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Objective: Postoperative communication errors contribute to patient harm and excess costs. There are no existing standards for postoperative handoff to the acute care inpatient unit. We aimed to compare the experiences and preferences of pediatric hospitalists and surgeons about the content and timing of this handoff., Methods: We conducted a cross-sectional multisite survey of pediatric hospitalists and surgeons at 4 hospitals using a novel survey tool developed through a systematic 7-step process. We collected data on the perceived frequency of communication for 37 handoff elements and how essential each element was for an ideal handoff. We used 5-point Likert scales of communication frequency and essentialness. Respondents identified perceived and preferred handoff timing. Mention frequency and timing data were analyzed with the Mann-Whitney U test and Fisher's exact test, respectively., Results: Seventy hospitalists (61%) and 27 surgeons (25%) responded to the survey. Over half of both hospitalist and surgeon respondents rated 13 handoff elements a 5 on the essentialness Likert scale. Surgeons perceived that 33 handoff elements were mentioned significantly more frequently than perceived by hospitalists (P < .05). Of hospitalists, 58% preferred that handoff occur immediately before the patient leaves the postanesthesia care unit. Of surgeons, 60% preferred that handoff occur immediately postoperatively., Conclusions: The 13 core elements we identified may facilitate the development of a standardized handoff checklist for postoperative communication between surgeons and hospitalists on acute care units. Areas of future study could include checklist validation, audits of handoff practice, and qualitative research on handoff preferences., Competing Interests: CONFLICT OF INTEREST DICLOSURES: The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: Rheumatoid arthritis (RA) has a "pre-RA" period in which multiple autoantibodies, including antibodies to citrullinated (cit) proteins (ACPA), rheumatoid factor (RF), anti-peptidyl arginine deiminase (anti-PAD), among others, have been described; however, few studies have tested all autoantibodies in a single pre-RA cohort. This study aims to evaluate the prevalence of multiple autoantibodies in pre-RA and potentially identify an autoantibody profile in pre-RA that indicates imminent onset of clinical RA., Methods: We evaluated 148 individuals with two pre- and one post-RA diagnosis samples available from the Department of Defense Serum Repository and matched controls. Samples were tested for immuglobulin (Ig) G anti-cyclic cit peptide-3 (anti-CCP3), five ACPA fine specificities, five anti-PAD isoforms, as well as RF IgA and RF IgM using commercial platforms; cutoffs were determined using levels present in <1% of controls., Results: Positivity of anti-CCP3, RF IgA and RF IgM, anti-PAD1, anti-cit-vimentin 2, anti-cit-fibrinogen, and anti-cit-histone 1 increased over time in pre-RA, although anti-PAD and ACPA fine specificities were predominately present within anti-CCP3-positive individuals. Within anti-CCP3-positive samples from the pre-RA period, positivity for RFs as well as anti-PAD and ACPA fine specificities classified samples as being closer to the time of RA diagnosis., Conclusion: Multiple autoantibodies are present in pre-RA and increase in positivity as the time of RA diagnosis approaches. These results confirm previous findings predicting imminent RA and provide a pathway using commercial-grade assays to assess the risk for and timing of development of clinical RA., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: This project aims to determine the feasibility of predicting future critical care bed availability using data-driven computational forecast modelling and routinely collected hospital bed management data., Methods: In this proof-of-concept, single-centre data informatics feasibility study, regression-based and classification data science techniques were applied retrospectively to prospectively collect routine hospital-wide bed management data to forecast critical care bed capacity. The availability of at least one critical care bed was forecasted using a forecast horizon of 1, 7 and 14 days in advance., Results: We demonstrated for the first time the feasibility of forecasting critical care bed capacity without requiring detailed patient-level data using only routinely collected hospital bed management data and interpretable models. Predictive performance for bed availability 1 day in the future was better than 14 days (mean absolute error 1.33 vs 1.61 and area under the curve 0.78 vs 0.73, respectively). By analysing feature importance, we demonstrated that the models relied mainly on critical care and temporal data rather than data from other wards in the hospital., Discussion: Our data-driven forecasting tool only required hospital bed management data to forecast critical care bed availability. This novel approach means no patient-sensitive data are required in the modelling and warrants further work to refine this approach in future bed availability forecast in other hospital wards., Conclusions: Data-driven critical care bed availability prediction was possible. Further investigations into its utility in multicentre critical care settings or in other clinical settings are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Intracranial pressure (ICP) monitoring is a very commonly performed neurosurgical procedure but there is a wide variation in how it is reported, hindering analysis of it. The current study sought to generate consensus on the reporting of ICP monitoring recording data., Research Question: "What should be included in an ICP monitoring report?", Material and Methods: The exercise was completed via a modified eDelphi survey. An expert panel discussion was held from which themes were identified and used to produce a code to annotate the transcript of the discussion. Statements were generated for a further two rounds of electronic questionnaires distributed via the REDcap platform. A Likert scale was used to grade agreement with each statement in the survey. A statement was accepted if more than 70% agreement was achieved between respondents. Data was collated using Microsoft Excel and analysed using R., Results: 149 relevant statements were identified from the transcript and categorised into recording parameters, waveform characteristics or reporting. A total of 22 statements were generated for the first round of the survey which was answered by 39 respondents. Following the electronic round of surveys consensus was achieved for all but one statement regarding the acceptability of automating ICP reporting. This was put forward to a second round after which 79% agreement was reached., Discussion and Conclusion: The themes and statements from this eDelphi can be used as a framework to allow the standardisation of the reporting of intracranial pressure monitoring data., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Numerous complex physiological models derived from intracranial pressure (ICP) monitoring data have been developed. More recently, techniques such as machine learning are being used to develop increasingly sophisticated models to aid in clinical decision-making tasks such as diagnosis and prediction. Whilst their potential clinical impact may be significant, few models based on ICP data are routinely available at a patient's bedside. Further, the ability to refine models using ongoing patient data collection is rare. In this paper we identify and discuss the challenges faced when converting insight from ICP data analysis into deployable tools at the patient bedside., Research Question: To provide an overview of challenges facing implementation of sophisticated ICP models and analyses at the patient bedside., Material and Methods: A narrative review of the barriers facing implementation of sophisticated ICP models and analyses at the patient bedside in a neurocritical care unit combined with a descriptive case study (the CHART-ADAPT project) on the topic., Results: Key barriers found were technical, analytical, and integrity related. Examples included: lack of interoperability of medical devices for data collection and/or model deployment; inadequate infrastructure, hindering analysis of large volumes of high frequency patient data; a lack of clinical confidence in a model; and ethical, trust, security and patient confidentiality considerations governing the secondary use of patient data., Discussion and Conclusion: To realise the benefits of ICP data analysis, the results need to be promptly delivered and meaningfully communicated. Multiple barriers to implementation remain and solutions which address real-world challenges are required., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Laura Moss reports financial support was provided by 10.13039/501100006041Innovate UK. Martin Shaw reports financial support was provided by 10.13039/501100006041Innovate UK. Ian Piper reports financial support was provided by 10.13039/501100006041Innovate UK. Christopher Hawthorne reports financial support was provided by 10.13039/501100006041Innovate UK., (© 2024 The Authors.)

