Spreading Activation Research Articles

Extension of microglial activation is associated with epilepsy and cognitive dysfunction in Tuberous sclerosis complex: A TSPO-PET study

Background and objectivesNeuroinflammation contributes to the severity of various neurological disorders, including epilepsy. Tuberous sclerosis complex (TSC) is a condition that results in the overactivation of the mammalian target of rapamycin (mTOR) pathway, which has been linked to the activation of microglia responsible for neuroinflammation. To clarify the involvement of neuroinflammation in the neuropathophysiology of TSC, we performed a positron emission tomography (PET) study using the translocator protein (TSPO) radioligand, [11C] DPA713, and investigated microglial activation in relation to neurological manifestations, especially epilepsy and cognitive function. MethodsThis cross-sectional study included 18 patients with TSC (6 in the no-seizure group, 6 in the refractory seizure group, and 6 in the mTOR-inhibitor [mTOR-i] group). All participants underwent [11C] DPA713-PET. PET results were superimposed with a 3D T2-weighted fluid-attenuated inversion-recovery (FLAIR) and T1-weighted image (T1WI) to evaluate the location of cortical tubers. Microglial activation was assessed using the standardized uptake value ratio (SUVr) of DPA713 binding. The volume ratio of the DPA713-positive area to the intracranial volume (volume ratio of DPA713/ICV) was calculated to evaluate the extent of microglial activation. A correlation analysis was performed to examine the relationship between volume ratio of DPA713/ICV and severity of epilepsy and cognitive function. ResultsMost cortical tubers with hyperintensity on FLAIR and hypo- or isointensity on T1WI showed microglial activation. The extent of microglial activation was significantly greater in the refractory seizure group than in the no-seizure or mTOR-i groups (p < 0.001). The extent of microglial activation in subjects without mTOR-i treatment correlated positively with epilepsy severity (r = 0.822, P = 0.001) and negatively with cognitive function (r = -0.846, p = 0.001), but these correlations were not present in the mTOR-i group (r = 0.232, P = 0.658, r = 0.371, P = 0.469, respectively). ConclusionNeuroinflammation is associated with the severity of epilepsy and cognitive dysfunction in brains with TSC. mTOR-i may suppress the extent of neuroinflammation in TSC. Investigating the spread of microglial activation using TSPO-PET in these patients may help to predict the progression of neuropathy by assessing the degree of neuroinflammation and therefore be useful for determining how aggressive the treatment should be and in assessing the effectiveness of such treatment in patients with TSC.

User Interactions in Online Travel Communities: A Social Network Perspective

Online travel communities (OTCs) enable users to interact and share travel information voluntarily. Extant research has primarily focused on the content generated through user interactions but neglected how user interactions are structured. This study employed exponential random graph models to examine the formation of user interactions and the outcomes of homophily in terms of network structure across levels (actor, dyad, triad, and network). A dataset of 2,926 posts and 25,854 replies involving 9,712 users in an OTC was used. Results reveal that users’ question initiating and replying ties in OTCs exhibit significant positive structural dependencies in terms of reciprocity, activity spread, generalized transitive closure, and multiple connectivity. Homophily serves as the basis of dyadic interactions and homophilous ties evolve after formation. The study advances hospitality and tourism network research and methodology by going beyond traditional dyadic user interactions, and provides insights into user interactions in OTCs from the social network perspective.

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity

BackgroundCortical electrical stimulation is a versatile technique for examining the structure and function of cortical regions and for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. New methodHere, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex. Neural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing. ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomical connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state. Comparison with existing methodsPrevious imaging studies investigating cross-regional responses to stimulation are limited to utilizing indirect hemodynamic responses and thus lack the temporal specificity of ICMS-evoked responses. ConclusionsThese results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity, enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.

Phenotypic plasticity in the monoclonal marbled crayfish is associated with very low genetic diversity but pronounced epigenetic diversity.

