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Emergency general surgeons often provide care to severely ill patients requiring surgical interventions and intensive support. One of the primary drivers of morbidity and mortality is perioperative bleeding. In general, when addressing life threatening haemorrhage, blood transfusion can become an essential part of overall resuscitation. However, under all circumstances, indications for blood transfusion must be accurately evaluated. When patients decline blood transfusions, regardless of the reason, surgeons should aim to provide optimal care and respect and accommodate each patient's values and target the best outcome possible given the patient's desires and his/her clinical condition. The aim of this position paper was to perform a review of the existing literature and to provide comprehensive recommendations on organizational, surgical, anaesthetic, and haemostatic strategies that can be used to provide optimal peri-operative blood management, reduce, or avoid blood transfusions and ultimately improve patient outcomes., (© 2024. The Author(s).)

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background and Aims: Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart., Methods: A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells., Results: In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1., Conclusions: Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: This study assessed wound healing in response to a superoxidised solution using an in vitro wound healing model., Method: Prewounded reconstructed full-thickness human skin models were treated with 10µl of either superoxidised solution (Hydrocyn aqua, Bactiguard South East Asia Sdn. Bhd., Malaysia) or Dulbecco's phosphate buffered saline (DPBS) and incubated at 37°C for up to seven days, with additional treatments added every 48 hours. On days 0, 1, 2, 5 and 7, triplicate samples were taken for specific immunostaining against cytokeratin 14 and vimentin. At each timepoint, horizontal and vertical wound diameters were measured to demonstrate wound closure. Maintenance media was taken at the same timepoints for the measurement of secreted proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-ɑ., Results: At day 1, the superoxidised solution induced significantly lower diameter measurements compared with baseline data at day 0. Both treatment groups demonstrated significantly lower diameter measurements by day 2 when compared with the baseline; however, the average wound size of samples treated with the superoxidised solution was significantly lower when compared to the DPBS-treated group (p<0.05). No significant difference in expression of any proinflammatory was identified at any timepoint., Conclusion: Application of the superoxidised solution resulted in significantly improved wound closure over the first 48 hours in comparison to DPBS-treatment. Furthermore, application of the superoxidised solution did not induce significant proinflammatory effects, despite the significantly reduced wound diameter.

Objectives: To compare racial differences and pelvis dimensions between Caucasians and African Americans (AAs) and to develop a risk calculator and scoring system to predict the risk of prolonged operative time and presence of positive surgical margins (PSM) based on these dimensions. Materials and Methods: A retrospective review of 88 consecutive patients undergoing robot-assisted laparoscopic prostatectomy with a preoperative prostate MRI conducted. Data extraction included demographic, perioperative, and postoperative oncologic outcomes. Prostate-specific antigen (PSA) was obtained within 3 months postsurgery. Wilcoxon rank sum and Fisher's exact tests were used to compare continuous and categorical data, respectively. Single and multivariable regression analysis were used to determine contribution of each factor to the composite outcomes. A risk score was created based on this analysis for predicting the composite outcome. Results: We identified 88 consecutive patients with localized prostate cancer that underwent a preoperative prostate MRI. No statistically significant differences were found with respect to age, body mass index, or any postoperative outcome. PSA was lower at diagnosis (6.49 vs 9.72, p  = 0.006) and operative times were shorter in Caucasians. Rates of PSM (13 vs 14, p  = 0.35), biochemical recurrence (4 vs 2, p  = 0.69), and complications did not vary between the groups. Caucasians had wider/shallower pelvis dimensions. Based on these variables, we found that the log (odds of OR time >3 hours or PSM) = -5.333 + 1.158 (if AA) +0.105 × PSA +0.076 × F -0.035 × G with an area under the receiver operating characteristic curve = 0.73. Using the predefined variables, patients can be risk stratified for PSM or prolonged operative times. Conclusions: Several pelvis dimensions were found to be shorter/narrower in AAs and were associated with longer operative times. The presented risk calculator and stratification system may be used to predict prolonged operative time or having PSM.

Image-guided assessment of bile ducts and associated anatomy during laparoscopic cholecystectomy can be achieved with intra-operative cholangiography (IOC) or laparoscopic ultrasound (LUS). Rates of robotically assisted cholecystectomy (RC) are increasing and herein we describe the technique of intra-corporeal biliary ultrasound during RC using the Da Vinci system. For intraoperative evaluation of the biliary tree during RC, in cases of suspected choledocholithiasis, the L51K Ultrasound Probe (Hitachi, Tokyo, Japan) is used. The extrahepatic biliary tree is scanned along its length, capitalising on the benefits of the full range of motion offered by the articulated robotic instruments and integrated ultrasonic image display using TilePro TM software. Additionally, this technique avoids the additional time and efforts required to undock and re-dock the robot that would otherwise be required for selective IOC or LUS. The average time taken to perform a comprehensive evaluation of the biliary tree, from the hepatic ducts to the ampulla of Vater, is 164.1 s. This assessment is supplemented by Doppler ultrasound, which is used to fully delineate anatomy of the porta hepatis, and accurate measurements of the biliary tree and any ductal stones can be taken, allowing for contemporaneous decision making and management of ductal pathologies. Biliary tract ultrasound has been shown to be equal to IOC in its ability to diagnose choledocholithiasis, but with the additional benefits of being quicker and having higher completion rates. We have described our practice of using biliary ultrasound during robotically assisted cholecystectomy, which is ergonomically superior to LUS, accurate and reproducible., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Competing Interests: The workshop was sponsored by GE healthcare. They provided VENUE family ultrasound systems and Vscan Air scanners. The authors have declared no financial interests.

Ventilator-associated pneumonia (VAP) has significant effects on patient outcomes, including prolonging the duration of both mechanical ventilation and stay in the intensive care unit (ICU). The aim of this study was to assess the association between non-invasive ventilation/oxygenation (NIVO) prior to intubation and the rate of subsequent VAP. This was a multicenter retrospective cohort study of adult patients who were admitted to the medical ICU from three tertiary care academic centers in three distinct regions. NIVO was defined as continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP), or high-flow nasal cannula (HFNC) for any duration during the hospitalization prior to intubation. The primary outcome variable was VAP association with NIVO. A total of 17,302 patients were included. VAP developed in 2.6% of the patients (444/17,302), 2.3% (285/12,518) of patients among those who did not have NIVO, 1.6% (30/1879) of patients who had CPAP, 2.5% (17/690) of patients who had HFNC, 8.1% (16/197) of patients who had BiPAP, and 4.8% (96/2018) of patients who had a combination of NIVO types. Compared to those who did not have NIVO, VAP was more likely to develop among those who had BiPAP (adj OR 3.11, 95% CI 1.80-5.37, p < 0.001) or a combination of NIVO types (adj OR 1.91, 95% CI 1.49-2.44, p < 0.001) after adjusting for patient demographics and comorbidities. The use of BiPAP or a combination of NIVO types significantly increases the odds of developing VAP once receiving IMV.

