Corrigendum: Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study.

[This corrects the article DOI: 10.3389/fchem.2023.1212744.].

Addressing Structural Racism Using a Whole-Scale Planning Process in a Single Academic Center.

Purpose: The murder of George Floyd in 2020 prompted a national demand for cultural transformation to confront the systemic racism prevalent in the country. Academic medical centers were not exempt from this urgent call. This article evaluates the efficacy of a strategic process in fostering cultural transformation within an academic medical system. Methods: A whole-scale strategic planning process was implemented over 13 months, involving multiple working groups representing key stakeholders from each entity across the system, an anonymous survey, a communication plan, and a balanced scorecard to monitor progress. More than 5500 voices, 160 recommendations, 122 data gathering sessions, and town hall meetings contributed to the creation and implementation of vital action items and a strategic framework. The Diversity Engagement Survey (DES) was administered 18 months following the process launch. Results: Of the 45,554 employees, students, faculty, and trainees, 96.5% completed unconscious bias education within the fiscal year and 76% of action items, termed "Just Do Its," were completed. Mission, vision, values, and strategic priorities were crafted to serve as a framework for intermediate and long-term actions. The DES revealed improvement in the "respect" attribute of an inclusive culture, and 64% of respondents confirmed that action for cultural transformation is addressing racism both within and outside of the institution. Conclusion: Implementing a shared purpose, engaging multiple working groups representing key stakeholders, and empowerment of stakeholders to implement changes, in conjunction with the development of a strategic framework addressing structural racism, resulted in the completion of vital action items to initiate cultural change.

Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.

Screening of Pharmaceutical Pollutants Along with Emerging Contaminants in the Sediments of the Periyar River, Located in Kerala (India) by Using High-Resolution Mass Spectrometry (UPLC-Q-ToF-MS).

In this study, ultra-performance liquid chromatography coupled with a quadruple time-of-flight mass spectrometry (UPLC-Q-ToF-MS) was employed to screen and identify pharmaceutical pollutants and emerging contaminants (ECs) in the Periyar River near Aster Medicity hospital, the dumping yard of Amrutha hospital, and the Vaduthala bridge regions in Kerala, India. The analysis was conducted in both positive and negative ionization modes using electrospray ionization (ESI). The QuEChERS method was employed for initial sediment sample preparation. Among the twenty-five identified ECs, four compounds were identified as pharmaceutical pollutants. This study have great significance as it represents the first comprehensive investigation of pharmaceutical pollutants in these hospital regions, highlighting the urgent need for further analysis and understanding of the situation. The presence of ECs poses an urgent need for attention due to the irreversible harm caused to the riverine ecosystem by the degradation of water quality resulting from industrial and domestic discharge.

Analytical approaches for the evaluation of data deficient simulated leachable compounds in ENDS products: a case study.

Leachable investigations are routinely undertaken across a range of sectors (e.g., pharmaceuticals, medical devices, etc.) to determine whether chemicals from a container closure system transfer into a product under normal conditions of use. For Electronic Nicotine Delivery Systems (ENDS) the container closure system includes all materials in contact with the e-liquid that is aerosolized and subsequently inhaled by the user. Currently, there is no guidance for conducting leachable studies for ENDS products, however, there are relevant guidance documents for orally inhaled drug products that can be applied to an ENDS container closure system. We present a case study of the analytical investigation of two leachable compounds identified in simulated leachable studies using aged JUULpods filled with unflavored e-liquid (PG/VG/nicotine/benzoic acid). Both compounds had limited toxicological information and were considered data deficient. A qualitative analysis of the aerosol collected from aged commercial JUULpods (Virginia Tobacco and Menthol), using a similar analytical method (LC-MS/MS) used in the simulated leachable studies, showed no trace or detectable levels of either leachable compound. Therefore, this qualitative analysis did not provide semi-quantitative values for the data-deficient leachable compounds necessary to support toxicological risk assessment. Further, no commercial authentic standards or reasonable synthetic route were available due to the molecular size and structural complexity of the compounds. Instead, method limits were established using an alternative approach to standard ICH guidelines. The experimentally determined method limit of quantitation, using spiked samples of simulated leachable e-liquid, provided conservative semi-quantitative values for each data deficient leachable compound in the aerosol that enabled a transfer efficiency from e-liquid to aerosol to be estimated. The transfer efficiency of each leachable compound was experimentally determined to be less than 2% based on the limit of quantitation, which then could be used to define a relevant exposure limit for the toxicological risk assessment. This work details a novel analytical approach for determining the transfer efficiency of data deficient leachable compounds from ENDS container closure systems into the ENDS aerosol to support toxicological health risk assessments.

