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Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum–resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.

This is the peer reviewed version of the following article: Nasika, C. [et al.]. Discrete empirical interpolation for hyper-reduction of hydro-mechanical problems in groundwater flow through soil. "International journal for numerical and analytical methods in geomechanics", 10 Abril 2023, vol. 47, núm. 5, p. 667-693, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/nag.3487. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. The recent surge in the availability of sensor data and computational resources has fostered the development of technologies for optimization, control, and monitoring of large infrastructures, integrating data and numerical modeling. The major bottleneck in this type of technologies is the model response time, since repetitive solutions are typically required. To reduce the computational time, reduced order models (ROMs) are used as surrogates for expensive finite element (FE) simulations enabling the use of complex models in this type of applications. In this work, ROMs are explored for the solution of the fully coupled hydro-mechanical system of equations that governs the water flow through partially saturated soil. The POD-based Reduced Basis Method and the Discrete Empirical Interpolation Method (DEIM), as well as its localized version (LDEIM), are examined in solving a parametrized problem simulating the mechanical loading of an embankment dam. Hydraulic and mechanical soil properties are considered as parameters. It is shown that the combination of these methods results in simulations that require 1/10 to 1/100 of the FE response time. Moreover, the method is shown to yield scaling efficiency gains with increasing problem size.

Изучаются задачи Коши для многомерной симметричной линейной гиперболической системы уравнений 1-го порядка с переменными коэффициентами и ее сингулярных возмущений - сильно параболической и гиперболической 2-го порядка систем уравнений с малым параметром $\tau>0$ при вторых производных по $x$ и $t$. Доказываются существование и единственность слабых решений всех трех систем и равномерные по $\tau$ оценки решений систем с возмущениями. Даются оценки разности решений исходной системы и систем с возмущениями, в том числе в норме $C(0,T;L^2(\mathbb{R}^n))$ порядка $O(\tau^{\alpha/2})$ при начальной функции $\mathbf w_0$ из пространств Соболева $H^\alpha(\mathbb{R}^n)$ для $\alpha=1,2$ и пространств Никольского $H_2^{\alpha}(\mathbb{R}^n)$ для $0

Geophysical observables, such as surface elevation, gravity field anomalies, seismic data, surface heat flow, etc, are essential pieces of information used to make inferences about the structure and dynamics of the Earth’s interior. Simultaneously fitting different observable datasets is crucial in order to obtain consistent models. Among geophysical data, gravity data from ESA’s GOCE satellite mission provides key information in properly constraining the Earth’s density distribution. WINTERC-G is a new global thermochemical model of the lithosphere and upper mantle (currently being extended into the transition zone and lower mantle) based on terrestrial and satellite gravity data (Fullea et al., 2021). The inversion procedure behind WINTERC-G has two main steps. In step 1, a 1D column-wise inversion of surface wave tomographic, surface elevation (isostasy) and heat flow data is performed. Then, in step 2, the output model from step 1 is used as prior information for the inversion of the gravity field data (filtered geoid anomalies and gravity gradients from GOCE at satellite height) to refine the 3D crustal density and upper mantle composition. The model predicts a residual, non-isostatic topography that can be considered as a proxy for dynamic topography. However, within a rigorous framework, dynamic topography cannot be simply taken as a non- isostatic residual, but it should be explicitly computed (i.e. solving the Stokes equation for a given rheological and density distribution) and consistently integrated into the joint inversion of the gravity field and the terrestrial observation with feedback from both the static and dynamic parts. The goal of DYGIRO project is to add a third step into the global WINTERC-G inversion scheme that consistently integrates dynamic topography as an additional model constrain. We present here the first steps of such integration at global scale. To do that, the dynamic topography is computed by solving the Stokes flow problem associated with the current WINTERC-G model down to the transition zone. The dynamic topography thus obtained is coupled with the static thermochemical model constrained by gravity and seismic data within an iterative scheme where the observed surface elevation coincides with the model’s isostatic plus dynamic elevation contributions. The high computational cost associated with the large- scale 3D flow computations will be alleviated by means of Reduced Order Models. Such models are based on the idea of creating surrogate models that approximate the solution at a much lower computational cost. Fullea, J. Lebedev, S., Martinec, Z., Celli, N. L. (2021). WINTERC-G: mapping the upper mantle thermochemical heterogeneity from coupled geophysical-petrological inversion of seismic waveforms, heat flow, surface elevation and gravity satellite data, Geophysical Journal International, 226(1), 146–191.

