Τετάρτη 24 Μαΐου 2017

PROPIONIBACTERIUM ACNES AND CHRONIC DISEASES : P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections e.g., surgery,post-neurosurgical infection,joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer,SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome, sarcoidosis and sciatica.


P. acnes bacteria live deep within follicles and pores, away from the surface of the skin. In these follicles, P. acnes bacteria use sebum, cellular debris and metabolic byproducts from the surrounding skin tissue as their primary sources of energy and nutrients. Elevated production of sebum by hyperactive sebaceous glands (sebaceous hyperplasia) or blockage of the follicle can cause P. acnes bacteria to grow and multiply.[6]

P. acnes bacteria secrete many proteins, including several digestive enzymes.[7] These enzymes are involved in the digestion of sebum and the acquisition of other nutrients. They can also destabilize the layers of cells that form the walls of the follicle. The cellular damage, metabolic byproducts and bacterial debris produced by the rapid growth of P. acnes in follicles can trigger inflammation.[8] This inflammation can lead to the symptoms associated with some common skin disorders, such as folliculitis and acne vulgaris.[9][10][11]

The damage caused by P. acnes and the associated inflammation make the affected tissue more susceptible to colonization by opportunistic bacteria, such as Staphylococcus aureus. Preliminary research shows healthy pores are only colonized by P. acnes, while unhealthy ones universally include the nonpore-resident Staphylococcus epidermidis, amongst other bacterial contaminants. Whether this is a root causality, just opportunistic and a side effect, or a more complex pathological duality between P. acnes and this particular Staphylococcus species is not known.[12]

P. acnes has also been found in corneal ulcers, and is a common cause of chronic endophthalmitis following cataract surgery. Rarely, it infects heart valves leading to endocarditis, and infections of joints (septic arthritis) have been reported.[5] Furthermore, Propionibacterium species have been found in ventriculostomy insertion sites, and areas subcutaneous to suture sites in patients who have undergone craniotomy. It is a common contaminant in blood and cerebrospinal fluid cultures.

P. acnes has been found in herniated discs.[13] The propionic acid which it secretes creates micro-fractures of the surrounding bone. These micro-fractures are sensitive and it has been found that antibiotics have been helpful in resolving this type of low back pain.[14]

P. acnes can be found in bronchoalveolar lavage of approximately 70% of patients with sarcoidosis and is associated with disease activity, but it can be also found in 23% of controls.[15][16] The subspecies of P. acnes that cause these infections of otherwise sterile tissues (prior to medical procedures), however, are the same subspecies found on the skin of individuals who do not have acne-prone skin, so are likely local contaminants. Moderate to severe acne vulgaris appears to be more often associated with virulent strains.[17]

P. acnes is an opportunistic pathogen, causing a range of postoperative and device-related infections e.g., surgery,[18] post-neurosurgical infection,[19] joint prostheses, shunts and prosthetic heart valves. P. acnes may play a role in other conditions, including inflammation of the prostate leading to cancer,[20] SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome, sarcoidosis and sciatica.[21]

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Elevated intrathoracic CO2 pressure during thoracoscopic surgery decreases regional cerebral oxygen saturation in neonates and infants—A pilot study

Summary

Background

Intraoperative hypercapnia and acidosis are risk factors during thoracoscopy in neonates and infants.

Methods

In a prospective pilot study, we evaluated the effects of thoracoscopy in neonates and infants on cerebral microcirculation, oxygen saturation, and oxygen consumption. Regional cerebral oxygen saturation and blood flow were measured noninvasively using a new device combining laser Doppler flowmetry and white light spectrometry. Additionally, cerebral fractional tissue oxygen extraction and approximated oxygen consumption were calculated.

Fifteen neonates and infants undergoing thoracoscopy were studied using the above-mentioned method. The chest was insufflated with carbon dioxide with a pressure of 2-6 mm Hg. Single lung ventilation was not used. As control group served 15 neonates and infants undergoing abdominal surgery.

Results

Data are presented as median and range. The 95% confidence intervals for differences of means (95% CI) are given for the mean difference from baseline values.

We observed a correlation between intrathoracic pressure exceeding 4 mm Hg and transient decrease in regional cerebral oxygen saturation of 12.7% (95% CI: 9.7–17.2, P<.001). Peripheral oxygen saturation was normal at the same time.

Intraoperative increase in arterial paCO2 (median maximum value: 48.8 mm Hg, range: [36.5-65.4]; 95% CI: −16.0 to −3.0, P=.002) and decrease in arterial pH (median minimum value: 7.3, range: [7.2-7.4]; 95% CI: 0.04-0.12, P=.008) were observed during thoracoscopy with both parameters recovering at the end of the procedure.

Periods of regional cerebral oxygen saturation below 20% from baseline were significantly more frequent during thoracoscopy as compared to the control group (median maximum value: 1.3%min/h, range: [0.0-66.2] vs median maximum value: 0.0%min/h, range: [0.0-4.0]; 95% CI: −16.6 to −1.1, P=.028).

Conclusion

We suggest that thoracoscopic surgery in neonates and infants, although generally safe, may be associated with a decrease in regional cerebral oxygen saturation correlating with the applied intrathoracic pressure. According to our data an inflation pressure >4 mm Hg should be avoided during thoracoscopic surgery.



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Dichotic Listening Deficit Associated With Solvent Exposure.Due to their lipophilic nature, solvents can adversely affect large white matter tracks such as the corpus callosum. Previous investigations reveal that long-term workplace exposure to solvents is also deleterious to various auditory processes.


Dichotic Listening Deficit Associated With Solvent Exposure.
από Landry, Simon P.; Fuente, Adrian στο Otology & Neurotology Published Ahead-of-Print
Μετάφραση άρθρου
Hypothesis: A significant left ear deficit can be observed in solvent-exposed individuals using the dichotic digit test. Background: Solvents are ubiquitous in global industrial processes. Due to their lipophilic nature, solvents can adversely affect large white matter tracks such as the corpus callosum. Previous investigations reveal that long-term workplace exposure to solvents is also deleterious to various auditory processes. Investigations in exposed populations suggest a decreased performance for dichotic listening. Methods: In this present study, we examined the lateralization of a dichotic digit test score for 49 solvent-exposed individuals along with 49 age- and sex-matched controls. We evaluated group differences between test scores and the right ear advantage using a laterality index (LI). Results: Individual ear results suggest that long-term workplace solvent exposure is associated with a significantly lower dichotic listening score for the left ear. A binaural compound score analysis using a laterality index supports this left-ear deficit. Conclusion: These results provide an insight on the effects of solvent exposure on dichotic listening abilities. Further research should investigate the importance of using dichotic listening tasks to screen for solvent-induced auditory dysfunction in exposed individuals. Copyright (C) 2017 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Company

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Epstein-Barr virus, human endogenous retroviruses (HERVs) and human herpesvirus 6 (HHV-6) but also less common viruses such as Saffold and measles viruses are associated with multiple sclerosis



Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Automatic multimodal detection for long-term seizure documentation in epilepsy

Seizure documentation and quantification represents the primary outcome measure of epilepsy therapy including antiepileptic drug treatment, epilepsy surgery, and neurostimulation. Presently, patients document their seizures using seizure diaries without systematic and objective validation approach by physicians. Recent publications showed that manual seizure counting suffers from underreporting with sensitivities of 50% during day and as low as 30% during night and can therefore be considered as highly unreliable (Blachut et al., 2015).

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Approaching threatening stimuli cause an expansion of defensive peripersonal space

When sudden environmental stimuli signalling threat occur in the portion of space surrounding the body (defensive peripersonal space), defensive responses are enhanced. Recently Bisio et al. (2017) showed that a marker of defensive peripersonal space, the defensive hand-blink reflex, is modulated by the motion of the eliciting threatening stimulus. These results can be parsimoniously explained by the continuous monitoring of environmental threats, resulting in an expansion of DPPS when threatening stimuli approach.



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Using theoretical models from adult stroke recovery to improve use of non-invasive brain stimulation for children with congenital hemiparesis

Non-invasive brain stimulation has been widely used for adults with stroke to improve upper limb motor function. A recent study by Kirton and colleagues (Kirton A, Ciechanski P, Zewdie E et al. Neurology 2017, doi: 10.1212/WNL.0000000000003518) applied non-invasive brain stimulation to children with congenital hemiparesis but found no significant effect of non-invasive brain stimulation on motor function. Here, we explore theories about cortical reorganization in both adult and children with hemiparesis and discuss how to improve the approaches of non-invasive brain stimulation to generate optimal motor improvement and development for children with congenital hemiparesis.



