Τετάρτη, 2 Αυγούστου 2017

A case of atypical Kabuki syndrome arising from a novel missense variant in HNRNPK

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A novel causative variant (c. 464T>C, p.Leu155Pro) in the heterogeneous nuclear ribonucleoprotein K (HNRNPK) gene.



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Emerging Evidence for the Association Between Non-Alcoholic Fatty Liver Disease and Cardiac Arrhythmias.



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The Temporal Stability of Visuomotor Adaptation Generalization

Movement adaptation in response to systematic motor perturbations exhibits distinct spatial and temporal properties. These characteristics are typically studied in isolation, leaving the interaction largely unknown. Here, we examined how the temporal decay of visuomotor adaptation influences the spatial generalization of the motor recalibration. First, we quantified the extent adaptation decayed over time. Subjects reached to a peripheral target and a rotation was applied to the visual feedback of the unseen motion. The retention of this adaptation over different delays (0 to 120 seconds) (1) decreased by 29.0 ± 6.8% at the longest delay, and (2) was represented by a simple exponential, with a time constant of 22.5 ± 5.6 seconds. Based on this relationship we simulated how the spatial generalization of adaptation would change with delay. To test this directly, we trained additional subjects with the same perturbation and assessed transfer to 19 different locations (spaced 15 degrees apart, symmetric around the trained location) and examined three delays (approximately 4, 12 and 25 sec). Consistent with the simulation, we found that generalization around the trained direction (± 15 degrees) significantly decreased with delay and distance, while locations > 60 degrees displayed near constant spatiotemporal transfer. Intermediate distances (30 and 45 degrees) showed a difference in transfer across space, but this amount was approximately constant across time. Interestingly, the decay at the trained direction was faster than that based purely on time suggesting that the spatial transfer of adaptation is modified by concurrent passive (time-dependent) and active (movement-dependent) processes.



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Altered tactile sensitivity in children with Attention Deficit Hyperactive Disorder

ADHD is characterized by an inability to concentrate, heightened activity, and hypermotoric behavior, but sensory, e.g. tactile, problems are common. The literature on tactile impairments in ADHD is limited, with most work employing clinical observations or questionnaires. Here, we study tactile processing in children with ADHD, and hypothesize that children with ADHD show reduced performance in tasks closely linked to inhibition. Sixty seven children with ADHD and 62 typically developing children performed a battery of tasks grouped in domains: simple and choice reaction time; static and dynamic detection threshold (probing feed-forward inhibition); amplitude discrimination without adaptation, and with dual, and single-site adaptation (probing lateral inhibition and adaptation); sequential and simultaneous frequency discrimination (previously linked to GABA); and temporal order judgment with and without a synchronous carrier stimulus. Children with ADHD could discriminate different amplitudes without adaptation suggesting lateral inhibition is intact, but were negatively affected in all adaptation conditions whereas TDC were only affected during single-site adaptation. Children with ADHD also showed normal frequency discrimination. Children with ADHD showed slower reaction times and higher detection threshold, likely driven by IQ and inattention, as reaction time and detection thresholds correlated with IQ and subtle motor signs. Children with ADHD show a pattern of altered tactile processing on specific tasks, suggesting that higher cognitive function and cortical mechanisms related to adaptation are affected in ADHD, but no clear conclusion can be drawn towards impaired inhibition.



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Theta-frequency selectivity in the somatic spike triggered average of rat hippocampal pyramidal neurons is dependent on HCN channels

The ability to distill specific frequencies from complex spatiotemporal patterns of afferent inputs is a pivotal functional requirement for neurons residing in networks receiving frequency-multiplexed inputs. Although the expression of theta-frequency subthreshold resonance is established in hippocampal pyramidal neurons, it is not known if their spike initiation dynamics manifest spectral selectivity or if their intrinsic properties are tuned to process gamma-frequency inputs. Here, we measured the spike-triggered average (STA) of rat hippocampal pyramidal neurons through electrophysiological recordings and quantified spectral selectivity in their spike initiation dynamics and their coincidence detection window (CDW). Our results revealed strong theta-frequency selectivity in the STA, which was also endowed with gamma-range CDW, with prominent neuron-to-neuron variability that manifested distinct pairwise dissociations and correlations with different intrinsic measurements. Furthermore, we demonstrate that the STA and its measurements substantially adapted to the state of the neuron defined by its membrane potential and to the statistics of its afferent inputs. Finally, we tested the effect of pharmacologically blocking the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels on the STA and found that the STA characteristic frequency reduced significantly to the delta-frequency band after HCN-channel blockade. This delta-frequency selectivity in the STA emerged in the absence of subthreshold resonance, which was abolished by HCN-channel blockade, thereby confirming computational predictions on the dissociation between these two forms of spectral selectivity. Our results expand the roles of HCN channels to theta-frequency selectivity in the spike initiation dynamics, apart from underscoring the critical role of interactions among different ion channels in regulating neuronal physiology.



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A latent low-dimensional common input drives a pool of motor neurons: a probabilistic latent state-space model

Motor neurons appear to be activated with a common input signal that modulates the discharge activity of all neurons in the motor nucleus. It has proven difficult for neurophysiologists to quantify the variability in a common input signal, but characterization of this signal may improve our understanding of how the activation signal varies across motor tasks. Contemporary methods of quantifying the common input to motor neurons relies on compiling discrete action potentials into continuous signals, assuming the motor pool acts as a linear filter, and requiring signals to be of sufficient duration. We introduce a space-state model in which the discharge activity of motor neurons is modeled as inhomogeneous Poisson processes and propose a method to quantify a latent trajectory that represents the common input received by motor neurons. The approach also approximates the synaptic noise in the common input signal. The model is validated with four datasets: a simulation of 120 motor units, a pair of integrate-and-fire neurons with a Renshaw cell providing inhibitory feedback, the discharge activity of 10 integrate-and-fire neurons, and the discharge times of concurrently active motor units during an isometric voluntary contraction. The simulations revealed that a latent state-space model can quantify the trajectory and variability of the common input signal across all four conditions. When compared with the cumulative spike train method, the state-space approach was more sensitive and was less influenced by the duration of the signal. The state-space approach appears capable of detecting rather modest changes in common input signals across conditions.



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Multiple spatial representations interact to increase reach accuracy when coordinating a saccade with a reach

Reaching is an essential behavior that allows primates to interact with the environment. Precise reaching to visual targets depends on our ability to localize and foveate the target. Despite this, how the saccade system contributes to improvements in reach accuracy remains poorly understood. To assess spatial contributions of eye movements to reach accuracy, we performed a series of behavioral psychophysics experiments in non-human primates (M. mulatta). We found that a coordinated saccade with a reach to a remembered target location increases reach accuracy without target foveation. The improvement in reach accuracy was similar to that obtained when the subject had visual information about the current target's location in the visual periphery and executed the reach while maintaining central fixation. Moreover, we found that the increase in reach accuracy elicited by a coordinated movement involved a spatial coupling mechanism between the saccade and reach movements. We observed significant correlations between the saccade and reach errors for coordinated movements. In contrast, when the eye and arm movements were made to targets in different spatial locations, the magnitude of the error, and the degree of correlation between the saccade and reach direction was determined by the spatial location of the eye and the hand targets. Hence, we propose that coordinated movements improve reach accuracy without target foveation, due to spatial coupling between the reach and saccade systems. Spatial coupling could arise from a neural mechanism for coordinated visual behavior that involves interacting spatial representations.



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Mechanisms for shaping receptive field in monkey area TE

Visual object information is conveyed from V1 to area TE along the ventral visual pathway with increasing receptive field (RF) sizes. The RFs of TE neurons are known to be large, but it is largely unknown how large RFs are shaped along the ventral visual pathway. Here, we addressed this question in two aspects, static and dynamic mechanisms, by recording neural responses from macaque area TE and V4 to object stimuli presented at various locations in the visual field. As a component related to static mechanisms, we found that, in area TE but not in V4, response latency to objects presented at fovea were different from objects in periphery. As a component of the dynamic mechanisms, we examined effects of spatial attention on the RFs of TE neurons. Spatial attention did not affect response latency, but modulated response magnitudes depending on attended location, shifting of the longitudinal axis of RFs toward the attended locations. In standard models of large RF formation, downstream neurons pool information from nearby RFs, and this process is repeated across the visual field and at each step along the ventral visual pathway. The present study revealed that this mechanism is not that simple: (1) different circuit mechanisms for foveal and peripheral visual fields may be situated between V4 and area TE, and (2) spatial attention dynamically changes shape of RFs.



