Σάββατο 2 Φεβρουαρίου 2019

Determinants of Severe Maternal Morbidity and Its Racial/Ethnic Disparities in New York City, 2008–2012

Abstract

Objectives Severe maternal morbidity (SMM) is an important indicator for identifying and monitoring efforts to improve maternal health. Studies have identified independent risk factors, including race/ethnicity; however, there has been limited investigation of the modifying effect of socioeconomic factors. Study aims were to quantify SMM risk factors and to determine if socioeconomic status modifies the effect of race/ethnicity on SMM risk. Methods We used 2008–2012 NYC birth certificates matched with hospital discharge records for maternal deliveries. SMM was defined using an algorithm developed by the Centers for Disease Control and Prevention. Mixed-effects logistic regression models estimated SMM risk by demographic, socioeconomic, and health characteristics. The final model was stratified by Medicaid status (as a proxy for income), education, and neighborhood poverty. Results Of 588,232 matched hospital deliveries, 13,505 (229.6 per 10,000) had SMM. SMM rates varied by maternal age, birthplace, education, income, pre-existing chronic conditions, pre-pregnancy weight status, trimester of prenatal care entry, plurality, and parity. Race/ethnicity was consistently and significantly associated with SMM. While racial differences in SMM risk persisted across all socioeconomic groupings, the risk was exacerbated among Latinas and Asian-Pacific Islanders with lower income when compared to white non-Latinas. Similarly, living in the poorest neighborhoods exacerbated SMM risk among both black non-Latinas and Latinas. Conclusions for Practice SMM determinants in NYC mirror national trends, including racial/ethnic disparities. However, these disparities persisted even in the highest income and educational groups suggesting other pathways are needed to explain racial/ethnic differences.



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Design, development, and evaluation of a local sensor-based gait phase recognition system using a logistic model decision tree for orthosis-control

Functionality and versatility of microprocessor-controlled stance-control knee-ankle-foot orthoses (M-SCKAFO) are dictated by their embedded control systems. Proper gait phase recognition (GPR) is required to ...

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Controlling a motorized orthosis to follow elbow volitional movement: tests with individuals with pathological tremor

There is a need for alternative treatment options for tremor patients who do not respond well to medications or surgery, either due to side effects or poor efficacy, or that are excluded from surgery. The stud...

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Class II transactivator (CIITA) mediates IFN-γ induced eNOS repression by enlisting SUV39H1

Publication date: Available online 1 February 2019

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

Author(s): Xinyu Weng, Yuanyuan Zhang, Zilong Li, Liming Yu, Feng Xu, Mingming Fang, Lei Hou, Junbo Ge, Yong Xu

Abstract

Endothelial nitric oxide synthase (eNOS), selectively expressed in vascular endothelial cells, plays important roles in a range of biological and pathological processes. eNOS levels can be altered by extrinsic and intrinsic cues at the transcriptional level. Here we examined the epigenetic mechanism whereby the pro-inflammatory cytokine interferon gamma (IFN-γ) represses eNOS transcription. In response to IFN-γ treatment, there was a simultaneous down-regulation of eNOS expression and up-regulation of class II trans-activator (CIITA). Over-expression of CIITA directly repressed eNOS promoter while CIITA knockdown attenuated IFN-γ induced eNOS repression. Chromatin immunoprecipitation (ChIP) assay revealed that IFN-γ stimulation promoted CIITA occupancy on the proximal eNOS (−430/−168). Coincidently, CIITA recruitment on the eNOS promoter was paralleled by the disappearance of trimethylated histone H3K4 (H3K4Me3) and the enrichment of trimethylated H3K9 (H3K9Me3) with no significant changes in the levels of trimethylated H3K27 (H3K27Me3) or trimethylated H4K20 (H4K20Me3). In accordance, CIITA depletion was associated with the normalization of H3K4Me3 and H3K9Me3 on the eNOS promoter. Mechanistically, CIITA interacted with and enlisted the histone H3K9 trimethyltransferase SUV39H1 to the eNOS promoter to repress transcription. IFN-γ treatment augmented SUV39H1 expression and promoted SUV39H1 recruitment to the eNOS promoter in endothelial cells. Silencing of SUV39H1 abrogated eNOS repression by IFN-γ by erasing H3K9Me3 from the eNOS promoter. In conclusion, our data reveal a novel role for CIITA in endothelial cells and present SUV39H1 as a druggable target in the intervention of endothelial dysfunction.



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Delineation of critical amino acids in activation function 1 of progesterone receptor for recruitment of transcription coregulators

