First Insight into the Degradome of Aspergillus ochraceus: Novel Secreted Peptidases and Their Inhibitors.

Aspergillus fungi constitute a pivotal element within ecosystems, serving as both contributors of biologically active compounds and harboring the potential to cause various diseases across living organisms. The organism's proteolytic enzyme complex, termed the degradome, acts as an intermediary in its dynamic interaction with the surrounding environment. Using techniques such as genome and transcriptome sequencing, alongside protein prediction methodologies, we identified putative extracellular peptidases within Aspergillus ochraceus VKM-F4104D. Following manual annotation procedures, a total of 11 aspartic, 2 cysteine, 2 glutamic, 21 serine, 1 threonine, and 21 metallopeptidases were attributed to the extracellular degradome of A. ochraceus VKM-F4104D. Among them are enzymes with promising applications in biotechnology, potential targets and agents for antifungal therapy, and microbial antagonism factors. Thus, additional functionalities of the extracellular degradome, extending beyond mere protein substrate digestion for nutritional purposes, were demonstrated.

KRAS, NRAS, BRAF, HER2 and MSI Status in a Large Consecutive Series of Colorectal Carcinomas.

This study aimed to analyze clinical and regional factors influencing the distribution of actionable genetic alterations in a large consecutive series of colorectal carcinomas (CRCs). KRAS, NRAS and BRAF mutations, HER2 amplification and overexpression, and microsatellite instability (MSI) were tested in 8355 CRC samples. KRAS mutations were detected in 4137/8355 (49.5%) CRCs, with 3913 belonging to 10 common substitutions affecting codons 12/13/61/146, 174 being represented by 21 rare hot-spot variants, and 35 located outside the "hot" codons. KRAS Q61K substitution, which leads to the aberrant splicing of the gene, was accompanied by the second function-rescuing mutation in all 19 tumors analyzed. NRAS mutations were detected in 389/8355 (4.7%) CRCs (379 hot-spot and 10 non-hot-spot substitutions). BRAF mutations were identified in 556/8355 (6.7%) CRCs (codon 600: 510; codons 594-596: 38; codons 597-602: 8). The frequency of HER2 activation and MSI was 99/8008 (1.2%) and 432/8355 (5.2%), respectively. Some of the above events demonstrated differences in distribution according to patients' age and gender. In contrast to other genetic alterations, BRAF mutation frequencies were subject to geographic variation, with a relatively low incidence in areas with an apparently warmer climate (83/1726 (4.8%) in Southern Russia and North Caucasus vs. 473/6629 (7.1%) in other regions of Russia, p = 0.0007). The simultaneous presence of two drug targets, BRAF mutation and MSI, was observed in 117/8355 cases (1.4%). Combined alterations of two driver genes were detected in 28/8355 (0.3%) tumors (KRAS/NRAS: 8; KRAS/BRAF: 4; KRAS/HER2: 12; NRAS/HER2: 4). This study demonstrates that a substantial portion of RAS alterations is represented by atypical mutations, KRAS Q61K substitution is always accompanied by the second gene-rescuing mutation, BRAF mutation frequency is a subject to geographical variations, and a small fraction of CRCs has simultaneous alterations in more than one driver gene.

Cost-Efficient Detection of NTRK1/2/3 Gene Fusions: Single-Center Analysis of 8075 Tumor Samples.

