Πέμπτη, 1 Δεκεμβρίου 2016

Nonlinear identification of the total baroreflex arc: higher-order nonlinearity

The total baroreflex arc is the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP). The nonlinear dynamics of this system were recently characterized. First, Gaussian white noise CSP stimulation was employed in open-loop conditions in normotensive and hypertensive rats with sectioned vagal and aortic depressor nerves. Nonparametric system identification was then applied to measured CSP and AP to establish a second-order nonlinear Uryson model. The aim in this study was to assess the importance of higher-order nonlinear dynamics via development and evaluation of a third-order nonlinear model of the total arc using the same experimental data. Third-order Volterra and Uryson models were developed by employing nonparametric and parametric identification methods. The R2 values between the AP predicted by the best third-order Volterra model and measured AP in response to Gaussian white noise CSP not utilized in developing the model were 0.69 ± 0.03 and 0.70 ± 0.03 for normotensive and hypertensive rats, respectively. The analogous R2 values for the best third-order Uryson model were 0.71 ± 0.03 and 0.73 ± 0.03. These R2 values were not statistically different from the corresponding values for the previously established second-order Uryson model, which were both 0.71 ± 0.03 (P > 0.1). Furthermore, none of the third-order models predicted well-known nonlinear behaviors including thresholding and saturation better than the second-order Uryson model. Additional experiments suggested that the unexplained AP variance was partly due to higher brain center activity. In conclusion, the second-order Uryson model sufficed to represent the sympathetically mediated total arc under the employed experimental conditions.



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Developmental plasticity of mitochondrial function in American alligators, Alligator mississippiensis

The effect of hypoxia on cellular metabolism is well documented in adult vertebrates, but information is entirely lacking for embryonic organisms. The effect of hypoxia on embryonic physiology is particularly interesting, as metabolic responses during development may have life-long consequences, due to developmental plasticity. To this end, we investigated the effects of chronic developmental hypoxia on cardiac mitochondrial function in embryonic and juvenile American alligators (Alligator mississippiensis). Alligator eggs were incubated in 21% or 10% oxygen from 20 to 90% of embryonic development. Embryos were either harvested at 90% development or allowed to hatch and then reared in 21% oxygen for 3 yr. Ventricular mitochondria were isolated from embryonic/juvenile alligator hearts. Mitochondrial respiration and enzymatic activities of electron transport chain complexes were measured with a microrespirometer and spectrophotometer, respectively. Developmental hypoxia induced growth restriction and increased relative heart mass, and this phenotype persisted into juvenile life. Embryonic mitochondrial function was not affected by developmental hypoxia, but at the juvenile life stage, animals from hypoxic incubations had lower levels of Leak respiration and higher respiratory control ratios, which is indicative of enhanced mitochondrial efficiency. Our results suggest developmental hypoxia can have life-long consequences for alligator morphology and metabolic function. Further investigations are necessary to reveal the adaptive significance of the enhanced mitochondrial efficiency in the hypoxic phenotype.



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P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation

The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms covary with sleep, including locomotor activity and core body temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep. We hypothesized that these parameters are also affected by the absence of the P2X7 receptor. Herein, we determine spontaneous expression of body temperature and locomotor activity in wild-type (WT) and P2X7R knockout (KO) mice and how they are affected by sleep deprivation (SD). We also compare hypothalamic, hippocampal, and cortical cytokine- and purine-related receptor and enzyme mRNA expressions before and after SD in WT and P2X7RKO mice. Next, in a hypothesis-generating survey of hypothalamic long noncoding (lnc) RNAs, we compare lncRNA expression levels between strains and after SD. During baseline conditions, P2X7RKO mice had attenuated temperature rhythms compared with WT mice, although locomotor activity patterns were similar in both strains. After 6 h of SD, body temperature and locomotion were enhanced to a greater extent in P2X7RKO mice than in WT mice during the initial 2-3 h after SD. Baseline mRNA levels of cortical TNF-α and P2X4R were higher in the KO mice than WT mice. In response to SD, the KO mice failed to increase hypothalamic adenosine deaminase and P2X4R mRNAs. Further, hypothalamic lncRNA expressions varied by strain, and with SD. Current data are consistent with a role for the P2X7R in thermoregulation and lncRNA involvement in purinergic signaling.



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Breathing while altricial: the ontogeny of ventilatory chemosensitivity in red-winged blackbird (Agelaius phoeniceus) nestlings

Altricial bird species, like red-winged blackbirds, hatch at an immature state of functional maturity with limited aerobic capacity and no endothermic capacity. Over the next 10–12 days in the nest, red-winged blackbirds develop increased metabolic capacity before fledging. Although ontogeny of respiration has been described in precocial birds, ontogeny of ventilatory chemosensitivity is unknown in altricial species. Here we examined developmental changes in chemosensitivity of tidal volume (Vt), breathing frequency (f), minute ventilation (Ve), and whole animal oxygen consumption (Vo2) from hatching to just before fledging in red-winged blackbirds on days 1, 3, 5, 7, and 9 posthatching (dph) in response to hypercapnia (2 and 4% CO2) and hypoxia (15 and 10% O2). Under control conditions, there was a developmental increase in Ve with age due to increased Vt. Hypercapnic and hypoxic chemosensitivities were present as early as 1 dph. In response to hypoxia, 1, 3, and 9 dph nestlings increased Ve at 10% O2, by increasing f with some change in Vt in younger animals. In contrast to early neonatal altricial mammals, the hypoxic response of nestling red-winged blackbirds was not biphasic. In response to hypercapnia, 3 dph nestlings increased Ve by increasing both f and Vt. From 5 dph on, the hypercapnic increase in Ve was accounted for by increased Vt and not f. Chemosensitivity to O2 and CO2 matures early in nestling red-winged blackbirds, well before the ability to increase Vo2 in response to cooling, and thus does not represent a limitation to the development of endothermy.



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Central vs. peripheral determinants of sympathetic neural recruitment: insights from static handgrip exercise and postexercise circulatory occlusion

Sympathetic outflow is modified during acute homeostatic stress through increased firing of low-threshold axons, recruitment of latent axons, and synaptic delay modifications. However, the role of central mechanisms versus peripheral reflex control over sympathetic recruitment remains unknown. Here, we examined sympathetic discharge patterns during fatiguing static handgrip (SHG) exercise and postexercise circulatory occlusion (PECO) to study the central vs. peripheral reflex elements of sympathetic neural coding. Muscle sympathetic nerve activity (MSNA; microneurography) was measured in six males (25 ± 3 yr) at baseline (3 min) and during 5 min of SHG exercise completed at 20% maximal voluntary contraction. Isolation of the peripheral metaboreflex component was achieved by PECO for 3 min. Action potential (AP) patterns were studied using wavelet-based methodology. Compared with baseline, total MSNA increased by minute 3 of SHG, remaining elevated throughout the duration of exercise and PECO (all P < 0.05). The AP content per burst increased above baseline by minute 4 of SHG (4 ± 2), remaining elevated at minute 5 (6 ± 4) and PECO (4 ± 4; all P < 0.05). Similarly, total AP clusters increased by minute 4 of SHG (5 ± 5) and remained elevated at minute 5 (6 ± 3) and PECO (7 ± 5; all P < 0.01), indicating recruitment of latent subpopulations. Finally, the AP cluster size-latency profile was shifted downward during minutes 4 (–32 ± 22 ms) and 5 (–49 ± 17 ms; both P < 0.05) of SHG but was not different than baseline during PECO (P > 0.05). Our findings suggest that central perceptual factors play a specific role in the synaptic delay aspect of sympathetic discharge timing, whereas peripheral reflex mechanisms affect recruitment of latent axons.



