Phenotype comparison confirms ZMYND11 as a critical gene for 10p15.3 microdeletion syndrome

Abstract

Proper epigenetic regulation processes are crucial in the normal development of the human brain. An ever-increasing group of neurodevelopmental disorders due to derangements of epigenetic regulation involve both microdeletion and monogenic syndromes. Some of these syndromes have overlapping clinical phenotypes due to haploinsufficiency-sensitive genes involved in microdeletions. It was shown recently that the ZMYND11 gene has important functions in epigenetic regulation as an unconventional transcription co-repressor of highly expressed genes, possibly acting in the repression of cryptic transcription from gene bodies. The aim of our study was to compare the clinical phenotypes of patients with 10p15.3 deletions with the phenotypes of patients with loss-of-function ZMYND11 mutations. The results of our study further confirm that the ZMYND11 gene is the critical gene for the clinical phenotype of 10p15.3 microdeletion involving the terminal ~4 Mb of chromosome 10p. In addition, accumulating clinical data allow for further characterisation of this syndrome, including neurodevelopmental disorder, characteristic dysmorphic features and some other more frequent symptoms, such as behavioural disturbances, hypotonia, seizures, low birth weight, short stature in those older than 10 years of age, genitourinary malformations and recurrent infections.

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Evidence Supporting Serology Based Pathway for Diagnosing Coeliac Disease In Asymptomatic Children From High-Risk Groups.

Objective: The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines for diagnosing coeliac disease (CD) in children were modified in 2012. They recommend that in symptomatic children with anti-tissue transglutaminase antibody (anti-tTG) titre of greater than 10-times upper limit of normal (>10xULN) and who have positive anti-endomysial antibody and HLA-DQ2/DQ8 haplotype, the diagnosis of CD can be based on serology. Aim of this study is to establish whether serology-based pathway of the ESPGHAN guidelines could also be reliably applied to asymptomatic children from high-risk groups. Methods: From March 2007 - February 2017 prospective data on anti-tTG titre, age, sex and reason for screening was collected at diagnostic endoscopy on all asymptomatic children being diagnosed with CD. The relationship between modified Marsh-Oberhuber classification histological grading and contemporaneous anti-tTG titres was analysed. Results: 157 asymptomatic children were diagnosed with CD. 84/157 (53.5%) had antitTG >10xULN (normal 200IU/ml and total villous atrophy was present in 29/53 (55%). Main reasons for serological screening were: type-1 diabetes mellitus (n = 36) and first-degree relatives with CD (n = 24). Mean age at diagnosis was 8.8 years. Serology-based diagnosis is cost-beneficial by around [pounds]1275/child in the United Kingdom. Conclusion: All 75 asymptomatic children from high-risk groups with anti-tTG >10xULN had histology proven CD. This study provides further evidence that the guidelines for diagnosing CD by the serology-based pathway should be extended to these children. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Proton Pump Inhibitors May Not be the First Line of Treatment for GERD in Infants.

No abstract available

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Health-Related Quality of Life in Adolescent Patients with Hepatitis C Genotype 1 Treated with Sofosbuvir and Ledipasvir.

Objective: To assess the impact of treatment with ledipasvir/sofosbuvir (LDV/SOF) on the health-related quality of life (HRQL) of pediatric patients with chronic hepatitis C virus (HCV) infection. Methods: Adolescents (12-17 years) with HCV were treated with LDV/SOF (90 mg/400 mg daily) for 12 weeks. HRQL was assessed using the PedsQLv4.0-SF15 completed by the children and caregivers before, during, and after treatment. Results: We included 100 adolescents with HCV genotype 1 infection [14.7 +/- 2.0 years, 1% known cirrhosis, 80% treatment-naive, 97% sustained virologic response (SVR-12)]. At baseline, HRQL the caregiver- perceived HRQL scores were lower than adolescents' self-reported scores (by 6.7-7.9 points, all p

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Hypertension and cataract surgery under loco-regional anaesthesia: not to be ignored?

