Τρίτη, 11 Δεκεμβρίου 2018

Authors’ Reply to Cross et al.: Comment on: “The Effectiveness of Resisted Sled Training (RST) for Sprint Performance: A Systematic Review and Meta-analysis”



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Comment on: “The Effectiveness of Resisted Sled Training (RST) for Sprint Performance: A Systematic Review and Meta-analysis”



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Usefulness of Thiopurine Monotherapy for Crohn’s Disease in the Era of Biologics: A Long-Term Single-Center Experience

Abstract

Background

Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage.

Aim

To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics.

Methods

The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added.

Results

A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17–84) years. Median follow-up was 43 (range 0.2–289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105–147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990–1995 (4.7% of all TF); 8 in 1996–2000 (5.4%); 22 in 2001–2005(15%); 41 in 2006–2010 (28%); 69 in 2011–2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002).

Conclusion

An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.



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Malan syndrome: Extension of genotype and phenotype spectrum

Malan syndrome and Marshall–Smith syndrome (MSS) are allelic disorders caused by mutation in NFIX gene. We report a 3‐year‐ 6 months‐ old female with clinical features suggestive of Malan syndrome with mutation in exon 2 of NFIX gene. NFIX gene, where most of the mutations in Malan syndrome are located. She did not have advanced bone age. The radiographs of long bones showed metaphyseal changes which were not reported previously. This study reports the first mutation proven case from India and highlights the overlap between MSS and Malan syndrome.



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Meetings Calendar



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Genotype and phenotype correlations for SHANK3 de novo mutations in neurodevelopmental disorders

Abstract

SHANK3 has been identified as the causative gene of 22q13.3 microdeletion syndrome phenotype. De novo mutations (DNMs) of SHANK3 were subsequently identified in patients with several neurodevelopmental disorders, including autism spectrum disorders (ASDs), schizophrenia (SCZ), a Rett syndrome‐like phenotype, and intellectual disability (ID). Although broad developmental phenotypes of these patients have been described in single studies, few studies have reviewed the genotype and phenotype relationships using a relatively large cohort of patients with SHANK3 DNMs. In this study, we identified a de novo splice mutation (NM_033517.1: c.2265+1G>A) that functionally impairs mRNA splicing, produces multiple splice variants, and results in the reduction of the amounts of mRNA. To analyze the genotype and phenotype correlations for SHANK3 DNMs, we reviewed 37 previously published patients with 28 SHANK3 DNMs. Our results revealed that haploinsufficiency of SHANK3 causes a broad spectrum of neurodevelopmental phenotypes with impaired social interaction, repetitive behavior, speech impairment, ID, and regression as the most common observations. Seizures, hypotonia, global development delay, dysmorphic features, and several other features also occurred recurrently. Specific phenotypes are also observed in certain genotypes. Our study provides the frequency of the heterogeneous co‐occurring conditions caused by SHANK3 DNMs, which will be beneficial for diagnosis and clinical management.



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Reply to the letter to editor regarding the article “Treatment of vertebral body hemangiomas with direct ethanol injection and short segment stabilization”

We thank you for giving us an opportunity to respond to the letter to the Editor by Wang et al. [1]. Doppman et al. [2] in 1994 described the first case report of this technique. Goyal et al. [3] (from our institute) performed percutaneous transpedicular injection under computed tomography guidance for 14 patients. They noted transient deterioration in all the patients. Eleven patients were stable or improved over long term correlated with reduction of epidural soft tissue seen on postoperative MRI.

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Letter to the editor regarding “Long term outcome of treatment of vertebral body hemangiomas with direct ethanol injection and short segment stabilization” by Chandra et al.

To the Editor:

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The oculoauriculofrontonasal syndrome: Further clinical characterization and additional evidence suggesting a nontraditional mode of inheritance

Abstract

The oculoauriculofrontonasal syndrome (OAFNS) is a rare disorder characterized by the association of frontonasal dysplasia (widely spaced eyes, facial cleft, and nose abnormalities) and oculo‐auriculo‐vertebral spectrum (OAVS)‐associated features, such as preauricular ear tags, ear dysplasia, mandibular asymmetry, epibulbar dermoids, eyelid coloboma, and costovertebral anomalies. The etiology is unknown so far. This work aimed to identify molecular bases for the OAFNS. Among a cohort of 130 patients with frontonasal dysplasia, accurate phenotyping identified 18 individuals with OAFNS. We describe their clinical spectrum, including the report of new features (micro/anophtalmia, cataract, thyroid agenesis, polymicrogyria, olfactory bulb hypoplasia, and mandibular cleft), and emphasize the high frequency of nasal polyps in OAFNS (56%). We report the negative results of ALX1, ALX3, and ALX4 genes sequencing and next‐generation sequencing strategy performed on blood‐derived DNA from respectively, four and four individuals. Exome sequencing was performed in four individuals, genome sequencing in one patient with negative exome sequencing result. Based on the data from this series and the literature, diverse hypotheses can be raised regarding the etiology of OAFNS: mosaic mutation, epigenetic anomaly, oligogenism, or nongenetic cause. In conclusion, this series represents further clinical delineation work of the rare OAFNS, and paves the way toward the identification of the causing mechanism.