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Optimal motor synergy extraction for novel actions and virtual environments

Dimensionality reduction techniques such as factor analysis can be used to identify the smallest number of components (motor synergies) that explain motion. Lambert-Shirzad and Van der Loos (2017) compared dimensionality reduction techniques in bimanual hand movements, concluding that non-negative matrix factorization was the optimal technique for extracting meaningful synergies. Their results provide a useful measure for examining how the motor system deals with novel motor tasks that allow the actor to engage with a virtual environment.



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A balance of outward and linear inward ionic currents is required for the generation of slow wave oscillations

Regenerative inward currents help produce slow oscillations through a negative-slope conductance region of their current-voltage relationship that is well approximated by a linear negative conductance. We used dynamic clamp injections of a linear current with such conductance, INL, to explore why some neurons can generate intrinsic slow oscillations whereas others cannot. We addressed this question, in synaptically isolated neurons of the crab Cancer borealis, after blocking action potentials. The pyloric network consists of a distinct pacemaker and follower neurons, all of which express the same complement of ionic currents. When the pyloric dilator (PD) neuron, a member of the pacemaker group, was injected with INL using dynamic clamp, it consistently produced slow oscillations. In contrast, all follower neurons failed to oscillate with INL. To understand these distinct behaviors, we compared outward current levels of PD, with those of follower lateral pyloric (LP) and ventral pyloric (VD) neurons. We found that LP and VD neurons had significantly larger high-threshold potassium currents (IHTK) than PD, and LP had lower transient potassium current, IA. Reducing IHTK pharmacologically enabled both LP and VD neurons to produce INL-induced oscillations, whereas modifying IA levels did not affect INL-induced oscillations. Using phase-plane and bifurcation analysis of a simplified model cell, we demonstrate that large levels of IHTK can block INL-induced oscillatory activity, whereas generation of oscillations is almost independent of IA levels. These results demonstrate the general importance of a balance between inward pacemaking currents and high-threshold K+ current levels in determining slow oscillatory activity.



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REEVALUATION OF REFLEX RESPONSES OF THE HUMAN MASSETER MUSCLE TO ELECTRICAL LIP STIMULATION

We examined the reflex response of the human masseter muscle to electrical stimulation of the lip using both single motor unit and surface electromyogram based methods. Using the classical analysis methods, reflex response to mild electrical stimuli generated two distinct short-lasting inhibitions. This pattern may reflect the development of combinations of short and long latency inhibitory postsynaptic potentials as a result of the mildly painful electrical lip stimulation. However, this pattern appearing in the classical analysis methods may have developed as a consequence of earlier responses and may not be genuine. This study examined the genuineness of these responses using both the classical analysis methods and the discharge rate method to uncover the realistic postsynaptic potentials in human trigeminal motor nucleus. Using the discharge rate method, we found that the electrical lip stimulation only generated a long-lasting single or compound inhibitory response which is followed by late long-lasting excitation. These findings have important implications on the re-drawing the neuronal pathways of the trigeminal nerve that are frequently used to judge neuromuscular disorders of the trigeminal region.



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Variations on a theme: Species differences in synaptic connectivity do not predict central pattern generator activity

A fundamental question in comparative neuroethology is the extent to which synaptic wiring determines behavior versus the extent to which it is constrained by phylogeny. We investigated this by examining the connectivity and activity of homologous neurons in different species. Melibe leonina and Dendronotus iris (Mollusca, Gastropoda, Nudibranchia) have homologous neurons and exhibit homologous swimming behaviors consisting of alternating left-right (LR) whole body flexions. Yet, a homologous interneuron (Si1) differs between the two species in its participation in the swim motor pattern (SMP) and synaptic connectivity. Here we examine Si1 homologs in two additional nudibranchs: Flabellina iodinea, which evolved LR swimming independently of Melibe and Dendronotus, and Tritonia diomedea, which swims with dorsal-ventral (DV) body flexions. In Flabellina, the contralateral Si1s exhibit alternating rhythmic bursting activity during the SMP and are members of the swim central pattern generator (CPG), as in Melibe. The Si1 homologs in Tritonia do not burst rhythmically during the DV SMP, but are inhibited and receive bilaterally synchronous synaptic input. In both Flabellina and Tritonia, the Si1 homologs exhibit reciprocal inhibition as in Melibe. However, in Flabellina the inhibition is polysynaptic, whereas in Tritonia it is monosynaptic, as in Melibe. In all species, the contralateral Si1s are electrically coupled. These results suggest that Flabellina and Melibe convergently evolved a swim CPG that contains Si1; however, they differ in monosynaptic connections. Connectivity is more similar between Tritonia and Melibe, which exhibit different swimming behaviors. Thus, connectivity between homologous neurons varies independently of both behavior and phylogeny.



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Automatic and intentional influences on saccade landing

Saccadic eye-movements enable us to rapidly direct our high-resolution fovea onto relevant parts of the visual world. However, while we can intentionally select a location as a saccade target, the wider visual scene also influences our executed movements. In the presence of multiple objects, eye-movements may be "captured" to the location of a distractor object, or be biased towards the intermediate position between objects (the "global effect"). Here we examined how the relative strengths of the global effect and visual object capture changed with saccade latency, the separation between visual items and stimulus contrast. Importantly, while many previous studies have omitted giving observers explicit instructions, we instructed participants to either saccade to a specified target object or to the midpoint between two stimuli. This allowed us to examine how their explicit movement goal influenced the likelihood that their saccades terminated at either the target, distractor, or intermediate locations. Using a probabilistic mixture model, we found evidence that both visual object capture and the global effect co-occurred at short latencies and declined as latency increased. As object separation increased, capture came to dominate the landing positions of fast saccades, with reduced global effect. Using the mixture model fits we dissociated the proportion of unavoidably captured saccades to each location from those intentionally directed to the task goal. From this we could extract the time-course of competition between automatic capture and intentional targeting. We show that task instructions substantially altered the distribution of saccade landing points, even at the shortest latencies.



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Spinal control of motor outputs by intrinsic and externally induced electric field potentials

Despite numerous studies on spinal neuronal systems, several issues regarding their role in motor behaviour remain unresolved. One of these issues is how electric fields associated with the activity of spinal neurons influence the operation of spinal neuronal networks and how effects of these field potentials are combined with other means of modulating neuronal activity. Another closely related issue is how external electric field potentials affect spinal neurons and how they can be used for therapeutic purposes such as pain relief or recovery of motor functions by trans-spinal direct current stimulation. Nevertheless, progress in our understanding of the spinal effects of electric fields and their mechanisms has been made over the last years and the aim of the present review is to summarize the recent findings in this field.



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Sodium pump regulation of locomotor control circuits

Sodium pumps are ubiquitously expressed membrane proteins that extrude three Na+ ions in exchange for two K+ ions using ATP as an energy source. Recent studies have illuminated additional, dynamic roles for sodium pumps in regulating the excitability of neuronal networks in an activity-dependent fashion. Here we review their role in a novel form of short-term memory within rhythmic locomotor networks. The data we review derives mainly from recent studies on Xenopus tadpoles and neonatal mice. The role and underlying mechanisms of pump action broadly match previously published data from an invertebrate, the Drosophila larva. We therefore propose a highly conserved mechanism by which sodium pump activity increases following a bout of locomotion. This results in an ultraslow afterhyperpolarisation (usAHP) of the membrane potential that lasts around 1 minute, but which only occurs in around half the network neurons. This usAHP in turn alters network excitability so that network output is reduced in a locomotor interval-dependent manner. The pumps therefore confer on spinal locomotor networks a temporary memory trace of recent network performance.



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Phencyclidine (PCP) administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration with the NMDA receptor antagonist, phencyclidine (PCP), during neurodevelopment affects functional network changes within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo following electrical brainstem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered neonatally with PCP. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist, MK-801, was exaggerated in neonatal PCP animals. These data suggests that NMDA receptor antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia.



