Background The absence of the susceptibility vessel sign (SVS) in patients treated with mechanical thrombectomy (MT) is associated with poor radiological and clinical outcomes after 3 months. Underlying conditions, such as cancer, are assumed to influence SVS status and could potentially impact the long-term outcome. We aimed to assess SVS status as an independent predictor of long-term outcomes in MT-treated patients. Methods SVS status was retrospectively determined in consecutive MT-treated patients at a comprehensive stroke center between 2010 and 2018. Predictors of long-term mortality and poor functional outcome (modified Rankin Scale (mRS) ≥3) up to 8 years were identified using multivariable Cox and logistic regression, respectively. Results Of the 558 patients included, SVS was absent in 13% (n=71) and present in 87% (n=487) on baseline imaging. Patients without SVS were more likely to have active cancer (P=0.003) and diabetes mellitus (P<0.001) at the time of stroke. The median long-term follow-up time was 1058 days (IQR 533–1671 days). After adjustment for active cancer and diabetes mellitus, among others, the absence of SVS was associated with long-term mortality (adjusted HR (aHR) 2.11, 95% CI 1.35 to 3.29) and poor functional outcome in the long term (adjusted OR (aOR) 2.90, 95% CI 1.29 to 6.55). Conclusion MT-treated patients without SVS have higher long-term mortality rates and poorer long-term functional outcome. It appears that this association cannot be explained by comorbidities alone, and further studies are warranted.
Abstract Introduction Clinical utility and diagnostic sensitivity of new‐generation flat‐panel computed tomography perfusion imaging (FPCTP) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCTP obtained directly after MT could provide additional potentially relevant information on tissue reperfusion status. Methods Qualitative, single‐center analysis of all consecutive acute stroke patients admitted between 06/2019 and 03/2021 who underwent MT and post‐interventional FPCTP (n=26). A core‐lab blinded to technical details and clinical data performed reperfusion grading on post‐interventional digital subtraction angiography (DSA) images and time‐sensitive FPCTP maps. All patients were classified according to agreement between DSA and FPCTP. Results In 10/26 patients FPCTP revealed new, potentially clinically relevant information. Core‐lab adjudicated dichotomized detection of hypoperfusion (present/absent) was concurring in 21/26 (81%) patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 (62%) patients, while in 5 (19%) patients with incomplete reperfusion, FPCTP showed additional hypoperfused areas missed on DSA. Of the remaining five patients subject to disagreement regarding the presence or absence of hypoperfusion, three showed complete reperfusion on DSA but hypoperfusion was noted on FPCTP, whereas two showed incomplete reperfusion on DSA without detectable hypoperfusion on FPCTP. FPCTP findings could have avoided Thrombolysis in Cerebral Infarction (TICI) overestimation in all false‐positive operator‐rated TICI3 cases. Conclusion In both core‐lab and real‐world operator assessment, FPCTP may provide additional clinically relevant information in a considerable percentage of patients undergoing MT. Hence, FPCTP may constitute a new standard for evaluating reperfusion efficacy and informed decision making in the angiography suite.
Abstract Introduction The benefit of additional reperfusion attempts in patients with partial angiographic reperfusion (TICI2b) is unknown. The PROCEED model predicts subsequent favorable occurrence of complete reperfusion (i.e. delayed reperfusion [DR]) at 24 hours after initial incomplete angiographic reperfusion at the conclusion of thrombectomy. This study aims to externally validate the PROCEED model using pooled data from multiple international trials that systematically performed follow‐up perfusion imaging. Methods Individual patient data for external validation were obtained from the EXTEND‐IA, EXTEND‐IA TNK part 1 and 2 trials (clinicaltrials.gov, unique‐identifier: NCT01492725, NCT02388061 and NCT03340493). The model’s primary outcome of interest was the occurrence of DR, defined as the absence of any focal perfusion deficit on follow‐up CT or MRI perfusion imaging maps, despite initial incomplete angiographic reperfusion on the final thrombectomy angiography series. The updated model’s performance was evaluated with discrimination, calibration and clinical decision curves. Results We analyzed 267 patients for the external validation, with median age of 74 (IQR 64 – 80), 44.2% were female and 62% had DR. The externally validated model had good discrimination (C‐statistic 0.81, 95% CI 0.72 – 0.86) and was well calibrated (intercept 0.22, 95% CI 0.18‐0.33 and slope 0.96, 95% CI 0.81‐1.23). With threshold probability of R=12% (i.e. 88% chance of having DR), pursuing additional reperfusion attempts to pursue complete angiographic reperfusion in a patient with high‐likelihood of DR were seven times worse (Cost:Benefit Ratio 1:7, Figure 1) than no further endovascular maneuver. In terms of standardized net reduction, the PROCEED model could reduce one in five unnecessary interventions without missing an intervention for any patient who would eventually have DR. Across a wide range of threshold probabilities, the model outperformed the scenario of the typical decision‐making process in the angiography suite, based on the current treatment guidelines. Conclusion The externally validated model had good predictive accuracy and discrimination. Depending on the acceptable risk threshold, the model may compliment clinical judgment of the treating physicians and inform on natural progression of untreated incomplete reperfusion.