Occupational fatality rates in the commercial fishing industry in the United States remain more than 20 times higher than the national average. The burden of commercial fishing fatalities due to unintentional falls overboard is highest in the Gulf of Mexico (GOM) shrimp fishery. The objective of this quasi-experimental, pre-/post-test project design was disseminating recovery slings to GOM captains/deckhands, training in their use, and assessing the attitudes, beliefs, and intentions of fishermen in their adoption. Due to the COVID-19 pandemic, a land-based simulation was used to train commercial fishermen at three port locations in use of crew overboard (COB) recovery slings. A survey was developed to assess the attitudes, beliefs, and intentions of commercial fishermen in COB recovery. Purposive sampling was employed to recruit 30-50 fishermen at each location. Following pre-/post-training surveys, fishermen received one recovery sling per vessel along with a task list of instructions for use of the sling. A third survey and task list questions were performed at 12-18 months. There were 119 recovery slings and training in their use provided to 123 commercial shrimp fishing vessel owners/captains and deckhands along the Texas and Louisiana Gulf Coast. Repeated measures analysis of variance of the three surveys showed that positive change in normative beliefs was significant for the importance of quickly and safely maneuvering the vessel to the crew member. This change was most significant over the period from the initial training and receipt of the recovery sling by the vessel captain/deckhand, to the time of follow-up 12-18 months later ( p  = .03). Regarding control beliefs, training was associated with immediate statistically significant improved confidence that, with assistance, the fisherman would be able to use the sling and other equipment to hoist the COB ( p  = .02). However, this confidence waned significantly over time ( p  = .03). Attitudes and beliefs of commercial fishermen in the GOM can be favorably influenced toward a COB recovery device, as well as their confidence, and intention to use such devices. However, results show that attitudes and beliefs may wane over time, emphasizing the importance of repeated training and survival drills in this industry.

The United States Department of Agriculture (USDA) Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents (Select Agents List) that threaten crops of economic importance to the United States and regulates the procedures governing containment, incident response, and the security of entities working with them. Every 2 years the USDA DASAT reviews their select agent list, utilizing assessments by subject matter experts (SMEs) to rank the agents. We explored the applicability of multi-criteria decision analysis (MCDA) techniques and a decision support framework (DSF) to support the USDA DASAT biennial review process. The evaluation includes both current and non-select agents to provide a robust assessment. We initially conducted a literature review of 16 pathogens against 9 criteria for assessing plant health and bioterrorism risk and documented the findings to support this analysis. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for ensuring accuracy. Scoring criteria were adopted to ensure consistency. The MCDA supported the expectation that select agents would rank high on the relative risk scale when considering the agricultural consequences of a bioterrorism attack; however, application of analytical thresholds as a basis for designating select agents led to some exceptions to current designations. A second analytical approach used agent-specific data to designate key criteria in a DSF logic tree format to identify pathogens of low concern that can be ruled out for further consideration as select agents. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pillai, Fruetel, West, Anderson, Hernandez, Ball, McNeil, Beck and Morse.)

The benefits of nature tourism, or nature-based travel, are plentiful. For example , participation in nature tours has positively impacted environmental attitudes and behaviors. Unfortunately, while psychologically beneficial, nature-based tourism can hurt the environment through a myriad of factors. Therefore, we must continue to explore ways to make the benefits of nature-based travel more sustainable and impactful. Research suggests that nature-based travel in virtual reality (VR) may impart numerous travel benefits, such as improving conservational behavior and interconnectedness with nature. While these early findings are promising, questions remain regarding the theoretical mechanisms underlying the effects of nature-based VR travel. Therefore, this study explores how VR may provide an avenue to make nature tourism more environmentally friendly while simultaneously making people more environmentally connected and conscious. Furthermore, a theoretical framework is posited that combines concepts from the spatial presence and narrative persuasion literature to help explain the effects. To accomplish these goals, an experiment was conducted using a two-condition (VR travel vs. TV control) between-subjects factorial design with random assignment. The participants were 66 college students from a large Midwestern University in the United States. Results indicated that there wasn't a statistically significant difference between the VR travel condition and the television (TV) control condition regarding the environmental outcome variables. However, while the nature-based VR travel experience did not appear to influence the environmental outcome variables directly, it did indirectly affect them through the mediating roles of spatial presence and narrative engagement.

Background: Gallstone disease poses a significant health burden in the United States. Choledocholithiasis and cholangitis are common complications of gallstone disease for which data on current epidemiological trends are lacking. We aimed to evaluate temporal changes in hospitalization, management, and outcomes for patients with choledocholithiasis and cholangitis., Methods: The National Inpatient Sample was used to identify discharges for choledocholithiasis and cholangitis between 2005 and 2014. Temporal trends were evaluated via annual percent changes (APCs). Joinpoint regression was used to assess inflection points. Multivariable regression models were used to evaluate associations of interest., Results: From 189,362 unweighted discharges for choledocholithiasis and/or cholangitis, there was an increase in discharges for choledocholithiasis (APC 2.3%, 95% confidence intervals, CI, 1.9-2.7%) and cholangitis (APC 1.5%, 95% CI 0.7-2.2%). Procedural interventions were more likely at urban hospitals for choledocholithiasis (adjusted odds ratio, aOR, 2.94, 95% CI 2.72 to 3.17) and cholangitis (aOR 2.97, 95% CI 2.50 to 3.54). In-hospital mortality significantly decreased annually for choledocholithiasis (aOR 0.90, 95% CI 0.88 to 0.93) and cholangitis (aOR 0.93, 95% CI 0.89 to 0.97). In-hospital mortality between rural and urban centers was comparable for choledocholithiasis (aOR 1.16, 95% CI 0.89 to 1.52) and cholangitis (aOR 1.12, 95% CI 0.72 to 1.72)., Conclusions: Hospitalizations for choledocholithiasis and cholangitis have increased between 2005 and 2014, reflecting a growing burden of gallstone disease. Hospital mortality between urban and rural centers is similar, however urban centers have a higher rate of procedural interventions suggesting limitations to accessing procedural interventions at rural centers., (© 2023. The Author(s).)

Intra-abdominal infections (IAI) are among the most common global healthcare challenges and they are usually precipitated by disruption to the gastrointestinal (GI) tract. Their successful management typically requires intensive resource utilization, and despite the best therapies, morbidity and mortality remain high. One of the main issues required to appropriately treat IAI that differs from the other etiologies of sepsis is the frequent requirement to provide physical source control. Fortunately, dramatic advances have been made in this aspect of treatment. Historically, source control was left to surgeons only. With new technologies non-surgical less invasive interventional procedures have been introduced. Alternatively, in addition to formal surgery open abdomen techniques have long been proposed as aiding source control in severe intra-abdominal sepsis. It is ironic that while a lack or even delay regarding source control clearly associates with death, it is a concept that remains poorly described. For example, no conclusive definition of source control technique or even adequacy has been universally accepted. Practically, source control involves a complex definition encompassing several factors including the causative event, source of infection bacteria, local bacterial flora, patient condition, and his/her eventual comorbidities. With greater understanding of the systemic pathobiology of sepsis and the profound implications of the human microbiome, adequate source control is no longer only a surgical issue but one that requires a multidisciplinary, multimodality approach. Thus, while any breach in the GI tract must be controlled, source control should also attempt to control the generation and propagation of the systemic biomediators and dysbiotic influences on the microbiome that perpetuate multi-system organ failure and death. Given these increased complexities, the present paper represents the current opinions and recommendations for future research of the World Society of Emergency Surgery, of the Global Alliance for Infections in Surgery of Surgical Infection Society Europe and Surgical Infection Society America regarding the concepts and operational adequacy of source control in intra-abdominal infections., (© 2023. The Author(s).)

