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    • Notes on the Lectures delivered by Nathaniel Potter, Professor of the Theory and Practice of Medicine in the University of Maryland at Baltimore

      Mainster, Samuel (1827)
      Handwritten class notes by Samuel Mainster, University of Maryland School of Medicine Class of 1828. One of three volumes by Mainster. Volume is part of the Dr. Milford “Mickey” M. Foxwell, Jr.’s Collection of Lecture Notes. Class notes are available in the Internet Archive, see link.
    • American Association of Colleges of Nursing Faculty Vacancy Survey 2022

      University of Maryland, Baltimore. School of Nursing (2022)
    • Structural and Functional Integration of KCNMA1-linked Channelopathy Variants

      Tammen, Kelly K.; Moldenhauer, Hans J.; Meredith, Andrea L. (2022-09)
      KCNMA1 encodes the pore forming alpha subunit for the voltage- and calcium-gated potassium (BK) channel, associated with a neurological disorder of unknown etiology. Currently, KCNMA1-linked channelopathy variants lack integration between disease and structural datasets, obscuring relationships between variants and known channel functions. To address this, we produced a comprehensive annotation of a human BK channel isoform containing alternative exons at sites 1 and 3 and the NRKEMVYR C-terminus (NM_001271518.2). Protein sequence was annotated with 106 patient variants and 572 tags (structural/functional domains, single nucleotide polymorphisms (SNPs), posttranslational modifications, pharmacological modulation, and others) and contextualized within the cryo-EM structure (PDB ID: 6V38). We hypothesized that pathogenic variants would localize within structurally and functionally defined BK channel modules. We found a cluster of loss-of-function (LOF) variants in at the selectivity filter and in the beginning of RCK1, while gain-of-function (GOF) lack obvious physical proximity. Interestingly, transmembrane segments S3 and S4 and the RCK1-RCK2 linker harbor no patient-associated variants, only a few conservative SNPs. Combing Rare Exome Variant Ensemble Learner REVEL) pathogenicity analysis with structural mapping, we identified residues within the selectivity filter and S6 domains as ‘highly pathogenic’ with scores of 0.95 ± 0.02 and 0.95 ± 0.03 respectively, RCK1 and disordered segments within RCK1 and RCK2 were ‘likely pathogenic’ (0.54 ± 0.17 and 0.54 ± 0.15, respectively), and the extracellular N-terminus and intracellular loops were ‘likely nonpathogenic’ (0.34 ± 0.29 and 0.32 ± 0.08, respectively). Finally, an overlap was observed between LOF variants and antagonistic pharmacological modulators, but no proximity relationship was identified between GOF variants and agonists. Thus, our sequence and structural metadata produced unique views that extend predictions for variant pathogenicity in KCNMA1-linked channelopathy.
    • Optic Nerve Head scRNA-Seq enables a strategy to identify tissue-specific neural progenitor functions

      Bernstein, Steven L.; Mehrabyan, Zara; Guo, Yan, M.D.; Hoang, Thanh; Blackshaw, Seth (2022-08)
    • Comprehensive evaluations of diurnal NO measurements during DISCOVER-AQ 2011: effects of resolution-dependent representation of NO emissions.

      Li, Jianfeng; Wang, Yuhang; Zhang, Ruixiong; Smeltzer, Charles; Weinheimer, Andrew; Herman, Jay; Boersma, K Folkert; Celarier, Edward A; Long, Russell W; Szykman, James J; et al. (European Geophysical Society, 2022-07-23)
      Nitrogen oxides (NO x =NO+NO2) play a crucial role in the formation of ozone and secondary inorganic and organic aerosols, thus affecting human health, global radiation budget, and climate. The diurnal and spatial variations in NO2 are functions of emissions, advection, deposition, vertical mixing, and chemistry. Their observations, therefore, provide useful constraints in our understanding of these factors. We employ a Regional chEmical and trAnsport model (REAM) to analyze the observed temporal (diurnal cycles) and spatial distributions of NO2 concentrations and tropospheric vertical column densities (TVCDs) using aircraft in situ measurements and surface EPA Air Quality System (AQS) observations as well as the measurements of TVCDs by satellite instruments (OMI: the Ozone Monitoring Instrument; GOME-2A: Global Ozone Monitoring Experiment - 2A), ground-based Pandora, and the Airborne Compact Atmospheric Mapper (ACAM) instrument in July 2011 during the DISCOVER-AQ campaign over the Baltimore-Washington region. The model simulations at 36 and 4 km resolutions are in reasonably good agreement with the regional mean temporospatial NO2 observations in the daytime. However, we find significant overestimations (underestimations) of model-simulated NO2 (O3) surface concentrations during night-time, which can be mitigated by enhancing nocturnal vertical mixing in the model. Another discrepancy is that Pandora-measured NO2 TVCDs show much less variation in the late afternoon than simulated in the model. The higher-resolution 4 km simulations tend to show larger biases compared to the observations due largely to the larger spatial variations in NO x emissions in the model when the model spatial resolution is increased from 36 to 4 km. OMI, GOME-2A, and the high-resolution aircraft ACAM observations show a more dispersed distribution of NO2 vertical column densities (VCDs) and lower VCDs in urban regions than corresponding 36 and 4 km model simulations, likely reflecting the spatial distribution bias of NO x emissions in the National Emissions Inventory (NEI) 2011.
    • Impact of Palliative Care on Interhospital Transfers to the Intensive Care Unit.

