Τετάρτη, 17 Φεβρουαρίου 2016

Cerebellar contributions to self-motion perception: evidence from patients with congenital cerebellar agenesis

The cerebellum was historically considered a brain region dedicated to motor control but it has become clear that it also contributes to sensory processing, particularly when sensory discrimination is required. Prior work, for example, has demonstrated a cerebellar contribution to sensory discrimination in the visual and auditory systems. The cerebellum also receives extensive inputs from the motion and gravity sensors in the vestibular labyrinth, but its role in the perception of head motion and orientation has received little attention. Drawing on the lesion-deficit approach to understanding brain function, we evaluated the contributions of the cerebellum to head motion perception by measuring perceptual thresholds in two subjects with congenital agenesis of the cerebellum. We used a set of passive motion paradigms that activated the semicircular canals or otolith organs in isolation or combination, and compared results of the agenesis patients with healthy control subjects. Perceptual thresholds for head motion were elevated in the agenesis subjects for all motion protocols, most prominently for paradigms that only activated otolith inputs. These results demonstrate that the cerebellum increases the sensitivity of the brain to the motion and orientation signals provided by the labyrinth during passive head movements.



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Saccades create similar mislocalizations in visual and auditory space

Orienting our eyes to a light, a sound or a touch occurs effortlessly, despite the fact that sound and touch have to be converted from head- and body-based coordinates to eye-based coordinates to do so. We asked whether the oculomotor representation is also used for localization of sounds even when there is no saccade to the sound source. To address this, we examined whether saccades introduced similar errors of localization judgments for both visual and auditory stimuli. Sixteen subjects indicated the direction of a visual or auditory apparent motion seen or heard between two targets presented either during fixation or straddling a saccade. Compared to the fixation baseline, saccades introduced errors in direction judgments for both visual and auditory stimuli: in both cases, apparent motion judgments were biased in direction of the saccade. These saccade-induced effects across modalities give rise to the possibility of shared, cross-modal, location coding for perception and action.



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Influence of vigilance state on physiologic consequences of seizures and seizure-induced death in mice

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of twelve adult male mice were instrumented for EEG, EMG and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared to those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities which can predict which individuals have higher risk for seizure-induced death.



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Synaptic and network consequences of monosynaptic nociceptive inputs of parabrachial nucleus origin in the central amygdala

A large majority of neurons in the superficial layer of the dorsal horn project to the lateral parabrachial nucleus (LPB). LPB neurons then project to the capsular part of the CeA (CeC), a key structure underlying the nociception-emotion link. LPB-CeC synaptic transmission is enhanced in various pain models by using electrical stimulation of putative fibers of LPB origin in brain slices. However this approach has limitations for examining direct monosynaptic connections devoid of directly stimulating fibers from other structures and local GABAergic neurons. To overcome these limitations, we infected the LPB of rats with an adeno-associated virus vector expressing channelrhodopsin-2 and prepared coronal and horizontal brain slices containing the amygdala. We found that blue light stimulation resulted in monosynaptic excitatory postsynaptic currents (EPSCs) with very small latency fluctuations followed by a large polysynaptic inhibitory postsynaptic current in CeC neurons regardless of the firing pattern type. Intraplantar formalin injection at 24 h before slice preparation significantly increased EPSC amplitude in late firing-type CeC neurons. These results indicate that direct monosynaptic glutamatergic inputs from the LPB not only excite CeC neurons but also regulate CeA network signaling through robust feed-forward inhibition, which is under plastic modulation in response to persistent inflammatory pain.



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Hypergravity within a critical period impacts on the maturation of somatosensory cortical maps and their potential for use-dependent plasticity in the adult.

We investigated experience-dependent plasticity of somatosensory maps in rat S1 cortex during early development. We analyzed both short- and long-term effects of exposure to 2G hypergravity (HG) during the first 3 postnatal weeks on forepaw representations. We also examined the potential of adult somatosensory maps for experience-dependent plasticity after early HG rearing. At P22, HG was found to induce an enlargement of cortical zones driven by nail displacements and a contraction of skin sectors of the forepaw map. In these remaining zones serving the skin, neurons displayed expanded glabrous skin receptive fields (RFs). HG also induced a bias in the directional sensitivity of neuronal responses to nail displacement. HG-induced map changes were still found after 16 weeks of housing in normogravity (NG). However, the glabrous skin RFs recorded in HG rats decreased to values similar to that of NG rats, as early as the end of the 1st week of housing in normogravity. Moreover, the expansion of the glabrous skin area and RF size decrease normally induced in adults by an enriched environment (EE) did not occur in the HG rats, even after 16 weeks of EE housing in normogravity. Our findings reveal that early postnatal experience critically and durably shapes S1 forepaw maps and limits their potential to be modified by novel experience in adulthood.



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Correlations between prefrontal neurons form a small world network that optimizes the generation of multineuron sequences of activity

Sequential patterns of prefrontal activity are believed to mediate important behaviors, e.g. working memory, but it remains unclear exactly how they are generated. In accordance with previous studies of cortical circuits, we found that prefrontal microcircuits in young adult mice spontaneously generate many more stereotyped sequences of activity than expected by chance. However, the key question of whether these sequences depend on a specific functional organization within the cortical microcircuit, or emerge simply as a byproduct of random interactions between neurons, remains unanswered. We observed that correlations between prefrontal neurons do follow a specific functional organization; they have a small world topology. However, until now it has not been possible to directly link small world topologies to specific circuit functions, e.g., sequence generation. Therefore, we developed a novel analysis to address this issue. Specifically, we constructed surrogate datasets that have identical levels of network activity at every point in time, but nevertheless represent various network topologies. We call this method SHuffling Activity to Rearrange Correlations (SHARC). We found that only surrogate datasets based on the actual small world functional organization of prefrontal microcircuits were able to reproduce the levels of sequences observed in actual data. As expected, small world datasets contained many more sequences than surrogate datasets with randomly arranged correlations. Surprisingly, small world datasets also outperformed datasets in which correlations were maximally clustered. Thus, the small-world functional organization of cortical microcircuits, which effectively balances the random and maximally clustered regimes, is optimal for producing stereotyped sequential patterns of activity.



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Odors Enhance Slow-Wave Activity in Non Rapid Eye Movement Sleep

Most forms of supra-threshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K-complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive K-complexes. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 F, mean age 26.5±2.5 years) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single-night. Each participant was exposed to one of four odorants: lavender oil (n=13), vetiver oil (n=5), vanillin, (n=12) or ammonium sulfide (n=4), for durations of 5, 10 and 20 seconds every 9-15 minutes. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement (NREM) sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow frequency oscillations.



