[Are the concepts of "chronic mania" in German-speaking psychiatry around 1900 early contributions to the disorder of the adult form of attention deficit hyperactivity disorder (ADHD)?] / Sind die Konzepte zur "chronischen Manie" der deutschsprachigen Psychiatrie um 1900 frühe Beiträge zum Störungsbild der adulten Form der Aufmerksamkeitsdefizit­/Hyperaktivitätsstörung (ADHS)?

The adult form of attention deficit hyperactivity disorder (ADHD) has increasingly become a focus of adult psychiatry. Despite long-established diagnostic criteria and specific therapeutic approaches for the disorder, the common misconception that ADHD is a "fad" has persisted. Examining the history of psychiatry can make an educational contribution by showing that the adult form of ADHD is a continuously existing illness phenomenon. The present study examines the discussion of sometimes prominent authors about "chronic mania" in German-speaking psychiatry around 1900. The individual concepts were analyzed for their content and compared with each other and with modern diagnostic manuals for adult ADHD. The aim of this work is to question and discuss whether these "chronic-manic concepts" are part of the conceptual history of adult ADHD and whether a gap in the history of this disorder can be filled with their help. It is concluded that in the early twentieth century neurologists reported and discussed about patients who nowadays would almost certainly receive the diagnosis of ADHD. The psychiatrists had difficulty in classifying this disorder into their nosological schemes but their "chronic-manic concepts" show clear parallels to the current diagnostic criteria for adult ADHD and its symptoms.

Risk factors for smoking in adolescence: evidence from a cross-sectional survey in Switzerland.

BACKGROUND: Cigarette smoking during adolescence is a major public health concern with far-reaching health implications. Adolescents who smoke are at an increased risk of developing long-term health problems and are more likely to continue smoking into adulthood. Therefore, it is vital to identify and understand the risk factors that contribute to adolescent smoking - which in turn facilitate the development of targeted prevention and intervention programs. METHODS: Data was drawn from a cross-sectional survey conducted between October and December 2021, encompassing adolescents of adolescents aged 14 to 19 residing in Switzerland (n = 2,683). Multiple logistic regression analysis was employed to explore which demographic, household, behavioural and psychographic factors are associated with current smoking status. RESULTS: The regression results showed higher odds of smoking for female respondents (OR 1.39; p-value 0.007); older adolescents (OR 1.30; p-value < 0.001); those living in the French-speaking part of Switzerland (OR 1.39; p-value 0.021), in suburban areas (OR 1.35; p-value 0.023) and with a smoker in the same household (OR 2.41; p-value < 0.001); adolescents consuming alcohol (OR 4.10; p-value < 0.001), cannabis products (OR 6.72; p-value < 0.001) and hookah (OR 5.07; p-value < 0.001) at least once a month; respondents not engaging in sports (OR 1.90; p-value < 0.001) or music (OR 1.42; p-value 0.031) as top five leisure activities and those experiencing high stress levels at home (OR 1.74; p-value < 0.001). Adolescents with high scores in health awareness (OR 0.33; p-value < 0.001), on the relational self-esteem scale (OR 0.78; p-value 0.054) and on the general well-being scale (OR 0.52; p-value 0.022) were less likely to smoke than their counterparts with lower scores. High risk-seeking was associated with higher odds of smoking (OR 2.15; p-value < 0.001). CONCLUSIONS: Our results suggest the importance of a comprehensive approach at both individual and institutional levels to reduce smoking rates in adolescents. More specifically, a holistic strategy that encompasses adolescents, families, schools and policymakers ranging from strengthening adolescents' self-esteem, smoking cessation support for parents, to increasing engagement in musical and physical activities, and enhancing health awareness in the school curriculum.

Classification in Early Fire Detection Using Multi-Sensor Nodes-A Transfer Learning Approach.

