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Patients suffering from malignant diseases have a high risk of developing severe or critical forms of COVID-19 (Coronavirus Disease 2019). Chronic lymphocytic leukaemia (CLL) is characterized by dysregulated adaptive and innate immune responses, because both T and B cells, the function of phagocytes and the activity of the complement system may be affected. Severe SARS-CoV-2 infection also influences the immunological functions mainly via causing the depletion of CD4+ and CD8+ T cells. We present the cases of two patients, whose

The Great Hungarian Plain (GHP) served as a geographic funnel for population mobility throughout prehistory. Genomic and isotopic research demonstrates non-linear genetic turnover and technological shifts between the Copper and Iron Ages of the GHP, which influenced the dietary strategies of numerous cultures that intermixed and overlapped through time. Given the complexities of these prehistoric cultural and demographic processes, this study aims to improve our understanding of diachronic and culture-specific dietary signatures. Here we report on stable carbon and nitrogen isotope values from 75 individuals from twenty sites in the GHP dating to a ~ 3000-year time span between the Early Bronze and Early Iron Ages. The samples broadly indicate a terrestrial C3 diet with nuanced differences amongst cultures, suggesting exogenous influences that manifested in subsistence strategies. Compared to the Iron Age, the Bronze Age samples have slightly elevated δ15N values implying higher reliance on protein. Interestingly, carbon values typical of C4 vegetation indicate the consumption of millet, or a grain with comparable δ13C values during the Middle Bronze Age. Overall, our results suggest a gradual transition in dietary patterns from the Early Bronze to Early Iron Age, demonstrating a relationship between subsistence and time periods, congruent with the archaeological record.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared “predicted” genetic contributions to height from paleogenomic data and “achieved” adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

The article concentrates on the issue of Hungarian education reforms brought about by radical political changes, in particular, the country’s admittance to the European Union. The paper outlines priorities in educational process transformation, as well as risks emerging in the system of teacher education and lifelong learning. The challenges associated with our times transform the teacher’s consciousness, shiftingfocus to the mandatory use of information technology, the activation of students’ information mobility, and the detailed analysis of employers’ requirements. The study reveals the Hungarian government’s key activities in relation to the socialization of the Roma minority and other national minorities compactly residing in Ukraine. The research illustrated educational resources used to train teachers at educational institutions to instill tolerance and mutual respect. The 2020s’ are marked by powerful globalization and political factors penetrating all spheres of social life. The dynamic formation of the civilized information society is accompanied by a number of contradictions and conflicts, the strengthening of social ties, and changing living conditions (R.ti, 2009), (V.g. and Vass 2006). Despite numerous methodological and conceptual studies, the issues of updating the modern teacher’s training to enableteachers to train and educate students and adequately react to challenges imposed by digitalization remain open. In this respect, the experience of European states that successfully carried out a number of educational reforms is of great scientific interest and deserves to be systematically studied, popularized and introduced into the domestic educational system. One of such countries is Hungary, which borders on Ukraine both territorially and functionally (Transcarpathia is compactly inhabited by Hungarian national minorities). The aim of the article is to substantiate the essence of the key educational reforms in Hungary and to identify the risks and priorities brought about by transformational changes in the country.

