bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial propionyl‐ and butyrylcholine as novel regulators of colonic ion transport
Authors: Moreno Sarah , Gerbig Stefanie , Schulz Sabine , Spengler Bernhard , Diener Martin , Bader Sandra 
Published: July 2016

AbstractBackground and PurposeThe colonic surface epithelium produces acetylcholine, released after the binding of propionate to GPCRs for this short‐chain fatty acid (SCFA). This epithelial acetylcholine then induces anion secretion via stimulation of acetylcholine receptors. The key enzyme responsible for acetylcholine synthesis, choline acetyltransferase, is known to be unselective as regards the fatty acid used for esterification of choline. As the colonic epithelium is permanently exposed to high concentrations of different SCFAs produced by bacterial fermentation, we investigated whether choline esters other than acetylcholine, propionylcholine and butyrylcholine, are produced by the colonic epithelium, too, and whether these ‘atypical’ esters are able to stimulate the acetylcholine receptors involved in the regulation of colonic ion transport.Experimental ApproachDesorption electrospray ionization mass spectroscopy (DESI‐MS), Ussing chamber and Ca2+‐imaging experiments were performed on rat distal colon.Key ResultsDESI‐MS analyses revealed the production of acetylcholine, propionylcholine and butyrylcholine in the surface epithelium. Relative expression rates were 2–3% in comparison with acetylcholine. In Ussing chamber experiments, both atypical choline esters caused a concentration‐dependent increase in short‐circuit current, that is, stimulated anion secretion. Inhibitor experiments in the absence and presence of the submucosal plexus revealed the involvement of neuronal and epithelial acetylcholine receptors. While butyrylcholine obviously stimulated both nicotinic and muscarinic receptors, propionylcholine predominantly acted on muscarinic receptors.Conclusions and ImplicationsThese results suggest a novel pathway for communication between intestinal microbes producing SCFA and the host via modification of epithelial production of choline esters involved in the paracrine regulation of the colonic epithelium.
Cytokine and microbial profiles in relation to the clinical outcome following treatment of peri‐implantitis
Authors: Renvert Stefan , Widén Cecilia , Persson Rutger G. 
Published: July 2016

AbstractAimTo study whether cytokine levels and bacterial counts in p atients with peri‐implantitis reflect clinical treatment outcome following non‐surgical management.Materials and MethodsLuminex magnet bead technology and checkerboard DNA–DNA hybridization were used to assess treatment outcome after treatment at the implant with the most severe peri‐implantitis in 41 participants.ResultsStudy group mean age was 40.3 years (SD ± 9.9). Stable treatment outcome after 6 months (no further bone loss, probing pocket depth decrease ≥0.5 mm, no bleeding/suppuration) was identified in 9 of 41 (22%) participants. Peri‐implant crevicular fluid (PICF) levels were also lower for Il‐1β (P < 0.01), and with trends of lower cytokine levels in PICF for TNF‐α (P = 0.071), PDGFBB (P = 0.071), as well as for VEGF (vascular endothelial growth factor) (P = 0.071), and bacterial counts for Actinomyces israelii, Aggregatibacter actonomycetemcomitans (Y4), Campylobacter gracilis, Echerichia coli, Fusobacterium periodonticum, Leptotrichia buccalis, Parvimonas micra, Staphylococcus haemolyticus, Streptococcus anginosus, and Tannerella forsythia. Increasing levels of IL‐1 β and S. aureus (r2 = 0.856) were found only at implants with non‐stable outcome. A reduction of PICF levels for selected cytokines and bacteria studied had a sensitivity of 0.77, and a specificity of 0.80 against the clinical outcome as gold standard. Data analysis failed to differences in treatments (PerioFlow® versus YAG: ER laser) for changes in the expression of cytokines and bacteria studied.ConclusionsAt 6 months, clinically stable treatment outcome of peri‐implantitis is associated lower levels of putative pathogens total bacterial load with ≥30% reduction of IL1‐β, L‐6, and VEGF levels in PICF.
Sleep and Pain in Pediatric Illness: A Conceptual Review
Authors: Allen Jennifer M. , Graef Danielle M. , Ehrentraut Jennifer H. , Tynes Brooklee L. , Crabtree Valerie M. 
Published: July 2016