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Intestinal inflammation without weight loss decreases bone density and growth

Increasing evidence indicates a strong link between intestinal health and bone health. For example, inflammatory bowel disease can cause systemic inflammation, weight loss, and extra-intestinal manifestations, such as decreased bone growth and density. However, the effects of moderate intestinal inflammation without weight loss on bone health have never been directly examined; yet this condition is relevant not only to IBD but to conditions of increased intestinal permeability and inflammation, as seen with ingestion of high-fat diets, intestinal dysbiosis, irritable bowel syndrome, metabolic syndrome, and food allergies. Here, we induced moderate intestinal inflammation without weight loss in young male mice by treating with a low dose of dextran sodium sulfate (1%) for 15 days. The mice displayed systemic changes marked by significant bone loss and a redistribution of fat from subcutaneous to visceral fat pad stores. Bone loss was caused by reduced osteoblast activity, characterized by decreased expression of osteoblast markers (runx2, osteocalcin), histomorphometry, and dynamic measures of bone formation. In addition, we observed a reduction in growth plate thickness and hypertrophic chondrocyte matrix components (collagen X). Correlation analyses indicate a link between gut inflammation and disease score, but more importantly, we observed that bone density measures negatively correlated with intestinal disease score, as well as colon and bone TNF-α levels. These studies demonstrate that colitis-induced bone loss is not dependent upon weight loss and support a role for inflammation in the link between gut and bone health, an important area for future therapeutic development.



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8-Prenylnaringenin promotes recovery from immobilization-induced disuse muscle atrophy through activation of the Akt phosphorylation pathway in mice

8-Prenylnaringenin (8-PN) is a prenylflavonoid that originates from hop extracts and is thought to help prevent disuse muscle atrophy. We hypothesized that 8-PN affects muscle plasticity by promoting muscle recovery under disuse muscle atrophy. To test the promoting effect of 8-PN on muscle recovery, we administered an 8-PN mixed diet to mice that had been immobilized with a cast to one leg for 14 days. Intake of the 8-PN mixed diet accelerated recovery from muscle atrophy, and prevented reductions in Akt phosphorylation. Studies on cell cultures of mouse myotubes in vitro demonstrated that 8-PN activated the PI3K/Akt/P70S6K1 pathway at physiological concentrations. A cell-culture study using an inhibitor of estrogen receptors and an in vivo experiment with ovariectomized mice suggested that the estrogenic activity of 8-PN contributed to recovery from disuse muscle atrophy through activation of an Akt phosphorylation pathway. These data strongly suggest that 8-PN is a naturally occurring compound that could be used as a nutritional supplement to aid recovery from disuse muscle atrophy.



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Edge orientation signals in tactile afferents of macaques

The orientation of edges indented into the skin has been shown to be encoded in the responses of neurons in primary somatosensory cortex in a manner that draws remarkable analogies to their counterparts in primary visual cortex. According to the classical view, orientation tuning arises from the integration of untuned input from thalamic neurons with aligned but spatially displaced receptive fields (RFs). In a recent microneurography study with human subjects, the precise temporal structure of the responses of individual mechanoreceptive afferents to scanned edges was found to carry information about their orientation. This putative mechanism could in principle contribute to or complement the classical rate-based code for orientation. In the present study, we further examine orientation information carried by mechanoreceptive afferents of Rhesus monkeys. To this end, we record the activity evoked in cutaneous mechanoreceptive afferents when edges are indented into or scanned across the skin. First, we confirm that information about the edge orientation can be extracted from the temporal patterning in afferent responses of monkeys, as is the case in humans. Second, we find that while the coarse temporal profile of the response can be predicted linearly from the layout of the RF, the fine temporal profile cannot. Finally, we show that orientation signals in tactile afferents are often highly dependent on stimulus features other than orientation, which complicates putative decoding strategies. We discuss the challenges associated with establishing a neural code at the somatosensory periphery, where afferents are exquisitely sensitive and nearly deterministic.



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Entanglement between thermoregulation and nociception in the rat: the case of morphine

In thermoneutral conditions, rats display cyclic variations of the vasomotion of the tail and paws, the most widely used target organs in current acute or chronic animal models of pain. Systemic morphine elicits their vasoconstriction followed by hyperthermia in a naloxone-reversible and dose-dependent fashion. The dose-response curves were steep with ED50 in the 0.5–1 mg/kg range. Given the pivotal functional role of the rostral ventromedial medulla (RVM) in nociception and the rostral medullary raphe (rMR) in thermoregulation, two largely overlapping brain regions, the RVM/rMR was blocked by muscimol: it suppressed the effects of morphine. "On-" and "off-" neurons recorded in the RVM/rMR are activated and inhibited by thermal nociceptive stimuli, respectively. They are also implicated in regulating the cyclic variations of the vasomotion of the tail and paws seen in thermoneutral conditions. Morphine elicited abrupt inhibition and activation of the firing of on- and off-cells recorded in the RVM/rMR. By using a model that takes into account the power of the radiant heat source, initial skin temperature, core body temperature, and peripheral nerve conduction distance, one can argue that the morphine-induced increase of reaction time is mainly related to the morphine-induced vasoconstriction. This statement was confirmed by analyzing in psychophysical terms the tail-flick response to random variations of noxious radiant heat. Although the increase of a reaction time to radiant heat is generally interpreted in terms of analgesia, the present data question the validity of using such an approach to build a pain index.



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Developmental experience-dependent plasticity in the first synapse of the Drosophila olfactory circuit

Evidence accumulating over the past 15 years soundly refutes the dogma that the Drosophila nervous system is hardwired. The preponderance of studies reveals activity-dependent neural circuit refinement driving optimization of behavioral outputs. We describe developmental, sensory input-dependent plasticity in the brain olfactory antennal lobe, which we term long-term central adaption (LTCA). LTCA is evoked by prolonged exposure to an odorant during the first week of posteclosion life, resulting in a persistently decreased response to aversive odors and an enhanced response to attractive odors. This limited window of early-use, experience-dependent plasticity represents a critical period of olfactory circuit refinement tuned by initial sensory input. Consequent behavioral adaptations have been associated with changes in the output of olfactory projection neurons to higher brain centers. Recent studies have indicated a central role for local interneuron signaling in LTCA presentation. Genetic and molecular analyses have implicated the mRNA-binding fragile X mental retardation protein and ataxin-2 regulators, Notch trans-synaptic signaling, and cAMP signal transduction as core regulatory steps driving LTCA. In this article, we discuss the structural, functional, and behavioral changes associated with LTCA and review our current understanding of the molecular pathways underlying these developmental, experience-dependent changes in the olfactory circuitry.