The majority of NTRK1, NTRK2, and NTRK3 rearrangements result in increased expression of the kinase portion of the involved gene due to its fusion to an actively transcribed gene partner. Consequently, the analysis of 5'/3'-end expression imbalances is potentially capable of detecting the entire spectrum of NTRK gene fusions. Archival tumor specimens obtained from 8075 patients were subjected to manual dissection of tumor cells, DNA/RNA isolation, and cDNA synthesis. The 5'/3'-end expression imbalances in NTRK genes were analyzed by real-time PCR. Further identification of gene rearrangements was performed by variant-specific PCR for 44 common NTRK fusions, and, whenever necessary, by RNA-based next-generation sequencing (NGS). cDNA of sufficient quality was obtained in 7424/8075 (91.9%) tumors. NTRK rearrangements were detected in 7/6436 (0.1%) lung carcinomas, 11/137 (8.0%) pediatric tumors, and 13/851 (1.5%) adult non-lung malignancies. The highest incidence of NTRK translocations was observed in pediatric sarcomas (7/39, 17.9%). Increased frequency of NTRK fusions was seen in microsatellite-unstable colorectal tumors (6/48, 12.5%), salivary gland carcinomas (5/93, 5.4%), and sarcomas (7/143, 4.9%). None of the 1293 lung carcinomas with driver alterations in EGFR/ALK/ROS1/RET/MET oncogenes had NTRK 5'/3'-end expression imbalances. Variant-specific PCR was performed for 744 tumors with a normal 5'/3'-end expression ratio: there were no rearrangements in 172 EGFR/ALK/ROS1/RET/MET-negative lung cancers and 125 pediatric tumors, while NTRK3 fusions were detected in 2/447 (0.5%) non-lung adult malignancies. In conclusion, this study describes a diagnostic pipeline that can be used as a cost-efficient alternative to conventional methods of NTRK1-3 analysis.

Rapid and Cost-Efficient Detection of RET Rearrangements in a Large Consecutive Series of Lung Carcinomas.

RET-kinase-activating gene rearrangements occur in approximately 1-2% of non-small-cell lung carcinomas (NSCLCs). Their reliable detection requires next-generation sequencing (NGS), while conventional methods, such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) or variant-specific PCR, have significant limitations. We developed an assay that compares the level of RNA transcripts corresponding to 5'- and 3'-end portions of the RET gene; this test relies on the fact that RET translocations result in the upregulation of the kinase domain of the gene and, therefore, the 5'/3'-end expression imbalance. The present study included 16,106 consecutive NSCLC patients, 14,449 (89.7%) of whom passed cDNA quality control. The 5'/3'-end unbalanced RET expression was observed in 184 (1.3%) tumors, 169 of which had a sufficient amount of material for the identification of translocation variants. Variant-specific PCR revealed RET rearrangements in 155/169 (91.7%) tumors. RNA quality was sufficient for RNA-based NGS in 10 cases, 8 of which carried exceptionally rare or novel (HOOK1::RET and ZC3H7A::RET) RET translocations. We also applied variant-specific PCR for eight common RET rearrangements in 4680 tumors, which emerged negative upon the 5'/3'-end unbalanced expression test; 33 (0.7%) of these NSCLCs showed RET fusion. While the combination of the analysis of 5'/3'-end RET expression imbalance and variant-specific PCR allowed identification of RET translocations in approximately 2% of consecutive NSCLCs, this estimate approached 120/2361 (5.1%) in EGFR/KRAS/ALK/ROS1/BRAF/MET-negative carcinomas. RET-rearranged tumors obtained from females, but not males, had a decreased level of expression of thymidylate synthase (p < 0.00001), which is a known predictive marker of the efficacy of pemetrexed. The results of our study provide a viable alternative for RET testing in facilities that do not have access to NGS due to cost or technical limitations.

New approach to soil management focusing on soil health and air quality: one earth one life (critical review).