Introduction: Intracranial pressure (ICP) monitoring is commonly used in investigating the aetiology of chronic paediatric neurological conditions. A series of high-amplitude spikes has been observed in overnight ICP recordings of some children, many of whom have hydrocephalus or craniosynostosis., Research Question: This clinical evaluation aimed to define the spike pattern, describe the patient group in which it is most likely to occur, and conduct high-resolution waveform analysis., Material and Methods: ICP waveforms from 40 patients aged 0-5 years (inclusive), recorded between 2017 and 2021 at the Royal Hospital for Children Glasgow, were retrospectively analysed. The pattern was defined through visual inspection of regions of interest by two reviewers. Patients were stratified using demographic and clinical data. R software was used to perform regression and high-resolution waveform analyses., Results: The spike pattern was defined as the presence of 2 consecutive spikes with an amplitude of at least 8 mmHg, with a gap of at least 30 min between spikes. In the adjusted Poisson regression, age was significantly associated with the number of spikes (IRR 0.8, 95% CI 0.70 to 0.92, p-value 0.001)., Discussion and Conclusion: Younger age was significantly associated with an increased number of spikes in this cohort. Investigation of clinical consequences of the spikes is warranted., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Amarah Saeed reports financial support was provided by Neuro Anaesthesia & Critical Care Society (via National Institute of Academic Anaesthesia). Amarah Saeed reports financial support was provided by 10.13039/501100000294Medical Research Scotland., (© 2024 The Authors.)

