Neutrophil Extracellular Traps Initiate Gallstone Formation.

The presence of gallstones (cholelithiasis) is a highly prevalent and severe disease and one of the leading causes of hospital admissions worldwide. Due to its substantial health impact, we investigated the biological mechanisms that lead to the formation and growth of gallstones. We show that gallstone assembly essentially requires neutrophil extracellular traps (NETs). We found consistent evidence for the presence of NETs in human and murine gallstones and describe an immune-mediated process requiring activation of the innate immune system for the formation and growth of gallstones. Targeting NET formation via inhibition of peptidyl arginine deiminase type 4 or abrogation of reactive oxygen species (ROS) production, as well as damping of neutrophils by metoprolol, effectively inhibit gallstone formation in vivo. Our results show that after the physicochemical process of crystal formation, NETs foster their assembly into larger aggregates and finally gallstones. These insights provide a feasible therapeutic concept to prevent cholelithiasis in patients at risk.

Cracking the black box of deep sequence-based protein-protein interaction prediction.

Identifying protein-protein interactions (PPIs) is crucial for deciphering biological pathways. Numerous prediction methods have been developed as cheap alternatives to biological experiments, reporting surprisingly high accuracy estimates. We systematically investigated how much reproducible deep learning models depend on data leakage, sequence similarities and node degree information, and compared them with basic machine learning models. We found that overlaps between training and test sets resulting from random splitting lead to strongly overestimated performances. In this setting, models learn solely from sequence similarities and node degrees. When data leakage is avoided by minimizing sequence similarities between training and test set, performances become random. Moreover, baseline models directly leveraging sequence similarity and network topology show good performances at a fraction of the computational cost. Thus, we advocate that any improvements should be reported relative to baseline methods in the future. Our findings suggest that predicting PPIs remains an unsolved task for proteins showing little sequence similarity to previously studied proteins, highlighting that further experimental research into the 'dark' protein interactome and better computational methods are needed.

Endothelial transmigration hotspots limit vascular leakage through heterogeneous expression of ICAM-1.

Upon inflammation, leukocytes leave the circulation by crossing the endothelial monolayer at specific transmigration "hotspot" regions. Although these regions support leukocyte transmigration, their functionality is not clear. We found that endothelial hotspots function to limit vascular leakage during transmigration events. Using the photoconvertible probe mEos4b, we traced back and identified original endothelial transmigration hotspots. Using this method, we show that the heterogeneous distribution of ICAM-1 determines the location of the transmigration hotspot. Interestingly, the loss of ICAM-1 heterogeneity either by CRISPR/Cas9-induced knockout of ICAM-1 or equalizing the distribution of ICAM-1 in all endothelial cells results in the loss of TEM hotspots but not necessarily in reduced TEM events. Functionally, the loss of endothelial hotspots results in increased vascular leakage during TEM. Mechanistically, we demonstrate that the 3 extracellular Ig-like domains of ICAM-1 are crucial for hotspot recognition. However, the intracellular tail of ICAM-1 and the 4th Ig-like dimerization domain are not involved, indicating that intracellular signaling or ICAM-1 dimerization is not required for hotspot recognition. Together, we discovered that hotspots function to limit vascular leakage during inflammation-induced extravasation.

Requirement of Site-Specific Tyrosine Phosphorylation of Cortactin in Retinal Neovascularization and Vascular Leakage.