The presence of sight-impairing opacification, cataract, is an age-related condition. Modern phacoemulsification procedures allow cataract removal safely and efficiently under loco-regional anaesthesia.¹ Increasing numbers of patients with comorbid conditions, including dementia, diabetes mellitus, cardiovascular disease on concurrent antithrombotics and hypertension, present for cataract surgery. The British Journal of Anaesthesia has recently addressed anaesthesia-related issues for ophthalmic surgery in patients with dementia,² diabetes mellitus³ and anticoagulation.⁴ This editorial addresses issues related specifically to hypertension. Hypertension impacts 1 billion adults across the globe affecting up to 80% of patients in the general population aged 60 yr and older.⁵⁶ Like the sensation of a fishbone stuck in the throat, the impact of hypertension on perioperative outcome after cataract surgery should not be ignored without meticulous interrogation.

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Peripheral i.v. analysis (PIVA) of venous waveforms for volume assessment in patients undergoing haemodialysis

Abstract

Background

The assessment of intravascular volume status remains a challenge for clinicians. Peripheral i.v. analysis (PIVA) is a method for analysing the peripheral venous waveform that has been used to monitor volume status. We present a proof-of-concept study for evaluating the efficacy of PIVA in detecting changes in fluid volume.

Methods

We enrolled 37 hospitalized patients undergoing haemodialysis (HD) as a controlled model for intravascular volume loss. Respiratory rate (F₀) and pulse rate (F₁) frequencies were measured. PIVA signal was obtained by fast Fourier analysis of the venous waveform followed by weighing the magnitude of the amplitude of the pulse rate frequency. PIVA was compared with peripheral venous pressure and standard monitoring of vital signs.

Results

Regression analysis showed a linear correlation between volume loss and change in the PIVA signal (R²=0.77). Receiver operator curves demonstrated that the PIVA signal showed an area under the curve of 0.89 for detection of 20 ml kg⁻¹ change in volume. There was no correlation between volume loss and peripheral venous pressure, blood pressure or pulse rate. PIVA-derived pulse rate and respiratory rate were consistent with similar numbers derived from the bio-impedance and electrical signals from the electrocardiogram.

Conclusions

PIVA is a minimally invasive, novel modality for detecting changes in fluid volume status, respiratory rate and pulse rate in spontaneously breathing patients with peripheral i.v. cannulas.

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Lost in translation? Comparing the effectiveness of electronic-based and paper-based cognitive aids

It is now established that the use of cognitive aids, such as checklists and algorithms leads to improved technical¹ and team performance² during anaesthetic emergencies. The unpredictable nature of emergencies means that it is difficult to examine these outside of a simulation setting. Consequently, it is challenging to prove these observed behaviours translate to improved patient outcomes, although many anecdotal reports exist.³⁴ Research is now focused on the nature of these cognitive aids and how they can be integrated into the clinical setting, working with, rather than against the instincts of experienced practitioners.⁵

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SmartPilot ® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study

Abstract

Background

Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot^® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery.

Methods

This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the "appropriate anaesthesia zone" defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45–60 and systolic arterial pressure of 80–140 mm Hg. Postoperative complications were recorded for one month in a blinded manner.

Results

Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0–40) vs 5 (0–116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2–20) vs 8 (2–60) days, P=0.017).

Conclusions

SmartPilot^® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients.

Clinical trial registration.

NCT 02556658.

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Does variable training lead to variable care?

Entrants to anaesthesia training programs in the developed world are broadly comparable in terms of readiness for specialist training as a result of global standards established by the World Federation for Medical Education. While the context of national health systems has undeniable significance, the competencies required to provide anaesthesia for patients undergoing surgery should also be broadly comparable. In this issue of the British Journal of Anaesthesia, Jonker and colleagues¹ report wide variability in anaesthesia training programmes across the European Union (EU), and variable certification processes. Could this potentially result in variable quality in patient care? Jonker and colleagues propose that variability of training and certification limits the easy movement of anaesthetists around the EU. National health systems around the world remain dependent on a mobile workforce, often trained in other jurisdictions. Determining if a foreign graduate is competent is a key concern for employers.

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Point-of-care paediatric gastric sonography: can antral cut-off values be used to diagnose an empty stomach?

Abstract

Background

Gastric sonography is emerging as a valuable clinical point-of-care tool to assess aspiration risk. A recent study proposed that a single cut-off cross-sectional area (CSA) in the supine position could diagnose an empty stomach in the parturient. This study establishes the sensitivity and specificity of a single CSA cut-off measurement in both supine and right lateral decubitus (RLD) positions in the diagnosis of an empty antrum in paediatric patients.