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A common control signal and a ballistic stage can explain the control of coordinated eye-hand movements

Voluntary control has been extensively studied in the context of eye and hand movements made in isolation; yet little is known about the nature of control during eye-hand coordination. We probed this using a redirect task. Here subjects had to make reaching/pointing movements accompanied by coordinated eye movements, but had to change their plans when the target occasionally changed its position during some trials. Using a race model framework, we found that separate effector-specific mechanisms maybe recruited to control eye and hand movements when executed in isolation, but when the same effectors are coordinated, a unitary mechanism to control coordinated eye-hand movements is employed. Specifically, we found that performance curves were distinct for the eye and hand when these movements were executed in isolation but were comparable when executed together. Second, the time to switch motor plans, called the target step reaction time (TSRT) was different in the eye-alone and hand-alone conditions but were similar in the coordinated condition under assumption of a ballistic stage of ~ 40 ms, on average. Interestingly, the existence of this ballistic stage could predict the extent of eye-hand dissociations seen in individual subjects. Finally, when subjects were explicitly instructed to control specifically a single effector (eye or hand), redirecting one effector had a strong affect on the performance of the other effector. Taken together, these results suggest that a common control signal and a ballistic stage are recruited when coordinated eye-hand movement plans require alteration.



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Incorporating spike-rate adaptation into a rate code in mathematical and biological neurons

For a slowly-varying stimulus, the simplest relationship between a neuron's input and output is a rate code, in which the spike rate is a unique function of the stimulus at that instant. In the case of spike-rate adaptation, there is no unique relationship between input and output, because the spike rate at any time depends both on the instantaneous stimulus and on prior spiking (the "history"). To improve the decoding of spike trains produced by neurons that show spike-rate adaptation, we developed a simple scheme that incorporates "history" into a rate code. We utilized this rate-history code successfully to decode spike trains produced by (1) mathematical models of a neuron in which the mechanism for adaptation (IAHP) is specified, and (2) the gastropyloric receptor (GPR2), a stretch-sensitive neuron in the stomatogastric nervous system of the crab Cancer borealis, that exhibits long-lasting adaptation of unknown origin. Moreover, when we modified the spike rate either mathematically in a model system or by applying neuromodulatory agents to the experimental system, we found that changes in the rate-history code could be related to the biophysical mechanisms responsible for altering the spiking.



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Spectral breadth and laminar distribution of thalamocortical inputs to A1

The GABAergic agonist muscimol is used to inactivate brain regions in order to reveal afferent inputs in isolation. However, muscimol's use in primary auditory cortex (A1) has been questioned on the grounds that it may unintentionally suppress thalamocortical inputs. We tested whether muscimol can preferentially suppress cortical, but not thalamocortical, circuits in urethane-anesthetized mice. We recorded tone-evoked, current-source density (CSD) profiles to determine frequency receptive fields (RFs) for three current sinks: the "layer 4" sink (fastest-onset, middle-layer sink), and current sinks 100 µm above ("layer 2/3") and 300 µm below ("layer 5/6") the main input. We first determined effects of muscimol dose (0.01-1 mM) on the characteristic frequency (CF) tone-evoked layer 4 sink. An "ideal" dose (100 µM) had no effect on the CF-evoked sink onset latency or initial response, but reduced peak amplitude by >80%, implying inhibition of intracortical, but not thalamocortical, activity. We extended the analysis to current sinks in layers 2/3 and 5/6, and for all three sinks determined RF breadth (quarter-octave steps, 20 dB above CF threshold). Muscimol reduced RF breadth 42% in layer 2/3 (from 2.4 ± 0.14 to 1.4 ± 0.11 octaves), 14% in layer 4 (2.2 ± 0.12 to 1.9 ± 0.10 octaves), and not at all in layer 5/6 (1.8 ± 0.10 to 1.7 ± 0.12 octaves). The results provide an estimate of the laminar and spectral extent of thalamocortical projections, and support the hypothesis that intracortical pathways contribute to spectral integration in A1.



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Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated electrocardiogram (ECG) traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 minutes of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressures (BP) from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, while their mean HR was significantly lower after adjusting for age, body mass index, and gender, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) blood pressure at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects initially diagnosed as neurologically normal, but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy (SUDEP).



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Viral vector-based tools advance knowledge of basal ganglia anatomy and physiology

Viral vectors were originally developed to deliver genes into host cells for therapeutic potential. However, viral vector use in neuroscience research has increased because they enhance interpretation of the anatomy and physiology of brain circuits compared to conventional tract tracing or electrical stimulation techniques. Viral vectors enable neuronal or glial sub-populations to be labeled or stimulated, which can be spatially restricted to a single target nucleus or pathway. Here, we review the use of viral vectors to examine the structure and function of motor and limbic basal ganglia (BG) networks in normal and pathological states. We outline the use of viral vectors, particularly lentivirus and adeno-associated virus, in circuit tracing, optogenetic stimulation and designer drug stimulation experiments. Key studies that have used viral vectors to trace and image pathways and connectivity at gross or ultrastructural levels are reviewed. We explain how optogenetic stimulation and designer drugs used to modulate a distinct pathway and neuronal sub-population have enhanced our mechanistic understanding of BG function in health and pathophysiology in disease. Finally, we outline how viral vector technology may be applied to neurological and psychiatric conditions to offer new treatments with enhanced outcomes for patients.



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Neuromagnetic correlates of adaptive plasticity across the hand-face border in human primary somatosensory cortex

It is well established that permanent or transient reduction of somatosensory inputs, following hand deafferentation or anesthesia, induces plastic changes across the hand-face border, supposedly responsible for some altered perceptual phenomena such as tactile sensations being referred from the face to the phantom hand. It is also known that transient increase of hand somatosensory inputs, via repetitive somatosensory stimulation (RSS) at a fingertip, induces local somatosensory discriminative improvement, accompanied by cortical representational changes in SI. We recently demonstrated that RSS at the tip of the right index finger induces similar training-independent perceptual learning across the hand-face border, improving somatosensory perception at the lips (Muret et al., 2014). Whether neural plastic changes across the hand-face border accompany such remote and adaptive perceptual plasticity remains unknown. Here we used magnetoencephalography to investigate the electrophysiological correlates underlying RSS-induced behavioral changes across the hand-face border. The results highlight significant changes in dipole location after RSS, both for the stimulated finger and for the lips. These findings reveal plastic changes that cross the hand-face border following an increase, instead of a decrease, in somatosensory inputs.



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An asymmetrical outer retinal response to drifting sawtooth gratings

Electroretinogram (ERG) studies have demonstrated that the retinal response to temporally-modulated fast-ON and fast-OFF sawtooth flicker is asymmetrical. The response to spatiotemporal sawtooth stimuli has not yet been investigated. Perceptually, such drifting gratings or diamond plaids shaded in a sawtooth pattern appear brighter when movement produces fast-OFF relative to fast-ON luminance profiles. The neural origins of this illusion remain unclear (although a retinal basis has been suggested). Thus we presented toad eyecups with sequential epochs of sawtooth, sine-wave, and square-wave gratings drifting horizontally across the retina at temporal frequencies of 2.5 - 20Hz. All ERGs revealed a sustained DC trans-tissue potential during drift, plus a peak at drift offset. The amplitudes of both phenomena increased with temporal frequency. Consistent with the human perceptual experience of sawtooth gratings, the sustained DC potential effect was greater for fast-OFF cf fast-ON sawtooth. Modelling suggested that the dependence of temporal luminance contrast on stimulus device frame rate contributed to the temporal frequency effects, but could not explain the divergence in response amplitudes for the two sawtooth profiles. The difference between fast-ON and fast-OFF sawtooth profiles also remained following pharmacological suppression of post-receptoral activity with Tetrodotoxin (TTX), 2-Amino-4-Phosphonobutric acid (APB), and cis-Piperidine-2,3-dicarboxylic Acid (PDA). Our results indicate that the DC potential difference originates from asymmetries in the photoreceptoral response to fast-ON and fast-OFF sawtooth profiles, thus pointing to an outer retinal origin for the motion induced drifting sawtooth brightness illusion.



