The hippocampus (HPC) is essential for navigation and memory, tracking environmental continuity and change, including navigation relative to moving targets. CA1 ensembles expressing immediate-early gene (IEG) Arc and Homer1a RNA are contextually specific. While IEG expression correlates with HPC-dependent task demands, the effects of behavioral demands on IEG-expressing ensembles remain unclear. In three experiments, we investigated the effects of context switch, sustained presence, and task demands on dorso-proximal CA1 IEG+ ensembles in rats. Experiment 1 showed that the size of IEG+ (Arc, Homer1a RNA) ensembles dropped to baseline during uninterrupted 30-min exploration, reflecting familiarization, unless a context switch was present. Context-specificity of the ensembles depended on both environment identity and timing of the context switch. Experiment 2 found no effect of HPC-dependent mobile robot avoidance or HPC-independent avoidance of a stationary robot on IEG+ ensembles beyond mere exploration. Experiment 3 replicated these findings for c-Fos protein. The data suggest that IEG+ ensembles are driven by a context switch and shrink over time during sustained presence in the same environment. We found no evidence of task demands or their change affecting the size, stability over time, or task-specificity of IEG+ ensembles. These results shed light on the temporal dynamics of CA1 IEG+ ensembles, and their control by contextual and behavioral factors.
- MeSH
- Behavior, Animal physiology MeSH
- Cytoskeletal Proteins genetics metabolism MeSH
- CA1 Region, Hippocampal * metabolism physiology MeSH
- Homer Scaffolding Proteins * metabolism genetics MeSH
- Rats MeSH
- Genes, Immediate-Early * physiology MeSH
- Rats, Long-Evans * MeSH
- Nerve Tissue Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Antagonistic activity of brain networks likely plays a fundamental role in how the brain optimizes its performance by efficient allocation of computational resources. A prominent example involves externally/internally oriented attention tasks, implicating two anticorrelated, intrinsic brain networks: the default mode network (DMN) and the dorsal attention network (DAN). To elucidate electrophysiological underpinnings and causal interplay during attention switching, we recorded intracranial EEG (iEEG) from 25 epilepsy patients with electrode contacts localized in the DMN and DAN. We show antagonistic network dynamics of activation-related changes in high-frequency (> 50 Hz) and low-frequency (< 30 Hz) power. The temporal profile of information flow between the networks estimated by functional connectivity suggests that the activated network inhibits the other one, gating its activity by increasing the amplitude of the low-frequency oscillations. Insights about inter-network communication may have profound implications for various brain disorders in which these dynamics are compromised.
- MeSH
- Adult MeSH
- Electroencephalography MeSH
- Electrophysiological Phenomena MeSH
- Epilepsy physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Brain * physiology physiopathology MeSH
- Nerve Net * physiology MeSH
- Attention * physiology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). METHODS: Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. RESULTS: Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score ≥2.1 and failed ≥2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. CONCLUSIONS: The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.
- MeSH
- Analgesics therapeutic use MeSH
- Spondylitis, Ankylosing * drug therapy MeSH
- Anti-Inflammatory Agents, Non-Steroidal therapeutic use MeSH
- Antirheumatic Agents * therapeutic use MeSH
- Humans MeSH
- Spondylarthritis * drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Schizophrenia research has increased in recent decades and focused more on its neural basis. Decision-making and cognitive flexibility are the main cognitive functions that are impaired and considered schizophrenia endophenotypes. Cognitive impairment was recently connected with altered functions of N-methyl-d-aspartate (NMDAR) glutamatergic receptors, which increased cortical activity. Selective NMDAR antagonists, such as MK-801, have been used to model cognitive inflexibility in schizophrenia. Decreased GABAergic inhibitory activity has been shown elsewhere with enhanced cortical activity. This imbalance in the excitatory/inhibitory may reduce the entrainment of prefrontal gamma and hippocampal theta rhythms and result in gamma/theta band de-synchronization. The current study established an acute MK-801 administration model of schizophrenia-like cognitive inflexibility in rats and used the attentional set-shifting task in which rats learned to switch/reverse the relevant rule. During the task, we used in vivo optogenetic stimulations of parvalbumin-positive interneurons at specific light pulses in the prefrontal cortex and ventral hippocampus. The first experiments showed that acute dizocilpine in rats produced schizophrenia-like cognitive inflexibility. The second set of experiments demonstrated that specific optogenetic stimulation at specific frequencies of parvalbumin-positive interneurons in the prefrontal cortex and ventral hippocampus rescued the cognitive flexibility rats that received acute MK-801. These findings advance our knowledge of the pivotal role of parvalbumin interneurons in schizophrenia-like cognitive impairment and may guide further research on this severe psychiatric disorder.
