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Felix JF Herth,1 Armin Ernst,2 Kimberly M Baker,3 Jim J Egan,4 Mark H Gotfried,5 Peter Hopkins,6 Franz Stanzel,7 Arschang Valipour,8 Manfred Wagner,9 Christian Witt,10 Steven Kesten,11 Gregory Snell121Pneumology and Critical Care Medicine, Thoraxklinik Heidelberg, Heidelberg, Germany; 2St Elizabeth's Medical Center, Boston, MA, USA; 3University of Iowa, Iowa City, IA, USA; 4Advanced Lung Disease Program, Mater Misericordiae University Hospital, Dublin, Ireland; 5Pulmonary Associates, Phoenix, AZ, USA; 6Lung Transplant Unit, Prince Charles Hospital, Chermside, Australia; 7Zentrum für Pneumologie, Hemer, Germany; 8Ludwig-Boltzmann-Institute for COPD, Otto-Wagner-Hospital, Vienna, Austria; 9Klinikum Nürnberg, Nürnberg, Germany; 10Pneumology, Charité Campus-Mitte, Berlin, Germany; 11Uptake Medical Corp, Tustin, CA, USA; 12Allergy Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, AustraliaIntroduction: Endoscopic lung volume reduction has been developed as a therapeutic option for advanced emphysema. Six-month results following treatment with endoscopic thermal vapor ablation (InterVapor™; Uptake Medical, Tustin, CA) were described previously, and here we report observations from the 12-month assessment.Methods: Two multicenter, international, single-arm trials of InterVapor (unilateral upper lobe treatment) in patients with upper lobe predominant emphysema were conducted. Inclusion criteria: forced expiratory volume in 1 second (FEV1) 15%–45% predicted, residual volume > 150%, total lung capacity > 100%, 6-minute walk distance (6MWD) > 140 m, and diffusing capacity for carbon monoxide > 20% predicted. Efficacy endpoints: spirometry, body plethysmography, lung volumes by high-resolution computed tomography, St George's Respiratory Questionnaire, modified Medical Research Council dyspnea scale, and 6MWD. All adverse events were collected and independently adjudicated.Results: Forty four patients were treated at a mean (standard deviation) age of 63 (5.6) years, FEV1 0.86 mL (0.25 mL) (n = 22 men and 22 women). Mean (standard deviation) changes from baseline at 12 months were: FEV1 86.2 mL (173.8 mL), St George's Respiratory Questionnaire -11.0 (14.0) units, treated lobar volume from high-resolution computed tomography -751.8 mL (653.9 mL), residual volume -302.8 mL (775.6 mL), 6MWD 18.5 m (63.7 m), and modified Medical Research Council dyspnea scale score -0.83 (0.97) (P < 0.05 for all except 6MWD). Improvements were numerically larger at 6 versus 12 months. GOLD stage III and IV patients had similar outcomes at 6 months; however, improvements relative to baseline were numerically higher in GOLD stage IV patients. Larger improvements were observed in patients with higher heterogeneity. In total, 39 serious adverse events were reported in 23 patients with 10 events in 8 patients between 6 and 12 months.Conclusion: Unilateral lobar InterVapor treatment of heterogeneous emphysema improved lung function and health outcomes 1 year following treatment. The magnitude of improvement was larger at 6 months compared to 12 months. Improvements relative to baseline continue to be exhibited at 12 months despite the expected disease related decline over time.Clinical trials: NCT 01041586 and NCT 01102712Keywords: emphysema, bronchoscopy, lung volume reduction, thermal energy

Objective: Certain modifiable risk factors lead to higher health care costs and reduced worker productivity. A predictive return-on-investment (ROI) model was applied to an obesity management intervention to demonstrate the use of econometric modeling in establishing financial justification for worksite health promotion. Methods: Self-reported risk factors (n = 890) were analyzed using chi square and t test methods. Changes in risk factors, demographics, and financial measures comprised the model inputs that determined medical and productivity savings. Results: Over 1 year, 7 of 10 health risks decreased. Of total projected savings ($311,755), 59% were attributed to reduced health care expenditures ($184,582) and 41% resulted from productivity improvements ($127,173), a $1.17 to $1.00 ROI. Conclusions: Using an ROI model to project program savings is a practical way to provide financial justification for investment in worksite health promotion when risk reduction data are available. [ABSTRACT FROM AUTHOR]

The beneficial effects of blood transfusions have been described and widely accepted. Multiple factors, including shortages, costs, infectious risks, immunologic risks, and the risk/benefit ratio to the patient, have made the medical community reassess the guidelines for transfusion. Cardiac surgery presents a unique subset of patients, because intervention at multiple stages in the care of these patients is possible to decrease the need for transfusion. An algorithm for a cardiac surgery program was developed and a reassessment performed. Once it was seen that no detrimental effect on patient care occurred, the program was expanded, was enhanced, and subsequently has been offered to the rest of the health care system. This program has resulted in a decrease in cost while maintaining patient outcomes. The success of the program is believed to be a result of the multidisciplinary approach taken, with a commitment from all members of the blood reduction team being the key component of this success. [ABSTRACT FROM AUTHOR]

