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Background: This retrospective comparative cohort study aimed to evaluate the effects of COVID-19 on professionalism within the perioperative environment of a tertiary cancer center across three periods: pre-pandemic, pandemic, and an interventional endemic phase., Methods: A retrospective observational review of a prospectively maintained safety event report (SER) database at MD Anderson Cancer Center, with an intervention during the COVID-19 endemic phase, was conducted. This was performed to compare the incidence of professionalism-related events (PRE), which are included in the SER database, during the COVID-19 pandemic period (March 2020 to May 2022), with a pre-pandemic period (September 2011 to February 2020) and a postintervention endemic phase (June 2022 to March 2023). Study interventions included the application of the Vanderbilt Professionalism Escalation Model with broad staff and surgical team education., Results: During the study period, 17,425 SERs were reviewed. Of these, 11,731 (mean 115.0 SERs/month) were reported in the pre-pandemic period, 4,004 SERs (mean 148.3 SERs/month) in the pandemic period, and 1,690 SERs (mean 169.0 SERs/month) in the endemic phase (p = 0.001). There was a statistically significant increase in the incidence of PRE during the pandemic compared to the pre-pandemic and endemic periods. Specifically, 264 PRE (1.5%) were identified during the study period: 114 PRE (mean 1.1 PRE/month) in the pre-pandemic period, 121 PRE (mean 4.5 PRE/month) in the pandemic period, and 29 PRE (mean 2.9 PRE/month) in the endemic phase (p = 0.001). The increase in PRE during the pandemic period corresponded to a concomitant increase in staff turnover rates (15.5%) compared to the pre-pandemic period (8.3%). However, a time shift of four months into the postintervention endemic phase demonstrated a successful reduction to less than pre-pandemic levels of staff turnover (6.7%, p = 0.001)., Conclusion: The COVID-19 pandemic was associated with a significant increase in SERs describing professionalism lapses among health care providers in the perioperative environment. Hospital organizations must recognize the impact of professionalism on morale and turnover and seek to mitigate its effects. Education, promoting individual accountability, confidential reporting, addressing wellness concerns, and providing modes of resilience can enhance workplace culture and potentially cultivate better employee retention rates., (Copyright © 2024 The Joint Commission. Published by Elsevier Inc. All rights reserved.)