Clonal organisms are particularly useful to investigate the contribution of epigenetics to phenotypic plasticity, because confounding effects of genetic variation are negligible. In the last decade, the apomictic parthenogenetic marbled crayfish, Procambarus virginalis, has been developed as a model to investigate the relationships between phenotypic plasticity and genetic and epigenetic diversity in detail. This crayfish originated about 30 years ago by autotriploidy from a single slough crayfish Procambarus fallax. As the result of human releases and active spreading, marbled crayfish has established numerous populations in very diverse habitats in 22 countries from the tropics to cold temperate regions. Studies in the laboratory and field revealed considerable plasticity in coloration, spination, morphometric parameters, growth, food preference, population structure, trophic position, and niche width. Illumina and PacBio whole-genome sequencing of marbled crayfish from representatives of 19 populations in Europe and Madagascar demonstrated extremely low genetic diversity within and among populations, indicating that the observed phenotypic diversity and ability to live in strikingly different environments are not due to adaptation by selection on genetic variation. In contrast, considerable differences were found between populations in the DNA methylation patterns of hundreds of genes, suggesting that the environmentally induced phenotypic plasticity is mediated by epigenetic mechanisms and corresponding changes in gene expression. Specific DNA methylation fingerprints persisted in local populations over successive years indicating the existence of epigenetic ecotypes, but there is presently no information as to whether these epigenetic signatures are transgenerationally inherited or established anew in each generation and whether the recorded phenotypic plasticity is adaptive or nonadaptive.

Selective activation of the hypothalamic orexinergic but not melanin-concentrating hormone neurons following pilocarpine-induced seizures in rats.

Sleep disorders are common comorbidities in patients with temporal lobe epilepsy (TLE), but the underlying mechanisms remain poorly understood. Since the lateral hypothalamic (LH) and the perifornical orexinergic (ORX) and melanin-concentrating hormone (MCH) neurons are known to play opposing roles in the regulation of sleep and arousal, dysregulation of ORX and MCH neurons might contribute to the disturbance of sleep-wakefulness following epileptic seizures. To test this hypothesis, rats were treated with lithium chloride and pilocarpine to induce status epilepticus (SE). Electroencephalogram (EEG) and electromyograph (EMG) were recorded for analysis of sleep-wake states before and 24 h after SE. Double-labeling immunohistochemistry of c-Fos and ORX or MCH was performed on brain sections from the epileptic and control rats. In addition, anterograde and retrograde tracers in combination with c-Fos immunohistochemistry were used to analyze the possible activation of the amygdala to ORX neural pathways following seizures. It was found that epileptic rats displayed prolonged wake phase and decreased non-rapid eye movement (NREM) and rapid eye movement (REM) phase compared to the control rats. Prominent neuronal activation was observed in the amygdala and the hypothalamus following seizures. Interestingly, in the LH and the perifornical nucleus, ORX but not MCH neurons were significantly activated (c-Fos+). Neural tracing showed that seizure-activated (c-Fos+) ORX neurons were closely contacted by axon terminals originating from neurons in the medial amygdala. These findings suggest that the spread of epileptic activity from amygdala to the hypothalamus causes selective activation of the wake-promoting ORX neurons but not sleep-promoting MCH neurons, which might contribute to the disturbance of sleep-wakefulness in TLE.

European experience of the organization of physical culture and sports societies - the National Bureau of Tourism in the Carpathians (Romania, interwar period)