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Intercepting virtual balls approaching under different gravity conditions: evidence for spatial prediction

To accurately time motor responses when intercepting falling balls we rely on an internal model of gravity. However, whether and how such a model is also used to estimate the spatial location of interception is still an open question. Here, we addressed this issue by asking 25 participants to intercept balls projected from a fixed location 6 m in front of them and approaching along trajectories with different arrival locations, flight durations, and gravity accelerations (0g and 1g). The trajectories were displayed in an immersive virtual reality system with a wide field of view. Participants intercepted approaching balls with a racket and they were free to choose the time and place of interception. We found that participants often achieved a better performance with 1g than 0g balls. Moreover, the interception points were distributed along the direction of a 1g path for both 1g and 0g balls. In the latter case, interceptions tended to cluster on the upper half of the racket, indicating that participants aimed at a lower position than the actual 0g path. These results suggest that an internal model of gravity was probably used in predicting the interception locations. However, we found that the difference in performance between 1g and 0g balls was modulated by flight duration, the difference being larger for faster balls. In addition, the number of peaks in the hand speed profiles increased with flight duration suggesting that visual information was used to adjust the motor response, correcting the prediction to some extent.



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Altered modulation of sensorimotor rhythms with chronic paralysis

After paralysis, the disconnection between the cortex and its peripheral targets leads to neuroplasticity throughout the nervous system. However, it is unclear how chronic paralysis specifically impacts cortical oscillations associated with attempted movement of impaired limbs. We hypothesized that mu (8-13Hz) and beta (15-30Hz) event-related desynchronization (ERD) would be less modulated for individuals with hand paralysis due to cervical spinal cord injury (SCI). To test this, we compared the modulation of ERD from magnetoencephalography (MEG) during attempted and imagined grasping performed by participants with cervical SCI (n = 12) and able-bodied controls (n = 13). Seven participants with tetraplegia were able to generate some electromyography (EMG) activity during attempted grasping, while the other five were not. The peak and area of ERD were significantly decreased for individuals without volitional muscle activity when they attempted to grasp compared to able-bodied subjects and participants with SCI with some residual EMG activity. However, no significant differences were found between subject groups during mentally simulated tasks (i.e. motor imagery) where no muscle activity or somatosensory consequences were expected. These findings suggest that individuals who are unable to produce muscle activity are capable of generating ERD when attempting to move, but the characteristics of this ERD are altered. However, for people who maintain volitional muscle activity after SCI, there are no significant differences in ERD characteristics compared to able-bodied controls. These results provide evidence that ERD is dependent on the level of intact muscle activity after SCI.



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The influence of pain on motor preparation in the human brain

The protective function of pain depends on appropriate motor responses to avoid injury and promote recovery. The preparation and execution of motor responses is, thus, an essential part of pain. However, it is not yet fully understood how pain and motor processes interact in the brain. We here used electroencephalography to investigate the effects of pain on motor preparation in the human brain. 20 healthy human participants performed a motor task in which they performed button presses to stop increasingly painful thermal stimuli when they became intolerable. In another condition, participants performed button presses without concurrent stimulation. The results show that the amplitudes of preparatory event-related desynchronizations at alpha and beta frequencies did not differ between conditions. In contrast, the amplitude of the preparatory readiness potential was reduced when a button press was performed to stop a painful stimulus as compared to a button press without concomitant pain. A control experiment with non-painful thermal stimuli showed a similar reduction of the readiness potential when a button press was performed to stop a non-painful thermal stimulus. Together, these findings indicate that painful and non-painful thermal stimuli can similarly influence motor preparation in the human brain. Pain-specific effects on motor preparation in the human brain remain to be demonstrated.



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Pre-movement planning processes in people with congenital mirror movements

Congenital mirrormovements (CMM), a disorder characterised by unintentional mirroring of motor systems on the contralateral side of voluntary movements, usually of the hands and wrists, is regarded as a rare condition of human movement (Schott and Wyke, 1981); its prevalence is unknown. CMM can be difficult to detect due to its isolated occurrence in the distal portions of the upper limbs in most individuals affected, and in particular, because there are no other known comorbidities (Franz, 2003; Franz et al., 2015).

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Emerging Evidence for the Association Between Non-Alcoholic Fatty Liver Disease and Cardiac Arrhythmias.



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Accelerating Wright-Fisher Forward Simulations on the Graphics Processing Unit

Forward Wright-Fisher simulations are powerful in their ability to model complex demography and selection scenarios, but suffer from slow execution on the CPU, thus limiting their usefulness. The single-locus Wright-Fisher forward algorithm is, however, exceedingly parallelizable, with many steps which are so-called embarrassingly parallel, consisting of a vast number of individual computations that are all independent of each other and thus capable of being performed concurrently. The rise of modern Graphics Processing Units (GPUs) and programming languages designed to leverage the inherent parallel nature of these processors have allowed researchers to dramatically speed up many programs that have such high arithmetic intensity and intrinsic concurrency. The presented GPU Optimized Wright-Fisher simulation, or GO Fish for short, can be used to simulate arbitrary selection and demographic scenarios while running over 250-fold faster than its serial counterpart on the CPU. Even modest GPU hardware can achieve an impressive speedup of over two orders of magnitude. With simulations so accelerated, one can not only do quick parametric bootstrapping of previously estimated parameters, but also use simulated results to calculate the likelihoods and summary statistics of demographic and selection models against real polymorphism data - all without restricting the demographic and selection scenarios that can be modeled or requiring approximations to the single-locus forward algorithm for efficiency. Further, as many of the parallel programming techniques used in this simulation can be applied to other computationally intensive algorithms important in population genetics, GO Fish serves as an exciting template for future research into accelerating computation in evolution. GO Fish is part of the Parallel PopGen Package available at: http://ift.tt/2vrgFUF



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Effects of anaesthesia and analgesia on long-term outcome after total knee replacement: A prospective, observational, multicentre study.

BACKGROUND: Perioperative regional anaesthesia may protect from persistent postsurgical pain (PPSP) and improve outcome after total knee arthroplasty (TKA). OBJECTIVES: Aim of this study was to evaluate the impact of regional anaesthesia on PPSP and long-term functional outcome after TKA. DESIGN: A web-based prospective observational registry. SETTING: Five Italian Private and University Hospitals from 2012 to 2015. PATIENTS: Undergoing primary unilateral TKA, aged more than 18 years, informed consent, American Society of Anesthesiologists (ASA) physical status classes 1 to 3, no previous knee surgery. INTERVENTION(S): Personal data (age, sex, BMI and ASA class), preoperative pain assessed by numerical rating scale (NRS) score, and risk factors for PPSP were registered preoperatively. Data on anaesthetic and analgesic techniques were collected. Postoperative pain (NRS), analgesic consumption, major complications and patient satisfaction were registered up to the time of discharge. PPSP was assessed by a blinded investigator during a phone call after 1, 3 and 6 months, together with patient satisfaction, quality of life (QOL) and walking ability. MAIN OUTCOME MEASURES: Experience of PPSP according to the type of peri-operative analgesia. RESULTS: Five hundred sixty-three patients completed the follow-up. At 6 months, 21.6% of patients experienced PPSP, whereas autonomy was improved only in 56.3%; QOL was worsened or unchanged in 30.7% of patients and improved in 69.3%. Patients receiving continuous regional anaesthesia (epidural or peripheral nerve block) showed a lower NRS through the whole peri-operative period up to 1 month compared with both single shot peripheral nerve block and those who did not receive any type of regional anaesthesia. No difference was found between these latter two groups. Differences in PPSP at 3 or 6 months were not significantly affected by the type of anaesthesia or postoperative analgesia. A higher NRS score at 1 month, younger age, history of anxiety or depression, pro-inflammatory status, higher BMI and a lower ASA physical status were associated with a higher incidence of PPSP and worsened QOL at 6 months. CONCLUSION: Continuous regional anaesthesia provides analgesic benefit for up to 1 month after surgery, but did not influence PPSP at 6 months. Better pain control at 1 month was associated with reduced PPSP. Patients with higher expectations from surgery, enhanced basal inflammation and a pessimistic outlook are more prone to develop PPSP. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02147730 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP (C) 2017 European Society of Anaesthesiology

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Respiratory Mechanical and Cardiorespiratory Consequences of Cycling with Aerobars.

