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In modern agriculture, nano-priming represents an innovative approach, harnessing the power of nanotechnology to enhance crop yields and nutrition. However, to effectively harness the potential of nanoparticles (NPs) for agriculture applications, understanding their mode of action and optimal application rates for positive effects on microgreen growth and physiology is critical. In this interdisciplinary study, we investigated the priming of sunflower seeds with a range of concentrations (25, 50, and 100 mg/L) of ferric oxide (Fe2O3) nanoparticles (FeNPs) and compared them with control samples. Our findings revealed a significant increase in plant biomass, leaf size, and photosynthetic activity in treated samples. The activities of photosystems I and II increased with higher FeNPs concentration. The treated samples exhibited elevated levels of total phenolics, anthocyanin, and antioxidant enzyme activity, along with increased macronutrients and micronutrients. These findings highlight the potential of FeNPs as a promising tool for enhancing plant growth and physiology in sunflower microgreens.

Salt stress poses a significant challenge to global agriculture, adversely affecting crop yield and food production. The current study investigates the potential of Zinc Oxide (ZnO) nanoparticles (NPs) in mitigating salt stress in common beans. Salt-stressed bean plants were treated with varying concentrations of NPs (25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L) using three different application methods: foliar application, nano priming, and soil application. Results indicated a pronounced impact of salinity stress on bean plants, evidenced by a reduction in fresh weight (24%), relative water content (27%), plant height (33%), chlorophyll content (37%), increased proline (over 100%), sodium accumulation, and antioxidant enzyme activity. Application of ZnO NPs reduced salt stress by promoting physiological growth parameters. The NPs facilitated enhanced plant growth and reduced reactive oxygen species (ROS) generation by regulating plant nutrient homeostasis and chlorophyll fluorescence activity. All the tested application methods effectively mitigate salt stress, with nano-priming emerging as the most effective approach, yielding results comparable to control plants for the tested parameters. This study provides the first evidence that ZnO NPs can effectively mitigate salt stress in bean plants, highlighting their potential to address salinity-induced growth inhibition in crops.

Background: Interventions targeting urine culture stewardship can improve diagnostic accuracy for urinary tract infections (UTI) and decrease inappropriate antibiotic treatment of asymptomatic bacteriuria. We aimed to determine if a clinical decision support (CDS) tool which provided guidance on and required documentation of the indications would decrease inappropriately ordered urine cultures in an academic healthcare network that already uses conditional (e.g. reflex) urine testing. Methods: In October 2022, four hospitals within one academic healthcare network transitioned to a new electronic health record (EHR). We developed an embedded CDS tool that provided guidance on ordering either a urinalysis (UA) with reflex to urine culture or a non-reflex urine culture (e.g. for pregnant patients) based on the indication for testing (Figure 1). We compared median monthly UA with reflex culture and non-reflex urine culture order rates pre- (8/2017–9/2022) and post- (10/2022–9/2023) intervention using the Wilcoxon rank-sum test. We used interrupted time-series analyses allowing a one-month time window for the intervention effect to assess changes in monthly UA with reflex culture, non-reflex urine culture, and total urine culture order rates associated with the intervention. Using SAS 9.4, we generated Durbin-Watson statistics to assess for autocorrelation and adjusted for this using a stepwise autoregressive model. Result: The median monthly UA with reflex culture order rates per 1000 patient-days were similar pre- and post- intervention at 36.7 (interquartile range [IQR]: 31.0–39.7) and 35.4 (IQR: 32.8–37.0), respectively (Figure 2). Non-reflex and total urine culture rates per 1000 patient-days decreased from 8.5 (IQR: 8.1–9.1) to 4.9 (IQR: 4.7–5.1) and from 20.0 (IQR: 18.9–20.7) to 14.4 (IQR: 14.0–14.6) post-intervention, respectively. Interrupted time-series analyses revealed that the intervention was associated with a decrease in the monthly non-reflex urine culture by 4.8 cultures/1000 patient-days (p< 0.001) and in the total urine culture monthly order rates by 5.0 cultures/ 1000 patient-days (p < 0 .001) [Figures 3a and b]. The UA with reflex order rate did not significantly change with the intervention (not pictured). Conclusion: In an academic healthcare network that already employed conditional urine testing, the implementation of an EHR-based diagnostic stewardship tool led to additional decreases in both non-reflex and total urine cultures ordered.