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Myeloid sarcoma of the sigmoid colon: an unusual presentation of a rare condition



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sept8a and sept8b mRNA expression in the developing and adult zebrafish

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Publication date: November 2017
Source:Gene Expression Patterns, Volumes 25–26
Author(s): Constantin Berger, Frederik Helmprobst, Prisca Chapouton, Christina Lillesaar, Christian Stigloher
Septins are highly conserved GTP-binding proteins involved in numerous cellular processes. Despite a growing awareness of their roles in the cell biology, development and signal transmission in nervous systems, comparably little is known about precise septin expression. Here, we use the well-established model organism zebrafish (Danio rerio) to unravel the expression of sept8a and sept8b, with special focus on the CNS. We performed whole mount RNA in situ hybridization on zebrafish 1–4 dpf in combination with serial sectioning of epon-embedded samples as well as on brain sections of adult zebrafish to obtain precise histological mapping of gene expression. Our results show a common expression of both genes at embryonic stages, whereas sept8a is mainly restricted to the gill arches and sept8b to specific brain structures at later stages. Brains of adult zebrafish reveal a large spatial overlap of sept8a and sept8b expression with few regions uniquely expressing sept8a or sept8b. Our results indicate a neuronal expression of both genes, and additionally suggest expression of sept8b in glial cells. Altogether, this study provides a first detailed insight into the expression of sept8a and sept8b in zebrafish and contributes to a more comprehensive understanding of septin biology in vertebrate model systems.



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Dorsal fin development in flounder, Paralichthys olivaceus: Bud formation and its cellular origin

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Publication date: November 2017
Source:Gene Expression Patterns, Volumes 25–26
Author(s): Jie Chen, Xiaoyu Liu, Xiaohua Yao, Fei Gao, Baolong Bao
The development of the median fin has not been investigated extensively in teleosts, although in other fishes it has been proposed that it involves the same genetic programs operating in the paired appendages. Adult median fins develop from the larval bud; therefore an investigation of fin bud formation and its cellular origin is essential to understanding the maturation mechanisms. In Paralichthys olivaceus, skeletogenesis proceeds from an anterior to posterior direction providing a good opportunity to study the formation of dorsal fin bud. An apical ectodermal ridge appeared at the basal stratum of the presumptive dorsal fin was first observed at 3 days post hatching. Then the apical ectodermal fold formed as the bud outgrew in 6 days post-hatch larvae. The bud continued to grow, breaking through the dorsal fin fold in 9 days post-hatch larvae. At 13 days post-hatch, the bud grew beyond the edge of the fin fold and formed into the four future rays. Molecular markers of cell type showed the existence of neural crest cells, scleroblasts and sclerotomes in the dorsal fin bud. The earliest gene expression in the dorsal fin bud was Hoxd10 at 3 days post-hatch larvae, then Hoxd9, Hoxd11 and Hoxd12. This indicates Hoxd10 might be a candidate molecular marker of the bud formation site. Some key molecular markers for paired appendage development, such as FGF8, Wnt7, and Shh were expressed at the apical ectodermal ridge and later the apical ectodermal fold. Moreover, the form of the dorsal fin bud could be inhibited by Hh pathway inhibitor, further indicating that common basic molecular mechanisms might be utilized by median fins.



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Embryonic expression of festina lente (fel), a novel maternal gene, in the oligochaete annelid Tubifex tubifex

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Publication date: November 2017
Source:Gene Expression Patterns, Volumes 25–26
Author(s): Takuma Nakamura, Inori Shiomi, Takashi Shimizu
We have cloned and characterized the expression of a novel maternal gene festina lente (designated Ttu-fel) from the clitellate annelid Tubifex tubifex. Northern blot analyses have shown that Ttu-fel mRNA is approximately 8 kbp in length and that its expression is restricted to oocytes undergoing maturation division and early embryos up to 22-cell stage. Maternal transcripts of Ttu-fel are first detected in oocytes in the ovary of young adults (ca. 40 days after hatching); its expression continues in growing oocytes in the ovisac. Ttu-fel mRNA is distributed broadly throughout the egg undergoing maturation divisions. During the process of ooplasmic segregation that results in the pole plasm formation, Ttu-fel mRNA becomes concentrated to the animal and vegetal poles. The RNA in the animal hemisphere is distributed in a gradient with highest concentration in the cortical region. During the first two cleavages, Ttu-fel mRNA is segregated to CD cell then to D cell; it is subsequently inherited by the three D quadtrant micromeres, 1d, 2d and 3d. Around the time of transition to 22-cell stage, Ttu-fel mRNA becomes undetectable throughout the embryo.



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Characterization of Sgo1 expression in developing and adult mouse

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Publication date: November 2017
Source:Gene Expression Patterns, Volumes 25–26
Author(s): Andrew T. Song, Antonella Galli, Severine Leclerc, Stanley Nattel, Craig Mandato, Gregor Andelfinger
SGO1 has been characterized in its function in correct cell division and its role in centrosome cohesion in the nucleus. However, its organ-specific maturation-related expression pattern in vivo remains largely uncharacterized. Here, we show clear SGO1 expression in post-developmental neuronal cells and cytoplasmic localisation in nucleated cells with a transgenic mice model and immunohistochemistry of wild type mice. We demonstrate extranuclear expression of Sgo1 in the developing heart and gut, which have been shown to be dysregulated in humans with homozygous SGO1 mutation. Additionally, we show Sgo1 expression in select population of retinal cells in developing and post-developmental retina. Our expression analysis strongly suggests that the function of SGO1 goes beyond its well characterized role in cell division.



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Editorial board members

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Publication date: January 2017
Source:Gene Expression Patterns, Volumes 23–24





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JMJ24 antagonizes histone H3K9 demethylase IBM1/JMJ25 function and interacts with RNAi pathways for gene silencing

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Publication date: November 2017
Source:Gene Expression Patterns, Volumes 25–26
Author(s): Laure Audonnet, Yuan Shen, Dao-Xiu Zhou
Dimethylation of histone H3 lysine 9 (H3K9me2) is a heterochromatic mark linked to DNA methylation and gene repression. Removal of H3K9me2 from gene bodies by the jmjC histone demethylase IBM1/JMJ25 inhibits DNA methylation and derepresses gene expression. In this work, we analyzed the function of a closely related homolog of IBM1/JMJ25, namely JMJ24. We show that jmj24 mutations produced a number of subtle developmental defects, while affecting only a relatively small number of genes at the vegetative stage. Interestingly, jmj24 mutation could complement plant growth defects and expression changes caused by the ibm1 mutation. In addition, we show that JMJ24 may synergistically interact with the RNAi pathways involving siRNAs. The present data suggest that JMJ24 may have a function to counteract IBM1/JMJ25 in gene expression and may cooperate with RNAi pathways for gene silencing.



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The expression of sialyltransferases is regulated by the bioavailability and biosynthesis of sialic acids

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Publication date: January 2017
Source:Gene Expression Patterns, Volumes 23–24
Author(s): Kaya Bork, Wenke Weidemann, Beatrice Berneck, Magdalena Kuchta, Dorit Bennmann, Annett Thate, Otmar Huber, Vinayaga S. Gnanapragassam, Rüdiger Horstkorte
Glycosylation is the most frequent and important post-translational modification of proteins. It occurs on specific consensus sequences but the final structure of a particular glycan is not coded on the DNA, rather it depends on the expression of the required enzymes and the availability of substrates (activated monosaccharides). Sialic acid (Sia) is the terminal monosaccharide of most glycoproteins or glycolipids (= glycoconjugates) and involved in a variety of function on molecular (e.g. determination of protein stability and half-life) and cellular level (e.g. influenza infection). Sia are synthesized in the cytosol from UDP-GlcNAc by the Roseman-Warren pathway. The key enzyme of this pathway is the UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE). Sia are transferred on glycoconjugates by a family of Golgi-located enzymes, so called sialyltransferases (ST). There are 20 (human) ST known, which all transfer CMP-activated Sia to specific acceptor-sites on glycoconjugates. The regulation of the expression of ST is still not understood. Using a GNE-deficient embryonic stem cell line, which cannot synthesize Sia endogenously and by supplementation of soluble Sia precursors, we present data that the cellular availability of Sia strongly regulates the expression of ST on the level of transcription. In summary, we suggest that the concentration of the donor substrate of sialyltransferases, which can be regarded as a sensor for the environmental conditions of a cell, regulates not only total sialylation, but also the quality of sialylation. This allows a cell to response to altered environmental conditions.



