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Linguatula serrata ("tongue worm") is a zoonotic intranasal parasite found globally in wild dogs, free-ranging dogs, some domestic dogs, and vulpids. Since there are no sensitive tests currently available, infections are underdiagnosed. This is a pilot observational prospective study aimed at determining whether nasal linguatulosis can be diagnosed using CT. The secondary aims were to evaluate radiography, rhinoscopy, and nasal egg swabs as methods in the diagnosis of tongue worms. Fifty-four wild canids and three vulpids euthanased by gunshot were sourced from pest-control officers. Cadaver heads were subjected to helical CT examination, nasal-swabbed for tongue worm eggs, and necropsied. Radiographs and rhinoscopy were performed on cadavers suspected to be infected based on preliminary CT examination. Tongue worms were retrieved at necropsy in 25 dogs and one fox. CT findings in animals with no nasal cavity ballistic damage were reviewed in six infected dogs and one infected fox. Adult female tongue worms were identified in 4 of 6 dogs and 1 of 1 fox as long, tubular, slightly heterogeneously attenuating structures in the mid to caudal nasal cavities. They were not clearly visible in CT scans when surrounded by nasal fluid, and small parasites (male and immature females) were not discernible. Radiographic findings were mild and nonspecific. One tongue worm was detected in 1 of 12 dogs examined rhinoscopically. Tongue worm eggs were found in swabs from 7 of 25 dogs. While small tongue worms could not be detected with CT, CT proved to be a useful diagnostic method for visualizing adult female tongue worms., (© 2024 The Author(s). Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

This study explored the body mass (BM) management practices among competitive male and female Olympic weightlifting athletes, hypothesizing that athletes compete in lighter weight categories than their habitual training weight (i.e., making weight). Utilizing a validated, anonymous survey, data were collected from 149 Olympic weightlifting athletes (>18 years; female = 94). The survey comprised five sections: demographics, training/competition history, weight history, source of influence, and BM management practices. The prevalence, magnitude, and methods employed for BM management were analyzed with subgroup analysis using one-way analysis of variance. Post hoc testing including Spearman's rho and chi-square analysis was completed when a significant effect was found. Three quarters (76%) of athletes acknowledged using chronic weight loss and/or acute weight loss strategies to make weight. Usual BM loss (2%-3%) in the week before competition was within recommended guidelines. Gradual dieting, fluid restriction, and low food weight, high-calorie options were the most commonly used BM management strategies. Female athletes were more likely to use gradual dieting (p = .043; r = .104) and were less likely to increase their exercise (p = .046; r = -.105) and utilize fasting (p = .038; r = .05) compared with their male counterparts. Women further identified dietitians/nutritionists (p = .006; r = .022) as a highly influential source of information. This research offers new insights into the BM management practices of Olympic weightlifting athletes, identifying that the majority of athletes compete at a BM lighter than their habitual training weight, achieved using a range of chronic weight loss and acute weight loss strategies.

Micro-computed tomography (micro-CT) is an emerging tool in parasitology that can assist in analysing morphology and host-parasitic interactions. It is a non-destructive, cross-sectional imaging technique that offers good resolution and the ability to create three-dimensional (3D) reconstructions. Here, we used micro-CT to study Linguatula serrata , which is a zoonotic pentastome parasite that infects dogs and ruminants throughout the world. The aims of this study were to describe the internal and external anatomy of adult L. serrata specimens using micro-CT, and to describe and compare specimens stained with 0.3% phosphotungstic acid (PTA) and 1% iodine (I 2 ). Ten adult L. serrata specimens were subjected to micro-CT examination. The specimens were fixed in 70% ethanol and stained with 0.3% PTA or 1% I 2 . Both stains offered good tissue contrast. The main identifying external features of L. serrata (hooks, mouth, buccal cadre) were clearly visible. Virtual sections and 3D reconstructions provided a good overview of the coelomic cavity, with visualisation of the digestive tract, nervous system, and male and female reproductive organs. These micro-CT images and morphological descriptions may serve as an anatomical reference for L. serrata , in particular, the internal anatomy which has not been described in recent years., Competing Interests: There is no identifiable Conflict of Interest., (© 2024 The Authors.)

Poor response to Bacillus Calmette-Guérin (BCG) immunotherapy remains a major barrier in the management of patients with non-muscle invasive bladder cancer (NMIBC). Multiple factors are associated with poor outcomes, including biological aging and female sex. More recently, it has emerged that a B-cell-infiltrated pretreatment immune microenvironment of NMIBC tumors can influence the response to intravesically administered BCG. The mechanisms underlying the roles of B cells in NMIBC are poorly understood. Here, we show that B-cell-dominant tertiary lymphoid structures (TLSs), a hallmark feature of the chronic mucosal immune response, are abundant and located close to the epithelial compartment in pretreatment tumors from BCG non-responders. Digital spatial proteomic profiling of whole tumor sections from male and female patients with NMIBC who underwent treatment with intravesical BCG, revealed higher expression of immune exhaustion-associated proteins within the tumor-adjacent TLSs in both responders and non-responders. Chronic local inflammation, induced by the N-butyl-N-(4-hydroxybutyl) nitrosamine carcinogen, led to TLS formation with recruitment and differentiation of the immunosuppressive atypical B-cell (ABC) subset within the bladder microenvironment, predominantly in aging female mice compared to their male counterparts. Depletion of ABCs simultaneous to BCG treatment delayed cancer progression in female mice. Our findings provide evidence indicating a role for ABCs in BCG response and will inform future development of therapies targeting the B-cell-exhaustion axis., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background: Synovial macrophages (SMs) are important effectors of joint health and disease. A novel Cx3CR1 + TREM2 + SM population expressing the tight junction protein claudin-5, was recently discovered in synovial lining. Ablation of these SMs was associated with onset of arthritis. Proteoglycan 4 (PRG4) is a mucinous glycoprotein that fulfills lubricating and homeostatic roles in the joint. The aim of this work is to study the role of PRG4 in modulating synovitis in the context of SM homeostasis and assess the contribution of xanthine oxidase (XO)-hypoxia inducible factor alpha (HIF-1α) axis to this regulation., Methods: We used Prg4 FrlioxP/FrtloxP ;R26 FlPoER/+ , a novel transgenic mouse, where the Prg4 Frt allele normally expresses the PRG4 protein and was designed to flank the first two exons of Prg4 with a flippase recognition target and "LOXP" sites. Inducing flippase activity with tamoxifen (TAM) inactivates the Frt allele and thus creates a conditional knockout state. We studied anti-inflammatory SMs and XO by quantitative immunohistochemistry, isolated RNA and studied immune pathway activations by multiplexed assays and isolated SMs and studied PRG4 signaling dysfunction in relation to glycolytic switching due to pro-inflammatory activation. Prg4 inactivated mice were treated with oral febuxostat, a specific XO inhibitor, and quantification of Cx3CR1 + TREM2 + SMs, XO immunostaining and synovitis assessment were conducted., Results: Prg4 inactivation induced Cx3CR1 + TREM2 + SM loss ( p < 0.001 ) and upregulated glycolysis and innate immune pathways in the synovium. In isolated SMs, Xdh ( p < 0.01 ) and Hif1a ( p < 0.05 ) were upregulated. Pro-inflammatory activation of SMs was evident by enhanced glycolytic flux and XO-generated reactive oxygen species (ROS). Febuxostat reduced glycolytic flux ( p < 0.001 ) and HIF-1α levels ( p < 0.0001 ) in SMs. Febuxostat also reduced systemic inflammation ( p < 0.001 ), synovial hyperplasia ( p < 0.001 ) and preserved Cx3CR1 + TREM2 + SMs ( p < 0.0001 ) in synovia of Prg4 inactivated mice., Conclusions: PRG4 is a biologically significant modulator of synovial homeostasis via inhibition of XO expression and downstream HIF-1a activation. PRG4 signaling is anti-inflammatory and promotes synovial homeostasis in chronic synovitis, where direct XO inhibition is potentially therapeutic in chronic synovitis., Competing Interests: Competing Interest: LZ, TZ, AM, DJ have nothing to disclose. GJ authored patents on rhPRG4, holds equity and is a paid consultant in Lubris LLC, MA, USA. TS authored patents on rhPRG4, holds equity and is a paid consultant in Lubris LLC, MA, USA KE authored patents on rhPRG4. Authors have no non-financial competing interests related to this manuscript.