BACKGROUND: Retinal neovascularization is a major cause of vision impairment. Therefore, the purpose of this study is to investigate the mechanisms by which hypoxia triggers the development of abnormal and leaky blood vessels. METHODS: A variety of cellular and molecular approaches as well as tissue-specific knockout mice were used to investigate the role of Cttn (cortactin) in retinal neovascularization and vascular leakage. RESULTS: We found that VEGFA (vascular endothelial growth factor A) stimulates Cttn phosphorylation at Y421, Y453, and Y470 residues in human retinal microvascular endothelial cells. In addition, we observed that while blockade of Cttn phosphorylation at Y470 inhibited VEGFA-induced human retinal microvascular endothelial cell angiogenic events, suppression of Y421 phosphorylation protected endothelial barrier integrity from disruption by VEGFA. In line with these observations, while blockade of Cttn phosphorylation at Y470 negated oxygen-induced retinopathy-induced retinal neovascularization, interference with Y421 phosphorylation prevented VEGFA/oxygen-induced retinopathy-induced vascular leakage. Mechanistically, while phosphorylation at Y470 was required for its interaction with Arp2/3 and CDC6 facilitating actin polymerization and DNA synthesis, respectively, Cttn phosphorylation at Y421 leads to its dissociation from VE-cadherin, resulting in adherens junction disruption. Furthermore, whereas Cttn phosphorylation at Y470 residue was dependent on Lyn, its phosphorylation at Y421 residue required Syk activation. Accordingly, lentivirus-mediated expression of shRNA targeting Lyn or Syk levels inhibited oxygen-induced retinopathy-induced retinal neovascularization and vascular leakage, respectively. CONCLUSIONS: The above observations show for the first time that phosphorylation of Cttn is involved in a site-specific manner in the regulation of retinal neovascularization and vascular leakage. In view of these findings, Cttn could be a novel target for the development of therapeutics against vascular diseases such as retinal neovascularization and vascular leakage.

ARAP3 protects from excessive formylated peptide-induced microvascular leakage by acting on endothelial cells and neutrophils.

Vascular permeability is temporarily heightened during inflammation, but excessive inflammation-associated microvascular leakage can be detrimental, as evidenced in the inflamed lung. Formylated peptides regulate vascular leakage indirectly via formylated peptide receptor-1 (FPR1)-mediated recruitment and activation of neutrophils. Here we identify how the GTPase-activating protein ARAP3 protects against formylated peptide-induced microvascular permeability via endothelial cells and neutrophils. In vitro, Arap3-/- endothelial monolayers were characterised by enhanced formylated peptide-induced permeability due to upregulated endothelial FPR1 and enhanced vascular endothelial cadherin internalisation. In vivo, enhanced inflammation-associated microvascular leakage was observed in Arap3-/- mice. Leakage of plasma protein into the lungs of Arap3-/- mice increased within hours of formylated peptide administration. Adoptive transfer experiments indicated this was dependent upon ARAP3 deficiency in both immune and non-immune cells. Bronchoalveolar lavages of formylated peptide-challenged Arap3-/- mice contained neutrophil extracellular traps (NETs). Pharmacological inhibition of NET formation abrogated excessive microvascular leakage, indicating a critical function of NETs in this context. The observation that Arap3-/- mice developed more severe influenza suggests these findings are pertinent to pathological situations characterised by abundant formylated peptides. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Transient Leakage Electroluminescence of Quantum-Dot Light-Emitting Diodes.

Parasitic emission or leakage emission caused by electron leakage to a hole transport layer in quantum-dot light-emitting diodes (QLEDs) critically impacts device efficiency and operational stability. The buildup dynamics of such emission channels, however, was insufficiently researched. Herein, we investigate transient electroluminescence dynamics of leakage emission in red/green/blue (R/G/B) QLEDs and reveal notable contrast for R and G. In RQLEDs, leakage emission exhibits delayed turning-on than primary emission, which is attributed to much slower filling up from lower-energy electron states and the initial quenching by nonradiative recombination with trapped holes. For GQLEDs, leakage emission turns on much more concurrently, and emission preferably starts from higher energy states. For R/G QLEDs, under varied offset voltage modulation, the current efficiency of primary emission is invert-correlated to leakage emission, reconfirming leakage emission as a loss indicator.

Phospholipid Bilayer Inspired Sandwich Structural Nanofibrous Membrane for Atmospheric Water Harvesting and Selective Release.

