Hr Period Research Articles

Cardiovascular Evaluation in Bitches in Oestrus, Pregnancy and Puerperium

Background: Pregnancy may change maternal hemodynamic, which is considered a physiological mechanism for adaptation. Cardiac output tends to be influenced by reductions in vascular resistance and increases in uterine vasculature, as well as reduced autonomic tone combined with gestational physiological anaemia and increased blood volume due to increased plasma volume and hormonal mechanisms. In bitches, few studies have been conducted investigating the changes of the system and the clinical implications for the mother and foetuses due to poor cardiac adaptation during pregnancy.Materials, Methods & Results: Systolic blood pressure (SBP), electrocardiographic and Doppler echocardiographic measurements and serum sodium (Na), potassium (K), calcium (Ca) and phosphorus (P) levels were evaluated in six bitches of reproductive age. An evaluation was performed in oestrus (M0), followed by evaluations at 25 (M1), 45 (M2), and 60 days (M3) after the last natural or artificial insemination and 15 days after delivery (M4). For the statistical analysis, the means, medians and the standard deviation were calculated. The data were analysed using ANOVA and the Tukey test, with significance level of 5%. A descriptive analysis was performed for color Doppler in echocardiogram evaluation, cardiac axis and rhythm in electrocardiogram evaluation. In the electrolytic evaluation, significant differences were found only in the serum levels of Na, noticed as a reduction in M0-M1 and M3-M2 and an increase in M1-M2 and M3-M4. No significant differences were observed in the SBP, although there was a tendency to SBP reduction. ECG parameters were not significantly different, with no rhythm or conduction disturbances. There was not a significant difference in HR. Four animals (66.6%) had axis deviation to the right when comparing the oestrous phase with the final quarter of pregnancy. The echocardiographic parameters did not show significant changes.Discussion: The reduction observed in Na can occur by salt depletion, by dilutional or metabolic mechanisms. In contrast, the elevation in Na concentration could occur as a result of fluid and electrolyte retention by kidneys during gestation. The absence of electrocardiographic changes may be justified by the stability of mean serum potassium concentrations. An increase in HR five days before the expected calving time, demonstrating the maximum cardiac activity in this gestational phase, is related by other authors, therefore, in the present study, the absence of significant change in HR can be explained by the period in which the data collection was performed, 45 days of gestation, being therefore prior to the period of greatest HR. The cardiac axis deviation can be explained by the distension of the gravid uterus that cause compression of the adjacent organs, leading to diaphragmatic compression and consequent repositioning of the thoracic structures. A tendency to SBP reduction observed is directly influenced by peripheral vascular resistance and cardiac output that occur during pregnancy. Although the echocardiographic findings did not show changes, it is suggested that there are changes related to increased blood volume in pregnancy to provide an appropriate blood flow to the conceptus. It was concluded that pregnancy and the postpartum period in bitches did not cause changes in electrolytes levels, SBP values, echocardiographic and electrocardiographic parameters as compared to values obtained during oestrus.

Gazing at the ultraslow magnetar in RCW 103 with NuSTAR and Swift

We report on a new NuSTAR observation and on the ongoing Swift XRT monitoring campaign of the peculiar source 1E 161348-5055, located at the centre of the supernova remnant RCW 103, which is recovering from its last outburst in June 2016. The X-ray spectrum at the epoch of the NuSTAR observation can be described by either two absorbed blackbodies ($kT_{BB_1}$ ~ 0.5 keV, $kT_{BB_2}$ ~ 1.2 keV) or an absorbed blackbody plus a power law ($kT_{BB_1}$ ~ 0.6 keV, $\Gamma$ ~ 3.9). The observed flux was ~ 9 $\times$ 10$^{-12}$ erg s$^{-1}$ cm$^{-2}$, ~ 3 times lower than what observed at the outburst onset, but about one order of magnitude higher than the historical quiescent level. A periodic modulation was detected at the known 6.67 hr periodicity. The spectral decomposition and evolution along the outburst decay are consistent with 1E 161348-5055 being a magnetar, the slowest ever detected.

