Sleep-Wake Patterns during the Acute Phase after First-Ever Stroke

This study describes the pattern of day and night sleep and explores relationships between these patterns and sociodemographic and clinical factors as well as sleep environmental context and the patient's subjective sleep quality. Data from 110 patients with first-ever stroke was collected by structured interview surveys, medical record, and objective estimated sleep data from wrist actigraphy. The variability in estimated sleep is large. Half the patients slept either <6 hours or >8 hours per night, and 78% had more than nine awakenings per night. Men slept less than women, and patients sleeping at home had fewer awakenings than those who slept in hospital. It was estimated sleep during daytime in all, except 4, patients. Longer stay in hospital was related to more daytime sleep, and the subjective sleep quality correlated with estimated sleep time, wake time, and wake percentage

The Course of Fatigue during the First 18 Months after First-Ever Stroke: A Longitudinal Study

Background. Little is known about the course of poststroke fatigue. Objectives. To describe the course of poststroke fatigue in relation to the patient's level of physical functioning, depressive symptoms, and self-reported history of prestroke fatigue. Methods. A longitudinal study using structured face-to-face interviews, questionnaires, and patients' medical records. Data were collected from 95 patients in Norway with first-ever stroke. Fatigue was measured with the Fatigue Severity Scale 7 item version and assessed for change between the acute phase, six, 12, and 18 months after stroke using 2-way ANOVA repeated-measures analyses. Results. The patients' level of fatigue did not change over time. However, those who reported prestroke fatigue showed a relatively high level of fatigue over time in the poststroke period, while patients with no history of pre-stroke fatigue showed a stable course of relatively low fatigue over time. Conclusion. Studies on poststroke fatigue should control for the patient's pre-stroke fatigue level

LEGUS Discovery of a Light Echo Around Supernova 2012aw

We have discovered a luminous light echo around the normal Type II-Plateau Supernova (SN) 2012aw in Messier 95 (M95; NGC 3351), detected in images obtained approximately two years after explosion with the Wide Field Channel 3 on-board the Hubble Space Telescope (HST) by the Legacy ExtraGalactic Ultraviolet Survey (LEGUS). The multi-band observations span from the near-ultraviolet through the optical (F275W, F336W, F438W, F555W, and F814W). The apparent brightness of the echo at the time was ~21--22 mag in all of these bands. The echo appears circular, although less obviously as a ring, with an inhomogeneous surface brightness, in particular, a prominent enhanced brightness to the southeast. The SN itself was still detectable, particularly in the redder bands. We are able to model the light echo as the time-integrated SN light scattered off of diffuse interstellar dust in the SN environment. We have assumed that this dust is analogous to that in the Milky Way with R_V=3.1. The SN light curves that we consider also include models of the unobserved early burst of light from the SN shock breakout. Our analysis of the echo suggests that the distance from the SN to the scattering dust elements along the echo is ~45 pc. The implied visual extinction for the echo-producing dust is consistent with estimates made previously from the SN itself. Finally, our estimate of the SN brightness in F814W is fainter than that measured for the red supergiant star at the precise SN location in pre-SN images, possibly indicating that the star has vanished and confirming it as the likely SN progenitor.Comment: 10 pages, 9 figures, to appear in the Astrophysical Journa

Hierarchical Star Formation in Nearby LEGUS Galaxies

Hierarchical structure in ultraviolet images of 12 late-type LEGUS galaxies is studied by determining the numbers and fluxes of nested regions as a function of size from ~1 to ~200 pc, and the number as a function of flux. Two starburst dwarfs, NGC 1705 and NGC 5253, have steeper number-size and flux-size distributions than the others, indicating high fractions of the projected areas filled with star formation. Nine subregions in 7 galaxies have similarly steep number-size slopes, even when the whole galaxies have shallower slopes. The results suggest that hierarchically structured star-forming regions several hundred parsecs or larger represent common unit structures. Small galaxies dominated by only a few of these units tend to be starbursts. The self-similarity of young stellar structures down to parsec scales suggests that star clusters form in the densest parts of a turbulent medium that also forms loose stellar groupings on larger scales. The presence of super star clusters in two of our starburst dwarfs would follow from the observed structure if cloud and stellar subregions more readily coalesce when self-gravity in the unit cell contributes more to the total gravitational potential.Comment: 9 pages, 4 figures, accepted for ApJ

How did smokers respond to standardised cigarette packaging with new, larger health warnings in the United Kingdom during the transition period? A cross-sectional online survey