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Testing the hypothesis of neurodegeneracy in respiratory network function with a priori transected arterially perfused brainstem preparation of rat.

Degeneracy of respiratory network function would imply that anatomically discrete aspects of the brainstem are capable of producing respiratory rhythm. To test this theory we a priori transected brainstem preparations before re-perfusion and re-oxygenation at 4 rostro-caudal levels: 1.5 mm caudal to obex (n=5), at obex (n=5), 1.5 mm (n=7) and 3mm (n=6) rostral to obex. The respiratory activity of these preparations was assessed via recordings of phrenic (PNA), vagal (VNA) nerves and lumbar spinal expiratory motor output (L1). Preparations with a priori transection at level of the caudal brainstem did not produce stable rhythmic respiratory bursting, even when stimulating the arterial chemoreceptors with NaCN. Re-perfusion of brainstems that preserved the pre-Bötzinger complex (pre-BötC), showed spontaneous and sustained rhythmic respiratory bursting at low PNA amplitude that occurred simultaneously in all respiratory motor outputs. We refer to this rhythm as the pre-BötC burstlet-type rhythm. Conserving circuitry up to the pontine-medullary junction consistently produced robust high amplitude PNA at lower burst rates, while sequential motor patterning across the respiratory motor outputs remained absent. Some of the rostrally transected preparations expressed both burstlet-type and regular PNA amplitude rhythms. Further analysis showed that the burstlet-type rhythm and high amplitude PNA had 1:2 quantal relation with burstlets appearing to trigger high amplitude bursts. We conclude that no degenerate rhythmogenic circuits are located in the caudal medulla oblongata, and confirm the pre-BötC as the primary rhythmogenic kernel. The absence of sequential motor patterning in a priori transected preparations suggests that pontine circuits govern respiratory pattern formation.



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Mutant Screen Report: Microarray Analysis of Gene Expression in S. cerevisiae kap108{Delta} Mutants Upon Addition of Oxidative Stress.

Protein transport between the nucleus and cytoplasm of eukaryotic cells is tightly regulated, providing a mechanism for controlling intracellular localization of proteins and regulating gene expression. In this study, we have investigated the importance of nucleocytoplasmic transport mediated by the karyopherin Kap108 in regulating cellular responses to oxidative stress in Saccharomyces cerevisiae. We carried out microarray analyses on wild type and kap108 mutant cells grown under normal conditions, shortly after introduction of oxidative stress, after one hour of oxidative stress, and one hour after oxidative stress was removed. We observe more than 500 genes that undergo a 40% or greater change in differential expression between wild type and kap108 cells under at least one of these conditions. Genes undergoing changes in expression can be categorized in two general groups: 1) Those that are differentially expressed between wild-type and kap108 cells no matter the oxidative stress conditions, and 2) those that have patterns of response dependent upon both the absence of Kap108 and introduction or removal of oxidative stress. Gene Ontology analysis reveals that among the genes whose expression is reduced in the absence of Kap108 are those involved in stress response and intracellular transport, while those overexpressed are largely involved in mating and pheromone response. We also identified 25 clusters of genes that undergo similar patterns of change in gene expression when oxidative stresses are added and subsequently removed, including genes involved in stress response, oxidation-reduction processing, iron homeostasis, ascospore wall assembly, transmembrane transport, and cell fusion during mating. These data suggest that Kap108 is important for regulating expression of genes involved in a variety of specific cell functions.



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Mapping of Variable DNA Methylation across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome

DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Many studies have mapped DNA methylation changes associated with embryogenesis, cell differentiation and cancer at a genome-wide scale. Our understanding of genome-wide DNA methylation changes in a developmental or disease-related context has been steadily growing. However, the investigation of which CpGs are variably methylated in different normal cell or tissue types is still limited. Here we present an in-depth analysis of 54 single-CpG-resolution DNA methylomes of normal human cell types by integrating high-throughput sequencing-based methylation data. We found that the ratio of methylated to unmethylated CpGs is relatively constant regardless of cell type. However, which CpGs made up the unmethylated complement was cell-type specific. We categorized the 26 million human autosomal CpGs based on their methylation levels across multiple cell types to identify variably methylated CpGs. 22.6% exhibited variable DNA methylation across cell types included in our study. These variably methylated CpGs formed 660 thousand variably methylated regions (VMRs), encompassing 11% of the genome. By integrating a multitude of genomic data, we found that VMRs enrich for histone modifications indicative of enhancers, suggesting their role as regulatory elements marking cell type specificity. VMRs enriched for transcription factor binding sites in a tissue-dependent manner. Importantly, they enriched for GWAS variants, suggesting VMRs could potentially be implicated in disease and complex traits. Taken together, our results highlight the link among CpG methylation variation, genetic variation and disease risk for many human cell types.



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Genome-Based Selection and Characterization of Fusarium circinatum-Specific Sequences

Fusarium circinatum is an important pathogen of pine trees and its management in the commercial forestry environment relies largely on early detection, particularly in seedling nurseries. The fact that the entire genome of this pathogen is available opens new avenues for the development of diagnostic tools for this fungus. In this study we identified open reading frames (ORFs) unique to Fusarium circinatum and determined that they were specific to the pathogen. The ORF identification process involved bioinformatics-based screening of all the putative F. circinatum ORFs against public databases. This was followed by functional characterization of ORFs found to be unique to F. circinatum. We used PCR- and hybridization-based approaches to confirm the presence of selected unique genes in different strains of F. circinatum and their absence from other Fusarium species for which genome sequence data are not yet available. These included species that are closely related to F. circinatum as well as those that are commonly encountered in the forestry environment. Thirty six ORFs were identified as potentially unique to F. circinatum. Nineteen of these encode proteins with known domains while the other seventeen encode proteins of unknown function. The results of our PCR analyses and hybridization assays showed that three of the selected genes were present in all of the strains of F. circinatum tested and absent from the other Fusarium species screened. These data thus indicate that the selected genes are common and unique to F. circinatum. These genes thus could be good candidates for use in rapid, in-the-field diagnostic assays specific to F. circinatum. Our study further demonstrates how genome sequence information can be mined for the identification of new diagnostic markers for the detection of plant pathogens.