Effective early fire detection is crucial for preventing damage to people and buildings, especially in fire-prone historic structures. However, due to the infrequent occurrence of fire events throughout a building's lifespan, real-world data for training models are often sparse. In this study, we applied feature representation transfer and instance transfer in the context of early fire detection using multi-sensor nodes. The goal was to investigate whether training data from a small-scale setup (source domain) can be used to identify various incipient fire scenarios in their early stages within a full-scale test room (target domain). In a first step, we employed Linear Discriminant Analysis (LDA) to create a new feature space solely based on the source domain data and predicted four different fire types (smoldering wood, smoldering cotton, smoldering cable and candle fire) in the target domain with a classification rate up to 69% and a Cohen's Kappa of 0.58. Notably, lower classification performance was observed for sensor node positions close to the wall in the full-scale test room. In a second experiment, we applied the TrAdaBoost algorithm as a common instance transfer technique to adapt the model to the target domain, assuming that sparse information from the target domain is available. Boosting the data from 1% to 30% was utilized for individual sensor node positions in the target domain to adapt the model to the target domain. We found that additional boosting improved the classification performance (average classification rate of 73% and an average Cohen's Kappa of 0.63). However, it was noted that excessively boosting the data could lead to overfitting to a specific sensor node position in the target domain, resulting in a reduction in the overall classification performance.

Measuring maladaptive personality traits with the Structured Clinical Interview for DSM-IV Axis II Screening Questionnaire using a common metrics approach.

The classification of personality disorder (PD) is undergoing a paradigm shift in which categorically defined specific PDs are being replaced by dimensionally defined maladaptive trait domains. To bridge the classificatory approaches, this study attempts to use items from the categorical PD model in DSM-IV to measure the maladaptive trait domains described in DSM-5 Section III/ICD-11. A general population sample comprising 1228 participants completed the Screening Questionnaire of the Structured Clinical Interview for DSM-IV Axis II (SCID-II-SQ), the Personality Inventory for DSM-5 (PID-5), and the anankastia scale of the Personality Inventory for ICD-11 (PiCD). Using item response theory models and a psychometric linking technique, SCID-II-SQ items were evaluated for their contribution to measuring maladaptive trait domains. The best discriminating items were then selected to derive proxy scales. We found that convergent validity of these proxy scales was in a similar range to that of other self-report measures for PD, except for the proxy scale for PiCD anankastia. However, only the proxy scale for negative affectivity showed acceptable reliability that would allow its application in research settings. Future studies should seek to establish a common metric between specific PDs and maladaptive trait domains using self-report measures with higher specificity or semi-structured interviews.

Persistent Kv7.2/7.3 downregulation in the rat pilocarpine model of mesial temporal lobe epilepsy.

Mutations within the Kv7.2 and Kv7.3 genes are well described causes for genetic childhood epilepsies. Knowledge on these channels in acquired focal epilepsy, especially in mesial temporal lobe epilepsy (mTLE), however, is scarce. Here, we used the rat pilocarpine model of drug-resistant mTLE to elucidate both expression and function by quantitative polymerase-chain reaction, immunohistochemistry, and electrophysiology, respectively. We found transcriptional downregulation of Kv7.2 and Kv7.3 as well as reduced Kv7.2 expression in epileptic CA1. Consequences were altered synaptic transmission, hyperexcitability which consisted of epileptiform afterpotentials, and increased susceptibility to acute GABAergic disinhibition. Importantly, blocking Kv7 channels with XE991 increased hyperexcitability in control tissue, but not in chronically epileptic tissue suggesting that the Kv7 deficit had precluded XE991 effects in this tissue. Conversely, XE991 resulted in comparable reduction of the paired-pulse ratio in both experimental groups implying preserved presynaptic Kv7.2 function of Schaffer collateral terminals. Consistent with Kv7.2/7.3 downregulation, the Kv7.3 channel opener ß-hydroxybutyrate failed to mitigate hyperexcitability. Our findings demonstrate that compromised Kv7 function is not only relevant in genetic epilepsy, but also in acquired focal epilepsy. Moreover, they help explain reduced anti-seizure efficacy of Kv7 channel openers in drug-resistant epilepsy.

OHO: A Multi-Modal, Multi-Purpose Dataset for Human-Robot Object Hand-Over.