Publication date: Available online 1 February 2019

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

Author(s): Amanda Rui En Woo, Siu Kwan Sze, Hwa Hwa Chung, Valerie C.-L. Lin

Abstract

The activation functions AF1 and AF2 of nuclear receptors mediate the recruitment of coregulators in gene regulation. AF1 is mapped to the highly variable and intrinsically unstructured N terminal domain and AF2 lies in the conserved ligand binding domain. The unstructured nature of AF1 offers structural plasticity and hence functional versatility in gene regulation. However, little is known about the key functional residues of AF1 that mediates its interaction with coregulators. This study focuses on the progesterone receptor (PR) and reports the identification of K464, K481 and R492 (KKR) as the key functional residues of PR AF1. The KKR are monomethylated and function cooperatively. The combined mutations of KKR to QQQ render PR isoform B (PRB) hyperactive, whereas KKR to FFF mutations abolishes as much as 80% of PR activity. Furthermore, the hyperactive QQQ mutation rescues the loss of PR activity due to E911A mutation in AF2. The study also finds that the magnitudes of the mutational effect differ in different cell types as a result of differential effects on the functional interaction with coregulators. Furthermore, KKR provides the interface for AF1 to physically interact with p300 and SRC-1, and with AF2 at E911. Intriguingly, the inactive FFF mutant interacts strikingly stronger with both SRC-1 and AF2 than wt PRB. We propose a tripartite model to describe the dynamic interactions between AF1, AF2 and SRC-1 with KKR of AF1 and E911 of AF2 as the interface. An overly stable interaction would hamper the dynamics of disassembly of the receptor complex.



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Contextualized Treatment in Traumatic Brain Injury Inpatient Rehabilitation: Effects on Outcomes During the First Year after Discharge

Publication date: Available online 1 February 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Jennifer Bogner, Marcel Dijkers, Erinn M. Hade, Cynthia Beaulieu, Erin Montgomery, Clare Giuffrida, Misti Timpson, Juan Peng, Kamie Gilchrist, Aubrey Lash, Flora M. Hammond, Susan Horn, John Corrigan

Abstract
Objective

To evaluate the effect of providing a greater percentage of therapy as contextualized treatment on acute traumatic brain injury (TBI) rehabilitation outcomes.

Design

Propensity score methods are applied to the TBI-Practice-Based Evidence (TBI-PBE) database, a database consisting of multi-site, prospective, longitudinal observational data.

Setting

Acute inpatient rehabilitation.

Participants

Patients enrolled in the TBI-PBE study (n=1843), aged 14 years or older, who sustained a severe, moderate, or complicated mild TBI, receiving their first IRF admission in the US, and consented to follow-up 3 and 9 months post discharge from inpatient rehabilitation.

Interventions

Not applicable.

Main Outcome Measures

Participation Assessment with Recombined Tools-Objective- -17, FIMTM Motor and Cognitive scores, Satisfaction with Life Scale and Patient Health Questionnaire-9.

Results

Increasing the percentage of contextualized treatment during inpatient TBI rehabilitation leads to better outcomes, specifically in regard to community participation.

Conclusions

Increasing the proportion of treatment provided in the context of real-life activities appears to have a beneficial impact on outcome. Although the effect sizes are small, the results are consistent with other studies supporting functional-based interventions effecting better outcomes. Furthermore, any positive findings, regardless of size or strength, are endorsed as important by consumers (survivors of TBI). While the findings do not imply that decontextualized treatment should not be used, when the therapy goal can be addressed with either approach, the findings suggest that better outcomes may result if the contextualized approach is used.



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Soil-to-cassava plant transfer factor of natural radionuclides on a mining impacted soil in a tropical ecosystem of Nigeria

Publication date: May 2019

Source: Journal of Environmental Radioactivity, Volume 201

Author(s): N.E. Adesiji, J.A. Ademola

Abstract

The transfer factors (TFs) of naturally occurring radionuclides, 238U and 232Th from soil to different cassava plant compartments were calculated. Cassava is widely cultivated in Nigeria and contributes significantly to the food supply of the nation. There is sparsity of data on the TFs in Nigeria, and no TF data from any African country were included in the International Atomic Energy Agency's compilation of TFs for the tropical ecosystem. Samples of tin tailings and soil samples from virgin land were used to formulate three soil groups; group-A (soil from virgin land only), group-B (tailings only) and group-C (equal dry mass combination of tailings and soil from virgin land). Pot experiments were set up to determine the TFs of 238U and 232Th. The activity concentrations of 238U and 232Th in the dried samples of the soil and plant compartments were determined using a sodium iodide detector. The TF of 238U ranged from below detection limit (BDL) to 0.01 in the tuber samples, BDL to 0.23 in the stem samples and BDL to 0.90 in the leaf samples, while the TF of 232Th ranged between 0.006 and 0.49 for tuber samples, 0.03 and 0.65 in stem samples and 0.03 and 1.54 in the leaf samples. There were significant difference in the TF of 238U and 232Th between the soil groups. The leaf compartment generally had most of the highest TF values while the tuber samples had most of the lowest TF values for both radionuclides.



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Field effects studies in the Chernobyl Exclusion Zone: Lessons to be learnt

Publication date: Available online 1 February 2019

Source: Journal of Environmental Radioactivity

Author(s): N.A. Beresford, E.M. Scott, D. Copplestone

Abstract

In the initial aftermath of the 1986 Chernobyl accident there were detrimental effects recorded on wildlife, including, mass mortality of pine trees close to the reactor, reduced pine seed production, reductions in soil invertebrate abundance and diversity and likely death of small mammals.

More than 30 years after the Chernobyl accident there is no consensus on the longer-term impact of the chronic exposure to radiation on wildlife in what is now referred to as the Chernobyl Exclusion Zone. Reconciling this lack of consensus is one of the main challenges for radioecology. With the inclusion of environmental protection in, for instance, the recommendations of the International Commission on Radiological Protection (ICRP), we need to be able to incorporate knowledge of the potential effects of radiation on wildlife within the regulatory process (e.g. as a basis on which to define benchmark dose rates).

