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Background: Outcomes for children with heart disease improved over the past decades. Quality improvement (QI) research in paediatric cardiac critical care is a key driver of improvement. The availability and variability of QI research across the field is unknown. This project represents a step in understanding the role. The Pediatric Cardiac Intensive Care Society (PCICS) can serve to support institutions' needs, drive collaborations, and utilise available infrastructure at member institutions for improvement work., Methods: The PCICS Quality Improvement and Safety Committee developed a survey to assess the state of QI research. The survey was disseminated over several months and available via QR code at the World Congress of Pediatric Cardiology and Cardiac Surgery in 2023., Results: Fifty-eight respondents completed the survey representing at least 38 unique institutions. Most respondents participated in QI research (52/58, 90%). Most QI projects were single centre (41% of respondents), and of those, the majority were from a minority of institutions (13 institutions [34% of total institutions]). QI support is available at slightly more than half of units, and 55% (32/58) have access to a QI specialist. QI support and rate of publications is significantly lower for small/medium units as compared to large units. Respondents suggested most interest from PCICS in networking with other members with similar project ideas (50/58, 86%)., Conclusion: PCICS member institutions are committed to QI research, with limitations in support, local specialists, and networking. Increasing connectivity and accessibility to QI resources may reduce burden to individual members and institutions to achieve QI research.

The microaerophilic parasite Trichomonas vaginalis occurs worldwide and causes inflammation of the urogenital tract, especially in women. With 156 million infections annually, trichomoniasis is the most prevalent non-viral sexually transmitted disease. Trichomoniasis is treated with 5-nitroimidazoles, especially metronidazole, which are prodrugs that have to be reduced at their nitro group to be activated. Resistance rates to metronidazole have remained comparably low, but they can be higher in certain areas leading to an increase of refractory cases. Metronidazole resistance in T. vaginalis can develop in vivo in clinical isolates, or it can be induced in the laboratory. Both types of resistance share certain characteristics but differ with regard to the dependence of ambient oxygen to become manifest. Although several candidate factors for metronidazole resistance have been described in the past, e.g. pyruvate:ferredoxin oxidoreductase and ferredoxin or thioredoxin reductase, open questions regarding their role in resistance have remained. In order to address these questions, we performed a proteomic study with metronidazole-sensitive and -resistant laboratory strains, as well as with clinical strains, in order to identify factors causative for resistance. The list of proteins consistently associated with resistance was surprisingly short. Resistant laboratory and clinical strains only shared the downregulation of flavin reductase 1 (FR1), an enzyme previously identified to be involved in resistance. Originally, FR1 was believed to be an oxygen scavenging enzyme, but here we identified it as a ferric iron reductase which produces ferrous iron. Based on this finding and on further experimental evidence as presented herein, we propose a novel mechanism of metronidazole activation which is based on ferrous iron binding to proteins, thereby rendering them susceptible to complex formation with metronidazole. Upon resolution of iron-protein-metronidazole complexes, metronidazole radicals are formed which quickly react with thiols or proteins in the direct vicinity, leading to breaks in the peptide backbone., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose.

Background: Poppy seed (PS) can be a cause of severe allergic reactions, especially in individuals with concurrent allergy to tree nuts and other seeds, but diagnostic criteria and sensitization patterns are lacking., Objective: To assess the role of PS extract and individual allergens in diagnosing PS allergy and their cross-reactivities with tree nuts and buckwheat., Methods: Our retrospective study included 36 PS-sensitized patients; 10 with a positive and 26 with a negative oral food challenge (OFC). We identified individual PS allergens and compared the diagnostic performance of specific IgE (sIgE) to PS extract with its allergens. Cross-reactivities between PS and related allergens from other seeds were assessed by a competitive enzyme-linked immunosorbent assay., Results: We identified 4 novel PS allergens: Pap s 1 (vicilin), Pap s 1 (27-424) (α-hairpinin), Pap s 2 (legumin), and Pap s 3 (small hydrophilic seed protein). A positive OFC correlated with higher PS-sIgE levels and elevated sIgE levels for the PS allergens, except for Pap s 3. PS and α-hairpinin-sIgE effectively differentiated allergic from tolerant patients, with area under the curve values of 0.95 and 0.94. PS-sIgE >10.00 kU A /L exhibited 90% sensitivity and 73% specificity, whereas α-hairpinin-sIgE >2.60 kU A /L showed 100% sensitivity and 77% specificity. PS vicilin and legumin highly cross-reacted with hazelnut and buckwheat homologs, whereas α-hairpinin-sIgE cross-reacted with the related almond allergen., Conclusions: This is the most extensive study on PS allergy to date. PS and α-hairpinin-sIgE are highly sensitive indicators of clinical reactivity to PS, whereas vicilin and legumin-sIgE contribute to concurrent sensitization to hazelnut and buckwheat., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The OpenFlexure Microscope is an accessible, three-dimensional-printed robotic microscope, with sufficient image quality to resolve diagnostic features including parasites and cancerous cells. As access to lab-grade microscopes is a major challenge in global healthcare, the OpenFlexure Microscope has been developed to be manufactured, maintained and used in remote environments, supporting point-of-care diagnosis. The steps taken in transforming the hardware and software from an academic prototype towards an accepted medical device include addressing technical and social challenges, and are key for any innovation targeting improved effectiveness in low-resource healthcare. This article is part of the Theo Murphy meeting issue 'Open, reproducible hardware for microscopy'.