In the context of collaborative robotics, handing over hand-held objects to a robot is a safety-critical task. Therefore, a robust distinction between human hands and presented objects in image data is essential to avoid contact with robotic grippers. To be able to develop machine learning methods for solving this problem, we created the OHO (Object Hand-Over) dataset of tools and other everyday objects being held by human hands. Our dataset consists of color, depth, and thermal images with the addition of pose and shape information about the objects in a real-world scenario. Although the focus of this paper is on instance segmentation, our dataset also enables training for different tasks such as 3D pose estimation or shape estimation of objects. For the instance segmentation task, we present a pipeline for automated label generation in point clouds, as well as image data. Through baseline experiments, we show that these labels are suitable for training an instance segmentation to distinguish hands from objects on a per-pixel basis. Moreover, we present qualitative results for applying our trained model in a real-world application.

Investigation of Helix-Pultruded CFRP Rebar Geometry Variants for Carbon-Reinforced Concrete Structures.

Carbon concrete is a new, promising class of materials in the construction industry. This corrosion-resistant reinforcement material leads to a reduction in the concrete cover required for medial shielding. This enables lean construction and the conservation of concrete and energy-intensive cement manufacturing. Bar-type reinforcement is essential for heavily loaded structures. The newly developed helix pultrusion is the first process capable of producing carbon fiber-reinforced polymer (CFRP) reinforcement bars with a topological surface in a single pultrusion process step, with fiber orientation tailored to the specific loads. The manufacturing feasibility and load-bearing capacity were thoroughly tested and compared with other design and process variants. Approaches to increase stiffness and strength while maintaining good concrete anchorage have been presented and fabricated. Tensile testing of the helical rebar variants with a 7.2 mm lead-bearing cross-section was conducted using adapted wedge grips with a 300 mm restraint length. The new helix geometry variants achieved, on average, 40% higher strengths and almost reached the values of the base material. Concrete pull-out tests were carried out to evaluate the bond properties. The helix contour design caused the bar to twist out of the concrete test specimen. Utilizing the Rilem beam test setup, the helical contour bars could also be tested. Compared with the original helix variant, the pull-out forces could be increased from 8.5 kN to up to 22.4 kN, i.e., by a factor of 2.5. It was thus possible to derive a preferred solution that is optimally suited for use in carbon concrete.

Laser-Based Door Localization for Autonomous Mobile Service Robots.

For autonomous mobile service robots, closed doors that are in their way are restricting obstacles. In order to open doors with on-board manipulation skills, a robot needs to be able to localize the door's key features, such as the hinge and handle, as well as the current opening angle. While there are vision-based approaches for detecting doors and handles in images, we concentrate on analyzing 2D laser range scans. This requires less computational effort, and laser-scan sensors are available on most mobile robot platforms. Therefore, we developed three different machine learning approaches and a heuristic method based on line fitting able to extract the required position data. The algorithms are compared with respect to localization accuracy with help of a dataset containing laser range scans of doors. Our LaserDoors dataset is publicly available for academic use. Pros and cons of the individual methods are discussed; basically, the machine learning methods could outperform the heuristic method, but require special training data when applied in a real application.

Exploring the predictive validity of personality disorder criteria.

We tested the predictive validity of personality disorder (PD) indicators at different levels of aggregation, ranging from general PD severity to PD syndrome scales to individual PD criteria. We compared the predictive validity of models on these levels based on interview data on all 78 DSM-IV PD criteria, by using 19 outcome scales in three different samples (N = 651, N = 552, and N = 1,277). We hypothesized that criteria of personality pathology yield a significant increase in predictive validity compared with scales that are aggregated at the syndrome- or general severity-level. We assessed out of sample performance of predictive models in a repeated cross-validation design using regularized linear regression and regression forest algorithms. We observed no significant difference in predictive performance between models trained at the item-level and models trained on scale-level data. We further tested the predictive performance of the trained linear models across samples on outcome measures shared between samples and inspected models for criteria-level information they relied on to make predictions. Our results suggest that little predictive variance is lost when interview items assessing DSM-IV PD criteria are aggregated to dimensional PD scales. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The effect of a braking maneuver on the occupant's kinematics of a highly reclined seating position in a frontal crash.