In this paper, we use examples of reported effects on different wildlife groups inhabiting the Chernobyl Exclusion Zone (CEZ) as a framework to discuss potential reasons for the lack of consensus, consider important factors influencing dose rates organisms receive and make some recommendations on good practice.



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Heritable disorders of connective tissue: Description of a data repository and initial cohort characterization

We describe a data repository on heritable disorders of connective tissue (HDCT) assembled by the National Institutes of Health's National Institute on Aging (NIA) Intramural Research Program between 2001 and 2013. Participants included affected persons with a wide range of heritable connective tissue phenotypes, and unaffected family members. Elements include comprehensive history and physical examination, standardized laboratory data, physiologic measures and imaging, standardized patient‐reported outcome measures, and an extensive linked biorepository. The NIA made a commitment to make the repository available to extramural investigators and deposited samples at Coriell Tissue Repository (N = 126) and GenTAC registry (N = 132). The clinical dataset was transferred to Penn State University College of Medicine Clinical and Translational Science Institute in 2016, and data elements inventoried. The consented cohort of 1,009 participants averaged 39 ± 18 years (mean ± SD, range 2–95) at consent; gender distribution is 71% F and 83% self‐report Caucasian ethnicity. Diagnostic categories include Ehlers–Danlos syndrome (classical N = 50, hypermobile N = 99, vascular N = 101, rare types and unclassified N = 178), Marfan syndrome (N = 33), Stickler syndrome (N = 60), fibromuscular dysplasia (N = 135), Other HDCT (N = 72). Unaffected family members (N = 218) contributed DNA for the molecular archive only. We aim to develop further discrete data from unstructured elements, analyze multisymptom HDCT manifestations, encourage data use by other researchers and thereby better understand the complexity of these high‐morbidity conditions and their multifaceted effects on affected persons.



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Electroporated GLUT4‐7myc‐GFP detects in vivo glucose transporter 4 translocation in skeletal muscle without discernible changes in GFP‐patterns

New Findings

What is the central question of this study?

Resolving the mechanism(s) leading to glucose transporter 4 (GLUT4) translocation to the muscle surface membrane has great therapeutic potential. However, the measurement of GLUT4 translocation is technically challenging. Here, we asked whether electroporation of GLUT4‐7myc‐GFP into skeletal muscle could be used as a tool to study GLUT4 translocation in vivo.

What is the main finding and its importance?

By acutely inducing GLUT4‐7myc‐GFP expression in skeletal muscle, we verified that in vivo exercise and AICAR stimulation increased the GLUT4 presence in the sarcolemma measured as myc‐signal. Importantly, the increased myc‐signal in the sarcolemma was not accompanied by major visual changes in the distribution of the GFP signal.

Abstract

Insulin and exercise lead to translocation of the glucose transporter 4 (GLUT4) to the surface membrane of skeletal muscle fibres. This process is pivotal for facilitating glucose uptake into skeletal muscle. To study this, a robust assay to directly measure the translocation of GLUT4 in adult skeletal muscle is needed. Here, we aimed to validate a simple GLUT4 translocation assay using a genetically encoded biosensor in mouse skeletal muscle. We transfected GLUT4‐7myc‐GFP into mouse muscle to study live GLUT4 movement and to evaluate GLUT4 insertion in the muscle surface membrane following in vivo running exercise and pharmacological activation of AMP activated protein kinase (AMPK). Transfection led to expression of GLUT4‐7myc‐GFP that were dynamic in live flexor digitorum brevis fibres and which, upon insulin stimulation, exposed the myc‐epitope extracellularly. Running exercise, as well as AMPK‐activation by 5‐Aminoimidazole‐4‐carboxamide ribonucleotide, induced ∼125% and ∼100% increase in extracellularly exposure of GLUT4 in the surface membrane of tibialis anterior muscle. Interestingly, the clear increase in surface‐exposed GLUT4 content by insulin, exercise or AMPK activation was not accompanied by any discernible reorganization of the GLUT4‐GFP signal. In conclusion, we provide a detailed description of an easy to use translocation assay to study GLUT4 accumulation at the surface membrane by exercise and exercise‐mimicking stimuli. Notably, our analyses revealed that increased GLUT4 surface membrane accumulation was not accompanied by a discernible change in the GLUT4 localization pattern.

