Πέμπτη, 3 Αυγούστου 2017

Frontal asymmetry as a mediator and moderator of emotion: An updated review

Abstract

For over 35 years, research has examined frontal alpha EEG asymmetry, discussed in terms of relative left frontal activity (rLFA) in the present review, as a concurrent and prospective marker of affective processing and psychopathology. Because rLFA may index (a) neural correlates of frontal asymmetry, or (b) psychological constructs to which frontal asymmetry relates, rLFA can advance our understanding of both neural and psychological models of emotion and psychopathology. In order to improve such understanding, the specific role of rLFA in extending or challenging existing theory must be clear to researchers and readers alike. In particular, in 2004, Coan and Allen argued that examination of rLFA as a mediator or moderator may improve our theoretical understanding of rLFA. Despite being a commonly cited paper in the field, most rLFA research today still fails to acknowledge the statistical role of rLFA in the research. The aim of the present paper is to (a) convince the reader of the importance of distinguishing rLFA as a predictor, outcome, mediator, or moderator in order to conduct theory-driven research, and (b) highlight some of the major advances in rLFA literature since the review by Coan and Allen (2004) in the framework of mediators and moderators. We selected a broad range of search terms to capture relevant rLFA research and included only those studies utilizing established methods for rLFA measurement.



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Intertrial RT variability affects level of target-related interference in cued task switching

Abstract

In cued task switching, performance relies on proactive and reactive control processes. Proactive control is evident in the reduction in switch cost under conditions that promote advance preparation. However, the residual switch cost that remains under conditions of optimal proactive control indicates that, on switch trials, the target continues to elicit interference that is resolved using reactive control. We examined whether posttarget interference varies as a function of trial-by-trial variability in preparation. We investigated target congruence effects on behavior and target-locked ERPs extracted across the response time (RT) distribution, using orthogonal polynomial trend analysis (OPTA). Early N2, late N2, and P3b amplitudes were differentially modulated across the RT distribution. There was a large congruence effect on late N2 and P3b, which increased with RT for P3b amplitude, but did not vary with trial type. This suggests that target properties impact switch and repeat trials equally and do not contribute to residual switch cost. P3b amplitude was larger, and latency later, for switch than repeat trials, and this difference became larger with increasing RT, consistent with sustained carryover effects on highly prepared switch trials. These results suggest that slower, less prepared responses are associated with greater target-related interference during target identification and processing, as well as slower, more difficult decision processes. They also suggest that neither general nor switch-specific preparation can ameliorate the effects of target-driven interference. These findings highlight the theoretical advances achieved by integrating RT distribution analyses with ERP and OPTA to examine trial-by-trial variability in performance and brain function.



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Abiotic stresses influence the transcript abundance of PIP and TIP aquaporins in Festuca species

Abstract

Festuca arundinacea and F. pratensis are the models in forage grasses to recognize the molecular basis of drought, salt and frost tolerance, respectively. Transcription profiles of plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) aquaporin genes were obtained for leaves of Festuca species treated with different abiotic stimuli. F. arundinacea plants were exposed to drought and salt stress, whereas F. pratensis plants were cold-hardened. Changes in genes expression measured with use of real time qRT-PCR method were compared between two genotypes characterized with a significantly different level of each stress tolerance. Under drought the transcript level of PIP1;2 and TIP1;1 aquaporin decreased in both analyzed F. arundinacea genotypes, whereas for PIP2;1 only in a high drought tolerant plant. A salt treatment caused a reduction of PIP1;2 transcript level in a high salt tolerant genotype and an increase of TIP1;1 transcript abundance in both F. arundinacea genotypes, but it did not influence the expression of PIP2;1 aquaporin. During cold-hardening a decrease of PIP1;2, PIP2;1, and TIP1;1 aquaporin transcripts was observed, both in high and low frost tolerant genotypes. The obtained results revealed that the selected genotypes responded in a different way to abiotic stresses application. A reduced level of PIP1;2 transcript in F. arundinacea low drought tolerant genotype corresponded with a faster water loss and a lowering of photosynthesis efficiency and gas exchange during drought conditions. In F. pratensis, cold acclimation was associated with a lower level of aquaporin transcripts in both high and low frost tolerant genotypes. This is the first report on aquaporin transcriptional profiling under abiotic stress condition in forage grasses.



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Hypercapnia-induced active expiration increases in sleep and enhances ventilation in unanaesthetized rats

Abstract

Expiration is passive at rest but becomes active through recruitment of abdominal muscles under increased respiratory drive. Hypercapnia-induced active expiration has not been well explored in unanaesthetized rats. We hypothesized that (i) CO2-evoked active expiration is recruited in a state-dependent manner i.e. differently in sleep or wakefulness and (ii) that recruitment of active expiration enhances ventilation, hence having an important functional role in meeting metabolic demand. To test these hypotheses Wistar rats (280–330 g) were implanted with electrodes for electroencephalography (EEG) and electromyography (EMG) of the neck, diaphragm (DIA) and abdominal (ABD) muscles. Active expiratory events were considered as rhythmic ABDEMG activity interposed to DIAEMG. Animals were exposed to room air followed by hypercapnia (7% CO2) with EEG, EMG and ventilation (V̇E) recorded throughout the experimental protocol. No active expiration was observed during room air exposure. During hypercapnia, CO2-evoked active expiration was predominantly recruited during non-REM sleep. Its increased occurrence during sleep was evidenced by the decreased DIA-to-ADB ratio (1:1 ratio means that each DIA event is followed by an ABD event, indicating a high occurrence of ABD activity). Moreover, V̇E was also enhanced (P < 0.05) in periods with active expiration. V̇E had a positive correlation (P < 0.05) with the peak amplitude of ABDEMG activity. The data strongly demonstrate that hypercapnia-induced active expiration increases during sleep and provide an important functional role to support V̇E in conditions of increased respiratory demand.

This article is protected by copyright. All rights reserved



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Analgesics and Sport Performance: Beyond the Pain Modulating Effects

Analgesics are widely used in sport to treat pain and inflammation associated with injury. However, there is growing evidence that some athletes might be taking these substances in an attempt to enhance performance. While the pharmacological action of analgesics and their use in treating pain with and without anti-inflammatory effect is well established, their effect on sport performance is debated. The aim of this review was to evaluate the evidence of whether analgesics are capable of enhancing exercise performance, and if so, to what extent.

