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Abstract Background Older adults commonly experience chronic medical conditions and are at risk of cognitive impairment as a result of age, chronic comorbidity, and medications prescribed to manage multiple chronic conditions. Anticholinergic medications are common treatments for chronic conditions and have been repeatedly associated with poor cognitive outcomes, including delirium and dementia, in epidemiologic studies. However, no study has definitively evaluated the causal relationship between anticholinergics and cognition in a randomized controlled trial design. Utilizing our prior experience in deprescribing anticholinergic medications in various clinical environments, we designed an outpatient deprescribing intervention to prospectively test the potential causal relationship between anticholinergics and cognition in primary care older adults. Methods This cluster randomized clinical trial will be conducted to evaluate the impact of an anticholinergic deprescribing intervention compared to usual care on outcomes of cognition and safety in primary care older adults. Participants will include those aged 65 years and over, receiving primary care in the greater Indianapolis area, using a strong anticholinergic within the last 2 weeks or with evidence of high-risk exposure in the past year. Those excluded will have a diagnosis of Alzheimer’s disease or related dementia, or serious mental illness. The trial plans to enroll 344 participants who will be cluster-randomized at the level of primary care physician to avoid contamination. Participants will complete outcome assessments every 6 months up to 2 years by blinded outcome assessors. The primary outcome of the study is a composite measure of cognition that includes domains assessing executive cognitive function, language, and memory. Secondary outcomes include patient-reported measures of pain intensity, depression, anxiety, sleep disturbance, and health-related quality of life. Discussion The R2D2 trial will be the largest and longest prospective randomized trial testing the impact of an anticholinergic-specific deprescribing intervention on cognition in primary care older adults. Results could influence deprescribing methodology and provide new insight on the relationship between anticholinergics and cognition. Trial registration ClinicalTrials.gov NCT04270474. Registered on February 17, 2020.

A substitution of FBS in culturing of bovine satellite cells for the purpose of culturing meat is presented, addressing both basal media and growth factors in relation to proliferating and differentiating cells.

Organic hydroxynitrates (HNs) are key products of hydrocarbon oxidation in the atmosphere. Understanding the fate and processing of these molecules is critical due to their function in the sequestration of NOx species from the atmosphere and in the formation of secondary organic aerosol. However, the direct study of individual HNs’ reactivity has been largely hindered by the lack of authentic standards which has further limited the ability to deconvolute the role of structural features. Herein, we report the kinetic stabilities of six biogenic volatile organic compound-derived HN in acidified single-phase organic/water matrices. Lifetimes for tertiary HNs ranged from 15 min to 6.4 h, whereas secondary HN varied from 56 days to 2.1 years. Product analysis highlights the role that additional non-hydrolysis reactions have in the condensed phase conversion of HNs. This work provides the first evidence for the structural dependence of HN stability in bulk mixed media.

Background: Older adults commonly experience chronic medical conditions and are at risk of cognitive impairment as a result of age, chronic comorbidity, and medications prescribed to manage multiple chronic conditions. Anticholinergic medications are common treatments for chronic conditions and have been repeatedly associated with poor cognitive outcomes, including delirium and dementia, in epidemiologic studies. However, no study has definitively evaluated the causal relationship between anticholinergics and cognition in a randomized controlled trial design. Utilizing our prior experience in deprescribing anticholinergic medications in various clinical environments, we designed an outpatient deprescribing intervention to prospectively test the potential causal relationship between anticholinergics and cognition in primary care older adults. Methods: This cluster randomized clinical trial will be conducted to evaluate the impact of an anticholinergic deprescribing intervention compared to usual care on outcomes of cognition and safety in primary care older adults. Participants will include those aged 65 years and over, receiving primary care in the greater Indianapolis area, using a strong anticholinergic within the last 2 weeks or with evidence of high-risk exposure in the past year. Those excluded will have a diagnosis of Alzheimer's disease or related dementia, or serious mental illness. The trial plans to enroll 344 participants who will be cluster-randomized at the level of primary care physician to avoid contamination. Participants will complete outcome assessments every 6 months up to 2 years by blinded outcome assessors. The primary outcome of the study is a composite measure of cognition that includes domains assessing executive cognitive function, language, and memory. Secondary outcomes include patient-reported measures of pain intensity, depression, anxiety, sleep disturbance, and health-related quality of life. Discussion: The R2D2 trial will be the largest and longest prospective randomized trial testing the impact of an anticholinergic-specific deprescribing intervention on cognition in primary care older adults. Results could influence deprescribing methodology and provide new insight on the relationship between anticholinergics and cognition. Trial registration: ClinicalTrials.gov NCT04270474. Registered on February 17, 2020. [ABSTRACT FROM AUTHOR]