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High-frequency neural activity predicts word parsing in ambiguous speech streams

During speech listening, the brain parses a continuous acoustic stream of information into computational units (e.g., syllables or words) necessary for speech comprehension. Recent neuroscientific hypotheses have proposed that neural oscillations contribute to speech parsing, but whether they do so on the basis of acoustic cues (bottom-up acoustic parsing) or as a function of available linguistic representations (top-down linguistic parsing) is unknown. In this magnetoencephalography study, we contrasted acoustic and linguistic parsing using bistable speech sequences. While listening to the speech sequences, participants were asked to maintain one of the two possible speech percepts through volitional control. We predicted that the tracking of speech dynamics by neural oscillations would not only follow the acoustic properties but also shift in time according to the participant's conscious speech percept. Our results show that the latency of high-frequency activity (specifically, beta and gamma bands) varied as a function of the perceptual report. In contrast, the phase of low-frequency oscillations was not strongly affected by top-down control. Whereas changes in low-frequency neural oscillations were compatible with the encoding of prelexical segmentation cues, high-frequency activity specifically informed on an individual's conscious speech percept.



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Superentrainment of muscle sympathetic nerve activity during sinusoidal galvanic vestibular stimulation

Sinusoidal galvanic vestibular stimulation (sGVS), delivered at frequencies ranging from 0.08 to 2.0 Hz, induces vestibular illusions of side-to-side motion and robust modulation of muscle sympathetic nerve activity (MSNA) to the lower legs. We have previously documented, in seated subjects, de novo synthesis of bursts of MSNA that are temporally locked to the sinusoidal stimulus rather than to the cardiac-related rhythm. Here we tested the hypothesis that this vestibular entrainment of MSNA is higher in the upright than in the supine position. MSNA was recorded from the common peroneal nerve in 10 subjects lying on a tilt table. Bipolar binaural sGVS (±2 mA, 200 cycles) was applied to the mastoid processes at 0.2, 0.8, and 1.4 Hz in the supine and upright (75°) positions. In four subjects, "superentrainment" of MSNA occurred during sGVS, with strong bursts locked to one phase of the sinusoidal stimulus. This occurred more prominently in the upright position. On average, cross-correlation analysis revealed comparable vestibular modulation of MSNA in both positions at 0.2 Hz (84.9 ± 3.6% and 78.7 ± 5.7%), 0.8 Hz (77.4 ± 3.9% and 74.4 ± 8.9%), and 1.4 Hz (69.8 ± 4.6% and 80.2 ± 7.4%). However, in the supine position there was a significant linear fall in the magnitude of vestibular modulation with increasing frequency, whereas this was not present in the upright position. We conclude that vestibular contributions to the control of blood pressure are higher in the upright position.



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Early information processing contributions to object individuation revealed by perception of illusory figures

To isolate multiple coherent objects from their surrounds, each object must be represented as a stable perceptual entity across both time and space. Recent theoretical and empirical work has proposed that this process of object individuation is a mid-level operation that emerges around 200–300 ms after stimulus onset. However, this hypothesis is based on paradigms that have potentially obscured earlier effects. Furthermore, no study to date has directly assessed whether object individuation occurs for task-irrelevant objects. In the present study we used electroencephalography (EEG) to measure the time course of individuation, for stimuli both within and outside the focus of attention, to assess the information processing stage at which object individuation arises for both types of objects. We developed a novel paradigm involving items defined by illusory contours, which allowed us to vary the number of to-be-individuated objects while holding the physical elements of the display constant (a design characteristic not present in earlier work). As early as 100 ms after stimulus onset, event-related potentials tracked the number of objects in the attended hemifield, but not those in the unattended hemifield. By contrast, both attended and unattended objects could be individuated at a later stage. Our findings challenge recent conceptualizations of the time course of object individuation and suggest that this process arises earlier for attended than unattended items, implying that voluntary spatial attention influences the time course of this operation.



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Circuits for presaccadic visual remapping

Saccadic eye movements rapidly displace the image of the world that is projected onto the retinas. In anticipation of each saccade, many neurons in the visual system shift their receptive fields. This presaccadic change in visual sensitivity, known as remapping, was first documented in the parietal cortex and has been studied in many other brain regions. Remapping requires information about upcoming saccades via corollary discharge. Analyses of neurons in a corollary discharge pathway that targets the frontal eye field (FEF) suggest that remapping may be assembled in the FEF's local microcircuitry. Complementary data from reversible inactivation, neural recording, and modeling studies provide evidence that remapping contributes to transsaccadic continuity of action and perception. Multiple forms of remapping have been reported in the FEF and other brain areas, however, and questions remain about the reasons for these differences. In this review of recent progress, we identify three hypotheses that may help to guide further investigations into the structure and function of circuits for remapping.



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Glycolysis selectively shapes the presynaptic action potential waveform

Mitochondria are major suppliers of cellular energy in neurons; however, utilization of energy from glycolysis vs. mitochondrial oxidative phosphorylation (OxPhos) in the presynaptic compartment during neurotransmission is largely unknown. Using presynaptic and postsynaptic recordings from the mouse calyx of Held, we examined the effect of acute selective pharmacological inhibition of glycolysis or mitochondrial OxPhos on multiple mechanisms regulating presynaptic function. Inhibition of glycolysis via glucose depletion and iodoacetic acid (1 mM) treatment, but not mitochondrial OxPhos, rapidly altered transmission, resulting in highly variable, oscillating responses. At reduced temperature, this same treatment attenuated synaptic transmission because of a smaller and broader presynaptic action potential (AP) waveform. We show via experimental manipulation and ion channel modeling that the altered AP waveform results in smaller Ca2+ influx, resulting in attenuated excitatory postsynaptic currents (EPSCs). In contrast, inhibition of mitochondria-derived ATP production via extracellular pyruvate depletion and bath-applied oligomycin (1 μM) had no significant effect on Ca2+ influx and did not alter the AP waveform within the same time frame (up to 30 min), and the resultant EPSC remained unaffected. Glycolysis, but not mitochondrial OxPhos, is thus required to maintain basal synaptic transmission at the presynaptic terminal. We propose that glycolytic enzymes are closely apposed to ATP-dependent ion pumps on the presynaptic membrane. Our results indicate a novel mechanism for the effect of hypoglycemia on neurotransmission. Attenuated transmission likely results from a single presynaptic mechanism at reduced temperature: a slower, smaller AP, before and independent of any effect on synaptic vesicle release or receptor activity.