SummaryBackgroundSleep disruption is a common comorbidity of pediatric pain. Consequences of pain and disrupted sleep, evidence for the pain‐sleep relation, and how aspects of illness, treatment, and pharmacological pain management may contribute to or exacerbate these issues are presented.AimsThis conceptual review explored the relation between pain and sleep in children diagnosed with chronic medical or developmental conditions. The goal of this review is to expand upon the literature by examining common themes in sleep disturbances associated with painful conditions across multiple pediatric illnesses. Populations reviewed include youth with intellectual and developmental disabilities (IDD), migraines, cystic fibrosis (CF), sickle cell disease (SCD), cancer, juvenile idiopathic arthritis (JIA), juvenile fibromyalgia (JFM), and functional gastrointestinal disorders (FGIDs).ResultsConsistent evidence demonstrates that children with medical or developmental conditions are more vulnerable to experiencing pain and subjective sleep complaints than healthy peers. Objective sleep concerns are common but often under‐studied. Evidence of the pain–sleep relationship exists, particularly in pediatric SCD, IDD, and JIA, with a dearth of studies directly examining this relation in pediatric cancer, JFM, CF, and FGIDs. Findings suggest that assessing and treating pain and sleep disruption is important when optimizing functional outcomes.ConclusionIt is essential that research further examine objective sleep, elucidate the pain–sleep relationship, consider physiological and psychosocial mechanisms of this relationship, and investigate nonpharmacological interventions aimed at improving pain and sleep in vulnerable pediatric populations.
Melatonin Stimulates the SIRT1/Nrf2 Signaling Pathway Counteracting Lipopolysaccharide (LPS)‐Induced Oxidative Stress to Rescue Postnatal Rat Brain
Authors: Shah Shahid Ali , Khan Mehtab , Jo Myeung‐Hoon , Jo Min Gi , Amin Faiz Ul , Kim Myeong Ok 
Published: July 2016

SummaryAimsLipopolysaccharide (LPS) induces oxidative stress and neuroinflammation both in vivo and in vitro. Here, we provided the first detailed description of the mechanism of melatonin neuroprotection against LPS‐induced oxidative stress, acute neuroinflammation, and neurodegeneration in the hippocampal dentate gyrus (DG) region of the postnatal day 7 (PND7) rat brain.MethodsThe neuroprotective effects of melatonin against LPS‐induced neurotoxicity were analyzed using multiple research techniques, including Western blotting, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) in PND7 rat brain homogenates and BV2 cell lysates in vitro. We also used EX527 to inhibit silent information regulator transcript‐1 (SIRT1).ResultsA single intraperitoneal (i.p) injection of LPS to PND7 rats significantly induced glial cell activation, acute neuroinflammation, reactive oxygen species (ROS) production and apoptotic neurodegeneration in hippocampal DG region after 4 h. However, the coadministration of melatonin significantly inhibited both LPS‐induced acute neuroinflammation and apoptotic neurodegeneration and improved synaptic dysfunction in the hippocampal DG region of PND7 rats. Most importantly, melatonin stimulated the SIRT1/Nrf2 (nuclear factor‐erythroid 2‐related factor 2) signaling pathway to reduce LPS‐induced ROS generation. The beneficial effects of melatonin were further confirmed in LPS‐stimulated BV2 microglia cell lines in vitro using EX527 as an inhibitor of SIRT1. LPS‐induced oxidative stress, Nrf2 inhibition, and neuroinflammation are SIRT1‐dependent in BV2 microglia cell lines.ConclusionThese results demonstrated that melatonin treatment rescued the hippocampal DG region of PND7 rat brains against LPS‐induced oxidative stress damage, acute neuroinflammation, and apoptotic neurodegeneration via SIRT1/Nrf2 signaling pathway activation.
Viral colonization in exhaled breath condensate of lung cancer patients: Possible role of EBV and CMV
Authors: Carpagnano Giovanna E. , Lacedonia Donato , Natalicchio Maria Iole , Cotugno Grazia , Zoppo Luigi , Martinelli Domenico , Antonetti Raffaele , Foschino‐Barbaro Maria Pia 
Published: July 2016