According to the Host Manipulation Hypothesis, parasites modify the phenotype of their host to enhance host–host transmission and thereby increase fitness. Metacercarial infection of some amphibians changes host behavior, including locomotion, and thereby enhances predation by the definitive host. To further test this hypothesis, it is first necessary to determine whether a parasite actually modifies a host’s phenotype. In the southern Appalachian Mountains of the US, metacercariae of the trematode Metagonimoides oregonensis (Price, 1931) encyst in the musculature of its second intermediate host, the salamander Desmognathus amphileucus Bishop, 1941. Metacercarial infections of musculature in fish negatively affect host swimming performance. Therefore, we tested the hypothesis that infection by M. oregonensis affects walking in the aquatic larvae of D. amphileucus. We compared this mode of locomotion between infected and uninfected larvae by placing them in 1 m troughs of water and allowing them to wander freely until they stopped. Non-parametric (Kaplan–Meier) survival analysis determined that infected salamanders stopped significantly sooner than uninfected ones. Because infected salamanders move less, the presence of this parasite may contribute to genetic divergence in these salamanders by slowing dispersal and concomitant gene flow. Our results suggest that macroparasites can potentially modify a host’s behavior with biological consequences beyond enhancement of parasite transmission.

The p63 protein is a master regulatory transcription factor that plays crucial roles in cell differentiation, adult tissue homeostasis, and chromatin remodeling, and its dysregulation is associated with genetic disorders, physiological and premature aging, and cancer. The effects of p63 are carried out by two main isoforms that regulate cell proliferation and senescence. p63 also controls the epigenome by regulating interactions with histone modulators, such as the histone acetyltransferase p300, deacetylase HDAC1/2, and DNA methyltransferases. miRNA-p63 interactions are also critical regulators in the context of cancer metastasis. This review aims to elaborate on the diverse roles of p63, focusing on disease, development, and the mechanisms controlling genome organization and function.

The Army Combat Fitness Test (ACFT) is a multi-event assessment battery designed to determine the combat readiness of U.S. Army personnel. However, for Reserve Officers’ Training Corps (ROTC) programs the logistical demands of collegiate life make repeated administration of the ACFT challenging. The present study sought to design and evaluate a single, multimodal exercise tolerance test (METT) capable of serving as a time-efficient proxy measure of combat readiness. Methods: Using a formal instrument design process, we constructed the METT to mimic the demands of the ACFT and assessed its reliability, validity, and responsiveness. Results: The METT demonstrates minimal measurement error (i.e., a 2% coefficient of variation), concurrent validity with the ACFT (R2 = 0.327, F = 10.67, p < 0.001), the ability to classify cadets who may be at-risk for failing the ACFT (X2 = 8.16, p = 0.017, sensitivity = 0.878, specificity = 0.667), and appropriate change following a training intervention (5.69 ± 8.9%). Conclusions: The METT has the potential to provide a means to monitor progress, identify areas for improvement, and guide informed decision-making regarding individualization of cadet combat training plans.