One of the goals of geophysicists is mapping and understanding the current structure of the Earth including its variations in composition, temperature and dynamical state. This structure is only accessible via indirect observations and, therefore, the mathematical problem to be solved is of an inverse kind. Within the inverse solver, many forward problems will be tested until finding a configuration compatible with the observations. This work deals with the problem statement and numerical solution of the forward thermal problem that arises from an inverse solver. In this case, we will use a simple parameterization of the Lithosphere-Asthenosphere Boundary (LAB), but the results are useful for other parametric description (e.g. one parameter per each cell). A simplified model is used to show the ill-posedness of the mathematical problem arising when the LAB --an isotherm whose location is determined by the input parameters-- is imposed within the domain, over-constraining the forward problem. This is well-known in the community and several authors have proposed different approaches to circumvent it. Nevertheless, the strategies used in practice usually involve some non-physical procedures such as transitional regions where two different temperature fields are made compatible by smearing out differences. Generally, the solution in these regions does not comply with the governing equation and exhibits a non-physical behaviour. In this work, we propose a specific problem statement for the temperature with interior essential conditions. The resulting problem is mathematically sound and results in a two-step numerical solver. This guarantees a self-consistent temperature field, in the sense that it respects the thermal governing equations everywhere. The numerical domain is divided into two subdomains (lithosphere and asthenosphere) that are solved separately in the same mesh, using an unfitted mesh methodology. First, the temperature of the lithosphere is computed using the essential condition on the LAB. Second, the temperature in the mantle is obtained by minimizing a residual that measures the compatibility between the two subdomains in terms of LAB temperatures and across-LAB fluxes. This is done by adjusting the proper fluxes at the bottom of the numerical domain. Several examples are presented showing that the obtained temperature fields are stable and oscillation-free. Moreover, the resulting fluxes at the bottom of the domain are reasonable and compatible with the expected values.

Objectives: This study investigates current policies, key issues, and needs for pandemic planning in pediatrics in Canada. Methods: Online pandemic plans from national, provincial and territorial government websites were reviewed to identify: plans for children and families, and psychosocial and ethical issues. A survey was administered to gather participants' perspectives on the needs in pediatric planning, as well as important elements of their organizations' and regions' pandemic plans. A thematic analysis was conducted on qualitative survey responses. Results: The majority of existing plans did not adequately address the unique needs of pediatric populations, and mainly focused on medical and policy concerns. Several gaps in plans were identified, including the need for psychosocial supports and ethical decision-making frameworks for children and families. Similarly, survey respondents identified parallel gaps, in their organization's or region's plans. Conclusions: Although many plans provide guidelines for medical and policy issues in pediatrics, much more work remains in psychosocial and ethical planning. A focus on children and families is needed for pandemic planning in pediatrics to ensure best outcomes for children and families.

Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [438, 437, 32]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibacterials, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [32].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [33]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [693] and aliases.

The Southern Atlantic-Southwest Indian ridges (SASWIR) host mid-ocean ridge basalts with a residual subduction-related geochemical fingerprint (i.e., a ghost-arc signature) of unclear origin. Here, we show through an analysis of plate kinematic reconstructions and seismic tomography models that the SASWIR subduction-modified mantle source formed in the Jurassic close to the Georgia Islands slab (GI) and remained near-stationary in the mantle reference frame. In this analysis, the GI lies far inboard the Jurassic Patagonian-Antarctic Peninsula active margin. This was formerly attributed to a large-scale flat subduction event in the Late Triassic-Early Jurassic. We propose that during this flat slab stage, the subduction-modified mantle areas beneath the Mesozoic active margin and surrounding sutures zones may have been bulldozed inland by >2280 km. After the demise of the flat slab, this mantle anomaly remained near-stationary and was sampled by the Karoo mantle plume 183 Million years (Myr) ago and again since 55 Myr ago by the SASWIR. We refer to this process as asthenospheric anomaly telescoping. This study provides a hitherto unrecognized geodynamic effect of flat subduction, the viability of which we support through numerical modeling. G. M. G. and C. R. N. recognize the support given by CONICET and the funding given by the Universidad Nacional de la Patagonia San Juan Bosco (Grant number: CIUNPAT no. 1399). S. Z. and J. L. acknowledge the funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 777778. S.Z. acknowledges the funding of Project PID2020-113463RB-C32 funded by MCIN/AEI /10.13039/501100011033 and the funding of Generalitat de Catalunya via the 2021 SGR 01049.