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{alpha}7-nAChR agonist enhances neural plasticity in the hippocampus via a GABAergic circuit

Agonists of the α7-nicotinic acetylcholine receptor (α7-nAChR) have entered clinical trials as procognitive agents for treating schizophrenia and Alzheimer's disease. The most advanced compounds are orthosteric agonists, which occupy the ligand binding site. At the molecular level, agonist activation of α7-nAChR is reasonably well understood. However, the consequences of activating α7-nAChRs on neural circuits underlying cognition remain elusive. Here we report that an α7-nAChR agonist (FRM-17848) enhances long-term potentiation (LTP) in rat septo-hippocampal slices far below the cellular EC50 but at a concentration that coincides with multiple functional outcome measures as we reported in Stoiljkovic M, Leventhal L, Chen A, Chen T, Driscoll R, Flood D, Hodgdon H, Hurst R, Nagy D, Piser T, Tang C, Townsend M, Tu Z, Bertrand D, Koenig G, Hajós M. Biochem Pharmacol 97: 576–589, 2015. In this same concentration range, we observed a significant increase in spontaneous -aminobutyric acid (GABA) inhibitory postsynaptic currents and a moderate suppression of excitability in whole cell recordings from rat CA1 pyramidal neurons. This modulation of GABAergic activity is necessary for the LTP-enhancing effects of FRM-17848, since inhibiting GABAA α5-subunit-containing receptors fully reversed the effects of the α7-nAChR agonist. These data suggest that α7-nAChR agonists may increase synaptic plasticity in hippocampal slices, at least in part, through a circuit-level enhancement of a specific subtype of GABAergic receptor.



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Normal correspondence of tectal maps for saccadic eye movements in strabismus

The superior colliculus is a major brain stem structure for the production of saccadic eye movements. Electrical stimulation at any given point in the motor map generates saccades of defined amplitude and direction. It is unknown how this saccade map is affected by strabismus. Three macaques were raised with exotropia, an outwards ocular deviation, by detaching the medial rectus tendon in each eye at age 1 mo. The animals were able to make saccades to targets with either eye and appeared to alternate fixation freely. To probe the organization of the superior colliculus, microstimulation was applied at multiple sites, with the animals either free-viewing or fixating a target. On average, microstimulation drove nearly conjugate saccades, similar in both amplitude and direction but separated by the ocular deviation. Two monkeys showed a pattern deviation, characterized by a systematic change in the relative position of the two eyes with certain changes in gaze angle. These animals' saccades were slightly different for the right eye and left eye in their amplitude or direction. The differences were consistent with the animals' underlying pattern deviation, measured during static fixation and smooth pursuit. The tectal map for saccade generation appears to be normal in strabismus, but saccades may be affected by changes in the strabismic deviation that occur with different gaze angles.



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Neuron-glia cross talk revealed in reverberating networks by simultaneous extracellular recording of spikes and astrocytes' glutamate transporter and K+ currents

Astrocytes uptake synaptically released glutamate with electrogenic transporters (GluT) and buffer the spike-dependent extracellular K+ excess with background K+ channels. We studied neuronal spikes and the slower astrocytic signals on reverberating neocortical cultures and organotypic slices from mouse brains. Spike trains and glial responses were simultaneously captured from individual sites of multielectrode arrays (MEA) by splitting the recorded traces into appropriate filters and reconstructing the original signal by deconvolution. GluT currents were identified by using dl-threo-β-benzyloxyaspartate (TBOA). K+ currents were blocked by 30 μM Ba2+, suggesting a major contribution of inwardly rectifying K+ currents. Both types of current were tightly correlated with the spike rate, and their astrocytic origin was tested in primary cultures by blocking glial proliferation with cytosine β-d-arabinofuranoside (AraC). The spike-related, time-locked inward and outward K+ currents in different regions of the astrocyte syncytium were consistent with the assumptions of the spatial K+ buffering model. In organotypic slices from ventral tegmental area and prefrontal cortex, the GluT current amplitudes exceeded those observed in primary cultures by several orders of magnitude, which allowed to directly measure transporter currents with a single electrode. Simultaneously measuring cell signals displaying widely different amplitudes and kinetics will help clarify the neuron-glia interplay and make it possible to follow the cross talk between different cell types in excitable as well as nonexcitable tissue.



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L-type calcium channels refine the neural population code of sound level

The coding of sound level by ensembles of neurons improves the accuracy with which listeners identify how loud a sound is. In the auditory system, the rate at which neurons fire in response to changes in sound level is shaped by local networks. Voltage-gated conductances alter local output by regulating neuronal firing, but their role in modulating responses to sound level is unclear. We tested the effects of L-type calcium channels (CaL: CaV1.1–1.4) on sound-level coding in the central nucleus of the inferior colliculus (ICC) in the auditory midbrain. We characterized the contribution of CaL to the total calcium current in brain slices and then examined its effects on rate-level functions (RLFs) in vivo using single-unit recordings in awake mice. CaL is a high-threshold current and comprises ~50% of the total calcium current in ICC neurons. In vivo, CaL activates at sound levels that evoke high firing rates. In RLFs that increase monotonically with sound level, CaL boosts spike rates at high sound levels and increases the maximum firing rate achieved. In different populations of RLFs that change nonmonotonically with sound level, CaL either suppresses or enhances firing at sound levels that evoke maximum firing. CaL multiplies the gain of monotonic RLFs with dynamic range and divides the gain of nonmonotonic RLFs with the width of the RLF. These results suggest that a single broad class of calcium channels activates enhancing and suppressing local circuits to regulate the sensitivity of neuronal populations to sound level.



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Elucidating the neural circuitry underlying planning of internally-guided voluntary action

In an attempt to elucidate the neural circuitry of planning of internally guided voluntary action, Ariani et al. (2015) used a delayed-movement design and multivariate pattern analysis of functional MRI data and found areas decoding internally elicited action plans, stimulus-elicited action plans, and both types of plans. In interpreting their results in the context of a heuristic decision model of voluntary action, encompassing "what" action to perform, "when" to perform it, and "whether" to perform it at all, we highlight at least some neural dissociation of these components. More to that, we note that the exact neural circuitry of each component might vary depending on the performed action type, and finally, we underscore the importance of understanding the temporal specifics of such circuitries to further elucidate how they are involved and interact during voluntary action planning.



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Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits

Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits.



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Dissociable roles of preSMA in motor sequence chunking and hand switching--a TMS study

Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within-chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously.



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Functional connectivity in the neuromuscular system underlying bimanual coordination

Neural synchrony has been suggested as a mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in bimanual coordination, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using EEG and muscle activity of the flexor pollicis brevis of both hands using high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index RV in the time and frequency domain. Functional connectivity was assessed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. The synergy index increased in the high coordination condition. RV was higher in the high coordination condition in frequencies between 0 and 0.5 Hz; for the 0.5- to 2-Hz frequency band, this pattern was inverted. Corticomuscular coherence in the beta band (16–30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5–12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between RV and corticomuscular coherence and a positive correlation between RV and intermuscular coherence. Our findings suggest two distinct neural pathways: 1) corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; and 2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.



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Seeing pain and pleasure on self and others: behavioral and psychophysiological reactivity in immersive virtual reality

Studies have explored behavioral and neural responses to the observation of pain in others. However, much less is known about how taking a physical perspective influences reactivity to the observation of others' pain and pleasure. To explore this issue we devised a novel paradigm in which 24 healthy participants immersed in a virtual reality scenario observed a virtual: needle penetrating (pain), caress (pleasure), or ball touching (neutral) the hand of an avatar seen from a first (1PP)- or a third (3PP)-person perspective. Subjective ratings and physiological responses [skin conductance responses (SCR) and heart rate (HR)] were collected in each trial. All participants reported strong feelings of ownership of the virtual hand only in 1PP. Subjective measures also showed that pain and pleasure were experienced as more salient than neutral. SCR analysis demonstrated higher reactivity in 1PP than in 3PP. Importantly, vicarious pain induced stronger responses with respect to the other conditions in both perspectives. HR analysis revealed equally lower activity during pain and pleasure with respect to neutral. SCR may reflect egocentric perspective, and HR may merely index general arousal. The results suggest that behavioral and physiological indexes of reactivity to seeing others' pain and pleasure were qualitatively similar in 1PP and 3PP. Our paradigm indicates that virtual reality can be used to study vicarious sensation of pain and pleasure without actually delivering any stimulus to participants' real body and to explore behavioral and physiological reactivity when they observe pain and pleasure from ego- and allocentric perspectives.



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Role of motor execution in the ocular tracking of self-generated movements

When human observers track the movements of their own hand with their gaze, the eyes can start moving before the finger (i.e., anticipatory smooth pursuit). The signals driving anticipation could come from motor commands during finger motor execution or from motor intention and decision processes associated with self-initiated movements. For the present study, we built a mechanical device that could move a visual target either in the same direction as the participant's hand or in the opposite direction. Gaze pursuit of the target showed stronger anticipation if it moved in the same direction as the hand compared with the opposite direction, as evidenced by decreased pursuit latency, increased positional lead of the eye relative to target, increased pursuit gain, decreased saccade rate, and decreased delay at the movement reversal. Some degree of anticipation occurred for incongruent pursuit, indicating that there is a role for higher-level movement prediction in pursuit anticipation. The fact that anticipation was larger when target and finger moved in the same direction provides evidence for a direct coupling between finger and eye motor commands.



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Physiology and anatomy of neurons in the medial superior olive of the mouse

In mammals with good low-frequency hearing, the medial superior olive (MSO) computes sound location by comparing differences in the arrival time of a sound at each ear, called interaural time disparities (ITDs). Low-frequency sounds are not reflected by the head, and therefore level differences and spectral cues are minimal or absent, leaving ITDs as the only cue for sound localization. Although mammals with high-frequency hearing and small heads (e.g., bats, mice) barely experience ITDs, the MSO is still present in these animals. Yet, aside from studies in specialized bats, in which the MSO appears to serve functions other than ITD processing, it has not been studied in small mammals that do not hear low frequencies. Here we describe neurons in the mouse brain stem that share prominent anatomical, morphological, and physiological properties with the MSO in species known to use ITDs for sound localization. However, these neurons also deviate in some important aspects from the typical MSO, including a less refined arrangement of cell bodies, dendrites, and synaptic inputs. In vitro, the vast majority of neurons exhibited a single, onset action potential in response to suprathreshold depolarization. This spiking pattern is typical of MSO neurons in other species and is generated from a complement of Kv1, Kv3, and IH currents. In vivo, mouse MSO neurons show bilateral excitatory and inhibitory tuning as well as an improvement in temporal acuity of spiking during bilateral acoustic stimulation. The combination of classical MSO features like those observed in gerbils with more unique features similar to those observed in bats and opossums make the mouse MSO an interesting model for exploiting genetic tools to test hypotheses about the molecular mechanisms and evolution of ITD processing.



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Slow gamma rhythms in CA3 are entrained by slow gamma activity in the dentate gyrus

In hippocampal area CA1, slow (~25–55 Hz) and fast (~60–100 Hz) gamma rhythms are coupled with different CA1 afferents. CA1 slow gamma is coupled to inputs from CA3, and CA1 fast gamma is coupled to inputs from the medial entorhinal cortex (Colgin LL, Denninger T, Fyhn M, Hafting T, Bonnevie T, Jensen O, Moser MB, Moser EI. Nature 462: 353–357, 2009). CA3 gives rise to highly divergent associational projections, and it is possible that reverberating activity in these connections generates slow gamma rhythms in the hippocampus. However, hippocampal gamma is maximal upstream of CA3, in the dentate gyrus (DG) region (Bragin A, Jando G, Nadasdy Z, Hetke J, Wise K, Buzsaki G. J Neurosci 15: 47–60, 1995). Thus it is possible that slow gamma in CA3 is driven by inputs from DG, yet few studies have examined slow and fast gamma rhythms in DG recordings. Here we investigated slow and fast gamma rhythms in paired recordings from DG and CA3 in freely moving rats to determine whether slow and fast gamma rhythms in CA3 are entrained by DG. We found that slow gamma rhythms, as opposed to fast gamma rhythms, were particularly prominent in DG. We investigated directional causal influences between DG and CA3 by Granger causality analysis and found that DG slow gamma influences CA3 slow gamma. Moreover, DG place cell spikes were strongly phase-locked to CA3 slow gamma rhythms, suggesting that DG excitatory projections to CA3 may underlie this directional influence. These results indicate that slow gamma rhythms do not originate in CA3 but rather slow gamma activity upstream in DG entrains slow gamma rhythms in CA3.



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Effect of aging and exercise on the tendon

Here, we review the literature on how tendons respond and adapt to ageing and exercise. With respect to aging, there are considerable changes early in life, but this seems to be maturation rather than aging per se. In vitro data indicate that aging is associated with a decreased potential for cell proliferation and a reduction in the number of stem/progenitor-like cells. Further, there is persuasive evidence that turnover in the core of the tendon after maturity is very slow or absent. Tendon fibril diameter, collagen content, and whole tendon size appear to be largely unchanged with aging, while glycation-derived cross-links increase substantially. Mechanically, aging appears to be associated with a reduction in modulus and strength. With respect to exercise, tendon cells respond by producing growth factors, and there is some support for a loading-induced increase in tendon collagen synthesis in humans, which likely reflects synthesis at the very periphery of the tendon rather than the core. Average collagen fibril diameter is largely unaffected by exercise, while there can be some hypertrophy of the whole tendon. In addition, it seems that resistance training can yield increased stiffness and modulus of the tendon and may reduce the amount of glycation. Exercise thereby tends to counteract the effects of aging.



