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Neurodiversity has come hugely to the fore in recent years in a variety of contexts, and is now subject to academic debate, activist discussion, and increasingly embedded in a range of institutional and corporate settings in the Global North, from workplaces to early years education, from psychotherapy to mainstream political discourses. The term has gained traction in Medical Humanities, as well as debate within bioethics, philosophy of psychology, and of law. Institutionally, it is now relied on in therapeutic practice, autism service provision, as well as in higher education, in particular. In this conceptual article we examine what is at stake in these usages and the implications in need of scrutiny. We resituate neurodiversity in relation to questions of disability by examining the deployment of neurology as the basis for identity, rights and benefits. The emergence of the term and the understandings to which it gives rise, we argue, leave out urgent questions of what is at stake for disabled people in a political climate of increasing harshness and ableism., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Significant progress has been made in preventing severe COVID-19 disease through the development of vaccines. However, we still lack a validated baseline predictive biologic signature for the development of more severe disease in both outpatients and inpatients infected with SARS-CoV-2. The objective of this study was to develop and externally validate, via 5 international outpatient and inpatient trials and/or prospective cohort studies, a novel baseline proteomic signature, which predicts the development of moderate or severe (vs mild) disease in patients with COVID-19 from a proteomic analysis of 7000 + proteins. The secondary objective was exploratory, to identify (1) individual baseline protein levels and/or (2) protein level changes within the first 2 weeks of acute infection that are associated with the development of moderate/severe (vs mild) disease. For model development, samples collected from 2 randomized controlled trials were used. Plasma was isolated and the SomaLogic SomaScan platform was used to characterize protein levels for 7301 proteins of interest for all studies. We dichotomized 113 patients as having mild or moderate/severe COVID-19 disease. An elastic net approach was used to develop a predictive proteomic signature. For validation, we applied our signature to data from three independent prospective biomarker studies. We found 4110 proteins measured at baseline that significantly differed between patients with mild COVID-19 and those with moderate/severe COVID-19 after adjusting for multiple hypothesis testing. Baseline protein expression was associated with predicted disease severity with an error rate of 4.7% (AUC = 0.964). We also found that five proteins (Afamin, I-309, NKG2A, PRS57, LIPK) and patient age serve as a signature that separates patients with mild COVID-19 and patients with moderate/severe COVID-19 with an error rate of 1.77% (AUC = 0.9804). This panel was validated using data from 3 external studies with AUCs of 0.764 (Harvard University), 0.696 (University of Colorado), and 0.893 (Karolinska Institutet). In this study we developed and externally validated a baseline COVID-19 proteomic signature associated with disease severity for potential use in both outpatients and inpatients with COVID-19., (© 2023. The Author(s).)

Background: Traumatic rib fractures are associated with high morbidity and mortality. Clinical decision support systems (CDSS) have been shown to improve adherence to evidence-based (EB) practice and improve clinical outcomes. The objective of this study was to investigate if a rib fracture CDSS reduced hospital length of stay (LOS), 90-day and 1-year mortality, unplanned ICU transfer, and the need for mechanical ventilation. The independent association of two process measures, an admission EB order set and a pain-inspiratory-cough score early warning system, with LOS were investigated., Methods: The CDSS was scaled across nine US trauma centers. Following multiple imputation, multivariable regression models were fit to evaluate the association of the CDSS on primary and secondary outcomes. As a sensitivity analysis, propensity score matching was also performed to confirm regression findings., Results: Overall, 3,279 patients met inclusion criteria. Rates of EB practices increased following implementation. On risk-adjusted analysis, in-hospital LOS preintervention versus postintervention was unchanged (incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 0.97-1.15, p = 0.2) but unplanned transfer to the ICU was reduced (odds ratio, 0.28; 95% CI, 0.09-0.84, p = 0.024), as was 1-year mortality (hazard ratio, 0.6; 95% CI, 0.4-0.89, p = 0.01). Provider utilization of the admission order bundle was 45.3%. Utilization was associated with significantly reduced LOS (IRR, 0.87; 95% CI, 0.77-0.98; p = 0.019). The early warning system triggered on 34.4% of patients; however, was not associated with a significant reduction in hospital LOS (IRR, 0.76; 95% CI, 0.55-1.06; p = 0.1)., Conclusion: A novel, user-centered, comprehensive CDSS improves adherence to EB practice and is associated with a significant reduction in unplanned ICU admissions and possibly mortality, but not hospital LOS., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Background & Aims: Pancreatitis is a disease continuum, starting with acute pancreatitis (AP) and progressing in some cases to recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP). Currently, there are no approved therapies or early diagnostic or prognostic biomarkers for pancreatitis. The current study examined whether patient serum immune profiling could identify noninvasive biomarkers and provide mechanistic insight into the disease continuum of pancreatitis., Methods: Using Olink immunoassay, we assessed the protein levels of 92 immune markers in serum samples from participants enrolled in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) study of the Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) consortium. Samples (N = 231) were obtained from individuals without pancreatic disease (n = 56) and from those with chronic abdominal pain (CAP) (n = 24), AP (n = 38), RAP (n = 56), and CP (n = 57)., Results: A total of 33 immune markers differentiated the combined pancreatitis groups from controls. Immune markers related to interleukin (IL) 17 signaling distinguished CP from AP and RAP. Similarly, the serum level of IL17A and C-C motif chemokine ligand 20 differentiated CP from CAP, suggesting the involvement of T helper 17 cells in CP pathogenesis. The receiver operator characteristic curve with 2 immune markers (IL17A and sulfotransferase 1A1) could differentiate CP from CAP (optimistic area under the curve = 0.78). The macrophage classical activation pathway elevated along the continuum of pancreatitis, suggesting an accumulation of proinflammatory signals over disease progression. Several immune markers were associated with smoking, alcohol, and diabetes status., Conclusions: Immune profiling of serum samples from a large pancreatitis cohort led to identifying distinct immune markers that could serve as potential biomarkers to differentiate the varying pancreatitis disease states. In addition, the finding of IL17 signaling in CP could provide insight into the immune mechanisms underlying disease progression., (Copyright © 2023 AGA Institute. All rights reserved.)