Teaching argument writing in math class: challenges and solutions to improve the performance of 4th and 5th graders with disabilities.

Incorporating argument writing as a learning activity has been found to increase students' mathematics performance. However, teachers report receiving little to no preservice or inservice preparation to use writing to support students' learning. This is especially concerning for special education teachers who provide highly specialized mathematics instruction (i.e., Tier 3) to students with mathematics disabilities (MLD). The purpose of this study was to examine the effectiveness of teachers providing content-focused open-ended questioning strategies, which included both argument writing and foundational fraction content, using Practice-Based Professional Development (PBPD) and Self-Regulated Strategy Development (SRSD) for implementing a writing-to-learn strategy called FACT-R2C2. We report the relative number of higher-order mathematical content questions that teachers asked during instruction, from among three different-level question types: Level 1: yes/no questions focused on the mathematics content; Level 2: one-word responses focused on the mathematics content; and Level 3: higher-order open-ended responses centered around four mathematical practices from the Common Core State Standards for Mathematics. Within a well-controlled single-case multiple-baseline design, seven special education teachers were randomly assigned to each PBPD + FACT-R2C2 intervention tier. Results indicated that: (1) teachers' relative use of Level 3 questions increased following the introduction of the FACT intervention; (2) this increase was apart from the professional development training that the teachers had initially received; and (3) students' writing quality improved to some extent with the increase in teachers' relative use of Level 3 questions. Implications and future directions are discussed.

CALM gatekeeper training is associated with increased confidence in utilizing means reduction approaches to suicide prevention among college resident assistants.

BACKGROUND: Most suicide prevention programs focus on increasing knowledge regarding the problem of suicide, yet many fail to include information on the science and application of means reduction approaches. In an attempt to address this gap in practice, the Counseling on Access to Lethal Means (CALM) program was developed to educate clinicians on the importance of means reduction interventions. METHODS: In the current study, a gatekeeper CALM training was delivered to 167 resident assistants. Confidence levels regarding suicide prevention and means reduction skills were assessed at baseline, post-training, and after a 6-week follow-up. RESULTS: Results were suggestive of medium to large training effects. Though there was a small decay of training effects at follow-up, the effects were durable when compared to baseline levels. CONCLUSION: Given these findings, future gatekeeper trainings should be provided more consistently to help sustain the effects and data on the implementation of CALM principles should be measured during follow-up assessments.

Free Appropriate Public Education in the Time of COVID-19.

In the spring of 2020, public schools across the United States were forced to close their campuses due to an emerging public health crisis caused by the detection of the first cases of the COVID-19 virus. Although schools closed their buildings, the delivery of educational services did not stop. This included the ongoing provision of services mandated by federal law under the Americans With Disabilities Act (ADA) and the Individuals With Disabilities Education Act (IDEA), which establish educational protections, processes, and rights for students with disabilities and their families to ensure educational equity. In this article, we describe the potential legal implications of COVID-19 for schools, students with disabilities, and their families with a focus on challenges faced in rural areas. Strategies for mitigating legal impacts are described.

Discovery of a Thermostable GH10 Xylanase with Broad Substrate Specificity from the Arctic Mid-Ocean Ridge Vent System.