Atmospheric water harvesting (AWH) has been broadly exploited to meet the challenge of water shortage. Despite the significant achievements of AWH, the leakage of hydroscopic salt during the AWH process hinders its practical applications. Herein, inspired by the unique selective permeability of the phospholipid bilayer, a sandwich structural (hydrophobic-hydrophilic-hydrophobic) polyacrylonitrile nanofibrous membrane (San-PAN) was fabricated for AWH. The hydrophilic inner layer loaded with LiCl could capture water from the air. The hydrophobic microchannels in the outer layer could selectively allow the free transmission of gaseous water molecules but confine the hydroscopic salt solution in the hydrophilic layer, achieving continuous and recyclable water sorption/desorption. As demonstrated, the as-prepared AWH devices presented high-efficient adsorption kinetics from 1.66 to 4.08 g g-1 at 30% to 90% relative humidity. Thus, this work strengthens the understanding of the water transmission process along microchannels and provides insight into the practical applications of AWH.

The paracrine isthmin1 transcriptionally regulated by C/EBPß exacerbates pulmonary vascular leakage in murine sepsis.

It is known that pulmonary vascular leakage, a key pathological feature of sepsis-induced lung injury, is largely regulated by perivascular cells. However, the underlying mechanisms have not been fully uncovered. In the present study, we aimed to evaluate the role of isthmin1, a secretory protein originating from alveolar epithelium, in the pulmonary vascular leakage during sepsis and to investigate the regulatory mechanisms of isthmin1 gene transcription. We observed an elevated isthmin1 gene expression in the pulmonary tissue of septic mice induced by cecal ligation and puncture (CLP), as well as in primary murine alveolar type II epithelial cells (ATII) exposed to lipopolysaccharide (LPS). Furthermore, we confirmed that isthmin1 derived from ATII contributes to pulmonary vascular leakage during sepsis. Specifically, adenovirus-mediated isthmin1 disruption in ATII led to a significant attenuation of the increased pulmonary microvascular endothelial cell (PMVEC) hyperpermeability in a PMVEC/ATII coculture system when exposed to LPS. In addition, adeno-associated virus 9 (AAV9)-mediated knockdown of isthmin1 in the alveolar epithelium of septic mice significantly attenuated pulmonary vascular leakage. Finally, mechanistic studies unveiled that nuclear transcription factor CCAAT/enhancer binding protein (C/EBP)ß participates in isthmin1 gene activation by binding directly to the cis-regulatory element of isthmin1 locus and may contribute to isthmin1 upregulation during sepsis. Collectively, the present study highlighted the impact of the paracrine protein isthmin1, derived from ATII, on the exacerbation of pulmonary vascular permeability in sepsis and revealed a new regulatory mechanism for isthmin1 gene transcription.NEW & NOTEWORTHY This article addresses the role of the alveolar epithelial-secreted protein isthmin1 on the exacerbation of pulmonary vascular permeability in sepsis and identified nuclear factor CCAAT/enhancer binding protein (C/EBP)ß as a new regulator of isthmin1 gene transcription. Targeting the C/EBPß-isthmin1 regulatory axis on the alveolar side would be of great value in the treatment of pulmonary vascular leakage and lung injury induced by sepsis.