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Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin

Sudden Infant Death Syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state. Two week-old tryptophan hydroxylase 2-deficient (TPH2-/-) and wild-type (WT) rat pups were placed in plethysmographic chambers supplied with room air. At the onset of active (AS) or quiet sleep (QS), separate groups of rats were exposed to hypercapnia (5% CO2), or mild hypoxia (~17% O2) or maintained in room air. Upon arousal, rats received room air. Apnea indices and latencies to spontaneous arousal from AS and QS were determined for pups exposed only to room air. Arousal latencies were also calculated for TPH2-/- and WT pups exposed to hypoxia or hypercapnia. Compared to WT, TPH2-/- pups hypoventilated in all states, but were profoundly more apneic solely in AS. TPH2-/- pups had delayed arousal in response to increasing CO2, and AS selectively delayed the arousal of TPH2-/- pups, irrespective of the gas they breathed. Thus, infants who are deficient in CNS 5-HT may be at increased risk for SIDS in active sleep due to increased apnea and delayed arousal compared to quiet sleep.



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Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn

Excessive liquid in airways and/or in distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near term rabbit kittens (30 days gestation; term ~32 days) were delivered, had lung liquid drained and either had no liquid replaced (Control, n=7) or 30 mL/kg of liquid was re-added to the airways (liquid added; LA, n=7). Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration and airway size were analysed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 mL/kg was significantly greater in LA compared to Control kittens (35.0±0.7 vs 26.8±0.4 cmH2O; P<0.001). LA kittens required greater time to achieve lung aeration (106±14 vs. 60±6 inflations; P=0.03) and had expanded chest walls as evidenced by an increased total chest area (32±9%; P<0.0001), lung height (17±6%; P=0.02) and curvature of the diaphragm (19±8%; P=0.04). LA kittens had lower functional residual capacity during step-wise changes in positive end expiratory pressures (PEEP; 5, 3, 0, 5 cmH20). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near term babies with TTN after birth.



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THE INTERPLAY BETWEEN IRON AND OXYGEN HOMEOSTASIS WITH A PARTICULAR FOCUS ON THE HEART

Iron is subject to tight homeostatic control in mammals. At the systemic level, iron homeostasis is controlled by the liver-derived hormone hepcidin acting on its target ferroportin in the gut, spleen and liver, which form the sites of iron uptake, recycling and storage, respectively. At the cellular level, iron homeostasis is dependent on the iron regulatory proteins IRP1/IRP2. Unique chemical properties of iron underpin its importance in biochemical reactions involving oxygen. As such, it is not surprising that there are reciprocal regulatory links between iron and oxygen homeostasis, operating both at the systemic and cellular levels. Hypoxia activates the IRP pathway, and in addition suppresses liver hepcidin through endocrine factors that have yet to be fully elucidated. This review summarises current knowledge on the interplay between oxygen and iron homeostasis, and describes recent insights gained into this interaction in the context of the heart. These include the recognition that the hepcidin/ferroportin axis plays a vital role in the regulation of intracellular iron homeostasis as well as regulating systemic iron availability. As is the case for other aspects of iron homeostasis, hypoxia significantly modulates the function of the hepcidin/ferroportin pathway in the heart. Key areas still to understand are the interactions between cardiac iron and diseases of the heart where hypoxia is a recognised component



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The effect of a pre-hop on the muscle-tendon interaction during vertical jumps

Many movements use stretch-shortening cycles of a muscle-tendon unit (MTU) for storing and releasing elastic energy. The required stretching of medial gastrocnemius (MG) tendinous tissue during jumps, however, requires large length changes of the muscle fascicles, due to the lack of MTU length changes. This has a negative impact on the force generating capacity of the muscle fascicles. The purpose of this study was to induce a MG MTU stretch prior to shortening by adding a pre-hop to the squat jump. Eleven well-trained athletes specialized in jumping performed a pre-hop squat jump (PHSJ) and a standard squat jump (SSJ). Kinematic data was collected using a 3D-motion capture system and used in a musculoskeletal model to calculate MTU lengths. B-mode ultrasonography of the MG was used to measure fascicle length and pennation angle during the jumps. By combining the muscle-tendon unit lengths, fascicle lengths and pennation angles, the stretch and recoil of the series elastic element of MG was calculated using a simple geometric muscle-tendon model. Our results show less length changes of the muscle fascicles during the upward motion and lower maximal shortening velocities, increasing the moment generating capacity of the plantar flexors, reflected in the higher ankle joint moment in the PHSJ as compared to the SSJ. Although muscle-tendon interaction during the PHSJ was more optimal, athletes were not able to increase their jump height compared to the SSJ.



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Running training experience attenuates disuse atrophy in fast-twitch skeletal muscles of rats

Responsiveness to physiological stimuli, such as exercise and muscular inactivation, differs in individuals. However, the mechanisms responsible for these individual differences remain poorly understood. We tested whether a prior experience of exercise training affects the responses of skeletal muscles to unloading. Young rats were assigned to perform daily running training using a treadmill for 8 weeks. After an additional 8 weeks of normal habitation, the rats were hindlimb unloaded by tail suspension for 1 week. Fast-twitch plantaris, gastrocnemius, and tibialis anterior muscles did not atrophy after unloading in rats with training experience, although soleus muscle lost weight similar to sedentary rats. We also analyzed the transcriptome in plantaris muscle using RNA sequencing followed by hierarchical clustering analysis and found that a subset of genes that were generally up-regulated in sedentary rats after unloading were less responsive in rats with training experience. The distribution of histone 3 was diminished at the loci of these genes during the training period. Although the deposition of histone 3 was restored after an additional period of normal habitation, the incorporation of H3.3 variant was promoted in rats with training experience. This remodeling of nucleosomes closely correlated to the conformational changes of chromatin and suppressed gene expression in response to unloading. These results suggest that exercise training stimulated the early turnover of histone components, which may alter the responsiveness of gene transcription to physiological stimuli.