Methods

Following induction of anaesthesia, antral sonography was performed in supine and RLD positions in 100 fasted paediatric patients prior to upper endoscopic evaluation. Following upper endoscopy, any residual stomach content was suctioned under direct visualization and antral sonography was immediately performed. Antral CSA values were compared using Wilcoxon signed rank test. Receiver operator characteristic (ROC) curves were plotted to estimate the discriminating power of antral sonography position in the diagnosis of an empty antrum.

Results

Significant differences were found between pre-suctioned and post-suctioned CSA values in the RLD position. The cut-off CSAs of the empty antrum in the supine and RLD positions were 2.19 cm² (sensitivity 75%, specificity 36%) and 3.07 cm² (sensitivity 76%, specificity 67%), respectively.

Conclusions

The RLD position produces the most sensitive and specific CSA cut-off value where an antral CSA of ≤ 3.07 cm² in the RLD position presents with acceptable performance in the ability to discriminate an empty antrum in paediatric patients over 1 yr of age. As age increases, the sensitivity and specificity of this test increases in the RLD position.

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Use of a hand-held digital cognitive aid in simulated crises: the MAX randomized controlled trial

Abstract

Background

Cognitive aids improve the technical performance of individuals and teams dealing with high-stakes crises. Hand-held electronic cognitive aids have rarely been investigated. A randomized controlled trial was conducted to investigate the effects of a smartphone application, named MAX (for Medical Assistance eXpert), on the technical and non-technical performance of anaesthesia residents dealing with simulated crises.

Methods

This single-centre randomized, controlled, unblinded trial was conducted in the simulation centre at Lyon, France. Participants were anaesthesia residents with >1 yr of clinical experience. Each participant had to deal with two different simulated crises with and without the help of a digital cognitive aid. The primary outcome was technical performance, evaluated as adherence to guidelines. Two independent observers remotely assessed performance on video recordings.

Results

Fifty-two residents were included between July 2015 and February 2016. Six participants were excluded for technical issues; 46 participants were confronted with a total of 92 high-fidelity simulation scenarios (46 with MAX and 46 without). Mean (sd) age was 27 (1.8) yr and clinical experience 3.2 (1.0) yr. Inter-rater agreement was 0.89 (95% confidence interval 0.85–0.92). Mean technical scores were higher when residents used MAX [82 (11.9) vs 59 (10.8)%; P<0.001].

Conclusion

The use of a hand-held cognitive aid was associated with better technical performance of residents dealing with simulated crises. These findings could help digital cognitive aids to find their way into daily medical practice and improve the quality of health care when dealing with high-stakes crises.

Clinical trial registration

NCT02678819.

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Volumes of the spinal canal and caudal space in children zero to three years of age assessed by magnetic resonance imaging: implications for volume dosage of caudal blockade

Abstract

Background

The primary aim of this study was to objectively assess the different spinal and caudal volumes that are of interest for caudal block volume dosing.

Methods

Three directly assessed (volume of spinal canal/caudal space, volume of the dural sac and volume of spinal cord) and two derived volumes (volume of the epidural space and cerebrospinal fluid volume) were determined from magnetic resonance images (MRI) in 20 children (zero - three yr of age). The assessed volumes were correlated to age, height and weight. Furthermore, the volumes of the epidural space from caudal canal to three different clinically relevant target levels (L 1, Th 10 and Th 6) and the epidural volume of each individual spinal segment at the caudal, lumbar and thoracic levels were calculated.

Results

All volumes correlated in a linear manner to length and weight (R² 0.614 – 0.867) whereas a curvilinear correlation was associated with best curve fit for age (R² 0.696 – 0.883). The median volumes of the epidural space from caudal canal to L 1, Th 10 and Th 6 were 1.30 ml kg⁻¹ (95%CI 1.08-1.51), 1.57 ml kg⁻¹ (95%CI 1.29-1.81) and 1.78 ml kg⁻¹ (95%CI 1.52-2.08), respectively. The median volumes of the epidural space per vertebral segment were Thoracic: 0.60 ml (95%CI 0.38-0.75); Lumbar: 1.18 ml (95%CI 0.94-1.43) and Caudal: 0.85 ml (95%CI 0.56-1.18).