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Table of Contents



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Enhancing the natural history awareness of lumbar disc displacement and facilitating rehabilitation following surgery

We scrutinized the systematic review article by Huysmanset al. [1] with interest. Indeed, Huysmans et al. addressed an important issue for the spinal community with their PROSPERO-registered review protocol. They unraveled the state-of-art scenarios of returning to work and sick leave duration following surgery for lumbar radiculopathy. Notably, lumbar radiculopathy, or lumbar disc displacement (MeSH terms) with sciatica and/or leg pain, is among the most common spinal disorders, greatly affecting patients' welfare [2].

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Editorial Board



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Anti-obesity effects of kaempferol by inhibiting adipogenesis and increasing lipolysis in 3T3-L1 cells

Abstract

Kaempferol is a natural flavonoid widely found in fruits, vegetables, and tea. Kaempferol possesses beneficial biological properties such as anti-inflammatory and antioxidant activities. Positive energy balance during obesity correlates with a pro-inflammatory chronic state. In this context, we hypothesized that kaempferol might promote anti-obesity effects by modulating adipogenesis and lipolytic pathways. Adipocyte viability at 24, 48, and 72 h was measured by an ATP-based assay. Pre-adipocytes (day 0) or mature adipocytes (day 12) were treated with 60 μM kaempferol until day 21 to evaluate its potential anti-adipogenic and lipolytic effect, respectively. Total lipid accumulation was assessed using Oil Red O staining assay. Gene expression was measured by RT-qPCR to evaluate the effect of kaempferol on adipogenesis and lipolysis gene expression. Our results showed a dose-dependent effect of kaempferol treatment on cell viability promoting cell death at higher than 60 μM concentration. Pre-adipocytes stimulation by 60 μM kaempferol resulted in 62% adipogenesis inhibition whereas in mature adipocytes, it reduced 39% intracellular lipid accumulation. Also, 60 μM kaempferol treatment decreased Cebpa mRNA expression when compared to control cells. In contrast, Pnpla2 and Lipe gene expression were upregulated in 3T3-L1 cells incubated with 60 μM kaempferol. In summary, our results showed that kaempferol modulates adipogenic differentiation in 3T3-L1 cells by promoting downregulation of Cebpa gene expression and decreasing lipid accumulation in mature adipocytes by its positive effects on Pnpla2 and Lipe mRNA levels. Kaempferol might display an anti-obesity effect.



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Epidemiology and Resource Utilization of Simple Febrile Seizure-associated Hospitalizations in the United States, 2003-2012

imageBackground: Simple febrile seizure (SFS) affects 2% to 4% of children under 6 years of age. The purpose of this study is to examine the epidemiologic patterns and resource utilization of SFS-associated hospitalizations in children aged younger than 6 years of age in the United States. Materials and Methods: This study is a serial, retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Databases for the years 2003, 2006, 2009, and 2012. SFS-associated hospitalizations were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis code 780.31. We calculated the proportion of hospitalizations in pediatric patients under 6 years of age due to SFS and all other nonbirth causes, the rate of SFS-associated hospitalizations per 100,000 population, the mean length of stay and inflation-adjusted hospital costs of SFS-associated hospitalizations, as well as patient demographics and hospital characteristics. Results: From 2003 to 2012, the weighted proportion of hospitalizations due to SFS declined from 0.83% to 0.41% (P

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Perioperative Intravenous Fluid in Children Undergoing Brain Tumor Resection: Balancing the Threats to Homeostasis

imageNo abstract available

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A Summary of Preclinical Poster Presentations at the Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Symposium

The potential for long-term neurotoxic effects of anesthetics on the developing human brain has led to intensified research in this area. To date, the human evidence has been inconclusive, but a large body of animal evidence continues to demonstrate cause for concern. On April 14 and 15, 2018 the sixth biennial Pediatric Anesthesia and Neurodevelopmental Assessment (PANDA) study symposium was held at Morgan Stanley Children's Hospital of New York. This symposium brought together clinicians and researchers and served as a platform to review preclinical and clinical data related to anesthesia and neurotoxicity in developing brains. The program participants included many active investigators in the field of anesthesia neurotoxicity as well as stakeholders from different backgrounds with the common interest of potential anesthetic neurotoxicity in children. The moderated poster session included presentations of preclinical animal research studies. These studies focused on defining the anesthetic-induced neurotoxicity phenotype, understanding the mechanism of injury and discovering potential inhibitors of neurotoxic effects.

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The Impact of Intraoperative Magnetic Resonance Imaging on Patient Safety Management During Awake Craniotomy

imageBackground: Awake craniotomy paired with intraoperative magnetic resonance imaging (iMRI) is now the established technique for maximizing surgical resection, while preserving neurological function. However, leaving an unsecured airway patient in the iMRI gantry represents considerable risk. Our study aimed at identifying the incidence of critical adverse events in unsecured airway patients during iMRI as part of awake craniotomy. Materials and Methods: We conducted a clinical chart review of consecutive awake craniotomies performed between November 1999 and December 2015. Sequences of iMRI performed without invasive airway management were selected for assessment and the incidence of critical adverse events, including general convulsive seizure, respiratory arrest, nausea/vomiting and agitation, was identified. Results: Critical adverse events occurred in 21 of 356 unsecured airway patients within 24 of the 579 iMRI sequences. In cases using the low-field strength open MRI scanner, emergency termination of scans due to patient decline was recorded in only 4 cases: no cases of cardiac arrest, accidental death, or thermal injury were recorded. Compared with cardiovascular monitoring, patient respiratory status was poorly recorded. Conclusions: In terms of anesthesia, concurrent use of iMRI for awake craniotomy is clinically acceptable providing potential intraoperative complications can be controlled. Further, the configuration of the iMRI scanner as well as the reduced exposure from the lower magnetic field strength was found to impact patient safety management. Therefore when a conscious patient is left in the gantry without airway support, it is advisable that levels of oxygenation and ventilation should be monitored at all times.

