Πέμπτη 9 Ιουνίου 2016

Rate modulation of human anconeus motor units during high-intensity dynamic elbow extensions

Investigations of high-intensity isometric fatiguing protocols report decreases in motor unit firing rates (MUFRs), but little is known regarding changes in MUFRs following fatigue induced by high-intensity dynamic contractions. The purpose was to evaluate MUFRs of the anconeus (an accessory elbow extensor), and elbow extension power production as a function of time to task failure (TTF) during high velocity fatiguing concentric contractions against a moderately heavy resistance. Fine-wire intramuscular electrode pairs were inserted into the anconeus to record MUs in 12 male participants (25±3y), over repeated sessions on separate days. MUs were tracked throughout a three-stage, varying-load, dynamic elbow extension protocol designed to extend the task duration for >1 minute thereby inducing substantial fatigue. Mean MUFRs and peak power were calculated for three relative time ranges: 0-15% TTF (beginning), 45-60% TTF (middle) and 85-100% TTF (end). Mean duration of the overall fatigue protocol was ~80 seconds. Following the protocol, isometric MVC, highest velocity at 35% MVC load, and peak power decreased 37%, 60%, and 64% compared to baseline, respectively. Data from 20 anconeus MUs tracked successfully throughout the protocol indicated a reduction in MUFRs in relation to power loss from 36 Hz/160W (0-15% TTF) to 28 Hz/97W (45-60% TTF) to 23 Hz/43W (85-100% TTF). During these high-intensity maximal effort concentric contractions, anconeus MUFRs decreased substantially (> 35%). Although the absolute MUFRs were higher in the present study than those reported previously for other muscles during sustained high-intensity isometric tasks, the relative decrease in MUFRs was similar between the two tasks.



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Airway mechanics and lung tissue viscoelasticity: effects of altered blood hematocrit in the pulmonary circulation

The contribution of the hematocrit (Hct) of the blood in the pulmonary vasculature to the overall lung mechanics has not been characterized. We therefore set out to establish how changes of the Hct level in the pulmonary circulation affect the airway and lung tissue viscoelastic properties. The Hct level of the blood in an isolated perfused rat lung model was randomly altered. Intermediate (26.5%), followed by low (6.6%) or normal Hct (43.7%) were set in 2 consecutive sequences. The pulmonary capillary pressure was maintained constant throughout the experiment and the pulmonary hemodynamic parameters were monitored continuously. The airway resistance (Raw), the viscous (G) and elastic (H) parameters and the hysteresivity (=G/H) of the lung tissues were obtained from measurements of forced oscillatory input impedance data. Raw was not affected by the alterations of the Hct levels. As concerns the lung tissues, the decrease of Hct to intermediate or low levels resulted in close to proportional decreases in the viscoelastic parameters G (16.5±7.7%, 12.1±9.5%, p<0.005) and H (13.2±8.6%, 10.8±4.7%, p<0.001). No significant changes in were detected in a wide range of Hct, which indicates that coupled processes cause alterations in the resistive and elastic properties of the lungs following Hct changes in the pulmonary circulation. The diminishment of the viscous and elastic parameters of the pulmonary parenchyma following a reduction of blood Hct demonstrate the significant contribution of the red blood cells to the overall lung viscoelasticity.



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Faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart related to cytosolic inorganic phosphate (Pi) accumulation

A model of the cell bioenergetic system was used to compare the effect of oxidative phosphorylation (OXPHOS) deficiencies in a broad range of moderate ATP demand in skeletal muscle and heart. Computer simulations revealed that kinetic properties of the system are similar in both cases despite the much higher mitochondria content and 'basic' OXPHOS activity in heart than in skeletal muscle, because of a much higher each-step activation (ESA) of OXPHOS in skeletal muscle than in heart. Large OXPHOS deficiencies lead in both tissues to a significant decrease in VO2 and PCr and increase in cytosolic ADP, Pi and H+. The main difference between skeletal muscle and heart is a much higher cytosolic Pi concentration in healthy tissue and much higher cytosolic Pi accumulation (level) at low OXPHOS activities in the former, caused by a higher PCr level in healthy tissue (and higher total phosphate pool) and smaller Pi redistribution between cytosol and mitochondria at OXPHOS deficiency. This difference does not depend on ATP demand in a broad range. A much greater Pi increase and PCr decrease during rest-to-moderate-work transition in skeletal muscle at OXPHOS deficiencies than at normal OXPHOS activity significantly slows down the VO2 on-kinetics. Because high cytosolic Pi concentrations cause fatigue in skeletal muscle and can compromise force generation in skeletal muscle and heart, this system property can contribute to the faster and stronger manifestation of mitochondrial diseases in skeletal muscle than in heart. Shortly, skeletal muscle with large OXPHOS deficiencies becomes fatigued already during low/moderate exercise.



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Effects of aging on mitochondrial function in skeletal muscle of Quarter Horses

Skeletal muscle function, aerobic capacity and mitochondrial (Mt) function have been found to decline with age in humans and rodents. However, not much is known about age-related changes in Mt function in equine skeletal muscle. Here, we compared fiber type composition and Mt function in Gluteus medius and Triceps brachii muscle between young (age 1.8±0.1 years, n=24) and aged (age 17-25 years, n=10) Quarter Horses. The percentage of myosin heavy chain (MyHC)-IIX was lower in aged compared to young muscles (Gluteus, P=0.092; Triceps, P=0.012), while the percentages of MyHC-I (Gluteus; P<0.001) and MyHC-IIA (Triceps; P=0.023) were increased. Mass-specific Mt density, indicated by citrate synthase activity, was unaffected by age in Gluteus, but decreased in aged Triceps (P=0.023). Cytochrome c oxidase (COX) activity per mg tissue and per Mt unit decreased with age in Gluteus (P<0.001 for both) and Triceps (P<0.001; P=0.003, respectively). Activity of 3-Hydroxyacyl-CoA dehydrogenase per mg tissue was unaffected by age, but increased per Mt unit in aged Gluteus and Triceps (P=0.023, P<0.001, respectively). Mt respiration of permeabilized muscle fibers per mg tissue was unaffected by age in both muscles. Main effects of age appeared when respiration was normalized to Mt content, with increases in LEAK, OXPHOS capacity and electron transport system capacity (P=0.038; P=0.045; P=0.007, respectively), independent of muscle. In conclusion, equine skeletal muscle aging was accompanied by a shift in fiber type composition, decrease in Mt density and COX activity, but preserved Mt respiratory function.



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The Effects of a Roundtrip Trans-American Jet Travel on Physiological Stress, Neuromuscular Performance and Recovery

The purpose was to examine a round trip trans-American jet travel on performance, hormonal alterations, and recovery. Ten matched pairs of recreationally trained men were randomized to either a compression group (COMP) (n= 10, age: 23.1 ± 2.4 years, height: 174.8 ± 5.3cm, body mass: 84.96 ± 10.16 kg, body fat: 15.3 ± 6.0%) or control group (CONT) (n= 9, age: 23.2 ± 2.3 years, height: 177.5 ± 6.3cm, body mass: 84.35 ± 8.99 kg, body fat: 15.1 ± 6.4%). Subjects flew directly from Hartford, CT to Los Angeles, CA one day prior to a simulated sport competition (SSC) designed to create muscle damage and returned the next night on a overnight flight back home. Both groups demonstrated jet lag symptoms and associated decreases in sleep quality at all time points. Melatonin significantly (P < 0.05) increased over the first two days and then remained constant after the SSC. Epinephrine, testosterone, cortisol values significantly increased above resting values before and after the SSC with norepinephrine increases only after the SSC. Physical performances significantly decreased from control values on each day for the CONT group with COMP group exhaibiting no significant declines. Muscle damage markers were significantly elevated following the SSC with the COMP group having significantly lower values while maintaining neuromuscular performance measures that were not different from baseline testing. Trans-American jet travel significantly impacted parameters related to jet lag, sleep quality, hormonal responses, muscle tissue damage markers, and physical performance with an attenuation observed with extended wear compression garments.



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The relation between cardiac output kinetics and skeletal muscle oxygenation during moderate exercise in moderately impaired patients with chronic heart failure

Oxygen uptake (VO2) kinetics are prolonged in patients with chronic heart failure (CHF). This may be caused by impaired oxygen delivery or skeletal muscle derangements. We investigated whether impaired cardiac output (Q) kinetics limit skeletal muscle oxygen delivery relative to the metabolic demands at submaximal exercise in CHF patients by evaluating the relation between Q kinetics and skeletal muscle deoxygenation. Forty-three CHF patients, NYHA II-III, performed a constant-load exercise test at 80% of the VAT to assess VO2 kinetics (VO2). Q kinetics (Q) were assessed by a radial artery pulse contour analysis method. Skeletal muscle deoxygenation was assessed by near infrared spectroscopy at the m. vastus lateralis, using the minimal value of the tissue saturation index during onset of exercise (TSImin). Patients were categorized in slow and normal Q responders relative to metabolic demands (Q/ VO2 ≥ 1 and Q/ VO2 < 1, respectively) Q (62 +/- 29s) and VO2 (60+/-21s) were significantly related (r=0.66, p= 0.001). There was a significant correlation between Q and TSImin in the slow Q responders (rs= -0.57, p=0.005, n=22 (51%)) In conclusion, in moderately impaired CHF patients with relatively slow Q kinetics, central hemodynamics may limit skeletal muscle oxygenation during moderate-intensity exercise.