Objective: We critically evaluated the surgical literature to explore the prevalence and describe how equity assessments occur when using clinical decision support systems., Background: Clinical decision support (CDS) systems are increasingly used to facilitate surgical care delivery. Despite formal recommendations to do so, equity evaluations are not routinely performed on CDS systems and underrepresented populations are at risk of harm and further health disparities. We explored surgical literature to determine frequency and rigor of CDS equity assessments and offer recommendations to improve CDS equity by appending existing frameworks., Methods: We performed a scoping review up to Augus 25, 2021 using PubMed and Google Scholar for the following search terms: clinical decision support, implementation, RE-AIM, Proctor, Proctor's framework, equity, trauma, surgery, surgical. We identified 1415 citations and 229 abstracts met criteria for review. A total of 84 underwent full review after 145 were excluded if they did not assess outcomes of an electronic CDS tool or have a surgical use case., Results: Only 6% (5/84) of surgical CDS systems reported equity analyses, suggesting that current methods for optimizing equity in surgical CDS are inadequate. We propose revising the RE-AIM framework to include an Equity element (RE 2 -AIM) specifying that CDS foundational analyses and algorithms are performed or trained on balanced datasets with sociodemographic characteristics that accurately represent the CDS target population and are assessed by sensitivity analyses focused on vulnerable subpopulations., Conclusion: Current surgical CDS literature reports little with respect to equity. Revising the RE-AIM framework to include an Equity element (RE 2 -AIM) promotes the development and implementation of CDS systems that, at minimum, do not worsen healthcare disparities and possibly improve their generalizability., Competing Interests: C.J.T. is a PI for 2 RCTs investigating ARBs in the treatment of COVID-19 among inpatient and outpatients. Co-Is include N.E.I. C.J.T. is supported by an AHRQ K12HS026379 focused on scaling of thoracic trauma clinical decision support systems. NIH NHLBI T32HL07741 (N.E.I.). T.J.L. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number K23 GM140268. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. G.B.M. is supported by AHRQ R01HS024532-01A1, NIH/NIGMS R01 GM120079, NIH/NCRR U01 TR002062, NIH/NIDA R33 DA046084, NIH/NCATS UL1 TR002494. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Federated learning (FL) allows multiple distributed data holders to collaboratively learn a shared model without data sharing. However, individual health system data are heterogeneous. "Personalized" FL variations have been developed to counter data heterogeneity, but few have been evaluated using real-world healthcare data. The purpose of this study is to investigate the performance of a single-site versus a 3-client federated model using a previously described Coronavirus Disease 19 (COVID-19) diagnostic model. Additionally, to investigate the effect of system heterogeneity, we evaluate the performance of 4 FL variations., Materials and Methods: We leverage a FL healthcare collaborative including data from 5 international healthcare systems (US and Europe) encompassing 42 hospitals. We implemented a COVID-19 computer vision diagnosis system using the Federated Averaging (FedAvg) algorithm implemented on Clara Train SDK 4.0. To study the effect of data heterogeneity, training data was pooled from 3 systems locally and federation was simulated. We compared a centralized/pooled model, versus FedAvg, and 3 personalized FL variations (FedProx, FedBN, and FedAMP)., Results: We observed comparable model performance with respect to internal validation (local model: AUROC 0.94 vs FedAvg: 0.95, P = .5) and improved model generalizability with the FedAvg model (P < .05). When investigating the effects of model heterogeneity, we observed poor performance with FedAvg on internal validation as compared to personalized FL algorithms. FedAvg did have improved generalizability compared to personalized FL algorithms. On average, FedBN had the best rank performance on internal and external validation., Conclusion: FedAvg can significantly improve the generalization of the model compared to other personalization FL algorithms; however, at the cost of poor internal validity. Personalized FL may offer an opportunity to develop both internal and externally validated algorithms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

As telehealth continues to evolve, there is a subsequent need to develop efficient and effective teaching models in this realm. Primary care is well positioned to teach telehealth because of the breadth of medical conditions treated. It is crucial that learners and medical educators are prepared for learning and educating in this growing paradigm. This article offers an organized approach to education in telehealth that includes preparation, observation, assessment, and feedback., Competing Interests: Disclosure The authors have no relevant disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The purpose of our study was to evaluate the perceptions of clinical faculty while working with medical students in a novel setting of virtual care following the COVID-19 pandemic., Activity: A survey of faculty, fellows, and residents was conducted to assess educators' perceptions of virtual teaching before trying it and after 3 months of experience., Results: Perceived effectiveness of teaching students acute care significantly improved as did perceived effectiveness of teaching chronic care., Discussion: We anticipate that continued experience and comfort with virtual platforms would boost this perception further, allowing faculty development to be honed for optimal teaching in this new paradigm., Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01685-9., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2022.)

Interprofessional experiences during medical school are often delivered during pre-clinical years, but less is known about the value of clinical students. Our institution implemented a specialty-specific interprofessiona curriculum during Residency Preparation Courses (RPCs) for senior students including didactics, clinical experiences, and a simulated paging curriculum. Our aim was to determine whether this intervention improved perceptions of interprofesiona roles. We distributed anonymous surveys before (pre-survey) and after (post-survey, collected within 2 weeks of course completion) the RPC to 90 students with questions related to interprofessional roles using a 5-point scale (1 =  strongly disagree , 5 =  strongly agree ). Three months after the start of residency, we sent follow-up surveys inquiring about the usefulness of RPC components (1 =  not at all useful , 5 =  extremely useful ). Response rates were 84.4% pre-survey, 63.3% post-survey, and 41.1% follow-up survey. Post-surveys indicated improvement in self-reported ability in all domains: understanding one's contributions to interprofessional teams (3.9 to 4.4, p < .0001), understanding other team members' contributions (3.9 to 4.4, p < .0001), learning from interprofessional team members (4.2 to 4.6, p = .0002), accounting for interprofessional perspectives (4.2 to 4.6, p < .0001), and co-developing effective care plans (3.9 to 4.4, p < .0001). Follow-up surveys rated clinical experiences as slightly-to-moderately useful (2.3 ± 1.0) and paging curriculum very-to-extremely useful (4.3 ± 1.0). This study demonstrates the value of interprofessional education for advanced students.

