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A theoretical approach based on Periodic Boundary Conditions (PBC) and a Linear Combination of Atomic Orbitals (LCAO) in the framework of the density functional theory (DFT) is used to investigate the molecular mechanism that rules the piezoelectric behavior of poly(vinylidene fluoride) (PVDF) polymer in the crystalline β-phase. We present several computational tests highlighting the peculiar electrostatic potential energy landscape the polymer chains feel when they change their orientation by a rigid rotation in the lattice cell. We demonstrate that a rotation of the permanent dipole through chain rotation has a rather low energy cost and leads to a lattice relaxation. This justifies the macroscopic strain observed when the material is subjected to an electric field. Moreover, we investigate the effect on the molecular geometry of the expansion of the lattice parameters in the (a, b) plane, proving that the rotation of the dipole can take place spontaneously under mechanical deformation. By band deconvolution of the IR and Raman spectra of a PVDF film with a high content of β-phase, we provide the experimental phonon wavenumbers and relative band intensities, which we compare against the predictions from DFT calculations. This analysis shows the reliability of the LCAO approach, as implemented in the CRYSTAL software, for calculating the vibrational spectra. Finally, we investigate how the IR/Raman spectra evolve as a function of inter-chain distance, moving towards the isolated chain limit and to the limit of a single crystal slab. The results show the relevance of the inter-molecular interactions on the vibrational dynamics and on the electro-optical features ruling the intensity pattern of the vibrational spectra. [ABSTRACT FROM AUTHOR]

Currently available performance-based methodologies for assessing the fragility of structures subjected to tsunami neglect the effects of tsunami-induced vertical loads due to internal buoyancy. This paper adopts a generalized methodology for the performance assessment of structures that integrates the effects of buoyancy loads on interior slabs during a tsunami inundation. The methodology is applied in the fragility assessment of three case-study frames (low, mid and high-rise), representative of existing masonry-infilled reinforced concrete (RC) buildings typical of Mediterranean region. The paper shows the effect of modelling buoyancy loads on damage evolution and fragility curves associated with different structural damage mechanisms for existing RC frames with breakaway infill walls including consideration of blow-out slabs. The outcomes attest that buoyancy loads affect the damage assessment of buildings during a tsunami, especially in the case of mid and high-rise structures with blow-out slabs. The rate of occurrence of slabs uplift failure increases with the number of stories of the building, indicating the need to account for such damage mechanism when assessing the performance of structures. It is also found that buoyancy loads slightly affect the fragility curves associated to other structural damage mechanisms for existing RC buildings commonly monitored for fragility assessment. [ABSTRACT FROM AUTHOR]

To assess the health condition of structures and infrastructure during their service lives, continuous vibration-based monitoring represents a viable and cost-effective solution. Model updating and digital twins are increasingly adopted for damage detection. However, significant gaps and uncertainties in damage quantification still arise. This work presents original data from output-only modal identification tests on full-scale, two-storey reinforced concrete (RC) frames subjected to pseudo-dynamic loading to simulate seismic damage. The frames are tested with two masonry infill wall configurations with three-sided and four-sided boundary conditions, and the observed seismic damage is correlated to a damage scale. Output-only modal identification tests are performed before and after testing to catch variations in modal properties due to observed damage. Experimental data are used to build a refined finite element model able to reliably simulate the static and dynamic performance of the infilled RC frames before and after damage. The model allowed for the further assessment of the variation in natural frequencies of tested specimens at different earthquake intensities, the correlation of such variations to damage levels, and identification of the contribution of structural and non-structural components to the overall frequency variation. [ABSTRACT FROM AUTHOR]