BS02. Severity of unwitnessed seizures estimated using postictal single-channel electrocardiogram recordings

Introduction Epilepsy patients are often susceptible to cardiorespiratory adverse events during and immediately after the seizure. Unwitnessed seizures during sleep are associated with the highest rate of SUDEP - a common cause of mortality in epilepsy. To improve surveillance, different wearable sensors (like seizure warning watches) are developed for seizure advisory systems. These devices are restricted to detecting ictal events from heart rate variability, motion, and muscle activities. As the risk of cardiorespiratory complications extends beyond seizure to postictal period, it may be worthwhile to develop novel extracranial physiological biomarkers that can be used to estimate the severity of seizures from the postictal period. During a convulsive seizure, movement artifact often precludes reliable data interpretation, and hence the motivation of this study is to identify parameters at the post ictal period when artifact is expected to be less. Using advanced signal processing and machine learning tools we systematically analyzed multiple parameters obtained from a single-channel electrocardiogram to estimate the severity of seizure and epilepsy. Methods Patients admitted to a level-IV epilepsy center for video scalp EEG monitoring were included in this study. Only patients with confirmed seizures were selected. A single lead EKG was recorded simultaneously with video EEG (Natus Xltek system). Sampling frequency was 256 Hz. The EKG was analyzed in time-frequency and nonlinear domains - mean HR, standard HR, mean RR interval, RMSSD, HF, LF, approximate and sample entropy. Two minutes of epoch were selected for a baseline (at least 6 h apart from a seizure), pre seizure and post seizure. The study goal was to identify parameters following seizure termination hence seizure was not analyzed. ANOVA was performed to select features and machine learning tools (deep learning and SVM) were used for classification. Seizure severity was scored by using duration, type (focal vs. generalized seizure), Chalfont Scale and SUDEP score. Results Forty patients (M = 28) with a mean age of 32-years were included in this retrospective study. Seventy-eight seizures (49 focal seizures) were analyzed. In the postictal period, the mean and standard deviation of HR increased while the mean RR decreased significantly in comparison to baseline or pre-seizure state. Both sample and approximate entropy decreased significantly in the postictal state. Deep learning ML classified post ictal state from pre ictal or baseline with higher accuracy (>90%) by using combination of approximate entropy, mean RR. However, other features like LF, HF are still analyzed for higher accuracy and to estimate seizure severity. Conclusion In this novel study, we aim to identify physiological parameters that can estimate severity of seizures from post ictal EKG recordings. Our preliminary analyses shows post ictal mean RR, HR and approximate entropy as candidate reliable markers for estimating seizure severity.

LO92: Development of a predictive model for hospital admissions by utilizing frequencies of specific CEDIS presenting complaints

Introduction: With hospital occupancy rates frequently approaching 100%, even small variations in daily admission numbers can have a large impact. The ability to predict variance in emergency admission rates would provide administrators with a significant advantage in managing hospital daily bed requirements. There is a growing interest in patterns of hospital admissions, and many EDs utilize historical admission patterns to attempt to predict daily bed requirements. Previous studies have utilized patient demographics and past medical history to develop an admission likelihood model. We wished to examine the predictive strength of individual CEDIS presenting complaints (PC) on admission likelihood Methods: Using a database analysis of over 285,000 ED presentations (2013-2017), we calculated visit frequencies and admission rates by PC. Using a logistic regression analysis PCs were ordered from high to medium predictive strength. Results: Of 285,155 presentations, there were 38,090 hospital admissions, a rate of 13.36%. Based on the number of visit frequencies and admission rates, the PCs demonstrating high predictive strength were Direct Referral (effect=0.36, binomial CI: 0.28 to 0.44); Shortness of Breath (0.32: 0.26 to 0.41); General Weakness; Weakness/Query CVA; & Chest Pain Cardiac Features (each 0.30: 0.25 to 0.42); Altered level of consciousness (0.24: 0.16 to 0.31); and Confusion (0.18: 0.08 to 0.26). With our sample size, all remaining CEDIS PCs had low predictive value (the effect is <0.1), or were not predictive at all. Conclusion: We have demonstrated that, for our population, certain PCs are associated with an increased likelihood of admission and have quantified this effect using logistic regression analysis. Variance from the average daily admission rate may be predicted, in our population, by identifying these PCs at registration.We plan to develop a tool, based on this data and implemented at registration, to predict cumulative likely daily admission requirements as patients present over a 24hr period.

CK1/Doubletime activity delays transcription activation in the circadian clock.

In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex. Our results indicate that phosphorylation of PER residue S589 stabilizes and activates PER inhibitory function in the presence of TIM, but promotes PER degradation in its absence. The role of DBT in regulating PER activity, stabilization and degradation ensures that these events are chronologically and biochemically linked, and contributes to the timing of an essential delay that influences the period of the circadian clock.

