The critical dynamics of hippocampal seizures.

Epilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability. Whether such dynamical signatures can be measured before impending seizures remains uncertain. Here, we verified that predictions on bifurcations applied to the onset of hippocampal seizures, providing concordant results from in silico modeling, optogenetics experiments in male mice and intracranial EEG recordings in human patients with epilepsy. Leveraging pharmacological control over neural excitability, we showed that the boundary between physiological excitability and seizures can be inferred from dynamical signatures passively recorded or actively probed in hippocampal circuits. Of importance for the design of future neurotechnologies, active probing surpassed passive recording to decode underlying levels of neural excitability, notably when assessed from a network of propagating neural responses. Our findings provide a promising approach for predicting and preventing seizures, based on a sound understanding of their dynamics.

Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

BACKGROUND AND OBJECTIVES: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/study/NCT04796597.

Last glacial loess dynamics in the Southern Caucasus (NE-Armenia) and the phenomenon of missing loess deposition during MIS-2.

The Marine Isotope Stage (MIS) 2 is considered the coldest, driest and stormiest period during the last Glacial-Interglacial cycle in large parts of Eurasia. This resulted from strongly decreased northern hemisphere temperature and related maximum extension of northern ice sheets that strongly reinforced large-scale circulation modes such as westerlies and East Asian Winter Monsoon driven by the Siberian High. Normally, this intensified circulation is reflected by maximum loess deposition in numerous loess regions spanning Europe and Asia. However, here we present a new loess record from the Caucasus region in NE-Armenia providing evidence in support of heavily reduced or even lacking loess formation during the MIS-2. Owing to implementations of comprehensible luminescence dating work and a provenance survey using rock magnetic and geochemical data, we are able to define distinct loess formation phases and to retrace sediment transport pathways. By comparing our results to other Eurasian palaeo-records, we unveil general atmospheric circulation modes that are most likely responsible for loess formation in the Southern Caucasus. Moreover, we try to test different scenarios to explain lacking loess formation during MIS-2. In line with other archive information, we suggest that loess formation was hampered by higher regional moisture conditions caused by a southward-shift of westerlies and renewed moisture absorption over the Black Sea. Our results show that modifications of MIS-2 circulation modes induced a very heterogeneous moisture distribution, particularly in the lower mid-latitudes of Eurasia producing a juxtaposition of very dry (morphodynamically active) and moderately dry (morphodynamically stable) areas.

Long-term Results of Conservative Therapy of Adolescent Idiopathic Scoliosis Using the Cheneau Brace.

Adolescent idiopathic scoliosis is a disease of the growing skeleton. The goal in therapy is to decelerate or to prevent progression of the spinal curve. As part of a retrospective study the patient group of the scoliosis surgery from 1995-2016 was analysed according to the inclusion criteria of the Scoliosis research Society (SRS). 159 of 643 of the patients fullfilled the specific criteria. The assessment of effectiveness was based on the progression of the angle of curvature. If it was ≤5° it was judged positively. The therapy in accordance to Cheneau is a full-time bracing orthosis. Data from 159 patients - 136 fem. (85.5%), 23 male (14.5%) was analysed. The average age at the beginning of treatment was 13.3±1.7 years. The average duration was 3.47±1.2 years. The average Cobb-angle before treatment was 28.39°±9.44°. At the completion is was 27.7°±12.34°. Stabilisation of scoliosis (≤5°) was achieved for 136 of the patients (85.5%). The final follow-up showed a progression of the Cobb angel>5° in 23 cases, of which 19 had to undergo secondary surgery. The length of therapy had a positive influence (p=0.057) on the result. Brace treatment constitutes an effective method of therapy at curvatures between 20-40°. Short duration of therapy correlates with a expressively increased risk towards progression (p=0.057). The Cheneau brace treatment constitutes an effective treatment at curvature angles between 20-40°. The risk of progression can be reduced by a timely and correct identification.

Archaeopedological analysis of colluvial deposits in favourable and unfavourable areas: reconstruction of land use dynamics in SW Germany.

Colluvial deposits, as the correlate sediments of human-induced soil erosion, depict an excellent archive of land use and landscape history as indicators of human-environment interactions. This study establishes a chronostratigraphy of colluvial deposits and reconstructs past land use dynamics in the Swabian Jura, the Baar and the Black Forest in SW Germany. In the agriculturally favourable Baar area multiple main phases of colluvial deposition, and thus intensified land use, can be identified from the Neolithic to the Modern times. In the unfavourable Swabian Jura increased colluvial deposition began later compared to the more favourable areas in the Baar. The same holds true for the unfavourable areas of the Black Forest, but intensified land use can only be reconstructed for the Middle Ages and Early Modern times instead of for the Bronze and Iron Age as in the Swabian Jura. Land use intensity and settlement dynamics represented by thick, multilayered colluvial deposits increase in the Baar and the Black Forest during the Middle Ages. In between those phases of geomorphodynamic activity and colluviation, stable phases occur, interpreted as phases with sustainable land use or without human presence.