Broiler chicks' responses following combined IBV live attenuated Massachusetts and 793B strains through gel, spray or oculonasal (ON) vaccination routes were cross-compared. Subsequently, the responses following IBV M41 challenge of the unvaccinated and vaccinated groups were also assessed. Post-vaccination humoral and mucosal immune responses, alongside viral load kinetics in swabs and tissues, were determined using commercial ELISA assays, monoclonal antibody-based IgG and IgA ELISA assays and qRT-PCR respectively. After challenged with IBV-M41 strain, humoral and mucosal immune responses, ciliary protection, viral load kinetics, and immune gene mRNA transcriptions between the three vaccination methods were examined and compared. Findings showed that post-vaccinal humoral and mucosal immune responses were similar in all three vaccination methods. Post vaccinal viral load kinetics is influenced by method of administration. The viral load peaked in the ON group within the tissues and the OP/CL swabs in the first and third weeks respectively. Following M41 challenge, ciliary protection and mucosal immune responses were not influenced by vaccination methods as all three methods offered equal ciliary protection. Immune gene mRNA transcriptions varied by vaccination methods. Significant up-regulation of MDA5, TLR3, IL-6, IFN-α and IFN-β genes were recorded for ON method. For both spray and gel methods, significant up-regulation of only MDA5 and IL-6 genes were noted. The spray and gel-based vaccination methods gave equivalent levels of ciliary protection and mucosal immunity to M41 virulent challenge comparable to those provided by the ON vaccination. Analysis of viral load and patterns of immune gene transcription of the vaccinated-challenged groups revealed high similarity between turbinate and choanal cleft tissues compared to HG and trachea. With regards to immune gene mRNA transcription, for all the vaccinated-challenged groups, similar results were found except for IFN-α, IFN-β and TLR3, which were up-regulated only in ON compared to gel and spray vaccination methods., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Postoperative pulmonary complications increase mortality after cardiac surgery. Conventional ultrafiltration may reduce pulmonary complications by removing mediators of bypass-induced inflammation and countering hemodilution. We tested the primary hypothesis that conventional ultrafiltration reduces postoperative pulmonary complications, and secondarily, improves early pulmonary function assessed by the ratio of PaO 2 to fractional inspired oxygen concentration., Methods: This retrospective analysis compared the incidence of postoperative pulmonary complications in adult patients who underwent cardiac surgery, with and without the use of conventional ultrafiltration, by using logistic regression with adjustment for confounding variables. The primary outcome was a composite of reintubation, prolonged ventilation, pneumonia, or pleural effusion. Secondarily, we examined early postoperative lung function using a quantile regression model. We also explored whether red blood cell transfusion differed between groups., Results: Of 8026 patients, 1043 (13%) received conventional ultrafiltration. After adjustment for confounding variables, the incidence of the composite primary outcome was higher in the conventional ultrafiltration group (12.1% vs 9.9%; P = .03), with an estimated odds ratio of 1.25 (95% CI, 1.02-1.53; P = .03). The median (quantiles) PaO 2 -to-fractional inspired oxygen concentration ratio was 373 (303-433) vs 368 (303-428), with the estimated adjusted difference in medians of 5 (95% CI, -5.9 to 16; P = .37). The estimated odds ratio of intraoperative transfusion was 1.38 (95% CI, 1.19-1.60; P < .0001) and for postoperative transfusion was 1.30 (95% CI, 1.14-1.49; P = .0001)., Conclusions: Use of conventional ultrafiltration was not associated with a reduction in the composite of postoperative pulmonary complications or improved early pulmonary function. We found no evidence of benefit from use of conventional ultrafiltration during cardiac surgery., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To understand how micropolitan public health workers (PHWs) experienced burnout antecedents during the COVID-19 pandemic., Methods: We conducted in-depth guided discussions with 34 representatives from 16 micropolitan public health departments using semistructured, open-ended questions about departments' experiences during the COVID-19 pandemic. We coded discussion transcripts to develop themes according to the Six Areas of Worklife model., Results: PHWs described antecedents of burnout that stemmed from organizational and external forces, most notably within the workload, control, reward, and values dimensions of the Six Areas of Worklife model, as well as instances of workplace violence., Conclusions: Our findings support organization-level approaches to reducing and preventing burnout in the micropolitan public health workforce. We discuss addressing specific dimensions of the Six Areas of Worklife model when designing burnout solutions for this essential workforce., Competing Interests: Conflicts of Interest: The authors declare that they have no conflicts of interest., (Copyright © 2023 American College of Occupational and Environmental Medicine.)

The United States Department of Agriculture (USDA), Division of Agricultural Select Agents and Toxins (DASAT) established a list of biological agents and toxins (Select Agent List) that potentially threaten agricultural health and safety, the procedures governing the transfer of those agents, and training requirements for entities working with them. Every 2 years the USDA DASAT reviews the Select Agent List, using subject matter experts (SMEs) to perform an assessment and rank the agents. To assist the USDA DASAT biennial review process, we explored the applicability of multi-criteria decision analysis (MCDA) techniques and a Decision Support Framework (DSF) in a logic tree format to identify pathogens for consideration as select agents, applying the approach broadly to include non-select agents to evaluate its robustness and generality. We conducted a literature review of 41 pathogens against 21 criteria for assessing agricultural threat, economic impact, and bioterrorism risk and documented the findings to support this assessment. The most prominent data gaps were those for aerosol stability and animal infectious dose by inhalation and ingestion routes. Technical review of published data and associated scoring recommendations by pathogen-specific SMEs was found to be critical for accuracy, particularly for pathogens with very few known cases, or where proxy data (e.g., from animal models or similar organisms) were used to address data gaps. The MCDA analysis supported the intuitive sense that select agents should rank high on the relative risk scale when considering agricultural health consequences of a bioterrorism attack. However, comparing select agents with non-select agents indicated that there was not a clean break in scores to suggest thresholds for designating select agents, requiring subject matter expertise collectively to establish which analytical results were in good agreement to support the intended purpose in designating select agents. The DSF utilized a logic tree approach to identify pathogens that are of sufficiently low concern that they can be ruled out from consideration as a select agent. In contrast to the MCDA approach, the DSF rules out a pathogen if it fails to meet even one criteria threshold. Both the MCDA and DSF approaches arrived at similar conclusions, suggesting the value of employing the two analytical approaches to add robustness for decision making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pillai, West, Anderson, Fruetel, McNeil, Hernandez, Ball, Beck and Morse.)

Background: Gallstone disease remains a major health issue. There have been significant changes in the management and demographics of patients with these conditions. We aimed to evaluate trends in hospitalization, management, and post-procedural adverse events for patients with gallstone disease., Methods: The National Inpatient Sample was used to identify discharges for symptomatic cholelithiasis and cholecystitis between 2005 and 2014. Temporal trends were evaluated by calculating annual percent changes (APCs). Joinpoint regression was used to assess inflection points. Multivariable regression models were used to evaluate associations between urban and rural divisions and mortality, use of interventional procedures, and post-procedural adverse events., Results: From 77,394,755 unweighted discharges, there was a decline in discharges for cholelithiasis (APC - 5.5%, 95% confidence intervals, CI, - 7.6 to - 3.4%) and cholecystitis from 2012 to 2014 (APC - 4.5%, 95% CI - 7.2 to - 1.7%). Interventions were more likely at urban hospitals for symptomatic cholelithiasis (odds ratio, OR, 1.49, 95% CI 1.24 to 1.66) and cholecystitis (OR 1.96, 95% CI 1.86 to 2.05). In-hospital mortality significantly decreased annually for patients with cholecystitis (OR 0.92, 95% CI 0.91 to 0.93). In-hospital mortality between rural and urban centers was comparable for symptomatic cholelithiasis (OR 1.27, 95% CI 0.79 to 2.03) and cholecystitis (OR 0.93, 95% CI 0.84 to 1.04)., Conclusions: Hospitalizations for gallstone disease have decreased since the 2010s. In-hospital mortality between urban and rural centers is similar, but urban hospitals utilize a higher rate of procedural interventions. Future studies should evaluate practice trends and costs across inpatient and ambulatory settings between rural and urban divisions., (© 2023. The Society for Surgery of the Alimentary Tract.)

Objectives: Health systems worldwide are faced with the challenge of adequately staffing their hospital services. Much of the current research and subsequent policy has been focusing on nurse staffing and minimum ratios to ensure quality and safety of patient care. Nonetheless, nurses are not the only profession who interact with patients, and, therefore, not the only professional group who has the potential to influence the outcomes of patients while in hospital. We aimed to synthesise the evidence on the relationship between multi-disciplinary staffing levels in hospital including nursing, medical and allied health professionals and the risk of death., Methods: Systematic review. We searched Embase, Medline, CINAHL, and the Cochrane Library for quantitative or mixed methods studies with a quantitative component exploring the association between multi-disciplinary hospital staffing levels and mortality., Results: We included 12 studies. Hospitals with more physicians and registered nurses had lower mortality rates. Higher levels of nursing assistants were associated with higher patient mortality. Only two studies included other health professionals, providing scant evidence about their effect., Conclusions: Pathways for allied health professionals such as physiotherapists, occupational therapists, dietitians, pharmacists, to impact safety and other patient outcomes are plausible and should be explored in future studies., (© 2023. The Author(s).)