Objective: To investigate immune dysregulation in the peripheral blood that contributes to the pre-rheumatoid arthritis (RA) stage of RA development in anticitrullinated protein antibody (ACPA)+ individuals., Methods: Using 37 markers by mass cytometry, we investigated peripheral blood mononuclear cells (PBMCs) from ACPA+ at-risk individuals, ACPA+ early untreated patients with RA, and ACPA- controls in the Tokyo Women's Medical University cohort (n = 17 in each group). Computational algorithms, FlowSOM and Optimized t-Distributed Stochastic Neighbor Embedding, were employed to explore specific immunologic differences between study groups. These findings were further evaluated, and longitudinal changes were explored, using flow cytometry and PBMCs from the US-based Targeting Immune Responses for Prevention of RA cohort that included 11 ACPA+ individuals who later developed RA (pre-RA), of which 9 had post-RA diagnosis PBMCs (post-RA), and 11 ACPA- controls., Results: HLA-DR + peripheral helper T (Tph) cells, activated regulatory T cells, PD-1 hi CD8 + T cells, and CXCR5 - CD11c - CD38 + naive B cells were significantly expanded in PBMCs from at-risk individuals and patients with early RA from the Tokyo Women's Medical University cohort. Expansion of HLA-DR + Tph cells and CXCR5 - CD11c - CD38 + naive B cells was likewise found in both pre-RA and post-RA time points in the Targeting Immune Responses for Prevention of RA cohort., Conclusion: The expansion of HLA-DR + Tph cells and CXCR5 - CD11c - CD38 + naive B cells in ACPA+ individuals, including those who developed inflammatory arthritis and classified RA, supports a key role of these cells in transition from pre-RA to classified RA. These findings may identify a new mechanistic target for treatment and prevention in RA., (© 2024 American College of Rheumatology.)