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Large-Scale Survey of Intraspecific Fitness and Cell Morphology Variation in a Protoploid Yeast Species

It is now clear that the exploration of the genetic and phenotypic diversity of non-model species greatly improves our knowledge in biology. In this context, we recently launched a population genomic analysis of the protoploid yeast Lachancea kluyveri (formerly Saccharomyces kluyveri), highlighting a broad genetic diversity ( = 17 x 10-3) compared to the yeast model organism, Saccharomyces cerevisiae ( = 4 x 10-3). Here, we sought to generate a comprehensive view of the phenotypic diversity in this species. In total, 27 natural L. kluyveri isolates were subjected to trait profiling using the following independent approaches: (i) analyzing growth in 55 growth conditions and (ii) investigating 501 morphological changes at the cellular level. Despite higher genetic diversity, the fitness variance observed in L. kluyveri is lower than that in S. cerevisiae. However, morphological features show an opposite trend. In addition, there is no correlation between the origins (ecological or geographical) of the isolate and the phenotypic patterns, demonstrating that trait variation follows neither population history nor source environment in L. kluyveri. Finally, pairwise comparisons between growth rate correlation and genetic diversity show a clear decrease in phenotypic variability linked to genome variation increase, whereas no such a trend was identified for morphological changes. Overall, this study reveals for the first time the phenotypic diversity of a distantly related species to S. cerevisiae. Given its genetic properties, L. kluyveri might be useful in further linkage mapping analyses of complex traits, and could ultimately provide a better insight into the evolution of the genotype-phenotype relationship across yeast species.



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National disparities in minimally invasive surgery for rectal cancer

Abstract

Background

Social and racial disparities have been identified as factors contributing to differences in access to care and oncologic outcomes in patients with colorectal cancer. The aim of this study was to investigate national disparities in minimally invasive surgery (MIS), both laparoscopic and robotic, across different racial, socioeconomic and geographic populations of patients with rectal cancer.

Methods

We utilized the American College of Surgeons National Cancer Database to identify patients with rectal cancer from 2004 to 2011 who had undergone definitive surgical procedures through either an open, laparoscopic or robotic approach. Inclusion criteria included only one malignancy and no adjuvant therapy. Multivariate analysis was performed to investigate differences in age, gender, race, income, education, insurance coverage, geographic setting and hospital type in relation to the surgical approach.

Results

A total of 8633 patients were identified. The initial surgical approach included 46.5 % open (4016), 50.9 % laparoscopic (4393) and 2.6 % robotic (224). In evaluating type of insurance coverage, patients with private insurance were most likely to undergo laparoscopic surgery [OR (odds ratio) 1.637, 95 % CI 1.178–2.275], although there was a less statistically significant association with robotic surgery (OR 2.167, 95 % CI 0.663–7.087). Patients who had incomes greater than $46,000 and received treatment at an academic center were more likely to undergo MIS (either laparoscopic or robotic). Race, education and geographic setting were not statistically significant characteristics for surgical approach in patients with rectal cancer.

Conclusions

Minimally invasive approaches for rectal cancer comprise approximately 53 % of surgical procedures in patients not treated with adjuvant therapy. Robotics is associated with patients who have higher incomes and private insurance and undergo surgery in academic centers.



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Impact of single-incision laparoscopic cholecystectomy (SILC) versus conventional laparoscopic cholecystectomy (CLC) procedures on surgeon stress and workload: a randomized controlled trial

Abstract

Introduction

Single-incision laparoscopic cholecystectomy (SILC) may lead to higher patient satisfaction; however, SILC may expose the surgeon to increased workload. The goal of this study was to compare surgeon stress and workload between SILC and conventional laparoscopic cholecystectomy (CLC).

Methods

During a double-blind randomized controlled trial comparing patient outcomes for SILC versus CLC (NCT0148943), surgeon workload was assessed by four measures: surgery task load index questionnaire (Surg-TLX), maximum heart rate, salivary cortisol level, and instruments usability survey. The maximum heart rate and salivary cortisol levels were sampled from the surgeon before the random assignment of the surgical procedure, intraoperatively after the cystic duct was clipped, and at skin closure. After each procedure, the surgeon completed the Surg-TLX and an instrument usability survey. Student's t tests, Wilcoxon rank sum test, and Kruskal–Wallis nonparametric ANOVAs on the dependent variables by the technique (SILC vs. CLC) were performed with α = 0.05.

Results

Twenty-three SILC and 25 CLC procedures were included in the intent-to-treat analysis. No significant differences were observed between SILC and CLC for patient demographics and procedure duration. SILC had significantly higher post-surgery surgeon maximum heart rates than CLC (p < 0.05). SILC also had significantly higher mean change in the maximum heart rate between during and post-procedure (p < 0.05) than CLC. Salivary cortisol level was significantly higher during SILC than CLC (p < 0.01). Awkward manipulation of the instruments and limited fine motions were reported significantly more frequently with SILC than CLC (p < 0.01). In the surgeon-reported Surg-TLX, subscale of physical demand was significantly more demanding for SILC than CLC (p < 0.05).

Conclusions

Surgeon heart rate, salivary cortisol level, instrument usability, and Surg-TLX ratings indicate that SILC is significantly more stressful and physically demanding than the CLC. Surgeon stress and workload may impact patients' outcomes; thus, ergonomic improvement on SILC is necessary.



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Effectiveness of peroral direct cholangioscopy using an ultraslim endoscope for the treatment of hepatolithiasis in patients with hepaticojejunostomy (with video)

Abstract

Background

Hepatolithiasis is a postoperative complication of hepaticojejunostomy (HJ) performed for various pancreatobiliary diseases. Hepatolithiasis can cause repeated cholangitis. Complete stone removal and bile stasis elimination are therefore necessary. Here, we evaluated the effectiveness of peroral direct cholangioscopy (PDCS) using an ultraslim endoscope for treating hepatolithiasis in HJ patients.

Methods

We studied 14 patients with hepatolithiasis who underwent bowel reconstruction with HJ between April 2012 and May 2014. Diagnostic and therapeutic endoscopic retrograde cholangiography using a short double-balloon enteroscope (DBE) was initially performed. Following stone removal, the DBE was exchanged for an ultraslim endoscope through the balloon overtube for PDCS.

Results

The success rate of PDCS procedure was 85.7 % (12/14). In 5 of 12 (41.7 %) patients with successful PDCS, the residual stones were detected and removed completely using a 5-Fr basket catheter and suction after normal saline irrigation. In the remaining 7 (58.3 %) patients, no residual stone was detected. The median procedure time was 14 min (range 8–36) with no serious postoperative complications. The median follow-up time after PDCS was 21 months (range 5–26), and only 1 patient (8.3 %) had IHBD stone recurrence with an anastomotic stricture.

Conclusions

PDCS using an ultraslim endoscope appears to be useful for detecting and removing residual stones following hepatolithiasis treatment using a DBE. The combined use of a DBE and PDCS may reduce the risk of hepatolithiasis recurrence in HJ patients.