OBJECTIVE: This study aims to make the comparison of the kinematics and possible injury values of the occupant in the highly reclined seating position in two cases: the first case is without the braking maneuver prior to the frontal crash, and the second case is considering the braking maneuver prior to the impact. METHODS: This study used the MADYMO human body model 50th percentile mid-size male seated on the front passenger seat model with the seatback reclined rearward 53° (fully reclined seatback) to simulate the occupant biomechanics and behavior during a frontal collision. To achieve the study aim, two simulation models were created. The first model is called the non-precrash model (VaAM-O). It was set to simulate the occupant kinematics in the fully reclined initial seating posture in the 200 ms of a crash without the braking maneuver before the crash. The second model, called the precrash model (VaAM-I), identified the occupant's initial position after the car model performed a 1s deceleration of a braking maneuver. VaAM-I has then also simulated the occupant kinematics in 200 ms of a crash. RESULTS: This study showed a significant difference in the occupant's posture at the beginning of the crash phase in the two cases. The upper torso of VaAM-I rotated up and moved forward earlier than VaAM-O prior to the crash phase due to the influence of the braking maneuver, and at the 50 ms, when the airbag deployed completely, the head had no contact with the airbag, and the head in VaAM-I forwarded to the airbag closer than VaAM-O about 24% of the distance to the airbag. CONCLUSIONS: This study supplements the value data for the study of the out-of-position OOP of the occupant in the frontal crash. The contact force and position contact between the head and the airbag could attract the audience's attention. On the other hand, a comparison of the seatbelt force and the seatbelt contacts the body between the conventional seatbelt as in this study, and the seat-integrated seatbelt system in the case wherein the occupant seats on the front seat with a highly reclined seatback should be performed.

The In-Vitro Activity of a Cold Atmospheric Plasma Device Utilizing Ambient Air against Bacteria and Biofilms Associated with Periodontal or Peri-Implant Diseases.

Due to its antimicrobial and healing-promoting effects, the application of cold atmospheric plasma (CAP) appears to be a promising modality in various fields of general medicine and dentistry. The aim of the present study was to evaluate the antibacterial and anti-biofilm activity of a handheld device utilizing ambient air for plasma generation. Suspensions of 11 oral bacteria (among them Fusobacterium nucleatum, Porphyromonas gingivalis, Parvimonas micra, Streptococcus gordonii, and Tannerella forsythia) were exposed to CAP for 10, 30, 60, and 120 s. Before and after treatment, colony forming unit (CFU) counts were determined. Then, 12-species biofilms were cultured on dentin and titanium specimens, and CAP was applied for 30, 60, and 120 s before quantifying CFU counts, biofilm mass, and metabolic activity. A reduction of ≥3 log10 CFU, was found for ten out of the eleven tested species at 30 s (except for T. forsythia) and for all species at 60 s. For biofilm grown on dentin and titanium specimens, the log10 reductions were 2.43 log10 CFU/specimen and by about 4 log10 CFU/specimen after 120 s of CAP. The CAP application did not reduce the biomass significantly, the metabolic activity of the biofilms on dentin and titanium decreased by 98% and 95% after 120 s of CAP. An application of 120 s of CAP had no cytotoxic effect on gingival fibroblasts and significantly increased the adhesion of gingival fibroblasts to the titanium surface. These results are promising and underline the potential of CAP for implementation in periodontal and peri-implantitis therapy.

Planar Proton Minibeam Irradiation Elicits Spatially Confined DNA Damage in a Human Epidermis Model.