The challenges facing the health care industry in the post-coronavirus disease 2019 (COVID-19) pandemic world are numerous, jeopardizing wellness, and performance. Maintaining engagement and fulfillment of anesthesiologists in their work is now a critical issue in various practice settings: academic, private practice, and corporate medicine. In this article, we offer insights on how mentorship, sponsorship, and allyship are important in the advancement of the anesthesiology workforce including women and underrepresented minorities inclusive of race, gender, and disability. Mentorship, sponsorship, and allyship require a framework that intentionally addresses the programmatic structures needed to optimize the environment for increasing women, underrepresented minorities, and other diverse groups. These 3 distinct yet interrelated concepts are defined with a discussion on the value of implementation. In addition, the concept of "belonging" and its importance in enhancing the culture in anesthesiology is explored. We believe that part of the solution to wellness, recruitment and retention and improved job satisfaction of clinicians is having an environment where mentorship, sponsorship, and allyship are foundational., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Objective: To evaluate variability among hospitals in susceptibility of common uropathogens to antimicrobial agents frequently used in transurethral procedures in order to examine whether state-based guidelines might be more appropriate than national prophylactic guidelines., Methods: Hospital-level antibiograms were requested from all hospitals throughout the state of Missouri. We studied Escherichia coli, Klebsiella, and Proteus sensitivities to evaluate common guideline recommended antimicrobials including trimethoprim sulfamethoxazole (TMP-SMX), third-generation cephalosporins, cefazolin, penicillin combinations, gentamicin, and fluoroquinolones. We evaluated variability and association between hospital characteristics and antimicrobial sensitivities., Results: Data was requested from 81 hospitals across the state and 38 provided the requested data (47% response rate). Susceptibility was highest for third-generation cephalosporins for E. coli (mean of 94%), Proteus (96%), and Klebsiella (96%). Gentamicin also had high susceptibility for the bacteria studied; 94% for E. coli and 96% for Klebsiella. Current first line recommended agents showed more modest coverage for E. coli (cefazolin 84%, TMP-SMX 78%), Proteus (cefazolin 82%, TMP-SMX 71%), and Klebsiella (cefazolin 90%, TMP-SMX 89%)., Conclusion: Post transurethral procedure infections are common. Rates can be limited with appropriate prophylaxis. Deciding on empirical coverage must take into account local resistance patterns. There is substantial variability among and within states in antimicrobial susceptibility for common uropathogens. When selecting antimicrobial prophylaxis, urologists should consider local- rather than state- or nation-level antibiograms, given the considerable variability. Future studies should consider the merits of very-broad spectrum prophylaxis and the potential role of molecular urinary pathogen (and pathogen-resistance) testing when selecting an optimal regimen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mycobacterium tuberculosis is a highly specialized human pathogen. The success of M. tuberculosis is due to its ability to replicate within host macrophages, resist host immune responses, and ultimately enter a persistent state during a latent tuberculosis infection. Understanding how M. tuberculosis adapts to and replicates in the intracellular environment of the host is crucial for the development of novel, targeted therapeutics. We report the characterization of an M. tuberculosis mutant lacking Rv3249c, a TetR transcriptional regulator. We show that Rv3249c directly represses the adjacent alkB-rubA-rubB operon encoding an alkane hydroxylase/rubredoxin system. For consistency with related systems, we have named the rv3249c gene alkX . The alkX mutant survived better than wild-type M. tuberculosis inside macrophages. This could be phenocopied by overexpression of the alkB-rubA-rubB locus. We hypothesized that the improved intracellular survival phenotype is a result of increased fitness of the mutant; however, we found that the alkX mutant had a defect when grown on some host-associated carbon sources in vitro . We also found that the alkX mutant had a defect in biofilm formation, also linked to the overexpression of the alkB-rubAB genes. Combined, these results define the primary role of AlkX as a transcriptional repressor of the alkB-rubAB operon and suggest the operon contributes to intracellular survival of the pathogen. IMPORTANCE Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is the leading cause of death worldwide due to a single infectious agent. It is important to understand how M. tuberculosis adapts to and replicates in the intracellular environment of the host. In this study, we characterized the TetR transcriptional regulator Rv3249c and show that it regulates a highly conserved alkane hydroxylase/rubredoxin system. Our data demonstrate that the AlkBRubAB system contributes to the success of the bacterium in host macrophages.

The role of boron in terrestrial plant physiology is diverse and increasingly well understood, but its role in marine aquatic eukaryotes is less clear. Our research reveals a distinctive and large offset in boron isotopes from seawater, irrespective of seaweed type or season. We show that the offset is consistent with the incorporation of borate from seawater. Boron is a known micronutrient in plants but very few studies have used boron isotopes to investigate boron's role in plant physiology. Seaweed, as the most primitive multicellular plant, has an important role in investigating wider plant adaptations that use boron to meet functional needs. Furthermore, seaweed and other plants are a key base nutrient provider in food webs, supplying boron to consumers and playing a critical role in boron environmental cycling.

Objectives: To eliminate catheter-associated urinary tract infections in a pediatric cardiac ICU., Design: Quality improvement methodology., Setting: Twenty-five bed cardiac ICU in a quaternary freestanding children's hospital., Patients: All patients with an indwelling urinary catheter admitted to the cardiac ICU., Interventions: Catheter-associated urinary tract infection was defined according to National Healthcare Safety Network criteria. Failure modes and effects analysis and Pareto charts were used to determine etiology of process failures. We implemented a team-based multi-interventional approach in 2012 using the Model for Improvement, which included as follows: 1) establish indications for inserting and/or maintaining bladder catheterization, 2) standardization of maintenance care for the indwelling urinary catheters, 3) protocol for management of the leaking urinary catheters, 4) incorporation of urinary catheter days and prompts for removal in daily rounds, and 5) review of all cases of prolonged indwelling urinary catheter use (> 3 d). Process control charts were used to evaluate change., Measurements and Main Results: From 2011 to 2018, we showed an early and sustained improvement in catheter-associated urinary tract infection prevention standards compliance from 44% to 96% (52% improvement). These interventions showed a reduction and then elimination of catheter-associated urinary tract infections from January 2012 to the present day, despite fluctuations in total indwelling urinary catheter days., Conclusions: Utilization of quality improvement methodology allowed us to identify components of care that contributed to catheter-associated urinary tract infections. After addressing these issues, we noted a substantial reduction and then elimination of catheter-associated urinary tract infections in our pediatric cardiac ICU. Widely disseminating these interventions across multiple pediatric hospitals to determine the ability to achieve similar results are important next steps.

