Πέμπτη 12 Ιανουαρίου 2017
Acute Response of the Infraspinatus and Biceps Tendons to Pitching in Youth Baseball.
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Exercise guidelines to promote cardiometabolic health in spinal cord injured humans: time to raise the intensity?
Publication date: Available online 13 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tom E. Nightingale, Richard S. Metcalfe, Niels BJ. Vollaard, James L.J. Bilzon
Spinal cord injury (SCI) is a life changing event that, as a result of paralysis, negatively influences habitual levels of physical activity and hence cardiometabolic health. Performing regular structured exercise therefore appears extremely important in persons with SCI. However, exercise options are mainly limited to the upper-body, which involves a smaller activated muscle mass compared to the mainly leg-based activities commonly performed by non-disabled individuals. Current exercise guidelines for SCI focus predominantly on relative short durations of moderate-intensity aerobic arm cranking exercise, yet contemporary evidence suggests this is not sufficient to induce meaningful improvements in risk factors for the prevention of cardiometabolic disease in this population. As such, these guidelines and their physiological basis, require reappraisal. In this special communication, we propose that high-intensity interval training (HIIT) may be a viable alternative exercise strategy, to promote vigorous-intensity exercise and prevent cardiometabolic disease in persons with SCI. Supplementing the limited data from SCI cohorts with consistent findings from studies in non-disabled populations, we present strong evidence to suggest that HIIT is superior to moderate-intensity aerobic exercise for improving cardiorespiratory fitness, insulin sensitivity and vascular function. The potential application and safety of HIIT in this population is also discussed. We conclude that increasing exercise intensity could offer a simple, readily available, time-efficient solution to improve cardiometabolic health in persons with SCI. We call for high-quality randomised controlled trials to examine the efficacy and safety of HIIT in this population.
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Neural activity reveals perceptual grouping in working memory
Source:International Journal of Psychophysiology
Author(s): Laura R. Rabbitt, Daniel M. Roberts, Craig G. McDonald, Matthew S. Peterson
There is extensive evidence that the contralateral delay activity (CDA), a scalp recorded event-related brain potential, provides a reliable index of the number of objects held in visual working memory. Here we present evidence that the CDA not only indexes visual object working memory, but also the number of locations held in spatial working memory. In addition, we demonstrate that the CDA can be predictably modulated by the type of encoding strategy employed. When individual locations were held in working memory, the pattern of CDA modulation mimicked previous findings for visual object working memory. Specifically, CDA amplitude increased monotonically until working memory capacity was reached. However, when participants were instructed to group individual locations to form a constellation, the CDA was prolonged and reached an asymptote at two locations. This result provides neural evidence for the formation of a unitary representation of multiple spatial locations.
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Loss of protoheme IX farnesyltransferase in mature dentate granule cells impairs short term plasticity onto CA3 pyramidal cells
Abstract
Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protoheme IX farnesyltransferase transcribed by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term plasticity and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses with CA3 pyramidal cells via large mossy-fibre boutons, but rather to all synapses formed by dentate granule cells. Therefore, presynaptic mitochondrial function is critical for the short-term dynamics of synapse function, which may contribute to the cognitive deficits observed in pathological mitochondrial dysfunction.
This article is protected by copyright. All rights reserved
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The statistics of the vestibular input experienced during natural self-motion differ between rodents and primates
Abstract
It is widely believed that sensory systems are adapted to the statistical structure of natural stimuli, thereby optimizing coding. Recent evidence suggests that this is also the case for the vestibular system, which senses self-motion and in turn contributes to essential brain functions ranging from the most automatic reflexes to spatial perception and motor coordination. However, little is known about the statistics of self-motion stimuli actually experienced by freely moving animals in their natural environments. Accordingly, here we examined the natural self-motion signals experienced by mice and monkeys: two species commonly used to study vestibular neural coding. First, we found that probability distributions for all six dimensions of motion (3 rotations, 3 translations) in both species deviated from normality due to long tails. Interestingly, the power spectra of natural rotational stimuli displayed similar structure for both species and were not well fit by power laws. This result contrasts with reports that the natural spectra of other sensory modalities (i.e., vision, auditory, and tactile) instead show a power-law relationship with frequency, which indicates scale invariance. Analysis of natural translational stimuli revealed important species differences as power spectra deviated from scale invariance for monkeys but not for mice. By comparing our results to previously published data for humans, we found the statistical structure of natural self-motion stimuli in monkeys and humans more closely resemble one another. Our results thus predict that, overall, neural coding strategies used by vestibular pathways to encode natural self-motion stimuli are fundamentally different in rodents and primates.
This article is protected by copyright. All rights reserved
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Diagnostic accuracy of demarcation of undifferentiated-type early gastric cancer after Helicobacter pylori eradication
Abstract
Background
It is unknown whether Helicobacter pylori (H. pylori) eradication is beneficial when demarcating undifferentiated-type early gastric cancers (UD-type EGCs). This study aimed to determine whether H. pylori eradication is beneficial, and also when benefits become detectable.
Methods
Sixty lesions that were detected as a ≤20-mm lesion without metastasis or ulceration on routine examination, diagnosed as UD-type EGC on biopsy, and treated with endoscopic submucosal dissection between January 2010 and January 2015 were studied. Magnifying endoscopy with narrow-band imaging (ME-NBI) was performed to demarcate the lesions. The most oral and most anal sites were marked. After endoscopic therapy, the markings were compared with the pathological examination results to calculate accurate diagnosis rates, which were compared between 27 patients with H. pylori eradication and 33 patients without. Mean intercrypt distance ratio and inflammatory cell infiltration were also compared, as were seven patients who underwent the procedure 1 month after H. pylori eradication and 20 patients who underwent the procedure more than 1 month after H. pylori eradication.
Results
Accurate diagnosis rates were 92.2% with eradication and 60.6% without. Mean intercrypt distance ratios were 1.95 and 1.59, respectively. Neutrophil infiltration was mild in the eradication group. Significant differences were observed in each parameter (p < 0.05). No significant difference was observed between the 1-month eradication and >1-month eradication subgroups in terms of accurate diagnosis rate, mean intercrypt distance ratio, or histological grade of any item.
Conclusions
This study suggests that H. pylori eradication therapy aids the accurate delineation of UD-type EGC in ME-NBI.
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Effects of estrogen on esophageal function through regulation of Ca 2+ -related proteins
Abstract
Background
The calcium ion is important for physiological functions in all tissues and organs and essential to many vital functions, including hormone secretion and muscle contraction. The intracellular concentration of calcium is regulated by calcium related proteins such as CaBP-9k, PMCA1, and NCX1. In this study, we investigated the relationship between calcium regulation and esophageal functions such as mucin secretion and smooth muscle contraction.
Methods
To evaluate the influence of sex steroid hormones, immature rats were treated for 3 days with estradiol (E2), progesterone (P4), and their antagonists (ICI 182,780, and RU486). Esophageal function, transcription level, and localization of CaBP-9k, PMCA1, NCX1, ERα, and MUC2 were examined in the esophagus.
Results
Transcriptional level of Cabp-9k and Muc2 was increased by E2, but not by P4. CaBP-9k, PMCA1, and MUC2 were mainly localized in the mucosal layer. Acidic mucosubstances in the esophagus were increased by E2 and recovered by ICI treatment. Unlike the expression of Cabp-9k, mRNA levels of Pmca1, Ncx1, and Erα were only decreased in response to E2, and recovered by ICI co-treatment group. The contraction of the esophagus and mRNA level of Mylk were reduced by E2. Overall, E2 upregulated mucus secretion, but downregulated muscle contraction in the esophagus through regulation of the expression of calcium related genes and the resultant intracellular calcium level.
Conclusions
The regulation of E2 in the function of esophagus may be applied to treat esophageal diseases such as reflux esophagitis, achalasia, and esophageal cancer.