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A generalized method for controlling end-tidal respiratory gases during nonsteady physiological conditions

While forcing of end-tidal gases by regulating inspired gas concentrations is a common technique for studying cardiorespiratory physiology, independently controlling end-tidal gases is technically challenging. Feedforward control methods are challenging because end-tidal values vary as a dynamic function of both inspired gases and other nonregulated physiological parameters. Conventional feedback control is limited by delays within the lungs and body tissues and within the end-tidal forcing system itself. Consequently, modern end-tidal forcing studies have generally restricted their analysis to simple time courses of end-tidal gases and to resting steady-state conditions. To overcome these limitations, we have designed and validated a more generalized end-tidal forcing system that removes the need for manual tuning and rule-of-thumb based control heuristics, while allowing for accurate control of gases along spontaneous and complicated time courses and under nonsteady physiological conditions. On average during resting, steady walking, and walking with time varying speed, our system achieved step changes in PetCO2 within 3.0 ± 0.9 (mean ± SD) breaths and PetO2 within 4.4 ± 0.9 breaths, while also maintaining small steady-state errors of 0.1 ± 0.2 mmHg for PetCO2 and 0.3 ± 0.8 mmHg for PetO2. The system also accurately tracked more complicated changes in end-tidal values through a bandwidth of 1/10 the respiratory (sampling) frequency, a practical limit of feedback control systems. The primary mechanism enabling this controller performance is a generic mathematical model of the cardiopulmonary system that captures the breath-by-breath relationship between inspired and end-tidal gas concentrations, with secondary contributions from reduced delays in controlled air delivery.



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The effect of endothelin A and B receptor blockade on cutaneous vascular and sweating responses in young men during and following exercise in the heat

During exercise, cutaneous vasodilation and sweating responses occur, whereas these responses rapidly decrease during postexercise recovery. We hypothesized that the activation of endothelin A (ETA) receptors, but not endothelin B (ETB) receptors, attenuate cutaneous vasodilation during high-intensity exercise and contribute to the subsequent postexercise suppression of cutaneous vasodilation. We also hypothesized that both receptors increase sweating during and following high-intensity exercise. Eleven men (24 ± 4 yr) performed an intermittent cycling protocol consisting of two 30-min bouts of moderate- (40% Vo2peak) and high-intensity (75% Vo2peak) exercise in the heat (35°C), each separated by a 20- and 40-min recovery period, respectively. Cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal microdialysis skin sites: 1) lactated Ringer (control), 2) 500 nM BQ123 (a selective ETA receptor blocker), 3) 300 nM BQ788 (a selective ETB receptor blocker), or 4) a combination of BQ123 + BQ788. There were no between-site differences in CVC during each exercise bout (all P > 0.05); however, CVC following high-intensity exercise was greater at BQ123 (56 ± 9%max) and BQ123 + BQ788 (55 ± 14%max) sites relative to the control site (43 ± 12%max) (all P ≤ 0.05). Sweat rate did not differ between sites throughout the protocol (all P > 0.05). We show that neither ETA nor ETB receptors modulate cutaneous vasodilation and sweating responses during and following moderate- and high-intensity exercise in the heat, with the exception that ETA receptors may partly contribute to the suppression of cutaneous vasodilation following high-intensity exercise.



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Blind percutaneous liver biopsy in infants and children: Comparison of safety and efficacy of percussion technique and ultrasound assisted technique

Publication date: Available online 30 November 2016
Source:Arab Journal of Gastroenterology
Author(s): Engy A. Mogahed, Yasmeen A. Mansy, Yasmeen Al Hawi, Rokaya El-Sayed, Mona El-Raziky, Hanaa El-Karaksy
Background and study aimsLiver biopsy remains the most reliable method to diagnose various hepatic disorders in children. We aimed to assess the technical success and complication rate of ultrasound (US) assisted percutaneous liver biopsy versus transthoracic percussion guided technique in paediatrics.Patients and methodsThis randomized controlled study included all cases performing liver biopsy at Paediatric Hepatology Unit, Cairo University Paediatric Hospital over 12months.ResultsPatients were 102 cases; 62 were males, with age range 18days to 12years. Fifty seven procedures were done using the percussion guided technique and 45 cases were US assisted. The total number of complicated biopsies was 14 (13.7%), with more serious complications occurring in the percussion group. Complications were more frequent with younger age, lower platelet count, number of passes and occurrence of hypotension.ConclusionUS assisted percutaneous liver biopsy, although more costly, but may be safer to perform particularly in younger age.



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Appraise the Health-Related Quality of Life among Trauma Patients

2016-12-01T16-50-10Z
Source: International Journal of Health and Rehabilitation Sciences (IJHRS)
Ravi Kant Jain, Neelesh Dhadse, Chirag Sethi, Ravindra Kumar, Susmit Kosta.
Background: Limb injures is revolve a life-changing event that can cause significant disruptions in many important areas of life. Objectives: The objective of our study was to appraise the Health Related Quality of Life (HRQOL) and psychosocial factors associated with pain and disability in patients following Upper limb (UL) and lower limb (LL) trauma patients Materials and methods: A sample of convenience 300 adult male and female patients who met the inclusion criteria was included. A short form (36) health status questionnaire was filled by a single author from each patient after one year of follow up. This part was utilized to assess the QOL among limbs traumas patients. Results: Intraclass correlation coefficients were greater than 0.7 in five of the eight domains of SF 36 except mental health, social function and general health. Chronbachs α was higher than 0.8 all the domains except in social function domain. There was no difference in Health Related Quality of Life in patients with upper and lower limb trauma. However there was significant difference in 4 domains related to physical components of SF 36 survey form between male and females. Conclusion: Both upper and lower limb trauma similarly affects the Health Related Quality of Life in all age group of patients. Keywords: Sf-36, Trauma, HRQOL


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The Relationship Between Race, Patient Activation, and Working Alliance: Implications for Patient Engagement in Mental Health Care

Abstract

This study explored the relationship between race and two key aspects of patient engagement—patient activation and working alliance—among a sample of African-American and White veterans (N = 152) seeking medication management for mental health conditions. After adjusting for demographics, race was significantly associated with patient activation, working alliance, and medication adherence scores. Patient activation was also associated with working alliance. These results provide support for the consideration of race and ethnicity in facilitating patient engagement and patient activation in mental healthcare. Minority patients may benefit from targeted efforts to improve their active engagement in mental healthcare.



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Association Between Mental Health Staffing Level and Primary Care-Mental Health Integration Level on Provision of Depression Care in Veteran’s Affairs Medical Facilities

Abstract

We examined the association of mental health staffing and the utilization of primary care/mental health integration (PCMHI) with facility-level variations in adequacy of psychotherapy and antidepressants received by Veterans with new, recurrent, and chronic depression. Greater likelihood of adequate psychotherapy was associated with increased (1) PCMHI utilization by recurrent depression patients (AOR 1.02; 95% CI 1.00, 1.03); and (2) staffing for recurrent (AOR 1.03; 95% CI 1.01, 1.06) and chronic (AOR 1.02; 95% CI 1.00, 1.03) depression patients (p < 0.05). No effects were found for antidepressants. Mental health staffing and PCMHI utilization explained only a small amount of the variance in the adequacy of depression care.



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Optimal Design and Manufacture of Active Rod Structures with Spatially Variable Materials

3D Printing and Additive Manufacturing , Vol. 0, No. 0.


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Local Viscosity Control Printing for High-Throughput Additive Manufacturing of Polymers

3D Printing and Additive Manufacturing , Vol. 0, No. 0.


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Curved Layer Fused Filament Fabrication Using Automated Toolpath Generation

3D Printing and Additive Manufacturing , Vol. 0, No. 0.


