Τρίτη 5 Σεπτεμβρίου 2017

Use of the “dual construct” for the management of complex spinal reconstructions

Surgical management of complex spinal reconstructions remains a clinical challenge, as pseudoarthrosis with subsequent rod breakage can occur. Increased rod density in the form of "satellite" or "outrigger" rods have been described; however rod-fracture above or below satellite rods persist and can result in dissociation of the construct, loss of correction, and recurrence of deformity. The use of four distinct and mechanically independent rods (Dual Construct) reduces this concern. Since the original case description in 2006, there have been no other studies that utilize the Dual Construct for the surgical management of complex spinal reconstructions.

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The Qualitative Grading of Muscle Fat Infiltration in Whiplash Using Fat/Water Magnetic Resonance Imaging

Development of muscle fat infiltration (MFI) in the neck muscles is associated with poor functional recovery following whiplash injury. Custom software and time-consuming manual segmentation of magnetic resonance (MR) images is required for quantitative analysis and presents as a barrier for clinical translation.

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Establishing benchmarks for the volume-outcome relationship for common lumbar spine surgical procedures

The importance of surgeon volume as a quality measure has been defined for a number of surgical specialties. Meaningful procedural volume benchmarks have not been established, however, particularly with respect to lumbar spine surgery.

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Transcriptome Analysis Suggests That Chromosome Introgression Fragments from Sea Island Cotton (Gossypium barbadense) Increase Fiber Strength in Upland Cotton (Gossypium hirsutum)

As high-strength cotton fibers are critical components of high quality cotton, developing cotton cultivars with high strength fibers as well as high yield is a top priority for cotton development. Recently, chromosome segment substitution lines (CSSLs) have been developed from high-yield Upland cotton (Gossypium hirsutum) crossed with high-quality Sea Island cotton (G. barbadense). Here, we constructed a CSSL population by crossing CCRI45, a high-yield Upland cotton cultivar, with Hai1, a Sea Island cotton cultivar with superior fiber quality. We then selected two CSSLs with significantly higher fiber strength than CCRI45 (MBI7747 and MBI7561), and one CSSL with lower fiber strength than CCRI45 (MBI7285) for further analysis. We sequenced all four transcriptomes at four different time points post-anthesis, and clustered the 44,678 identified genes by function. We identified 2200 "common differentially expressed genes (DEGs)": those that were found in both high quality CSSLs (MBI7747 and MBI7561), but not in the low quality CSSL (MBI7285). Many of these genes were associated with various metabolic pathways that affect fiber strength. Upregulated DEGs were associated with polysaccharide metabolic regulation, single-organism localization, cell wall organization, and biogenesis, while the downregulated DEGs were associated with microtubule regulation, the cellular response to stress, and the cell cycle. Further analyses indicated that three genes, XLOC_036333 (mannosyl-oligosaccharide-alpha-mannosidase mns1), XLOC_029945 (FLA8), and XLOC_075372 (snakin-1) were potentially important for the regulation of cotton fiber strength. Our results suggest that these genes may be good candidates for future investigation of the molecular mechanisms of fiber strength formation, and for the improvement of cotton fiber quality through molecular breeding.



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Early closure of fistula using neo-adjuvant intra-arterial chemotherapy in locally advanced anal cancer

Locally advanced anal cancer patients, especially with T4 disease and fistula, have a dismal prognosis. Neo-adjuvant intra-arterial chemotherapy before standard chemoradiation has been shown to be promising in this setting.

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Early closure of fistula using neo-adjuvant intra-arterial chemotherapy in locally advanced anal cancer

Locally advanced anal cancer patients, especially with T4 disease and fistula, have a dismal prognosis. Neo-adjuvant intra-arterial chemotherapy before standard chemoradiation has been shown to be promising in this setting.

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The Associative Brain at Work: Evidence from Paired Associative Stimulation Studies in Humans

Donald Hebb's now-famous rule of synaptic plasticity states: "When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased." Although not explicitly stated, the phrase "takes part in firing it" suggests very strongly that there is a close temporal connection between occurrence of the input (A) and the firing of cell B.

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The histone lysine methyltransferase Ezh2 is required for maintenance of the intestine integrity and for caudal fin regeneration in zebrafish