- MeSH
- Dizocilpine Maleate * pharmacology MeSH
- Hippocampus metabolism MeSH
- Interneurons metabolism MeSH
- Cognition MeSH
- Rats MeSH
- Optogenetics MeSH
- Parvalbumins metabolism MeSH
- Prefrontal Cortex metabolism MeSH
- Receptors, N-Methyl-D-Aspartate metabolism MeSH
- Schizophrenia * MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Recently nanoparticle enhanced Laser Induced Breakdown Spectroscopy (NELIBS) is getting a growing interest as an effective alternative method for improving the analytical performance of LIBS. On the other hand, the plasmonic effect during laser ablation can be used for a different task rather than elemental analysis. In this paper, the dependence of NELIBS emission signal enhancement on nanoparticle-protein solutions dried on a reference substrate (metallic titanium) was investigated. Two proteins were studied: Human Serum Albumin (HSA) and Cytochrome C (CytC). Both proteins have a strong affinity for the gold nanoparticles (AuNPs) due to the bonding between the single free exterior thiol (associated with a cysteine residue) and the gold surface to form a stable protein corona. Then, since the protein sizes are vastly different, a different number of protein units is needed to cover AuNP surface to form a protein layer. The NP-protein solution was dropped and dried onto the titanium substrate. Then the NELIBS signal enhancement of Ti emission lines was correlated to the solution characteristics as determined with Dynamic Light Scattering (DLS), Surface Plasmon Resonance (SPR) spectroscopy and Laser Doppler Electrophoresis (LDE) for ζ-potential determination. Moreover, the dried solutions were studied with TEM (Transmission Electron Microscopy) for the inspection of the inter-particle distance. The structural effect of the NP-protein conjugates on the NELIBS signal reveals that NELIBS can be used to determine the number of protein units required to form the nanoparticle-protein corona with good accuracy. Although the investigated NP-protein systems are simple cases in biological applications, this work demonstrates, for the first time, a different use of NELIBS that is beyond elemental analysis and it opens the way for sensing the nanoparticle protein corona.
- MeSH
- Metal Nanoparticles * MeSH
- Lasers MeSH
- Humans MeSH
- Protein Corona * MeSH
- Spectrum Analysis MeSH
- Gold MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Cílem této studie bylo představit české veřejnosti návrh clusteringu a switchingu v testu verbální fluence (VF), adaptovat vybrané klasifikace do českého prostředí a posoudit jejich relevanci. Článek se zabývá hodnocením uspořádání slov do celků (tzv. clusterů) a plynulosti přepínání mezi nimi (switching). Tento v zahraničí rozšířený přístup k analýze protokolů VF nebyl doposud v češtině systematizován. Čtenář je seznámen s teoretickým pozadím hodnocení clusterů a switchů ve fonologické verzi (PVF) i kategoriální verzi (SVF) a některými vybranými klasifikacemi – např. Troyer et al. (1997), Abwender et al. (2001), Libon et al. (2009) či Tallberg et al. (2011). Klasifikace Troyerové et al. (1997), která je celosvětově nejcitovanější, byla převzata a autoři článku se vyjádřili k jednotlivým pravidlům z pohledu českého jazyka i kulturního prostředí (Studie 1). Ve Studii 2 byly u deseti vybraných protokolů dvěma posuzovateli oskórovány fonematické clustery v PVF a sémantické clustery v SVF. Vypočtená shoda posuzovatelů ukázala v obou případech na dobrou až výbornou shodu. Jedná se o velmi slibný, nicméně stále teoretický koncept, jehož aplikace do praxe si žádá další zkoumání.
The main goal of this study was to introduce the evaluation procedure in Verbal fluency task – clustering and switching – to the Czech public, to adapt this procedure to the Czech language and to judge its relevance. The review focuses on the way of arranging the words into the clusters (so called clustering) and switching between them. This procedure is extended in foreign research but it has not yet been systematically adapted in the Czech context. In the article the theoretical background of clustering and switching in phonological verbal fluency (PVF) and also in semantic verbal fluency (SVF) is introduced and few classifications of clustering are described – e.g. Troyer et al. (1997), Abwender et al. (2001), Libon et al. (2009) and Tallberg et al. (2011). In Study 1, the most cited classification by Troyer et al. (1997) is adapted to the Czech language and the differences between the original version and Czech adaptation are discussed. In Study 2, ten protocols were rated by two raters and the inter-rater reliability was calculated. The value of Cohen,s kappa showed moderate to excellent agreement. This approach is very promising but it requires further research.