Conclusions

The spinal volumes of interest show a linear correlation to height and weight whereas a curvilinear correlation was found for age. The volume of the epidural space per segment was found to be significantly higher at the lumbar level compared with the caudal and thoracic levels.

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Heterogeneity of studies in anesthesiology systematic reviews: a meta-epidemiological review and proposal for evidence mapping

Abstract

Heterogeneity among the primary studies included in a systematic review (SR) is one of the most challenging considerations for systematic reviewers. Current practices in anaesthesiology SRs have not been evaluated, but traditional methods may not provide sufficient information to evaluate the true nature of these differences. We address these issues by examining the practices for evaluating heterogeneity in anesthesiology reviews. Also, we propose a mapping method for presenting heterogeneous aspects of the primary studies in SRs.We evaluated heterogeneity practices reported in SRs published in highly ranked anesthesiology journals and Cochrane reviews. Elements extracted from the SRs included heterogeneity tests, models used, analyses conducted, plots used, and I² values. Additionally, we selected a SR to develop an evidence map in order to display clinical heterogeneity.Our statistical analysis showed 150/207 SRs reporting a test for statistical heterogeneity. Plots were used in 138 reviews to display heterogeneity. Subgroup analyses were the most commonly reported analysis (54%). Meta-regression and sensitivity analyses were used sparingly (25%; 23% respectively). A random effects model was most commonly reported (33%). Heterogeneity statistics across meta-analyses suggested that, in our sample, the majority (55%) did not present sufficient heterogeneity to be of great concern. Cochrane reviews (n=58) were also analysed. Plots were used in 88% of Cochrane reviews. Subgroup analysis was used in 59% Cochrane reviews, while sensitivity analysis was used in 62%.Many reviews did not provide sufficient detail regarding heterogeneity. We are calling for improvement to reporting practices.

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Low-dose buprenorphine infusion to prevent postoperative hyperalgesia in patients undergoing major lung surgery and remifentanil infusion: a double-blind, randomized, active-controlled trial

Abstract

Background

. Postoperative secondary hyperalgesia arises from central sensitization due to pain pathways facilitation and/or acute opioid exposure. The latter is also known as opioid-induced hyperalgesia (OIH). Remifentanil, a potent μ-opioid agonist, reportedly induces postoperative hyperalgesia and increases postoperative pain scores and opioid consumption. The pathophysiology underlying secondary hyperalgesia involves N-methyl-D-aspartate (NMDA)-mediated pain pathways. In this study, we investigated whether perioperatively infusing low-dose buprenorphine, an opioid with anti-NMDA activity, in patients receiving remifentanil infusion prevents postoperative secondary hyperalgesia.

Methods

. Sixty-four patients, undergoing remifentanil infusion during general anaesthesia and major lung surgery, were randomly assigned to receive either buprenorphine i.v. infusion (25 μg h⁻¹ for 24 h) or morphine (equianalgesic dose) perioperatively. The presence and extent of punctuate hyperalgesia were assessed one day postoperatively. Secondary outcome variables included postoperative pain scores, opioid consumption and postoperative neuropathic pain assessed one and three months postoperatively.

Results

. A distinct area of hyperalgesia or allodynia around the surgical incision was found in more patients in the control group than in the treated group. Mean time from extubation to first morphine rescue dose was twice as long in the buprenorphine-treated group than in the morphine-treated group: 18 vs 9 min (P=0.002). At 30 min postoperatively, patients receiving morphine had a higher hazard ratio for the first analgesic rescue dose than those treated with buprenorphine (P=0.009). At three months, no differences between groups were noted.

Conclusions

. Low-dose buprenorphine infusion prevents the development of secondary hyperalgesia around the surgical incision but shows no long-term efficacy at three months follow-up.

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Review: Brown’s Atlas of Regional Anesthesia . E Farag and L Mounir-Soliman (editors) & Brown’s Regional Anesthesia Review . E Farag and L Mounir-Soliman (editors)

Review: Brown's Atlas of Regional Anesthesia.FaragE and Mounir-SolimanL (editors), 5^th edn, 2017. Published by Elsevier. Pp. 376. Price $199.99. ISBN-13: 978-0323354905.