Background: Central line-associated bloodstream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI) are key healthcare-associated infection (HAI) quality metrics. In this qualitative analysis, we aimed to identify common issues contributing to CLABSIs and CAUTIs occurring during the COVID-19 pandemic. Methods: In an academic healthcare network in Atlanta, GA, four hospitals perform real-time, apparent cause analyses (ACAs) for all CLABSIs and CAUTIs. Contributing factors are entered as free text into an electronic database. We analyzed data from 8/2020–8/2022. We first performed a qualitative open card sort of all reported contributing factors to CLABSI and created a novel framework based on mutually defined critical tasks (e.g., line insertion) and cross-cutting issues (e.g., communication breakdown). Contributing factors could describe ≥1 critical task and/or ≥1 cross-cutting issue. After establishing interrater reliability, a multidisciplinary group applied this framework to classify each contributing factor. For CAUTI, we used the same set of cross-cutting issues but identified new critical tasks via open card sorting. We then used the framework to classify each CAUTI contributing factor. We used descriptive statistics to identify frequent critical tasks and cross-cutting issues. Results: We reviewed 350 CLABSI ACAs with 602 contributing factors and 240 CAUTI ACAs with 405 contributing factors (Figure 1). Our classification framework comprised 11 cross-cutting issues and 9 critical tasks for CLABSI and 7 critical tasks for CAUTI (Figure 2). CLABSI: The critical tasks most often reported were bathing (19%), central line dressing maintenance (15%), and assessing central line indication (8%; Figure 3). Within these tasks, the most frequent issues described for bathing were the task not being performed (20%) and unclear documentation (18%); for dressing maintenance, the task was not performed (15%), not documented (15%), or poorly performed due to lack of competency (15%); and for assessing line indication, there was frequent communication breakdown (33%). CAUTI: The critical tasks most often reported were urinary catheter care (26%) and assessing the indication for urinary catheter (22%; Figure 4). Within these tasks, urinary catheter care was frequently not documented (38%) or not performed (16%); assessing urinary catheter necessity was often not documented (29%) or involved breakdown of communication (19%). Conclusion: We created a novel framework to evaluate common causes of HAIs in an academic healthcare network. This framework can be used to identify and track gaps over time and to develop quality improvement initiatives targeting key tasks and associated factors, such as communication difficulties when assessing device indications.

Um den technologischen und gesellschaftlichen Herausforderungen der Gegenwart gerecht zu werden, bedürfen die MINT-Disziplinen dringend eines kritisch-reflexiven, diversitätssensiblen Korrektivs. Die vorliegende qualitative Studie liefert eine umfassende Bestandsaufnahme des Ist-Zustandes im Bereich Gender Studies in MINT und schlägt Maßnahmen für eine nachhaltige Integration von gender- und diversitätsrelevanten Inhalten in den MINT-Disziplinen vor. Sie identifiziert drei Desiderata: eine bessere Verankerung und Akzeptanz der Geschlechterforschung in MINT auf institutioneller Ebene, einen Stellenausbau für Professuren mit der Denomination Gender Studies in MINT und die Eröffnung langfristiger Perspektiven für Stelleninhaber*innen in diesem Bereich.

The phytohormone auxin, indole-3-acetic acid (IAA), plays a prominent role in plant development. Auxin homeostasis is coordinately regulated by auxin synthesis, transport, and inactivation; however, the physiological contribution of auxin inactivation to auxin homeostasis has not been determined. The GH3 IAA-amino acid conjugating enzymes play a central role in auxin inactivation. Chemical inhibition of GH3 proteins in planta is challenging because the inhibition of these enzymes leads to IAA overaccumulation that rapidly induces GH3 expression. Here, we report the characterization of a potent GH3 inhibitor, kakeimide, that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown of the auxin inactivation pathway demonstrates that auxin turnover is very rapid (about 10 min) and indicates that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.

BACKGROUND: Black patients are disproportionately affected by COVID-19. The purpose of this study was to compare risks of hospitalization of Black and non-Black COVID-19 patients presenting to the emergency department and, of those hospitalized, to compare mortality and acute kidney injury. METHODS: A retrospective cohort of 831 adult COVID-19 patients (68.5% Black) who presented to the emergency departments of four academic hospitals, March 1, 2020-May 31, 2020. The primary outcome was risk of hospitalization among Blacks vs. non-Blacks. Secondary outcomes were mortality and acute kidney injury, among hospitalized patients. RESULTS: The crude odds of hospitalization were not different in Black vs. non-Black patients; however, with adjustment for age, Blacks had 55% higher odds of hospitalization. Mortality differed most in the model adjusted for age alone. Acute kidney injury was more common in the Black hospitalized patients, regardless of adjustment. Stratified analyses suggested that disparities in the risk of hospitalization and of in-hospital acute kidney injury were highest in the youngest patients. CONCLUSIONS: Our report shows that Black and non-Black patients presenting to the emergency department with COVID-19 had similar risks of hospitalization and, of those who were hospitalized, similar mortality when adjusted for multiple factors. Blacks had higher risk of acute kidney injury. Our results suggest that examination of disparities without exploration of the individual effects of age and comorbidities may mask important patterns. While stratified analyses suggest that disparities in outcomes may differ substantially by age and comorbid conditions, further exploration among these important subgroups is needed to better target interventions to reduce disparities in COVID-19 clinical outcomes.

BackgroundThe relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.MethodsIn this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.ResultsBecause of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).ConclusionsPRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908.