Human culture, biology, and health were shaped dramatically by the onset of agriculture ~12,000 years before present (BP). Subsistence shifts from hunting and gathering to agriculture are hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a simultaneous decline in physiological health as inferred from paleopathological analyses and stature reconstructions of skeletal remains. A key component of the health decline inference is that relatively shorter statures observed for early farmers may (at least partly) reflect higher childhood disease burdens and poorer nutrition. However, while such stresses can indeed result in growth stunting, height is also highly heritable, and substantial inter-individual variation in the height genetic component within a population is typical. Moreover, extensive migration and gene flow were characteristics of multiple agricultural transitions worldwide. Here, we consider both osteological and ancient DNA data from the same prehistoric individuals to comprehensively study the trajectory of human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared ‘predicted’ genetic contributions to height from paleogenomic data and ‘achieved’ adult osteological height estimated from long bone measurements on a per-individual basis for n=160 ancient Europeans from sites spanning the Upper Paleolithic to the Iron Age (~38,000-2,400 BP). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −4.47 cm relative to individuals from the Upper Paleolithic and Mesolithic (P=0.016). The average osteological vs. expected stature then increased relative to the Neolithic over the Copper (+2.67 cm, P=0.052), Bronze (+3.33 cm, P=0.032), and Iron Ages (+3.95 cm, P=0.094). These results were partly attenuated when we accounted for genome-wide genetic ancestry variation in our sample (which we note is partly duplicative with the individual polygenic score information). For example, in this secondary analysis Neolithic individuals were −3.48 cm shorter than expected on average relative to individuals from the Upper Paleolithic and Mesolithic (P=0.056). We also incorporated observations of paleopathological indicators of non-specific stress that can persist from childhood to adulthood in skeletal remains (linear enamel hypoplasia, cribra orbitalia, and porotic hyperostosis) into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.

Monitoring measurable residual disease (MRD) in acute myeloid leukemia (AML) plays an important role in predicting relapse and outcome. The applicability of the leukemia-initiating nucleophosmin1 (NPM1) gene mutations in MRD detection is well-established, while that of isocitrate dehydrogenase1/2 (IDH1/2) mutations are matter of debate. The aim of this study was to investigate the stability of NPM1 and IDH1/2 mutations at diagnosis and relapse retrospectively in 916 adult AML patients. The prognostic value of MRD was evaluated by droplet digital PCR on the DNA level in a selected subgroup of patients in remission. NPM1 re-emerged at relapse in 91% (72/79), while IDH1/2 in 87% (20/23) of mutation-positive cases at diagnosis. NPM1 mutation did not develop at relapse, on the contrary novel IDH1/2 mutations occurred in 3% (3/93) of previously mutation-negative cases. NPM1 MRD-positivity after induction (n = 116) proved to be an independent, adverse risk factor (MRDpos 24-month OS: 39.3±6.2% versus MRDneg: 58.5±7.5%, p = 0.029; HR: 2.16; 95%CI: 1.25–3.74, p = 0.006). In the favorable subgroup of mutated NPM1 without fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) or with low allelic ratio, NPM1 MRD provides a valuable prognostic biomarker (NPM1 MRDpos versus MRDneg 24-month OS: 42.9±6.7% versus 66.7±8.6%; p = 0.01). IDH1/2 MRD-positivity after induction (n = 62) was also associated with poor survival (MRDpos 24-month OS: 41.3±9.2% versus MRDneg: 62.5±9.0%, p = 0.003; HR 2.81 95%CI 1.09–7.23, p = 0.032). While NPM1 variant allele frequency decreased below 2.5% in remission in all patients, IDH1/2 mutations (typically IDH2 R140Q) persisted in 24% of cases. Our results support that NPM1 MRD even at DNA level is a reliable prognostic factor, while IDH1/2 mutations may represent pre-leukemic, founder or subclonal drivers.

A common feature of tectonic reconstructions is the migration of subduction zones and their interactions, resulting in complex tectonic patterns. Reduced migration rates, uplift, strong rotations, and slab break-off are all tectonics features commonly associated with convergent margin interactions, showing that while subduction zones' motions fundamentally shape tectonics settings, their interactions hold the key to their complexities. Fundamental properties such as slab buoyancy, dip direction, and coupled mantle flow determine the motions of single hinge zones. When these zones approach, stress transfers between the slabs through the lithosphere and the mantle, thereby altering the subduction force balance, favoring, opposing, or diverting further motions. We illustrate the range of configurations reported in tectonic reconstructions and address their dynamics through the results of analog and numerical models of subduction dynamics in the upper mantle. The Cenozoic evolution of the Mediterranean provides relevant examples of such interactions, where the coeval activity of several subduction zones during the Africa-Europe convergence has strongly overprinted the current tectonics. A comparison of new analog models with the deep dynamics of the Mediterranean shows how the interactions among slabs and mantle may have shaped the distribution of basins and mountain belts, their uplift, and volcanism in this tectonic province.