Radiation therapy is a frequently used modality for the treatment of solid cancers. Although the mechanisms of cell kill are similar for all forms of radiation, the in vivo properties of photon and proton beams differ greatly and maybe exploited to optimize clinical outcomes. In particular, proton particles lose energy in a predictable manner as they pass through the body. This property is used clinically to control the depth at which the proton beam is terminated, and to limit radiation dose beyond the target region. This strategy can allow for substantial reductions in radiation dose to normal tissues located just beyond a tumor target. However, the degradation of proton energy in the body remains highly sensitive to tissue density. As a consequence, any changes in tissue density during the course of treatment may significantly alter proton dosimetry. Such changes may occur through alterations in body weight, respiration, or bowel filling/gas, and may result in unfavorable dose deposition. In this manuscript, we provide a detailed method for the delivery of proton therapy using both passive scatter and pencil beam scanning techniques for prostate cancer. Although the described procedure directly pertains to prostate cancer patients, the method may be adapted and applied for the treatment of virtually all solid tumors. Our aim is to equip readers with a better understanding of proton therapy delivery and outcomes in order to facilitate the appropriate integration of this modality during cancer therapy.

Obstetrical chain placement requires location of specific landmarks and a certain dexterity that must be practiced. Use of low-fidelity models may not always provide students with a realistic experience. In this study we developed an anatomically correct high-fidelity calf leg model that would serve as a better teaching model for pre-clinical veterinary students than a pre-existing low-fidelity polyvinyl chloride (PVC) model. One hundred and twenty pre-clinical veterinary students were instructed how to use obstetrical chains with a low-fidelity PVC model and the anatomically correct high-fidelity calf leg model. After a 45-minute lab, students were surveyed on their experience with both models. Overall students felt the anatomically correct high-fidelity calf leg model increased accuracy in chain placement and provided more accurate landmarks, a more realistic model, and more real-life scenario training.

The mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The m ycobacterial m embrane p rotein l arge (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and Mycobacterium tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature consistent with an important role in the basic physiology of the bacterium. MmpL3 is essential and transports trehalose monomycolate to the mycobacterial surface. In this report, we characterize the role of MmpL11 in M. tuberculosis. M. tuberculosis mmpL11 mutants have altered biofilms associated with lower levels of mycolic acid wax ester and long-chain triacylglycerols than those for wild-type bacteria. While the growth rate of the mmpL11 mutant is similar to that of wild-type M. tuberculosis in macrophages, the mutant exhibits impaired survival in an in vitro granuloma model. Finally, we show that the survival or recovery of the mmpL11 mutant is impaired when it is incubated under conditions of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell wall lipid substrates are important for survival in the context of adaptive immune pressure and for nonreplicating persistence, both of which are critically important aspects of M. tuberculosis pathogenicity., (Copyright © 2017 American Society for Microbiology.)