Abstract Background: Among inpatients, peer-comparison of prescribing metrics is challenging due to variation in patient-mix and prescribing by multiple providers daily. We established risk-adjusted provider-specific antibiotic prescribing metrics to allow peer-comparisons among hospitalists. Methods: Using clinical and billing data from inpatient encounters discharged from the Hospital Medicine Service between January 2020 through June 2021 at four acute care hospitals, we calculated bimonthly (every two months) days of therapy (DOT) for antibiotics attributed to specific providers based on patient billing dates. Ten patient-mix characteristics, including demographics, infectious disease diagnoses, and noninfectious comorbidities were considered as potential predictors of antibiotic prescribing. Using linear mixed models, we identified risk-adjusted models predicting the prescribing of three antibiotic groups: broad spectrum hospital-onset (BSHO), broad-spectrum community-acquired (BSCA), and anti-methicillin-resistant Staphylococcus aureus (Anti-MRSA) antibiotics. Provider-specific observed-to-expected ratios (OERs) were calculated to describe provider-level antibiotic prescribing trends over time. Results: Predictors of antibiotic prescribing varied for the three antibiotic groups across the four hospitals, commonly selected predictors included sepsis, COVID-19, pneumonia, urinary tract infection, malignancy, and age >65 years. OERs varied within each hospital, with medians of approximately 1 and a 75th percentile of approximately 1.25. The median OER demonstrated a downward trend for the Anti-MRSA group at two hospitals but remained relatively stable elsewhere. Instances of heightened antibiotic prescribing (OER >1.25) were identified in approximately 25% of the observed time-points across all four hospitals. Conclusion: Our findings indicate provider-specific benchmarking among inpatient providers is achievable and has potential utility as a valuable tool for inpatient stewardship efforts.

Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phenotypes to the vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts a selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by videomicroscopy. We define five capillary subsets, including a capillary resident precursor (CRP) that displays stem cell and migratory gene signatures, and contributes to homeostatic BEC turnover and to neogenesis of high endothelium after immunization. Cell alignments show retention of developmental programs along trajectories from CRP to mature venous and arterial populations. Our single cell atlas provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis.

BackgroundFaltering in linear growth and neurobehavioural development during early childhood are often assumed to have common causes because of their consistent association. This notion has contributed to a global focus on the promotion of nutrition during pregnancy and childhood to improve both conditions. Our aim was to assess whether effects of interventions on linear growth are associated with effects on developmental scores and to quantify these associations.MethodsIn this systematic review and meta-analysis, we included randomised trials done during pregnancy and in children aged 0-5 years that reported effects of any intervention on length-for-age or height-for-age Z scores (LAZ or HAZ) and on any of the following outcomes: motor, cognitive or mental, language, and social-emotional or behavioural development. We searched MEDLINE (Ovid), CINAHL (EBSCO), and PsycINFO (EBSCO) from database inception to June 25, 2019. Study-level data were extracted and, when required, authors were contacted for missing information. We calculated weighted meta-regression coefficients of the association between standardised effect sizes of interventions on LAZ or HAZ and developmental outcome scores and calculated pooled effect sizes for different types of intervention.FindingsOf the 7207 studies identified, we included 75 studies with 122 comparisons between intervention and control groups and outcomes reported for 72 275 children. Across all interventions, effect sizes on LAZ or HAZ were significantly associated with effect sizes on social-emotional scores (β 0·23, 95% CI 0·05 to 0·41; p=0·02), but not on cognitive (0·18, -0·36 to 0·72; p=0·51), language (0·12, -0·07 to 0·31; p=0·21), or motor development scores (0·23, -0·05 to 0·50; p=0·11). In studies that provided nutritional supplements, we observed positive significant pooled effect sizes on all five outcomes of LAZ or HAZ (effect size 0·05, 95% CI 0·01-0·09; p=0·01; n=50), cognitive or mental (0·06, 0·03-0·10; p

In children under 5, a hemoglobin (Hb) cutoff of 11 g/dL is recommended by the World Health Organization to define anemia, yet few studies have examined whether this cut point accurately coincides with negative functional consequences. This systematic review and meta-analysis of iron intervention and observational studies aimed to clarify the consequences of low Hb concentration in children under age 5 years on growth, development, and chronic disease (functional outcomes) across the full range of Hb values. A literature search returned 5049 studies; of these, 56 intervention and 20 observational studies fit the inclusion criteria. Among iron supplementation trials, a metaregression indicated significant associations between intervention effects on Hb and their effects on motor and mental development. For each 1 standard deviation (SD) increase in Hb, motor scores increased by 0.28 SD and mental scores increased by 0.24 SD. Iron supplementation trials among children with lower Hb concentrations at baseline showed stronger associations between their effects on Hb and their effects on mental development (P-interaction = 0.008). Heterogeneity among observational studies precluded calculation of pooled associations between Hb and functional outcomes. Available evidence was not able to establish an inflection point at which decreasing Hb begins to be associated with negative functional outcomes. Future research is needed to examine associations of Hb with growth and development in populations with varying levels of Hb, inflammation, and in different ages and settings.