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Is the bougie redundant in direct laryngoscopic grade 3 intubations?

A 51-year-old woman presented for major elective colorectal surgery with predicted difficult intubation (Mallampati score 3, small mouth opening) and a video laryngoscope was prepared as a 'plan B'. After induction, the patient's lungs were easily ventilated with a bag valve mask. Direct laryngoscopy was performed that demonstrated a grade 3 view. An experienced operator intubated successfully using a bougie, which was carefully advanced in one attempt blindly behind the epiglottis into the trachea.

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In the October BJA …

This issue of the BJA contains a special section on pain medicine that includes articles on acute and chronic pain in the context of anaesthesia. The main section of the Journal includes a number of articles relevant to perioperative outcomes in sepsis and septic shock, and in cardiac, abdominal, and lung resection surgery. There are also articles on the impact of non-depolarising neuromuscular blocking agents, beta-blockers, and statins on perioperative outcomes. The Neurosciences and Neuroanaesthesia section features three articles and three editorials related to anaesthetic effects on neuronal network connectivity as it relates to unconsciousness. And the Quality and Patient Safety section features an article with an editorial on the impact of anaesthetist gender on communication in simulated crisis situations.

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The paradox in the current use of videolaryngoscopes in the UK

Editor—The recent national survey by Cook and Kelly¹ is the first to provide a comprehensive overview of the current usage and practices of videolaryngoscopes (VLs) in UK clinical practice. We feel we can add to this area and would like to present some of the results of a regional survey on VLs that we conducted to gain an understanding of current practices and decision-making in the use of VLs in general airway management in the operating theatre (OT). The survey was conducted electronically via SurveyMonkey (San Mateo, CA, USA) and was distributed to 10 departments of anaesthesia in the London Deanery (London, UK) in December 2016. There were 171 responses collected between December 2016 and January 2017 with a response rate of about 51%, including 44% consultants, 21% specialty Registrar (StR) yr 7–yr 5, 14% StR yr 4–yr 3, and 7% core trainees. Selected findings from the survey were as follows:

• When asked whether VLs should be first line management strategy for anticipated difficult intubation (where bag mask ventilation was not predicted difficult), when given the choice between a VL and a Macintosh laryngoscope short/long blade +/–bougie, 51% of those surveyed preferred to use a VL.
• When asked whether VLs should be used routinely for intubation in all patients, regardless of predicted difficulty of intubation, 14% of respondents thought that VLs should be used routinely.
• When asked how many uses it approximately required to gain subjective competence in the use of any VL, 68% of respondents felt it required over 10 uses, 32% felt it required over 20 uses and 13% felt it required over 30 uses.
• When asked whether anaesthetists should begin their core training with VLs alongside the Macintosh laryngoscope as first line for all intubations, 10% of respondents were of the opinion that this should be the case.

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Diastolic dysfunction and sepsis: the devil is in the detail

Diastolic dysfunction is the consequence of impaired left ventricular relaxation, decreased recoil and decreased ventricular compliance.¹ Before the era of tissue Doppler imaging (TDI), pulmonary vein Doppler imaging in conjunction with transmitral Doppler, was a major tool in identifying diastolic dysfunction, also in septic shock patients.² Pulmonary vein Doppler assessment with a systolic (S) < diastolic (D) flow velocity supports the finding of elevated left ventricular filling pressures in a euvolaemic patient.

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Preadmission statin use improves the outcome of less severe sepsis patients - a population-based propensity score matched cohort study

Abstract

Background

Randomized controlled trials on the post-admission use of statins in sepsis patients have not shown a survival benefit. Whether preadmission use of statins would confer any beneficial effects in sepsis patients has not been well studied.

Methods

We conducted a population-based cohort study on a national health insurance claims database between 1999 and 2011. Sepsis patients were identified by ICD-9 codes compatible with the third International consensus definitions for sepsis. Use of statin was defined as the cumulative use of any statin for more than 30 days before the indexed sepsis admission. We determined the association between statin use and sepsis outcome by multivariate-adjusted Cox proportional hazard models and propensity score matched analysis. To minimize baseline imbalance between statin users and non-statin users, we matched/adjusted for social economic status, comorbidities, proxies for healthy lifestyle, health care facility utilization, and use of medications.