Objective: The asthma practice guidelines developed by the National Institutes of Health include a system for classifying asthma severity. The goal of the present study was to assess the interrater reliability of this classification system by measuring agreement among pediatric asthma specialists.Design: A survey containing eight case summaries was mailed to 24 board-certified pediatric allergists and pulmonologists, who were asked to classify each case according to the national guidelines. The case summaries included the patient's medical history, physical examination, and chest radiograph and pulmonary function test results. Physicians were also asked to interpret the pulmonary function tests, to indicate the main factors used to classify each case (daytime symptoms, nighttime symptoms, pulmonary function testing, or various combinations), and to make treatment recommendations. kappa statistics were used to measure agreement.Results: Fourteen of 24 surveys mailed (58%) were completed and returned. Agreement was poor for classifying asthma (kappa = 0.29; 95% confidence interval [CI], 0.25 to 0.33) and for the main factors used to make the classifications (kappa = 0.19; 95% CI, 0.14 to 0.23). Specialists exhibited higher agreement in their interpretation of pulmonary function tests (no asthma, kappa = 0.66; asthma on baseline, kappa = 0.53; exercise-induced asthma, kappa = 0.65). While physicians' treatment recommendations were consistent with their severity classifications, the low level of agreement in those classifications led to substantial variability in the treatments recommended.Conclusions: The low level of agreement among pediatric asthma specialists in classifying asthma severity suggests the need to refine the classification system used in the national guidelines to help ensure the consistent application of those guidelines. [ABSTRACT FROM AUTHOR]

Background: Diagnostic errors are a global patient safety challenge. Over 75% of diagnostic errors in ambulatory care result from breakdowns in patient-clinician communication. Encouraging patients to speak up and ask questions has been recommended as one strategy to mitigate these failures., Objectives: The goal of the scoping review was to identify, summarize, and thematically map questions patients are recommended to ask during ambulatory encounters along the diagnostic process. This is the first step in a larger study to co-design a patient-facing question prompt list for patients to use throughout the diagnostic process., Methods: Medline and Google Scholar were searched to identify question lists in the peer-reviewed literature. Organizational websites and a search engine were searched to identify question lists in the gray literature. Articles and resources were screened for eligibility and data were abstracted. Interrater reliability (K = 0.875) was achieved., Results: A total of 5509 questions from 235 resources met inclusion criteria. Most questions (n = 4243, 77.02%) were found in the gray literature. Question lists included an average of 23.44 questions. Questions were most commonly coded along the diagnostic process categories of treatment (2434 questions from 250 resources), communication of the diagnosis (1160 questions, 204 resources), and outcomes (766 questions, 172 resources)., Conclusions: Despite recommendations for patients to ask questions, most question prompt lists focus on later stages of the diagnostic process such as communication of the diagnosis, treatment, and outcomes. Further research is needed to identify and prioritize diagnostic-related questions from the patient perspective and to develop simple, usable guidance on question-asking to improve patient safety across the diagnostic continuum., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

The rational design of atropisomeric small molecules is becoming increasingly common in chemical synthesis as a result of the unique advantages this property provides in drug discovery, asymmetric catalysis, and chiroptical activity. In this study, we designed a synthesis of a configurationally stable β-carboline in six steps. Our synthesis made use of an innovative Grignard addition/elimination reaction that formed an yne-ynamide precursor that then reacted with ethyl cyanoformate in a rhodium(I)-catalyzed [2+2+2] cyclotrimerization reaction to give the atropisomeric β-carboline in excellent yield, good enantioselectivity, and excellent regioselectivity. Extensive optimization of this transformation is described. Racemization kinetics experiments were also conducted on the individual atropisomers and their absolute configurations were determined by circular dichroism.

Gape-limited predators (e.g., snakes, many fish) are not generally expected to pose a predation threat to prey that are too large for them to swallow. However, the extent to which snakes predate on prey that exceed their gape limitation remains largely unknown. We conducted the first study to investigate the influence of both prey and predator sizes on the frequency of ingestion success by snakes in a natural system. We combined survival monitoring of an avian prey species ( Aplonis opaca ) via radio-telemetry with a survey of the size distribution of their major predator ( Boiga irregularis ) on Guam. This allowed us to assess (1) the frequency of unsuccessful ingestion by the predator, (2) whether the size of the prey predicts ingestion success, (3) whether the size of the predator predicts ingestion success, and (4) the relationship between prey and predator sizes in successful ingestion attempts. We found that nearly half (47.95%) of ingestion attempts by snakes on fledgling birds were unsuccessful, and no instances where unsuccessful ingestion caused the mortality of the snake. Attempts to consume smaller fledglings were as likely to be unsuccessful as attempts to swallow larger fledglings. However, snakes that successfully ingested fledglings were among the largest snakes in the population, and larger than average conspecifics attracted to endothermic prey. The smallest snakes that successfully ingested fledglings attained remarkably high relative prey mass values for their species, consuming prey weighing up to 79.9% of their own mass. Our study indicates that B. irregularis routinely predate prey that are too large for them to successfully ingest, which causes mortality to the prey but poses little risk to the predator. The potential reward for snakes in consuming oversized prey may outweigh the inherent risks, while instances of predation that do not result in consumption may have considerable impacts on prey populations., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Objectives: Chimeric Antigen Receptor (CAR) T-cell treatment is associated with several unique toxicities, and the short-term symptom trajectory in the immediately after therapy is well-documented. However, little is known about patients' long-term symptom experience. The study aimed to elicit the symptom experience of adult patients in remission after CAR T-cell therapy for B cell lymphoma., Data Sources: A qualitative descriptive design with thematic analysis was utilized. Recruitment occurred at a tertiary academic medical center using the following inclusion criteria: adult recipient of CAR T-cell therapy for B-cell lymphoma between 3 and 12 months prior to enrollment, and currently in remission. Semi-structured interviews were conducted, transcripts were inductively coded, and team members met weekly to ensure rigor. The final sample included 10 patients: Seven received tisagenlecleucel and three received lisocabtagene marleucel and were a median of 169 days post-infusion and 65 years of age., Conclusions: Participants continued to report symptoms, including fatigue, neuropathy, low endurance, insomnia, memory problems, and pain. Most symptoms improved over time. Some symptoms interfered with social activities, work, driving, and physical activity, though participants reported that most symptoms existed prior to CAR T-cell therapy, and overall, found CAR T-cell therapy acceptable., Implications for Nursing Practice: Patients in remission after CAR T-cell therapy often continue to experience symptoms. Nurses should continue to assess this growing patient population and determine if patients require additional symptom management or support. Further research is needed to understand long-term symptom trajectory and associations with prior lines of therapy and CAR T-cell therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lucy Andersen reports statistical analysis was provided by School of Nursing Doctoral Student Organization at the University of Pennsylvania. Lucy Andersen reports a relationship with Janssen Pharmaceuticals Inc that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Connexin 43 (Cx43) is a protein encoded by the GJA1 gene and is a component of cell membrane structures called gap junctions, which facilitate intercellular communication. Prior evidence indicates that elevated GJA1 expression in the HER2-positive (HER2+) subtype of breast cancer is associated with poor prognosis. Prior evidence also suggests that HER2+ breast cancers that have become refractory to HER2-targeted agents have a loss of Cx43 gap junction intercellular communication (GJIC). In this study, a Cx43-targeted agent called alpha-connexin carboxyl-terminal peptide (aCT1) is examined to determine whether GJIC can be rescued in refractory HER2+ breast cancer cells. A proposed mechanism of action for aCT1 is binding to the tight junction protein Zonal Occludens-1 (ZO-1). However, the true scope of activity for aCT1 has not been explored. In this study, mass spectrometry proteomic analysis is used to determine the breadth of aCT1-interacting proteins. The NanoString nCounter Breast Cancer 360 panel is also used to examine the effect of aCT1 on cancer signaling in HER2+ breast cancer cells. Findings from this study show a dynamic range of binding partners for aCT1, many of which regulate gene expression and RNA biology. nCounter analysis shows that a number of pathways are significantly impacted by aCT1, including upregulation of apoptotic factors, leading to the prediction and demonstration that aCT1 can boost the cell death effects of cisplatin and lapatinib in HER2+ breast cancer cells that have become resistant to HER2-targeted agents.