Publication date: Available online 5 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Barbara Dupret, Pamela Völkel, Constance Vennin, Robert-Alain Toillon, Xuefen Le Bourhis, Pierre-Olivier Angrand
The histone lysine methyltransferase EZH2, as part of the Polycomb Repressive Complex 2 (PRC2), mediates H3K27me3 methylation which is involved in gene expression program repression. Through its action, EZH2 controls cell-fate decisions during the development and the differentiation processes. Here, we report the generation and the characterization of an ezh2-deficient zebrafish line. In contrast to its essential role in mouse early development, loss of ezh2 function does not affect zebrafish gastrulation. Ezh2 zebrafish mutants present a normal body plan but die at around 12 dpf with defects in the intestine wall, due to enhanced cell death. Thus, ezh2-deficient zebrafish can initiate differentiation toward the different developmental lineages but fail to maintain the intestinal homeostasis. Expression studies revealed that ezh2 mRNAs are maternally deposited. Then, ezh2 is ubiquitously expressed in the anterior part of the embryos at 24 hpf, but its expression becomes restricted to specific regions at later developmental stages. Pharmacological inhibition of Ezh2 showed that maternal Ezh2 products contribute to early development but are dispensable to body plan formation. In addition, ezh2-deficient mutants fail to properly regenerate their spinal cord after caudal fin transection suggesting that Ezh2 and H3K27me3 methylation might also be involved in the process of regeneration in zebrafish.

Graphical abstract

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Molecular analysis of oxalate-induced endoplasmic reticulum stress mediated apoptosis in the pathogenesis of kidney stone disease

Abstract

Oxalate, a non-essential end product of metabolism, causes hyperoxaluria and eventually calcium oxalate (CaOx) stone disease. Kidney cells exposed to oxalate stress results in generation of reactive oxygen species (ROS) and progression of stone formation. Perturbations in endoplasmic reticulum (ER) result in accumulation of misfolded proteins and Ca2+ ions homeostasis imbalance and serve as a common pathway for various diseases, including kidney disorders. ER stress induces up-regulation of pro-survival protein glucose-regulated protein 78 (GRP78) and pro-apoptotic signaling protein C/EBP homologous protein (CHOP). Since the association of oxalate toxicity and ER stress on renal cell damage is uncertain, the present study is an attempt to elucidate the interaction of GRP78 with oxalate by computational analysis and study the role of ER stress in oxalate-mediated apoptosis in vitro and in vivo. Molecular docking results showed that GRP78-oxalate/CaOx interaction takes place. Oxalate stress significantly up-regulated expression of ER stress markers GRP78 and CHOP both in vitro and in vivo. Exposure of oxalate increased ROS generation and altered antioxidant enzyme activities. N-Acetyl cysteine treatment significantly ameliorated oxalate-mediated oxidative stress and moderately attenuated ER stress marker expression. The result indicates oxalate toxicity initiated oxidative stress-induced ER stress and also activating ER stress mediated apoptosis directly. In addition, the up-regulation of transforming growth factor β-1 revealed oxalate may induce kidney fibrosis through ER stress-mediated mechanisms. The present study provide insights into the pathogenic role of oxidative and ER stress by oxalate exposure in the formation of calcium oxalate stone.



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Reinforcing Value of Caffeinated and Noncaffeinated Beverages After Acute Exposure in Children and Adolescents

Journal of Caffeine Research , Vol. 0, No. 0.


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Reinforcing Value of Caffeinated and Noncaffeinated Beverages After Acute Exposure in Children and Adolescents

Journal of Caffeine Research , Vol. 0, No. 0.


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New Kan. ambulance built specifically for twin babies

Instead of only loading a patient from the back, a second patient can be loaded from the side

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DXE Medical, Inc. announces new name

DUBLIN, Ohio – DXE Medical, Inc., a Sarnova company specializing in cardiac products, services and solutions, announced today that it is changing its name to Cardio Partners, Inc. The new name, effective today, is meant to reflect the company's newly expanded cardiac preparedness service offering. DXE Medical specialized in distributing new and recertified emergency equipment and refurbishment ...

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DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease [Genetics]

The human genome contains ∼30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ∼9,000 CGIs lying within gene bodies become methylated during development and differentiation. Both promoter and intragenic CGIs may also become abnormally methylated as a result of genome rearrangements and in...

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Vertebrate-like CRYPTOCHROME 2 from monarch regulates circadian transcription via independent repression of CLOCK and BMAL1 activity [Genetics]

Circadian repression of CLOCK-BMAL1 by PERIOD and CRYPTOCHROME (CRY) in mammals lies at the core of the circadian timekeeping mechanism. CRY repression of CLOCK-BMAL1 and regulation of circadian period are proposed to rely primarily on competition for binding with coactivators on an α-helix located within the transactivation domain (TAD) of...

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Sensitized mutagenesis screen in Factor V Leiden mice identifies thrombosis suppressor loci [Genetics]

Factor V Leiden (F5L) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized N-ethyl-N-nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for F5L (F5L/L) and haploinsufficient for tissue factor pathway inhibitor (Tfpi+/−). F8 deficiency enhanced the...

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Stalled replication forks generate a distinct mutational signature in yeast [Genetics]

Proliferating cells acquire genome alterations during the act of DNA replication. This leads to mutation accumulation and somatic cell mosaicism in multicellular organisms, and is also implicated as an underlying cause of aging and tumorigenesis. The molecular mechanisms of DNA replication-associated genome rearrangements are poorly understood, largely due to methodological...