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Natural orifice transluminal endoscopic surgery-assisted versus laparoscopic ovarian cystectomy (NAOC vs. LOC): a case-matched study

Abstract

Background

Natural orifice transluminal endoscopic surgery (NOTES) has shown its prospection as a minimally invasive endoscopic surgery. This study aimed to examine the safety and efficacy of combined NOTES and vaginal approach, natural orifice transluminal endoscopic surgery-assisted ovarian cystectomy (NAOC), in the conservative management of benign ovarian tumors.

Methods

Records were reviewed for the 34 consecutive NAOC procedures between May 2011 and March 2014. Age, body mass index, parity, size of the mass, and bilaterality of the mass were used to select comparable patient who had undergone laparoscopic ovarian cystectomy (LOC).

Results

A total of 277 patients were recruited in this study (243 LOCs and 34 NAOCs, respectively). There was no incidence of switching to abdominal laparotomy. Length of operation and length of postoperative stay were significantly greater in the LOC group than in the NAOC group, but total hospital charges were similar in both groups. There was no difference in febrile morbidity between the two groups but more estimated blood loss (EBL) in NAOC group, although EBL was <50 mL in the two groups. Linear correlations of mass size with operating time and EBL existed in LOC group, but not in NAOC group.

Conclusion

NAOC can be safely performed for benign and large ovarian tumors. Besides, NAOC offers a superior operative efficiency compared with LOC.



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Long-term knowledge retention following simulation-based training for electrosurgical safety: 1-year follow-up of a randomized controlled trial

Abstract

Background

Despite the value of simulation for surgical training, it is unclear whether acquired competencies persist long term. A prior randomized trial showed that structured simulation improves knowledge of the safe use of electrosurgery (ES) amongst trainees up to 3 months after the curriculum (Madani et al. in Surg Endosc 28(10):2772–2782, 2014). We now analyse long-term knowledge retention. This study estimates the effects of a structured simulation-based curriculum to teach the safe use of ES on knowledge after 1 year.

Methods

Trainees previously participated in a 1-h didactic ES course, followed by randomization into one of two groups: an unstructured hands-on session where trainees used ES devices (control group) or a goal-directed hands-on training session (Sim group). Knowledge of pre- and post-curriculum (immediate, 3 months and 1 year) and knowledge of ES safety were assessed using different multiple-choice examinations. Data are expressed as median (interquartile range), *p < 0.05.

Results

Fifty-nine trainees participated (30 control group; 29 Sim group). Despite equal baseline examination scores, Sim group demonstrated higher scores compared to control immediately (89 % [83; 94] vs. 83 % [71; 86]*), 3 months (77 % [69; 90] vs. 60 % [51; 80]*) and 1 year after curriculum (70 % [61; 74] vs. 60 % [31; 71]*). One-year score remained significantly greater compared to baseline in the Sim group (70 % [61; 74] vs. 49 % [43; 57]*), but was similar to baseline in the control group (60 % [31; 71] vs. 45 % [34; 52]).

Conclusions

After ES simulation training, retention of competencies persists longer when the hands-on component is designed to reinforce specific learning objectives in a structured curriculum. Despite routine clinical use of ES devices, knowledge degrades overtime, suggesting the need for ongoing formal educational activities to reinforce curricular objectives.



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Long-term results of a randomized controlled trial of T2 versus T2–T3 ablation in endoscopic thoracic sympathectomy for palmar hyperhidrosis

Abstract

Background

Despite good short-term results and patient satisfaction with endoscopic thoracic sympathectomy (ETS), there has been much debate on the level of sympathectomy for treatment of palmar hyperhidrosis (PH) in terms of long-term clinical outcomes.

Objective

The aim of the study was to analyze the long-term recurrence and compensatory hyperhidrosis (CH) rates of ETS, comparing single-level T2 against multi-level T2–T3 ablation in single patients.

Methods

Patients who had undergone treatment for PH with unilateral T2 and contralateral T2–T3 ablation in ETS were retrospectively reviewed. They were subjected to telephone interview using standardized set of interview script and questionnaire with a scoring system similar to hyperhidrosis disease severity scale. All patients were evaluated for comparison of symptom resolution, site and severity of CH, and satisfaction rates. To compare between T2 and T2–T3, the level of sympathectomy on one side is matched to the ipsilateral recurrence of PH and CH occurrence.

Results

Twenty-two patients with a mean age of 36.5 years could be reached. The mean follow-up was 8 years (range 38–153 months). The global recurrence rate for PH is 18 %. CH was observed in 20 (91 %) patients, and trunk compensation was the most common (18/22–82 %), followed by lower limb (14/22–64 %) and axilla (10/22–45 %). Overall, 72.8 % (16) of the patients were satisfied with the operation. Among the six patients who were not satisfied, two patients reported recurrence of symptoms, while four patients experienced some form of compensation. There was no absolute difference in the severity of sweating bilaterally for patients who reported recurrence of PH. The site and severity of CH were also bilaterally symmetrical for all patients.

Conclusion

There was no difference in recurrence rates and CH between single-level (T2) and multi-level (T2–T3) ETSs in the long term.



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Laparoscopic hepaticojejunostomy after bile duct injury

Abstract

Background

The incidence of bile duct injuries (BDI) after cholecystectomy, which is a life-threatening condition that has several medical and legal implications, currently stands at about 0.6 %. The aim of this study is to describe our experience as the first center to use a laparoscopic approach for BDI repair.

Methods

A prospective study between June 2012 and September 2014 was developed. Twenty-nine consecutive patients with BDI secondary to cholecystectomy were included. Demographics, comorbidities, presenting symptoms, details of index surgery, type of lesion, preoperative and postoperative diagnostic work-up, and therapeutic interventions were registered. Videos and details of laparoscopic hepaticojejunostomy (LHJ) were recorded. Injuries were staged using Strasberg classification. A side-to-side anastomosis with Roux-en-Y reconstruction was always used. In patients with E4 and some E3 injuries, a segment 4b or 5 section was done to build a wide anastomosis. In E4 injuries, a neo-confluence was performed. Complications, mortality, and long-term evolution were recorded.

Results

Twenty-nine patients with BDI were operated. Women represented 82.7 % of the cases. The median age was 42 years (range 21–74). Injuries at or above the confluence occurred in 62 %, and primary repair at our institution was performed at 93.1 % of the cases. Eight neo-confluences were performed in all E4 injuries (27.5 %). The median operative time was 240 min (range 120–585) and bleeding 200 mL (range 50–1100). Oral intake was started in the first 48 h. Bile leak occurred in 5 cases (17.2 %). Two patients required re-intervention (6.8 %). No mortality was recorded. The maximum follow-up was 36 months (range 2–36). One patient with E4 injury developed a hepaticojejunostomy (HJ) stenosis after 15 months. This was solved with endoscopic dilatation.

Conclusions

The benefits of minimally invasive approaches in BDI seem to be feasible and safe, even when this is a complex and catastrophic scenario.