In the article "European experience of the organization of physical culture and sports societies - the National Bureau of Tourism in the Carpathians (Romania, interwar period)" analyzed the European experience of the organization of physical culture and sports societies on the example of the activities of the National Bureau of Tourism in the Carpathians (Romania) in the interwar period. The authors identified the peculiarities of starting tourism work with the population on the Romanian lands in the 19th century, highlighted the purpose of the activities of such associations - the development of tourism, the mass involvement of representatives of all social strata of the population in such activities and the formation of a unified system (development of territorial objects, formation of a system of training specialists , spread of such activity), etc. Aspects of the activity of "Alpine Society of Transylvania", "Transylvanian Carpathian Association", "Romanian Geographical Society of Bucharest", "Group of Travelers", "Hanul Drumeților" were analyzed. The principles of the activity of the state National Bureau of Tourism in the Carpathians (1936) are outlined. It was determined that the idea of E. Rakovice to create a state institution of tourism began to be realized in 1926, when, according to the provisions of the law on health protection, the National Bureau of Tourism was created, subordinate to the Ministry of Health, whose main task was to coordinate the organization and activities of balneological centers in the country. However, such a narrow, limited field of activity did not reflect the entire necessary volume of development and popularity of tourism in the interwar period. The article highlights the achievements of the National Bureau in the studied period: the location of health resorts and tourist resorts was classified and determined; on his initiative, the construction of hotels was started; shelter houses were built in the mountain areas of Ranka, Obarsia Lotruluy, Babele, Chukas; developed winter sports, in particular skiing and bobsleigh, by designing and building bobsleighs tracks in Carpathian resorts. The authors note that the change of regime in Romania led to the fact that the tourist associations were dissolved in 1948, and all their property was transferred to the National Bureau of Tourism. Romania was the only country of the Soviet bloc that stopped the activities of all tourist associations and organizations.

No need to forget, just keep the balance: Hebbian neural networks for statistical learning

Language processing in humans has long been proposed to rely on sophisticated learning abilities including statistical learning. Endress and Johnson (E&J, 2021) recently presented a neural network model for statistical learning based on Hebbian learning principles. This model accounts for word segmentation tasks, one primary paradigm in statistical learning. In this discussion paper we review this model and compare it with the Hebbian model previously presented by Tovar and Westermann (T&W, 2017a; 2017b; 2018) that has accounted for serial reaction time tasks, cross-situational learning, and categorization paradigms, all relevant in the study of statistical learning. We discuss the similarities and differences between both models, and their key findings. From our analysis, we question the concept of “forgetting” in the model of E&J and their suggestion of considering forgetting as the critical ingredient for successful statistical learning. We instead suggest that a set of simple but well-balanced mechanisms including spreading activation, activation persistence, and synaptic weight decay, all based on biologically grounded principles, allow modeling statistical learning in Hebbian neural networks, as demonstrated in the T&W model which successfully covers learning of nonadjacent dependencies and accounts for differences between typical and atypical populations, both aspects that have not been fully demonstrated in the E&J model. We outline the main computational and theoretical differences between the E&J and T&W approaches, present new simulation results, and discuss implications for the development of a computational cognitive theory of statistical learning.

Automatic priming, schema induction and spread of activation in l2 lexical access: Do differences in vocabulary size and depth of priming remain invariant?

This study investigated automatic priming, schema induction, spread of activation and L2 lexical access through vocabulary size and depth. Employing theoretical framework of the distributed memory representation, the underlying assumption was that conceptual knowledge was identified through connection weights linking processing units that were universal rather than local. Using experimental pre-test-post-test design with purposive sampling of estimated one hundred and fifty (150) students from three (3) Senior High Schools, the critical findings in this study were that cognitive differences in automatic priming, schema induction and spread of activation predicted enhanced reading comprehension in L2, especially how fast one could infer from text since these cognitive processes helped to reduce cognitive load involved in reading. The second finding was that ability to use automatic priming, schema induction and spread of activation reduced mental load to facilitate comprehension by the size and level of vocabulary readers possessed in long-term memory. Third finding was that priming, spread of activation and schema induction increased with increasing attentional control. Readers with high attentional control were more likely to be involved in a proactive expectancy strategic use of priming, spread of activation and schema induction to generate possible targets. These cognitive differences remain invariant in readers, unless classroom practices are deliberately designed to help less enhanced readers strategies to promote schema induction, priming and spread of activation.