GLPMs represent a population of fetal liver derived large peritoneal cavity Gata6+ macrophages, with the capacity to invade the tissues they surround. Here, in experimental colon cancer liver metastasis models, the authors show that GLPMs invade liver metastasis directly from the peritoneum, promoting liver metastases growth.

Invariant natural killer T (iNKT) cells are tissue-resident immune cells recognizing lipid antigens. Here the authors find that liver, but not lung nor spleen, iNKT cells alter their transcriptome upon systemic treatment of lipid nanoparticles for the induction of regulatory B cells and suppression of liver and pancreas autoimmunity in mouse models.

αLβ2 (LFA-1) mediated interactions with ICAM-1 and ICAM-2 predominate leukocyte-vascular interactions, but their functions in extravascular cell-cell communications is still debated. The roles of these two ligands in leukocyte trafficking, lymphocyte differentiation, and immunity to influenza infections were dissected in the present study. Surprisingly, double ICAM-1 and ICAM-2 knock out mice (herein ICAM-1/2-/- mice) infected with a lab adapted H1N1 influenza A virus fully recovered from infection, elicited potent humoral immunity, and generated normal long lasting anti-viral CD8+ T cell memory. Furthermore, lung capillary ICAMs were dispensable for both NK and neutrophil entry to virus infected lungs. Mediastinal lymph nodes (MedLNs) of ICAM-1/2-/- mice poorly recruited naïve T cells and B lymphocytes but elicited normal humoral immunity critical for viral clearance and effective CD8+ differentiation into IFN-γ producing T cells. Furthermore, whereas reduced numbers of virus specific effector CD8+ T cells accumulated inside infected ICAM-1/2-/- lungs, normal virus-specific TRM CD8+ cells were generated inside these lungs and fully protected ICAM-1/2-/- mice from secondary heterosubtypic infections. B lymphocyte entry to the MedLNs and differentiation into extrafollicular plasmablasts, producing high affinity anti-influenza IgG2a antibodies, were also ICAM-1 and ICAM-2 independent. A potent antiviral humoral response was associated with accumulation of hyper-stimulated cDC2s in ICAM null MedLNs and higher numbers of virus-specific T follicular helper (Tfh) cells generated following lung infection. Mice selectively depleted of cDC ICAM-1 expression supported, however, normal CTL and Tfh differentiation following influenza infection, ruling out essential co-stimulatory functions of DC ICAM-1 in CD8+ and CD4+ T cell differentiation. Collectively our findings suggest that lung ICAMs are dispensable for innate leukocyte trafficking to influenza infected lungs, for the generation of peri-epithelial TRM CD8+ cells, and long term anti-viral cellular immunity. In lung draining LNs, although ICAMs promote lymphocyte homing, these key integrin ligands are not required for influenza-specific humoral immunity or generation of IFN-γ effector CD8+ T cells. In conclusion, our findings suggest unexpected compensatory mechanisms that orchestrate protective anti-influenza immunity in the absence of vascular and extravascular ICAMs.

Abdominal surgery can often lead to complications including the formation of peritoneal adhesions and the molecular mechanisms underlying this process are still unknown. Here, the authors suggest that bacterial contamination drives adhesion formation through mesothelial EGFR signalling.

There is limited information regarding how telemedicine visits compare with in-person visits regarding diabetes outcomes in an ambulatory care setting. Our objective was to compare proportions of patients in ambulatory setting with uncontrolled diabetes among those with telemedicine visits versus in-person only visits and examine differences by age, race, gender, ethnicity, and insurance status. Adults with diabetes who attended an ambulatory primary or specialty clinic visit between May 2020 and May 2021 were included. Demographics including age, race, ethnicity, gender, insurance, and comorbidities were extracted from the electronic medical record. Patients were compared among three visit groups: those with in-person only visits, those with only one telemedicine visit, and those with 2 + telemedicine visits. The primary outcome was uncontrolled diabetes, defined as HbA1c ≥ 9.0 %. Multivariable logistic regression was used to assess differences in uncontrolled diabetes between visit groups following risk adjustment. A total of 18,148 patients met inclusion criteria and 2,101 (11.6 %) had uncontrolled diabetes. There was no difference in proportion of patients with uncontrolled diabetes between visit groups (in-person only visits: 834 (11.6 %); one telemedicine visit: 558 (11.8 %); 2 + telemedicine visits: 709 (11.4 %); p = 0.80)). Patients with 2 + telemedicine visits had significantly lower odds of uncontrolled diabetes compared to in-person only visits after risk adjustment (OR: 0.88; 95 % CI: 0.79–0.99, p = 0.03). Compared with in-person ambulatory visits, telemedicine visits were associated with a lower odds of uncontrolled diabetes. Further work is warranted to explore the relationship between telemedicine visits and diabetes outcomes.