OBJECTIVE: To update the 2012 EULAR/ERA-EDTA recommendations for the management of lupus nephritis (LN). METHODS: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. RESULTS: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria <0.5-0.7 g/24 hours with (near-)normal glomerular filtration rate) by 12 months, but this can be extended in patients with baseline nephrotic-range proteinuria. Hydroxychloroquine is recommended with regular ophthalmological monitoring. In active proliferative LN, initial (induction) treatment with mycophenolate mofetil (MMF 2-3 g/day or mycophenolic acid (MPA) at equivalent dose) or low-dose intravenous cyclophosphamide (CY; 500 mg × 6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. MMF/CNI (especially tacrolimus) combination and high-dose CY are alternatives, for patients with nephrotic-range proteinuria and adverse prognostic factors. Subsequent long-term maintenance treatment with MMF or azathioprine should follow, with no or low-dose (<7.5 mg/day) glucocorticoids. The choice of agent depends on the initial regimen and plans for pregnancy. In non-responding disease, switch of induction regimens or rituximab are recommended. In pure membranous LN with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite renin-angiotensin-aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. CONCLUSIONS: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.
- MeSH
- Antirheumatic Agents therapeutic use MeSH
- Azathioprine therapeutic use MeSH
- Kidney Failure, Chronic etiology therapy MeSH
- Glucocorticoids therapeutic use MeSH
- Glomerular Filtration Rate MeSH
- Hydroxychloroquine therapeutic use MeSH
- Immunosuppressive Agents therapeutic use MeSH
- Calcineurin Inhibitors therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Mycophenolic Acid therapeutic use MeSH
- Humans MeSH
- Lupus Nephritis complications drug therapy pathology physiopathology MeSH
- Proteinuria etiology therapy MeSH
- Societies, Medical * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Practice Guideline MeSH
- Geographicals
- Europe MeSH
Cieľom štúdie je overiť reliabilitu, konvergentnú a divergentnú validitu Pamäťového testu pre bilingválnu detskú populáciu s materinským jazykom maďarským (PTB). Štruktúra PTB a jeho administrácia vychádza z Pamäťového testu učenia, nie je však jeho prekladom. Obsahová validita testu bola overená expertmi. Výskumný súbor tvorilo 224 respondentov, 118 dievčat a 106 chlapcov s priemerným vekom 11,84 (SD = 1,93). Každý respondent bol testovaný individuálne nasledujúcimi výskumnými metódami: PTB, Re produkcia bezvýznamných slov (RBS) a Wechslerova inteligenčná škála (WISC IV). Reliabilita PTB vyjadrená koreláciou paralelných foriem testu je 0,79, hodnota Cronbachovej alphy je 0,7–0,77. Korelácia výkonu v PTB a RBS odrážajúca konvergentnú validitu je slabá až stredne silná. Medzi indexmi verbálneho porozumenia a pracovnej pamäti z WISC IV a PTB sa potvrdila iba veľmi slabá až slabá korelácia, poukazujúca na divergentnú validitu PTB. Reliabilita testu je dostatočná, kým konvergentná a divergentná validita čaká na opätovné overenie. Výsledky práce môžu tvoriť východiskový bod pre doplňujúce psychometrické postupy.
Objective: Despite the broad scientific interest in bilingual advantage/disadvantage in the domain of cognitive and executive functions, little attention is paid to the actual language of applied psychodiagnostic tools. However, the performance of bilingual clients may be lessened by the absence of match between their first language and the language of the psychological questionnaire. When bilinguals take verbal working memory tests in their second language, the operation of phonological loop is paired with language code switching, making the performance more difficult. In Slovakia, an estimated 9% of the population claim Hungarian to be their first language; however, adequate psychodiagnostic tools are not available for their psychological evaluation. The aim of the present study was to prepare a Memory test for bilingual children with Hungarian as their first language (PTB) and to verify its reliability, convergent and divergent validity.Methods: The PTB resembles the Auditory Verbal Learning test (Pamäťový test učenia) as it consists of 15 words for memorizing (set A) and 15 words for interference as well as 15 words for retest (set B). One has to memorize and recall set A for five times after it is read out by the administrator, then memorize and recall the words for inference (after being read out) and for the sixth time recall the words from set A without them being read out. Finally, after 30 minutes, one has to recall once again the words from set A without them being previously read out. The PTB is not a translated form of the Auditory Verbal Learning test. It consists of new, updated words frequently used by Slovak citizens with Hungarian as their first language in a specific geographical region. The content validity of the PTB was verified by experts. The research group comprised 224 respondents, 118 girls and 106 boys, with the average age of 11,84 (SD = 1,93). Each respondent was tested individually by the following research methods: the PTB, reproduction of meaningless words, and the Wechsler intelligence scale for children (WISC IV) in Hungarian. The reproduc tion of meaningless words requires the activity of phonological loop, being active also during memory tasks similar to the PTB. For this reason, a comparison of results obtained by these two methods can clarify the convergent validity of the PTB. While declaring discri minant validity we compared the achievement in the PTB with the verbal