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W artykule skupiono się na zdiagnozowaniu problemów społeczno-przestrzennych Malty jako kraju wielokulturowego. Badania prowadzono w oparciu o zdefiniowanie potrzeb mieszkańców kraju oraz na analizie rozwoju społeczno-przestrzennego reprezentatywnej dla Malty – Vallety. Wnioski z badań posłużyły jako punkt wyjścia do próby wytyczenia kierunków kształtowania nowego ładu przestrzennego dla miasta. Badania prowadzono w ramach współpracy Politechniki Krakowskiej z Konsulatem Republiki Malty w Krakowie. Powstały propozycje projektowe współczesnych założeń architektoniczno-urbanistycznych w stolicy Malty uwzględniające wytyczne wynikające z wniosków z przeprowadzonych badań. Propozycje te zostały przedstawione w pracach dyplomowych magisterskich studentów drugiego stopnia kierunku Architektura na Wydziale Architektury Politechniki Krakowskiej. A Multi-Cultural City’s New Spatial Order: Valletta, Malta This paper focuses on diagnosing the socio-spatial problems of Malta as a multi-cultural country. The study was based on defining the needs of the country’s citizens and an analysis of the socio-spatial development of Valletta – as a city representative of Malta. The conclusions of this investigation served as a starting point for an attempt to formulate guidelines for shaping a new spatial order for the city. The study was performed as a part of cooperation between the Cracow University of Technology with the Consulate of the Republic of Malta in Cracow. Design proposals of contemporary architectural and urban complexes in Malta’s capital that included said guidelines were drafted. These proposals were presented in Master’s thesis projects prepared by second-cycle students of the Architecture course taught at the Faculty of Architecture of the Cracow University of Technology.

W artykule przedstawiono wyniki badań dotyczących spojrzenia mieszkańców Mazur na współczesny kształt budownictwa mieszkaniowego jednorodzinnego i przeznaczonego na turystykę w ich regionie. Wnioski z badań posłużyły jako punkt wyjścia do przygotowania propozycji projektowych współczesnych założeń krajobrazowo mieszkalnych z wykorzystaniem domów na wynajem, czy gospodarstw agroturystycznych. Dyplomowe prace inżynierskie studentów architektury są odpowiedzią na preferencje formalne mieszkańców. Zakres czasowy części opartej na badaniu ankietowym dotyczy XXI wieku, a części dotyczącej analiz archetypu sięga wieku XVII. Masurian Model of Contemporary Regionalism This paper presents the results of a survey that explored how the residents of Masuria perceived the contemporary form of singlefamily and tourist housing in their region. The conclusions of this study were used as a starting point for preparing design proposals of contemporary landscape and housing layouts based on homes for rent or agricultural tourism facilities. Bachelor of Engineering in Architecture thesis projects became an answer to the formal preferences of the residents. The temporal scope of the section presenting the survey study concerns the twenty-first century, while the archetype analysis section reaches back to the seventeenth century.

Objective We use the dynamic electroencephalography–functional magnetic resonance imaging (EEG-fMRI) method to incorporate variability in the amplitude and field of the interictal epileptic discharges (IEDs) into the fMRI analysis. We ask whether IED variability analysis can (a) identify additional activated brain regions during the course of IEDs, not seen in standard analysis; and (b) demonstrate the origin and spread of epileptic activity. We explore whether these functional changes recapitulate the structural connections and propagation of epileptic activity during seizures. Methods Seventeen patients with focal epilepsy and at least 30 IEDs of a single type during simultaneous EEG-fMRI were studied. IED variability and EEG source imaging (ESI) analysis extracted time-varying dynamic changes. General linear modeling (GLM) generated static functional maps. Dynamic maps were compared to static functional maps. The dynamic sequence from IED variability was compared to the ESI results. In a subset of patients, we investigated structural connections between active brain regions using diffusion-based fiber tractography. Results IED variability distinguished the origin of epileptic activity from its propagation in 15 of 17 (88%) patients. This included two cases where no result was obtained from the standard GLM analysis. In both of these cases, IED variability revealed activation in line with the presumed epileptic focus. Two cases showed no result from either method. Both had very high spike rates associated with dysplasia in the postcentral gyrus. In all 15 cases with dynamic activation, the observed dynamics were concordant with ESI. Fiber tractography identified specific white matter pathways between brain regions that were active at IED onset and propagation. Significance Dynamic techniques involving IED variability can provide additional power for EEG-fMRI analysis, compared to standard analysis, revealing additional biologically plausible information in cases with no result from the standard analysis and gives insight into the origin and spread of IEDs.