Zero Trust security has recently gained attention in enterprise network security. One of its key ideas is making network-level access decisions based on trust scores. However, score-based access control in the enterprise domain still lacks essential elements in our understanding, and in this paper, we contribute with respect to three crucial aspects. First, we provide a comprehensive list of 29 trust attributes that can be used to calculate a trust score. By introducing a novel mathematical approach, we demonstrate how to quantify these attributes. Second, we describe a dynamic risk-based method to calculate the trust threshold the trust score must meet for permitted access. Third, we introduce a novel trust algorithm based on Subjective Logic that incorporates the first two contributions and offers fine-grained decision possibilities. We discuss how this algorithm shows a higher expressiveness compared to a lightweight additive trust algorithm. Performance-wise, a prototype of the Subjective Logic-based approach showed similar calculation times for making an access decision as the additive approach. In addition, the dynamic threshold calculation showed only 7% increased decision-making times compared to a static threshold.
African swine fever virus (ASFV) is a complex DNA virus causing severe hemorrhagic disease in domestic pigs and wild boar. The disease has spread worldwide, with important socio-economic consequences. Early virus detection and control measures are crucial as there are no effective vaccines nor antivirals on the market. While the diagnosis of ASFV is fast and based primarily on qPCR, the detection of infectious ASFV is a labor-intensive process requiring susceptible macrophages and subsequent antibody-based staining or hemadsorption. The latter cannot detect ASFV isolates devoid of functional CD2v (EP402R) expression. Here, we report the development of a plasmid-based reporter assay (RA) for the sensitive detection and titration of infectious ASFV. To this end, we constructed a plasmid for secreted NanoLuc® luciferase (secNluc) expression driven by the ASFV DNA polymerase gene G1211R promoter. Infection of plasmid-transfected immortalized porcine kidney macrophages (IPKM) followed by measurement of secNluc from cell culture supernatants allowed reliable automated quantification of infectious ASFV. The RA-based titers matched the titers determined by conventional p72-staining or hemadsorption protocols. The novel assay is specific for ASFV as it does not detect classical swine fever virus nor porcine reproductive and respiratory syndrome virus. It is applicable to ASFV of different genotypes, virulence, and sources, including ASFV from sera and whole blood from infected pigs as well as non-hemadsorbing ASFV.
INTRODUCTION Diatom tests are rarely used during autopsy to confirm drowning as the cause of death (COD) because of limitations of the current literature involving these techniques. Instead, experts rely on physical examination by the pathologist. Due to interpretive concerns regarding Diatom tests, they are often insufficient in establishing a diagnosis, but offer the potential to be an extremely useful diagnostic tool with further understanding. The aim of study is to optimize "Diatom Tests" for use in forensic medicine in Bosnia and Herzegovina. METHODS A randomized prospective experimental study was conducted, using albino Wistar rat models (Rattus norvegicus), at the Veterinary Facility, University of Sarajevo. Thirty-two adult albino rats, were used and distributed into groups as follows: Group A (6 deceased rats with COD other than drowning, but due to mechanical asphyxia, which were then submerged for 1 h after death); Group B (6 deceased rats with COD other than drowning, but due to mechanical asphyxia, which were then submerged for 72 h after death); Group C (6 rats that were immediately autopsied after drowning, with COD determined as drowning); Group D (6 rats that underwent a 48-hour postmortem period after drowning); Group E (COD: drowning, post-mortem 72hrs after death, remained submerged in water until PM). Live algological material was collected for the research of the systematics of algae from the Bosna river, Sarajevo, and transported to the University of Sarajevo (Department of Biology, Faculty of Science). Periphyllon, epiphyllon and epipelon were used to collect phytobenthos. The material was fixed with 4% formalin solution. Laboratory processing of diatoms was performed using the methods described by Hustedt (16). In the process of obtaining pure diatom valves, part of the material is digested with potassium permanganate (KMnO4), sulfuric acid (H2SO4), and oxalic acid (C2H2O4). In the next step, the cleaned diatom valves were mounted in Canadian balsam. A light microscope under 1000x magnification (Best Scope 2020) was used to evaluate and analyze the species. The identification of diatoms was performed using the reference of Cantonati et al (17). The nomenclature of diatom species was performed according to Guiry & Guiry's worldwide electronic internet database. RESULTS No diatoms were found in Groups A and B. However, Navicula sp. and Sellaphora sp. cf., were discovered during bone analysis of Group C where rats were immediately autopsied after drowning. Hantzschia amphioxus taxon was present in Group D, which underwent a 48-hour postmortem period after drowning and before samples were taken. In Groups C and D, where drowning was the COD, Diatoma vulgaris i Pinnularia major, Achnanthidium minutissimum i Melosira varians were present in the tooth samples. CONCLUSION Optimization of the "Diatom Test" method could potentially lead to its future use as a routine method within experimental settings. This experimental study is a starting point that guides forenscic medicine pracitioners towards the optimization of tests and sampling in cases of unexplained etiology, where preserved soft tissue structures is not available. In these cases, teeth and bones serve as accessible materials for diagnosing COD, alongside standardized nonspecific findings in the absence of organs for micro- and macroanalysis.
