Behavioral state modulates the activity of brainstem sensorimotor neurons

Sensorimotor processing must be modulated according to the animal's behavioral state. A previous study demonstrated that motion responses were strongly state dependent in birds. Vestibular eye and head responses were significantly larger and more compensatory during simulated flight, and a flight-specific vestibular tail response was also characterized. In the current study, we investigated the neural substrates for these state-dependent vestibular behaviors by recording extracellularly from neurons in the vestibular nuclear complex and comparing their spontaneous activity and sensory responses during default and simulated flight states. We show that motion-sensitive neurons in the lateral vestibular nucleus are state dependent. Some neurons increased their spontaneous firing rates during flight, though their increased excitability was not reflected in higher sensory gains. However, other neurons exhibited state-dependent gating of sensory inputs, responding to rotational stimuli only during flight. These results demonstrate that vestibular processing in the brainstem is state dependent and lay the foundation for future studies to investigate the synaptic mechanisms responsible for these modifications

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain

Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as (13)CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-(13)C]lactate tracer and (13)C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75-80% of (13)CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional extraction and uptake suggest that arterial lactate supplementation may be used to compensate for decreased CMRgluc following TBI

Can providing safe cycling infrastructure encourage people to cycle more when it rains? The use of crowdsourced cycling data (Strava)

Many local authorities in the UK and other developed countries have spent a substantial amount of time and money providing safe cycling infrastructure to improve cycling environments. However, it is not clear whether these expensive physical investments are an effective strategy to encourage people to cycle more in cities where there is a high level of precipitation. The evidence is limited, partly due to data limitations. We used crowdsourced cycling data (taken from the Strava activity-tracking app) and fixed-effects panel regression models to investigate whether providing safe cycling infrastructure could be an effective way to overcome adverse weather conditions. We selected the city centre of Glasgow, Scotland because of the current size and scope of investments. We found that providing safe cycle paths could encourage people to cycle more, especially on dry days. However, findings suggested that rainy cities like Glasgow may not have realised the full benefits of safe cycling infrastructure because there are larger reductions in the volume of cycling on rainy days on these routes. Planners, especially from cities with a high level of precipitation, should consider how to improve cycle paths to overcome adverse weather and other policies (e.g., providing shower facilities at workplaces, incentives to cycle, etc.) to increase cyclists’ resilience to bad weather

The Hot R Coronae Borealis Star DY Centauri is a Binary

The remarkable hot R Coronae Borealis (RCB) star DY Cen is revealed to be the first and only binary system to be found among the RCB stars and their likely relatives, including the extreme helium stars and the hydrogen-deficient carbon stars. Radial velocity determinations from 1982 to 2010 have shown that DY Cen is a single-lined spectroscopic binary in an eccentric orbit with a period of 39.67 days. It is also one of the hottest and most H-rich member of the class of RCB stars. The system may have evolved from a common envelope to its current form.Spanish Ministry of Economy and Competitiveness AYA-2011-27754McDonald Observator

Risk of adverse events among older adults following co-prescription of clarithromycin and statins not metabolized by cytochrome P450 3A4

Background: The cytochrome P450 3A4 (CYP3A4) inhibitor clarithromycin may also inhibit liverspecific organic anion-transporting polypeptides (OATP1B1 and OATP1B3). We studied whether concurrent use of clarithromycin and a statin not metabolized by CYP3A4 was associated with an increased frequency of serious adverse events. Methods: Using large health care databases, we studied a population-based cohort of older adults (mean age 74 years) who were taking a statin not metabolized by CYP3A4 (rosuvastatin [76% of prescriptions], pravastatin [21%] or fluvastatin [3%]) between 2002 and 2013 and were newly prescribed clarithromycin (n = 51 523) or azithromycin (n = 52 518), the latter an antibiotic that inhibits neither CYP3A4 nor OATP1B1 and OATP1B3. Outcomes were hospital admission with a diagnostic code for rhabdomyolysis, acute kidney injury or hyperkalemia, and allcause mortality. All outcomes were assessed within 30 days after co-prescription. Results: Compared with the control group, patients co-prescribed clarithromycin and a statin not metabolized by CYP3A4 were at increased risk of hospital admission with acute kidney injury (adjusted relative risk [RR] 1.65, 95% confidence interval [CI] 1.31 to 2.09), admission with hyperkalemia (adjusted RR 2.17, 95% CI 1.22 to 3.86) and all-cause mortality (adjusted RR 1.43, 95% CI 1.15 to 1.76). The adjusted RR for admission with rhabdomyolysis was 2.27 (95% CI 0.86 to 5.96). The absolute increase in risk for each outcome was small and likely below 1%, even after we considered the insensitivity of some hospital database codes. Interpretation: Among older adults taking a statin not metabolized by CYP3A4, co-prescription of clarithromycin versus azithromycin was associated with a modest but statistically significant increase in the 30-day absolute risk of adverse outcomes

Modeling Multi-Wavelength Stellar Astrometry. I. SIM Lite Observations of Interacting Binaries

Interacting binaries consist of a secondary star which fills or is very close to filling its Roche lobe, resulting in accretion onto the primary star, which is often, but not always, a compact object. In many cases, the primary star, secondary star, and the accretion disk can all be significant sources of luminosity. SIM Lite will only measure the photocenter of an astrometric target, and thus determining the true astrometric orbits of such systems will be difficult. We have modified the Eclipsing Light Curve code (Orosz & Hauschildt 2000) to allow us to model the flux-weighted reflex motions of interacting binaries, in a code we call REFLUX. This code gives us sufficient flexibility to investigate nearly every configuration of interacting binary. We find that SIM Lite will be able to determine astrometric orbits for all sufficiently bright interacting binaries where the primary or secondary star dominates the luminosity. For systems where there are multiple components that comprise the spectrum in the optical bandpass accessible to SIM Lite, we find it is possible to obtain absolute masses for both components, although multi-wavelength photometry will be required to disentangle the multiple components. In all cases, SIM Lite will at least yield accurate inclinations, and provide valuable information that will allow us to begin to understand the complex evolution of mass-transferring binaries. It is critical that SIM Lite maintains a multi-wavelength capability to allow for the proper deconvolution of the astrometric orbits in multi-component systems.Comment: 12 pages, 6 figures, 6 tables. Accepted for publication in the Astrophysical Journa