Background: Trauma clinical decision support systems improve adherence with evidence-based practice but suffer from poor usability and the lack of a user-centered design. The objective of this study was to compare the effectiveness of user and expert-driven usability testing methods to detect usability issues in a rib fracture clinical decision support system and identify guiding principles for trauma clinical decision support systems., Methods: A user-driven and expert-driven usability investigation was conducted using a clinical decision support system developed for patients with rib fractures. The user-driven usability evaluation was as follows: 10 clinicians were selected for simulation-based usability testing using snowball sampling, and each clinician completed 3 simulations using a video-conferencing platform. End-users participated in a novel team-based approach that simulated realistic clinical workflows. The expert-driven heuristic evaluation was as follows: 2 usability experts conducted a heuristic evaluation of the clinical decision support system using 10 common usability heuristics. Usability issues were identified, cataloged, and ranked for severity using a 4-level ordinal scale. Thematic analysis was utilized to categorize the identified usability issues., Results: Seventy-nine usability issues were identified; 63% were identified by experts and 48% by end-users. Notably, 58% of severe usability issues were identified by experts alone. Only 11% of issues were identified by both methods. Five themes were identified that could guide the design of clinical decision support systems-transparency, functionality and integration into workflow, automated and noninterruptive, flexibility, and layout and appearance. Themes were preferentially identified by different methods., Conclusion: We found that a dual-method usability evaluation involving usability experts and end-users drastically improved detection of usability issues over single-method alone. We identified 5 themes to guide trauma clinical decision support system design. Performing usability testing via a remote video-conferencing platform facilitated multi-site involvement despite a global pandemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) are widely used medications with an unacceptably high rate of prescription errors and are a leading cause of adverse drug events. Clinical decision support, including medication alerts, can be an effective implementation strategy to reduce prescription errors, but quality is often inconsistent. User-centered design (UCD) approaches can improve the effectiveness of alerts., Objectives: To design effective DOAC prescription alerts through UCD and develop a set of generalizable design recommendations., Methods: This study used an iterative UCD process with practicing clinicians. In three rapid iterative design and assessment stages, prototype alert designs were created and refined using a test electronic health record (EHR) environment and simulated patients. We identified key emergent themes across all user observations and interviews. The themes and final designs were used to derive a set of design guidelines., Results: Our UCD sample comprised 13 prescribers, including advanced practice providers, physicians in training, primary care physicians, and cardiologists. The resulting alert designs embody our design recommendations, which include establishing intended indication, clarifying dosing by renal function, tailoring alert language in drug interactions, facilitating trust in alerts, and minimizing interaction overhead., Conclusions: Through a robust UCD process, we have identified key recommendations for implementing medication alerts aimed at improving evidence-based DOAC prescribing. These recommendations may be applicable to the implementation of DOAC alerts in any EHR systems., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: Chronic pancreatitis (CP) is a chronic fibroinflammatory condition of the pancreas difficult to diagnose in early stages. Novel biomarkers useful to facilitate early diagnosis or treatment responses may be found in biofluids. Although saliva can be easily and noninvasively collected from patients, useful salivary biomarkers from CP patients have not yet been identified., Methods: Here, we analyzed the proteome by quantitative proteomics, cytokine/chemokine levels by Luminex analysis, prostaglandin E2 (PGE2) levels by a mass spectrometry-based assay, and bacterial species diversity by 16S ribosomal ribonucleic acid sequencing in saliva samples from confirmed CP patients and healthy controls., Results: Our results indicate the presence of various differentially expressed proteins, cytokines/chemokines, and a loss of oral bacterial diversity in the saliva of CP patients. The PGE2 levels trend toward elevation in CP patients. Area under the receiver operating characteristic curve models for proteomic, cytokine, and PGE2 assays ranged from 0.59 to 0.90., Conclusions: Collectively, our studies identify a range of putative CP biomarkers and alterations in human saliva requiring further validation. The biomarker discovery approaches we used might lead to identification of biomarkers useful for CP diagnosis and monitoring., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: In the midst of the opioid crisis, increasing attention has been given to assessing and addressing substance use disorders (SUDs) among transgender and gender diverse (TGD) populations. As electronic health records begin to more uniformly collect gender identity data, clinicians and public health professionals are better able to examine the prevalence of SUDs and the receipt of SUD treatment services in these populations., Methods: We utilized cross-sectional electronic health records data from January 2005 to December 2019 from a large safety-net hospital in Massachusetts. A cohort of TGD patients was identified using self-reported gender identity data as well as diagnostic and procedures codes associated with receipt of gender-affirming care (n = 2000). We calculated odds of SUD diagnosis and receipt of medications for SUD among TGD patients., Results: Among a cohort of 2000 TGD patients, 8.8% had a SUD diagnosis. SUD diagnoses were more common among older, Black, and transmasculine patients, as well as those holding public health insurance. SUD diagnoses were less likely among those reporting college-level education. Of those with an opioid use disorder (OUD), 46% were prescribed an FDA-approved medication for OUD., Conclusions: SUD diagnoses among TGD patients were associated with demographic, socioeconomic, and gender-related factors. We found a modestly lower prevalence of non-tobacco SUD among our cohort of TGD patients than the national average of 7.4%. Despite a relatively better receipt of prescription treatment services than the national average, the low rate of treatment overall represents a missed opportunity to address SUDs in these vulnerable populations., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 American Society of Addiction Medicine.)

Objectives: Delayed-presentation diaphragm hernias are uncommon, and surgical management varies widely across practices. We describe our surgical experience with delayed-presentation diaphragm hernias as a case series of 14 patients, 9 of whom underwent minimally invasive repair., Methods: We performed a retrospective chart review of our prospective database of all patients treated surgically for delayed-presentation diaphragm hernia at our institution from January 1, 2005, to April 30, 2021. We excluded patients with poststernotomy, post-left ventricular assist device, and previously diagnosed congenital hernias. We recorded patient demographics, etiology, laterality, chronicity, operative details, postoperative complications, and long-term results., Results: We performed surgical repair of delayed-presentation diaphragm hernia in 14 patients. Eleven patients (79%) were male, the median age was 61 (18-83) years, the median body mass index was 29.2 (14.5-33.7), and 8 (57%) hernias were left-sided. Etiology was trauma (n = 7, 50%), iatrogenic (n = 5, 36%), and unknown (n = 2, 14%). Median time to presentation in patients with traumatic and iatrogenic hernias was 7.5 years (6 weeks to 38 years). Nine patients (64%) underwent minimally invasive repair, and 5 patients (36%) underwent open repair. We used a synthetic patch in all but 2 patients (86%). Median length of stay was 5 (3-27) days. Two patients (14%) had major complications. There were no deaths. Twelve patients (86%) had follow-up imaging at a median follow-up of 17 months (1-192) with zero recurrences., Conclusions: Our experience suggests that a minimally invasive or an open approach to patients with a delayed-presentation diaphragm hernia is safe and effective. We recommend tailoring the surgical approach based on patient characteristics, anatomic considerations, and surgeons' experience., (© 2022 The Author(s).)