A two-domain GH10 xylanase-encoding gene (amor_gh10a) was discovered from a metagenomic data set, generated after in situ incubation of a lignocellulosic substrate in hot sediments on the sea floor of the Arctic Mid-Ocean Ridge (AMOR). AMOR_GH10A comprises a signal peptide, a carbohydrate-binding module belonging to a previously uncharacterized family, and a catalytic glycosyl hydrolase (GH10) domain. The enzyme shares the highest sequence identity (42%) with a hypothetical protein from a Verrucomicrobia bacterium, and its GH10 domain shares low identity (24 to 28%) with functionally characterized xylanases. Purified AMOR_GH10A showed thermophilic and halophilic properties and was active toward various xylans. Uniquely, the enzyme showed high activity toward amorphous cellulose, glucomannan, and xyloglucan and was more active toward cellopentaose than toward xylopentaose. Binding assays showed that the N-terminal domain of this broad-specificity GH10 binds strongly to amorphous cellulose, as well as to microcrystalline cellulose, birchwood glucuronoxylan, barley ß-glucan, and konjac glucomannan, confirming its classification as a novel CBM (CBM85).IMPORTANCE Hot springs at the sea bottom harbor unique biodiversity and are a promising source of enzymes with interesting properties. We describe the functional characterization of a thermophilic and halophilic multidomain xylanase originating from the Arctic Mid-Ocean Ridge vent system, belonging to the well-studied family 10 of glycosyl hydrolases (GH10). This xylanase, AMOR_GH10A, has a surprisingly wide substrate range and is more active toward cellopentaose than toward xylopentaose. This substrate promiscuity is unique for the GH10 family and could prove useful in industrial applications. Emphasizing the versatility of AMOR_GH10A, its N-terminal domain binds to both xylans and glycans, while not showing significant sequence similarities to any known carbohydrate-binding module (CBM) in the CAZy database. Thus, this N-terminal domain lays the foundation for the new CBM85 family.

Dose response effects of cognitive-behavioral therapy in a school mental health program.

School mental health (SMH) programs have been shown to be effective in providing evidence-based interventions to underserved youth. However, limitations of SMH programs are that they can entail holiday breaks, typically do not operate through summer, and often require pulling students from class to receive therapy. These limitations suggest that treatment must be expeditious and potent. Although researchers have investigated dose response to treatment, no studies were located that addressed dose response to treatment in SMH programs. The present study addressed this gap by evaluating the dose response to SMH treatment in a sample of 133 adolescents. Adolescents were assessed at baseline, post-treatment, and at multiple time points throughout treatment. An average treatment response of a 26.81-point decrease in Youth Outcome Questionnaire (YOQ-30) score was found across 14 sessions of cognitive-behavioral therapy (CBT). Further, adolescents exhibited reliable change in YOQ-30 score within an average of 2.91 sessions. Finally, it was found that baseline scores on the Depression and Hyperactivity subscales of the Behavior Assessment System for Children, 2nd Edition, along with YOQ-30 score, predicted treatment response. These findings advance our understanding of dose response to CBT in SMH settings, and create opportunities to better inform effective treatment strategies in similar contexts.

What a medical school chair wants from the dean.

Economic pressure has led the evolution of the role of the medical school dean from a clinician educator to a health care system executive. In addition, other dynamic requirements also have likely led to changes in their leadership characteristics. The most important relationship a dean has is with the chairs, yet in the context of the dean's changing role, little attention has been paid to this relationship. To frame this discussion, we asked medical school chairs what characteristics of a dean's leadership were most beneficial. We distributed a 26-question survey to 885 clinical and basic science chairs at 41 medical schools. These chairs were confidentially surveyed on their views of six leadership areas: evaluation, barriers to productivity, communication, accountability, crisis management, and organizational values. Of the 491 chairs who responded (response rate =55%), 88% thought that their dean was effective at leading the organization, and 89% enjoyed working with their dean. Chairs indicated that the most important area of expertise of a dean is to define a strategic vision, and the most important value for a dean is integrity between words and deeds. Explaining the reasons behind decisions, providing good feedback, admitting errors, open discussion of complex or awkward topics, and skill in improving relations with the teaching hospital were judged as desirable attributes of a dean. Interestingly, only 23% of chairs want to be a dean in the future. Financial acumen was the least important skill a chair thought a dean should hold, which is in contrast to the skill set for which many deans are hired and evaluated. After reviewing the literature and analyzing these responses, we assert that medical school chairs want their dean to maintain more traditional leadership than that needed by a health care system executive, such as articulating a vision for the future and keeping their promises. Thus, there appears to be a mismatch between what medical school chairs perceive they need from their dean and how the success of a dean is evaluated.