Results

We identified 52 737 sepsis patients, of which 3599 received statin treatment. Statins use was associated with a reduced 30-day mortality after multivariable adjustment (HR 0.86, 95% CI, 0.78–0.94) and propensity score matching (HR, 0.88; 95% CI, 0.78–0.99). On subgroup analysis, the beneficial effects of statins were not significant in patients receiving ventilator support or requiring ICU admission.

Conclusions

In this national cohort study, preadmission statin therapy before sepsis development was associated with a 12% reduction in mortality when compared with patients who never received a statin. There were no consistent beneficial effects of statins in all patient subgroups.

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Readmission after surgery: are neuromuscular blocking drugs a cause?

Neuromuscular blocking drugs (NMBDs) play an integral role in balanced anaesthesia. They improve intubating conditions, reduce iatrogenic damage to the upper airway and decrease postoperative hoarseness.¹ They also improve surgical operating conditions.² But use of NMBDs always carries the risk of residual neuromuscular block postoperatively. About 30% of all patients who receive NMBDs intraoperatively show signs of residual neuromuscular block when arriving in the post-anaesthesia care unit.^3–5 It has been suggested that residual neuromuscular block can cause postoperative pulmonary complications.^6–8

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Tissue Doppler assessment of diastolic function and relationship with mortality in critically ill septic patients: a systematic review and meta-analysis

Abstract

Background

Myocardial dysfunction may contribute to circulatory failure in sepsis. There is growing evidence of an association between left ventricular diastolic dysfunction (LVDD) and mortality in septic patients. Utilizing echocardiography, we know that tissue Doppler imaging (TDI) variables e′ and E/e′ are reliable predictors of LVDD and are useful measurements to estimate left ventricular (LV) filling pressures.

Methods

We conducted a systematic review and meta-analysis to investigate the association of e′ and E/e′ with mortality of patients with severe sepsis or septic shock. In the primary analysis, we included studies providing transthoracic TDI data for e′ and E/e′ and their association with mortality. Subgroup analyses were conducted according to myocardial regional focus of TDI assessment (septal, lateral or averaged). Three secondary analyses were performed: one included data from a transoesophageal study, another excluded studies reporting data at a very early (<6 h) or late (>48 h) stage following diagnosis, and the third pooled data only from studies excluding patients with heart valve disease.

Results

The primary analysis included 16 studies with 1507 patients with severe sepsis and/or septic shock. A significant association was found between mortality and both lower e′ [standard mean difference (SMD) 0.33; 95% confidence interval (CI): 0.05, 0.62; P=0.02] and higher E/e′ (SMD –0.33; 95% CI: –0.57, –0.10; P=0.006). In the subgroup analyses, only the lateral TDI values showed significant association with mortality (lower e′ SMD 0.45; 95% CI: 0.11, 0.78; P=0.009; higher E/e′ SMD –0.49; 95% CI: –0.76, –0.22; P=0.0003). The findings of the primary analysis were confirmed by all secondary analyses.

Conclusions

There is a strong association between both lower e′ and higher E/e′ and mortality in septic patients.

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Age and inflammation after cardiac surgery

The cardiac surgical population is aging and these patients have increased expectations with respect to quantity and quality of postoperative survival. Some of the physiological changes related to aging that impact surgical outcomes are better understood than others, and recently we are also beginning to gain a better understanding of the impact of aging on immunity and the immune response to surgery.¹²

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An algorithm for suboptimally placed supraglottic airway devices: the choice of videolaryngoscope

Editor—We agree with Zundert and colleagues¹ that anaesthetists sometimes accept lower standards for supraglottic airway device (SAD) placement than for tracheal tube placement. They advocate the use of videolaryngoscopy to correct a suboptimal SAD position using an algorithm, however they do not make any specific recommendation about which type of videolaryngoscope to use. A variety of classifications of videolaryngoscopes exist,^2–5 and some classes (for example, channelled videolaryngoscopes) might prove to be very difficult to use in this situation; some may even cause trauma in the reduced space available when an SAD is present. Zundert and colleagues ⁶ have previously referenced the C-MAC videolaryngoscope (Karl Storz, Tuttlingen, Germany) in this situation, but presumably other Macintosh-type bladed scopes would be acceptable. We would be keen to learn whether they have experience of other videolaryngoscopes, and we also wondered whether they had considered the place of the optical stylet.