      Siddiqui, Safanah Tabassum; Xiao, Emily; Patel, Sonika; Motwani, Kiran; Shah, Keneil; Ning, Xinyuan; Robinett, Kathryn S (Sciendo, 2022-05-12)
      Community hospitals will often transfer their most complex, critically ill patients to intensive care units (ICUs) of tertiary care centers for specialized, comprehensive care. This population of patients has high rates of morbidity and mortality. Palliative care involvement in critically ill patients has been demonstrated to reduce over-utilization of resources and hospital length of stays. We hypothesized that transfers from community hospitals had low rates of palliative care involvement and high utilization of ICU resources. In this single-center retrospective cohort study, 848 patients transferred from local community hospitals to the medical ICU (MICU) and cardiac care unit (CCU) at a tertiary care center between 2016-2018 were analyzed for patient disposition, length of stay, hospitalization cost, and time to palliative care consultation. Of the 848 patients, 484 (57.1%) expired, with 117 (13.8%) having expired within 48 hours of transfer. Palliative care consult was placed for 201 (23.7%) patients. Patients with palliative care consult were statistically more likely to be referred to hospice (p<0.001). Over two-thirds of palliative care consults were placed later than 5 days after transfer. Time to palliative care consult was positively correlated with length of hospitalization among MICU patients (r=0.79) and CCU patients (r=0.90). Time to palliative consult was also positively correlated with hospitalization cost among MICU patients (r=0.75) and CCU patients (r=0.86). These results indicate early palliative care consultation in this population may result in timely goals of care discussions and optimization of resources.
    • Drug costs in context: assessing drug costs in cost-of-illness analyses.

      Mattingly, T Joseph; Weathers, Shannon (Bioexcel Publishing Ltd., 2022-07-21)
      Cost-of-illness (COI) studies attempt to measure and describe the costs associated or attributed to a specific disease, but there are several considerations for measuring and interpreting drug costs estimates. The complexity of the pharmaceutical supply chain and contractual relationships between manufacturers, wholesalers, pharmacies and payers create challenges for researchers attempting to include drug costs in COI analyses. This article aims to provide contextual information for a general audience interested in conducting or evaluating COI studies that may include drug costs and to describe key factors to consider when reviewing drug costs in the peer-reviewed literature.
    • Exploring the impacts of learning modality changes: Validation of the learning modality change community of inquiry and self-efficacy scales

      Jia, Yuane; Gesing, Peggy; Jun, Hyun Jin; Burbage, Amanda K.; Hoang, Thuha; Kulo, Violet; Cestone, Christina; McBrien, Sarah; Tornwall, Joni (Springer Nature, 2022-01-01)
      The rapid learning environment transition initiated by the COVID-19 pandemic impacted students’ perception of, comfort with, and self-efficacy in the online learning environment. Garrison’s Community of Inquiry framework provides a lens for examining students’ online learning experiences through three interdependent elements: social presence, cognitive presence, and teaching presence. Researchers in this study developed and validated the Learning Modality Change Community of Inquiry and Self-Efficacy scales to measure health professions students’ self-efficacy with online learning, while exploring how cognitive, social, and teaching presence is experienced by students who transition from one learning environment to another. The two scales demonstrate strong validity and reliability evidence and can be used by educators to explore the impacts of learning modality changes on student learning experiences. As learning environments continue to evolve, understanding the impact of these transitions can inform how educators consider curriculum design and learning environment changes. © 2022, The Author(s).
    • Differential effects of metformin-mediated BSEP repression on pravastatin and bile acid pharmacokinetics in humans: A randomized controlled trial.