comprehension index and the working memory index from WISC IV. According to the factor analysis, verbal subtests such as similarities, vocabulary, information and digit span loaded a different factor from The Rey Auditory Verbal Learning Test that is very similar to the PTB.Results: The reliability of the PTB as a correlation between the two forms of tests is 0,79 (p=0,01), Cronbach’s alpha for set A is 0,7, while it is 0,77 for set B. Also, weak to moderate positive correlations (0,21–0,44; p=0,01) were found between the PTB and the reproduction of meaningless words; weak positive correlations were found between the PTB and the verbal comprehension index (0,06–0,18; p=0,01) and the working memory index (0,08 0,29; p=0,01).Discussion and conclusion: The obtained results of reliability are comparable to the reliability of The Rey Auditory Verbal Learning Test (0,6–0,77) and are considered sufficient. The rates of the other reliability indicators are acceptable; however, they are little lower than those obtained during The Rey Auditory Verbal Learning Test. The rate of correlation between the PTB and the reproduction of meaningless words indicating conver gent validity is acceptable as a significant difference being detected between the memorizing capacity and the accuracy of meaningful and meaningless words. Lack of correlation between the PTB and the verbal comprehension index is in line with the factor analysis of Ryan, Rosenberg and Mittenberg (1984), and thus ratifies the discriminant validity of the PTB. The weak correlation between the PTB and the working memory index may be unexpected as both measure hypothetically the same domains. However, in a spectre of research results, the ability of memorizing a digit span may differ from the ability of memorizing verbal spans. Indicators of reliability, convergent and divergent validity of the PTB are sufficient but further reassessment is needed.
Mounting an immune response is an energy-consuming process. Activating immune functions requires the synthesis of many new molecules and the undertaking of numerous cellular tasks and it must happen rapidly. Therefore, immune cells undergo a metabolic switch, which enables the rapid production of ATP and new biomolecules. Such metabolism is very nutrient-demanding, especially of glucose and glutamine, and thus the immune response is associated with a systemic metabolic switch, redirecting nutrient flow towards immunity and away from storage and consumption by non-immune processes. The immune system during its activation becomes privileged in terms of using organismal resources and the activated immune cells usurp nutrients by producing signals which reduce the metabolism of non-immune tissues. The insect fat body plays a dual role in which it is both a metabolic organ, storing energy and providing energy to the rest of the organism, but also an organ important for humoral immunity. Therefore, the internal switch from anabolism to the production of antimicrobial peptides occurs in the fat body during infection. The mechanisms regulating metabolism during the immune response ensure adequate energy for an effective response (resistance) but they must be properly regulated because energy is not unlimited and the energy needs of the immune system thus interfere with the needs of other physiological traits. If not properly regulated, the immune response may in the end decrease fitness via decreasing disease tolerance.
- MeSH
- Energy Metabolism immunology MeSH
- Insecta immunology metabolism MeSH
- Immunity, Innate * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The effects of high-dose ethanol intoxication on cognitive flexibility processes are not well understood, and processes related to hangover after intoxication have remained even more elusive. Similarly, it is unknown in how far the complexity of cognitive flexibility processes is affected by intoxication and hangover effects. We performed a neurophysiological study applying high density electroencephalography (EEG) recording to analyze event-related potentials (ERPs) and perform source localization in a task switching paradigm which varied the complexity of task switching by means of memory demands. The results show that high-dose ethanol intoxication only affects task switching (i.e. cognitive flexibility processes) when memory processes are required to control task switching mechanisms, suggesting that even high doses of ethanol compromise cognitive processes when they are highly demanding. The EEG and source localization data show that these effects unfold by modulating response selection processes in the anterior cingulate cortex. Perceptual and attentional selection processes as well as working memory processes were only unspecifically modulated. In all subprocesses examined, there were no differences between the sober and hangover states, thus suggesting a fast recovery of cognitive flexibility after high-dose ethanol intoxication. We assume that the gamma-aminobutyric acid (GABAergic) system accounts for the observed effects, while they can hardly be explained by the dopaminergic system.
- MeSH
- Gyrus Cinguli physiology physiopathology MeSH
- Breath Tests MeSH
- Adult MeSH
- Electroencephalography MeSH
- Evoked Potentials physiology MeSH
- gamma-Aminobutyric Acid MeSH
- Cognition physiology MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Brain physiology physiopathology MeSH
- Synaptic Transmission physiology MeSH
- Alcoholic Intoxication physiopathology psychology MeSH
- Task Performance and Analysis MeSH
- Attention MeSH
- Reaction Time MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH