Παρασκευή 9 Μαρτίου 2018

The relationship between GABA and stress… “it's complicated”

Abstract

GABA is well-known to be a critical regulator of the body's physiological response to stress through tight regulation of hypothalamic-pituitary-adrenal (HPA) axis function.

This article is protected by copyright. All rights reserved



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Dynamics of neuro-effector coupling at ‘cardiac sympathetic’ synapses

Abstract

Aim

Cardiac sympathetic neurons (SNs) finely tune the rate and strength of heart contractions to match the blood demand, both at rest and during acute stresses, through the release of norepinephrine (NE). Junctional sites at the interface between the two cell types have been observed, but whether direct neuro-cardiac coupling has a role in heart physiology has not thus far been clearly demonstrated.

Methods and Results

We investigated the dynamics of SN/cardiomyocyte intercellular signalling, both by FRET-based imaging of cAMP in co-cultures, as a readout of cardiac β-AR activation, and in vivo, using optogenetics in transgenic mice with SN-specific expression of Channelrhodopsin-2. We demonstrate that SNs and cardiomyocytes interact at specific sites both in the human and rodent heart, and in co-cultures. Accordingly, neuronal activation elicited intracellular cAMP increases only in directly contacted myocytes and cell-cell coupling utilized a junctional extracellular signalling domain with elevated NE concentration. In the living mouse, optogenetic activation of cardiac SNs innervating the sino-atrial node resulted in an instantaneous chronotropic effect, which shortened the heartbeat interval with single beat precision. Remarkably, inhibition of the optogenetically elicited chronotropic responses required a high dose of propranolol (20-50 mg/Kg), suggesting that sympathetic neurotransmission in the heart occurs at locally elevated NE concentration.

Conclusions

Our in vitro and in vivo data suggest that the control of cardiac function, by SNs, occurs via direct intercellular coupling due to the establishment of a specific junctional-site.

This article is protected by copyright. All rights reserved



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Measuring Pavlovian appetitive conditioning in humans with the postauricular reflex

Abstract

Despite its evolutionary and clinical significance, appetitive conditioning has been rarely investigated in humans. It has been proposed that this discrepancy might stem from the difficulty in finding suitable appetitive stimuli that elicit strong physiological responses. However, this might also be due to a possible lack of sensitivity of the psychophysiological measures commonly used to index human appetitive conditioning. Here, we investigated whether the postauricular reflex—a vestigial muscle microreflex that is potentiated by pleasant stimuli relative to neutral and unpleasant stimuli—may provide a valid psychophysiological indicator of appetitive conditioning in humans. To this end, we used a delay differential appetitive conditioning procedure, in which a neutral stimulus was contingently paired with a pleasant odor (CS+), while another neutral stimulus was not associated with any odor (CS−). We measured the postauricular reflex, the startle eyeblink reflex, and skin conductance response (SCR) as learning indices. Taken together, our results indicate that the postauricular reflex was potentiated in response to the CS+ compared with the CS−, whereas this potentiation extinguished when the pleasant odor was no longer delivered. In contrast, we found no evidence for startle eyeblink reflex attenuation in response to the CS+ relative to the CS−, and no effect of appetitive conditioning was observed on SCR. These findings suggest that the postauricular reflex is a sensitive measure of human appetitive conditioning and constitutes a valuable tool for further shedding light on the basic mechanisms underlying emotional learning in humans.



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Characterization of Carbapenemase-Producing Enterobacteriaceae from Patients in Amman, Jordan

Microbial Drug Resistance, Ahead of Print.


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Self-regulatory strategies as correlates of physical activity behavior in persons with multiple sclerosis

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Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Katie L. Cederberg, Julia M. Balto, Robert W. Motl
ObjectiveTo examine self-regulation strategies as correlates of physical activity in persons with multiple sclerosis (MS).DesignCross-sectional, or survey, study.SettingUniversity-based research laboratory.ParticipantsConvenience sample of 68 persons with MS.InterventionsNot applicable.Main Outcome MeasuresExercise Self-Efficacy Scale (EXSE), Physical Activity Self-Regulation Scale (PASR-12), and Godin Leisure-Time Exercise Questionnaire (GLTEQ).ResultsCorrelation analyses indicated that GLTEQ scores were positively and significantly associated with overall self-regulation (r=0.43), self-monitoring (r=0.45), goal-setting (r=0.27), reinforcement (r=0.30), time management (r=0.41), and relapse prevention (r=0.53) PASR-12 scores. Regression analyses indicated that relapse prevention (B=5.01; SE B=1.74; β=0.51) and self-monitoring (B=3.65; SE B=1.71; β=0.33) were unique predictors of physical activity behavior, and relapse prevention demonstrated a significant association with physical activity behavior that was accounted for by EXSE.ConclusionsOur results indicate that self-regulatory strategies, particularly relapse prevention, may be important correlates of physical activity behavior that can inform the design of future behavioral interventions in MS.



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Rhythm perception and production abilities and their relationship to gait after stroke

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Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kara K. Patterson, Jennifer S. Wong, Svetlana Knorr, Jessica A. Grahn
ObjectivesTo assess rhythm abilities, describe their relationship to clinical presentation, and to determine if rhythm production independently contributes to temporal gait asymmetry post-stroke.DesignCross-sectional.SettingLarge urban rehabilitation hospital and university.ParticipantsIndividuals with subacute and chronic stroke (n=39) and data for healthy adults extracted from a pre-existing database (n=21).InterventionNot applicable.Main outcome measuresStroke group: National Institutes of Health Stroke Scale (NIHSS), Chedoke-McMaster Stroke Assessment (CMSA) leg and foot scales, Montreal Cognitive Assessment (MoCA), rhythm perception and production (Beat Alignment Test; BAT) and spatiotemporal gait parameters were assessed. Temporal gait asymmetry (TGA) was quantified with the swing time symmetry ratio. Healthy group: age and beat perception scores assessed by BAT. Rhythm perception of the stroke group and healthy adults was compared with ANOVA. Spearman correlations quantified the relationship between rhythm perception and production abilities and clinical measures. Multiple linear regression assessed the contribution of rhythm production along with motor impairment and time post stroke to TGA.ResultsRhythm perception in the stroke group was worse than healthy adults (F(1,56) = 17.5, p=0.0001) Within the stroke group, rhythm perception was significantly correlated with CMSA leg (rs =0.33, p=0.04), and foot (rs =0.49, p=0.002) scores but not NIHSS or MOCA scores. The model for TGA was significant (F(3,35)=12.8, p<0.0001) with CMSA leg scores, time post-stroke and asynchrony of rhythm production explaining 52% of the variance.ConclusionsRhythm perception is impaired after stroke and temporal gait asymmetry relates to impairments in producing rhythmic movement. These results may have implications for the use of auditory rhythmic stimuli to cue motor responses post-stroke. Future work will explore brain responses to rhythm processing post-stroke.



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The Use of Virtual Technology as an Intervention for Wheelchair Skills Training: A Systematic Review

Publication date: Available online 10 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jean-François Lam, Laurent Gosselin, Paula W. Rushton
ObjectiveTo provide a comprehensive description of the current state of knowledge regarding the use of virtual technology (VT) for wheelchair skills training.Data sourcesThe Cochrane Library, MEDLINE, CINAHL, EMBASE, ACM, IEEE Xplore, Inspec, and Web of Science databases were searched for relevant articles from 1990 to February 2016.Study selectionWe included peer-reviewed studies or long conference proceedings that examined the use of VT as a medium to provide a wheelchair skills training intervention for any population with any diagnosis using any research design. One investigator screened the titles and abstracts, then 2 investigators independently reviewed the full-text articles. Disagreements regarding inclusion were resolved by consensus or a third reviewer. Ten studies were included out of 4994 initially identified.Data extractionTwo investigators extracted data to systematically assess the studies' findings into 6 tables (study design and participant characteristics, equipment and technology used, intervention characteristics, outcome measures, and outcomes).Data synthesisMost studies demonstrated that VT wheelchair skills training showed improved outcomes such as simulation score, completion time, and number of collisions in the virtual environment and/or in real world. However, subject characteristics, equipment, virtual environment, intervention tasks, and outcome measures varied across the studies.ConclusionsThere exists a variety of studies using VT as an intervention for wheelchair skills training. Given the positive outcomes for most of the studies, it appears as though VT may indeed be a solution that can help to alleviate barriers to wheelchair skills training and subsequently improve wheelchair user skill.



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Aerobic stimulus induced by virtual reality games in stroke survivors

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Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Julio Cesar Silva de Sousa, Camila Torriani-Pasin, Amanda Barboza Tosi, Rafael Yokoyama Fecchio, Luiz Augusto Riani da Costa, Cláudia Lúcia de Moraes Forjaz
ObjectiveTo evaluate whether virtual reality games (VRG) in stroke survivors produce significant and reproducible heart rate (HR) and oxygen consumption (VO2) responses during their execution, corresponding to an intensity between the anaerobic threshold (AT) and the respiratory compensation point (RCP).DesignSingle subjects repeated measure designSettingStroke survivors registered from a rehabilitation programParticipantsTwelve chronic hemiparetic stroke survivors (10 men, 58 ± 12 years) rated at 3 or 4 in the Functional Ambulation Categories (FAC).InterventionsSubjects underwent, in a random order, two identical sessions of VRG (console Xbox360+Kinect) and one control session (CONT – 38 min watching a movie). The VRG sessions were composed by four sets of VRG (3 min of Boxing, 1 min for changing the game and 4 min of Tennis) interspaced by 2 min of rest.Main Outcome MeasuresHR and VO2 were measured during the experimental sessions and compared to HR and VO2 obtained at AT and RCP assessed in a maximal cardiopulmonary exercise test.ResultsHR and VO2 during VRG presented good reproducibility (intraclass correlation coefficient > 0.91 and > 0.85 and coefficient of variation < 6.7 and < 13.7%, respectively). HR during VRG was similar to AT and significantly lower than RCP (p<0.05), while VO2 was significantly lower than AT and RCP (p<0.05).ConclusionsAn acute session of VRG composed by Tennis and Boxing games of the console XBox360+Kinect promotes reproducible responses of HR and VO2 that corresponded, respectively, to AT and below AT, characterizing a low intensity aerobic stimulus.



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The Effects of Timing and Intensity of Neurorehabilitation on Functional Outcome after Traumatic Brain Injury: a Systematic Review & Meta-Analysis

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Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marsh Königs, Eva A. Beurskens, Lian Snoep, Erik J.A. Scherder, Jaap Oosterlaan
ObjectiveTo systematically review evidence on the effects of timing and intensity of neurorehabilitation on the functional recovery of patients with moderate to severe traumatic brain injury (TBI) and aggregate the available evidence using meta-analytic methods.Data sourcesPubmed, Embase, PsycINFO and Cochrane Database.Data selectionElectronic databases were searched for prospective controlled clinical trials assessing the effect of timing or intensity of multidisciplinary neurorehabilitation programs on functional outcome of patients with moderate or severe TBI. A total of 5,961 unique records were screened for relevance, of which 58 full-text articles were assessed for eligibility by two independent authors. Eleven articles were included for systematic review and meta-analysis.Data extractionTwo independent authors performed data extraction and risk of bias analysis using the Cochrane Collaboration Tool. Discrepancies between authors were resolved by consensus.Data synthesisSystematic review of a total of six randomized controlled trials, one quasi-randomized trails and four controlled trials revealed consistent evidence for a beneficial effect of early onset neurorehabilitation in the trauma center and intensive neurorehabilitation in the rehabilitation facility on functional outcome, as compared to usual care. Meta-analytic quantification revealed a large-sized positive effect for early onset rehabilitation programs (d = 1.02, p < .001, 95%-confidence interval [CI]: 0.56-1.47) and a medium-sized positive effect for intensive neurorehabilitation programs (d = 0.67, p < .001. 95%-CI: 0.38-0.97) as compared to usual care. These effects were replicated based on solely studies with a low overall risk of bias.ConclusionsThe available evidence indicates that early onset neurorehabilitation in the trauma center and more intensive neurorehabilitation in the rehabilitation facility promote functional recovery of patients with moderate to severe TBI as compared to usual care. These findings support the integration of early onset and more intensive neurorehabilitation in the chain of care for patients with TBI.



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Repeat-Specific Functions for the C-Terminal Domain of RNA Polymerase II in Budding Yeast

The C-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII) is required to regulate transcription and to integrate it with other essential cellular processes. In the budding yeast Saccharomyces cerevisiae, the CTD of Rpb1p consists of 26 conserved heptad repeats that are post-translationally modified to orchestrate protein factor binding at different stages of the transcription cycle. A long-standing question in the study of the CTD is if there are any functional differences between the 26 repeats. In this study, we present evidence that repeats of identical sequence have different functions based on their position within the CTD. We assembled plasmids expressing Rpb1p with serine to alanine substitutions in three defined regions of the CTD and measured a range of phenotypes for yeast expressing these constructs. Mutations in the beginning and middle regions of the CTD had drastic, and region-specific effects, while mutating the distal region had no observable phenotype. Further mutational analysis determined that Ser5 within the first region of repeats was solely responsible for the observed growth differences and sequencing fast-growing suppressors allowed us to further define the functional regions of the CTD. This mutational analysis is consistent with current structural models for how the RNAPII holoenzyme and the CTD specifically would reside in complex with Mediator and establishes a foundation for studying regioselective binding along the repetitive RNAPII CTD.



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Germline Variants in the POT1-Gene in High-Risk Melanoma Patients in Austria

Risk of melanoma is in part determined by genetic factors. Currently the only established high penetrance familial melanoma genes are CDKN2A and CDK4. Recent studies reported germline variants in POT1 in melanoma families. In the present study, we sequenced the entire POT1 gene in 694 patients from the M3-study. Patients with multiple primary melanomas (n=163) or with a positive family history (n=133) were classified as high-risk melanoma patients. Additionally, 200 single primary melanoma patients and 198 non-melanoma controls were sequenced. For prediction analysis 10 different tools were used. In total 53 different variants were found, of which 8 were detected in high-risk melanoma patients, only. Two out of these 8 variants were located in exons and were non-synonymous: g.124510982 G>A (p.R80C) and g.124491977 T>G (p.N300H). While g.124491977 T>G was predicted to be neutral, 80% of the prediction tools classified g.124510982 G>A as deleterious. The variant, g.124467236 T>C, which possibly causes a change in the splice site was identified in a case with a positive family history in the present study. Another variant in the 5-UTR, g.124537261 A>G, was found in 2 high-risk patients. So, in conclusion, melanoma associated POT1 germline variants seem to be rare. Further studies are required to evaluate the role of POT1 for genetic counselling.



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Robust {Phi}C31-Mediated Genome Engineering in Drosophila melanogaster Using Minimal attP/attB Phage Sites

Effective genome engineering should lead to a desired locus change with minimal adverse impact to the genome itself. However, flanking loci with site-directed recombinase recognition sites, such as those of the phage FC31 integrase, allows for creation of platforms for cassette exchange and manipulation of genomic regions in an iterative manner, once specific loci have been targeted. Here we show that a genomic locus engineered with inverted minimal phage FC31 attP/attB sites can undergo efficient recombinase-mediated cassette exchange (RMCE) in the fruit fly Drosophila melanogaster.



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Managing Your Anesthesiology Practice for the Future

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Publication date: Available online 9 March 2018
Source:Anesthesiology Clinics
Author(s): Amr E. Abouleish, Stanley W. Stead




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Electroencephalographic correlates of low-frequency vagus nerve stimulation therapy for Crohn’s disease

Crohn's disease (CD) is a chronic inflammatory bowel disease traditionally requiring treatments with important side effects, such as anti-TNF (tumor necrosis factor) therapy, which is efficient only for 30 to 40% patients who, moreover, can become non-responders later (up to 50% of them) (Olesen et al., 2016). This therapy can further generate adverse effects like infections and up to half of the CD patients will not continue therapy (non-compliance). Therefore, because vagus nerve stimulation (VNS) is thought to activate the cholinergic anti-inflammatory pathway, an anti-tumor necrosis factor (TNF) pathway partly through the action of acetylcholine on immune cells releasing TNF (Bonaz et al., 2013), VNS is being evaluated in CD patients as an alternative (or a complement) to pharmaceutical treatments (Bonaz et al., 2016;2017a).

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Systemic effects of deep brain stimulation on synergic control in Parkinson’s disease

Deep brain stimulation (DBS) of nuclei within the basal ganglia, typically the subthalamic nucleus and globus pallidus, has been used as an effective treatment of Parkinson's disease (PD), commonly in combination with dopamine-replacement medications (reviewed in Kalia et al., 2013; DeLong and Wichmann, 2015). Many studies have reported significant positive effects of DBS on clinical indices such as Unified Parkinson's Disease Rating Scale (UPDRS) scores and general characteristics of movements such as maximal force, peak velocity, and movement time (Brown et al., 1999; Alberts et al., 2008; Daneault et al., 2016).

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Emotion identification and aging: Behavioral and neural age-related changes

Emotion identification is a key element of nonverbal communication, with emotions often expressed through changes in facial expression, eye contact, body posture and movement. Across the life span, accurate identification of emotional expressions is essential for successful interpersonal functioning (Carstensen et al., 1997). Inferring the emotions that others are experiencing is an important feature in avoiding conflict and providing social support. Furthermore, intact emotion identification skills are essential to regulate behavior.

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Modulation of the endocrine transcriptional program by targeting histone modifiers of the H3K27me3 mark

Publication date: Available online 9 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Marta Fontcuberta-PiSunyer, Sara Cervantes, Eulàlia Miquel, Sergio Mora-Castilla, Louise C. Laurent, Angel Raya, Ramon Gomis, Rosa Gasa
Posttranscriptional modifications of histones constitute an epigenetic mechanism that is closely linked to both gene silencing and activation events. Trimethylation of Histone3 at lysine 27 (H3K27me3) is a repressive mark that associates with developmental gene regulation during differentiation programs. In the developing pancreas, expression of the transcription factor Neurogenin3 in multipotent progenitors initiates endocrine differentiation that culminates in the generation of all pancreatic islet cell lineages, including insulin-producing beta cells. Previously, we showed that Neurogenin3 promoted the removal of H3K27me3 marks at target gene promoters in vitro, suggesting a functional connection between this factor and regulators of this chromatin mark. In the present study, we aimed to specifically evaluate whether targeting the activity of these histone modifiers can be used to modulate pancreatic endocrine differentiation. Our data show that chemical inhibition of the H3K27me3 demethylases Jmjd3/Utx blunts Neurogenin3-dependent gene activation in vitro. Conversely, inhibition of the H3K27me3 methyltransferase Ezh2 enhances both the transactivation ability of Neurogenin3 in cultured cells and the formation of insulin-producing cells during directed differentiation from pluripotent cells. These results can help improve current protocols aimed at generating insulin-producing cells for beta cell replacement therapy in diabetes.

Graphical abstract

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Single-incision laparoscopic cholecystectomy is responsible for increased adverse events: results of a meta-analysis of randomized controlled trials

Abstract

Background

Over the last decade, single-incision laparoscopic cholecystectomy (SLC) has gained popularity, although it is not evident if benefits of this procedure overcome the potential increased risk. Aim of the study is to compare the outcome of SLC with conventional multi-incision laparoscopic cholecystectomy (MLC) in a meta-analysis of randomized controlled trials only.

Methods

A systematic Medline, Embase, and Cochrane Central Register of Controlled Trials literature search of articles on SLC and MLC for any indication was performed in June 2017. The main outcomes measured were overall adverse events, pain score (VAS), cosmetic results, quality of life, and incisional hernias. Linear regression was used to model the effect of each procedure on the different outcomes.

Results

Forty-six trials were included and data from 5141 participants were analysed; 2444 underwent SLC and 2697 MLC, respectively. Mortality reported was nil in both treatment groups. Overall adverse events were higher in the SLC group (RR 1.41; p < 0.001) compared to MLC group, as well severe adverse events (RR 2.06; p < 0.001) and even mild adverse events (RR 1.23; p = 0.041). This was confirmed also when only trials including 4-port techniques (RR 1.37, p = 0.004) or 3-port techniques were considered (RR 1.89, p = 0.020). The pain score showed a standardized mean difference (SMD) of − 0.36 (p < 0.001) in favour of SLC. Cosmetic outcome by time point scored a SMD of 1.49 (p < 0.001) in favour of SLC. Incisional hernias occurred more frequently (RR 2.97, p = 0.005) in the SLC group.

Conclusions

Despite SLC offers a better cosmetic outcome and reduction of pain, the consistent higher rate of adverse events, both severe and mild, together with the higher rate of incisional hernias, should suggest to reconsider the application of single incision techniques when performing cholecystectomy with the existing technology.