In hybrid metal halide perovskites, chiroptical properties typically arise from structural symmetry breaking by incorporating a chiral A-site organic cation within the structure, which may limit the compositional space. Here we demonstrate highly efficient remote chirality transfer where chirality is imposed on an otherwise achiral hybrid metal halide semiconductor by a proximal chiral molecule that is not interspersed as part of the structure yet leads to large circular dichroism dissymmetry factors (g CD ) of up to 10 -2 . Density functional theory calculations reveal that the transfer of stereochemical information from the chiral proximal molecule to the inorganic framework is mediated by selective interaction with divalent metal cations. Anchoring of the chiral molecule induces a centro-asymmetric distortion, which is discernible up to four inorganic layers into the metal halide lattice. This concept is broadly applicable to low-dimensional hybrid metal halides with various dimensionalities (1D and 2D) allowing independent control of the composition and degree of chirality., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Factors contributing to individual differences in knee osteoarthritis remain elusive. Dispositional traits and socioeconomic status are independent predictors of mental and physical health, although significant variability remains. Dispositional traits serve as the biological interface for life experiences., Objectives: We investigate group differences based on dispositional traits and poverty status, specific to (1) pain intensity and functional limitations and (2) biological measures, a clinical composite and brain age., Methods: Adults aged 45 to 85 years with knee pain associated with chronic musculoskeletal pain provided information on demographics, socioeconomic and psychosocial factors, pain, and physical function. Kellgren-Lawrence scores were determined from knee radiographs, the clinical composite from fasting blood draws, and brain age from MRI data., Results: One hundred seventy-three individuals participated in the study. Of those, 117 had protective dispositional traits (81 above poverty/36 in poverty), and 56 had vulnerable dispositional traits (24 above poverty/32 in poverty). With sex, study site, Kellgren-Lawrence score, and age/or image quality as covariates, significant group differences were observed across clinical pain ( P < 0.001), functional limitations ( P ≤ 0.001), and brain age ( P ≤ 0.002) measures. Although not significant, the clinical composite measure aligned with the other outcome measures and demonstrated the hormesis inverted U pattern., Conclusions: Groups based on dispositional traits and socioeconomic status explain differing clinical outcomes. Consistent with the allostatic load and hormesis inverted U models, one group was in an adaptive health status, 2 groups were showing signs of developing load, and the fourth group showing signs of overload, at risk of worse health outcomes., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Heat shock proteins (HSPs) are essential to cellular protection against heat stress. However, the causes of inter-individual variation in HSP regulation remain unclear. This study aimed to test the impact of early-life conditions on the HSP response to heat in zebra finches. In this arid-adapted bird, incubating parents emit "heat-calls" at high temperatures, which adaptively alter offspring's phenotypes. Embryos were exposed to heat-calls or control-calls, and at 13 days post-hatch nestlings were separated into two different experiments to test responses to either chronic nest temperature ("in-nest" experiment) or an acute "heat-challenge". Blood samples were collected to measure levels of heat shock cognate 70, heat shock protein 90α, corticosterone and the heterophil-to-lymphocyte (H/L) ratio. In the in-nest experiment, both HSPs were upregulated in response to increasing nest temperatures only in control-calls nestlings (HSC70: p = 0.010, HSP90α: p = 0.050), which also had a marginally higher H/L ratio overall than heat-call birds ( p = 0.066). These results point to a higher heat sensitivity in control-call nestlings. Furthermore, comparing across experiments, only the H/L ratio differed, being higher in heat-challenged than in in-nest nestlings ( p = 0.009). Overall, this study shows for the first time that a prenatal acoustic signal of heat affects the nestling HSP response to postnatal temperature.

Background: Older adults commonly experience chronic medical conditions and are at risk of cognitive impairment as a result of age, chronic comorbidity, and medications prescribed to manage multiple chronic conditions. Anticholinergic medications are common treatments for chronic conditions, and have been repeatedly associated with poor cognitive outcomes, including delirium and dementia, in epidemiologic studies. However, no study has definitively evaluated the causal relationship between anticholinergics and cognition in a randomized controlled trial design. Utilizing our prior experience in deprescribing anticholinergic medications in various clinical environments, we designed an outpatient deprescribing intervention to prospectively test the potential causal relationship between anticholinergics and cognition in primary care older adults., Methods: This cluster randomized clinical trial will be conducted to evaluate the impact of an anticholinergic deprescribing intervention compared to usual care on outcomes of cognition and safety in primary care older adults. Participants will include those aged 65 years and over, receiving primary care in the greater Indianapolis area, using a strong anticholinergic within the last two weeks or with evidence of high-risk exposure in the past year. Those excluded will have a diagnosis of Alzheimer's disease or related dementia, or serious mental illness. The trial plans to enroll 344 participants who will be cluster-randomized at the level of primary care physician to avoid contamination. Participants will complete outcome assessments every six months up to 2 years by blinded outcome assessors. The primary outcome of the study is a composite measure of cognition that includes domains assessing executive cognitive function, language, and memory. Secondary outcomes include patient-reported measures of pain intensity, depression, anxiety, sleep disturbance, and health-related quality of life., Discussion: The R2D2 trial will be the largest and longest prospective randomized trial testing the impact of an anticholinergic-specific deprescribing intervention on cognition in primary care older adults. Results could influence deprescribing methodology and provide new insight on the relationship between anticholinergics and cognition., Competing Interests: Competing Interests All other authors report no conflicts of interest.