The paper explores the role of UK union health and safety representatives and changes to representative structures governing workplace and organisational Occupational Health and Safety (OHS) during COVID-19. It draws upon a survey of 648 UK Trade Union Congress (TUC) Health and Safety (H&S) representatives, as well as case studies of 12 organisations in eight key sectors. The survey indicates expanded union H&S representation, but only half of the respondents reported H&S committees in their organisations. Where formal representative mechanisms existed, they provided the basis for more informal day-to-day engagement between management and the union. However, the present study suggests that the legacy of deregulation and the absence of organisational infrastructures meant that the autonomous collective representation of workers' interests over OHS, independent of structures, was crucial to risk prevention. While joint regulation and engagement over OHS was possible in some workplaces, OHS in the pandemic has been contested. Contestation challenges pre-COVID-19 scholarship suggestingthat H&S representatives had been captured by management in the context of unitarist practice. The tension between union power and the wider legal infrastructure remains salient.

Introduction: Role extension into novel areas of ultrasound practice can be challenging for health care professionals. Expansion into existing areas of advanced practice typically occurs using established processes and accredited training; however, in areas where there is no formal training, there can be a lack of support for how to develop new and progressive clinical roles., Topic Description: This article presents how the use of a framework approach for establishing areas of advanced practice can support individuals and departments with safely and successfully developing new roles in ultrasound. The authors illustrate this via the example of a gastrointestinal ultrasound role, developed in an NHS department., Discussion: The framework approach comprises three elements, each interdependent upon and inform each other: (A) Scope of practice, (B) Education and competency and (C) Governance. (A) Defines (and communicates) the role extension and area(s) of subsequent ultrasound imaging, interpretation and reporting. By identifying the why, how and what is required this informs (B) the education and assessment of competency for those taking on new roles or areas of expertise. (C) Is informed by (A) and is an ongoing process of quality assurance to safeguard high standards in clinical care. In supporting role extension, this approach can facilitate new workforce configurations, skill expansion and enable increasing service demands to be met., Summary: By defining and aligning the components of scope of practice, education/competency and governance, role development in ultrasound can be initiated and sustained. Role extension utilising this approach brings benefits for patients, clinicians and departments., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Aims: To estimate the potential cost-effectiveness of adalimumab compared with standard care alone for the treatment of early-stage Dupuytren's disease (DD) and the value of further research from an NHS perspective., Methods: We used data from the Repurposing anti-TNF for Dupuytren's disease (RIDD) randomized controlled trial of intranodular adalimumab injections in patients with early-stage progressive DD. RIDD found that intranodular adalimumab injections reduced nodule hardness and size in patients with early-stage DD, indicating the potential to control disease progression. A within-trial cost-utility analysis compared four adalimumab injections with no further treatment against standard care alone, taking a 12-month time horizon and using prospective data on EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and resource use from the RIDD trial. We also developed a patient-level simulation model similar to a Markov model to extrapolate trial outcomes over a lifetime using data from the RIDD trial and a literature review. This also evaluated repeated courses of adalimumab each time the nodule reactivated (every three years) in patients who initially responded., Results: The within-trial economic evaluation found that adalimumab plus standard care cost £503,410 per quality-adjusted life year (QALY) gained versus standard care alone over a 12-month time horizon. The model-based extrapolation suggested that, over a lifetime, repeated courses of adalimumab could cost £14,593 (95% confidence interval £7,534 to £42,698) per QALY gained versus standard care alone. If the NHS was willing to pay £20,000/QALY gained, there is a 77% probability that adalimumab with retreatment is the best value for money., Conclusion: Repeated courses of adalimumab are likely to be a cost-effective treatment for progressive early-stage DD. The value of perfect parameter information that would eliminate all uncertainty around the parameters estimated in RIDD and the duration of quiescence was estimated to be £105 per patient or £272 million for all 2,584,411 prevalent cases in the UK. Cite this article: Bone Jt Open  2022;3(11):898-906.

Background: Left ventricular late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) has been associated with increased risk for life-threatening ventricular tachyarrhythmias. The differences in association between LGE characteristics and prognosis in patients with ischemic (ICM) vs. non-ischemic (NICM) cardiomyopathy is incompletely understood., Methods: A total of 168 consecutive patients who underwent CMR imaging with either ICM or NICM were included in our study. LGE extent, location and pattern were examined for association to the primary endpoint of ventricular tachycardia (VT) and secondary endpoint of major adverse cardiac events (MACE)., Results: Of 68 (41%) patients with ICM and 97 (59%) patients with NICM, median LGE mass was 15% (IQR 9-28) for the ICM group and 10% (IQR 6-15) for the NICM group. On multivariate analysis for both groups, LGE characteristics were prognostic while LVEF was not. In patients with ICM, septal and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median) and inferior wall LGE independently predicted the primary endpoint. In patients with NICM, anterior, inferior and apical segment LGE, and involvement of multiple walls predicted both endpoints on multivariate analysis. LGE extent (≥median, number of LGE segments, LGE stratified per 5% increase) and midwall LGE were independent predictors of the primary endpoint., Conclusions: Although LGE was an independent predictor of prognosis in both groups, LGE extent, location, and pattern characteristics were more powerful correlates to worse outcomes in patients with NICM than ICM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tat, Ball, Camren, Wroblewski, Dajani, Goldberg, Kinno, Sanagala, Syed, Wilber and Rabbat.)

Background: Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team., Material and Methods: An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript., Conclusion: Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies., (© 2022. The Author(s).)

Background: This study reports early mortality and survival from colorectal cancer in relation to the pattern of treatments delivered by the multidisciplinary team (MDT) meeting at a high-volume institution in England over 14 years., Methods: All patients diagnosed with colorectal cancer and discussed during MDT meetings from 2003 to 2016 at a single institution were reviewed. Three time intervals (2003-2007, 2008-2012, and 2013-2016) were compared regarding initial surgical management (resection, local excision, non-resection surgery, and no surgery), initial oncological therapy, 90-day mortality, and crude 2-year survival for the whole cohort. Sub-analyses were performed according to age greater or less than 80 years., Results: The MDT managed 4617 patients over 14 years (1496 in the first interval and 1389 in the last). Over this time, there was a reduction in emergency resections from 15.5 per cent to 9.0 per cent (P < 0.0001); use of oncological therapies increased from 34.6 per cent to 41.6 per cent (P < 0.0001). The 90-day mortality after diagnosis of colorectal cancer dropped from 14.8 per cent to 10.7 per cent (P < 0.001) and 2-year survival improved from 58.6 per cent to 65 per cent (P < 0.001). Among patients aged 80 years or older (425 and 446, in the first and last intervals respectively) there was, in addition, a progressive increase in 'no surgery' rate from 33.6 per cent to 50.2 per cent (P < 0.0001) and a reduction in elective resections from 42.4 per cent to 33.9 per cent (P = 0.010). The 90-day mortality after elective resection fell from 10.0 per cent (18 of 180) to 3.3 per cent (5 of 151; P = 0.013)., Conclusions: Survival from colorectal cancer improved significantly over 14 years. Among patients aged ≥80 years, major changes in the type of treatment delivered were associated with a decrease in postoperative mortality., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

A novel approach for rapid (15s) detection and quantification of predominant cannabinoids in hemp was developed using Fourier-transformed near-infrared spectroscopy (FT-NIR), enabling real-time and field-based applications. Hemp samples (n = 91) were obtained from certified online vendors, the OARDC Weed Lab, and a local Ohio farm. Reference data of major cannabinoids content were determined by uHPLC-MS/MS. Spectral data were collected by a miniaturized, battery-operated FT-NIR instrument, and combined with the reference data to generate partial least squares regression (PLSR) models. uHPLC-MS/MS analysis showed two samples had over 0.36% of Δ9-tetrahydrocannabinol (Δ 9 -THC), and 64% (32 out of 50) of online-bought hemp samples were not in compliance with their total cannabidiol (CBD) content declaration. PLSR prediction models showed excellent correlation (Rpre = 0.91-0.95) and a low standard error of prediction (SEP = 0.02-0.61%). This method could be used as an alternative to traditional methods for in-situ assessment of hemp quality., (Copyright © 2022 Elsevier B.V. All rights reserved.)