Poloxamer 188 does not Target Altered Ca2+ Channels in Cardiomyocytes during Hypoxia/Reoxygenation Injury

IntroductionIschemia/reperfusion (I/R) injury is a complex pathological event. Membrane disruptions and altered calcium (Ca2+) transport during ischemia, continue in early reperfusion. With Ca2+ being a major regulator of cardiomyocyte function, increases in intracellular Ca2+ ([Ca2+]i) can have detrimental effects. Ca2+ may not only enter through membrane disruptions, but through altered Ca2+ channels or exchangers. The tri‐block copolymer cell membrane stabilizer, Poloxamer 188 (P188), has been shown to be protective, by targeting membrane disruptions caused by I/R. However, it is not known if P188 also targets altered Ca2+ channels or exchangers. We investigated the potential role of Ca2+ channels and exchangers that may contribute to increased Ca2+ influx during ischemia, and more importantly, reperfusion. Pharmacologic compounds were used to modify Ca2+ influx, and assess the effect of P188 present during reperfusion, on these modifications.HypothesisP188, with its unique hydrophobic/hydrophilic properties, protects cardiomyocytes (CMs) against hypoxia/reoxygenation (H/R; simulated I/R) injury by stabilizing membrane disruptions and blocking altered Ca2+ channels or exchangers.MethodsIsolated CMs were kept in control/normoxic (C/N) conditions or underwent 5 hrs of hypoxia (0.01% O2; serum‐ & glucose‐free medium), then 2 hrs reoxygenation (21% O2; complete medium). The pharmacologic compounds S‐(−)‐BayK8644 (a L‐type Ca2+ channel agonist), R‐(+)‐BayK8644 (a L‐type Ca2+ channel blocker), dobutamine (a β1 receptor agonist/activator of the voltage‐gated Na+ channel), and KB‐R7943 (a blocker of the reverse mode of the Na+/Ca2+ exchanger) were used. Each was used under both C/N and H/R conditions, and added at the start of reoxygenation (or final 2 hr period in C/N conditions) ± 100μM P188. Endpoints were markers of cell number/viability and [Ca2+]i. Statistics: ANOVA and SNK post hoc comparisons, p<0.05 *vs C/N, **vs H/R, Ɨ vs vehicle.ResultsUnder C/N conditions, S‐(−)‐BayK8644 significantly increased [Ca2+]i, but dobutamine did not, over a 2 hr period. P188 had no effect on attenuating the Ca2+ influx caused by S‐(−)‐BayK8644. R‐(+)‐BayK8644 significantly decreased Ca2+ influx. Under H/R conditions, S‐(−)‐BayK8644 and dobutamine significantly increased [Ca2+]i over the 2 hr reoxygenation period. P188 had no effect on attenuating the Ca2+ influx caused by the above compounds; however, P188 did significantly decrease the Ca2+ influx caused by the H/R itself. R‐(+)‐BayK8644 and KB‐R7943 significantly decreased Ca2+ influx that occurred during the 2 hr reoxygenation period; and, when P188 was also present, this decrease in Ca2+ influx was significantly enhanced.ConclusionsIn CMs, P188 does not appear to target Ca2+ channels or exchangers when administered during reoxygenation. The protective effect of P188 most likely comes from its ability to repair membrane disruptions, and thus restore membrane integrity and cellular function.Support or Funding InformationThis work was supported by institutional funds, NIH grant (5R01 HL123227), and a Merit Review Award (I01 BX003482) from the U.S. Department of Veteran Affairs Biomedical Laboratory R&D Service.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cyrotherapy Reduces Macrophage Infiltration and Inflammatory Mediators Following Muscle Injury

Cryotherapy following muscle injury is a commonly used treatment in sports medicine. However, there are conflicting reports on the efficacy of cryotherapy to reduce inflammation. The infiltration of macrophages and macrophage produced growth factors are now considered important mediators of the healing process. The purpose of our study was to evaluate the effects of cryotherapy on inflammation associated with muscle regeneration in mice. Following BaCl2 injury, we observed a significant reduction in macrophage infiltration in mice that received cryotherapy (20 min of ice therapy every 2hr during consecutive 12 hr wake cycles) over a 48 hr period. qPCR analysis of mRNA expression for wnt proteins and inflammatory mediators revealed a statistically significant reduction in wnt 2b, 3, 5a, 11, 16 and NFk‐β, TNF‐α, TGF‐β, and IGF‐1. Given that wnt proteins are important during development of muscle and in many tissue regeneration models, we believe this supports the notion that the reduction in inflammation afforded by cryotherapy may correspond with a delay in muscle healing. Studies are ongoing to determine the long‐term effects of cryotherapy on macrophage‐mediated muscle regeneration and extracellular matrix remodeling.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