Introduction: Little is known about the proteomic changes at the portals of entry in rainbow trout after infection with the myxozoan parasites, Myxobolus cerebralis , and Tetracapsuloides bryosalmonae . Whirling disease (WD) is a severe disease of salmonids, caused by the myxosporean M. cerebralis , while, proliferative kidney disease (PKD) is caused by T. bryosalmonae , which instead belongs to the class Malacosporea. Climate change is providing more suitable conditions for myxozoan parasites lifecycle, posing a high risk to salmonid aquaculture and contributing to the decline of wild trout populations in North America and Europe. Therefore, the aim of this study was to provide the first proteomic profiles of the host in the search for evasion strategies during single and coinfection with M. cerebralis and T. bryosalmonae ., Methods: One group of fish was initially infected with M. cerebralis and another group with T. bryosalmonae . After 30 days, half of the fish in each group were co-infected with the other parasite. Using a quantitative proteomic approach, we investigated proteomic changes in the caudal fins and gills of rainbow trout before and after co-infection., Results: In the caudal fins, 16 proteins were differentially regulated post exposure to M. cerebralis , whereas 27 proteins were differentially modulated in the gills of the infected rainbow trout post exposure to T. bryosalmonae . After co-infection, 4 proteins involved in parasite recognition and the regulation of host immune responses were differentially modulated between the groups in the caudal fin. In the gills, 11 proteins involved in parasite recognition and host immunity, including 4 myxozoan proteins predicted to be virulence factors, were differentially modulated., Discussion: The results of this study increase our knowledge on rainbow trout co-infections by myxozoan parasites and rainbow trout immune responses against myxozoans at the portals of entry, supporting a better understanding of these host-parasite interactions., 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 © 2024 Saleh, Hummel, Schlosser, Razzazi-Fazeli, Bartholomew, Holzer, Secombes and El-Matbouli.)

Background: Despite the burden of CHD, a high cost and utilization condition, an implementation of long-term outcome measures is lacking. The objective of this study is to pilot the implementation of the International Consortium of Health Outcomes Measurement CHD standard set in patients undergoing pulmonary valve replacement, a procedure performed in mostly well patients with diverse CHD., Methods: Patients ≥ 8 years old undergoing catheterization-based pulmonary valve replacement were approached via various approaches for patient-reported outcomes, with a follow-up assessment at 3 months post-procedure. Implementation strategy analysis was performed via a hybrid type 2 design., Results: Of the 74 patients undergoing pulmonary valve replacement, 32 completed initial patient-reported outcomes with variable response rates by strategy (email and in-person explanation 100%, email only 54%, and email followed by text/call 64%). Ages ranged 8-67 years (mean 30). Pre-procedurally, 34% had symptomatic arrhythmias, which improved post-procedure. For those in school, 43% missed ≥ 6 days per year, and over half had work absenteeism. Financial concerns were reported in 34%. Patients reported high satisfaction with life (50% [n = 16]) and health-related quality of life (90% [n = 26]). Depression symptoms were reported in 84% (n = 27) and anxiety in 62.5% (n = 18), with tendency towards improvement post-procedurally., Conclusion: Pilot implementation of the International Consortium of Health Outcomes Measurement CHD standard set in pulmonary valve replacement patients reveals a significant burden of disease not previously reported. Barriers to the implementation include a sustainable, automated system for patient-reported outcome collection and infrastructure to assess in real time. This provides an example of implementing cardiac outcomes set in clinical practice.