The force of the myosin motor sets cooperativity in thin filament activation of skeletal muscles

Contraction of striated muscle is regulated by a dual mechanism involving both thin, actin-containing filament and thick, myosin-containing filament. Thin filament is activated by Ca2+ binding to troponin, leading to tropomyosin displacement that exposes actin sites for interaction with myosin motors, extending from the neighbouring stress-activated thick filaments. Motor attachment to actin contributes to spreading activation along the thin filament, through a cooperative mechanism, still unclear, that determines the slope of the sigmoidal relation between isometric force and pCa (−log[Ca2+]), estimated by Hill coefficient nH. We use sarcomere-level mechanics in demembranated fibres of rabbit skeletal muscle activated by Ca2+ at different temperatures (12–35 °C) to show that nH depends on the motor force at constant number of attached motors. The definition of the role of motor force provides fundamental constraints for modelling the dynamics of thin filament activation and defining the action of small molecules as possible therapeutic tools.

EXTH-94. LOCALIZED INTRATUMORAL TREATMENT WITH ADOPTIVE T CELL THERAPY FOLLOWED BY ONCOLYTIC ADENOVIRUS DELTA-24-RGDOX INDUCES SUSTAINABLE REGRESSION OF DISSEMINATED SOLID TUMORS THROUGH ANTIGEN SPREAD

Abstract Tumor-targeting biological therapies, including adoptive T cell therapy (ACT) and oncolytic viruses, are being tested clinically to address the challenges in treating advanced solid tumors with heterogeneity and immune suppressive microenvironment (TME). Since complementary properties of these two approaches have been observed, we hypothesize that localized intratumoral treatment with combination of ACT and Delta-24-RGDOX (third generation oncolytic adenovirus developed by our group) induces not only potent therapeutic effect in treated tumor but also abscopal benefit to eliminate distant disseminated tumors. Using a B16-C57BL/6 melanoma model with disseminated tumors in C57BL/6 mice, we found gp100-specific CD8+ T cells injected into the first subcutaneous (s.c.) tumor showed tropism for distant s.c. and intracranial tumors, tumor draining lymph nodes, compared to spleen, blood and normal brain hemisphere. In a B16-OVA-C57BL/6 s.c./s.c. tumor model, Delta-24-RGDOX injections following gp100-specific T cells in the first tumor increased total cytotoxic T cell presence within both tumors, including gp100- and OVA- specific T cells. Further analysis revealed that Delta-24-RGDOX reduced the exhaustion of OVA-specific T cells while that of gp100-specific T cells kept at a low level. Moreover, Delta-24-RGDOX augmented the activity of the splenocytes against the tumor cells and other tumor-associated antigens (OVA, TRP2) than gp100. Consequentially, the combination of OVA-specific T cells and Delta-24-RGDOX was more potent to inhibit the injected and untreated distant tumor growth and caused improved survival rate than either of the agent alone (p &amp;lt; 0.05). Importantly, we observed relapse of the regressed tumors in the T cell treatment group, but not in the combination group. The survivors developed immune memory against rechallenging with B16-OVA cells. Collectively, our data demonstrate that localized treatment with intratumoral ACT followed by Delta-24-RGDOX induces global immune activation and antigen spread to expand antitumor T cell repertoire, leading to efficacious systemic anti-tumor immunity and sustainable tumor regression.

Synchronization clusters located on epileptic onset zones in neocortical epilepsy

BackgroundBrain function is thought to rely on complex interactions of dynamic neural systems, which depend on the integrity of structural and functional networks. Focal epilepsy is considered to result from excessive focal synchronization in the network. Synchronization analysis of multichannel electrocorticography (ECoG) contributes to the understanding of and orientation of epilepsy. The aim of this study was to explore the synchronization in multichannel ECoG recordings from patients with neocortical epilepsy and characterize neural activity inside and outside the onset zone.MethodsFour patients with neocortical epilepsy, who became seizure-free for more than 1 year after surgery guided by ECoG monitoring, were included in this study. ECoG data recorded during pre-surgical evaluation were analyzed. Synchronizations in phase and amplitude of different frequency bands between ECoG channels was analyzed using MATLAB. We generated 100 surrogate data from the original ECoG data using Amplitude Adjusted Fourier Transform to calculate the enhanced synchronization. The relationship between synchronization characteristics and seizure onset zone was analyzed.ResultsWe found synchronization clusters in the 14–30 Hz and 30–80 Hz bands around the onset areas during both interictal and the beginning of ictal periods in all four patients.ConclusionsThe enhanced-synchronization clusters play a central role in epilepsy, and may activate the onset areas and contribute to the spreading of epileptiform activity.