Soil plays a key role in ecosphere and air quality regulation. Obsolete environmental technologies lead to soil quality loss, air, water, and land systems pollution. Pedosphere and plants are intertwined with the air quality. Ionized O2 is capable to intensify atmosphere turbulence, providing particulate matter (PM2.5) coalescence and dry deposition. Addressing environmental quality, a Biogeosystem Technique (BGT*) heuristic transcendental (nonstandard and not direct imitation of nature) methodology has been developed. A BGT* main focus is an enrichment of Earth's biogeochemical cycles through land use and air cleaning. An intra-soil processing, which provides the soil multilevel architecture, is one of the BGT* ingredients. A next BGT* implementation is intra-soil pulse continuously discrete watering for optimal soil water regime and freshwater saving up to 10-20 times. The BGT* comprises intra-soil dispersed environmentally safe recycling of the PM sediments, heavy metals (HMs) and other pollutants, controlling biofilm-mediated microbial community interactions in the soil. This provides abundant biogeochemical cycle formation and better functioning of the humic substances, biological preparation, and microbial biofilms as a soil-biological starter, ensuring priority plants and trees nutrition, growth and resistance to phytopathogens. A higher underground and aboveground soil biological product increases a reversible C biological sequestration from the atmosphere. An additional light O2 ions photosynthetic production ensures a PM2.5 and PM0.1 coalescence and strengthens an intra-soil transformation of PM sediments into nutrients and improves atmosphere quality. The BGT* provides PM and HMs intra-soil passivation, increases soil biological productivity, stabilizes a climate system of the earth and promotes a green circular economy.

Do sparse brain activity patterns underlie human cognition?

Accumulating multivariate pattern analysis (MVPA) results from fMRI studies suggest that information is represented in fingerprint patterns of activations and deactivations during perception, emotions, and cognition. We postulate that these fingerprint patterns might reflect neuronal-population level sparse code documented in two-photon calcium imaging studies in animal models, i.e., information represented in specific and reproducible ensembles of a few percent of active neurons amidst widespread inhibition in neural populations. We suggest that such representations constitute a fundamental organizational principle via interacting across multiple levels of brain hierarchy, thus giving rise to perception, emotions, and cognition.

Action in auctions: neural and computational mechanisms of bidding behaviour.

Competition for resources is a fundamental characteristic of evolution. Auctions have been widely used to model competition of individuals for resources, and bidding behaviour plays a major role in social competition. Yet, how humans learn to bid efficiently remains an open question. We used model-based neuroimaging to investigate the neural mechanisms of bidding behaviour under different types of competition. Twenty-seven subjects (nine male) played a prototypical bidding game: a double action, with three "market" types, which differed in the number of competitors. We compared different computational learning models of bidding: directional learning models (DL), where the model bid is "nudged" depending on whether it was accepted or rejected, along with standard reinforcement learning models (RL). We found that DL fit the behaviour best and resulted in higher payoffs. We found the binary learning signal associated with DL to be represented by neural activity in the striatum distinctly posterior to a weaker reward prediction error signal. We posited that DL is an efficient heuristic for valuation when the action (bid) space is continuous. Indeed, we found that the posterior parietal cortex represents the continuous action space of the task, and the frontopolar prefrontal cortex distinguishes among conditions of social competition. Based on our findings, we proposed a conceptual model that accounts for a sequence of processes that are required to perform successful and flexible bidding under different types of competition.

Neural Mechanisms of Cognitive Dissonance (Revised): An EEG Study.

Cognitive dissonance theory suggests that our preferences are modulated by the mere act of choosing. A choice between two similarly valued alternatives creates psychological tension (cognitive dissonance) that is reduced by a postdecisional reevaluation of the alternatives. We measured EEG of human subjects during rest and free-choice paradigm. Our study demonstrates that choices associated with stronger cognitive dissonance trigger a larger negative frontocentral evoked response similar to error-related negativity, which has in turn been implicated in general performance monitoring. Furthermore, the amplitude of the evoked response is correlated with the reevaluation of the alternatives. We also found a link between individual neural dynamics (long-range temporal correlations) of the frontocentral cortices during rest and follow-up neural and behavioral effects of cognitive dissonance. Individuals with stronger resting-state long-range temporal correlations demonstrated a greater postdecisional reevaluation of the alternatives and larger evoked brain responses associated with stronger cognitive dissonance. Thus, our results suggest that cognitive dissonance is reflected in both resting-state and choice-related activity of the prefrontal cortex as part of the general performance-monitoring circuitry.SIGNIFICANCE STATEMENT Contrary to traditional decision theory, behavioral studies repeatedly demonstrate that our preferences are modulated by the mere act of choosing. Difficult choices generate psychological (cognitive) dissonance, which is reduced by the postdecisional devaluation of unchosen options. We found that decisions associated with a higher level of cognitive dissonance elicited a stronger negative frontocentral deflection that peaked ∼60 ms after the response. This activity shares similar spatial and temporal features as error-related negativity, the electrophysiological correlate of performance monitoring. Furthermore, the frontocentral resting-state activity predicted the individual magnitude of preference change and the strength of cognitive dissonance-related neural activity.

Correlation of cue-locked FRN and feedback-locked FRN in the auditory monetary incentive delay task.

Reflecting the discrepancy between received and predicted outcomes, the reward prediction error (RPE) plays an important role in learning in a dynamic environment. A number of studies suggested that the feedback-related negativity (FRN) component of an event-related potential, known to be associated with unexpected outcomes, encodes RPEs. While FRN was clearly shown to be sensitive to the probability of outcomes, the effect of outcome magnitude on FRN remains to be further clarified. In studies on the neural underpinnings of reward anticipation and outcome evaluation, a monetary incentive delay (MID) task proved to be particularly useful. We investigated whether feedback-locked FRN and cue-locked dN200 responses recorded during an auditory MID task were sensitive to the probability and magnitude of outcomes. The cue-locked dN200 is associated with the update of information about the magnitude of prospective outcomes. Overall, we showed that feedback-locked FRN was modulated by both the magnitude and the probability of outcomes during an auditory version of MID task, whereas no such effect was found for cue-locked dN200. Furthermore, the cue-locked dN200, which is associated with the update of information about the magnitude of prospective outcomes, correlated with the standard feedback-locked FRN, which is associated with a negative RPE. These results further expand our knowledge on the interplay between the processing of predictive cues that forecast future outcomes and the subsequent revision of these predictions during outcome delivery.

The linker region plays a regulatory role in assembly and activity of the Vps4 AAA ATPase.

The AAA-type ATPase Vps4 functions with components of the ESCRT (endosomal sorting complex required for transport) machinery in membrane fission events that are essential for endosomal maturation, cytokinesis, and the formation of retroviruses. A key step in these events is the assembly of monomeric Vps4 into the active ATPase complex, which is aided in part by binding of Vps4 via its N-terminal MIT (microtubule interacting and trafficking) domain to its substrate ESCRT-III. We found that the 40-amino acid linker region between the MIT and the ATPase domain of Vps4 is not required for proper function but plays a role in regulating Vps4 assembly and ATPase activity. Deletion of the linker is expected to bring the MIT domains into close proximity to the central pore of the Vps4 complex. We propose that this localization of the MIT domain in linker-deleted Vps4 mimics a repositioning of the MIT domain normally caused by binding of Vps4 to ESCRT-III. This structure would allow the Vps4 complex to engage ESCRT-III subunits with both the pore and the MIT domain simultaneously, which might be essential for the ATP-driven disassembly of ESCRT-III.

Evaluating the Influence of Musical and Monetary Rewards on Decision Making through Computational Modelling.

A central question in behavioural neuroscience is how different rewards modulate learning. While the role of monetary rewards is well-studied in decision-making research, the influence of abstract rewards like music remains poorly understood. This study investigated the dissociable effects of these two reward types on decision making. Forty participants completed two decision-making tasks, each characterised by probabilistic associations between stimuli and rewards, with probabilities changing over time to reflect environmental volatility. In each task, choices were reinforced either by monetary outcomes (win/lose) or by the endings of musical melodies (consonant/dissonant). We applied the Hierarchical Gaussian Filter, a validated hierarchical Bayesian framework, to model learning under these two conditions. Bayesian statistics provided evidence for similar learning patterns across both reward types, suggesting individuals' similar adaptability. However, within the musical task, individual preferences for consonance over dissonance explained some aspects of learning. Specifically, correlation analyses indicated that participants more tolerant of dissonance behaved more stochastically in their belief-to-response mappings and were less likely to choose the response associated with the current prediction for a consonant ending, driven by higher volatility estimates. By contrast, participants averse to dissonance showed increased tonic volatility, leading to larger updates in reward tendency beliefs.