Importance: The increasing problem of drug resistance and emerging pathogens is an urgent global health problem that necessitates the development and expansion of tools for studying fungal drug resistance and pathogenesis. Prior studies in Candida glabrata , Candida auris , and Candida albicans have been mainly limited to the use of NatMX/SAT1 and HphMX/CaHyg for genetic manipulation in prototrophic strains and clinical isolates. In this study, we demonstrated that NatMX/SAT1, HphMX, KanMX, and/or BleMX drug resistance cassettes when coupled with a CRISPR-ribonucleoprotein (RNP)-based system can be efficiently utilized for deleting or modifying genes in the ergosterol pathway of C. glabrata , C. auris , and C. albicans . Moreover, the utility of these tools has provided new insights into ERG genes and their relationship to azole resistance in Candida . Overall, we have expanded the toolkit for Candida pathogens to increase the versatility of genetically modifying complex pathways involved in drug resistance and pathogenesis., Competing Interests: The authors declare no conflict of interest.

Background: Psilocybin-assisted therapies (PAT) are reemerging as a treatment for complex distress often prompting mystical experiences, enhanced meaning, and spiritual wellbeing. We sought to investigate how measures of spirituality are employed in experimental studies of PAT conducted with seriously ill adults. Methods: We included experimental studies of psilocybin conducted with seriously ill adults, which employed measures that contained spirituality and mysticism concepts within their domains or subdomains. Included studies were peer-reviewed and published in English language (up to December 2021). Results: Seven articles met our inclusion criteria. A total of 12 unique instruments were identified. The most frequently used instruments were the Mystical Experience Questionnaire (MEQ30), the Functional Assessment of Chronic Illness Therapy-Spirituality (FACIT-Sp-12), and the Demoralization Scale (DS-I/II) (used in four studies each), followed by the Persisting Effects Questionnaire (PEQ) (used in three studies). Overall, studies did not consistently define and contextualize spirituality domains and subdomains studied. Conclusions: Despite well-recognized significance of spirituality in PAT, there was considerable heterogeneity in number and types of spirituality measures employed across studies. There also seemed a lack of attention to defining and operationalizing spirituality and its domains and subdomains. This is notable as spirituality and overlapping concepts (eg mystical experiences) contributes substantially to this body of research and patients' therapeutic outcomes. Towards developing more rigorous science of spirituality in PAT research, there is a critical need to evaluate and refine measures of spirituality to enhance their utility and replicability, limit participant burden, and better contextualize spirituality-related findings and outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Adhesion to living and non-living surfaces is an important virulence trait of the fungal pathogen Candida albicans. Biofilm formation in this organism depends on the expression of a number of cell surface proteins including the hypha-specific protein Als3p. Loss of ALS3 impairs biofilm formation and decreases cell-cell adhesion. We wanted to test whether constitutively expressing ALS3 could compensate for defects in adhesion and biofilm formation observed in mutant strains that lack key transcriptional regulators of biofilm formation Efg1p and Cph1p. We found that ALS3 improved adhesion and biofilm formation in the efg1Δ and efg1Δ cph1Δ mutant strains, but had less effect on the cph1Δ strain., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Schena et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Juvenile Dermatomyositis (JDM) is a rare, chronic, and life-threatening childhood autoimmune disease. Currently, there are recommended, reliable and validated measurement tools for assessment of skin disease activity in JDM including the Disease Activity Score (skinDAS), Cutaneous Assessment Tool (CAT), and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). The Physician's global assessment skin visual analog scale (Skin VAS) is also widely used for skin activity in JDM. For the purpose of comparative international studies, we wanted to compare these tools to the Physician's skin VAS (as a standard) to identify which performs better., Objectives: We sought to compare the correlations of these scoring tools, and separately assess the responsiveness each tool demonstrates following patient treatment, in order to see if one tool may be preferred. This was determined by assessing how well these tools correlate with each other, and the Physician's skin VAS over time, as well as the responsiveness of each tool after patient treatment., Methods: Skin scores were recorded at a baseline (first visit after June 1 st , 2018) and all follow-up office visits at the Juvenile Dermatomyositis Clinic. Following baseline visits, patients were followed up as clinically indicated. A subset of newly diagnosed patients (inception cohort) was identified. Correlations were assessed at the baseline visit and over time for the whole cohort. The correlations over time were derived using Generalized Estimating Equations (GEEs). Standardized response means with 95% confidence intervals were calculated to test score responsiveness for the nested inception cohort., Results: The skinDAS, CAT and CDASI all correlated highly with each other and with the Physician's skin VAS. The three scoring tools accurately reflected Physician's skin VAS scores over time. In addition, all tools showed moderate to high responsiveness following treatment., Conclusion: All studied skin score tools performed well in our study and appear to be useful. Since no tool far outperforms the others, arbitrary consensus will be needed to select a single standard measurement tool for the purposes of efficiency and global comparability., (© 2023. The Author(s).)