MP09-05 SILK-ELASTINLIKE POLYMERS ENHANCE THE ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF SEMISYNTHETIC GLYCOSAMINOGLYCANS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2018MP09-05 SILK-ELASTINLIKE POLYMERS ENHANCE THE ANTI-INFLAMMATORY AND ANALGESIC PROPERTIES OF SEMISYNTHETIC GLYCOSAMINOGLYCANS Mark Martin Jensen, Wanjian Jia, Austin Schults, Kyle Isaacson, Douglas Steinhauff, Bryant Green, Marcelo Correa, Jeremiah Alt, Joseph Cappello, Hamid Ghandehari, and Siam Oottamasathien Mark Martin JensenMark Martin Jensen More articles by this author , Wanjian JiaWanjian Jia More articles by this author , Austin SchultsAustin Schults More articles by this author , Kyle IsaacsonKyle Isaacson More articles by this author , Douglas SteinhauffDouglas Steinhauff More articles by this author , Bryant GreenBryant Green More articles by this author , Marcelo CorreaMarcelo Correa More articles by this author , Jeremiah AltJeremiah Alt More articles by this author , Joseph CappelloJoseph Cappello More articles by this author , Hamid GhandehariHamid Ghandehari More articles by this author , and Siam OottamasathienSiam Oottamasathien More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.331AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Rapid clearance, mucosal barriers, and tight epithelium create strong natural barriers within the bladder and bowel, reducing the efficacy of biologics and small molecule therapeutics. Silk-like and Elastin-like motifs were genetically recombined to create silk-elastinlike protein polymers (SELPs) that transition to solid matrices from injectable solutions in response to body temperature. Semi-synthetic glycosaminoglycan ethers (SAGEs) are a novel therapeutic class of polysaccharides that have both anti-inflammatory and analgesic properties. We hypothesized that SELP could be leveraged to overcome physiological barriers and enhance delivery and efficacy of water-soluble therapeutics, such as SAGE, to bladder and rectal tissues (see Figure 1). METHODS Material properties of SELP 815K, SELP 415K, Poloxamer 407 (PLX), and Poly(lactide-co-glycolide)-Poly(ethylene glycol)-Poly(lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer based thermoresponsive delivery systems were evaluated using gelation time assays, rheology, scanning electron microscopy, in vivo delivery of fluorescently labeled SAGE, and enhancement of SAGE efficacy to ameliorate radiation-induced inflammation (RII) or LL-37 induced cystitis (IC) in murine models. Therapeutic efficacy was assessed using gross anatomical inspection, histology, ELISA for MPO activity, and other inflammatory markers, along with mechanical pain sensitization via Von Frey filament testing. RESULTS SELP 815K at 12% (w/w) solution in saline transitioned from an injectable fluidic solution to form a robust gel within 3 minutes after heating to 37 °C. SELP released SAGE over a 24 hr period in a controlled and tunable fashion. Both SELPs had lower injection viscosities but sill formed stronger gels compared to PLGA-PEG-PLGA and PLX. SELP enhanced the accumulation of SAGE in both rectal and bladder tissues and significantly improve the amelioration of pain and inflammatory responses in both models (P<0.001). CONCLUSIONS These results demonstrate the utility of SELP to enhance the delivery of SAGE within the rectum and bladder to improve treatment options for RII, IC, and other diseases afflicting the gastrointestinal and genitourinary systems. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e107 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mark Martin Jensen More articles by this author Wanjian Jia More articles by this author Austin Schults More articles by this author Kyle Isaacson More articles by this author Douglas Steinhauff More articles by this author Bryant Green More articles by this author Marcelo Correa More articles by this author Jeremiah Alt More articles by this author Joseph Cappello More articles by this author Hamid Ghandehari More articles by this author Siam Oottamasathien More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Altered brain perfusion patterns in wakefulness and slow-wave sleep in sleepwalkers.