Abstract: Orthostatic hypotension is a prevalent clinical condition, caused by heterogenous etiologies and associated with significant morbidity and mortality. Management is particularly challenging in patients with uncontrolled hypertension. A thorough assessment is needed to draw an appropriate management plan. The treatment aims to improve postural symptoms while minimizing side effects and reducing iatrogenic exacerbation of supine hypertension. A personalized management plan including rationalizing medications, patient education, identification, and avoidance of triggers, as well as nonpharmacological therapies such as compression devices, dietary modifications, and postural aids, make the first steps. Among pharmacological therapies, midodrine and fludrocortisone are the most prescribed and best studied; pyridostigmine, atomoxetine, and droxidopa are considered next. Yohimbine remains an investigational agent. A multidisciplinary team may be required in some patients with multiple comorbidities and polypharmacy. However, there is a lack of robust efficacy and safety evidence for all therapies. Building robust real-world and stratified clinical trials based on underlying pathophysiology may pave the way for further drug development and better clinical strategies and in this challenging unmet medical need., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: We aimed to assess the relationship between the distance traveled to receive treatment for urolithiasis and early outcomes., Methods: This is a population-based study of patients who received interventions for urolithiasis in Ontario between 2003 and 2019 using administrative data. Patients were stratified into three groups according to the distance travelled. Descriptive statistics and the Chi-squared test were used to examine differences between these groups based on the urolithiasis treatment of choice. The primary outcomes were reoperation rates and readmission rates. To identify the factors associated with the co-primary outcomes, both univariate and multivariable logistic regression models were employed., Results: A total of 127 195 patients were included in the final analysis, with the majority of patients (n=100 124, 78.7%) having their stone procedure within 30 km from their residence, whereas 9586 patients (7.5%) travelled a distance greater than 90 km. Most of those that travelled >90 km were for extracorporeal shock wave lithotripsy (ESWL) (59%). Type of procedure and region of residence were the only variables that appeared to have a clinically relevant association with greater distance travelled. Unadjusted analysis suggested longer distance travelled was associated with a decrease in the need for a repeat procedure; however, this was likely confounded by an association between distance traveled and procedure type. In adjusted analysis, early post-procedure health resource use did not appear to be dramatically increased with greater distance from care. Indeed, readmission rates at 30 days were marginally lower among those who travelled 30-60 km vs. <30 km (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.80-0.92, and had no detectable difference at >90 km vs. <30 km (OR 0.97, 95% CI 0.88, 1.08). These observations of fewer or no difference in readmissions and emergency visits for those that travelled the greatest distances generally held true in the subgroup analysis for each surgical procedure., Conclusions: This population-based study found no clinically remarkable associations between the distance travelled for urolithiasis treatment and early outcomes. In fact, some marginal decreases in resource use were observed with greater travel distance perhaps reflecting some effect of travel to higher volume referral centers or enhanced processes for those that needed to travel farther for care. This information could be important for clinicians to help appropriate counselling and health systems planning.

Introduction: Previous studies have demonstrated the benefits of tranexamic acid (TXA) administration in combination with packed red blood cell (PRBC) transfusion in trauma patients without increasing the risk of venous thromboembolism (VTE). However, the effect of TXA in combination with whole blood (WB) has not been studied. Injury, abbreviated injury severity scores (ISS and AIS) and the need for blood transfusions are historically associated with VTE. The objective of this study was to determine the relationship between VTE and the combination of TXA administration and transfusion of PRBCs vs. WB., Methods: Our institutional trauma registry was queried for trauma patients between 2015 and 2022 who received either WB ​+ ​TXA or PRBC ​+ ​TXA either prehospital or within 4 ​h of arrival. Multivariate analysis was utilized to determine independent risk factors for VTE, which were defined as either a deep vein thrombosis (DVT) or a pulmonary embolism (PE). Model covariates included age, mechanism of injury (MOI), ISS, lower extremity AIS, comorbid conditions, and shock index (SI). Additional outcomes analyzed were hospital length of stay (LOS), ICU LOS, and ventilator days., Results: Three hundred and five patients had complete data and were included in the analysis. Of those, 251 received WB ​+ ​TXA and 54 received PRBC ​+ ​TXA. A total of 34 patients were found to have VTE event (11.1 ​%); 28 (11.2 ​%) and 6 (11.1 ​%) from the WB ​+ ​TXA and PRBC ​+ ​TXA groups, respectively. An elevated pre-hospital SI was independently associated with increased VTE rate (OR 1.85, 95 ​% CI 1.07-3.20). WB transfusion, TXA administration, ISS, and MOI did not influence the rate of VTE., Conclusion: These data demonstrate that the combination of WB ​+ ​TXA administered to trauma patients has no higher risk of VTE than patients who receive PRBC ​+ ​TXA, a comparison that has not been studied clinically to date. Despite the pro thrombotic state enhanced by TXA and the decreased dilutional coagulopathy seen in WB resuscitation, there was no increased risk of VTE compared to TXA ​+ ​PRBC. There is no evidence that TXA combined with whole blood transfusion is associated with an increased risk of VTE. However, higher pre-hospital SI was associated with an elevated rate of VTE. These clinical features provide insight into patients who may be at an increased risk of developing VTE and may benefit from targeted prevention strategies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Infertility refers to the inability to conceive after 12 months of regular, unprotected sexual intercourse. Psychosocial aspects of infertility research are predominant in developed countries. A scoping review of psychosocial aspects of infertility research conducted in Africa between 2000 and 2022 was conducted. Twelve databases and grey literature were searched for articles. Studies were included if they were published in English and included findings from patients diagnosed with primary or secondary infertility. A total of 2 372 articles were initially found and screening resulted in 116 articles being included in the scoping review. Most of the studies (81%) were conducted in Nigeria, Ghana and South Africa. Psychosocial aspects explored included quality of life, barriers to treatment, attitudes and stigma, and sociocultural and religious aspects of infertility, among others. The review maps published psychosocial research in the context of infertility in Africa and identifies gaps for future research., (© 2024. The Author(s).)