Four phase III clinical trials of oral direct factor Xa or thrombin inhibitors demonstrated significantly lower intracranial hemorrhage compared to warfarin in patients with nonvalvular-atrial fibrillation. This is counter-intuitive to the principle that inhibiting thrombosis should increase hemorrhagic risk. We tested the novel hypothesis that anti-thrombin activity decreases the risk of intracerebral hemorrhage by directly inhibiting thrombin-mediated degradation of cerebral microvessel basal lamina matrix, responsible for preventing hemorrhage. Collagen IV, laminin, and perlecan each contain one or more copies of the unique α-thrombin cleavage site consensus sequence. In blinded controlled experiments, α-thrombin significantly degraded each matrix protein in vitro and in vivo in a concentration-dependent fashion. In vivo stereotaxic injection of α-thrombin significantly increased permeability, local IgG extravasation, and hemoglobin (Hgb) deposition together with microvessel matrix degradation in a mouse model. In all formats the direct anti-thrombin dabigatran completely inhibited matrix degradation by α-thrombin. Fourteen-day oral exposure to dabigatran etexilate-containing chow completely inhibited matrix degradation, the permeability to large molecules, and cerebral hemorrhage associated with α-thrombin. These experiments demonstrate that thrombin can degrade microvessel matrix, leading to hemorrhage, and that inhibition of microvessel matrix degradation by α-thrombin decreases cerebral hemorrhage. Implications for focal ischemia and other conditions are discussed. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of alteplase for ischemic stroke treatment is limited, partly due to the occurrence of intracranial and extracranial hemorrhage. Mutant pro-urokinase (m-proUK) does not deplete fibrinogen and lyses fibrin only after induction with alteplase. Therefore, this treatment has the potential to be safer and more efficacious than treatment with alteplase alone. The aim of this study is to assess the safety and efficacy of thrombolytic treatment consisting of a small bolus alteplase followed by m-proUK compared with standard thrombolytic treatment with alteplase in patients presenting with ischemic stroke.Methods: DUMAS is a multicenter, phase II trial with a prospective randomized open-label blinded end-point (PROBE) design, and an adaptive design for dose optimization. Patients with ischemic stroke, who meet the criteria for treatment with intravenous (IV) alteplase can be included. Patients eligible for endovascular thrombectomy are excluded. Patients are randomly assigned (1:1) to receive a bolus of IV alteplase (5mg) followed by a continuous IV infusion of m-proUK (40 mg/h during 60 min) or usual care with alteplase (0.9 mg/kg). Depending on the results of interim analyses, the dose of m-proUK may be revised to a lower dose (30 mg/h during 60 min) or a higher dose (50 mg/h during 60 min). We aim to include 200 patients with a final diagnosis of ischemic stroke. The primary outcome is any post-intervention intracranial hemorrhage (ICH) on neuroimaging at 24 h according to the Heidelberg Bleeding Classification, analyzed with binary logistic regression. Efficacy outcomes include stroke severity measured with the National Institutes of Health Stroke Scale (NIHSS) at 24 h and 5-7 days, score on the modified Rankin scale (mRS) assessed at 30 days, change (pre-treatment vs. post-treatment) in abnormal perfusion volume, and blood biomarkers of thrombolysis at 24 h. Secondary safety endpoints include symptomatic intracranial hemorrhage, death, and major extracranial hemorrhage. This trial will use a deferred consent procedure.Discussion: When dual thrombolytic therapy with a small bolus alteplase and m-proUK shows the anticipated effect on the outcome, this will lead to a 13% absolute reduction in the occurrence of ICH in patients with ischemic stroke.Trial Registration: NL7409 (November 26, 2018)/NCT04256473 (February 5, 2020). [ABSTRACT FROM AUTHOR]

The flow of information between farms and slaughterhouses about animal health, is a fundamental process for modern meat inspection. The information provided by Food Chain Information (FCI) systems in medium-small sized slaughterhouses in central Italy, focusing on the data provided on the animal's health status, was performed through a five-year survey together with the number of organ and carcass condemnation for bovine, swine and ovine. The annual prevalence of condemnation was higher in bovine (from 10.49% in 2015 to 17.16% in 2019) than swine (from 6.39% in 2015 to 12.64% in 2019) and ovine (from 8.05% in 2019 to 8.98% in 2017), and an overall prevalence increase was observed in bovine and swine, throughout the years. The frequent lack of Food Chain Information (FCI) from farms to slaughterhouses should be emphasised, taking into consideration that a poor implementation of the system by farmers, could lead to a persistent risk of disease at farm level for these two species. [ABSTRACT FROM AUTHOR]