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Effect of hypoxia and hyperoxia on exercise performance in healthy individuals and in patients with pulmonary hypertension: A systematic review

Exercise performance is determined by oxygen supply to working muscles and vital organs. In healthy individuals, exercise performance is limited in the hypoxic environment at altitude, when oxygen delivery is diminished due to the reduced alveolar and arterial oxygen partial pressures. In patients with pulmonary hypertension, exercise performance is already reduced near sea level due to impairments of the pulmonary circulation and gas exchange and, presumably, these limitations are more pronounced at altitude. In studies performed near sea level in healthy subjects as well as in patients with pulmonary hypertension (PH) maximal performance during progressive ramp exercise and endurance of submaximal constant load exercise were substantially enhanced by breathing oxygen-enriched air. Both in healthy individuals and in PH-patients these improvements were mediated by a better arterial, muscular and cerebral oxygenation along with a reduced sympathetic excitation, as suggested by the reduced heart rate and alveolar ventilation at submaximal isoloads, and an improved pulmonary gas exchange efficiency, especially in patients with PH. In summary, in healthy individuals and in patients with pulmonary hypertension, alterations in the inspiratory PO2 by exposure to hypobaric hypoxia or normobaric hyperoxia reduce or enhance exercise performance, respectively, by modifying oxygen delivery to the muscles and the brain, by effects on cardiovascular and respiratory control and by alterations in pulmonary gas exchange. The understanding of these physiologic mechanisms helps counselling individuals planning altitude or air travel and prescribing oxygen therapy to patients with pulmonary hypertension.



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The acute effects of long acting bronchodilators on small airways detected in COPD patients by single breath N2 test and lung P-V curve

Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence, the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (mean age (SD): 70±7 years; 82% males) with moderate to very severe COPD. Patients underwent body-plethysmography, arterial blood gas-analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single breath nitrogen test (SBN) and transpulmonary pressure-volume curve (PL-V), before and one hour after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the GOLD scale, and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5±4% and -2.5±2.1%, both P<0.001), with an increase in both slope and height of phase IV, and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3±3 mmHg and 2±2%, both P<0.001); their changes negatively correlated with those of phase III slope (r=-0.659 and r=-0.454, both P<0.01). The vital capacity (VC) increased substantially but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small airways damage and positively affect gas exchange.



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ANAL ULCERATIONS IN CROHN’S DISEASE: NATURAL HISTORY IN THE ERA OF BIOLOGICAL THERAPY

The natural history of anal ulcerations in Crohn's disease remains unknown.

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ANAL ULCERATIONS IN CROHN’S DISEASE: NATURAL HISTORY IN THE ERA OF BIOLOGICAL THERAPY

The natural history of anal ulcerations in Crohn's disease remains unknown.

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Stretch-reflex threshold modulation during active elbow movements in post-stroke survivors with spasticity

Spasticity is a common complication of stroke, occurring in ∼20-50% of patients in the first year (Wissel et al., 2013) and often associated with other sensory and motor impairments (e.g., muscle weakness, loss of dexterity). Spasticity is generally assessed by resistance or EMG responses to passive muscle stretches and has been attributed to exaggerated spinal stretch reflexes (SRs) and alterations in intrinsic muscle properties (Dietz and Sinkjaer, 2007). For example, motor units of spastic muscles often have an impaired ability to relax (Lewek et al., 2007), prolonged spontaneous firing (Mottram et al., 2010) and low firing rates (Young and Mayer, 1982; Gemperline et al., 1995).

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Cortical involvement in myopathies: insights from transcranial magnetic stimulation

There is increasing evidence that a significant brain dysfunction occurs in patients affected by several myopathies. For instance, some patients with muscle diseases, such as dystrophinopathies, exhibit intellectual disabilities and mental retardation (Emery, 1987; North et al., 1996; Mehler, 2000), while in subjects with facioscapulohumeral muscular dystrophy (FSHD) epilepsy is one of the most frequent manifestations of cerebral involvement (Saito et al., 2007; Grosso et al., 2011).

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Clinical practice guideline for enhanced recovery after colon and rectal surgery from the American Society of Colon and Rectal Surgeons (ASCRS) and Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)



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The costal remains of the El Sidrón Neanderthal site (Asturias, northern Spain) and their importance for understanding Neanderthal thorax morphology

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Publication date: October 2017
Source:Journal of Human Evolution, Volume 111
Author(s): Daniel García-Martínez, Markus Bastir, Rosa Huguet, Almudena Estalrrich, Antonio García-Tabernero, Luis Ríos, Eugenia Cunha, Marco de la Rasilla, Antonio Rosas
The study of the Neanderthal thorax has attracted the attention of the scientific community for more than a century. It is agreed that Neanderthals have a more capacious thorax than modern humans, but whether this was caused by a medio-lateral or an antero-posterior expansion of the thorax is still debated, and is key to understanding breathing biomechanics and body shape in Neanderthals. The fragile nature of ribs, the metameric structure of the thorax and difficulties in quantifying thorax morphology all contribute to uncertainty regarding precise aspects of Neanderthal thoracic shape. The El Sidrón site has yielded costal remains from the upper to the lower thorax, as well as several proximal rib ends (frequently missing in the Neanderthal record), which help to shed light on Neanderthal thorax shape. We compared the El Sidrón costal elements with ribs from recent modern humans as well as with fossil modern humans and other Neanderthals through traditional morphometric methods and 3D geometric morphometrics, combined with missing data estimation and virtual reconstruction (at the 1st, 5th and 11th costal levels). Our results show that Neanderthals have larger rib heads and articular tubercles than their modern human counterparts. Neanderthal 1st ribs are smaller than in modern humans, whereas 5th and 11th ribs are considerably larger. When we articulated mean ribs (size and shape) with their corresponding vertebral elements, we observed that compared to modern humans the Neanderthal thorax is medio-laterally expanded at every level, especially at T5 and T11. Therefore, in the light of evidence from the El Sidrón costal remains, we hypothesize that the volumetric expansion of the Neanderthal thorax proposed by previous authors would mainly be produced by a medio-lateral expansion of the thorax.



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Unique EMS Leadership Training Video Series in the Works

Triple Zilch Productions, LLC will develop an EMS leadership training video series in conjunction with NEMSMA ST. LOUIS — Triple Zilch Productions, LLC and the National EMS Management Association, Inc. (NEMSMA) announce the development of a new and unique EMS Leadership training video series. The series will be produced and developed by Triple Zilch Productions in St. Louis, Missouri which specializes ...

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Leveraging the Medical Context to Increase Upper Extremity Reconstruction among Patients with Tetraplegia: A Qualitative Analysis

Publication date: Available online 3 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Chelsea A. Harris, John-Michael Muller, Melissa J. Shauver, Kevin C. Chung
Objectives(1) To characterize patients' medical experiences from initial injury until they become candidates for Upper Extremity Reconstruction (UER). (2) To identify points in this medical context that may be most amenable to interventions designed to increase UER utilization.DesignA qualitative cross-sectional study using grounded theory methodology and constant comparative analysis of data collected through semi-structured individual interviews.SettingCommunityParticipantsA sample of individuals with C4-C8 cervical spinal injuries (N=19) who sustained injuries at least one year prior to interview. Nine patients had undergone reconstruction, ten had not. The study sample was predominantly male (79%), white (89%), and ASIA Grade A-D were represented (Grade A: 42%; Grade B: 32%; Grade C 16%; Grade D 10%).InterventionsnoneMain Outcome MeasuresParticipant self-report of their medical experiences from the time of injury through the early recovery period.ResultsWe identified three domains that formed patients' medical context prior to UER candidacy: (1) their ability to achieve and maintain health; (2) their relationship with health care providers; and (3) their expectations regarding clinicians' tetraplegia-specific expertise. Trust emerged as a major theme driving potential intervention targets. Patients transferred to referral centers had higher trust in tertiary providers relative to local physicians. In the outpatient setting, patients' trust correlated with the tetraplegia-specific expertise level they perceived the specialty to have (high for PM&R, intermediate for urology, low for primary care).ConclusionsIn appropriate candidates, UER produces substantial functional gains, but reconstruction remains underutilized in the tetraplegic population. By analyzing how patients achieve health and build trust in early recovery/injury, our study provides strategies to improve UER access. We propose that interventions targeting highly trusted points of care (transfer hospitals) and avoiding low-trust points (PCPs, home health) will be most effective. Urology may represent a novel entry point for UER interventions.



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Investigating The Efficacy of Web-based Transfer Training on Independent Wheelchair Transfers through Randomized Control Trials

Publication date: Available online 3 August 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Lynn Worobey, Stephanie Rigot, Nathan Hogaboom, Chris Venus, Michael L. Boninger
ObjectivesTo determine the efficacy of a web-based transfer training module at improving transfer technique across three groups: web-based training, in-person training (current standard of practice), and a waitlist control group (WLCG). Secondarily, to determine subject factors that can be used to predict improvements in transfer ability after training.DesignRandomized control trials.SettingSummer and winter sporting events for disabled veterans.ParticipantsA convenience sample of manual and power wheelchair users who could transfer independently (n=71).InterventionsAn individualized, in-person transfer training session or a web-based transfer training module. The WLCG received the web training at their follow-up visit.Main Outcome MeasureTransfer assessment instrument (TAI) part 1 score was used to assess transfers at baseline, skill acquisition immediately post-training, and skill retention after a 1-2 day follow-up period.ResultsThe in-person and web-based training groups improved their median [interquartile range] TAI scores from 7.98 [7.18-8.46] to 9.13 [8.57-9.58, p<0.01], and from 7.14 [6.15-7.86] to 9.23 [8.46-9.82, p<0.01], respectively, compared to the WLCG that had a median score of 7.69 for both assessments [baseline: 6.15-8.46, follow-up control: 5.83-8.46]. Participants retained improvements at follow-up (p>0.05). A lower initial TAI score was found to be the only significant predictor of a larger percent change in TAI score after receiving training.ConclusionsTransfer training can improve technique with changes retained within a short follow-up window, even among experienced wheelchair users. Web-based transfer training demonstrated comparable improvements to in-person training. With almost half of the United States population consulting online resources before a healthcare professional, web-based training may be an effective method to increase knowledge translation.



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Identification of an atypical microdeletion generating the RNF135 - SUZ12 chimeric gene and causing a position effect in an NF1 patient with overgrowth

Abstract

Neurofibromatosis type I (NF1) microdeletion syndrome, which is present in 4–11% of NF1 patients, is associated with a severe phenotype as it is caused by the deletion of NF1 and other genes in the 17q11.2 region. The variable expressivity of the disease makes it challenging to establish genotype–phenotype correlations, which also affects prognosis and counselling. We here describe a 3-year-old NF1 patient with an atypical deletion and a complex phenotype. The patient showed overgrowth, café au lait spots, inguinal freckling, and neurological abnormalities. The extent of the deletion was determined by means of array comparative genomic hybridisation, and its breakpoints were isolated by means of long-range polymerase chain reaction. Sequence analysis of the deletion junction fragment revealed the occurrence of an Alu-mediated recombination that led to the generation of a chimeric gene consisting of three exons of RNF135 and eleven exons of SUZ12. Interestingly, the deletion shares a common RNF135-centred region with another deletion described in a non-NF1 patient with overgrowth. In comparison with the normal RNF135 allele, the chimeric transcript was 350-fold over-expressed in peripheral blood, and the ADAP2 gene located upstream of RNF135 was also up-regulated. In line with this, the deletion causes the loss of a chromatin TD boundary, which entails the aberrant adoption of distal cis-acting regulatory elements. These findings suggest that RNF135 haploinsufficiency is related to overgrowth in patients with NF1 microdeletion syndrome and, for the first time, strongly indicate a position effect that warrants further genotype–phenotype correlation studies to investigate the possible existence of previously unknown pathogenic mechanisms.



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Caffeine Studies, Gender and Prior Consumption of Caffeine

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


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Senators reintroduce act to build national EMS memorial

By EMS1 Staff WASHINGTON — A group of senators are beginning a second push for an act concerning the construction of an EMS memorial. WDTV reported that Senators Shelley Moore Capito, Chris Coons, Tom Cotton, Bill Cassidy, Jeanne Shaheen and Elizabeth Warren reintroduced the National Emergency Medical Services Commemorative Work Act. The act would allow a commemorative work honoring EMS providers ...

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College graduates travel Calif. coast in ambulance

Before moving to Florida to start their careers, Christa and JD Hammer are spending the summer in a refurbished ambulance

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Caffeine Studies, Gender and Prior Consumption of Caffeine

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


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Th1 Pathway: The Missing Link Between Inflammatory Bowel Disease and Microscopic Colitis?



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The physicochemical distribution of 131I in a municipal wastewater treatment plant

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Volker Hormann, Helmut W. Fischer
As a consequence of therapeutic and diagnostic treatment of patients with thyroid diseases, 131I is introduced into the sewage system on a regular basis. This presents an opportunity to use the 131I as a tracer to study its partitioning and transport within a wastewater treatment plant (WWTP). In the case of nuclear accidents where 131I is one of the most prominent nuclides, an understanding of iodine partitioning and transport will be valuable for developing models that may prognosticate the activity concentrations in sludge and outflow, especially after an accidental input. In this study, samples from various locations inside a municipal WWTP were taken and for each sample, three different fractions were separated by a chemical extraction process. These fractions were analysed for their 131I activity concentrations by gamma-ray spectroscopy. While about 30% of the radioiodine activity in the inflow is associated with organic molecules, this amounts to about 90% after biological treatment. This is caused by the accumulation of 131I bound to organic matter in the return sludge and by a transfer of 131I from the inorganic to the organic fractions, most likely mediated by microbial action. In the outflow, inorganic and low-molecular 131I is dominant, but the overall activity concentration is reduced to about 50–75%.



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Pre-movement planning processes in people with congenital mirror movements

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Publication date: Available online 2 August 2017
Source:Clinical Neurophysiology
Author(s): E.A. Franz, Y. Fu
ObjectivePre-movement processes were investigated in people with Congenital mirrormovement (CMM), a rare disorder in which bilateral movement (mirroring) occurs in the upper distal extremities (primarily the hands and fingers) during intended unilateral movements. Abnormal density of ipsilateral corticospinal projections is an established hallmark of CMM. This study tested whether the Lateralized Readiness Potential (LRP), which reflects movement planning and readiness, is also abnormal in people with CMM.MethodsTwenty-eight neurologically-normal controls and 8 people with CMM were tested on a unimanual Go/No-go task while electroencephalography (EEG) was recorded to assess the LRP.ResultsNo significant group differences were found in reaction time (RT). However, significantly smaller LRP amplitudes were found, on average, in the CMM group compared to Controls at central-motor (C3,C4) sites in stimulus-locked and response-locked epochs; similar group differences were also found at further frontal sites (F3,F4) during response-locked epochs.ConclusionsAbnormal brain activity in pre-movement processes associated with response planning and preparation is present in people with CMM.SignificanceAberrant bilateral activity during pre-movement processes is clearly implicated; whether part of the etiology of CMM, or as a mechanism of neuro-compensation, is not yet known.



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Biosimilar Drugs for Inflammatory Bowel Disease: Is Similar Good Enough?



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Understanding the Differences Between Gastroparesis and Gastroparesis-Like Syndrome: Filling a GaPing Hole?



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Vonoprazan-Based Helicobacter pylori Eradication Therapy: Time to Get Kompetitive?



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Letter to the editor regarding “The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair”



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Implications of Pediatric Frova length in airway management



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Comment to “Intraoperative apnea in children after buffered 5% povidone-iodine site sterilization for strabismus surgery”



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Combination of intranasal dexmedetomidine and oral midazolam as sedation for pediatric MRI



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In this issue: September 2017



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Issue Information



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The association between caudal anesthesia and increased risk of postoperative surgical complications in boys undergoing hypospadias repair: Comment on data sparsity



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The radiological home: Pediatric anesthesiologist's role in risk assessment for imaging procedures



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Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats

Abstract

Background

Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive.

Aim

In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction.

Methods

The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca2+/calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well.

Results

Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca2+/calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well.

Conclusion

In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.



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Experimental and modelling evidence of shortening heat in cardiac muscle

Abstract

When a muscle shortens against an afterload, the heat that it liberates is greater than that produced by the same muscle contracting isometrically at the same level of force. This excess heat is defined as 'shortening heat', and has been repeatedly demonstrated in skeletal muscle but not in cardiac muscle. Given the micro-structural similarities between these two muscle types, and since we imagine that shortening heat is the thermal accompaniment of cross-bridge cycling, we have re-examined this issue. Using our flow-through microcalorimeter, we measured force and heat generated by isolated rat trabeculae undergoing isometric contractions at different muscle lengths and work-loop (shortening) contractions at different afterloads. We simulated these experimental protocols using a thermodynamically-constrained model of cross-bridge cycling and probed the mechanisms underpinning shortening heat. Predictions generated by the model were subsequently validated by a further set of experiments. Both our experimental and modelling results show convincing evidence for the existence of shortening heat in cardiac muscle. Its magnitude is inversely related to the afterload or, equivalently, directly related to the extent of shortening. Computational simulations reveal that the heat of shortening arises from the cycling of cross-bridges, and that the rate of ATP hydrolysis is more sensitive to change of muscle length than to change of afterload. Our results clarify a long-standing uncertainty in the field of cardiac muscle energetics.

This article is protected by copyright. All rights reserved



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Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger–Ellison Syndrome

Abstract

Zollinger–Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used 111indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, 68gallium (68Ga)-labeled somatostatin radiotracers (i.e., 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.



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A New Fully Covered Self-Expandable Metal Stent for the Treatment of Postsurgical Benign Biliary Strictures

Abstract

Background

Endotherapy with plastic stent (PS) placement is the main modality for treating benign biliary strictures (BBSs). Fully covered self-expandable metal stents (FCSEMSs) are being increasingly used for BBS management, with high stricture resolution. However, traditional metal tents are associated with high migration, causing treatment failure.

Methods

We investigated the efficacy and safety of a new FCSEMS for postsurgical BBS treatment and compared these parameters between the FCSEMS and PS treatment through retrospective analysis. The primary outcome measurements included stricture resolution, stricture recurrence, and complications.

Results

In total, 69 patients were included, of whom 32 underwent FCSEMS treatment and 37 underwent PS treatment. The technical success rate and the number of endoscopic retrograde cholangiopancreatography procedures were similar between the groups. The median stenting duration was 5.2 months (range 1.5–15.3) in the FCSEMS group and 10.7 months (range 2.5–22.6) in the PS group (P < 0.01). The stents removal rate was 96.9% in the FCSEMS group and 94.6% in the PS group. The stricture resolution rate based on intention-to-treat analysis was 83.8% in the PS group and 84.4% (27/32) in the FCSEMS group (P = 0.947), whereas the rates from per-protocol analysis were 88.6% (31/35) and 87.1% (27/31), respectively (P = 0.574). Early and late complications were similar between the groups. The median follow-up time was 43 months (range 13–71). The stricture recurrence rate was 11.1% (3/27) in the FCSEMS group and 16.1% (5/31) in the PS group (P = 0.435).