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Synergistic Effects of Tetrandrine with Posaconazole Against Aspergillus fumigatus
Microbial Drug Resistance , Vol. 0, No. 0.
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Heterogeneity of Carbapenem Resistance Mechanisms Among Gram-Negative Pathogens in Lebanon: Results of the First Cross-Sectional Countrywide Study
Microbial Drug Resistance , Vol. 0, No. 0.
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Sleep during an Antarctic summer expedition: new light on "polar insomnia".
Sleep complaints are consistently cited as the most prominent health and well-being problem in Arctic and Antarctic expeditions, without clear evidence to identify the causal mechanisms. The present investigation aimed at studying sleep and determining circadian regulation and mood during a 4 months Antarctic summer expedition. All data collection was performed during the continuous illumination of the Antarctic summer. After an habituation night and acclimatization to the environment (3 weeks), ambulatory polysomnography (PSG) was performed in 21 healthy male subjects, free of medication. 18 hours profile (saliva sampling every 2 hr) of cortisol and melatonin were assessed. Mood, sleepiness and subjective sleep quality were assessed and the psychomotor vigilance task was administered. PSG showed, in addition to high sleep fragmentation, a major decrease in slow wave sleep (SWS) and an increase in stage R sleep. Furthermore, the ultradian rhythmicity of sleep was altered, with SWS occurring mainly at the end of the night and stage R sleep at the beginning. Cortisol secretion profiles were normal; melatonin secretion however showed a severe phase delay. There were no mood alterations according to the POMS scores, but the PVT showed an impaired vigilance performance. These results confirm previous reports on "polar insomnia" -the decrease in SWS- and present novel insight -the disturbed ultradian sleep structure. A hypothesis is formulated linking the prolonged SWS latency to the phase delay in melatonin.
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MODERATE-INTENSITY RESISTANCE EXERCISE ALTERS SKELETAL MUSCLE MOLECULAR AND CELLULAR STRUCTURE AND FUNCTION IN INACTIVE, OLDER ADULTS WITH KNEE OSTEOARTHRITIS
High-intensity resistance exercise (REX) training increases physical capacity, in part, by improving muscle cell size and function. Moderate-intensity REX, which is more feasible for many older adults with disease and disability, also increases physical function, but the mechanisms underlying such improvements are not understood. Therefore, we measured skeletal muscle structure and function from the molecular to the tissue level in response to 14 weeks of moderate-intensity, REX in physically-inactive, older adults with knee osteoarthritis (n=17; 70 +/- 1 yrs). Although REX training increased quadriceps muscle cross-sectional area (CSA), average single fiber CSA was unchanged due to reciprocal changes in myosin heavy chain (MHC) I and IIA fibers. Intermyofibrillar mitochondrial content increased with training, due to increases in mitochondrial size in men, but not women, with no changes in sub-sarcolemmal mitochondria in either sex. REX increased whole muscle contractile performance similarly in men and women. In contrast, adaptations in single muscle fiber force production per CSA (ie, tension) and contractile velocity varied between men and women in a fiber type-dependent manner, with adaptations being explained at the molecular level by differential changes in myosin-actin cross-bridge kinetics and mechanics and single fiber MHC protein expression. Our results are notable compared to studies of high-intensity REX because they show that the effects of moderate-intensity REX in older adults on muscle fiber size/structure and myofilament function are absent or modest. Moreover, our data highlight unique sex-specific adaptations due to differential cellular and sub-cellular structural and functional changes.
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Kinetics of circulating progenitor cell mobilization during submaximal exercise
Circulating progenitor cells (CPCs) are a heterogeneous population of stem/progenitor cells in peripheral blood that includes hematopoietic stem and progenitor cells (HSPCs and HSCs), endothelial progenitor cells (EPCs), and mesenchymal stem cells (MSCs). CPC mobilization during exercise remains uncharacterized in young adults. The purpose of this study was to investigate the kinetics of CPC mobilization during and after submaximal treadmill running and their relationship to mobilization factors. Seven men (age=25.3±2.4 years, BMI=23.5±1.0 kg/m2, VO2peak=60.9±2.74 ml/kg/min) ran on a treadmill for 60 minutes at 70% VO2peak. Blood sampling occurred before (Pre), during (20 min [20e], 40 min [40e], 60min [60e]), and after (15 min [15p], 60 min [60p], 120 min [120p]) exercise for quantification of CPCs (CD34+) HSPCs (CD34+/CD45low), HSCs (CD34+/CD45low/CD38-), CD34+MSCs (CD45-/CD34+/CD31-/CD105+), CD34-MSCs (CD45-/CD34-/CD31-/CD105+), and EPCs (CD45-/CD34+/CD31+) via flow cytometry. CPC concentration increased compared to Pre at 20e and 40e (2.7 and 2.4 fold respectively, p<0.05). HSPCs and HSCs increased at 20e compared to 60p (2.7 and 2.8 fold respectively, p<0.05), while EPCs and both MSC populations did not change. CXCL12 (1.5 fold; p<0.05) and SCF (1.3 fold; p<0.05) were increased at 40e, and remained elevated post-exercise. The peak increase in these populations was positively correlated to concentration of EPCs during exercise with no relationship to CXCL12 and SCF. Our data show the kinetics of progenitor cell mobilization during exercise that could provide insight into cellular mediators of exercise-induced adaptations, and have implication for the use of exercise as an adjuvant therapy for CPC collection in hematopoietic stem cell transplant.
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Adenosine receptor dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans
Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, placebo controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen (PETO2) and carbon dioxide (PETCO2), ventilation (pneumotachography), blood pressure (finger-photoplethysmography), heart-rate (electrocardiogram), CBF (duplex ultrasound), and intra-cranial blood velocities (transcranial Doppler ultrasound) were measured during five-minute stages of isocapnic hypoxia at sea-level (98, 90, 80, & 70% SaO2). Ventilation, PETO2 and PETCO2, blood pressure, heart-rate and CBF were also measured upon exposure (128±31 minutes following arrival) to high-altitude (3800m) and six-hours following theophylline administration. At sea-level, although the CBF response to hypoxia was unaltered pre/post placebo, it was reduced following theophylline (P<0.01); a finding explained by a lower PETCO2 (P<0.01). Upon mathematical correction for PETCO2, the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e. response slope) was not different between trials, irrespective of PETCO2. At high-altitude, theophylline (n=6) had no effect on CBF compared to placebo (n=6) when end-tidal gases were comparable (P>0.05). We conclude that adenosine receptor dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans.
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The cerebrovascular response to lower body negative pressure versus head-up tilt
Lower body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (-50 mmHg) versus head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler determined cerebral blood flow velocity (CBFv) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT leading to a ~15% difference in CPP between LBNP and HUT (p≤0.020). Mean CBFv initially decreased similarly in response to LBNP and for HUT but from minute 3 on, the decline became ~50% smaller (p≤0.029) during LBNP. The reduction in end-tidal PCO2 was comparable but with an earlier return towards baseline values in response to LBNP but not during HUT (p=0.008). We consider the larger decrease in CBFv during HUT versus LBNP attributable to the pronounced reduction in PetCO2 and to gravitational influences on CPP and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality.
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Losartan Reduces the Immediate and Sustained Increases in Muscle Sympathetic Nerve Activity after Hyper-Acute Intermittent Hypoxia.
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia (IH), which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using Losartan attenuates the immediate and immediately persistent increases in (a) SNA discharge and (b) mean arterial pressure (MAP) after hyper-acute intermittent hypoxia training (IHT) using a randomized, placebo controlled repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in 9 healthy human subjects, while muscle sympathetic nerve activity (MSNA) was recorded in 7 subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled 2-3 breaths of nitrogen, followed by a 20-second apnea and 40 seconds of room air breathing every minute for 20 minutes. Hyper-acute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mm Hg mm Hg, all P < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mm Hg, all P >0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT.