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Feed-forward and Reciprocal Inhibition for Gain and Phase Timing Control in a Computational Model of Repetitive Cough

We investigated the hypothesis, motivated in part by a coordinated computational cough network model, that second-order neurons in the nucleus tractus solitarius (NTS) act as a filter that shapes afferent input to the ventral respiratory network (VRC) during the production of cough. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms of the parasternal (inspiratory) and rectus abdominis (expiratory) muscles and esophageal pressure were recorded. In vivo data revealed that expiratory motor drive during bouts of repetitive coughs is nonstationary: peak expulsive amplitude increases from the first cough, peaks about the eighth or ninth cough, and then decreases through the remainder of the bout. Model simulations indicated that feed-forward inhibition of a single second-order neuron population is not sufficient to account for all the dynamic features of a repetitive cough bout. When a single second-order population was split into two sub-populations (inspiratory and expiratory), the resultant model produced simulated expiratory motor bursts that were comparable to in vivo data. However, expiratory phase durations during these simulations of repetitive coughing were more stationary than those in vivo. Simulations in which reciprocal inhibitory processes between inspiratory-decrementing and expiratory-augmenting-late neurons were introduced exhibited nonstationary expiratory phase durations. These results support the prediction that serial and parallel processing of airway afferent signals in the NTS play a role in generation of the motor pattern for cough.



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The action of the diaphragm on the rib cage

When the diaphragm contracts, pleural pressure falls, exerting a caudal and inward force on the entire rib cage. However, the diaphragm also exerts forces in the cranial and outward direction on the lower ribs. One of these forces, the "insertional force", is applied by the muscle at its attachments to the lower ribs. The second, the "appositional force", is due to the transmission of abdominal pressure to the lower rib cage in the zone of apposition. In the control condition at FRC, the effects of these two forces on the lower ribs are nearly equal and outweigh the effect of pleural pressure, whereas for the upper ribs, the effect of pleural pressure is greater. The balance between these effects, however, may be altered. When the abdomen is given a mechanical support, the insertional and appositional forces are increased, so that the muscle produces a larger expansion of the lower rib cage and, with it, a smaller retraction of the upper rib cage. In contrast, at higher lung volumes, the zone of apposition is decreased and pleural pressure is the dominant force on the lower ribs as well. Consequently, although the force exerted by the diaphragm on these ribs remains inspiratory, rib displacement is reversed into a caudal-inward displacement. This mechanism likely explains the inspiratory retraction of the lateral walls of the lower rib cage observed in many subjects with COPD (Hoover's sign). These observations support the use of a three-compartment, rather than a two-compartment model, to describe chest wall mechanics.



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The Correlation Between Brain Near-Infrared Spectroscopy and Cerebral Blood Flow in Piglets with Intracranial Hypertension

Cerebral perfusion pressure (CPP) is used as a surrogate for measurement of cerebral blood flow (CBF) but its determination requires that intracranial pressure be directly measured. Near-infrared spectroscopy (NIRS) can non-invasively measure tissue oxygenation. We hypothesized that NIRS would correlate well with CBF, with cerebral metabolism of oxygen (CMRO2) and glucose and with lactate production as CPP was reduced. Seven anesthetized piglets were subjected to reductions in CPP to 60, 50, 40, 30 and 20 mmHg by infusing an artificial cerebral spinal fluid into the lateral ventricle of the brain. After a period of equilibration, NIRS over the left temporal cortex and regional CBF (microspheres) were measured at each CPP level as well as arterial and internal jugular PaO2, glucose and lactate. CMRO2 and glucose consumption and lactate production were calculated by standard formulae. NIRS correlated very well (p<0.05) with CBF in the left temporal cortex (mean r[95% CI] =0.95[0.91-0.99]) and with left hemispheric CMRO2 (0.94[0.90-0.98]), glucose consumption (0.87[0.76-0.97]) and lactate production (0.89[0.81-0.97]). The correlation of NIRS with CBF was slightly better (p<0.05) than that of CPP with CBF (0.89[0.84-0.94]). In this model of global cerebral hypertension, NIRS correlated well with CBF and measures of cerebral metabolism and might be useful as a surrogate for CPP. Further studies are warranted to determine if NIRS is associated with these variables in focal cerebral injury.



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The different effects of strength and endurance exercise training on COX-2 and mPGES-expression in mouse brain are independent of peripheral inflammation

Acute endurance exercise has been shown to modulate COX-2-expression, which is suggested to affect neuronal plasticity and learning. Here, we investigated the effect of regular strength and endurance training on cerebral COX-2-expression, inflammatory markers in the brain and circulating cytokines. Male C57BL/6N mice were assigned to either a sedentary control group (CG), an endurance training group (EG; treadmill running for 30 min/day, 5x/week, 10 weeks) or a strength training group (SG; strength training by isometric holding, same duration as EG). Four days after the last bout of exercise, blood and brain were collected and analyzed using real-time-PCR, western blot and a multiplexed immunoassay. In EG, COX-2 mRNA-expression in the cortex/hippocampus increased compared to CG. A significant increase of COX-2 protein levels was observed in both cortex/hippocampus and hypothalamus of mice from the SG. Nuclear factor (NF)B protein levels were significantly increased in mice from both exercise groups (hypothalamus). A significant increase in the expression of microsomal prostaglandin synthase, an enzyme downstream of COX-2, was found in the hypothalamus of both the EG and SG. While most inflammatory factors like IL-1α, IL-18and IL-2, decreased after training, a positive association was found between COX-2 mRNA-expression (cortex/hippocampus) and plasma IL-6 in the EG. Taken together, this study demonstrates that both endurance as well as strength training induces COX-2-expression in the cortex/hippocampus and hypothalamus of mice. A potential mediator of COX-2-expression after training might be circulating IL-6. However, further research is necessary to elucidate the role of inflammatory pathways on brain plasticity after training.



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Epidemiological and clinical scenario of chronic liver diseases in Italy: Data from a multicenter nationwide survey

The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years.

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Autoimmunity and lymphoproliferation markers in naïve HCV-RNA positive patients without clinical evidences of autoimmune/lymphoproliferative disorders

HCV can lead to both chronic liver disease and B-cell lymphoproliferative disorders. A strong association exists between HCV and mixed cryoglobulinaemia (MC).

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Cancer and inflammatory bowel disease in the elderly

Cancer may be a complication of inflammatory bowel disease (IBD) or its treatments. In older Crohn's disease and ulcerative colitis patients, the risk of malignancy is of particular concern. IBD diagnosis at an advanced age is associated with earlier development of colitis-associated colorectal cancer. Thiopurine use in older IBD patients is tied to an increased risk of non-Hodgkin's lymphoma, nonmelanoma skin cancer, and urinary tract cancers. Additionally, older age is accompanied by multimorbidity, an increased risk of malnutrition, and decreased life expectancy, factors that complicate the management of cancer in the elderly.

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Inside EMS Podcast: Remembering Richard Beebe, EMS educator/paramedic

Download this podcast on iTunes, SoundCloud or via RSS feed

In this week's Inside EMS Podcast, co-hosts Chris Cebollero and Kelly Grayson pay tribute to EMS educator and friend Rich Beebe who passed away from injuries sustained in a motorcycle collision. Chris and Kelly also discuss Kelly's recent article, My love-hate relationship with EMS.



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Two classes of excitatory synaptic responses in rat thalamic reticular neurons

The thalamic reticular nucleus (nRt), composed of GABAergic cells providing inhibition of relay neurons in dorsal thalamus, receives excitation from neocortex and thalamus. The two excitatory pathways promoting feedback or feedforward inhibition of thalamocortical neurons, contribute to sensory processing and rhythm generation. While synaptic inhibition within nRt has been carefully characterized, little is known regarding the biophysics of synaptic excitation. To characterize the functional properties of thalamocortical and corticothalamic connections to nRt, we recorded minimal electrically-evoked EPSCs from nRt cells in vitro. A hierarchical clustering algorithm distinguished two types of events. Type 1 events had larger amplitudes and faster kinetics, largely mediated by AMPA receptors, whereas Type 2 responses had more prominent NMDA receptor contribution. Type 1 responses showed subnormal axonal propagation and paired pulse depression, consistent with thalamocortical inputs. Furthermore responses kinetically similar to Type 1 events were evoked by glutamate-mediated activation of thalamic neurons. Type 2 responses, by contrast, likely arise from corticothalamic inputs, with larger NMDA conductance and weak Mg2+-dependent block, suggesting that NMDA receptors are critical for cortical excitation of reticular neurons. The long-lasting action of NMDA receptors would promote reticular cells burst firing and produce powerful inhibitory output to relay neurons proposed to be important in triggering epilepsy. This work provides the first complete voltage clamp analysis of kinetics and voltage dependence of AMPA and NMDA responses of TC and CT synapses in nRt, and will be critical in optimizing biologically realistic neural network models of thalamocortical circuits relevant to sensory processing and thalamocortical oscillations.



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Proactive Modulation of Long-Interval Intracortical Inhibition during Response Inhibition

Daily activities often require sudden cancellation of pre-planned movement, termed response inhibition. When only a subcomponent of a whole response must be suppressed (required herein on Partial trials), the ensuing component is markedly delayed. The neural mechanisms underlying partial response inhibition remain unclear. We hypothesized that Partial trials would be associated with non-selective corticomotor suppression and that GABAB-receptor mediated inhibition within primary motor cortex might be responsible for the non-selective corticomotor suppression contributing to Partial trial response delays. Sixteen right-handed participants performed a bimanual anticipatory response inhibition task while single and paired-pulse transcranial magnetic stimulation was delivered to elicit motor evoked potentials in the left first dorsal interosseous muscle. Lift times, amplitude of motor evoked potentials and long-interval intracortical inhibition were examined across the different trial types (Go, Stop-Left, Stop-Right, Stop-Both). Go trials produced a tight distribution of lift times around the target, whereas those during Partial trials (Stop-Left and Stop-Right) were substantially delayed. The modulation of motor evoked potential amplitude during Stop-Right trials reflected anticipation, suppression and subsequent re-initiation of movement. Importantly, suppression was present across all Stop trial types, indicative of a "default" non-selective inhibitory process. Compared with blocks containing only Go trials, inhibition increased when Stop trials were introduced but did not differ between trial types. The amount of inhibition was positively correlated with lift times during Stop-Right trials. Tonic levels of inhibition appear to be proactively modulated by task context and influence the speed at which unimanual responses occur after a non-selective "brake" is applied.