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S2 Strategic Defense presents Project Blue Line

BARTLETT, Ill. - S2 Strategic Defense, a Chicagoland based Defensive Tactics Training Firm is now opening their Project Blue Line as a way for citizens and officers to support the blue line. The project allows citizens to donate/pledge the S2 Critical Response Kit to be gifted to an officer. The kit contains a CAT tourniquet, Modular Tourniquet holder, HyFin Chest Seal, Combat Gauze, and Contents Card ...

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Immunoglobulin G4-related hepatic inflammatory pseudotumor invading the abdominal wall

Abstract

A 50-year-old woman presented with epigastralgia. Computed tomography (CT) of the abdomen revealed a 6-cm well-enhanced mass extending from the left lobe of the liver to the abdominal wall, suggestive of cholangiocarcinoma. Liver and skin mass biopsies did not provide evidence of hepatic malignancy but were rich in plasma cells and sclerotic lesions. Subsequent detection of elevated serum immunoglobulin G4 (IgG4) led to a diagnosis IgG4-related inflammatory pseudotumor (IPT) of the liver. Treatment with systemic corticosteroids resulted in rapid clinical improvement. This case is the first report of an IgG4-related hepatic IPT invading the abdominal wall.



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NY ambulance, fire truck collide at crash scene

A fire official said the fire truck got stuck in the mud and leaned over to one side to make contact with the ambulance

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Watch: Shot EMT student recounts harrowing attack

By EMS1 Staff

BATON ROUGE, La. —  After being shot and run over twice while aiding a shooting victim, 17-year-old Daniel Wesley spoke to reporters about the incident from his hospital bed.

Wesley was returning home from a shopping trip with his mother when he saw a woman lying on the side of the road. While attempting to render aid, he was shot and run over twice by the shooter, Terrell Walker. He underwent surgery this week for injuries he sustained to his leg and arm. The victim, April Peck, did not survive. 

"We were tending to the victim, and all of a sudden we get hit by the car," Wesley said. "And I somehow ended up in the median."

Wesley said Walker got out of the vehicle and told him, "If you're helping her, you're gonna die too." He was then shot in his posterior. Walker attempted to shoot other responders in the area, but no one else was shot. He returned to the vehicle and shot Wesley a second time in the arm. After being shot in his posterior, he instructed a bystander to put pressure on the gunshot wound. 

"My feet were hanging off the curb, and whenever he pulled away, he hit my legs and broke my femur in half," Wesley said. "And then, basically, EMS took over from there."

When asked what he was thinking during the incident, Wesley said, "I was thinking, 'I'm not gonna die. He said I'm gonna kill you, and I was like, no you're not.' Just remain calm."

When Wesley pulled over to aid Peck, he said no one was in the area and that he thought he would be fine. "The first thing you're taught, as an EMT … it's your safety over everyone else's."

Wesley initially had intentions to join the Army as a medic, but now he says, "I have screws in both hands, my elbow and a metal rod in my knee, so that's probably gonna be out of the picture. My backup plan was to be an EMT and work my way up to a paramedic, but I don't know what it is now." However, he still intends to work in the medical field. 

In the aftermath of the incident, Wesley said he tried to make light of the situation by making jokes and staying positive. Due to the intense pain in his arm, however, he had to postpone physical therapy earlier this week. Wesley said he was able to take a few steps recently. He has made progress since, and there are no other surgeries planned. He did say that after surgery, he asked his father to put on the Duke football game. Wesley's recovery time is approximately two months, but he aims to shorten it. 

One reporter asked Wesley, "You stopped out of the goodness of your heart, would you do that again?"

"I don't see why not," Wesley said. "I wish I could have done more. I'm glad no one else got shot."

Prior to his interview, Wesley was visited by Walker's cousin, who brought flowers and a card. "She was just apologizing and stuff, so I called her over to give her a hug and hold her hand. It's in the past."

Wesley said he forgives Walker. "I don't know why he did it, I kind of want to know why, but yeah, it's in the past and I can't change it. Everything happens for a reason, I'm alive."

The governor also paid Wesley a visit. When asked if he needed anything, Wesley asked him if he could get a vending machine with root beer in it. "Two minutes later, I have a crate of root beer. I already drank one."

"Thank y'all for the support. Imma be back. Love y'all," Wesley said.



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EMS agencies must learn from worsening UK ambulance crisis

The ambulance trust system in England has been in crisis for several years. Not enough providers, too many calls and long waiting lines at hospitals for paramedics waiting to offload patients have combined to create a national EMS system that is unable to respond to emergency calls for assistance in a consistent, timely manner. Moreover, the incredible workloads have resulted in an increasingly burned out workforce, with well-intentioned people unable to handle the stress any longer and leaving.

Of course, it's true that the U.K. and U.S. systems are entirely different from each other. But we are seeing the same pressures being placed on American systems that are gutting the trusts. U.S. hospitals have fewer beds to admit patients, causing emergency department gurneys to fill up and EMS personnel unable to handoff or offload their patients.

Many U.S. providers are unable to maintain response times due to the high volume of low acuity calls. Financial pressures from lower reimbursements that are unable to cover operating costs are causing agencies to reduce the number of ambulances available for calls.

Adding more ambulances is definitely not part of a solution to a complex, multifaceted problem. Changes in how health care is provided — and reimbursed — will prohibit the growth of a traditional 911-only systems.

Taxpayers aren't going to foot the bill either. Given the impending shift of political winds in the federal government, there will be little appetite by government to take on additional financial burden of public safety and health.

Frankly, it's time to re-engineer our thoughts of field care medicine. Traditional 911 system response hasn't been appropriate for the majority of calls for a long time. It's been due to the constraints of reimbursement. We only got paid if we took the patient to an emergency department.

It's what the unsuspecting public felt was "needed" as well. Countless television shows and health care advertising that reinforces the notion that one only got "better" by going to a hospital. The same shows glamorize the flashy lights and blaring sirens and the heart pounding drama of saving countless lives only to attract newcomers to the business that is so not filled with television "reality."

How do we transition the paradigm of field medicine" By embracing what works and changing what doesn't work.

An increasing number of EMS systems are implementing community based systems of care, often in conjunction with hospitals, hospice care, physicians and mental health providers. Other agencies are beginning to reconceptualize "emergency calls" so that response times to true emergencies are met. Beyond the confines of the ambulance service, large health systems are investing in more preventive strategies for the overall health of their member populations, potentially reducing the number of patients that enter the 911 system.

A few years back, it was said that a fast, cheap and high quality EMS system didn't exist. It could be fast and cheap, but not high quality. Or, the system could be of high quality, but it wouldn't be fast or cheap. I would posit that we could have a system that would have all three attributes, as long as we drop the tradition-laden constraints of EMS dogma that will keep us permanently in the dark ages.