A Ni/1-bpp catalyst was demonstrated to be effective in the Negishi alkylation with multiple classes of alkylpyridinium salts, including α-primary and α-secondary. These conditions are also effective for benzylic pyridinium salts, demonstrating the successful Negishi alkylation of benzylic pyridinium salts for the first time. Further, 14 derivatives of 1-bpp were prepared with a variety of steric and electronic properties to study how these changes impact the success of the Negishi alkylation.

Introduction: Medication for addiction treatment (MAT) for opioid use disorder (OUD) in pregnant women is known to improve neonatal health outcomes. Despite the benefits of this evidence-based treatment for OUD, MAT has been underutilized during pregnancy among certain racial/ethnic groups of women in the United States. The purpose of this study was to examine racial/ethnic differences and factors that affect MAT administration among pregnant women with OUD seeking treatment at publicly funded facilities., Methods: We used data from the 2010-2019 Treatment Episode Data Set system. The analytic sample included 15,777 pregnant women with OUD. We built logistic regression models to examine associations between race/ethnicity and MAT and determine differences and similarities in factors that may influence the use of MAT across racial/ethnic groups of pregnant women with OUD., Results: Although in this sample only 31.6 % received MAT, an increasing trend of MAT receipt has been observed during 2010-2019. Approximately 44 % of the Hispanic pregnant women received MAT, and this was significantly higher than non-Hispanic Black (27.1 %) and White (31.3 %) women. Even after adjusting for potential confounders, the adjusted odds of receiving MAT during pregnancy were lower for Black (AOR = 0.57, 95 % CI 0.44, 0.75) and White (AOR = 0.75, 95 % CI 0.61, 0.91) women compared to Hispanic women. Not being in the labor force increased the odds of receiving MAT in Hispanic women relative to their employed counterparts while homelessness or dependent living decreased the odds of MAT for White women compared to those living independently. Regardless of their racial/ethnic background, pregnant women younger than 29 years old were less likely to receive MAT relative to older women; however, if they were arrested once prior to admission to treatment, they had significantly higher odds of receiving MAT than those with no arrests. Treatment of at least 7 months was associated with a higher likelihood of MAT across all racial/ethnic groups., Conclusions: This study highlights the underutilization of MAT, particularly among pregnant Black and White women who seek treatment for OUD in publicly funded treatment facilities. A multi-dimensional approach to MAT intervention programs is needed to increase MAT for all pregnant women and reduce racial/ethnic inequities., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To survey persons with type 2 diabetes (PWD) on their experiences with diabetes education to better understand what it means when a PWD says they have "had diabetes education.", Methods: We conducted a cross-sectional descriptive study among a convenience sample of adult PWD receiving primary care and/or diabetes self-management education and support in a mid-Atlantic regional US healthcare system. Descriptive, bivariate, and regression analyses were used to describe and explore the diabetes education experience., Results: Participants (n = 498) were majority female, African American, and non-Hispanic. Half reported having "had diabetes education." Of those, 44% had only one session. Education was most often provided in clinical settings by a dietitian (68%) or doctor (51%), in one-on-one (70%) sessions. While most participants reported receiving core diabetes knowledge, fewer reported education on topics that are not related to their daily routine, such as what to do about diabetes medications when sick., Conclusion: The self-reported diabetes education experience varies in content, modality, setting, and education provider. Education receipt is low, and for those who receive education, the amount is low., Practical Implications: The diabetes education experience may fall short of the comprehensive US National Standards-recommended process. Innovative strategies are needed to address these gaps., Competing Interests: Declaration of conflicting interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The Cdc14 phosphatase family is highly conserved in fungi. In Saccharomyces cerevisiae, Cdc14 is essential for down-regulation of cyclin-dependent kinase activity at mitotic exit. However, this essential function is not broadly conserved and requires only a small fraction of normal Cdc14 activity. Here, we identified an invariant motif in the disordered C-terminal tail of fungal Cdc14 enzymes that is required for full enzyme activity. Mutation of this motif reduced Cdc14 catalytic rate and provided a tool for studying the biological significance of high Cdc14 activity. A S. cerevisiae strain expressing the reduced-activity hypomorphic mutant allele ( cdc14 hm ) as the sole source of Cdc14 proliferated like the wild-type parent strain but exhibited an unexpected sensitivity to cell wall stresses, including chitin-binding compounds and echinocandin antifungal drugs. Sensitivity to echinocandins was also observed in Schizosaccharomyces pombe and Candida albicans strains lacking CDC14 , suggesting this phenotype reflects a novel and conserved function of Cdc14 orthologs in mediating fungal cell wall integrity. In C. albicans, the orthologous cdc14 hm allele was sufficient to elicit echinocandin hypersensitivity and perturb cell wall integrity signaling. It also caused striking abnormalities in septum structure and the same cell separation and hyphal differentiation defects previously observed with cdc14 gene deletions. Since hyphal differentiation is important for C. albicans pathogenesis, we assessed the effect of reduced Cdc14 activity on virulence in Galleria mellonella and mouse models of invasive candidiasis. Partial reduction in Cdc14 activity via cdc14 hm mutation severely impaired C. albicans virulence in both assays. Our results reveal that high Cdc14 activity is important for C. albicans cell wall integrity and pathogenesis and suggest that Cdc14 may be worth future exploration as an antifungal drug target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Milholland, AbdelKhalek, Baker, Hoda, DeMarco, Naughton, Koeberlein, Lorenz, Anandasothy, Esperilla-Muñoz, Narayanan, Correa-Bordes, Briggs and Hall.)