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Stochastic Slowly Adapting Ionic Currents May Provide a Decorrelation Mechanism For Neural Oscillators by Causing Wander in the Intrinsic Period

Oscillatory neurons integrate their synaptic inputs in fundamentally different ways than normally quiescent neurons. We show that the oscillation period of invertebrate endogenous pacemaker neurons wanders, producing random fluctuations in the interspike intervals (ISI) on a time scale of seconds to minutes, which decorrelates pairs of neurons in hybrid circuits constructed using the dynamic clamp. The autocorrelation of the ISI sequence remained high for many ISIs, but the autocorrelation of the ISI series had on average a single nonzero value, which was negative at a lag of one interval. We reproduced these results using a simple integrate-and fire model with a stochastic population of channels carrying an adaptation current with a stochastic component that was integrated with a slow time scale, suggesting that a similar population of channels underlies the observed wander in the period. Using autoregressive integrated moving average (ARIMA) models, we found that a single integrator and a single moving average with a negative coefficient could simulate both the experimental data and the IF model. Feeding white noise into an integrator with a slow time constant is sufficient to produce the autocorrelation structure of the ISI series. Moreover, the moving average clearly accounted for the autocorrelation structure of the ISI series and is biophysically implemented in the IF model using slow stochastic adaptation. The observed autocorrelation structure may be a neural signature of slow stochastic adaptation, and wander generated in this manner may be a general mechanism for limiting episodes of synchronized activity in the nervous system.



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Octopamine stabilizes conduction reliability of an unmyelinated axon during hypoxic stress

Mechanisms that could mitigate the effects of hypoxia on neuronal signalling are incompletely understood. We show that axonal performance of a locust visual interneuron varied depending on oxygen availability. To induce hypoxia, trachea supplying the thoracic nervous system were surgically lesioned and action potentials in the axon of the Descending Contralateral Movement Detector (DCMD) neuron passing through this region were monitored extracellularly. The conduction velocity and fidelity of action potentials decreased throughout a 45 minute experiment in hypoxic preparations whereas conduction reliability remained constant when the trachea were left intact. The reduction in conduction velocity was exacerbated for action potentials firing at high instantaneous frequencies. Bath application of octopamine mitigated the loss of conduction velocity and fidelity. Action potential conduction was more vulnerable in portions of the axon passing through the mesothoracic ganglion than in the connectives between ganglia indicating that hypoxic modulation of the extracellular environment of the neuropil has an important role to play. In intact locusts, octopamine and its antagonist, epinastine, had effects on the entry to, and recovery from, anoxic coma consistent with octopamine increasing overall neural performance during hypoxia. These effects could have functional relevance for the animal during periods of environmental or activity-induced hypoxia.



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Startle reveals decreased response preparatory activation during a stop-signal task

In a stop-signal task participants are instructed to initiate a movement in response to a go-signal, but to inhibit this movement if an infrequent stop-signal is presented after the go. Reaction time (RT) in a stop-signal task is typically longer compared to a simple-RT task, which may be attributed to a reduced readiness to initiate the response caused by the possibility of having to inhibit the response. The purpose of this experiment was to probe the preparatory activation level of the motor response during a stop-signal task using a startling acoustic stimulus (SAS), which has been shown to involuntarily trigger sufficiently prepared responses at a short latency. Participants completed two separate tasks; a simple-RT task, followed by a stop-signal RT task. During both tasks, a SAS (120dB) was pseudo-randomly presented concurrent with the go-signal. As expected, RT during the simple-RT task was significantly shorter than during the stop-signal task. A significant reduction in RT was noted when a SAS was presented during the simple-RT task, however, during the stop-signal task a SAS resulted in either a significant speeding or moderate delay in RT. Additionally, the subset of SAS trial responses with the shortest RT latencies produced during the stop-signal task were also delayed compared to the short latency SAS trial responses observed during the simple-RT task. Despite evidence that a response was prepared in advance of the go-signal during a stop-signal task it appears that the amount of preparatory activation was reduced compared to that achieved during a simple-RT task.



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Decisions in motion: Vestibular contributions to saccadic target selection

The natural world continuously presents us with many opportunities for action, thus a process of target selection must precede action execution. While there has been considerable progress in understanding target selection in stationary environments, little is known about target selection when we are in motion. Here we investigated the effect of self-motion signals on saccadic target selection in a dynamic environment. Human subjects were sinusoidally translated (f=0.6 Hz, 30 cm peak-to-peak displacement) along an inter-aural axis using a vestibular sled. During the motion two visual targets were presented asynchronously but equidistantly on either side of fixation. Subjects had to look at one of these targets as quickly as possible. Using an adaptive approach, the time delay between these targets was adjusted until the subject selected both targets equally often. We determined this balanced time delay for different phases of the motion in order to distinguish the effects of body acceleration and velocity on saccadic target selection. Results show that acceleration (or position, as these are indistinguishable during sinusoidal motion), but not velocity, affect target selection for saccades. Subjects preferred to look at targets in the direction of the acceleration - the leftward target was preferred when the sled accelerated to the left, and vice versa. Saccadic reaction times mimicked this selection bias by being reliably shorter to targets in the direction of acceleration. Our results provide evidence that saccade target selection mechanisms are modulated by self-motion signals, which could be derived directly from the otolith system.



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Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex

Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC (IFG pars orbitalis) functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (inferior frontal gyrus [IFG] pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with post-retrieval control. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular resolution diffusion spectrum imaging and functional connectivity analysis in un-anesthetized humans to address whether the organization of white matter connectivity differs between subregions of left VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Though several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the mid-frontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of left VLPFC support prior functional distinctions across subregions observed in task-based and functional connectivity fMRI. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general.



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Paired Associative Transspinal and Transcortical Stimulation Produces Plasticity in Human Cortical and Spinal Neuronal Circuits

Anatomical, physiological, and functional connectivity exists between the neurons of the primary motor cortex (M1) and spinal cord. Paired associative stimulation (PAS) produces enduring changes in M1 based on the Hebbian principle of associative plasticity. The present study aimed to establish neurophysiological changes in human cortical and spinal neuronal circuits by pairing noninvasive transspinal stimulation with transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40 min at precise interstimulus intervals with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor threshold, and reduced the soleus H-reflex low-frequency mediated homosynaptic depression. Transcortical-transspinal PAS did not affect intracortical circuits, decreased M1 excitability, and reduced the soleus H-reflex paired stimulation pulses mediated postactivation depression. Both protocols affected the excitation threshold of group Ia afferents and motor axons. These findings clearly indicate that pairing transspinal with transcortical stimulation produces cortical and spinal excitability changes based on the timing interval and functional network interactions between the two associated inputs. This new PAS paradigm may constitute a significant neuromodulation method with physiological impact, because it can be used to concomitantly alter excitability of intracortical circuits, corticospinal neurons, and spinal inhibition in humans.



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A physiological and behavioral system for hearing restoration with cochlear implants

Cochlear implants are neuroprosthetic devices that provide hearing to deaf patients, although outcomes are highly variable even with prolonged training and use. The central auditory system must process cochlear implant signals, but it is unclear how neural circuits adapt - or fail to adapt - to such inputs. Understanding these mechanisms is required for development of next-generation neuroprosthetics that interface with existing neural circuits and enable synaptic plasticity to improve perceptual outcomes. Here we describe a new system for cochlear implant insertion, stimulation, and behavioral training in rats. Animals were first ensured to have significant hearing loss via physiological and behavioral criteria. We developed a surgical approach for multi-channel (2-channel or 8-channel) array insertion, comparable to implantation procedures and depth in humans. Peripheral and cortical responses to stimulation were used to objectively program the implant. Animals fitted with implants learned to use them for an auditory-dependent task that assesses frequency detection and recognition, in a background of environmentally- and self-generated noise, and ceased responding appropriately to sounds when the implant was temporarily inactivated. This physiologically-calibrated and behaviorally-validated system provides a powerful opportunity to study the neural basis of neuroprosthetic device use and plasticity.



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Influence of forearm muscle metaboreceptor activation on sweating and cutaneous vascular responses during dynamic exercise

We examined whether the sustained activation of metaboreceptor in forearm during cycling exercise can modulate sweating and cutaneous vasodilation. On separate days, 12 young participants performed a 1.5-min isometric handgrip exercise at 40% maximal voluntary contraction followed by 1) 9-min forearm ischemia (Occlusion, to activate metaboreceptor) or 2) no ischemia (Control) in thermoneutral conditions (27°C, 50%) with mean skin temperature clamped at 34°C. Thirty seconds after the handgrip exercise, participants cycled for 13.5 min at 40% Vo2 max. For Occlusion, forearm ischemia was maintained for 9 min followed by no ischemia thereafter. Local sweat rate (SR, ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) on the contralateral nonischemic arm as well as esophageal and skin temperatures were measured continuously. The period of ischemia in the early stages of exercise increased SR (+0.03 mg·cm–2·min–1, P < 0.05) but not CVC (P > 0.05) above Control levels. No differences were measured in the esophageal temperature at which onset of sweating (Control 37.19 ± 0.09 vs. Occlusion 37.07 ± 0.09°C) or CVC (Control 37.21 ± 0.08 vs. Occlusion 37.08 ± 0.10°C) as well as slopes for these responses (all P > 0.05). However, a greater elevation in SR occurred thereafter such that SR was significantly elevated at the end of the ischemic period relative to Control (0.37 ± 0.05 vs. 0.23 ± 0.05 mg·cm–2·min–1, respectively, P < 0.05) despite no differences in esophageal temperature. We conclude that the activation of forearm muscle metaboreceptor can modulate sweating, but not CVC, during cycling exercise without affecting the core temperature-SR relationship.



