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BACKGROUND: We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT). METHODS: We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours. RESULTS: We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64-81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short. CONCLUSIONS: We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials. TRIAL REGISTRATION NUMBER: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03192332.

Introduction Stroke and vascular cognitive impairment (VCI) are major global public health pandemics. The increased incidence of stroke and VCI is in part due to modifiable risk factors (MRFs), with hypertension (HTN) being the strongest single MRF. Even though the underlying causes of HTN are multifactorial, lifestyle choices (eg, poor diet, physical inactivity, alcohol consumption) are chief contributors. Lifestyle medicine (LSM) is a medical and evidence-based discipline that is a promising approach for preventing stroke and cognitive impairment, including VCI. The empirical evidence from systematic reviews, meta-analyses and large population-based studies has reported on the effectiveness of LSM interventions. However, the evaluation of such complex, social and behavioural interventions warrants more information to allow its successful implementation into innovative clinical care models. More importantly, we need to understand how such interventions work, who it works for and under what circumstances to successfully manage HTN and other MRFs (eg, hyperlipidaemia, smoking, alcohol use and diet).Methods and analysis This realist review will follow the Realist and Meta-narrative Evidence Synthesis: Evolving Standards. The review will comprise four stages: (1) clarify the scope, (2) search for the evidence, (3) critically appraise primary studies and extract data focusing on the context, mechanism and outcome configuration and (4) synthesise evidence and draw conclusions.Ethics and dissemination Research ethics board approval is not required for this review. The primary output of this review will be an evidence-based programme theory for LSM interventions for the management of HTN and other MRFs to reduce the risk of stroke and VCI. Findings from this review will be disseminated at three levels: micro (eg, patients, caregivers, clinicians, non-research partners), meso (eg, public, national not-for-profit organisations, professional associations and centres) and macro (eg, policymakers and government partners).PROSPERO registration number CRD42024511566.

The burden of noncommunicable chronic diseases has relevant and negative consequences to persons, health care systems, and economies worldwide. Chronic diseases are the leading cause of disability and mortality and are responsible for 90% of health care expenditure. The most common chronic diseases are diabetes mellitus (DM), cardiovascular disease, and cerebrovascular disease (stroke and vascular cognitive impairment). Modifiable risk factors (MRFs) for these conditions include hypertension, hyperlipidemia, smoking, poor diet, and low-physical activity; with hypertension being the most prevalent MRF. Most MRFs can be successfully targeted through lifestyle medicine (LSM), which is a medical specialty that addresses the root causes of chronic diseases through its primary, secondary, and tertiary preventative approaches. Lifestyle medicine comprises 6 pillars (nutrition, physical activity, sleep health, stress reduction, social connections, and substance use) which through various behavioral approaches, focus on regular physical activity, healthy eating, good quality and quantity sleep, and meaningful social connections coupled with the reduction of stress and substance use. This paper will briefly review the evidence and promise of individual LSM pillars in addressing the underlying MRFs of DM, cardiovascular and cerebrovascular disease (specifically stroke and vascular cognitive impairment). Lifestyle medicine holds a great promise for comprehensive and much improved population health. However, the adoption of LSM at the societal scale requires a multifaceted approach and widespread integration would galvanize a paradigm shift to prevent, treat or reverse chronic diseases from the root causes and achieve health equity.