Przedstawione w artykule wyniki badań dotyczących spojrzenia mieszkańców Wenecji na problemy nurtujące ich miasto posłużyły jako punkt wyjścia do rozważań na temat możliwości zaradzenia tym problemom przy wykorzystaniu potencjału jaki niesie XXI wiek. Dyplomowe prace magisterskie studentów architektury mogą być doskonałym poligonem doświadczalnym i miejscem prowadzenia badań i przedstawiania propozycji dla stworzenia wyobrażeń o lepszej przyszłości. Przedstawione w publikacji rozwiązania funkcjonalno-przestrzenne pozwalają spojrzeć w oryginalny sposób na część problemów Wenecji, o których dyskutuje się od lat jak wpływanie wielkich statków wycieczkowych na wody laguny, tłumy turystów, poszukiwanie nowych przestrzeni dla mieszkańców, rozwijanie rynku pracy, czy proponowanie nowych form zwiedzania miasta. Contemporary functional and spatial challanges of Venice based on local perception The findings presented in this study, which focused on how Venice’s residents perceive the problems their city suffers from, served as a starting point for a discussion on the potential to address them by using the potential of the twenty-first century. Thesis design projects by architecture students can serve as an excellent testing ground for studies and presenting proposals of visions of a better future. The functio-spatial solutions presented in this paper can provide an original perspective on some of Venice’s much-discussed problems, such as enormous cruise ships entering the lagoon’s waters, tourist crowds and the search for new spaces for residents, employment market development or proposing new forms of sightseeing in the city.

Artykuł przedstawia efekt badań dotyczących potencjału współczesnego Rio de Janeiro jako miejsca dla projektu XXI wieku. Analiza architektury miasta w kontekście uwarunkowań społecznych, przestrzennych i przyrodniczych oraz analiza istniejących tam najważniejszych miejsc kulturotwórczych stały się punktem wyjścia do określenia ideowych wytycznych do projektu konkursowego Atheneum Architektury w Rio de Joneiro, który został przedstawiony w publikacji. Badania prowadzono w oparciu o metodę analizy krytycznej literatury oraz badania in citu. Athenaeum of twenty-first-century architecture: Rio de Janeiro This paper presents the outcomes of a study on the potential of contemporary Rio de Janeiro to act as a site for a twenty-first century project. An analysis of the city’s architecture in the context of social, spatial and wildlife-related determinants and an analysis of extant major culture-forming places became the starting point for determining conceptual guidelines for the competition design of the Architecture Athenaeum in Rio de Janeiro, which has been presented in the paper. The research was based on critical analysis of the literature and on-site studies.

Introduction: Advances in computer image analysis have enabled the use of new functional imaging methods in the diagnosis of laryngeal diseases. Particularly interesting techniques of dynamic laryngeal imaging involve High Speed Videoendoscopy (HSV). This still-developed technique allows to overcome the limitations of laryngovideostroboscopy (LVS) and a more detailed analysis of the glottal function based on the image of the actual vibrations of the vocal folds. It also enables the determination of objective coefficients parameterizing phonatory vibrations of the vocal folds. Aim: The aim of this pilot study was to evaluate the use of a high-speed videoendoscopy set with laser illumination for the diagnosis of glottic pathology in ENT practice. Material and methods: The study included 40 patients who underwent LVS followed by HSV. The modern HSV examination kit – Advanced Larynx Imager System (ALIS), used for the first time in a clinical setting in Poland, is characterized by significantly improved, compared to the previously used high-speed cameras, operational parameters – a light head, the possibility of continuous lighting operation without excessive heating of the head tip, registration of the image in full color scale. Thanks to such modernization, the safety and course of the examination do not differ from laryngoscopy conducted with commonly used recorders. The device owes some of these improvements to a laser illuminator which was used for the first time as the main light source in a high-speed camera. In the study, two cases were selected to present the results of HSV and the analysis of the generated kymograms – a woman with no glottic pathology and a man with a polyp of the right vocal fold. In the first case, the HSV examination compared with the LVS revealed a discrete glottis functional disorder in the form of a tendency to hyperphonation. The patient with an organic lesion had a clearly visible irregularity of vocal fold vibrations, which also allowed to trace mucosal wave disturbances related to its reflection from the pathological structure of the glottis and the formation of a return wave, both on the fold affected by the lesion and, to a lesser extent, contralaterally. The glottic dysfunctions observed in the studied patients were confirmed in the generated kymograms and the graphs of the glottal width waveform (GWW), as well as in the parameters calculated on their basis, assessing the frequency and amplitude of phonatory vibrations. Conclusions: The use of high-speed videoendoscopy allows for a much more accurate assessment of the phonatory function of the glottis than in laryngovideostroboscopy. The presented HSV system allows for obtaining high quality kinematic images of the larynx, color fidelity, and contrast. The use of this technology in laryngological practice enables precise structural and functional assessment of the glottis and detection of discrete phonation disorders that elude the techniques used so far.

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

Education systems are struggling to effectively integrate in their study programs the Sustainable Development Goals (SDGs) which define the challenges we need to overcome as a society in the 21st century. This study revealed the special agency that architecture and built environment have in shaping our social, economic, and natural environment using system and design thinking. Despite the several studies on the metacognitive design process, several cognitive traps still exist when developing design thinking in architecture education. This study investigated design thinking and self-directed learning in undergraduate architecture students. Responses collected from a sample of 117 undergraduates were subjected to bootstrapping in structural equation modelling to find significant relationships of reversed action when design thinking is used for developing self-directed learning. The findings suggest that design thinking is strongly connected with self-directed learning, and as shown in the resulting model, all components of self-directed learning are strongly explained by design thinking variables. This can provide insights for curriculum designers and educators on how to shape effective design thinking processes in architecture education to overcome existing shortcomings while improving interpersonal skills, creativity and digital skills, make pedagogical changes, and enhance redesign of learning outcomes towards sustainable architecture.

Temporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

Rationale Regular cannabis use (i.e. ≥ monthly) is highly prevalent, with past year use being reported by ~ 200 million people globally.High reactivity to cannabis cues is a key feature of regular cannabis use and has been ascribed to greater cannabis exposure and craving, but the underlying neurobiology is yet to be systematically integrated. Objectives We aim to systematically summarise the findings from fMRI studies which examined brain function in cannabis users while exposed to cannabis vs neutral stimuli during a cue-reactivity fMRI task. Methods A systematic search of PsycINFO, PubMed and Scopus databases was pre-registered in PROSPERO (CRD42020171750) and conducted following PRISMA guidelines. Eighteen studies met inclusion/exclusion criteria. Samples comprised 918 participants (340 female) aged 16–38 years. Of these, 603 were regular cannabis users, and 315 were controls. Results The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex ). Conclusions Exposure to cannabis-cues may elicit greater brain function and thus trigger cravings in regular cannabis users and thus trigger cannabis craving. Standardised and longitudinal assessments of cannabis use and related problems are required to profile with greater precision the neurobiology of cannabis cue-reactivity, and its role in predicting cravings and relapse.

Aims\ud The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis.\ud \ud Methods\ud Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy.\ud \ud Results\ud We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia.\ud \ud Conclusions\ud These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

Brain atrophy in human epilepsy syndromes is explainable by network architecture and strongest in hub regions., Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1021 adults with epilepsy compared to 1564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy colocalized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Negative effects of age on atrophy further revealed a strong influence of connectome architecture in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided deeper insights into the macroscale features that shape the pathophysiology of common epilepsies.

SUMMARYEpilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.

The currently used educational technology with artificial-intelligence-powered solutions, although rather instrumental, may lead to discontinuity in learning, as it lacks social and emotional value, which is an essential part of education for sustainable development and results in an immersive experience through which higher-order thinking skills can be adopted. This paper aims to explore transformative learning (TL) and innovation skill improvement accommodated by transactional distance theory in a 16-week remote sustainable architecture design course. The analysis identified the following: (a) significant progress in students’ attitudes toward uncertainty and criticality while social support differs due to the influence of classmates, faculty staff, teamwork, writing and reading assignments, promoters from industry and extracurricular activities; (b) significant progress in TL achievement while innovation skill development differs significantly across the groups in which online collaborative learning was found as an influencer in creativity and motivation; (c) self-efficacy influenced by feedback in and on actions, such as essay and other writing assignments, verbal persuasions and positive social comparisons; (d) lack of development of situational awareness, continuity of learning and interactions/situations to empower teammates in handling conflicts to develop leadership ability; (e) decrease in risk-taking ability, especially in a group of students in which social support was limited due to the absence of challenging situations and tasks. The results support the use of remote intervention directed at prosocial motivations and action-focused group goals.

Cocaine dependence (CD) is highly comorbid with personality disorders, with implications for poorer treatment response. The neurobiological mechanisms of this comorbidity are unclear. We aimed to test the role of comorbid personality disorders in the neuroanatomy of CD. We examined 4 groups using high-resolution structural neuroimaging, psychological questionnaires and cognitive tests: CD (n = 19), CD and personality disorder type B (CD + B, n = 21), CD and personality disorder C (CD + C, n = 13) and 21 controls. We compared groups in neuroanatomy and hypothesised that (i) CD would show altered striatal areas ascribed to reward processing (i.e., accumbens, caudate and putamen), (ii) CD + B and CD + C would show altered areas supporting emotional regulation/social valuation and anxiety/avoidance (i.e., OFC and amygdala). The CD + B group had larger caudate volumes than CD (p = .01, d = 0.94) and reduced lateral OFC thickness than CD + C (p = .056, d = 0.71). Exploratory correlations showed that altered neural integrity of the OFC and of the caudate nucleus in these groups exacerbated with worse personality disorder severity and impulsivity scores. CD with and without comorbid personality disorders may have partially distinct underlying mechanisms and targets for treatment.

BIM w planowaniu przestrzennym – omowienie mozliwości wykorzystania makiet BIM w procesie optymalizacji zarządzania przestrzenią w skali urbanistycznej

The 21st century brought about a greater evolution in the field of designing than the one when the drawing board was replaced with the CAD software. We are dealing now with extremely dynamic development of technology and with the need to comply with requirements relating to sustainable design. Sustainable design requires strict coordination at all stages and within the scope of all specialties it concerns. Therefore, supporting tools have emerged – software in the BIM standard (Building Information Modelling). It enables to introduce a number of essential parameters and to perform preliminary analyses relating to sustainable design already at very early stages of the process of developing the concept of a building. The results of such analyses allow to correct the design assumptions adopted and to optimise them. Teaching sustainable design with the support of these technologies is extremely helpful for architects and engineers today, and it can become indispensable in the future. Hence education in this scope and integration of the urban / architectural design with the construction design seems to be necessary starting from the first years of study at faculties of architecture.

This paper constitutes a compilation of the results of a research topic focusing on the integrated energy design. It discusses the process of design preparation at the stage of the architectural concept, initial power-related assumptions, getting familiar with basic construction materials and technologies, forms of education in the field, and project completion. The research was conducted on the basis of periodical international students’ workshops, the first stage of which takes place in Cracow, at the Faculty of Architecture of the Cracow University of Technology. The workshops are then continued in Strasbourg. At this stage they comprise theoretical classes at the campus of Lycee le Corbusier, as well as visits to construction sites of housing estates, and design works. The publication demonstrates benefits stemming from combining theory with practice in teaching students within the scope of the Smart Project assumptions, as well as students’ designs as the effects of the cooperation.