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Phenytoin-induced Excessive Sedation During Awake Craniotomy: An Unusual Observation

No abstract available

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Introduction to “Anesthesia and Neurodevelopment in Children”: A Supplement from the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium

No abstract available

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Analgesia Nociception Index Monitoring During Supratentorial Craniotomy

imageBackground: Objective monitoring of pain during and after surgery has been elusive. Recently, Analgesia Nociception Index (ANI) monitor based on the high frequency component of heart rate variability has been launched into clinical practice. We monitored analgesia during craniotomy using ANI monitor and compared it with cardiovascular parameters and response entropy (RE) of entropy monitor. Materials and Methods: In 21 patients undergoing a craniotomy for a supratentorial lesion, we monitored ANI, heart rate (HR), mean arterial pressure (MAP), state entropy, and RE throughout the surgery. Also, ANI, hemodynamic variables and spectral entropy values were noted at the times of maximal stimulation, such as induction, intubation, head pin fixation, skin incision, craniotomy, durotomy, and skin closure. We also compared ANI with RE during administration of bolus doses of fentanyl. Results: There was an inverse correlation between ANI values and the hemodynamic changes. When the HR and MAP increased, ANI decreased suggesting a good correlation between hemodynamics and ANI values during the times of maximal stimulation. State entropy and RE did not change significantly in response to bolus doses of fentanyl administered during the course of surgery, while ANI increased significantly. Conclusion: In neurosurgical patients undergoing elective supratentorial craniotomy, ANI measures response to noxious stimuli with at least as much reliability as hemodynamic variables and changes in ANI parallel the changes in HR and MAP. ANI is superior to RE for measurement of response to noxious stimuli.

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Engaging Stakeholders to Promote Safe Anesthesia and Sedation Care in Young Children

An important aspect of any research endeavor is engaging various stakeholders to work toward the common goal of pushing knowledge forward about the question at hand. Research into pediatric anesthetic neurotoxicity could benefit greatly from interventions designed to improve the efforts and dedication of government agencies, pharmaceutical companies, research communities, and most importantly, patients. The Pediatric Anesthesia Neurodevelopment Assessment (PANDA) symposium is a biennial meeting where updates in research in the field are presented, and issues relevant to the community are discussed in round table discussions. Here, we summarize a discussion that took place at the 2018 meeting regarding new methods of engaging various stakeholders, as well as perspectives from other stakeholders. Topics discussed included an online portal to better reach patients, experiences with a public-private partnership, steps by the National Institutes of Health to improve engagement with research and improve the dissemination of results, and the experiences of the United States Food and Drug Administration attempting to improve stakeholder engagement following the passage of a new law to promote drug development. The round table discussion provided interesting insights into a critical research topic, and shared first-hand experience of attempts to improve engagement with a variety of stakeholders.

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Using Neuroimaging to Study the Effects of Pain, Analgesia, and Anesthesia on Brain Development

Neuroimaging has been increasingly used as a modality to study the impact of pain, analgesia, and anesthetics on pediatric neurodevelopment. The sixth biennial Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium addressed the 2016 US Food and Drug Administration drug safety warning regarding the potential neurotoxic effects of commonly used anesthetic and sedative medications in children, and included a session discussing the use of various neuroimaging techniques, to detect structural, metabolic, and functional brain changes that can occur with exposure to pain and to anesthetic medications. The presenters concluded that advanced multimodal magnetic resonance imaging techniques are useful in detecting the aforementioned changes, which were found to be pain-specific and anesthetic agent-specific.

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Anesthesia and Neurodevelopment in Children: Many Important Questions Remain Unanswered

imageNo abstract available

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Developmental Neurotoxicity: An Update

In the section of "Developmental Neurotoxicity: An Update" of the Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) symposium 2018 the speakers presented the current literature in translational and clinical research. Dr. Brambrink spoke about translational research in anesthetic neurotoxicity, beginning with discovery in the rodent model, then focusing on evidence from nonhuman primates. Dr. Waspe applied the methodology of Adverse Outcome Pathways from the field of toxicology to developmental neurotoxicity of anesthetics. Dr. O'Leary presented relevant clinical studies that were published in 2017 divided by a focus on academic performance, clinical outcomes or diagnoses, or neuropsychological testing.

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Cognitive Aids for the Diagnosis and Treatment of Neuroanesthetic Emergencies: Consensus Guidelines on Behalf of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee

imageCognitive aids and evidence-based checklists are frequently utilized in complex situations across many disciplines and sectors. The purpose of such aids is not simply to provide instruction so as to fulfill a task, but rather to ensure that all contingencies related to the emergency are considered and accounted for and that the task at hand is completed fully, despite possible distractions. Furthermore, utilization of a checklist enhances communication to all team members by allowing all stakeholders to know and understand exactly what is occurring, what has been accomplished, and what remains to be done. Here we present a set of evidence-based critical event cognitive aids for neuroanesthesia emergencies developed by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee.

