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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.

The experiments were carried out in the PF-1000 plasma-focus device at the maximum current reaching about 2 MA, at the deuterium or neon filling and with deuterium injected from a gas-puff nozzle placed on the axis of the anode face. Ball-like structures of diameters of 1-12 mm were identified in interferometric and XUV pinhole camera frames. We made the statistical description of their parameters. A lifetime of the ball-like structures was in the range from 30 to 210 ns, and in some cases even more. These structures appeared mostly at the surface of the imploding plasma shell and they did not change their position in relation to the anode end. During the evolution of these structures, interferometric fringes were observed near the surfaces of the structures only, and their internal parts were initially chaotic (without noticeable) fringes. Subsequently the number of interferometric fringes increased (the internal ‘chaotic’ area was filled with fringes too) and later on it decreased. The radii of the ball-like structures were mostly increasing during their existence. The maximum electron density reached the value of 1024 to 1025 m-3. The ball-like structures decayed by absorption inside the expanded pinch column and/or gradually expired in rare plasma outside of the dense plasma column.

Experimental studies of discharges in the plasma focus facility with neon filling and respective numerical simulations employing the radiative Lee code are reported. The pinch currents exceed the Pease-Braginskii current, which indicates that radiative losses are larger than heating and that contraction of the formed plasma should occur. Both of these effects were indeed observed. Parallel numerical simulations were crucial for the identification of such an effect.

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.

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.

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.

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.

In our earlier papers it was demonstrated that the plasma pressure decreases with the growing atomic number of the target material. In this context a question arose about the possibility to collimate the Al plasma outflow by using the plastic plasma as a compressor. For that purpose a plastic target with an Al cylindrical insert of 400 μm in diameter was used. The experiment was carried out at the PALS laser facility. The laser provided a 250 ps (FWHM) pulse with the energy of 130 J at the third harmonic frequency (λ3 = 0.438 μm). The focal spot diameters (ΦL) 800, 1000, and 1200 μm ensured predominance of the plastic plasma, its transversal extension being large enough for the effective Al plasma compression. To study the Al plasma stream propagation and its interaction with the plastic plasma, a 3-frame interferometric system and 4-frame x-ray camera were used. The information on distribution of electron temperature in the outflowing Al plasma was provided by x-ray spectroscopy. The experimental results reported in the paper are discussed by virtue of a simple theoretical analysis.

Abstract Background Fever is one of the most commonly observed abnormal signs in patients with critical illness. However, there is a paucity of evidence to guide the management of febrile patients without acute brain injury and little is known about the biologic response to treatment of fever. As such, observational studies suggest that the treatment of fever is inconsistent. This pilot clinical trial will assess the safety and feasibility of treating febrile critically ill adult patients with an aggressive versus a permissive temperature control strategy. The biologic response to these two different temperature control strategies will also be assessed through analysis of a panel of inflammatory mediators. Findings The study population will include febrile adult patients admitted to one of two general medical-surgical intensive care units (ICUs) in Calgary, Alberta, Canada. Patients will be randomized to either an aggressive or permissive fever treatment strategy. The aggressive group will receive acetaminophen 650 mg enterally every 6 hours upon reaching a temperature ≥ 38.3°C and external cooling will be initiated for temperatures ≥ 39.5°C, whereas the permissive group will receive acetaminophen 650 mg every 6 hours upon reaching a temperature ≥ 40.0°C and external cooling for temperatures ≥ 40.5°C. The study will take place over 12 months with the goal of enrolling 120 patients. The primary outcome will be 28-day mortality after study enrolment, with secondary outcomes that will include markers of feasibility (e.g. the enrolment rate, and the number of protocol violations), and levels of select inflammatory and anti-inflammatory mediators. Discussion Results from this study will lead to a better understanding of the inflammatory effects of anti-pyretic therapy and will evaluate the feasibility of a future clinical trial to establish the best treatment of fever observed in nearly one half of patients admitted to adult ICUs. Trial Registration ClinicalTrials.gov: NCT01173367

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.

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:

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 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]

[Display omitted] Familial Mediterranean fever (FMF), caused by mutations in the pyrin-encoding MEFV gene, is characterized by uncontrolled caspase-1 activation and IL-1β secretion. A similar mechanism drives inflammation in cryopyrin-associated periodic fever syndrome (CAPS) caused by mutations in NLRP3. CAPS and FMF, however, result in largely different clinical manifestations, pointing to additional, autoinflammatory pathways involved in FMF. Another hallmark of FMF is extraordinarily high expression of S100A8 and S100A9. These alarmins are ligands of Toll-like receptor 4 and amplifiers of inflammation. However, the relevance of this inflammatory pathway for the pathogenesis of FMF is unknown. This study investigated whether mutations in pyrin result in specific secretion of S100A8/A9 alarmins through gasdermin D pores' amplifying FMF pathology. S100A8/A9 levels in FMF patients were quantified by enzyme-linked immunosorbent assay. In vitro models with knockout cell lines and specific protein inhibitors were used to unravel the S100A8/A9 secretion mechanism. The impact of S100A8/A9 to the pathophysiology of FMF was analyzed with FMF (MEFV V726A/V726A) and S100A9 −/− mouse models. Pyrin-S100A8/A9 interaction was investigated by coimmunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay studies. The S100A8/A9 complexes directly interacted with pyrin. Knocking out pyrin, caspase-1, or gasdermin D inhibited the secretion of these S100 alarmins. Inflammatory S100A8/A9 dimers were inactivated by tetramer formation. Blocking this inactivation by targeted S100A9 deletion in a murine FMF model demonstrated the relevance of this novel autoinflammatory pathway in FMF. This is the first proof that members of the S100 alarmin family are released in a pyrin/caspase-1/gasdermin D–dependent pathway and directly drive autoinflammation in vivo. [ABSTRACT FROM AUTHOR]