Objective The aim of this report is to present our clinical experience of electroencephalography–functional magnetic resonance imaging (EEG-fMRI) in localizing the epileptogenic focus, and to evaluate the clinical impact and challenges associated with the use of EEG-fMRI in pharmacoresistant focal epilepsy. Methods We identified EEG-fMRI studies (n = 118) in people with focal epilepsy performed at our center from 2003 to 2018. Participants were referred from our Comprehensive Epilepsy Program in an exploratory research effort to address often difficult clinical questions, due to complex and difficult-to-localize epilepsy. We assessed the success of each study, the clinical utility of the result, and when surgery was performed, the postoperative outcome. Results Overall, 50% of EEG-fMRI studies were successful, meaning that data were of good quality and interictal epileptiform discharges were recorded. With an altered recruitment strategy since 2012 with increased inclusion of patients who were inpatients for video-EEG monitoring, we found that this patients in this selected group were more likely to have epileptic discharges detected during EEG-fMRI (96% of inpatients vs 29% of outpatients, P

ObjectiveTo examine cerebral cortex thickness in asymptomatic first-degree relatives of patients with mesial temporal lobe epilepsy (MTLE).MethodsWe investigated 127 asymptomatic first-degree relatives of patients with MTLE due to hippocampal sclerosis (HS) (mean age ± SD = 39.4 ± 13 years) and 203 healthy control individuals (mean age ± SD = 36.0 ± 11 years). Participants underwent a comprehensive clinical evaluation and structural brain MRI at 3 study sites. Images were processed simultaneously at each site using a surface-based morphometry method to quantify global brain measures, hippocampal volumes, and cerebral cortical thickness. Differences in brain measures between relatives of patients and controls were examined using generalized models, while controlling for relevant covariates, including age and sex.ResultsNone of the asymptomatic first-degree relatives of MTLE + HS patients showed evidence of HS on qualitative image assessments. Compared to the healthy controls, the asymptomatic relatives of patients displayed no significant differences in intracranial volume, average hemispheric surface area, or hippocampal volume. Similarly, no significant cerebral cortical thinning was identified in the relatives of patients. This was consistent across the 3 cohorts.ConclusionLack of cortical thickness changes in the asymptomatic relatives of patients indicates that the previously characterized MTLE + HS-related cortical thinning is not heritable, and is likely driven by disease-related factors. This finding therefore argues for early and aggressive intervention in patients with medically intractable epilepsy.

ObjectiveThe process of manually marking up epileptic spikes for simultaneous electroencephalogram (EEG) and resting state functional MRI (rsfMRI) analysis in epilepsy studies is a tedious and subjective task for a human expert. The aim of this study was to evaluate whether automatic EEG spike detection can facilitate EEG-rsfMRI analysis, and to assess its potential as a clinical tool in epilepsy.MethodsWe implemented a fast algorithm for detection of uniform interictal epileptiform discharges (IEDs) in one-hour scalp EEG recordings of 19 refractory focal epilepsy datasets (from 16 patients) who underwent a simultaneous EEG-rsfMRI recording. Our method was based on matched filtering of an IED template (derived from human markup) used to automatically detect other ‘similar’ EEG events. We comprehensively compared simultaneous EEG-rsfMRI results between automatic IED detection and standard analysis with human EEG markup only.ResultsIn contrast to human markup, automatic IED detection takes a much shorter time to detect IEDs and export an output text file containing spike timings. In 13/19 focal epilepsy cases, statistical EEG-rsfMRI maps based on automatic spike detection method were comparable with human markup, and in 6/19 focal epilepsy cases it revealed additional brain regions not seen with human EEG markup. Additional events detected by our automated method independently revealed similar patterns of activation to a human markup. Overall, automatic IED detection provides greater statistical power in EEG-rsfMRI analysis compared to human markup in a short timeframe.ConclusionsAutomatic spike detection is a simple and fast method that can reproduce comparable and, in some cases, even superior results compared to the common practice of manual EEG markup in EEG-rsfMRI analysis of epilepsy.SignificanceOur study shows that IED detection algorithms can be effectively used in epilepsy clinical settings. This work further helps in translating EEG-rsfMRI research into a fast, reliable and easy-to-use clinical tool for epileptologists. Our IED detection approach will be publicly available as a MATLAB package at: https://github.com/omidvarnia/Automatic_focal_spike_detection.HighlightsAutomatic spike detection increases the number of detected uniform epileptic interictal discharges and enhances statistical power of EEG-rsfMRI inter-subject variability maps,Automatic spike detection can identify additional activated brain regions with presumed epileptogenic focus not seen in standard analysis based on human markup,Automatic spike detection can shorten the IED identification process.