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Sub-concussive trauma, acute concussion, and history of multiple concussions: Effects on quiet stance postural control stability

Publication date: Available online 8 March 2018
Source:International Journal of Psychophysiology
Author(s): J.K. Dierijck, A.D. Wright, J.D. Smirl, K. Bryk, P. van Donkelaar
Although balance control has been studied extensively following acute concussion, little is known regarding repetitive sub-concussive head impacts or chronic exposure to multiple concussive events. Quiet stance postural control was characterized in contact sport athletes at pre-season (n = 135) and post-season (n = 48) to evaluate the effects of subconcussive trauma to the head. To determine the impact of acute concussion on postural control, athletes diagnosed with a concussion during the season (n = 12) were tested at 72-h, 2-weeks, and 1-month post-injury. Because only 4 of the concussed athletes completed baseline testing, control athletes (n = 12) matched for sport, age, body mass index (BMI), and previous concussion history served as a comparison group. Finally, the effects of previous concussion history on quiet stance postural control were determined by comparing pre-season data in contact sport athletes with either zero (Hx0, n = 50) or three or more (Hx3+, n = 25) previous concussions. A force plate was used to compare changes in centre-of-pressure root-mean-square displacement (RMSdisp) and mean-velocity (COPvel) in the anterior/posterior (AP) and medial/lateral (ML) directions. One-minute trials were performed with feet hip-width apart, hands-on-hips, and A) eyes-open and B) eyes-closed. Biomechanical head-impact exposure (impacts over 10 g) was indexed over the season using mastoid-fixed impact sensors. In acutely injured athletes, repeated-measures ANOVA revealed a significant effect of time for RMSdisp AP with increased displacement at 2 weeks compared to 72 h (p = 0.008, 95% CI: −0.180, −0.310 cm). No other COP variables were affected by acute concussion. Moreover, there was no effect of concussion history or repeated sub-concussive impacts on any quiet stance metric. Additionally, head-impact exposure metrics were not correlated with COP metrics. Taken together, the data suggests alterations in COP sway during quiet stance persist in the acute 2-week period after injury. These findings were not present with either a history of multiple concussions or exposure to sub-concussive head impacts indicating acute concussion does not have appear to have long term effects for these measures.



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New-onset atrial fibrillation: an update

Abstract

New-onset atrial fibrillation (NOAF) is the most common perioperative complication of heart surgery, typically occurring in the perioperative period. NOAF commonly occurs in patients who are elderly, or have left atrial enlargement, or left ventricular hypertrophy. Various factors have been identified as being involved in the development of NOAF, and numerous approaches have been proposed for its prevention and treatment. Risk factors include diabetes, obesity, and metabolic syndrome. For prevention of NOAF, β-blockers and amiodarone are particularly effective and are recommended by guidelines. NOAF can be treated by rhythm/rate control, and antithrombotic therapy. Treatment is required in patients with decreased cardiac function, a heart rate exceeding 130 beats/min, or persistent NOAF lasting for ≥ 48 h. It is anticipated that anticoagulant therapies, as well as hemodynamic management, will also play a major role in the management of NOAF. When using warfarin as an anticoagulant, its dose should be adjusted based on PT-INR. PT-INR should be controlled between 2.0 and 3.0 in patients aged < 70 years and between 1.6 and 2.6 in those aged ≥ 70 years. Rate control combined with antithrombotic therapies for NOAF is expected to contribute to further advances in treatment and improvement of survival.



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Effects of Two Hours of Heavy-Intensity Exercise on the Power–Duration Relationship

AbstractIntroductionChanges in the parameters of the power-time relationship (critical power (CP) and W′) during endurance exercise would have important implications for performance. We tested the hypotheses that CP and W′, estimated using the end-test power (EP) and the work done above EP (WEP), respectively, during a the 3-min all-out test (3MT), can be reliably determined, and would be lower, after completing 2-h of heavy-intensity exercise.MethodsIn study 1, six cyclists completed a 3MT immediately following 2-h of heavy-intensity exercise on two occasions to establish the reliability of EP and WEP. In study 2, nine cyclists completed a control 3MT, and a fatigued 3MT and constant-power-output tests to 30 min or the limit of tolerance (Tlim) below and above F-EP after 2-h of heavy-intensity exercise.ResultsIn study 1, EP (273±52 vs. 276±58 W) and WEP (12.4±4.3 vs. 12.8±4.3 kJ) were not different (P>0.05) and were highly correlated (r=0.99; PF-EP and Tlim was shorter than 30 min during exercise 0.05) and were highly correlated (r=0.99; PF-EP and Tlim was shorter than 30 min during exercise

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Pre-Pregnancy Fitness and Risk of Gestational Diabetes: A Longitudinal Analysis