Preterm birth is the leading cause of infant mortality resulting in over one million neonatal deaths annually. Maternal urinary tract infection (UTI) during pregnancy increases risk for preterm birth; however, biological processes mediating UTI-associated preterm birth are not well-described. We established a murine maternal UTI model in which challenge with uropathogenic E. coli resulted in preterm birth in about half of dams. Dams experiencing preterm birth displayed excessive bladder inflammation and altered uteroplacental T cell polarization compared to non-laboring infected dams, with no differences in bacterial burdens. Additional factors associated with preterm birth included higher proportions of male fetuses and lower maternal serum IL-10. Furthermore, exogenous maternal IL-10 treatment absolved UTI-associated preterm birth but contributed to fetal growth restriction in this model. Using urine samples from a cohort of human pregnancies with or without UTI, we correlated urinary cytokines with birth outcomes and urine culture status. These analyses yielded a non-invasive, highly predictive three-model system for evaluating preterm birth risk implicating cytokines IL-10, IL-15, IL-1β, and IL-1RA. Our unique bimodal murine model coupled with patient samples provides a platform to investigate immunological and microbial factors governing UTI-associated preterm birth, revealing novel therapeutic opportunities to predict or prevent preterm birth., Competing Interests: Conflict of interest statement: The authors have declared that no conflict of interest exists.

Objective: To explore stakeholder views on the structures and processes supporting planned and unplanned interprofessional education (IPE) during experiential learning (EL) placements for student pharmacists in Scotland., Methods: Online semistructured group interviews were conducted with academic staff, practice educators, and EL facilitators (preceptors). Recordings were transcribed verbatim and analyzed thematically. Systems theory underpinned the study. Ethical approval was granted by the School of Pharmacy and Life Sciences Ethics Review Committee at Robert Gordon University., Results: Three main themes were identified: current IPE delivery and context, factors affecting IPE delivery and student pharmacist learning, and rethinking current IPE provision. Stakeholder views provided valuable insights into presage factors relating to contextual elements (cultural, logistical, regulatory) and their influence on IPE delivery and interprofessional learning. EL facilitator and student pharmacist characteristics were also highlighted as influencing factors; process factors included examples of planned and unplanned IPE experiences on offer in community, hospital, primary care, and specialist areas of pharmacy practice; product factors highlighted the importance of IPE to support the development of collaborative competencies. Future developments need to focus on a continuum of IPE learning and a coordinated approach between higher education institutions and placement providers and interprofessional practice teams., Conclusion: Curricular development and implementation of new IPE is not without its challenges. This study has provided a strong foundation that will inform future developments to ensure new initiatives are conducive to supporting effective interprofessional learning during placements., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Halide argyrodite solid-state electrolytes of the general formula Li 6 PS 5 X exhibit complex static and dynamic disorder that plays a crucial role in ion transport processes. Here, we unravel the rich interplay between site disorder and dynamics in the plastic crystal argyrodite Li 6 PS 5 CN and the impact on ion diffusion processes through a suite of experimental and computational methodologies, including temperature-dependent synchrotron powder X-ray diffraction, AC electrochemical impedance spectroscopy, 7 Li solid-state NMR, and machine learning-assisted molecular dynamics simulations. Sulfide and (pseudo)halide site disorder between the two anion sublattices unilaterally improves long-range lithium diffusion irrespective of the (pseudo)halide identity, which demonstrates the importance of site disorder in dictating bulk ionic conductivity in the argyrodite family. Furthermore, we find that anion site disorder modulates the presence and time scales of cyanide rotational dynamics. Ordered configurations of anions enable fast, quasi-free rotations of cyanides that occur on time scales of 10 11 Hz at T = 300 K. In contrast, we find that cyanide dynamics are slow or frozen in Li 6 PS 5 CN when site disorder between the cyanide and sulfide sublattices is present at T = 300 K. We rationalize the observed differences in cyanide dynamics in the context of elastic dipole interactions between neighboring cyanide anions and local strain induced by the configurations of site disorder that may impact the energetic landscape for cyanide rotational dynamics. Through this study, we find that anion disorder plays a decisive role in dictating the extent and time scales of both lithium ion and cyanide dynamics in Li 6 PS 5 CN., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Large composite structures, such as those used in wind energy applications, rely on the bulk polymerization of thermosets on an impressively large scale. To accomplish this, traditional thermoset polymerizations require both elevated temperatures (>100 °C) and extended cure durations (>5 h) for complete conversion, necessitating the use of oversize ovens or heated molds. In turn, these requirements lead to energy-intensive polymerizations, incurring high manufacturing costs and process emissions. In this study, we develop thermoset polymerizations that can be initiated at room temperature through a transformative "chemical heating" concept, in which the exothermic energy of a secondary reaction is used to facilitate the heating of a primary thermoset polymerization. By leveraging a redox-initiated methacrylate free radical polymerization as a source of exothermic chemical energy, we can achieve peak reaction temperatures >140 °C to initiate the polymerization of epoxy-anhydride thermosets without external heating. Furthermore, by employing Trojan horse methacrylate monomers to induce mixing between methacrylate and epoxy-anhydride domains, we achieve the synthesis of homogeneous hybrid polymeric materials with competitive thermomechanical properties and tunability. Herein, we establish a proof-of-concept for our innovative chemical heating method and advocate for its industrial integration for more energy-efficient and streamlined manufacturing of wind blades and large composite parts more broadly., Competing Interests: The authors declare the following competing financial interest(s): MLM, NAR, and RDA have submitted patent applications on recyclable-by-design materials and the DC strategy. All other authors declare no competing interests., (© 2024 The Authors. Published by American Chemical Society.)