Objective The dominant model of cognitive impairment in focal epilepsy has emphasised structural bases for cognitive deficits. Current theories of cognition in the healthy brain emphasise the importance of the reweighting of brain network interactions in support of task performance. Here, we explore the hypothesis that cognitive deficits in epilepsy arise through abnormalities of dynamic functional network interactions. Method We studied 19 healthy controls and 37 temporal lobe epilepsy (TLE) patients, using a behavioural measure of verbal fluency (the Controlled Oral Word Association Test) and an fMRI verbal fluency paradigm (Orthographic Lexical Retrieval). Results Behaviourally, verbal fluency was significantly impaired in TLE. Psychophysiological interaction analyses of the fMRI data, which capture state-dependent changes in network connectivity, revealed reduced task-dependent modulations of connectivity from left superior medial frontal cortex to left middle frontal gyrus in TLE patients. Individual differences in verbal fluency among TLE cases was correlated with task-dependent changes in connectivity from left posterior cingulate to left superior medial frontal cortex, and from left superior medial frontal cortex to a range of right predominant brain areas. Interpretation These data reveal that the typical pattern of task-driven shifts in network connectivity is not observed in TLE. Our observations go beyond simple structure-function associations and suggest that failure of network flexibility can be an important contributor to cognitive impairment in epilepsy.

Social, economic, spatial and construction-related problems of zwierzyniec. The four seasons

ObjectiveTo map functional MRI (fMRI) connectivity within and between the somatosensory cortex, putamen, and ventral thalamus in individuals from a family with a GABAergic deficit segregating with febrile seizures and genetic generalized epilepsy.MethodsWe studied 5 adults from a family with early-onset absence epilepsy and/or febrile seizures and a GABAA receptor subunit gamma2 pathogenic variant (GABRG2[R43Q]) vs 5 age-matched controls. We infer differences between participants with the GABRG2 pathogenic variant and controls in resting-state fMRI connectivity within and between the somatosensory cortex, putamen, and ventral thalamus.ResultsWe observed increased fMRI connectivity within the somatosensory cortex and between the putamen and ventral thalamus in all individuals with the GABRG2 pathogenic variant compared with controls. Post hoc analysis showed less pronounced changes in fMRI connectivity within and between the primary visual cortex and precuneus.ConclusionsAlthough our sample size was small, this preliminary study suggests that individuals with a GABRG2 pathogenic variant, raising risk of febrile seizures and generalized epilepsy, display underlying increased functional connectivity both within the somatosensory cortex and in striatothalamic networks. This human network model aligns with rodent research and should be further validated in larger cohorts, including other individuals with generalized epilepsy with and without known GABA pathogenic variants.

Glucocorticoids (GCs) are very effective at preventing carcinogen- and tumor promoter-induced skin inflammation, hyperplasia, and mouse skin tumor formation. The effects of GCs are mediated by a well-known transcription factor, the glucocorticoid receptor (GR). GR acts via two different mechanisms: transcriptional regulation that requires DNA-binding (transactivation) and DNA binding-independent protein-protein interactions between GR and other transcription factors, such as nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1; transrepression). We hypothesize that the transrepression activities of the GR are sufficient to suppress skin tumor promotion. We obtained two GCs (RU24858 and RU24782) that have dissociated downstream effects and induce only transrepression activities of the GR in a number of systems. These compounds bind the GR with high affinity and repress AP-1 and NF-κB activities while showing a lack of GR transactivation. RU24858, RU24782, or control full GCs desoximetasone (DES) and fluocinolone acetonide (FA) were applied to the dorsal skin of SENCAR mice prior to application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), two times per week for 2 weeks. DES, FA and RU24858 reversed TPA-induced epidermal hyperplasia and proliferation, while RU24782 treatment had no effect on these markers of skin tumor promotion. All tested compounds decreased TPA-induced c-jun mRNA levels in skin. DES, FA, and RU24858, but not RU24782, were also able to reverse TPA-induced increases in the mRNA levels of COX-2 and iNOS. These findings show that RU24858 but not RU24782 reduced TPA-induced epidermal hyperplasia, proliferation, and inflammation, while both compounds reversed c-jun mRNA increases in the skin.

The purpose of our study was to determine the effect of the combined action of phytochemicals on the early stages of skin tumorigenesis, i.e. initiation and promotion. We tested calcium D-glucarate (CG) given in the diet, while resveratrol (RES) and ursolic acid (UA) were applied topically. The 7,12-dimethylbenz[a]anthracene (DMBA)-initiated, 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted multistage skin carcinogenesis model in SENCAR mice was used. Mice received one topical dose of DMBA, then after one month, two weekly doses of TPA for 14 weeks until sacrifice. RES or UA were applied 20 min prior to DMBA or TPA treatment and 2% dietary CG was given from 2 weeks prior to 2 weeks after the DMBA dose or continually beginning 2 weeks prior to the first dose of TPA. UA applied alone and in combination with CG during the promotion stage was the only inhibitor of tumor multiplicity and tumor incidence. A number of combinations reduced epidermal proliferation, but only UA and the combination UA+CG applied during promotion significantly reduced epidermal hyperplasia. DMBA/TPA application resulted in significant increases in c-jun and p50, which were reversed by a number of different treatments. DMBA/TPA treatment also strongly increased mRNA levels of inflammation markers COX-2 and IL-6. All anti-promotion treatments caused a marked decrease in COX-2 and IL-6 expression compared to the DMBA/TPA control. These results show that UA is a potent inhibitor of skin tumor promotion and inflammatory signaling and it may be useful in the prevention of skin cancer and other epithelial cancers in humans.