Purpose: Aerobars place a cyclist in a position where the trunk is flexed forward and the elbows are close to the midline of the body. This position is known to improve cycling aerodynamics and time trial race performance compared to upright cycling positions. However, the aggressive nature of this position may have important cardiorespiratory and metabolic consequences. The purpose of this investigation was to examine the respiratory mechanical, ventilatory, metabolic, and sensory consequences of cycling while using aerobars during laboratory based cycling. Methods: Eleven endurance trained male cyclists (age=26+/-9 years, V[Combining Dot Above]O2peak=55+/-5 ml/kg/min) were recruited. Visit 1 consisted of an incremental cycling test to determine peak power output. Visit 2 consisted of 6-minute bouts of constant load cycling at 70% of peak incremental power output in the aerobar position, drop position, and upright position while grasping the brake hoods. Metabolic and ventilatory responses were measured using a commercially available metabolic cart and respiratory pressures were measured using an esophageal catheter. Results: Cycling in the aerobar position significantly increased the work of breathing (Wb), power of breathing (Pb), minute ventilation, ventilatory equivalent for oxygen and carbon dioxide, and transdiaphragmatic pressure compared to the upright position. Increases in the Wb and Pb in the aerobars relative to the upright position were strongly correlated with the degree of thoracic restriction, measured as the shoulder-to-aerobar width ratio (Wb: r=0.80, p=0.01; Pb: r=0.69, p=0.04). Conclusions: Aerobars significantly increase the mechanical cost of breathing and leads to greater ventilatory inefficiency compared to upright cycling. Future work is needed to optimize aerobar width to minimize the respiratory mechanical consequences while optimizing aerodynamics. (C) 2017 American College of Sports Medicine

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Endurance Exercise Attenuates Postprandial Whole-Body Leucine Balance in Trained Men.

Purpose: Endurance exercise increases indices of small intestinal damage and leucine oxidation, which may attenuate dietary amino acid appearance and postprandial leucine balance during postexercise recovery. Therefore, the purpose of this study was to examine the impact of an acute bout of endurance exercise on postprandial leucine kinetics and net leucine balance. Methods: In a crossover design, seven trained young men (age = 25.6 +/- 2.3 y; VO2peak = 61.4 +/- 2.9 ml[middle dot]kg-1[middle dot]min-1; mean +/- SEM) received a primed constant infusion of L-[1-13C]leucine before and after ingesting a mixed macronutrient meal containing 18 g whole egg protein intrinsically labeled with L-[5,5,5-2H3]leucine, 17 g fat, and 60 g carbohydrate at rest and after 60 min of treadmill running at 70% VO2peak. Results: Plasma intestinal fatty acid binding protein concentrations and leucine oxidation both increased (P

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Comparison of Lower Limb and Back Exercises for Runners with Chronic Low Back Pain.

Introduction: This single-blind randomized trial was conducted to compare the treatment effect of lower limb (LL) exercises versus conventional lumbar extensor (LE) and lumbar stabilization (LS) exercises in recreational runners with chronic low back pain (cLBP), since there is currently no specific protocol for managing runners with cLBP. Methods: 84 recreational runners with cLBP were allocated to three exercise groups (LL, LE, LS) for an 8-week intervention. Outcome measures included self-rated pain and running capability, lower limb strength, back muscles function, and running gait. Participants were assessed at pre-, mid- and end-intervention; selected outcomes also followed up at three and six months. Generalized estimating equation was adopted to examine group-by-time interaction. Results: LL group improved 0.949 points per time point in Patient Specific Functional Scale (p

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Exercise Protects Skeletal Muscle during Chronic Doxorubicin Administration.

PURPOSE: To assess the ability for exercise training performed before and during bi-weekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce muscle fiber size, and that exercise training would attenuate these responses. METHODS: Eight-week old ovariectomized female Sprague-Dawley rats were randomized to one of four treatments: Exercise+DOX (Ex-Dox); Ex+Vehicle (Ex-Veh), Sedentary+DOX (Sed-Dox); and Sed+Veh (Sed-Veh). DOX (4mg/kg) or vehicle (saline) intraperitoneal injections were performed bi-weekly for a total of 3 injections (cumulative dose 12mg/kg). Ex animals performed interval exercise (4x4min, 85-90 %VO2peak) 5d/week starting one week prior to the first injection and continued throughout study duration. Animals were euthanized ~5d following the last injection, during which the soleus muscle was dissected and prepared for immunoblot and immunohistochemical analyses. RESULTS: REDD1 mRNA and protein were increased only in Sed-Dox (P0.05). LC3BI was higher and the LC3BII/I ratio was lower in Sed-Dox vs. Sed-Veh (P0.05). CONCLUSION: These data suggest that DOX may inhibit mTORC1 activity and reduce MHCI and MHCIIa fiber size, potentially through elevated REDD1, and that exercise may provide a therapeutic strategy to preserve skeletal muscle size during chronic DOX treatment. (C) 2017 American College of Sports Medicine

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Bioenergetics and ATP Synthesis during Exercise: Role of Group III/IV Muscle Afferents.

Purpose: To investigate the role of the group III/IV muscle afferents in the bioenergetics of exercising skeletal muscle beyond constraining the magnitude of metabolic perturbation. Methods: Eight healthy men, performed intermittent isometric knee-extensor exercise to task failure at ~58% maximal voluntary contraction (MVC) under control conditions (CTRL) and with lumbar intrathecal fentanyl to attenuate group III/IV leg muscle afferents (FENT). Intramuscular concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), diprotonated phosphate (H2PO4[spacing macron]), adenosine triphosphate (ATP), and pH were determined using phosphorous magnetic resonance spectroscopy (31P-MRS). Results: The magnitude of metabolic perturbation was significantly greater in FENT compared to CTRL for [Pi] (37.8 +/- 16.8 vs. 28.6 +/- 8.6 mM), [H2PO4[spacing macron]] (24.3 +/- 12.2 vs. 17.9 +/- 7.1 mM), and [ATP] (75.8 +/- 17.5 vs. 81.9 +/- 15.8 % of baseline), while there was no significant difference in [PCr] (4.5 +/- 2.4 vs. 4.4 +/- 2.3 mM) or pH (6.51 +/- 0.10 vs. 6.54 +/- 0.14). The rate of perturbation in [PCr], [Pi], [H2PO4[spacing macron]], and pH was significantly faster in FENT compared to CTRL. Oxidative ATP synthesis was not significantly different between conditions. However, anaerobic ATP synthesis, through augmented creatine kinase and glycolysis reactions, was significantly greater in FENT than CTRL, resulting in a significantly greater ATP cost of contraction (0.049 +/- 0.016 vs. 0.038 +/- 0.010 mM[middle dot]min-1[middle dot]N-1). Conclusion: Not only do group III/IV muscle afferents constrain magnitude of perturbation in intramuscular Pi, H2PO4[spacing macron], and ATP during small muscle mass exercise, but also appear to play a role in maintaining efficient skeletal muscle contractile function in men. (C) 2017 American College of Sports Medicine

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Impact of Physical Load on Aerobic Exercise Performance during Heat Stress.

Heavy external loads and heat exposure can negatively impact exercise performance. Independent effects of heat and load have been studied previously; however the combined effects remain unknown. Purpose: To investigate the impact of increasing external loads on 5 km treadmill time trial (TT) performance in 20[degrees]C (Temp) and 40[degrees]C (Hot) environmental conditions and to construct an ecologically relevant performance prediction decision-aid. Methods: 26 male and 4 female volunteers (age 23.5 +/- 6.9 years, weight 76.0 +/- 8.9 kg, height 1.75 +/- 0.07 m; VO2peak, 50.7 +/- 4.5 ml/kg/min) participated in a counter-balanced, mixed model design with each subject assigned to a load group (20%, 30%, or 50% body mass (BM); n=10 per group). Volunteers performed 3, self-paced 5km familiarization time trials (TT) (treadmill) without external load. Each volunteer then performed a 5 km TT in each environment with loads of either 20% (n=10), 30% (n=10) or 50% (n=10) body weight. Results: 1) loads of (20%, 30% and 50% of BM) impaired 5 km TT performance compared that when unloaded (P

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Editorial Board

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Publication date: September 2017
Source:Journal of Human Evolution, Volume 110





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Why and how are we living longer?

New Findings

  • What is the topic of this review?

    The reasons for the continuing increase in human life expectancy are examined in the light of progress in understanding the physiological basis of ageing. Prospects for further extending the health span – the period free of age-related disability and disease – are critically assessed.

  • What advances does it highlight?

    No active programming directly causes ageing, which instead results as a side effect of how evolution optimises the physiological allocation of resources between growth, reproduction and maintenance. Under pressure of natural selection, there was insufficient priority in maintaining the body well enough that it could endure without progressive accumulation of multiple kinds of molecular and cellular damage.

Understanding human ageing is a major challenge for the physiological sciences. It is made all the more urgent by the survival of inreasing numbers of people to advanced old age and by a shift in the underlying causes of the continuing increase in life expectancy. The previous increase was caused almost entirely by the prevention of deaths in the early and middle years of life; a process that has seen such success that in developed countries there remains little scope for significant further increase from this cause. The more recent increase is driven by something new. We are reaching old age in generally better health, and it is the death rates at advanced ages that are now falling fast. At the same time, biology has established that there is almost certainly no fixed programme for ageing, which is caused instead by the lifelong accumulation of damage. It is becoming evident that the ageing process is much more malleable than we used to think. We need urgently to establish the factors that govern this malleability and to identify the interactions between, on the one hand, intrinsic biological processes that drive the many chronic diseases and disabilities for which age is by far the largest risk factor and, on the other hand, the social and lifestyle factors that influence our individual trajectories of health in old age. Ageing is no longer as mysterious and intractable a process as used to be thought, offering new opportunities for contributions from other branches of the physiological sciences.

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Evidence for specificity of the impact of punishment on error-related brain activity in high versus low trait anxious individuals

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Publication date: Available online 2 August 2017
Source:International Journal of Psychophysiology
Author(s): Alexandria Meyer, Magda Gawlowska
A previous study suggests that when participants were punished with a loud noise after committing errors, the error-related negativity (ERN) was enhanced in high trait anxious individuals. The current study sought to extend these findings by examining the ERN in conditions when punishment was related and unrelated to error commission as a function of individual differences in trait anxiety symptoms; further, the current study utilized an electric shock as an aversive unconditioned stimulus. Results confirmed that the ERN was increased when errors were punished among high trait anxious individuals compared to low anxious individuals; this effect was not observed when punishment was unrelated to errors. Findings suggest that the threat-value of errors may underlie the association between certain anxious traits and punishment-related increases in the ERN.



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Assessment of the septal area neuronal activity during penile erections in rapid eye movement sleep and waking in the rats

Abstract

To understand the central mechanism of penile erections during rapid eye movement (REM) sleep and waking, single units were recorded from the septal area in un-anesthetized head-restrained rats simultaneous with erections. Erectile events were assessed by pressure in the bulb of the corpus spongiosum of the penis and bulbospongiosus-muscle activity. Of 143 recorded neurons, 36% showed increased activity (E-type) and 24% decreased activity (I-type) during different phases of erection in REM sleep, while 10% were E-type and 35% were I-type during erections in waking. Most E-type neurons were recorded from the dorsal and intermediate part of lateral septum, whereas I-type neurons were from the medial septum. The findings illustrate the extensive network of various types of neurons in the septal area that fire in concert in relation to erection during REM sleep and waking. This study provides a unique prospective of the septal area for perpetuation of erectile circuitry during sleep.



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Evolution of mitochondrial energy metabolism genes associated with hydrothermal vent adaption of Alvinocaridid shrimps

Abstract

Most of Alvinocaridid shrimps live in hydrothermal vents, where is a wicked environment with highly toxic chemistry, hypoxia, acidic pH, and sulfide deposits. In order to adapt to this environment, change in energy metabolism may be one of the primary factors. However, the genetic basis of energy metabolism underlying this environment remains unexplored. Here, we present the first systematic investigation of mitochondrial genes in Alvinocarididae. The analysis demonstrated that ATP6, ND4 and ND6 were subjected to strong positive selection leading to last common ancestors of Alvinocarididae, and ATP8, ND5, COX1 and COX2 were determined to have undergone positive selection in the interior lineages of Alvinocarididae. Considering that about 95% of ATP is supplied by mitochondria via oxidative phosphorylation, and body detoxification process associated with cytochrome c. Positive selection in these genes suggested that Alvinocaridid shrimps might have acquired an enhanced capacity for energy metabolism and detoxification in extreme hydrothermal vent field.



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Six-minute walk performance in persons with multiple sclerosis while using passive or powered ankle-foot orthoses

Publication date: Available online 2 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Morgan K. Boes, Rachel E. Bollaert, Richard Kesler, Yvonne C. Learmonth, Mazharul Islam, Matthew N. Petrucci, Robert W. Motl, Elizabeth T. Hsiao-Wecksler
ObjectiveTo determine if a powered ankle-foot orthosis that provides dorsiflexor and plantarflexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS)DesignShort-term interventionSettingUniversity research laboratoryParticipantsSixteen participants with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive ankle-foot orthosis (AFO). Participants were persons with moderate to severe neurological disability.InterventionsThree 6-minute walk tests (6MW), one per footwear condition: shoes (no AFO), prescribed passive AFO, and powered portable AFO (PPAFO). Assistive devices were worn on the impaired limb.Main Outcome MeasuresDistance walked and metabolic cost of transport were collected during each 6MW and compared between footwear conditions.ResultsEach participant completed all three 6MW tests within the experimental design. PPAFO use resulted in a shorter 6MW distance than a passive AFO or shoes. There were no differences in metabolic cost of transport based on footwear.ConclusionsThe current embodiment of this portable powered AFO did not improve endurance walking performance based on 6MW in a sampling of participants with gait impairment due to MS. Further research is required to determine if expanded training or modified design of this powered orthosis can be effective at improving endurance walking performance in persons with gait impairment due to MS.



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Risk prediction instruments in geriatric surgery are available but often ignored

No abstract available

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Compressed air injection technique for Shamrock lumbar plexus block

imageNo abstract available

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History of anaesthesia: The ketamine story – past, present and future

imageNo abstract available

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Rocuronium is more hepatotoxic than succinylcholine in vitro

imageBACKGROUND: The development of liver failure is a major problem in critically ill patients. The hepatotoxicity of many drugs, as one important reason for liver failure, is poorly screened for in human models. Rocuronium and succinylcholine are neuromuscular blocking agents used for tracheal intubation and for rapid-sequence induction. OBJECTIVE: We used an in-vitro test with a permanent cell line and compared rocuronium and succinylcholine for hepatotoxicity. DESIGN: In-vitro study. SETTING: A basic science laboratory, University Hospital Rostock, Germany. MATERIAL/(PATIENTS): The basic test compound is the permanent human liver cell line HepG2/C3A. In a standardised microtitre plate assay the toxicity of different concentrations of rocuronium, succinylcholine and plasma control was tested. INTERVENTIONS: After two incubation periods of 3 days, the viability of cells (XTT test, lactate dehydrogenase release and trypan blue staining), micro-albumin synthesis and the cytochrome 1A2 activity (metabolism of ethoxyresorufin) were measured. MAIN OUTCOME MEASURES: Differences between rocuronium and succinylcholine were assessed using the Kruskal–Wallis one-way test and two-tailed Mann–Whitney U test. RESULTS: Rocuronium, but not succinylcholine, led to a significant dose-dependent decrease of viability, albumin synthesis and cytochrome 1A2 activity of test cells. CONCLUSION: An in-vitro test with a cell line showed hepatotoxicity of rocuronium that was dose-dependent. Further studies are needed to investigate the underlying mechanisms of the effects of rocuronium on hepatic cellular integrity. TRIAL REGISTRATION: Not suitable.

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Efficacy and safety of buprenorphine in peripheral nerve blocks: A meta-analysis of randomised controlled trials

imageBACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, a variety of additives to local anaesthetics have been investigated to prolong postoperative analgesia following single-shot nerve blocks. OBJECTIVE(S): The aims of the current meta-analysis were to assess the efficacy and safety of the addition of perineural buprenorphine to local anaesthetic compared with local anaesthetic alone, or combined with systemic administration of buprenorphine, or other perineural opioids for peripheral nerve blocks. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: The following data sources were systematically searched: MEDLINE, CENTRAL and EMBASE (till 03/2016). ELIGIBILITY CRITERIA: All RCTs focusing on the efficacy and safety of perineural buprenorphine combined with local anaesthetic compared with local anaesthetic alone, or in combination with systemic buprenorphine, or other perineural opioids for peripheral nerve blocks were included. RESULTS: We included 13 RCTs (685 patients). Participants treated with perineural buprenorphine combined with local anaesthetic showed a longer duration of analgesia compared with those receiving local anaesthetic alone [mean difference 8.64 h, 95% confidence interval (CI) (6.44 to 10.85); P 

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Postoperative nausea and vomiting: solutions and questions

No abstract available

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Injectate spread following anterior sub-costal and posterior approaches to the quadratus lumborum block: A comparative cadaveric study

imageBACKGROUND: The dermatomal level of analgesia achieved with quadratus lumborum blocks varies according to the location of injection. The most commonly used approaches are either at the postero-lateral aspect or anterior to the quadratus lumborum muscle. OBJECTIVE: To determine whether the site of injection of contrast dye around the quadratus lumborum muscle of cadavers affects the extent and mechanism of dye spread. DESIGN: Observational human cadaver study. SETTING: Cleveland Clinic cadaveric laboratory. PARTICIPANTS: Six fresh human cadavers. INTERVENTIONS: The cadavers received either a posterior quadratus lumborum block or an anterior subcostal quadratus lumborum block on each side. MAIN OUTCOME MEASURES: Cadavers were dissected to determine the extent of dye spread. RESULTS: The posterior quadratus lumborum block approach revealed consistently deep staining of the iliohypogastric, ilioinguinal, subcostal nerve, T11 to 12 and L1 nerve roots. In addition, staining of the middle thoracolumbar fascia was seen in all specimens but only variable staining of T10 nerve roots. The anterior subcostal quadratus lumborum block approach in all specimens demonstrated predictable deep staining of the iliohypogastric and ilioinguinal nerves, subcostal nerves, T11 to 12 and L1 nerve roots, and in addition traversing the arcuate ligaments to involve T9 to 12 nerve roots with variable staining of higher thoracic nerve roots. CONCLUSIONS: Our cadaveric study demonstrates that injection of dye on the posterior aspect of quadratus lumborum muscle led to injectate spread through the lateral and posterior abdominal wall but with limited cranial spread, whereas the anterior approach produced broader coverage of the lower to mid-thoracic region. Clinical translation of these findings to determine the practical significance is warranted.

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Anaesthesiology and ethics: Presumed consent with real consequences

No abstract available

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Thoracic paravertebral block for postoperative pain management after renal surgery: A randomised controlled trial

imageBACKGROUND: Thoracic paravertebral block (ThPVB) combined with general anaesthesia is used in thoracic and general surgery. It provides effective analgesia, reduces surgical stress response and the incidence of chronic postoperative pain. OBJECTIVE: To assess the efficacy of ThPVB in reducing opioid requirements and decreasing the intensity of pain after renal surgery. DESIGN: A randomised, open label study. SETTING: A single university hospital. Study conducted from August 2013 to February 2014. PARTICIPANTS: In total, 68 patients scheduled for elective renal surgery (open nephrectomy or open nephron-sparing surgery). INTERVENTIONS: Preoperative ThPVB with 0.5% bupivacaine combined with general anaesthesia, followed by postoperative oxycodone combined with nonopioid analgesics as rescue drugs. Follow-up period: 48 h. MAIN OUTCOME MEASURES: Total dose of postoperative oxycodone required, pain intensity, occurrence of opioid related adverse events, ThPVB-related adverse events and patient satisfaction. RESULTS: A total of 68 patients were randomised into two groups and, of these, 10 were subsequently excluded from analysis. Patients in group paravertebral block (PVB; n = 27) had general anaesthesia and ThPVB, and those in group general (anaesthesia) (GEN) (n = 31) formed a control group receiving general anaesthesia only. Compared with patients in group GEN, patients who received ThPVB required 39% less i.v. oxycodone over the first 48 h and had less pain at rest (P 

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Plasma levels of local anaesthetic following supraclavicular block

imageNo abstract available

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Loss of resistance: A randomised controlled trial assessing four low-fidelity epidural puncture simulators

imageBACKGROUND: Detecting loss of resistance (LOR) can either be taught with dedicated simulators, with a cost ranging from €1500 to 3000, or with the 'Greengrocer's Model', requiring simply a banana. OBJECTIVES: The purpose of this study was to compare three dedicated epidural puncture training simulators and a banana in their ability to simulate LOR. Our hypothesis was that there was a difference between the four simulators when comparing the detection of LOR. DESIGN: Single-blinded, randomised, controlled study. SETTING: Department of Anaesthesiology and Pain Therapy, Bern University Hospital, Switzerland. PARTICIPANTS: Fifty-five consultant anaesthesiologists. INTERVENTIONS: The participants were asked to insert an epidural catheter in four different epidural puncture training simulators: Lumbar Puncture Simulator II (Kyoto Kagaku, Kyoto, Japan), Lumbar Epidural Injection Trainer (Erler-Zimmer, Lauf, Germany), Normal Adult Lumbar Puncture/Epidural Tissue (Simulab Corp., Seattle, Washington, USA) and a banana. The simulators were placed in identical boxes to blind the participants. MAIN OUTCOME MEASURES: The primary outcome was the detection of LOR rated on a 100-mm visual analogue scale, in which 0 mm represented 'completely unrealistic' and 100 mm represented 'indistinguishable from a real patient'. RESULTS: The mean visual analogue scale scores for LOR in the four simulators were significantly different: 60 ± 25 mm [95% confidence interval (CI), 55 to 65 mm], 50 ± 29 mm (95% CI, 44 to 55 mm), 64 ± 24 mm (95% CI, 58 to 69 mm) and 49 ± 32 mm (95% CI, 44 to 54 mm); P less than 0.001, Friedman test. CONCLUSION: Two of the three dedicated epidural simulators were rated more realistic in detecting LOR than the banana, but some participants preferred the banana to the other three simulators. Given the relative cost of a banana compared with a dedicated simulator, we suggest that a banana be used to teach the technique of LOR for epidural puncture. TRIAL REGISTRATION: KEK Nr: Req-2015-z087.

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Should the transversus abdominis plane block be performed for laparoscopic colorectal surgery?

No abstract available

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Impact of reversal strategies on the incidence of postoperative residual paralysis after rocuronium relaxation without neuromuscular monitoring: A partially randomised placebo controlled trial

imageBACKGROUND: Electronic neuromuscular monitoring is not widely used to determine either the reversal requirements for neuromuscular block before extubation of the trachea, or to determine if there is any subsequent postoperative residual neuromuscular block (PORNB). OBJECTIVES: To investigate the incidence of PORNB using acceleromyography after spontaneous recovery of rocuronium-induced block and to compare this with the administration of sugammadex, neostigmine or a placebo. DESIGN: Partially randomised, partially randomised, placebo-controlled, double-blind, four-group parallel-arm study. SETTING: Single-centre study performed between October 2013 and December 2015 in a university hospital. PATIENTS: Of the 134 eligible patients, 128 gave their consent and 125 of these completed the study. INTERVENTIONS: Patients received general anaesthesia with propofol, sevoflurane, fentanyl and rocuronium. Neuromuscular transmission was measured by acceleromyography (TOF-Watch-SX; Organon Teknika B.V., Boxtel, the Netherlands) but the anaesthetist was blind to the results. If the anaesthetist deemed pharmacological reversal to be necessary before extubation of the trachea then patients were assigned randomly to receive either sugammadex (2.0 mg kg−1), neostigmine (0.05 mg kg−1) or a placebo. In the postanaesthesia care unit, an independent anaesthetist, unaware of the treatment given, assessed the neuromuscular function using acceleromyography. MAIN OUTCOME MEASURES: The incidence of a normalised train-of-four ratio less than 0.9 on arrival in the recovery room. RESULTS: In total, 125 patients were recruited. Neuromuscular block was allowed to recover spontaneously in 50 patients, whereas the remainder received either sugammadex (27), neostigmine (26) or placebo (22). The number of cases with PORNB were one (3.7%), four (15%), 13 (26%) and 10 (45%) after sugammadex, neostigmine, spontaneous recovery and placebo, respectively. Sugammadex and neostigmine were more effective than placebo [odds ratio (OR): 0.05, 95% confidence interval (CI): 0.005 to 0.403, P = 0.005; OR: 0.22, 95% CI: 0.056 to 0.85, P = 0.028, respectively]. Sugammadex performed better than spontaneous recovery (OR: 0.11, 95% CI: 0.014 to 0.89, P = 0.039) unlike neostigmine (OR: 0.52, 95% CI: 0.15 to 1.79, P = 0.297). Yet, antagonism (pooled data) was more effective than spontaneous recovery (OR: 0.3, 95% CI: 0.1 to 0.9, P = 0.03). CONCLUSION: Although pharmacological reversal based on clinical signs was superior to spontaneous recovery it did not prevent PORNB, irrespective of the reversal agent. TRIAL REGISTRATION: The study is registered under EUDRACT number 2013-001965-17.

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Reply to: postoperative nausea and vomiting: solutions and questions

No abstract available

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Effects of calcium chloride coadministered with neostigmine on neuromuscular blockade recovery: A double-blind randomised study

imageBACKGROUND: Ionised calcium plays an important role in neuromuscular transmission, but its effects on the reversal of nondepolarising neuromuscular blockade have not been fully evaluated. OBJECTIVE: We examined whether calcium chloride coadministered with neostigmine could enhance the rate of neuromuscular recovery. DESIGN: Randomised double-blind trial. SETTING: A tertiary teaching hospital. PATIENTS: In total, 53 patients undergoing elective surgery under general anaesthesia with neuromuscular monitoring by acceleromyography using a TOF-Watch SX monitor. INTERVENTIONS: Patients were randomly allocated to receive either 5 mg kg−1 of calcium chloride (calcium group, n = 26) or the same volume of normal saline (control group, n = 27) coadministered with 25 μg kg−1 of neostigmine and 15 μg kg−1 of atropine at the end of surgery. MAIN OUTCOME MEASURES: The primary end point was the neuromuscular recovery time [time from neostigmine administration to recovery of the TOF ratio (TOFr) to 0.9]. Secondary end points included the TOFr at 5, 10 and 20 min after neostigmine administration and the incidence of postoperative residual curarisation (PORC), defined as a TOFr less than 0.9 at each time point. RESULTS: The neuromuscular recovery time was significantly faster in the calcium group than in the control group (median [Q1 to Q3]; 5.0 [3.0 to 7.0] vs. 6.7 [5.7 to 10.0] min, respectively; P = 0.007). At 5 min after neostigmine administration, the TOFr was higher [87 (74 to 100) vs. 68 (51 to 81)%, respectively; P = 0.002] and the incidence of PORC was lower (50.0 vs. 81.5%, respectively; P = 0.016) in the calcium group than in the control group. There were no differences between the two groups with respect to the TOFr or incidence of PORC at 10 and 20 min after neostigmine administration. CONCLUSION: Calcium chloride coadministered with neostigmine enhanced neuromuscular recovery in the early period of nondepolarising neuromuscular blockade reversal.