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What errors make a laparoscopic cancer surgery unsafe? An ad hoc analysis of competency assessment in the National Training Programme for laparoscopic colorectal surgery in England

Abstract

Background

The National Training Programme for laparoscopic colorectal surgery in England was implemented to ensure training was supervised, structured, safe and effective. Delegates were required to pass a competency assessment (sign-off) before undertaking independent practice. This study described the types of errors identified and associated these errors with competency to progress to independent laparoscopic colorectal practice.

Methods

All sign-off submissions from the start of the process in January 2008 until July 2013 were included. Content analysis was used to categorise errors. Bayes factor (BF) was used to measure the impact of individual error on assessment outcome. A smaller BF indicates that an error has stronger associations with unsuccessful assessments. Bayesian network was employed to graphically represent the reasoning process whereby the chance of successful assessment diminished with the identification of each error. Quality of the error feedback was measured by the area under the ROC curve which linked the predictions from the Bayesian model to the expert verdict.

Results

Among 370 assessments analysed, 240 passed and 130 failed. On average, 2.5 different types of error were identified in each assessment. Cases that were more likely to fail had three or more different types of error (χ 2 = 72, p < 0.0001) and demonstrated poorer technical skills (CAT score <2.7, χ 2 = 164, p < 0.0001). Case complexity or right- versus left-sided resection did not have a significant impact. Errors associated with dissection (BF = 0.18), anastomosis (BF = 0.23) and oncological quality (BF = 0.19) were critical determinants of surgical competence, each reducing the odds of pass by at least fourfold. The area under the ROC curve was 0.84.

Conclusions

Errors associated with dissection, anastomosis and oncological quality were critical determinants of surgical competency. The detailed error analysis reported in this study can guide the design of future surgical education and clinical training programmes.



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Safety and feasibility of endoscopic biliary radiofrequency ablation treatment of extrahepatic cholangiocarcinoma

Abstract

Background

Biliary bipolar radiofrequency ablation (RFA) is a new treatment for extrahepatic cholangiocarcinoma (CCA) currently under evaluation. The purpose of this study was to evaluate the safety, particularly biliary fistula occurrence, and the feasibility of biliary RFA in a homogeneous group of patients treated using the same RFA protocol.

Methods

Twelve patients with inoperable or unresectable CCA were included in a bicentric case series study. After removal of biliary plastic stents, a radiofrequency treatment with a new bipolar probe (Habib™ EndoHBP®) was applied. The energy was delivered by a RFA generator (VIO® 200 D), supplying electrical energy at 350 kHz and 10 W for 90 s. At the end of the procedure, one or more biliary stents were left in place. Adverse events were assessed per-procedure and during follow-up visits.

Results

CCA was confirmed in all patients by histology (66 %), locoregional evolution or metastatic evolution. The types of CCA were Bismuth I stage (N = 4), Bismuth II stage (N = 3), Bismuth III stage (N = 2) and Bismuth IV stage (N = 3). No serious adverse events occurred within 30 days following endoscopic treatment: One patient had a sepsis due to bacterial translocation on day 1 and another had an acute cholangitis on day 12 due to early stent migration. No immediate or delayed biliary fistula was reported. The ergonomics of the probe made treatment easy in 100 % of cases. Mean survival was 12.3 months.

Conclusion

Endoscopic radiofrequency treatment of inoperable CCA appears without major risks and is feasible. No major adverse events or biliary fistula were identified.



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10 cm H 2 O PEEP application in laparoscopic surgery and cerebral oxygenation: a comparative study with INVOS and FORESIGHT

Abstract

Introduction

In the present study, changes in hemodynamic parameters and cerebral oxygen saturation (rSO2) associated with 10 cm H2O PEEP application were investigated, which is assumed beneficial for the respiratory functions and oxygenation during laparoscopic cholecystectomy (LC) applied at 30° head-up left side position. Data gathered via two devices, namely INVOS and FORESIGHT, were compared.

Methods

After both the ethics committee approval from the hospital and patients' written consents were obtained, patients undergoing elective laparoscopic surgery (only ASA I–II) were randomly divided into two groups (Clinical trials protocol NCT02071550). Sensors of INVOS and FORESIGHT devices were placed on the right side at the forehead region. In total, 11 evaluation periods were formed, namely pre-induction (1st period), post-induction (2nd period), abdominal insufflation outset (3rd period), post-insufflation at 5-min intervals (4th, 5th, 6th, 7th, and 8th period), at the end of insufflation (9th period), at the end of operation (10th period), and at the end of anesthesia (11th period). While one of the groups did not receive PEEP (ZEEP group), the other group received 10 cm H2O along with abdominal insufflation (PEEP group). Demographic data, hemodynamic values, and rSO2 values were recorded for both groups at all 11 periods.

Results

A total of 44 patients in two groups, each group containing 22 individuals, were included in the study. Systolic, diastolic, and mean arterial pressures, etCO2 and SO2 values, and demographic data were found to be similar in both groups. Heart rate was observed to be higher in the PEEP group starting with the PEEP administration. INVOS rSO2 values were found similar in both groups. However, FORESIGHT rSO2 values were found to be higher in the PEEP group compared to the ZEEP group. No patient had cerebral desaturation in both groups throughout the study.

Discussion

Application of PEEP with 10 cm H2O during abdominal insufflation could increase the rSO2 value and heart rate in patients undergoing laparoscopic cholecystectomy. However, all changes observed were within normal limits. FORESIGHT device yielded more compatible results with hemodynamic data compared to INVOS.



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Fibrin sealant for mesh fixation in laparoscopic groin hernia repair does not increase long-term recurrence

Abstract

Background

Methods of groin hernia repair include laparoscopic techniques using tissue-penetrating mesh fixation or non-penetrating fixation. Concerns regarding hernia repair include postoperative chronic pain, sexual dysfunction, and recurrence. Earlier estimations of recurrence rates have largely been based on nationwide databases, where reoperation rates have been used as a surrogate measure for recurrence, which may underestimate the true recurrence rates. The aim of this study was to evaluate long-term recurrence in patients who had undergone transabdominal pre-peritoneal (TAPP) laparoscopic groin hernia repair using either fibrin sealant or tacks for mesh fixation.

Methods

This study used data from the Danish Hernia Database to create the following cohort: All patients operated laparoscopically for primary groin hernia with a TAPP procedure using fibrin sealant for mesh fixation. These patients were matched 1:2 with patients, where the mesh was fixated using tacks. A validated questionnaire was sent to all included patients to determine recurrence, which was defined as reoperation or clinical diagnosis of recurrence by a physician. Follow-up was from index operation to either reoperation date, date of clinical recurrence diagnosis, or response date.

Results

A total of 2273 persons (n = 2340 groins) were included, of which 1535 returned the questionnaire, resulting in a response rate of 66.2 % with a median follow-up time of 31 months (range 0–62). Among these, 114 (7.4 %) recurrences were found, of which 30 (5.8 %) were in the fibrin sealant group and 84 (8.3 %) in the tacks group (p = 0.084). The Cox regression analysis found no difference in recurrence with the use of tacks compared to fibrin sealant (hazard ratio 0.8) [95 % CI (0.5–1.2)].