Sturge-Weber syndrome is a rare, sporadic, neurocutaneous disorder classically characterized by a facial nevus in the trigeminal distribution (port wine stain), leptomeningeal angiomatosis, and glaucoma, although intracranial changes can be present without cutaneous involvement.1 Seizures occur in up to 75% of individuals, are often associated with headache, and stroke-like episodes causing prolonged neurologic deficits are also described.1,2

Background: One of the social groups that influence the activation of the city to the greatest extent are young people, including students. Social spaces dedicated to this group are to embellish the city, have a positive effect on its image, but they are also to be useful. Methods: This paper has been written on the basis of the Author’s study devoted to finding an answer to the question how much a social group that uses a specific space influences the activation of this space. The examined social group were young people, students from two cities: Toronto and Cracow. The spaces used in the study are places separated from school and university buildings, intended for individual study for high school and university students. Results: The results of the study indicate that one of the important factors that according to young people studying in the cities improve the quality of the social space is the existence of legibly marked places intended for individual study, that is places where students can study and spend time after their classes and lectures. Such places animate and activate the space connected with them. Conclusion: The social group of young people who still attend schools and universities constitutes a very important factor of the activation of cities. Providing young people with an attractive offer connected with their individual education has an invigorating effect on the city.

Activated glucocorticoid receptor (GR) acts via two different mechanisms: transcriptional regulation that requires DNA-binding, and protein–protein interaction between GR and other transcription factors, such as nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1). It has been postulated that many important effects of glucocorticoids, including their anti-inflammatory properties, depend on GR’s transrepressive effects on NF-κB and AP-1. In the present study, we have employed a TPA-induced model of skin inflammation and epidermal hyperplasia to determine whether partial activation of the glucocorticoid receptor by Compound A (CpdA) is sufficient to reverse the effect of TPA treatment. CpdA is a nonsteroidal GR modulator with high binding affinity, is capable of partial activation of GR. Topical application of TPA twice per week for two weeks results in inflammation and epidermal hyperplasia. TPA treatment also elevates levels of c-jun (AP-1 component), cyclooxygenase-2 (COX-2), p50 (NF-κB component), interleukin-6 (IL-6) and tumor necrosis factor (TNF) in the skin. Fluocinolone acetonide (FA) (a full GR agonist) was able to completely reverse the above effects of TPA. When applied alone, CpdA increased the epidermal thickness and keratinocyte proliferation as well as levels of c jun, COX-2, IL-6 and IFN-γ. However CpdA treatment resulted in a decrease in the number of p50 positive cells induced by TPA, suggesting its role in inhibition of NF-κB. The level of metallothionein-1 mRNA, regulated by GR was also significantly decreased in skin samples treated with CpdA. Our results suggest that CpdA is able to inhibit GR transactivation and activate only some transrepression properties of GR.

The purpose of our study was to determine the inhibitory effect of combined phytochemicals on chemically induced murine skin tumorigenesis. Our hypothesis was that concurrent topical and dietary treatment with selected compounds would lead to more efficient prevention of skin cancer. We tested ellagic acid and calcium D-glucarate as components of diets, while resveratrol was applied topically; grape seed extract was applied topically or in the diet. The 4-week inflammatory-hyperplasia assay based on the 7,12-dimethylbenz[a]anthracene (DMBA)–induced skin carcinogenesis model in SENCAR mice was used. We have found that all the selected combinations caused a marked decrease of epidermal thickness compared with the DMBA-treated group and also with groups treated with a single compound and DMBA. All combinations of resveratrol with other compounds showed a synergistic effect on hyperplasia and Ha-ras mutations. Skin tissue of mice receiving the combinations showed decreased cell proliferation and Bcl2 expression; decreased p21, a regulator of cell cycle; and decreased marker of inflammation cyclooxygenase-2. All the selected combinations diminished the DMBA-induced mRNA expression of the CYP1B1 level, and also caused a marked decrease of proto-oncogenes c-jun and c-fos, components of transcription factor activator protein. In conclusion, all combinations showed either additive or synergistic effects and their joint actions allowed for decreasing the doses of the compounds. Especially, resveratrol combinations with ellagic acid, grape seed extract, and other phytochemicals are very potent inhibitors of skin tumorgenesis, based on the suppression of epidermal hyperplasia as well as on the modulation of intermediate biomarkers of cell proliferation, cell survival, inflammation, oncogene mutation, and apoptosis. Cancer Prev Res; 3(2); 170–8

The purpose of this study was to examine the effect of tricyclic antidepressant desipramine (DMI) on the growth inhibition and translocation of the glucocorticoid receptor (GR) from the cytoplasm to the nucleus in cancerous and noncancerous cell lines and the effect of DMI on GR-mediated transcription. Nontumorigenic, immortalized keratinocytes cell line (3PC), papilloma (MT1/2), and squamous cell carcinoma (Ca3/7) cell lines were initially used to study the cell growth inhibition by DMI. Although, the growth of all three cell lines was suppressed by DMI, it was more effective in Ca3/7 cells. Therefore, we next examined the effect of DMI on Ca3/7 cells, resistant to growth inhibition by the synthetic glucocorticoid fluocinolone acetonide (FA). DMI inhibited cell proliferation in a time-dependent manner. The translocation of GR was induced by FA alone, DMI alone, and combination of both agents. FA induced GR-mediated transcription in Ca3/7 cells transfected with a luciferase reporter gene under the control of glucocorticoid response element (GRE), but DMI alone did not affect GR-mediated transcription. However, DMI inhibited FA-induced, GR-mediated transcription when both agents were given together. Pretreatment with DMI followed by combination of DMI and FA decreased GR-mediated transcription more than pretreatment with FA. The expression of metallothionein-1 (Mt-1) gene, which is regulated by GR, was induced significantly by the combination of DMI and FA, and enhanced significantly by pretreatment with FA but not DMI. DMI is suggested to inhibit the growth of Ca3/7 cells and to affect GR-mediated transcription.