The maternal-to-zygotic transition (MZT) is a conserved developmental process where the maternally-derived protein and mRNA cache is replaced with newly made zygotic gene products. We have previously shown that in Drosophila the deposited RNA-binding proteins ME31B, Cup, and Trailer Hitch (TRAL) are ubiquitylated by the CTLH E3 ligase and cleared. However, the organization and regulation of the CTLH complex remain poorly understood in flies. In particular, Drosophila lacks an identifiable substrate adaptor, and the mechanisms restricting degradation of ME31B and its cofactors to the MZT are unknown. Here, we show that the developmental specificity of the CTLH complex is mediated by multipronged regulation, including transcriptional control by the transcription factor OVO and autoinhibition of the E3 ligase. One major regulatory target is the subunit Muskelin, which we demonstrate acts as a substrate adaptor for the Drosophila CTLH complex. Although conserved, Muskelin has structural roles in other species, suggesting a surprising functional plasticity. Finally, we find that Muskelin has few targets beyond the three known RNA binding proteins, showing exquisite target specificity. Thus, multiple levels of integrated regulation restrict the activity of the embryonic CTLH complex to early embryogenesis, seemingly with the goal of regulating three important RNA binding proteins., Competing Interests: COMPETING INTEREST STATEMENT The authors declare no competing interests.

Background: Interprofessional education can prepare the workforce for collaborative practice in complex health and social care systems., Aim: To examine the nature and extent of interprofessional education in schools of pharmacy in the United Kingdom., Method: An online questionnaire was developed using systems theory, published literature and input from an interprofessional expert panel; it included closed and open-ended questions and a demographic section. Following piloting, it was distributed to 31 schools of pharmacy. Descriptive statistics were used for quantitative data, and a content analysis approach for qualitative data., Results: Ten schools of pharmacy responded. All reported delivering compulsory interprofessional education. Most (80%) reported an interprofessional steering group overseeing development. Formative and/or summative assessment varied depending on year of study. Mechanism and purpose of evaluation varied with respondents reporting Kirkpatrick Evaluation Model Levels 1-3 (100%; 80%; 70%). Two themes were identified: "Variation in Interprofessional Education Approaches and Opportunities" and "Factors Influencing Development and Implementation of Interprofessional Education". Formal teaching was mainly integrated into other modules; various pedagogic approaches and topics were used for campus-based activities. Respondents referred to planned interprofessional education during practice-based placements; some still at pilot stage. Overall, respondents agreed that practice-based placements offered opportunistic interprofessional education, but a more focused approach is needed to maximise student pharmacists' learning potential., Conclusion: Most interprofessional education offered in undergraduate pharmacy curricula in the United Kingdom is campus-based; the nature and extent of which varies between programmes. Very few examples of practice-based activities were reported. Results may inform future interprofessional education curricular development., (© 2023. The Author(s).)