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Protecting the Brain With Xenon Anesthesia for Neurosurgical Procedures

imageXenon possesses some, but not all, of the clinical features of an ideal anesthetic agent. Besides well-known advantages of rapid awakening, stable hemodynamics and lack of biotransformation, preclinical data lead to the expectation of xenon's advantageous use for settings of acute ongoing brain injury; a single randomized clinical trial using an imaging biomarker for assessing brain injury corroborated xenon's preclinical efficacy in protecting the brain from further injury. In this review, we discuss the mechanisms and hence the putative applications of xenon for brain protection in neurosurgery. Although the expense of this rare monoatomic gas will likely prevent its widespread penetration into routine clinical neurosurgical practice, we draw attention to the theoretical benefits of xenon anesthesia over other anesthetic regimens for awake craniotomy and for neurosurgery in older, high-risk, and sicker patients.

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The Best of the Old With Promise of the New: The Format of the Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care is Changing

No abstract available

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Balanced Crystalloids Versus Saline for Perioperative Intravenous Fluid Administration in Children Undergoing Neurosurgery: A Randomized Clinical Trial

imageBackground: Balanced crystalloid solutions induce less hyperchloremia than normal saline, but their role as primary fluid replacement for children undergoing surgery is unestablished. We hypothesized that balanced crystalloids induce less chloride and metabolic derangements than 0.9% saline solutions in children undergoing brain tumor resection. Methods: In total, 53 patients (age range, 6 mo to 12 y) were randomized to receive balanced crystalloid (balanced group) or 0.9% saline solution (saline group) during and after (for 24 h) brain tumor resection. Serum electrolyte and arterial blood gas analyses were performed at the beginning of surgery (baseline), after surgery, and at postoperative day 1. The primary trial outcome was the absolute difference in serum chloride concentrations (post-preopΔCl−) measured after surgery and at baseline. Secondary outcomes included the post-preopΔ of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a 4-point scale evaluated by the surgeon for assessing brain edema. Results: Saline infusion increased post-preopΔCl (6 [3.5; 8.5] mmol/L) compared with balanced crystalloid (0 [−1.0; 3.0] mmol/L; P

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The Effects of Leukocyte Filtration on Cell Salvaged Autologous Blood Transfusion on Lung Function and Lung Inflammatory and Oxidative Stress Reactions in Elderly Patients Undergoing Lumbar Spinal Surgery

imageBackground: This study was designed to investigate the effects of leukocyte filtration of autologous salvaged blood on lung function, lung inflammatory reaction, and oxidative stress reaction in elderly patients undergoing lumbar spinal surgery. Materials and Methods: Sixty elderly patients undergoing lumbar spinal surgery were randomly divided into 2 groups: Leukocyte Filter group and Control group. Serum levels of inflammatory markers including white blood cell and polymorphonuclear count, neutrophil elastase, serum surfactant protein A, methane dicarboxylic aldehyde, superoxide dismutase, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and respiratory function markers including dynamic respiratory system compliance, oxygenation index, and respiratory index were measured immediately before induction of anesthesia (T0), immediately before blood transfusion (T1), and 1 (T2), 6 (T3), and 12 hours (T4) after end of blood transfusion. Results: The Leukocyte Filter group had higher dynamic respiratory system compliance at T2, oxygenation index at T2 and T3, respiratory index and superoxide dismutase at T2, T3, and T4 than those in the Control group (P

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Outcomes of Anesthesia Selection in Endovascular Treatment of Acute Ischemic Stroke

imageBackground: The association between anesthesia type and outcomes in patients with acute ischemic stroke undergoing endovascular treatment (EVT) remains a subject of ongoing debate. Methods: This prospective nonrandomized controlled trial included 149 consecutive patients with acute anterior circulation stroke who underwent EVT. The primary outcome was functional independence assessed by the modified Rankin Scale (mRS) after 3 months. Results: A total of 105 (70.5%) and 44 (29.5%) patients undergoing EVT who received conscious sedation (CS) and general anesthesia (GA), respectively. The patients who received GA had similar demographics and basic National Institute of Health Stroke Scale scores (17 vs. 16, P>0.05) as the patients who received CS. The recanalization time (304 vs. 311 min, P=0.940) and the recanalization rate (86.4% vs. 84.1%, P=0.170) did not differ between the patients receiving the different types of anesthesia. The National Institute of Health Stroke Scale at 24 hours was lower in the patients who received CS than in those who received GA (β=−2.26, 95% confidence interval, −5.30 to 0.79). The independence (modified Rankin Scale score 0 to 2) at 3 months was equal between patients who received GA and those who received CS (odds ratio=0.73, 95% confidence interval, 0.32-1.68). The mortality and the morbidity rates did not differ. Conclusions: The data indicated that the selection of GA or CS during EVT had no impact on the independent outcomes of patients with anterior circulation occlusion.