Introduction: In the United Kingdom, standardised packaging for cigarettes was phased in between May 2016 and May 2017. We assessed whether there was an association between using standardised packs and warning salience, thoughts about the risks of smoking, thoughts about quitting, and awareness and use of stop-smoking websites. Methods: We conducted a cross-sectional online survey with current smokers aged 16 and over (N = 1865) recruited in two regions of England between February-April 2017, when both standardised and fully-branded packs were on the market. Participants were asked about use of standardised packs, warning salience (noticing, reading closely), and whether the packs they were using increased thoughts of the risks of smoking and quitting. They were also asked about awareness of stop-smoking websites, source of awareness (including warnings on packs), and whether they had visited a stop-smoking website. Results: Most participants reported currently using standardised packs (76.4%), 9.3% were not currently using them but had previously used them, and 14.3% had never used them. Compared with never users, current users were more likely to have noticed the warnings on packs often/very often (AOR (95%CI) = 2.76 (2.10, 3.63)), read them closely often/very often (AOR(95%CI) = 2.16 (1.51, 3.10)), thought somewhat/a lot about the health risks of smoking (AOR(95%CI) = 1.92 (1.38, 2.68)), and thought somewhat/a lot about quitting (AOR(95%CI) = 1.90 (1.30, 2.77)). They were also more likely to have noticed a stop-smoking website on packs. Conclusions: Consistent with the broad objectives of standardised packaging, we found that it was associated with increased warning salience and thoughts about risks and quittingOutput Status: Forthcoming/Available Onlin

Intracranial injection of AAV expressing NEP but not IDE reduces amyloid pathology in APP+PS1 transgenic mice

The accumulation of β-amyloid peptides in the brain has been recognized as an essential factor in Alzheimer\u27s disease pathology. Several proteases, including Neprilysin (NEP), endothelin converting enzyme (ECE), and insulin degrading enzyme (IDE), have been shown to cleave β-amyloid peptides (Aβ). We have previously reported reductions in amyloid in APP+PS1 mice with increased expression of ECE. In this study we compared the vector-induced increased expression of NEP and IDE. We used recombinant adeno-associated viral vectors expressing either native forms of NEP (NEP-n) or IDE (IDE-n), or engineered secreted forms of NEP (NEP-s) or IDE (IDE-s). In a six-week study, immunohistochemistry staining for total Aβ was significantly decreased in animals receiving the NEP-n and NEP-s but not for IDE-n or IDE-s in either the hippocampus or cortex. Congo red staining followed a similar trend revealing significant decreases in the hippocampus and the cortex for NEP-n and NEP-s treatment groups. Our results indicate that while rAAV-IDE does not have the same therapeutic potential as rAAV-NEP, rAAV-NEP-s and NEP-n are effective at reducing amyloid loads, and both of these vectors continue to have significant effects nine months post-injection. As such, they may be considered reasonable candidates for gene therapy trials in AD

LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice

Inflammation and microglial activation are associated with Alzheimer's disease (AD) pathology. Somewhat surprisingly, injection of a prototypical inflammatory agent, lipopolysaccharide (LPS) into brains of amyloid precursor protein (APP) transgenic mice clears some of the pre-existing amyloid deposits. It is less well understood how brain inflammation modulates tau pathology in the absence of Aβ. These studies examined the role of LPS-induced inflammation on tau pathology. We used transgenic rTg4510 mice, which express the P301L mutation (4R0N TauP301L) and initiate tau pathology between 3-5 months of age. First, we found an age-dependent increase in several markers of microglial activation as these rTg4510 mice aged and tau tangles accumulated. LPS injections into the frontal cortex and hippocampus induced significant activation of CD45 and arginase 1 in rTg4510 and non-transgenic mice. In addition, activation of YM1 by LPS was exaggerated in transgenic mice relative to non-transgenic animals. Expression of Ser199/202 and phospho-tau Ser396 was increased in rTg4510 mice that received LPS compared to vehicle injections. However, the numbers of silver-positive neurons, implying presence of more pre- and mature tangles, was not significantly affected by LPS administration. These data suggest that inflammatory stimuli can facilitate tau phosphorylation. Coupled with prior results demonstrating clearance of Aβ by similar LPS injections, these results suggest that brain inflammation may have opposing effects on amyloid and tau pathology, possibly explaining the failures (to date) of anti-inflammatory therapies in AD patients

Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition

INTRODUCTION: Tau pathology is associated with a number of age-related neurodegenerative disorders. Few treatments have been demonstrated to diminish the impact of tau pathology in mouse models and none are yet effective in humans. Histone deacetylase 6 (HDAC6) is an enzyme that removes acetyl groups from cytoplasmic proteins, rather than nuclear histones. Its substrates include tubulin, heat shock protein 90 and cortactin. Tubastatin A is a selective inhibitor of HDAC6. Modification of tau pathology by specific inhibition of HDAC6 presents a potential therapeutic approach in tauopathy. METHODS: We treated rTg4510 mouse models of tau deposition and non-transgenic mice with tubastatin (25 mg/kg) or saline (0.9%) from 5 to 7 months of age. Cognitive behavior analysis, histology and biochemical analysis were applied to access the effect of tubastatin on memory, tau pathology and neurodegeneration (hippocampal volume). RESULTS: We present data showing that tubastatin restored memory function in rTg4510 mice and reversed a hyperactivity phenotype. We further found that tubastatin reduced the levels of total tau, both histologically and by western analysis. Reduction in total tau levels was positively correlated with memory improvement in these mice. However, there was no impact on phosphorylated forms of tau, either by histology or western analysis, nor was there an impact on silver positive inclusions histologically. CONCLUSION: Potential mechanisms by which HDAC6 inhibitors might benefit the rTg4510 mouse include stabilization of microtubules secondary to increased tubulin acetylation, increased degradation of tau secondary to increased acetylation of HSP90 or both. These data support the use of HDAC6 inhibitors as potential therapeutic agents against tau pathology