AbstractIntroductionToday, an increasing interest is being addressed to the viral etiology of lung tumors. As a consequence, research efforts are currently being directed to the identification of the new viruses involved in lung carcinogenesis toward which the screening programs could be directed.ObjectivesThe aim of this study was to investigate the airways colonization by the Epstein‐Barr virus (EBV) and Citomegalovirus (CMV) in patients affected by lung cancer using, as a respiratory non‐invasive sample, the exhaled breath condensate (EBC).MethodsAbout 70 lung‐cancer patients and 40 controls were enrolled. All subjects underwent bronchial brushing and EBC collection. EBV‐DNA and CMV‐DNA were evaluated in both samples by real‐time PCR assay.ResultsThey were able to detect EBV and CMV in the EBC. An increase of the EBV positivity in non‐small cell lung cancer (NSCLC) patients compared with controls and of the CMV in advanced stages of lung cancer were observed. The association of the positivity of the cytology and the CMV test (in EBC or brushing) slightly increased the sensitivity of malignant diagnosis.ConclusionEBV and CMV resulted detectable in the EBC. In consideration of the potential involvement of these viruses in lung cancer, which was confirmed in this study, future studies in this direction were supported.
Colonoscopy bowel preparation quality improvement for patients with decompensated cirrhosis undergoing evaluation for liver transplantation
Authors: Clayton Donnesha B. , Palmer William C. , Robison Sarah W. , Heckman Michael G. , Chimato Nicolette T. , Harnois Denise M. , Francis Dawn L. 
Published: July 2016

AbstractBackground/AimsInadequate bowel preparations can necessitate early repeat of colonoscopy and increased healthcare costs. Established risk factors for suboptimal bowel preparation are known, yet data are lacking in the specific subgroup of patients with decompensated cirrhosis. The primary aim of this study was to reduce inadequate bowel preparation rates in patients with decompensated cirrhosis undergoing evaluation for liver transplant via a quality improvement initiative targeting patient education.MethodsA total of 121 patients undergoing evaluation at our institution prior to implementation of the quality improvement initiative and 91 patients undergoing evaluation after implementation were included. The initiative was an educational intervention via a 6‐minute colonoscopy and split‐prep bowel preparation educational video during the initial liver transplantation evaluation visit for all patients with scheduled colonoscopy.ResultsInadequate bowel preparation was observed in 36 patients (29.8%) in the pre‐intervention period compared to 29 patients (31.9%) in the post‐intervention period. This corresponded to a lack of a significant difference in both single‐variable analysis and multivariable analysis. Of note, there was a significantly higher rate of inadequate bowel preparation as ascites worsened (P=.028).ConclusionPatient educational video failed to improve bowel preparations in patients undergoing colonoscopy with decompensated cirrhosis.
Effect of moderately intense perioperative glucose control on renal allograft function: a pilot randomized controlled trial in renal transplantation
Authors: Parekh Justin , Roll Garrett R. , Wisel Steven , Rushakoff Robert J. , Hirose Ryutaro 
Published: July 2016

AbstractRecipient diabetes accounts for ~34% of end‐stage renal disease in patients awaiting renal transplantation and has been linked to poor graft function. We conducted a single‐center, open‐label, randomized controlled trial to determine whether moderately intense glucose control during allograft reperfusion would reduce the incidence of poor graft function. Adult diabetics undergoing deceased donor renal transplant were randomized to moderately intense glucose control (n=30) or standard control (n=30). The primary outcome was poor graft function (dialysis within seven days of transplant or failure of serum creatinine to fall by 10% for three consecutive days). Recipients with moderately intense glucose control had less poor graft function in the intention‐to‐treat (43.3% vs 73.3%, P=.02) and per‐protocol analysis (43.2% vs 81%, P<.01). Recipients with moderately intense control also had higher glomerular filtration rate (GFR) at 30 days after transplant in the per‐protocol and intention‐to‐treat analyses. There were no episodes of severe hypoglycemia in either group and no differences in mortality, seizures, stroke, graft loss, or biopsy‐proven rejection. Moderately intense glucose control at the time of allograft reperfusion reduces the incidence of poor graft function in diabetic renal transplant recipients and improves glomerular filtration rate at 30 days.
Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk
Authors: Fox Christine K , Mackay Mark T , Dowling Michael M , Pergami Paola , Titomanlio Luigi , Deveber Gabrielle ,   the SIPS Investigators
Published: July 2016