Background: CHD is a lifelong condition with a significant burden of disease to patients and families. With increased survival, attention has shifted to longer-term outcomes, with a focus on social determinants of health. Among children with CHD, socioeconomic status is associated with disparities in outcomes. Household material hardship is a concrete measure of poverty and may serve as an intervenable measure of socioeconomic status., Methods: A longitudinal survey study was conducted at multiple time points (at acute hospitalisation, then 12-24 months later in the chronic phase) to determine the prevalence of household material hardship among parents of children with advanced heart disease and quality of life during long-term follow-up., Results: The analytic cohort was 160 children with a median patient age of 1 year (IQR 1,4) with 54% of patients <2 years. During acute hospitalisation, over one-third of families reported household material hardship (37%), with significantly lower household material hardship in the chronic phase at 16% (N = 9 of 52). For parents reporting household material hardship during acute hospitalisation, 50% had resolution of household material hardship by the chronic phase. Household material hardship-exposed children were significantly more likely to be publicly insured (56% versus 20%, p = 0.03) with lower quality of life than those without household material hardship (64% versus 82%, p = 0.013)., Conclusion: The burden of heart disease during the chronic phase of illness is high. Household material hardship may serve as a target to ensure equity in the care and outcomes of CHD patients and their families.

Background: The new XR-Series haematology analyser from Sysmex provides increased throughput and automation, along with a new reagent in WDF channel for optimised WBC differential., Methods: An analytical performance study for the XR analyser was conducted to evaluate the WDF channel parameters in comparison to the instrument specifications. Additionally, 7460 samples were measured on XR and XN analysers to compare selected parameters and flags, and 930 randomly selected samples were further evaluated with microscopy., Results: All investigated aspects of the analytical performance study for the XR fell within the manufacturer specifications. The correlation coefficients between the two systems for the parameters tested were greater than 0.983 for the main CBC and DIFF parameters, greater than 0.909 for the Extended Inflammation Parameters, and greater than 0.932 for the parameters used in the workflow rulesets of the Extended IPU. Similarly high sensitivities for the detection of abnormal cells were observed for the 'Blasts/Abn Lympho?' flag (XN: 100%, XR: 99.0%) and WPC abnormal flags ('Blasts?' or 'Abn Lympho?') (XN: 97.0%, XR: 96.0%). XN with WPC channel had a 26% reduction of false positive smears compared to XR with 22% reduction, a statistically non-significant difference., Conclusion: The XR analyser had very good analytical performance, and highly comparable results to the predecessor XN analyser in all investigated parameters, flags and workflow aspects., Competing Interests: Katharina Dammert, Konstantinos Mintzas, Jarob Saker and Ondrej Valina are employed by Sysmex Europe SE. Kenichi Fujimaki and Immaculate Magonde are employed by Sysmex R&D center Europe. Yoshiko Hamaguchi is employed by Sysmex Corporation. Other authors have no competing interests., (© 2024 The Authors. Published by Elsevier B.V.)

Bottom-up proteomic approaches depend on the efficient digestion of proteins into peptides for mass spectrometric analysis. Sample preparation strategies, based on magnetic beads, filter-aided systems, or in-solution digests, are commonly used for proteomic analysis. Time-intensive methods like filter-aided sample preparation (FASP) have led to the development of new, more time-efficient filter-based strategies like suspension trappings (S-Traps) or magnetic bead-based strategies like SP3. S-Traps have been reported as an alternative proteomic sample preparation method as they allow for high sodium dodecyl sulfate (SDS) concentrations to be present in the sample. In this study, we compare the efficiency of different protocols for FASP, SP3, and S-Trap-based digestion of proteins after extraction from Trichomonas vaginalis . Overall, we found a high number of protein IDs for all tested methods and a high degree of reproducibility within each method type. However, FASP with a 3 kDa cutoff filter unit outperformed the other methods analyzed, referring to the number of protein IDs. This is the first work providing the direct comparison of four different bottom-up proteomic approaches regarding the most efficient proteomic sample preparation protocol for the human parasite T. vaginalis ., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: There are little reported data on the perspectives of fathers caring for children with chronic conditions. Although survival of children with advanced heart disease has improved, long-term morbidity remains high. This study describes the experience and prognostic awareness of fathers of hospitalised children with advanced heart disease., Methods: Cross-sectional survey study of parents caring for children hospitalised with advanced heart disease admitted for ≥ 7 days over a one-year period. One parent per patient completed surveys, resulting in 27 father surveys. Data were analysed using descriptive methods., Results: Nearly all (96%) of the fathers reported understanding their child's prognosis "extremely well" or "well," and 59% felt they were "very prepared" for their child's medical problems. However, 58% of fathers wanted to know more about prognosis, and 22% thought their child's team knew something about prognosis that they did not. Forty-one per cent of fathers did not think that their child would have lifelong limitations, and 32% anticipated normal life expectancies. All 13 fathers who had a clinical discussion of what would happen if their child got sicker found this conversation helpful. Nearly half (43%) of the fathers receiving new prognostic information or changes to treatment course found it "somewhat" or "a little" confusing., Conclusions: Fathers report excellent understanding of their child's illness and a positive experience around expressing their hopes and fears. Despite this, there remain many opportunities to improve communication, prognostic awareness, and participation in informed decision-making of fathers of children hospitalised with advanced heart disease.