The increasing attention of governments and insurance companies toward the evaluation of tsunamis' impacts on coastal communities led to a renewed interest in assessing the behavior of existing buildings under onshore tsunami flows. Codes and standards regulating assessment procedures for existing structures under tsunami loading are currently missing, and only a few design codes for vertical evacuation shelters can be found. Furthermore, structural analysis methods currently assume watertight buildings for the assessment of their performance under tsunami inundation. In this work, a methodology for assessing the performance of reinforced concrete (RC) buildings that considers explicitly the progressive failure of exterior breakaway infill walls hit by tsunami flows is proposed. The effects of the progressive failure of breakaway infill walls on the overall performance of RC buildings have been highlighted on case-study buildings representative of low-, mid- and high-rise buildings built before the 1980s in the Mediterranean area, characterized by masonry infill walls with low out-of-plane (OOP) capacity. In the absence of specific guidelines for assessment, load models provided by existing tsunami design codes for evacuation buildings were adopted and opportunely modified for the case of buildings with breakaway infill walls. The explicit consideration of the failure of exterior breakaway infill walls completely changed the distributions of loads inside the structure, leading to different structural capacity and damage evolution with respect to watertight buildings. The height of the building affected the global capacity but did not influence the damage evolution. The proposed methodology can represent a suitable solution for a realistic performance assessment of frame structures with breakaway claddings. [ABSTRACT FROM AUTHOR]

Inorganic composites for enhancing the in-plane shear capacity of masonry walls with irregular texture were investigated on twenty-one panels under diagonal compression tests. Three specimens were used as control and twelve specimens were strengthened with two Fibre Reinforced Mortars (FRM-A and FRM-B), characterized by a different content of fibres embedded in the lime-based matrix. The remaining six specimens were strengthened with Fabric Reinforced Cementitious Mortars (FRCM), consisting in a GFRP grid embedded in a fibre reinforced matrix (the same used for FRM-A). The influence of single-side and double-side strengthening configurations on the capacity of strengthened panels was also investigated, to point out the reduction in strengthening effectiveness in case of single-sided applications. The results showed that all the inorganic composites adopted for the strengthening techniques provided a substantial increase of shear capacity. The grid in FRCM strengthened panels played an important role in both strength and deformation capacity at peak. The different fibres content (lower than 50% in weight) in FRM systems slightly affected the overall performance of panels. Finally, analytical predictions of experimental results were reported and discussed and a preliminary analytical model for estimating the FRM shear contribution was proposed, obtaining a good agreement with test results. [ABSTRACT FROM AUTHOR]

This paper deals with the structural behaviour and the damage assessment of Italian "modern" masonry buildings during seismic events. "Modern" masonry buildings are characterized by a box-like structural behaviour, due to the presence of effective connections between horizontal floors and vertical load-bearing walls, which prevents local mechanisms such as the overturning of external façades during earthquakes. "Modern" masonry buildings were built in Italy since the first decades of XX century in those regions classified as seismic zone and since 1937 in the whole country, following the Italian code prescriptions that implicitly interdicted the erection of "ancient" masonry buildings. Starting from an in deep historical analysis of the Italian seismic codes' prescriptions for the design of "modern" masonry buildings, the typical characteristics of the most frequent structural typologies of unreinforced masonry buildings are outlined. Then, the typical damage mechanisms observed in "modern" masonry buildings damaged after the L'Aquila earthquake (2009) are reported in relation with both the global and local behaviour of the whole building and its structural elements. The analysis demonstrated that "modern" masonry buildings experienced a good box-like seismic performance, which avoided global or local collapses, but shown severe damage to piers and spandrels related to their reduced in-plane shear capacity. Given the lack of data on such kind of structural typology, this study is fundamental for understanding and modelling the seismic behaviour of "modern" masonry buildings designed before '80s according to different seismic design prescriptions and for defining effective strengthening solutions for reducing their seismic vulnerability. [ABSTRACT FROM AUTHOR]