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Prolonged Anesthetic Exposure in Children and Factors Associated With Exposure Duration

imageIntroduction: Anesthetic exposure duration has come under scrutiny because of a Food and Drug Administration warning against prolonged use of anesthesia in children, defined as exposures longer than 3 hours. Methods: Data for 2,613,344 pediatric anesthetic records from the American Society of Anesthesiologist's National Anesthesia Clinical Outcomes Registry from 2010 to 2015 were analyzed to describe anesthetic duration and the prevalence of prolonged exposures in children. Common pediatric inpatient procedures were independently assessed to determine factors associated with exposure duration. Results: The overall mean pediatric anesthetic duration was 83.3±107.4 minutes (median, 57 min). Prolonged exposures comprised 7% of pediatric anesthetic records, and 15% of anesthetic records in infants. After restricting to common pediatric inpatient procedures (n=96,603) and adjusting for procedure type using a Poisson model, compared with children 10 years or older, exposures in infants were 20.5% longer (anesthetic duration ratio [ADR], 1.205; 95% confidence interval [CI], 1.202–1.208). Longer exposures were also seen with a variety of other patient and hospital factors including ASA 4 patients versus ASA 1 patients, (ADR, 1.381; 95% CI, 1.376-1.386), and university hospitals versus surgery centers (ADR, 1.241; 95% CI, 1.236-1.246). Conclusions: Most pediatric anesthetic exposures last

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Radiographic Predictors of Difficult Laryngoscopy in Acromegaly Patients

imageBackground: Patients with acromegaly have a high risk of difficult laryngoscopy. However, clinical predictors, such as upper lip bite test or modified Mallampati class, show limited predictive performance for difficult laryngoscopy in such patients. In this retrospective study, we evaluated radiographic indices obtained from skull lateral x-ray and ostiomeatal unit computed tomography images to predict difficult laryngoscopy in acromegaly patients. Materials and Methods: Data on demographics, preoperative serum levels of pituitary hormones, and radiographic indices were collected from 90 acromegaly patients that underwent transsphenoidal removal for pituitary tumor from January 2010 to December 2016. Difficult laryngoscopy was defined as Cormack-Lehane grade ≥III. Results: Difficult laryngoscopy occurred in 21 (23%) patients. In univariate analysis, age and radiographic indices indicating tongue size, such as tongue area (TA) on ostiomeatal unit computed tomography, linear distance from the alveolar line of the mandible to the hyoid bone, and linear distance from the interior border of the mandible to the hyoid bone on skull lateral x-ray, were associated with difficult laryngoscopy. In multivariate analysis, age (odds ratio [95% confidence interval], 1.084 [1.037-1.190]; P=0.002) and TA (1.002 [1.000-1.003], P=0.014) were independent risk factors for difficult laryngoscopy. The area under the curve of the combined model of age and TA was 0.80. Conclusions: Old age and radiographic predictors indicating large tongue size (large TA, long alveolar line of the mandible to the hyoid bone and mandible to the hyoid bone) were associated with an increased rate of difficult laryngoscopy in acromegaly patients. Preoperative radiographic measurements of tongue size can be helpful for safe airway management in such patients.

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Chemical Eye Injury in a Case of Cervical Spine Surgery

imageNo abstract available

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Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases [Genetics]

Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223...

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SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines [Genetics]

DNA damage tolerance (DDT) releases replication blockage caused by damaged nucleotides on template strands employing two alternative pathways, error-prone translesion DNA synthesis (TLS) and error-free template switch (TS). Lys164 of proliferating cell nuclear antigen (PCNA) is SUMOylated during the physiological cell cycle. To explore the role for SUMOylation of PCNA...

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Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration [Genetics]

Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie...

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Modulation of vitamin D signaling by the pioneer factor CEBPA

Publication date: Available online 11 December 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Veijo Nurminen, Antonio Neme, Sabine Seuter, Carsten Carlberg

Abstract

The myeloid master regulator CCAAT enhancer-binding protein alpha (CEBPA) is known as a pioneer factor. In this study, we report the CEBPA cistrome of THP-1 human monocytes after stimulation with the vitamin D receptor (VDR) ligand 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) for 2, 8 and 24 h. About a third of the genomic VDR binding sites co-located with those of CEBPA. In parallel, the binding strength of 5% of the CEBPA cistrome, i.e. some 1500 sites, is significantly (p < 0.001) affected by 1,25(OH)2D3. Transcriptome-wide analysis after CEBPA silencing indicated that the pioneer factor enhances both the basal expression and ligand inducibility of 70 vitamin D target genes largely involved in lipid signaling and metabolism. In contrast, CEBPA suppresses 82 vitamin D target genes many of which are related to the modulation of T cell activity by monocytes. The inducibility of the promoter-specific histone marker H3K4me3 distinguishes the former class of genes from the latter. Moreover, prominent occupancy of the myeloid pioneer factor PU.1 on 1,25(OH)2D3-sensitive CEBPA enhancers mechanistically explains the dichotomy of vitamin D target genes. In conclusion, CEBPA supports vitamin D signaling concerning actions of the innate immune system, but uses the antagonism with PU.1 for suppressing possible overreactions of adaptive immunity.