Background: Comprehensive clinical decision support (CDS) care maps can improve the delivery of care and clinical outcomes. However, they are frequently plagued by usability problems and poor user acceptance., Objective: This study aims to characterize factors influencing successful design and use of comprehensive CDS care maps and identify themes associated with end-user acceptance of a thoracic trauma CDS care map earlier in the process than has traditionally been done. This was a planned adaptive redesign stage of a User Acceptance and System Adaptation Design development and implementation strategy for a CDS care map. This stage was based on a previously developed prototype CDS care map guided by the Unified Theory of Acceptance and Use of Technology., Methods: A total of 22 multidisciplinary end users (physicians, advanced practice providers, and nurses) were identified and recruited using snowball sampling. Qualitative interviews were conducted, audio-recorded, and transcribed verbatim. Generation of prespecified codes and the interview guide was informed by the Unified Theory of Acceptance and Use of Technology constructs and investigative team experience. Interviews were blinded and double-coded. Thematic analysis of interview scripts was conducted and yielded descriptive themes about factors influencing the construction and potential use of an acceptable CDS care map., Results: A total of eight dominant themes were identified: alert fatigue (theme 1), automation (theme 2), redundancy (theme 3), minimalistic design (theme 4), evidence based (theme 5), prevent errors (theme 6), comprehensive across the spectrum of disease (theme 7), and malleability (theme 8). Themes 1 to 4 addressed factors directly affecting end users, and themes 5 to 8 addressed factors affecting patient outcomes. More experienced providers prioritized a system that is easy to use. Nurses prioritized a system that incorporated evidence into decision support. Clinicians across specialties, roles, and ages agreed that the amount of extra work generated should be minimal and that the system should help them administer optimal care efficiently., Conclusions: End user feedback reinforces attention toward factors that improve the acceptance and use of a CDS care map for patients with thoracic trauma. Common themes focused on system complexity, the ability of the system to fit different populations and settings, and optimal care provision. Identifying these factors early in the development and implementation process may facilitate user-centered design and improve adoption., (©Emma K Jones, Alyssa Banks, Genevieve B Melton, Carolyn M Porta, Christopher J Tignanelli. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 16.03.2022.)

Background: The concomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS), and the design of a pilot pragmatic implementation trial., Methods: A participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: the nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review., Discussion: This pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase the use of best practices for upper GI bleeding risk reduction., Trial Registration: ClinicalTrials.gov NCT05085405 . Registered on October 19, 2021-retrospectively registered., (© 2022. The Author(s).)

Background and Aims: Acute pancreatitis (AP) is an inflammatory disease with mild to severe course that is associated with local and systemic complications and significant mortality. Uncovering inflammatory pathways that lead to progression and recovery will inform ways to monitor and/or develop effective therapies., Methods: We performed single-cell mass Cytometry by Time Of Flight (CyTOF) analysis to identify pancreatic and systemic inflammatory signals during mild AP (referred to as AP), severe AP (SAP), and recovery using 2 independent experimental models and blood from patients with AP and recurrent AP. Flow cytometric validation of monocytes subsets identified using CyTOF analysis was performed independently., Results: Ly6C + inflammatory monocytes were the most altered cells in the pancreas during experimental AP, recovery, and SAP. Deep profiling uncovered heterogeneity among pancreatic and blood monocytes and identified 7 novel subsets during AP and recovery, and 6 monocyte subsets during SAP. Notably, a dynamic shift in pancreatic CD206 + macrophage population was observed during AP and recovery. Deeper profiling of the CD206 + macrophage identified 7 novel subsets during AP, recovery, and SAP. Differential expression analysis of these novel monocyte and CD206 + macrophage subsets revealed significantly altered surface (CD44, CD54, CD115, CD140a, CD196, podoplanin) and functional markers (interferon-γ, interleukin 4, interleukin 22, latency associated peptide-transforming growth factor-β, tumor necrosis factor-α, T-bet, RoRγt) that were associated with recovery and SAP. Moreover, a targeted functional analysis further revealed distinct expression of pro- and anti-inflammatory cytokines by pancreatic CD206 + macrophage subsets as the disease either progressed or resolved. Similarly, we identified heterogeneity among circulating classical inflammatory monocytes (CD14 + CD16 - ) and novel subsets in patients with AP and recurrent AP., Conclusions: We identified several novel monocyte/macrophage subsets with unique phenotype and functional characteristics that are associated with AP, recovery, and SAP. Our findings highlight differential innate immune responses during AP progression and recovery that can be leveraged for future disease monitoring and targeting., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: To utilize a Luminex platform to examine multiple cytokines simultaneously as well as clinical laboratory testing to identify markers that predict acute pancreatitis severity in the pediatric population on admission., Study Design: Patients (<19 years of age) prospectively enrolled over a 4-year period in a single institution acute pancreatitis database were included in separate derivation and validation cohorts. Plasma samples were obtained within 48 hours of admission and stored for analysis. Samples from mild acute pancreatitis and severe acute pancreatitis (moderately severe and severe combined) were analyzed using Luminex panels and C-reactive protein (CRP) testing., Results: The derivation cohort examined 62 cytokines in 66 subject samples (20 control, 36 mild acute pancreatitis, 10 severe acute pancreatitis) and identified interleukin 6 (IL-6) (P = .02) and monocyte chemotactic protein-1 (MCP-1) (P = .02) as cytokines that were differentially expressed between mild and severe acute pancreatitis. Our validation cohort analyzed 76 cytokines between 10 controls, 19 mild acute pancreatitis, and 6 severe acute pancreatitis subjects. IL-6 (P = .02) and MCP-1 (P = .007) were again found to differentiate mild acute pancreatitis from severe acute pancreatitis. CRP values were obtained from 53 of the subjects, revealing a strong association between elevated CRP values and progression to severe disease (P < .0001)., Conclusions: This study identified and validated IL-6 and MCP-1 as predictors of severe acute pancreatitis using 2 distinct cohorts and showed that CRP elevation is a marker of progression to severe acute pancreatitis. These biomarkers have not been extensively studied in the pediatric acute pancreatitis population. Our data allows for risk-stratification of patients with acute pancreatitis, and represent novel insight into the immunologic response in severe acute pancreatitis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The fourth year of medical school (M4) should prepare students for residency yet remains generally unstructured, with ill-defined goals. The primary aim of this study was to determine whether there were performance changes in evidence-based medicine (EBM) and urgent clinical scenarios (UCS) assessments before and after M4 year., Method: University of Michigan Medical School graduates who matched into internship at Michigan Medicine completed identical assessments on EBM and UCS at the beginning of M4 year and 13 months later during postgraduate year 1 (PGY1) orientation. Individual scores on these assessments were compared using paired t test analysis. The associations of academic performance, residency specialty classification, and initial performance on knowledge changes were analyzed., Results: During academic years 2014 and 2015, 76 students matched into a Michigan Medicine internship; 52 completed identical EBM stations and 53 completed UCS stations. Learners' performance on the EBM assessment decreased from M4 to PGY1 (mean 93% [SD = 7%] vs. mean 80% [SD = 13%], P < .01), while performance on UCS remained stable (mean 80% [SD = 9%] vs. mean 82% [SD = 8%], P = .22). High M4 performers experienced a greater rate of decline in knowledge level compared with low M4 performers for EBM (-20% vs. -4%, P = .01). Residency specialty and academic performance did not affect performance., Conclusions: This study demonstrated degradation of performance in EBM during the fourth year and adds to the growing literature that highlights the need for curricular reform during this year.