This paper is a sequel to the 1998 review paper “Scientific status of the Dense Plasma Focus” with 16 authors belonging to 16 nations, whose initiative led to the establishment of the International Center for Dense Magnetized Plasmas (ICDMP) in the year 2000. Its focus is on understanding the principal defining characteristic features of the plasma focus in the light of the developments that have taken place in the last 20 years, in terms of new facilities, diagnostics, models, and insights. Although it is too soon to proclaim with certainty what the plasma focus phenomenon is, the results available to date conclusively indicate what it is demonstrably not. The review looks at the experimental data, cross-correlated across multiple diagnostics and multiple devices, to delineate the contours of an emerging narrative that is fascinatingly different from the standard narrative, which has guided the consensus in the plasma focus community for several decades, without invalidating it. It raises a question mark over the Fundamental Premise of Controlled Fusion Research, namely, that any fusion reaction having the character of a beam-target process must necessarily be more inefficient than a thermonuclear process with a confined thermal plasma at a suitably high temperature. Open questions that need attention of researchers are highlighted. A future course of action is suggested that individual plasma focus laboratories could adopt in order to positively influence the future growth of research in this field, to the general benefit of not only the controlled fusion research community but also the world at large.

Bloodstream infection is a hallmark of sepsis, a medically emergent condition requiring rapid treatment. However, upregulation of host defense proteins through toll-like receptors and NFκB requires hours after endotoxin detection. Using confocal pulmonary intravital microscopy, we identified that the lung provides a TLR4-Myd88-and abl tyrosine kinase-dependent niche for immediate CD11b-dependent neutrophil responses to endotoxin and Gram-negative bloodstream pathogens. In an in vivo model of bacteremia, neutrophils crawled to and rapidly phagocytosed Escherichia coli sequestered to the lung endothelium. Therefore, the lung capillaries provide a vascular defensive niche whereby endothelium and neutrophils cooperate for immediate detection and capture of disseminating pathogens.

Abdominal surgeries are frequently associated with the development of post-surgical adhesions. These are irreversible fibrotic scar bands that appear between abdominal organs and the abdominal wall. Patients suffering from adhesions are at risk of severe complications, such as small bowel obstruction, chronic pelvic pain, or infertility. To date, no cure exists, and the understanding of underlying molecular mechanisms of adhesion formation is incomplete. The current paradigm largely relies on sterile injury mouse models. However, abdominal surgeries in human patients are rarely completely sterile procedures. Here, we describe a modular surgical procedure for simultaneous or separate induction of sterile injury and microbial contamination. Combined, these insults synergistically lead to adhesion formation in the mouse peritoneal cavity. Surgical trauma is confined to a localized sterile injury of the peritoneum. Microbial contamination of the peritoneal cavity is induced by a limited perforation of the microbe-rich large intestine or by injection of fecal content. The presented protocol extends previous injury-based adhesion models by an additional insult through microbial contamination, which may more adequately model the clinical context of abdominal surgery.Graphical abstract:

(English abstract below!) *Das nach der Wiener Frauenrechtlerin Rosa Mayreder benannte College existierte von 1999 bis 2012 als Bildungseinrichtung im Rahmen der Wiener Volkshochschulen. Der Beitrag erörtert an diesem Beispiel Bildungskonzeptionen, die an der Schnittstelle von Universität und außeruniversitärer Erwachsenenbildung angesiedelt sind. Nach einem kurzen Streifzug durch die Entstehungsgeschichte des Rosa-Mayreder-College und seiner Zielsetzungen folgt eine Fokussierung auf das Studienangebot „Feministisches Grundstudium“ und seine Durchführungspraxis. Im zweiten Teil des Beitrags erinnert die Autorin mit kritischen Bemerkungen an gesellschaftspolitische und ökonomische Entwicklungen seit den 1990er Jahren. Diese sind der Ausgangspunkt für ihre Überlegungen einer möglichen Alternative zu Bildungsökonomisierung und Selbstoptimierung – sowohl im Erwachsenenbildungskontext als auch im spezifisch akademischen Feld wissenschaftlicher Weiterbildung.* *** *Named after the Viennese women’s rights’ activist Rosa Mayreder, the college existed as an educational institution within the Vienna adult education centres from 1999 to 2012. Based on this example, the article examines ideas of education at the interface between the university and adult education outside the university. After a short stroll through the history of the development of Rosa Mayreder College and its goals, the focus is on the “Basic Feminist Education” study program and its implementation in practice. In the second half of the article, the author makes some critical observations of sociopolitical and economic developments since the 1990s. They provide the starting point for her thoughts on a possible alternative to the economization of education and selfoptimization— both in the context of adult education and in the specifically academic field of scientific continuing education.*

This paper presents the filamentary structure of the pinched column in a smaller plasma focus device filled with deuterium. The deflections were observed using schlieren and differential interferometry techniques. The observed filaments have a transverse diameter of 40–200 μm, which could be interpreted based on the electric current hypothesis as local concentrations of electric current. The evolution of filaments was compared with global structures recorded by extra ultraviolet frames. These results provide a basis for considering the possibility of a filamentary composition of the poloidal current in compact structures. The model of filaments with a helical shape of electrical current may be able to explain the central narrow and dense cord in the axis of the column, the different lifetimes of the structures, and the submillimeter sources of fast electrons and ions. [ABSTRACT FROM AUTHOR]

The origin and diversity of blood vascular endothelial cells (BEC) in lymphoid tissues is unclear. Here, the authors profile murine BECs from peripheral lymph nodes by single cell analysis and identify subsets of cells specialised for immune cell recruitment and vascular homeostasis.