Introduction: The apicomplexan parasite Cystoisospora suis has global significance as an enteropathogen of suckling piglets. Its intricate life cycle entails a transition from an asexual phase to sexual development, ultimately leading to the formation of transmissible oocysts., Methods: To advance our understanding of the parasite's cellular development, we complemented previous transcriptome studies by delving into the proteome profiles at five distinct time points of in vitro cultivation through LC/MS-MS analysis., Results: A total of 1,324 proteins were identified in the in vitro developmental stages of C. suis , and 1,082 proteins were identified as significantly differentially expressed. Data are available via ProteomeXchange with identifier PXD045050. We performed BLAST, GO enrichment, and KEGG pathway analyses on the up- and downregulated proteins to elucidate correlated events in the C. suis life cycle. Our analyses revealed intriguing metabolic patterns in macromolecule metabolism, DNA- and RNA-related processes, proteins associated with sexual stages, and those involved in cell invasion, reflecting the adaptation of sexual stages to a nutrient-poor and potentially stressful extracellular environment, with a focus on enzymes involved in metabolism and energy production., Discussion: These findings have important implications for understanding the developmental biology of C. suis as well as other, related coccidian parasites, such as Eimeria spp. and Toxoplasma gondii . They also support the role of C. suis as a new model for the comparative biology of coccidian tissue cyst stages., 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 Cruz-Bustos, Dolezal, Feix, Ruttkowski, Hummel, Razzazi-Fazeli and Joachim.)

Epithelioid trophoblastic tumor (ETT) is a rare neoplasm derived from chorionic intermediate trophoblast cells, representing less than 2% of all gestational trophoblastic neoplasms. Classically, ETT presents as a uterine mass in women of reproductive age following a term pregnancy. The time from pregnancy to tumor development varies from months to several years. ETT most often arises in the endometrium, followed by the cervix. Extrauterine ETT are extremely infrequent, with few cases reported in the literature. We report a case of a 41-year-old woman, with history of three term pregnancies who presented with abdominal pain and elevated beta human chorionic gonadotropin (β-hCG) level, ten years after her last pregnancy. Imaging reported a 3.5 cm adnexal mass, suspicious for ectopic pregnancy. Hysterectomy and mass resection revealed a 4.7 cm, tan-yellow, necrotic mass adjacent to the broad ligament. Histologic evaluation in conjunction with immunohistochemical stains revealed a tumor consistent with ETT. No connection to the endometrium was found grossly or microscopically. DNA fingerprinting analysis revealed the tumor to have two copies of paternal alleles, as seen in molar gestations. One of the primary differential diagnoses for ETT is squamous cell carcinoma due to similar morphologic features. In challenging cases, genetic analysis demonstrating paternally derived genes can establish the diagnosis. In this report, we discuss the challenges in the diagnosis of extrauterine ETT, due to its rarity and highly variable presentation, given that appropriate diagnosis is critical for correct patient management.

Hospital noise can be problematic for both patients and staff and consistently is rated poorly on national patient satisfaction surveys. A surge of research in the last two decades highlights the challenges of healthcare acoustic environments. However, existing research commonly relies on conventional noise metrics such as equivalent sound pressure level, which may be insufficient to fully characterize the fluctuating and complex nature of the hospital acoustic environments experienced by occupants. In this study, unsupervised machine learning clustering techniques were used to extract patterns of activity in noise and the relationship to patient perception. Specifically, nine patient rooms in three adult inpatient hospital units were acoustically measured for 24 h and unsupervised machine learning clustering techniques were applied to provide a more detailed statistical analysis of the acoustic environment. Validation results of five different clustering models found two clusters, labeled active and non-active, using k-means. Additional insight from this analysis includes the ability to calculate how often a room is active or non-active during the measurement period. While conventional LAeq was not significantly related to patient perception, novel metrics calculated from clustered data were significant. Specifically, lower patient satisfaction was correlated with higher Active Sound Levels, higher Total Percent Active, and lower Percent Quiet at Night metrics. Overall, applying statistical clustering to the hospital acoustic environment offers new insights into how patterns of background noise over time are relevant to occupant perception., (© 2023 Acoustical Society of America.)