This article is protected by copyright. All rights reserved



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Editorial Board



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Clear fluids fasting for elective paediatric anaesthesia: The European Society of Anaesthesiology consensus statement

No abstract available

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Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study

imageBACKGROUND Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN A retrospective cohort study. SETTING Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P 

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Use of the Totaltrack VLM as a rescue device following failed tracheal intubation

imageNo abstract available

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Epidemiology and incidence of severe respiratory critical events in ear, nose and throat surgery in children in Europe: A prospective multicentre observational study

imageBACKGROUND Ear, nose and throat (ENT) surgery, the most frequently performed surgical procedure in children, is a strong predictor for peri-operative respiratory complications. However, there is no clear information about peri-operative respiratory severe critical events (SCEs) associated with anaesthesia management of ENT children in Europe. OBJECTIVE To characterise the epidemiology and incidence of respiratory SCEs during and following ENT surgery in Europe and to identify the risk factors for their occurrence. DESIGN A secondary analysis of the Anaesthesia PRactice In Children Observational Trial, a prospective observational multicentre cohort trial. SETTING The study included 261 centres across 33 European countries and took place over a consecutive 2-week recruitment period between April 2014 and January 2015. PATIENTS We extracted data from 5592 ENT surgical procedures that were performed on 5572 children aged 6.0 (3.6) years (mean (SD)) from the surgical database and compared these with data from 15 952 non-ENT surgical children aged 6.7 (4.8) years. MAIN OUTCOME MEASURES The primary outcome was the incidence of respiratory SCEs (laryngospasm, bronchospasm and new onset of postoperative stridor). Secondary outcomes were the differences in epidemiology between ENT children and non-ENT surgical children and the risk factors for the occurrence of respiratory SCEs. RESULTS The incidence (95% confidence interval) of any respiratory SCE (laryngospasm, bronchospasm and postoperative stridor) was 3.93% (3.46 to 4.48) and was significantly higher than that observed in non-ENT surgical children [2.61% (2.37 to 2.87)], with a relative risk of 1.51 (1.28 to 1.77), P less than 0.0001. Younger age (14% decrease in critical events by increasing year, P 

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Laryngotracheal stenosis in children following cardiac surgery: A retrospective review

imageNo abstract available

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Comparison of rocuronium requirement in children with continuous infusion versus intermittent bolus: A randomised controlled trial

imageBACKGROUND Minimising rocuronium administration during paediatric surgery helps to reduce the incidence of residual muscular blockade. OBJECTIVE To determine whether intermittent bolus injection (Bolus group) or continuous infusion (group) requires the lesser amount of rocuronium. DESIGN A randomised, single-blind controlled trial. SETTING A single university hospital from March to June 2017. PATIENTS Sixty-six children undergoing general anaesthesia. INTERVENTIONS Dose of rocuronium for maintenance of muscle relaxation in either Bolus or continuous infusion group. Train-of-four (TOF) count of two was maintained during surgery. When TOF count reached three, 0.1 mg kg−1 of rocuronium was administered in Bolus group or infused at an increased rate of 0.1 mg kg−1 h−1 in continuous infusion group. MAIN OUTCOME MEASURES Primary outcome was the dose of rocuronium given (μg kg−1 min−1). The recovery time from the TOF count four to TOF 0.7 (RT0.7), and 0.9 (RT0.9) were recorded. All adverse events were recorded up to 30 min after extubation. RESULTS Mean (SD) rocuronium dose in the Bolus group was 6.1 (0.9), [95% confidence interval (95% CI) 5.7 to 6.4] μg kg−1 min−1 and 4.9 (1.0), (95% CI 4.6 to 5.3) μg kg−1 min−1 in the continuous infusion group (P = 0.001). RT0.7 was 24.0 (13.7), 95% CI 19.3 to 28.7) min in the Bolus group, and 25.7 (16.0), (95% CI 20.2 to 31.2) min in the continuous infusion group (P = 0.73). RT0.9 was 30.7 (17.1), (95% CI 24.9 to 36.5) min in the Bolus group, and 30.0 (17.6), (95% CI 24.0 to 36.0) min in the continuous infusion group (P  = 0.91). The incidence of adverse events was not significantly different between two groups. CONCLUSION In children undergoing general anaesthesia, the dose of rocuronium given by continuous administration was less than that with intermittent bolus. TRIAL REGISTRATION ClinicalTrials.gov (identifier: NCT03060707).

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Use of palonosetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in women 60 years of age or older undergoing laparoscopic cholecystectomy: A randomised double-blind study

imageNo abstract available

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Ultrasound-guided vs. palpation-guided techniques for radial arterial catheterisation in infants: A randomised controlled trial

imageBACKGROUND The usefulness of ultrasound-guided techniques for radial arterial catheterisation has been well identified; however, its usefulness has not been completely evaluated in infants under 12 months of age, who are generally considered the most difficult group for arterial catheterisation. OBJECTIVE We evaluated whether ultrasound guidance would improve success rates and reduce the number of attempts at radial arterial catheterisation in infants. DESIGN A randomised, controlled and patient-blinded study. SETTING Single-centre trial, study period from June 2016 to February 2017. PATIENTS Seventy-four infants undergoing elective cardiac surgery. INTERVENTION Patients were allocated randomly into either ultrasound-guided group (group US) or palpation-guided group (group P) (each n=37) according to the technique applied for radial arterial catheterisation. All arterial catheterisations were performed by one of two experienced anaesthesiologists based on group assignment and were recorded on video. MAIN OUTCOME MEASURES The primary endpoint was the first-pass success. The number of attempts and total duration of the procedure until successful catheterisation were also analysed. RESULTS The first-pass success rate was significantly higher in the group US than in the group P (68 vs. 38%, P = 0.019). In addition, fewer attempts were needed for successful catheterisation in the group US than in the group P (median 1 [IQR 1 to 2] vs. 2 [1 to 4], P = 0.023). However, the median [IQR] procedural time (s) until successful catheterisation in the two groups was not significantly different (102 [49 to 394] vs. 218 [73 to 600], P = 0.054). CONCLUSION The current study demonstrated that the ultrasound-guided technique for radial arterial catheterisation in infants effectively improved first-pass success rate and also reduced the number of attempts required. TRIAL REGISTRATION ClinicalTrials.gov NCT02795468.