Knowledge of the molecular mechanisms of acute pancreatitis is largely based on studies using rodents. To assess similar mechanisms in humans, we performed ex vivo pancreatitis studies in human acini isolated from cadaveric pancreata from organ donors. Because data on these human acinar preparations are sparse, we assessed their functional integrity and cellular and organellar morphology using light, fluorescence, and electron microscopy; and their proteome by liquid chromatography-tandem mass spectrometry. Acinar cell responses to the muscarinic agonist carbachol (CCh) and the bile acid taurolithocholic acid 3-sulfate were also analyzed. Proteomic analysis of acini from donors of diverse ethnicity showed similar profiles of digestive enzymes and proteins involved in translation, secretion, and endolysosomal function. Human acini preferentially expressed the muscarinic acetylcholine receptor M3 and maintained physiological responses to CCh for at least 20 hours. As in rodent acini, human acini exposed to toxic concentrations of CCh and taurolithocholic acid 3-sulfate responded with trypsinogen activation, decreased cell viability, organelle damage manifest by mitochondrial depolarization, disordered autophagy, and pathological endoplasmic reticulum stress. Human acini also secreted inflammatory mediators elevated in acute pancreatitis patients, including IL-6, tumor necrosis factor-α, IL-1β, chemokine (C-C motif) ligands 2 and 3, macrophage inhibitory factor, and chemokines mediating neutrophil and monocyte infiltration. In conclusion, human cadaveric pancreatic acini maintain physiological functions and have similar pathological responses and organellar disorders with pancreatitis-causing treatments as observed in rodent acini., (Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Conventional teaching regarding palatal injection for the removal of maxillary teeth dictates the administration of buccal and palatal injections. Recently, some investigators have questioned the necessity of the palatal injection, suggesting that contemporary local anesthetics might diffuse sufficiently across the buccopalatal cortical bone distance. It has been suggested that because the buccopalatal cortical bone distance increases anteriorly to posteriorly in the maxilla, the success of maxillary extractions with buccal injection only might be related to the anteroposterior position of the tooth. Evidence from clinical trials has only recently become available. Since 2006, 15 clinical trials that examined outcomes of maxillary tooth extractions performed with buccal injection of local anesthetic only have been published. However, there are limited data available on the clinical practice of surgeons., Materials and Methods: An online survey was sent to 276 full members of the Canadian Association of Oral and Maxillofacial Surgeons. Respondents were asked about their use of palatal injection for the removal of maxillary teeth under local anesthesia, including how often they administer a palatal injection for maxillary extractions in each region of the maxilla., Results: Ninety-two responses were received (33%). Most practitioners deliver a palatal injection for every maxillary tooth extraction under local anesthesia. However, there is a substantial number who do not always administer a palatal injection (ie, they give it "most of the time," "occasionally," or "never"). This number decreased in a linear fashion anteriorly to posteriorly in the maxilla (incisors, 17 of 89; canines, 16 of 88; premolars, 13 of 88; first and second molars, 10 of 89; third molars, 10 of 88)., Conclusion: Some surgeons who do not always administer a palatal injection for extraction of maxillary teeth under local anesthesia. The number is larger for anterior compared with posterior teeth., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Zymogen secretory granules in pancreatic acinar cells express two vesicle-associated membrane proteins (VAMP), VAMP2 and -8, each controlling 50% of stimulated secretion. Analysis of secretion kinetics identified a first phase (0-2 min) mediated by VAMP2 and second (2-10 min) and third phases (10-30 min) mediated by VAMP8. Induction of acinar pancreatitis by supramaximal cholecystokinin (CCK-8) stimulation inhibits VAMP8-mediated mid- and late-phase but not VAMP2-mediated early-phase secretion. Elevation of cAMP during supramaximal CCK-8 mitigates third-phase secretory inhibition and acinar damage caused by the accumulation of prematurely activated trypsin. VAMP8 -/- acini are resistant to secretory inhibition by supramaximal CCK-8, and despite a 4.5-fold increase in total cellular trypsinogen levels, are fully protected from intracellular trypsin accumulation and acinar damage. VAMP8-mediated secretion is dependent on expression of the early endosomal proteins Rab5, D52, and EEA1. Supramaximal CCK-8 (60 min) caused a 60% reduction in the expression of D52 followed by Rab5 and EEA1 in isolated acini and in in vivo The loss of D52 occurred as a consequence of its entry into autophagic vacuoles and was blocked by lysosomal cathepsin B and L inhibition. Accordingly, adenoviral overexpression of Rab5 or D52 enhanced secretion in response to supramaximal CCK-8 and prevented accumulation of activated trypsin. These data support that acute inhibition of VAMP8-mediated secretion during pancreatitis triggers intracellular trypsin accumulation and loss of the early endosomal compartment. Maintaining anterograde endosomal trafficking during pancreatitis maintains VAMP8-dependent secretion, thereby preventing accumulation of activated trypsin., (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objectives: Although many medical schools include arts-based activities in their curricula, empirical evidence is lacking regarding how the creation of art might impact medical students and their professional development. We used a qualitative research design in order to understand this process., Methods: We conducted and analysed interviews with 16 medical students who had created and presented original artwork in the context of a required narrative-based undergraduate medical education programme. Teams of students collaborated to create interpretive projects based on common themes arising from conversations with individuals with chronic illness and their families. Open-ended questions were utilised to explore the conceptualisation and presentation of the projects, the dynamics of teamwork and the meaning(s) they might have for the students' professional development. We identified themes using repeated contextual reading of the transcripts, which also enhanced accuracy of the interpretations and ensured saturation of themes., Results: Several major themes and sub-themes were identified. The creation of art led to a sense of personal growth and development, including reflection on past life experiences, self-discovery and an awareness of art as a creative outlet. Students also reported an enhanced sense of community and the development of skills in collaboration. Lastly, students reflected on the human dimensions of illness and medical care and identified an enhanced awareness of the experience of those with illness., Conclusions: A programme involving the creation of art based on stories of illness encouraged students' explorations of conceptions of the self, family and society, as well as illness and medical care, while enhancing the development of a collaborative and patient-centred worldview. Creative art can be a novel educational tool to promote a reflective, humanistic medical practice., (© 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

