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The minimally invasive CardioQPTM oesophageal Doppler probe estimates cardiac output by measuring blood flow velocity in the descending aorta. Individual variables to enter are patient’s age, weight and height. We measured cardiac output simultaneously with CardioQP and pulmonary artery catheter thermodilution techniques during heart catheterisation in 40 paediatric patients with congenital heart defects. Median [range] age was 8.2 years [0.5–16.7 years], cardiac output values measured by thermodilution and CardioQP were 3.6 l.min−1 [1.2–7.1 l.min−1] and 3.0 l.min−1 [0.7–6.7 l.min−1], respectively. These values showed only moderate correlation (r = 0.809; p < 0.0001). Bias and precision were 0.66 l.min−1 and 1.79 l.min−1 (95% limits of agreement: −1.13 to +2.45 l.min−1). Based on our preliminary experience, cardiac output values measured by CardioQP in children do not reliably represent cardiac output values compared with the thermodilution technique. We suggest measurement of individual aortic diameter to improve performance of the CardioQP. [ABSTRACT FROM AUTHOR]

Purpose: Sentinel lymph node biopsy (SLNB) is a staging procedure used to guide treatment for patients with breast cancer. Multiple variations in the SLNB technique have been described. We questioned how technique impacts the number of sentinel lymph nodes (SLNs) removed and associated complications., Methods: Patients with breast cancer who were treated with lumpectomy and SLNB between 2018 and 2023 were analyzed. Patients were excluded if they had prior ipsilateral breast or axillary surgery or chest wall radiation, underwent neoadjuvant chemotherapy or endocrine therapy, or subsequently required ALND. Demographics, surgical technique, and operative and pathological data were collected. Complication rates were compared between more (4+) or fewer (1-3) SLNs removed., Results: A total of 643 patients were included, with an average of 2.44 LNs removed (range 1-11). The overall complication rate was 19.8%, with a 4.4% lymphedema rate. The lymphedema rate was higher among patients who had more nodes removed. An average of 2.5 LNs were removed with dual mapping vs. 2.0 with technetium alone (p = 0.15). Breast massage had no effect on the number of SLNs removed (p = 0.12) but did impact blue dye uptake (p = 0.001)., Conclusions: Surgical technique did not significantly impact the number of nodes removed. Removing more nodes was associated with a greater risk of lymphedema., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Certain cationic peptides interact with biological membranes. These often-complex interactions can result in peptide targeting to the membrane, or in membrane permeation, rupture, and cell lysis. We investigated the relationship between the structural features of membrane-active peptides and these effects, to better understand these processes. To this end, we employed a computational method for morphing a membranolytic antimicrobial peptide into a nonmembranolytic mitochondrial targeting peptide by "directed simulated evolution." The results obtained demonstrate that superficially subtle sequence modifications can strongly affect the peptides' membranolytic and membrane-targeting abilities. Spectroscopic and computational analyses suggest that N- and C-terminal structural flexibility plays a crucial role in determining the mode of peptide-membrane interaction.