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High resolution methylation analysis of the HoxA5 regulatory region in different somatic tissues of laboratory mouse during development

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Publication date: January 2017
Source:Gene Expression Patterns, Volumes 23–24
Author(s): Puja Sinha, Kiran Singh, Manisha Sachan
Homeobox genes encode a group of DNA binding regulatory proteins whose key function occurs in the spatial-temporal organization of genome during embryonic development and differentiation. The role of these Hox genes during ontogenesis makes it an important model for research. HoxA5 is a member of Hox gene family playing a central role during axial body patterning and morphogenesis. DNA modification studies have shown that the function of Hox genes is partly governed by the methylation-mediated gene expression regulation. Therefore the study aimed to investigate the role of epigenetic events in regulation of tissue-specific expression pattern of HoxA5 gene during mammalian development. The methodology adopted were sodium bisulfite genomic DNA sequencing, quantitative real-time PCR and chromatin-immunoprecipitation (ChIP). Methylation profiling of HoxA5 gene promoter shows higher methylation in adult as compared to fetus in various somatic tissues of mouse being highest in adult spleen. However q-PCR results show higher expression during fetal stages being highest in fetal intestine followed by brain, liver and spleen. These results clearly indicate a strict correlation between DNA methylation and tissue-specific gene expression. The findings of chromatin-immunoprecipitation (ChIP) have also reinforced that epigenetic event like DNA methylation plays important role in the regulation of tissue specific expression of HoxA5.



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Regional localization of activin-βA, activin-βC, follistatin, proliferation, and apoptosis in adult and developing mouse prostate ducts

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Publication date: January 2017
Source:Gene Expression Patterns, Volumes 23–24
Author(s): Elspeth Gold, Sylvia Zellhuber-McMillan, Gail Risbridger, Francesco Elia Marino
Activins and inhibins, members of the TGF-β superfamily, are growth and differentiation factors involved in the regulation of several biological processes, including reproduction, development, and fertility. Previous studies have shown that the activin-βA subunit plays a pivotal role in prostate development. Activin-A inhibits branching morphogenesis in the developing prostate, and its expression is associated with increased apoptosis in the adult prostate. Follistatin, a structurally unrelated protein to activins, is an antagonist of activin-A. A balance between endogenous activin-A and follistatin is required to maintain prostatic branching morphogenesis. Deregulation of this balance leads to branching inhibition or excessive branching and increased maturation of the stroma surrounding the differentiating epithelial ducts. Recent work identified another member of the TGF-β superfamily, the activin-βC subunit, as a novel antagonist of activin-A. Over-expression of activin-C (βC-βC) alters prostate homeostasis, by interfering with the activin-A signaling. The current study characterized the spatiotemporal localization of activin-A, activin-C and follistatin in the adult and developing mouse prostate using immunohistochemical analysis. Results showed activin-C and follistatin are differentially expressed during prostate development and suggested that the antagonistic property of follistatin is secondary to the action of activin-C. In conclusion, the present study provides evidence to support a role of activin-C in prostate development and provides new insights in the spatiotemporal localization of activins and their antagonists during mouse prostate development.



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A recessive mutation in beta-IV-spectrin ( SPTBN4 ) associates with congenital myopathy, neuropathy, and central deafness

Abstract

Congenital myopathies are a heterogeneous group of muscle disorders that are often genetically determined. Here, we investigated a boy with congenital myopathy, deafness, and neuropathy from a consanguineous Kurdish family by autozygosity mapping and whole exome sequencing. We found a homozygous nonsense mutation in SPTBN4 [c.1597C>T, NM_020971.2; p.(Q533*), NP_066022.2; ClinVar SUB2292235] encoding βIV-spectrin, a non-erythrocytic member of the β-spectrin family. Western blot confirmed the absence of the full-length 288 kDa isoform in muscle and of a specific 72 kDa isoform in fibroblasts. Clinical symptoms of the patient largely corresponded to those described for the quivering mouse, a loss-of-function animal model. Since the human phenotype of βIV-spectrin deficiency included a myopathy with incomplete congenital fiber-type disproportion, we investigated muscle of the quivering (qv4J) mouse and found complete absence of type 1 fibers (fiber-type 2 uniformity). Immunohistology confirmed expression of βIV-spectrin in normal human and mouse muscle at the sarcolemma and its absence in patient and quivering (qv4J) mouse. SPTBN4 mRNA-expression levels in healthy skeletal muscle were found in the range of other regulatory proteins. More patients have to be described to confirm the triad of congenital myopathy, neuropathy and deafness as the defining symptom complex for βIV-spectrin deficiency.



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A distal auxiliary element facilitates cleavage and polyadenylation of Dux4 mRNA in the pathogenic haplotype of FSHD

Abstract

The degenerative muscle disorder facioscapulohumeral dystrophy (FSHD) is thought to be caused by the inappropriate expression of the Double Homeobox 4 (Dux4) protein in muscle cells leading to apoptosis. Expression of Dux4 in the major form of FSHD is a function of two contributing molecular changes: contractions in the D4Z4 microsatellite repeat region where Dux4 is located and an SNP present within a region downstream of the D4Z4. This SNP provides a functional, yet non-consensus polyadenylation signal (PAS) is used for the Dux4 mRNA 3′ end processing. Surprisingly, the sequences flanking the Dux4 PAS do not resemble a typical cleavage and polyadenylation landscape with no recognizable downstream sequence element and a suboptimal cleavage site. Here, we conducted a systematic analysis of the cis-acting elements that govern Dux4 cleavage and polyadenylation. Using a transcriptional read-through reporter, we determined that sequences downstream of the SNP located within the β-satellite region are critical for Dux4 cleavage and polyadenylation. We also demonstrate the feasibility of using antisense oligonucleotides to target these sequences as a means to reduce Dux4 expression. Our results underscore the complexity of the region immediately downstream of the D4Z4 and uncover a previously unknown function for the β-satellite region in Dux4 cleavage and polyadenylation.



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Are you smarter than the average paramedic? Test your EMS IQ!

Take our 10-question quiz to test your knowledge, then share your results and challenge your colleagues to prove their expertise

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Tropical Enteropathies

Abstract

Purpose of Review

The term 'tropical enteropathy' originated in observations in the 1960s that small intestinal morphology and function differed in the tropics from the norms found in temperate climates. It was subsequently shown that this enteropathy is more closely related to environmental conditions than latitude, and it was re-labelled 'environmental enteropathy'. It is now recognised that environmental enteropathy (also now called environmental enteric dysfunction) has implications for the health and linear growth of children in low- and middle-income countries, and it may underlie poor responses to oral vaccination in these countries. The purpose of this review is to define and clarify this enteropathy despite the confusing terminology it has attracted and to contrast it with other enteropathic states.

Recent Findings

Recent work has begun to demonstrate the nature of the mucosal lesion and the relationship with microbial translocation which is currently thought to link a failure of mucosal barrier function and the cascade of systemic inflammation which inhibits growth. The evidence is still correlative rather than definitive, but derives some additional support from animal models. There are some common features between environmental enteropathy and other enteropathies, but there are important differences also. The mechanism of the link between enteropathy and vaccine failure is not understood, and neither is it clear how the more severe form of enteropathy, which we refer to as malnutrition enteropathy, is driven by nutrient depletion and intestinal infection.

Summary

Tropical enteropathies form a group of disorders which include environmental and nutritional enteropathies. The long-term health implications of these disorders for health in low-income countries are just being explored, but the scale of their effects is very large, with millions of people affected.



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Laparoscopic duodenoduodenostomy with parallel anastomosis for duodenal atresia

Abstract

Background

Currently, a diamond-shaped anastomosis is preferred for the surgical repair of duodenal atresia (DA) in both open and laparoscopic surgery. We report the results of laparoscopic duodenoduodenostomy with parallel anastomosis (LDPA) in DA.

Methods

We retrospectively reviewed 22 patients who underwent laparoscopic duodenoduodenostomy from February 2005 to May 2015 in Samsung Medical Center. All patients underwent operation within the first month after birth. Patients who were transversely anastomosed after duodenotomy and patients who underwent simultaneous operation on combined anomalies were excluded. Parallel anastomosis was used in all surgeries. Four trocars were used in laparoscopic repair. After mobilization of both proximal and distal ends, the proximal end was incised transversely and the distal end was incised longitudinally. Duodenoduodenostomy with parallel anastomosis using a 5-0 glyconate monofilament was performed with interrupted sutures.

Results

Eleven patients (50 %) were male. Median gestational age was 36 + 6 weeks (32 + 7–40 + 6). Median age at the time of operation and median body weight were 3 days (1–12) and 2.53 kg (1.63–3.18), respectively. All patients were diagnosed prenatally and 16 patients (72.7 %) had associated anomalies. Median operation time was 142 min (96–290) and median postoperative day to start oral feeding was 5 days (3–9) and median postoperative day of reaching full feeding was 11 days (6–19). Median postoperative day was 13 days (10–60). There was no anastomotic leakage or stenosis. Median follow up was 3.5 months (1–21). Currently, there is no late complication.