Conclusions

The new FCSEMS and the PS approach showed similar efficacy and safety in postsurgical BBS treatment. However, the FCSEMS required fewer procedural steps and shorter stenting time, making it an effective alternative modality.



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Exercise training in Tg{alpha}q*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgαq*44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor- coactivator-α (PGC-1α)]. In the untrained Tgαq*44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance.

NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed in transgenic chronic heart failure mice, evaluated in the critical period between the occurrence of an impairment of cardiac function and the terminal stage of the disease. Exercise training improved exercise performance and cardiac function, but it did not affect the impaired mitochondrial respiration. Factors "upstream" of mitochondria, including an enhanced cardiovascular O2 delivery, were mainly responsible for the functional improvement.



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A model for in vivo analysis of sudomotor sympathetic C-fiber activation and human sweat gland output

Quantitative assessment of small-fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small-fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small-fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 to 64 Hz, a quantitative relationship between the area under the SR–time curve and log10 stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: baseline, plateau, EC50, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg/ml) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce the quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR.

NEW & NOTEWORTHY A model for quantitative assessment of C-fiber function in human skin using intradermal electrical stimulation and local sweat rate measurements has been developed. This new electrically induced sweating model is nonpainful and allows for a complete stimulus-response curve plotting the area under the local sweat rate-time curve vs. the log10 stimulus frequency. The model has good reproducibility and should provide a means of assessing the progression of small C-fiber peripheral neuropathy in humans.



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Increased left ventricular extracellular volume and enhanced twist function in type 1 diabetic individuals

Individuals with type 1 diabetes (T1D) characteristically have high glycemic levels that over time can result in reactive fibrosis and abnormalities in myocardial function. T1 mapping with magnetic resonance imaging (MRI) can estimate the extent of reactive fibrosis by measurement of the extracellular volume fraction (ECV). The extent of alterations in the ECV and associated changes in left ventricular (LV) function and morphology in individuals with T1D is unknown. Fourteen individuals with long-term T1D and 14 sex-, age-, and body mass index-matched controls without diabetes underwent MRI measurement of myocardial T1 and ECV values as well as LV function and morphology. Ventricular mass, volumes, and global function (LVEF and circumferential/longitudinal/radial strain) were similar in those with T1D and controls. However, those with T1D had larger myocardial ECV (22.1 ± 1.8 vs. 20.1 ± 2.1, P = 0.008) and increased native (noncontrast) myocardial T1 values (1,211 ± 44 vs. 1,172 ± 43 ms, P < 0.001) as compared with controls. Both the ECV and native T1 values significantly correlated with several components of torsion and circumferential-longitudinal shear strain (Ecl, the shear strain component associated with twist). Individuals with T1D had increased systolic torsion (P = 0.035), systolic torsion rate (P = 0.032), peak Ecl (P = 0.001), and rates of change of systolic (P = 0.007) and diastolic (P = 0.007) Ecl. Individuals with T1D, with normal structure, LVEF, and strain, have increased extracellular volume and increased native T1 values with associated augmented torsion and Ecl. These measures may be useful in detecting the early stages of diabetic cardiomyopathy and warrant larger prospective studies.

NEW & NOTEWORTHY Individuals with type 1 diabetes, with normal left ventricular structure and function (ejection fraction and strain), have signs of interstitial fibrosis, measured with MRI as increased extracellular volume fraction and increased native myocardial T1, which significantly correlated with a number of measures of augmented left ventricular twist function. These measures may be useful in detecting the early stages of diabetic cardiomyopathy.



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Individual hemoglobin mass response to normobaric and hypobaric "live high-train low": A one-year crossover study

The purpose of this research was to compare individual hemoglobin mass (Hbmass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-day LHTL training camps in either HH or NH. All athletes slept at 2,250 meters and trained at altitudes <1,200 meters. Hbmass was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre) and immediately after (post) each 18-day training camp. Hbmass increased similarly in HH (916–957 g, 4.5 ± 2.2%, P < 0.001) and in NH (918–953 g, 3.8 ± 2.6%, P < 0.001). Hbmass changes did not differ between HH and NH (P = 0.42). There was substantial interindividual variability among subjects to both interventions (i.e., individual responsiveness or the individual variation in the response to an intervention free of technical noise): 0.9% in HH and 1.7% in NH. However, a correlation between intraindividual Hbmass changes (%) in HH and in NH (r = 0.52, P = 0.048) was observed. HH and NH evoked similar mean Hbmass increases following LHTL. Among the mean Hbmass changes, there was a notable variation in individual Hbmass response that tended to be reproducible.

NEW & NOTEWORTHY This is the first study to compare individual hemoglobin mass (Hbmass) response to normobaric and hypobaric live high-train low using a same-subject crossover design. The main findings indicate that hypobaric and normobaric hypoxia evoked a similar mean increase in Hbmass following 18 days of live high-train low. Notable variability and reproducibility in individual Hbmass responses between athletes was observed, indicating the importance of evaluating individual Hbmass response to altitude training.



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Physical activity modulates corticospinal excitability of the lower limb in young and old adults

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to elicit MEPs in the active vastus lateralis muscle (10% maximal voluntary contraction) with 5% increments in stimulator intensity until the maximum MEP amplitude. Stimulus-response curves of MEP amplitudes were fit with a four-parameter sigmoidal curve and the maximal slope calculated (slopemax). Habitual PA was assessed with tri-axial accelerometry and participants categorized into either those meeting the recommended PA guidelines for optimal health benefits (>10,000 steps/day, high-PA; n = 21) or those not meeting the guidelines (<10,000 steps/day, low-PA; n = 41). The MEP amplitudes and slopemax were greater in the low-PA compared with the high-PA group (P < 0.05). Neither age nor sex influenced the stimulus-response curve parameters (P > 0.05), suggesting that habitual PA influenced the excitability of the corticospinal tract projecting to the lower limb similarly in both young and old adults. These findings provide evidence that achieving the recommended PA guidelines for optimal health may mediate its effects on the nervous system by decreasing corticospinal excitability.

