Treatment of Headache in Aneurysmal Subarachnoid Hemorrhage: Multimodal Approach

Sudden severe headache is a cardinal symptom and the most common complaint amongst patients presenting with aneurysmal subarachnoid hemorrhage. The multifactorial etiology of these headaches makes pharmacotherapy problematic. Current aneurysmal subarachnoid hemorrhage guidelines have limited or no recommendations for headache treatment. Our institution utilizes a multimodal pharmacotherapy protocol in the management of aneurysmal subarachnoid hemorrhage headache. The purpose of this study was to evaluate the efficacy of the current aneurysmal subarachnoid hemorrhage headache treatment approach at our institution. This was a retrospective cohort study of patients presenting with aneurysmal subarachnoid hemorrhage. A multimodal aneurysmal subarachnoid hemorrhage headache treatment protocol was implemented in February 2014. After an eight-month washout period, patients treated between September 2014 and November 2017 represented the study cohort. Data collected included severity of aneurysmal subarachnoid hemorrhage and headache, interventions to secure the aneurysm, pain score response related to specific analgesic administered, and discharge status. Multivariate analysis and linear regression were used to identify predictors of treatment efficacy. A total of 249 patients were identified in the study cohort. The majority of patients were female (61.4%) with a median age of 54 years (±12.5), median Hunt and Hess score of 2 (interquartile range 2–3), and mean length of hospitalization of 15.2 days. Magnesium infusion had the largest reduction in mean pain score compared to baseline pain score (−0.75; p = 0.0002). In this retrospective cohort study involving patients presenting with headache secondary to aneurysmal subarachnoid hemorrhage, no agent resulted in a clinically significant improvement on headache pain scores

Metadata Deep Dive: Results from a Detailed Quality Assessment of NASA's Earth Observation Metadata

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Evaluation of headache severity after aneurysmal subarachnoid hemorrhage

AbstractObjectiveThe most common complaint from patients after subarachnoid hemorrhage (SAH) is headache. The headache appears to be persistent and often severe. Although this problem is pervasive in the care of SAH patients, very little data have been published to describe the nature and severity of the headache nor is there evidence-based guidance on the appropriate treatment of headache due to SAH.MethodsThis was a retrospective medical record review of adults with aneurysmal SAH. Basic demographics, along with pain scores and analgesic medication administration, were collected. Patients with early vasospasm (within 7days of ictus) were compared with patients with no vasospasm.ResultsThe patient population was characteristic of the typical SAH population. Approximately 31.5% of patients exhibited early vasospasm. These patients had higher pain scores (median 8/10) than did patients without vasospasm (median 6/10) and required more analgesics such as acetaminophen/butalbital/caffeine. Treatment success with any analgesic used in this population was minimal. The pain scores associated with headache increased over the first 7days in both groups.ConclusionsHeadache after SAH is persistent and treatment refractory. There may be an association with development of vasospasm and worsening of headache. Novel treatment strategies to attenuate headache in this population are needed

Similarities and differences in circuit responses to applied Gly \u3csup\u3e1\u3c/sup\u3e -SIFamide and peptidergic (Gly \u3csup\u3e1\u3c/sup\u3e -SIFamide) neuron stimulation