Nurses routinely assess pain in hospitalized patients; similar assessment of dyspnea is increasing. Most nurses start with a yes-no question when assessing pain or dyspnea; many record "no" as a zero rating, skipping the rating scale. We tested the hypothesis that recording "no" answers as "zero" fails to detect the symptoms that would have been detected with a rating scale. Nurses asked 60 patients yes-no questions about the presence of dyspnea and pain, then asked patients to rate the symptoms using a 0-10 scale. All "yes" answers were followed by a concordant rating (i.e., greater than zero). More than 25% of "no" answers were followed by a discordant rating (> zero). Documenting "no" as "zero" missed information potentially useful in care planning; patients who rate dyspnea above zero are at greater risk of adverse outcomes. This information can also provide opportunity to start a discussion with patients who may benefit from symptom management.

Axially chiral atropisomers have energetic barriers to rotation, Δ G rot , that prevent racemization of the respective enantiomers. We used computational modeling to develop a suite of 10 bio-inspired 1-aryl-β-carbolines with varying Δ G rot , from which a strong structure-activity relationship was observed for 2-substituted-1-naphthyl substituents. We then synthesized two of these atropisomers, 1d and 1f , by a four-step racemic synthesis and resolved the enantiomers via chiral chromatography. Racemization studies revealed experimental Δ G rot values of 39.5 and 33.0 kcal/mol for 1d and 1f , respectively, which were consistent with our computational results. These atropisomers exhibited long half-lives, which allowed for their physicochemical characterization and stereochemical assignment via UV-vis spectroscopy, fluorescence spectroscopy, electronic circular dichroism, and vibrational circular dichroism.

Background and Objective: The goal of this study was to determine the anatomic outcome of traumatic retinal detachment (RD) from combat ocular trauma., Materials and Methods: Retrospective study of patients sustaining a traumatic RD in Operation Iraqi Freedom and Operation Enduring Freedom who were evacuated to Walter Reed Army Medical Center from 2001 to 2011. The Fisher exact test, Wilcoxon rank sum test, and Agresti and Coull methods were used for analyses., Results: There were 143 eyes of 134 patients in which a traumatic RD developed, of a total of 890 eyes of 652 patients in the Walter Reed Ocular Trauma Database. Based on our results, predictors for failure to reattach the retina include maculaoff status ( P = .0002), open-globe injury ( P = .03), proliferative vitreoretinopathy postoperatively ( P = .002), and presence of hyphema ( P = .02). Intraocular foreign body and time to initial retinal surgery did not increase risk for failure. Thirty-four percent (34%) of eyes failed to be reattached., Conclusions: Traumatic RD due to injury sustained in a combat zone resulted in poor prognosis, with 82.09% of eyes with RD having a best-corrected visual acuity worse than 20/200. The anatomic success of RD repair was shown to be 65.71%, likely owing to the severity of the injuries, concomitant systemic injuries, and delayed surgical intervention. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:493-501.] .

The novel coronavirus may impact exercise habits of those with intellectual disabilities. Due to the mandated discontinuation of face-to-face research, investigators must adapt projects to protect all involved while collecting objective physical activity metrics. This brief report outlines a modification process of research methods to adhere to social distancing mandates present during COVID-19. Actions taken included electronic consent and assent forms, an electronic survey, and mailing an accelerometer with included instructions. The amended research methods were implemented without risk for virus transmission or undue burden on the research team, participant, or caregiver. Recruitment was likely impacted by the coronavirus-mediated quarantine, plausibly resulting in bias. Objective physical activity data collection can be sufficiently modified to protect those with intellectual disabilities and investigators. Future research designs may require greater participant incentives and the creation of in-home participation.