Lectins are used as defense effector proteins against predators, parasites and pathogens by animal, plant and fungal innate defense systems. These proteins bind to specific glycoepitopes on the cell surfaces and thereby interfere with the proper cellular functions of the various antagonists. The exact cellular toxicity mechanism is in many cases unclear. Lectin CCL2 of the mushroom Coprinopsis cinerea was previously shown to be toxic for Caenorhabditis elegans and Drosophila melanogaster. This toxicity is dependent on a single, high-affinity binding site for the trisaccharide GlcNAc(Fucα1,3)β1,4GlcNAc, which is a hallmark of nematode and insect N-glycan cores. The carbohydrate-binding site is located at an unusual position on the protein surface when compared to other β-trefoil lectins. Here, we show that CCL2 forms a compact dimer in solution and in crystals. Substitution of two amino acid residues at the dimer interface, R18A and F133A, interfered with dimerization of CCL2 and reduced toxicity but left carbohydrate-binding unaffected. These results, together with the positioning of the two carbohydrate-binding sites on the surface of the protein dimer, suggest that crosslinking of N-glycoproteins on the surface of intestinal cells of invertebrates is a crucial step in the mechanism of CCL2-mediated toxicity. Comparisons of the number and positioning of carbohydrate-binding sites among different dimerizing fungal β-trefoil lectins revealed a considerable variability in the carbohydrate-binding patterns of these proteins, which are likely to correlate with their respective functions., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sustained identification of innovative chemical entities is key for the success of chemical biology and drug discovery. We report the fragment-based, computer-assisted de novo design of a small molecule inhibiting Helicobacter pylori HtrA protease. Molecular binding of the designed compound to HtrA was confirmed through biophysical methods, supporting its functional activity in vitro. Hit expansion led to the identification of the currently best-in-class HtrA inhibitor. The results obtained reinforce the validity of ligand-based de novo design and binding-kinetics-guided optimization for the efficient discovery of pioneering lead structures and prototyping drug-like chemical probes with tailored bioactivity., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Lectins are non-immunoglobulin carbohydrate-binding proteins without enzymatic activity towards the bound carbohydrates. Many lectins of e.g. plants or fungi have been suggested to act as toxins to defend the host against predators and parasites. We have previously shown that the Coprinopsis cinerea lectin 2 (CCL2), which binds to α1,3-fucosylated N-glycan cores, is toxic to Caenorhabditis elegans and results in developmental delay and premature death. In this study, we investigated the underlying toxicity phenotype at the cellular level by electron and confocal microscopy. We found that CCL2 directly binds to the intestinal apical surface and leads to a highly damaged brush border with loss of microvilli, actin filament depolymerization, and invaginations of the intestinal apical plasma membrane through gaps in the terminal web. We excluded several possible toxicity mechanisms such as internalization and pore-formation, suggesting that CCL2 acts directly on intestinal apical plasma membrane or glycocalyx proteins. A genetic screen for C. elegans mutants resistant to CCL2 generated over a dozen new alleles in bre 1, ger 1, and fut 1, three genes required for the synthesis of the sugar moiety recognized by CCL2. CCL2-induced intestinal brush border defects in C. elegans are similar to the damage observed previously in rats after feeding the dietary lectins wheat germ agglutinin or concanavalin A. The evolutionary conserved reaction of the brush border between mammals and nematodes might allow C. elegans to be exploited as model organism for the study of dietary lectin-induced intestinal pathology in mammals.

Discrimination between self and non-self is a prerequisite for any defence mechanism; in innate defence, this discrimination is often mediated by lectins recognizing non-self carbohydrate structures and so relies on an arsenal of host lectins with different specificities towards target organism carbohydrate structures. Recently, cytoplasmic lectins isolated from fungal fruiting bodies have been shown to play a role in the defence of multicellular fungi against predators and parasites. Here, we present a novel fruiting body lectin, CCL2, from the ink cap mushroom Coprinopsis cinerea. We demonstrate the toxicity of the lectin towards Caenorhabditis elegans and Drosophila melanogaster and present its NMR solution structure in complex with the trisaccharide, GlcNAcβ1,4[Fucα1,3]GlcNAc, to which it binds with high specificity and affinity in vitro. The structure reveals that the monomeric CCL2 adopts a β-trefoil fold and recognizes the trisaccharide by a single, topologically novel carbohydrate-binding site. Site-directed mutagenesis of CCL2 and identification of C. elegans mutants resistant to this lectin show that its nematotoxicity is mediated by binding to α1,3-fucosylated N-glycan core structures of nematode glycoproteins; feeding with fluorescently labeled CCL2 demonstrates that these target glycoproteins localize to the C. elegans intestine. Since the identified glycoepitope is characteristic for invertebrates but absent from fungi, our data show that the defence function of fruiting body lectins is based on the specific recognition of non-self carbohydrate structures. The trisaccharide specifically recognized by CCL2 is a key carbohydrate determinant of pollen and insect venom allergens implying this particular glycoepitope is targeted by both fungal defence and mammalian immune systems. In summary, our results demonstrate how the plasticity of a common protein fold can contribute to the recognition and control of antagonists by an innate defence mechanism, whereby the monovalency of the lectin for its ligand implies a novel mechanism of lectin-mediated toxicity.