The purpose of this review was to determine if postoperative sequelae (facial swelling, trismus, pain) and neurological complications are reduced when mandibular third molars are surgically extracted using a piezoelectric device for osteotomy compared with conventional rotary burs, and to determine if there is a difference in operating time between the two techniques. Clinical trials were identified through a search (April 2015) on the PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases. Studies were assessed by study type, characteristics of participants, sample size, surgical technique, cointerventions, outcomes, risk of bias, and findings. We calculated a Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) rating of confidence in the effect estimates. We identified 2515 citations and found 15 eligible clinical trials. Patients who had osteotomies with the piezoelectric device had less facial swelling (standard mean difference -1.15; 95% CI -2.02 to -0.27; p<0.0001), trismus (greater maximum mouth opening, standard mean difference 0.78; 95% CI 0.56 to 1.00; p=0.33) and pain (standard mean difference -0.84; 95% CI -1.55 to -0.13; p<0.0001) at day 1, less facial swelling at day 7 (standard mean difference -0.98; 95% CI -1.52 to -0.44; p=0.05), and a reduced risk of neurological complications (odds ratio (OR) 0.28; 95% CI 0.09 to 0.89; p=0.79). Trismus at day 7 and pain at day 5 did not differ significantly between the two methods. Operating time was longer with the piezoelectric device (standard mean difference 0.83; 95% CI 0.57 to 1.09; p=0.001). The confidence in the effect estimates was low or very low across all outcomes. The findings raise the possibility of an improved clinical healing response to osteotomy with the piezoelectric device compared with one done with conventional rotary burs for surgical extractions of mandibular third molars., (Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

There is a growing body of work examining whether a palatal injection is necessary for the extraction of maxillary teeth with contemporary local anaesthetics. The available literature was reviewed systematically by conducting a search of the PubMed, EMBASE, and Cochrane CENTRAL databases for trials examining outcomes of maxillary tooth extraction where buccal injection of local anaesthetic only was used for one or more test groups. The selected studies were reviewed for study type, sample size, quality, participant characteristics and methodology, outcome variables, and findings. Fifteen studies met the inclusion criteria. Six of the studies were randomized controlled trials. Four studies were controlled clinical trials that did not report randomization. Five were clinical trials that were not controlled and examined outcomes of one or more test groups. The pain of local anaesthetic injection(s) in the test group (buccal injection only) versus control group (buccal and palatal injection), number of cases requiring supplemental buccal or palatal injection in cases of unsuccessful local anaesthesia, and pain during the procedure were designated as primary outcomes. Pain on probing of the mucosa was designated as a secondary outcome. All nine controlled studies that assessed pain during the procedure found no statistically significant difference between the test and control groups., (Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Pancreatic acinar cells have an expanded apical endosomal system, the physiological and pathophysiological significance of which is still emerging. Phosphatidylinositol-3,5-bisphosphate (PI(3,5)P 2 ) is an essential phospholipid generated by PIKfyve, which phosphorylates phosphatidylinositol-3-phosphate (PI(3)P). PI(3,5)P 2 is necessary for maturation of early endosomes (EE) to late endosomes (LE). Inhibition of EE to LE trafficking enhances anterograde endosomal trafficking and secretion at the plasma membrane by default through a recycling endosome (RE) intermediate. We assessed the effects of modulating PIKfyve activity on apical trafficking and pancreatitis responses in pancreatic acinar cells., Methods: Inhibition of EE to LE trafficking was achieved using pharmacological inhibitors of PIKfyve, expression of dominant negative PIKfyve K1877E, or constitutively active Rab5-GTP Q79L. Anterograde endosomal trafficking was manipulated by expression of constitutively active and dominant negative Rab11a mutants. The effects of these agents on secretion, endolysosomal exocytosis of lysosome associated membrane protein (LAMP1), and trypsinogen activation in response to high-dose CCK-8, bile acids and cigarette toxin was determined., Results: PIKfyve inhibition increased basal and stimulated secretion. Adenoviral overexpression of PIKfyve decreased secretion leading to cellular death. Expression of Rab5-GTP Q79L or Rab11a-GTP Q70L enhanced secretion. Conversely, dominant-negative Rab11a-GDP S25N reduced secretion. High-dose CCK inhibited endolysosomal exocytosis that was reversed by PIKfyve inhibition. PIKfyve inhibition blocked intracellular trypsin accumulation and cellular damage responses to high CCK-8, tobacco toxin, and bile salts in both rodent and human acini., Conclusions: These data demonstrate that EE-LE trafficking acutely controls acinar secretion and the intracellular activation of zymogens leading to the pathogenicity of acute pancreatitis.

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.

Acinar cell zymogen granules (ZG) express 2 isoforms of the vesicle-associated membrane protein family (VAMP2 and -8) thought to regulate exocytosis. Expression of tetanus toxin to cleave VAMP2 in VAMP8 knock-out (-/-) acini confirmed that VAMP2 and -8 are the primary VAMPs for regulated exocytosis, each contributing ∼50% of the response. Analysis of VAMP8(-/-) acini indicated that although stimulated secretion was significantly reduced, a compensatory increase in constitutive secretion maintained total secretion equivalent to wild type (WT). Using a perifusion system to follow secretion over time revealed VAMP2 mediates an early rapid phase peaking and falling within 2-3 min, whereas VAMP8 controls a second prolonged phase that peaks at 4 min and slowly declines over 20 min to support the protracted secretory response. VAMP8(-/-) acini show increased expression of the endosomal proteins Ti-VAMP7 (2-fold) and Rab11a (4-fold) and their redistribution from endosomes to ZGs. Expression of GDP-trapped Rab11a-S25N inhibited secretion exclusively from the VAMP8 but not the VAMP2 pathway. VAMP8(-/-) acini also showed a >90% decrease in the early endosomal proteins Rab5/D52/EEA1, which control anterograde trafficking in the constitutive-like secretory pathway. In WT acini, short term (14-16 h) culture also results in a >90% decrease in Rab5/D52/EEA1 and a complete loss of the VAMP8 pathway, whereas VAMP2-secretion remains intact. Remarkably, rescue of Rab5/D52/EEA1 expression restored the VAMP8 pathway. Expressed D52 shows extensive colocalization with Rab11a and VAMP8 and partially copurifies with ZG fractions. These results indicate that robust trafficking within the constitutive-like secretory pathway is required for VAMP8- but not VAMP2-mediated ZG exocytosis., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation, and/or postweaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy, and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. The Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high fat-fed dams took longer, swam farther, and faster to try and find the hidden platform during the 5-day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high fat-fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the N-methyl-d-aspartate receptor (NMDA) receptor subunit NR2B as well as synaptophysin were significantly decreased in response to both maternal and postweaning diets. Synaptotagmin was significantly increased in offspring from high fat-fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.

