Impact of Light at Night on Cardiac Arrest Outcome

Professional Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)Little is known about the influence of hospital environment on patient recovery. Nighttime light exposure is particularly prevalent in the hospital setting and may be detrimental because of its neuroinflammatory effects. We used a mouse model of cardiac arrest (CA) to test the hypothesis that exposure to dim light at night after cerebral ischemia impairs recovery. Mice housed in a standard light/dark cycle (LD) underwent a CA or SHAM procedure, then either remained in LD or were exposed to a light/dim light cycle (dLAN). Mortality during the first week after CA was 4-fold higher in mice exposed to dLAN relative to LD. Furthermore, surviving dLAN-CA mice had greater neuroinflammation and hippocampal cell death than LD-CA mice. dLAN likely affects CA recovery by elevating inflammation; selective inhibition of IL-1β or TNFα ameliorated the effects of dLAN light on CA recovery. In addition, restricting the wavelength of the nighttime light exposure to nm, eliminated the detrimental effects of light exposure on CA outcome. Together, these data suggest that lighting in clinical settings may affect patient recovery.A five-year embargo was granted for this item

Identifying Optimal Stocking Strategies to Support Recovery of an Endemic Lake Sucker

Endemic fishes in the intermountain west experienced significant population declines in the 20th century due to a variety of disturbances, including habitat fragmentation, water development, and the introduction of non-native, predatory fish species. The combination of habitat degradation with increased predation risk can severely limit natural recruitment for native fish species, and in response, fisheries manager shave employed a variety of recovery strategies to prevent extinction. Among the most prominent strategies is artificial propagation and subsequent release of individuals into the natural environment (i.e., stocking). Artificial propagation is an expensive endeavor, and when not coupled with a research component, can lead to poor post-stocking survival and inefficient use of limited recovery resources. The June sucker, an imperiled species endemic to Utah Lake, UT, has been supplemented through artificial propagation since the 1990s. Approximately 800,000 June suckers have been stocked from multiple sources at varying sizes and across different seasons. Here, I analyzed the effects of stocking origin, size, and season on post-stocking survival for June suckers. Additionally, because the goal of hatchery programs is to maximize efficiency, I examined costs and benefits of stocking different sizes of fish. In doing so, I highlight operational changes that will more effectively augment adult abundance, which in turn will reduce extinction risk for the June sucker and other imperiled fish species in the intermountain west

Illuminating the deleterious effects of light at night

Technological advances, while providing many benefits, often create circumstances that differ from the conditions in which we evolved. With the wide-spread adoption of electrical lighting during the 20th century, humans became exposed to bright and unnatural light at night for the first time in their evolutionary history. Electrical lighting has led to the wide-scale practice of 24-hour shift-work and has meant that what were once just “daytime” activities now run throughout the night; in many ways Western society now functions on a 24-hour schedule. Recent research suggests that this gain in freedom to function throughout the night may also come with significant repercussions. Disruption of our naturally evolved light and dark cycles can result in a wide range of physiological and behavioral changes with potentially serious medical implications. In this article we will discuss several mechanisms through which light at night may exert its effects on cancer, mood, and obesity, as well as potential ways to ameliorate the impact of light at night

3D-Ultrasound Based Mechanical and Geometrical Analysis of Abdominal Aortic Aneurysms and Relationship to Growth

The heterogeneity of progression of abdominal aortic aneurysms (AAAs) is not well understood. This study investigates which geometrical and mechanical factors, determined using time-resolved 3D ultrasound (3D + t US), correlate with increased growth of the aneurysm. The AAA diameter, volume, wall curvature, distensibility, and compliance in the maximal diameter region were determined automatically from 3D + t echograms of 167 patients. Due to limitations in the field-of-view and visibility of aortic pulsation, measurements of the volume, compliance of a 60 mm long region and the distensibility were possible for 78, 67, and 122 patients, respectively. Validation of the geometrical parameters with CT showed high similarity, with a median similarity index of 0.92 and root-mean-square error (RMSE) of diameters of 3.5 mm. Investigation of Spearman correlation between parameters showed that the elasticity of the aneurysms decreases slightly with diameter (p = 0.034) and decreases significantly with mean arterial pressure (p < 0.0001). The growth of a AAA is significantly related to its diameter, volume, compliance, and surface curvature (p < 0.002). Investigation of a linear growth model showed that compliance is the best predictor for upcoming AAA growth (RMSE 1.70 mm/year). To conclude, mechanical and geometrical parameters of the maximally dilated region of AAAs can automatically and accurately be determined from 3D + t echograms. With this, a prediction can be made about the upcoming AAA growth. This is a step towards more patient-specific characterization of AAAs, leading to better predictability of the progression of the disease and, eventually, improved clinical decision making about the treatment of AAAs