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The role of RNA adenosine demethylases in the control of gene expression

Publication date: Available online 11 December 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Veronika Rajecka, Tomas Skalicky, Stepanka Vanacova

Abstract

RNA modifications are being recognized as an essential factor in gene expression regulation. They play essential roles in germ line development, differentiation and disease. In eukaryotic mRNAs, N6-adenosine methylation (m6A) is the most prevalent internal chemical modification identified to date. The m6A pathway involves factors called writers, readers and erasers. m6A thus offers an interesting concept of dynamic reversible modification with implications in fine-tuning the cellular metabolism. In mammals, FTO and ALKBH5 have been initially identified as m6A erasers. Recently, FTO m6A specificity has been debated as new reports identify FTO targeting N6,2′-O-dimethyladenosine (m6Am). The two adenosine demethylases have diverse roles in the metabolism of mRNAs and their activity is involved in key processes, such as embryogenesis, disease or infection. In this article, we review the current knowledge of their function and mechanisms and discuss the existing contradictions in the field. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.



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Monitoring 137Cs concentrations in bird species occupying different ecological niches; game birds and raptors in Fukushima Prefecture

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Rie Saito, Masahiko Kabeya, Yui Nemoto, Hitoshi Oomachi

Abstract

This study was conducted to assess radiocesium accumulation in birds after the accident at Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Station in 2011, with a particular focus on 137Cs, which has a long physical half-life. Results of 137Cs monitoring in four game bird species including two pheasant species and two duck species (copper pheasant, green pheasant, spot-billed duck and mallard) were assessed in Fukushima Prefecture. We also obtained samples from rescued raptors that died during treatment or rehabilitation at the Wildlife Symbiosis Centre in Fukushima Prefecture because of severe injury. We measured the muscle concentrations of 137Cs in four of these raptor species (black kite, northern goshawk, peregrine falcon and ural owl). Comparison of the two pheasant species showed that the copper pheasants inhabiting forested areas had higher 137Cs concentrations in muscle (Bq/kg, fresh mass) than the green pheasants inhabiting mountainous areas near human habitation (i.e., Satoyama). No clear tendencies were observed in 137Cs concentration in muscle of copper pheasants over time, but a tendency to decrease was observed in green pheasants over time. The difference in tendencies between species may be attributable to differences in their food habits and its 137Cs concentration, and also differences in the situation of 137Cs accumulation in their habitat. No significant differences were observed in 137Cs concentration in muscle between the resident spot-billed duck and migratory mallard because of the comparatively short biological of effective half-life of radiocesium. Analysis of 137Cs concentration in muscle of raptor revealed that the concentration was similar to, or lower than, those of pheasants and ducks.



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Atmospheric transport of 131I and 137Cs from Fukushima by the East Asian northeast monsoon

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): P.K. Long, P.D. Hien, N.H. Quang

Abstract

The Lagrangian particle dispersion model FLEXPART was used to simulate atmospheric dispersion of radionuclides from the Fukushima nuclear power plant (FNPP) towards the Tropical Western Pacific (TWP) and Southeast Asia (SEA). The simulation model distinguished between hemispherical transport via the jet stream and regional transport within the marine boundary layer by the East Asian northeast monsoon. This regional transport was driven by anticyclonic circulation over southern Japan and the western Pacific resulting from a recurrent eastward extension of the Siberian High to the Pacific Ocean. Activity concentrations of 131I and 137Cs measured at ten monitoring stations in TWP and SEA were used to validate the particle dispersion model. Good agreement between the FLEXPART model and observations yields confidence regarding its application to assess radiation impacts and support emergency planning in response to a possible future nuclear accident in the region.



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Efficiency and mechanism of adsorption of low concentration uranium in water by extracellular polymeric substances

Publication date: February 2019

Source: Journal of Environmental Radioactivity, Volume 197

Author(s): Xiao Li Wang, Ye Li, Jing Huang, Yu Zhi Zhou, Bo Lin Li, Dong Bin Liu

Abstract

Extracellular polymeric substances (EPS) of uranium adsorbent was first extracted from the aerobic activated sludge of municipal wastewater treatment plant as raw material. The structure and surface morphology of EPS was characterized by FTIR, SEM-EDX, 3D-EEM, and XPS. The 3D-EEM spectra of EPS revealed that there are Tryptophan-like protein and Humus which can adsorb uranium in the EPS. The results of XPS indicated that the EPS surface contained active functional groups (sbndCOOH,sbndCONH2,-H2PO4,sbndOH,sbndNH2 and so on) which all react with uranium, and the C, N, O elements play an important role in the reaction. The static batch test was used to study the adsorption behavior of uranium on the EPS, and the effects of pH, dosage of EPS and initial concentration of the solution on the removal of uranium by EPS were investigated. The adsorption isotherm, thermodynamics and kinetic models were used to match the mechanism of the interaction between EPS and uranium. Batch adsorption experiments revealed that the pH value had a great influence on the adsorption effect of EPS, and the optimal solution pH for uranium adsorption was around 6.0 with the removal efficiency of uranium was about 93% in the condition of neutral. Freundlich (R2 ≈ 0.997) and Langmuir (R2 ≈ 0.9931) models can get a good fitting effect, indicating that the adsorption of uranium by EPS had both monolayer adsorption and multilayer adsorption. EPS and uranium were combined disorderly and ion exchange mechanism could be involved. In this study, the active groups on the surface of EPS were also involved in the chemisorption process of uranium adsorption. The maximum adsorption capacity of EPS by Langmuir fitting was 333.3 mg/g. We conclude EPS is a potential adsorbent for radionuclide treatment.