The relationship between charitable giving and emotional facial expressions: Results from affective computing.

This study investigated the relationship between emotional states (valence, arousal, and six basic emotions) and donation size in pet charities, and it compared the effectiveness of affective computing and emotion self-report methods in assessing attractiveness. Using FaceReader software and self-report, we measured the emotional states of participants (N = 45) during the donation task. The results showed that sadness, happiness, and anger were significantly related to donation size. Sadness and anger increased donations, whereas happiness decreased them. Arousal was not significantly correlated with the willingness to donate. These results are supported by both methods, whereas the self-reported data regarding the association of surprise, fear, and disgust with donation size are inconclusive. Thus, unpleasant emotions increase donation size, and combining affective computing with self-reported data improves the prediction of the effectiveness of a charity appeal. This study contributes to the understanding of the relationship between emotions and charitable behavior toward pet charities and evaluates the effectiveness of marketing mix elements using affective computing. The limitations include the laboratory setting for this experiment and the lack of measurement of prolonged and repeated exposure to unpleasant charity appeals.

Regionally specific cortical lateralization of abstract and concrete verb processing: Magnetic mismatch negativity study.

The neural underpinnings of processing concrete and abstract semantics remain poorly understood. Previous fMRI studies have shown that multimodal and amodal neural networks respond differentially to different semantic types; importantly, abstract semantics activates more left-lateralized networks, as opposed to more bilateral activity for concrete words. Due to the lack of temporal resolution, these fMRI results do not allow to easily separate language- and task-specific brain responses and to disentangle early processing stages from later post-comprehension phenomena. To tackle this, we used magnetoencephalography (MEG), a time-resolved neuroimaging technique, in combination with a task-free oddball mismatch negativity (MMN) paradigm, an established approach to tracking early automatic activation of word-specific memory traces in the brain. We recorded the magnetic MMN responses in 30 healthy adults to auditorily presented abstract and concrete action verbs to assess lateralization of word-specific lexico-semantic processing in a set of neocortical areas. We found that MMN responses to these stimuli showed different lateralization patterns of activity in the upper limb motor area (BA4) and parts of Broca's area (BA45/BA47) within ∼100-350 ms after the word disambiguation point. Importantly, the greater leftward response lateralization for abstract semantics was due to the lesser involvement of the right-hemispheric homologues, not increased left-hemispheric activity. These findings suggest differential region-specific involvement of bilateral sensorimotor systems already in the early automatic stages of processing abstract and concrete action semantics.

Response to trametinib, hydroxychloroquine, and bevacizumab in a young woman with NRAS-mutated metastatic intrahepatic cholangiocarcinoma: a case report.

Systemic chemotherapy is the main treatment option for patients with advanced intrahepatic cholangiocarcinoma (iCCA), however, its efficacy is limited. Herein, we report a young patient with NRAS-mutated chemoresistant metastatic iCCA, who received second-line therapy with a combination of trametinib (MEK1/2 inhibitor), hydroxychloroquine (autophagy inhibitor), and bevacizumab (angiogenesis inhibitor). A significant response was achieved during therapy, resulting in a 25% decrease in the size of tumor lesions after 2 months of treatment and an improvement in the patient's condition. The duration of this response was 4 months, but the patient died 10 months after the initiation of this triple therapy. This case report and the analysis of other available studies warrant further investigations on combined MEK and autophagy inhibition in RAS-mutated tumors.

Comparing experience- and description-based economic preferences across 11 countries.