IntroductionThe 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoint for brain health, we tested the hypothesis that a higher BCS is associated with a reduced incidence of future depression. Additionally, we examined its association with a brain health composite outcome comprising stroke, dementia, and late-life depression.MethodsThe BCS was derived from the United Kingdom Biobank baseline evaluation in participants with complete data on BCS items. Associations of BCS with the risk of subsequent incident late-life depression and the composite brain health outcome were estimated using multivariable Cox proportional hazard models. These models were adjusted for age at baseline and sex assigned at birth.ResultsA total of 363,323 participants were included in this analysis, with a median BCS at baseline of 12 (IQR: 11-14). There were 6,628 incident cases of late-life depression during a median follow-up period of 13 years. Each five-point increase in baseline BCS was associated with a 33% lower risk of incident late-life depression (95% CI: 29%-36%) and a 27% lower risk of the incident composite outcome (95% CI: 24%-30%).DiscussionThese data further demonstrate the shared risk factors across depression, dementia, and stroke. The findings suggest that a higher BCS, indicative of healthier lifestyle choices, is significantly associated with a lower incidence of late-life depression and a composite brain health outcome. Additional validation of the BCS is warranted to assess the weighting of its components, its motivational aspects, and its acceptability and adaptability in routine clinical care worldwide.

This study examines the effects of La3+ doping on (Pb0.75Ba0.25)(Zr0.70Ti0.30)O3(PBZT) ceramics, which were synthesized using the conventional solid-state reaction method. X-ray diffraction analysis confirmed that the PBZT structure, including PBZT doped with La3+ at concentrations x = 1 at.% and x = 2 at.%, exhibited a rhombohedral (R3c) space group, while higher doping levels of x = 3 at.% and x = 4 at.% led to a dominant cubic (Pm-3m) phase with approximately 30% of a remnant rhombohedral component. Scanning electron microscopy (SEM, JEOL JSM-7100F TTL LV, Jeol Ltd., Tokyo, Japan) and energy dispersive X-ray spectroscopy (EDS) were utilized to investigate the structure and morphology of these ceramics. The findings indicated that the chemical composition of the ceramic samples closely corresponded to the initial stoichiometry of the ceramic powder. An increase in the amount of lanthanum results in a decrease in the average grain size of the ceramics. The electrical properties were further evaluated using complex impedance spectroscopy (IS) over a range of temperatures and frequencies, as well as temperature dependence of DC conductivity. The similarity in the changes in activation energy for DC conductivity and grain boundary conductivity, caused by lanthanum ion modification, allows for the conclusion that grain boundaries are the primary microstructural element responsible for conductivity in these materials.

'Education for all' and widening access to education with the aim of creating more social equality are longterm goals of the European education policy. Although there was an education expansion in the last decades in most of European countries, educational attainment and achievement still reflect social inequalities: students with less advantaged socio-economic backgrounds are still significantly underrepresented in higher educational institutions and need supporting measures for educational success. Roma students in particular suffer from multiple deprivation: Firstly, because a large part of the Roma population lives in poverty. Secondly, because their different cultural traditions often lead to discrimination in school education. Roma women additionally suffer from social injustice and deprivation because of the gender aspect: the traditional Roma culture defines the place of women to be with the family at home and an educational career is not necessary for that. Mentoring programmes are considered as successful in helping disadvantaged pupils and students to achieve better results in education. A special form of mentoring programmes is often included as a part of teacher education with the goal of not only helping disadvantaged children but also preparing future teachers to cope with diversity in schools. This article introduces practical and conceptual issues regarding mentoring programmes for disadvantaged children focussing on two perspectives: on the impact on the mentees -- disadvantaged children with special regard to Roma students, and on the effect on the mentors -- students in teacher training.