Background: Dietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow's milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow's milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow's milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes., Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology., Results: Eligibility criteria were met by 17 trials (n = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow's milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow's milk resulted in moderate reductions in non-HDL-C (mean difference, - 0.26 mmol/L [95% confidence interval, - 0.43 to - 0.10]), systolic blood pressure (- 8.00 mmHg [- 14.89 to - 1.11]), and diastolic blood pressure (- 4.74 mmHg [- 9.17 to - 0.31]); small important reductions in LDL-C (- 0.19 mmol/L [- 0.29 to - 0.09]) and c-reactive protein (CRP) (- 0.82 mg/L [- 1.26 to - 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified., Conclusions: Current evidence provides a good indication that replacing cow's milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets., Trial Registration: ClinicalTrials.gov identifier, NCT05637866., (© 2024. The Author(s).)

The gut microbiome of infants with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) is at risk of profound alteration. The aim of this study was to examine the gut microbiome pre- and post-bypass surgery to explore potential implications of altered gut biodiversity. A prospective cohort study involving infants with CHD who underwent CPB was performed. Faecal samples were collected from infants alongside the collection of demographic and clinical data in order to examine gut microbiome changes before and after surgery. 16S rRNA sequencing analysis was performed on DNA isolated from stool samples to determine changes in gut microbiome composition. Thirty-three patients were recruited, with samples from thirteen of these available for final analysis. Compared with healthy, matched controls, at a genus level, pre-operative samples for infants with CHD demonstrated a higher relative abundance of Escherichia-Shigella (31% vs 2-6%) and a lower relative abundance of Bifidobacterium (13% vs 40-60%). In post-operative samples, the relative abundance of Escherichia-Shigella (35%), Enterococcus (11%), Akkermansia (6%), and Staphylococcus (5%) were higher than pre-op samples. One infant developed post-operative necrotising-enterocolitis (NEC). They displayed a marked abundance of the Enterococcus (93%) genus pre-operatively. This study demonstrates that infants with CHD have an altered gut microbiome when compared with healthy controls and there might be a possible link between an abundance of virulent species and NEC., (© 2024. The Author(s).)

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance. Besides the impact of uncertainties from stellar models and galactic chemical evolution simulations, this discrepancy was further obscured by rather divergent theoretical estimates for the neutron capture cross section of its radioactive precursor in the neutron-capture flow, ^{204}Tl (t&#95;{1/2}=3.78  yr), and by the lack of experimental data on this reaction. We present the first ever neutron capture measurement on ^{204}Tl, conducted at the CERN neutron time-of-flight facility n&#95;TOF, employing a sample of only 9 mg of ^{204}Tl produced at the Institute Laue Langevin high flux reactor. By complementing our new results with semiempirical calculations we obtained, at the s-process temperatures of kT≈8  keV and kT≈30  keV, Maxwellian-averaged cross sections (MACS) of 580(168) mb and 260(90) mb, respectively. These figures are about 3% lower and 20% higher than the corresponding values widely used in astrophysical calculations, which were based only on theoretical calculations. By using the new ^{204}Tl MACS, the uncertainty arising from the ^{204}Tl(n,γ) cross section on the s-process abundance of ^{204}Pb has been reduced from ∼30% down to +8%/-6%, and the s-process calculations are in agreement with the latest solar system abundance of ^{204}Pb reported by K. Lodders in 2021.

Introduction: This article politicizes a reimbursement model proposed by some professional nursing associations that aim to better align the price of nursing labor (nurses' pay) to the value of nursing and make nurses' contributions more visible., Methods: Using the concept of "missing care," the critique reveals how professionalization directs attention to individual-level interactions between care seekers and practitioners while obscuring from view the harm inflicted by social institutions and structures constitutive of a capitalist political economy and the related carceral state., Results: Direct reimbursement models render practitioners complicit in the harms perpetrated and perpetuated by the health care industrial complex while professionalization processes are deployed to reduce cognitive dissonance (and moral injury) produced by combining harm with nursing's normative principles., Discussion: We describe and trace the complementary capitalist imperatives of extraction-based profit maximization and efficiency through the health care industrial complex to demonstrate how formative those imperatives are of the health care system, care-seekers' outcomes, nurses' experiences, nonconsensual modes of data collection, and surveillance., Conclusion: The naturalization of racial capitalism and the precarity and violence it entails foreclose the creation of ethical alternatives that prioritize well-being instead of the pursuit of profit that could bring the provision of and payment for care closer to the normative principles held by practitioners., (© The Author(s) 2024. Published by Mary Ann Liebert, Inc.)