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Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle

We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean ± SD: age, 27 ± 4 yr; Vo2 peak, 45.7 ± 9 ml·kg–1·min–1) performed three experimental trials in a randomized order: 1) RE (8 x 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 x 2 min at 120% lactate threshold (LT); HIT + RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT + RE). Vastus lateralis muscle biopsies were obtained immediately before RE, either without (REST) or with (POST) preceding endurance exercise and +1 h (RE + 1 h) and +3 h (RE + 3 h) after RE. Prior HIT and MICT similarly reduced muscle glycogen content and increased ACCSer79 and p70S6KThr389 phosphorylation before subsequent RE (i.e., at POST). Compared with MICT, HIT induced greater mTORSer2448 and rps6Ser235/236 phosphorylation at POST. RE-induced increases in p70S6K and rps6 phosphorylation were not influenced by prior HIT or MICT; however, mTOR phosphorylation was reduced at RE + 1 h for MICT + RE vs. both HIT + RE and RE. Expression of miR-133a, miR-378, and miR-486 was reduced at RE + 1 h for HIT + RE vs. both MICT + RE and RE. Postexercise mTORC1 signaling following RE is therefore not compromised by prior HIT or MICT, and concurrent exercise incorporating HIT, but not MICT, reduces postexercise expression of miRNAs implicated in skeletal muscle adaptation to RE.



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DEPTOR in POMC neurons affects liver metabolism but is dispensable for the regulation of energy balance

We have recently demonstrated that specific overexpression of DEP-domain containing mTOR-interacting protein (DEPTOR) in the mediobasal hypothalamus (MBH) protects mice against high-fat diet-induced obesity, revealing DEPTOR as a significant contributor to energy balance regulation. On the basis of evidence that DEPTOR is expressed in the proopiomelanocortin (POMC) neurons of the MBH, the present study aimed to investigate whether these neurons mediate the metabolic effects of DEPTOR. Here, we report that specific DEPTOR overexpression in POMC neurons does not recapitulate any of the phenotypes observed when the protein was overexpressed in the MBH. Unlike the previous model, mice overexpressing DEPTOR only in POMC neurons 1) did not show differences in feeding behavior, 2) did not exhibit changes in locomotion activity and oxygen consumption, 3) did not show an improvement in systemic glucose metabolism, and 4) were not resistant to high-fat diet-induced obesity. These results support the idea that other neuronal populations are responsible for these phenotypes. Nonetheless, we observed a mild elevation in fasting blood glucose, insulin resistance, and alterations in liver glucose and lipid homeostasis in mice overexpressing DEPTOR in POMC neurons. Taken together, these results show that DEPTOR overexpression in POMC neurons does not affect energy balance regulation but could modulate metabolism through a brain-liver connection.



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Effect of formoterol, a long-acting {beta}2-adrenergic agonist, on muscle strength and power output, metabolism, and fatigue during maximal sprinting in men

The aim was to investigate the effect of the long-acting β2-adrenergic agonist formoterol on muscle strength and power output, muscle metabolism, and phosphorylation of CaMKII Thr287 and FXYD1 during maximal sprinting. In a double-blind crossover study, 13 males [Vo2 max: 45.0 ± 0.2 (means ± SE) ml·min–1·kg–1] performed a 30-s cycle ergometer sprint after inhalation of either 54 μg of formoterol (FOR) or placebo (PLA). Before and after the sprint, muscle biopsies were collected from vastus lateralis and maximal voluntary contraction (MVC), and contractile properties of quadriceps were measured. Oxygen uptake was measured during the sprint. During the sprint, peak power, mean power, and end power were 4.6 ± 0.8, 3.9 ± 1.1, and 9.5 ± 3.2% higher (P < 0.05) in FOR than in PLA, respectively. Net rates of glycogenolysis and glycolysis were 45.7 ± 21.0 and 28.5 ± 13.4% higher (P < 0.05) in FOR than in PLA, respectively, and the decrease in ATP content was lower (P < 0.05) in FOR than in PLA (3.7 ± 1.5 vs. 8.0 ± 1.6 mmol/kg dry weight). There was no difference in breakdown of phosphocreatine and oxygen uptake between treatments. Before and after the sprint, MVC and peak twitch force were higher (P < 0.05) in FOR than in PLA. No differences were observed in phosphorylation of CaMKII Thr287 and FXYD1 between treatments before the sprint, whereas phosphorylation of CaMKII Thr287 and FXYD1 was greater (P < 0.05) in FOR than in PLA after the sprint. In conclusion, formoterol-induced enhancement in power output during maximal sprinting is associated with increased rates of glycogenolysis and glycolysis that may counteract development of fatigue.



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Aerobic exercise augments muscle transcriptome profile of resistance exercise

Recent reports suggest that aerobic exercise may boost the hypertrophic response to short-term resistance training. This study explored the effects of an acute aerobic exercise bout on the transcriptional response to subsequent resistance exercise. Ten moderately trained men performed ~45 min cycling on one leg followed by 4 x 7 maximal knee extensions for each leg, 15 min later. Thus, one limb performed aerobic and resistance exercise (AE + RE) while the opposing leg did resistance exercise only (RE). Biopsies were obtained from the vastus lateralis muscle of each leg 3 h after the resistance exercise bout. Using DNA microarray, we analyzed differences [≥1.5-fold, false discovery rate (FDR) ≤10%] in gene expression profiles for the two modes of exercise. There were 176 genes up (127)- or downregulated (49) by AE + RE compared with RE. Among the most significant differentially expressed genes were established markers for muscle growth and oxidative capacity, novel cytokines, transcription factors, and micro-RNAs (miRNAs). The most enriched functional categories were those linked to carbohydrate metabolism and transcriptional regulation. Upstream analysis revealed that vascular endothelial growth factor, cAMP-response element-binding protein, Tet methylcytosine dioxygenase, and mammalian target of rapamycin were regulators highly activated by AE + RE, whereas JnK, NF-β, MAPK, and several miRNAs were inhibited. Thus, aerobic exercise alters the skeletal muscle transcriptional signature of resistance exercise to initiate important gene programs promoting both myofiber growth and improved oxidative capacity. These results provide novel insight into human muscle adaptations to diverse exercise modes and offer the very first genomic basis explaining how aerobic exercise may augment, rather than compromise, muscle growth induced by resistance exercise.



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Sex- and corticotropin-releasing factor receptor 2- dependent actions of urocortin 1 during inflammation

We investigated whether corticotropin-releasing factor receptor 2 (CRF2) and its high-affinity agonist urocortin 1 (Ucn1) mediate sex-specific signaling and immune responses. Intrarectal trinitrobenzene sulfonic acid was used to induce experimental colitis in wild-type, CRF2 knockout (CRF2KO), and heterozygous (CRF2Ht) mice of both sexes. Changes in plasma extravasation, organ weight, survival, immune cell numbers, inflammatory cytokines, and the MAPK signaling pathway were assessed. Stored intestinal biopsies from patients with Crohn's disease (CD) and age- and sex-matched individuals without inflammatory bowel disease (IBD) were examined by immunofluorescence and confocal microscopy to characterize Ucn1 and CRF receptor expression. CRF2Ht mice of both sexes showed decreased survival during colitis compared with other genotypes. Ucn1 improved survival in male mice alone. Ucn1 restored colon length and spleen and adrenal weight and decreased colonic TNF-α, IL-6, and IL-1β levels in male CRF2Ht mice alone. CRF2Ht mice of both sexes showed decreased phosphorylation of MAPK p38 and heat shock protein 27 (Hsp27) levels. Ucn1 restored p-Hsp27 levels in male CRF2Ht mice alone. Expression of the chaperone protein Hsp90 decreased during colitis, except in male CRF2Ht mice. Taken together, our data indicate that sex shows significant interaction with genotype and Ucn1 during colitis. Human duodenal and colonic biopsies revealed that sex-specific differences exist in levels of CRF receptors and Ucn1 expression in patients with CD compared with the matched non-IBD subjects. To conclude, Ucn1 mediates sex-specific immune and cellular signaling responses via CRF2, emphasizing the need for inclusion of females in preclinical studies.



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Regulation of lung maturation by prolyl hydroxylase domain inhibition in the lung of the normally grown and placentally restricted fetus in late gestation

Intrauterine growth restriction induced by placental restriction (PR) in sheep leads to chronic hypoxemia and reduced surfactant maturation. The underlying molecular mechanism involves altered regulation of hypoxia signaling by increased prolyl hydroxylase domain (PHD) expression. Here, we evaluated the effect of intratracheal administration of the PHD inhibitor dimethyloxalylglycine (DMOG) on functional, molecular, and structural determinants of lung maturation in the control and PR sheep fetus. There was no effect of DMOG on fetal blood pressure or fetal breathing movements. DMOG reduced lung expression of genes regulating hypoxia signaling (HIF-3α, ACE1), antioxidant defense (CAT), lung liquid reabsorption (SCNN1-A, ATP1-A1, AQP-1, AQP-5), and surfactant maturation (SFTP-A, SFTP-B, SFTP-C, PCYT1A, LPCAT, ABCA3, LAMP3) in control fetuses. There were very few effects of DMOG on gene expression in the PR fetal lung (reduced lung expression of angiogenic factor ADM, water channel AQP-5, and increased expression of glucose transporter SLC2A1). DMOG administration in controls reduced total lung lavage phosphatidylcholine to the same degree as in PR fetuses. These changes appear to be regulated at the molecular level as there was no effect of DMOG on the percent tissue, air space, or numerical density of SFTP-B positive cells in the control and PR lung. Hence, DMOG administration mimics the effects of PR in reducing surfactant maturation in the lung of control fetuses. The limited responsiveness of the PR fetal lung suggests a potential biochemical limit or reduced plasticity to respond to changes in regulation of hypoxia signaling following exposure to chronic hypoxemia in utero.