Introduction: Partial pressure of brain tissue oxygen (PbtO2) has been shown to be a safe an effective monitoring modality to compliment intracranial pressure (ICP) monitoring. It is related to metabolic activity, disease severity and mortality., Research Question: Understanding the complex relationship between PbtO2 and ICP for patients with traumatic brain injury will enable better clinical decision making beyond simple threshold treatment strategies., Material and Methods: Patients with PbtO2 monitoring were identified from the BrainIT database, a multi-centre dataset, containing minute by minute PbtO2 and ICP readings. Missing data was imputed and a multi-level log-normal regression model with a compound symmetry correlation structure was built. This accounted for any increased correlation due to the repeated measurements. The model was adjusted for mean arterial pressure and the partial pressure of carbon dioxide. Non-linearity was assessed using analysis of deviance and trends using expected marginal means., Results: 11 subjects with over 82,000 readings were included. They had a median age of 38 (IQR: 37-47), 73% were male, a median length of stay of 11.8 (IQR: 6.6-19.7) days and a median extended Glasgow outcome scale of 7.00 (IQR: 5-8).There is a statistically significant (p < 0.001) non-linear effect of ICP on PbtO2. With an overall increase in PbtO2 of 5.2% (95% CI 4%-6.4%, p < 0.001) for a 10 mmHg increase in ICP below 22 mmHg and a decrease of 5.5% (95% CI 2.7%-8.3%, p=<0.001) in PbtO2 for a 10 mmHg increase in ICP above 22 mmHg. As well as a decrease of 40.9% (95% CI 2.3%-64.3%, p = 0.040) in PbtO2 per day in the intensive care unit., Discussion and Conclusion: This model demonstrates that there is a significant non-linear relationship between ICP and PbtO2, however, this is a small heterogeneous cohort and further validation will be required., Competing Interests: The authors declare that they have no competing interests.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The characteristics of a neighborhood's built environment may influence health-promoting behaviors, interactions between neighbors, and perceptions of safety. Although some research has reported on how youth in high-violence communities navigate danger, less work has investigated how these youth perceive the built environment, their desires for these spaces, and how these desires relate to their conceptions of safety and perceptions of other residents. To fill this gap, this study used focus group data from 51 youth ages 13-24 living in New Orleans, Louisiana. Four themes were developed using reflexive thematic analysis: community violence is distressing and disruptive, youth use and want to enjoy their neighborhood, systemic failure contributes to negative outcomes, and resources and cooperation create safety. This analysis indicates that young people desire to interact with the built environment despite the threat of community violence. They further identified built environment assets that facilitate socialization and recreation, such as local parks, and social assets in the form of cooperation and neighbor-led civic engagement initiatives. In addition, the youth participants demonstrated awareness of structural inequities that influence neighborhood health and violence-related outcomes. This study contributes to efforts to understand how youth with high levels of community violence exposure understand and interact with the built and social environments., (© 2024. The Author(s).)

Background: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response., Methods: In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics., Results: Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/ml at low and high dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/ml at low and high dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47 ± 0.20 µg/ml. The steady state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51 ± 0.04 µg/ml. A concentration of 1 µg/ml ENA-001 was required for full reversal of the propofol effect at the propofol concentration that reduced the hypoxic ventilatory response by 50%., Conclusions: In this pilot study, the authors demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Pyrolysis is the process whereby carbonaceous materials, such as biosolids, are heated between 400°C and 900°C in the absence of oxygen. Three main products are generated: a solid product called biochar, a py-liquid that consists of aqueous phase and non-aqueous phase liquid, and py-gas. The biochar holds value as a beneficial soil amendment and sequesters carbon. The py-liquid is potentially hazardous and needs to be dealt with (including potentially reducing it on-site via catalysis or thermal oxidation). Py-gas can be used on-site for energy recovery. Pyrolysis has gained recent interest due to concern over per- and polyfluoroalkyl substances (PFAS) in biosolids. Although pyrolysis can remove PFAS from biosolids, it has been shown to produce PFAS that reside in py-liquid, and the fate in py-gas remains a knowledge gap. More research is needed to help close the PFAS and fluorine mass balance through pyrolysis influent and effluent products because pyrolysis alone does not destroy all PFAS. The moisture content of biosolids substantially affects the energy balance for pyrolysis. Utilities that already produce a dried biosolids product are in a better position to install pyrolysis. Pyrolysis has both defined benefits (solids reduction, PFAS removal from biosolids, and biochar production) as well as remaining questions (the fate of PFAS in py-gas and py-liquid, mass balance on nutrients, and py-liquid handling options) that will be answered through more pilot and full-scale demonstrations. Regulations and local policies (such as carbon sequestration credits) could affect pyrolysis implementation. Pyrolysis should be considered as an option in the biosolids stabilization toolbox with application being based on individual circumstances of a utility (e.g., energy, moisture content of biosolids, PFAS). PRACTITIONER POINTS: Pyrolysis has known benefits but limited full-scale operational data. Pyrolysis removes PFAS from biochar, but PFAS fate in gas phase is unknown. Moisture content of influent feed solids affects energy balance of pyrolysis. Policy on PFAS, carbon sequestration, or renewable energy could impact pyrolysis., (© 2023 Water Environment Federation.)