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Hierarchy in disruption of large-scale networks across altered arousal states

Understanding how anaesthetics act within neural circuits to induce altered arousal states that range from sedation to general anaesthesia is an important question in neuroscience. Studies in laboratory animals demonstrate that anaesthetics including propofol, ether derivatives, and dexmedetomidine induce activity patterns in brainstem arousal nuclei that are similar to natural sleep.^1–3 However, anaesthetic drug action in brainstem arousal nuclei may provide only a partial answer to explain the behavioural and neurophysiological distinctions between anaesthesia-induced states and sleep, because anaesthetics also significantly modulate neuronal activity in other brain regions such as the thalamus and cortex.⁴⁵ Insights into how anaesthetics disrupt networks that sustain consciousness have been constrained by the practical and ethical challenges involved in noninvasively studying human brain activity. Guldenmund and colleagues⁶ used human neuroimaging to study large-scale network disruptions that are associated with dexmedetomidine and propofol sedation, two anaesthetic drugs with different receptor level targets.

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Humour therapy intervention to reduce stress and anxiety in paediatric anaesthetic induction, a pilot study

Editor—Hospitalization is a particularly negative experience for the paediatric population. Infants experiencing surgery can develop problematic behaviour, such as preoperative anxiety (50–75%)¹ and postoperative negative behavioural changes (75%), sleep and eating disorders, cognitive alterations, enuresis and disobedience. These complications can persist for several months after the surgical procedure.² In addition, it is well known that stress slows the healing process, decreases inflammatory responses, and likewise increases fear and anxiety. From a pathophysiological point of view, the increase in levels of circulating cortisol, secondary to an increase in the production of corticotropin releasing hormone and the action of the autonomic nervous system, can create harmful effects in different organs and tissues.³ Salivary cortisol has been used in several studies to measure levels of stress in children, as an index of the amount in blood, but which is a noninvasive procedure ideal for use in the paediatric population.

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Fading whispers down the lane: signal propagation in anaesthetized cortical networks

An active area of enquiry in the neuroscientific investigation of general anaesthesia is the question of whether anaesthetic-induced unconsciousness is mediated by bottom-up or top-down mechanisms in the brain. Candidates for the bottom-up approach include suppression of arousal centres in the brainstem and diencephalon,¹² activation of sleep-promoting neurones or nuclei in similar locations,¹³ blockade of sensory information en route from the thalamus to the cortex,⁴ and a disabled thalamic conductor for the neuronal orchestra of the cortex.⁵ Candidates for the top-down approach include direct effects on long-latency activity in cortical networks,⁶ with a consequent disruption of higher-order information synthesis that occurs beyond the level of the primary sensory cortex.^7–9 This bottom-up vs top-down distinction is almost surely artificial given the integrated circuits required for the normal function of neural systems and the widespread effects of general anaesthetics on the brain. We recently proposed that anaesthetics alter the level of consciousness (e.g. awake vs somnolent) through bottom-up mechanisms while degrading the contents of consciousness (e.g. the particular qualities of experience) through top-down mechanisms.¹⁰ Developing a clearer understanding of these processes is important because it can inform (i) the neurobiology of consciousness, a fundamental question in science, and (ii) our approach to brain monitoring, a fundamental and unmet challenge in clinical anaesthesia. However, it is difficult to address this question by investigating individual brain areas or molecular targets in the laboratory and also difficult to distinguish cortical and subcortical mechanisms through human neuroimaging and neurophysiology. In this issue of the British Journal of Anaesthesia, Hentschke and colleagues¹¹ examine an intermediate level of neuroanatomy and neurophysiology in a cortical slice model, finding more profound effects of isoflurane on signal propagation through the cortex than to the cortex.

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Disruption of cortical network activity by the general anaesthetic isoflurane

Abstract

Background

Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear.

Methods

We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices.

Results

Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05–0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents.

Conclusions

Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.

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Speaking up: does anaesthetist gender influence teamwork and collaboration?