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Modern Day Trauma Care for the Anesthesiologist

Publication date: Available online 10 December 2018

Source: Anesthesiology Clinics

Author(s): Maureen McCunn, Mohammed Iqbal Ahmed, Catherine M. Kuza



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Perioperative Care of the Trauma Patient: New Concepts Since Wartime Learning

Publication date: Available online 10 December 2018

Source: Anesthesiology Clinics

Author(s): Lee A. Fleisher



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Stochastic resonance stimulation improves balance in children with cerebral palsy: a case control study

Stochastic Resonance (SR) Stimulation has been used to enhance balance in populations with sensory deficits by improving the detection and transmission of afferent information. Despite the potential promise of...

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Exercise therapy in addition to an orthosis reduces pain more than an orthosis alone in patients with thumb base osteoarthritis: a propensity score matching study

Publication date: Available online 11 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): R.M. Wouters, J. Tsehaie, H.P. Slijper, S.E.R. Hovius, R. Feitz, Hand-Wrist Study Group, R.W. Selles

Abstract
Objective

To compare the effect of exercises and orthotics with orthotics alone on pain and hand function in patients with thumb base (CMC-1) osteoarthritis (OA) and to predict outcomes on pain and hand function of exercises and orthotics.

Design

Prospective cohort study with propensity score matching

Setting

Data collection took place in thirteen outpatient clinics for hand surgery and hand therapy in the Netherlands.

Participants

A consecutive, population-based sample of 173 patients with CMC-1 OA was included in this study of which 84 were matched on baseline demographics and baseline primary outcomes.

Interventions

Exercises and orthotics versus orthotics alone.

Main Outcome Measure(s)

Primary outcomes included pain and hand function at three months, measured using Visual Analogue Scales (0-100, VAS) and the Michigan Hand outcomes Questionnaire (0-100, MHQ).

Results

A larger decrease in VAS pain at rest (11.1 points difference, 95% Confidence interval(CI): 1.9, 20.3, p=0.002) and during physical load (22.7 points difference, 95% CI: 13.6, 31.0, p<0.001,) was found in the exercise + orthotic group compared to the orthotic group. Additionally, larger improvement was found for the MHQ subscales pain, work performance, aesthetics and satisfaction in the exercise + orthotic group. No differences were found on other outcomes. Baseline scores of metacarpophalangeal flexion, presence of scapho-trapezio-trapezoid OA, VAS pain at rest, heavy physical labor and MHQ total predicted primary outcomes for the total exercise + orthotic group (N=131).

Conclusions

Conservative treatment for patients with CMC-1 OA should include exercises, since there is a relatively large treatment effect compared to using an orthosis alone. Future research should study exercises and predictors in a more standardized setting to confirm this finding.



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Efficacy of participation-focused therapy on performance of physical activity participation goals and habitual physical activity in children with cerebral palsy: a randomized controlled trial

Publication date: Available online 11 December 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Sarah E. Reedman, Roslyn N. Boyd, Stewart G. Trost, Catherine Elliott, Leanne Sakzewski

Abstract
Objective

To determine the efficacy of a participation-focused therapy (ParticiPAte CP) on leisure-time physical activity goal performance and satisfaction and habitual physical activity (HPA) in children with cerebral palsy (CP).

Design

Randomized waitlist-controlled trial.

Setting

Home and community.

Participants

Thirty-seven children Gross Motor Function Classification System (GMFCS) I-III were recruited (18 males, mean age 10y 0mo [SD 1y 5mo]) from a population-based register.

Interventions

Participants were randomized to ParticiPAte CP (an 8-week goal-directed, individualized, participation-focused therapy delivered by a physical therapist) or waitlist usual care.

Main Outcome Measures

The primary outcome was Canadian Occupational Performance Measure (COPM). Accelerometers were worn for objective measurement of HPA (min·day-1 moderate to vigorous physical activity, MVPA, and sedentary time). Barriers to participation, community participation, and quality of life outcomes were also collected. Data were analysed by intention-to-treat using generalized estimating equations.

Results

ParticiPAte CP led to significant improvements in goal performance (MD=3.58, 95% CI=2.19 to 4.97, p<0.001), satisfaction (MD=1.87, 95% CI=0.37 to 3.36, p=0.014), and barriers to participation (MD=26.39, 95% CI=6.13 to 46.67, p=0.011) compared with usual care at eight weeks. There were no between group differences on min·day-1 MVPA at eight weeks (MD=1.17, 95% CI=-13.27 to 15.61, p=0.874). There was a significant difference in response to intervention between participants who were versus were not meeting HPA guidelines at baseline (MD=15.85, 95% CI=3.80 to 27.89, p<0.0061). Following ParticiPAte CP, low active participants had increased average MVPA by 5.98 (SD=12.16) min·day-1.

Conclusion

ParticiPAte CP was effective at increasing perceived performance of leisure-time physical activity goals in children with CP GMFCS I-III by reducing modifiable barriers to participation. This did not translate into change in HPA on average, however low active children may have a clinically meaningful response.