The infrared (IR) spectrum of an adamantyl endcapped α, ω-polyyne (the hexayne, Ad-C12-Ad) is investigated both experimentally and computationally. A new IR band is observed upon UV photoexcitation of the compound (embedded in a poly methyl methacrylate matrix at 78 K), thus, revealing the existence of new photogenerated molecular structure trapped at low temperature. Complete reversibility is found, thus, demonstrating that the photoexcitation is responsible for the generation of metastable excited states of the molecule. Density functional theory and time dependent density functional theory calculations indicate that these metastable states result from the forbidden singlet (S1) or triplet (T1) excited states, and geometry optimizations of the polyyne trapped in either S1 and/or T1 states demonstrate that the carbon chain takes on a cumulenic structure. Comparison of the experimental and the computed IR spectra for the molecule trapped in the forbidden states confirms that the new IR features are clear markers of cumulenic species. The temperature and time dependent behavior of the new IR band is analyzed, while the experimentally determined value of the activation energy highlights the low stability of these molecular structures. [ABSTRACT FROM AUTHOR]

We analyze the infrared and Raman spectra (both experimentally and with the aid of quantum chemical calculations) of a series of polyenals which provide us with the fortunate case of a set of polyene chains with one of the end groups consisting of a C==O group which not only does take part in the conjugation but also pulls electrons from the chain making the whole system highly polar, thus affecting the vibrational transition moments. In the following we show, for the first time, that it is possible to derive experimental phonon dispersion curves and these prove to be different for each chain length. We support our experimental findings with Density Functional Theory quantum chemical calculations which reproduce with sufficient accuracy the IR and Raman spectral pattern and at the same time help in disentangling the assignment of the fine structure observed in the experimental spectra. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

We observed fine fibrin deposition along the paravascular spaces in naive animals, which increased dramatically following subarachnoid hemorrhage (SAH). Following SAH, fibrin deposits in the areas remote from the hemorrhage. Traditionally it is thought that fibrinogen enters subarachnoid space through damaged blood brain barrier. However, deposition of fibrin remotely from hemorrhage suggests that fibrinogen chains Aα, Bβ, and γ can originate in the brain. Here we demonstrate in vivo and in vitro that astroglia and neurons are capable of expression of fibrinogen chains. SAH in mice was induced by the filament perforation of the circle of Willis. Four days after SAH animals were anesthetized, transcardially perfused and fixed. Whole brain was processed for immunofluorescent (IF) analysis of fibrin deposition on the brain surface or in brains slices processed for fibrinogen chains Aα, Bβ, γ immunohistochemical detection. Normal human astrocytes were grown media to confluency and stimulated with NOC-18 (100 μM), TNF-α (100 nM), ATP-γ-S (100 μM) for 24 h. Culture was fixed and washed/permeabilized with 0.1% Triton and processed for IF. Four days following SAH fibrinogen chains Aα IF associated with glia limitans and superficial brain layers increased 3.2 and 2.5 times (p < 0.05 and p < 0.01) on the ventral and dorsal brain surfaces respectively; fibrinogen chains Bβ increased by 3 times (p < 0.01) on the dorsal surface and fibrinogen chain γ increased by 3 times (p < 0.01) on the ventral surface compared to sham animals. Human cultured astrocytes and neurons constitutively expressed all three fibrinogen chains. Their expression changed differentially when exposed for 24 h to biologically significant stimuli: TNFα, NO or ATP. Western blot and RT-qPCR confirmed presence of the products of the appropriate molecular weight and respective mRNA. We demonstrate for the first time that mouse and human astrocytes and neurons express fibrinogen chains suggesting potential presence of endogenous to the brain fibrinogen chains differentially changing to biologically significant stimuli. SAH is followed by increased expression of fibrinogen chains associated with glia limitans remote from the hemorrhage. We conclude that brain astrocytes and neurons are capable of production of fibrinogen chains, which may be involved in various normal and pathological processes. [ABSTRACT FROM AUTHOR]