Scope: Red meat, a staple food of Western diets, can also induce IgE-mediated allergic reactions. Yet, apart from the heat-labile protein serum albumin and the carbohydrate α-Gal, the molecules causing allergic reactions to red meat remain unknown., Methods and Results: IgE reactivity profiles of beef-sensitized individuals are analyzed by IgE-immunoblotting with protein extracts from raw and cooked beef. Two IgE-reactive proteins are identified by peptide mass fingerprinting as myosinlight chain 1 (MYL1) and myosin light chain 3 (MYL3) in cooked beef extract and are designated Bos d 13 isoallergens. MYL1 and MYL3 are produced recombinantly in Escherichia coli. ELISAs proved their IgE reactivity and circular dichroism analysis showed that they represent folded molecules with remarkable thermal stability. In vitro gastrointestinal digestion experiments showed the higher stability of rMYL1 as compared to rMYL3. Exposure of a monolayer of Caco-2 cells to rMYL1 indicated that the molecule is able to cross intestinal epithelial cells without disturbing the integrity of the tight junctions, suggesting the sensitizing capacity of MYL1., Conclusion: MYLs are identified as novel heat-stable bovine meat allergens., (© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.)

The anaerobic gut bacteria and opportunistic pathogen Bacteroides fragilis can cause life-threatening infections when leaving its niche and reaching body sites outside of the gut. The antimicrobial metronidazole is a mainstay in the treatment of anaerobic infections and also highly effective against Bacteroides spp. Although resistance rates have remained low in general, metronidazole resistance does occur in B . fragilis and can favor fatal disease outcomes. Most metronidazole-resistant Bacteroides isolates harbor nim genes, commonly believed to encode for nitroreductases which deactivate metronidazole. Recent research, however, suggests that the mode of resistance mediated by Nim proteins might be more complex than anticipated because they affect the cellular metabolism, e.g., by increasing the activity of pyruvate:ferredoxin oxidoreductase (PFOR). Moreover, although nim genes confer only low-level metronidazole resistance to Bacteroides , high-level resistance can be much easier induced in the laboratory in the presence of a nim gene than without. Due to these observations, we hypothesized that nim genes might induce changes in the B . fragilis proteome and performed comparative mass-spectrometric analyses with B . fragilis 638R, either with or without the nimA gene. Further, we compared protein expression profiles in both strains after induction of high-level metronidazole resistance. Interestingly, only few proteins were repeatedly found to be differentially expressed in strain 638R with the nimA gene, one of them being the flavodiiron protein FprA, an enzyme involved in oxygen scavenging. After induction of metronidazole resistance, a far higher number of proteins were found to be differentially expressed in 638R without nimA than in 638R with nimA . In the former, factors for the import of hemin were strongly downregulated, indicating impaired iron import, whereas in the latter, the observed changes were not only less numerous but also less specific. Both resistant strains, however, displayed a reduced capability of scavenging oxygen. Susceptibility to metronidazole could be widely restored in resistant 638R without nimA by supplementing growth media with ferrous iron sulfate, but not so in resistant 638R with the nimA gene. Finally, based on the results of this study, we present a novel hypothetic model of metronidazole resistance and NimA function., 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 Paunkov, Hummel, Strasser, Sóki and Leitsch.)

Phytogenic compounds may influence salivation or salivary properties. However, their effects on the bovine salivary proteome have not been evaluated. We investigated changes in the bovine salivary proteome due to transition from forage to high-concentrate diet, with and without supplementation with a phytogenic feed additive. Eight non-lactating cows were fed forage, then transitioned to a 65% concentrate diet (DM basis) over a week. Cows were control (n = 4, CON) or supplemented with a phytogenic feed additive (n = 4, PHY). Proteomic analysis was conducted using liquid chromatography coupled with mass spectrometry. We identified 1233 proteins; 878 were bovine proteins, 189 corresponded to bacteria, and 166 were plant proteins. Between forage and high-concentrate, 139 proteins were differentially abundant (P < 0.05), with 48 proteins having a log2FC difference > |2|. The salivary proteome reflected shifts in processes involving nutrient utilization, body tissue accretion, and immune response. Between PHY and CON, 195 proteins were differently abundant (P < 0.05), with 37 having a log2FC difference > |2|; 86 proteins were increased by PHY, including proteins involved in smell recognition. Many differentially abundant proteins correlated (r > |0.70|) with salivary bicarbonate, total mucins or pH. Results provide novel insights into the bovine salivary proteome using a non-invasive approach, and the association of specific proteins with major salivary properties influencing rumen homeostasis. SIGNIFICANCE: Phytogenic compounds may stimulate salivation due to their olfactory properties, but their effects on the salivary proteome have not been investigated. We investigated the effect of high-concentrate diets and supplementation with a phytogenic additive on the salivary proteome of cows. We show that analysis of cows' saliva can be a non-invasive approach to detect effects occurring not only in the gut, but also systemically including indications for gut health and immune response. Thus, results provide unique insights into the bovine salivary proteome, and will have a crucial contribution to further understand animal response in terms of nutrient utilization and immune activity due to the change from forage to a high-energy diet. Additionally, our findings reveal changes due to supplementation with a phytogenic feed additive with regard to health and olfactory stimulation. Furthermore, findings suggest an association between salivary proteins and other components like bicarbonate content., Competing Interests: Declaration of Competing Interest Nicole Reisinger is employed by BIOMIN Holding GmbH, which is part of DSM, a company that manufactures and trades feed additives. However, this fact did not influence the analysis of data nor the interpretation of results., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