Staphylococcus aureus encodes many proteins that act as virulence factors, leading to a variety of diseases, including mastitis in cows. Among these virulence factors, SpA, ClfA, ClfB, FnbA, and FnbB are important for the ability of S. aureus to adhere to and invade host cells as well as to evade host immune responses. The interaction between these S. aureus surface proteins and human immunoglobulin G and fibrinogen that are coupled to latex particles is utilized to induce latex agglutination reactions, which are used widely in diagnostic kits for confirmation of presumptive S. aureus isolates. In this study, the Staphaurex latex agglutination test was performed on a collection of confirmed bovine mastitis S. aureus isolates. Notably, 54% (43/79 isolates) of these isolates exhibited latex agglutination-negative phenotypes (Staphaurex-negative result). To gain insights into the reasons for the high frequency of Staphaurex-negative bovine mastitis S. aureus isolates, the spa, clfA, clfB, fnbA, and fnbB genes were examined. Specific genetic changes in spa, clfA, and fnbA, as well as a loss of fnbB, which may impair SpA, ClfA, FnbA, and FnbB functions in latex agglutination reactions, were detected in Staphaurex-negative S. aureus isolates. The genetic changes included a premature stop codon in the spa gene, leading to a truncated SpA protein that is unable to participate in S. aureus cell-mediated agglutination of latex particles. In addition, clfA and fnbA genetic polymorphisms were detected that were linked to ClfA and FnbA amino acid changes that may significantly reduce fibrinogen-binding activity. The genetic variations in these S. aureus isolates might also have implications for their bovine mastitis virulence capacity.

Objective: To compare the assessment of cardiac output (CO) in children using the noninvasive Ultrasound Cardiac Output Monitor (USCOM) with the invasive pulmonary artery catheter (PAC) thermodilution cardiac output measurement., Design and Setting: Prospective observational study in a tertiary center for pediatric cardiology of a university children's hospital., Patients: Twenty-four pediatric patients with congenital heart disease without shunt undergoing cardiac catheterization under general anesthesia., Measurements and Results: CO was measured by USCOM using a suprasternal CO Doppler probe in children undergoing cardiac catheterization. USCOM data were compared to CO simultaneously measured by PAC thermodilution technique. Measurements were repeated three times within 5 min in each patient. A mean percentage error not exceeding 30% was defined as indicating clinical useful reliability of the USCOM. CO values measured by PAC ranged from 1.3 to 5.3 l/min (median 3.6 l/min). Bias and precision were -0.13 and 1.34 l/min, respectively. The mean percentage error of CO measurement by the USCOM compared to PAC thermodilution technique was 36.4% for USCOM., Conclusions: Our preliminary data demonstrate that cardiac output measurement in children using the USCOM does not reliably represent absolute CO values as compared to PAC thermodilution. Further studies must evaluate the impact of incorporating effective aortic valve diameters on CO measurement using the USCOM.

Background: The purpose of this study was to determine if inspiratory pressure from intermittent positive pressure ventilation may be sufficient to inflate the cuff (thus 'auto-inflation') and thereby seal the trachea., Methods: In a laboratory model we investigated the ability of cuffs of seven 5.0 mm internal diameter (ID) tracheal tubes (Sheridan CF, Mallinckrodt Hi-Contour, Mallinckrodt Sealguard, Mallinckrodt Safety-Flex, Portex Soft Seal, Rueschelit Super-Safety Clear and Microcuff PET) to seal the trachea by auto-inflation, i.e. by using the inspiratory pressure to expand and keep open the cuff within the trachea. A mechanical lung connected to a model trachea made from clear, rigid polyvinylchloride (PVC) (12 mm ID) was used to simulate changes in inspiratory pressures. Respirator settings were: fresh gas flow (air) 6 lxmin(-1); positive end-expiratory pressure 5 cmH(2)O; respiratory rate 20 brxmin(-1); I : E ratio = 1 : 2; inspiratory pressure 5, 10, 15, 20, and 25 cmH(2)O. Percentage of expiratory to inspiratory tidal volume (E : I V(t) volume ratio) was calculated., Results: Using lubricated Mallinckrodt Seal Guard tube cuffs E : I V(t) volume ratio was almost 100% at a peak inspiratory pressure of 10 cmH(2)o whereas in tube cuffs particularly made of PVC an E : I ratio was achieved only at higher inspiratory pressures, if at all., Conclusions: Auto-inflation in the Mallinckrodt Seal Guard with high volume-low pressure polyurethane cuff can produce adequate tracheal sealing in the model trachea used. The implication is that such auto-inflation should decrease the risk of tracheal injury from acute or persistent cuff hyperinflation.