Differences in the spatial fidelity of evoked and spontaneous signals in the degenerating retina.

Vision restoration strategies aim to reestablish vision by replacing the function of lost photoreceptors with optoelectronic hardware or through gene therapy. One complication to these approaches is that retinal circuitry undergoes remodeling after photoreceptor loss. Circuit remodeling following perturbation is ubiquitous in the nervous system and understanding these changes is crucial for treating neurodegeneration. Spontaneous oscillations that arise during retinal degeneration have been well-studied, however, other changes in the spatiotemporal processing of evoked and spontaneous activity have received less attention. Here we use subretinal electrical stimulation to measure the spatial and temporal spread of both spontaneous and evoked activity during retinal degeneration. We found that electrical stimulation synchronizes spontaneous oscillatory activity, over space and through time, thus leading to increased correlations in ganglion cell activity. Intriguingly, we found that spatial selectivity was maintained in rd10 retina for evoked responses, with spatial receptive fields comparable to wt retina. These findings indicate that different biophysical mechanisms are involved in mediating feed forward excitation, and the lateral spread of spontaneous activity in the rd10 retina, lending support toward the possibility of high-resolution vision restoration.

Unstable diffusion in social networks

How and to what extent will new activities spread through social ties? To answer this question, we present an analytical framework that allows us to describe the diffusion dynamics on complex networks more accurately than the conventional mean-field approach. Based on two classes of network games, we find that the spread of multiple activities is expressed as a saddle path, and thus, inherently unstable. In particular, when the two activities are sufficiently substitutable, either of them will dominate the other by chance even if they are equally attractive ex ante. We argue that, in environments where such symmetry-breaking occurs, any average-based approximation method may not correctly capture the Nash equilibrium — the steady state of an actual diffusion process.

A Data-Driven Approach to Analyze Mobility Patterns and the Built Environment: Evidence from Brescia, Catania, and Salerno (Italy)

Investigating the correlation between urban mobility patterns and the built environment is crucial to support an integrated approach to transportation and land-use planning in modern cities. In this study, we aim to conduct a data-driven analysis of these two interrelated parts of the urban environment through the estimation of a set of metrics to assist city planners in making well-informed strategic decisions. Metrics are computed by aggregating and correlating different types of data sources. Floating Car Data (FCD) are used to compute metrics on mobility demand and traffic patterns. The built environment metrics are mainly derived from population and housing census data, as well as by investigating the topology and the functional classification adopted in the OpenStreetMap Repository to describe the importance and the role of each street in the overall network. Thanks to this set of metrics, accessibility indexes are then estimated to capture and explain the interaction between traffic patterns and the built environment in three Italian cities: Brescia, Catania, and Salerno. The results confirm that the proposed data-driven approach can extract valuable information to support decisions leading to more sustainable urban mobility volumes and patterns. More specifically, the application results show how the physical shape of each city and the related street network characteristics affect the accessibility profiles of different city zones and, consequently, the associated traffic patterns and travel delays. In particular, the combined analysis of city layouts, street network distributions, and floating car profiles suggests that cities such as Brescia, which is characterized by a homogeneously distributed radial street system, exhibit a more balanced spread of activities and efficient mobility behaviors.