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Contribution of Rostral Fluid Shift to Intrathoracic Airway Narrowing in Asthma
Introduction: In asthma, supine posture and sleep increase intrathoracic airway narrowing. When supine, due to gravity, fluid moves out of the legs and accumulates in the thorax. We hypothesized that fluid shift out of the legs into the thorax contributes to the intrathoracic airway narrowing in asthma. Methods: Healthy and asthmatic subjects sat for 30min and then lay supine for 30min. To simulate overnight fluid shift, supine subjects were randomized to receive increased fluid shift out of the legs using lower body positive pressure (LBPP, 10 to 30min) or none (control), and crossed over. Using forced oscillation at 5Hz, respiratory resistance (R5) and reactance (X5, reflecting respiratory stiffness), and using bioelectrical impedance, leg and thoracic fluid volumes (LFV, TFV) were measured while seated and supine (0min, 30min). Results: In 17 healthy subjects (age:51.8±10.9 years, FEV1/FVC Z-score: -0.4±1.1), changes in R5 and X5 were similar in both study arms (p>0.05). In 15 asthmatics (58.5±9.8 years, -2.1±1.3), R5 and X5 increased in both arms (R5:0.6±0.9 vs. 1.4±0.8 cmH2O/L/s, X5:0.3±0.7 vs. 1.1±0.9 cmH2O/L/s). The increases in R5 and X5 were 2.3 and 3.7 times larger with LBPP than control, however (p=0.008, p=0.006). The main predictor of increases in R5 with LBPP was increases in TFV (r=0.73, p=0.002). In asthmatics, the magnitude of increases in X5 with LBPP was comparable to that with posture change from sitting to supine (1.1±0.9 vs. 1.4±0.9 cmH2O/L/s, p=0.32). Conclusion: In asthmatics, fluid shift from the legs to the thorax while supine contributed to increases in the respiratory resistance and stiffness.
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Impact of TGF-{beta} inhibition during acute exercise on Achilles tendon extracellular matrix
The purpose of this study was to evaluate the role of TGF-β1 in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of each Achilles tendon was injected with a TGF-β1 receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser423/425) (P < 0.05) and 2.5-fold greater ERK1/2 phosphorylation (P < 0.05) when compared with sham (P < 0.05). Injection of the inhibitor did not alter collagen content in either group (P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower (P < 0.05) in tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower (P < 0.05) in tendons injected with inhibitor when compared with sham. Decorin expression was not altered by inhibitor in either group (P > 0.05). On the basis of evaluation of hematoxylin and eosin (H&E) stained cross sections, cell numbers were not altered by inhibitor treatment in either group (P > 0.05). Evaluation of H&E-stained sections revealed no effect of inhibitor on collagen fibril morphology. In contrast, scores for regional variation in cellularity decreased in exercised rats (P < 0.05). No differences in fiber arrangement, structure, and nuclei form were noted in either group (P > 0.05). Our findings suggest that TGF-β1 signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercise-dependent manner.
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Mesenteric vascular dysregulation and intestinal inflammation accompanies experimental spinal cord injury
Cervical and high thoracic spinal cord injury (SCI) drastically impairs autonomic nervous system function. Individuals with SCI at thoracic spinal level 5 (T5) or higher often present cardiovascular disorders that include resting systemic arterial hypotension. Gastrointestinal (GI) tissues are critically dependent upon adequate blood flow and even brief periods of visceral hypoxia triggers GI dysmotility. The aim of this study was to test the hypothesis that T3-SCI induces visceral hypoperfusion, diminished postprandial vascular reflexes, and concomitant visceral inflammation. We measured in vivo systemic arterial blood pressure and superior mesenteric artery (SMA) and duodenal blood flow in anesthetized T3-SCI rats at 3 days and 3 wk postinjury either fasted or following enteral feeding of a liquid mixed-nutrient meal (Ensure). In separate cohorts of fasted T3-SCI rats, markers of intestinal inflammation were assayed by qRT-PCR. Our results show that T3-SCI rats displayed significantly reduced SMA blood flow under all experimental conditions (P < 0.05). Specifically, the anticipated elevation of SMA blood flow in response to duodenal nutrient infusion (postprandial hyperemia) was either delayed or absent after T3-SCI. The dysregulated SMA blood flow in acutely injured T3-SCI rats coincides with abnormal intestinal morphology and elevation of inflammatory markers, all of which resolve after 3 wk. Specifically, Icam1, Ccl2 (MCP-1), and Ccl3 (MIP-1α) were acutely elevated following T3-SCI. Our data suggest that arterial hypotension diminishes mesenteric blood flow necessary to meet mucosal demands at rest and during digestion. The resulting GI ischemia and low-grade inflammation may be an underlying pathology leading to GI dysfunction seen following acute T3-SCI.
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Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment
White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16–24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30–40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation.
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Vitamin D supplementation reduces some AT1-AA-induced downstream targets implicated in preeclampsia including hypertension
Autoantibodies to the ANG II type I receptor (AT1-AA) are associated with preeclampsia (PE). We found that vitamin D supplementation reduced AT1-AA and blood pressure (MAP) in the RUPP rat model of PE. However, it was undetermined whether the decrease in AT1-AA was the mechanism whereby vitamin D lowered MAP or if it were through factors downstream of AT1-AA. Uterine artery resistance index, placental ET-1, and soluble FMS-like tyrosine kinase-1 are increased with AT1-AA-induced hypertension and are considered markers of PE in pregnant women. Therefore, we hypothesized that vitamin D would reduce PE factors during AT1-AA-induced hypertension and could lower blood pressure in a model of hypertension during pregnancy without PE features. Either ANG II (50 ng·kg–1·day) or AT1-AA (1:40) was infused from gestational day (GD) 12–19. vitamin D2 (VD2, 270 IU/day) or vitamin D3 (VD3, 15 IU/day) was administered orally from GD14–GD18. MAP (mmHg) increased in AT1-AA (121 ± 4) and ANG II (113 ± 1)-infused pregnant rats compared with normal pregnant rats (NP) (101 ± 2) but was lower in AT1-AA+VD2 (105 ± 2), AT1-AA+VD3 (109 ± 2), ANG II+VD2 (104 ± 4), and ANG II+VD3 (104 ± 3). VD2 and/or VD3 improved PE features associated with AT1-AA during pregnancy, while ANG II did not induce such features, supporting the hypothesis that AT1-AA induces PE features during pregnancy, and these are improved with vitamin D. In this study, we demonstrate that vitamin D improved many factors associated with PE and reduced blood pressure in a hypertensive model without PE features, indicating that vitamin D could be beneficial for various hypertensive disorders of pregnancy.
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Relationship between oxidative stress and brain swelling in goldfish (Carassius auratus) exposed to high environmental ammonia
Buildups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). We investigated brain swelling and its possible relationship to oxidative stress in the brain and liver of goldfish acutely exposed to high external ammonia (HEA; 5 mmol/l NH4Cl) at two different acclimation temperatures (14°C, 4°C). Exposure to HEA at 14°C for 72h resulted in increased internal ammonia and glutamine concentrations in the brain, and it caused cellular oxidative damage in the brain and liver. However, oxidative damage was most pronounced in brain, in which there was a twofold increase in thiobarbituric acid–reactive substances, a threefold increase in protein carbonylation, and a 20% increase in water volume (indicative of brain swelling). Increased activities of catalase, glutathione peroxidase, and glutathione reductase in the brain suggested that goldfish upregulate their antioxidant capacity to partially offset oxidative stress during hyperammonemia at 14°C. Notably, acclimation to colder (4°C) water completely attenuated the oxidative stress response to HEA in both tissues, and there was no change in brain water volume despite similar increases in internal ammonia. We suggest that ammonia-induced oxidative stress may be responsible for the swelling of goldfish brain during HEA, but further studies are needed to establish a mechanistic link between reactive oxygen species production and brain swelling. Nevertheless, a high capacity to withstand oxidative stress in response to variations in internal ammonia likely explains why goldfish are more resilient to this stressor than most other vertebrates.