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Indoles from commensal bacteria extend healthspan [Genetics]

Multiple studies have identified conserved genetic pathways and small molecules associated with extension of lifespan in diverse organisms. However, extending lifespan does not result in concomitant extension in healthspan, defined as the proportion of time that an animal remains healthy and free of age-related infirmities. Rather, mutations that extend lifespan...

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The evolution of human sleep: Technological and cultural innovation associated with sleep-wake regulation among Hadza hunter-gatherers

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Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): David R. Samson, Alyssa N. Crittenden, Ibrahim A. Mabulla, Audax Z.P. Mabulla
Sleep is necessary for the survival of all mammalian life. In humans, recent investigations have generated critical data on the relationship between sleep and ecology in small-scale societies. Here, we report the technological and social strategies used to alter sleep environments and influence sleep duration and quality among a population of hunter-gatherers, the Hadza of Tanzania. Specifically, we investigated the effects that grass huts, sound levels, and fire had on sleep. We quantitatively compared thermal stress in outdoor environments to that found inside grass hut domiciles to test whether the huts function as thermoregulated microhabitats during the rainy season. Using physiological equivalent temperature (PET), we found that the grass huts provide sleep sites with less overall variation in thermal stress relative to outside baseline environments. We also investigated ambient acoustic measures of nighttime environments and found that sound significantly covaried with sleep-wake activity, with greater sound levels associating with less sleep. Finally, after controlling for ecological variables previously shown to influence sleep in this population, fire was shown to neither facilitate nor discourage sleep expression. Insofar as data among contemporary sub-tropical foragers can inform our understanding of past lifeways, we interpret our findings as suggesting that after the transition to full time terrestriality, it is likely that early Homo would have had novel opportunities to manipulate its environments in ways that could have significantly improved sleep quality. We further conclude that control over sleep environment would have been essential for migration to higher latitudes away from equatorial Africa.



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Editorial Board

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Publication date: October 2017
Source:Journal of Human Evolution, Volume 111





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Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks

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Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): Mark Hallett, Riccardo Di Iorio, Paolo Maria Rossini, Jung E Park, Robert Chen, Pablo Celnik, Antonio P. Strafella, Hideyuki Matsumoto, Yoshikazu Ugawa
The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain.



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Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

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Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): Christos Tsiokos, Mahsa Malekmohammadi, Nicholas Au Yong, Nader Pouratian
ObjectiveRecent discoveries suggest that it is most likely the coupling of β oscillations (13-30 Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology.MethodsWe analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia.ResultsWithin GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200-300 Hz) and distinct β-low γ (40-80 Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R=-0.44, P=0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands.ConclusionsPAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal.SignificanceThis study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD.



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The Associative Brain at Work: Evidence from Paired Associative Stimulation Studies in Humans

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Publication date: Available online 5 September 2017
Source:Clinical Neurophysiology
Author(s): A. Suppa, A. Quartarone, H. Siebner, R. Chen, V. Di Lazzaro, P. Del Giudice, Walter Paulus, J.C. Rothwell, U. Ziemann, J. Classen
The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.



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Impaired visuomotor generalization by inconsistent attentional contexts

In daily life, people are constantly presented with situations in which they have to learn and acquire new motor skills in complex environments, where attention is often distracted by other events. Being able to generalize and perform the acquired motor action in different environments is a crucial part of visuomotor learning. The current study examined whether attentional distraction impairs generalization of visuomotor adaptation or whether consistent distraction can operate as an internal cue to facilitate generalization. Using a dual-task paradigm combining visuomotor rotational adaptation and an attention-demanding secondary task, we showed that switching the attentional context from training (dual-task) to generalization (single-task) reduced the range of transfer of visuomotor adaptation to untrained directions. However, when consistent distraction was present throughout training and generalization, visuomotor generalization was equivalent to without distractions at all. Furthermore, this attentional context-dependent generalization was evident even when sensory modality of distractions differed between training and generalization. Therefore, the general nature of the dual tasks, rather than the specific stimuli, is associated with visuomotor memory and serves as a critical cue for generalization. Taken together, we demonstrated that attention plays a critical role during sensorimotor adaptation in selecting and associating multisensory signals with motor memory. This finding provides insight into developing learning programs that are generalizable in complex daily environments.

NEW & NOTEWORTHY Learning novel motor actions in complex environments with attentional distraction is a critical function. Successful motor learning involves the ability to transfer the acquired skill from the trained to novel environments. Here, we demonstrate attentional distraction does not impair visuomotor adaptation. Rather, consistency in the attentional context from training to generalization modulates the degree of transfer to untrained locations. The role of attention and memory must, therefore, be incorporated into existing models of visuomotor learning.