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The effect of virtual reality bronchoscopy simulator training on performance of bronchoscopic-guided intubation in patients: A randomised controlled trial

imageBACKGROUND The use of a flexible optical bronchoscopic (FOB) for intubation is an essential airway management skill. OBJECTIVE(S) Our primary objective was to compare the effects of simulator training (ORSIM high-fidelity simulator) with no simulation training on the performance of FOB intubation in anaesthetised patients. DESIGN Randomised controlled trial. SETTING Single-centre tertiary hospital; trial conducted between April 2015 to May 2016. PARTICIPANTS Medical students, anaesthesia assistants and anaesthesia residents with experience of less than five FOB intubations from whom informed consent was obtained. INTERVENTION Students, anaesthesia assistants and anaesthesia residents viewed a didactic presentation before performing an initial FOB intubation in an anaesthetised patient. Intubations were recorded and evaluated using the Global Rating Scale (GRS) and checklist scores. Subsequently, participants were randomised to control group (Group CON) and had no simulation training, or to a simulation group (Group SIM) and underwent 60 min of simulation practice. Within a week, participants performed a second FOB intubation and were similarly evaluated. MAIN OUTCOME MEASURES Pretraining and posttraining intubation time, GRS and checklist scores. RESULTS Baseline characteristics were similar between groups. In Group SIM, there was significant improvement between pre and posttraining GRS [22.9 ± 8.1 vs. 28.2 ± 7.3, mean difference (95% CI) 5.3 (0.3 to 10.3), P = 0.04], and intubation time [177.6 ± 77.6 vs. 119.3 ± 52.2 s, mean difference (95% CI) −58.4 (−100.3 to −16.5) s, P = 0.01]. There was no difference in Group CON, between pre and posttraining intubation time, GRS or checklist. CONCLUSION We conclude, posttraining performance of FOB intubation, as measured by intubation time and GRS, improved in Group SIM, while it was unchanged in the Group CON. The ORSIM simulator may be a useful adjunct in acquiring FOB intubation skills. CLINICAL TRIAL NUMBER AND REGISTRY ClinicalTrials.gov ID: NCT02699242.

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Bupivacaine infiltration in children for postoperative analgesia after tonsillectomy: A randomised controlled trial

imageBACKGROUND Adenotonsillectomy is a frequently performed procedure in paediatric day-case surgery. Postoperative pain can be significant and standard analgesia protocols are often insufficient. OBJECTIVE Our primary objective was to investigate if infiltration of the peritonsillar space with bupivacaine would reduce the need for postoperative opioids compared with pre-emptive intravenous tramadol. DESIGN A double-blind, randomised controlled trial. SETTING Ambulatory surgical day care centre, University Hospitals of Leuven, Belgium, from January 2012 to September 2016. PATIENTS Two hundred children, between 4 and 10 years old, undergoing elective adenotonsillectomy were included in the study. INTERVENTION Children were randomly allocated to receive either a bolus of 3 mg kg−1 intravenous tramadol or infiltration of the tonsillar lodge with 5-ml bupivacaine 0.25%. Reasons for exclusion were American Society of Anesthesiologists classification greater than 2, allergies to the investigated products, psychomotor retardation, bleeding disorders and lack of proficiency in Flemish. MAIN OUTCOME MEASURES The primary endpoint was the number of children in need of piritramide postoperatively. Secondary outcomes included the cumulative dose of postoperative piritramide, pain scores and the incidence of postoperative nausea and vomiting during the first 24 postoperative hours, time to discharge and adverse effects. RESULTS The proportion of children in need of postoperative piritramide was significantly lower in the tramadol group than in children with peritonsillar infiltration (57 vs. 81%, P 

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Calculation improves the estimation of needle depth from skin to thoracic epidural space in infants

imageNo abstract available

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Use of tracheal ultrasound combined with clinical parameters to select left double-lumen tube size: A prospective observational study