A major mechanism through which neutrophils have been suggested to modulate tumor progression involves the interaction and subsequent modulation of other infiltrating immune cells. B cells have been found to infiltrate various cancer types and play a role in tumor immunity, offering new immunotherapy opportunities. Nevertheless, the specific impact of tumor-associated neutrophils (TAN) on B cells has largely been overlooked. In the current study, we aimed to characterize the role of TANs in the recruitment and modulation of B cells in the tumor microenvironment (TME). We showed that TANs actively participate in the recruitment of B cells to the TME and identified TNFα as the major cytokine mediating B-cell chemotaxis by TANs. The recruitment of CD45+B220+CD138− splenic B cells by TANs in vitro resulted in B-cell phenotypic modulation, with 68.6% ± 2.1% of the total migrated B cells displaying a CD45−B220+CD138+ phenotype, which is typical for plasma cells. This phenotype mirrored the large proportion (54.0% ± 6.1%) of CD45−B220+CD138+ intratumoral B cells (i.e., plasma cells) in Lewis lung carcinoma tumors. We next confirmed that the differentiation of CD45+B220+CD138− B cells to functionally active CD45−B220+CD138+ plasma cells required contact with TANs, was independent of T cells, and resulted in IgG production. We further identified membranal B-cell activating factor (BAFF) on TANs as a potential contact mechanism mediating B-cell differentiation, as blocking BAFF-receptor (BAFF-R) significantly reduced IgG production by 20%. Our study, therefore, demonstrates that TANs drive the recruitment and modulation of B cells into plasma cells in the TME, hence opening new avenues in the targeting of the immune system in cancer.

Supplementary Figures 1-5 with legends

Melanoma tumor cells secrete lysosomes which are taken up by dendritic cells

Cell numbers of multiple immune cell substes, and mainly dendritic cells, are decreased over time in melanoma tumors.

Tumor antigens are drained into sentinel lymph nodes independently of dendritic cell migration.

The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage. Analysis of the immune systems of the organisms revealed that the numbers of tumor-infiltrating dendritic cells (TIDC) drastically decreased with time. Further, in contrast to the current paradigm, once melanoma was established, TIDC did not migrate into sentinel lymph nodes. Instead, they underwent local cell death due to excessive phagocytosis of lysosomes. Importantly, TIDC were required to license the cytotoxic activity of tumor CD8+ T cells, and in their absence, T cells did not lyse melanoma cells. Our results offer a paradigm shift regarding the role of TIDC and a framework to increase the efficacy of immunotherapies.Significance:This work redefines the role of monocyte-derived dendritic cells in melanoma and provides a novel strategy to increase the efficacy of T-cell–based immunotherapies in nonresponding individuals.

Proteins associated with myeloid dendritic cells positively correlate with improved survival of melanoma patients

Tumor-infiltrating dendritic cells promote, in a contact-dependant manner, secretion of lytic granules by CD8+ T cells.

Higher doses of immunmotherapy do not induce tumor regression when administrated to large melanoma lesions.

While Immunotherapy has revolutionized the treatment of several cancers such as lung cancer, melanoma, and other cancers, most colorectal cancer patients remain resistant. This resistance to immunotherapy may partially stem from the fact that colorectal cancer very commonly metastasizes to the liver. The liver is known to play an immunotolerant role in in other contexts such as organ transplantation, viral disease, and autoimmune disease. Recent studies reveal the mechanisms in which liver metastases restrict the efficacy of immunotherapy. This effect was shown to be reversable in colorectal cancer mice models, when colorectal liver metastases were irradiated. It is possible that targeting liver metastases with locoregional therapies such as ablation, resection or irradiation may reverse the immunosuppressive effect of liver microenvironment and potentiate immunotherapy systemically. During the past decade, several clinical trials are trying to extrapolate the results achieved in animal model to clinical trials by combining immunotherapy with locoregional therapy. In this scoping review, the current clinical and translational literature was surveyed, to determine whether there is evidence to support the validity of this concept in human patients. If indeed immunotherapy can be potentiated for MS- Stable colorectal cancer utilizing locoregional interventions, a wide array of innovative protocols can be utilized to help cancer patients who have no other available treatment options and thus revolutionize the treatment of cancer patients with liver metastases.