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Reply to: risk prediction instruments in geriatric surgery are available but often ignored

No abstract available

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A new myofilament contraction model with ATP consumption for ventricular cell model

Abstract

A new contraction model of cardiac muscle was developed by combining previously described biochemical and biophysical models. The biochemical component of the new contraction model represents events in the presence of Ca2+–crossbridge attachment and power stroke following inorganic phosphate release, detachment evoked by the replacement of ADP by ATP, ATP hydrolysis, and recovery stroke. The biophysical component focuses on Ca2+ activation and force (F b) development assuming an equivalent crossbridge. The new model faithfully incorporates the major characteristics of the biochemical and biophysical models, such as F b activation by transient Ca2+ ([Ca2+]–F b), [Ca2+]–ATP hydrolysis relations, sarcomere length–F b, and F b recovery after jumps in length under the isometric mode and upon sarcomere shortening after a rapid release of mechanical load under the isotonic mode together with the load–velocity relationship. ATP consumption was obtained for all responses. When incorporated in a ventricular cell model, the contraction model was found to share approximately 60% of the total ATP usage in the cell model.



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Fire chief on importance of leadership to sudden cardiac arrest survival

hqdefault.jpg

Hilton Head Island Fire Chief Brad Tadlock talks about leadership in improving outcomes from out of hospital cardiac arrest.

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Fire chief on importance of leadership to sudden cardiac arrest survival

hqdefault.jpg

Hilton Head Island Fire Chief Brad Tadlock talks about leadership in improving outcomes from out of hospital cardiac arrest.

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Fire chief on importance of leadership to sudden cardiac arrest survival

hqdefault.jpg

Hilton Head Island Fire Chief Brad Tadlock talks about leadership in improving outcomes from out of hospital cardiac arrest.

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Fire chief on importance of leadership to sudden cardiac arrest survival

hqdefault.jpg

Hilton Head Island Fire Chief Brad Tadlock talks about leadership in improving outcomes from out of hospital cardiac arrest.

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Police in at least 4 Dallas suburbs contend with 911 woes

Some T-Mobile customers were able to call 911, but were not being heard when a dispatcher answered

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Paramedic - Town of South Kingstown, RI

The Town of South Kingstown's Emergency Medical Services Department is conducting a recruitment to establish eligibility lists for full time Paramedic level openings as well as per diem Paramedic and/or EMT-C level positions. The EMS Department consists of sixteen full time Paramedic providers, several per diem EMT-C and Paramedic providers, and is lead by the EMS Director. The Department serves ...

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A step in the wrong direction: Reducing EMS certification levels

Earlier this week, legislators in New York state began a painful discussion on whether to allow EMS services to reduce the level of certification in its ambulances. This action is in response to the dwindling number of volunteers who respond to calls. Certified first responders would be used instead of requiring a minimum EMT level. This is a major step in the wrong direction. Over the past 50 years ...

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Expanding the phenotype of DST-related disorder: A case report suggesting a genotype/phenotype correlation

The gene DST encodes for the large protein BPAG1 involved in hemidesmosomes. Its alternative splicing gives rise to tissue-enriched isoforms in brain, muscle, and skin. The few patients described so far with bi-allelic mutations in the DST gene have either a skin phenotype of epidermolysis bullosa simplex or a neurological phenotype. Here, we report a 17-year-old female individual presenting with a more complex phenotype consisting of both skin and neuronal involvement, in addition to several previously unreported findings, such as iris heterochromia, cataract, hearing impairment, syringomyelia, behavioral, and gastrointestinal issues, osteoporosis, and growth hormone deficiency. Family-trio whole exome sequencing revealed that she was a compound heterozygous for two variants in the DST gene with highly-predicted functional impact, c.3886A>G (p.R1296X) in exon 29 and c.806C>T (p.H269R) in exon 7. Interestingly, exon 7 is included in the neuronal isoform whereas exon 29 is expressed in both skin and neuronal isoforms. The patient we described is the first case with a mutation affecting an exon expressed in both the neuronal and skin isoforms that can explain the more complex phenotype compared to previously reported cases.



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Two unrelated children with overlapping 6q25.3 deletions, motor speech disorders, and language delays

Interstitial and terminal 6q25 deletions are associated with developmental delays, hypotonia, eye pathologies, craniofacial dysmorphologies, and structural brain anomalies. In most cases, speech and language deficits are not described in detail. We report on a case (Patient 1, age 7 years) with a de novo 6q25.3-qter deletion, 11.1 Mb long and encompassing 108 genes, and a case (Patient 2, age 5 years) with an inherited interstitial 6q25.3 deletion, located within Patient 1's deletion region and 403 kb long, the smallest 6q25 deletion reported to date. Both children have hypotonia, motor speech disorders, and expressive language delays. Patient 1's speech was characterized by childhood apraxia of speech (CAS) and dysarthria. Other findings include developmental delay, ataxic cerebral palsy, optic nerve dysplagia, and atypical brain morphologies regarding the corpus callosum and gyration patterns, a clinical profile that closely matches a previously reported case with a nearly identical deletion. Patient 2 had speech characterized by CAS and typical nonverbal processing abilities. His father, a carrier, had typical speech and language but showed difficulties with complex motor speech and hand motor tasks, similar to other adults with residual signs of CAS. The small deletion in this family contains the IGF2R-AIRN-SLC22A2-SLC22A3 gene cluster, which is associated with imprinting and maternal-specific expression of Igf2R, Slc22a2, and Slc22a3 in mice, whereas imprinting in humans is a polymorphic trait. The shared phenotypes in the two patients might be associated with the deletion of the gene cluster.



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State-by-State Variation in the Number of Children and Young Adults in Nursing Homes, 2005–2012

Abstract

Objectives One goal of Healthy People 2020 is to reduce the number of children and young adults living in nursing homes. However, little is known about the prevalence of nursing home use among children and young adults on a state-by-state basis. The objective of this study was to determine the prevalence of nursing home use among children and young adults in each state from 2005 to 2012. The study also looked for prevalence trends between 2005 and 2012. Methods The Centers for Medicare and Medicaid Services Minimum Data Set and US Census data were used to calculate the prevalence of nursing home residents among children and young adults aged 0–30 in each US state in 2012 and assess trends in each state from 2005 to 2012. Results In 2012, the prevalence of nursing home residents among children and young adults aged 0–30 varied across states, ranging from 14 in 100,000 (New Jersey) to 0.8 in 100,000 (Alaska). Testing for trends from 2005 to 2012 also revealed significant trends (p < 0.05), with Florida trending upward with borderline statistical significance (p = 0.05) and six states trending downward. Conclusion There is wide variation in the prevalence of nursing home residents among children and young adults aged 0–30 across states. There is also variation in the nursing home prevalence trends across states. Observed variations may represent potential opportunities for some states to reduce their population of children and young adults in nursing homes.