imageBACKGROUND Left double-lumen tubes (LDLTs) are used in thoracic surgery to allow one-lung ventilation. Their size is usually chosen on the basis of clinical parameters (height, sex). Double-lumen endobronchial tubes are frequently undersized/oversized, risking tube displacement or tracheal trauma. A correlation between ultrasound tracheal diameter and left main bronchus dimension has been demonstrated. OBJECTIVES We hypothesised that the insertion of undersized/oversized double-lumen tubes is frequent when the size is selected using standard criteria, and that the use of ultrasound to estimate tracheal diameter may help to reduce the frequency of insertion of oversized tubes. DESIGN Two-step prospective observational study. SETTING The operating room of a French University hospital from January 2016 to February 2017. PATIENTS We enrolled 102 and 50 consecutive patients undergoing elective thoracic surgery in Steps 1 and 2 (males 63.7 and 60.0%, age 63 (13) and 63 (11) years, height 170 (13) and 169 (9) cm, respectively). INTERVENTION In Step 1, the size of the LDLT inserted was selected on the basis of clinical parameters. Ultrasound data about tracheal diameter were collected to determine cut-off points associating height and tracheal diameter. Cut-off values for ultrasound tracheal diameter were applied retrospectively to test their capability to reduce the insertion rate of oversized tube. In Step 2, the LDLT size was chosen according to the determined combined cut-off values. MAIN OUTCOME MEASURE LDLT size was considered adequate if the bronchial cuff volume required for isolation of the lung (i.e. no difference between inspiratory and expiratory lung volumes) was 0.5 to 2.5 ml of air; undersized and oversized tubes required more than 2.5 ml and less than 0.5 ml, respectively. RESULTS In Step 1, LDLT size was appropriate/undersized/oversized in 40 (39.2%)/23 (22.6%)/39 (38.6%) of patients. Cut-off values derived from ultrasound measurements would have reduced the use of oversized tubes by 20.6% (P 

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Intra-operative difficult airway identification and critical airway communication: how effective are we?: A retrospective review of 6318 cases

imageNo abstract available

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Measurement of forces applied using a Macintosh direct laryngoscope compared with a Glidescope video laryngoscope in patients with predictors of difficult laryngoscopy: A randomised controlled trial

imageBACKGROUND In patients with predictive features associated with easy direct laryngoscopy, videolaryngoscoy with the GlideScope has been shown to require less force when compared with Macintosh direct laryngoscopy. OBJECTIVE The aim of this study was to compare forces applied with Glidescope vs. Macintosh laryngoscopes in patients with predictive features associated with difficult direct laryngoscopy. DESIGN A randomised study. SETTING Toronto General Hospital, a university tertiary centre in Canada. PATIENTS Forty-four patients aged over 18 years, with one or more features of difficult intubation, undergoing elective surgery requiring single-lumen tracheal intubation. INTERVENTION We measured the force applied to oropharyngeal tissues by attaching three FlexiForce Sensors (A201-25) to the concave surface of Macintosh and GlideScope laryngoscope blades. Anaesthetists or experienced anaesthesia residents performed laryngoscopies with both devices in a randomised sequence. MAIN OUTCOME MEASURES The primary outcome was peak force. The secondary outcomes were average force and impulse force. The latter is the integral of the force over the time during which the force acted. RESULTS Complete data were available for 40 individuals. Peak and average forces decreased with GlideScope (17 vs. 21 N, P = 0.03, and 6 vs. 11 N, P 

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Levobupivacaine scalp nerve block: haemodynamics and anaesthesia requirements in supratentorial craniotomy P 096: Erratum

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The Role of PHOX2B‐derived astrocytes in chemosensory control of breathing and sleep homeostasis

Key points

The embryonic PHOX2B‐progenitor domain generates neuronal and glial cells which together are involved in chemosensory control of breathing and sleep homeostasis. Ablating PHOX2B‐derived astrocytes significantly contributes to secondary hypoxic respiratory depression as well as abnormalities in sleep homeostasis. PHOX2B‐derived astrocyte ablation results in axonal pathologies in the retrotrapezoid nucleus.

Abstract

We identify a population of ∼ 800 RTN astrocytes derived from PHOX2B‐positive, OLIG3‐negative progenitor cells, that interact with PHOX2B‐expressing RTN chemosensory neurons. PHOX2B‐derived astrocyte ablation during early life results in adult‐onset O2 chemoreflex deficiency. These animals also display changes in sleep homeostasis, including fragmented sleep and disturbances in delta power after sleep deprivation, all without observable changes in anxiety or social behaviours. Ultrastructural evaluation of the RTN demonstrates that PHOX2B‐derived astrocyte ablation results in features characteristic of degenerative neuro‐axonal dystrophy, including abnormally dilated axon terminals and increased amounts of synapses containing autophagic vacuoles/phagosomes. We conclude that PHOX2B‐derived astrocytes are necessary for maintaining a functional O2 chemosensory reflex in the adult, modulate sleep homeostasis, and are key regulators of synaptic integrity in the RTN region, which is necessary for the chemosensory control of breathing. These data also highlight how defects in embryonic development may manifest as neurodegenerative pathology in an adult.

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Calcium modulation of cardiac sodium channels

Abstract

Modification of voltage‐gated Na+ channel (NaV) function by intracellular calcium ([Ca2+]i) has been a topic of much controversy. Early studies relied on measuring NaV function in the absence or presence of [Ca2+]i, and generated seemingly disparate results. Subsequent investigations revealed the mechanism(s) of [Ca2+]i driven NaV modulation are complex and involve multiple accessory proteins. The Ca2+ sensing protein Calmodulin (CaM) has a central role in tuning NaV function to [Ca2+]i, but the mechanism has been obscured by other proteins (such as Fibroblast Growth Factors (FGF) or CaM dependent Kinase II (CaMKII)) as they can also modify channel function, or exert an influence in a Ca2+ dependent manner. Significant progress has been made in understanding the architecture of full‐length ion channels and the structural and biophysical details of NaV‐accessory protein interactions. Interdisciplinary structure‐function studies are beginning to resolve the effect each interaction has on NaV gating. Carefully designed structure‐guided or strategically selected disease‐associated mutations are able to impair NaV‐accessory protein interactions without altering other properties of channel function. Recently CaM was found to engage part of NaV1.5 that is required for channel inactivation with high affinity. Careful impairment of this interaction disrupted NaV1.5's ability to recover from inactivation. Such results support a paradigm of CaM Facilitated Recovery from Inactivation (CFRI). Understanding how NaV‐CaM, CaMKII, and FGF/FHF interactions affect the timing or function of CFRI in cardiomyocytes remain open questions that are discussed herein. Moreover if CFRI dysfunction or premature activation underlie certain NaV channelopathies are important questions that will require further investigation.