      Metry, Melissa; Krug, Samuel A; Karra, Vijaya Kumari; Kane, Maureen A; Fink, Jeffrey C; Shu, Yan; Wang, Hongbing; Polli, James E (Wiley-Blackwell, 2022-07-28)
      Metformin has been shown to repress transcription of the bile salt export pump (BSEP) in human primary hepatocytes. The primary objective of this study was to assess the effect of oral metformin on the human pharmacokinetics (PKs) of two BSEP probe substrates: pravastatin and chenodeoxycholic acid (CDCA; also known as chenodiol). Endogenous bile acid levels were assessed as a secondary measure of metformin impact. An open-label, randomized, single-dose, placebo-controlled, fasted, crossover PK study was conducted in 12 healthy adult volunteers. Metformin (500 mg b.i.d.) or placebo (b.i.d.) was administered orally for 6 days. On day 7, a single dose of the BSEP substrates pravastatin (80 mg) and CDCA (250 mg) were administered orally. Plasma samples were quantified for pravastatin, CDCA, and endogenous bile acids. Compared to placebo, metformin increased pravastatin plasma exposure, did not impact CDCA plasma exposure, and reduced conjugated primary bile acid levels in the blood. These results are consistent with metformin repressing BSEP expression. This differential effect reflects the degree of enterohepatic recirculation of victim substrates. © 2022 The Authors.
    • Characterization of interaction between blood coagulation factor VIII and LRP1 suggests dynamic binding by alternating complex contacts.

      Chun, Haarin; Kurasawa, James H; Olivares, Philip; Marakasova, Ekaterina S; Shestopal, Svetlana A; Hassink, Gabriela U; Karnaukhova, Elena; Migliorini, Mary; Obi, Juliet O; Smith, Ally K; et al. (Wiley-Blackwell, 2022-07-10)
      Background: Deficiency in blood coagulation factor VIII (FVIII) results in life-threating bleeding (hemophilia A) treated by infusions of FVIII concentrates. To improve disease treatment, FVIII has been modified to increase its plasma half-life, which requires understanding mechanisms of FVIII catabolism. An important catabolic actor is hepatic low density lipoprotein receptor-related protein 1 (LRP1), which also regulates many other clinically significant processes. Previous studies showed complexity of FVIII site for binding LRP1. Objectives: To characterize binding sites between FVIII and LRP1 and suggest a model of the interaction. Methods: A series of recombinant ligand-binding complement-type repeat (CR) fragments of LRP1 including mutated variants was generated in a baculovirus system and tested for FVIII interaction using surface plasmon resonance, tissue culture model, hydrogen–deuterium exchange mass spectrometry, and in silico. Results: Multiple CR doublets within LRP1 clusters II and IV were identified as alternative FVIII-binding sites. These interactions follow the canonical binding mode providing major binding energy, and additional weak interactions are contributed by adjacent CR domains. A representative CR doublet was shown to have multiple contact sites on FVIII. Conclusions: FVIII and LRP1 interact via formation of multiple complex contacts involving both canonical and non-canonical binding combinations. We propose that FVIII-LRP1 interaction occurs via switching such alternative binding combinations in a dynamic mode, and that this mechanism is relevant to other ligand interactions of the low-density lipoprotein receptor family members including LRP1. © 2022 The Authors.
    • Not Feeling Swell: Superior Vena Cava (SVC) Syndrome Falsely Attributed to COVID-19 Vaccine Reaction

      McNeilly, Bryan P.; Wilkerson, R. Gentry (Elsevier, 2022-01-01)
      Background: The mass immunization campaign against Coronavirus disease 2019 (COVID-19) has resulted in more patients presenting to the emergency department (ED) with concern for a vaccine reaction. Case Report: A 68-year-old man presented to the ED reporting an allergic reaction to the COVID-19 vaccine. He initially noted swelling of his face, neck, and right arm after receiving the first dose of the vaccine. After his second dose of the vaccine, the swelling became more pronounced and prompted him to seek care. On examination, he had fullness of the neck and engorgement of the left external jugular vein, which were exacerbated when the patient raised his arms above his head, consistent with Pemberton's sign. Apart from the swelling of the head and neck, there were no other findings consistent with an allergic reaction. The presence of Pemberton's sign prompted a computed tomography scan of the chest with contrast, which revealed a paratracheal mass measuring 4.5 × 2.0 cm with marked narrowing of the superior vena cava (SVC). The patient was admitted to the hospital for SVC syndrome, and further workup revealed a non-small cell lung cancer. Why Should an Emergency Physician Be Aware of This?: Patients may misattribute their symptoms to a COVID vaccine reaction when they are, in fact, experiencing a more serious underlying disease. This case highlights the importance of a thorough physical examination and maintaining a broad differential diagnosis. In this case, the presence of Pemberton's sign raised suspicion for SVC syndrome, and prompted further workup. © 2022
    • Development of a post-mortem human specimen flow model for advanced bleeding control training