Global Prevalence of Fecal Incontinence in Community-Dwelling Adults: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Fecal incontinence (FI) can considerably impair quality of life. Through a systematic review and meta-analysis, we sought to determine the global prevalence and geographic distribution of FI and to characterize its relationship with sex and age. METHODS: We searched PubMed, Web of Science, and Cochrane Library databases to identify population-based surveys of the prevalence of FI. RESULTS: Of the 5175 articles identified, the final analysis included 80 studies; the median response rate was 66% (interquartile range [IQR], 54%-74%). Among 548,316 individuals, the pooled global prevalence of FI was 8.0% (95% confidence interval [CI], 6.8%-9.2%); by Rome criteria, it was 5.4% (95% CI, 3.1%-7.7%). FI prevalence was greater for persons aged 60 years and older (9.3%; 95% CI, 6.6%-12.0%) compared with younger persons (4.9%; 95% CI, 2.9%-6.9%) (odds ratio [OR], 1.75; 95% CI, 1.39-2.20), and it was more prevalent among women (9.1%; 95% CI, 7.6%-10.6%) than men (7.4%; 95% CI, 6.0%-8.8%]) (OR, 1.17; 95% CI, 1.06-1.28). The prevalence was highest in Australia and Oceania, followed by North America, Asia, and Europe, but prevalence could not be estimated in Africa and the Middle East. The risk of bias was low, moderate, and high for 19 (24%), 46 (57%), and 15 (19%) studies, respectively. Exclusion of studies with high risk of bias did not affect the prevalence of FI or heterogeneity. In the meta-regression, the high study heterogeneity (I2 = 99.61%) was partly explained by age. CONCLUSIONS: Approximately 1 in 12 adults worldwide have FI. The prevalence is greater among women and older people.

The effects of spatial leakage correction on the reliability of EEG-based functional connectivity networks.

Electroencephalography (EEG) functional connectivity (FC) estimates are confounded by the volume conduction problem. This effect can be greatly reduced by applying FC measures insensitive to instantaneous, zero-lag dependencies (corrected measures). However, numerous studies showed that FC measures sensitive to volume conduction (uncorrected measures) exhibit higher reliability and higher subject-level identifiability. We tested how source reconstruction contributed to the reliability difference of EEG FC measures on a large (n = 201) resting-state data set testing eight FC measures (including corrected and uncorrected measures). We showed that the high reliability of uncorrected FC measures in resting state partly stems from source reconstruction: idiosyncratic noise patterns define a baseline resting-state functional network that explains a significant portion of the reliability of uncorrected FC measures. This effect remained valid for template head model-based, as well as individual head model-based source reconstruction. Based on our findings we made suggestions how to best use spatial leakage corrected and uncorrected FC measures depending on the main goals of the study.

Spatiotemporal signal space separation for regions of interest: Application for extracting neuromagnetic responses evoked by deep brain stimulation.

Magnetoencephalography (MEG) recordings are often contaminated by interference that can exceed the amplitude of physiological brain activity by several orders of magnitude. Furthermore, the activity of interference sources may spatially extend (known as source leakage) into the activity of brain signals of interest, resulting in source estimation inaccuracies. This problem is particularly apparent when using MEG to interrogate the effects of brain stimulation on large-scale cortical networks. In this technical report, we develop a novel denoising approach for suppressing the leakage of interference source activity into the activity representing a brain region of interest. This approach leverages spatial and temporal domain projectors for signal arising from prespecified anatomical regions of interest. We apply this denoising approach to reconstruct simulated evoked response topographies to deep brain stimulation (DBS) in a phantom recording. We highlight the advantages of our approach compared to the benchmark-spatiotemporal signal space separation-and show that it can more accurately reveal brain stimulation-evoked response topographies. Finally, we apply our method to MEG recordings from a single patient with Parkinson's disease, to reveal early cortical-evoked responses to DBS of the subthalamic nucleus.

The effect of pre- and post-harvest sodium nitroprusside treatments on the physiological changes of cut Alstroemeria aurea 'Orange Queen' during vase life.