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Cerebral blood flow autoregulation in ischemic heart failure
Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO2 (capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20–45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO2 (34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.
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Passive heat acclimation improves skeletal muscle contractility in humans
The aim of this study was to investigate the effect of repeated passive heat exposure (i.e., acclimation) on muscle contractility in humans. Fourteen nonheat-acclimated males completed two trials including electrically evoked twitches and voluntary contractions in thermoneutral conditions [Cool: 24°C, 40% relative humidity (RH)] and hot ambient conditions in the hyperthermic state (Hot: 44–50°C, 50% RH) on consecutive days in a counterbalanced order. Rectal temperature was ~36.5°C in Cool and was maintained at ~39°C throughout Hot. Both trials were repeated after 11 days of passive heat acclimation (1 h per day, 48–50°C, 50% RH). Heat acclimation decreased core temperature in Cool (–0.2°C, P < 0.05), increased the time required to reach 39°C in Hot (+9 min, P < 0.05) and increased sweat rate in Hot (+0.7 liter/h, P < 0.05). Moreover, passive heat acclimation improved skeletal muscle contractility as evidenced by an increase in evoked peak twitch amplitude both in Cool (20.5 ± 3.6 vs. 22.0 ± 4.0 N·m) and Hot (20.5 ± 4.7 vs. 22.0 ± 4.0 N·m) (+9%, P < 0.05). Maximal voluntary torque production was also increased both in Cool (145 ± 42 vs. 161 ± 36 N·m) and Hot (125 ± 36 vs. 145 ± 30 N·m) (+17%, P < 0.05), despite voluntary activation remaining unchanged. Furthermore, the slope of the relative torque/electromyographic linear relationship was improved postacclimation (P < 0.05). These adjustments demonstrate that passive heat acclimation improves skeletal muscle contractile function during electrically evoked and voluntary muscle contractions of different intensities both in Cool and Hot. These results suggest that repeated heat exposure may have important implications to passively maintain or even improve muscle function in a variety of performance and clinical settings.
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Insights into the pathophysiology of ulcerative colitis: interleukin-13 modulates STAT6 and p38 MAPK activity in the colon epithelial sodium channel
Effect of reproductive ageing on pregnant mouse uterus and cervix
Abstract
Advanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth, and post-term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young), 5 (intermediate) months vs. 8 months (older) of age using infra-red video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3 month old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin-43 mRNA expression were reduced in myometrium from 8 month vs. 3 month old mice (P < 0.05, P < 0.01 respectively) in tandem with more frequent, but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, but there were no age-induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8 month old mice provide a useful model of reproductive ageing. This study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women.
This article is protected by copyright. All rights reserved
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Oxford Knee Score
- Non-operative Knee Osteoarthritis (Knee OA)
- Total Knee Replacement (TKR)
Knee OA:
(Harris et al, 2013; n = 134; mean age = 59)
- SEM = 2.65 (OKS)
- SEM = 6.2 (OKS-FCS)
- SEM = 6.9 (OKS-PCS)
TKR:
(Collins et al, 2011; pooled subject data from Dawson et al. 1998, Impellizzeri et al. 2010, Dunbar et al. 2000, Dunbar et al. 2001)
- SEM = 2.2
(Dawson et al, 1998; n = 117; median age = 73)
12 item OKS before TKR and at 6-month follow up | |||||
Standard Deviation | r value | (1-r) | Square Root of (1-r) | SEM | |
Q1 | 0.6 | 0.6 | 0.4 | 0.63 | 0.37 |
Q2 | 1.04 | 0.53 | 0.47 | 0.68 | 0.71 |
Q3 | 0.79 | 0.64 | 0.36 | 0.6 | 0.47 |
Q4 | 0.97 | 0.54 | 0.46 | 0.67 | 0.65 |
Q5 | 0.85 | 0.57 | 0.43 | 0.65 | 0.55 |
Q6 | 0.9 | 0.45 | 0.55 | 0.74 | 0.66 |
Q7 | 0.9 | 0.56 | 0.44 | 0.66 | 0.59 |
Q8 | 1.08 | 0.47 | 0.53 | 0.72 | 0.78 |
Q9 | 0.84 | 0.69 | 0.31 | 0.55 | 0.46 |
Q10 | 1.22 | 0.47 | 0.53 | 0.72 | 0.88 |
Q11 | 1.13 | 0.61 | 0.39 | 0.62 | 0.70 |
Q12 | 0.88 | 0.65 | 0.35 | 0.59 | 0.52 |
SUM | 10.6 | 6.18 | 5.18 | ||
AVG | 0.88 | 0.515 | 0.485 | 0.69 | 0.61 |
(Impellizzeri et al, 2010; n = 79; mean age = 69 (7) years; 6 months post TKA)
- SEM = 2.2
Knee OA:
(Harris et al, 2013)
- MDC = ±6 (OKS)
- MDC = ±16 (OKS-PCS)
- MDC = ±15 (OKS-FCS)
TKR:
(Collins et al, 2011)
- MDC = 6.1
(Impellizzeri et al, 2010)
- MDC = 6.1
Knee OA:
(Harris et al, 2013)
- MCID = 6 (OKS)
- MCID = 14 (OKS-PCS)
- MCID = 10 (OKS-FCS)
Knee OA:
(Harris et al, 2013)
- Baseline Mean OKS = 30.29 (10)
- Baseline Mean OKS-PCS = 59.36 (22)
- Baseline Mean OKS-FCS = 67.22 (21)
- 3 Month Follow Up Mean OKS = 32.15 (11)
- 3 Month Follow Up Mean OKS-PCS = 65.13 (24)
- 3 Month Follow Up Mean OKS-FCS = 68.66 (23)
TKA:
(Dawson et al, 1998)
- Pre-operative Mean = 44.61
- 6 Month Follow Up Mean = 29.33
(Jenny et al, 2012; n = 200; mean age = 71 (9))
- Mean OKS = 43.7 (before surgery)
- Mean OKS = 20.5 (after surgery)
(Madsen et al, 2013; n = 80)
OKS in patients in group-based rehab vs. supervised home training s/p TKA | |||
Intervention | Control | p-value | |
3 months | 7.9 ± 5.9 | 8.4 ± 6.7 | 0.7 |
6 months | 10.5 ± 7.5 | 9.7 ± 8.5 | 0.7 |
Knee OA:
(Harris et al, 2013)
- Excellent Test-Retest Reliability
- ICC = 0.93 (OKS)
- ICC = 0.91 (OKS-PCS)
- ICC = 0.92 (OKS-FCS)
TKA:
(Collins et al. 2011)
- Excellent Test-Retest Reliability
- ICC = 0.91-0.94
- Coefficient of Reliability = 6.45 (Bland and Altman method)
(Dawson et al, 1998)
- Excellent Test-Retest Reliability
- r = 0.92
(Impellizzeri et al, 2010)
- Excellent Test-Retest Reliability
- ICC = 0.91
Knee OA:
(Harris et al, 2013)
- Excellent Internal Consistency
- Cronbach's α = 0.94 (OKS)
- Cronbach's α = 0.88 (OKS-FCS)
- Cronbach's α = 0.90 (OKS-PCS)
(Xie et al, 2011; n = 187; mean age = 64)
- Excellent Internal Consistency
- Cronbach's α = .896
TKA Patients:
(Collins et al, 2011)
- Excellent Internal Consistency
- Cronbach's α = 0.87-0.93
(Dawson et al, 1998)
- Excellent Internal Consistency
- Cronbach's α = 0.87 (pre-op)
- Cronbach's α = 0.93 (6-months post-op)
(Dunbar et al, 2001; n = 1,200; mean age = 78)
- Excellent Internal Consistency
- Cronbach's α = 0.93
