Context Dependent Benzodiazepine Modulation of GABAA Receptor Opening Frequency

The anxiolytic, hypnotic, and anti-convulsant properties of benzodiazepines (BDZs) require modulation of distinct GABAA receptor α-subtypes. BDZ modulation of GABAA receptors is often described in terms of increased opening frequency, and contrasted with the increased open durations occurring with barbiturate modulation. Several studies spanning single channel, rapid kinetic, and whole cell techniques have suggested that BDZs effect this observed change in frequency through increased affinity for GABA. BDZ-sensitive αβγ isoforms exist at extrasynaptic as well as synaptic locations, where they encounter markedly different concentration and time-course of GABA exposure. Interestingly, this affinity-based mechanism (specifically, decreasing the GABA unbinding rate) is only predicted to increase opening frequency under conditions that allow the unbinding and rebinding cycles typical of prolonged exposure to low GABA concentrations, which are more likely to occur at extrasynaptic GABAA receptors. In contrast, when rebinding is less likely, such as may occur in certain synaptic conditions, the number, but not the frequency, of channel openings increases in response to BDZ modulation. In conclusion, not only can multiple kinetic mechanisms alter channel opening frequency, but a single mechanism – increased affinity – impacts opening frequency differently under different contexts of GABAA receptor activation

Decreased Nocturnal Awakenings in Young Adults Performing Bikram Yoga: A Low-Constraint Home Sleep Monitoring Study

This pilot study evaluated the impact of Bikram Yoga on subjective and objective sleep parameters. We compared subjective (diary) and objective (headband sleep monitor) sleep measures on yoga versus nonyoga days during a 14-day period. Subjects (n = 13) were not constrained regarding yoga-practice days, other exercise, caffeine, alcohol, or naps. These activities did not segregate by choice of yoga days. Standard sleep metrics were unaffected by yoga, including sleep latency, total sleep time, and percentage of time spent in rapid eye movement (REM), light non-REM, deep non-REM, or wake after sleep onset (WASO). Consistent with prior work, transition probability analysis was a more sensitive index of sleep architecture changes than standard metrics. Specifically, Bikram Yoga was associated with significantly faster return to sleep after nocturnal awakenings. We conclude that objective home sleep monitoring is feasible in a low-constraint, real-world study design. Further studies on patients with insomnia will determine whether the results generalize or not

Restricted Diffusion in the Splenium of the Corpus Callosum After Cardiac Arrest

The value of MRI findings for coma prognostication is a question of great clinical and pathological relevance. We describe MRI evidence of restricted diffusion in the splenium in 5 patients with coma after cardiopulmonary resuscitation following cardiac arrest. The most common clinical presentation of corpus callosum lesions (of any cause) is altered mental status, consistent with the global importance of these extensive inter-hemispheric fibers. In our four cases with bilateral splenium restricted diffusion, none of the patients recovered consciousness. One patient with a unilateral (likely embolic) restricted diffusion lesion had excellent recovery. In contrast to unilateral ischemic callosal lesions, we believe that generalized, midline splenium restricted diffusion occurring after cardiopulmonary arrest represents Wallerian degeneration of interhemispheric neurons rather than direct ischemic damage to the white matter or axons of the callosum and thus will likely portend a poor prognosis

Consumer sleep monitors: is there a baby in the bathwater?

The rapid expansion of consumer sleep devices is outpacing the validation data necessary to assess the potential use of these devices in clinical and research settings. Common sleep monitoring devices utilize a variety of sensors to track movement as well as cardiac and respiratory physiology. The variety of sensors and user-specific factors offer the potential, at least theoretically, for clinically relevant information. We describe the current challenges for interpretation of consumer sleep monitoring data, since the devices are mainly used in non-medical contexts (consumer use) although medically-definable sleep disorders may commonly occur in this setting. A framework for addressing questions of how certain devices might be useful is offered. We suggest that multistage validation efforts are crucially needed, from the level of sensor data and algorithm output, to extrapolations beyond healthy adults and into other populations and real-world environments

The properties of the clumpy torus and BLR in the polar-scattered Seyfert 1 galaxy ESO 323-G77 through X-ray absorption variability