BackgroundStroke incidence among young adults of working age (under 65 years of age) has significantly increased in the past decade, with major individual, social, and economic implications. There is a paucity of research exploring the needs of this patient population. This study assessed: (1) young adult stroke patients' physical, psychological, and occupational functioning and health-related quality of life (HRQoL); and (2) post-stroke care preferences using patient-reported outcome measures (PROMs), with attention to gender differences.MethodsA cross-sectional pilot study was conducted. Sociodemographic and clinical characteristics were collected through chart review and data on occupational function, physical, psychological, and social wellbeing >90 days post-stroke through a self-reported survey. Descriptive statistics, gender-based, and regression analyses were conducted.ResultsThe sample included 85 participants. Participants reported impairments in both, occupational functioning, with 58.7% not returned to work (RTW), and HRQoL, specifically with social activities (37%), anxiety (34%), and cognitive function (34%). Women had significantly (p < 0.05) worse physical symptoms (sleep disturbance and fatigue), emotional health (depression, stigma, emotional dyscontrol) scores, and sense of self-identify post-stroke. Over 70% of participants preferred in-person post-stroke care led by health care providers and felt they would have benefited from receiving information on physical health (71.4%), emotional and psychological health (56.0%), RTW (38.1%), and self-identity (26.2%) post-stroke. Women preferred cognitive behavioral therapy (p = 0.018) and mindfulness-based stress reduction therapy (p = 0.016), while men preferred pharmacotherapy (p = 0.02) for psychological symptoms.ConclusionThis is the first study to report impaired HRQoL, psychological and occupational functioning using PROMs, with significant gender differences and preferences for post-stroke care delivery among young adult stroke patients at >90 days after stroke. The findings highlight the importance of needs, gender, and age-specific post-stroke education and interventions.

Augmented reality technology has been introduced during recent years into everyday clinical practice. Several surgical specialties have begun using such technology for preoperative planning as well as intraoperatively. Regarding vascular surgery, a limited number of reports have described the benefits, mainly for endovascular procedures. We aim to present a novel three-dimensional holographic system we used to perform an open vascular procedure.

Abstract Th-containing superconducting high entropy system with the nominal composition (NbTa) $$_{0.67}$$ 0.67 (MoWTh) $$_{0.33}$$ 0.33 was synthesized. Its structural and physical properties were investigated by X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, specific heat, resistivity and magnetic measurements. Two main phases of alloy were observed: major bcc structure and minor fcc. The experimental results were supported by numerical simulation by the DFT Korringa-Kohn-Rostoker method with the coherent potential approximation (KKR-CPA).

Lead-boron special glass was doped into Ba0.996La0.004Ti0.999O3 (BLT4) ceramics in order to control the sintering process and grain growth, consequently obtaining materials with a well-developed microstructure. Changes in the microstructure resulted in a significant decrease in electrical permittivity along with a substantial increase in its frequency dispersion. Glass-doped ceramics, similar to pure BLT4, are characterized by a first-order phase transition from the ferroelectric phase to the paraelectric phase. The temperature of this transition shifts slightly towards higher values with the increase in glass dopant concentration.

The perovskite-structured materials Pb0.75Ba0.251−xCax(Zr0.7Ti0.3)O3 for x = 1 and 2 at.% were synthesized using the conventional mixed-oxide method and carbonates. Microstructural analysis, performed using a scanning electron microscope, revealed rounded grains with relatively inhomogeneous sizes and distinct grain boundaries. X-ray diffraction confirmed that the materials exhibit a rhombohedral structure with an R3c space group at room temperature. Piezoelectric resonance measurements were conducted to determine the piezoelectric and elastic properties of the samples. The results indicated that a small amount of calcium doping significantly enhanced the piezoelectric coefficient d31. The calcium-doped ceramics exhibited higher electrical permittivity across the entire temperature range compared to the pure material, as well as a significant value of remanent polarization. These findings indicate that the performance parameters of the base material have been significantly improved, making these ceramics promising candidates for various applications.

The present study examined the relationships between the standardized applied behavior analysis (ABA) direct assessment, the PEAK Comprehensive Assessment (PCA), and established assessments commonly used in educational and clinical settings, including the Childhood Autism Rating Scale - Third Edition (CARS-3), the PDD Behavior Inventory (PDDBI), the Vineland Adaptive Behavior Scale - Second Edition (VABS-2), and intelligence, including the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) and the Wechsler Intelligence Scale for Children (WISC-V). Utilizing a sample of 73 children with autism ranging from 3 to 21 years old, the present study found the PCA to be significantly correlated with the established measures. The result suggests evidence of convergent validity of the PCA, and internal consistency among its subtests. Implications of this behavior-analytic standardized assessment were discussed.