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Vibration over the larynx increases swallowing and cortical activation for swallowing

Sensory input can alter swallowing control in both the cortex and brainstem. Electrical stimulation of superior laryngeal nerve afferents increases reflexive swallowing in animals, with different frequencies optimally effective across species. Here we determined 1) if neck vibration overlying the larynx affected the fundamental frequency of the voice demonstrating penetration of vibration into the laryngeal tissues, and 2) if vibration, in comparison with sham, increased spontaneous swallowing and enhanced cortical hemodynamic responses to swallows in the swallowing network. A device with two motors, one over each thyroid lamina, delivered intermittent 10-s epochs of vibration. We recorded swallows and event-related changes in blood oxygenation level to swallows over the motor and sensory swallowing cortexes bilaterally using functional near infrared spectroscopy. Ten healthy participants completed eight 20-min conditions in counterbalanced order with either epochs of continuous vibration at 30, 70, 110, 150, and 70 + 110 Hz combined, 4-Hz pulsed vibration at 70 + 110 Hz, or two sham conditions without stimulation. Stimulation epochs were separated by interstimulus intervals varying between 30 and 45 s in duration. Vibration significantly reduced the fundamental frequency of the voice compared with no stimulation demonstrating that vibration penetrated laryngeal tissues. Vibration at 70 and at 150 Hz increased spontaneous swallowing compared with sham. Hemodynamic responses to swallows in the motor cortex were enhanced during conditions containing stimulation compared with sham. As vibratory stimulation on the neck increased spontaneous swallowing and enhanced cortical activation for swallows in healthy participants, it may be useful for enhancing swallowing in patients with dysphagia.

NEW & NOTEWORTHY Vibratory stimulation at 70 and 150 Hz on the neck overlying the larynx increased the frequency of spontaneous swallowing. Simultaneously vibration also enhanced hemodynamic responses in the motor cortex to swallows when recorded with functional near-infrared spectroscopy (fNIRS). As vibrotactile stimulation on the neck enhanced cortical activation for swallowing in healthy participants, it may be useful for enhancing swallowing in patients with dysphagia.



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Response preparation and execution during intentional bimanual pattern switching

During continuous bimanual coordination, in-phase (IP; 0° relative phase) and anti-phase (AP; 180° relative phase) patterns can be stably performed without practice. Paradigms in which participants are required to intentionally switch between these coordination patterns have been used to investigate the interaction between the performer's intentions and intrinsic dynamics of the body's preferred patterns. The current study examined the processes associated with switching preparation and execution through the use of a startling acoustic stimulus (SAS) as the switch stimulus. A SAS is known to involuntarily trigger preprogrammed responses at a shortened latency and, thus, can be used to probe advance preparation. Participants performed cyclical IP and AP bimanual elbow extension-flexion movements in which they were required to switch patterns in response to an auditory switch cue, which was either nonstartling (80 dB) or a SAS (120 dB). Results indicated that reaction time to the switch stimulus (i.e., switch onset) was significantly reduced on startle trials, indicative of advance preparation of the switch response. Similarly, switching time was reduced on startle trials, which was attributed to increased neural activation caused by the SAS. Switching time was also shorter for AP to IP trials, but only when the switching stimulus occurred at either the midpoint or reversal locations within the movement cycle, suggesting that the switch location may affect the intrinsic dynamics of the system.

NEW & NOTEWORTHY The current study provides novel information regarding preparation and execution of intentional switching between in-phase and anti-phase bimanual coordination patterns. Using a startling acoustic stimulus, we provide strong evidence that the switching response is prepared before the switch stimulus, and switch execution is accelerated by the startling stimulus. In addition, the time required to switch between patterns and relative limb contribution is dependent upon where in the movement cycle the switch stimulus occurred.



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Impact of glutamatergic and serotonergic neurotransmission on diaphragm muscle activity after cervical spinal hemisection

Incomplete cervical spinal cord hemisection at C2 (SH) disrupts descending excitatory drive to phrenic motoneurons, paralyzing the ipsilateral diaphragm muscle. Spontaneous recovery over time is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-d-aspartate (NMDA) and serotonergic 5-HT2A receptors. We hypothesized that NMDA and 5-HT2A receptor-mediated neurotransmission play a role in ipsilateral diaphragm muscle activity post-SH. Adult male Sprague-Dawley rats were implanted with bilateral diaphragm EMG electrodes for chronic EMG recordings up to 28 days post-SH (SH 28D). The extent of recovery was calculated by peak root-mean-square (RMS) EMG amplitude. In all animals, absence of ipsilateral activity was verified at 3 days post-SH. Diaphragm EMG activity was also recorded during exposure to hypoxia-hypercapnia (10% O2-5% CO2). In SH animals displaying recovery of ipsilateral diaphragm EMG activity at SH 28D, cervical spinal cord segments containing the phrenic motor nucleus (C3–C5) were surgically exposed and either the NMDA receptor antagonist d-2-amino-5-phosphonovalerate (d-AP5; 100 mM, 30 μl) or 5-HT2A receptor antagonist ketanserin (40 mM, 30 μl) was instilled intrathecally. Following d-AP5, diaphragm EMG amplitude was reduced ipsilaterally, during both eupnea (42% of pre-d-AP5 value; P = 0.007) and hypoxia-hypercapnia (31% of pre-d-AP5 value; P = 0.015), with no effect on contralateral EMG activity or in uninjured controls. Treatment with ketanserin did not change ipsilateral or contralateral RMS EMG amplitude in SH animals displaying recovery at SH 28D. Our results suggest that spinal glutamatergic NMDA receptor-mediated neurotransmission plays an important role in ipsilateral diaphragm muscle activity after cervical spinal cord injury.