Abrupt sand-dune accumulation at the northeastern margin of the Tibetan Plateau challenges the wet MIS3a inferred from numerous lake-highstands.

Over the Tibetan Plateau and adjacent regions, numerous (14)C-based lake records revealed a ubiquitous wet climatic period during 40-25 ka (late MIS 3), which is in contradiction with the global pattern of generally cold and dry climates. This paper focuses on OSL dating results of a large set of sand dunes and alluvial sediments (50 OSL ages) from the Qinwangchuan (QWC) Basin at the northeast edge of the Tibetan Plateau, with the aim to test the validity of the anomalous wet condition for the late MIS 3 interval, evidenced by numerous lake highstands. The abrupt sand dune accumulation as indication of increased aridity in the study area was OSL dated to ~40-13 ka. This dry climatic inference of the sand dune system from QWC apparently shows no wet MIS 3a event. Thus, the anomalous wet conditions revealed by high lake levels for the late MIS 3 phase may not be a universal phenomena across entire western China.

Freezing point osmometry of milk to determine the additional water content--an issue in general quality control and German food regulation.

BACKGROUND: The determination of the osmolality of aqueous samples using a freezing point osmometer is a well-established, routine laboratory method. In addition to their use in clinical and pharmaceutical laboratories, freezing point osmometers are also employed in food testing laboratories. One application is the determination of the osmolality of milk. Although cow's milk is a natural product whose water content is approximately 87%, the osmolality of milk is a significant value when the milk is collected from a larger population of animals. This value is used in milk processing to control the water content, based on the German Food Control Regulations for Milk. RESULTS: Measurement of the freezing point and osmolality of milk samples was performed with a Knauer Semi-Micro Freezing Point Osmometer. Osmolality was measured for the untreated milk samples and following their dilution (by volume) with 10% and 50% water. The measurements were made after 1, 4 and 7 days to evaluate changes over time. All measurement values for the undiluted milk were spread over a small interval with an average of 271 mOsmol/kg. After mixing the milk samples with 10% water, the average decreased to 242 mOsmol/kg, while mixing with 50% water resulted in an average osmolality of 129 mOsmol/kg. There was no significant change for the osmolality within the 7 days (measurements from days 1, 4 and 7). CONCLUSION: The results observed demonstrate clearly that the additional water content of milk can be determined easily using a freezing point osmometer. Milk samples that contain additional water have a significantly decreased osmolality, corresponding to an increased freezing point. The effect on osmolality of ageing the milk samples could not be determined in this study's time-dependent measurements.

Quantitative determination of free intracellular alpha-keto acids in neutrophils.

For the first time, a procedure is described for the quantitative analysis of free alpha-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.

Effects of propofol and taurine on intracellular free amino acid profiles and immune function markers in neutrophils in vitro.

We have examined the effects of propofol, taurine, and the combination of propofol and taurine on amino acid profiles and the immune function markers superoxide anion (O2-), hydrogen peroxide (H2O2), and released myeloperoxidase (MPO) activity in neutrophils (PMN). Propofol led to significant changes in the dynamic PMN-free amino acid pool. Exogenous taurine significantly reduced PMN neutral amino acid and alpha-aminobutyrate (alpha-aba) as intracellular taurine increased. Incubation with propofol plus taurine resulted in lower intracellular taurine levels and elevated alpha-aba and neutral amino acid concentrations compared to propofol alone. Concerning PMN immune function markers, propofol significantly decreased O2- and H2O2 formation and released MPO. Taurine led to an increased release of MPO and concomitant significantly reduced O2- and H2O2 levels. When propofol and taurine were applied together they appeared to act additively with regard to superoxide and hydrogen peroxide formation. In the case of MPO, taurine neutralized propofol's effects, supporting the idea that MPO activity may be regulated by taurine. We believe therefore that taurine is important for strengthening PMN host defense capability, although the mechanisms are not yet clear. Moreover, taurine appears to act primarily by altering the PMN osmotic balance, while propofol seems to affect PMN amino acid metabolism and/or uptake and release.