OR12-5 | LBSAT57 Long-term Follow-Up of Pheochromocytoma/Paraganglioma (PPGL) after first diagnosis: a retrospective single-center study of 173 patients

Abstract Background Pheochromocytoma (Pheo)/Paraganglioma (PGL), together PPGL, are rare but life-threatening tumors, with tumor relapse (TR) rates after initial surgery of 16.5%, and genetic mutations in about 30-40% of patients. Long-term follow-up (FU) and genetic testing in all patients are recommended. Questions remain, however, as to the most suitable duration of FU, the prognostic value of genetic diagnoses and of clinical, biochemical or radiological findings during FU, of the incidence of TR after recommended 10 years FU of low-risk sporadic Pheos, or of TR on morbidity and mortality. Objective, patients, and methods: We retrospectively determined the overall survival (OAS), progression-free survival (PFS) and tumor-recurrence (TR) in 173 patients with PPGL initially operated and followed-up at a single tertiary referral center from 1988 to 2020 by Kaplan-Meier Estimates, and assessed age, sex, hormonal activity, tumor size, and metastatic spread at first diagnosis, pathohistological PASS score, mutation-positive PPGLs (MP-PPGL), TR, and comorbidities (associated with increased cardiovascular risk) as to independent prognostic markers thereof by multivariate Cox-regression. Certificats of the Austrian death registry were also obtained. Results In 8 (5%) PPGLs there was no FU in the charts, but death certified occurring 65±28 (mean±SD, median 2.7) months after first diagnosis. Mean (±SD) age of the remaining 165 (43.9% female) patients (94.5 Pheos, 3.0% multiple PGLs, 2.5% head-and-neck PGLs) was 49(±16) years, mean (range) FU 90(3-537) months. 93 (54%) patients underwent genetic testing, 37 (40%, 21% of entire cohort) had MP-PPGL (mean±SD age 33.8±13.2 yrs, OAS 391 months). 5 of these 37 (13.5%), and 7 of 57 (12%) mutation-negative (MN-PPGL, mean±SD age 53.3±14.8 years, p&amp;lt;0.01 vs. MP-PPGL, OAS 190 months) died during FU (p=0.03). Male sex, higher age, presence of comorbidities, and primary metastatic disease were independent negative prognostic factors for OAS by univariate, but only age and metastatic disease remained significant by multivariate analysis. As to PFS, higher age and no hormonal activity were negatively associated by univariate, but not by multivariate analysis, as were all other tested parameters. Conclusions The cohort of our study is the third-largest original report on long-term FU and prognostic markers in PPGL. While others (Ayola-Ramirez et al, JECM 2011) in 371 patients found tumor size and sympathetic PGL independently associated with OAS, we did not. Patients may have harbored more aggressive tumors in that study, as higher primary metastatic spread (25% of Pheos, 60% of sympathetic PGL) was identified. We identified only age and metastatic disease as independent predictors of OAS, in line with data from Korea (Kim J H, et al., Endocrinol Metab. [Seoul]) in 1048 patients (9% with primary metastatis) and with a metaanalysis comprising 703 PPGLs (Crona J, Endocr Relat Cancer, 2019). Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

Speech Culture at the beginning of the XXI Century in the context of New Media Phenomenon