Neutrophils mobilize rapidly and travel through the vasculature and microcirculation en masse in response to inflammatory stimuli. Here the authors use a microfluidic device and intravital microscopy to show neutrophils move through tissues in a highly ordered pattern, taking turns to file into alternate branches at bifurcations.

Lamina propria macrophages are at the frontline of defense against intestinal pathogens. Here the authors reveal that CCR2 and NR4A1-dependent CX3CR1+ macrophages form a dense network around the vessels in the lamina propria, and implicate this anatomical structure into prevention of systemic bacterial dissemination.

Background: Neutrophils play a role in innate immunity and are critical for clearance of Staphylococcus aureus. Current understanding of neutrophil bactericidal effects is that NADPH oxidase produces reactive oxygen species (ROS), mediating bacterial killing. Neutrophils also contain numerous mitochondria; since these organelles lack oxidative metabolism, their function is unclear. We hypothesize that mitochondria in human neutrophils contribute to the bactericidal capacity of S. aureus. Methods: and Findings: Using human neutrophils isolated from healthy volunteers (n = 13; 7 females, 6 males), we show that mitochondria are critical in the immune response to S. aureus. Using live-cell and fixed confocal, and transmission electron microscopy, we show mitochondrial tagging of bacteria prior to ingestion and surrounding of phagocytosed bacteria immediately upon engulfment. Further, we demonstrate that mitochondria are ejected from intact neutrophils and engage bacteria during vital NETosis. Inhibition of the mitochondrial electron transport chain at Complex III, but not Complex I, attenuates S. aureus killing by 50 ± 7%, comparable to the NADPH oxidase inhibitor apocynin. Similarly, mitochondrial ROS scavenging using MitoTEMPO attenuates bacterial killing 112 ± 60% versus vehicle control. Antimycin A treatment also reduces mitochondrial ROS production by 50 ± 12% and NETosis by 53 ± 5%. Conclusions: We identify a previously unrecognized role for mitochondria in human neutrophils in the killing of S. aureus. Inhibition of electron transport chain Complex III significantly impairs antimicrobial activity. This is the first demonstration that vital NETosis, an early event in the antimicrobial response, occurring within 5 min of bacterial exposure, depends on the function of mitochondrial Complex III. Mitochondria join NADPH oxidase as bactericidal ROS generators that mediate the bactericidal activities of human neutrophils.

Acute respiratory distress syndrome (ARDS) is a life-threatening syndrome, constituted by respiratory failure and diffuse alveolar damage that results from dysregulated local and systemic immune activation, causing pulmonary vascular, parenchymal, and alveolar damage. SARS-CoV-2 infection has become the dominant cause of ARDS worldwide, and emerging evidence implicates neutrophils and their cytotoxic arsenal of effector functions as central drivers of immune-mediated lung injury in COVID-19 ARDS. However, key outstanding questions are whether COVID-19 drives a unique program of neutrophil activation or effector functions that contribute to the severe pathogenesis of this pandemic illness and whether this unique neutrophil response can be targeted to attenuate disease. Using a combination of high-dimensional single-cell analysis and ex vivo functional assays of neutrophils from patients with COVID-19 ARDS, compared with those with non-COVID ARDS (caused by bacterial pneumonia), we identified a functionally distinct landscape of neutrophil activation in COVID-19 ARDS that was intrinsically programmed during SARS-CoV-2 infection. Furthermore, neutrophils in COVID-19 ARDS were functionally primed to produce high amounts of neutrophil extracellular traps. Surprisingly, this unique pathological program of neutrophil priming escaped conventional therapy with dexamethasone, thereby revealing a promising target for adjunctive immunotherapy in severe COVID-19.