ABSTRACTPurposeTo assess the associations of pre-pregnancy cardiorespiratory fitness, moderate-to vigorous-intensity physical activity (MVPA), and time spent watching television with subsequent development of gestational diabetes mellitus (GDM).MethodsParticipants were 1,333 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have diabetes either at baseline (1985-86) or prior to births occurring after baseline. Baseline fitness was estimated using a graded symptom-limited maximal exercise treadmill test and expressed in metabolic equivalent (MET) units. Baseline MVPA (exercise units/day) was measured using the CARDIA physical activity history questionnaire, and television viewing (hours/day) was assessed by self-report in 1990-91. Logistic regression analysis was used to derive odds ratios (OR) and 95% confidence intervals (CI), adjusting for time from baseline to delivery and baseline study center, age, race, education, parity, family history of diabetes, smoking, alcohol, saturated fat intake, waist circumference, HOMA-IR, and HDL-Cholesterol.ResultsOver 25 years of follow up, 164 women developed GDM. The odds of developing GDM were 21% lower for each 1 standard deviation increment in baseline level of fitness (2.3 METs; OR 0.79, 95% CI 0.65, 0.96). Pre-pregnancy MVPA and television viewing were not statistically associated with the development of GDM.ConclusionStudy findings indicate that objectively assessed pre-pregnancy fitness, but not self-reported MVPA or television time, is associated with GDM. Clinicians should counsel women on the benefits of improving fitness in the pre-conception period, particularly among women at greater risk for GDM. Purpose To assess the associations of pre-pregnancy cardiorespiratory fitness, moderate-to vigorous-intensity physical activity (MVPA), and time spent watching television with subsequent development of gestational diabetes mellitus (GDM). Methods Participants were 1,333 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have diabetes either at baseline (1985-86) or prior to births occurring after baseline. Baseline fitness was estimated using a graded symptom-limited maximal exercise treadmill test and expressed in metabolic equivalent (MET) units. Baseline MVPA (exercise units/day) was measured using the CARDIA physical activity history questionnaire, and television viewing (hours/day) was assessed by self-report in 1990-91. Logistic regression analysis was used to derive odds ratios (OR) and 95% confidence intervals (CI), adjusting for time from baseline to delivery and baseline study center, age, race, education, parity, family history of diabetes, smoking, alcohol, saturated fat intake, waist circumference, HOMA-IR, and HDL-Cholesterol. Results Over 25 years of follow up, 164 women developed GDM. The odds of developing GDM were 21% lower for each 1 standard deviation increment in baseline level of fitness (2.3 METs; OR 0.79, 95% CI 0.65, 0.96). Pre-pregnancy MVPA and television viewing were not statistically associated with the development of GDM. Conclusion Study findings indicate that objectively assessed pre-pregnancy fitness, but not self-reported MVPA or television time, is associated with GDM. Clinicians should counsel women on the benefits of improving fitness in the pre-conception period, particularly among women at greater risk for GDM. Corresponding Author: Kara M. Whitaker, E112 Field House, Iowa City, IA; Telephone: 319-335-7907; Fax: 319-335-6669; E-mail: kara-whitaker@uiowa.edu The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005). The analyses were supported by grants from R01 DK090047 (Gunderson, PI) and K01 DK059944 (Gunderson, PI) from the National Institute of Diabetes, Digestive and Kidney Diseases. KMW was supported by research training grant T32 HL007779. CEL, PJS, and EPG report grant funding from the National Institutes of Health (NIH) during the conduct of this study. EPG also reports funding from Jansen Pharmaceutical Inc. that was unrelated to this study. No other conflicts of interest were reported. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the NHLBI, the NIH, the U.S. Department of Health and Human Services, or ACSM. The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 1 March 2018 © 2018 American College of Sports Medicine

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The role of simulation training in anesthesiology resident education

Abstract

An increasing number of reports indicate the efficacy of simulation training in anesthesiology resident education. Simulation education helps learners to acquire clinical skills in a safe learning environment without putting real patients at risk. This useful tool allows anesthesiology residents to obtain medical knowledge and both technical and non-technical skills. For faculty members, simulation-based settings provide the valuable opportunity to evaluate residents' performance in scenarios including airway management and regional, cardiac, and obstetric anesthesiology. However, it is still unclear what types of simulators should be used or how to incorporate simulation education effectively into education curriculums. Whether simulation training improves patient outcomes has not been fully determined. The goal of this review is to provide an overview of the status of simulation in anesthesiology resident education, encourage more anesthesiologists to get involved in simulation education to propagate its influence, and stimulate future research directed toward improving resident education and patient outcomes.



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Identification of transposable elements fused in the exonic region of the olive flounder genome

Abstract

Transposable elements (TEs) are mobile genetic sequences that comprise a large portion of vertebrate genomes. The olive flounder (Paralichthys olivaceus) is a valuable marine resource in East Asia. The scope of most genomic studies on the olive flounder is limited to its immunology as their focus is the prevention of mass mortality of this species. Thus, for a broader understanding of the species, its genomic information is consistently in demand. Transcripts sequences were acquired from transcriptome analysis using gill tissues of 12 olive flounders. Distribution of TEs inserted in exonic region of the olive flounder genome was analyzed using RepeatMasker (http://www.repeatmasker.org/). We found 1140 TEs in the exonic region of the genome and long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs) insertions occurred with forward orientation preferences. Transposons belonging to the hAt, Gypsy, and LINE 1 (L1) subfamilies were the most abundant DNA transposons, LTRs, and long interspersed elements (LINEs), respectively. Finally, we carried out a gene ontology analysis to determine the function of TE-fused genes. These results provide some genomic information about TEs that is useful for future research on changes in properties and functions of genes by TEs in the olive flounder genome.



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The D313Y genotype—Pathogenic mutation or polymorphism?

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Recovery in the Severely Impaired Arm Post-stroke after Mirror Therapy – a Randomized Controlled Study