Conclusions

LDPA can be performed easily to patients who have DA in neonatal period. It is anatomically natural and the risk of leakage or stenosis does not seem significant. Therefore, parallel anastomosis should be considered as a safe procedural option for laparoscopic duodenoduodenostomy in DA.



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Mortality after esophagectomy is heavily impacted by center volume: retrospective analysis of the Nationwide Inpatient Sample

Abstract

Background

The effects of hospital volume on in-hospital mortality after esophageal resection are disputed in the literature. We sought to analyze treatment effects in patient subpopulations that undergo esophagectomy for cancer based on hospital volume.

Methods

We performed a retrospective analysis of the Nationwide Inpatient Sample from 1998 to 2011. Patients who underwent open or laparoscopic transhiatal and transthoracic esophageal resection were identified using ICD-9 codes. Patients <18 years and those with peritoneal disease were excluded. Multivariate logistic regression analyses were used with mortality as the independent variable to evaluate the effect of low (<6), intermediate (6–19), and high (20) hospital volume of esophagectomies. These analyses were repeated in different subsets of patients to determine whether hospital volume affected mortality depending on the subpopulation evaluated. Subgroups were created depending on age, race, gender, operative approach, comorbidities, and tumor pathology.

Results

A total of 23,751 patients were included. The overall perioperative mortality rate was 7.7 % (low volume: 11.4 %; intermediate volume: 8.39 %, high volume: 4.01 %), and multivariate analysis revealed that high hospital volume had a protective effect (OR 0.54, 95 % CI 0.45–0.65). On subgroup analyses for low- and intermediate-volume hospitals, mortality was uniformly elevated for the subpopulations when comparing to high-volume hospitals (p < 0.05). There was no difference in mortality between low- and medium-volume hospitals and between subgroups.

Conclusion

No lower mortality risk subgroup could be identified in this nationwide collective. This analysis emphasizes that perioperative mortality after esophagectomy for cancer is lower in high-volume hospitals.



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Esophageal bougination: a novel ex vivo endoscopic training model correlated with clinical data

Abstract

Background

Esophageal bougination is a worldwide standard endoscopic procedure. Clinical methods and recommendations are based on clinical experiences only. Mechanical properties have never been described. Aim of the study was to establish a realistic ex vivo training model. Therefore, detailed assessment of relevant mechanical features of esophageal bougination should be evaluated ex vivo and in patient setting and correlated against.

Patients and methods

A three-step concept was used to evaluate mechanical properties at stenosis level. First, insertion forces were evaluated in an ex vivo linear single stenosis model during steady mechanical insertion. Second, adding friction and properties of the pharynx and upper esophagus, the model was integrated in an artificial endoscopic training model (ELITE training model). Third, in vivo measurements were taken to correlate ex vivo data with parameters of a realistic patient setting.

Results

With the presented setup, we were able to assess insertion force and pressure levels in an artificial stricture using different sizes of commercially available standard bougies. In all models, there was a relevant increase in insertion force with higher stricture pressure levels. Insertion force levels in the ELITE model show higher levels compared to the linear stenosis model. Having regard to the maximum forces in patients, there is also a constant increase in mean insertion force according to higher bougie sizes, but lower forces were measured as in the ELITE model.

Discussion

The applied models are suitable to appraise mechanical properties of esophageal bougination in an ex vivo model and patient setting. Forces could be constituted reliable, significant increase was documented according to stenosis level and results were comparable to patient data. This was comparable to patient data. Further clinical evaluation in different kinds of stenosis is necessary.



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The surgical outcomes of robot-assisted laparoscopic pancreaticoduodenectomy versus laparoscopic pancreaticoduodenectomy for periampullary neoplasms: a comparative study of a single center

Abstract

Background

Pancreaticoduodenectomy (PD) is a difficult and complex operation. The introduction of robotics has opened up new angles in pancreatic surgery. This study aims to assess the surgical outcomes of robot-assisted laparoscopic pancreaticoduodenectomy relative to its laparoscopic counterpart.

Methods

A retrospective study was designed to compare the surgical outcomes of 27 robot-assisted laparoscopic pancreaticoduodenectomy (RPD) and 25 laparoscopic pancreaticoduodenectomy (LPD). Perioperative data, including operating time, complication, morbidity and mortality, estimated blood loss, and postoperative length of stay, were analyzed.

Results

The robotic group exhibited significantly shorter operative time (mean 387 vs. 442 min), shorter hospital stay (mean 17 vs. 24 days), and less blood loss (mean 219 vs. 334 ml) than those in the LPD group. No statistical difference was observed between the two groups in terms of complication rate, mortality rate, R0 resection rate, and number of harvested lymph node.

Conclusions

RPD is more efficient and secure process than LPD among properly selected patients. RPD is therefore a feasible alternative to the laparoscopic procedure. Further studies are needed to evaluate the cost effectiveness of the robotic approach for PD.



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Self-assessment in laparoscopic surgical skills training: Is it reliable?

Abstract

Background

The concept of self-assessment has been widely acclaimed for its role in the professional development cycle and self-regulation. In the field of medical education, self-assessment has been most used to evaluate the cognitive knowledge of students. The complexity of training and evaluation in laparoscopic surgery has previously acted as a barrier in determining the benefits self-assessment has to offer in comparison with other fields of medical education.

Methods

Thirty-five surgical residents who attended the 2-day Laparoscopic Surgical Skills Grade 1 Level 1 curriculum were invited to participate from The Netherlands, India and Romania. The competency assessment tool (CAT) for laparoscopic cholecystectomy was used for self- and expert-assessment and the resulting distributions assessed.

Results

A comparison between the expert- and self-assessed aggregates of scores from the CAT agreed with previous studies. Uniquely to this study, the aggregates of individual sub-categories—'use of instruments'; 'tissue handling'; and errors 'within the component tasks' and the 'end product' from both self- and expert-assessments—were investigated. There was strong positive correlation (r s > 0.5; p < 0.001) between the expert- and self-assessment in all categories with only the 'tissue handling' having a weaker correlation (r s = 0.3; p = 0.04). The distribution of the mean of the differences between self-assessment and expert-assessment suggested no significant difference between the scores of experts and the residents in all categories except the 'end product' evaluation where the difference was significant (W = 119, p = 0.03).

Conclusion

Self-assessment using the CAT form gives results that are consistently not different from expert-assessment when assessing one's proficiency in surgical skills. Areas where there was less agreement could be explained by variations in the level of training and understanding of the assessment criteria.



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Development of an evidence-based training program for laparoscopic hysterectomy on a virtual reality simulator

Abstract

Background

Substantial evidence in the scientific literature supports the use of simulation for surgical education. However, curricula lack for complex laparoscopic procedures in gynecology. The objective was to evaluate the validity of a program that reproduces key specific components of a laparoscopic hysterectomy (LH) procedure until colpotomy on a virtual reality (VR) simulator and to develop an evidence-based and stepwise training curriculum.

Methods

This prospective cohort study was conducted in a Marseille teaching hospital. Forty participants were enrolled and were divided into experienced (senior surgeons who had performed more than 100 LH; n = 8), intermediate (surgical trainees who had performed 2–10 LH; n = 8) and inexperienced (n = 24) groups. Baselines were assessed on a validated basic task. Participants were tested for the LH procedure on a high-fidelity VR simulator. Validity evidence was proposed as the ability to differentiate between the three levels of experience. Inexperienced subjects performed ten repetitions for learning curve analysis. Proficiency measures were based on experienced surgeons' performances. Outcome measures were simulator-derived metrics and Objective Structured Assessment of Technical Skills (OSATS) scores.

Results

Quantitative analysis found significant inter-group differences between experienced intermediate and inexperienced groups for time (1369, 2385 and 3370 s; p < 0.001), number of movements (2033, 3195 and 4056; p = 0.001), path length (3390, 4526 and 5749 cm; p = 0.002), idle time (357, 654 and 747 s; p = 0.001), respect for tissue (24, 40 and 84; p = 0.01) and number of bladder injuries (0.13, 0 and 4.27; p < 0.001). Learning curves plateaued at the 2nd to 6th repetition. Further qualitative analysis found significant inter-group OSATS score differences at first repetition (22, 15 and 8, respectively; p < 0.001) and second repetition (25.5, 19.5 and 14; p < 0.001).

Conclusions

The VR program for LH accrued validity evidence and allowed the development of a training curriculum using a structured scientific methodology.



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The effect of different training exercises on the performance outcome on the da Vinci Skills Simulator

Abstract

Background

Increasing usage of robotic surgery presents surgeons with the question of how to acquire the special skills required. This study aimed to analyze the effect of different exercises on their performance outcomes.

Methods

This prospective study was conducted on the da Vinci Skills Simulator from December 2014 till August 2015. Sixty robotic novices were included and randomized to three groups of 20 participants each. Each group performed three different exercises with comparable difficulty levels. The exercises were performed three times in a row within two training sessions, with an interval of 1 week in between. On the final training day, two new exercises were added and a questionnaire was completed. Technical metrics of performance (overall score, time to complete, economy of motion, instrument collisions, excessive instrument force, instruments out of view, master work space range, drops, missed targets, misapplied energy time, blood loss and broken vessels) were recorded by the simulator software for further analysis.

Results

Training with different exercises led to comparable results in performance metrics for the final exercises among the three groups. A significant skills gain was recorded between the first and last exercises, with improved performance in overall score, time to complete and economy of motion for all exercises in all three groups.

Conclusions

As training with different exercises led to comparable results in robotic training, the type of exercise seems to play a minor role in the outcome. For a robotic training curriculum, it might be important to choose exercises with comparable difficulty levels. In addition, it seems to be advantageous to limit the duration of the training to maintain the concentration throughout the entire session.



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Cost-effectiveness of a new strategy to identify uncomplicated gallstone disease patients that will benefit from a cholecystectomy

Abstract

Background

The aim of this study was to determine the cost-effectiveness of a new strategy for the preoperative detection of patients that will likely benefit from a cholecystectomy, using simple criteria that can be applied by surgeons. Criteria for a cholecystectomy indication are: (1) having episodic pain; (2) onset of pain 1 year or less before the outpatient clinic visit.

Methods

The cost-effectiveness of the new strategy was evaluated against current practice using a decision analytic model. The incremental cost-effectiveness of applying criteria for a cholecystectomy for a patient with abdominal pain and gallstones was compared to applying no criteria. The incremental cost-effectiveness ratio (ICER) was expressed as extra costs to be invested to gain one more patient with absence of pain. Scenarios were analyzed to assess the influence of applying different criteria.

Results

The new strategy of applying one out of two criteria resulted in a 4 % higher mean proportion of patients with absence of pain compared to current practice with similar costs. The 95 % upper limit of the ICER was €4114 ($4633) per extra patient with relief of upper abdominal pain. Application of two out of two criteria resulted in a 3 % lower mean proportion of patients with absence of pain with lower costs.

Conclusion

The new strategy of using one out of two strict selection criteria may be an effective but also a cost-effective method to reduce the proportion of patients with pain after cholecystectomy.



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Less pain after transvaginal cholecystectomy: single-center pooled analysis

Abstract

Background

We previously reported outcome after transvaginal cholecystectomy (TVC) from two cohort studies and a randomized controlled trial. We now present a pooled analysis of postoperative pain scores.

Design

Single-center data of postoperative pain after TVC from a level II hospital between October 2007 and June 2012.

Methods

Female patients, above 18 years with symptomatic cholecystolithiasis, received either TVC or conventional laparoscopic cholecystectomy (CLC). Follow up 4 days. The primary outcome of the study was pain after surgery. Pain was measured via a visual rating scale. Descriptive statistics include age, body mass index (BMI), ASA grade, surgical times, number of trocars, complications and hospital stay as well as pain medication. Pain data were assessed against histologic findings.

Results

The combined register included 316 patients. Of these, 7 patients were excluded from analysis due to conversion to open surgery, complications and denial of follow-up. There were 141 patients in the TVC and 168 in the CLC group. There was no difference in age, ASA grade, surgical times, complications or hospital stay. BMI was significantly different with an average BMI of 27.1 in the TVC and 28.7 in the CLC group (p = 0.027). The numbers of trocars were significantly different as expected. There was no difference in postoperative pain medication. Pain scores were significantly different on day two to four. Multivariate testing revealed no dependence between postoperative pain and histologic findings.

Conclusion

On smaller patient numbers, we were previously unable to demonstrate a consistently, significant difference for postoperative pain in our cohort and randomized studies. The pooled analysis suggests that there is an advantage with less postoperative pain after transvaginal compared to standard laparoscopic cholecystectomy.



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Inside EMS Podcast: How to recognize lazy students, bad instructors

<!--cke_bookmark_117S--><!--cke_bookmark_117E--> Download this podcast on iTunes, SoundCloud or via RSS feed ​​In this Inside EMS Podcast episode, co-hosts Chris Cebollero and Kelly Grayson discuss a fan email regarding a student that is completing EMT school. The student explains that they are not comfortable in their skills, knowledge and ability to pass the National Registry ...

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DC Fire and EMS celebrates EMS Week with CPR challenge

"May Madness" encourages responders to "own the code" and improve survival rates for cardiac arrest victims

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Editorial Board

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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Table of Contents

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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What Adherence Measures Should Be Used in Trials of Home-Based Rehabilitation Interventions? A Systematic Review of the Validity, Reliability, and Acceptability of Measures

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6
Author(s): Rachael Frost, Sara Levati, Doreen McClurg, Marian Brady, Brian Williams
ObjectiveTo systematically review methods for measuring adherence used in home-based rehabilitation trials and to evaluate their validity, reliability, and acceptability.Data SourcesIn phase 1 we searched the CENTRAL database, NHS Economic Evaluation Database, and Health Technology Assessment Database (January 2000 to April 2013) to identify adherence measures used in randomized controlled trials of allied health professional home-based rehabilitation interventions. In phase 2 we searched the databases of MEDLINE, Embase, CINAHL, Allied and Complementary Medicine Database, PsycINFO, CENTRAL, ProQuest Nursing and Allied Health, and Web of Science (inception to April 2015) for measurement property assessments for each measure.Study SelectionStudies assessing the validity, reliability, or acceptability of adherence measures.Data ExtractionTwo reviewers independently extracted data on participant and measure characteristics, measurement properties evaluated, evaluation methods, and outcome statistics and assessed study quality using the COnsensus-based Standards for the selection of health Measurement INstruments checklist.Data SynthesisIn phase 1 we included 8 adherence measures (56 trials). In phase 2, from the 222 measurement property assessments identified in 109 studies, 22 high-quality measurement property assessments were narratively synthesized. Low-quality studies were used as supporting data. StepWatch Activity Monitor validly and acceptably measured short-term step count adherence. The Problematic Experiences of Therapy Scale validly and reliably assessed adherence to vestibular rehabilitation exercises. Adherence diaries had moderately high validity and acceptability across limited populations. The Borg 6 to 20 scale, Bassett and Prapavessis scale, and Yamax CW series had insufficient validity. Low-quality evidence supported use of the Joint Protection Behaviour Assessment. Polar A1 series heart monitors were considered acceptable by 1 study.ConclusionsCurrent rehabilitation adherence measures are limited. Some possess promising validity and acceptability for certain parameters of adherence, situations, and populations and should be used in these situations. Rigorous evaluation of adherence measures in a broader range of populations is needed.



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Editors' Selections From This Issue: Volume 98 / Number 6 / June 2017

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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Masthead

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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Archives Manuscript Reviewers

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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Correction

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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Information/Education Pages (I/EPs)

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Publication date: June 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 6





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DC fire, EMS celebrates EMS Week with CPR challenge

"May Madness" encourages responders to "own the code" and improve survival rates for cardiac arrest victims

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Correspondence to Gripp et al. nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation



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Kir2.1 and K2P1 channels reconstitute two levels of resting membrane potential in cardiomyocytes

Abstract

Strong inward rectifier K+ (Kir2) channels primarily maintain normal resting membrane potential of cardiomyocytes. In sub-physiological extracellular K+ concentrations or pathological hypokalaemia, human cardiomyocytes show both hyperpolarized and depolarized resting membrane potentials; these depolarized potentials cause cardiac arrhythmia; however, the underlying mechanism is unknown. Here we show that Kir2.1 currents non-linearly counterbalance hypokalaemia-induced K2P1 leak cation currents, reconstituting two levels of resting membrane potential in cardiomyocytes. Under hypokalaemic conditions, both human cardiomyocytes derived from induced pluripotent stem cells with enhanced Kir2.1 expression and mouse HL-1 cardiomyocytes with ectopic expression of K2P1 channels recapitulate two levels of resting membrane potential. These cardiomyocytes display N-shaped current-voltage relationships that cross the voltage axis three times, and the first and third zero-current potentials match the two levels of resting membrane potential. Inhibition of K2P1 expression eliminates the phenomenon, indicating contributions of Kir2.1 and K2P1 channels to two levels of resting membrane potential. Second, in Chinese hamster ovary cells that heterologously express the channels, Kir2.1 currents non-linearly counterbalance hypokalaemia-induced K2P1 leak cation currents, yielding the N-shaped current-voltage relationships, causing resting membrane potential spontaneously jump from hyperpolarization at the first zero-current potential to depolarization at the third zero-current potential, again recapitulating two levels of resting membrane potential. These findings reveal ionic mechanisms of two levels of resting membrane potential, demonstrate a previously unknown mechanism of regulation of excitability, and support the hypothesis that Kir2 currents non-linearly balance inward background cation currents, accounting for two levels of resting membrane potential of human cardiomyocytes.