Plant secondary cell walls (SCWs) are composed of a heterogeneous interplay of three major biopolymers: cellulose, hemicelluloses, and lignin. Details regarding specific intermolecular interactions and higher-order architecture of the SCW superstructure remain ambiguous. Here, we use solid-state nuclear magnetic resonance (ssNMR) measurements to infer refined details about the structural configuration, intermolecular interactions, and relative proximity of all three major biopolymers within air-dried Populus wood. To enhance the utility of these findings and enable evaluation of hypotheses in a physics-based environment in silico, the NMR observables are articulated into an atomistic, macromolecular model for biopolymer assemblies within the plant SCW. Through molecular dynamics simulation, we quantitatively evaluate several variations of atomistic models to determine structural details that are corroborated by ssNMR measurements.

Cross-linked elastomers are stretchable materials that typically are not recyclable or biodegradable. Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are soft and ductile, making these bio-based polymers good candidates for biodegradable elastomers. Elasticity is commonly imparted by a cross-linked network structure, and covalent adaptable networks have emerged as a solution to prepare recyclable thermosets via triggered rearrangement of dynamic covalent bonds. Here, we develop biodegradable and recyclable elastomers by chemically installing the covalent adaptable network within biologically produced mcl-PHAs. Specifically, an engineered strain of Pseudomonas putida was used to produce mcl-PHAs containing pendent terminal alkenes as chemical handles for postfunctionalization. Thiol-ene chemistry was used to incorporate boronic ester (BE) cross-links, resulting in PHA-based vitrimers. mcl-PHAs cross-linked with BE at low density (<6 mole %) affords a soft, elastomeric material that demonstrates thermal reprocessability, biodegradability, and denetworking at end of life. The mechanical properties show potential for applications including adhesives and soft, biodegradable robotics and electronics.

Background: Rab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. Additionally, sea urchin Rab35 regulates actin organization and is required for gastrulation. In mice, loss of Rab35 in the CNS disrupts hippocampal development and neuronal organization. Outside of the CNS, the functions of mammalian Rab35 in vivo are unknown., Methods: We generated and analyzed the consequences of both congenital and conditional null Rab35 mutations in mice. Using a LacZ reporter allele, we assessed Rab35 expression during development and postnatally. We assessed Rab35 loss in the kidney and ureter using histology, immunofluorescence microscopy, and western blotting., Results: Congenital Rab35 loss of function caused embryonic lethality: homozygous mutants arrested at E7.5 with cardiac edema. Conditional loss of Rab35, either during gestation or postnatally, caused hydronephrosis. The kidney and ureter phenotype were associated with disrupted actin cytoskeletal architecture, altered Arf6 epithelial polarity, reduced adherens junctions, loss of tight junction formation, defects in EGFR expression and localization, disrupted cell differentiation, and shortened primary cilia., Conclusion: Rab35 is essential for mammalian development and the maintenance of kidney and ureter architecture. Loss of Rab35 leads to non-obstructive hydronephrosis, making the Rab35 mutant mouse a novel mammalian model to study mechanisms underlying this disease.

We assessed Oxivir Tb wipe disinfectant residue in a controlled laboratory setting to evaluate low environmental contamination of SARS-CoV-2. Frequency of viral RNA detection was not statistically different between intervention and control arms on day 3 (P=0.14). Environmental contamination viability is low; residual disinfectant did not significantly contribute to low contamination.