The present study assessed brain perfusion patterns with single-photon emission computed tomography (SPECT) during sleepwalkers' post-sleep deprivation slow-wave sleep (SWS) and resting-state wakefulness. Following a 24 hr period of sleep deprivation, 10 sleepwalkers and 10 sex- and age-matched controls were scanned with a high-resolution SPECT scanner. Participants were injected with 99mTc-ethylene cysteinate dimer after 2 min of stable SWS within their first sleep cycle as well as during resting-state wakefulness, both after a subsequent 24 hr period of sleep deprivation. When compared with controls' brain perfusion patterns during both SWS and resting-state wakefulness, sleepwalkers showed reduced regional cerebral perfusion in several bilateral frontal regions, including the superior frontal, middle frontal, and medial frontal gyri. Moreover, reduced regional cerebral perfusion was also found in sleepwalkers' left postcentral gyrus, insula, and superior temporal gyrus during SWS compared with controls. During resting-state wakefulness compared with controls, reduced cerebral perfusion was also found in parietal and temporal regions of sleepwalkers' left hemisphere, whereas the right parahippocampal gyrus showed increased regional cerebral perfusion. Our results reveal patterns of reduced regional cerebral perfusion in sleepwalkers' frontal and parietal areas when compared with controls, regions previously associated with SWS generation and episode occurrence. Additionally, reduced perfusion in the dorsolateral prefrontal cortex and insula during recovery SWS is consistent with the clinical features of somnambulistic episodes, including impaired awareness and reduced pain perception. Altered regional cerebral perfusion patterns during sleepwalkers' resting-state wakefulness may be related to daytime functional anomalies in this population.

Effect of Pomegranate extract on P53 expression in Cancer Cell line (Hep-2)

Background: Pomegranate (Punica granatum) fruits are widely consumed as juice. The potent antioxidant and antiatherosclerotic activities of pomegranate are attributed to its polyphenols. Aim: Pomegranate extract were evaluated for in vitro cytotoxic and its effect on the level of p53 in Hep2 (Human larynx epidermal carcinoma). Methods: Aqueous extraction of pomegranate was prepared and in vitro cytotoxicity and amount of p53 was evaluated on cancer cell line Hep2 (Human larynx epidermal carcinoma). Results: The study showed that the pomegranate extract has greatest antiproliferative activity by inhibition proliferation from 13% to 73.9%, at 10 µg/ml and 24 hr period of exposure. Also, the study showed significant decrease of p53 in treated group in comparison to control. Conclusions: According to the in vitro antiproliferative activity, inhibition of p53 expression pomegramate extracts may be possess a potent anticancer activity.

What goes up must come down: Diel vertical migration in the deep‐water sablefish (Anoplopoma fimbria) revealed by pop‐up satellite archival tags

AbstractThe sablefish (Anoplopoma fimbria) is a long‐lived species with wide distribution throughout the North Pacific Ocean. While adult sablefish are considered a deep‐water fish, diet analyses suggest that they undergo vertical migrations that could be related to prey movement and feeding. Pop‐up satellite archival tags (PSATs) were used to observe the fine‐scale depth selection behavior of adult sablefish tagged off the Washington coast during the summer from June to August. Tags were physically retrieved after they surfaced using direction‐finding equipment so that complete datasets over the entire deployment were obtained from 14 tags. PSATs that recorded depth and temperature every 4 min during the deployment confirm that sablefish inhabit depths of 750 m or greater. However, a majority of the tagged fish underwent extensive vertical migrations that averaged 254.4 m overall and occurred at a 24 hr periodicity. Variations were observed among individuals in the amount of the deployment during which vertical migrations occurred, ranging from 12.37% to 63.48% of the time. During the vertical migration, fish ascended towards the surface at night and descended prior to daylight (i.e., diel vertical migration). Sablefish generally inhabited temperatures of 5°C but during the vertical migrations were found at temperatures from 6 to 10°C. Sablefish are opportunistic feeders with a large proportion of their diet being fish, euphausiids and cephalopods. Because these prey items also exhibit diel vertical migrations, it is possible that the vertical migratory behavior displayed by the sablefish was in response to the movements or the location of their prey.

