Expression von BK-Kanälen in humanen Gliomen unterschiedlicher Malignität

Die funktionelle Bedeutung von spannungsabhängigen Ionenkanälen für Wachstum und Beweglichkeit von Tumorzellen ist seit längerem bekannt. Insbesondere die Ca2+-aktivierten spannungssensitiven Kaliumkanäle sind bei der Betrachtung humaner Gliome aufgefallen. Die vorliegende Arbeit zeigt anhand 5 verschiedener Normalgewebe, 8 Astrozytomen Grad II, 3 Astrozytomen Grad III, 10 primären Glioblastomen und 4 sekundären Glioblastomen, dass der BK-Kanal und seine Untereinheiten ein vom Malignitätsgrad abhängiges Expressionsmuster aufweisen. Mittels RT-PCR konnte eine Herunterregulation des Kanals bei Gliomen im Vergleich mit Normalgeweben und bei steigender Malignität der Gliome festgestellt werden. Ein statistisch signifikanter Unterschied in der Kanalexpression konnte für die a-Untereinheit und die ß2/ß4-Untereinheiten gezeigt werden. Für die ß3-Untereinheit wurden keine PCR-Produkte erzielt -- wahrscheinlich war die zu beobachtende mRNA-Menge zu gering. Aufgrund einer fehlenden Reproduzierbarkeit bei der Amplifikation der ß1-Untereinheit konnte die Tendenz einer Heraufregulierung in Gliomen, die in einigen Experimenten beobachte wurde, nicht validiert werden. Unter Verwendung eines Microarrays der Firma Affymetrix, mit dem die a- und die ß1-Untereinheit des BK-Kanals untersucht wurden, ließen sich die Daten der RT-PCR für die a-Untereinheit bestätigen. Weiterhin zeigte sich eine positive Korrelation der Expression der ß1-Untereinheit mit dem Grad der Malignität -- die ß1-Untereinheit des BK-Kanals könnte somit eine dominante Untereinheit in Gliomen darstellen. Anhand der Daten des Microarrays konnten zusätzlich Veränderungen an einer Vielzahl von Ionenkanälen nachgewiesen werden, die eine Charakterisierung und Differenzierung niedergradiger und höhergradiger Gliome ermöglichten. In einem weiteren Ansatz konnte eine minimale Anzahl von Genen ermittelt werden, die eine Diskriminierung der Gewebe ermöglichte und somit als molekulare Diskriminierungsmarker in Frage kommen. Dies waren in unseren Gewebeserien die Gene CLIC1, CLIC4, P2RX7, CHRM3 (Heraufregulierung in Gliomen), ITPR1 und KCNJ4 (Herunterregulierung in Gliomen); sie diskriminieren Gliomentitäten und Malignitätsgrade. Die deutliche Verminderung der Expression des BK-Kanals auf mRNA-Niveau lässt eine geringere Bedeutung des BK-Kanals in Gliomen vermuten, als zu Beginn der Untersuchung angenommen wurde. Einzig die ß1-Untereinheit zeigte in den Daten des Microarrays eine signifikante Expressionssteigerung in Gliomen. Diese Untereinheit könnte in Verbindung zur Malignisierung in Hirntumoren und resultierenden funktionellen Modifikation der membranalen und intrazellulären Ca2+-Kanälen stehen

Acoustic Stimuli Can Improve and Impair Somatosensory Perception

The integration of stimuli from different sensory modalities forms the basis for human perception. While the relevant impact of visual stimuli on the perception of other sensory modalities is recognized, much less is known about the impact of auditory stimuli on general sensory processing. This study aims to investigate the effect of acoustic stimuli on the processing of somatosensory stimuli using real noise (i.e., unpleasant everyday noise, RN) and neutral white noise ( WN ). To this purpose, we studied 20 healthy human subjects between 20 and 29 years of age (mean: 24, SD: ±1.9 years sex ratio 1:1). Somatosensory perception was evaluated using mechanical detection threshold (MDT) of the skin on the back of the dominant hand. To investigate the underlying mechanisms in the brain, fMRI was performed while applying acoustic stimulation (RN and WN) and tactile stimulation of the dominant hand. Here we show that acoustic stimulation with noise alters the perception of touch on the skin. We found that the effect of RN and WN differed. RN leads to an improved tactile perception, whereas WN impaired tactile perception. These changes go along with significant differences in brain activity and connectivity. WN is associated with a significant increase in brain activity in multiple brain areas such as the auditory and somatosensory cortex, parietal association cortex, and the thalamus compared to RN . With tactile stimulation of the skin, the flow of information in these brain areas is altered. While with RN the information flow from the thalamus to the somatosensory cortex is prominent, the network activity pattern changes under WN revealing an increase in interaction between multiple networks. Unpleasant noise inhibits the multisensory integration and enables a more efficient unimodal perception in the somatosensory system, improving perception. Whether this is to be interpreted as a temporary increase in phasic alertness or by a stronger filter function of the thalamus with a preference for unimodal stimuli is still open for debate

Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study

Background COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890)

Impact of an online guided physical activity training on cognition and gut-brain axis interactions in older adults: protocol of a randomized controlled trial

IntroductionBy 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes.Methods and analysisOne-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory.Clinical trial registration:https://drks.de/search/de/trial/DRKS0002802

The Processing of Somatosensory Information shifts from an early parallel into a serial processing mode: a combined fMRI/MEG study.