Ancient DNA sampling methods—although optimized for efficient DNA extraction—are destructive, relying on drilling or cutting and powdering (parts of) bones and teeth. As the field of ancient DNA has grown, so have concerns about the impact of destructive sampling of the skeletal remains from which ancient DNA is obtained. Due to a particularly high concentration of endogenous DNA, the cementum of tooth roots is often targeted for ancient DNA sampling, but standard destructive sampling methods often result in the loss of at least one entire root. Here, we present a minimally destructive method for extracting ancient DNA from dental cementum present on the surface of tooth roots. This method does not require destructive drilling or grinding, and, following extraction, the tooth remains safe to handle and suitable for most morphological studies, as well as other biochemical studies, such as radiocarbon dating. We extracted and sequenced ancient DNA from 30 teeth (and 9 corresponding petrous bones) using this minimally destructive extraction method in addition to a typical tooth sampling method. We find that the minimally destructive method can provide ancient DNA that is of comparable quality to extracts produced from teeth that have undergone destructive sampling processes. Further, we find that a rigorous cleaning of the tooth surface combining diluted bleach and UV light irradiation seems sufficient to minimize external contaminants usually removed through the physical removal of a superficial layer when sampling through regular powdering methods.

Asthenospheric shear causes some minerals, particularly olivine, to develop anisotropic textures that can be detected seismically. In laboratory experiments, these textures are also associated with anisotropic viscous behavior, which should be important for geodynamic processes. To examine the role of anisotropic viscosity for asthenospheric deformation, we developed a numerical model of coupled anisotropic texture development and anisotropic viscosity, both calibrated with laboratory measurements of olivine aggregates. This model characterizes the time‐dependent coupling between large‐scale formation of lattice‐preferred orientation (i.e., texture) and changes in asthenospheric viscosity for a series of simple deformation paths that represent upper mantle geodynamic processes. We find that texture development beneath a moving surface plate tends to align the a axes of olivine into the plate motion direction, which weakens the effective viscosity in this direction and increases plate velocity for a given driving force. Our models indicate that the effective viscosity increases for shear in the horizontal direction perpendicular to the a axes. This increase should slow plate motions and new texture development in this perpendicular direction and could impede changes to the plate motion direction for tens of millions of years. However, the same well‐developed asthenospheric texture may foster subduction initiation perpendicular to the plate motion and deformations related to transform faults, as shearing on vertical planes seems to be favored across a sublithospheric olivine texture. These end‐member cases examining shear deformation in the presence of a well‐formed asthenospheric texture illustrate the importance of the mean olivine orientation, and its associated viscous anisotropy, for a variety of geodynamic processes.