(Jenny et al, 2013: n = 100; mean age = 72)
- Excellent Internal Consistency
- Cronbach's α = 0.91
(Jenny et al, 2012)
- Satisfactory Internal Consistency
- Cronbach's α = .88 (pre-op)
- Cronbach's α = .66 (post-op)
TKA:
(Jenny et al, 2012)
Concurrent Validity compared to AKS
- Strong negative correlation pre operatively between OKS and both the AKS knee and function scores (r = -.33; r = -.47)
- Weak negative correlation post operatively between OKS and AKS knee score (r = -.19)
- Strong negative correlation post operatively between OKS and AKS function score (r = -.49)
Knee OA:
(Harris et al, 2013)
Baseline Spearman's correlations between scores | |||
OKS | OKS-PCS | OKS-FCS | |
ICOAP | -0.88 | -0.88 | -0.79 |
KOOS-PS | -0.85 | -0.78 | -0.87 |
PCS-12 | 0.65 | ||
MCS-12 | 0.37 | ||
All correlations were significant at the 0.01 level |
3-month Spearman's correlations between scores | |||
OKS | OKS-PCS | OKS-FCS | |
ICOAP | -0.67 | -0.67 | -0.60 |
KOOS-PS | -0.62 | -0.55 | -0.62 |
All correlations were significant at the 0.01 level ICOAP = Intermittent and Constant Osteoarthritis Pain KOOS-PS = Knee Injury and Osteoarthritis Score - Physical Function Short Form PCS-12 = Physical Component Summary of SF-12 MCS-12 = Mental Component Summary of SF-12 |
(Xie et al, 2011)
- Convergent Validity
- OKS strongly correlated with SF 6D (role limitation, social function and pain) and with EQ- SD (mobility, self care, usual activities and pain/discomfort) and Mobility-VAS (p =.51 -.82)
- OKS moderately correlated with SF-6D physical functioning (p =.44)
- OKS weakly correlated with SF-6D vitality (p = .35)
- Divergent Validity
- OKS strongly correlated with SF-6D mental health (p =.51)
- OKS moderately correlated with EQ-5D anxiety/depression (p = .41)
TKA:
(Collins et al, 2011)
- Good correlation with knee-specific and general health questionnaires, such as the Western Ontario and McMaster Universities Osteoarthritis Index, American Knee Society Score, Knee Outcome Survey Activities of Daily Living Scale, and pain and physical function components of the Short Form 36 and Health Assessment Questionnaire. See Dawson et al. and Impellizzeri et al.
(Dawson et al, 1998)
- Moderate correlation with AKS
- Significant agreement with parts of the SF36 and HAQ (physical function and pain)
Correlation between the 12-item knee score and the AKS score, SF36 and HAQ assessments in 117 patients before operation and in 85 at the six-month follow-up | ||
Correlation Coefficient | ||
Test | Preop | Postop |
AKS assessment | ||
Knee Score | -0.47** | -- |
Function | -0.54** | -- |
SF36 | ||
Physical | -0.69** | -0.66** |
Pain | -0.71** | -0.78** |
Role-physical | -0.52** | -0.43** |
Role-mental | -0.25** | -0.46** |
Social function | -0.56** | -0.78** |
Mental health | -0.19* | -0.41** |
Energy | -0.35** | -0.62** |
Health perceptions | -0.07 | -0.41** |
HAQ | ||
Pain VAS | 0.53** | -- |
Disability index | 0.61** | -- |
*p<0.05, **p<0.01 |
(Dunbar et al, 2000)
- The Oxford-12 correlated most closely with the physical domains.
- The Oxford-12 correlated poorly with the eating domain of the SIP (rho = 0.14) thus demonstrating good divergent construct validity.
(Impellizzeri et al, 2010)
Average Correlations between Instruments | |
Oxford Knee Score | |
WOMAC Pain | 0.67* |
WOMAC Stiffness | 0.45* |
WOMAC Function | 0.67* |
KOS-ADLS Symptoms | -0.48* |
KOS-ADLS Function | -0.62* |
KOS-ADLS Total Score | -0.62* |
SF-12 PC | -0.50* |
SF-12 MC | -0.17 |
*P<.001 |
- The OKS was highly correlated with KOS-ADLS function and WOMAC pain and function subscales but less well correlated with those of the WOMAC stiffness and KOS-ADLS symptom scales.
(Jenny et al, 2013)
- Poor Correlation - OKS with AKSS: 0.20 (P<.001)
- Poor Correlation - OKS with HAAS: 0.19 (P<.001)
Knee OA:
(Xie et al, 2011)
- All items were shown to be relevant.
TKA:
(Collins et al, 2011)
- Extensive input from patients in the development of the OKS ensures content validity.
(Dawson et al, 1998)
- Items were selected based on interviews with patients considering a TKR to identify how they identified and reported problems with their knees. A questionnaire was drafted and tested on a different set of patients, requesting additional comments related to their knee problems that were not addressed. Modifications were made and this procedure was repeated 2 additional times to produce the final questionnaire.
TKA:
(Dunbar et al, 2000)
- Floor effect in 6.8% of patients
- Ceiling effect in 0.1% of patients
(Impellizzeri et al, 2010)
- No floor or ceiling effects prior to TKA
- No floor effects 6 months postoperatively
- Ceiling effects 6 months postoperatively in 27% of patients
(Jenny et al, 2012)
- Pre-Op Group: no floor effect, small ceiling effect (7%)
- Post-Op Group: substantial floor effect (33%), no ceiling effect
- Calculated using original scoring scale
(Jenny et al, 2013)
- Ceiling effect = 33%
Knee OA:
(Harris et al, 2013)
- Small change from baseline to 3 month follow-up
- OKS: ES = 0.19
- OKS-PCS: ES = 0.26
- OKS-FCS: ES = 0.07
TKA:
(Collins et al, 2011)
- ES = 0.9 – 2.19
- SRM = 0.7
(Dawson et al, 1998)
- Large responsiveness from pre-operative to the 6 month follow-up (ES = 2.19)
(Impellizzeri et al, 2010)
- Large Responsiveness
- Effect Size = 0.9
- SRM = 0.7
(Lin et al, 2013)
- Excellent Responsiveness
- Most responsive compared to EQ-VAS and EQ-5D
- SRM: 1.50 (large magnitude of effect)
Knee OA:
(Harris et al, 2013)
- The OKS could be used in clinical practice to monitor disease progression in individual patients undergoing non-operative management for knee OA.
TKA:
(Collins et al, 2011)
- Clinicians should be aware that some patients may require explanation of individual items, which could introduce interviewer bias.
(Dawson et al, 1998)
- This tool is intended specifically with knee surgery alone.
Collins, Natalie J, Misra, Devyani, Felson, David T, Crossley, Kay M, & Roos, Ewa M. (2011). Measures of knee function: International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS‐PS), Knee Outcome Survey Activities of Daily Living Scale (KOS‐ADL), Lysholm Knee Scoring Scale, Oxford Knee Score (OKS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Activity Rating Scale (ARS), and Tegner Activity Score (TAS). Arthritis care & research, 63(S11), S208-S228.
Dawson, Jill, Fitzpatrick, Ray, Murray, David, & Carr, Andrew. (1998). Questionnaire on the perceptions of patients about total knee replacement. Journal of Bone & Joint Surgery, British Volume, 80(1), 63-69.