NEW & NOTEWORTHY Transcranial magnetic stimulation was used to determine whether achieving the recommended 10,000 steps/day for optimal health influenced the excitability of the corticospinal tract projecting to the knee extensor muscles. Irrespective of age and sex, individuals who achieved >10,000 steps/day had lower corticospinal excitability than those who performed <10,000 steps/day, possibly representing greater control of inhibitory and excitatory networks. Physical activity involving >10,000 steps/day may mediate its effects on the nervous system by decreasing corticospinal excitability.



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Ten days of repeated local forearm heating does not affect cutaneous vascular function

The aim of the present study was to determine whether 10 days of repeated local heating could induce peripheral adaptations in the cutaneous vasculature and to investigate potential mechanisms of adaptation. We also assessed maximal forearm blood flow to determine whether repeated local heating affects maximal dilator capacity. Before and after 10 days of heat training consisting of 1-h exposures of the forearm to 42°C water or 32°C water (control) in the contralateral arm (randomized and counterbalanced), we assessed hyperemia to rapid local heating of the skin (n = 14 recreationally active young subjects). In addition, sequential doses of acetylcholine (ACh, 1 and 10 mM) were infused in a subset of subjects (n = 7) via microdialysis to study potential nonthermal microvascular adaptations following 10 days of repeated forearm heat training. Skin blood flow was assessed using laser-Doppler flowmetry, and cutaneous vascular conductance (CVC) was calculated as laser-Doppler red blood cell flux divided by mean arterial pressure. Maximal cutaneous vasodilation was achieved by heating the arm in a water-spray device for 45 min and assessed using venous occlusion plethysmography. Forearm vascular conductance (FVC) was calculated as forearm blood flow divided by mean arterial pressure. Repeated forearm heating did not increase plateau percent maximal CVC (CVCmax) responses to local heating (89 ± 3 vs. 89 ± 2% CVCmax, P = 0.19), 1 mM ACh (43 ± 9 vs. 53 ± 7% CVCmax, P = 0.76), or 10 mM ACh (61 ± 9 vs. 85 ± 7% CVCmax, P = 0.37, by 2-way repeated-measures ANOVA). There was a main effect of time at 10 mM ACh (P = 0.03). Maximal FVC remained unchanged (0.12 ± 0.02 vs. 0.14 ± 0.02 FVC, P = 0.30). No differences were observed in the control arm. Ten days of repeated forearm heating in recreationally active young adults did not improve the microvascular responsiveness to ACh or local heating.

NEW & NOTEWORTHY We show for the first time that 10 days of repeated forearm heating is not sufficient to improve cutaneous vascular responsiveness in recreationally active young adults. In addition, this is the first study to investigate cutaneous cholinergic sensitivity and forearm blood flow following repeated local heat exposure. Our data add to the limited studies regarding repeated local heating of the cutaneous vasculature.



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Influence of sex, menstrual cycle, and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Women experience orthostatic intolerance more than men, and they experience faintness more in the early follicular [i.e., low-hormone (LH)] than luteal [i.e., high-hormone (HH)] phase of the menstrual cycle. Men (n = 13, 25.8 ± 1.8 yr old) and women in the LH (days 2–5; placebo) and HH (days 18–24; high dose) phases of the menstrual cycle with (OC; n = 14, 22.0 ± 0.8 yr old) or without (NOC; n = 12, 21.8 ± 0.5 yr old) oral contraceptive (OC) use underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume [stroke volume index (SVi)], cardiac output index, heart rate, end-tidal CO2, and middle cerebral artery (MCA) blood flow velocity were measured. When subjected to the Valsalva maneuver, all women had a greater increase in diastolic and mean MCA blood flow velocity than men (P ≤ 0.065), with no significant effect of menstrual cycle phase or OC use. When subjected to the supine-sit-stand protocol, men had lower MCA blood flow velocity (P < 0.038) than all women, and SVi was higher in men than in the NOC group in all postures (P < 0.011) and in the OC group in the LH phase of the menstrual cycle during standing (P = 0.010). Only men experienced higher resistance index (P < 0.001) and pulsatility index (P < 0.001) with standing. The OC group had lower end-tidal CO2 (P = 0.002) than the NOC group (P = 0.030) and men (P ≤ 0.067). SVi (P = 0.004) and cardiac output index (P = 0.008) were higher in the OC than NOC group. A tendency toward a lower mean MCA blood flow velocity (P = 0.058) and higher SVi (P = 0.059) and pulsatility index (P = 0.058) was noted in the HH than LH phase. Mean arterial pressure was higher in the OC than NOC group in the LH phase (P = 0.049) and lower in the HH than LH phase (P = 0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular, and/or cerebrovascular physiology.

NEW & NOTEWORTHY We have found sex differences in the cerebrovascular response to the Valsalva maneuver and standing. Men have greater cerebral vasoconstriction (or women have greater cerebral vasodilation) during late phase II of the Valsalva maneuver, and the cerebrovascular resistance index increases in men, but not in women, during standing. Furthermore, our findings indicate that both the menstrual cycle phase and oral contraceptive use can influence cardiovascular function both at rest and during active standing.



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Beta-1 vs. beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans

During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate x systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective β-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t-tests. Esmolol ( = 3296 ± 1204) and propranolol ( = 2997 ± 699) caused similar reductions in peak RPP compared with saline ( = 5384 ± 1865). In support of our hypothesis, CBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing CBV to RPP. In summary, not only does selective β1 blockade reduce myocardial oxygen demand during exercise, but it also unveils β2-receptor-mediated coronary exercise hyperemia.

NEW & NOTEWORTHY In this study, we evaluated the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with esmolol compared with propranolol. These findings increase our understanding of the individual and combined roles of coronary β1 and β2 adrenergic receptors in humans.