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Differential expression of two genes Oct-4 and MUC5AC associates with poor outcome in patients with gastric cancer

Clinical and Experimental Pharmacology and Physiology

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AstraZeneca gets breakthrough status for blood cancer drug

Reuters Health News

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A modified response of NAFLD patients with non-significant fibrosis in nutritional counseling according to GCKR rs1260326

European Journal of Nutrition

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Providers back population health management despite Affordable Care Act uncertainty

Healthcare Finance News

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An update on the impact of food allergy on anxiety and quality of life

Current Opinion in Pediatrics

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Ransomware attack on South Dakota provider breaches data on 10,000 patients

Healthcare Finance News

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Clinical presentation of terbinafine-induced severe liver injury and the value of laboratory monitoring: A critically appraised topic

British Journal of Dermatology

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Systematic review: Probiotics for functional constipation in children

European Journal of Pediatrics

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Comparison of STONE, CROES and Guys nephrolithometry scoring systems for predicting stone-free status and complication rates after percutaneous nephrolithotomy in obese patients

Urolithiasis

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Comparison of standard triple therapy regimen with sequential therapy regimen containing levofloxacin used for the eradication of helicobacter pylori in patients with gastrointestinal infection caused by helicobacter pylori

Middle East Journal of Family Medicine

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The effects of traffic light labelling versus cartoon labelling on food and beverage purchases in a childrens hospital setting

Pediatric Obesity

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miR-203 as a novel biomarker for the diagnosis and prognosis of colorectal cancer: A systematic review and meta-analysis

OncoTargets and Therapy

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More than a third of US adults prescribed opioids in 2015

Reuters Health News

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Real-world effectiveness and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir with or without ribavirin for patients with chronic hepatitis C virus genotype 1b infection in Taiwan

Journal of Gastroenterology and Hepatology

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Idiosyncratic drug induced liver injury in African–Americans is associated with greater morbidity and mortality compared to Caucasians

The American Journal of Gastroenterology

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Retrospective comparison of S-1 plus cisplatin versus S-1 monotherapy for the treatment of advanced gastric cancer patients with positive peritoneal cytology but without gross peritoneal metastasis

International Journal of Clinical Oncology

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A community-based motivational personalised lifestyle intervention to reduce BMI in obese adolescents: Results from the Healthy Eating and Lifestyle Programme (HELP) randomised controlled trial

Archives of Diseases in Childhood

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An effective antiviral approach targeting hepatitis B virus with NJK14047, a novel and selective biphenyl amide p38 mitogen-activated protein kinase inhibitor

Antimicrobial Agents and Chemotherapy

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The effectiveness of a novel highly flexible-tip guidewire on selective biliary cannulation compared to conventional guidewire: A randomized controlled study

Digestive Endoscopy

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Helicobacter pylori infection and severity of coronary atherosclerosis in patients with chronic coronary artery disease

Therapeutics and Clinical Risk Management

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Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth

Abstract

The use of proton pump inhibitors (PPIs) may potentially predispose to the development of small intestinal bacterial overgrowth (SIBO), but this association is controversial due to conflicting results from studies conducted to date. The aim of this meta-analysis was to evaluate the association between the use of PPIs and the risk of SIBO. We systematically searched the online PubMed, Embase, and Cochrane Library databases and Web of Science for relevant articles published up to November 2016. Two researchers identified and extracted data independent of each other. The pooled analysis was performed using the generic inverse-variance random-effects model. Subgroup and sensitivity analysis were conducted to assess the stability and heterogeneity of the pooled results. The risk of publication bias was evaluated by assessing for funnel plot asymmetry and by Egger's test and Begg's test. A total of 19 articles met the eligibility criteria for the meta-analysis, reporting on 7055 subjects. The pooled odds ratio (OR) showed a statistically significant association between increased risk of SIBO and PPI use (OR 1.71, 95% confidence interval 1.20–2.43). Subgroup analyses demonstrated an association between SIBO and PPI use in studies that employed small bowel aspirates culture and glucose hydrogen breath tests (GHBT) as diagnostic tests for SIBO. Our meta-analysis suggests that the use of PPI moderately increases the risk of SIBO, thereby highlighting the need for appropriate prescribing of PPIs.



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Control of the depth and rate of breathing: metabolic vs. non-metabolic inputs

Abstract

We read with great interest the review paper by Tipton et al. (2017). The authors examined the ventilatory response to a wide range of stressors, with a special interest in the differential regulation of respiratory frequency (fR) and tidal volume (VT).

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Injury and Liability Associated With Spine Surgery.

Background: Although spine surgery is associated with significant morbidity, the anesthesia liability profile for spine surgery is not known. We examined claims for spine procedures in the Anesthesia Closed Claims Project database to evaluate patterns of injury and liability. Materials and Methods: A retrospective cohort study was performed. Inclusion criteria were anesthesia claims provided for surgical procedures in 2000 to 2014. We compared mechanisms of injury for cervical spine to thoracic or lumbar spine procedures using [chi]2 and the Fisher exact test. Univariate and multivariate logistic regression analyses were used to determine factors associated with permanent disabling injury in spine surgery claims. Results: The 207 spine procedure (73% thoracic/lumbar; 27% cervical) claims comprised >10% of claims. Permanent disabling injuries to nerves, the spinal cord, and the eyes or visual pathways were more common with spine procedures than in nonspine procedures. Hemorrhage and positioning injuries were more common in thoracic/lumbar spine claims, whereas difficult intubation was more common in cervical spine claims. Multiple logistic regression demonstrated prone positioning (odds ratio=3.50; 95% confidence interval, 1.30-9.43) and surgical duration of >=4 hours increased the odds of severe permanent injury in spine claims (odds ratio=2.73; 95% confidence interval, 1.11-6.72). Conclusions: Anesthesia claims related to spine surgery were associated with severe permanent disability primarily from nerve and eye injuries. Prone positioning and surgical duration of >=4 hours were associated with permanent disabling injuries. Attention to positioning, resuscitation during blood loss, and reducing length of surgery may reduce these complications. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

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Comparison of 3% Hypertonic Saline and 20% Mannitol for Reducing Intracranial Pressure in Patients Undergoing Supratentorial Brain Tumor Surgery: A Randomized, Double-blind Clinical Trial.

Background: In the present study, we hypothesized that 3% hypertonic saline (HS) is more effective than 20% mannitol to reduce intracranial pressure (ICP) and to modify brain bulk in patients undergoing an elective supratentorial craniotomy. Materials and Methods: After institutional review board approval, patients scheduled to undergo supratentorial craniotomy were enrolled into this prospective, randomized, double-blind study. The patients were monitored for routine hemodynamic parameters, depth of anesthesia, and ICP. They received 5 mL/kg 20% mannitol (n=20) or 3% HS (n=19) as infusion for 15 minutes. The patients' ICP values were monitored during hypertonic fluid infusion and throughout 30 minutes after infusion as a primary outcome. Secondary outcomes were hemodynamic variables, serum sodium value, blood gases, and surgeon brain relaxation assessment score (1=relaxed, 2=satisfactory, 3=firm, 4=bulging). In addition, the length of intensive care unit and hospital stay were recorded. Results: Demographic and tumor characteristics were similar between groups. The basal (before hypertonic infusion, ICPT0) and last (30 min after hypertonic infusion finished, ICPT45) ICP values were 13.7+/-3.0 and 9.5+/-1.9 mm Hg, respectively, for the M group, which were comparable with the corresponding levels of 14.2+/-2.8 and 8.7+/-1.1 mm Hg in the HS group (P>0.05). The median amount of ICP reduction between T0 and T45 timepoints were 4 (1 to 7) and 5 (1 to 9) mm Hg for group M and group HS, respectively (P=0.035). Baseline central venous pressure, pulse pressure variation, and serum sodium and lactate values were similar between groups, but the last measured pulse pressure variation and lactate value were lower, and sodium value was higher in group HS than in group M (P

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Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia: Predictors of Good Outcome.

Background: The choice of anesthetic technique, general anesthesia (GA) versus Monitored Anesthesia Care, may impact the outcome of patients undergoing endovascular treatment of acute ischemic stroke (AIS). The aim of this study was to identify the factors associated with good discharge outcome in patients receiving GA for AIS. Materials and Methods: Electronic medical records of patients above 18 years old who underwent endovascular treatment of AIS under GA at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome was defined as discharge modified Rankin Score 0 to 2 and poor outcome as modified Rankin Score 3 to 6; logistic regression analysis was performed to examine the association between the clinical characteristics and the outcome. Results: In total, 88 patients (56 males), aged 63+/-15 years with median National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic blood pressure below the guideline recommended 140 mm Hg under GA. After adjusting for age and NIHSS score, the independent predictors of good discharge outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14; confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular treatment (OR, 26.31; CI, 4.80-144.12; P

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Randomized Controlled Trial of the Clinical Efficacy of Multiport Versus Uniport Wire-Reinforced Flexible Catheters for Labor Epidural Analgesia.

BACKGROUND: The purpose of this prospective, randomized, controlled trial was to determine whether multiple ports improve the analgesic efficacy of wire-reinforced flexible catheters used for labor epidural analgesia (LEA). METHODS: Six hundred fifty laboring patients were randomized to receive epidural analgesia using either a multiport or uniport wire-reinforced flexible catheter. The primary outcome was analgesic success, defined as the incidence of adequate analgesia following the initial bolus given to initiate LEA. Secondary outcomes included the number of patients requiring clinician interventions during maintenance of LEA; anesthetic success, defined as the incidence of adequate anesthesia following the initial bolus given to establish surgical anesthesia for cesarean delivery; and maternal satisfaction with the overall quality of LEA. RESULTS: There was no significant difference in analgesic success at initiation of LEA between the uniport and the multiport wire-reinforced flexible catheter (93.6% vs 89.5%, respectively; difference of 4.1% [95% confidence interval, -0.4% to 8.5%]; P = .077). There was also no difference in the number of patients requiring clinician interventions during maintenance of LEA and in anesthetic success at the establishment of surgical anesthesia for cesarean delivery between the 2 catheter types. CONCLUSIONS: Multiple ports do not appear to improve the analgesic efficacy of wire-reinforced flexible catheters used for LEA. (C) 2017 International Anesthesia Research Society

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Variability in the Use of Protective Mechanical Ventilation During General Anesthesia.