This article is protected by copyright. All rights reserved



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Sedentary behaviour is a key determinant of metabolic inflexibility

Abstract

Metabolic flexibility is defined as the ability to adapt substrate oxidation rates in response to changes in fuel availability. The inability to switch between the oxidation of lipid and carbohydrate appears to be an important feature of chronic disorders such as obesity and type 2 diabetes. Laboratory assessment of metabolic flexibility has traditionally involved measurement of the respiratory quotient (RQ) by indirect calorimetry during the fasted to fed transition (e.g. mixed meal challenge) or during a hyperinsulinemic-euglycemic clamp. Under these controlled experimental conditions, 'metabolic inflexibility' is characterized by lower fasting fat oxidation (higher fasting RQ) and/or an impaired ability to oxidize carbohydrate during feeding or insulin-stimulated conditions (lower postprandial or clamp RQ). This experimental paradigm has provided fundamental information regarding the role of substrate oxidation in the development of obesity and insulin resistance. However, the key determinants of metabolic flexibility among relevant clinical populations remain unclear. Herein, we propose that habitual physical activity levels are a primary determinant of metabolic flexibility. We present evidence demonstrating that high levels of physical activity predict metabolic flexibility; while physical inactivity and sedentary behaviours trigger a state of metabolic 'inflexibility', even among individuals who meet physical activity recommendations. Furthermore, we describe alternative experimental approaches to studying the concept of metabolic flexibility across a range of activity and inactivity. Finally, we address the promising use of strategies that aim to reduce sedentary behaviours as therapy to improve metabolic flexibility and reduce weight gain risk.

This article is protected by copyright. All rights reserved



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Patient care, advocacy are powerful bedfellows

By Carissa B. Caramanis As a mom and an EMT with a similar story, I was touched by Jimmy Kimmel's emotional monologue about his newborn son Billy. With more than 10 million YouTube views, it's a critical reminder of two underlying messages. First, just like Kimmel, I recognized no child makes it through a serious health issue without an amazing care team; and second, anyone in a caregiving ...

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Campaign aims to raise awareness of active shooter threat, rescue task force

The emerging threats facing today's responders, how a rescue task force response model works and what equipment and armor technology is available was discussed at the launch during EMS Week

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Processing of word stress related acoustic information: A multi-feature MMN study

Publication date: Available online 23 May 2017
Source:International Journal of Psychophysiology
Author(s): Ferenc Honbolygó, Orsolya Kolozsvári, Valéria Csépe
In the present study, we investigated the processing of word stress related acoustic features in a word context. In a passive oddball multi-feature MMN experiment, we presented a disyllabic pseudo-word with two acoustically similar syllables as standard stimulus, and five contrasting deviants that differed from the standard in that they were either stressed on the first syllable or contained a vowel change. Stress was realized by an increase of f0, intensity, vowel duration or consonant duration. The vowel change was used to investigate if phonemic and prosodic changes elicit different MMN components. As a control condition, we presented non-speech counterparts of the speech stimuli.Results showed all but one feature (non-speech intensity deviant) eliciting the MMN component, which was larger for speech compared to non-speech stimuli. Two other components showed stimulus related effects: the N350 and the LDN (Late Discriminative Negativity). The N350 appeared to the vowel duration and consonant duration deviants, specifically to features related to the temporal characteristics of stimuli, while the LDN was present for all features, and it was larger for speech than for non-speech stimuli. We also found that the f0 and consonant duration features elicited a larger MMN than other features.These results suggest that stress as a phonological feature is processed based on long-term representations, and listeners show a specific sensitivity to segmental and suprasegmental cues signaling the prosodic boundaries of words. These findings support a two-stage model in the perception of stress and phoneme related acoustical information.



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Sex differences in physiological response to the combination of stress and smoking

Publication date: Available online 23 May 2017
Source:International Journal of Psychophysiology
Author(s): Michael Kotlyar, Paul Thuras, Dorothy K. Hatsukami, Mustafa al'Absi
Stressful situations are among the most commonly cited smoking triggers. Smoking and stress exposure each individually increase cardiovascular and hypothalamic-pituitary-adrenal measures with larger increases occurring when stress and smoking are combined. In this analysis, sex differences in the physiological response to the combination of stress and smoking are examined. Smokers (36 males; 34 females) completed a laboratory session in which systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), plasma epinephrine (Epi), norepinephrine and cortisol concentrations were measured at rest, while smoking a cigarette, during a speech task occurring immediately after smoking and at several time-points following the stressor. Significant period by sex effects were observed for HR, SBP, DBP and EPI but not for cortisol or norepinephrine concentrations. For SBP (p=0.002), the increase between resting and speech were larger in men than in women, primarily due to a larger increase between smoking and speech occurring in men. A similar pattern was observed for DBP and Epi with a significantly larger EPI increase from smoking to speech observed in men than in women (p=0.016). A different pattern emerged for HR - the total increase was larger in women (p<0.001), due to a larger rest to smoking increase (p<0.001). In most measures therefore, overall increases were greater in men than women, primarily due to larger smoking to speech increases. Additional research is needed to determine the clinical implications of these results as they apply to sex difference in smoking cessation success rates and in the cardiovascular risks of smoking.



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To the heart of activation heat

Abstract

Cardiac muscle functions as a molecular machine that converts an electrical stimulus into a Ca2+-dependent mechanical contraction.

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Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion

Abstract
Background: In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients.Methods: Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 μg ml−1. Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state.Results: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 μg ml−1 were −22.6 (−28.8 to −12.6) and 31.9 (24.8–36.8) for the M-Marsh model and 9.0 (1.7–16.4) and 28.5 (21.7–32.8) for the Schnider model, respectively. These values at Ce ≥ 4 μg ml−1 were −9.6 (−16.0 to −6.0) and 24.7 (21.1–27.9) for the M-Marsh model and 19.8 (12.9–25.7) and 36.2 (31.4–39.7) for the Schnider model, respectively.Conclusions: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce3 μg ml−1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 μg ml−1. Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients.Clinical trial registration: KCT0001502.

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Per Diem Paramedic - Upper Kittitas County Medic One

Paramedic Kittitas County Public Hospital District #2 (KCPHD 2) is accepting applications to establish an eligibility list for per diem Paramedic. Current Salary Depends on prior experience Paramedic $16.22 - $22.46 – Per Diem Hourly $54,125 - $74,915 Full Time Annual Application An official District application, resume, along with copies of your drivers' license, required certifications ...

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Per Diem EMT - Upper Kittitas County Medic One

Please visit www.ukcmedicone.org for more information. EMT Kittitas County Public Hospital District #2 (KCPHD 2) is accepting applications to establish an eligibility list for per diem EMT. Current Salary Depends on prior experience EMT $12.75 - $17.64 – Per Diem Hourly $42,545 - $58,875 – Full Time Annual Application An official District application, resume, along with copies of your drivers' ...