Purpose: High doses of ionizing radiation in radiotherapy can elicit undesirable side effects to the skin. Proton minibeam radiotherapy (pMBRT) may circumvent such limitations due to tissue-sparing effects observed at the macro scale. Here, we mapped DNA damage dynamics in a 3D tissue context at the sub-cellular level. Methods: Epidermis models were irradiated with planar proton minibeams of 66 µm, 408 µm and 920 µm widths and inter-beam-distances of 2.5 mm at an average dose of 2 Gy using the scanning-ion-microscope SNAKE in Garching, GER. γ-H2AX + 53BP1 and cleaved-caspase-3 immunostaining revealed dsDNA damage and cell death, respectively, in time courses from 0.5 to 72 h after irradiation. Results: Focused 66 µm pMBRT induced sharply localized severe DNA damage (pan-γ-H2AX) in cells at the dose peaks, while damage in the dose valleys was similar to sham control. pMBRT with 408 µm and 920 µm minibeams induced DSB foci in all cells. At 72 h after irradiation, DNA damage had reached sham levels, indicating successful DNA repair. Increased frequencies of active-caspase-3 and pan-γ-H2AX-positive cells revealed incipient cell death at late time points. Conclusions: The spatially confined distribution of DNA damage appears to underlie the tissue-sparing effect after focused pMBRT. Thus, pMBRT may be the method of choice in radiotherapy to reduce side effects to the skin.

Development of a Short and ICD-11 Compatible Measure for DSM-5 Maladaptive Personality Traits Using Ant Colony Optimization Algorithms.

While Diagnostic and Statistical Manual of Mental Disorders-Fifth edition (DSM-5) Section III and ICD-11 (International Classification of Diseases 11th-Revision) both allow for dimensional assessment of personality pathology, the models differ in the definition of maladaptive traits. In this study, we pursued the goal of developing a short and reliable assessment for maladaptive traits, which is compatible with both models, using the item pool of the Personality Inventory for DSM-5 (PID-5). To this aim, we applied ant colony optimization algorithms in English- and German-speaking samples comprising a total N of 2,927. This procedure yielded a 34-item measure with a hierarchical latent structure including six maladaptive trait domains and 17 trait facets, the "Personality Inventory for DSM-5, Brief Form Plus" (PID5BF+). While latent structure, reliability, and criterion validity were ascertained in the original and in two separate validation samples (n = 849, n = 493) and the measure was able to discriminate personality disorders from other diagnoses in a clinical subsample, results suggest further modifications for capturing ICD-11 Anankastia.

Rheological Model to Describe the Cyclic Load-Bearing Behaviour of Strain-Hardening Cement-Based Composites (SHCC).

The mechanical behaviour of strain-hardening cement-based composites (SHCC) under monotonic tensile loading has been the subject of research for many years. The recent research on the SHCC's performance under cyclic loading has enabled the identification of a wide variety of damage phenomena different to those observed under monotonic loading. The article at hand first summarises the experimental evidence of such phenomena in the context of the material performance observed. On this basis, the mechanisms behind these phenomena are discussed and explained using rheological modelling.

Increasing the Fatigue Resistance of Strain-Hardening Cement-Based Composites (SHCC) by Experimental-Virtual Multi-Scale Material Design.

Strain-hardening cement-based composites are a promising class of materials for a wide variety of applications due to their considerable tensile strength and pronounced ductility caused by the development of multiple fine cracks. Nevertheless, the safe use of such composites requires sound knowledge of their mechanical behaviour under different types of loading, particularly under fatigue loading, while considering distinct influences like initial crack width and fibre orientation. To deepen this knowledge, single-fibre pull-out tests on PVA-fibres from a cementitious matrix were carried out to gain information about the micro-mechanical and degradation processes of the fibre. It could be shown that the fibres tend to rupture instead of being pulled out under quasi-static loading. When changing the loading regime to alternating loading, this failure mechanism shifts to pull-out. By varying the experimental parameters such as initial crack width, inclination angle or compressive-force level a clear influence on the fibre's crack bridging capacity could be observed associated with effects on the degradation processes. Based on the data obtained, a micro-mechanical numerical model was developed to support the assumptions and observations from single-fibre pull-out tests and to enable predictions of the performance of the material on the microscale under cyclic loading.

Point Cloud Hand-Object Segmentation Using Multimodal Imaging with Thermal and Color Data for Safe Robotic Object Handover.