Recent evidence indicates that reward value encoding in humans is highly context dependent, leading to suboptimal decisions in some cases, but whether this computational constraint on valuation is a shared feature of human cognition remains unknown. Here we studied the behaviour of n = 561 individuals from 11 countries of markedly different socioeconomic and cultural makeup. Our findings show that context sensitivity was present in all 11 countries. Suboptimal decisions generated by context manipulation were not explained by risk aversion, as estimated through a separate description-based choice task (that is, lotteries) consisting of matched decision offers. Conversely, risk aversion significantly differed across countries. Overall, our findings suggest that context-dependent reward value encoding is a feature of human cognition that remains consistently present across different countries, as opposed to description-based decision-making, which is more permeable to cultural factors.

Neuromodulation of choice-induced preference changes: the tDCS study of cognitive dissonance.

Introduction: Difficult choices between two equally attractive options result in a cognitive discrepancy between dissonant cognitions such as preferences and actions often followed by a sense of psychological discomfort known as cognitive dissonance. It can lead to changes in the desirability of options: the chosen option becomes more desirable, whereas the rejected option is devalued. Despite the ample experimental evidence to show this effect, the neural mechanisms and timing of such choice-induced preference changes are not fully understood. Methods: In this study, we used transcranial direct current stimulation (tDCS) to modulate the activity of the posterior medial frontal cortex (pMFC), which has been associated with conflict monitoring and choice-induced preference changes in neuroimaging studies. Prior to a revised version of Brehm's free-choice paradigm, participants in two experiments underwent cathodal (inhibitory) or anodal (excitatory) tDCS of the pMFC compared to sham (placebo) stimulation prior to the choice phase. Results: Our results showed that cathodal tDCS significantly decreased the choice-induced preference change relative to a sham, but only in direct comparisons of rejected options. No significant effect of anodal tDCS in comparison with sham was observed. Discussion: This study replicates the general behavioral effect of cognitive dissonance and provide partial support for the theory of the pMFC contribution to choice-related cognitive dissonance and subsequent preference changes, with possible limitations of an under-sampling for the obtained effect size and an asymmetry in the inhibitory-excitatory effects of non-invasive tDCS.

Neurochronometry of choice-induced preference changes: when do preferences actually change?

According to cognitive dissonance theory, a discrepancy between preferences and actions may lead to the revaluation of preferences, increasing preference for the chosen options and decreasing for the rejected options. This phenomenon is known as the spreading of alternatives (SoA), which results in a choice-induced preference change (CIPC). Previous neuroimaging studies have identified several brain regions that play a role in cognitive dissonance. However, the neurochronometry of the cognitive mechanisms underlying CIPC is a topic of debate. In other words, does it occur during the difficult choice, immediately after the choice, or when people encounter the options again? Furthermore, it remains unclear what is the exact time point, relative to the onset of facing options, either within the choice or after it, when the attitudes start to be revised. We argue that applying online protocols of transcranial magnetic stimulation (TMS), during or immediately after the choice process, could be the most efficient way to better understand the temporal dynamics of the SoA effect. TMS allows for achieving high temporal and spatial resolution, modulating the activity of areas of interest, and examining the causal relationships. Besides, unlike the offline TMS, the online instrument allows tracking of the neurochronometry of attitude change, by varying stimulation onsets and durations with respect to the option stimuli. Based on scrupulous analysis of previous findings, employing online TMS studies of conflict monitoring, cognitive control, and CIPC neuroimaging results, we conclude that the use of online TMS is critical to examine the neurochronometry of CIPC.

Screening of proteases produced by Aspergillus micromycetes active against proteins of the hemostasis system.