Objective: To focus on the intersection of perception, diagnosis, stigma, and weight bias in the management of obesity and obtain consensus on actionable steps to improve care provided for persons with obesity., Methods: The American Association of Clinical Endocrinology (AACE) convened a consensus conference of interdisciplinary health care professionals to discuss the interplay between the diagnosis of obesity using adiposity-based chronic disease (ABCD) nomenclature and staging, weight stigma, and internalized weight bias (IWB) with development of actionable guidance to aid clinicians in mitigating IWB and stigma in that context., Results: The following affirmed and emergent concepts were proposed: (1) obesity is ABCD, and these terms can be used in differing ways to communicate; (2) classification categories of obesity should have improved nomenclature across the spectrum of body mass index (BMI) using ethnic-specific BMI ranges and waist circumference (WC); (3) staging the clinical severity of obesity based on the presence and severity of ABCD complications may reduce weight-centric contribution to weight stigma and IWB; (4) weight stigma and internalized bias are both drivers and complications of ABCD and can impair quality of life, predispose to psychological disorders, and compromise the effectiveness of therapeutic interventions; (5) the presence and of stigmatization and IWB should be assessed in all patients and be incorporated into the staging of ABCD severity; and (6) optimal care will necessitate increased awareness and the development of educational and interventional tools for health care professionals that address IWB and stigma., Conclusions: The consensus panel has proposed an approach for integrating bias and stigmatization, psychological health, and social determinants of health in a staging system for ABCD severity as an aid to patient management. To effectively address stigma and IWB within a chronic care model for patients with obesity, there is a need for health care systems that are prepared to provide evidence-based, person-centered treatments; patients who understand that obesity is a chronic disease and are empowered to seek care and participate in behavioral therapy; and societies that promote policies and infrastructure for bias-free compassionate care, access to evidence-based interventions, and disease prevention., Competing Interests: Disclosures The Task Force was empaneled in accordance with AACE Conflict of Interest (COI) Policy and approved by the AACE COI Subcommittee. All members of the expert Task Force completed AACE’s disclosure form regarding any multiplicities of interests related to commercial and direct financial relationships within the preceding 12 months with companies that develop products connected with endocrine disorders. Categories for disclosure include employment, stock or other ownership, direct financial relationships (eg, speaker or consultant), research funding, authorship or panel involvement on a guidance document related to an overlapping topic, or other situations related to a perceived COI. The AACE COI Subcommittee reviewed these disclosures against an AACE-approved list of ineligible companies for this consensus statement and reached consensus regarding members who could serve on the Task Force in the nonconflicted majority, those who could serve in the conflicted minority with management strategy, and those who were disqualified from serving on the Task Force. The AACE CPG Oversight Committee reviewed and approved the AACE COI Subcommittee’s decisions regarding manageable COI and empanelment. Members of this Task Force were reminded to update potential disclosures if new potential conflicts arose during their appointments and to verify currency of disclosures. AACE made every effort to minimize the potential for conflicts of interest that could influence the recommendations of this CPG. Disclosures related to obesity are provided below; however, none were deemed as conflicts of interest as there were no discussions of treatment or management options in the development of the consensus statement. B.A. serves on speakers’ bureaus for Astra Zeneca, Corcept, Eli Lilly, and Novo Nordisk. J.A. serves on advisory boards for Eli Lilly and Novo Nordisk. W.G. serves as a volunteer consultant on advisory boards for Jazz Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Pfizer without financial compensation, serves on advisory boards for Alnylam Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Fractyl Health, and Novo Nordisk with financial compensation, and receives research support as a site principal investigator for clinical trials sponsored by his institution and funded by Eli Lilly, Novo Nordisk, Epitomee, and Pfizer. T.K. is the owner of Ted Kyle Consulting, LLC and a consultant for Gelesis, Johnson & Johnson, Novo Nordisk, and Nutrisystem. K.N., M.A., M.B., and M.C. have nothing to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Differences in the ability of neutrophils to perform relevant effector functions has been identified in a variety of disease states. Although neutrophil functional heterogeneity is increasingly recognized during disease, few studies have examined neutrophil functional heterogeneity during periods of health. In this study, we systematically characterize neutrophil functional heterogeneity in a cohort of healthy human subjects using a range of biologically relevant agonists including immune complexes, bacterial ligands, and pathogens. With repeated testing over several years, we show that neutrophil functional capability represents a fixed phenotype for each individual. This neutrophil phenotype is preserved across a range of agonists and extends to a variety of effector functions including degranulation, neutrophil extracellular trap release, reactive oxygen species generation, phagocytosis, and bacterial killing. Using well-phenotyped healthy human subjects, we demonstrate that neutrophil functional heterogeneity is characterized by differences in neutrophil gene expression patterns. Altogether, our findings demonstrate that while neutrophil function is highly heterogeneous among healthy subjects, each individual's functional capability represents a fixed phenotype defined by a distinct neutrophil gene expression profile. These findings may be relevant during disease states where the ability to perform relevant neutrophil effector functions may impact disease course and/or clinical outcome., (©2022 Society for Leukocyte Biology.)