Hospital CEO salaries have grown quickly over the past two decades. We investigate correlates of rising nonprofit hospital CEO pay between 2012 and 2019 by merging compensation data from Candid's IRS 990 forms with hospital data from the National Academy for State Health Policy Hospital Cost Tool. Almost half of the measured increase in CEO compensation (44.5%) accrued to a "base case" CEO, who was leading a non-teaching hospital system or independent hospital with fewer than 100 beds that earned 0 profits and provided no charity care. Another 28.5% of the measured salary increase resulted from changes in the generosity with which observable metrics were rewarded, particularly the reward for heading a system with 500 or more beds. The remaining 27% resulted mostly from hospital systems or single hospitals that increased their profits or bed size over time. The increase in CEO compensation associated with leading larger healthcare systems and earning greater profits may explain the increase in healthcare system consolidation which has occurred over the last several years., Competing Interests: I have read the journal’s policy, and the authors of this manuscript have the following competing interests: the authors receive funding from Arnold Ventures. VH and MNS receive funding from the Health Care Service Corporation and the National Academy of State Health Policy. The funders had no role in study design, data collection and analysis, publication decision, or manuscript preparation. VH is a member of the Blue Cross Blue Shield of Texas Community Advisory Board, Community Health Choice: Houston Business Coalition on Healthcare Advisory Board, Texas Employers for Affordable Health Care Advisory Board, and the Blue Cross Blue Shield Research Alliance. VH receives support for attending membership committee meetings from the National Academy of Medicine. VH owned stock in IBM. “However, this does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2024 Jenkins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Purpose: The detection of congenital heart disease (CHD) before neonatal surgery is crucial for anaesthetic and perioperative management. There are no established criteria for pre-operative echocardiography in neonates. We aimed to survey current practice in the United Kingdom and evaluate the reliability of antenatal screening and postnatal clinical assessment in detecting CHD before surgery., Method: A 9-point questionnaire was sent to all paediatric surgical centres in the United Kingdom to assess their practice. Subsequently, a single-centre retrospective review of all neonatal surgery over 5 years (2015-2020) was conducted in our tertiary paediatric/neonatal hospital. Data included pre-operative clinical assessment, performance of chest radiograph and echocardiography. Indications for echocardiography were categorised and assessed using sensitivity, specificity, positive predictive value and negative predictive value., Results: All 26 paediatric surgical centres responded to our survey. 23/26 (88.5%) did not have established criteria or guidelines for pre-operative echocardiography. There was a large variation in which surgical conditions required a pre-operative scan and whether a normal clinical examination was considered sufficient to not require one. For the retrospective review, 454 patients were identified. There were 40 cases with CHDs (8.8%), 13 were classed as major or moderate. Indications for echocardiography were categorised into abnormal foetal cardiac screening, medical/surgical conditions associated with CHD and an abnormal cardiorespiratory examination. Sensitivity, specificity, positive predictive value and negative predictive value for major and moderate CHD were 46%, 99%, 67%, 98% for abnormal foetal screening, 46%, 97%, 35%, 98% for associated medical conditions, 62%, 66%, 6%, 98% for associated surgical conditions, and 100%, 66%, 9%, 100% for abnormal clinical examination., Conclusion: The use of pre-operative echocardiography in neonates is not standardised across the UK. The results from our cohort demonstrate that foetal echocardiography is not sufficient to capture all major and moderate CHDs, but the absence of abnormal clinical examination is highly reliable in ruling out them out. Specifying a list of medical/surgical of conditions associated with CHD warranting pre-operative echocardiography may improve yield, but this depends on the availability of resources and expertise., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist., (Copyright © 2024 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Rationale: Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy. Objectives: We aimed to establish the genetic basis of chronic thromboembolic pulmonary hypertension to gain insight into its pathophysiological contributors. Methods: We conducted a genome-wide association study on 1,907 European cases and 10,363 European control subjects. We coanalyzed our results with existing results from genome-wide association studies on deep vein thrombosis, pulmonary embolism, and idiopathic pulmonary arterial hypertension. Measurements and Main Results: Our primary association study revealed genetic associations at the ABO, FGG, F11, MYH7B, and HLA-DRA loci. Through our coanalysis, we demonstrate further associations with chronic thromboembolic pulmonary hypertension at the F2, TSPAN15, SLC44A2, and F5 loci but find no statistically significant associations shared with idiopathic pulmonary arterial hypertension. Conclusions: Chronic thromboembolic pulmonary hypertension is a partially heritable polygenic disease, with related though distinct genetic associations with pulmonary embolism and deep vein thrombosis.

Background: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression., Objective: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2., Study Design: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF 10 -DEIA-LiPA 25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model., Results: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups., Conclusion: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Significant morbidity and mortality from COVID-19-related illnesses have been observed among people of color within the United States. While theories involving healthcare inequity and political division have emerged to explain this observation, the role of chronic stress and inflammation is also being explored. Toxic stress is experienced disproportionately by race, ethnicity, and socioeconomic status and increases frailty and vulnerability to diseases such as COVID-19. C-reactive protein (CRP) is a biomarker associated with the inflammatory response that is typically elevated due to exposure to acute or chronic traumatic stress, as well as COVID-19. This study explored the relationship between CRP and Hispanic/non-Hispanic ethnicity among adults hospitalized with COVID-19 via a secondary analysis of retrospective electronic health record (EHR) data collected from a community healthcare system in Southern California. A total of 1,744 cases representing hospitalized adults with COVID-19 were reviewed. Data were extracted from the EHR to reflect demographics, medical diagnoses, medications, CRP, and comorbidity burden. Frequencies, percentages, and measures of central tendency were assessed to understand the distribution of data. Associations were conducted using Pearson's r and the chi-square test of independence. Differences between groups were examined via independent samples t -tests. The sample was 52% Hispanic, 56% male, and the mean age was 62 years ( SD = 16.1). The mean age of Hispanic cases was younger than non-Hispanic cases ( p < .001, η = 0.289). Serum CRP was significantly higher in the Hispanic cases, with a high degree of association ( p < .001, η = 0.472). In addition, higher CRP levels were significantly associated with the need for mechanical ventilation ( p < .001, φ c = 0.216). No significant relationships were found between CRP and age, body mass index (BMI), or comorbidity burden. Findings challenge the assumption that the disproportionate morbidity and mortality suffered by the Hispanic population due to COVID-19 was due to age, BMI, or comorbidities such as metabolic syndrome or heart disease. CRP in the Hispanic population should be further investigated to understand its relationship to chronic stress, frailty, and risk for COVID-19 in this population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: The aim of this study was to describe the characteristics of clients receiving home-based dietetic intervention and to evaluate the effectiveness of these interventions in improving nutritional status, functional status, and quality of life in a culturally and socioeconomically diverse client group., Methods: Participants referred to a home-based dietetic service were recruited to this prospective cohort study. Dietetic interventions were recommended at baseline and reviewed at 3-month follow-up. Assessment of nutritional, functional and quality of life markers was measured using the Mini Nutritional Assessment (MNA), Timed Up and Go (TUG) and EQ-5D-5L, respectively, at baseline and after home-based dietetic intervention., Results: Participants (n = 99) were recruited from consecutive referrals. Participant's weight, body mass index (BMI), total daily energy and protein intake, MNA total score, and TUG significantly improved after a 3-month nutrition intervention (effect sizes 0.257, 0.257, 0.580, 0.533, 0.577 and 0.281, respectively). The most common interventions dietitians utilised were nutrition education, use of oral nutritional supplements (ONS) and meal fortification. In total, 339 dietetic interventions were recommended to participants at baseline with 197 (58.11%) implemented at 3 months, with meal planning and referral to other relevant allied health or Commonwealth Home Support Program (CHSP) services the most implemented interventions., Conclusions: Home-based dietetic intervention improves nutritional status, functional status and quality of life in community-dwelling older adults referred for dietetic input. Improvements observed in nutritional and functional status were consistent with benchmarks of change from published literature., (© 2024 AJA Inc’.)