The version of record is available online at: http://dx.doi.org/10.1007/s10237-022-01577-2 Scaffolds are microporous biocompatible structures that serve as material support for cells to proliferate, differentiate and form functional tissue. In particular, in the field of bone regeneration, insertion of scaffolds in a proper physiological environment is known to favour bone formation by releasing calcium ions, among others, triggering differentiation of mesenchymal cells into osteoblasts. Computational simulation of molecular distributions through scaffolds is a potential tool to study the scaffolds’ performance or optimal designs, to analyse their impact on cell differentiation, and also to move towards reduction in animal experimentation. Unfortunately, the required numerical models are often highly complex and computationally too costly to develop parametric studies. In this context, we propose a computational parametric reduced-order model to obtain the distribution of calcium ions in the interstitial fluid flowing through scaffolds, depending on several physical parameters. We use the well-known Proper Orthogonal Decomposition (POD) with two different variations: local POD and POD with quadratic approximations. Computations are performed using two realistic geometries based on a foamed and a 3D-printed scaffolds. The location of regions with high concentration of calcium in the numerical simulations is in fair agreement with regions of bone formation shown in experimental observations reported in the literature. Besides, reduced-order solutions accurately approximate the reference finite element solutions, with a significant decrease in the number of degrees of freedom, thus avoiding computationally expensive simulations, especially when performing a parametric analysis. The proposed reduced-order model is a competitive tool to assist the design of scaffolds in osteoinduction research. The authors acknowledge the financial support from the Ministerio de Ciencia e Innovación (MCIN/ AEI/10.13039/501100011033) through the grants PID2020-113463RBC32, PID2020-113463RB-C33, CEX2018-000797-S and PID2019-103892RB-I00, and the Generalitat de Catalunya for the Serra Hunter Fellowship of ME and the ICREA Academia Award of MPG.

The geodynamic evolution of the Western Mediterranean related to the closure of the Ligurian-Tethys ocean is not yet fully resolved. We present a new 3D numerical model of double subduction with opposite polarities fostered by the inherited segmentation of the Ligurian-Tethys margins and rifting system between Iberia and NW Africa. The model is constrained by plate kinematic reconstructions and assumes that both Alboran-Tethys and Algerian-Tethys plate segments are separated by a NW-SE transform zone enabling that subduction polarity changes from SE-dipping in the Alboran-Tethys segment to NW-dipping in the Algerian-Tethys segment. The model starts about late Eocene times at 36.5 Ma and the temporal evolution of the simulation is tied to the geological evolution by comparing the rates of convergence and trench retreat, and the onset and end of opening in the Alboran Basin. Curvature of the Alboran-Tethys slab is imposed by the pinning of its western edge when reaching the end of the transform zone in the adjacent west-Africa continental block. The progressive curvature of the trench explains the observed regional stress reorientation changing from N-S to NW-SE and to E-W in the central and western regions of the Alboran Basin. The increase of the retreat rates from the Alboran-Tethys to the Algerian-Tethys slabs is compatible with the west-to-east transition from continental-to-magmatic-to-oceanic crustal nature and with the massive and partially synchronous calc-alkaline and alkaline magmatism., This work is funded by the SUBTETIS (PIE-CSIC-201830E039, CSIC), ALORBE (PIE-CSIC-202030E310), GeoCAM (PGC2018-095154-B-I00, Spanish Government), Equinor R&T Fornebu (Norway), and the Generalitat de Catalunya grant (AGAUR 2017 SGR 847). We also thank the computer resources at MareNostrum and the technical support provided by the Barcelona Supercomputing Center (BSC) through several projects (AECT-2019-1-0013 and AECT-2019-2-0005). S. Z. has been funded by the MCIN/AEI doi:10.13039/501100011033 through project PID2020-113463RB-C32, and by EU H2020 MSCA grant agreement No 777778. This work has been done in the framework of the Unidad Asociada of LACAN-UPC with CSIC and using the facilities of the Laboratory of Geodynamic Modelling from Geo3BCN-CSIC.