Similarities and differences in circuit responses to applied Gly 1 -SIFamide and peptidergic (Gly 1 -SIFamide) neuron stimulation. J Neurophysiol 121: 950 –972, 2019. First published January 16, 2019; doi:10.1152/jn.00567.2018.—Microcircuit modulation by peptides is well established, but the cellular/synaptic mechanisms whereby identified neurons with identified peptide transmitters modulate microcircuits remain unknown for most systems. Here, we describe the distribution of GYRKPPFNGSIFamide (Gly 1 -SIFamide) immunoreactivity (Gly 1 -SIFamide-IR) in the stomatogastric nervous system (STNS) of the crab Cancer borealis and the Gly 1 -SIFamide actions on the two feeding-related circuits in the stomatogastric ganglion (STG). Gly 1 -SIFamide-IR localized to somata in the paired commissural ganglia (CoGs), two axons in the nerves connecting each CoG with the STG, and the CoG and STG neuropil. We identified one Gly 1 -SIFamide-IR projection neuron innervating the STG as the previously identified modulatory commissural neuron 5 (MCN5). Brief (~10 s) MCN5 stimulation excites some pyloric circuit neurons. We now find that bath applying Gly 1 -SIFamide to the isolated STG also enhanced pyloric rhythm activity and activated an imperfectly coordinated gastric mill rhythm that included unusually prolonged bursts in two circuit neurons [inferior cardiac (IC), lateral posterior gastric (LPG)]. Furthermore, longer duration (±30 s) MCN5 stimulation activated a Gly 1 -SIFamide-like gastric mill rhythm, including prolonged IC and LPG bursting. The prolonged LPG bursting decreased the coincidence of its activity with neurons to which it is electrically coupled. We also identified local circuit feedback onto the MCN5 axon terminals, which may contribute to some distinctions between the responses to MCN5 stimulation and Gly 1 -SIFamide application. Thus, MCN5 adds to the few identified projection neurons that modulate a well-defined circuit at least partly via an identified neuropeptide transmitter and provides an opportunity to study peptide regulation of electrical coupled neurons in a functional context. NEW & NOTEWORTHY Limited insight exists regarding how identified peptidergic neurons modulate microcircuits. We show that the modulatory projection neuron modulatory commissural neuron 5 (MCN5) is peptidergic, containing Gly 1 -SIFamide. MCN5 and Gly 1 -SIFamide elicit similar output from two well-defined motor circuits. Their distinct actions may result partly from circuit feedback onto the MCN5 axon terminals. Their similar actions include eliciting divergent activity patterns in normally coactive, electrically coupled neurons, providing an opportunity to examine peptide modulation of electrically coupled neurons in a functional context

Culture of equine fibroblast-like synoviocytes on synthetic tissue scaffolds towards meniscal tissue engineering: a preliminary cell-seeding study

Introduction. Tissue engineering is a new methodology for addressing meniscal injury or loss. Synovium may be an ideal source of cells for in vitro meniscal fibrocartilage formation, however, favorable in vitro culture conditions for synovium must be established in order to achieve this goal. The objective of this study was to determine cellularity, cell distribution, and extracellular matrix (ECM) formation of equine fibroblast-like synoviocytes (FLS) cultured on synthetic scaffolds, for potential application in synovium-based meniscal tissue engineering. Scaffolds included open-cell poly-L-lactic acid (OPLA) sponges and polyglycolic acid (PGA) scaffolds cultured in static and dynamic culture conditions, and PGA scaffolds coated in poly-L-lactic (PLLA) in dynamic culture conditions.Materials and Methods. Equine FLS were seeded on OPLA and PGA scaffolds, and cultured in a static environment or in a rotating bioreactor for 12 days. Equine FLS were also seeded on PGA scaffolds coated in 2% or 4% PLLA and cultured in a rotating bioreactor for 14 and 21 days. Three scaffolds from each group were fixed, sectioned and stained with Masson’s Trichrome, Safranin-O, and Hematoxylin and Eosin, and cell numbers and distribution were analyzed using computer image analysis. Three PGA and OPLA scaffolds from each culture condition were also analyzed for extracellular matrix (ECM) production via dimethylmethylene blue (sulfated glycosaminoglycan) assay and hydroxyproline (collagen) assay. PLLA coated PGA scaffolds were analyzed using double stranded DNA quantification as areflection of cellularity and confocal laser microscopy in a fluorescent cell viability assay.Results. The highest cellularity occurred in PGA constructs cultured in a rotating bioreactor, which also had a mean sulfated glycosaminoglycan content of 22.3 µg per scaffold. PGA constructs cultured in static conditions had the lowest cellularity. Cells had difficulty adhering to OPLA and the PLLA coating of PGA scaffolds; cellularity was inversely proportional to the concentration of PLLA used. PLLA coating did not prevent dissolution of the PGA scaffolds. All cell scaffold types and culture conditions produced non-uniform cellular distribution.Discussion/Conclusion. FLS-seeding of PGA scaffolds cultured in a rotating bioreactor resulted in the most optimal cell and matrix characteristics seen in this study. Cells grew only in the pores of the OPLA sponge, and could not adhere to the PLLA coating of PGA scaffold, due to the hydrophobic property of PLA. While PGA culture in a bioreactor produced measureable GAG, no culture technique produced visible collagen. For this reason, and due to the dissolution of PGA scaffolds, the culture conditions and scaffolds described here are not recommended for inducing fibrochondrogenesis in equine FLS for meniscal tissue engineering