Spontaneous retroperitoneal hematoma (SRH) is a rare complication of anticoagulation therapy. Presentation may vary from limb paresis to hypovolemic shock due to blood loss. The optimal treatment is controversial. It can be managed conservatively or surgically. We report a case of a 73-year-old man presenting with progressively worsening abdominal pain and severe pain radiating to his left lower limb twenty-five days after his pulmonary endarterectomy (PEA) surgery. He was on anticoagulation per our institutional protocol for PEA patients. Investigations revealed a large, spontaneously occurring iliopsoas hematoma. Our patient was treated conservatively, and the SRH stabilised., (© 2024. The Author(s).)

Pulmonary arterial sarcomas (PAS) are rare aggressive tumours occurring mainly in the pulmonary trunk. We report a case of PAS involving the pulmonary trunk wall and valve, with uniform wall thickening which represents an atypical imaging manifestation of this tumour. A 63-year-old male presented with vague respiratory symptoms with rapid progression. CTPA showed low density filling defects in both pulmonary arteries and PET scan showed increased uptake in the pulmonary trunk, which along with raised ESR suggested Pulmonary Vasculitis. Echo imaging showed Right ventricular hypertrophy and pulmonary stenosis. Response to steroid therapy was minimal and his symptoms worsened. A referral for second opinion was made and he was diagnosed with PAS. He underwent Pulmonary thromboendarterectomy with Pulmonary valve replacement. Post-operative histopathology confirmed the diagnosis. PAS is rare and frequently misdiagnosed. Surgical resection is not curative, but together with chemotherapy can prolong survival., (© 2024. Crown.)

Case: We report a rare case of mycobacterial periprosthetic joint infection (PJI) after primary total knee arthroplasty 14 years earlier. Progressive knee pain over three years with a negative PJI infectious workup led to revision total knee arthroplasty. A surprising result was isolation of Mycobacterium avium from tissue cultures taken at time of revision surgery. After six months of antibiotic treatment, the patient is alive with well- functioning pain-free TKA at over one-year follow-up., Conclusion: Periprosthetic joint infection can present acutely or chronically years following total knee arthroplasty. Depending on the infecting organism, patients can present with sepsis, or a more indolent slower course that mimics aseptic loosening. In the absence of positive pre-operative labs and cultures, and based on the Musculoskeletal Infection Society (MSIS) criteria, aseptic loosening is a diagnosis of exclusion. An atypical infectious organism should be considered a possible cause and may require specialized cultures of operative specimens.

Background: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete., Methods: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed., Results: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g)., Conclusion: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full., (© 2024 AABB.)

Background: It has been suggested that the Lethal Triad be modified to include hypocalcemia, coined as the Lethal Diamond. Hypocalcemia in trauma has been attributed to multiple mechanisms, but new evidence suggests that traumatic injury may result in the development of hypoCa independent of blood transfusion. We hypothesize that hypocalcemia is associated with increased blood product requirements and mortality., Methods: A retrospective study of 1,981 severely injured adult trauma patients from 2016 to 2019. Ionized calcium (iCa) levels were obtained on arrival and subjects were categorized by a threshold iCa level of 1.00 mmol/L and compared. Univariable and multivariable logistic regression analysis was performed., Results: The hypocalcemia (iCa <1.00 mmol/L) group had increased rate of overall (p = 0.001), 4-hr (p = 0.007), and 24-hr (p = 0.003) mortality. There was no difference in prehospital transfusion volume between groups (p = 0.25). Hypocalcemia was associated with increased blood product requirements at 4 h (p <0.001), 24 h (p <0.001), and overall hospital length of stay (p <0.001). Logistic regression analysis showed increased odds of 4-hour mortality (OR 0.077 [95 % CI 0.011, 0.523], p = 0.009) and 24-hour mortality (OR 0.121 [95 % CI 0.019, 0.758], p = 0.024) for every mmol/L increase in iCa., Conclusions: This study shows the association of hypoCa and traumatic injury. Severe hypoCa was associated with increased odds of early and overall mortality and increased blood product requirements. These results support the need for future prospective trials assessing the role of hypocalcemia in trauma., Competing Interests: Declaration of competing interest The views represented in this presentation do not represent the views of the Department of Defense, United States Government, or any branches of the United States Military, No relevant financial relationships to disclose. The authors have no relevant conflicts of interest. Data access from institutional database and electronic medical records. Data can be accessed upon request., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We describe three cases of critical acute myositis with myocarditis occurring within 22 days of each other at a single institution, all within 1 month of receiving the initial cycle of the anti-PD-1 drug pembrolizumab. Analysis of T cell receptor repertoires from peripheral blood and tissues revealed a high degree of clonal expansion and public clones between cases, with several T cell clones expanded within the skeletal muscle putatively recognizing viral epitopes. All patients had recently received a COVID-19 mRNA booster vaccine prior to treatment and were positive for SARS-CoV2 Spike antibody. In conclusion, we report a series of unusually severe myositis and myocarditis following PD-1 blockade and the COVID-19 mRNA vaccination., Competing Interests: Competing interests: RAW, WY, CAT, EJ, RC, OT, TJ, BS, MH, DJ, RP, EI, SJ, DM-P, NC and MP: no competing interests. MRM reports grants from Roche, grants from Astrazeneca, grants from GSK, other from Novartis, grants and other from Immunocore, other from BMS, other from Pfizer, other from Merck/MSD, other from Regeneron, other from BiolineRx, other from Replimune, grants from GRAIL; all outside the submitted work; ISDR reports consultancy for Novartis, Travere Therapeutics, Q32Bio and is an unpaid Director of Oxford Pathology Education Limited, Oramis Digital Autopsy, UK Renal Pathology; all outside submitted work. BF has received speaker fees from GSK, Immunocore, BMS and reports consultancy for Roche, Pathios Therapeutics, NICE advisory, UCB; NC has received honoraria Pierre Fabre, BMS., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Incomplete penetrance is the rule rather than the exception in Mendelian disease. In syndromic monogenic disorders, phenotypic variability can be viewed as the combination of incomplete penetrance for each of multiple independent clinical features. Within genetically identical individuals, such as isogenic model organisms, stochastic variation at molecular and cellular levels is the primary cause of incomplete penetrance according to a genetic threshold model. By defining specific probability distributions of causal biological readouts and genetic liability values, stochasticity and incomplete penetrance provide information about threshold values in biological systems. Ascertainment of threshold values has been achieved by simultaneous scoring of relatively simple phenotypes and quantitation of molecular readouts at the level of single cells. However, this is much more challenging for complex morphological phenotypes using experimental and reductionist approaches alone, where cause and effect are separated temporally and across multiple biological modes and scales. Here I consider how causal inference, which integrates observational data with high confidence causal models, might be used to quantify the relative contribution of different sources of stochastic variation to phenotypic diversity. Collectively, these approaches could inform disease mechanisms, improve predictions of clinical outcomes and prioritize gene therapy targets across modes and scales of gene function. This article is part of a discussion meeting issue 'Causes and consequences of stochastic processes in development and disease'.