Cut flowers deteriorate rapidly after harvest, lasting mere days. To extend their vase life, various postharvest techniques are employed. Due to limited knowledge about the postharvest physiology of Alstroemeria cut flowers and the specific role of secondary compounds and antioxidant systems in their protection, this study investigated the optimal dosage of sodium nitroprusside (SNP) as a nitric oxide (NO) donor to enhance quality and antioxidant defenses. Preharvest foliar application of SNP at 0, 50, 100, and 200 µM followed by short-term pulsing treatments upon harvest at the same concentrations were applied in a factorial design. Results revealed that a preharvest 100 µM SNP treatment combined with a 50 µM postharvest pulse significantly increased the total amount of phenols (over 20%), antioxidant capacity (more than doubled), and the activity of two antioxidant enzymes (ascorbate peroxidase by over 35% and guaiacol peroxidase by about 20%). Notably, this combination also diminished ion leakage (by about 20%), ultimately extending the vase life by more than 40% compared to untreated plants. Therefore, SNP application at these specific dosages proves effective in bolstering Alstroemeria cut flower quality and vase life through enhanced total phenols and a strengthened antioxidant system.

Physiological and molecular changes of onion (Allium cepa L.) seeds under different aging conditions.

BACKGROUND: Onion seeds have limited storage capacity compared to other vegetable seeds. It is crucial to identify the mechanisms that induce tolerance to storage conditions and reduce seed deterioration. To address this goal, an experiment was conducted to evaluate changes in germination, biochemical, physiological, and molecular characteristics of onion seed landraces (Horand, Kazerun landraces and Zargan cultivar) at different aging levels (control, three-days and six-days accelerated aging, and natural aging for one year). RESULTS: The findings suggest that there was an increase in glucose, fructose, total sugar, and electrolyte leakage in the Horand (HOR), Kazerun (KAZ) landraces, and Zarghan (ZAR) cultivar, with Kazerun exhibiting the greatest increase. The percentage and rate of germination of Kazerun decreased by 54% and 33%, respectively, in six-day accelerated aging compared to the control, while it decreased by 12% and 14%, respectively, in Horand. Protein content decreased with increasing levels of aging, with a decrease of 26% in Kazerun landrace at six days of aging, while it was 16% in Horand landrace. The antioxidant activities of catalase, superoxide dismutase, and glutathione peroxidase decreased more intensively in Kazerun. The expression of AMY1, BMY1, CTR1, and NPR1 genes were lower in Kazerun landraces than in Horand and Zargan at different aging levels. CONCLUSIONS: The AMY1, BMY1, CTR1, and NPR1 genes play a pivotal role in onion seed germination, and their downregulation under stressful conditions has been shown to decrease germination rates. In addition, the activity of CAT, SOD, and GPx enzymes decreased by seed aging, and the amount of glucose, fructose, total sugar and electrolyte leakage increased, which ultimately led to seed deterioration. Based on the results of this experiment, it is recommended to conduct further studies into the molecular aspects involved in onion seed deterioration. More research on the genes related to this process is suggested, as well as investigating the impact of different priming treatments on the genes expression involved in the onion seed aging process.

Enhancing the Efficiency of Flexible, Large-Area, ITO-Free Organic Photovoltaic Devices.

The development of flexible ITO-free devices is crucial for the industrial advancement of organic photovoltaic (OPV) technology. Here, a novel ITO-free device architecture is proposed, and ITO-free OPV devices are realized on glass substrates with performance comparable to that of ITO-based devices. It is also demonstrated that the performance of ITO-free devices on polyethylene terephthalate (PET) substrates is limited due to the higher surface roughness of PET, leading to high voltage losses, low device quantum efficiency, and high device leakage current. To address the issue of high roughness on the PET surface, a polyimide (PI) modification strategy is developed and the PI-modified PET is employed as the substrate to construct flexible ITO-free OPV devices and large-area modules with an active area of up to 16.5 cm2. This approach leads to decreased trap-assisted recombination losses, enhanced exciton dissociation efficiency, and a reduced density of pinholes in flexible OPV devices, resulting in improved photovoltaic performance under both strong and weak illumination conditions. The outcomes of this work are expected to advance the industrial development of flexible organic photovoltaic technology.

Carbon Dots with Spatially-Mediated-N/S-Co-Doping Enabling One-Year Stable Lubricant with Oil Leakage Detection Capability.