The purpose of the article is to reveal the peculiarities of the formation of speech culture at the current stage of the development of society through the prism of the phenomenon of new media. Research methodology. Research methods are represented by a combination of various research approaches – an activity and axiological approach to the study of prayer culture in its connection with the language culture of new media and speech practices of the modern media space; system approach, which is implemented in the unity of structural-functional and elemental analysis. The method of terminological analysis was applied to clarify the content and scope of the concept of "new media"; methods of systemic analysis and synthesis, which contributed to clarifying the role and place of new media in modern society; the typological method contributed to the identification of influencing factors on the transformation of speech culture in new media and the determination of the features of this process. Scientific novelty. The transformational processes of speech culture in the context of the formation and popularisation of new media have been studied; the concept of "new media" has been clarified and supplemented; mediatisation as a process of influence of new media on the development of speech culture has been specified; the peculiarities of speech culture formation in the modern information society through the prism of new media as a unique information and communication phenomenon of the 21st century have been revealed; it has been found out that in the context of the specifics of the media space of the 21st century new media offer a variety of alternative approaches to any cultural practice, including broadcasting. Conclusions. The active development and large-scale spread of innovative means of communication based on the use of computer technologies significantly influence the strengthening of communication processes, activating changes directly in the language of communication. The development of information and communication technologies at the beginning of the 21st century. largely determines the direction of development of the modern language of communication and the transformational processes of speech culture. The spread of new media, which is directly related to innovative interactive information technologies controlled directly by users, along with changes in the forms and types of communication, led to transformational processes of speech culture. Under the influence of new media, the norms of speech culture are changing, which leads to a decrease in the quality of language culture. Modern media space, in contrast to traditional media of the 20th century – radio, television and print media – cannot be characterised as a model and standard of speech culture due to the presence in media texts of grammatical and spelling errors, elements of clericalism, outdated clichés, limited vocabulary and reluctance to use synonyms, the presence of street lexicon, barbarism, elements of colloquial language, activation spread of foreign vocabulary, illiterate construction of phrases, and incorrect use of words in a stable word combination. The language of new media is a unique organism that exists and develops according to its own rules. Non-compliance with the norms of speech culture, stylistics, violation of spelling rules, deliberate distortion of vocabulary, the use of foreign vocabulary, increased use of peculiar vulgar, and sometimes exaggerated mincing jargon are common in the Internet space. In this context, the promotion of the native language, the struggle for its purity and compliance with the rules, regardless of the field in which it is used, is of particular importance. Given the blurring of boundaries between real and virtual communication on the Internet, a high speech culture should become an example to follow.&#x0D; Key words: speech culture, new media, Internet, media space, mediatisation.

Identifying core strategies and mechanisms for spreading a national medicines optimisation programme across England—a mixed-method study applying qualitative thematic analysis and Qualitative Comparative Analysis

BackgroundAchieving widespread adoption of innovations across health systems remains a challenge. Past efforts have focused on identifying and classifying strategies to actively support innovation spread (replicating an innovation across sites), but we lack an understanding about the mechanisms which such strategies draw on to deliver successful spread outcomes. There is also no established methodology to identify core strategies or mechanisms which could be replicated with fidelity in new contexts when spreading innovations. We aimed to understand which strategies and mechanisms are connected with successful spread using the case of a national medicines optimisation programme in England.MethodsThe study applied a comparative mixed-method case study approach. We compared spread activity in 15 Academic Health Science Networks (AHSN) in England, applied to one innovation case, Transfers of Care Around Medicines (TCAM). We followed two methodological steps: (1) qualitative thematic analysis of primary data collected from 18 interviews with AHSN staff members to identify the strategies and mechanisms and related contextual determinants and (2) Qualitative Comparative Analysis (QCA) combining secondary quantitative data on spread outcome and qualitative themes from step 1 to identify the core strategies and mechanisms.ResultsWe identified six common spread strategy-mechanism constructs that AHSNs applied to spread the TCAM national spread programme: (1) the unique intermediary position of the AHSN as “honest broker” and local networking organisation, (2) the right capacity and position of the spread facilitator, (3) an intersectoral and integrated stakeholder engagement approach, (4) the dynamic marriage of the innovation with local health and care system needs and characteristics, (5) the generation of local evidence, and (6) the timing of TCAM. The QCA resulted in the core strategy/mechanism of a timely start into the national spread programme in combination with the employment of a local, senior pharmacist as an AHSN spread facilitator.ConclusionsBy qualitatively comparing experiences of spreading one innovation across different contexts, we identified common strategies, causal mechanisms, and contextual determinants. The QCA identified one core combination of two strategies/mechanisms. The identification of core strategies/mechanisms and common pre-conditional and mediating contextual determinants of a specific innovation offers spread facilitators and implementers a priority list for tailoring spread activities.