Purpose: The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores., Methods: In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression., Results: A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (OR adj 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (OR adj 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (OR adj 0.1; p = 0.01) and of needing any help (OR adj 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (OR adj 0.4, p = 0.42)., Conclusions: The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question., (© 2023. The Author(s).)

Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs). At these sites, B cells mutate their antibody-encoding genes in the dark zone, followed by preferential selection of the high-affinity variants in the light zone by T cells. The strength of the T cell-derived selection signals is proportional to the B cell receptor affinity and to the magnitude of subsequent Myc expression. However, because the lifetime of Myc mRNA and its corresponding protein is very short, it remains unclear how T cells induce sustained Myc levels in positively selected B cells. Here, by direct visualization of mRNA and active transcription sites in situ, we found that an increase in transcriptional bursts promotes Myc expression during B cell positive selection in GCs. Elevated T cell help signals predominantly enhance the percentage of cells expressing Myc in GCs as opposed to augmenting the quantity of Myc transcripts per individual cell. Visualization of transcription start sites in situ revealed that T cell help promotes an increase in the frequency of transcriptional bursts at the Myc locus in GC B cells located primarily in the LZ apical rim. Thus, the rise in Myc , which governs positive selection of B cells in GCs, reflects an integration of transcriptional activity over time rather than an accumulation of transcripts at a specific time point.

Background: Radiotherapy is a standard treatment modality in cancer therapy, particularly for lung cancer. Diffusing alpha-emitters Radiation Therapy sources (hereafter, "Alpha DaRTs") are fixed with Ra-244 (half-life =3.6 days) that releases alpha-emitting atoms into the tumor tissue to an effective range of a few millimeters., Methods: The feasibility, usability, and safety of Alpha DaRTs deployment and implantation via bronchoscopy into the lung parenchyma and mediastinum in a big animal model of healthy swine was studied in two phases: (I) inert and (II) active Alpha DaRTs deployment. The Alpha DaRTs were inserted in both individual and cluster patterns based on a predefined plan. Swine health was monitored throughout the study. The usability of bronchoscopic deployment and implantation was evaluated using a user questionnaire. The movement and migration of the Alpha DaRTs were assessed. Necropsy was performed, and lungs were evaluated via gross pathology and histopathology., Results: A total of 158 Alpha DaRTs were inserted successfully in the lung parenchyma and mediastinum of five swine in two phases. It was possible to deliver and place the Alpha DaRTs in clusters of no more than 4 mm distance between the Alpha DaRTs. No adverse event or change in the health and general condition of animals was observed. Hematologic evaluation did not show any clinically significant abnormality related to the Alpha DaRTs. Histopathology demonstrated local mild inflammatory changes, minimal fibrosis, and dystrophic mineralization with giant cells. Minimal movement and no migration of Alpha DaRTs were observed., Conclusions: Bronchoscopic deployment of Alpha DaRTs in the lung parenchyma and mediastinum of the porcine animal is feasible, precise, and safe., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-23-639/coif). All authors report that this study was funded by Alpha Tau Medical. A.S. (Ali Sadoughi) has been compensated for the expenses of educational and training events by Merit Medical, Olympus, Siemens, AcuityMD and Boston Scientific, served on advisory board for Mauna Kea, received consulting fee from Alpha Tau Medical and Olympus, and has stock option at Alpha Tau. N.O. received research funds from AstraZeneca and Merck and received consulting fees from AstraZeneca, Genentech and Merck. The authors have no other conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