The study of slab-slab interactions has come to the front of geodynamics researches to explain geological and geophysical observations from tectonically complex areas. Here we aim to better understand the geodynamics of the Central Mediterranean, where the Adria plate subducts on its two opposite sides. Additionally, the slab below the Central South Apennines has been progressively breaking off during the last 3 Myr. The role of a slab window in a single slab or in an outward dipping double-sided subduction system is addressed by analog models at the scale of the upper mantle, realized using glucose syrup and silicone putty, to model the interaction between the Earth's mantle and the lithosphere. Our results show that the presence of a slab window modifies the pattern of mantle circulation, as well as the trench geometry and kinematics. In particular, the opening of the slab window induces the formation of two arcs flanking the window, while the mantle flows through it and turns toward the arcs, creating a small-scale toroidal flow. The effect of a slab window is more pronounced on double subduction systems, as the outflow through the window is amplified, while internal deformation is induced in the plate by the opposite slab pull force. These experimental results suggest that the origin of the Apenninic and the Calabrian arcs is the result of the formation of a slab window, providing a new interpretation of the surface deformation and the SKS shear wave splitting pattern of the Adria microplate.Plain Language Summary The Adria microplate in the Central Mediterranean is an important part of the tectonic puzzle between the converging Africa and Eurasia plates. The heavy lithosphere sinks into the underlying mantle on two sides of the Adria plate, under the Apennines in the west and under the Dinarides in the east. During the most recent few millions of years, the lithosphere started to detach from the surface in the Central South Apennines while sinking into the mantle. This opened a slab window, an additional escape route for the mantle, which is squeezed by the two subducting lithospheres. We scaled down and simplified this setting in order to model and investigate the role of the dual subduction and the opening slab window in the evolution of the Central Mediterranean by means of analog models. Our results show that the two opposite subduction zones have a regional tectonics effect via the complex subduction-induced mantle circulation. Furthermore, the detaching lithosphere modifies the geometry of the subduction zone, which results in a double-arc geometry resembling the Northern Apennines and Calabria.

Gaps within a subducting plate can alter the surrounding mantle flow field and the overall subduction zone dynamics by allowing hot sub-slab mantle to flow through the gaps and into the mantle wedge. This through-slab flow can produce melting of the slab gap edges as well as significant upwelling that can lead to anomalous alkaline volcanism and/or dynamic uplift in the overriding plate, while the altered mantle flow patterns affect the trench evolution. Numerous geodynamic models have investigated the processes that form slab gaps, but few studies have examined the dynamics of slab gap-altered mantle flow, its effects on trench morphology and kinematics, or the controlling parameters on these processes. Here, laboratory subduction models with a pre-cut gap in a subducting silicone plate are used to explore how slab gap size, and slab gap depth influence the surrounding mantle flow field and trench dynamics. Results suggest that both the vertical extent and the depth of the top (trailing edge) of the slab gap are crucial parameters for modulating overall subduction dynamics. They show that a slab gap, which occurs near the surface and initially comprises 30% of the subducting plate width, can extend enough vertically in the slab to produce significant vertical flow through the gap. Changes to the trench geometry and kinematics are also evident in the models, such that double- and triple-arc geometries are formed during subduction of a shallow slab gap. All of these results are consistent with observations of slab gaps and their induced surface expressions, or the lack thereof, in Eastern Anatolia, East Java, Italy, and Argentina.

Subduction-induced mantle circulation plays an important role in the dynamics of convergent margins. Different components of the flow, i.e. toroidal and poloidal, provide relevant driving forces for back-arc basin formation, overriding plate deformation, curvature of subduction zones and volcanic activity. Here, we investigate on the emergence and controls on the toroidal component of the subduction–induced mantle flow by means of numerical modeling. To characterize the toroidal cell's three-dimensional flow, size and length-scales and its disposing factors, we test separately a series of lithospheric and mantle parameters, such as the density difference and viscosity ratio between the slab and the mantle, the width of the slab, as opposed to the size, the stratification and the rheology of the mantle. Out of the tested parameters, the numerical results show that the strength of the flow depends on the mantle viscosity and the magnitude of the slab pull force, that is slab-mantle density difference and the mantle thickness, however the characteristic length, axis and the shape of the toroidal cell are almost independent of the slab's properties and mainly depend on the thickness of the convecting mantle.