AimTo determine epilepsy risk factors after pediatric stroke.MethodA cohort of children with arterial ischemic stroke (birth–18y) was enrolled at 21 centers and followed for 1 year. Acute seizures (≤7d after stroke) and active epilepsy (at least one unprovoked remote seizure plus maintenance anticonvulsant at 1y) were identified. Predictors were determined using logistic regression.ResultsAmong 114 patients (28 neonates and 86 children) enrolled, 26 neonates (93%) and 32 children (37%) had an acute seizure. Acute seizures lasted longer than 5 minutes in 23 patients (40%) and were frequently recurrent: 33 (57%) had 2 to 10 seizures and 11 (19%) had more than 10. Among 109 patients with 1‐year follow‐up, 11 (10%) had active epilepsy. For each year younger, active epilepsy was 20% more likely (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6–0.99, p=0.041). Prolonged or recurrent acute seizures also increased epilepsy risk. Each additional 10 minutes of the longest acute seizure increased epilepsy risk fivefold (OR 4.7, 95% CI 1.7–13). Patients with more than 10 acute seizures had a 30‐fold increased epilepsy risk (OR 30, 95% CI 2.9–305).InterpretationPediatric stroke survivors, especially younger children, have a high risk of epilepsy 1 year after stroke. Prolonged or recurrent acute seizures increase epilepsy risk in a dose‐dependent manner.
Timing matters: open‐loop stimulation does not improve overnight consolidation of word pairs in humans
Authors: Weigenand Arne , Mölle Matthias , Werner Friederike , Martinetz Thomas , Marshall Lisa 
Published: July 2016

AbstractThe application of auditory clicks during non‐rapid eye movement (NREM) sleep phase‐locked to the up state of the slow oscillation (closed‐loop stimulation) has previously been shown to enhance the consolidation of declarative memories. We designed and applied sequences of three clicks during deep NREM sleep to achieve a quasi‐phase‐dependent open‐loop stimulation. This stimulation was successful in eliciting slow oscillation power in the stimulation period. Although fast and slow spindle power were markedly decreased during the stimulation period, memory consolidation did not differ from control. During putative up states fast spindle power remained, however, at control levels. We conclude that concurrence of slow oscillations and fast spindles suffices to maintain memory consolidation at control levels despite an overall decreased spindle activity.
Melanopsin supports irradiance‐driven changes in maintained activity in the superior colliculus of the mouse
Authors: Dasilva Miguel , Storchi Riccardo , Davis Katherine E. , Grieve Kenneth L. , Lucas Robert J. 
Published: July 2016

AbstractMelanopsin phototransduction allows intrinsically photosensitive retinal ganglion cells (ipRGCs) to maintain firing under sustained illumination and to encode irradiance. ipRGCs project to different parts of the visual system, including the superficial superior colliculus (sSC), but to date there is no description of melanopsin contributions to the activity of that nucleus. We sought to fill that gap using extracellular recordings to describe light response in the sSC. We failed to observe light responses in the sSC of mice lacking rod and cone function, in which melanopsin provides the only photoreception. Nor did the sSC of intact animals track very gradual ramps in irradiance, a stimulus encoded by melanopsin for other brain regions. However, in visually intact mice we did find maintained responses to extended light steps (30 s) and to an irradiance ramp upon which a high frequency (20 Hz) temporal white noise was superimposed. Both of these responses were deficient when the spectral composition of the stimulus was changed to selectively reduce its effective irradiance for melanopsin. Such maintained activity was also impaired in mice lacking melanopsin, and this effect was specific, as responses of this genotype to higher spatiotemporal frequency stimuli were normal. We conclude that ipRGCs contribute to irradiance‐dependent modulations in maintained activity in the sSC, but that this effect is less robust than for other brain regions receiving ipRGC input.
Functional consequences of experience‐dependent plasticity on tactile perception following perceptual learning
Authors: Trzcinski Natalie K. , Gomez‐Ramirez Manuel , Hsiao Steven S. 
Published: July 2016

AbstractContinuous training enhances perceptual discrimination and promotes neural changes in areas encoding the experienced stimuli. This type of experience‐dependent plasticity has been demonstrated in several sensory and motor systems. Particularly, non‐human primates trained to detect consecutive tactile bar indentations across multiple digits showed expanded excitatory receptive fields (RFs) in somatosensory cortex. However, the perceptual implications of these anatomical changes remain undetermined. Here, we trained human participants for 9 days on a tactile task that promoted expansion of multi‐digit RFs. Participants were required to detect consecutive indentations of bar stimuli spanning multiple digits. Throughout the training regime we tracked participants’ discrimination thresholds on spatial (grating orientation) and temporal tasks on the trained and untrained hands in separate sessions. We hypothesized that training on the multi‐digit task would decrease perceptual thresholds on tasks that require stimulus processing across multiple digits, while also increasing thresholds on tasks requiring discrimination on single digits. We observed an increase in orientation thresholds on a single digit. Importantly, this effect was selective for the stimulus orientation and hand used during multi‐digit training. We also found that temporal acuity between digits improved across trained digits, suggesting that discriminating the temporal order of multi‐digit stimuli can transfer to temporal discrimination of other tactile stimuli. These results suggest that experience‐dependent plasticity following perceptual learning improves and interferes with tactile abilities in manners predictive of the task and stimulus features used during training.
An integrative in silico system for predicting dysregulated genes in the human epileptic focus: Application to SLC transporters
Authors: Mirza Nasir , Vasieva Olga , Appleton Richard , Burn Sasha , Carr Daniel , Crooks Daniel , du Plessis Daniel , Duncan Roderick , Farah Jibril Osman , Josan Vivek , Miyajima Fabio , Mohanraj Rajiv , Shukralla Arif , Sills Graeme J. , Marson Anthony G. , Pirmohamed Munir 
Published: July 2016