ABSTRACTObjectiveThis study aimed to examine the effectiveness of mirror therapy (MT) on recovery in the severely impaired arm after stroke.DesignUsing single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to received MT (n=20) or control therapy (CT) (n=21), 30min. twice daily for 4 weeks in addition to conventional rehabilitation. During MT and CT, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for MT, but mirror was absent for CT so that subjects could watch both arms in exercise. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were the outcome measurements.ResultsAfter the intervention, both MT and CT groups had significant arm recovery similarly in FMA (p=0.867), WMFT-Time (p=0.947) and WMFT-Functional Ability Scale (p=0.676).ConclusionMT or CT which involved exercises concurrently for the paretic and unaffected arms during subacute stroke promoted similar motor recovery in the severely impaired arm. Objective This study aimed to examine the effectiveness of mirror therapy (MT) on recovery in the severely impaired arm after stroke. Design Using single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to received MT (n=20) or control therapy (CT) (n=21), 30min. twice daily for 4 weeks in addition to conventional rehabilitation. During MT and CT, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for MT, but mirror was absent for CT so that subjects could watch both arms in exercise. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were the outcome measurements. Results After the intervention, both MT and CT groups had significant arm recovery similarly in FMA (p=0.867), WMFT-Time (p=0.947) and WMFT-Functional Ability Scale (p=0.676). Conclusion MT or CT which involved exercises concurrently for the paretic and unaffected arms during subacute stroke promoted similar motor recovery in the severely impaired arm. Corresponding Author: Dr. Stephanie S.Y. AU-YEUNG, Address: Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hunghom, Kowloon, Hong Kong SAR, China, Email: (1) auyeung.stephanie@yahoo.com; (2) stephanie.auyeung@polyu.edu.hk Conflict of interests The Authors declare that there is no conflict of interest. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The study was presented as poster presentation on 21-22 July, 2016 in International Conference on Neuro Oncology and Rehabilitation, Brisbane, Queensland, Australia. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Keeping it short and (not so) simple: characterizing hERG kinetics with sinusoidal waves

Abstract

Mathematical models and numerical simulation have tremendously enhanced our understanding of the mechanisms that underlie cardiac electrical and contractile function and their derangements, as well as the consequences of pharmacologic intervention.

This article is protected by copyright. All rights reserved



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Issue Information



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Cover Image

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The cover image, by G. Şimşek Kaya et al., is based on the Original Article Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders, DOI: 10.1111/joor.12608.



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Differences between horse selection based on two forms of osteochondrosis in fetlock

Abstract

Horses lose potential opportunities because of health problems. Available breeding strategies are not effective enough, probably also because of the different definition used and its genetic usefulness. The aim of the study was to compare the genetic background estimated by the genome-wide association study (GWAS) for osteochondrosis using two different scaling osteochondrosis (OC)/healthy and osteochondrosis dissecans (OCD)/healthy systems for evaluating the disease status of investigated fetlock joints. Two hundred one Warmblood horses trained for performance tests (87 stallions and 114 mares) were phenotyped and genotyped. Four fetlock x-ray images per horse were collected using the RTG Girth HF 80 and Vet Scan ray 3600. The DNA of each horse was genotyped using the BeadChip 70K. To identify SNPs that significantly affect the probability of osteochondrosis, two different methods were applied: the Cochran-Armitage test based on an additive mode of inheritance and logistic regression. The genetic background for osteochondrosis, expressed in the number of SNPs found with significant associations with osteochondrosis, was higher by evaluation in the scale of OCD/healthy horses (16 SNPs on several chromosomes mainly on the ECA1 and ECA10) than OC/healthy (2 SNPs on the ECA15 and one SNP on the ECA10). Detailed definition of osteochondrosis is needed in breeding and in veterinary practice. The genetic background for osteochondrosis and osteochondrosis dissecans seems not the same. Suggestive SNPs could be the candidate markers for osteochondrosis but should be checked on a larger population before usage.



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An evaluation of kurtosis beamforming in magnetoencephalography to localize the epileptogenic zone in drug resistant epilepsy patients

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Publication date: Available online 9 March 2018
Source:Clinical Neurophysiology
Author(s): Michael B.H. Hall, Ida A. Nissen, Elisabeth C.W. van Straaten, Paul L. Furlong, Caroline Witton, Elaine Foley, Stefano Seri, Arjan Hillebrand
ObjectiveKurtosis beamforming is a useful technique for analysing magnetoencephalograpy (MEG) data containing epileptic spikes. However, the implementation varies and few studies measure concordance with subsequently resected areas. We evaluated kurtosis beamforming as a means of localizing spikes in drug-resistant epilepsy patients.MethodsWe retrospectively applied kurtosis beamforming to MEG recordings of 22 epilepsy patients that had previously been analysed using equivalent current dipole (ECD) fitting. Virtual electrodes were placed in the kurtosis volumetric peaks and visually inspected to select a candidate source. The candidate sources were compared to the ECD localizations and resection areas.ResultsThe kurtosis beamformer produced interpretable localizations in 18/22 patients, of which the candidate source coincided with the resection lobe in 9/13 seizure-free patients and in 3/5 patients with persistent seizures. The sublobar accuracy of the kurtosis beamformer with respect to the resection zone was higher than ECD (56% and 50%, respectively), however, ECD resulted in a higher lobar accuracy (75%, 67%).ConclusionsKurtosis beamforming may provide additional value when spikes are not clearly discernible on the sensors and support ECD localizations when dipoles are scattered.SignificanceKurtosis beamforming should be integrated with existing clinical protocols to assist in localizing the epileptogenic zone.