Active and fossil subduction systems consisting of two adjacent plates with opposite retreating directions occur in several areas on Earth, as the Mediterranean or Western Pacific. The goal of this work is to better understand the first-order plate dynamics of these systems using the results of experimental models. The laboratory model is composed of two separate plates made of silicon putty representing the lithosphere, on top of a tank filled with glucose syrup representing the mantle. The set of experiments is designed to test the influence of the width of plates and the initial separation between them on the resulting trench velocities, deformation of plates, and mantle flow. Results show that the mantle flow induced by both plates is asymmetric relative to the axis of each plate causing a progressive merging of the toroidal cells that prevents a steady state phase of the subduction process and generates a net outward drag perpendicular to the plates. Trench velocities increase when trenches approach each other and decrease when they separate after their intersection. The trench curvature of both plates increases linearly with time during the entire evolution of the process regardless their width and initial separation. The interaction between the return flows associated with each retreating plate, particularly in the interplate region, is stronger for near plate configurations and correlates with variations of rollback velocities. We propose that the inferred first-order dynamics of the presented analog models can provide relevant clues to understand natural complex subduction systems. ©2018. American Geophysical Union. All Rights Reserved., The work of M. P., M. F., and J. V. is part of the projects ALPIMED (PIE-CSIC- 201530E082) and MITE (CGL2014- 59516-P) and partly financed by the Generalitat de Catalunya (2014-SGR-1471 and 2017-SGR-847). The work of S. Z. is funded by the Spanish Ministry of Economy and Competitiveness through grant CICYT DPI2017-85139-C2-2-R and Generalitat de Catalunya (2017-SGR-1278).

Slab‐slab interaction is a characteristic feature of tectonically complex areas. Outward dipping double‐sided subduction is one of these complex cases, which has several examples on Earth, most notably the Molucca Sea and Adriatic Sea. This study focuses on developing a framework for linking plate kinematics and slab interactions in an outward dipping subduction geometry. We used analog and numerical models to better understand the underlying subduction dynamics. Compared to a single subduction model, double‐sided subduction exhibits more time‐dependent and vigorous toroidal flow cells that are elongated (i.e., not circular). Because both the Molucca and Adriatic Sea exhibit an asymmetric subduction configuration, we also examine the role that asymmetry plays in the dynamics of outward dipping double‐sided subduction. We introduce asymmetry in two ways; with variable initial depths for the two slabs (“geometric” asymmetry), and with variable buoyancy within the subducting plate (“mechanical” asymmetry). Relative to the symmetric case, we probe how asymmetry affects the overall slab kinematics, whether asymmetric behavior intensifies or equilibrates as subduction proceeds. While initial geometric asymmetry disappears once the slabs are anchored to the 660 km discontinuity, the mechanical asymmetry can cause more permanent differences between the two subduction zones. In the most extreme case, the partly continental slab stops subducting due to the unequal slab pull force. The results show that the slab‐slab interaction is most effective when the two trenches are closer than 10–8 cm in the laboratory, which is 600–480 km when scaled to the Earth.

Density anomalies beneath the lithosphere are expected to generate dynamic topography at the Earth's surface due to the induced mantle flow stresses which scale linearly with density anomalies, while the viscosity of the upper mantle is expected to control uplift rates. However, limited attention has been given to the role of the lithosphere. Here we present results from analogue modeling of the interactions between a density anomaly rising in the mantle and the lithosphere in a Newtonian system. We find that, for instabilities with wavelengths of the same order of magnitude as lithosphere thickness, the uplift rate and the geometry of the surface bulge are inversely correlated to the lithosphere thickness. We also show that a layered lithosphere may modulate the topographic signal. With respect to previous approaches our models represent a novel attempt to unravel the way normal stresses generated by mantle flow are transmitted through a rheologically stratified lithosphere and the resulting topographic signal. © 2017. American Geophysical Union. All Rights Reserved., T.W.B. was partially supported through NASA OSP 201601412-001.

The interaction of neighboring subducting lithospheres is a characteristic feature of many tectonically complex areas. Here we use numerical modeling to study the interactions between two oppositely dipping, adjacent subducting lithospheres and to understand their impact on the subduction evolution, mantle flow, and stress propagation through the mantle. As slabs subduct, rollback, and approach, they strongly affect each other if plate edges are at distances

Recent modeling shows that surface processes, such as erosion and deposition, may drive the deformation of the Earth's surface, interfering with deeper crustal and mantle signals. To investigate the coupling between the surface and deep process, we designed a three-dimensional laboratory apparatus, to analyze the role of erosion and sedimentation, triggered by deep mantle instability. The setup is constituted and scaled down to natural gravity field using a thin viscous sheet model, with mantle and lithosphere simulated by Newtonian viscous glucose syrup and silicon putty, respectively. The surface process is simulated assuming a simple erosion law producing the downhill flow of a thin viscous material away from high topography. The deep mantle upwelling is triggered by the rise of a buoyant sphere. The results of these models along with the parametric analysis show how surface processes influence uplift velocity and topography signals.