NON-IONIC SURFACTANT VESICLES (NIOSOMES) BASED NOVEL OPHTHALMIC FORMULATION OF TIMOLOL MALEATE

The objective of the present work was to develop drug loaded niosomal ophthalmic formulation of timolol maleate (an antiglaucomal drug) for enhanced trans-corneal drug permeation and better ocular bioavailability. Timolol loaded niosomes were prepared by thin film hydration method using rotary evapoarator and ultra-sonicated for size reducation using probe sonicator. The nano-vesicle (niosomal) formulation was optimized by selecting surfactant content, cholesterol content and sonication time as independent variables and particle (vesicle) size, drug entrapment efficiency and % drug release as response variables for optimization studies. The timolol maleate niosomal (TMN) formulation was evaluated for particle size, pH and osmolality and was found to possess the desired properties. The developed TMN formulation was studied for % cumulative in-vitro drug release using bottle rotating apparatus (electrolab) and was found to be 79.98% over 8 hr period exhibiting sustained drug release profile. The ex-vivo trans-corneal drug permeation profile of developed TMN was studied using modified franz-diffusion cell apparatus (Permegear) and the % cumulative drug permeation across freshly excised goat cornea was found to be 65.90 % in 8 hrs duration, which was approximately 1.5 times higher than the conventional eye drop formulation. The developed TMN was also proved to be isotonic and non-irritant in HET-CAM ocular irritancy test. It was therefore, concluded from above studies, that the developed timolol maleate niosomal (TMN) formulation is better than conventional eye drops due to longer corneal retention, sustained drug release and better trans-corneal drug permeation and thereby higher ocular bioavailability, hence, would need less frequent administration.Â

Campylobacter jejuni-Induced Intussusception Recurrence Within a 30-hour Period

Intussusception represents the most common etiology for intestinal obstruction in early childhood. It represents telescoping of the small bowel potentially resulting in ischemia and perforation. It is recognized as potentially recurrent in up to 10% of cases. A mass lesion providing a lead point is a risk factor for recurrence. Symptoms include acute intermittent abdominal pain, and bloody stools. Campylobacter jejuni is a gram-negative bacterium that causes enteritis and is known to cause intussusception. However, there are no reported cases of Campylobacter causing recurrent intussusception within a 30 hr period. We report a previously healthy 2 year old male who presented with a 7 day history of diarrhea, fever, 3 day history of bloody stools, spasmodic abdominal pain, and 1 self-limited episode of rectal prolapse. He was seen on 3 occasions in an emergency department. At the first visit, he was sent home with a kit for stool study, as he was unable to produce a bowel movement. On final return, an abdominal ultrasound reported short segment intussusception in the right lower quadrant. He developed recurrent ileocolic intussusception (3 recurrences total within 30 hours). All 3 episodes were successfully reduced via barostatic enema. For suspected lead point, he underwent exploratory laparoscopy; none was identified. After exploratory laparoscopy, his parent developed bloody stools prompting stool studies from our patient for investigation of infectious etiologies which were positive for Campylobacter jejuni. He was treated with Azithromycin. Small bowel obstruction from intussusception can complicate several luminal processes resulting in bowel wall thickening or mass acting as a lead point. While infectious etiologies are a risk factor for intussusception, this is the first report of recurrent intussusception associated with Campylobacter jejuni enteritis. In this case, stool collection for studies was unsuccessful until his parent presented with similar symptoms. Despite there being no recommendations currently for stool studies in the evaluation of intussusception in society guidelines, the authors would speculate that stool studies for enteric pathogens should be routinely obtained in children presenting with intussusception and treated wherever identified, potentially impacting the risk of recurrence. Current treatment recommendations for complicated cases of bacterial enteritis secondary to Campylobacter jejuni include macrolide antibiotics.

Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D.

Experience and activity refine cortical circuits through synapse elimination, but little is known about the activity patterns and downstream molecular mechanisms that mediate this process. We used optogenetics to drive individual mouse CA1 hippocampal neurons to fire in theta frequency bursts to understand how cell autonomous, postsynaptic activity leads to synapse elimination. Brief (1 hr) periods of postsynaptic bursting selectively depressed AMPA receptor (R) synaptic transmission, or silenced excitatory synapses, whereas more prolonged (24 hr) firing depressed both AMPAR and NMDAR EPSCs and eliminated spines, indicative of a synapse elimination. Both synapse silencing and elimination required de novo transcription, but only silencing required the activity-dependent transcription factors MEF2A/D. Burst firing induced MEF2A/D-dependent induction of the target gene Arc which contributed to synapse silencing and elimination. This work reveals new and distinct forms of activity and transcription-dependent synapse depression and suggests that these processes can occur independently.