Little is known about cancellation frequencies in telemedicine vs. in-person appointments and its impact on clinical outcomes. Our objective was to examine differences between in-person and video telemedicine appointments in terms of cancellation rates by age, race, ethnicity, gender, and insurance, and compare 30-day inpatient hospitalizations rates and 30-day emergency department visit rates between the two visit types. Demographic characteristics and comorbidities for adults scheduled for an Emory Healthcare ambulatory clinic appointment from June 2020 to December 2020 were extracted from the electronic medical record. Each appointment was identified as either a video telemedicine or in-person clinic appointment. The outcomes were ambulatory clinic cancellation rates, 30-day hospitalization rates, and 30-day emergency department visit rates. Multivariable logistic regression was used to assess differences between appointment types. A total of 1,652,623 ambulatory clinic appointments were scheduled. Ambulatory appointment cancellations rates were significantly lower among telemedicine compared to in-person appointments overall (20.4% vs. 31.0%, p

Abstract Background The 10th revision of International Classification of Disease, Clinical Modification (ICD10‐CM) increased the number of codes to identify non‐traumatic subarachnoid hemorrhage from 1 to 22. ICD10‐CM codes are able to specify the location of aneurysms causing subarachnoid hemorrhage (aSAH); however, it is not clear how frequently or accurately these codes are being used in practice. Objective To systematically evaluate the usage and accuracy of location‐specific ICD10‐CM codes for aSAH. Methods We extracted all uses of ICD10‐CM codes for non‐traumatic subarachnoid hemorrhage (I60.x) during the first 3 years following the implementation of ICD10‐CM from the billing module of the electronic health record (EHR) for UCHealth. For those codes that specified aSAH location (I60.0‐I60.6), EHR documentation was reviewed to determine whether there was an active aSAH, any patient history of aSAH, or unruptured intracranial aneurysm/s and the locations of those outcomes. Results Between 1 October 2015 and 30 September 2018, there were 3119 instances of non‐traumatic subarachnoid hemorrhage ICD10‐CM codes (I60.00‐I60.9), of which 297 (9.5%) code instances identified aSAH location (I60.0‐I60.6). The usage of location‐specific codes increased from 5.7% in 2015 to 11.2% in 2018. These codes accurately identified current aSAH (64%), any patient history of aSAH (84%), and any patient history of intracranial aneurysm (87%). The accuracy of identified outcome location was 53% in current aSAH, 72% for any history of aSAH, and 76% for any history of an intracranial aneurysm. Conclusions Researchers should use ICD10‐CM codes with caution when attempting to detect active aSAH and/or aneurysm location.

Intracellular infection with the parasite Leishmania major features a state of concomitant immunity in which CD4+ T helper 1 (Th1) cell-mediated immunity against reinfection coincides with a chronic but sub-clinical primary infection. In this setting, the rapidity of the Th1 response at a secondary site of challenge in the skin represents the best correlate of parasite elimination and has been associated with a reversal in Leishmania-mediated modulation of monocytic host cells. Remarkably, the degree to which Th1 cells are absolutely reliant upon the time at which they interact with infected monocytes to mediate their protective effect has not been defined. In the present work, we report that CXCR3-dependent recruitment of Ly6C+ Th1 effector (Th1EFF) cells is indispensable for concomitant immunity and acute (

Summary: Skin is one of the most common sites of host immune response against Staphylococcus aureus infection. Here, through a combination of in vitro assays, mouse models, and intravital imaging, we find that S. aureus immune evasion in skin is controlled by a cascade composed of the ArlRS two-component regulatory system and its downstream effector, MgrA. S. aureus lacking either ArlRS or MgrA is less virulent and unable to form correct abscess structure due to de-repression of a giant surface protein, Ebh. These S. aureus mutants also have decreased expression of immune evasion factors (leukocidins, chemotaxis-inhibitory protein of S. aureus [CHIPS], staphylococcal complement inhibitor [SCIN], and nuclease) and are unable to kill neutrophils, block their chemotaxis, degrade neutrophil extracellular traps, and survive direct neutrophil attack. The combination of disrupted abscess structure and reduced immune evasion factors makes S. aureus susceptible to host defenses. ArlRS and MgrA are therefore the main regulators of S. aureus immune evasion and promising treatment targets.

The analysis of Z-pinch implosion dynamics plays one of the most important roles in the study of pulsed power discharges. At the same time, it is difficult to determine the density distribution together with the current density (current coupling to the imploding layer) to provide more detailed information about the dynamics. Numerical simulations can now provide high-resolution results that are almost unattainable in experiments. The challenge, however, is to obtain reliable results that are close enough to the experimental data to describe individual physical phenomena. In this paper, we show that it is possible to use a combination of experimental data and magnetohydrodynamic (MHD) simulations to verify and identify the physical processes during the stagnation of a Z-pinch. We focus on the analysis of the density profile from experimental data of the mega-ampere plasma focus PF-1000 and its reconstruction using an extended MHD code. Thanks to multi-frame interferometry, we recorded a total of 29 interferometric images of two shots, each in a 200 ns time window around the pinch phase. We were then able to obtain density profiles and observe the reflection of the shock wave from the axis. By the appropriate choice of initial conditions and boundary values in the simulation, we were able to obtain reasonable agreement with the experimental values. We also evaluated the possible shortcomings of the 1D simulation, such as mass loss and current flow at the periphery. [ABSTRACT FROM AUTHOR]