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Leptin receptor null mice with reexpression of LepR in GnRHR expressing cells display elevated FSH levels but remain in a prepubertal state

Leptin signals energy sufficiency to the reproductive hypothalamic-pituitary-gonadal (HPG) axis. Studies using genetic models have demonstrated that hypothalamic neurons are major players mediating these effects. Leptin receptor (LepR) is also expressed in the pituitary gland and in the gonads, but the physiological effects of leptin in these sites are still unclear. Female mice with selective deletion of LepR in a subset of gonadotropes show normal pubertal development but impaired fertility. Conditional deletion approaches, however, often result in redundancy or developmental adaptations, which may compromise the assessment of leptin's action in gonadotropes for pubertal maturation. To circumvent these issues, we adopted a complementary genetic approach and assessed if selective reexpression of LepR only in gonadotropes is sufficient to enable puberty and improve fertility of LepR null female mice. We initially assessed the colocalization of gonadotropin-releasing hormone receptor (GnRHR) and LepR in the HPG axis using GnRHR-IRES-Cre (GRIC) and LepR-Cre reporter (tdTomato or enhanced green fluorescent protein) mice. We found that GRIC and leptin-induced phosphorylation of STAT3 are expressed in distinct hypothalamic neurons. Whereas LepR-Cre was observed in theca cells, GRIC expression was rarely found in the ovarian parenchyma. In contrast, a subpopulation of gonadotropes expressed the LepR-Cre reporter gene (tdTomato). We then crossed the GRIC mice with the LepR null reactivable (LepRloxTB) mice. These mice showed an increase in FSH levels, but they remained in a prepubertal state. Together with previous findings, our data indicate that leptin-selective action in gonadotropes serves a role in adult reproductive physiology but is not sufficient to allow pubertal maturation in mice.



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Periods of cardiovascular susceptibility to hypoxia in embryonic american alligators (Alligator mississippiensis)

During embryonic development, environmental perturbations can affect organisms' developing phenotype, a process known as developmental plasticity. Resulting phenotypic changes can occur during discrete, critical windows of development. Critical windows are periods when developing embryos are most susceptible to these perturbations. We have previously documented that hypoxia reduces embryo size and increases relative heart mass in American alligator, and this study identified critical windows when hypoxia altered morphological, cardiovascular function and cardiac gene expression of alligator embryos. We hypothesized that incubation in hypoxia (10% O2) would increase relative cardiac size due to cardiac enlargement rather than suppression of somatic growth. We exposed alligator embryos to hypoxia during discrete incubation periods to target windows where the embryonic phenotype is altered. Hypoxia affected heart growth between 20 and 40% of embryonic incubation, whereas somatic growth was affected between 70 and 90% of incubation. Arterial pressure was depressed by hypoxic exposure during 50–70% of incubation, whereas heart rate was depressed in embryos exposed to hypoxia during a period spanning 70–90% of incubation. Expression of Vegf and PdgfB was increased in certain hypoxia-exposed embryo treatment groups, and hypoxia toward the end of incubation altered β-adrenergic tone for arterial pressure and heart rate. It is well known that hypoxia exposure can alter embryonic development, and in the present study, we have identified brief, discrete windows that alter the morphology, cardiovascular physiology, and gene expression in embryonic American alligator.



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Twelve hours of heat stress induces inflammatory signaling in porcine skeletal muscle

Heat stress causes morbidity and mortality in humans and animals and threatens food security by limiting livestock productivity. Inflammatory signaling may contribute to heat stress-mediated skeletal muscle dysfunction. Previously, we discovered increased circulating endotoxin and intramuscular oxidative stress and TNF-α protein abundance, but not inflammatory signaling following 24 and 72 h of heat stress. Thus the purpose of this investigation was to clarify the role of inflammatory signaling in heat-stressed skeletal muscle. Crossbred gilts (n = 8/group) were assigned to either thermal neutral (24°C), heat stress (37°C), or pair-fed thermal neutral (24°C) conditions for 12 h. Following treatment, animals were euthanized, and the semitendinosus red (STR) and white (STW) were recovered. Heat stress did not alter inflammatory signaling in STW. In STR, relative heat shock protein abundance was similar between groups, as was nuclear content of heat shock factor 1. In whole homogenate, relative abundance of the NF-B activator inhibitory B kinase-α was increased by heat stress, although abundance of NF-B was similar between groups. Relative abundance of phosphorylated NF-B was increased by heat stress in nuclear fractions. Activator protein-1 (AP-1) signaling was similar between groups. While there were few differences in transcript expression between thermal neutral and heat stress, 80 and 56% of measured transcripts driven by NF-B or AP-1, respectively, were increased by heat stress compared with pair-fed thermal neutral. Heat stress also caused a reduction in IL-6 transcript and relative protein abundance. These data demonstrate that short-term heat stress causes inflammatory signaling through NF-B in oxidative, but not glycolytic, skeletal muscle.



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5 critical EMS leadership traits to achieve the IHI Triple Aim

By Roxanne Shanks

To know the skills EMS leaders need for the future, we need to understand where the rest of health care is headed. Many leaders are embracing the new era of health care by aligning their organizations with other health care providers in adopting the Triple Aim framework.

This framework was developed by the Institute for Healthcare Improvement and describes an approach to optimizing health system performance. The three dimensions are:

  • Improving the patient experience of care (including quality and satisfaction);
  • Improving the health of populations; and
  • Reducing the per capita cost of health care.

EMS has definitely had some champions in creating innovative solutions for integrating themselves into the overall health care system and achieving the Triple Aim. This has been accomplished through services like mobile integrated health care, nurse triage lines, and community paramedicine.

As we continue to evolve and look to the future of health care and the role EMS professionals will play, there are five competencies we must focus on to achieve the Triple Aim. The five leadership competencies can be aligned with each dimension to continue to elevate the EMS profession as a vital part of the health care system.

Improving the patient experience of care (including quality and satisfaction)

1. Interpersonal skills leadership competency

  • Builds relationships.
  • Fosters teamwork.
  • Develops others.
  • Inspires other.

2. Getting results leadership competency

  • Focuses on quality and safety.
  • Sets stretch goals.
  • Aligns and prioritizes.
  • Improves performance outcomes.

Improving the health of populations

3. Character leadership competency

  • Exhibits professional behaviors.
  • Practices honesty and Integrity.
  • Is self-aware and reflective.
  • Accepts costs of leadership.

4. Leading change leadership competency

  • Creates a vision.
  • Builds strategy.
  • Champions change.
  • Maintains competitive awareness.
  • Innovates.

Aim 3: Reducing the per capita cost of health care

5. Personal Capability leadership competency

  • Exhibits knowledge and expertise.
  • Solves problems.
  • Has business acumen.
  • Is a continuous learner.
  • Demonstrates thought leadership.

Understanding the leadership competencies
Here is additional information on the five leadership competencies and their applicability to EMS leaders striving to achieve the Triple Aim.

1. Interpersonal skills
We all know that the ability to work within a team and show empathy for our patients makes us better EMS practitioners. But in some ways, these skills are even more important when we move up the ranks.

Being an EMS chief today doesn't mean writing policies in a silo or simply handing out orders. Collaboration with other health care and public safety organizations is critical, as is inspiring one's staff to perform at the highest level.

And with budgets tighter than ever, being able to engage the community, municipal leaders, hospitals and others and tell them the story of your organization — and how it helps people — might mean the difference between getting a budget increase or having to downsize.

2. Getting results
It is fairly common to set a goal and aim for that target, but this leadership competency is more encompassing in how you go about getting those results. Is it critical to focus efforts on key metrics, and only measure what adds value to your organization and the communities you serve.

Once you have the metrics identified, align activities to those goals, identify performance gaps along the way and effectively develop and prioritize solutions. This is a methodical approach you must do on a regular basis. It also is one that can be taught to and instilled in future leaders and refined as they progress through their careers.

3. Character
When you look at the character of the leaders in your organization it really starts with trust. Is the leader able to trust others and is she trustworthy" Trust is the foundation that allows the leader to exercise maturity and judgement in decisions: focusing on doing the right thing rather than the popular thing.

This competency is not so much about a skillset as it is about how one manages personal weaknesses, leverages personal strengths and takes ownership when mistakes are made.

4. Leading change
A large majority of successful leaders have an innate ability to lead change in an organization. For others, leading change is a learned ability.

In a constantly changing environment, it is essential that leaders have a vision and successfully communicate it, not only to those within their organizations, but externally as well. They must be aware of customer needs, understand the forces driving change and overcome resistance to the change.

Finally, focusing on the bigger picture by distinguishing between opportunities for transformational change and times better suited to an incremental move is key to their overall success.

5. Personal capability
If you have been in EMS for very long you have no doubt struggled to find qualified individuals who can step into key leadership roles and thrive. It is essential to have leaders who have the expertise required of the role.

At a time when managing budgets and understanding reimbursement and new payment models is essential, leaders must demonstrate strong financial and business acumen. Our industry is changing; being able to grasp issues relevant to not only your organization, but the entire industry, is critical.