Background: Despite extensive literature demonstrating differing experiences in menopause around the world, documentation of the experience of menopause in Australian Aboriginal women is scarce, and thus their menopausal experience is relatively unknown. This study aimed to understand Australian Aboriginal women's understanding and experience of menopause and its impact on their lives., Methods: The study was an exploratory qualitative study. Twenty-five Aboriginal women were recruited from a regional centre in the Mid-West region of Western Australia using opportunistic and snowballing sampling. Interviews and focus group discussions were undertaken from February 2011 to February 2012 using open-ended questioning with a yarning technique. Thematic analysis was undertaken of the transcribed interviews., Results: A number of themes were revealed. These related to the language used, meanings and attitudes to menopause, symptoms experienced, the role of men, a lack of understanding, coping mechanisms and the attribution of menopausal changes to something else. The term "change of life" was more widely recognised and signified the process of ageing, and an associated gain of respect in the local community. A fear of menopausal symptoms or uncertainty about their origin was also common. Overall, many women reported insufficient understanding and a lack of available information to assist them and their family to understand the transition., Conclusion: There are similarities between Aboriginal and non-Aboriginal experiences of menopause, including similar symptom profiles. The current language used within mainstream health settings may not be appropriate to this population if it fails to recognise the importance of language and reflect the attributed meaning of menopause. The fear of symptoms and uncertainty of their relationship to menopause demonstrated a need for more information which has not adequately been supplied to Australian Aboriginal women through current services. While this study is with a select population of Aboriginal Australian women, it reveals the importance of acknowledging differences, particularly in use of language to convey ideas and support Aboriginal women experiencing menopause.

Background: There is great variation in experience of menopause in women around the world. The purpose of this study was to review current understanding of Australian Aboriginal and Torres Strait Islander (Indigenous) women's experiences of menopause. The literature pertaining to the perception, significance and experience of menopause from a number of cultural groups around the world has been included to provide context for why Indigenous women's experience might be important for their health and differ from that reported in other studies of Australian women and menopause., Methods: A search of databases including Ovid Medline, Pubmed, Web of Science, AUSThealth, AMED, EMBASE, Global Health and PsychINFO was undertaken from January 2011 to April 2011 using the search terms menopause, Indigenous, Aboriginal, attitudes, and perceptions and repeated in September 2012., Results: Considerable research shows significant variation across cultures in the menopausal experience. Biological, psychological, social and cultural factors are associated with either positive or negative attitudes, perceptions or experiences of menopause in various cultures. Comparative international literature shows that neither biological nor social factors alone are sufficient to explain the variation in experiences of the menopausal transition. However, a strong influence of culture on the menopause experience can be found. The variation in women's experience of menopause indicates that different cultural groups of women may have different understandings and needs during the menopausal transition. While considerable literature exists for Australian women as a whole, there has been little investigation of Australian Indigenous women, with only two research studies related to Indigenous women's experiences of menopause identified., Conclusions: Differences in biocultural experience of menopause around the world suggest the importance of biocultural research. For the Indigenous women of Australia, the relative contribution of culture, social disadvantage and poor general health compared with non-Indigenous women to the experience of menopause is unknown. As such, further research and understanding of the experience of Indigenous women around Australia is needed. This information could assist individuals, families, cultural groups and healthcare providers to enhance management and support for Indigenous Australian women.

The role of carbohydrates on mood and cognition is fairly well established, however research examining the behavioural effects of the other macronutrients is limited. The current study compared the effects of a 25 g glucose drink to energetically matched protein and fat drinks and an inert placebo. Following a blind, placebo-controlled, randomised crossover design, 18 healthy young adults consumed drinks containing fat, glucose, protein and placebo. Cognitive performance was examined at baseline and again 15- and 60 min post drink. Mood was assessed at baseline and then 10-, 35- and 80 min post drink. Attention and speed were enhanced 15 min following fat or glucose ingestion and working memory was enhanced 15 min following protein ingestion. Sixty minutes post drink memory enhancements were observed after protein and memory impairment was observed following glucose. All drinks increased ratings of alertness. The findings suggest that macronutrients: (i) have different windows of opportunity for effects (ii) target different cognitive domains., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The welfare of farmed fish has attracted attention in recent years, which has resulted in notable changes within the aquaculture industry. However, a lack of communication between stakeholders and opposing ethical views are perceived as barriers to achieving consensus on how to improve farmed fish welfare. To address these issues, we developed an interactive approach that could be used during stakeholder meetings to (1) improve communication between different stakeholder groups, (2) build consensus on priorities for farmed fish welfare and (3) establish mechanisms to address welfare priorities. We then applied this approach during a meeting of stakeholders to identify current and future priorities for farmed fish welfare in the UK. During the meeting in the UK, stakeholders initially identified 32 areas that they felt were in need of development for future improvements in farmed fish welfare. These were further refined via peer review and discussion to the seven most important "priority" areas. Establishing a "better understanding of what good fish welfare is" emerged as the highest priority area for farmed fish welfare. The second highest priority area was "the need for welfare monitoring and documentation systems", with mortality recording proposed as an example. The other five priority areas were "[improved understanding of] the role of genetic selection in producing fish suited to the farming environment", "a need for integration and application of behavioural and physiological measures", "the need for a more liberal regime in Europe for introducing new medicines", "a need to address the issues of training existing and new workers within the industry", and "ensuring best practise in aquaculture is followed by individual businesses". Feedback from attendees, and the meeting outputs, indicated that the approach had been successful in improving communication between stakeholders and in achieving consensus on the priorities for farmed fish welfare. The approach therefore proved highly beneficial for future improvements in fish welfare in the UK.