Conclusion

We found no significant difference in long-term reoperation rates and clinical recurrences in patients undergoing TAPP repair with meshes fixated with fibrin sealant compared with tacks.



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Taxonomy of instructions given to residents in laparoscopic cholecystectomy

Abstract

Background

Although simulation-based training allows residents to become proficient in surgical skills outside the OR, residents still depend on senior surgeons' guidance in transferring skills accumulated from simulators into the operating room. This study aimed to identify and classify explicit instructions made by attending surgeons to their residents during laparoscopic surgery. Through these instructions, we examined the role gaze guidance plays in OR-based training.

Methods

A total of ten laparoscopic cholecystectomy cases being performed by PGY4 residents were analyzed. The explicit directional instructions given by the mentoring attending surgeons to their residents were identified and classified into four categories based on their locations in the coordinate system. These categories were further combined into two classes, based on the target of instructions. The frequencies of instructions in the two classes were compared, and effect size was calculated.

Results

There were 1984 instructions identified in the ten cases. The instructions were categorized into instrument guidance (38.51 %) and gaze guidance (61.49 %). The instrument guidance focused on moving the instruments to perform surgical tasks, including directions to targets, instrument manipulation, and instrument interaction. The gaze guidance focused on achieving common ground during the operation, including target identification and target fixation. The frequency of gaze guidance is significantly higher than instrument guidance in a laparoscopic cholecystectomy (p < 0.001) with a large effect size (r = 0.6).

Conclusions

Gaze guidance has become the main focus of OR-based training. The results show a tight connection between adopting expert gaze and performing surgical tasks and suggest that gaze training should be integrated into the simulation training.



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Function of high-resolution manometry in the analysis of peroral endoscopic myotomy for achalasia

Abstract

Background

Peroral endoscopic myotomy (POEM) was introduced as a new effective therapeutic option for esophageal achalasia.

Method

A total of 112 achalasia patients categorized into three subtypes by HRM who underwent POEM were enrolled in our study. Eckardt score and HRM were performed preoperation, 6 months, and 1 year after POEM to evaluate the effectiveness, safety, and feasibility of POEM and to investigate the treatment response to POEM for the three subtypes of achalasia, classified by high-resolution manometry (HRM).

Results

POEM was successfully performed in all patients. Compared with pre-POEM scores, the Eckardt scores were significantly reduced from 7.3 ± 1.4 to 1.0 ± 0.8 6 months after POEM and to 1.2 ± 0.6 1 year after POEM (p < 0.05). The LESP before treatment was 41.8 ± 15.3 mmHg, compared with a LESP of 18.4 ± 7.1 mmHg 6 months after POEM and 20.7 ± 7.5 mmHg 1 year after POEM (p < 0.05). In addition, POEM decreased the 4-s IRP from 33.4 ± 9.0 to 14.6 ± 3.8 mmHg 6 months after POEM and to 16.4 ± 3.9 mmHg 1 year after POEM (p < 0.05). The 4-s IRP was reduced to <15 mmHg in 64 of 112 patients. Type II had the best response to POEM, while type III exhibited the worst response.

Conclusions

POEM appears to be an effective and less invasive treatment for achalasia. HRM can be useful in the classification of achalasia, while these subclassifications help to predict the responsiveness to POEM.



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Predictive value of background experiences and visual spatial ability testing on laparoscopic baseline performance among residents entering postgraduate surgical training

Abstract

Background

Emerging evidence suggests that despite dedicated practice, not all surgical trainees have the ability to reach technical competency in minimally invasive techniques. While selecting residents that have the ability to reach technical competence is important, evidence to guide the incorporation of technical ability into selection processes is limited. Therefore, the purpose of the present study was to evaluate whether background experiences and 2D–3D visual spatial test results are predictive of baseline laparoscopic skill for the novice surgical trainee.

Methods

First-year residents were studied. Demographic data and background surgical and non-surgical experiences were obtained using a questionnaire. Visual spatial ability was evaluated using the PicSOr, cube comparison (CC) and card rotation (CR) tests. Technical skill was assessed using the camera navigation (LCN) task and laparoscopic circle cut (LCC) task. Resident performance on these technical tasks was compared and correlated with the questionnaire and visual spatial findings.

Results

Previous experience in observing laparoscopic procedures was associated with significantly better LCN performance, and experience in navigating the laparoscopic camera was associated with significantly better LCC task results. Residents who scored higher on the CC test demonstrated a more accurate LCN path length score (r s(PL) = −0.36, p = 0.03) and angle path (r s(AP) = −0.426, p = 0.01) score when completing the LCN task. No other significant correlations were found between the visual spatial tests (PicSOr, CC or CR) and LCC performance.

Conclusion

While identifying selection tests for incoming surgical trainees that predict technical skill performance is appealing, the surrogate markers evaluated correlate with specific metrics of surgical performance related to a single task but do not appear to reliably predict technical performance of different laparoscopic tasks. Predicting the acquisition of technical skills will require the development of a series of evidence-based tests that measure a number of innate abilities as well as their inherent interactions.



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Effectiveness of platelet inhibition on major adverse cardiac events in non-cardiac surgery after percutaneous coronary intervention: a prospective cohort study

Background

Platelet inhibition is mandatory therapy after percutaneous coronary intervention (PCI). Withdrawal of oral antiplatelet agents has been linked to increased incidence of postoperative adverse cardiac events in post-PCI patients having non-cardiac surgery (NCS). There is limited knowledge of temporal changes in platelet inhibition in this high-risk surgical population. We therefore performed a multicentre prospective cohort study evaluating perioperative platelet function and its association with postoperative major adverse cardiac events (MACE).

Methods

In 201 post-PCI patients having NCS, we assessed the association between platelet function and postoperative MACE. We performed perioperative platelet function testing using a platelet mapping assay (PMA). Troponin-I was measured every 8 h for 2 days, then daily until day 5. Myocardial infarction was assessed using the third universal definition. We used multivariable logistic regression to assess the association between platelet inhibition and MACE.

Results

Major adverse cardiac events occurred in 40 patients within 30 days of surgery. Thirty-two of these events were non-ST-elevation myocardial infarction, four ST-elevation myocardial infarction, and four exacerbation of congestive heart failure. We were unable to show an association between platelet inhibition and MACE. The PMA showed declining levels of platelet inhibition the longer the antiplatelet therapy was withheld before surgery. Logistic regression did not show an association between preoperative platelet function or the type of stent and MACE. We found an increased cardiac risk of MACE after surgery within 6 weeks of PCI.

Conclusions

The incidence of MACE in patients undergoing NCS after previous PCI is high in spite of adequate perioperative antiplatelet therapy.

Clinical trial registration

NCT 01707459 (registered at http://ift.tt/PmpYKN).