Introduction: Prehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature to identify early clinical features and portable devices for the detection of ICH in the prehospital setting., Methods: Three databases were searched via Ovid (MEDLINE, EMBASE and CENTRAL) from inception to August 2022 using prespecified search strategies. One reviewer screened all titles, abstracts and full-text articles for eligibility, while a second reviewer independently screened 20% of the literature during each screening stage. Data extracted were tabulated to summarise the key findings., Results: A total of 6803 articles were screened for eligibility, of which 22 studies were included for analysis. Among them, 15 studies reported on early clinical features, while 7 considered portable devices. Associations between age, sex and comorbidities with the presence of ICH varied across studies. However, most studies reported that patients with ICH exhibited more severe neurological deficits (n=6) and higher blood pressure levels (n=11) at onset compared with other stroke and non-stroke diagnoses. Four technologies were identified for ICH detection: microwave imaging technology, volumetric impedance phase shift spectroscopy, transcranial ultrasound and electroencephalography. Microwave and ultrasound imaging techniques showed promise in distinguishing ICH from other diagnoses., Conclusion: This scoping review has identified potential clinical features for the identification of ICH in suspected stroke patients. However, the considerable heterogeneity among the included studies precludes meta-analysis of available data. Moreover, we have explored portable devices to enhance ICH identification. While these devices have shown promise in detecting ICH, further technological development is required to distinguish between stroke subtypes (ICH vs ischaemic stroke) and non-stroke diagnoses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The purpose of this study was to give voice to the lived experiences of nurses and law enforcement officers whose professional responsibilities converge in the acute care setting, while gaining insight into the perspectives and interpretations of their experiences. Using interpretative phenomenological analysis, this quality study contributes to a growing body of literature exploring the influence of law enforcement in the hospital. Overwhelmingly, participants in this study expressed a contentious dynamic, fueled by arguments, struggles for power, and a feeling of coming from "different worlds." The influence of socially and spatially constructed territories was critical points of contention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Given the urgency of transitioning towards sustainable nutrition, dietary shifts that provide co-benefits to human health and the environment are imperative. There is currently no database of the environmental impacts of foods that reflects Canada's unique geographical and agri-climatic context and regional inputs and emissions. To determine sustainable diets, harmonising nutritional considerations with environmental impacts is also essential for an equitable comparison of foods. We aimed to develop a Canadian Food Life Cycle Inventory database and a multidimensional index to enable a joint assessment of the health and environmental impacts of foods in Canada., Methods: The Canadian Food Life Cycle Inventory database uses life cycle assessment methodology to evaluate environmental impacts. The datasets mirror Canada's food consumption patterns, averaging the spectrum of agricultural practices weighted by domestic production and import shares. The database is structured according to the nomenclature and categorisation of the Canadian Nutrient File. Environmental sustainability is assessed using a cradle-to-grave approach, including indicators such as greenhouse gas emissions, eutrophication, particulate matter, freshwater usage, land use, non-renewable energy consumption, and food loss and waste. Environmental impacts are quantified through an environmental impact score (EIS) assigned to each impact category for a given food. The EIS-nutrition (EIS-N) integrates the evaluation of nutritional quality with environmental impacts using Nutri-Score, a validated food nutrient-profiling tool. The EIS-N is modelled as a ratio of the EIS to the Nutri-Score values., Findings: Preliminary results show the greatest environmental impacts for animal-based foods, particularly beef, in agreement with current literature. Foods with greater nutritional quality also generally show greater environmental sustainability, with some exceptions for particular impact categories., Interpretation: The database and index have potential to serve as powerful tools to support researchers, policy makers, and consumers, harnessing big data to drive efficient food and climate solutions for systems transformation., Funding: Province of Ontario and University of Toronto, CIHR SMART Healthy Cities Training Platform, and University of Toronto's Temerty Faculty of Medicine., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Dynein-2 is a large multiprotein complex that powers retrograde intraflagellar transport (IFT) of cargoes within cilia/flagella, but the molecular mechanism underlying this function is still emerging. Distinctively, dynein-2 contains two identical force-generating heavy chains that interact with two different intermediate chains (WDR34 and WDR60). Here, we dissect regulation of dynein-2 function by WDR34 and WDR60 using an integrative approach including cryo-electron microscopy and CRISPR/Cas9-enabled cell biology. A 3.9 Å resolution structure shows how WDR34 and WDR60 use surprisingly different interactions to engage equivalent sites of the two heavy chains. We show that cilia can assemble in the absence of either WDR34 or WDR60 individually, but not both subunits. Dynein-2-dependent distribution of cargoes depends more strongly on WDR60, because the unique N-terminal extension of WDR60 facilitates dynein-2 targeting to cilia. Strikingly, this N-terminal extension can be transplanted onto WDR34 and retain function, suggesting it acts as a flexible tether to the IFT "trains" that assemble at the ciliary base. We discuss how use of unstructured tethers represents an emerging theme in IFT train interactions., (© 2024. The Author(s).)

Background: A significant aspect of the SARS-CoV-2 pathology involves oxidative stress, characterized by an imbalance between the production of harmful free radicals and the body's antioxidant defenses. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance., Objectives: This systematic review and meta-analysis aimed to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2 infection., Methods: We searched the peer-reviewed indexed literature on MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, International Pharmaceutical Abstracts, and Scopus, from inception to July 2023., Results: The search identified 3306 articles from which 25 were included for quantitative synthesis, with 5 studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding intensive care unit admissions and hospital stays. Vitamin A studies indicated improvements in inflammatory markers. Vitamin C studies displayed inconsistent effects on clinical improvement and hospitalization. Combination treatments suggested benefits in symptom clearance and cytokine storm reduction. Meta-analysis of vitamin C studies found no significant difference in C-reactive protein concentrations (-0.50; 95% CI: -3.63, 2.63; I 2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I 2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I 2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: -2.37; 95% CI: -2.99, -1.76; I 2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias., Conclusions: The review presents mixed efficacy of antioxidant therapies for SARS-CoV-2, with some studies indicating potential benefits. Further well-designed large-scale RCTs are warranted to determine the definitive role of antioxidants in SARS-CoV-2 treatment.This systematic review was registered at PROSPERO as CRD42023430805., Competing Interests: The authors report no conflicts of interest., (© 2024 The Author(s).)

