy death in Valve recipients (23.3%). Following matching, CABG 5-year survival was lower than NS (p

Patients with severe pulmonary arterial hypertension undergoing lung transplant are at risk of developing left ventricular dysfunction (LVD). We present a case of severe LVD following transplant to highlight the challenges in diagnosis and suggest measures to reduce the risk of cardiogenic shock and end-organ injury.

BackgroundTreatment and prophylaxis options for neonatal HIV are limited. This study aimed to develop a population pharmacokinetic model to characterize the disposition of maraviroc in neonates to inform dosing regimens and expand available options.MethodsUsing maraviroc concentrations from neonates who received either a single dose or multiple doses of 8 mg/kg of maraviroc in the first 6 weeks of life, a population pharmacokinetic model was developed to determine the effects of age, sex, maternal efavirenz exposure and concomitant ARV therapy on maraviroc disposition. The final model was used in Monte Carlo simulations to generate expected exposures with recommended dosing regimens.ResultsA total of 396 maraviroc concentrations, collected in the first 4 days of life, at 1 week, at 4 weeks and at 6 weeks, from 44 neonates were included in the analysis. After allometrically scaling for weight, age less than 4 days was associated with a 44% decreased apparent clearance compared with participants 7 days to 6 weeks of life. There were no differences identified in apparent clearance or volume of distribution from ages 7 days to 6 weeks, sex, maternal efavirenz exposure or concomitant nevirapine therapy. Monte Carlo simulations with FDA-approved weight band dosing resulted in the majority of simulated patients (84.3%) achieving an average concentration of ≥75 ng/mL.ConclusionsWhile maraviroc apparent clearance is decreased in the first few days of life, the current FDA-approved maraviroc weight band dosing provides maraviroc exposures for neonates in the first 6 weeks of life, which were consistent with adult maraviroc exposure range. Maraviroc provides another antiretroviral treatment option for very young infants.

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, Cancer and Cardiovascular Disease, on October 18-19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age-related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer-related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer death, and people who have both cancer and CVD do more poorly than those who have only cancer or only CVD. Issues addressed in this bench-to-bedside conference include mechanisms of cancer and CVD co-development in older adults, cardiotoxic effects of cancer therapy, and management of comorbid cancer and CVD. Presenters discussed approaches to ensure equitable access to clinical trials and health care for diverse populations of adults with CVD and cancer, mechanisms of cancer therapy cardiotoxicity, and management of comorbid CVD and cancer, including the role of patient values and preferences in treatment decisions. Workshop participants identified many research gaps and questions that could lead to an enhanced understanding of comorbid CVD and cancer and to better and more equitable management strategies.

Background: Several studies have tried to find a link between timing of lung transplant surgery and patient outcomes. However, there has been conflicting results. This study sought to evaluate the association of operative times and recipient outcomes. Methods: Primary adults lung transplants were identified from the United Network for Organ Sharing Database. Patients were stratified based on time of lung transplant: T1 (12 AM-6 AM); T2 (6 AM-12 PM); T3 (12 PM-6 PM); T4 (6 PM-12 AM). Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results: Within the T4 group, there was a significant increase in length of stay and incidence of primary graft dysfunction, though minor. Unadjusted survival analysis with Kaplan-Meier methods demonstrated that there was no significant difference in long-term survival among the 4 groups (p = 0.55). Following adjustment, no operative time was independently associated with decreased long-term mortality. Variables that were significantly associated with increased long-term mortality included recipient diabetes, creatinine, hospitalization status, intensive care unit status, cigarette use, and donation after circulatory death donor status. Conclusions: Though operative times during the T4 period were associated with increased peri-operative complications, this had no effect on long-term survival. While thoracic transplantation can safely occur no matter what time of day, transplantation should preferentially be performed during normal surgical work hours for the longevity and work life balance of transplant providers and surgeons.

Background: The association of social vulnerability (SV) and cardiac transplant survival remains poorly defined, particularly related to long-term outcomes. The purpose of this study was to define the impact of SV on survival among heart transplant recipients with at least 1 year of survival post-transplant. Methods: Heart transplant recipients were identified using the United Network for Organ Sharing database between June 1, 2006, and December 31, 2020. The Center for Disease Control’s Social Vulnerability Index (SVI) database was used to stratify patients based on SVI into 3 groups: low:

Background. Outcomes in heart transplantation are affected by a variety of variables and patient factors. However, the impact of circadian rhythms, gene expression, and transcription remain underexplored. We thus evaluated the potential role of donor heart cross-clamp times on short-term and long-term outcomes after heart transplantation. Methods. A total of 31 713 heart transplants were identified from the United Network for Organ Sharing Database. Patients were first stratified on the basis of time of donor procurement: 12 am to 12 pm or 12 pm to 12 am. To evaluate a possible effect of circadian rhythms, donor time was further divided into 5 groups based on preclinical data: 4 am to 8 am; 8 am to 11 am; 11 am to 5 pm; 5 pm to 10 pm; 10 pm to 4 am. Groups were assessed with comparative statistics. Long-term survival was evaluated using Kaplan-Meier methods and a multivariate Cox proportional hazard model. Results. Patients who received hearts recovered between 12 am and 12 pm had significantly higher survival than those who received hearts recovered between 12 pm and 12 am. This survival difference was observed in both unadjusted (P = 0.002) and adjusted analyses (hazard ratio [HR]: 0.93; 95% confidence interval [CI], 0.89-0.97; P

Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the “germ hypothesis” of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: “New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease.” Discussion centered around the antimicrobial protection hypothesis of amyloid accumulation, and other mechanisms by which microbes could influence AD pathology including immune cell activation, changes in blood-brain barrier, or direct neurotoxicity. This summary of proceedings reviews the content presented in the symposium and provides a summary of major topics and key questions discussed in the workshop.

BACKGROUND: Upper endoscopy (EGD) is frequently performed in patients with esophageal complaints following anti-reflux surgery such as fundoplication. Endoscopic evaluation of fundoplication wrap integrity can be challenging. Our primary aim in this pilot study was to evaluate the accuracy and confidence of assessing Nissen fundoplication integrity and hiatus herniation among gastroenterology (GI) fellows, subspecialists, and foregut surgeons. METHODS: Five variations of post-Nissen fundoplication anatomy were included in a survey of 20 sets of EGD images that was completed by GI fellows, general GI attendings, esophagologists, and foregut surgeons. Accuracy, diagnostic confidence, and inter-rater agreement across providers were evaluated. RESULTS: There were 31 respondents in the final cohort. Confidence in pre-survey diagnostics significantly differed by provider type (mean confidence out of 5 was 1.8 for GI fellows, 2.7 for general GI attendings, 3.6 for esophagologists, and 3.6 for foregut surgeons, P = 0.01). The mean overall accuracy was 45.9%, which significantly differed by provider type with the lowest rate among GI fellows (37%) and highest among esophagologists (53%; P = 0.01). The accuracy was highest among esophagologists across all wrap integrity variations. Inter-rater agreement was low across wrap integrity variations (Krippendorfs alpha

A retrospective review of the UNOS/OPTN Database was performed from 1 October 1987–31 December 2019. Recipients were classified as LSu (15+ years survival without GF/ReTx), normal survival (3–15 years) and short survival (