Background and Objectives: Reflection after patient encounters is an important aspect of clinical learning. After our medical school instituted a reflection paper assignment for all clerkships, we wanted to learn about the types of encounters that students found meaningful on a family medicine clerkship and how they impacted students' learning., Methods: Family and Community Medicine Clerkship students completed a reflection paper after the clerkship, based on guidelines that were used for all clerkship reflection papers at our medical school. Two reviewers independently organized student responses into themes and then jointly prioritized common themes and negotiated any initial differences into other themes., Results: A total of 272 reflection papers describing an actual learning moment in patient care were submitted during the study period of January 2011--December 2012. In describing actions performed, students most frequently wrote about aspects of patient-centered care such as listening to the patient, carefully assessing the patient's condition, or giving a detailed explanation to the patient. In describing effects of those actions, students wrote about what they learned about the patient-physician interaction, the trust that patients demonstrated in them, the approval they gained from their preceptors, and the benefits they saw from their actions., Conclusions: An important contribution of a family medicine clerkship is the opportunity for students to further their skills in patient-centered care and realize the outcomes of providing that type of care.

Mycobacterium tuberculosis is a pathogenic bacterial species, which is neither Gram positive nor Gram negative. It has a unique cell wall, making it difficult to kill and conferring resistance to antibiotics that disrupt cell wall biosynthesis. Thus, the mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the mycobacterial membrane protein large (MmpL) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complicated regulatory network system. Here we report crystallographic structures of two forms of the TetR-family transcriptional regulator Rv0302, which participates in regulating the expression of MmpL proteins. The structures reveal a dimeric, two-domain molecule with architecture consistent with the TetR family of regulators. Comparison of the two Rv0302 crystal structures suggests that the conformational changes leading to derepression may be due to a rigid body rotational motion within the dimer interface of the regulator. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by this protein. In addition, our isothermal titration calorimetry and electrophoretic mobility shift experiments indicate that fatty acids may be the natural ligand of this regulator. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters., (© 2015 The Protein Society.)

The mycobacterial cell wall is critical to the virulence of these pathogens. Recent work shows that the MmpL (mycobacterial membrane protein large) family of transporters contributes to cell wall biosynthesis by exporting fatty acids and lipidic elements of the cell wall. The expression of the Mycobacterium tuberculosis MmpL proteins is controlled by a complex regulatory network, including the TetR family transcriptional regulators Rv3249c and Rv1816. Here we report the crystal structures of these two regulators, revealing dimeric, two-domain molecules with architecture consistent with the TetR family of regulators. Buried extensively within the C-terminal regulatory domains of Rv3249c and Rv1816, we found fortuitous bound ligands, which were identified as palmitic acid (a fatty acid) and isopropyl laurate (a fatty acid ester), respectively. Our results suggest that fatty acids may be the natural ligands of these regulatory proteins. Using fluorescence polarization and electrophoretic mobility shift assays, we demonstrate the recognition of promoter and intragenic regions of multiple mmpL genes by these proteins. Binding of palmitic acid renders these regulators incapable of interacting with their respective operator DNAs, which will result in derepression of the corresponding mmpL genes. Taken together, these experiments provide new perspectives on the regulation of the MmpL family of transporters., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

As demonstrated by the 2011 publication of the National Heart, Lung, and Blood Institute Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, the information available regarding the treatment of pediatric lipid disorders has greatly expanded. HMG-CoA reductase inhibitor, or statin, therapy is now considered a first-line pharmacologic intervention for pediatric patients with severe dyslipidemias failing treatment with diet and exercise alone. Despite their ability to effectively reduce cholesterol levels, bile acid sequestrants continue to pose challenges for pediatric patients because of their unpalatability and are typically used as adjunctive therapy or for patients not able to tolerate statins. Fibric acid derivatives, as a class of medications, not only lack a Food and Drug Administration (FDA)-approved agent, but also continue to lack significant pediatric safety and efficacy data. Niacin, a potential adjunct therapy, lacks FDA approval for pediatric patients and is plagued by significant adverse effects making it an unlikely therapy option for pediatric patients. Ezetimibe provides clinicians with an alternative adjunct therapy option when synergistically paired with an HMG-CoA reductase inhibitor or it can be used as monotherapy for patients intolerant to statins and bile acid sequestrants. Finally, despite several marketed formulations, omega-3 fish oils currently lack FDA approval in pediatric patients and have failed to demonstrate statistically significant lipid lowering in pediatric and adolescent patients. Although recent years have witnessed a dramatic increase in data available for the use of lipid-lowering medications for pediatric patients, long-term study data are still generally lacking and continues to present an active focus of research., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)