There is significant uncertainty in describing prognosis and a lack of reliable entry criteria for palliative care studies in children with advanced heart disease (AHD). This study evaluates the utility of the surprise question-"Would you be surprised if this child died within the next year?"-to predict one-year mortality in children with AHD and assess its utility as entry criteria for future trials. This is a prospective cohort study of physicians and nurses caring for children (1 month-19 years) with AHD hospitalized ≥ 7 days. AHD was defined as single ventricle physiology, pulmonary vein stenosis or pulmonary hypertension, or any cardiac diagnosis with signs of advanced disease. Primary physicians were asked the surprise question and medical record review was performed. Forty-nine physicians responded to the surprise question for 152 patients. Physicians responded "No, I would not be surprised if this patient died" for 54 (36%) patients, 20 (37%) of whom died within 1 year, predicting one-year mortality with 77% sensitivity, 73% specificity, 37% positive predictive value, and 94% negative predictive value. Patients who received a "No" response had an increased 1-year risk of death (hazard ratio 7.25, p < 0.001). Physician years of experience, subspecialty, and self-rated competency were not associated with the accuracy of the surprise question. The surprise question offers promise as a bedside screening tool to identify children with AHD at high risk for mortality and help physicians identify patients who may benefit from palliative care and advance care planning discussions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Proteome analyses can be used to detect biomarkers for the healthy and diseased organism. However, data in cats are scarce, and no information is available on the potential impact of nutritional interventions on the feline urine proteome. In the present study, a label-free shotgun proteomics approach was performed to investigate the urinary proteins of four healthy adult cats. Each animal received a high-protein complete diet without (w/o) or with supplements that could affect the protein metabolism: arginine (+100% compared to the arginine concentration in the w/o diet), ornithine (+200% compared to the arginine concentration in the w/o diet) or zeolite (0.375 g/kg body weight/day). Our results demonstrate a huge number of proteins in the urine of cats (516 ± 49, 512 ± 39, 399 ± 149 and 455 ± 134 in the w/o, arginine, ornithine and zeolite group, respectively), which are associated with several biological processes. In addition, up- and downregulated urinary proteins could be detected in the dietary supplementation periods. Overall, the present pilot study provides basic data on the urine proteome of healthy adult cats. With increasing information, the numerousness of urinary proteins implies the potential to identify biomarkers and metabolic pathways in the feline organism.

Histomonas meleagridis, a poultry-specific intestinal protozoan parasite, is histomonosis's etiological agent. Since treatment or prophylaxis options are no longer available in various countries, histomonosis can lead to significant production losses in chickens and mortality in turkeys. The surfaceome of microbial pathogens is a crucial component of host-pathogen interactions. Recent proteome and exoproteome studies on H. meleagridis produced molecular data associated with virulence and in vitro attenuation, yet the information on proteins exposed on the cell surface is currently unknown. Thus, in the present study, we identified 1485 proteins and quantified 22 and 45 upregulated proteins in the virulent and attenuated strains, respectively, by applying cell surface biotinylation in association with high-throughput proteomic analysis. The virulent strain displayed upregulated proteins that could be linked to putative virulence factors involved in the colonization and establishment of infection, with the upregulation of two candidates being confirmed by expression analysis. In the attenuated strain, structural, transport and energy production proteins were upregulated, supporting the protozoan's adaptation to the in vitro environment. These results provide a better understanding of the surface molecules involved in the pathogenesis of histomonosis, while highlighting the pathogen's in vitro adaptation processes.