NEW & NOTEWORTHY Spontaneous recovery following C2 spinal hemisection (SH) is associated with increased phrenic motoneuron expression of glutamatergic and serotonergic receptors. In this study, we show that pharmacological inhibition of glutamatergic N-methyl-d-aspartate (NMDA) receptors blunts ipsilateral diaphragm activity post-SH. In contrast, pharmacological inhibition of serotonergic 5-HT2A receptors does not change diaphragm EMG activity post-SH. Our results suggest that NMDA receptor-mediated glutamatergic neurotransmission plays an important role in enhancing rhythmic respiratory-related diaphragm activity after spinal cord injury.



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Aging does not affect the intralimb coordination elicited by slip-like perturbation of different intensities

This study was aimed at verifying whether aging modifies intralimb coordination strategy during corrective responses elicited by unexpected slip-like perturbations delivered during steady walking on a treadmill. To this end, 10 young and 10 elderly subjects were asked to manage unexpected slippages of different intensities. We analyzed the planar covariation law of the lower limb segments, using the principal component analysis, to verify whether elevation angles of older subjects covaried along a plan before and after the perturbation. Results showed that segments related to the perturbed limbs of both younger and older people do not covary after all perturbations. Conversely, the planar covariation law of the unperturbed limb was systematically held for younger and older subjects. These results occurred despite differences in spatio-temporal and kinematic parameters being observed among groups and perturbation intensities. Overall, our analysis revealed that aging does not affect intralimb coordination during corrective responses induced by slip-like perturbation, suggesting that both younger and older subjects adopt this control strategy while managing sudden and unexpected postural transitions of increasing intensities. Accordingly, results corroborate the hypothesis that balance control emerges from a governing set of biomechanical invariants, that is, suitable control schemes (e.g., planar covariation law) shared across voluntary and corrective motor behaviors, and across different sensory contexts due to different perturbation intensities, in both younger and older subjects. In this respect, our findings provide further support to investigate the effects of specific task training programs to counteract the risk of fall.

NEW & NOTEWORTHY This study was aimed at investigating how aging affects the intralimb coordination of lower limb segments, described by the planar covariation law, during unexpected slip-like perturbations of increasing intensity. Results revealed that neither the aging nor the perturbation intensity affects this coordination strategy. Accordingly, we proposed that the balance control emerges from an invariant set of control schemes shared across different sensory motor contexts and despite age-related neuromuscular adaptations.



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Evidence of adaptations of locomotor neural drive in response to enhanced intermuscular connectivity between the triceps surae muscles of the rat

The aims of this study were to investigate changes 1) in the coordination of activation of the triceps surae muscle group, and 2) in muscle belly length of soleus (SO) and lateral gastrocnemius (LG) during locomotion (trotting) in response to increased stiffness of intermuscular connective tissues in the rat. We measured muscle activation and muscle belly lengths, as well as hindlimb kinematics, before and after an artificial enhancement of the connectivity between SO and LG muscles obtained by implanting a tissue-integrating surgical mesh at the muscles' interface. We found that SO muscle activation decreased to 62%, while activation of LG and medial gastrocnemius muscles increased to 134 and 125%, respectively, compared with the levels measured preintervention. Although secondary additional or amplified activation bursts were observed with enhanced connectivity, the primary pattern of activation over the stride and the burst duration were not affected by the intervention. Similar muscle length changes after manipulation were observed, suggesting that length feedback from spindle receptors within SO and LG was not affected by the connectivity enhancement. We conclude that peripheral mechanical constraints given by morphological (re)organization of connective tissues linking synergists are taken into account by the central nervous system. The observed shift in activity toward the gastrocnemius muscles after the intervention suggests that these larger muscles are preferentially recruited when the soleus has a similar mechanical disadvantage in that it produces an unwanted flexion moment around the knee.

NEW & NOTEWORTHY Connective tissue linkages between muscle-tendon units may act as an additional mechanical constraint on the musculoskeletal system, thereby reducing the spectrum of solutions for performing a motor task. We found that intermuscular coordination changes following intermuscular connectivity enhancement. Besides showing that the extent of such connectivity is taken into account by the central nervous system, our results suggest that recruitment of triceps surae muscles is governed by the moments produced at the ankle-knee joints.