Dunbar, Michael J, Robertsson, Otto, Ryd, Leif, & Lidgren, Lars. (2000). Translation and validation of the Oxford-12 item knee score for use in Sweden. Acta Orthopaedica, 71(3), 268-274.
Dunbar, MJ, Robertsson, Otto, Ryd, Leif, & Lidgren, Lars. (2001). Appropriate questionnaires for knee arthroplasty RESULTS OF A SURVEY OF 3600 PATIENTS FROM THE SWEDISH KNEE ARTHROPLASTY REGISTRY. Journal of Bone & Joint Surgery, British Volume, 83(3), 339-344x.
Harris, Kristina K, Dawson, Jill, Jones, Luke D, Beard, David J, & Price, Andrew J. (2013). Extending the use of PROMs in the NHS—using the Oxford Knee Score in patients undergoing non-operative management for knee osteoarthritis: a validation study. BMJ open, 3(8), e003365.
Impellizzeri, Franco M, Mannion, Anne F, Leunig, Michael, Bizzini, Mario, & Naal, Florian D. (2011). Comparison of the reliability, responsiveness, and construct validity of 4 different questionnaires for evaluating outcomes after total knee arthroplasty. The Journal of arthroplasty, 26(6), 861-869.
Jenny, J-Y, & Diesinger, Y. (2012). The Oxford Knee Score: compared performance before and after knee replacement. Orthopaedics & Traumatology: Surgery & Research, 98(4), 409-412.
Jenny, Jean-Yves, Louis, Pascal, & Diesinger, Yann. (2013). High Activity Arthroplasty Score has a Lower Ceiling Effect Than Standard Scores After Knee Arthroplasty. The Journal of arthroplasty.
Lin, Fang-Ju, Samp, Jennifer, Munoz, Alexis, Wong, Pei Shieen, & Pickard, A Simon. (2013). Evaluating change using patient-reported outcome measures in knee replacement: the complementary nature of the EQ-5D index and VAS scores. The European Journal of Health Economics, 1-8.
Madsen, Majbritt, Larsen, Kristian, Madsen, Inger Kirkegård, Søe, Hanne, & Hansen, Torben Bæk. (2013). Late group-based rehabilitation has no advantages compared with supervised home-exercises after total knee arthroplasty. Danish medical journal, 60(4), A4607-A4607.
Roland, Martin, & Morris, Richard. (1983). A study of the natural history of back pain: part I: development of a reliable and sensitive measure of disability in low-back pain. spine, 8(2), 141-144.
Xie, Feng, Ye, Hua, Zhang, Yu, Liu, Xia, Lei, Ting, & LI, Shu‐Chuen. (2011). Extension from inpatients to outpatients: validity and reliability of the Oxford Knee Score in measuring health outcomes in patients with knee osteoarthritis. International journal of rheumatic diseases, 14(2), 206-210.
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Advanced EMT - Nashville, TN - Lifeguard Ambulance
As a Lifeguard EMT, many times you have the opportunity to be the best part of someone's very bad day. With this in mind, we're not just looking to hire the first individual that walks through the door. The ideal Lifeguard EMT will be compassionate, mission focused, understanding, patient, highly skilled and very customer focused. It's our goal at Lifeguard to show our employees that we care as much ...
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Effect of Vonoprazan, a Potassium-Competitive Acid Blocker, on the 13 C-Urea Breath Test in Helicobacter pylori -Positive Patients
Abstract
Background and Aim
Vonoprazan (VPZ) is a new oral potassium-competitive acid blocker that has recently become available. The aim of this study was to investigate the effects of VPZ on the urease activity of H. pylori as measured by the 13C-urea breath test (13C-UBT).
Patients and Methods
A total of 60 patients (26 men, 34 women; mean age 53.2 ± 13.6 years) who were diagnosed as H. pylori-positive were recruited. The patients were randomly allocated to three treatment groups: lansoprazole (LPZ) 30 mg (n = 20), VPZ 20 mg (n = 20) once daily for 3 weeks, or the control group (n = 20). The 13C-UBT was carried out at baseline and after 3 weeks of treatment, and the baseline and after treatment results then compared. Δ13C‰ ≥ 2.5‰ was considered H. pylori-positive.
Results
Four patients failed to complete the medication and were omitted from the analysis; data from the LPZ group (n = 18), VPZ group (n = 18), and control group (n = 20) were analyzed. The control group showed no significant change in 13C-UBT data between baseline and the completion of 3-week treatment (baseline: 26.6 ± 23.0‰, completion: 21.1 ± 13.1‰). The 13C-UBT data at week 3 were significantly decreased in both the VPZ group (baseline: 32.8 ± 22.7‰, completion: 7.6 ± 9.2‰, p = 0.0002) and the LPZ group (baseline: 41.8 ± 33.4‰; completion: 9.6 ± 8.8‰, p = 0.0006) compared to baseline.
Conclusions
VPZ treatment reduced the value of UBT, warning that UBT for patients with VPZ treatment should be evaluated carefully.
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MicroRNA-19b Expression in Human Biliary Atresia Specimens and Its Role in BA-Related Fibrosis
Abstract
Background and Aim
Biliary atresia (BA) is a pediatric liver disease with unknown underlying etiology. MicroRNAs (miRNAs) represent a family of small noncoding RNAs. Among them, miR-19b has been suggested to function in the diseased liver. We therefore decided to investigate its potential role in BA.
Methods
We used infant-derived specimens to analyze miR-19b expression in a tissue- and cell-specific fashion, predicted interaction with genes, and finally performed a functional study in vitro.
Results
Patients with BA showed significantly lower miR-19b level in liver compared with controls, and pediatric end-stage liver disease (PELD) score was inversely correlated with miR-19b level. In vitro, miR-19b was significantly downregulated in activated hepatic stellate cells (HSCs) and exerted inhibitory effects on HSC activation, as confirmed by decreased alpha-smooth muscle actin (α-SMA) and type I collagen expression. Moreover, one mRNA target gene (TGFβR2) was identified. Computational prediction of miR-19b binding to the 3′-untranslated region (UTR) of TGFβR2 was validated by luciferase reporter assay. Furthermore, miR-19b mimic negatively regulated transforming growth factor-beta (TGF-β) signaling components, as demonstrated by decreased drosophila mothers against decapentaplegic homolog 3 (SMAD3) expression and blocking of TGF-β-induced expression of a1(I) and a2(I) procollagen miRNAs.
Conclusions
Our data indicate that miR-19b may be involved in BA-related fibrosis.
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Optimization of the Return-to-Sport Paradigm After Anterior Cruciate Ligament Reconstruction: A Critical Step Back to Move Forward
Abstract
Athletes who have sustained an anterior cruciate ligament (ACL) injury often opt for an ACL reconstruction (ACLR) with the goal and expectation to resume sports. Unfortunately, the proportion of athletes successfully returning to sport is relatively low, while the rate of second ACL injury has been reported to exceed 20% after clearance to return to sport, especially within younger athletic populations. Despite the development of return-to-sport guidelines over recent years, there are still more questions than answers on the most optimal return-to-sport criteria after ACLR. The primary purpose of this review was to provide a critical appraisal of the current return-to-sport criteria and decision-making processes after ACLR. Traditional return-to-sport criteria mainly focus on time after injury and impairments of the injured knee joint. The return-to-sport decision making is only made at the hypothetical 'end' of the rehabilitation. We propose an optimized criterion-based multifactorial return-to-sport approach based on shared decision making within a broad biopsychosocial framework. A wide spectrum of sensorimotor and biomechanical outcomes should be assessed comprehensively, while the interactions of an individual athlete with the tasks being performed and the environment in which the tasks are executed are taken into account. A layered approach within a smooth continuum with repeated athletic evaluations throughout rehabilitation followed by a gradual periodized reintegration into sport with adequate follow-up may help to guide an individual athlete toward a successful return to sport.