Recommendations to Sustain the Academic Mission Ecosystem at U.S. Medical Schools.

Academic medical center (AMC) faculty, administrators, and leaders have the critical tasks of teaching and training the next generation of health care providers and biomedical researchers, as well as generating new knowledge that improves the health of all. In the United States, medical schools and their affiliated hospitals train remarkably high-quality physicians and scientists, and the research conducted at these institutions results in advances in health. To that end, AMCs have become essential engines for driving better health in the United States and the rest of the world; they also have become essential engines driving the economies of their respective communities and regions. The education and research missions, however, require subsidization because tuition and extramural grant funding do not cover the costs of these endeavors. This subsidization largely has come from revenues generated by AMCs' clinical endeavors. The viability of this cross-subsidization, however, is increasingly threatened in the current clinical environment. The authors of this Perspective discuss these issues in depth and provide some concrete recommendations to address these challenges. They hope to stimulate discussion and, ultimately, ensure the financial viability of U.S. AMCs-a national resource of utmost importance. Recommendations to sustain research include creating strategic biomedical research plans, developing a defined and sustained model to support National Institutes of Health funding that keeps pace with inflation, and evolving funding mechanisms. Recommendations to sustain medical education include limiting student debt, creating more cost-effective curricula, and ensuring that clinical training opportunities that meet national standards are available to students.

Biochemical and Cellular Characterization and Inhibitor Discovery of Pseudomonas aeruginosa 15-Lipoxygenase.

Pseudomonas aeruginosa is an opportunistic pathogen that can cause nosocomial and chronic infections in immunocompromised patients. P. aeruginosa secretes a lipoxygenase, LoxA, but the biological role of this enzyme is currently unknown. LoxA is poorly similar in sequence to both soybean LOX-1 (s15-LOX-1) and human 15-LOX-1 (37 and 39%, respectively) yet has kinetics comparably fast versus those of s15-LOX-1 (at pH 6.5, Kcat = 181 ± 6 s(-1) and Kcat/KM = 16 ± 2 µM(-1) s(-1)). LoxA is capable of efficiently catalyzing the peroxidation of a broad range of free fatty acid (FA) substrates (e.g., AA and LA) with high positional specificity, indicating a 15-LOX. Its mechanism includes hydrogen atom abstraction [a kinetic isotope effect (KIE) of >30], yet LoxA is a poor catalyst against phosphoester FAs, suggesting that LoxA is not involved in membrane decomposition. LoxA also does not react with 5- or 15-HETEs, indicating poor involvement in lipoxin production. A LOX high-throughput screen of the LOPAC library yielded a variety of low-micromolar inhibitors; however, none selectively targeted LoxA over the human LOX isozymes. With respect to cellular activity, the level of LoxA expression is increased when P. aeruginosa undergoes the transition to a biofilm mode of growth, but LoxA is not required for biofilm growth on abiotic surfaces. However, LoxA does appear to be required for biofilm growth in association with the host airway epithelium, suggesting a role for LoxA in mediating bacterium-host interactions during colonization.

Research in academic medical centers: two threats to sustainable support.

Reductions in federal support and clinical revenue jeopardize biomedical research and, in turn, clinical medicine.