The days of just promoting the most talented clinical staff member into a leadership role are gone. This is not to say you won't have clinical staff who have the capabilities to assume a leadership role and be successful, but they will be the minority. Look for employees who invest in their own learning and have an insatiable curiosity.

Progressing from emerging to seasoned leader
As you evaluate these competencies in yourself or in others, consider two things. In any action leaders take, there is what they actually do, and more importantly how they go about doing it.

Interpersonal skills and leading change are how leaders act, while personal capability and getting results are what they do. In the middle of all of this is the leaders' character.

You've heard the saying, "They get results, but leave dead bodies along the side of the road." This type of leadership has no place in the new world of integrated health care. Character and leading change are the hardest competencies to change; the other three are easier to teach and eventually improve.

As you move from the first characteristic to the last under each competency, you will see the natural evolution from an emerging leader to a more seasoned leader. This is a growth process. But with dedication and experience, leaders can develop these competencies as they progress through their careers.

About the Author
Roxanne Shanks, MBA, is a senior associate at Fitch & Associates. She serves as the CEO for LifeFlight Eagle Air Medical Program in Kansas City, Mo., and also as the executive director for the Association of Critical Care Transport in Platte City, Mo. She has an extensive background in health care leadership with more than 20 years of experience in progressively responsible clinical and leadership roles within an integrated delivery system. She can be reached at rshanks@lifeflighteagle.org.



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5 critical EMS leadership traits to achieve the IHI Triple Aim

EMS chiefs must develop the right competencies and skills in order to thrive in a changing health care landscape

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EMT / Security Officer - Jackson Rancheria Casino Resort

The Security Officer/E.M.T. position is responsible for understanding and complying with company and security department policies and procedures. Under direction from the Security Shift Supervisor and Shift Manager performs various staff support assignments, in addition to normal emergency response activities; performs related work as assigned. Security Officer When required assist local, state, federal ...

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Electrode montage and gaze effects on ocular vestibular evoked myogenic potentials (oVEMPs)

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Publication date: Available online 8 June 2016
Source:Clinical Neurophysiology
Author(s): Sendhil Govender, Petrina Y. Cheng, Danielle L. Dennis, James G. Colebatch
ObjectivesTo investigate the properties of lateral electrode locations compared to the conventional ones and to bipolar compared to chin-referenced montages for recording ocular vestibular evoked myogenic potentials (oVEMPs).MethodsA total of 18 subjects were studied using 5 electrode locations around the eye, including the conventional location and more lateral ones (i.e. M, ML and L electrodes near the orbital margin, R1 and R2 electrodes below the two more medial ones). Unilateral air-conducted (AC) sound, bone-conducted (BC) impulses at the mastoid and BC vibration (500 Hz) at the forehead were used. These were applied while the subjects looked in neutral gaze and with 4 levels of increasing elevation. A subset of 10 subjects were also studied when looking downwards at 4 levels. Five bipolar montages were created offline by subtraction.ResultsThe M and ML electrodes had the largest responses but responses were seen for all 5 electrodes. The chin reference was associated with substantial pickup from the contralateral side (as judged using unilateral AC stimulation). The M-R1 (conventional) montage showed a significantly non-linear response to gaze angle, unlike the ML montages. The ML-R1 montage gave the largest responses. There was a clear change in latency for the conventional montage with downgaze for the AC and BC impulsive stimuli.ConclusionsThe ML active electrode has a more stable n1 latency, a larger and a more linear response to gaze angle than the conventional recording site, probably due to contamination by pickup of inferior rectus activity when using the conventional site.SignificanceThe ML location is a better site for the active pickup for recording oVEMPs if the main object of study is the inferior oblique muscle and particularly if subjects have difficulty with upgaze.



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Identification of infants at high familiar risk for language-learning disorders (LLD) by combining machine learning techniques with EEG-based brain network metrics

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Publication date: July 2016
Source:Clinical Neurophysiology, Volume 127, Issue 7
Author(s): Stavros I. Dimitriadis




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Contents

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Publication date: July 2016
Source:Clinical Neurophysiology, Volume 127, Issue 7





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Editorial Board

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Publication date: July 2016
Source:Clinical Neurophysiology, Volume 127, Issue 7





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A Meta-Analysis of the Effects of Aging on Motor Cortex Neurophysiology Assessed by Transcranial Magnetic Stimulation

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Publication date: Available online 8 June 2016
Source:Clinical Neurophysiology
Author(s): Apoorva Bhandari, Natasha Radhu, Faranak Farzan, Benoit H. Mulsant, Tarek K. Rajji, Zafiris J. Daskalakis, Daniel M. Blumberger
ObjectiveTranscranial magnetic stimulation (TMS) is a non-invasive tool used for studying cortical excitability and plasticity in the human brain. This review aims to quantitatively synthesize the literature on age-related differences in cortical excitability and plasticity, examined by TMS.MethodsA literature search was conducted using MEDLINE, Embase, and PsycINFO from 1980 to December 2015. We extracted studies with healthy old (50-89 years) versus young (16-49 years) individuals that utilized the following TMS measures: resting motor threshold (RMT), short-interval cortical inhibition (SICI), short-latency afferent inhibition (SAI), cortical silent period (CSP), intracortical facilitation (ICF), and paired associative stimulation (PAS).ResultsWe found a significant increase in RMT (g = 0.414, 95% confidence interval (CI) [0.284, 0.544], p<0.001), a significant decrease in SAI (g=0.778, 95% CI [0.478, 1.078], p<0.001), and a trending decrease in LTP-like plasticity (g=-0.528, 95% CI [-1.157, 0.100 p<0.1) with age.ConclusionsOur findings suggest an age-dependent reduction in cortical excitability and sensorimotor integration within the human motor cortex.SignificanceAlterations in the ability to regulate cortical excitability, sensorimotor integration and plasticity may underlie several age-related motor deficits.



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The Suppression Curve as a quantitative approach for measuring brain maturation in preterm infants

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Publication date: Available online 8 June 2016
Source:Clinical Neurophysiology
Author(s): A. Dereymaeker, N. Koolen, K. Jansen, J. Vervisch, E. Ortibus, M. De Vos, S. Van Huffel, G. Naulaers
ObjectivesWe apply the suppression curve (SC) as an automated approach to describe the maturational change in EEG discontinuity in preterm infants. This method allows to define normative values of interburst intervals (IBIs) at different postmenstrual ages (PMA).MethodsNinety-two multichannel EEG recordings from 25 preterm infants (born ⩽32 weeks) with normal developmental outcome at 9 months, were first analysed using the Line Length method, an established method for burst detection. Subsequently, the SC was defined as the 'level of EEG discontinuity'. The mean and the standard deviation of the SC, as well as the IBIs from each recording were calculated and correlated with PMA.ResultsOver the course of development, there is a decrease in EEG discontinuity with a strong linear correlation between the mean SC and PMA till 34 weeks. From 30 weeks PMA, differences between discontinuous and continuous EEG become smaller, which is reflected by the decrease of the standard deviation of the SC. IBIs are found to have a significant correlation with PMA.ConclusionsAutomated detection of individual maturational changes in EEG discontinuity is possible with the SC. These changes include more continuous tracing, less amplitude differences and shorter suppression periods, reflecting development of the vigilance states.SignificanceThe suppression curve facilitates automated assessment of EEG maturation. Clinical applicability is straight forward since values for IBIs according to PMA are generated automatically.



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Motor Evaluation Scale for Upper Extremity in Stroke

Link to instrument: Link On Stroke Engine
Acronym:
MESUPES
Purpose:
A 17-item objective evaluation scale designed to assess quality of movement of arm and hand function after stroke
Description:

The scale consists of 17 items into two subscales:
MESUPES-Arm function: 8 items (scores 0-5)
MESUPES-Hand function: 9 items (scores 0-2)

During the MESUPES-Arm function, the movements are scored in three consecutive phases:

  1. The task is performed passively and tone is evaluated (0-1)
  2. The therapist performs the movement while the patients assists and the presence of normal muscle contractions is scored (2)
  3. The patient performs the movement by him/herself and the range of motion that is executed in a qualitatively normal way is scored (3-5)

The first four items are performed in supine; all other items are performed in a sitting position with hips and knees in 90° flexion and elbows on the table. The patient cannot be assessed if he/she cannot maintain an upright position for the tasks in sitting position.

The therapist should wait until tone is normalized before starting a new task. If the patient is not able to achieve a relaxed starting position, he/she is awarded a score of 0 for the item.

The MESUPES-Hand function is divided in two parts:

  1. Patients are instructed to perform specific active hand or finger movements and patients are scored for correctly executed range of motion (0-2) (6 items)
  2. Patients are instructed to perform functional tasks and the correct orientation of hand and fingers during the performance is scored (0-2) (3 items)

Range = 0-58; Item scores are summed (Total score /58; MESUPES-Arm test /40; MESUPES-Hand test /18)

Instructions can be found in Van de Winckel et al., 2006, and on http://ift.tt/28nJD3i

Area of Assessment: Dexterity, Range of Motion, Upper Extremity Function
Body Part: Upper Extremity
ICF Domain: Body Structure, Body Function, Activity
Domain: Motor
Assessment Type: Performance Measure
Length of Test: 06 to 30 Minutes
Time to Administer:
10 minutes (range 5-15 min)
5 min for patients with very poor or very good motor function
15 min for patients with more severe hypertonia
Number of Items: 17
Equipment Required:
  • Plinth or mat
  • Desk and chair (patient is sitting with hip and knees in 90° flexion)
  • Ruler or wooden block marked with 1 cm and 2 cm to measure range of movement during hand tasks
  • Plastic bottle (cylinder, diameter 2.5 cm, height 8 cm; 20 fl oz or 591 ml soda or water bottle)
  • Dice (1.5 cm x 1.5 cm)
  • Smaller plastic bottle (such as a wipe out/correction fluid bottle: cylinder, diameter 2.5 cm, height 8 cm)
Training Required:

Instructions are provided with the assessment sheet in Van de Winckel et al. (2006) and on http://ift.tt/28nJD3i . Instructions are self-explanatory for trained clinicians in stroke rehabilitation. A tutorial video is in the making. Questions on the use of the MESUPES can be addressed to Dr. Ann Van de Winckel (avandewi@umn.edu).