The effects of two cyclic nucleotide phosphodiesterase type 4 (PDE4) inhibitors on proliferation of cell lines representing different stages of mouse skin tumorigenesis were studied. Skin papillomas and carcinomas become resistant to the growth inhibition by glucocorticoids. Their control of cellular functions is mediated by a well-known transcription factor, glucocorticoid receptor. The primary aim of the present study was to determine whether the PDE4 inhibitors, that raise intracellular cAMP levels, can increase the sensitivity of mouse skin papillomas and carcinomas to the glucocorticoids. We sought to establish the effect of cAMP signaling on the glucocorticoid receptor function using well-known model representing non-tumorigenic keratinocyte cell line (3PC), papilloma (MT1/2) and squamous cell carcinoma cell line (Ca3/7). These cells were treated with the glucocorticoid fluocinolone acetonide (FA) alone or in concert with PDE4 inhibitors – rolipram or YM976. Results of our study revealed that both PDE4 inhibitors may increase the sensitivity of transformed cell lines to the growth inhibitory effect of FA. In the transformed cell lines, changes in the viability of cells were accompanied by an increase in mRNA level of two negative regulators of the cell cycle – p21 and p27 proteins. Co-treatment with PDE4 inhibitors and FA caused inhibition of an endogenous glucocorticoid-responsive gene (MT-1) expression. Thus, the PDE4 inhibitors exerted a differential effect on non-transformed and transformed keratinocytes and on glucocorticoid receptor signal transduction. These findings warrant further studies to clarify the mechanism by which PDE4 inhibitors modulate glucocorticoid receptor signal transduction in transformed cells.

The tomato microarray TOM1 offers the possibility to monitor the levels of several thousand transcripts in parallel. The microelements represented on this tomato microarray have been putatively assigned to unigenes, and organised in functional classes using the MapMan ontology (Thimm et al., 2004. Plant J. 37: 914-939). This ontology was initially developed for use with the Arabidopsis ATH1 array, has a low level of redundancy, and can be combined with the MapMan software to provide a biologically structured overview of changes of transcripts, metabolites and enzyme activities. Use of this application is illustrated using three case studies with published or novel TOM1 array data sets for Solanaceous species. Comparison of previously reported data on transcript levels in potato leaves in the middle of the day and the middle of the night identified coordinated changes in the levels of transcripts of genes involved in various metabolic pathways and cellular events. Comparison with diurnal changes of gene expression in Arabidopsis revealed common features, illustrating how MapMan can be used to compare responses in different organisms. Comparison of transcript levels in new experiments performed on the leaves of the cultivated tomato S. lycopersicum and the wild relative S. pennellii revealed a general decrease of levels of transcripts of genes involved in terpene and, phenylpropanoid metabolism as well as chorismate biosynthesis in the crop compared to the wild relative. This matches the recently reported decrease of the levels of secondary metabolites in the latter. In the third case study, new expression array data for two genotypes deficient in TCA cycle enzymes is analysed to show that these genotypes have elevated levels of transcripts associated with photosynthesis. This in part explains the previously documented enhanced rates of photosynthesis in these genotypes. Since the Solanaceous MapMan is intended to be a community resource it will be regularly updated on improvements in tomato gene annotation and transcript profiling resources.

Thaumatin represents a unique class of the sweet-tasting plant proteins. Transgenic cucumber (Cucumis sativus L.) plants with stable integrated constructs consisting of the cauliflower mosaic virus 35S promoter and thaumatin II cDNA were produced. Transformed cucumber plants were obtained using Agrobacterium tumefaciens, with one, two or five integration sites in diploid cucumber and with inheritance confirmed by a 3:1 Mendelian ratio and normal morphologies and viable seeds. Inter- and intra-transformant variabilities in the expression of the thaumatin II gene were observed. The variability was independent of integrated copy number of the T-DNA. Variation in thaumatin II protein accumulation levels in the ripe fruits and the lack of correlation between protein and mRNA levels were observed, suggesting that thaumatin may be controlled at the levels of both transcription and translation. Transgenic fruits accumulating thaumatin II protein exhibited sweet phenotype and positive correation between thaumatin accumulation levels and sweet taste intensity was noticed. Thaumatin II belongs to the pathogenesis-related (PR) proteins family. Some of the T2 progeny plants expressing thaumatin II protein did not exhibit tolerance for pathogenic fungus Pseudoperonospora cubensis. These results, together with previously reported results, suggest no relationship between transgenic protein levels and the increased tolerance phenotype.