Purpose: Postoperative nausea and vomiting (PONV) after adenotonsillectomy in children is, in spite of the prophylactic administration of tropisetron, still a frequent event. The aim of this study was to evaluate the benefit of the additional systemic administration of low-dose dexamethasone (0.15 mg x kg(-1)) for the prevention of PONV., Methods: With hospital ethics committee approval, we investigated children undergoing adenotonsillectomy receiving tropisetron (0.1 mg x kg(-1); maximum dose, 2 mg) or tropisetron (0.1 mg x kg(-1); maximum dose, 2 mg) plus dexamethasone (0.15 mg x kg(-1); maximum dose, 6 mg) intraoperatively. The incidence of vomiting episodes and the need for postoperative analgesics were recorded. Patient data were analyzed using the t-test and the chi(2) test (significance level of P = 0.05). Data values are means +/- SD., Results: Ninety children (39 girls and 51 boys), aged 5.6 +/- 2.8 years and weighing 21.9 +/- 8.8 kg, were enrolled in the study. The overall incidence of vomiting was 38.9% within the first 24 h (67 vomiting events) and 44.4% within 48 h postoperatively (87 vomiting events). The incidence of vomiting in the tropisetron-only group was 53.3% (24/45) at 24 h and 60% (27/45) at 48 h (24 h: P < 0.001 and 48 h: P = 0.04) and 24.4% (11/45) at 24 h and 28.9% (13/45) at 48 h in the tropisetron-dexamethasone group. The need for postoperative nalbuphine was double in patients treated with tropisetron-dexamethasone (0.61 mg +/- 0.36 mg x kg(-1) x 48 h(-1)) compared to that in patients receiving only tropisetron (0.31 mg +/- 0.28 mg x kg(-1) x 48 h(-1); P < 0.0001)., Conclusion: A low-dose bolus of dexamethasone (0.15 mg x kg(-1)) in combination with tropisetron, compared to tropisetron alone, considerably reduced the incidence of vomiting in children following pediatric adenotonsillectomy.

Background: In preformed cuffed tracheal tubes the position of the cuff within the airway is given by its distance to the tube bend placed at the lower teeth. The aim of this study was to compare the design of cuffed and uncuffed preformed pediatric oral tracheal tubes with regard to anatomical landmarks., Methods: Complete series of cuffed and uncuffed preformed oral pediatric tracheal tubes sized from internal diameter 3.0-7.0 mm if available were ordered from five different manufacturers. The distance from the bend to the distal tube tip and to the upper border of the cuff were measured and compared with anatomical airway landmarks in the developing child., Results: Between cuffed and uncuffed tracheal preformed tubes up to 37 mm differences in the bend-to-tracheal tube tip distances were found for given age groups. Thus uncuffed preformed tracheal tubes were more at risk for inadvertent endobronchial intubation than cuffed preformed tracheal tubes. Comparison of bend-to-upper border of the cuff distances with teeth-to-vocal cord distances calculated from anatomical data revealed that several of the tracheal tube cuffs become positioned within the subglottic larynx or even within the vocal cords when inserted according to the bend., Conclusions: There is a need for improvement in cuffed preformed pediatric tracheal tubes, namely a standard bend-to-tracheal tube tip distance to allow a safe insertion depth, a short cuff placed on the tube shaft as distally as possible and an intubation depth mark to verify a proper position of the cuff in the trachea.