We assessed environmental contamination of inpatient rooms housing coronavirus disease 2019 (COVID-19) patients in a dedicated COVID-19 unit. Contamination with severe acute respiratory syndrome coronavirus 2 was found on 5.5% (19/347) of surfaces via reverse transcriptase polymerase chain reaction and 0.3% (1/347) of surfaces via cell culture. Environmental contamination is uncommon in hospitals rooms; RNA presence is not a specific indicator of infectious virus., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: We describe the Clickbusters initiative implemented at Vanderbilt University Medical Center (VUMC), which was designed to improve safety and quality and reduce burnout through the optimization of clinical decision support (CDS) alerts., Materials and Methods: We developed a 10-step Clickbusting process and implemented a program that included a curriculum, CDS alert inventory, oversight process, and gamification. We carried out two 3-month rounds of the Clickbusters program at VUMC. We completed descriptive analyses of the changes made to alerts during the process, and of alert firing rates before and after the program., Results: Prior to Clickbusters, VUMC had 419 CDS alerts in production, with 488 425 firings (42 982 interruptive) each week. After 2 rounds, the Clickbusters program resulted in detailed, comprehensive reviews of 84 CDS alerts and reduced the number of weekly alert firings by more than 70 000 (15.43%). In addition to the direct improvements in CDS, the initiative also increased user engagement and involvement in CDS., Conclusions: At VUMC, the Clickbusters program was successful in optimizing CDS alerts by reducing alert firings and resulting clicks. The program also involved more users in the process of evaluating and improving CDS and helped build a culture of continuous evaluation and improvement of clinical content in the electronic health record., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Longitudinal Integrated Clerkships exist in undergraduate medicine courses. A pilot Pharmacy Longitudinal Clerkship (pPLC) was funded to investigate delivery of this model of clinical education for student pharmacists., Objective(s): To investigate the development, implementation and initial evaluation of a pPLC., Methods: The 11-week pPLC was delivered to two students in two GP practices in Scotland. Mixed theory-based methods were used to gather information on the pPLC structures and processes required and qualitative semi-structured Theoretical Domains Framework (TDF) based interviews explored outcomes with key stakeholders. Informed written consent was obtained. Interviews were audio-recorded, transcribed verbatim and analysed thematically. University Ethics approval was granted., Results: Data were generated on resources and processes required for a pPLC including funds budgeted for and actually spent on staffing, student travel/subsistence and student clinical 'Kit Bags', learning outcomes, curriculum and training timetable, GP Practice/University contracts. Interviews were completed with the two students, three linked GP clinical supervisors and two Regional Tutors involved. The seven themes were identified and mapped to seven TDF domains including: increased levels of student confidence, and increased student enthusiasm for a career in pharmacy, need for definition of the role of the Regional Tutor for the PLC and GP positivity towards the expected outcomes of clerkship model versus traditional placements., Conclusion: Findings are limited by the small number of participants and settings, but evaluation was positive and the work garnered information on requirements for resources and processes. This will inform 'roll out' of the PLC.

Background: Shedding of Clostridioides difficile spores from infected individuals contaminates the hospital environment and contributes to infection transmission. We assessed whether antibiotic selection affects C. difficile shedding and contamination of the hospital environment., Methods: In this prospective, unblinded, randomized controlled trial of hospitalized adults with C. difficile infection, patients were randomized 1:1:1 to receive fidaxomicin, oral vancomycin, or metronidazole. The primary outcome was change in environmental contamination rate during treatment. Secondary outcomes included stool shedding, total burden of contamination, and molecular relatedness of stool versus environmental C. difficile isolates., Results: Of 33 patients enrolled, 31 (94%) completed the study. Fidaxomicin (-0.36 log10 colony-forming units [CFUs]/d [95% confidence interval (CI), -.52 to -.19]; P < .01) and vancomycin (-0.17 log10 CFUs/d [-.34 to -.01]; P = .05) were associated with more rapid decline in C. difficile shedding than metronidazole (-0.01 log10 CFUs/d [95% CI, -.10 to .08). Both vancomycin (6.3% [95% CI, 4.7-8.3) and fidaxomicin (13.1% [10.7-15.9]) were associated with lower rates of environmental contamination than metronidazole (21.4% [18.0-25.2]). With specific modeling of within-subject change over time, fidaxomicin (adjusted odds ratio, 0.83 [95% CI, .70-.99]; P = .04) was associated with more rapid decline in environmental contamination than vancomycin or metronidazole. Overall, 207 of 233 environmental C. difficile isolates (88.8%) matched patient stool isolates by ribotyping, without significant difference by treatment., Conclusions: Fidaxomicin, and to a lesser extent vancomycin, reduces C. difficile shedding and contamination of the hospital environment relative to metronidazole. Treatment choice may play a role in reducing healthcare-associated C. difficile transmission., Clinical Trials Registration: NCT02057198., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)