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Nonlinearities of heart rate variability in animal models of impaired cardiac control: contribution of different time scales

Heart rate variability (HRV) has been extensively explored by traditional linear approaches (e.g., spectral analysis); however, several studies have pointed to the presence of nonlinear features in HRV, suggesting that linear tools might fail to account for the complexity of the HRV dynamics. Even though the prevalent notion is that HRV is nonlinear, the actual presence of nonlinear features is rarely verified. In this study, the presence of nonlinear dynamics was checked as a function of time scales in three experimental models of rats with different impairment of the cardiac control: namely, rats with heart failure (HF), spontaneously hypertensive rats (SHRs), and sinoaortic denervated (SAD) rats. Multiscale entropy (MSE) and refined MSE (RMSE) were chosen as the discriminating statistic for the surrogate test utilized to detect nonlinearity. Nonlinear dynamics is less present in HF animals at both short and long time scales compared with controls. A similar finding was found in SHR only at short time scales. SAD increased the presence of nonlinear dynamics exclusively at short time scales. Those findings suggest that a working baroreflex contributes to linearize HRV and to reduce the likelihood to observe nonlinear components of the cardiac control at short time scales. In addition, an increased sympathetic modulation seems to be a source of nonlinear dynamics at long time scales. Testing nonlinear dynamics as a function of the time scales can provide a characterization of the cardiac control complementary to more traditional markers in time, frequency, and information domains.

NEW & NOTEWORTHY Although heart rate variability (HRV) dynamics is widely assumed to be nonlinear, nonlinearity tests are rarely used to check this hypothesis. By adopting multiscale entropy (MSE) and refined MSE (RMSE) as the discriminating statistic for the nonlinearity test, we show that nonlinear dynamics varies with time scale and the type of cardiac dysfunction. Moreover, as complexity metrics and nonlinearities provide complementary information, we strongly recommend using the test for nonlinearity as an additional index to characterize HRV.



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The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed.

NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change.



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Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

Abstract

Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.



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Endotoxaemia during left ventricular assist device insertion: relationship between risk factors and outcome

Br J Anaesth (2004) 92 (1): 131–133.

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Functional indexes of reactive cognitive control: ERPs in cued go/no-go tasks

Abstract

We aimed to determine the functional meaning of latent (hidden) components decomposed from ERPs, in the context of a go/no-go paradigm. To accomplish this, we used a new group blind source separation method, based on joint diagonalization of covariance matrices of ERPs. Four variants of a frequently used go/no-go paradigm were designed, in which operations of reactive cognitive control, such as conflict detection and action inhibition, were independently manipulated. The results showed that a latent component, generated in the anterior cingulate cortex, induced N2/P3 fluctuation only in conditions in which the prepotent model was violated, and thus can be associated with conflict detection operations. In contrast, the two latent components generated in the vicinity of the central sulcus induced P3-like fluctuations in conditions in which the prepared action was suppressed, and thus can be associated with action inhibition operations. The advantages and limitations of the new blind source separation method in relation to ERP research are also discussed.



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

Journal of Gastroenterology

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US Republican makes first move to work with Democrats on healthcare

Reuters Health News

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Naloxegol in opioid-induced constipation: A new paradigm in the treatment of a common problem

Patient Preference and Adherence

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Two biggest US drug purchasers keep key Novo Nordisk drugs on 2018 list

Reuters Health News

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The intestinal microbiome in infectious diseases: The clinical relevance of a rapidly emerging field

Open Forum Infectious Diseases

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Nut and peanut butter consumption and the risk of esophageal and gastric cancer subtypes

American Journal of Clinical Nutrition

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Effect of intragastric FODMAP infusion on upper gastrointestinal motility, gastrointestinal, and psychological symptoms in irritable bowel syndrome vs healthy controls

Neurogastroenterology & Motility

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Effect of green tea supplements on liver enzyme elevation: Results from a randomized intervention study in the United States

Cancer Prevention Research

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Fecal incontinence is associated with mortality among older adults with complex needs: An observational cohort study

The American Journal of Gastroenterology

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Noninvasive biomarkers as surrogate predictors of clinical and endoscopic remission after infliximab induction in patients with refractory ulcerative colitis

Saudi Journal of Gastroenterology

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Efficacy and safety of nortriptyline in functional dyspepsia in Asians: A randomized double-blind placebo-controlled trial

Journal of Gastroenterology and Hepatology

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After successful hepatitis C virus antiviral therapy: It looks that normal alanine aminotransferase level is not the normal

Journal of Clinical Laboratory Analysis

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Typical adults eat enough salt to damage the heart

Reuters Health News

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Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: Impact of a sustained virological response

Alimentary Pharmacology and Therapeutics

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Indicators of suboptimal tumor necrosis factor antagonist therapy in inflammatory bowel disease

Digestive and Liver Diseases

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Characterizing normal bowel frequency and consistency in a representative sample of adults in the United States (NHANES)

The American Journal of Gastroenterology

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Hypoalbuminemia is a predictor of mortality and rebleeding in peptic ulcer bleeding under proton pump inhibitor use

Journal of the Formosan Medical Association

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A phase ii study with lead-in safety cohort of 5-fluorouracil, oxaliplatin, and lapatinib in combination with radiation therapy as neoadjuvant treatment for patients with localized HER2-positive esophagogastric adenocarcinomas

The Oncologist

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Biological agents in gastrointestinal cancers: Adverse effects and their management

Journal of Gastrointestinal Oncology

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Long-term treatment of eosinophilic esophagitis with swallowed topical corticosteroids: Development and evaluation of a therapeutic concept

The American Journal of Gastroenterology

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A case of sigmoid colon adenocarcinoma diagnosed as facial cutaneous metastasis for survival after operation for 37 months

Abstract

Cutaneous metastasis of an internal malignancy is uncommon and is estimated to occur in 0.7–9% of patients with internal cancer including autopsy cases. We would like to report a case of long survival of sigmoid colon adenocarcinoma diagnosed as an instance of facial cutaneous metastasis. A 68-year-old male was admitted to our hospital for a tumor mass on the left side of his cheek. In his past history, acute myocardial infarction had occurred 2 years earlier. He also had chronic renal failure and chronic obstructive pulmonary disease. Histologic findings from the biopsy sample of this facial lesion were moderately differentiated adenocarcinoma. Colonoscopy revealed a tumor 20 mm × 30 mm in diameter in the sigmoid colon. Histologic findings of the biopsy sample of this tumor also indicated moderately differentiated adenocarcinoma. The patient was diagnosed with sigmoid colon cancer with cutaneous metastasis to the face. We performed a sigmoidectomy with lymph node dissection and resection of the facial cutaneous metastasis. After being discharged, low dose chemotherapy was performed in consideration of the patient's renal function. Although long-term management of his general condition was provided, the patient died 37 months after surgery because of chronic heart failure.



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