Objective: To compare the learning curve of clinicians with different levels of embryo transfer (ET) experience using the American Society for Reproductive Medicine (ASRM) Embryo Transfer Simulator., Design: Prospective cohort study., Setting: Single large university-affiliated in vitro fertilization center., Patients: Participants with 3 levels of expertise with ET were recruited: "group 1" (Reproductive Endocrinology and Infertility attendings), "group 2" (Reproductive Endocrinology and Infertility nurses, advance practice providers, or medical assistants), and "group 3" (Obstetrics and Gynecology resident physicians)., Interventions: All participants completed ET simulation training using uterine cases A, B, and C (easiest to most difficult) of the ASRM ET Simulator. Participants completed each case 5 times for a total of 15 repetitions., Main Outcome Measures: The primary outcome was ET simulation scores analyzed at each attempt for each uterine case, with a maximum score of 155. Secondary outcomes included self-assessed comfort levels before and after the completion of the simulation and total duration of ET. Comfort was assessed using a 5-point Likert scale., Results: Twenty-seven participants with 3 different levels of expertise with ET were recruited from December 2020 to February 2021. For cases A and B, median total scores were not significantly different between groups 1 and 3 at first or last attempts. Group 2 did not perform as well as group 3 at the beginning of case A or group 1 at the end of case B. All groups demonstrated a decrease in total time from the first attempt to the last attempt for both cases. For case C, the "difficult" uterus, groups 2 and 3 exhibited the greatest improvement in total median score: from 0 to 75 from the first to last attempt. Group 1 scored equally well from first through last attempts. Although no one from group 2 or 3 achieved a passing score with the first attempt (80% of the max score), approximately 30% had passing scores at the last attempt. Groups 1 and 3 showed a significant decrease in total time across attempts for case C. Following simulation, 100% of groups 2 and 3 reported perceived improvement in their skills. Group 3 showed significant improvement in comfort scores with Likert scores of 1.71 ± 0.76 and 1.0 ± 0.0 for the "Easy" and "Difficult" cases, respectively, before simulation and 4.57 ± 0.53 and 2.4 ± 1.1 after simulation., Conclusions: The ASRM ET Simulator was effective in improving both technical skill and comfort level, particularly for those with little to no ET experience and was most marked when training on a difficult clinical case., (© 2022 The Authors.)

Fungal infections are a major health concern because of limited antifungal drugs and development of drug resistance. Candida can develop azole drug resistance by overexpression of drug efflux pumps or mutating ERG11 , the target of azoles. However, the role of epigenetic histone modifications in azole-induced gene expression and drug resistance is poorly understood in Candida glabrata. In this study, we show that Set1 mediates histone H3K4 methylation in C. glabrata. In addition, loss of SET1 and histone H3K4 methylation increases azole susceptibility in both C. glabrata and S. cerevisiae. This increase in azole susceptibility in S. cerevisiae and C. glabrata strains lacking SET1 is due to distinct mechanisms. For S. cerevisiae, loss of SET1 decreased the expression and function of the efflux pump Pdr5, but not ERG11 expression under azole treatment. In contrast, loss of SET1 in C. glabrata does not alter expression or function of efflux pumps. However, RNA sequencing revealed that C. glabrata Set1 is necessary for azole-induced expression of all 12 genes in the late ergosterol biosynthesis pathway, including ERG11 and ERG3. Furthermore, chromatin immunoprecipitation analysis shows histone H3K4 trimethylation increases upon azole-induced ERG gene expression. In addition, high performance liquid chromatography analysis indicated Set1 is necessary for maintaining proper ergosterol levels under azole treatment. Clinical isolates lacking SET1 were also hypersusceptible to azoles which is attributed to reduced ERG11 expression but not defects in drug efflux. Overall, Set1 contributes to azole susceptibility in a species-specific manner by altering the expression and consequently disrupting pathways known for mediating drug resistance.

Imerslund-Gräsbeck syndrome is an autosomal recessive disorder of vitamin B12 malabsorption presenting with megaloblastic anemia and mild proteinuria in childhood. The disorder is caused by biallelic pathogenic variants in the CUBN or AMN genes, which encode proteins involved in B12 absorption. We present the case of a 17-month-old boy with failure to thrive, pancytopenia, and fevers. His megaloblastic anemia was overlooked leading to unnecessary invasive testing. Findings on bone marrow biopsy prompted investigation for genetic disorders of B12 metabolism. Exome sequencing uncovered 1 known pathogenic variant and 1 novel likely pathogenic variant in CUBN, confirming the diagnosis of Imerslund-Gräsbeck syndrome., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A major advancement in the use of radio telemetry has been the development of automated radio tracking systems (ARTS), which allow animal movements to be tracked continuously. A new ARTS approach is the use of a network of simple radio receivers (nodes) that collect radio signal strength (RSS) values from animal-borne radio transmitters. However, the use of RSS-based localization methods in wildlife tracking research is new, and analytical approaches critical for determining high-quality location data have lagged behind technological developments. We present an analytical approach to optimize RSS-based localization estimates for a node network designed to track fine-scale animal movements in a localized area. Specifically, we test the application of analytical filters (signal strength, distance among nodes) to data from real and simulated node networks that differ in the density and configuration of nodes. We evaluate how different filters and network configurations (density and regularity of node spacing) may influence the accuracy of RSS-based localization estimates. Overall, the use of signal strength and distance-based filters resulted in a 3- to 9-fold increase in median accuracy of location estimates over unfiltered estimates, with the most stringent filters providing location estimates with a median accuracy ranging from 28 to 73 m depending on the configuration and spacing of the node network. We found that distance filters performed significantly better than RSS filters for networks with evenly spaced nodes, but the advantage diminished when nodes were less uniformly spaced within a network. Our results not only provide analytical approaches to greatly increase the accuracy of RSS-based localization estimates, as well as the computer code to do so, but also provide guidance on how to best configure node networks to maximize the accuracy and capabilities of such systems for wildlife tracking studies., Competing Interests: The authors have no conflict of interest to declare., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Background/purpose: To characterize the nature of posterior segment ocular injuries in combat trauma., Methods: Eyes in the Walter Reed Ocular Trauma Database were evaluated for the presence of posterior segment injury. Final visual outcomes in open-globe versus closed-globe injuries and by zone of injury and the types of posterior segment injuries in open-globe versus closed-globe injuries were assessed., Results: Four hundred fifty-two of 890 eyes (50.8%) had at least one posterior segment injury. The mechanism of injury was most commonly an improvised explosive device in 280 (62.0%) eyes. Sixty-one patients (13.5%) had a Zone I injury, 50 (11.1%) a Zone II injury, and 341 (75.4%) a Zone III injury. Patients with Zone I injuries were more likely to have a final visual acuity of 20/200 or better compared with patients with either a Zone II (P < 0.001) or Zone III injury (P = 0.007). Eyes with a closed-globe injury were more likely to have a final visual acuity of 20/200 or better compared with those with an open-globe injury (P < 0.001). Furthermore, closed-globe injury compared with open-globe injury had a lower risk of vitreous hemorrhage (odds ratio 0.32, P < 0.001), proliferative vitreoretinopathy (odds ratio 0.14, P < 0.001), and retinal detachment (odds ratio 0.18, P < 0.001) but a higher risk of chorioretinal rupture (odds ratio 2.82, P < 0.001) and macular hole (odds ratio 3.46, P = 0.004)., Conclusion: Patients with combat ophthalmic trauma had similar posterior segment injury patterns to civilian trauma in open-globe versus closed-globe injuries. Zone II and III injuries were associated with a worse visual prognosis.