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Report: Lax ambulance rules put paramedics, patients at risk

The study found that 84 percent of EMS providers in the patient compartments of ambulances that crashed weren't using their own restraints

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Levels of toxic metals and trace elements in autopsy liver tissue samples

2016-12-01T07-22-30Z
Source: Medicine Science | International Medical Journal
Servet Birgin Iritas, Ahmet Hakan Dinc, Aybike Dip, Bahri Melih Unal, Mevlut Ertan, Tulin Soylemezoglu.
The aim of the study is to determine the levels of toxic metals (cadmium and lead) and trace elements (zinc and copper) in the liver tissues of autopsy cases in Ankara and to evaluate the statistical relationship of these metals with subjects physical properties, smoking status, occupational exposure and environmental factors. Results are expected to establish the average burden of involved metals in liver tissue of Turkish population. Hepatic trace elements and toxic metal levels were assessed in 119 autopsy cases. Digestion procedure for liver tissues was carried out using a Mars Xpress microwave system (CEM, Matthews, USA) with PTFE microwave digestion vessels. Lead and cadmium were analyzed by Graphite Furnace Atomic Spectrometry; copper and zinc were analyzed by Flame Atomic Absorption Spectrometry. Average liver levels of metals and trace elements were found 29.5 µg/g, 216 µg/g, 0.39 µg/g and 4.38 µg/g dry weight for copper, zinc, lead and cadmium, respectively. Copper and lead levels were found higher in men. There was a significant decrease in copper levels with age. Lead levels in city dwellers were significantly higher and there was no correlation between metal levels and occupations of the individuals. Significant increase in copper, lead and cadmium were observed in smokers liver tissues. All metal levels were compared with each other and positive correlation was found between zinc-copper, lead-zinc and copper-zinc levels (p˂0.01). In Turkey, it is the first study which gives liver tissue levels of trace elements and heavy metals of autopsy samples in a city which has a median-scale industrial development.


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Severe major depression: a case of neurobrucellosis

2016-12-01T07-22-30Z
Source: Medicine Science | International Medical Journal
Lara Utku Ince, Nursel Akti Kavuran, Abdulcemal Ozcan, Suheyla Unal.



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Langerhans Cell Histiocytosis In Postauricular Region

2016-12-01T06-58-27Z
Source: The Southeast Asian Journal of Case Report and Review
Karthikeyan Ramasamy, John Kiran Rayer, Sivaraman Ganesan, Arun Alexander, Sunil Kumar Saxena.
We present a rare case report of eosinophilic granuloma in 10 year old female which was managed surgically. We also review the case literature, the clinical presentations briefly with surgical management.


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Unique Pearls In Synergy-Atrial Myxoma And Hypertrophic Cardiomyopathy

2016-12-01T06-58-27Z
Source: The Southeast Asian Journal of Case Report and Review
Avinash Mani, Manoj Kumar, Vineeta Ojha.
Primary cardiac tumors are a rare occurrence amongst general population, myxoma being the most common benign primary cardiac tumor. Hypertrophic cardiomyopathy(HCM) is a genetic cardiovascular disorder which usually presents with syncope or palpitations. The case we present here is a unique amalgamation of both these pathologies which are uncommon as well as completely unrelated to each other as far as literature describes. The patient presented with symptoms of congestive cardiac failure without any history of syncope and palpitation ,however echocardiography revealed the presence of HCM as well as atrial myxoma. This case reveals that remote possibility of such coexisting conditions should be kept in mind in clinical practice and also the fact that HCM can notoriously remain undetected presenting only as heart failure instead of its usual clinical features.


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Maternal And Perinatal Outcome In Antepartum Hemorrhage :At Sir T Hospital

2016-12-01T06-58-27Z
Source: The Southeast Asian Journal of Case Report and Review
Mehul Patel, Kanaklatta Nakum, Mayank Lunagariya, Juhi Patel.
Introduction: Antepartum haemorrhage is one of the major causes of maternal mortality. It contributes to 15-20% of maternal mortality in India. Incidence of antepartum haemorrhage is varies from 2-5 % of all deliveries. APH arising from placental abruption and placenta praevia is associated with an increased risk of postpartum haemorrhage 1 .Maternal and perinatal complication of antepartum haemorrhage are anaemia, postpartum haemorrhage, shock, low birth weight, intrauterine death, and birth asphyxia. Aim & Objectives: 1) To study Maternal and Perinatal outcome in Antepartum haemorrhage. 2) to study factors associated with Antepartum haemorrhage. Method & Materials: It is retrospective study carried out on 56 women admitted with the diagnosis of antepartum haemorrhage at Sir T. Hospital Bhavnagar during August 2015 to July 2016. The diagnosis was made on the basis of history, Clinical examination and few cases aided by ultrasonography. Result: In present study the incidence of APH was 1.4%. out of 56 cases 66% were multigravida and 71% of them were of low socio economic status.56% had feature of pre-eclampsia. Maternal and perinatal mortality was very high with increase rates of anaemia (100%), caesarean section rate (61%), need of blood transfusion (86%), coagulation failure (13%), low birth weight (75%). Perinatal mortality was 43%.


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Report: Lax ambulance rules puts paramedics, patients at risk

The NHTSA study found that 84 percent of EMS workers in the patient compartments of ambulances that crashed were not using their own restraints

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Zika Virus and Patient Blood Management.

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Sporadic Zika virus infections had only occurred in Africa and Asia until an outbreak in Micronesia (Oceania) in 2007. In 2013 to 2014, several outer Pacific Islands reported local outbreaks. Soon thereafter, the virus was likely introduced in Brazil from competing athletes from French Polynesia and other countries that participated in a competition there. Transmission is thought to have occurred through mosquito bites and spread to the immunologically naive population. Being also a flavivirus, the Zika virus is transmitted by the Aedes mosquito that is endemic in South and Central America that is also the vector of West Nile virus, dengue, and chikungunya. In less than a year, physicians in Brazil reported a many-fold increase in the number of babies born with microcephaly. Despite initial skepticism regarding the causal association of the Zika virus epidemic and birth defects, extensive basic and clinical research evidence has now confirmed this relationship. In the United States, more than 4000 travel-associated infections have been reported by the middle of 2016 to the Centers for Disease Control and Prevention. Furthermore, many local mosquito-borne infections have occurred in Puerto Rico and Florida. Considering that the virus causes a viremia in which 80% of infected individuals have no symptoms, the potential for transfusion transmission from an asymptomatic blood donor is high if utilizing donor screening alone without testing. Platelet units have been shown to infect 2 patients via transfusion in Brazil. Although there was an investigational nucleic acid test available for testing donors, not all blood centers were initially required to participate. Subsequently, the US Food and Drug Administration issued a guidance in August 2016 that recommended universal nucleic acid testing for the Zika virus on blood donors. In this report, we review the potentially devastating effects of Zika virus infection during pregnancy and its implication in cases of Guillain-Barre syndrome in adults. Furthermore, we urge hospital-based clinicians and transfusion medicine specialists to implement perisurgical patient blood management strategies to avoid blood component transfusions with their potential risks of emerging pathogens, illustrated here by the Zika virus. Ultimately, this current global threat, as described by the World Health Organization, will inevitably be followed by future outbreaks of other bloodborne pathogens; the principles and practices of perioperative patient blood management will reduce the risks from not only known, but also unknown risks of blood transfusion for our patients. (C) 2016 International Anesthesia Research Society

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