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Prediction of secondary generalization from a focal onset seizure in intracerebral EEG

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Publication date: Available online 9 March 2018
Source:Clinical Neurophysiology
Author(s): P.A. Karthick, Hideaki Tanaka, Hui Ming Khoo, Jean Gotman
ObjectiveWe propose a system based on the first five seconds of intracerebrally recorded focal seizures to predict their evolution from focal to bilateral tonic-clonic seizure (FTC), to spread outside the onset zone but without tonic-clonic component (FS), or to a seizure remaining focal (F).MethodsNineteen time and frequency domain features were extracted from 39 seizures of 32 patients and were subjected to support vector machine based classification. Three prediction approaches regarding seizure evolution were 1)FTC vs FS vs F, 2)FTC vs FS or F and 3)FTC or FS vs F.ResultsWe used 21 seizures for training. Most features had significantly different distributions in the three seizure types (p<0.05). Eighteen seizures were used for testing. We predicted the evolution of 12 seizures in FTC vs FS vs F, 13 seizures in FTC vs FS or F and 14 seizures in FTC or FS vs F.ConclusionThe first five seconds of a focal seizure contains information regarding the eventual evolution of the seizure, which could be predicted in most seizures.SignificanceThe proposed system could alert the health care team when a patient is hospitalized for intracerebral EEG and improve safety and eventually result in an implantable device.



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Event-related brain potentials elicited by high-speed cooling of the skin: a robust and non-painful method to assess the spinothalamic system in humans

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Publication date: Available online 8 March 2018
Source:Clinical Neurophysiology
Author(s): Roxane de Keyser, Emanuel N. van den Broeke, Arthur Courtin, André Dufour, André Mouraux
ObjectiveTo investigate whether cool-evoked potentials (CEP) elicited by brisk innocuous cooling of the skin could serve as an alternative to laser-evoked potentials (LEP), currently considered as the best available neurophysiological tool to assess the spinothalamic tract and diagnose neuropathic pain.MethodsA novel device made of micro-Peltier elements and able to cool the skin at -300°C/s was used to record CEPs elicited by stimulation of the hand dorsum in 40 healthy individuals, characterize the elicited responses, and assess their signal-to-noise ratio. Various stimulation surfaces (40 mm2 and 120 mm2), cooling ramps (-200°C/s and -133°C/s) and temperature steps (20°C, 15°C, 10°C, 5°C) were tested to identify optimal stimulation conditions.ResultsCEPs were observed in all conditions and subjects, characterized by a biphasic negative-positive complex maximal at the vertex (Cz), peaking 190-400 ms after stimulus onset, preceded by a negative wave over central-parietal areas contralateral to the stimulated hand. Their magnitude was modulated by stimulation surface, cooling ramp and temperature step.ConclusionRapid innocuous skin cooling elicits robust CEPs at latencies compatible with the conduction velocity of Aδ-fibers.SignificanceCEPs can be a complementary tool to the recording of LEPS for assessing the function of small-diameter Aδ-fibers and the spinothalamic tract.



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A reappraisal of the mechanisms of action of ketamine to treat complex regional pain syndrome in the light of cortical excitability changes

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Publication date: Available online 8 March 2018
Source:Clinical Neurophysiology
Author(s): Marc Sorel, Naaman Zrek, Blanche Locko, Catherine Armessen, Samar S Ayache, Jean-Pascal Lefaucheur
ObjectiveTo evaluate the changes in glutamate/GABA balance of intracortical excitability produced by ketamine, delivered at subanaesthetic dose to treat patients with complex regional pain syndrome (CRPS).MethodsIn 19 patients with CRPS, we assessed the effect of a 5-day ketamine protocol on various clinical aspects, including pain and depression, and on cortical excitability parameters provided by transcranial magnetic stimulation testing.ResultsThe rest motor threshold (RMT) and the amplitude of the motor evoked potentials at 120% of RMT were not modified after ketamine therapy. In contrast, ketamine reduced intracortical facilitation (ICF) in both hemispheres and increased short-interval intracortical inhibition (SICI), which was defective at baseline only in the hemisphere corresponding to the painful side. These changes positively correlated with pain relief.ConclusionThis study shows for the first time that the remarkable analgesic effects produced by ketamine in CRPS patients is associated with cortical excitability changes in favour of an enhanced GABAergic transmission in the hemisphere corresponding to the painful side and an overall reduction of excitability in the contralateral hemisphere.SignificanceAnalgesic effects of ketamine cannot be resumed to its classical antigutamatergic action related to N-methyl-D-aspartate receptor blockade.



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Caring for patients with epilepsy: The many ways EEG is useful

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Publication date: Available online 8 March 2018
Source:Clinical Neurophysiology
Author(s): Marc R. Nuwer




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Prevalence of chronic postsurgical pain after thoracotomy and total knee arthroplasty: a retrospective multicenter study in Japan (Japanese Study Group of Subacute Postoperative Pain)

Abstract

We performed a multicenter observational study to assess the prevalence and risk factors of persistent pain after lung cancer surgery and total knee arthroplasty (TKA) in the Japanese population. After receiving Ethics Committee approval, a retrospective chart review was performed for patients who underwent surgery at seven university hospitals in Japan in 2013. A total of 511 patients who underwent lung cancer surgery and 298 patients who underwent TKA were included. The prevalence of chronic postsurgical pain (CPSP) at 3 and 6 months was 18 and 12% after lung surgery and 49 and 33% after TKA, respectively. The prevalence of analgesic use at 3 and 6 months was 16 and 9% after lung surgery and 34 and 22% after TKA, respectively. In both groups, preoperative analgesic use was associated with CPSP. Anesthetic methods or techniques during both types of surgery did not significantly affect the prevalence of CPSP. This is the first study in which the prevalence of CPSP after lung surgery and TKA in Japanese population was extensively evaluated in a multicenter trial. Further prospective studies are needed to confirm the prevalence of CPSP in the Japanese population and to identify risk factors and prevention methods.



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