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Fluorocitrate-mediated depolarization of astrocytes in the retrotrapezoid nucleus stimulates breathing

Evidence indicates that CO2/H+-evoked ATP released from retrotrapezoid nucleus (RTN) astrocytes modulates the activity of CO2-sensitive neurons. RTN astrocytes also sense H+ by inhibition of Kir4.1 channels; however, the relevance of this pH-sensitive current remains unclear since ATP release appears to involve CO2-dependent gating of connexin 26 hemichannels. Considering that depolarization mediated by H+ inhibition of Kir4.1 channels is expected to increase sodium bicarbonate cotransporter (NBC) conductance and favor Ca2+ influx via the sodium calcium exchanger (NCX), we hypothesize that depolarization in the presence of CO2 is sufficient to facilitate ATP release and enhance respiratory output. Here, we confirmed that acute exposure to fluorocitrate (FCt) reversibly depolarizes RTN astrocytes and increased activity of RTN neurons by a purinergic-dependent mechanism. We then made unilateral injections of FCt into the RTN or two other putative chemoreceptor regions (NTS and medullary raphe) to depolarize astrocytes under control conditions and during P2-recepetor blockade while measuring cardiorespiratory activities in urethane-anesthetized, vagotomized, artificially ventilated male Wistar rats. Unilateral injection of FCt into the RTN increased phrenic (PNA) amplitude and frequency without changes in arterial pressure. Unilateral injection of pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate (PPADS, a P2-receptor antagonist) into the RTN dampened both PNA amplitude and frequency responses to FCt. Injection of MRS2179 (P2Y1-receptor antagonist) into the RTN did not affect the FCt-induced respiratory responses. Fluorocitrate had no effect on breathing when injected into the NTS or raphe. These results suggest that depolarization can facilitate purinergic enhancement of respiratory drive from the RTN.

NEW & NOTEWORTHY Astrocytes in the retrotrapezoid nucleus (RTN) are known to function as respiratory chemoreceptors; however, it is not clear whether changes in voltage contribute to astrocyte chemoreception. We showed that depolarization of RTN astrocytes at constant CO2 levels is sufficient to modulate RTN chemoreception by a purinergic-dependent mechanism. These results support the possibility that astrocyte depolarization can facilitate purinergic enhancement of respiratory drive from the RTN.



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Top EMS Game Changers – #7: Intraosseous access

2003 AHA guidelines noted IOs provide a favorable alternative to traditional IV techniques for fluid and medication administration

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Are you fit enough to be a tactical medic? Test yourself with these 8 SWAT fitness exercises

TEMS medics need to be in top physical condition to respond with and care for SWAT officers

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How to prevent, manage knee pain in EMS

A few simple screening tools and stretches can strengthen muscles and prevent knee pain and more serious injury in at-risk EMS providers

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Effects of dominant and non-dominant passive arm manoeuvres on the neurovascular coupling response

Abstract

Purpose

Models designed to study neurovascular coupling (NVC) describe a possible cerebral hemisphere dominance dependent on task completed and preference in handedness. We investigated whether passive arm manoeuvre performed with dominant (Dom-Arm) or non-dominant arm (ND-Arm) stimulated haemodynamic differences in either contralateral (Cont-H) or ipsilateral (Ipsil-H) cerebral hemisphere.

Methods

Healthy individuals lying in supine position, had measurements of beat-to-beat blood pressure (BP, mmHg), electrocardiogram (HR, bpm), end-tidal CO2 (etCO2, mmHg), and bilateral insonation of the middle cerebral arteries (MCA, cm s−1). Arm movement was performed for 60 s with passive flexion and extension of the elbow (1 Hz), before manoeuvre was repeated on other arm. Data were normalised and effect of treatment was analysed for differences between manoeuvres and within each time period.

Results

Seventeen (eight males) healthy volunteers, aged 56 ± 7 years, were studied. Dom-Arm and ND-Arm manoeuvres stimulated a comparable temporal response in peripheral and cerebral haemodynamic parameters between Cont-H and Ipsil-H.

Conclusions

Both manoeuvres can be used to evoke similar bilateral MCA responses in assessing NVC. This finding should lead to more efficient protocols when using passive arm movement for NVC studies in healthy subjects.



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Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis

Abstract
Background. To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain.Methods. We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2–4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain.Results. Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate.Conclusions. Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.