Glucocorticoids (GCs) are very effective at preventing carcinogen- and tumor promoter-induced skin inflammation, hyperplasia, and mouse skin tumor formation. The effects of GCs are mediated by a well-known transcription factor, the glucocorticoid receptor (GR). GR acts via two different mechanisms: transcriptional regulation that requires DNA-binding (transactivation) and DNA binding-independent protein-protein interactions between GR and other transcription factors, such as nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1; transrepression). We hypothesize that the transrepression activities of the GR are sufficient to suppress skin tumor promotion. We obtained two GCs (RU24858 and RU24782) that have dissociated downstream effects and induce only transrepression activities of the GR in a number of systems. These compounds bind the GR with high affinity and repress AP-1 and NF-κB activities while showing a lack of GR transactivation. RU24858, RU24782, or control full GCs desoximetasone (DES) and fluocinolone acetonide (FA) were applied to the dorsal skin of SENCAR mice prior to application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), two times per week for 2 weeks. DES, FA and RU24858 reversed TPA-induced epidermal hyperplasia and proliferation, while RU24782 treatment had no effect on these markers of skin tumor promotion. All tested compounds decreased TPA-induced c-jun mRNA levels in skin. DES, FA, and RU24858, but not RU24782, were also able to reverse TPA-induced increases in the mRNA levels of COX-2 and iNOS. These findings show that RU24858 but not RU24782 reduced TPA-induced epidermal hyperplasia, proliferation, and inflammation, while both compounds reversed c-jun mRNA increases in the skin.

Background: The efficacy of tele health interventions for achieving comparable or improved clinical outcomes has not been established well. The objective of this systematic review was to assess the effectiveness of home tele health interventions for people with asthma. Methods: An electronic search was performed in three different databases (Medline, Embase and Cochrane Controlled Trials Register). English language articles were selected for inclusion if they met the following criteria: randomized controlled trial (RCT) comparing a receiving tele health care with receiving usual care, inclusion of patients with asthma of any level of severity, and evaluation of efficacy or quality of life. Results: A total of 24 articles met inclusion criteria and were assessed. The included studies investigated various types of telecommunications technology to support and deliver healthcare from a distance. Improvement in asthma symptoms, quality of life and self-care behaviors as well as reduction in hospitalizations and emergency department visits was observed in different studies. There was a high level of acceptance of using the tele health systems among both healthcare providers and individuals. However, no statistically significant difference between the groups was observed in most of included studies. Conclusions: Overall, home tele health interventions appear to enhance patient access to healthcare professionals. Tele health solutions for asthma care are feasible and well-accepted and increase self-management skills, but evidence for their effectiveness in improving clinical outcomes is not strong. More research is needed to assess the effects of the range of telemedicine technologies.

Carcinogen-mediated labilization of lysosomal enzymes such as β-glucuronidase (βG) is often associated with the general process of inflammation. Therefore, the primary goal of this study was to demonstrate that exposing the skin of SENCAR mice to the natural βG inhibitor D-glucaro-1,4-lactone (1,4-GL) and its precursor D-glucuronic acid-γ-lactone (GUL), prior to and during 7,12-dimethylbenz[α]anthracene (DMBA) treatment inhibits not only epidermal hyperplasia but also inflammation in the mouse skin complete carcinogenesis model, i.e., the 4-week inflammatory-hyperplasia assay. Topical administration of 1,4-GL or GUL prior to repetitive, high-dose DMBA treatment markedly and in a dose-related manner inhibited DMBA-induced epidermal hyperplasia (i.e., up to 57%). DMBA-mediated Ha-ras mutations in codon 61 were reduced by up to 78% by 1,4-GL. DMBA-induced inflammation, as measured by dermal leukocyte counts and immunologically, was inhibited by up to 37% by topical 1,4-GL but not by GUL. The inhibition of cellular proliferation and inflammation coincided with the inhibition of βG expression. Thus, the present study suggests that in the DMBA-induced complete skin carcinogenesis model, 1,4-GL when applied topically had both anti-proliferative properties as well as anti-inflammatory properties, whereas GUL had only anti-proliferative when applied topically. However, the number of inflammatory cells in the dermal portion of the skin of mice was significantly reduced by dietary treatment of GUL, whereas both topical and dietary treatments with 1,4-GL were very effective.

Overexposure of the skin to carcinogenic insults causes a variety of adverse effects, among them the development of skin carcinomas. Since there is a need to develop efficient chemopreventive agents based on nutrition, our goal was to determine antioxidant and anti-carcinogenic properties of grapes by evaluating grape powder developed by the California Table Grape Commission. In order to elucidate the mechanism(s) of action of grape powder, three of the major antioxidant components found in grapes-resveratrol, catechin, quercetin, and grape seed extract, containing a proanthocyanidin B-2-gallate-were evaluated for their abilities to inhibit oxidative stress and to protect the immune system. Tested antioxidants given topically and/or systemically strongly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced epidermal hyperplasia, proliferation, and inflammation. The hydroxylation of 2'-deoxyguanosine was markedly inhibited by topical and dietary administration of test variables, i.e., by approximately 40-70%. Simultaneous dietary and topical treatment with antioxidants reduced these biomarkers, showing strong additive and in some combinations synergistic effects. DMBA-mediated Ha-ras mutations in codon 61 were reduced by up to 50% with topical applications, but much higher inhibition was observed in mice treated with different combinations. The results of the present study clearly show impressive effects of combined topical and dietary treatments with above grape-derived antioxidants.