A deaminative reaction of Katritzky alkylpyridinium salts and sulfinimines has been developed to deliver enantiopure α-chiral amines. The success of this method relied on the discovery of a thermally promoted deamination via single-electron transfer of an anion-π complex of the alkylpyridinium cation with potassium carbonate. This method boasts excellent diastereoselectivity over the α-stereocenter as well as broad functional group and heterocycle tolerance.

To decrease diabetes morbidity and mortality rates, early interventions are needed to change lifestyles that are often cemented early, making school-based interventions important. However, with limited resources and lack of within-county diabetes data, it is difficult to determine which local areas require intervention. To identify at-risk school districts, this study mapped diabetes prevalence and related deaths by school district using geographic information systems (GIS). The 2010-2014 records of diabetes-related deaths were identified for 13 cities in Michigan, USA. Diabetes prevalence was estimated using the weighted average of population by school district from the '500 Cities Project' of the Centres of Disease Control and prevention (CDC). Prevalence and mortality rates were mapped by school district and the correlation between diabetes prevalence and mortality rate analysed using the Spearman's rank correlation. Years of potential life lost (YPLL) were calculated using a 75-year endpoint. The result indicated there were geographic variations in diabetes prevalence, mortality and YPLL across Michigan. Most census tracts in the cities of Detroit, Flint and downtown Grand Rapids had higher diabetes prevalence and mortality rate with rs (628)=0.52, P<0.005. School districts with high mortality rates also had high prevalence with rs (13)=0.72, P=0.002. Flint City School District showed a higher rate of diabetes prevalence, death and YPLL than others and should thus be considered a priority for diabetes prevention interventions. Using school districts as the geographic spatial unit of analysis, we identified local variation in diabetes burden for targeting school-based diabetes prevention interventions.

Public water systems must be tested frequently for coliform bacteria to determine whether other pathogens may be present, yet no testing or disinfection is required for private wells. In this paper, we identify whether well age, type of well, well depth, parcel size, and soil ratings for a leachfield can predict the probability of detecting coliform bacteria in private wells using a multivariate logistic regression model. Samples from 1163 wells were analyzed for the presence of coliform bacteria between October 2017 and October 2019 across Gaston County, North Carolina, USA. The maximum well age was 30 years, and bored wells (median age = 24 years) were older than drilled wells (median age = 19 years). Bored wells were shallower (mean depth = 18 m) compared to drilled wells (mean depth = 79 m). We found coliform bacteria in 329 samples, including 290 of 1091 drilled wells and 39 of 72 bored wells. The model results showed bored wells were 4.76 times more likely to contain bacteria compared to drilled wells. We found that the likelihood of coliform bacteria significantly increased with well age, suggesting that those constructed before well standards were enforced in 1989 may be at a higher risk. We found no significant association between poorly rated soils for a leachfield, well depth, parcel size and the likelihood of having coliform in wells. These findings can be leveraged to determine areas of concern to encourage well users to take action to reduce their risk of drinking possible pathogens in well water., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Diabetes survival skills education (DSSE) focuses on core knowledge and skills necessary for safe, effective, short-term diabetes self-care. Inpatient DSSE delivery approaches are needed. Diabetes to Go (D2Go) is an evidence-based DSSE program originally designed for outpatients., Methods: Implementation science principles were used to redesign D2Go for delivery by staff on medicine and surgery units in a tertiary care hospital to adults with type 2 diabetes (T2DM) using a tablet-based e-learning platform. Implementation efficacy was evaluated from staff and patient engagement perspectives. The Practical, Robust Implementation and Sustainability Model (PRISM) guided redesign. The team conducted qualitative evaluation (implementation barriers and facilitators); program redesign (via stakeholder feedback and education and human factors principles); implementation design for tablet delivery and patient engagement by unit staff; and a prospective implementation feasibility study., Results: Among 596 T2DM patients identified on three medical/surgical units, 415 (69.6%) were program eligible. Of those eligible, 59 (14.2%) received, accessed, and engaged with the platform; and among those, 43 (72.9%) completed the intervention, representing just 10.4% of those eligible. Multilevel implementation barriers were encountered: staff (receptivity, time, production pressures, culture); process (electronic health record [EHR] integration, patient identification, data tracking, bedside delivery); and patient (receptivity, acuity, availability, accessibility). Most completers required technology support., Conclusion: Time constraints, limited EHR integration, and patient barriers markedly impeded implementation of the delivery of diabetes education at the bedside, despite stated staff interest. As a result, uptake and adoption of a tablet-based DSSE e-learning program in a high-acuity care setting was limited., (Copyright © 2020. Published by Elsevier Inc.)