Efficacy and Safety of Vancomycin Loading Doses in Critically Ill Patients with Methicillin-Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Infection

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection

DEVILS: cosmic evolution of SED-derived metallicities and their connection to star formation histories

Gas-phase metallicities of galaxies are typically measured through auroral or nebular emission lines, but metallicity also leaves an imprint on the overall spectral energy distribution (SED) of a galaxy and can be estimated through SED fitting. We use the PROSPECT SED fitting code with a flexible parametric star formation history and an evolving metallicity history to self-consistently measure metallicities, stellar mass, and other galaxy properties for 90 000 galaxies from the Deep Extragalactic VIsible Legacy Survey (DEVILS) and Galaxy and Mass Assembly (GAMA) survey. We use these to trace the evolution of the mass–metallicity relation (MZR) and show that the MZR only evolves in normalization by 0.1 dex at stellar mass M = 1010.5 M. We find no difference in the MZR between galaxies with and without SED evidence of active galactic nuclei emission at low redshifts (z \u3c 0.3). Our results suggest an anticorrelation between metallicity and star formation activity at fixed stellar mass for galaxies with M \u3e 1010.5 M for z \u3c 0.3. Using the star formation histories extracted using PROSPECT we explore higher order correlations of the MZR with properties of the star formation history including age, width, and shape. We find that at a given stellar mass, galaxies with higher metallicities formed most of their mass over shorter time-scales, and before their peak star formation rate. This work highlights the value of exploring the connection of a galaxy’s current gas-phase metallicity to its star formation history in order to understand the physical processes shaping the MZR

The second set of pulsar discoveries by CHIME/FRB/Pulsar: 14 Rotating Radio Transients and 7 pulsars

The Canadian Hydrogen Mapping Experiment (CHIME) is a radio telescope located in British Columbia, Canada. The large field of view (FOV) of $\sim$ 200 square degrees has enabled the CHIME/FRB instrument to produce the largest FRB catalog to date. The large FOV also allows CHIME/FRB to be an exceptional pulsar and Rotating Radio Transient (RRAT) finding machine, despite saving only the metadata information of incoming Galactic events. We have developed a pipeline to search for pulsars/RRATs using DBSCAN, a clustering algorithm. Output clusters are then inspected by a human for pulsar/RRAT candidates and follow-up observations are scheduled with the more sensitive CHIME/Pulsar instrument. The CHIME/Pulsar instrument is capable of a near-daily search mode observation cadence. We have thus developed the CHIME/Pulsar Single Pulse Pipeline to automate the processing of CHIME/Pulsar search mode data. We report the discovery of 21 new Galactic sources, with 14 RRATs, 6 regular slow pulsars and 1 binary system. Owing to CHIME/Pulsar's daily observations we have obtained timing solutions for 8 of the 14 RRATs along with all the regular pulsars. This demonstrates CHIME/Pulsar's ability at finding timing solutions for transient sources

Proposed host galaxies of repeating fast radio burst sources detected by CHIME/FRB

We present a search for host galaxy associations for the third set of repeating fast radio burst (FRB) sources discovered by the CHIME/FRB Collaboration. Using the ~1 arcmin CHIME/FRB baseband localizations and probabilistic methods. We identify potential host galaxies of two FRBs, 20200223B and 20190110C at redshifts of 0.06024(2) and 0.12244(6), respectively. We also discuss the properties of a third marginal candidate host galaxy association for FRB 20191106C with a host redshift of 0.10775(1). The three putative host galaxies are all relatively massive, fall on the standard mass-metallicity relationship for nearby galaxies, and show evidence of ongoing star formation. They also all show signatures of being in a transitional regime, falling in the "green valley" which is between the bulk of star-forming and quiescent galaxies. The plausible host galaxies identified by our analysis are consistent with the overall population of repeating and non-repeating FRB hosts while increasing the fraction of massive and bright galaxies. Coupled with these previous host associations, we identify a possible excess of FRB repeaters whose host galaxies have M_u - M_r colors redder than the bulk of star-forming galaxies. Additional precise localizations are required to confirm this trend.Comment: 11 pages, submitted to AAS journal