This qualitative study explored the role of neglected properties and neighborhood environment characteristics on a sample of New Orleans, Louisiana residents' health and well-being, sense of community, sense of safety, and civic engagement. We hypothesized that residents would identify conditions of their neighborhood's physical environment, including neglected properties, as one factor that impacted their health and other aspects of well-being. Seventy-four (N = 74) participants, including women, men, youth, young adults, and community leaders, took part in 11 focus groups (n = 51) and 23 key informant interviews. Thematic content analysis through inductive and deductive coding cycles of interview transcripts revealed five main categories related to urban neighborhood-built and social environments: 1) health and well-being, 2) sense of community, 3) sense of safety, 4) civic engagement, and 5) youth and family violence. Ten themes were developed and included, for example, the role of neighborhoods in delineating access to health-promoting characteristics and resources; the role of neighborhood social networks as crime prevention strategies; resident-led decision-making in neighborhood improvements; the negative impact of neglected properties; and the role of the local government in improving physical infrastructure. These findings affirm that residents were aware of and impacted by the cyclical nature of built environment neglect on health and well-being, community violence, neighborhood cohesion, civic engagement, and youth violence. Participants recommended improving neighborhood conditions to shift resident mindsets about the health of neighborhoods, reduce violence, and improve quality of life., (© The Author(s) 2024.)

Background: Noradrenergic signaling declines in Parkinson's disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that β-acting drugs slow PD progression., Objective: The primary objective was to compare the safety and effects of 3 β-adrenoceptor (β-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of β-AR acting drugs in HVs and PD-patients., Methods: In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20μg on Day 1, 40μg on Day 2, 80μg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests., Results: Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral β2-AR effects were observed with clenbuterol., Conclusions: This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS.

Objectives: To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development., Methods: This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis' major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort., Results: Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27-3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20-2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10-8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity., Conclusions: Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Oliceridine (Olinvyk) is a μ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. This study was designed to determine the utility function of oliceridine versus morphine based on neurocognitive tests and cold pressor test., Methods: The study had a randomized, double-blind, placebo-controlled, partial block three-way crossover design. Experiments were performed in 20 male and female volunteers. The subjects received intravenous oliceridine (1 or 3 mg; cohorts of 10 subjects/dose), morphine (5 or 10 mg; cohorts of 10 subjects/dose), or placebo on three separate occasions. Before and after dosing, neurocognitive tests, cold pressor test, and plasma drug concentrations were obtained at regular intervals. Population pharmacokinetic-pharmacodynamic analyses served as the basis for construction of a utility function, which is an objective function of probability of benefit minus probability of harm. Antinociception served as the measure of benefit, and slowing of saccadic peak velocity and increased body sway as the measures of neurocognitive harm., Results: The oliceridine and morphine C50 values, i.e., the effect-site concentrations causing 50% effect, were as follows: antinociception, 13 ± 2 and 23 ± 7 ng/ml; saccadic peak velocity, 90 ± 14 and 54 ± 15 ng/ml; and body sway, 10 ± 2 and 5.6 ± 0.8 ng/ml, respectively. The ratio oliceridine/morphine of the therapeutic indices, C50(benefit)/C50(harm), were 0.34 (95% CI, 0.17 to 0.7; P < 0.01) for saccadic peak velocity and 0.33 (0.16 to 0.50; P < 0.01) for body sway. The oliceridine utility was positive across the effect-site concentration 5 to 77 ng/ml, indicative of a greater probability of benefit than harm. The morphine utility was not significantly different from 0 from 0 to 100 ng/ml. Over the concentration range 15 to 50 ng/ml, the oliceridine utility was superior to that of morphine (P < 0.01). Similar observations were made for body sway., Conclusions: These data indicate that over the clinical concentration range, oliceridine is an analgesic with a favorable safety profile over morphine when considering analgesia and neurocognitive function., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is 'at-risk' for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA. Tetramer studies show increased abundance of T cells recognizing citrullinated (cit) epitopes in At-Risk participants, including expansion of T cells reactive to citrullinated cartilage intermediate layer protein I (cit-CILP); these T cells have Th1, Th17, and T stem cell memory-like phenotypes. Antibody-antigen array analyses show that antibodies targeting cit-clusterin, cit-fibrinogen and cit-histone H4 are elevated in At-Risk and Early RA participants, with the highest levels of antibodies detected in those with Early RA. These findings indicate that an ACPA positive at-risk state is associated with multifaceted immune dysregulation that may represent a potential opportunity for targeted intervention., (© 2023. The Author(s).)