Type of training required: No Training
Cost: Free
Actual Cost: Cost of equipment.
Age Range: Adult: 18-64 years, Elderly adult: 65+
Administration Mode: Paper/Pencil
Diagnosis: Stroke
Populations Tested: Adults with stroke
Standard Error of Measurement (SEM):

Subacute to Chronic Stroke: (Johansson & Hager, 2011; n= 42; mean age = 56 (12) years; mean time post stroke = 7 months (range 3 - 15.3 months).

  • SEM for Arm test (/40) = 2.2 points
  • SEM for Hand test (/18) = 0.94 points
  • SEM for Total score (/ 58) = 2.68 points
Minimal Detectable Change (MDC):

Subacute to Chronic Stroke: (Johansson & Hager, 2011; n= 42; mean age = 56 (12) years; mean time post stroke = 7 months (range 3 - 15.3 months).

  • MDC for Arm test (/40) = 6.10 = 7 points
  • MDC for Hand test (/18) = 2.61 = 3 points
  • MDC for Total score (/58) = 7.43 = 8 points
Minimally Clinically Important Difference (MCID):
Not Established
Cut-Off Scores:
Not a diagnostic test
Normative Data:
Not Established
Test-retest Reliability:
Not Established
Interrater/Intrarater Reliability:

Subacute to Chronic Stroke: (Johansson & Hager, 2011; n= 42; mean age = 56 (12) years; mean time post stroke = 7 months (range 3 - 15.3 months) and Van de Winckel et al., 2006, n = 56.)

  • Excellent inter-rater reliability for Arm test (ICC = .95)
  • Excellent inter-rater reliability for Hand test (ICC = .97)
  • Excellent inter-rater reliability for Total score (ICC = .98)
  • Good to very good inter-rater reliability with weighted kappa coefficient = 0.62-0.79 (Van de Winckel et al., 2006); weighted kappa coefficient = 0.63-0.96 (Johansson & Hager, 2012);
  • Good to very good inter-rater reliability with weighted percentage agreement 85.71-98.21; Scores were not derived for hand function items as 42% of the sample scored 0 (Van de Winckel et al., 2006).
Internal Consistency:

Subacute to Chronic Stroke: (Van de Winckel et al., 2006, n = 56)

  • Excellent internal consistency for Arm test (person separation index in Rasch analysis, measurement for internal consistency comparable to Chronbach's alpha = 0.99)
  • Excellent internal consistency for Hand test (person separation index = 0.97)
Criterion Validity (Predictive/Concurrent):

Concurrent validity: Subacute to Chronic Stroke: (Johansson & Hager, 2012, n = 42)

  • Excellent concurrent validity between MESUPES Arm test and Modified Motor Assessment Scale (MMAS) (Spearman's rho = 0.84)
  • Excellent concurrent validity between MESUPES Hand test and MMAS (r = 0.80)
  • Excellent concurrent validity between MESUPES Total score and MMAS (r = 0.87)
Construct Validity (Convergent/Discriminant):
Not Established
Content Validity:

Subacute to Chronic Stroke: (Van de Winckel et al., 2006, n = 396)

  • Excellent content validity (unidimensionality of Arm test and Hand test): Rasch analysis was performed on the original scale of 22 items (Perfetti & Dal Pezzo, 1995). Five items were removed and the arm scale and hand scale were assessed separately. Rasch analysis of the remaining 8 arm items and 9 hand items and their fit statistics (i.e. χ2 comparing observed scores with a predicted model) confirmed unidimensionality of both arm (χ2 = 31.22, DF = 40, p = 0.84) and hand scales (χ2 = 46.21, DF = 45, p = 0.42).
  • Excellent internal consistency across subgroups of patients with stroke: Van de Winckel et al. (2006) demonstrated that the hierarchy of the items (from easy to difficult) is maintained across subgroups of adults with stroke: gender; age.
Face Validity:
Not Established
Floor/Ceiling Effects:

Subacute to Chronic Stroke: (Van de Winckel et al., 2006, n = 396)

  • Excellent: No floor- or ceiling effect observed for the Total test (min score of 0 on Total score = 8/396 or 0.02%) (max score of 58 on Total score = 12/396 or 0.03%)
  • Of note: The data on 396 patients with subacute to chronic stroke demonstrated that 163/396 (42%) do not recover hand function after stroke and therefore had a score of 0 on the hand items, whereas only 76/396 (19%) achieved a maximum score on the arm items.
Responsiveness:
Not Established
Considerations:
Because, tone, muscle contractions and active movements are scored, the scale can be used for patients with stroke with a wide range of motor impairments: from no active arm and hand function to minimal motor impairments.
Bibliography:

Johansson, G.M., Hager, C.K. (2011). "Measurement properties of the Motor Evaluation Scale for Upper Extremity in Stroke Patients (MESUPES)." Disabil Rehabil, 34(4):288-294.Find it on PubMed

Van de Winckel, A., et al. (2006). "Can quality of movement be measured? Rasch analysis and inter-rater reliability of the Motor Evaluation Scale for Upper Extremity in Stroke Patients (MESUPES)." Clin Rehab, 20(10): 871-884. Find it on PubMed

Year published: 2006
Instrument in PDF Format: Yes


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Decreased Sleep Stage Transition Pattern Complexity in Narcolepsy Type 1

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Publication date: Available online 8 June 2016
Source:Clinical Neurophysiology
Author(s): Raffaele Ferri, Fabio Pizza, Stefano Vandi, Martina Iloti, Giuseppe Plazzi
ObjectiveTo analyze the complexity of the nocturnal sleep stage sequence in central disorders of hypersomnolence (CDHs), with the hypothesis that narcolepsy type 1 (NT1) might exhibit distinctive sleep stage sequence organization and complexityMethodsSeventy-nine NT1 patients, 22 narcolepsy type 2 (NT2), 22 idiopathic hypersomnia (IH), and 52 patients with subjective hypersomnolence (sHS) were recruited and their nocturnal sleep was polysomnographically recorded and scored. Group between-stage transition probability matrices were obtained and comparedResultsPatients with NT1 differed significantly from all the other patient groups, the latter, in turn, were not different between each other. The individual probability of the R-to-N2 transition was found to be the parameter showing the difference of highest significance between the groups (lowest in NT1) and classified patients with or without NT1 with an accuracy of 78.9% (sensitivity 78.5% and specificity 79.2%), by applying a cut-off value of 0.15ConclusionsThe main result of this study is that the structure of the sleep stage transition pattern of hypocretin-deficient NT1 patients is significantly different from that of other forms of CDH and sHS, with normal hypocretin levelsSignificanceThe lower probability of R-to-N2 transition occurrence in NT1 appears to be a reliable polysomnographic feature with potential application at the individual level, for supportive diagnostic purposes.



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Total artificial heart bridges Mich. man 555 days to a heart transplant

Stan Larkin lived 555 days with the SynCardia total artificial heart until a successful heart transplant at the University of Michigan Health system

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Total artificial heart bridges Mich. man 555 days to a heart transplant

Stan Larkin lived 555 days with the SynCardia total artificial heart until a successful heart transplant at the University of Michigan Health system

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Total artificial heart bridges Mich. man 555 days to a heart transplant

Stan Larkin lived 555 days with the SynCardia total artificial heart until a successful heart transplant at the University of Michigan Health system

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Association analysis and population structure of flowering-related traits in super sweet corn inbred lines with simple sequence repeat markers

Abstract

This study assessed the genetic and phenotypic variation of 90 super sweet corn inbred lines and performed association analyses of six agronomical traits using 100 simple sequence repeats (SSR), ultimately detecting 590 alleles, with an average of 5.90 alleles per locus. The average genetic diversity and Polymorphism information content values were 0.54 and 0.50, respectively. Using population structure analysis, inbred lines were divided into three major groups and one admixed group. Association analysis was performed with a general linear model using a Q-matrix (Q GLM) and a mixed linear model using Q and K-matrices (Q + K MLM). Q GLM found 33 marker-trait associations involving 20 SSR markers that were associated with six agronomic traits. Q + K MLM identified four marker-trait associations involving three markers that were associated with traits of days of tasseling (DT) and days of silking (DS). Q GLM and Q + K MLM detected four significant marker-trait associations (SMTAs), with a level of significance of P < 0.01. In overlapping SMTAs, phi051 was associated with DT, umc1708 was associated with DS, and umc2341 was associated with two traits: DT and DS. The detection of loci associated with traits in this study may provide greater opportunities to improve quality by marker-assisted selection (MAS). Finally, these results will be helpful for breeders in choosing parental lines for crossing combinations as well as markers for using MAS in super sweet corn breeding programs in Korea.