Analisis Sentimen Pada Pembelajaran Daring Di Indonesia Melalui Twitter Menggunakan Naïve Bayes Classifier

Education is one of the areas most affected by the covid-19 pandemic. Education during the pandemic must continue. To reduce the spread of covid-19 and learning activities can run as usual, the government, in this case the Ministry of Education and Culture, has implemented a distance education system in Indonesia. In addition, the response from the community is very important for an evaluation of the applied online learning. With the implementation of the policy regarding online learning in Indonesia, it is necessary to conduct a sentiment analysis to find out how the responses, opinions, or comments from the public and online learning actors related to online learning are currently being implemented. So the author conducted a research entitled Sentiment Analysis on Online Learning in Indonesia Through Twitter Using the Naïve Bayes Classifier Method to measure student responses regarding online learning during the covid -19 pandemic in Indonesia. The results of the accuracy of this study is 99.8% and the classification error is 0.12%. Of the total data entered, 83 tweets or 20% were included in the positive class, the negative class was 317 tweets or 80%.

Dysfunctional microglia and tau pathology in Alzheimer's disease.

Extensive human studies and animal models show that chronic immune system stimulation involving microglia, inflammasome, complement activation, synthesis of cytokines, and reactive oxygen species exacerbates neurodegeneration in Alzheimer's disease (AD) and other tauopathies. Abnormalities in tau, Aβ, and microglial activation are frequently observed in dementia patients and indicate that these elements may work in concert to cause cognitive impairment. Contradicting reports from postmortem studies demonstrating the presence of Aβ aggregates in the brains of cognitively healthy individuals, as well as other investigations, show that tau aggregation is more strongly associated with synapse loss, neurodegeneration, and cognitive decline than amyloid pathology. Tau association with microtubules' surface promotes their growth and maintains their assembly, dynamicity, and stability. In contrast, the reduced affinity of hyperphosphorylated and mislocalized tau to microtubules leads to axonal deficits and neurofibrillary tangles (NFTs). Loss of microglial neuroprotective and phagocytic functions, as indicated by the faulty clearance of amyloid plaques, as well as correlations between microglial activation and tau tangle spread, all demonstrate the critical involvement of malfunctioning microglia in driving tau propagation. This review discusses the recent reports on the contribution of microglial cells to the development and progression of tau pathology. The detailed study of pathogenic mechanisms involved in interactions between neuroinflammation and tau spread is critical in identifying the targets for efficacious treatment strategies in AD.

Genetic variants IL18 -105G&gt;A and -137G&gt;C associated with susceptibility to migraine

IntroductionFew studies have been conducted into neurogenic inflammation and neuroinflammation in respect of migraine. However, evidence suggests that the immune system may exert an influence over trigeminal activation and cortical spreading depression in individuals suffering from migraine. The interleukin (IL)-18 is a pro-inflammatory cytokine and increased plasma levels have been confirmed in individuals with migraine. However, as yet, the genetic variants of IL-18 have not been investigated in the context of migraine. ObjectiveTo investigate the association between genetic variants IL18 -105G&gt;A (rs360717) and IL18 -137G&gt;C (rs187238) and susceptibility to migraine and its clinical characteristics. Subjects and MethodsCase control study comprising 307 participants, of whom 152 had a diagnosis of migraine and 155 were healthy controls, paired by sex, age, ethnicity and BMI. The clinical and demographic data were evaluated. The patients with migraine were interviewed using a structured form containing information about the type of migraine (with or without aura, episodic or chronic), age at onset of the disease, frequency of attacks, accompanying symptoms that triggered headaches. The patients also answered validated questionnaires to evaluate incapacity (Migraine Disability Assessment - MIDAS) and impact (Headache Impact Test - HIT-6) for migraine, the presence of allodynia (ASC-12), as well as symptoms of anxiety (State Anxiety Inventory - STAI 1 and 2), depression (Beck Depression Inventory) and a hyperacusis scale.The genetic variants IL18 -105G&gt;A (rs360717) and IL18 -137G&gt;C (rs187238) were identified using polymerase chain reaction (PCR) and the fluorescence levels of PCR products were evaluated using a Step One thermocycler (Applied Biosystems). The analyses were conducted using the dominant, codominant, recessive and overdominant genetic models. (To see the complete abstract, please, check out the PDF).