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate’s concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

We deal with the reduced four-equation model for dynamics of the heterogeneous compressible binary mixtures with the stiffened gas equations of state. We study its further reduced form, with the excluded volume concentrations and a quadratic equation for the common pressure of the components, that can be called a quasi-homogeneous form. We prove new properties of this equation, derive a simple formula for the squared speed of sound, give an alternative proof for a formula that relates it to the squared Wood speed of sound, and a short derivation of the pressure balance equation. For the first time, we introduce regularizations of the heterogeneous model (in the quasi-homogeneous form). In the 1D case, we construct the corresponding explicit two-level in time and symmetric three-point in space finite-difference schemes without limiters and present numerical results for various flows with shock waves., Comment: 16 hfgex, 7 figures, 1 table

We derive a linear system of ordinary differential equations (ODEs) to approximate the dynamics of natural gas in pipeline networks. Although a closed-form expression of the eigenvalues of the state matrix does not generally exist, the poles of an irrational transfer function corresponding to the linearized partial differential equations are used to approximate the eigenvalues of the ODE system. Our analysis qualitatively demonstrates that the eigenvalues of the state matrix of the entire network system are "pipeline separable" in the sense that the eigenvalues are dominated by the individual pipeline parameters and not the incidence connectivity of the network graph. The linear system is used as the dynamic constraints of a linear optimal control problem (OCP) to design the control actions of compressor units to minimize the energy that they expend. The motivation of this work is to reduce the computational complexity of optimizing gas dynamics in large networks to meet the unpredictable and highly variable demand from electric generators. The linear and corresponding nonlinear OCPs are discretized in time to obtain linear and nonlinear optimization problems, which are demonstrated on a test network to illustrate the validity of linear programming. Moreover, an analytical bound on the error between the solutions of the linear and nonlinear flow dynamics is presented using Lyapunov functions and verified computationally by plotting the error against the size of the flow variation around the steady-state solution.

The blending of hydrogen generated using clean energy into natural gas pipeline networks is proposed in order to utilize existing energy systems for their planned lifetimes while reducing their reliance on fossil fuels. We formulate a system of partial differential equations (PDEs) that govern the flow dynamics of mixtures of gases in pipeline networks under the influence of time-varying compressor and regulator control actions. The formulation is derived for general gas networks that can inject or withdraw arbitrary time-varying mixtures of gases into or from the network at arbitrarily specified nodes. The PDE formulation is discretized in space to form a nonlinear control system that is used to prove that homogeneous mixtures are well-behaved and heterogeneous mixtures may be ill-behaved in the sense of monotone-ordering of solutions. We use numerical simulations to compute interfaces in the parameter region of sinusoidal boundary conditions that delimit monotonic, periodic, and chaotic system responses. The interfaces suggest that any solution in the monotonic response region is not chaotic and will eventually approach a periodic orbit. The results are demonstrated using examples for a single pipeline and a small test network.

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social hierarchies that are often based on dominant-submissive relationships. The dominant-submissive relationship is a normal behavioral pattern among the individuals of a species. Traumatic brain injury is a frequent cause of social interaction impairment and the reorganization of dominant-submissive relationships in animal pairs. This protocol describes submissive behavior in adult male Sprague-Dawley rats after the induction of traumatic brain injury using a fluid-percussion model compared to naive rats through a series of dominant-submissive tests performed between 29 days and 33 days after induction. The dominant-submissive behavior test shows how brain injury can induce submissive behavior in animals competing for food. After traumatic brain injury, the rodents were more submissive, as indicated by them spending less time at the feeder and being less likely to arrive first at the trough compared to the control animals. According to this protocol, submissive behavior develops after traumatic brain injury in adult male rats.

IntroductionWe aimed to assess the clinical significance of M1-MCA occlusion with visualization of both MCA-M2 segments [“Tilted-V sign” (TVS)] on initial CT angiography (CTA) in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT).MethodsData for patients with consecutive AIS undergoing EVT for large vessel occlusion (LVO) in two academic centers are recorded in ongoing databases. Patients who underwent EVT for M1-MCA occlusions ≤ 6 h from symptom onset were included in this retrospective analysis.ResultsA total of 346 patients met the inclusion criteria; 189 (55%) had positive TVS. Patients with positive TVS were younger (68 ± 14 vs. 71 ± 14 years, P = 0.028), with similar rates of vascular risk factors and baseline modified Rankin scores (mRS) 0–2. The rates of achieving thrombolysis in cerebral ischemia (TICI) 2b-3 were similar to the two groups (79%), although successful first-pass recanalization was more common with TVS (64 vs. 36%, p = 0.01). On multivariate analysis, higher collateral score [odds ratio (OR) 1.38 per unit increase, p = 0.008] and lower age (OR 0.98 per year increase, p = 0.046) were significant predictors of TVS. Patients with positive TVS had higher post-procedural Alberta Stroke Program Early CT Score (ASPECTS; 6.9 ± 2.2 vs. 5.2 ± 2.3, p = 0.001), were discharged with lower National Institutes of Health Stroke Score (NIHSS; 6±6 vs. 9±7, p = 0.003) and higher rates of mRS 0–2 (29.5 vs. 12%, p = 0.001), and had lower rates of 90-day mortality (13.2 vs. 21.6%, p = 0.038). However, TVS was not an independent predictor of functional independence (OR 2.51; 95% CI 0.7–8.3).ConclusionTilted-V Sign, an easily identifiable radiological marker, is associated with fewer recanalization attempts, better functional outcomes, and reduced mortality.

Social work supervision addresses professional development, staff support, and management of direct service workers. It is important in aging-services settings because of the impacts of complex and evolving biopsychosocial forces in clients' lives. This article presents findings of the Supervisory Leaders in Aging (SLA) study based on data available one-year post completion. SLA is a 30-hour certificate program for supervisors from aging-services settings addressing best practices in supervision of gerontological practice. The study compares participants' self-assessment of use of supervisory best practices before attending a 3-month workshop series and at two times following graduation. This article reports findings from the analysis of data provided by 114 out of 129 supervisors who completed the program. Participants increased the frequency of use of best practices at both three and 12 months after graduation. These increases were conceptually meaningful and statistically significant among participants who were low users of best practices prior to the program. SLA has led to significant adoption and maintenance of supervisory best practices among participating social work supervisors and especially among those who have not previously adopted routine use of best practices. The interactive small-group learning activities of SLA's educational model should be promoted and the curriculum of best practices should be further refined and tested as SLA is implemented in other communities.

На основі аналізу статистичних даних, результатів власних досліджень та наукової літератури, що свідчить про актуальність створення в Україні системи паліативної та хоспісної допомоги (ПХД) населенню, важливість підготовки фахівців з питань ПХД, а також про низький рівень здоров’я медичних працівників, обґрунтовується необхідність оптимізації до- і післядипломної підготовки лікарів та середніх медичних працівників для забезпечення високої якості надання ПХД населенню та профілактики професійного вигорання. Мультидисциплінарна професійна підготовка медичних працівників з питань ПХД в рамках безперервної післядипломної освіти вимагає відповідного навчально-методичного забезпечення, а також залучення професорсько-викладацького складу різного профілю, що довело свою ефективність на кафедрі паліативної і хоспісної медицини Інституту сімейної медицини НМАПО імені П. Л. Шупика.

Early mortality remains a challenging therapeutic facet of the initial induction phase of intensive chemotherapy in patients with acute myeloid leukemia (AML). The impact of standard molecular evaluation and risk category of the European LeukemiaNet (ELN) 2017 classification model on early mortality has not been rigorously evaluated thus far. We reviewed the medical records of 320 consecutive adult patients with newly diagnosed AML treated with intensive induction chemotherapy in our center from 2007 to 2021. The median age was 56 years; 33 patients (10%) died during induction. Patient age, white blood cell count, hemoglobin level, platelet level, creatinine, uric acid, lactate dehydrogenase serum levels, and FLT3-ITD and CEBPA mutational status did not significantly impact early mortality. NPM1