BACKGROUND: The purpose of this study was to determine whether significant variation exists in the use of protective ventilation across individual anesthesia providers and whether this difference can be explained by patient, procedure, and provider-related characteristics. METHODS: The cohort consisted of 262 anesthesia providers treating 57,372 patients at a tertiary care hospital between 2007 and 2014. Protective ventilation was defined as a median positive end-expiratory pressure of 5 cm H2O or more, tidal volume of

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Effects of Esmolol on the Esophagogastric Junction: A Double-Blind, Randomized, Crossover Study on 14 Healthy Volunteers.

BACKGROUND: Passive regurgitation may occur throughout the perioperative period, increasing the risk for pulmonary aspiration and postoperative pulmonary complications. Hypnotics and opioids, especially remifentanil, that are used during anesthesia have been shown to decrease the pressure in the esophagogastric junction (EGJ), that otherwise acts as a barrier against passive regurgitation of gastric contents. Esmolol, usually used to counteract tachycardia and hypertension, has been shown to possess properties useful during general anesthesia. Like remifentanil, the [beta]-1-adrenoreceptor antagonist may be used to attenuate the stress reaction to tracheal intubation and to modify perioperative anesthetic requirements. It may also reduce the need for opioids in the postoperative period. Its action on the EGJ is however unknown. The aim of this trial was to compare the effects of esmolol and remifentanil on EGJ pressures in healthy volunteers, when administrated as single drugs. METHODS: Measurements of EGJ pressures were made in 14 healthy volunteers using high-resolution solid-state manometry. Interventions were administered in a randomized sequence and consisted of esmolol that was given IV as a bolus dose of 1 mg/kg followed by an infusion of 10 [mu]g[middle dot]kg-1[middle dot]min-1 over 15 minutes, and remifentanil with target-controlled infusion of 4 ng/mL over 15 minutes. Interventions were separated by a 20-minute washout period. Analyses of EGJ pressures were performed at baseline, and during drug administration at 2 (T2) and 15 minutes (T15). The primary outcome was the inspiratory EGJ augmentation, while the inspiratory and expiratory EGJ pressures were secondary outcomes. RESULTS: There was no effect on inspiratory EGJ augmentation when comparing remifentanil and esmolol (mean difference -4.0 mm Hg [-9.7 to 1.7]; P= .15). In contrast, remifentanil significantly decreased both inspiratory and expiratory pressures compared to esmolol (-12.2 [-18.6 to -5.7]; P= .003 and -8.0 [-13.3 to -2.8]; P= .006). CONCLUSIONS: Esmolol, compared with remifentanil, does not affect EGJ function. This may be an advantage regarding passive regurgitation and esmolol may thus have a role to play in anesthesia where maintenance of EGJ barrier function is of outmost importance. (C) 2017 International Anesthesia Research Society

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More Than a Tick Box: Medical Checklist Development, Design, and Use.

Despite improving patient safety in some perioperative settings, some checklists are not living up to their potential and complaints of "checklist fatigue" and outright rejection of checklists are growing. Problems reported often concern human factors: poor design, inadequate introduction and training, duplication with other safety checks, poor integration with existing workflow, and cultural barriers. Each medical setting-such as an operating room or a critical care unit-and different clinical needs-such as a shift handover or critical event response-require a different checklist design. One size will not fit all, and checklists must be built around the structure of medical teams and the flow of their work in those settings. Useful guidance can be found in the literature; however, to date, no integrated and comprehensive framework exists to guide development and design of checklists to be effective and harmonious with the flow of medical and perioperative tasks. We propose such a framework organized around the 5 stages of the checklist life cycle: (1) conception, (2) determination of content and design, (3) testing and validation, (4) induction, training, and implementation, and (5) ongoing evaluation, revision, and possible retirement. We also illustrate one way in which the design of checklists can better match user needs in specific perioperative settings (in this case, the operating room during critical events). Medical checklists will only live up to their potential to improve the quality of patient care if their development is improved and their designs are tailored to the specific needs of the users and the environments in which they are used. (C) 2017 International Anesthesia Research Society

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Multimedia Review for Postoperative Nausea and Vomiting: A Practical Guide.

No abstract available

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Dexmedetomidine-Associated Hyperthermia: A Series of 9 Cases and a Review of the Literature.

Dexmedetomidine, an [alpha]2-adrenergic agonist, can be used to perform mild to moderate sedation in critically ill patients. In this case series, 9 cardiovascular intensive care unit patients with hyperthermia during dexmedetomidine administration, suggestive of drug fever, are presented. Hyperthermia (>38.5[degrees]C) occurred 6 (4-10) hours (median [interquartile range]) after dexmedetomidine initiation at a dose of 1.0 (0.8-1.3) [mu]g/kg/h and was resolved 3 (1-8) hours after discontinuation of dexmedetomidine. All patients were screened for infectious and noninfectious causes of hyperthermia, and the findings were analyzed by 2 adverse drug reaction (ADR) assessment methods-the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment and the Naranjo ADR scale. This resulted in a "probable" ADR in all 9 patients (WHO) and a "probable" and "possible" ADR in 1 and 8 patients (Naranjo), respectively. This case series supports published case reports, suggesting that dexmedetomidine administration may be associated with the occurrence of clinically relevant hyperthermia. The underlying mechanisms and risk factors are uncertain and require further research. (C) 2017 International Anesthesia Research Society

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Regulatory Considerations for Physiological Closed-Loop Controlled Medical Devices Used for Automated Critical Care: Food and Drug Administration Workshop Discussion Topics.

Part of the mission of the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration is to facilitate medical device innovation. Therefore, CDRH plays an important role in helping its stakeholders such as manufacturers, health care professionals, patients, patient advocates, academia, and other government agencies navigate the regulatory landscape for medical devices. This is particularly important for innovative physiological closed-loop controlled (PCLC) devices used in critical care environments, such as intensive care units, emergency settings, and battlefield environments. CDRH's current working definition of a PCLC medical device is a medical device that incorporates physiological sensor(s) for automatic manipulation of a physiological variable through actuation of therapy that is conventionally made by a clinician. These emerging devices enable automatic therapy delivery and may have the potential to revolutionize the standard of care by ensuring adequate and timely therapy delivery with improved performance in high workload and high-stress environments. For emergency response and military applications, automatic PCLC devices may play an important role in reducing cognitive overload, minimizing human error, and enhancing medical care during surge scenarios (ie, events that exceed the capability of the normal medical infrastructure). CDRH held an open public workshop on October 13 and 14, 2015 with the aim of fostering an open discussion on design, implementation, and evaluation considerations associated with PCLC devices used in critical care environments. CDRH is currently developing regulatory recommendations and guidelines that will facilitate innovation for PCLC devices. This article highlights the contents of the white paper that was central to the workshop and focuses on the ensuing discussions regarding the engineering, clinical, and human factors considerations. (C) 2017 International Anesthesia Research Society

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Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance) adjuvant trastuzumab trial.

Objectives: The major clinical side effect of the ERBB2-targeted breast cancer therapy, trastuzumab, is a decline in the left ventricular ejection fraction (LVEF). Improved markers are needed to better identify patients susceptible to cardiotoxicity. Methods: The NCCTG N9831 trial compared adjuvant doxorubicin and cyclophosphamide followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or concurrent paclitaxel and trastuzumab (arm C) in patients with HER2-positive breast cancer. A genome-wide association study was performed on all patients with available DNA (N=1446). We used linear regression to identify single nucleotide polymorphisms (SNPs) associated with decline in LVEF, adjusting for age, baseline LVEF, antihypertensive medications, and the first two principle components. Results: In total, 618 863 SNPs passed quality control and DNA from 1191 patients passed genotyping quality control and were identified as Whites of non-Hispanic origin. SNPs at six loci were associated with a decline in LVEF (P=7.73x10-6 to 8.93x10-8), LDB2, BRINP1, chr6 intergenic, RAB22A, TRPC6, and LINC01060, in patients who received chemotherapy plus trastuzumab (arms BC, N=800). None of these loci were significant in patients who received chemotherapy only (arm A, N=391) and did not increase in significance in the combined analysis of all patients. We did not observe association, P

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