The ischemic penumbra is both a concept in understanding the evolution of cerebral tissue injury outcome of focal ischemia and a potential therapeutic target for ischemic stroke. In this review, we examine the evidence that angiogenesis can contribute to beneficial outcomes following focal ischemia in model systems. Several studies have shown that, following cerebral ischemia, endothelial proliferation and subsequent angiogenesis can be detected beginning four days after cerebral ischemia in the border of the ischemic core, or in the ischemic periphery, in rodent and non-human primate models, although initial signals appear within hours of ischemia onset. Components of the neurovascular unit, its participation in new vessel formation, and the nature of the core and penumbra responses to experimental focal cerebral ischemia, are considered here. The potential co-localization of vascular remodeling and axonal outgrowth following focal cerebral ischemia based on the definition of tissue remodeling and the processes that follow ischemic stroke are also considered. The region of angiogenesis in the ischemic core and its surrounding tissue (ischemic periphery) may be a novel target for treatment. We summarize issues that are relevant to model studies of focal cerebral ischemia looking ahead to potential treatments. [ABSTRACT FROM AUTHOR]

A comprehensive study of the evolution of the GDR properties from E* = 150 MeV to E* = 430 MeV has been undertaken in nuclei of mass A = 120 = 132. The experimental investigation was performed using MEDEA detector. An onset of a quenching of the GDR gamma yield was found at E* = 270 MeV comparing the experimental gamma-ray spectrum with statistical model calculation. The quenching effect increases at E* = 330 MeV and is even more pronounced when the analysis is extended to higher excitation energies using data from previously performed experiments. The comparison with phenomenological models describing the quenching phenomenon gives a qualitative explanation for the effect but is not able to reproduce its detailed features as a function of excitation energy. A smooth cut-off approach describes reasonably well the progressive disappearance of the dipole strength, which occurs around 220-230 MeV excitation energy, and shows that the GDR quenching is a rather sharp effect. [ABSTRACT FROM AUTHOR]

The vibrational infrared and Raman spectra of a series of t-butyl substituted oligomers of para-phenylenevinylene and of the corresponding polymer in the pristine and potassium-doped states have been recorded for the first time and interpreted on the basis of the theory of the effective conjugation coordinate. The Raman spectra of selectively deuteriated materials have also been analyzed. Evidence is found of strong phonon confinement. The information derived from the spectra is that the charge carrier is confined over a few monomer units and that when the polymer is doped with electron donors the benzene ring is preferentially perturbed. The data collected in this work are compared with the results from UV spectroscopy and ESR experiments which indicate a larger dimension of the charge carrier. The information which can be derived by using in a complementary way the data from these spectroscopies are presented and discussed. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Using a recently developed method, we show here that solvent effects on the first molecular hyperpolarizabilities of push-pull polyenes can be predicted by evaluation of the relaxation contribution βr to the hyperpolarizability from vibrational infrared and Raman intensities and vibrational frequencies. The molecules studied in this work are a few organic polymethine dyes with different donor and acceptor groups. The analysis of their vibrational spectra confirms the key role played by the structural parameters of the polyene chain in determining the nonlinear optical response. © 1995 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Background: More than one-third of the patients with ischemic stroke caused by an intracranial large vessel occlusion do not recover to functional independence despite fast and successful recanalization by acute mechanical thrombectomy (MT). This may partially be explained by incomplete microvascular reperfusion. Some antithrombotics, e.g., antiplatelet agents and heparin, may be able to restore microvascular reperfusion. However, antithrombotics may also increase the risk of symptomatic intracranial hemorrhage (sICH). The aim of this review was to assess the potential safety and functional outcome of periprocedural antiplatelet or heparin use during acute MT for ischemic stroke. Methods: We systematically searched PubMed, Embase, Medline, Web of Science, and Cochrane for studies investigating the safety and functional outcome of periprocedural antiplatelet or heparin treatment during acute MT for ischemic stroke. The primary outcome was the risk for sICH. Secondary outcomes were functional independence after 3-6 months (modified Rankin Scale 0-2) and mortality within 6 months. Results: 837 studies were identified through the search, of which 19 studies were included. The sICH risks of the periprocedural use of antiplatelets ranged from 6 to 17%, and for heparin from 5 to 12%. Two of four studies reporting relative effects of the use of antithrombotics are pointing toward an increased risk of sICH. Among patients treated with antiplatelet agents, functional independence varied from 23 to 60% and mortality from 18 to 33%. For heparin, this was, respectively, 19-54% and 19-33%. The three studies presenting relative effects of antiplatelets on functional independence showed neutral effects. Both studies reporting relative effects of heparin on functional independence found it to increase this chance. Conclusion: Randomized controlled trials investigating the effect of periprocedural antithrombotic treatment in MT are lacking. Some observational studies report a slight increase in sICH risk, which may be acceptable because they also suggest a beneficial effect on functional outcome. Therefore, randomized controlled trials are warranted to address the question whether the potentially higher risk of sICH could be outweighed by improved functional outcome. [ABSTRACT FROM AUTHOR]