This paper presents an application of neural networks operating on multimodal 3D data (3D point cloud, RGB, thermal) to effectively and precisely segment human hands and objects held in hand to realize a safe human-robot object handover. We discuss the problems encountered in building a multimodal sensor system, while the focus is on the calibration and alignment of a set of cameras including RGB, thermal, and NIR cameras. We propose the use of a copper-plastic chessboard calibration target with an internal active light source (near-infrared and visible light). By brief heating, the calibration target could be simultaneously and legibly captured by all cameras. Based on the multimodal dataset captured by our sensor system, PointNet, PointNet++, and RandLA-Net are utilized to verify the effectiveness of applying multimodal point cloud data for hand-object segmentation. These networks were trained on various data modes (XYZ, XYZ-T, XYZ-RGB, and XYZ-RGB-T). The experimental results show a significant improvement in the segmentation performance of XYZ-RGB-T (mean Intersection over Union: 82.8% by RandLA-Net) compared with the other three modes (77.3% by XYZ-RGB, 35.7% by XYZ-T, 35.7% by XYZ), in which it is worth mentioning that the Intersection over Union for the single class of hand achieves 92.6%.

[The German Version of the Level of Personality Functioning Scale-Brief Form 2.0 (LPFS-BF): Latent Structure, Convergent Validity and Norm Values in the General Population]. / Die deutsche Version der Level of Personality Functioning Scale-Brief Form 2.0 (LPFS-BF): Faktorenstruktur, konvergente Validität und Normwerte in der Allgemeinbevölkerung.

The Alternative DSM-5 Model of Personality Disorders describes the level of personality functioning, defined by impairments in self functioning (self pathology) and problems in interpersonal functioning (interpersonal pathology), as the core feature of all personality disorders. A brief self-report measure to assess the level of personality functioning, the Level of Personality Functioning Scale-Brief Form 2.0 (LPFS-BF) comprising 12 items, was developed by a Dutch work group. The present study aimed at a first and comprehensive psychometric evaluation of the German version of the LPFS-BF in a large and representative general population sample (n=2470) as well as a non-clinical sample (n=849), particularly focusing on the factor structure, convergent validity and norm values. Confirmatory factor analyses revealed that the theoretically assumed and for the original version empirically confirmed two-factor solution was replicated in both samples with acceptable fit. Reliability of the total scale as well as both subscales (defined by the internal consistency) was high in both samples (McDonalds ω ≥0.83). Satisfactory convergent validity was indicated by high correlations of the German version of the LPFS-BF with other measures assessing personality dysfunction (r ≥0.72). The association with current psychological distress was similarly high. In the general population sample, the mean norm value (T50) of the total scale was 15 and T70 was 33. Although psychometric evaluations of the German LPFS-BF in patients with mental disorders, particularly those with personality disorders, have not yet been performed, this measure can be recommended as it provides a quick and user-friendly impression of the severity of personality functioning in the domains of self and interpersonal pathology.

The Antimicrobial Effect of Cold Atmospheric Plasma against Dental Pathogens-A Systematic Review of In-Vitro Studies.

Interest in the application of cold atmospheric plasma (CAP) in the medical field has been increasing. Indications in dentistry are surface modifications and antimicrobial interventions. The antimicrobial effect of CAP is mainly attributed to the generation of reactive oxygen and reactive nitrogen species. The aim of this article is to systematically review the available evidence from in-vitro studies on the antimicrobial effect of CAP on dental pathogens. A database search was performed (PubMed, Embase, Scopus). Data concerning the device parameters, experimental set-ups and microbial cultivation were extracted. The quality of the studies was evaluated using a newly designed assessment tool. 55 studies were included (quality score 31-92%). The reduction factors varied strongly among the publications although clusters could be identified between groups of set pathogen, working gases, and treatment time intervals. A time-dependent increase of the antimicrobial effect was observed throughout the studies. CAP may be a promising alternative for antimicrobial treatment in a clinically feasible application time. The introduced standardized protocol is able to compare the outcome and quality of in-vitro studies. Further studies, including multi-species biofilm models, are needed to specify the application parameters of CAP before CAP should be tested in randomized clinical trials.

Correlation between Kir4.1 expression and barium-sensitive currents in rat and human glioma cell lines.