1. The role of the Harderian gland (HG), choanal cleft (CC) and turbinate in terms of IBV M41 viral load compared to the trachea, and immune (innate, cellular and mucosal) responses were studied in 21-day-old commercial broiler chickens.2. After virulent IBV M41 challenge, the antigen concentration detected either by quantitative RT-PCR or immunohistochemistry peaked at 2-3 days post challenge (dpc) in all tissues. Significant increases of lachrymal IBV-specific IgA and IgY levels were found at 4-5 dpc.3. Gene transcription showed a significant up-regulation of TLR3, MDA5, IL-6, IFN-α and IFN-β, where patterns and magnitude fold-change of mRNA transcription were dependent on the gene and tissue type.4. The results demonstrated active IBV M41 replication in the HG, CC and turbinate, comparable to levels of replication found in the trachea. Data on immune-related genes in head-associated tissues provide further understanding on the immunobiology of IBV and offer opportunities to identify their use as quantitative biomarkers in pathogenicity and vaccination-challenge studies.

Background: Dupuytren's disease is a common fibrotic condition that causes the fingers to flex irreversibly into the palm. Treatments for late-stage disease all have limitations, and there is no approved treatment for early-stage disease. We identified tumour necrosis factor as a therapeutic target in Dupuytren's disease, and in a dose ranging trial found 40 mg adalimumab in 0·4 mL to be most efficacious. Here we aimed to assess the effects of intranodular injection of adalimumab in early-stage disease., Methods: In this phase 2b, randomised, double-blind, placebo-controlled trial adults with early-stage Dupuytren's disease and an established clinically distinct nodule with a clear history of progression in the preceding 6 months were recruited from two clinical centres in the UK and were randomly assigned 1:1 to receive four injections of adalimumab or saline every 3 months. Participants and assessors were masked. The primary outcome was nodule hardness measured with a durometer at 12 months. Data were analysed by linear mixed effects regression models in the intention-to-treat population with multiple imputation for missing primary outcome data. The trial is registered at the ISRCTN registry, ISRCTN 27786905 and is complete., Findings: Between Feb 17, 2017, and Jan 11, 2019, 284 participants were screened in the UK and 140 were enrolled. 47 (34%) participants were female and 93 (66%) were male. Mean age of participants was 59·7 years (SD 10·0). Primary outcome data were available from 113 participants. Nodule hardness was lower (-4·6 AU [95% CI -7·1 to -2·2], p=0·0002) in the adalimumab compared with the saline group at 12 months. There were no related serious adverse events; the most common adverse events were minor injection site reactions., Interpretation: Intranodular injections of adalimumab in participants with early-stage Dupuytren's disease resulted in softening and reduction in size of the nodules. Longer follow-up would be required to assess the effect of tumour necrosis factor inhibition on disease progression, extension deficit and hand function., Competing Interests: Declaration of interests JN receives consulting fees and has received research grants from 180 Life Sciences Corp (180LS). MF has been executive co-chairman of 180LS since November 2020 and receives payment for this. JN and MF hold stock in 180LS, which has exclusively licensed intellectual property for the treatment of Dupuytren’s disease from the University of Oxford. SEL was appointed as a member of the Scientific Advisory Board of 180LS in Feb, 2022, and has not received any payments. The other authors declare no competing interests.

Objective: While interest in elective robotic surgery is growing, use in emergency setting remains limited due to challenges posed by sicker patients, advanced pathology and logistical issues. During the COVID-19 pandemic, robotic surgery could provide the benefit of having the surgeon away from the bedside and reducing the number of directly exposed medical staff. The objective of this study was to report patient outcomes and initial learning experience of emergency robotic colorectal surgery during the COVID-19 pandemic., Methods: A case series study was conducted, including patients undergoing emergency robotic colorectal surgery between February 2020 and February 2021 at Queen Alexandra Hospital in Portsmouth, UK. Patient data were collected from an ethics approved prospective database. Patient demographics, operative time, conversions and postoperative complications were recorded. In addition, readmissions, length of stay and short-term oncological outcomes were analyzed., Results: Ten patients with median age 64 y (range, 36-83 y) were included. Four patients had robotic complete mesocolic resection for obstructing cancers. Six had colorectal resections for benign disease in emergency setting. All were R0 with a mean lymph node harvest of 54 ± 13. Mean operative time was 249 ± 117 min, the median length of stay was 9.4 d (range, 5-22 d). Only one patient was given a temporary diverting ileostomy. There were no grade III/V complications and no 30-day mortality., Conclusions: Provided an experienced team and peri-operative planning, emergency robotic colorectal surgery can achieve favorable outcomes with benefits of radical lymph node dissection in oncological cases and avoidance of diverting stoma., (© 2022 Zhejiang University. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Autoimmune encephalitis represents an increasingly recognized group of immune-mediated disorders the affect the central nervous system. The purpose of this article is to highlight the characteristic MR imaging findings associated with autoimmune encephalitis, describe the pathophysiology, review antibodies that have been identified and their patterns of CNS involvement, and discuss approaches to management. Familiarity with the imaging and clinical features of autoimmune encephalitis will prompt the radiologist to suggest the diagnosis which can facilitate appropriate management., (Published by Elsevier Inc.)

Avian metapneumovirus (aMPV) causes respiratory disease and drops in egg production in chickens, and is routinely controlled by vaccination. However, the host's immune response to virulent challenge in vaccinated or unvaccinated broiler chickens is poorly characterized. We show that subtype B vaccination offers heterologous (subtype A challenge) and homologous (subtype B challenge) protection. Subtype B challenge caused significantly greater humoral antibody titres in vaccinated and unvaccinated chickens. In turbinate and lung tissues of unvaccinated-challenged chickens, IgA and IgY mRNA transcription was significantly up-regulated after subtype B challenge compared to subtype A. Cellular immunity (CD8-α and CD8-β) gene transcripts were significantly up-regulated during early and later stages of infection from subtype B or subtype A, respectively. Immune gene transcriptional responses (IL-1β, IL-6 and IL-18) were significantly up-regulated after challenge. Gene transcription results showed that mRNA expression levels of CD8-α, CD8-β, TLR3 and IL-6, particularly in turbinate and trachea tissues, are useful parameters to include in future aMPV vaccination-challenge studies.