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n&#95;TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values. Stellar model calculations indicate a reduction around 20% of the s-process contribution to the Galactic cerium abundance and smaller sizeable differences for most of the heavier elements. No variations are found in the nucleosynthesis from massive stars.

In this study we combined non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) with 40 h of constraint induced movement therapy (CIMT) in infants. All infants completed the full intervention with no adverse events. Therapists were able to maintain high treatment fidelity and reported high ratings for ease of use and child tolerance. Preliminary results show promising gains on motor outcomes: Mean QUEST increase 19.17 (minimal clinically important difference, MCID 4.89); Mean GMFM increase 13.33 (MCID 1%-3%). Infants also exceeded expectations on Goal Attainment Scores (+1). Early data is promising that taVNS paired with intensive motor CIMT is feasible, reliable, and safe in young infants with hemiplegia, and may help harness activity-dependent plasticity to enhance functional movement., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 McGloon, Humanitzki, Brennan, Summers, Brennan, George, Badran, Cribb, Jenkins and Coker-Bolt.)

Aims: The aim of this study is to assess and document engagement in type 2 diabetes mellitus (T2DM) self-care behaviors and self-reported diabetes knowledge among Marshallese adults living in the Republic of the Marshall Islands (RMI)., Methods: The study uses data from a T2DM health screening study completed in the RMI; survey and biometric data were captured as part of the health screenings. Study objectives were examined using descriptive statistics to describe the characteristics of the participants, their diabetes self-care behaviors, and their levels of self-reported diabetes knowledge., Results: Results indicate many Marshallese diagnosed with T2DM did not engage in adequate self-care behaviors, including blood sugar checks and foot examinations. Participants reported having forgone needed medical care and medication due to issues with cost and/or access, and participants reported low levels of diabetes knowledge., Conclusions: The results demonstrate the need for further work in improving engagement in diabetes self-care by Marshallese living in the RMI. Increased engagement in self-care and diabetes education programs may help Marshallese with T2DM to improve control of their glucose and avoid long-term health complications, as well as reduce costs to the healthcare system., Competing Interests: Declaration of Competing Interest The authors declared no competing interests., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Careful handling of missing data is crucial to ensure that clinical prediction models are developed, validated, and implemented in a robust manner. We determined the bias in estimating predictive performance of different combinations of approaches for handling missing data across validation and implementation. We found four strategies that are compatible across the model pipeline and have provided recommendations for handling missing data between model validation and implementation under different missingness mechanisms.

Quantum light emitters (also known as single photon emitters) are known to be the heart of quantum information technologies. Irrespective of possessing ideal single photon emitter properties, quantum emitters in 2-D hBN defect structures, exhibit constrained quantum light emission within the 300-700 nm range. However, this emission range cannot fully satisfy the needs of an efficient quantum communication applications such as quantum key distribution (QKD), which demands the quantum light emission in fiber optic telecom wavelength bands (from 1260 to 1625 nm) and the free space optical (FSO) (UV-C-solar blind band-100 to 280 nm) wavelength ranges. Hence, there is a necessity to tune the quantum light emission into these two bands. However, the most promising technique to tune the quantum light emitters in hBN here, is still a matter of debate and till date there is no experimental and theoretical assurances. Hence, this work will focus on one of the most promising simple techniques known as Stark electrical tuning of the quantum light emission of hBN defect structures (N B V N , V B , C B , C B V N , C B C N , C B C N C B C N complex, and V B O 2 ). These hBN defects are designed and sandwiched as metal/graphene/hBN defect structure/graphene/metal heterostructure and electrically tuned towards FSO and fiber optic bands (tuning range from UV-C to O-band IR region) region, using constrained DFT computations. The external electric field predicted to yield an atomic bond angle tilt associated with this point defect structure creates out-of-plane dipole moments, enabling the tuning of quantum emission. This electrical tuning technique leads to a simple passive photonic component which enables easier compatibility with quantum circuits and it is found to be one of the perfect alternative solutions, which does not require much external hardware setup to implement as compared to earlier published strain induced tuning experiments., (© 2024. The Author(s).)

Following the 1st Conference of the Global Collaboration on Traumatic Stress, the consortium committed to systematically integrating sex and gender considerations in their endeavours, which aligns with the European Journal of Psychotraumatology 's Gender Policy. This initiative is vital for understanding trauma's complex impacts, but also presents significant challenges in cross-cultural research. This letter, co-authored by researchers from across the globe, outlines these challenges and proposes mitigation strategies. First, definitions of sex and gender are provided from a Western perspective, while acknowledging cultural differences in these concepts. Second, the relevance of integrating sex and gender considerations in traumatic stress studies is briefly described. Third, cultural distinctions and legal contexts shaping the understanding and inclusion of these concepts, with non-Western and low-to-middle income regions facing significant legal and ethical obstacles are highlighted. Methodological challenges including measurement, recruitment, and statistical modelling are discussed, followed by recommendations including participatory approaches that involve members of the community, including sexual and gender minority individuals, as possible, throughout the research process, conducting risk analyses, employing sensitive quantitative and qualitative methods, and ensuring clear reporting and participant protection. To conclude, with this letter, we hope to instigate dialogue and foster innovative approaches to incorporating sex and gender considerations in cross-cultural studies of traumatic stress. Addressing these considerations is essential for ethical, meaningful research that respects and safeguards diverse experiences.

Healthcare under the auspices of late-stage capitalism is a total institution that mortifies nurses and patients alike, demanding conformity, obedience, perfection. This capture, which resembles Deleuze's enclosure, entangles nurses in carceral systems and gives way to a postenclosure society, an institution without walls. These societies of control constitute another sort of total institution, more covert and insidious for their invisibility (Deleuze, 1992). While Delezue (1992) named physical technologies like electronic identification badges as key to understanding these societies of control, the political economy of late-stage capitalism functions as a total institution with no cohesive, centralized, connected material apparatus required. In this manuscript, we outline the ways in which the healthcare industrial complex demands nurse conformity and how that, in turn, operationalizes nurses in service to the institution. This foundation leads to the assertion that nursing must foster a radical imagination for itself, unbound by reality as it presently exists, in order that we might conjure more just, equitable futures for caregivers and care receivers alike. To tease out what a radical imagination might look like, we dwell in paradox: getting folks the care they need in capitalist healthcare systems; engaging nursing's deep history to inspire alternative understandings for the future of the discipline; and how nursing might divest from extractive institutional structures. This paper is a jumping-off place to interrogate the ways institutions telescope and where nursing fits into the arrangement., (© 2023 John Wiley & Sons Ltd.)

