Contributions of Astrocyte and Neuronal Volume to CA1 Neuron Excitability Changes in Elevated Extracellular Potassium

Rapid increases in cell volume reduce the size of the extracellular space (ECS) and are associated with elevated brain tissue excitability. We recently demonstrated that astrocytes, but not neurons, rapidly swell in elevated extracellular potassium (∧[K+]o) up to 26 mM. However, effects of acute astrocyte volume fluctuations on neuronal excitability in ∧[K+]o have been difficult to evaluate due to direct effects on neuronal membrane potential and generation of action potentials. Here we set out to isolate volume-specific effects occurring in ∧[K+]o on CA1 pyramidal neurons in acute hippocampal slices by manipulating cell volume while recording neuronal glutamate currents in 10.5 mM [K+]o + tetrodotoxin (TTX) to prevent neuronal firing. Elevating [K+]o to 10.5 mM induced astrocyte swelling and produced significant increases in neuronal excitability in the form of mixed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-D-aspartate (NMDA) receptor mEPSCs and NMDA receptor-dependent slow inward currents (SICs). Application of hyperosmolar artificial cerebrospinal fluid (ACSF) by addition of mannitol in the continued presence of 10.5 mM K+ forced shrinking of astrocytes and to a lesser extent neurons, which resisted swelling in ∧[K+]o. Cell shrinking and dilation of the ECS significantly dampened neuronal excitability in 10.5 mM K+. Subsequent removal of mannitol amplified effects on neuronal excitability and nearly doubled the volume increase in astrocytes, presumably due to continued glial uptake of K+ while mannitol was present. Slower, larger amplitude events mainly driven by NMDA receptors were abolished by mannitol-induced expansion of the ECS. Collectively, our findings suggest that cell volume regulation of the ECS in elevated [K+]o is driven predominantly by astrocytes, and that cell volume effects on neuronal excitability can be effectively isolated in elevated [K+]o conditions

Dynamics of trapped bright solitons in the presence of localized inhomogeneities

We examine the dynamics of a bright solitary wave in the presence of a repulsive or attractive localized ``impurity'' in Bose-Einstein condensates (BECs). We study the generation and stability of a pair of steady states in the vicinity of the impurity as the impurity strength is varied. These two new steady states, one stable and one unstable, disappear through a saddle-node bifurcation as the strength of the impurity is decreased. The dynamics of the soliton is also examined in all the cases (including cases where the soliton is offset from one of the relevant fixed points). The numerical results are corroborated by theoretical calculations which are in very good agreement with the numerical findings.Comment: 8 pages, 5 composite figures with low res (for high res pics please go to http://www.rohan.sdsu.edu/~rcarrete/ [Publications] [Publication#41

Similarity Of Effects On EEG Parameters Of Aramaic, Greek Catholic And Krishnaic Prayers

The neurotropic effects of Prayer are manifested in two inhibitory and three activating patterns. The first inhibitory pattern reflects the decrease in elevated and upper limit levels of SPD of θ-and δ-rhythm in frontal loci and the second - decrease in normal SPD levels of β-and θ-rhythm in the frontal, central, temporal and parietal loci. The first activating pattern reflects a small increase in normal levels of β-rhythm index and asymmetry and SPD entropy in locus C3, as well as a further increase in elevated δ-rhythm SPD levels in loci P3 and T3. The second pattern reflects the slight increase in normal SPD levels of θ-rhythm in loci T3, T5, T6, O2 and α-rhythm in locus T5, as well as their indices and entropy SPD in locus O2. The third pattern reflects a slight increase in amplitude and SPD of α-rhythm in central, frontal, temporal and occipital loci

Mineral waters, metabolism, neuro-endocrine-immune complex, s. 252.

Dedicated to the 75th anniversary of Volodymyr Illich Kozyavkin with gratitude for the support of the Truskavetsian Scientific School of BalneologyThe monograph systematizes these writers and highlights the results of their own priority experimental and clinical-physiological studies of the impact of drinking mineral waters of Ukraine on neuroendocrine regulation, metabolism and immunity of healthy rats and patients in the process of rehabilitation of chronic pyelonephritis and cholecystitis in remission. In line with the concepts of functional-metabolic continuum and neuroendocrine-immune complex using the methods of factor, discriminant and canonical correlation analysis, it is demonstrated that mineral waters have both similar and specific physiologically favorable modulating effects on the parameters of the studied body systems. For specialists in medical rehabilitation, endocrinologists, immunologists, biochemists, pathophysiologists

Direct observation of Anderson localization of matter-waves in a controlled disorder

We report the observation of exponential localization of a Bose-Einstein condensate (BEC) released into a one-dimensional waveguide in the presence of a controlled disorder created by laser speckle . We operate in a regime allowing AL: i) weak disorder such that localization results from many quantum reflections of small amplitude; ii) atomic density small enough that interactions are negligible. We image directly the atomic density profiles vs time, and find that weak disorder can lead to the stopping of the expansion and to the formation of a stationary exponentially localized wave function, a direct signature of AL. Fitting the exponential wings, we extract the localization length, and compare it to theoretical calculations. Moreover we show that, in our one-dimensional speckle potentials whose noise spectrum has a high spatial frequency cut-off, exponential localization occurs only when the de Broglie wavelengths of the atoms in the expanding BEC are larger than an effective mobility edge corresponding to that cut-off. In the opposite case, we find that the density profiles decay algebraically, as predicted in [Phys. Rev. Lett. 98, 210401 (2007)]. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions

Combining Relative Chronology and AMS 14C Dating to Contextualize ‘Megasites’, Serial Migrations and Diachronic Expressions of Material Culture in the Western Tripolye Culture, Ukraine

Scholarship regarding the Eneolithic Cucuteni-Tripolye cultural complex of Romania, Moldova and Ukraine has recently focused on ‘megasites’ of the Western Tripolye culture (WTC) in Central Ukraine. However, in order to properly contextualize such unusual phenomena, we must explore the broader typo-chronology of the WTC, which is suggestive of a high degree of mobility and technological transfer between regions. We report 28 new AMS 14C dates from sites representing diagnostic types and propose a high-resolution chronological sequence for the WTC’s development. Our results support the relative chronology and offer an opportunity to propose a new chronological synthesis for the WTC

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362