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Gastric sub-epithelial tumors: Identification of gastrointestinal stromal tumors using CT with a practical scoring method

Gastric Cancer

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Gallstone disease and type 2 diabetes risk: A Mendelian randomization study

Hepatology

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Viscous lidocaine solution vs lidocaine spray for pharyngeal local anesthesia in upper gastroesophageal endoscopy

Journal of Research in Medical Sciences

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Impact of preoperative wait time on survival in patients with clinical stage II/III gastric cancer

Gastric Cancer

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Atrial fibrillation is highly prevalent yet undertreated in patients with biopsy-proven nonalcoholic steatohepatitis

Liver International

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Factors affecting non‐operative management of uncomplicated appendicitis in children: Should laparoscopic appendectomy be immediate, interval, or emergency?

Abstract

Introduction

We conducted a prospective non‐randomized comparison of children with uncomplicated appendicitis treated either by primary laparoscopic appendectomy (PLA) or by non‐operative management (NOM) followed by interval laparoscopic appendectomy (ILA) if NOM was successful or emergency laparoscopic appendectomy (ELA) if NOM was unsuccessful.

Methods

Before 2015, all patients with uncomplicated appendicitis underwent PLA using a standard three‐port technique. Postoperatively, piperacillin/tazobactam was administered until the white blood cell count was less than 10 000/μL and patients were afebrile. Since 2015, in cases of uncomplicated appendicitis, intravenous analgesia has been administered once after assessment, and then NOM has been immediately employed, with repeat doses of piperacillin/tazobactam administered every 8 h after admission. We have also used standard management cut‐off criteria to determine when to perform laparoscopic appendectomy after NOM: if NOM fails, ELA is performed within 6 h, and if NOM is successful, ILA is planned.

Results

There were 103 eligible subjects for this study. Eleven cases of suspected complicated appendicitis were excluded, leaving 34 PLA cases and 58 NOM cases. After NOM, 27 patients were treated with ILA and 31 with ELA. There was one recurrence after successful NOM, and in two cases, patients' parents refused to consent to ILA after successful NOM. There were more perforations and significantly more residual abscesses in ELA than in PLA. Operative time and postoperative hospitalization were significantly longer among ELA patients than among PLA patients, and operative time was significantly shorter during ILA than in PLA.

Conclusion

Further evaluation is required to confirm which patients will benefit most from NOM and what role PLA has in treating uncomplicated appendicitis.



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Previous Adverse Outcome of Term Pregnancy and Risk of Preterm Birth in Subsequent Pregnancy

Abstract

Objective Evaluate risk of preterm birth (PTB, < 37 completed weeks' gestation) among a population of women in their second pregnancy with previous full term birth but other adverse pregnancy outcome. Methods The sample included singleton live born infants between 2007 and 2012 in a birth cohort file maintained by the California Office of Statewide Health Planning and Development. The sample was restricted to women with two pregnancies resulting in live born infants and first birth between 39 and 42 weeks' gestation. Logistic regression was used to calculate the risk of PTB in the second birth for women with previous adverse pregnancy outcome including: small for gestational age (SGA) infant, preeclampsia, placental abruption, or neonatal death (≤ 28 days). Risks were adjusted for maternal factors recorded for second birth. Results The sample included 133,622 women. Of the women with any previous adverse outcome, 4.7% had a PTB while just 3.0% of the women without a previous adverse outcome delivered early (relative risk adjusted for maternal factors known at delivery 1.4, 95% CI 1.3–1.5). History of an SGA infant, placental abruption, or neonatal death increased the adjusted risk of PTB in their second birth by 1.5–3.7-fold. History of preeclampsia did not elevate the risk of a preterm birth in the subsequent birth. Conclusions for Practice The findings indicate that women with previous SGA infant, placental abruption, or neonatal death, despite a term delivery, may be at increased risk of PTB in the subsequent birth. These women may be appropriate participates for future interventions aimed at reduction in PTB.



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Surface contamination in the operating room: use of adenosine triphosphate monitoring

Abstract

Purpose

We prospectively investigated contamination of high-contact surfaces in the operating room (OR) using adenosine triphosphate (ATP) monitoring. We tested whether contamination would increase from morning (AM) to afternoon (PM), despite cleaning between cases. Second, we compared the degree of OR contamination to non-OR control sites.

Methods

ORs with high case volumes were selected for the study. Ten sites in each OR were swabbed using the AccuPoint® HC ATP Sanitation Monitoring device, which provided a numerical measure of contamination (relative light units, RLUs). According to the manufacturer, surfaces are considered clean at ≤ 400 RLUs. AM measurements were taken before the start of surgical cases and PM measurements were taken after cases were completed.

Results

Eighty morning and 70 afternoon samples were obtained from 8 ORs. Apart from the OR floor, laryngoscope handles had the highest level of morning contamination (1204 RLUs, interquartile range 345, 2603), with 75% of AM samples and 100% of PM samples exceeding 400 RLUs. This contamination was comparable to hospital toilet seats (87% of samples exceeding 400 RLUs). No sites showed statistically significant increases in contamination from AM to PM.

Conclusion

Apart from the OR floors, laryngoscope handles emerged as a key OR site where improved cleaning practices may reduce cross-contamination risk. While some sites showed increased contamination over the course of the day, none of these met statistical significance thereby offering tentative evidence that current cleaning practices during case turnover are effective for most sites.



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