SummaryObjectiveMany different gene families are currently being investigated for their potential role in epilepsy and in the response to antiepileptic drugs. A common research challenge is identifying the members of a gene family that are most significantly dysregulated within the human epileptic focus, before taking them forward for resource‐intensive functional studies. Published data about transcriptomic changes within the human epileptic focus remains incomplete. A need exists for an accurate in silico system for the prediction of dysregulated genes within the epileptic focus. We present such a bioinformatic system. We demonstrate the validity of our approach by applying it to the solute carrier (SLC) gene family. There are >400 known SLCs. SLCs have never been systematically studied in epilepsy.MethodsUsing our in silico system, we predicted the SLCs likely to be dysregulated in the epileptic focus. We validated our in silico predictions by identifying ex vivo the SLCs dysregulated in epileptic foci, and determining the overlap between our in silico and ex vivo results. For the ex vivo analysis, we used a custom oligonucleotide microarray containing exon probes for all known SLCs to analyze 24 hippocampal samples obtained from surgery for pharmacoresistant mesial temporal lobe epilepsy and 24 hippocampal samples from normal postmortem controls.ResultsThere was a highly significant (p < 9.99 × 10−7) overlap between the genes identified by our in silico and ex vivo strategies. The SLCs identified were either metal ion exchangers or neurotransmitter transporters, which are likely to play a part in epilepsy by influencing neuronal excitability.SignificanceThe identified SLCs are most likely to mediate pharmacoresistance in epilepsy by enhancing the intrinsic severity of epilepsy, but further functional work will be needed to fully evaluate their role. Our successful in silico strategy can be adapted in order to prioritize genes relevant to epilepsy from other gene families.
Cryoconite pans on Snowball Earth: supraglacial oases for Cryogenian eukaryotes?
Authors: Hoffman P. F. 
Published: July 2016

AbstractGeochemical, paleomagnetic, and geochronological data increasingly support the Snowball Earth hypothesis for Cryogenian glaciations. Yet, the fossil record reveals no clear‐cut evolutionary bottleneck. Climate models and the modern cryobiosphere offer insights on this paradox. Recent modeling implies that Snowball continents never lacked ice‐free areas. Wind‐blown dust from these areas plus volcanic ash were trapped by snow on ice sheets and sea ice. At a Snowball onset, sea ice was too thin to flow and ablative ice was too cold for dust retention. After a few millenia, sea ice reached 100 s of meters in thickness and began to flow as a ‘sea glacier’ toward an equatorial ablation zone. At first, dust advected to the ablative surface was recycled by winds, but as the surface warmed with rising CO2, dust aka cryoconite began to accumulate. As a sea glacier has no terminus, cryoconite saturated the surface. It absorbed solar radiation, supported cyanobacterial growth, and sank to an equilibrium depth forming holes and decameter‐scale pans of meltwater. As meltwater production rose, drainages developed, connecting pans to moulins, where meltwater was flushed into the subglacial ocean. Flushing cleansed the surface, creating a stabilizing feedback. If the dust flux rose, cryoconite was removed; if the dust flux waned, cryoconite accumulated. In addition to cyanobacteria, modern cryoconite holes are inhabited by green algae, fungi, protists, and certain metazoans. On Snowball Earth, cryoconite pans provided stable interconnected habitats for eukaryotes tolerant of fresh to brackish cold water on an ablation surface 60 million km2 in area. Flushing and burial of organic matter was a potential source of atmospheric oxygen. Dominance of green algae among Ediacaran eukaryotic primary producers is a possible legacy of Cryogenian cryoconite pans, but a schizohaline ocean—supraglacial freshwater and subglacial brine—may have exerted selective stress on early metazoans, or impeded their evolution.