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Laparoscopic repair of hiatal hernia after minimally invasive esophagectomy

Abstract

Introduction

Minimally invasive esophagectomy for cancer decreases respiratory postoperative complications but seems to be associated with higher occurrence of hiatal hernia (HH). This study describes the incidence of this complication and the results of surgical repair.

Methods

Among 390 patients with esophageal cancer treated by esophagectomies with laparoscopic gastric dissection from 2000 to 2013, 32 (8.2 %) patients developed HH. Demographics, diagnostic, surgical management and outcomes data were collected retrospectively.

Results

There were 25 men and 7 women with a median age of 60 years (39–78). The median time between esophagectomy and diagnosis of HH was 10 months (3 days–96 months). The most frequent symptoms at the time of diagnosis were pain (32 %), dyspnea (21 %) and vomiting (10 %), while HH was asymptomatic in 10 patients. HH was located in the left chest in 97 % of patients and involved either the transverse colon (91 %), or omentum (25 %) or the small bowel (12 %). The operation included the reintegration of the viscera associated with the closure of the pillars (100 %) and the establishment of a mesh (71 %). The operation was carried out by laparoscopy in 19 (59 %) patients and was conducted in emergency in 6 (19 %) patients. No patient died, and the overall morbidity was 25 %. After a median follow-up of 40 months (range 1–55), five patients died due to oncologic evolution and six (19 %) patients had recurrence of HH who required a second operation.

Conclusion

HH is a common complication after laparoscopic-assisted esophagectomy. Despite the use of mesh, postoperative morbidity and recurrence incidence remain high.



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theEMSstore and Witmer Public Safety Group Promote James Witmer to Chief Executive Officer

COATESVILLE, PA – theEMSstore, a division of Witmer Public Safety Group (WPSG), the nation's leading multi-channel distributor of public safety equipment, supplies, training, and service is pleased to announce the promotion of James Witmer to the role of Chief Executive Officer (CEO), effective February 10, 2016. Witmer, former Vice President of Sales, has been a crucial member of the WPSG ...

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Patient with ExD syndrome

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Patient with ExD syndrome before and after versed administration

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Patient with ExD syndrome before and after ketamine administration

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Patient with ExD syndrome

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Patient with ExD syndrome before and after versed administration

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Patient with ExD syndrome before and after ketamine administration

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Patient with ExD syndrome

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Patient with ExD syndrome before and after versed administration

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Patient with ExD syndrome before and after ketamine administration

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Patient with ExD syndrome

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Patient with ExD syndrome before and after versed administration

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Patient with ExD syndrome before and after ketamine administration

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FirstPass Informational Video



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The Benefits of Natural Environments for Physical Activity

Abstract

Urbanisation has a profound effect on both people and the environment, as levels of physical activity decline and many natural ecosystems become lost or degraded. Here we draw on emerging research to examine the role of green spaces in providing a venue for outdoor physical activity, and in enhancing the benefit of a given amount of physical activity for urban residents. We identify critical knowledge gaps, including (1) whether (and for whom) levels of physical activity increase as new green spaces are introduced or old spaces reinvigorated; (2) which characteristics of nature promote physical activity; (3) the extent to which barriers to outdoor physical activity are environmental or social; and (4) whether the benefits of physical activity and experiences of nature accrue separately or synergistically. A clear understanding of these issues will help guide effective investment in green space provision, ecological enhancement and green exercise promotion.



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A Review of the Anthropometric Characteristics, Grading and Dispensation of Junior and Youth Rugby Union Players in Australia

Abstract

The grading of Australian junior and youth rugby union players has received substantial media attention in recent years. Media reports have focussed on size mismatches observed between players, especially players with Polynesian heritage, and the concerned parents who fear for the safety of their child owing to perceived mismatches. Although such concerns are well meaning, few media reports recognise the need for substantial evidence to determine the best grading system for junior and youth rugby union players. The current study reviewed relevant literature pertinent to the grading and dispensation of junior and youth rugby union players. Using primary and secondary search strategies, a total of 33 articles reporting the anthropometric characteristics of junior and youth rugby players were identified. Anthropometric data from the literature were compared with normative population data and currently used dispensation criteria. Junior and youth rugby players were found to be taller and heavier than normative population data. Current dispensation criteria, in terms of body mass, were found to vary and it is suggested that criteria be revised and standardised across rugby unions throughout Australia. Although it is acknowledged that other factors are important for grading players, anthropometric characteristics should be considered as potential dispensation criteria to supplement current age-based grading for junior and youth rugby union players. Measuring the body mass and stature of each junior player upon pre-season registration is suggested, which would provide data to establish valid dispensation criteria for the following season.



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Atelectasis After Endoscopic Resection: Relations and Prediction



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Lack of anti-tumor activity by anti-VEGF treatments in hepatic hemangiomas

Angiogenesis

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Apolipoprotein E (APOE) allele frequencies in chronic and self-limited hepatitis C suggest a protective effect of APOE4 in the course of HCV infection

Liver International

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The FDA-approved drug irbesartan inhibits HBV-infection in HepG2 cells stably expressing sodium taurocholate co-transporting polypeptide

Antiviral Therapy

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The relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use

Digestive and Liver Diseases

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Hmgb1 promotes hepatitis C virus replication by interaction with stem-loop 4 in the viral 5' untranslated region

Journal of Virology

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Frequency and cause of persistent symptoms in celiac disease patients on a long-term gluten-free diet

Journal of Clinical Gastroenterology

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Molecular characterization of hepatitis B virus from chronically-infected patients in Niamey, Niger

International Journal of Infectious Diseases

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Sarcopenia in cirrhosis - aetiology, implications and potential therapeutic interventions

Alimentary Pharmacology and Therapeutics

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Males seropositive for hepatitis B surface antigen are at risk of lower bone mineral density: the 2008–2010 Korea National Health and Nutrition Examination Surveys

Hepatology International

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Short term colectomy rate and mortality for severe ulcerative colitis in the last 40 years. Has something changed?

Digestive and Liver Diseases

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Evaluation of endoscopic findings for discriminating between early carcinomas and low-grade adenomas in superficial elevated gastric lesions

The Turkish Journal of Gastroenterology

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Effect of gum chewing on reducing postoperative ileus and recovery after colorectal surgery: A randomised controlled trial

Complementary Therapies in Clinical Practice

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Diet and nutritional factors in inflammatory bowel diseases

World Journal of Gastroenterology

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SNPs in transporter and metabolizing genes as predictive markers for oxaliplatin treatment in colorectal cancer patients

International Journal of Cancer

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The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C

The Turkish Journal of Gastroenterology

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A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus

Journal of Viral Hepatitis

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Quantitative imaging biomarkers of NAFLD

Digestive Diseases and Sciences

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Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study

International Journal of Cancer

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A randomised controlled trial of meloxicam, a Cox-2 inhibitor, to prevent hepatocellular carcinoma recurrence after initial curative treatment

Hepatology International

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A large variety of clinical features and concomitant disorders in celiac disease – A cohort study in the Netherlands

Digestive and Liver Diseases

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