Background: Hypertension is a highly prevalent condition, with optimal treatment to BP targets conferring significant gains in terms of cardiovascular outcomes. Understanding why some patients do not achieve BP targets would be enhanced through greater understanding of their health-related quality of life (HRQoL). However, the only English language disease-specific instruments for measurement of HRQoL in hypertension have not been validated in accordance with accepted standards. It is proposed that the Spanish MINICHAL instrument for the assessment of HRQoL in hypertension could be translated, adapted and validated for use in the United Kingdom. The aim of the study was therefore to complete this process., Methods: The MINICHAL authors were contacted and the original instrument obtained. This was then translated into English by two independent English-speakers, with these versions then reconciled, before back-translation and subsequent production of a 2nd reconciled version. Thereafter, a final version was produced after cognitive debriefing, for administration and psychometric analysis in the target population of patients living in the Exeter area (Southwest UK) aged 18-80 years with treatment-naïve grade II-III hypertension, before, during and after 18 weeks' intensive treatment., Results: The English-language instrument was administered to 30 individuals (median age: 58.5 years, 53% male). Psychometric analysis demonstrated a floor effect, though no ceiling effect. Internal consistency for both state of mind (StM) and somatic manifestations (SM) dimensions of the instrument were acceptable (Cronbach's alpha = 0.81 and 0.75), as was test-retest reliability (ICC = 0.717 and 0.961) and construct validity, which was measured through co-administration with the EQ-5D-5L and Bulpitt-Fletcher instruments. No significant associations were found between scores and patient characteristics known to affect HRQoL. The EQ-5D-5L instrument found an improvement in HRQoL following treatment, with the StM and SM dimensions of the English language MINICHAL trending to support this (d = 0.32 and 0.02 respectively)., Conclusions: The present study details the successful English translation and validation of the MINICHAL instrument for use in individuals with hypertension. The data reported also supports an improvement in HRQoL with rapid treatment of grade II-III hypertension, a strategy which has been recommended by contemporaneous European guidelines. Trial registration ISRCTN registry number: 57475376 (assigned 25/06/2015)., (© 2022. The Author(s).)

Purpose of Review: Adaptive sports (AdS), sports modified or created to accommodate persons with disabilities, have been gaining popularity over the last decade. The benefits of exercise in the able-bodied population are well-established. Literature in adaptive sport and the para-athlete continues to improve but is not yet as comprehensive as their able-bodied peers, in part due to the heterogeneity of participants. In this review, we appraise the recent literature pertaining to AdS and identify developing areas within the field., Recent Findings: AdS have been shown to have positive health benefits as well as positive psychosocial benefits. Para-athletes often must overcome a variety of barriers to participation, such as transportation, accessibility, and socioeconomic factors. Facilitators to participation have also been identified, including pre-injury interest in sports, male sex, younger age, and more. In addition to well-known sports like handcycling and wheelchair basketball, adaptive sport continues to evolve, in part due to the COVID-19 pandemic, now including virtual options and E-sports. Para-athletes are also being more closely monitored and evaluated pre, peri, and post competition for injury and injury prevention, including in the realm of concussion management, requiring healthcare professionals, coaches, players, and all to gain further knowledge in adaptive sport and the participating para-athletes., Summary: The physical, psychological, and social benefits of adaptive sports for individuals with disabilities are numerous. Addressing barriers to participation, including novel forms of AdS that utilize innovative technology, may allow more individuals to benefit from AdS., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022.)

Childhood obesity is a growing concern as it can lead to lifelong health problems that carry over into adulthood. A substantial contributing factor to obesity is the physical activity (PA) habits that are formed in early childhood, as these habits tend to sustain throughout adulthood. To aid children in forming healthy PA habits, we designed a mixed reality system called the Virtual Fitness Buddy ecosystem, in which children can interact with a virtual pet agent. As a child exercises, their pet becomes slimmer, faster, and able to play more games with them. Our initial deployment of this project showed promise but was only designed for a short-term intervention lasting three days. More recently, we have scaled it from a pilot grade study to a 9-month intervention comprised of 422 children. Ultimately, our goal is to scale this project to be a nationwide primary prevention program to encourage moderate to vigorous PA in children. This article explores the challenges and lessons learned during the design and deployment of this system at scale in the field.

Objectives: To evaluate and calibrate two candidate preparations for the 4th International Standard for Ferritin (Human, Recombinant) (codes: 19/118 and 19/162) against the 3rd International Standard for Ferritin (Human, Recombinant) (code: 94/572), and three serum commutability samples in an international collaborative study involving 12 laboratories in nine countries., Methods: Eleven of the 12 participating laboratories performed Ferritin quantitation using automated assay platforms and one laboratory used a manual ELISA kit., Results: There was better overall agreement between all laboratories and between assay methods for the potency of preparation 19/118 than for preparation 19/162. The overall geometric mean potency (from all methods) of the candidate 4th International Standard, 19/118, was 10.5 µg/ampoule, with inter-laboratory variability, expressed as % geometric coefficient of variation (GCV), of 4.7%. Accelerated stability studies have predicted both 19/118 and 19/162 to be very stable for long term storage at -20 °C., Conclusions: The candidate 4th International Standard for Ferritin (Human, Recombinant) (19/118) has been shown to be immunologically similar to the 3rd International Standard for Ferritin (Human, Recombinant) (94/572). It was recommended to and accepted by the WHO Expert Committee on Biological Standardization that 19/118 be established as the 4th International Standard for Ferritin (Human, Recombinant) with an assigned potency of 10.5 µg/ampoule and expanded uncertainty limits 10.2-10.8 µg/ampoule (95% confidence; k =2.23)., (© 2021 Bernard Fox et al., published by De Gruyter, Berlin/Boston.)

The coronavirus disease 2019 (COVID-19) pandemic has impacted all aspects of people's lives, including how we work, play, learn, exercise, and socialize. Virtual reality (VR) technology has the potential to mitigate many of the challenges brought about by the pandemic, which has spurred increased adoption. However, relatively low adoption overall and limited software still restrict the power of VR to address COVID-19 difficulties effectively. This study examines how the perceived impacts of COVID-19 might lead to different VR uses and gratifications and device ownership / variability. Furthermore, we investigate the importance of social interactivity within VR for increasing adoption intentions. We surveyed 298 Amazon Mechanical Turk users during the Fall of 2020. Results indicate that the pandemic's perceived impacts influenced the likelihood of acquiring VR for education, tourism, and work. For VR ownership and variability, those who purchased VR during the pandemic were more likely to report buying it for work. Those with access to high-end VR hardware were more likely to report a broader range of uses, including socializing, health, and telemedicine. Validating the importance of various applications during the pandemic, we found that the desire for social interactivity mediates the impacts of COVID-19 on future adoption intentions. Theoretically, we propose several gratifications sought via the use of VR during the pandemic. Practically, we discuss recommendations for future VR research, marketing, and software design., 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., (© 2021 The Authors.)