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Total artificial heart bridges Mich. man 555 days to a heart transplant

Stan Larkin lived 555 days with the SynCardia total artificial heart until a successful heart transplant at the University of Michigan Health system

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Persistent nonalcoholic fatty liver disease increases risk for carotid atherosclerosis

Gastroenterology

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Preoperative modified FOLFIRINOX treatment followed by capecitabine-based chemoradiation for borderline resectable pancreatic cancer: Alliance for clinical trials in oncology trial a021101

JAMA Surgery

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Real world experience with natalizumab at a tertiary care pediatric IBD center

Journal of Pediatric Gastroenterology and Nutrition

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Efficacy and safety of a resorbable collagen membrane COVA+ for the prevention of postoperative adhesions in abdominal surgery

Surgical Endoscopy

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Prucalopride induces high-amplitude propagating contractions in the colon of patients with chronic constipation: a randomized study

Neurogastroenterology & Motility

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Time course and clinical implications of development of antibodies against adalimumab in patients with inflammatory bowel disease

Journal of Clinical Gastroenterology

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Modulation of tumor eIF4E by antisense inhibition: A phase I/II translational clinical trial of ISIS 183750 - an antisense oligonucleotide against eIF4E - in combination with irinotecan in solid tumors and irinotecan-refractory colorectal cancer

International Journal of Cancer

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Implementation of an advanced nursing directive for children with right lower quadrant pain: identifying those requiring further investigation and improving flow metrics

Pediatric Emergency Care

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Liver stiffness-based score in hepatoma risk assessment for chronic hepatitis C patients after successful anti-viral therapy

Liver International

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Integrative functional genomic delineation of the cascades of transcriptional changes involved in hepatocellular carcinoma progression

International Journal of Cancer

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Clinical outcomes of acid suppressive therapy use in hematology/oncology patients at an academic medical center

Annals of Pharmacotherapy

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Should immunomodulation therapy alter the surgical management in patients with rectovaginal fistula and Crohn's disease?

Diseases of the Colon and Rectum

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Morbidity and risk factors of laparoscopic-assisted ileostomies in children with ulcerative colitis

Journal of Pediatric Gastroenterology and Nutrition

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ERP Go/NoGo condition effects are better detected with separate PCAs

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Publication date: Available online 8 June 2016
Source:International Journal of Psychophysiology
Author(s): Robert J. Barry, Frances M. De Blasio, Jack S. Fogarty, Diana Karamacoska
We explored the separation of Go and NoGo effects in the ERP components elicited in an equiprobable Go/NoGo task, using different forms of temporal Principal Components Analysis (PCA).Following exploratory simulation studies assessing the PCA impact of latency jitter and between-condition latency differences in the P3 latency range, an empirical study compared results of a Combined PCA carried out using both Go and NoGo ERPs together as input, with those from two Separate PCAs carried out on the Go and NoGo ERPs separately.The simulation studies indicated that Separate PCAs provide adequate component recovery in the presence of P3 latency jitter, and that Combined PCAs provide good separation of components only when systematic condition-related latency differences are sufficiently large (here ~110ms).In the empirical data, broadly-similar components were obtained from the Combined and Separate PCAs, supporting previous findings from Combined PCA investigations, and the consequent interpretations of the sequential processing involved.However, the Separate PCAs generated latency differences for components in the Go and NoGo processing chains that better matched the late Go/NoGo ERP peaks, and produced better-defined and larger components that fitted the stages in a hypothetical processing schema developed for this paradigm.Overall, the Separate PCAs yielded a better partitioning of the ERP variance associated with the Go and NoGo conditions, and should be considered as the first choice in future investigations if systematic component or subcomponent latency differences are present or suspected.



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Validation and reliability of Global Operative Assessment of Laparoscopic Skills for surgical residents and consultants

2016-06-09T01-42-25Z
Source: Journal of the Pakistan Medical Association
Awais Amjad Malik, Awais Naeem, Asad Ali Toor, Samiullah Bhatti, Rashid Mansoor, Amin Mazhar, Waris Farooka, Mahmood Ayyaz.
Objective: To institute and validate the Global Assessment of Laparoscopic Surgery score as a measure of intraoperative performance. Methods: The observational study was conducted at the Services Hospital, Lahore, and the National Hospital and Medical Centre, Lahore, from August 1, 2013, to February 28, 2014, and comprised Residents, Senior Registrars and Consultants who were divided into 3 groups. The Junior group comprised Residents from years 1, 2 and3; the Intermediate group had year 4 Residents and Senior Registrars; and the Senior group included Consultants. All participants had their evaluation using Global Assessment of Laparoscopic Surgeryscore while performing dissection of gall bladder from the liver bed during laparoscopic cholecystectomy. SPSS 20 was used for statistical analysis. Results: Of the 24 subjects in the study, 12(50%) were Residents, 6(25%) Senior Registrars and 6(25%) Consultants. The mean score for Junior group was 7.64±0.988, for Intermediate group 16.25±2.602 and for Senior group 22.83±1.169The score was highly reliable with intra-class coefficient 0.96, and internal consistency was excellent with Cronbach's Alpha 0.981. Conclusion: Global Assessment of Laparoscopic Surgery was found to be a valid and reliable measure of intraoperative laparoscopic skills.


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Deletion upstream of SALL1 producing Townes–Brocks syndrome



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RIN2 syndrome: Expanding the clinical phenotype

Biallelic defects in the RIN2 gene, encoding the Ras and Rab interactor 2 protein, are associated with a rare autosomal recessive connective tissue disorder, with only nine patients from four independent families reported to date. The condition was initially termed MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis), based on the clinical features of the first identified family; however, with the expansion of the clinical phenotype in additional families, it was subsequently coined RIN2 syndrome. Hallmark features of this condition include dysmorphic facial features with striking, progressive facial coarsening, sparse hair, normal to enlarged occipitofrontal circumference, soft redundant and/or hyperextensible skin, and scoliosis. Patients with RIN2 syndrome present phenotypic overlap with other conditions, including EDS (especially the dermatosparaxis and kyphoscoliosis subtypes). Here, we describe a 10th patient, the first patient of Caucasian origin and the oldest reported patient so far, who harbors the previously identified homozygous RIN2 mutation c.1878dupC (p. (Ile627Hisfs*7)). Besides the hallmark features, this patient also presents problems not previously associated with RIN2 syndrome, including cervical vertebral fusion, mild hearing loss, and colonic fibrosis. We provide an overview of the clinical findings in all reported patients with RIN2 mutations and summarize some of the possible pathogenic mechanisms that may underlie this condition. © 2016 Wiley Periodicals, Inc.



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An in situ hybridization study of Hyaluronan synthase (Has) mRNA in developing mouse molar and incisor tooth germs

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Publication date: Available online 8 June 2016
Source:Gene Expression Patterns
Author(s): Tsuyoshi Morita, Kaoru Fujikawa, Otto Baba, Shunichi Shibata
Hyaluronan (HA) is a major constituent molecule in most extracellular matrices and is synthesized by Hyaluronan synthase (Has). In the present study, we examined expression patterns of Has1, -2, -3 mRNA in developing mouse molar and incisor tooth germs from embryonic day (E) 11.5 to postnatal day (P) 7, focusing on Hertwig's epithelial root sheath (HERS) and the apical bud in particular. Has1 mRNA expression was not detected in all tooth germs examined. Has2 mRNA was expressed in the surrounding mesenchyme from E12.0 to 18.0 in both molar and incisor tooth germs, but disappeared after birth. Meanwhile, Has3 mRNA was exclusively expressed within the enamel organ, especially in the inner enamel epithelium (IEE), stellate reticulum (SR), and stratum intermedium (SI) until the early bell stage at E16.0. Has3 mRNA disappeared as IEE differentiated into differentiating ameloblasts (dABs), but remained in SI until the root developmental stage of the molar tooth germ at P7. Has3 mRNA was also expressed in HERS until P7. In incisors, Has3 mRNA was expressed in the apical bud, especially in the transit-amplifying (TA) cell region from E16.0 to P7, and in the papillary layer (PL) adjacent to the mature enamel. These gene expression patterns suggested that Has3 is the main control factor for prenatal and postnatal HA synthesis of the tooth germ, and may in part regulate crown and root formation of the tooth germ, maintenance of stem cell niches in the apical bud as well as mineral transport in PL.



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Rights of authorship - where can justice be found?

2016-06-08T23-32-21Z
Source: Journal of the Pakistan Medical Association
Fatema Jawad.



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From the Editor's Desk

2016-06-08T23-32-21Z
Source: Journal of the Pakistan Medical Association
Fatema Jawad.



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Pediatric anesthesia editorial—propofol and remifentanil: to mix or not to mix



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Bubble induction



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In this issue July 2016



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Reply to Ideno, Satoshi; Seki, Hiroyuki; Morisaki, Hiroshi, regarding their comment ‘Consider an additional pressure-relief port before we abandon the use of the wall oxygen through a bronchoscope'



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Response to comment ‘Tsui, Ban; Tsui, Jenkin: ABC diaphragmatic evaluation for neonates’



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Anesthesia for muscle biopsy: when nothing bad happened, was no special care needed?



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A call to solve the puzzle together by building an evidence base for perioperative management of children with autism spectrum disorder



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ABC Diaphragmatic Evaluation for neonates



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Symptomatic endotracheal tube obstruction in infants intubated with Microcuff® endotracheal tubes



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Issue Information



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Correspondence Letter to the Editor regarding ‘The presumed central nervous system effects of rocuronium in a neonate and its reversal with sugammadex’ by Langley, McFadzean & McCormack



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Powered robotic exoskeletons in post-stroke rehabilitation of gait: a scoping review

Powered robotic exoskeletons are a potential intervention for gait rehabilitation in stroke to enable repetitive walking practice to maximize neural recovery. As this is a relatively new technology for stroke,...

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Instrumental indices for upper limb function assessment in stroke patients: a validation study

Robotic exoskeletons are increasingly being used in objective and quantitative assessment of upper limb (UL) movements. A set of instrumental indices computed during robot-assisted reaching tasks with the Arme...

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