The dispersion stability of nano-lubricating additives is crucial for the shelf life of lubricant and its practical applications. Nitrogen-sulfur co-doped carbon dots (N,S@CDs) via a one-step hydrothermal method with nitropyrene and thiourea as raw materials are hereby presented. The N and S elements are selectively distributed throughout the entire carbon skeleton with a doping amount of 22.6 at%. The as-synthesized N,S@CDs exhibit excellent dispersion stability in PEG200 and maintain stability for over one year. The experiment results indicate that N,S@CDs significantly improve the anti-wear and friction reduction properties of PEG200, while the friction coefficient is reduced from 0.25 to 0.09 with 1.5 wt% N,S@CDs addition, and the wear volume, depth, and width are reduced by 68%, 52%, and 57%, respectively. The good lubrication performance is attributed to N,S@CDs excellent dispersion stability, enhanced filling and polishing effects, and complex tribochemical reactions caused by heteroatom doping to form a stable protective film on the worn surface. Furthermore, the as-prepared N,S@CDs exhibit intrinsic fluorescence intensity in PEG200 with the photoluminescence quantum yield (PLQY) of 12.5% and remain fluorescent stable during the long-term friction process, therefore the N,S@CDs have a potential application prospect in non-destructive detection of oil leakage via fluorescence labeling method.

Scattered high-energy synchrotron radiation at the KARA visible-light diagnostic beamline.

To characterize an electron beam, visible synchrotron light is often used and dedicated beamlines at synchrotron sources are becoming a more common feature as instruments and methods for the diagnostics are, along with the accelerators, further developed. At KARA (Karlsruhe Research Accelerator), such a beamline exists and is based on a typical infrared/visible-light configuration. From experience at such beamlines no significant radiation was expected (dose rates larger than 0.5 µSv h-1). This was found not to be the case and a higher dose was measured which fortunately could be shielded to an acceptable level with 0.3 mm of aluminium foil or 2.0 mm of Pyrex glass. The presence of this radiation led to further investigation by both experiment and calculation. A custom setup using a silicon drift detector for energy-dispersive spectroscopy (Ketek GmbH) and attenuation experiments showed the radiation to be predominantly copper K-shell fluorescence and is confirmed by calculation. The measurement of secondary radiation from scattering of synchrotron and other radiation, and its calculation, is important for radiation protection, and, although a lot of experience exists and methods for radiation protection are well established, changes in machine, beamlines and experiments mean a constant appraisal is needed.

A flowchart for adequate controls in virus-based monosynaptic tracing experiments identified Cre-independent leakage of the TVA receptor in RΦGT mice.

BACKGROUND: A pseudotyped modified rabies virus lacking the rabies glycoprotein (G-protein), which is crucial for transsynaptic spread, can be used for monosynaptic retrograde tracing. By coupling the pseudotyped virus with transgene expression of the G-protein and the avian leukosis and sarcoma virus subgroup A receptor (TVA), which is necessary for cell entry of the virus, researchers can investigate specific neuronal populations. Responder mouse lines, like the RΦGT mouse line, carry the genes encoding the G-protein and TVA under Cre-dependent expression. These mouse lines are valuable tools because they reduce the number of viral injections needed compared to when using helper viruses. Since RΦGT mice do not express Cre themselves, introducing the pseudotyped rabies virus into their brain should not result in viral cell entry or spread. RESULTS: We present a straightforward flowchart for adequate controls in tracing experiments, which we employed to demonstrate Cre-independent expression of TVA in RΦGT mice. CONCLUSIONS: Our observations revealed TVA leakage, indicating that RΦGT mice should be used with caution for transgene expression of TVA. Inaccurate tracing outcomes may occur if TVA is expressed in the absence of Cre since background leakage leads to nonspecific cell entry. Moreover, conducting appropriate control experiments can identify the source of potential caveats in virus-based neuronal tracing experiments.

Updates to Incontinence After Prostate Treatment: AUA/GURS/SUFU Guideline (2024).