BACKGROUND Neuropathy is among the most often reported consequences of diabetes and the biggest cause of morbidity and mortality in people suffering from this life-long disease. Although different therapeutic methods are available for diabetic neuropathy, it is still the leading cause of limb amputations, and it significantly decreases patients' quality of life. AIM This study investigates potential novel therapeutic options that could ameliorate symptoms of DN. METHODOLOGY Research and review papers from the last 10 years were taken into consideration. RESULTS There are various traditional drugs and non-pharmacological methods used to treat this health condition. However, the research in the area of pathogenic-oriented drugs in the treatment of DN showed no recent breakthroughs, mostly due to the limited evidence about their effectiveness and safety obtained through clinical trials. Consequently, there is an urgent demand for the development of novel therapeutic options for diabetic neuropathy. CONCLUSION Some of the latest novel diagnostic methods for diagnosing diabetic neuropathy are discussed as well as the new therapeutic approaches, such as the fusion of neuronal cells with stem cells, targeting gene delivery and novel drugs.
Urban logistics implementation causes environmental pollution; therefore, it is necessary to consider the impact on the environment when carrying out such logistics. Electric vehicles are alternative vehicles that reduce the impact on the environment. For this reason, this study investigated which electric vehicle has the best indicators for urban logistics. An innovative approach when selecting such vehicles is the application of a fuzzy–rough method based on expert decision making, whereby the decision-making process is adapted to the decision makers. In this case, two methods of multi-criteria decision making (MCDM) were used: SWARA (stepwise weight assessment ratio analysis) and MARCOS (measurement alternatives and ranking according to compromise solution). By applying the fuzzy–rough approach, uncertainty is included when making a decision, and it is possible to use linguistic values. The results obtained by the fuzzy–rough SWARA method showed that the range and price of electric vehicles have the greatest influence on the selection of an electric delivery vehicle. The results of applying the fuzzy–rough MARCOS method indicated that the Kangoo E-Tech Electric vehicle has the best characteristics according to experts’ estimates. These results were confirmed by validation and the application of sensitivity analysis. In urban logistics, the selection of an electric delivery vehicle helps to reduce the impact on the environment. By applying the fuzzy–rough approach, the decision-making problem is adjusted to the preferences of the decision makers who play a major role in purchasing a vehicle.
Exclusive semileptonic b hadron decays (b → uℓν) serve as a sandbox for probing strong and electroweak interactions and for extracting the CKM element Vub. Instead, this work investigates their underexplored potential to reveal new short-distance physics. Utilizing SMEFT as a conduit to chart territory beyond the SM, we demonstrate that substantive new physics contributions in b → uℓν are necessarily linked to correlated effects in rare neutral-current b decays, neutral B meson mixing or high-mass Drell-Yan tails. We find that measurements of the latter processes strongly restrict the allowed deviations in the former. A complete set of tree-level mediators, originating from a perturbative ultraviolet model and matching at dimension 6, is thoroughly explored to support this assertion. As a showcase application, we examine the feasibility of a new physics interpretation of the recent tension in exclusive |Vub| extraction from B → Vℓν where V = (ρ, ω).
BACKGROUND Previously, we assessed the impact of restrictive diets, including caloric restriction (CR), intermittent fasting (IF), or fasting-mimicking diet (FMD), on a healthy gastrointestinal tract. We revealed that each of the diets shows anti-inflammatory outcomes. OBJECTIVE The current study aimed to verify the diets' applicability in treating colitis. METHODS We exposed a mouse model with mild chronic DSS colitis to ad libitum control feeding, CR, IF, or FMD. The collected samples were analyzed for markers of inflammation. RESULTS The diets reduced DSS-triggered increases in spleen weight and myeloperoxidase (MPO) activity. Diet intervention also influenced occludin levels, small intestine morphology, as well as cytokine and inflammatory gene expression, mainly in the mucosa of the proximal colon. The diets did not reverse DSS-enhanced gut permeability and thickening of the colon muscularis externa. Concerning inflammatory gene expression, the impact of DSS and the dietary intervention was limited to the colon as we did not measure major changes in the jejunum mucosa, Peyer's patches, and mesenteric lymph nodes. Further, rather modest changes in the concentration of intestinal bile acids were observed in response to the diets, while taurine and its conjugates levels were strongly affected. CONCLUSIONS Despite the differences in the dietary protocol, the tested diets showed very similar impacts and, therefore, may be interchangeable when aiming to reduce inflammation in the colon. However, FMD showed the most consistent beneficial impact.
Hypotensive influences of benzodiazepines and other GABAA receptor ligands, recognized in clinical practice, seem to stem from the existence of "vascular" GABAA receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABAA receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABAA γ2 and α1-5 subunit proteins. To confirm the role of "vascular" GABAA receptors, we investigated the vascular effects of standard benzodiazepines, midazolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ2 over other αxβ3γ2 GABAA receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazolam, both of which at 100 µmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABAA receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.
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