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Time-related changes in firing rates are influenced by recruitment threshold and twitch force potentiation in the first dorsal interosseous

Abstract

There are contradictory reports regarding changes in motor unit firing rates during steady force contractions. Inconsistencies are likely the result of previous studies disregarding motor unit recruitment thresholds and not examining firing rates on a subject-by-subject basis. It is hypothesized that firing rates are manipulated by twitch force potentiation during contractions. Therefore, this study examined time-related changes in firing rates at steady force in relation to motor unit recruitment threshold in the first dorsal interosseous and the influence of twitch force potentiation on such changes in young versus aged individuals. Subjects performed a 12 second steady force contraction at 50% maximal voluntary contraction with evoked twitches prior to and following the contraction to quantify potentiation. Firing rates, in relation to recruitment thresholds, were determined at the beginning, middle, and end of the steady force. There were no firing rate changes for aged individuals. For the young, firing rates decreased slightly for lower-threshold motor units but increased for higher-threshold motor units. Twitch force potentiation was greater for young than aged subjects, and changes in firing rates were correlated with twitch force potentiation. Thus, individuals with greater increases in firing rates of higher-threshold MUs and decreases in lower-threshold MUs possessed greater twitch force potentiation. Overall, changes in firing rates during brief steady force contractions are dependent on recruitment threshold, and partially explained by twitch force potentiation. Because firing rate changes were measured in relation to recruitment threshold, this study illustrates a more complete view of firing rate changes during steady force contractions.

This article is protected by copyright. All rights reserved



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Development and validation of the Patient-Physician Relationship Scale among patients with irritable bowel syndrome

Neurogastroenterology & Motility

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Under Obamacare, insurance companies provide more breast pumps

Reuters Health News

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Risk-adjusted adverse outcomes in complex abdominal wall hernia repair with biologic mesh: A case series of 140 patients

International Journal of Surgery

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Cigarette filters may increase lung cancer risk

Reuters Health News

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Effect of centralization on long-term survival after resection of pancreatic ductal adenocarcinoma

British Journal of Surgery

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Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: Prospective cohort study

BMJ

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Stress and sleep quality in doctors working on-call shifts are associated with functional gastrointestinal disorders

World Journal of Gastroenterology

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Clinical course of ulcerative colitis patients who develop acute pancreatitis

World Journal of Gastroenterology

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Effect of a low-rank denoising algorithm on quantitative magnetic resonance imaging-based measures of liver fat and iron

Journal of Computer Assisted Tomography

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Similar effectiveness of direct-acting antiviral against hepatitis C virus in patients with and without HIV infection

AIDS

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Role of fluorescence in situ hybridization in diagnosing cholangiocarcinoma in indeterminate biliary strictures

Journal of Gastroenterology and Hepatology

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Competing risks for mortality in patients with asymptomatic pancreatic cystic neoplasms: Implications for clinical management

The American Journal of Gastroenterology

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WHO assembly set to choose next chief among 3 candidates

AP

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Usefulness of detection of clarithromycin-resistant Helicobacter pylori from fecal specimens for young adults treated with eradication therapy

Helicobacter

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Intake of B vitamins and impairment in physical function in older adults

Clinical Nutrition

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MR-spectroscopy of hepatic-fat and adiponectin and leptin levels during testosterone therapy in type 2 diabetes. A randomized, double-blinded, placebo-controlled trial

European Journal of Endocrinology

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Diagnosis of lower gastrointestinal bleeding by multi-slice CT angiography: A meta-analysis

European Journal of Radiology

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A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: Randomised clinical study in healthy volunteers

Alimentary Pharmacology and Therapeutics

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Patient-reported dietetic care post hospital for free-living patients: A Canadian Malnutrition Task Force Study

Journal of Human Nutrition and Dietetics

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Hepatic intra-arterial injection of irinotecan drug eluting beads (DEBIRI) for patients with unresectable colorectal liver metastases: A systematic review

Surgical Oncology

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Chronic EMGs in treadmill running SOD1 mice reveal early changes in muscle activation

Abstract

To improve our understanding of early disease mechanisms and find reliable biomarkers of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, we measured electromyogram (EMG) activity in hind limb muscles of SOD1G93A mice. In contrast to clinical diagnostic measures using EMGs, which are performed on quiescent patients, we monitored activity during treadmill running in order to detect presymptomatic changes in motor patterning. Chronic EMG electrodes were implanted into vastus lateralis (VL), biceps femoris posterior (BFP), lateral gastrocnemius (LG), and tibialis anterior (TA) in mice from postnatal day (P) 55–100, and results were assessed using linear mixed models. We evaluated differences in parameters related to EMG amplitude (peak and area) and timing (phase and skew, a measure of burst shape) while animals ran on level and inclined treadmills. There were significant changes in both the timing of activity and the amplitude of EMG bursts in SOD1G93A mice. Significant differences between wild type and SOD1G93A mice were mainly observed when animals locomoted on inclined treadmills. All muscles had significant effects of mutation that were independent of age. These novel results indicate 1) locomotor EMG activity might be an early measure of disease onset 2) alterations in locomotor patterning may reflect changes in neuronal drive and compensation at the network level including altered activity of spinal interneurons and 3) the increased power output necessary on an inclined treadmill was important in revealing altered activity in SOD1G93A mice.

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The conserved domain in MORF proteins has distinct affinities to the PPR and E elements in PPR RNA editing factors

Publication date: Available online 23 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Eszter Bayer-Császár, Sascha Haag, Anja Jörg, Franziska Glass, Barbara Härtel, Toshihiro Obata, Etienne H. Meyer, Axel Brennicke, Mizuki Takenaka
In plant organelles specific nucleotide motifs at C to U RNA editing sites are recognized by the PLS-class of pentatricopeptide repeat (PPR) proteins, which are additionally characterized by a C-terminal E domain. The PPR elements bind the nucleotides in the target RNA, while the function of the E domain has remained unknown. At most sites RNA editing also requires multiple organellar RNA editing factor (MORF) proteins. To understand how these two types of proteins are involved in RNA editing complexes, we systematically analyzed their protein-protein interactions. In vivo pull-down and yeast two-hybrid assays show that MORF proteins connect with selected PPR proteins. In a loss of function mutant of MORF1, a single amino acid alteration in the conserved MORF domain abrogates interactions with many PLS-class PPR proteins, implying the requirement of direct interaction to PPR proteins for the RNA editing function of MORF1. Subfragment analyses show that predominantly the N-terminal/central regions of the MORF domain in MORF1 and MORF3 bind the PPR proteins. Within the PPR proteins, the E domains in addition to PPR elements contact MORF proteins. In chimeric PPR proteins, different E domains alter the specificity of the interaction with MORF proteins. The selective interactions between E domain containing PPR and MORF proteins suggest that the E domains and MORF proteins play a key role for specific protein complexes to assemble at different RNA editing sites.



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The time course of indirect moral judgment in gossip processing modulated by different agents

Abstract

Previous studies have investigated personal moral violations with different references (i.e., the protagonists in moral scenarios are the participants themselves or unknown other individuals). However, the roles of various agents in moral judgments have remained unclear. In the present study, ERPs were used to investigate moral judgments when the participants viewed gossip that described (im)moral behaviors committed by different agents (self, friend, celebrity). The results demonstrate that the P2 and late positive component (LPC) correspond to two successive processes of indirect moral judgment when individuals process gossip. Specifically, the P2 amplitude in the celebrity condition was more sensitive in distinguishing immoral behaviors from moral behaviors than that in the other two conditions, whereas the moral valence effect on the LPC was predominately driven by the self-reference. These findings expand our current understanding of moral judgments in a gossip evaluation task and demonstrate that the early processing of gossip depends on both the entertainment value of the agent and the salience of moral behaviors. Processing in the later stage reflects reactions to intensified affective stimuli, or reflects cognitive effort that was required to resolve the conflict between negative gossip about self and the self-positivity bias.



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Dexmedetomidine: the new all-in-one drug in paediatric anaesthesia?.

Purpose of review: Dexmedetomidine is a drug with sedative, anxiolytic, sympatholytic and analgesic properties, which is finding widespread practice in paediatric anaesthesia and related practices. The present review summarizes its pharmacology and current experience with the drug. Recent findings: Dexmedetomidine is proving useful in many diverse areas in paediatric anaesthesia where its sedative properties are useful for premedication, fibreoptic intubation and radiologic procedures. Its use as an adjunct for balanced anaesthesia where it can decrease the use of other drugs, reduce emergence delirium, postoperative shivering and vomiting. Muted apoptotic neuroprotective effects may realize benefits in neonates. Cardiac conduction delay, an adverse effect, may prove beneficial for arrhythmias after congenital cardiac surgery. Summary: Most of the paediatric published studies concerning dexmedetomidine are observational in nature, with limited control groups or comparators. Adverse effects (e.g. bradycardia) still require greater scrutiny in the paediatric population and particularly with respect to different age groups. Dexmedetomidine currently has a firm position in the armamentarium of anaesthesia pharmacology. It is not the new all-in-one drug, but it is shaping up as a valuable adjunct for diverse indications within paediatric anaesthesia. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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