The Viewing Geometry of Brown Dwarfs Influences Their Observed Colors and Variability Amplitudes

Abstract In this paper we study the full sample of known Spitzer [3.6 μm] and J-band variable brown dwarfs. We calculate the rotational velocities, , of 16 variable brown dwarfs using archival Keck NIRSPEC data and compute the inclination angles of 19 variable brown dwarfs. The results obtained show that all objects in the sample with mid-IR variability detections are inclined at an angle , while all objects in the sample displaying J-band variability have an inclination angle . J-band variability appears to be more affected by inclination than Spitzer [3.6 μm] variability, and is strongly attenuated at lower inclinations. Since J-band observations probe deeper into the atmosphere than mid-IR observations, this effect may be due to the increased atmospheric path length of J-band flux at lower inclinations. We find a statistically significant correlation between the color anomaly and inclination of our sample, where field objects viewed equator-on appear redder than objects viewed at lower inclinations. Considering the full sample of known variable L, T, and Y spectral type objects in the literature, we find that the variability properties of the two bands display notably different trends that are due to both intrinsic differences between bands and the sensitivity of ground-based versus space-based searches. However, in both bands we find that variability amplitude may reach a maximum at ∼7–9 hr periods. Finally, we find a strong correlation between color anomaly and variability amplitude for both the J-band and mid-IR variability detections, where redder objects display higher variability amplitudes.

Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles.

Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) have emerged as potential therapeutic agents for numerous applications. EVs offer potential advantages over cell‐based therapies with regard to safety, stability and clearance profiles, however production and potency limitations must be addressed to enable eventual translation of EV‐based approaches. Thus, we sought to examine the role of specific cell culture parameters on MSC EV production and bioactivity toward informing rational design parameters for scalable EV biomanufacturing. We report significantly reduced MSC EV vascularization bioactivity, as measured by an endothelial cell gap closure assay, with increasing passage in culture by trypsinization, especially beyond passage 4. We further show that increased frequency of EV collection yielded higher numbers of EVs from the same initial number of MSCs over a 24 hr period. Finally, we demonstrate that decreased cell seeding density in culture flasks resulted in increased production of EVs per cell in MSCs and other cell types. Overall, these studies highlight the need for careful consideration of the parameters of cell passage number and cell seeding density in the production of therapeutic EVs at laboratory scale and for rational design of large‐scale EV biomanufacturing schemes.

A Cell-Autonomous Mammalian 12 hr Clock Coordinates Metabolic and Stress Rhythms

Besides circadian rhythms, oscillations cycling with a 12hr period exist. However, the prevalence, origin, regulation, and function of mammalian 12hr rhythms remain elusive. Utilizing an unbiased mathematical approach identifying all superimposed oscillations, we uncovered prevalent 12hr gene expression andmetabolic rhythms in mouse liver, coupled with a physiological 12hr unfolded protein response oscillation. The mammalian 12hr rhythm is cell autonomous, driven by a dedicated 12hr pacemaker distinct from the circadian clock, and can be entrained invitro by metabolic and ER stress cues. Mechanistically, we identified XBP1s as a transcriptional regulator of the mammalian 12hr clock. Downregulation of the 12hr gene expression strongly correlates with human hepatic steatosis and steatohepatitis, implying its importance in maintaining metabolic homeostasis. The mammalian 12hr rhythm of gene expression also is conserved in nematodes and crustaceans, indicating an ancient origin of the 12hr clock. Our work sheds new light on how perturbed biological rhythms contribute to human disease.

Safety of Carotid Revascularization during the Acute Period of Neurological Symptom Onset in Women

Benefit from carotid revascularization is supposed to be lower in women due to increased periprocedural risks. The aim of this study was to investigate the risk of stroke/death after carotid intervention in women treated within 15days from last neurological event. Data from 282 consecutive patients treated during 2009-2015 by carotid endarterectomy or carotid stenting within 15days from neurological symptoms were analyzed by sex and stratified according to treatment delay toward symptoms onset. Eighty women (28.4%) underwent carotid stenosis correction: in 37 treatment was performed within 7days from symptoms (in 12 within 48hr); the remaining underwent carotid disease correction between day 8 and day 15 after the index event. Baseline comorbidity profile, presenting symptoms (stroke, transient ischemic attack, and recurrent symptoms) and treatment delay were comparable between sexes. The 30-day stroke/death rate was 2.5% in women (2/80) and 3.5% (7/202) in men (P=1.00). There was no 30-day death or cerebral hemorrhage in women and in patients treated within the first 48hours. In adjusted analyses, female sex was not associated with increased stroke/death risk. At 4 years, for women and men survival was 93.9% vs. 79.2% (P=0.047) and freedom from stroke 92.6% vs. 92.2% (P=0.76). Women with symptomatic carotid stenosis may benefit as men from intervention when performed within the acute (15days) or hyperacute (48hr) period after neurological event. Thirty-day stroke/death rate in this experience is lower or comparable to men's and treatment appears to be effective in preventing new strokes at midterm.