The question regarding whether somatosensory inputs are processed in parallel or in series has not been clearly answered. Several studies that have applied dynamic causal modeling (DCM) to fMRI data have arrived at seemingly divergent conclusions. However, these divergent results could be explained by the hypothesis that the processing route of somatosensory information changes with time. Specifically, we suggest that somatosensory stimuli are processed in parallel only during the early stage, whereas the processing is later dominated by serial processing. This hypothesis was revisited in the present study based on fMRI analyses of tactile stimuli and the application of DCM to magnetoencephalographic (MEG) data collected during sustained (260 ms) tactile stimulation. Bayesian model comparisons were used to infer the processing stream. We demonstrated that the favored processing stream changes over time. We found that the neural activity elicited in the first 100 ms following somatosensory stimuli is best explained by models that support a parallel processing route, whereas a serial processing route is subsequently favored. These results suggest that the secondary somatosensory area (SII) receives information regarding a new stimulus in parallel with the primary somatosensory area (SI), whereas later processing in the SII is dominated by the preprocessed input from the SI

The effects of deefferentation without deafferentation on functional connectivity in patients with facial palsy

Cerebral plasticity includes the adaptation of anatomical and functional connections between parts of the involved brain network. However, little is known about the network dynamics of these connectivity changes. This study investigates the impact of a pure deefferentation, without deafferentation or brain damage, on the functional connectivity of the brain. To investigate this issue, functional MRI was performed on 31 patients in the acute state of Bell's palsy (idiopathic peripheral facial nerve palsy). All of the patients performed a motor paradigm to identify seed regions involved in motor control. The functional connectivity of the resting state within this network of brain regions was compared to a healthy control group. We found decreased connectivity in patients, mainly in areas responsible for sensorimotor integration and supervision (SII, insula, thalamus and cerebellum). However, we did not find decreased connectivity in areas of the primary or secondary motor cortex. The decreased connectivity for the SII and the insula significantly correlated to the severity of the facial palsy. Our results indicate that a pure deefferentation leads the brain to adapt to the current compromised state during rest. The motor system did not make a major attempt to solve the sensorimotor discrepancy by modulating the motor program

Disrupted functional connectivity of the default mode network due to acute vestibular deficit

Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease

Effektivität, Effizienz und Sicherheit der Schlaganfall-Telemedizin in Zeiten der Corona-Pandemie

In der vorliegenden Studie wird spirituelle Kompetenz (SpK) in Psychiatrie und Psychotherapie praxisnah untersucht. Einleitend wird dargestellt, dass ebenso wie die World Psychiatric Association (WPA) und andere nationale psychiatrische Fachgesellschaften auch die Deutsche Gesellschaft für Psychiatrie und Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) ein Positionspapier zu Religiosität und Spiritualität (R/Sp) in Psychiatrie und Psychotherapie veröffentlicht hat, in dem sie Patientenzentrierung und spirituelle Kompetenz (SpK) der psychiatrischen Berufe fordert. Es wird erläutert, dass Kompetenzmangel das wichtigste Hindernis für die Implementierung von Spiritual Care (SpC) in die klinische Praxis darstellt. In dieser Untersuchung wird die Frage erforscht, wie psychiatrisch Tätige die SpK ihrer eigenen Berufsgruppe einschätzen und welche Variablen dieses Urteil beeinflussen. Insgesamt 391 psychiatrische Pflegekräfte, 75 Psychiater, 119 Therapeuten verschiedener Professionen und 62 andere (n = 647) aus Krankenhäusern in Deutschland und Österreich füllten den 'SpC Competency Questionnaire' (SCCQ) aus. Die Ergebnisse zeigten, dass Pflegekräfte, ältere und spirituell erfahrenere Personen die SpK der eigenen Berufsgruppe vergleichsweise höher einschätzten und seltener meinten, diesbezüglich nicht zuständig zu sein. Pflegende nannten häufiger als andere Berufsgruppen das Fehlen geeigneter Räumlichkeiten als Hindernis für die Implementierung von SpC. Eine höhere Einschätzung der SpK der eigenen Berufsgruppe ging mit höheren Werten in den SCCQ-Faktoren 'Selbsterfahrung und proaktive Öffnung', 'Team-Spirit', 'Wahrnehmungs-/Dokumentationskompetenz' einher. Es wird festgestellt, dass die Zuständigkeit der Gesundheitsberufe für SpC in Psychiatrie und Psychotherapie unter den deutschsprachigen psychiatrischen Berufsgruppen noch kontrovers diskutiert wird. Es wird angenommen, dass dies mit mangelnder Kompetenz in diesem Feld zusammenhängt

Abnormal Emotional Processing and Emotional Experience in Patients with Peripheral Facial Nerve Paralysis: An MEG Study

Abnormal emotional reactions of the brain in patients with facial nerve paralysis have not yet been reported. This study aims to investigate this issue by applying a machine-learning algorithm that discriminates brain emotional activities that belong either to patients with facial nerve paralysis or to healthy controls. Beyond this, we assess an emotion rating task to determine whether there are differences in their experience of emotions. MEG signals of 17 healthy controls and 16 patients with facial nerve paralysis were recorded in response to picture stimuli in three different emotional categories (pleasant, unpleasant, and neutral). The selected machine learning technique in this study was the logistic regression with LASSO regularization. We demonstrated significant classification performances in all three emotional categories. The best classification performance was achieved considering features based on event-related fields in response to the pleasant category, with an accuracy of 0.79 (95% CI (0.70, 0.82)). We also found that patients with facial nerve paralysis rated pleasant stimuli significantly more positively than healthy controls. Our results indicate that the inability to express facial expressions due to peripheral motor paralysis of the face might cause abnormal brain emotional processing and experience of particular emotions