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Cardiomyocyte substructure reverts to an immature phenotype during heart failure

Key points

As reactivation of the foetal gene program has been implicated in pathological remodelling during heart failure (HF), we examined whether cardiomyocyte subcellular structure and function revert to an immature phenotype during this disease. Surface and internal membrane structures appeared gradually during development, and returned to a juvenile state during HF. Similarly, dyadic junctions between the cell membrane and sarcoplasmic reticulum were progressively 'packed' with L‐type Ca2+ channels and Ryanodine Receptors during development, and 'unpacked' during HF. Despite similarities in subcellular structure, dyads were observed to be functional from early developmental stages, but exhibited an impaired ability to release Ca2+ in failing cardiomyocytes. Thus, while immature and failing cardiomyocytes share similarities in subcellular structure, these do not fully account for the marked impairment of Ca2+ homeostasis observed in HF.

Abstract

Reactivation of the foetal gene program has been implicated as a driver of pathological cardiac remodelling. We presently examined whether pathological remodelling of cardiomyocyte substructure and function during heart failure (HF) reflects a reversion to an immature phenotype. Using scanning electron microscopy, we observed that Z‐grooves and t‐tubule openings at the cell surface appeared gradually during cardiac development, and disappeared during HF. Confocal and super‐resolution imaging within the cell interior revealed similar structural parallels; disorganization of t‐tubules in failing cells was strikingly reminiscent of the late stages of postnatal development, with fewer transverse elements and a high proportion of longitudinal tubules. RyRs were observed to be laid down in advance of developing t‐tubules and similarly 'orphaned' in HF, although RyR distribution along Z‐lines was relatively sparse. Indeed, nanoscale imaging revealed coordinated packing of LTCCs and RyRs into dyadic junctions during development, and orderly unpacking during HF. These findings support a 'last in, first out' paradigm, as the latest stages of dyadic structural development are reversed during disease. Paired imaging of t‐tubules and Ca2+ showed that the disorganized arrangement of dyads in immature and failing cells promoted desynchronized and slowed Ca2+ release in these two states. However, while developing cells exhibited efficient triggering of Ca2+ release at newly formed dyads, dyadic function was impaired in failing cells despite similar organization of Ca2+ handling proteins. Thus, pathologically deficient Ca2+ homeostasis during HF is only partly linked to the re‐emergence of immature subcellular structure, and additionally reflects lost dyadic functionality.

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The neural sources of N170: Understanding timing of activation in face‐selective areas

Abstract

The N170 ERP component has been widely identified as a face‐sensitive neural marker. Despite extensive investigations conducted to examine the neural sources of N170, there are two issues in prior literature: (a) few studies used individualized anatomy as head model for the cortical source analysis of the N170, and (b) the relationship between the N170 and face‐selective regions from fMRI studies is unclear. Here, we addressed these questions by presenting pictures of faces and houses to the same group of healthy adults and recording structural MRI, fMRI, and high‐density ERPs in separate sessions. Source analysis based on the participant's anatomy showed that the middle and posterior fusiform gyri were the primary neural sources for the face‐sensitive aspects of the N170. Source analysis based on regions of interest from the fMRI revealed that the fMRI‐defined fusiform face area was the major contributor to the N170. The current study suggests that the fusiform gyrus is a major neural contributor to the N170 ERP component and provides further insights about the spatiotemporal characteristics of face processing.



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P300 and positive slow waves reveal the plausibility in inductive reasoning

Abstract

Category‐based induction is an advanced cognitive function that is based on our category‐level knowledge. Previous findings have recognized the distance effect in category‐based induction: Inductive strength is affected by the hierarchical distance between the premises and conclusions. However, the neural mechanisms underlying this effect require elucidation. In the present study, we investigated the neural mechanisms of the distance effect by using EEG technology and a new experimental paradigm—category‐based induction. In this paradigm, we used three hierarchical levels of categories—the subordinate category, the basic category, the superordinate category—and an irrelevant category. We further used these categories to create four types of trial that varied in the hierarchical distance between the premise and the conclusion: the subordinate‐basic, the basic‐superordinate, the subordinate‐superordinate, and the irrelevant‐superordinate trials. In each trial, participants judged the probability that the conclusion category had the same property as the premise category. Our behavioral results revealed that people responded more slowly in the irrelevant‐superordinate trials than in the basic‐superordinate and the subordinate‐basic trials. Our ERP results showed that the irrelevant‐superordinate trials elicited smaller P300 (250–500 ms) amplitudes than did the subordinate‐basic and the basic‐superordinate trials. In addition, the subordinate‐superordinate trials elicited smaller P300 and PSW (700–998 ms) amplitudes than did the subordinate‐basic and the basic‐superordinate combinations. These findings indicate that the amplitudes of P300 and PSW may reflect the distance effect in inductive reasoning: The further the premise‐conclusion hierarchical distance, the lower the inductive strength, and thus the smaller the P300 and PSW amplitudes.