PURPOSE: In 2023 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2019 publication of this Guideline. The resulting 2024 Guideline Amendment addresses updated recommendations to provide guidance for the care of patients with incontinence after prostate treatment (IPT). MATERIALS AND METHODS: In 2023, the IPT Guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines. There were 82 studies of interest initially identified in preliminary abstract review. Following full-text review, 17 studies met inclusion criteria and ultimately informed the statements of interest. RESULTS: The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance for the care of patients who experience IPT. These updates are detailed herein. CONCLUSIONS: As prostate treatments are refined, a decreasing incidence of incontinence is anticipated. This Guideline will require further review as the diagnostic and treatment options for patients with IPT continue to evolve.

Antivirulence activities of Rutin-loaded chitosan nanoparticles against pathogenic Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is an infectious bacterium that is frequently found in healthcare settings and the community. This study aimed to prepare rutin-loaded chitosan nanoparticles (Rut-CS NPs) and assess their antibacterial activity against pathogenic strains of S. aureus. RESULTS: The synthesized Rut-CS NPs exhibited an amorphous morphology with a size ranging from 160 to 240 nm and a zeta potential of 37.3 mV. Rut-CS NPs demonstrated significant antibacterial activity against S. aureus strains. Following exposure to Rut-CS NPs, the production of staphyloxanthin pigment decreased by 43.31-89.63%, leading to increased susceptibility of S. aureus to hydrogen peroxide. Additionally, visual inspection of cell morphology indicated changes in membrane integrity and permeability upon Rut-CS NPs exposure, leading to a substantial increase (107.07-191.08%) in cytoplasmic DNA leakage in the strains. Furthermore, ½ MIC of Rut-CS NPs effectively inhibited the biofilm formation (22.5-37.5%) and hemolytic activity (69-82.59%) in the S. aureus strains. CONCLUSIONS: Our study showcases that Rut-CS NPs can serve as a novel treatment agent to combat S. aureus infections by altering cell morphology and inhibiting virulence factors of S. aureus.

Intraoperative Fluid Balance and Perioperative Complications in Ovarian Cancer Surgery.

BACKGROUND: Fluid overload and hypovolemia promote postoperative complications in patients undergoing cytoreductive surgery for ovarian cancer. In the present study, postoperative complications and anastomotic leakage were investigated before and after implementation of pulse pressure variation-guided fluid management (PPVGFM) during ovarian cancer surgery. PATIENTS AND METHODS: A total of n = 243 patients with ovarian cancer undergoing cytoreductive surgery at the University Hospital Bonn were retrospectively evaluated. Cohort A (CA; n = 185 patients) was treated before and cohort B (CB; n = 58 patients) after implementation of PPVGFM. Both cohorts were compared regarding postoperative complications. RESULTS: Ultrasevere complications (G4/G5) were exclusively present in CA (p = 0.0025). No difference between cohorts was observed regarding severe complications (G3-G5) (p = 0.062). Median positive fluid excess was lower in CB (p = 0.001). This was independent of tumor load [peritoneal cancer index] (p = 0.001) and FIGO stage (p = 0.001). Time to first postoperative defecation was shorter in CB (CB: d2 median versus CA: d3 median; p = 0.001). CB had a shorter length of hospital stay (p = 0.003), less requirement of intensive medical care (p = 0.001) and postoperative ventilation (p = 0.001). CB received higher doses of noradrenalin (p = 0.001). In the combined study cohort, there were more severe complications (G3-G5) in the case of a PFE ≥ 3000 ml (p = 0.034) and significantly more anastomotic leakage in the case of a PFE ≥ 4000 ml (p = 0.006). CONCLUSIONS: Intraoperative fluid reduction in ovarian cancer surgery according to a PPVGFM is safe and significantly reduces ultrasevere postoperative complications. PFEs of ≥ 3000 ml and ≥ 4000 ml were identified as cutoffs for significantly more severe complications and anastomotic leakage, respectively.