Background: Intensivists are increasingly attuned to the postdischarge outcomes experienced by families because patient recovery and family outcomes are interdependent after childhood critical illness. In this scoping review of international contemporary literature, we describe the evidence of family effects and functioning postpediatric intensive care unit (PICU) as well as outcome measures used to identify strengths and weaknesses in the literature., Methods: We reviewed all articles published between 1970 and 2017 in PubMed, Embase, PsycINFO, Cumulative Index of Nursing and Allied Health Literature (CINAHL), or the Cochrane Controlled Trials Registry. Our search used a combination of terms for the concept of "critical care/illness" combined with additional terms for the prespecified domains of social, cognitive, emotional, physical, health-related quality of life (HRQL), and family functioning., Results: We identified 71 articles reporting on the postPICU experience of more than 2400 parents and 3600 families of PICU survivors in 8 countries. These articles used 101 different metrics to assess the various aspects of family outcomes; 34 articles also included open-ended interviews. Overall, most families experienced significant disruption in at least five out of six of our family outcomes subdomains, with themes of decline in mental health, physical health, family cohesion, and family finances identified. Almost all articles represented relatively small, single-center, or disease-specific observational studies. There was a disproportionate representation of families of higher socioeconomic status (SES) and Caucasian race, and there was much more data about mothers compared to fathers. There was also very limited information regarding outcomes for siblings and extended family members after a child's PICU stay., Conclusions: Significant opportunities remain for research exploring family functioning after PICU discharge. We recommend that future work include more diverse populations with respect to the critically ill child as well as family characteristics, include more intervention studies, and enrich existing knowledge about outcomes for siblings and extended family.

NX is a type A trichothecene produced by Fusarium graminearum with limited information on its toxicity. NX is structurally similar to deoxynivalenol (DON), only differing by the lacking keto group at C8. Because of the structural similarity of the two toxins as well as their potential co-occurrence in food and feed, it is of interest to determine the toxicity of this new compound. In this study, we compared the protein composition of the extracellular media of pig intestinal explants (secretome) exposed to 10 µM of DON or NX for 4 h compared with controls. The combination of two complementary quantitative proteomic approaches (a gel-based and a gel-free approach) identified 18 and 23 differentially abundant proteins (DAPs) for DON and NX, respectively, compared to controls. Functional analysis suggested that, whereas DON toxicity was associated with decreased cell viability and cell destruction, NX toxicity was associated with an enrichment of mitochondrial proteins in the secretome. The presence of these proteins may be associated with the already known ability of NX to induce an intestinal inflammation. Overall, our results indicated that DON- and NX-induced changes in the extracellular proteome of intestinal explants are different. The increased leakage/secretion of mitochondrial proteins by NX may be a feature of NX toxicity., (© 2022. The Author(s).)

Introduction: The success of quality improvement (QI) projects depends on many factors, with communication and knowledge of project-specific practice change being fundamental. This project aimed to improve the knowledge of active safety and QI projects., Methods: Two interventions were trialed to improve knowledge: paired email and meeting announcements followed by a daily huddle to review ongoing projects. Knowledge, measured as the ability to recall a project and its practice change, was the primary outcome. The frequency and duration of the Huddle were process and balancing measures, respectively., Results: Seven days after a meeting/email announcement, 3 of 13 (23%) faculty and fellows recalled the announced practice change. Investigators then tested the effects of the Huddle by assessing practitioners' knowledge of safety and QI project-related practice changes on the first and last day of a service week. The average percentage of items recalled increased from the beginning to end of a service week by 33% [46% to 79%, 95% confidence interval (CI) 12-53] for faculty and 27% (51% to 77%, 95% CI 13-40) for fellows. The Huddle occurred in four of seven (interquartile range 2-5) days/wk with a mean duration of 4.5 (SD 2) minutes. Follow-up assessment 2 years after Huddle implementation demonstrate sustained increase in item recall [faculty +36% (95% CI +13% to 40%); fellows +35% (95% CI +23% to 47%)]., Conclusions: A daily huddle to discuss safety and QI project-related practice change is an effective and time-efficient communication method to increase knowledge of active projects., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The National Aeronautics and Space Administration-European Space Agency (NASA-ESA) Mars Sample Return (MSR) campaign involves the collection of samples on Mars by the Perseverance (Mars 2020) rover and their return to Earth. To accomplish this, the Orbiting Sample container (OS) will be sent to Mars to accommodate the collected samples then launched from Mars and returned to Earth, where the samples will be removed for examination in the Sample Return Facility (SRF). Crucial to this entire sequence will be establishment of the required level of cleanliness inside the OS. In February 2021, the NASA Headquarters' Mars Sample Return Program and Office of Planetary Protection assembled an MSR OS Tiger Team (OSTT) to discuss the appropriate cleanliness level options of the interior of the OS. The team's remit was primarily focused on evaluating the trade-offs between Planetary Protection cleanliness levels 4a and 4b. These cleanliness levels are determined by the Committee on Space Research (COSPAR) planetary protection regulations, where 4a requires <300 bacterial spores/m 2 and <3 x 10 5 bacterial spores on the spacecraft (in this case, the interior of the OS) and 4b mandates the more stringent requirement of <30 bacterial spores on the spacecraft. This report documents the consensus opinion submitted by the OSTT that recommended the interior of the OS be cleaned to a 4a requirement with any feasible added effort toward 4b. This report provides, as well, the rationale for that decision.