Comparison of Objective and Subjective Sedentary Behavior

Physical activity decreases the risk of chronic disease, while sedentary behavior increases this risk. Questionnaires are an easy, inexpensive way to quantify sedentary behavior. However, there tends to be error with self-report. PURPOSE: To compare time in sedentary behaviors assessed via activity monitor (objective) with sedentary time assessed by self-report (subjective). METHODS: Office staff and administrators with a sedentary job description at a University were recruited. The activPAL3 activity monitor was placed on the participants’ (n=44) thigh and worn continuously for seven days. Participants completed the Occupational Sitting Questionnaire (OSPAQ) and Paffenbarger Physical Activity Questionnaire (PPAQ) for the timeframe that the activPAL3 was worn. Data were expressed in total time (hrs/day) spent sedentary over a typical work week. A Pearson Product Correlation was utilized to examine the relationship between the subjective sedentary time at work (OSPAQ) and over a 24 hr period (PPAQ) and objective (activPAL3) sedentary time. The agreement between the objective and subjective assessments was evaluated using a Bland-Altman analysis. Differences between objective and subjective scores for each individual were calculated and the mean error was determined. RESULTS: Participants were predominantly Caucasian (95%), middle-aged (48 y + 10), and had an average BMI (30. 5 + 8.2). A positive, weak correlation between sedentary time assessed subjectively from the OSPAQ (r = .100; p = .518) and PPAQ (r = .317; p = .036), and objectively by the activPAL3 activity monitor was found. The mean error of the sedentary time estimated during the workday was approximately one hour (1.07 + 1.02) and approximately four hours (3.52 + 2.31) for the entire day, with most participants underestimating sedentary time. The Bland Altman analysis found no systematic bias in the OSPAQ (p = .743), while a trend of proportional underestimation bias in the PPAQ (p = .001) was found relative to the activPAL3 measures. CONCLUSION: Self-reported sedentary time subjectively assessed by the PPAQ and OSPAQ was weakly correlated to sedentary time objectively assessed by the activPAL3 activity monitor over a 24 hour period and while at work. The lack of a relation demonstrated substantial error in self-reported assessment.

0738 EFFECTS OF SLEEP DEPRIVATION ON BRAIN PERFUSION PATTERNS IN SLEEPWALKERS’ WAKEFULNESS AND SLOW WAVE SLEEP

Several EEG-based studies have documented anomalies in the slow wave sleep (SWS) of adult sleepwalkers. Moreover, previous imaging studies have identified specific brain perfusion patterns in sleepwalkers during post sleep deprivation wakefulness as well as during a somnambulistic episode. However, neuroimaging has yet to be used to investigate sleepwalkers’ SWS. The present study measured regional cerebral blood flow (rCBF) with single photon emission computed tomography (SPECT) during sleepwalkers’ post sleep deprivation SWS and resting-state wakefulness. Following 24 hr period of sleep deprivation, 10 sleepwalkers (7F, 3M; mean age: 28.2 ± 6.9 years) and 10 sex and age-matched controls were injected with a unidose of 99mTc-ECD after 2 minutes of stable SWS within their first sleep cycle as well as during resting-state wakefulness. Participants were scanned after each injection with a high-resolution SPECT. Between group differences in rCBF were assessed using two-sample t-tests separately for SWS and wakefulness. Significance was set at p<0.005 at the voxel level uncorrected for multiple comparisons combined with >100 contiguous voxels by cluster. When compared to controls’ rCBF observed during SWS and resting-state wakefulness, sleepwalkers showed significant decreases in several bilateral frontal regions, including the superior frontal, middle frontal and medial frontal gyri. Most of these regions are included in the dorsolateral prefrontal cortex (DLPFC). During SWS, decreased rCBF was also found in sleepwalkers’ left postcentral gyrus, insula and superior temporal gyrus. During waking resting-state, decreased rCBF was also found in parietal and temporal regions of sleepwalkers’ left hemisphere. This study was the first to use neuroimaging to investigate sleepwalkers’ SWS. Decreased rCBF was found in sleepwalkers’ DLPFC and insula, two regions involved in consciousness and in the generation of slow wave activity. The data also reveal altered rCBF patterns during sleepwalkers’ resting-state wakefulness. These findings suggest that prefrontal and insular regions may be implicated in the pathophysiology of sleepwalking. This research was supported by a research grant from the Canadian Institutes of Health Research (CIHR).