Background and Purpose: For these intents, proteases cardiovascular disease is the primary cause of death; hence, accurate diagnosis and treatment are urgently required are regarded as prospective agents . High substrate specificity is needed for an effective enzyme, which makes Aspergillus micromycetes, known for producing proteases with precise action, biotechnologically promising. This study mainly aimed to look at the possibilities of Aspergillus species, which had never been mentioned in terms of general proteolytics. Materials and Methods: Every species was cultivated in two-stage submerged conditions with two different nitrogen sources; whereupon, proteolytic activity in culture fluid was determined. Chromogenic peptide substrates and fibrin plates were used to evaluate the thrombin, plasmin, factor Xa, urokinase, protein C-like, activating activities towards hemostasis proteins, as well as fibrinolytic and plasminogen-activating activities of these species. Results: It was found that A. aureolatus and A. tennesseensis are active proteolytics exhibiting plasmin-like activities (116.17 and 87.09 U×10-3, respectively), factor Xa-like activity (76.27 and 77.92 U×10-3, respectively) and urokinase activity (85.99 and 59.91 U×10-3, respectively). The thrombin-like activity was found for A. tabacinus (50.37 U×10-3), and protein C-like activity was noticeable for A. creber, A. jensenii, A. protuberus, and A. ruber (62.90, 65.51, 73.37, and 111.85 U×10-3, respectively). Additionally, more than half of species had the ability to directly activate plasminogen or operate as fibrinolytics. Conclusion: New proteolytic strains were discovered, offering hope for the therapy of cardiovascular disorders. The high specificity and activity of fungal enzymes make them useful in a variety of fields, including medicine and diagnostics.

Transspinal Direct Current Electrical Stimulation Selectively Affects the Excitability of the Corticospinal System, Depending on the Intensity but Not Motor Skills.

Transspinal direct current stimulation (tsDCS) is a non-invasive technique used to modulate spinal cord activity. However, the effects and mechanisms of this stimulation are currently not comprehensively known. This study aimed to estimate the effect of different intensities of tsDCS applied at the level of cervical enlargement of the spinal cord (C7-Th1 segments) on the excitability of the corticospinal system (CSS) and the correction of motor skills in healthy subjects. The effect of tsDCS was estimated by the motor-evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) in the primary motor cortex (M1). The study involved 54 healthy adults aged 22 ± 4 years. The application of 11 min anodal tsDCS at the level of the cervical spine C7-Th1 with a current intensity of 2.5 mA did not change the MEP amplitude of the upper limb muscles, in contrast to the data that we previously obtained with a current intensity of 1.5 mA. We also found no difference in the effect of 2.5 mA stimulation on motor skill correction in healthy subjects in the nine-hole peg test (9-HPT) and the serial reaction time task (SRT) as with 1.5 mA stimulation. Our data show that an increase in the intensity of stimulation does not lead to an increase in the effects but rather reduces the effects of stimulation. These results provide information about the optimally appropriate stimulation current intensities to induce CSS excitability and the ability of tsDCS to influence motor skills in healthy adults.

Similar Cognitive Skill Impairment in Children with Upper Limb Motor Disorders Due to Arthrogryposis Multiplex Congenita and Obstetrical Brachial Plexus Palsy.

Arthrogryposis multiplex congenita (AMC) and obstetrical brachial plexus palsy (OBPP) are motor disorders with similar symptoms (contractures and the disturbance of upper limb function). Both conditions present as flaccid paresis but differ from each other in the pathogenesis: AMC is a congenital condition, while OBPP results from trauma during childbirth. Despite this difference, these diseases are identical in terms of their manifestations and treatment programmes. We compared the cognitive skills of children with AMC and OBPP diagnoses with those of healthy children; we also compared the motor skills of impaired children with those of healthy ones. The patients in both groups significantly differed from the healthy children with regard to psychological parameters, such as 'visual memory capacity' and 'thinking'. Moreover, the two groups with children with AMC and OBPP significantly differed from each other in motor skill parameters, such as 'delayed motor development', 'general motor development', and the 'level of paresis'. Upper limb motor function in the OBPP children was less impaired compared to that of the AMC children. However, we did not find any significant differences in cognitive deficits between the AMC children and the OBPP children. This may indicate that motor impairment is more significant than the underlying cause for the development of cognitive impairment; however, the factors causing this phenomenon require further study (e.g., social environment, treatment, and rehabilitation programme).