Background & Aim: The development of hepatocellular carcinoma (HCC) is associated with the formation of communication networks leading to the recruitment of disease-modifying macrophages. However, how oncogenes in tumour cells control paracrine communication is not fully understood., Methods: Transgenic mice with liver-specific expression of the constitutively active yes-associated protein (YAP S127A ) or an orthotopic implantation model served as tumour models. FACS-sorted F4/80 + /CD11b dim /CD146 - /retinoid - macrophages from healthy and tumour-bearing livers were used for transcriptomic profiling. Expression data of 242 human HCCs and a tissue microarray consisting of 91 HCCs and seven liver tissues were analyzed., Results: Screening of primary tumour cells expressing YAP S127A identified CC chemokine ligand 2 (Ccl2) as a macrophage chemoattractant, whose expression was regulated in a YAP/TEA domain family member 4 (TEAD4)-dependent manner. Ccl2 expression was associated with a loss of Kupffer cells (KCs) and an increase in immature macrophages (Mɸ imm ) in hepatocarcinogenesis. Recruited Mɸ imm were characterized by a lack of functional polarization (M0 signature) and high expression of the Ccl2 receptors C-C motif chemokine receptor 2 (Ccr2), C-X3-C motif chemokine receptor 1 (Cx3cr1) and pro-angiogenic platelet-derived growth factors (Pdgfa/Pdgfb). Mɸ imm formed cellular clusters in the perivascular space, which correlated with vascular morphometric changes indicative for angiogenesis. In human HCCs, the M0 signature served as an identifier for poor clinical outcome and CCL2 correlated with YAP expression and vascular network formation., Conclusions: In conclusion, YAP/TEAD4-regulated Ccl2 associates with perivascular recruitment of unpolarized Mɸ imm and may contribute to a proangiogenic microenvironment in liver cancer., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Chicken immune responses to infectious bronchitis virus (IBV) vaccination can depend on route of administration, vaccine strain and bird age. Typically for layer chickens, IBV vaccinations are administered by spray in the hatchery at day-old and boosted at intervals with live vaccines via drinking water (DW). Knowledge of live attenuated IBV vaccine virus kinetics and the immune response in egg-laying hens is exceptionally limited. Here, we demonstrated dissemination of vaccine viruses and differences in hen innate, mucosal, cellular and humoral immune responses following vaccination with Massachusetts or 793B strains, administered by DW or oculonasal (ON) routes. Detection of IBV in the Mass-vaccinated groups was greater during early time-points, however, 793B was detected more frequently at later timepoints. Viral RNA loads in the Harderian gland and turbinate tissues were significantly higher for ON-Mass compared to all other vaccinated groups. Lachrymal fluid IgY levels were significantly greater than the control at 14 days post-vaccination (dpv) for both vaccine serotypes, and IgA mRNA levels were significantly greater in ON-vaccinated groups compared to DW-vaccinated groups, demonstrating robust mucosal immune responses. Cell mediated immune gene transcripts (CD8-α and CD8-β) were up-regulated in turbinate and trachea tissues. For both vaccines, dissemination and vaccine virus clearance was slower when given by DW compared to the ON route. For ON administration, both vaccines induced comparable levels of mucosal immunity. The Mass vaccine induced cellular immunity to similar levels regardless of vaccination method. When given either by ON or DW, 793B vaccination induced significantly higher levels of humoral immunity., (© 2021. The Author(s).)

The tsunami of change triggered by the COVID-19 pandemic has transformed society in a series of cascading crises. Unlike disasters that are more temporarily and spatially bounded, the pandemic has continued to expand across time and space for over a year, leaving an unusually broad range of second-order and third-order harms in its wake. Globally, the unusual conditions of the pandemic-unlike other crises-have impacted almost every facet of our lives. The pandemic has deepened existing inequalities and created new vulnerabilities related to social isolation, incarceration, involuntary exclusion from the labor market, diminished economic opportunity, life-and-death risk in the workplace, and a host of emergent digital, emotional, and economic divides. In tandem, many less advantaged individuals and groups have suffered disproportionate hardship related to the pandemic in the form of fear and anxiety, exposure to misinformation, and the effects of the politicization of the crisis. Many of these phenomena will have a long tail that we are only beginning to understand. Nonetheless, the research also offers evidence of resilience on several fronts including nimble organizational response, emergent communication practices, spontaneous solidarity, and the power of hope. While we do not know what the post COVID-19 world will look like, the scholarship here tells us that the virus has not exhausted society's adaptive potential., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2021 SAGE Publications.)

Background: Left ventricular (LV) hypertrophy (LVH) in uncontrolled hypertension is an independent predictor of mortality, though its regression with treatment improves outcomes. Retrospective data suggest that early control of hypertension provides a prognostic advantage and this strategy is included in the 2018 European guidelines, which recommend treating grade II/III hypertension to target blood pressure (BP) within 3 months. The earliest LVH regression to date was demonstrated by echocardiography at 24 weeks. The effect of a rapid guideline-based treatment protocol on LV remodelling, with very early BP control by 18 weeks remains controversial and previously unreported. We aimed to determine whether such rapid hypertension treatment is associated with improvements in LV structure and function through paired cardiovascular magnetic resonance (CMR) scanning at baseline and 18 weeks, utilising CMR mass and feature tracking analysis., Methods: We recruited participants with never-treated grade II/III hypertension, initiating a guideline-based treatment protocol which aimed to achieve BP control within 18 weeks. CMR and feature tracking were used to assess myocardial morphology and function immediately before and after treatment., Results: We acquired complete pre- and 18-week post-treatment data for 41 participants. During the interval, LV mass index reduced significantly (43.5 ± 9.8 to 37.6 ± 8.3 g/m 2 , p < 0.001) following treatment, accompanied by reductions in LV ejection fraction (65.6 ± 6.8 to 63.4 ± 7.1%, p = 0.03), global radial strain (46.1 ± 9.7 to 39.1 ± 10.9, p < 0.001), mid-circumferential strain (- 20.8 ± 4.9 to - 19.1 ± 3.7, p = 0.02), apical circumferential strain (- 26.0 ± 5.3 to - 23.4 ± 4.2, p = 0.003) and apical rotation (9.8 ± 5.0 to 7.5 ± 4.5, p = 0.003)., Conclusions: LVH regresses following just 18 weeks of intensive antihypertensive treatment in subjects with newly-diagnosed grade II/III hypertension. This is accompanied by potentially advantageous functional changes within the myocardium and supports the hypothesis that rapid treatment of hypertension could improve clinical outcomes., Trial Registration: ISRCTN registry number: 57475376 (assigned 25/06/2015)., (© 2021. The Author(s).)

A cluster of Achromobacter xylosoxidans, an emerging multidrug-resistant aquaphilic bacterium, was identified in 3 long-term-care facility residents. As Pseudomonas aeruginosa and Serratia marcescens were also present in clinical specimens, we conducted an investigation of all 3 water-associated species and identified P. aerguniosa and S. marcescens contamination at the facility. Sequencing analysis linked P. aeruginosa to a clinical isolate. Findings highlight the need for precautionary measures to prevent transmission of water-associated multidrug-resistant bacteria in long-term-care facilities., (Published by Elsevier Inc.)

The sport of Enduro is the newest International Cycling Union sanctioned discipline in mountain biking. There are a number of studies reporting mountain biking injury to date however there are none detailing injuries in Enduro. The aim of the present study was to determine the rate, severity and nature of rider injury during the Enduro World Series. Rider injury, and race and practice exposure data were recorded prospectively during 10 events across the 2017 and 2018 seasons. Incorporating 2010 riders (males 90%; females 10%) from 46 countries. 8.9% of riders were injured with mean 12.3 days time-loss per injury. Racing injury incidence was 38.3/1000 hours and practice injury incidence 3.6/1000 hours (p=0.01). The shoulder/clavicle (12.8% of all injuries), hand (9.0%) and head (9.0%) were the most injured locations. Concussion injury was the most frequent diagnosis (7.4%), and shoulder/clavicle fractures caused the greatest burden (442 total days lost). Of those with concussion 28.6% continued racing, and 42.9% reported no time-loss (i. e. time off) post-race. In conclusion, the rate of injury during EWS race events was comparable to Downhill racing. Targeted injury prevention strategies around rider concussion education and rider qualification criteria may help to reduce the risk of injury in Enduro., Competing Interests: CB is the Enduro World Series Managing Director., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Measurement of the psoas muscle area has been applied to estimate lean muscle mass as a surrogate marker of sarcopenia, but there is a paucity of evidence regarding the influence of sarcopenia on clinical outcomes following inflammatory bowel disease surgery. The aim of this study was to evaluate the association between MRI enterography defined sarcopenia and postoperative complications in patients undergoing elective ileocaecal resection for Crohn's disease. To obtain cross sectional area measurement of the psoas muscle, the freehand area tool was used to trace the margin of each psoas muscle at the level of L4, with the sum recorded as Total Psoas Area (TPA). The total cross sectional muscle area of the abdominal wall was recorded as Skeletal Muscle Area (SMA), while myosteatosis was measured by normalising the psoas muscle intensity with the mean intensity of the cerebrospinal fluid. The primary outcome was the incidence of 30-day postoperative complications in patients in the lowest quartile of TPA and SMA. 31 patients were included and ten patients (32.25%) developed postoperative complications within 30 days of surgery. The cut-off values for the lowest quartile for TPA were 11.93 cm 2 in men and 9.77 cm 2 in women, including a total of 8 patients (25.8%) with 5 patients in this group (62.5%) developing postoperative complications and 3 patients (37.5%) Clavien-Dindo class ≥ 3 complications. The cut-off values for the lowest quartile for SMA were 73.49 cm 2 in men and 65.85 cm 2 in women, with 4 patients out of 8 (50%) developing postoperative complications. Psoas muscle cross sectional area and skeletal mass area can be estimated on Magnetic Resonance Enterography as surrogate markers of sarcopenia with high inter-observer agreement., (© 2020. The Author(s).)

There is currently limited and mixed evidence for the cognitive benefits of Computerized Cognitive Training (CCT) and yoga in persons with Mild Cognitive Impairment (pwMCI). The objective of this study was to investigate the benefit of computerized cognitive training (CCT) vs. physical (yoga) intervention on cognitive abilities. Participants in this study were part of the larger Mayo Clinic's Healthy Action to Benefit Independence and Thinking (HABIT) program comparative effectiveness trial. The HABIT program is designed for pwMCI and their care partner and consists of five behavioral interventions: CCT, Memory Support System-Calendar (MSS-Calendar), wellness education, support groups, and yoga. The subtractive study design randomly withheld one of the interventions for a total of five study arms. Longitudinal mixed-effects regression models were used to investigate the hypothesis that CCT and yoga has a greater positive impact on psychomotor and basic attention abilities at 12 months post-intervention as compared to the other HABIT interventions. Findings showed CCT had a positive impact compared to yoga on the Cogstate psychomotor/attention composite at 12 months post-intervention (ES = 0.54; unadjusted p value = 0.007, adjusted p value = 0.021). The impact of yoga or combining CCT with yoga did not show statistically significant improvement. Continued CCT practice at home showed further benefit on psychomotor/attention at 12 months post-intervention. There was no significant benefit of CCT or yoga on Cogstate learning/working memory composite.

The development of anti-drug antibodies (ADAs) is a serious outcome of treatment strategies involving biological medicines. Coagulation factor VIII (FVIII) is used to treat haemophilia A patients, but its immunogenicity precludes a third of severe haemophiliac patients from receiving this treatment. The availability of patient-derived anti-drug antibodies can help us better understand drug immunogenicity and identify ways to overcome it. Thus, there were two aims to this work: (i) to develop and characterise a panel of recombinant, patient-derived, monoclonal antibodies covering a range of FVIII epitopes with varying potencies, kinetics and mechanism of action, and (ii) to demonstrate their applicability to assay development, evaluation of FVIII molecules and basic research. For the first objective we used recombinant antibodies to develop a rapid, sensitive, flexible and reproducible ex vivo assay that recapitulates inhibitor patient blood using blood from healthy volunteers. We also demonstrate how the panel can provide important information about the efficacy of FVIII products and reagents without the need for patient or animal material. These materials can be used as experimental exemplars or controls, as well as tools for rational, hypothesis-driven research and assay development in relation to FVIII immunogenicity and FVIII-related products., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

This study investigated the pathogenesis of infectious bronchitis virus (Gammacoronavirus) strain Q1 in two commercial broiler chicken lines, and the host immune response to infection. Chicks from each line were grouped into either infected or control. Following Q1 infection at day-old, fast (Line-A) and slow (Line-B) growing chicks were monitored for clinical signs and body weights. At 3, 7, 9, 14, 21 and 28 days post infection (dpi), five birds were humanely euthanised, and trachea, kidney and proventriculus tissues were collected for quantitative RT-PCR and histopathology. Blood was collected weekly to determine IBV-specific ELISA antibody titres. Q1 infection significantly reduced the body weights of Line-A chicks at 14 and 21 dpi, but there were no significant differences in Line-B. Through qRT-PCR, significantly higher viral loads were found in the trachea, proventriculus and kidney tissues of Line-A chicks at 7-9 dpi. At day-old and at 28 dpi, the mean antibody titre in Line-B was notably higher than Line-A. Significant IFN-α mRNA expression was noted in the trachea and kidneys of Line-A, whereas no change occurred in Line-B. Chicks in Line-B, compared to those in Line-A, demonstrated a tissue-dependent increase of IFN-β, TLR3, IL-1β and IL-6 and LITAF gene transcription responses to IBV Q1. It appears that the level of maternal antibodies, growth rates, and other inherent host genetic factors could have influenced the differences in viral loads and immune responses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As of April 16, 2021, U.S. correctional and detention facilities reported 399,631 cases of COVID-19 in incarcerated persons, resulting in 2,574 deaths (1). During July 14-November 30, 2020, COVID-19 was diagnosed in 382 persons incarcerated in Idaho correctional facilities with work-release programs. Work-release programs (which place incarcerated persons in community businesses) have social and economic benefits, but might put participants at increased risk for bidirectional transmission of SARS-CoV-2, the virus that causes COVID-19. The Idaho Department of Correction (IDOC) operates 13 state-run correctional facilities, including six low-security facilities dedicated to work-release programs. This report describes COVID-19 outbreaks in five IDOC facilities with work-release programs,* provides the mitigation strategies that IDOC implemented, and describes the collaborative public health response. As of November 30, 2020, 382 outbreak-related COVID-19 cases were identified among incarcerated persons in five Idaho correctional facilities with work-release programs; two outbreaks were linked to food processing plants. Mitigation strategies that helped to control outbreaks in IDOC facilities with work-release programs included isolation of persons with COVID-19, identification and quarantine of close contacts, mass testing of incarcerated persons and staff members, and temporary suspension of work-release programs. Implementation of public health recommendations for correctional and detention facilities with work-release programs, including mass testing and identification of high-risk work sites, can help mitigate SARS-CoV-2 outbreaks. Incarcerated persons participating in work-release should be included in COVID-19 vaccination plans., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Kris K. Carter is an ex-officio nonvoting member of the Idaho Governor’s COVID-19 Vaccine Advisory Committee. No other potential conflicts of interest were disclosed.

Blaine County, Idaho, a rural area with a renowned resort, experienced a COVID-19 outbreak early in the pandemic. We undertook an epidemiologic investigation to describe the outbreak and guide public health action. Confirmed cases of COVID-19 were identified from reports of SARS-CoV-2-positive laboratory test results to South Central Public Health District. Information on symptoms, hospitalization, recent travel, healthcare worker status, and close contacts was obtained by medical record review and patient interviews. Viral sequence analysis was conducted on a subset of available specimens. During March 13-April 10, 2020, a total of 451 COVID-19 cases among Blaine County residents (1,959 cases per 100,000 population) were reported, with earliest illness onset March 1. The median patient age was 51 years (interquartile range [IQR]: 37-63), 52 (11.5%) were hospitalized, and 5 (1.1%) died. The median duration between specimen collection and a positive laboratory result was 9 days (IQR: 4-10). Forty-four (9.8%) patients reported recent travel and an additional 37 cases occurred in out-of-state residents. Healthcare workers comprised 56 (12.4%) cases; 33 of whom worked at the only hospital in the county, leading to a 15-day disruption of hospital services. Among 562 close contacts monitored by public health authorities, laboratory-confirmed COVID-19 or compatible symptoms were identified in 51 (9.1%). Sequencing results from 34 specimens supported epidemiologic findings indicating travel as a source of SARS-CoV-2, and identified multiple lineages among hospital workers. Community mitigation strategies included school and resort closure, stay-at-home orders, and restrictions on incoming travelers. COVID-19 outbreaks in rural communities can disrupt health services. Lack of local laboratory capacity led to long turnaround times for COVID-19 test results. Rural communities frequented by tourists face unique challenges during the COVID-19 pandemic. Implementing restrictions on incoming travelers and other mitigation strategies helped reduce COVID-19 transmission early in the pandemic., Competing Interests: The authors have declared that no competing interests exist.