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Impact of minimally invasive vs. open distal pancreatectomy on use of adjuvant chemoradiation for pancreatic adenocarcinoma
The American Journal of Surgery
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Addition of ribavirin to daclatasvir plus asunaprevir for chronic hepatitis C 1b patients with baseline NS5A resistance-associated variants improved response
Journal of the Formosan Medical Association
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What is the most accurate lymph node staging method for perihilar cholangiocarcinoma? Comparison of UICC/AJCC pN stage, number of metastatic lymph nodes, lymph-node ratio, and log odds of metastatic lymph nodes
European Journal of Surgical Oncology
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Randomized phase II study of cetuximab versus irinotecan and cetuximab in patients with chemo-refractory KRAS codon G13D metastatic colorectal cancer (G13D-study)
Cancer Chemotherapy and Pharmacology
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Survival after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for advanced colorectal liver metastases: A case-matched comparison with palliative systemic therapy
Surgery
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Appropriate timing to start and optimal response evaluation of high-dose corticosteroid therapy for patients with acute liver failure
Journal of Gastroenterology
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Early-life antibiotic treatment enhances the pathogenicity of CD4+ T cells during intestinal inflammation
Journal of Leukocyte Biology
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Sofosbuvir-based treatment regimens: Real life results of 14 409 chronic HCV genotype 4 patients in Egypt
Alimentary Pharmacology and Therapeutics
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Comprehensive assessment of tumour budding on cytokeratin stains in colorectal cancer
Histopathology
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Characteristics of children with food protein-induced enterocolitis and allergic proctocolitis
Allergy and Asthma Proceedings
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Serratus anterior plane block for hybrid transthoracic esophagectomy: A pilot study
Journal of Pain Research
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Biopsychosocial predictors of interferon-related depression in patients with Hepatitis C
Asian Journal of Psychiatry
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Higher 25-hydroxyvitamin D levels are associated with greater odds of remission with anti-tumour necrosis factor- medications among patients with inflammatory bowel diseases
Alimentary Pharmacology and Therapeutics
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Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C
Journal of Hepatology
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Bone marrow fat content is correlated with hepatic fat content in paediatric non-alcoholic fatty liver disease
Clinical Radiology
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Protocol for enhanced recovery after surgery improves short-term outcomes for patients with gastric cancer: A randomized clinical trial
Gastric Cancer
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Impact of CT enterography on the diagnosis of small bowel gastrointestinal stromal tumors
Abdominal Imaging
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Randomized clinical trial comparing standard diet with perioperative oral immunonutrition in total gastrectomy for gastric cancer
British Journal of Surgery
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Correlation between quantitative and semiquantitative parameters in DCE-MRI with a blood pool agent in rectal cancer: Can semiquantitative parameters be used as a surrogate for quantitative parameters
Abdominal Imaging
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Secure, low-cost technique for laparoscopic hepatic resection using the crush-clamp method with a bipolar sealer
Asian Journal of Endoscopic Surgery
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Paramedic, $7,000 Signing Bonus! - American Ambulance
American Ambulance is offering a $7,000 signing bonus, PLUS $3,000 for currently accredited CCEMSA Paramedics, and up to $2,000* in relocation assistance! With offices in Fresno, Clovis and Hanford, American Ambulance is the sole 9-1-1 provider for over 6,500 square miles of Fresno and Kings Counties. Our service area ranges from the Sierra Nevada Mountains, through the San Joaquin Valley and into ...
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Quiz: How accurately can you triage 10 MCI patients?
EMS providers learn triage in their certification courses and occasionally review it during continuing education courses. Perhaps fortunately, it is infrequently used in the field. This EMS1.com and Limmer Creative quiz will be a good review for when you are first on scene for "the big one." How accurate will you be on these 10 simulated patients"
The quiz uses the START triage principles, but can be related to common principles used everywhere. Pick the triage category for each patient.
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Assessment of predictive factors for recurrence in laparoscopic ventral hernia repair using a bridging technique
Abstract
Aim
To assess the long-term incidence and predictive factors for recurrence after laparoscopic ventral hernia repair using a bridging technique.
Methods
The study group consisted of 213 consecutive patients operated by laparoscopy for primary ventral (n = 158) or incisional hernia (n = 55) between 2001 and 2014. Patients had a repair without fascia closure by intra-peritoneal onlay placement of a Parietex® composite mesh centred on the defect with an overlap of at least 3 cm. Clinical outcome was assessed by a combination of office consultation, patient's electronic medical file review and telephone interview.
Results
There were 144 men and 69 women with a mean age of 55 ± 12 years and a BMI of 32 ± 6. With a mean follow-up of 69 ± 44 months, a recurrent hernia was noted in 16 patients (7.5%). Univariate analysis showed a statistically significant higher recurrence rate in the following conditions: incisional hernia (15%), BMI ≥ 35 (21%), defect width >4 cm (27%), defect area >20 cm2 (27%), mesh overlap <5 cm (32%) and ratio of mesh area to defect area (M/D ratio) ≤12 (48%). Multivariate logistic analysis revealed that M/D ratio was the only independent predictive factor for recurrence (coefficient −0.79, OR 0.46, p < 0.002). With a M/D ratio ≤8, between 9 and 12, between 13 and 16, and ≥17, the recurrence rate was, respectively, 70, 35, 9 and 0% (p < 0.001).
Conclusions
In laparoscopic repair of ventral hernia using a bridging technique, an overlap of at least 5 cm is not all that is required to prevent hernia recurrence. The M/D ratio is the most important predictive factor for recurrence. A ratio of 13 appears as the threshold under which that technique cannot be recommended and 16 as the threshold over which the risk of recurrence is virtually nil. If a satisfactory M/D ratio cannot be achieved, other surgical repair should be proposed to the patient.
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Retention of laparoscopic and robotic skills among medical students: a randomized controlled trial
Abstract
Background
Although simulation training beneficially contributes to traditional surgical training, there are less objective data on simulation skills retention.
Objective
To investigate the retention of laparoscopic and robotic skills after simulation training.
Methods
We present the second stage of a randomized single-blinded controlled trial in which 40 simulation-naïve medical students were randomly assigned to practice peg transfer tasks on either laparoscopic (N = 20, Fundamentals of Laparoscopic Surgery, Venture Technologies Inc., Waltham, MA) or robotic (N = 20, dV-Trainer, Mimic, Seattle, WA) platforms. In the first stage, two expert surgeons evaluated participants on both tasks before (Stage 1: Baseline) and immediately after training (Stage 1: Post-training) using a modified validated global rating scale of laparoscopic and robotic operative performance. In Stage 2, participants were evaluated on both tasks 11–20 weeks after training.
Results
Of the 40 students who participated in Stage 1, 23 (11 laparoscopic and 12 robotic) underwent repeat evaluation. During Stage 2, there were no significant differences between groups in objective or subjective measures for the laparoscopic task. Laparoscopic-trained participants' performances on the laparoscopic task were improved during Stage 2 compared to baseline measured by time to task completion, but not by the modified global rating scale. During the robotic task, the robotic-trained group demonstrated superior economy of motion (p = .017), Tissue Handling (p = .020), and fewer errors (p = .018) compared to the laparoscopic-trained group. Robotic skills acquisition from baseline with no significant deterioration as measured by modified global rating scale scores was observed among robotic-trained participants during Stage 2.
Conclusion
Robotic skills acquired through simulation appear to be better maintained than laparoscopic simulation skills.
Clinical trial
This study is registered on ClinicalTrials.gov (NCT02370407).