      Vrancken, Suzanne M.; Borger van der Burg, Boudewijn L.S.; Stark, Pieter W.; van Waes, Oscar J.F.; DuBose, Joseph J.; Benjamin, Elizabeth R.; Lieber, André; Verhofstad, Michael H.J.; Kleinrensink, Gert Jan; Hoencamp, Rigo (Elsevier, 2022-01-01)
      Introduction: Prompt and effective hemorrhage control is paramount to improve survival in patients with catastrophic bleeding. In the ever-expanding field of bleeding control techniques, there is a need for a realistic training model to practice these life-saving skills. This study aimed to create a realistic perfused post-mortem human specimen (PMHS) flow model that is suitable for training various bleeding control techniques. Materials and Methods: This laboratory study was conducted in the SkillsLab & Simulation Center of Erasmus MC, University Medical Center Rotterdam, the Netherlands. One fresh frozen and five AnubiFiX® embalmed PMHS were used for the development of the model. Subsequent improvements in the exact preparation and design of the flow model were made based on model performance and challenges that occurred during this study and are described. Results: Circulating arteriovenous flow with hypertonic saline was established throughout the entire body via inflow and outflow cannulas in the carotid artery and jugular vein of embalmed PMHS. We observed full circulation and major hemorrhage could be mimicked. Effective bleeding control was achieved by placing a resuscitative endovascular balloon occlusion of the aorta (REBOA) catheter in the model. Regional perfusion significantly reduced the development of tissue edema. Conclusion: Our perfused PMHS model with circulating arterial and venous flow appears to be a feasible method for the training of multiple bleeding control techniques. Regional arteriovenous flow successfully reduces tissue edema and increases the durability of the model. Further research should focus on reducing edema and enhancing the durability of the model. © 2022 The Author(s)
    • Bacterial communities of hookah tobacco products are diverse and differ across brands and flavors.

      Malayil, Leena; Chattopadhyay, Suhana; Mongodin, Emmanuel F; Sapkota, Amy R (Springer Nature, 2022-08-05)
      Abstract: Young adults are increasingly using non-cigarette products, such as hookahs, since they are perceived as healthier alternatives to cigarette smoking. However, hookah users are exposed to not only carcinogenic compounds but also microorganisms that may play an active role in the development of both infectious and chronic diseases among users. Nevertheless, existing hookah research in this area has focused only on microorganisms that may be transferred to users through the smoking apparatus and not on bacterial communities associated with hookah tobacco. To address this knowledge gap, we conducted time-series experiments on commercially available hookah brands (Al Fakher (flavors: two apple, mint, and watermelon) and Fumari (flavors: white gummy bear, ambrosia, and mint chocolate chill)) stored under three different temperature and relative humidity conditions over 14 days. To characterize bacterial communities, the total DNA was extracted on days 0, 5, 9, and 14, PCR-amplified for the V3V4 region of the bacterial 16S rRNA gene, sequenced on the Illumina HiSeq platform, and analyzed using R. Diversity (alpha and beta) analyses revealed that the microbiotas of Fumari and Al Fakher products differed significantly and that flavor had a significant effect on the hookah microbiota. Overall, Pseudomonas, Bacillus, Sphingomonas, and Methylobacterium were the predominant bacterial taxa across all products. Additionally, we observed compositional differences between hookah brands across the 14-day incubation. These data suggest that the bacterial communities of hookah tobacco are diverse and differ across brands and flavors, which may have critical implications regarding exposures to specific bacteria among hookah users. Key points: • Commercial hookah products harbor diverse bacterial communities. • Brands and flavors impact the diversity of these communities. • Research on their viability and transmission to users’ respiratory tracts is needed. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s).
    • Rare genetic variants explain missing heritability in smoking.

      Jang, Seon-Kyeong; Evans, Luke; Fialkowski, Allison; Arnett, Donna K; Ashley-Koch, Allison E; Barnes, Kathleen C; Becker, Diane M; Bis, Joshua C; Blangero, John; Bleecker, Eugene R; et al. (Springer Nature, 2022-08-04)
      Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this ‘missing heritability’. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability (hSNP2) was estimated from 0.13 to 0.28 (s.e., 0.10–0.13) in European ancestries, with 35–74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5–4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability (hped2, 0.18–0.34). In the African ancestry samples, hSNP2 was estimated from 0.03 to 0.33 (s.e., 0.09–0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking. © 2022, The Author(s), under exclusive licence to Springer Nature Limited.
    • Editorial: Computational accounts of reinforcement learning and decision making in psychiatric disorders.