We report results from multi-epoch X-ray observations of the polar-scattered Seyfert 1 galaxy ESO 323-G77. The source exhibits remarkable spectral variability from months to years timescales. The observed spectral variability is entirely due to variations of the column density of a neutral absorber towards the intrinsic nuclear continuum. The column density is generally Compton-thin ranging from a few times 10$^{22}$ cm$^{-2}$ to a few times 10$^{23}$ cm$^{-2}$. However, one observation reveals a Compton-thick state with column density of the order of 1.5 $\times$ 10$^{24}$ cm$^{-2}$. The observed variability offers a rare opportunity to study the properties of the X-ray absorber(s) in an active galaxy. We identify variable X-ray absorption from two different components, namely (i) a clumpy torus whose individual clumps have a density of $\leq$ 1.7 $\times$ 10$^8$ cm$^{-3}$ and an average column density of $\sim$ 4 $\times$ 10$^{22}$ cm$^{-2}$, and (ii) the broad line region (BLR), comprising individual clouds with density of 0.1-8 $\times$ 10$^9$ cm$^{-3}$ and column density of 10$^{23}$-10$^{24}$ cm$^{-2}$. The derived properties of the clumpy torus can also be used to estimate the torus half-opening angle, which is of the order of 47 $^\circ$. We also confirm the previously reported detection of two highly ionized warm absorbers with outflow velocities of 1000-4000 km s$^{-1}$. The observed outflow velocities are consistent with the Keplerian/escape velocity at the BLR. Hence, the warm absorbers may be tentatively identified with the warm/hot inter-cloud medium which ensures that the BLR clouds are in pressure equilibrium with their surroundings. The BLR line-emitting clouds may well be the cold, dense clumps of this outflow, whose warm/hot phase is likely more homogeneous, as suggested by the lack of strong variability of the warm absorber(s) properties during our monitoring.Comment: 15 pages, 4 tables, and 9 figures. Accepted for publication in MNRA

Nuclear obscuration in the high-ionization Seyfert 2 galaxy Tol 0109-383

We report the BeppoSAX detection of a hard X-ray excess in the X-ray spectrum of the classical high-ionization Seyfert 2 galaxy Tol0109-383. The X-ray emission of this source observed below 7 keV is dominated by reflection from both cold and ionized gas, as seen in the ASCA data. The excess hard X-ray emission is presumably due to the central source absorbed by an optically thick obscuring torus with N(H)~2e24 cm-2. The strong cold X-ray reflection, if it is produced at the inner surface of the torus, is consistent with the picture where much of the inner nucleus of Tol0109-383 is exposed to direct view, as indicated by optical and infrared properties. However, the X-ray absorption must occur at small radii in order to hide the central X-ray source but leave the optical high-ionization emission line region unobscured. This may also be the case for objects like the Seyfert 1 galaxy Mrk231.Comment: 7 pages, MNRAS in pres

Brain Age from the Electroencephalogram of Sleep

The human electroencephalogram (EEG) of sleep undergoes profound changes with age. These changes can be conceptualized as "brain age", which can be compared to an age norm to reflect the deviation from normal aging process. Here, we develop an interpretable machine learning model to predict brain age based on two large sleep EEG datasets: the Massachusetts General Hospital sleep lab dataset (MGH, N = 2,621) covering age 18 to 80; and the Sleep Hearth Health Study (SHHS, N = 3,520) covering age 40 to 80. The model obtains a mean absolute deviation of 8.1 years between brain age and chronological age in the healthy participants in the MGH dataset. As validation, we analyze a subset of SHHS containing longitudinal EEGs 5 years apart, which shows a 5.5 years difference in brain age. Participants with neurological and psychiatric diseases, as well as diabetes and hypertension medications show an older brain age compared to chronological age. The findings raise the prospect of using sleep EEG as a biomarker for healthy brain aging

A Compton reflection dominated spectrum in a peculiar accreting neutron star

We report on a puzzling event occurred during a long BeppoSAX observation of the slow-rotating binary pulsar GX 1+4. During this event, lasting about 1 day, the source X-ray flux was over a factor 10 lower than normal. The low-energy pulsations disappeared while at higher energies they were shifted in phase. The spectrum taken outside this low-intensity event was well fitted by an absorbed cut-off power law, and exhibited a broad iron line at ~6.5 keV probably due to the blending of the neutral (6.4 keV) and ionised (6.7 keV) K_alpha iron lines. The spectrum during the event was Compton reflection dominated and it showed two narrow iron lines at ~6.4 keV and ~7.0 keV, the latter never revealed before in this source. We also present a possible model for this event in which a variation of the accretion rate thickens a torus-like accretion disc which hides for a while the direct neutron star emission from our line of sight. In this scenario the Compton reflected emission observed during the event is well explained in terms of emission reflected by the side of the torus facing our line of sight.Comment: 10 pages; to be published in MNRA