Acutely following focal cerebral ischemia disruption of the microvessel blood–brain barrier allows transit of plasma proteins into the neuropil as edema formation that coincides with loss of microvessel endothelial β1-integrins. We extend previous findings to show that interference with endothelial β1-integrin–matrix adhesion by the monoclonal IgM Ha2/5 increases the permeability of primary cerebral microvascular endothelial cell monolayers through reorganization of claudin-5, occludin, and zonula occludens-1 (ZO-1) from inter-endothelial borders. Interference with β1-integrin–matrix adhesion initiates F-actin conformational changes that coincide with claudin-5 redistribution. β1-integrin–matrix interference simultaneously increases phosphorylation of myosin light chain (MLC), while inhibition of MLC kinase (MLCK) and Rho kinase (ROCK) abolishes the Ha2/5-dependent increased endothelial permeability by 6 h after β1-integrin–matrix interference. These observations are supported by concordant observations in the cortex of a high-quality murine conditional β1-integrin deletion construct. Together they support the hypothesis that detachment of β1-integrins from abluminal matrix ligands increases vascular endothelial permeability through reorganization of tight junction (TJ) proteins via altered F-actin conformation, and indicate that the β1-integrin–MLC signaling pathway is engaged when β1-integrin detachment occurs. These findings provide a novel approach to the research and treatment of cerebral disorders where the breakdown of the blood–brain barrier accounts for their progression and complication. [ABSTRACT FROM AUTHOR]

Anthracene tetracene-doped crystals (TA) dispersed in a thin polymer film matrix have been reported as efficient down converting systems based on Förster Resonance Energy Transfer (FRET) which occurs efficiently from donor (anthracene) to acceptor (tetracene) molecules. In this work, we demonstrate that the efficiency of this system can be further improved by a metal-enhanced FRET, which is obtained by incorporating metal nanoparticles into the polymer matrix. We report on the preparation and optical responses of polymeric transparent thin films where dodecanethiol-capped silver or gold nanoparticles are dispersed with TA in a polymethylmethacrylate (PMMA) matrix. A maximum of 11-fold and 6.5-fold enhancement was achieved with silver and gold nanoparticles, respectively. Efficiency is discussed in terms of film morphology and plasmon resonance induced effects. [ABSTRACT FROM AUTHOR]

Dabigatran is effective in decreasing the risk of ischaemic stroke in patients with atrial fibrillation. However, like all anticoagulants, it is associated with a risk of bleeding. In cases of trauma or emergency surgery, emergency reversal of dabigatran-induced anticoagulation may be required. A specific reversal agent for dabigatran, idarucizumab, has been approved by the US Food and Drug Administration. Alternative reversal agents are available, such as prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs). In this review we evaluate the role of PCCs and aPCCs in the reversal of dabigatran anticoagulation and consider which tests are appropriate for monitoring coagulation in this setting. Pre-clinical studies, small clinical studies and case reports indicate that PCCs and aPCCs may be able to reverse dabigatran-induced anticoagulation in a dose-dependent manner. However, dosing based on coagulation parameters can be difficult because available assays may not provide adequate sensitivity and specificity for measuring anticoagulation induced by dabigatran or the countering effects of PCCs/aPCCs. In addition, PCCs or aPCCs can potentially provoke thromboembolic complications. Despite these limitations and the fact that PCCs and aPCCs are not yet licensed for dabigatran reversal, their use appears to be warranted in patients with life-threatening haemorrhage if idarucizumab is not available. [ABSTRACT FROM AUTHOR]