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Professionalism in Pediatric Anesthesiology: Affirmation of a definition based on results of a nationally‐administered survey of pediatric anesthesiologists

Abstract

Background

Previously published work established the need for a specialty‐specific definition of professionalism in pediatric anesthesiology. That work established a composite definition consisting of 11 domains and their component "defining themes" for professionalism in pediatric anesthesiology. As a next step towards assessing generalizability of our single‐center findings, we sought to gain input from a national sample of pediatric anesthesiologists.

Aim

To establish the construct validity of our previously published multidimensional definition of professionalism in pediatric anesthesiology using a nationally representative sample of pediatric anesthesiologists.

Methods

A survey was distributed via snowball sampling to the leaders of every pediatric anesthesiology fellowship program and pediatric anesthesia department or clinical division in the United States. Survey items were designed to validate individual component themes in the working definition. For affirmed items, the respondent was asked to rate the importance of the item. Respondents were also invited to suggest novel themes to be included in the definition.

Results

216 pediatric anesthesiologists representing a variety of experience levels and practice settings responded to the survey. All 40 themes were strongly supported by the respondents, with the least supported theme receiving 71.6% approval. 92.8% of respondents indicated that the 11 domains previously identified formed a comprehensive list of domains for professionalism in pediatric anesthesiology. Four additional novel themes were suggested by respondents, including wellness/self‐care/burnout prevention, political advocacy, justice within a practice organization, and respect for leadership/experienced partners. These are topics for future study. The survey responses also indicated a near‐universal agreement that didactic lectures would be ineffective for teaching professionalism.

Conclusion

This national survey of pediatric anesthesiologists serves to confirm the construct validity of our prior working definition of professionalism in pediatric anesthesiology, and has uncovered several opportunities for further study. This definition can be used for both curriculum and policy development within the specialty.

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Retrospective audit of airway management practices in children with craniocervical pathology

Abstract

Background

Craniocervical immobilisation using halo body orthoses may be required in the management of children with craniocervical junction pathology. To date, the effect of such immobilisation on perioperative anaesthetic management has not been addressed in large series.

Aim

To review the airway management of children requiring halo body orthoses undergoing general anaesthesia.

Methods

The study was a retrospective case note review from a single institution. The neurosurgical database was interrogated to identify all patients less than 16 years of age that required a halo body orthosis from 1996 to 2015. We used the electronic patient record to identify all procedures performed under general anaesthesia for these patients, either for halo application, or with the halo in situ. Details of techniques used for airway management were recorded, and paired data between individuals pre‐ and post‐halo application were compared. Demographic data, diagnosis and perioperative complications were also recorded.

Results

We identified 90 children that underwent placement of a halo body orthosis. A total of 269 anaesthetic records from these patients were analysed and classified as pre‐halo application, or halo in situ. Facemask ventilation was achieved in all patients, though some required simple airway adjuncts and may have been more difficult in the presence of the halo. Supraglottic airways were used successfully in many patients. There was a significant increase in the number of patients classed as Cormack and Lehane grades 3 or 4 on direct laryngoscopy with the halo in situ compared with before the halo was applied. The incidence of intubation using fibreoptic or videolaryngoscopy was higher with the halo in situ. Multiple intubation attempts were required in 3.4% (1/29) of patients undergoing anaesthesia for halo placement compared with 15.1% (11/73) undergoing anaesthesia with a halo in situ.

Conclusion

Airway management in children with cervical spine pathology should be anticipated to be more difficult than the general paediatric population. This is likely to be due to co‐existing pathology associated with cervical spine disease in children, limitation of neck movement to prevent further neurological injury, and the halo itself limiting access to the head. We recommend advanced preparation, and ensuring the immediate availability of an anaesthetist with skills in managing the paediatric difficult airway to avoid complications in this patient population.

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Effect of High-Intensity Exercise on Multiple Sclerosis Function and 31P MRS Outcomes

PURPOSE We determined if a high-intensity aerobic exercise program would be safe, improve expected fitness and clinical outcomes, and alter exploratory phosphorous magnetic resonance spectroscopy (31P MRS) outcomes in persons with multiple sclerosis (PwMS). METHODS This open-label prospective pilot study compared 2 cohorts of ambulatory PwMS matched for age, sex and VO2max. Cohorts underwent 8-weeks of high-intensity aerobic exercise (MS-Ex, n=10) or guided stretching (MS-Ctr, n=7). Aerobic exercise consisted of four 30-minute sessions per week while maintaining >70% maximal heart rate. Changes in cardiorespiratory fitness, clinical outcomes, and 31P MRS of tibialis anterior muscle (TA) and brain were compared. Cross-sectional 31P MRS comparisons were made between all MS participants and a separate matched healthy control (HC) population. RESULTS The MS-Ex cohort achieved target increases in VO2max (mean +12.7%, p=

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