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Neuropathic pain in cancer: systematic review, performance of screening tools and analysis of symptom profiles

Abstract
Background: The objectives of this study were to evaluate the methodological quality of rigorous neuropathic pain assessment tools in applicable clinical studies, and determine the performance of screening tools for identifying neuropathic pain in patients with cancer.Methods: Systematic literature search identified studies reporting use of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Douleur Neuropathique en 4 (DN4) or painDETECT (PDQ) in cancer patients with a clinical diagnosis of neuropathic or not neuropathic pain. Individual patient data were requested to examine descriptor item profiles.Results: Six studies recruited a total of 2301 cancer patients of which 1564 (68%) reported pain. Overall accuracy of screening tools ranged from 73 to 94%. There was variation in description and rigour of clinical assessment, particularly related to the rigour of clinical judgement of pain as the reference standard. Individual data from 1351 patients showed large variation in the selection of neuropathic pain descriptor items by cancer patients with neuropathic pain. LANSS and DN4 items characterized a significantly different neuropathic pain symptom profile from non-neuropathic pain in both tumour- and treatment-related cancer pain aetiologies.Conclusions: We identified concordance between the clinician diagnosis and screening tool outcomes for LANSS, DN4 and PDQ in patients with cancer pain. Shortcomings in relation to standardized clinician assessment are likely to account for variation in screening tool sensitivity, which should include the use of the neuropathic pain grading system. Further research is needed to standardize and improve clinical assessment in patients with cancer pain. Until the standardization of clinical diagnosis for neuropathic cancer pain has been validated, screening tools offer a practical approach to identify potential cases of neuropathic cancer pain.

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Non-steroidal anti-inflammatory drugs in the oncological surgical population: beneficial or harmful? A systematic review of the literature

Abstract
Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesic drugs. Recent studies have indicated a potential beneficial effect on long-term survival outcomes after cancer surgery but a negative impact on anastomotic leaks. The objective of this study was to objectively assess the implications of the perioperative NSAIDs use on anastomotic leaks and cancer recurrence.Methods: We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to mid-January 2017. Randomized controlled trials (RCTs) and observational studies in adults undergoing cancer surgery were included for quality assessment. We excluded animal studies, in vitro experiments and case reports. The selected sudies were graded using the Jadad score or Newcastle–Ottawa scale for RCTs and observational retrospective studies, respectively.Results: The systematic review identified 25 trials that explored the impact of NSAIDs on anastomotic leaks and 16 trials that assessed the association between perioperative NSAIDs and cancer recurrence. Meta-analyses were not performed because of high heterogeneity and low quality of the included studies.Conclusions: The literature is not conclusive on whether the use of NSAIDs is associated with anastomotic leaks after gastrointestinal cancer surgery. Also, the current evidence is equivocal regarding the effects of short-term NSAIDs on cancer recurrence after major cancer surgery. Three RCTs are being conducted to assess the impact of NSAIDs on cancer recurrence. There are no registered RCTs that are testing the hypothesis of whether the perioperative use of NSAIDs increases the rate of anastomotic leaks.

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Airborne radionuclides in the proglacial environment as indicators of sources and transfers of soil material

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Edyta Łokas, Przemysław Wachniew, Paweł Jodłowski, Michał Gąsiorek
A survey of artificial (137Cs, 238Pu, 239+240Pu, 241Am) and natural (226Ra, 232Th, 40K, 210Pb) radioactive isotopes in proglacial soils of an Arctic glacier have revealed high spatial variability of activity concentrations and inventories of the airborne radionuclides. Soil column 137Cs inventories range from below the detection limit to nearly 120 kBq m−2, this value significantly exceeding direct atmospheric deposition. This variability may result from the mixing of materials characterised by different contents of airborne radionuclides. The highest activity concentrations observed in the proglacial soils may result from the deposition of cryoconites, which have been shown to accumulate airborne radionuclides on the surface of glaciers. The role of cryoconites in radionuclide accumulation is supported by the concordant enrichment of the naturally occurring airborne 210Pb in proglacial soil cores showing elevated levels of artificial radionuclides. The lithogenic radionuclides show less variability than the airborne radionuclides because their activity concentrations are controlled only by the mixing of material derived from the weathering of different parent rocks. Soil properties vary little within and between the profiles and there is no unequivocal relationship between them and the radionuclide contents. The inventories reflect the pathways and time variable inputs of soil material to particular sites of the proglacial zone. Lack of the airborne radionuclides reflects no deposition of material exposed to the atmosphere after the 1950s or its removal by erosion. Inventories above the direct atmospheric deposition indicate secondary deposition of radionuclide-bearing material. Very high inventories indicate sites where transport pathways of cryoconite material terminated.



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The phenylephrine concentration-response relationship for blood pressure after nasal delivery in children.

Related Articles

The phenylephrine concentration-response relationship for blood pressure after nasal delivery in children.