      Chase, Henry W; Wilson, Robert C; Waltz, James A (Frontiers Media S.A., 2022-07-25)
    • Myths and Misconceptions of Airway Pressure Release Ventilation: Getting Past the Noise and on to the Signal

      Andrews, Penny; Shiber, Joseph; Madden, Maria; Nieman, Gary F.; Camporota, Luigi; Habashi, Nader M. (Frontiers Media S.A., 2022-07-25)
      In the pursuit of science, competitive ideas and debate are necessary means to attain knowledge and expose our ignorance. To quote Murray Gell-Mann (1969 Nobel Prize laureate in Physics): “Scientific orthodoxy kills truth”. In mechanical ventilation, the goal is to provide the best approach to support patients with respiratory failure until the underlying disease resolves, while minimizing iatrogenic damage. This compromise characterizes the philosophy behind the concept of “lung protective” ventilation. Unfortunately, inadequacies of the current conceptual model–that focuses exclusively on a nominal value of low tidal volume and promotes shrinking of the “baby lung” - is reflected in the high mortality rate of patients with moderate and severe acute respiratory distress syndrome. These data call for exploration and investigation of competitive models evaluated thoroughly through a scientific process. Airway Pressure Release Ventilation (APRV) is one of the most studied yet controversial modes of mechanical ventilation that shows promise in experimental and clinical data. Over the last 3 decades APRV has evolved from a rescue strategy to a preemptive lung injury prevention approach with potential to stabilize the lung and restore alveolar homogeneity. However, several obstacles have so far impeded the evaluation of APRV’s clinical efficacy in large, randomized trials. For instance, there is no universally accepted standardized method of setting APRV and thus, it is not established whether its effects on clinical outcomes are due to the ventilator mode per se or the method applied. In addition, one distinctive issue that hinders proper scientific evaluation of APRV is the ubiquitous presence of myths and misconceptions repeatedly presented in the literature. In this review we discuss some of these misleading notions and present data to advance scientific discourse around the uses and misuses of APRV in the current literature. Copyright © 2022 Andrews, Shiber, Madden, Nieman, Camporota and Habashi.
    • Detecting Cognitive Impairment and Dementia in the Emergency Department: A Scoping Review.

      Nowroozpoor, Armin; Dussetschleger, Jeff; Perry, William; Sano, Mary; Aloysi, Amy; Belleville, Michael; Brackett, Alexandria; Hirshon, Jon Mark; Hung, William; Moccia, Joan Michelle; et al. (Elsevier, 2022-08)
      OBJECTIVES: To identify research and practice gaps to establish future research priorities to advance the detection of cognitive impairment and dementia in the emergency department (ED). DESIGN: Literature review and consensus-based rankings by a transdisciplinary, stakeholder task force of experts, persons living with dementia, and care partners. SETTING AND PARTICIPANTS: Scoping reviews focused on adult ED patients. METHODS: Two systematic scoping reviews of 7 medical research databases focusing on best tools and approaches for detecting cognitive impairment and dementia in the ED in terms of (1) most accurate and (2) most pragmatic to implement. The results were screened, reviewed, and abstracted for relevant information and presented at the stakeholder consensus conference for discussion and ranked prioritization. RESULTS: We identified a total of 1464 publications and included 45 to review for accurate tools and approaches for detecting cognitive impairment and dementia. Twenty-seven different assessments and instruments have been studied in the ED setting to evaluate cognitive impairment and dementia, with many focusing on sensitivity and specificity of instruments to screen for cognitive impairment. For pragmatic tools, we identified a total of 2166 publications and included 66 in the review. Most extensively studied tools included the Ottawa 3DY and Six-Item Screener (SIS). The SIS was the shortest to administer (1 minute). Instruments with the highest negative predictive value were the SIS (vs MMSE) and the 4 A's Test (vs expert diagnosis). The GEAR 2.0 Advancing Dementia Care Consensus conference ranked research priorities that included the need for more approaches to recognize more effectively and efficiently persons who may be at risk for cognitive impairment and dementia, while balancing the importance of equitable screening, purpose, and consequences of differentiating various forms of cognitive impairment. CONCLUSIONS AND IMPLICATIONS: The scoping review and consensus process identified gaps in clinical care that should be prioritized for research efforts to detect cognitive impairment and dementia in the ED setting. These gaps will be addressed as future GEAR 2.0 research funding priorities.