Recent attention into sex and gender-based inequities surrounding outcomes for brain health disorders has generated momentum toward addressing what has been called the “brain health gap.” Importantly though, “women” are not uniform demographic group. In this perspective piece, we discuss misdiagnosis in stroke as an aspect of access and quality of care within brain health. Drawing on narrative data from a mixed methods study of young stroke survivors we suggest that while missed stroke isn't only an issue of gender, if we are going to understand gender-based gaps in access and navigation through stroke care, we have to understand how intersections of gender with age, ethnoracial identity, nationality, language, (dis)ability, and other aspects of social identity come together to create affordances as well as biases that contribute to stroke outcomes.

IntroductionThe 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke.MethodsThe BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40–69 years, recruited between 2006–2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline.ResultsThe BCS (median: 12; IQR:11–14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged 59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged 59.DiscussionThe BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide.

IntroductionSerological tests can be used to test whether an animal has been exposed to an infectious agent, and whether its immune system has recognized and produced antibodies against it. Paired samples taken several weeks apart then document an ongoing infection and/or seroconversion.MethodsIn the absence of a commercial kit, we developed an indirect enzyme-linked immunosorbent assay (ELISA) to detect the fungus-specific antibodies for Pseudogymnoascus destructans, the agent of white-nose syndrome in bats.Results and DiscussionSamples collected from European Myotis myotis (n=35) and Asian Myotis dasycneme (n=11) in their hibernacula at the end of the hibernation period displayed 100% seroprevalence of antibodies against P. destructans, demonstrating a high rate of exposure. Our results showed that the higher the titre of antibodies against P. destructans, the lower the infection intensity, suggesting that a degree of protection is provided by this arm of adaptive immunity in Palearctic bats. Moreover, P. destructans infection appears to be a seasonally self-limiting disease of Palearctic bats showing seroconversion as the WNS skin lesions heal in the early post-hibernation period.

Prebiotics are an effective technological element of increasing the productivity of animal husbandry. Currently, prebiotics are being broadly used in cuniculture. Those drugs are a promising means of stimulating growth and development of animals. Prebiotics optimize the metabolic processes and increase the level of nutrient metabolism. Our studies revealed the effect of a prebiotic drug, which contains lactic and succinic acids, aminoacids, vitamins А, В1, В2, В3, Е, on the growth intensity of rabbits. The studies were performed on the young 34 to 160-days-old rabbits of the Hyplus meat hybrid. Animals of the control group were fed ad libitum with full-diet granulated mixed feeds and had free access to water. Animals of the experimental groups were fed feeds of the control-group diet, supplemented by prebiotic additive Prebiolakt-Kr in the doses of 1.5, 2.0, and 2.5 g/kg of the live weight. Every 14 days during the feeding period, the growth intensity of the rabbits was controlled according to individual live weight and average daily increment. Addition of Prebiolakt-Kr to the rabbits’ diet increased the live weight of animals by the end of feeding. We verified and confirmed the positive effect of the prebiotic on the intensity of growth and development of the growing rabbits. According to the absolute increment, the advantage over the rabbits in the control accounted for 7.9–11.9%. Feeding the supplement increased the meat volumes of the rabbits. Also, Prebiolakt-Kr added to the diet caused higher chest girth/diagonal body length index. The animals that were receiving the prebiotic feed supplement used the diet more effectively and had better metabolism of nutrients. The studies revealed a dose-dependent effect of prebiotic on the growth intensity of the rabbits. At the same time, the best stimulating action was displayed by supplementing the diet of the young rabbits by 2.0 and 2.5 g/ind. of Prebiolakt-Kr. The conducted studies have confirmed the benefits of using prebiotic drugs in rabbit husbandry, which improve metabolism and increase body-weight gain.

Abstract Background Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia. Results We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures, 37 °C and 5 °C, to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or down-regulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat’s ability to repair molecular structures damaged due to the stress related to the temperature change. Conclusions The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats’ ability to act as reservoirs of zoonotic viruses such as lyssaviruses.