Intimate partner violence (IPV) among Black adolescents is a critical public health issue, as they report higher levels of IPV perpetration and victimization than their counterparts from other racial groups. Although practitioners frequently implement educational programs to reduce and prevent adolescent relationship violence among adolescents, the extent to which these interventions have been culturally tailored to Black youth is unclear. The purpose of this scoping review is to investigate the nature and effects of cultural tailoring in IPV interventions delivered to Black adolescent populations as well as any critical media literacy (CML) content therein. We conducted searches of three databases for peer-reviewed research published in the United States between 2000 and 2020 that evaluated an IPV-focused educational intervention with a predominantly Black adolescent sample. A total of eight original studies met our inclusion criteria. Findings showed that five of the articles mentioned some level of cultural tailoring for the participants. However, the level and nature of that tailoring ranged widely with regard to curriculum development, staffing, and other program elements. No studies included any elements of CML education. Overall results indicate positive effects of IPV interventions on adolescents and reduced acceptance of violence in romantic relationships. This scoping review highlights a lack of clarity on methods used for cultural tailoring of curriculum based IPV interventions, vague application of social learning theoretical frameworks, and the potential benefits of CML content.

Background: Borrelia persica causes tick-borne relapsing fever in Israel, the eastern Mediterranean basin, and Asia. Relapsing fever is associated with severe illness and potentially death in humans and animals. Since B. persica infection has rarely been described in wild animals, the aim of this study was to evaluate the prevalence of infection with B. persica in wild carnivores in Israel., Methods: Spleen and blood clot samples from wild carnivores, which underwent necropsy, were tested for the presence of Borrelia DNA by real-time polymerase chain reaction (PCR). PCR products were sequenced, and the spirochete loads were quantified using a specific quantitative PCR (qPCR)., Results: A total of 140 samples from 74 wild carnivores were analyzed for the presence of Borrelia DNA. Six out of the 74 (8.1%) animals were found positive for B. persica by PCR and sequencing of the flagellin B gene, of which 4/74 (5.4%) were also positive by PCR for the glycerophosphodiester phosphodiesterase (glpQ) gene. Positive samples were obtained from three European badgers, and one striped hyena, golden jackal, and red fox each. All B. persica-positive animals were young males (P < 0.0001). Quantifiable results were obtained from 3/5 spleen and 4/5 blood samples. The spirochete loads in the blood were significantly higher than those found in the spleen (P = 0.034)., Conclusions: The prevalence of B. persica infection found in wild carnivores brought for necropsy was unexpectedly high, suggesting that this infection is widespread in some wild animal species in Israel. This is the first report of B. persica infection in the European badger and striped hyena. These carnivores have a wide geographical range of activity, and the results of this survey raise the possibility that they may serve as reservoir hosts for B. persica., (© 2023. The Author(s).)