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A video presentation on technique of laparoscopic redo of stenotic gastrojejunostomy with hiatal hernioplasty and right crural release in a patient with previous Roux-en-Y gastric bypass
Equal patient satisfaction, quality of life and objective recurrence rate after laparoscopic hiatal hernia repair with and without mesh
Abstract
Introduction
Laparoscopic hiatal hernia repair has become standard practice for most surgeons performing antireflux surgery. Hiatal hernia repair consists of cruroplasty with sutures only or additional reinforcement using mesh. Use of mesh was initiated to reduce recurrence rates. Recent analyses show that use of mesh may influence radiologic recurrence rates, but it does not seem to prevent symptomatic recurrences and the need for reoperation. This study compares clinical and radiologic outcomes of primary cruroplasty and cruroplasty with non-absorbable mesh after laparoscopic hiatal hernia repair.
Methods
Retrospective analysis of prospectively followed cohort of patients undergoing laparoscopic correction of hiatal hernia type II–IV in two tertiary referral centers was carried out. Radiologic recurrence, symptomatic recurrence, reoperation rate, complications and patient-reported outcome measures were analyzed for all patients.
Results
A total of 189 patients were analyzed after laparoscopic hiatal hernia correction with an additional fundoplication [127 (67.2%) primary correction, 62 (32.8%) with mesh reinforcement]. After a mean follow-up of 39.3 months, the overall radiologic recurrence rate was 24.3%, which was equal in both groups [25.8% (mesh) vs 23.6% (no mesh), P = 0.331]. Symptomatic recurrence rate was 13.2% (16.1 vs 11.8%, P = 0.495) and reoperation rate 7.4% (9.7 vs 6.3%), which was comparable between the two groups. Complication rates were equal, and no serious mesh-related complications were reported. Health-related quality of life improved after surgery, dysphagia decreased and patient satisfaction was high for both groups without significant differences.
Conclusion
Radiologic recurrences, symptomatic recurrences and reoperation rates are equal after laparoscopic hiatal hernia repair with or without non-absorbable mesh reinforcement, irrespective of hernia size and type. Quality of life, dysphagia and patient satisfaction were comparable. No serious mesh-related complications occurred. The results of this study do not support the routine use of mesh in hiatal hernia repair.
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Non-inferiority of minimally invasive oesophagectomy: an 8-year retrospective case series
Abstract
Background
The trend towards laparoscopic surgery seen in other specialties has not occurred at the same pace in oesophagectomy. This stems from concerns regarding compromised oncological clearance, and complications associated with gastric tube necrosis and anastomotic failure. We present our experience of minimally invasive oesophagectomy (MIO) compared to open and hybrid surgery. We aim to ascertain non-inferiority of MIO by evaluating impact on survival, oncological clearance by resection margin and lymph node harvest and post-operative complications.
Methods
Data were sourced retrospectively 2008–2015. Three approaches were studied. MIO (3-stage Mckeown), hybrid (2-stage Ivor Lewis, laparoscopy, thoracotomy) and open (2-stage Ivor Lewis).
Results
Five-year survival was 54.2%. Surgical approach had no significant impact on survival at any stage of disease (Stage 0/I p = 0.98; stage II p = 0.2; stage III p = 0.76). There was no statistically significant difference in oncological clearance by resection margins between procedures when compared by disease stage (p = 0.49). A higher number of nodes were harvested in hybrid [median 27.5 (6–65)] and open surgeries [median 26 (4–54)] than in MIO [median 20 (7–44)] (p > 0.01). Numbers of nodes resected did not impact risk of recurrence [recurrence, median 25 (6–54), no recurrence, 26 (4–65)] (p = 0.25). Anastomotic strictures (22.4%) and potential leaks (17.9%) were more common in MIO (strictures p > 0.01, leaks p = 0.08), although associated morbidity was lower. Respiratory complications were less common in MIO (2.9%) versus hybrid (13.3%) (p = 0.02). Wound infection and chyle leak were also lower (wound 1.5% MIO 3.5% open, p = 0.6; chyle leak 1.5% MIO, 6.7% hybrid, p = 0.2).
Conclusions
Our results show no negative impact of MIO on survival or oncological clearance. Respiratory and wound complications are lower in MIO, but rates of anastomotic strictures and potential anastomotic leaks are increased. This may be due to the longer length of conduit and subclinical ischaemia at the anastomosis and merits further evaluation.
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Outcome of stent grafting for esophageal perforations: single-center experience
Abstract
Background
Recent studies showed that stent grafting is a promising technique for treatment of esophageal perforation. However, the evidence of its benefits is still scarce.
Methods
Forty-three consecutive patients underwent stent grafting for esophageal perforation at the Oulu University Hospital, Finland. The main endpoints of this study were early and mid-term mortality. Secondary outcome endpoints were the need of esophagectomy and additional surgical procedures on the esophagus and extraesophageal structures.
Results
Patients' mean age was 64.6 ± 13.4 years. The mean delay to primary treatment was 23 ± 27 h. The most frequent cause of perforation was Boerhaave's syndrome (46.5%). The thoraco-abdominal segment of the esophagus was affected in 58.1% of cases. Minor primary procedures were performed in 25 patients (58.1%) and repeat surgical procedures in 23 patients (53.5%). Forty-nine repeat stent graftings were performed in 22 patients (50%). Two patients (4.7%) underwent esophagectomy, one for unrelenting preprocedural stricture of the esophagus and another for persistent leakage of a perforated esophageal carcinoma. The mean length of stay in the intensive care unit was 6.0 ± 7.5 days and the in-hospital stay was 24.3 ± 19.6 days. In-hospital mortality was 4.6%. Three-year survival was 67.2%.
Conclusions
Stent grafting seems to be an effective less invasive technique for the treatment of esophageal perforation. Repeat stent grafting and procedures on the pleural spaces are often needed to control the site of perforation and for debridement of surrounding infected structures. Stent grafting allows the preservation of the esophagus in most of patients. The mid-term survival of these patients is suboptimal and requires further investigation.
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Clinical characteristics, risk factors and outcomes of asymptomatic rectal neuroendocrine tumors
Abstract
Background
Rectal neuroendocrine tumors (NET) are often asymptomatic and frequently discovered during health examinations. However, data on the risk factors of asymptomatic rectal NETs are lacking. We investigated the risk factors, clinical characteristics and outcomes of asymptomatic rectal NETs discovered during health screening.
Materials and methods
Asymptomatic subjects who underwent colonoscopy during routine health screening at a tertiary hospital from March 2009 to July 2014 were reviewed. Subjects with histologically confirmed rectal NETs were compared with healthy controls from the same population. Risk factors for rectal NETs were analyzed by multivariable analysis. Clinical outcomes of the resected NETs were also analyzed.
Results
A total of 21,706 Subjects underwent screening colonoscopy during the study period. 3417 were excluded from the study, and 180 rectal NET subjects were compared with 18,109 controls. Multivariable analysis showed that a previous history of malignancy (OR 2.960, 95% CI 1.673–5.237, p < 0.001), hypertriglyceridemia (OR 1.482, 95% CI 1.046–2.100, p = 0.027), higher fasting plasma glucose levels (OR 1.008, 95% CI 1.003–1.014, p = 0.001) and higher carcinoembryonic antigen levels (OR 1.019, 95% CI 1.003–1.035, p = 0.021) were significant risk factors while older age (OR 0.964, 95% CI 0.951–0.977, p < 0.001) was a preventive factor. One hundred and sixty nine subjects had endoscopic resection, five were treated by local surgery and six by radical surgery. Complete resection was achieved in 152 subjects. There were three cases of positive lymph nodes and one metastasis. Histology revealed four lymphatic, five vascular and two cases of perineural invasion. One hundred and fifty seven subjects were followed up for at least 1 year (median 38.6 months, 12–84 months). There were no recurrences during the follow-up period.
Conclusions
Younger age, previous history of malignancy, higher fasting plasma glucose levels and hypertriglyceridemia are significantly associated with rectal NET risk.
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