INTRODUCTION: Biosimilar versions of filgrastim [recombinant human granulocyte colony-stimulating factor (rhG-CSF)] are now widely available. To date, biosimilar rhG-CSF has demonstrated a comparable quality, safety and efficacy profile to the originator product (filgrastim [Neupogen((R))], Amgen Inc., CA, USA) in the prevention and management of neutropenia. Biosimilar rhG-CSFs have also been used to induce peripheral blood stem cell (PBSC) mobilization in patients undergoing autologous stem cell transplantation (AHSCT). The authors have examined the effectiveness of a biosimilar rhG-CSF (Zarzio((R)), Sandoz Biopharmaceuticals, Holzkirchen, Germany) in two retrospective studies across two medical centers in Hungary. METHODS: In Study 1, 70 patients with hematological malignancies scheduled to undergo AHSCT received chemotherapy followed by biosimilar rhG-CSF (2 x 5 mug) for facilitating neutrophil, leukocyte, and platelet engraftment. In study 2, 40 additional patients with lymphoid malignancies and planned AHSCT received chemotherapy followed by biosimilar rhG-CSF for PBSC mobilization. The effectiveness of treatment was assessed by the average yield of cluster of differentiation (CD) 34+ cells and the number of leukaphereses required. RESULTS: In Study 1 (patients undergoing AHSCT), the median age was 56 years and most patients were male (60%). The conditioning regimens were mainly high-dose melphalan (n = 41) and carmustine (BiCNU((R)), Bristol-Myers Squibb, NJ, USA), etoposide, cytarabine and melphalan BEAM (n = 21). Median times to absolute neutrophil and leukocyte engraftment were 9 (range 8-11 days) and 10 (8-12) days, respectively. Median time to platelet engraftment was 10.5 days (7-19 days). In Study 2, the patients' median age was 54 years and the majority (57.5%) were female. The median time interval between day 1 of mobilizing chemotherapy and first leukapheresis was 12 (9-27) days. In the autologous PBSC grafts, the median number of CD34+ cells harvested was 5.2 x 10(6)/kg (2.22-57.07 x 10(6)/kg). The median yield of CD34+ cells per leukapheresis product was 2.47 x 10(6)/kg. In total, 58 leukaphereses were performed in 40 successfully harvested patients. CONCLUSIONS: In line with previous studies with originator rhG-CSF, the findings of this study indicate that biosimilar rhG-CSF following AHSCT is effective and generally well tolerated in the engraftment setting. In addition, biosimilar rhG-CSF is comparable to the originator rhG-CSF in terms of kinetics of PBSC mobilization and yield of CD34+ cells. In conclusion, the authors have demonstrated that the use of biosimilar rhG-CSF is effective and safe in autologous PBSC mobilization and engraftment after AHSCT.

Background/Aims: Interleukin 1β (IL-1β) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1β on gastric emptying were investigated. Methods: The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1β in conscious rats. Results: IL-1β injected intracisternally (0.01–1 ng) or intravenously (0.01–10 ng) dose-dependently decreased gastric emptying by 10%–82% and 0%–89%, respectively. The median effective dose (ED 50 ) was 30-fold lower when IL-1β was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1β had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1β (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe 12 , Nle 21,38 ,C α MeLeu 37 ]CRF 12–41 (20 μg) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1β (0.1 ng). The antagonists alone had no effect on basal gastric emptying. Conclusions: IL-1β acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1β action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.