Unexpected sound omissions are signaled in human posterior superior temporal gyrus: An intracranial study

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes

Long-term effects of chronic light pollution on seasonal functions of European blackbirds (turdus merula)

Light pollution is known to affect important biological functions of wild animals, including daily and annual cycles. However, knowledge about long-term effects of chronic exposure to artificial light at night is still very limited. Here we present data on reproductive physiology, molt and locomotor activity during two-year cycles of European blackbirds (Turdus merula) exposed to either dark nights or 0.3 lux at night. As expected, control birds kept under dark nights exhibited two regular testicular and testosterone cycles during the two-year experiment. Control urban birds developed testes faster than their control rural conspecifics. Conversely, while in the first year blackbirds exposed to light at night showed a normal but earlier gonadal cycle compared to control birds, during the second year the reproductive system did not develop at all: both testicular size and testosterone concentration were at baseline levels in all birds. In addition, molt sequence in light-treated birds was more irregular than in control birds in both years. Analysis of locomotor activity showed that birds were still synchronized to the underlying light-dark cycle. We suggest that the lack of reproductive activity and irregular molt progression were possibly the results of i) birds being stuck in a photorefractory state and/or ii) chronic stress. Our data show that chronic low intensities of light at night can dramatically affect the reproductive system. Future studies are needed in order to investigate if and how urban animals avoid such negative impact and to elucidate the physiological mechanisms behind these profound long-term effects of artificial light at night. Finally we call for collaboration between scientists and policy makers to limit the impact of light pollution on animals and ecosystems

WWOX P47T partial loss-of-function mutation induces epilepsy, progressive neuroinflammation, and cerebellar degeneration in mice phenocopying human SCAR12

WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322). This mutation affecting the WW1 protein binding domain of WWOX, impairs its interaction with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T mutation that phenocopies human SCAR12. WwoxP47T/P47T mice displayed epilepsy, profound social behavior and cognition deficits, and poor motor coordination, and unlike KO models that survive only for 1 month, live beyond 1 year of age. These deficits progressed with age and mice became practically immobile, suggesting severe cerebellar dysfunction. WwoxP47T/P47T mice brains revealed signs of progressive neuroinflammation with elevated astro-microgliosis that increased with age. Cerebellar cortex displayed significantly reduced molecular and granular layer thickness and a strikingly reduced number of Purkinje cells with degenerated dendrites. Transcriptome profiling from various brain regions of WW domain LoF mice highlighted widespread changes in neuronal and glial pathways, enrichment of bioprocesses related to neuroinflammation, and severe cerebellar dysfunction. Our results show significant pathobiological effects and potential mechanisms through which WWOX partial LoF leads to epilepsy, cerebellar neurodegeneration, neuroinflammation, and ataxia. Additionally, the mouse model described here will be a useful tool to understand the role of WWOX in common neurodegenerative conditions in which this gene has been identified as a novel risk factor.Fil: Hussain, Tabish. University of Texas; Estados UnidosFil: Sanchez, Kevin. University of Texas at Austin; Estados UnidosFil: Crayton, Jennifer. University of Texas; Estados UnidosFil: Saha, Dhurjhoti. University of Texas; Estados UnidosFil: Jeter, Collene. University of Texas; Estados UnidosFil: Lu, Yue. University of Texas; Estados UnidosFil: Abba, Martín Carlos. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Seo, Ryan. Baylor College of Medicine; Estados UnidosFil: Noebels, Jeffrey L.. Baylor College of Medicine; Estados UnidosFil: Fonken, Laura. University of Texas at Austin; Estados UnidosFil: Aldaz, C. Marcelo. University of Texas; Estados Unido

Microglia: neuroimmune-sensors of stress

Exposure to stressors disrupts homeostasis and results in the release of stress hormones including glucocorticoids, epinepherine and norepinepherine. Interestingly, stress also has profound affects on microglia, which are tissue-resident macrophages in the brain parenchyma. Microglia express a diverse array of receptors, which also allows them to respond to stress hormones derived from peripheral as well as central sources. Here, we review studies of how exposure to acute and chronic stressors alters the immunophenotype and function of microglia. Further, we examine a causal for stress hormones in these effects of stress on microglia. We propose that microglia serve as immunosensors of the stress response, which puts them in the unique position to sense and respond rapidly to alterations in homeostasis and integrate the neural response to threats.</p