Background: The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.Methods: The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated.Results: Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage.Conclusions: This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

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During focal cerebral ischemia, the degradation of microvessel basal lamina matrix occurs acutely and is associated with edema formation and microhemorrhage. These events have been attributed to matrix metalloproteinases (MMPs). However, both known protease generation and ligand specificities suggest other participants. Using cerebral tissues from a non-human primate focal ischemia model and primary murine brain endothelial cells, astrocytes, and microglia in culture, the effects of active cathepsin L have been defined. Within 2 hours of ischemia onset cathepsin L, but not cathepsin B, activity appears in the ischemic core, around microvessels, within regions of neuron injury and cathepsin L expression. In in vitro studies, cathepsin L activity is generated during experimental ischemia in microglia, but not astrocytes or endothelial cells. In the acidic ischemic core, cathepsin L release is significantly increased with time. A novel ex vivo assay showed that cathepsin L released from microglia during ischemia degrades microvessel matrix, and interacts with MMP activity. Hence, the loss of microvessel matrix during ischemia is explained by microglial cathepsin L release in the acidic core during injury evolution. The roles of cathepsin L and its interactions with specific MMP activities during ischemia are relevant to strategies to reduce microvessel injury and hemorrhage. [ABSTRACT FROM AUTHOR]

Objective: This study investigated whether young adults (between 18 and 30 years at the time of the project) who were assessed for auditory processing disorder (APD) in childhood (between 7 and 16 years) experience persistence of listening and communication difficulties. Design: Participants completed a mixed methods questionnaire focusing on common areas of complaint in APD and two open-ended questions exploring participants' past and present experiences with listening and communication difficulties. Study sample: Ninety-seven of the 722 potential participants returned completed questionnaires, of whom 66 had been diagnosed with APD (APD group) at the time of their auditory processing assessment and 31 had not met diagnostic criteria (NAPD group) at that time. Results: Substantial commonality was noted in the reported listening and communication difficulties between the APD and NAPD participants. Volunteered comments aggregated into four major content themes which included: listening and communication difficulties; participants' sense of self; change; and participation. Members of the APD group reported greater communication difficulty than NAPD group members, irrespective of environmental listening conditions. Conclusions: Young adults with a prior referral for, and in some cases a diagnosis of, APD as children continue to experience auditory processing difficulties across a range of daily situations. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) increases the risk and severity of thromboembolic stroke. Generally, antithrombotic agents increase the hemorrhagic risk of thromboembolic stroke. However, significant reductions in thromboembolism and intracerebral hemorrhage have been shown with the antithrombin dabigatran compared with warfarin. As thrombin has been implicated in microvessel injury during cerebral ischemia, we hypothesized that dabigatran decreases the risk of intracerebral hemorrhage by direct inhibition of the thrombin-mediated increase in cerebral endothelial cell permeability. Primary murine brain endothelial cells (mBECs) were exposed to murine thrombin before measuring permeability to 4-kDa fluorescein isothiocyanate-dextran. Thrombin increased mBEC permeability in a concentration-dependent manner, without significant endothelial cell death. Pretreatment of mBECs with dabigatran completely abrogated the effect of thrombin on permeability. Neither the expressions of the endothelial cell β1-integrins nor the tight junction protein claudin-5 were affected by thrombin exposure. Oxygen-glucose deprivation (OGD) also increased permeability; this effect was abrogated by treatment with dabigatran, as was the additive effect of thrombin and OGD on permeability. Taken together, these results indicate that dabigatran could contribute to a lower risk of intracerebral hemorrhage during embolism-associated ischemia from AF by protection of the microvessel permeability barrier from local thrombin challenge. [ABSTRACT FROM AUTHOR]