Abstract Introduction Rotational thromboelastometry (ROTEM) has been shown to reduce the need for transfused blood products in adult and pediatric cardiac surgery patients. However, similar evidence in newborns, neonates, and young infants is lacking. We quantified ROTEM value changes in pediatric patients on cardiopulmonary bypass (CPB) before, during and after blood product transfusion. Methods Each surgery had at least four interventions: initiating CPB; platelet administration during rewarming phase; post-CPB and following protamine and human fibrinogen concentrate (HFC) administration; and further component therapy if bleeding persisted and ROTEM indicated a deficiency. ROTEM assays were performed prior to surgery commencement, on CPB prior to platelet administration and following 38 mL/kg platelets, and post-CPB after protamine and HFC administration. ROTEM assays were also performed in the post-CPB period after further blood component therapy administration. Results Data from 161 patients were analyzed. Regression models suggested significant changes in HEPTEM clotting time after all interventions. PLT administration during CPB improved HEPTEM α by 22.1° (p

Summary: Many patients with visceral inflammation develop pain and psychiatric comorbidities such as major depressive disorder, worsening the quality of life and increasing the risk of suicide. Here we show that neuroimmune activation in mice with dextran sodium sulfate-induced colitis is accompanied by the development of pain and depressive behaviors. Importantly, treatment with the flavonoid luteolin prevented both neuroimmune responses and behavioral abnormalities, suggesting a new potential therapeutic approach for patients with inflammatory bowel diseases. : Pathophysiology; Behavioral Neuroscience; Cellular Neuroscience; Immunity Subject Areas: Pathophysiology, Behavioral Neuroscience, Cellular Neuroscience, Immunity

Summary: Neutrophils with immunoregulatory properties, also referred to as type-2 neutrophils (N2), myeloid-derived suppressor cells (MDSCs), or tumor-associated neutrophils (TANs), comprise a heterogeneous subset of cells that arise from unknown precursors in response to poorly understood cues. Here, we find that, in several models of liver autoimmunity, pharmacologically induced, autoantigen-specific T regulatory type-1 (TR1) cells and TR1-cell-induced B regulatory (Breg) cells use five immunoregulatory cytokines to coordinately recruit neutrophils into the liver and program their transcriptome to generate regulatory neutrophils. The liver-associated neutrophils from the treated mice, unlike their circulating counterparts or the liver neutrophils of sick mice lacking antigen-specific TR1 cells, are proliferative, can transfer disease protection to immunocompromised hosts engrafted with pathogenic effectors, and blunt antigen-presentation and local autoimmune responses via cathelin-related anti-microbial peptide (CRAMP), a cathelicidin, in a CRAMP-receptor-dependent manner. These results, thus, identify antigen-specific regulatory T cells as drivers of tissue-restricted regulatory neutrophil formation and CRAMP as an effector of regulatory neutrophil-mediated immunoregulation.

Paracoccidioidomycosis is a systemic fungal disease, considered endemic in Latin America. Its etiological agents, fungi of the Paracoccidioides complex, have restricted geographic habitat, conidia as infecting form, and thermo-dimorphic characteristics. Polymorphonuclear neutrophils (PMNs) are responsible for an important defense response against fungus, releasing Neutrophil Extracellular Traps (NETs), which can wrap and destroy the yeasts. However, it has been described that some pathogens are able to evade from these DNA structures by releasing DNase as an escape mechanism. As different NETs patterns have been identified in PMNs cultures challenged with different isolates of Paracoccidioides brasiliensis, the general objective of this study was to identify if different patterns of NETs released by human PMNs challenged with Pb18 (virulent) and Pb265 (avirulent) isolates would be correlated with fungal ability to produce a DNase-like protein. To this end, PMNs from healthy subjects were isolated and challenged in vitro with both fungal isolates. The production, release, and conformation of NETs in response to the fungi were evaluated by Confocal Microscopy, Scanning Microscopy, and NETs Quantification. The identification of fungal DNase production was assessed by DNase TEST Agar, and the relative gene expression for hypothetical proteins was investigated by RT-qPCR, whose genes had been identified in the fungal genome in the GenBank (PADG_11161 and PADG_08285). It was possible to verify the NETs release by PMNs, showing different NETs formation when in contact with different isolates of the fungus. The Pb18 isolate induced the release of looser, larger, and more looking like degraded NETs compared to the Pb265 isolate, which induced the release of denser and more compact NETs. DNase TEST Agar identified the production of a DNase-like protein, showing that only Pb18 showed the capacity to degrade DNA in these plates. Besides that, we were able to identify that both PADG_08528 and PADG_11161 genes were more expressed during interaction with neutrophil by the virulent isolate, being PADG_08528 highly expressed in these cultures, demonstrating that this gene could have a greater contribution to the production of the protein. Thus, we identified that the virulent isolate is inducing more scattered and loose NETs, probably by releasing a DNase-like protein. This factor could be an important escape mechanism used by the fungus to escape the NETs action.

Abstract Objective: To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI). Design: We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention. Setting: An academic healthcare system with 4 hospitals. Patients: All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients. Intervention: Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing. Results: Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01). Conclusions: Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.