Thrombopoietin (THPO or TPO) is an essential cytokine for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Here, we report the 3.4 Å resolution cryoelectron microscopy structure of the extracellular TPO-TPO receptor (TpoR or MPL) signaling complex, revealing the basis for homodimeric MPL activation and providing a structural rationalization for genetic loss-of-function thrombocytopenia mutations. The structure guided the engineering of TPO variants (TPO mod ) with a spectrum of signaling activities, from neutral antagonists to partial- and super-agonists. Partial agonist TPO mod decoupled JAK/STAT from ERK/AKT/CREB activation, driving a bias for megakaryopoiesis and platelet production without causing significant HSC expansion in mice and showing superior maintenance of human HSCs in vitro. These data demonstrate the functional uncoupling of the two primary roles of TPO, highlighting the potential utility of TPO mod in hematology research and clinical HSC transplantation., Competing Interests: Declaration of interests K.C.G., N.T., and I.S.H. are inventors on a United States provisional patent (63/519,687, filed 15 August 2023) related to the mutant TPO molecules described in the manuscript., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Magnetic resonance imaging scanner faults can be missed during routine quality assurance (QA) if they are subtle, intermittent, or the test being performed is insensitive to the type of fault. Coil element malfunction is a common fault within MRI scanners, which may go undetected for quite some time. Consequently, this may lead to poor image quality and the potential for misdiagnoses., Purpose: Daily QA typically consists of an automated signal to noise ratio test and in some instances this test is insensitive to coil element malfunction. Instead of relying on daily QA testing, it was proposed to utilize patient images in conjunction with a trained neural network to detect coil element malfunction, even when it presents as a very subtle defect. The advantage to using patient images over phantom testing is real-time monitoring can be achieved. This allows clinical staff to focus more on patient throughput without being burdened by daily testing., Methods: A neural network was trained using simulated coil failure in 3958 abdominal or pelvic images from 497 patients. The accuracy of the trained network was then tested on an unseen dataset of 109 images from which 44 patients which had coil element malfunction present. Five MRI radiographers were shown 249 images with and without real coil malfunction to assess their accuracy compared to the neural network in identifying the scanner fault., Results: The neural network achieved an accuracy of 91.74% in identifying coil element malfunction in the unseen data. Radiographers tasked with identifying coil element malfunction had an average accuracy of 59.99%. In the same test case, the neural network outperformed all radiographers with an accuracy of 91.56%., Conclusion: This work demonstrates that neural networks trained with artificial data can successfully identify MRI scanner coil element malfunction in clinical images. The method provided better accuracy than MRI radiographers (technologists) at identifying coil element malfunction and highlights the potential utility of AI methods as an alternative to support traditional QA. Further, our methodology of training neural networks with simulated data could potentially identify other faults, allowing centers to produce robust fault detection systems with minimal data., (© 2023 American Association of Physicists in Medicine.)

Purpose: The aim of this study was to validate the new European Organisation for Research and Treatment of Cancer Quality of Life Thyroid Cancer Module (EORTC QLQ-THY34). Methods: We enrolled 437 thyroid cancer patients from 17 countries. One group ( n  = 303), undergoing treatment or best supportive care, completed the questionnaires at three time points (before therapy [t1], 6 weeks later [t2], and 6 months after t2 [t3]). A second group (survivors ≥2 years after diagnosis, n  = 134) completed it at a random baseline time point and a second time 1 week later. We determined internal consistency (using Cronbach's alpha), the scale structure (with confirmatory factor analysis), and discriminant validity (using known-group comparisons). Group 1 data were used to assess responsiveness and group 2 data to determine test-retest reliability using intra-class correlations (ICC). Results: All 34 items fulfilled the criteria to be kept in the questionnaire. Cronbach's alpha was >0.70 in 8 of the 9 multi-item scales. All standardized factor loadings exceeded 0.40, confirming the proposed scale structure. The ICC was >0.70 in all scales expressing good test-retest reliability. Differences in scale scores between patients with different histology were >5 points in all scales. In all but one of the pre-specified scales ( Dry Mouth ), changes over time were ≥|4| points between at least two time points. Conclusion: The EORTC QLQ-THY34 with its 9 multi-item and 8 single-item scales is a reliable and valid tool to measure quality of life in thyroid cancer patients and can be used in future trials and studies.

Background: This survey-based study identified views on antiobesity medications in youth referred to a weight management program. Methods: One parent completed a 14-item Research Electronic Data Capture (REDcap) survey regarding openness to medication use in youth with obesity at their first visit in a weight management program. Medical data were extracted from the medical records of all responders. Results: Ninety-four percent (116/125) of parents approached completed the survey (youths' demographic: mean age = 14.1 years old, 46.8% female, 68.8% Hispanic). Results indicate that 75% of parents surveyed were open to medication use. There was no difference in sex, age, insurance, severity of obesity, or family history between parents who were and were not open to medication (all p  > 0.05). Hispanic ethnicity was associated with greater openness to medication use (odds ratio: 3.4, 95% confidence interval: 1.4-8.5, p  = 0.007). Conclusions: These results highlight the importance of parental perceptions of medication use for obesity treatment and suggest a need for improved education about the role of medication in the management of pediatric obesity.