Biological complexity is achieved through elaborate interactions between relatively few individual components. Affinity purification (AP) has allowed these networks of protein-protein interactions that regulate key biological processes to be interrogated systematically. In order to perform these studies at the required scale, easily transfectable immortalized cell lines have typically been used. Gene-editing now affords the systematic creation of isogenic mouse models carrying endogenous tags for affinity proteomics. This may allow protein-protein interactions to be characterized in the appropriate tissue for a particular biological process or disease phenotype under physiological conditions, and for interaction landscapes to be compared across tissues. Here we demonstrate application to intraflagellar transport (IFT) proteins, which are WD40-domain-containing proteins that are essential for the formation and function of all types of cilia. We describe a method to generate mice with an endogenous C-terminal streptavidin/FLAG tag, using Ift80 as an example, and demonstrate the successful implementation of AP in this model. This method can easily be adapted for N- and C-terminal tagging of many other proteins in vivo., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

Objective: The objective of this study was to offer further evidence of the utility of metabolic monitoring in early recognition of sepsis. Metabolic derangement in sepsis is of increasing interest. Sepsis was redefined as a dysregulated host response to infection, and studies have since emerged advising that disrupted metabolic pathways in sepsis may interfere with the host's ability to convert oxygen to useable energy. Indirect calorimetry (IC) is a metabolic monitoring technology that measures oxygen consumption (V02) and resting energy expenditure (REE). IC offers clinically important, specific information in terms of patient's metabolic state and has been shown to differentiate patients with sepsis from those without. Additionally, IC is more specific than predictive equations used as the established standard for clinical nutrition., Research Methods and Procedures: Data for this retrospective descriptive study were obtained from chart review of records of critically ill patients who received metabolic monitoring while under the care of the nutrition support team. Data were retrieved from January through March of 2020. The cases included were from January 2018 through January 2020. Variables included key demographics, sepsis diagnosis and specific metabolic variables of cellular respiration and energy expenditure., Results: For this all-male sample (N = 56), mean age was 56 years (±17.5). Significant differences were noted in V02 between the two groups of cases (sepsis and non-sepsis); (p = .026, Cohen's d = 0.618); and REE (p = .032, Cohen's d = 0.607). A strong association was found between V02 and sepsis (Eta 0.981). REE as measured by IC was statistically more specific than predictive equation (p < .001, Cohen's d = 0.527)., Conclusions: VO2 and REE were significantly altered in subjects with sepsis in this study, demonstrating that IC may be a useful tool in identifying sepsis. This study was based on an earlier pilot which yielded similar results. Indirect calorimetry can be easily performed clinically, offering specific metabolic information that can be helpful in the determination of a diagnosis of sepsis., Patient or Public Contribution: No patient or public contribution to this manuscript. The study design, analysis of retrospective data, and manuscript preparation were completed entirely by the authors., Implications for Clinicians: Sepsis remains one of the number one killers of hospitalized patients globally Current means of identifying sepsis remain overly sensitive and under-specific, making recognition of sepsis challenging for Emergency Clinicians Metabolic monitoring can be done easily in the clinical setting by nurses and respiratory therapists. Metabolic monitoring has the capability of offering further information specific to the identification of sepsis, and to further understanding of the altered metabolic phenotype of patients with sepsis., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Bardet-Biedl syndrome (BBS) is an archetypal ciliopathy caused by dysfunction of primary cilia. BBS affects multiple tissues, including the kidney, eye and hypothalamic satiety response. Understanding pan-tissue mechanisms of pathogenesis versus those which are tissue-specific, as well as gauging their associated inter-individual variation owing to genetic background and stochastic processes, is of paramount importance in syndromology. The BBSome is a membrane-trafficking and intraflagellar transport (IFT) adaptor protein complex formed by eight BBS proteins, including BBS1, which is the most commonly mutated gene in BBS. To investigate disease pathogenesis, we generated a series of clonal renal collecting duct IMCD3 cell lines carrying defined biallelic nonsense or frameshift mutations in Bbs1 , as well as a panel of matching wild-type CRISPR control clones. Using a phenotypic screen and an unbiased multi-omics approach, we note significant clonal variability for all assays, emphasising the importance of analysing panels of genetically defined clones. Our results suggest that BBS1 is required for the suppression of mesenchymal cell identities as the IMCD3 cell passage number increases. This was associated with a failure to express epithelial cell markers and tight junction formation, which was variable amongst clones. Transcriptomic analysis of hypothalamic preparations from BBS mutant mice, as well as BBS patient fibroblasts, suggested that dysregulation of epithelial-to-mesenchymal transition (EMT) genes is a general predisposing feature of BBS across tissues. Collectively, this work suggests that the dynamic stability of the BBSome is essential for the suppression of mesenchymal cell identities as epithelial cells differentiate.

Emulsion-templated foams have displayed promise as injectable bone grafts; however, the use of a surfactant as an emulsifier resulted in relatively small pores and impedes cell attachment. Hydroxyapatite nanoparticles were explored as an alternative stabilizer to address these limitations. To this end, hydroxyapatite nanoparticles were first modified with myristic acid to generate the appropriate balance of hydrophobicity to stabilize a water-in-oil emulsion of neopentyl glycol diacrylate and 1,4-butanedithiol. In situ surface modification of the resulting foam with hydroxyapatite was confirmed with elemental mapping and transmission electron microscopy. Nanoparticle-stabilized foams displayed improved human mesenchymal stem cell viability (91 ± 5%) over surfactant-stabilized foams (23 ± 11%). Although the pore size was appropriate for bone grafting applications (115 ± 71 μm), the foams lacked the interconnected architecture necessary for cell infiltration. We hypothesized that a co-stabilization approach with both surfactant and nanoparticles could be used to achieve interconnected pores while maintaining improved cell attachment and larger pore sizes. A range of hydroxyapatite nanoparticle and surfactant concentrations were investigated to determine the effects on microarchitecture and cell behavior. By balancing these interactions, a co-stabilized foam was identified that possessed large, interconnected pores (108 ± 67 μm) and improved cell viability and attachment. The co-stabilized foam was then evaluated as an injectable bone graft including network formation, microscale integration with bone, push out strength, and compressive properties. Overall, this work demonstrated that in situ surface modification with nHA improved cell attachment while retaining desirable bone grafting features and injectability.

Competing Interests: Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: none.