Objectives: Despite being widely consumed, the effects of multi-vitamin supplements on psychological functioning have received little research attention., Methods: Using a mobile phone testing paradigm, 198 males (30-55 years) in full-time employment took part in this randomised, placebo-controlled, double-blind, parallel-groups trial assessing the effects of a multi-vitamin/mineral on cognitive performance and psychological state/mood. Participants completed two cognitive tasks and a number of visual analogue scales (VAS) before and after a full day's work, on the day before, and 7, 14, 21 and 28 days after, commencing their treatment., Results: Participants in the vitamin/mineral group rated themselves as having greater 'physical stamina' across assessments and weeks. They also rated themselves as having had greater 'concentration' and 'mental stamina' during the working day at the assessment carried out after a day's work, but not at the time of the assessment completed prior to work. Participants in this group also reported greater subjective 'alertness' on Bond-Lader mood scales during the post-work assessment on day 14 and both the pre and post-work assessments on day 28., Conclusions: These findings complement the results from the laboratory-based, randomised-controlled trial in the same cohort and suggest that healthy members of the general population may benefit from augmented levels of vitamins/minerals via direct dietary supplementation., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objective: Obese subjects with orthopedic trauma exhibit increased inflammation and an increased risk of pulmonary edema. Prostaglandin E(2) (PGE(2) ) production is elevated during inflammation and associated with increased vascular permeability. We hypothesize that pulmonary edema in obesity following orthopedic trauma is due to elevated PGE(2) and resultant increases in pulmonary permeability., Methods: Orthopedic trauma was induced in both hindlimbs in lean (LZ) and obese Zucker rats (OZ). On the following day, plasma interleukin-6 (IL-6) and PGE(2) levels, pulmonary edema, and pulmonary gas exchange capability were compared between groups: LZ, OZ, LZ with trauma (LZT), and OZ with trauma (OZT). Vascular permeability in isolated lungs was measured in LZ and OZ before and after application of PGE(2) ., Results: As compared with the other groups, the OZT exhibited elevated plasma IL-6 and PGE(2) levels, increased lung wet/dry weight ratio and bronchoalveolar protein concentration, and an impaired pulmonary gas exchange. Indomethacin treatment normalized plasma PGE(2) levels and pulmonary edema. Basal pulmonary permeability in isolated lungs was higher in OZ than LZ, with a further increase in permeability following treatment with PGE(2) ., Conclusions: These results suggest that pulmonary edema in OZ following orthopedic trauma is due to an elevated PGE(2) and resultant increases in pulmonary permeability., (© 2010 John Wiley & Sons Ltd.)

Trefoil factor family 2 (TFF2) is up-regulated in Helicobacter spp.-infected gastric tissues of both humans and mice. To ascertain the biological effects of TFF2 in vivo, TFF2(-/-) C57BL/6 x Sv129 and wild-type (WT) C57BL/6 x Sv129 mice were orally infected with Helicobacter pylori SS1. Mice were evaluated for gastric H. pylori colonization, pathology, and cytokine profiles at 6 and 19 months post inoculation (pi). At 6 months pi, there was a significant difference (P < 0.05) for epithelial criteria (mucosal defects, atrophy, hyperplasia, pseudopyloric metaplasia, and dysplasia) in the corpus of TFF2(-/-) versus WT mice. At 19 months pi, a similar statistical difference in epithelial parameters was noted in the antrum of TFF2(-/-) versus WT mice (P < 0.01). All of the TFF2(-/-) H. pylori-infected mice had high-grade antral dysplasia, including gastric intraepithelial neoplasia, which was statistically significant (P < 0.05) compared with the infected WT mice. Levels of interferon-gamma were markedly elevated in the gastric mucosa of infected TFF2(-/-) mice at both 6 and 19 months pi. TFF2 provided a cytoprotective and/or anti-inflammatory effect against the progression of premalignant lesions of the gastric corpus at 6 months pi and in the pyloric antrum in H. pylori-infected mice at 19 months pi. These data support a protective role for TFF2 in part by modulating levels of gastric interferon-gamma in the development of H. pylori-associated premalignancy of the distal stomach.

1. A field experiment was conducted with commercial broiler breeder females to assess the hypothesis that the provision of bunches of string and bales of wood shavings would provide attractive environmental enrichment and improve welfare by decreasing aggression and feather damage. 2. The experiment was a randomised block factorial design conducted in a commercial flock of 21,600 female broiler breeders in 12 pens of 1800 chicks. Treatments were environmental enrichment (4 plastic coated bales of wood shavings and 50 bunches of string) from hatch (EE1) or 8 weeks of age (EE2) and a control treatment with no environmental enrichment. There were 4 replicates (rooms). 3. Bird activity was videotaped at 5, 10 and 16 weeks of age and subsequently scored for the number of birds using the perch or pecking at a bale, drinker, litter and section of the wall at 10-min intervals for 4 h throughout the photoperiod (24 times/d). Aggression was assessed by determining the number of aggressive acts in 2-min intervals during 8 periods of the day. The skin and feather condition of 25 birds in each pen were scored at 6, 12 and 18 weeks and the condition of the string bunches was scored at the end of the experiment. 4. The proportion of birds pecking the bales, wall and litter declined and the proportion pecking at the drinker and using the perch increased with age. The number of birds pecking at the bale was similar in EE1 and EE2 at 10 and 16 weeks of age. 5. The string bunches were not extensively used. The condition of the bunches of string in EE2 was worse than in EE1 at the end of the experiment. 6. The number of aggressive acts increased with age and there was no consistent difference between treatments. 7. There was an increase with age in the damage score for feathers over the back and wings and around the tail and vent but no differences between treatments.8. Provision of litter in the form of unopened bales of wood shavings was a commercially acceptable form of environmental enrichment, but there was no evidence that behavioural changes associated with feed restriction, including the prevalence of aggression, were improved.

1. Broiler breeder females were fed restricted allocations of a standard wheat-soy ration to meet target body weights. They were housed on raised plastic slotted floors (S) or wood shavings litter (L) from hatch to 8 weeks when each pen of 12 birds was transferred to another pen in the same block in a 2 x 2 factorial experiment (LL, LS, SL and SS). Measures of bird welfare were taken at 4 weeks of age, and at 9 and 10 weeks following transfer to the new pens. 2. At 4 weeks of age, birds reared on S spent more time standing, pecking the feeder, the wall and other birds and less time pecking the floor compared with those on L. Gentle feather pecks, strong feather pecks and strong feather pulls were more common in S than L. 3. Mean body weight was higher and coefficient of variation lower in birds on L than S at the end of the experiment. Feather loss and damage scores at 10 weeks were higher for birds reared from hatch to 8 weeks on S. 4. Birds that were reared on S continued to peck more at the pen walls after transfer to new pens but there was no other carry-over effect on behaviour. Birds on S at 9 and 10 weeks pecked more at the walls and less often at the floor, and rested less often. There was more feather pecking on S than on L in the second week post transfer. 5. Tonic immobility was greater and plasma corticosterone concentrations were lower at the end of the experiment in birds on L than S at 9 and 10 weeks of age. The heterophil-lymphocyte ratio was similar between treatments at 4 weeks and after the birds were moved to a new pen. 6. The results are consistent with the view that litter and wall pecking has de-arousing properties and that this activity is re-directed foraging that diminishes the stress of feed restriction.