Macadamia nut is an increasingly popular food item of a healthy diet. However, macadamia nut is also a potent allergenic food. To date, there is little information about the allergenic proteins involved. In this study, using sera from macadamia nut allergic individuals, four IgE-binding proteins were detected. Their identities were determined by tandem mass spectrometry with de novo sequencing. Three IgE-reactive proteins, the vicilin Mac i 1, the legumin Mac i 2 and the antimicrobial peptide 2a/Mac i 1 (28-76) were purified from the nut while the non-specific lipid transfer protein was produced as a recombinant in Pichia pastoris. IgE-binding assays using sera from well-characterized groups of tree nut and/or peanut allergic patients revealed that the allergens were mainly recognized by sera from macadamia nut allergic individuals. Hence, these newly discovered allergens will enable molecular diagnostics to identify patients at high risk of macadamia nut allergy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Dichlorodiphenyltrichloroethane (DDT), a persistent organochlorine pesticide, has been linked to adverse biological effects in organisms. However, there is limited knowledge about its toxic effects on marine organisms and the underlying molecular mechanisms. This study investigated the toxic effects of DDT in the hooded oyster Saccostrea cucullata. The oysters were exposed to DDT at concentrations of 0, 10, 50, 100, 500, 1000 and 2000 µg/L for 96 h and the LC 50 (96 h) was 891.25 µg/L. Two sublethal concentrations (10 and 100 µg/L) were used to investigate the histopathological effects and the proteome response. Histopathological results showed that DDT caused the alteration of mantle tissue. This included the induction of mucocytes in the epithelium and the inflammatory effect in the connective tissue indicated by the enlargement of blood sinus and hemocyte aggregation within the sinus. Proteomic results showed that, amongst approximately 500 protein spots that were detected across 2DE gels, 51 protein spots were differentially expressed (P < 0.01; fold change > 1.2). Of these, 29 protein spots were identified by LC-MS/MS. These included 23 up-regulated, 5 down-regulated and 1 fluctuating spots. Thus, we observed that stress response and cytoskeletal proteins are the central targets of DDT action. Furthermore, DDT alters the expression of proteins involved in energy metabolism, calcium homeostasis and other proteins of unknown function. Additionally, proteomic results clearly elucidated the molecular response of the histopathological changes which were driven by the alteration of cytoskeletal proteins. Our results improve the current knowledge of toxicity of the DDT to histology and molecular response of oyster proteome to DDT exposure. In addition, histopathological changes will be beneficial for the development of an appropriate guideline for health assessment of this species in ecotoxicological context., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dental anxiety is of public health importance because it leads to postponed dental treatment, which comes with health complications. The present study investigated whether there is a correlation between the degree of dental anxiety and other kinds of anxiety and whether there are prognostic factors for the different kinds of anxiety., Method: In the sample (N = 156) from a dental practice in a large German city, 62% of patients received a check-examination and 38% received dental surgery. The target variables were recorded with validated questionnaires: dental anxiety (IDAF-4c+), subclinical anxiety (SubA), anxiety of negative evaluation (SANB-5), current general anxiety (STAI state), loneliness (LS-S) and self-efficacy (GSW-6). The applied statistics were: t-tests for 31 variables, correlation matrix and multivariate and bivariate regression analyses., Results: The dental surgery patients displayed more dental anxiety and more dental interventions than the check-examination group. The main result was a positive correlation of all kinds of anxiety with each other, a positive correlation of loneliness and neuroticism with all forms of anxiety and a negative correlation between all forms of anxiety and self-efficacy. Especially dental anxiety is positively associated with other kinds of anxiety. In multivariate regression models only neuroticism is associated with dental anxiety, but feelings of loneliness are positively associated with with the other kinds of anxiety assessed in this study. The higher the self-efficacy, the lower the level of general anxiety., Conclusions: In dentistry, anxiety from negative experiences with buccal interventions should be distinguished from anxiety caused by personality traits. Self-efficacy tends to protect against anxiety, while loneliness and neuroticism are direct or indirect risk factors for anxiety in this urban dentistry sample. Dental anxiety seems to be independent from biographical strains but not from neuroticism. In practice, more attention must be paid to anxiety control, self-management and efforts to improve the confidence of patients with emotional lability, less self-confidence and propensity to shame., (© 2021. The Author(s).)

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions., Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression., Results: Both treatments resulted in substantial improvements at post (PeEx-I: d within  = 1.50, PeEx-S: d within  = 1.78) and follow-up (PeEx-I: d within  = 2.34; PeEx-S: d within  = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR PeEx-I  = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse., Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner., (© 2021 The Authors. Depression and Anxiety Published by Wiley Periodicals LLC.)