Gliomas are the most common primary brain tumors and often become apparent through symptomatic epileptic seizures. Glial cells express the inwardly rectifying K+ channel Kir4.1 playing a major role in K+ buffering, and are presumably involved in facilitating epileptic hyperexcitability. We therefore aimed to investigate the molecular and functional expression of Kir4.1 channels in cultured rat and human glioma cells. Quantitative PCR showed reduced expression of Kir4.1 in rat C6 and F98 cells as compared to control. In human U-87MG cells and in patient-derived low-passage glioblastoma cultures, Kir4.1 expression was also reduced as compared to autopsy controls. Testing Kir4.1 function using whole-cell patch-clamp experiments on rat C6 and two human low-passage glioblastoma cell lines (HROG38 and HROG05), we found a significantly depolarized resting membrane potential (RMP) in HROG05 (-29 ± 2 mV, n = 11) compared to C6 (-71 ± 1 mV, n = 12, P < 0.05) and HROG38 (-60 ± 2 mV, n = 12, P < 0.05). Sustained K+ inward or outward currents were sensitive to Ba2+ added to the bath solution in HROG38 and C6 cells, but not in HROG05 cells, consistent with RMP depolarization. While immunocytochemistry confirmed Kir4.1 in all three cell lines including HROG05, we found that aquaporin-4 and Kir5.1 were also significantly reduced suggesting that the Ba2+-sensitive K+ current is generally impaired in glioma tissue. In summary, we demonstrated that glioma cells differentially express functional inwardly rectifying K+ channels suggesting that impaired K+ buffering in cells lacking functional Ba2+-sensitive K+ currents may be a risk factor for increased excitability and thereby contribute to the differential epileptogenicity of gliomas.

Stereotactically Injected Kv1.2 and CASPR2 Antisera Cause Differential Effects on CA1 Synaptic and Cellular Excitability, but Both Enhance the Vulnerability to Pro-epileptic Conditions.

PURPOSE: We present a case of voltage-gated potassium channel (VGKC) complex antibody-positive limbic encephalitis (LE) harboring autoantibodies against Kv1.2. Since the patient responded well to immunotherapy, the autoantibodies were regarded as pathogenic. We aimed to characterize the pathophysiological role of this antibody in comparison to an antibody against the VGKC-associated protein contactin-associated protein-2 (CASPR2). METHODS: Stereotactic injection of patient sera (anti-Kv1.2-associated LE or anti-CASPR2 encephalopathy) and a control subject was performed into the hippocampus of the anesthetized rat in vivo, and hippocampal slices were prepared for electrophysiological purposes. Using extra- and intracellular techniques, synaptic transmission, long-term potentiation (LTP) and vulnerability to pro-epileptic conditions were analyzed. RESULTS: We observed that the slope of the field excitatory postsynaptic potential (fEPSP) was significantly increased at Schaffer collateral-CA1 synapses in anti-Kv1.2-treated and anti-CASPR2-treated rats, but not at medial perforant path-dentate gyrus synapses. The increase of the fEPSP slope in CA1 was accompanied by a decrease of the paired-pulse ratio in anti-Kv1.2, but not in anti-CASPR2 tissue, indicating presynaptic site of anti-Kv1.2. In addition, anti-Kv1.2 tissue showed enhanced LTP in CA1, but dentate gyrus LTP remained unaltered. Importantly, LTP in slices from anti-CASPR2-treated animals did not differ from control values. Intracellular recordings from CA1 neurons revealed that the resting membrane potential and a single action potential were not different between anti-Kv1.2 and control tissue. However, when the depolarization was prolonged, the number of action potentials elicited was reduced in anti-Kv1.2-treated tissue compared to both control and anti-CASPR2 tissue. In contrast, polyspike discharges induced by removal of Mg2+ occurred earlier and more frequently in both patient sera compared to control. CONCLUSION: Patient serum containing anti-Kv1.2 facilitates presynaptic transmitter release as well as postsynaptic depolarization at the Schaffer-collateral-CA1 synapse, but not in the dentate gyrus. As a consequence, both synaptic transmission and LTP in CA1 are facilitated and action potential firing is altered. In contrast, anti-CASPR2 leads to increased postsynaptic potentials, but without changing LTP or firing properties suggesting that anti-Kv1.2 and anti-CASPR2 differ in their cellular effects. Both patient sera alter susceptibility to epileptic conditions, but presumably by different mechanisms.