Paediatr Anaesth. 2017 Sep 04;:

Authors: Anderson BJ, Christensen LK, Armstead VE, Bilyeu DP, Johnson KE, Friesen RH

Abstract
BACKGROUND: Intranasal phenylephrine is commonly used to vasoconstrict the nasal mucosa, reducing bleeding associated with nasotracheal intubation or endoscopic sinus surgery. There are few data quantifying either absorption pharmacokinetics or phenylephrine concentration effect on blood pressure in children.
METHODS: Published observations of plasma concentration and blood pressure changes after phenylephrine nasal administration (0.1 mL kg(-1) , 0.25% or 0.5%) in children (n = 52, 2-12 years, 10-40 kg) were pooled with those in adults (23-81 years) given phenylephrine 2.5% (n = 10) and 10% (n = 10) eyedrops. Further pharmacokinetic (PK) data were available from healthy volunteers given oral phenylephrine 10 mg alone, with blood for concentration assay taken at 5, 15, 30, 45 minutes and 1, 2, 3, 6 hours (n = 28). Intravenous time-concentration data were available from four healthy volunteers given phenylephrine 1 mg and who had blood taken for assay on 17 occasions over the subsequent 4 hours. Data were analyzed using an integrated pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed-effects models. Allometry, scaled to a 70-kg person, was used for PK size standardization. Effect was described using an EMAX model.
RESULTS: A two-compartment model was used to fit PK data while an additional compartment, linked by an equilibration half-time (T1/2 keo), was used to describe effect. PK parameter estimates for the nasal formulation were clearance (CL) 160 L h(-1) , central volume of distribution (V1) 13.3 L, intercompartment clearance (Q) 25.3 L h(-1) , peripheral volume of distribution (V2) 225 L, absorption half-time (Tabs) 6.2 minutes, absorption lag time (Tlag) 1.5 minutes, and bioavailability (F) 0.183. Bioavailability and absorption of the ophthalmic solution were concentration dependent (F 0.13, Tabs 5.5 minutes for 2.5% solution; F 0.15, Tabs 9.6 minutes for 10% solution). Absorption of the oral formulation was slow (Tabs 48 minutes) with poor bioavailability (F 0.0128). The pediatric PD interrogation revealed a baseline mean arterial pressure of 60 mm Hg, a maximum effect (EMAX ) of 25 mm Hg, and an EC50 of 10.3 μg L(-1) . The effect on vasculature was immediate and T1/2 keo was not estimable.
CONCLUSION: Absorption of phenylephrine through the nasal mucosa was rapid and similar to the ophthalmic formulation. Bioavailability was also similar to the ophthalmic formulation. The maximum effect (EMAX ) in children was half that in adults (EMAX 50 mm Hg).

PMID: 28868789 [PubMed - as supplied by publisher]



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Tissue iron quantification in chronic liver diseases using MRI shows a relationship between iron accumulation in liver, spleen, and bone marrow

Clinical Radiology

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Only 3.3% of emergency room visits are 'avoidable,' study says

Healthcare Finance News

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Molecular characterization of hepatitis B virus in Vietnam

BMC Infectious Diseases

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CVS Caremark suffers envelope breach of HIV information as Aetna faces lawsuit for similar issue

Healthcare Finance News

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Long-term outcomes of patients with early gastric cancer found to have lesions for which endoscopic treatment is not indicated on histopathological evaluation after endoscopic submucosal dissection

Surgical Endoscopy

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Use of biologic therapy by pregnant women with inflammatory bowel disease does not affect infant response to vaccines

Clinical Gastroenterology and Hepatology

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Gastric bypass surgery does not increase the risk for sight-threatening diabetic retinopathy

Acta Ophthalmologica

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Therapy of GERD and FD overlap with symptoms after usual-dose PPI: Acotiamide plus usual-dose PPI vs. double-dose PPI

Journal of Gastroenterology and Hepatology

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An evidence-based approach to the surgical interventions for severe pancreatic fistula after pancreatoduodenectomy

The Surgeon

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Systematic review with meta-analysis: The association between hepatitis E seroprevalence and haemodialysis

Alimentary Pharmacology and Therapeutics

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Optimal lymphadenectomy in small bowel neuroendocrine tumors: Analysis of the NCDB

Journal of Gastrointestinal Surgery

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Association between inflammatory diet pattern and risk of colorectal carcinoma subtypes classified by immune responses to tumor

Gastroenterology

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Most physical therapists face sexual harassment from patients

Reuters Health News

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Role of age and race in the risk of hepatocellular carcinoma in veterans with hepatitis B virus infection

Clinical Gastroenterology and Hepatology

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Serum CA19-9 response is an early predictive marker of efficacy of regorafenib in refractory metastatic colorectal cancer

Oncology

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Temporal trends, clinical patterns, and outcomes of NAFLD-related HCC in patients undergoing liver resection over a 20-year period

Alimentary Pharmacology and Therapeutics

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MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans

Neurogastroenterology & Motility

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Relationship between serum HBV RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients

Journal of Hepatology

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Infrahepatic inferior vena cava clamping with Pringle maneuvers for laparoscopic extracapsular enucleation of giant liver hemangiomas

Surgical Endoscopy

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Association of covered metallic stents with cholecystitis and stent migration in malignant biliary stricture

Gastrointestinal Endoscopy

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