Background: In areas where obstetric services are not available, emergency departments often become the default for unplanned obstetric care, yet emergency nurses are not universally trained in the identification and treatment of obstetric emergencies. The purpose of this study was to explore emergency nurses' perception of acuity in the triage of pregnant or postpartum patients presenting to the emergency department with high-risk complaints and to identify facilitators and challenges to the accurate identification and treatment of these patients., Method: A mixed-methods study was conducted using chart review data (N = 12,766) and focus group data (N = 39) from five emergency departments in the eastern United States., Results: In 86.5% of cases, pregnancy status was not documented. Ninety-four percent of pregnant patients with a systolic blood pressure over 140 mmHg were under-triaged. The overall theme of the qualitative data was acuity blindness, with identified barriers to assessment that included educational needs and triage processes and workflow issues., Conclusion: There are significant knowledge deficits in the care of patients presenting with high-risk conditions associated with pregnancy. [J Contin Educ Nurs. 2021;52(1):21-29.]., (Copyright 2021, SLACK Incorporated.)

Background: One of modifiable risk factors of diabetes is unhealthy diet which is related to obesity. Individuals with childhood obesity are at higher risk of adulthood obesity. School-based diabetes prevention programs are important to reduce childhood obesity. When resources are limited, evidence-based priority need to be undertaken. However, data related to childhood obesity was not widely available, the study used diabetes-related death records as the proxy of diabetes burden. This study aimed to map and identify geographic variation of diabetes-related mortality rate by school district level in Michigan to be used for policy-relevant information. Design and Methods: This study used death records in Michigan. Diabetes-related mortality rate and years potential life lost (YPLL) was calculated at the school district level. Spatial autocorrelation local Moran's I and geographically weighted regression were used to evaluate spatial pattern of age-adjusted diabetes-related mortality rate by school districts. Results: The age-adjusted diabetes-related mortality rate ranged from 17.0 (95% CI, 8.6-25.5) to 171.3 (95% CI, 135.9-206.7) deaths per 100,000 population. The YPLL per person ranged from 0 to 19.3 years (95% CI, 15.5-23.1). High rates of diabetes-related mortality rate and YPLL clustered in East central and Southeastern region of Lower Peninsula Michigan including Flint, Kearsley, Beecher, Westwood Heights, Detroit, Ecorse, River Rouge, Taylor, Allen Park and Lincoln Consolidated school districts. Conclusions: There was variation in diabetes burden examined by diabetes-related mortality rate and YPLL at the school district level within Michigan State. The high cluster can be prioritized for the intervention programs., (©Copyright: the Author(s).)

Background and Objective: To determine the risk factors associated with developing proliferative vitreoretinopathy (PVR) from combat ocular injuries in U.S. service members., Patients and Methods: Retrospective review of associated risk factors and outcomes of PVR within the Walter Reed Ocular Trauma Database. Ocular injuries in U.S. service members wounded during Operation Enduring Freedom and Operation Iraqi Freedom from 2001 to 2011 were assessed, and of these all cases of PVR were studied. Principal outcome measures were the risk factors associated with PVR development and rate of final visual acuity (VA) less than 20/200., Results: Eight hundred ninety eyes of 651 U.S. service members were evaluated. A total of 76 eyes (8.5%) of 66 patients developed PVR. Five patients had bilateral PVR. Nineteen patients had bilateral eye injuries. Sixty-one eyes (80.2%) had a final VA less than 20/200. PVR was found to be a significant risk factor for a poor final VA (P < .001). Retinal detachment (RD) was found in 52 eyes (68.4%) of patients. In patients with a RD, intraocular foreign bodies (IOFBs) (P < .001), unsuccessful repair (P = .002), and macular hemorrhage (P = .04) were significant risk factors for the development of PVR. Time to initial retina surgery was not found to be a risk factor for PVR development (P = .5). Time to initial retina surgery was available in 41 patients and the time to surgery on average was 22.56 days (range: 3 to 87 days)., Conclusions: PVR occurs frequently in combat trauma and is a significant cause of poor final VA. In patients with PVR and RD, injuries caused by an IOFB, macular hemorrhage, or unsuccessful repair were significant risk factors for the development of PVR. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:556-563.]., (Copyright 2020, SLACK Incorporated.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

OBJECTIVE: To adapt a diabetes survival skills education (DSSE) program for delivery on inpatient behavioral health units (BHUs) and to evaluate implementation feasibility within nursing unit workflow. METHODS: We employed mixed methods to codesign, implement, and evaluate a DSSE program for inpatient BHUs. The Diabetes to Go core program incorporates linking knowledge deficits to video education content, a companion book on diabetes survival skills, and education for nurses on delivery processes and teaching content. The Diabetes to Go adaptation for BHUs was codesigned in partnership with BHU staff and patients. Implementation evaluation included patient surveys and nursing staff feedback obtained during field observations. RESULTS: A total of 89 patients participated in nine group education sessions among whom 17 (20%) had diabetes. Nursing unit staff and patients expressed willingness to engage in program design. Barriers to implementation were encountered in both groups including lack of standardization of education content by nurse facilitators and difficulty engaging patients for the time required for completion of surveys plus group education. Preferred education media for both nurses and patients was a book. Diabetes knowledge deficits were identified among over two thirds of participants with diabetes. CONCLUSIONS: Group class may not be the optimal delivery model for specialized DSSE on BHUs. It remains to be determined if individual diabetes education alone or a model which combines individual and group sessions is preferable. Translation of standardized approaches for diabetes education on inpatient BHUs will require further redesign to meet the unique needs of this population.