Speaking up can be defined as explicitly communicating observations or concerns, requesting clarification or explanation, or explicitly challenging a colleague's decision or action.¹ Speaking up provides an opportunity to intervene before patient harm occurs, or to mitigate actual harm, and is a key element in effective teamwork and collaboration.² The importance of speaking up is most evident in its absence, where colleagues remain silent or make ineffectual attempts at speaking up, and erroneous actions proceed to cause patient harm. There are many prominent examples where failing to speak up in an effective manner has contributed to accidents and catastrophes in aviation,³ space exploration⁴ and in healthcare.⁵

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Prediction of persistent post-surgery pain by preoperative cold pain sensitivity: biomarker development with machine-learning-derived analysis

Abstract

Background

To prevent persistent post-surgery pain, early identification of patients at high risk is a clinical need. Supervised machine-learning techniques were used to test how accurately the patients' performance in a preoperatively performed tonic cold pain test could predict persistent post-surgery pain.

Methods

We analysed 763 patients from a cohort of 900 women who were treated for breast cancer, of whom 61 patients had developed signs of persistent pain during three yr of follow-up. Preoperatively, all patients underwent a cold pain test (immersion of the hand into a water bath at 2–4 °C). The patients rated the pain intensity using a numerical ratings scale (NRS) from 0 to 10. Supervised machine-learning techniques were used to construct a classifier that could predict patients at risk of persistent pain.

Results

Whether or not a patient rated the pain intensity at NRS=10 within less than 45 s during the cold water immersion test provided a negative predictive value of 94.4% to assign a patient to the "persistent pain" group. If NRS=10 was never reached during the cold test, the predictive value for not developing persistent pain was almost 97%. However, a low negative predictive value of 10% implied a high false positive rate.

Conclusions

Results provide a robust exclusion of persistent pain in women with an accuracy of 94.4%. Moreover, results provide further support for the hypothesis that the endogenous pain inhibitory system may play an important role in the process of pain becoming persistent.

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Special section on pain: progress in pain assessment and management

This issue of the British Journal of Anaesthesia has a special section on pain, featuring a number of editorials, reviews and original articles across a range of areas in pain medicine. The last BJA special issue on pain medicine was in July 2013, entitled "Managing pain: recent advances and new challenges", as summarized in the lead editorial of that issue.¹ A similar title could be used for this month's special section. Pain medicine continues to evolve, with advances in acute, chronic and cancer pain understanding and management. However, the challenges remain, and arguably, increase, as our population ages: Pain is one of the biggest causes of disability globally, with musculoskeletal pain being the leading cause of disability in most countries in 2015.²³ Managing pain successfully - acute, chronic or cancer - is an area where there is potential major clinical benefit both at an individual and societal level.

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Response to: Emergency front-of-neck access: scalpel or cannula—and the parable of Buridan’s ass

Editor—I was interested to read the editorial by Greenland and colleagues¹ that contributes further to the debate that has raged for some time over whether a cannot intubate, cannot oxygenate (CICO) situation should be managed with a fine needle or scalpel cricothyroidotomy approach.

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Guidelines for perioperative pain management: need for re-evaluation

Optimal perioperative pain management facilitates postoperative ambulation and rehabilitation, and is considered a prerequisite to enhancing recovery after surgery.¹² Despite well-documented benefits, postoperative pain continues to be inadequately treated.^3–5 Although the reasons for the lack of appropriate pain management are not precisely known, conflicting and confusing evidence as well as lack of clear guidance could be contributing factors.

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Norwegian Air Ambulance FW - Lufttransport THX For G o o d job.

After M a n n y years of safe operation, Norwegiann Gov. opted for an foreigain operator for ower Fixed-Wing ambulances... ( It`s a different storry to operate anny aicraft in Sweeden, compared to Norway... (-Cindergarden V.S Uni. ..! ) It shall be innteresting ... ExEMTNor

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Linkage Analysis and Association Mapping QTL Detection Models for Hybrids Between Multiparental Populations from Two Heterotic Groups: Application to Biomass Production in Maize (Zea mays L.)

Identification of loci (QTL) involved in the variation of hybrid value is of key importance for cross-pollinated species such as maize (Zea mays L.). In a companion paper we illustrated a new QTL mapping population design involving a factorial mating between two multi-parental segregating populations. Six biparental line populations were developed from four founder lines in the Dent and Flint heterotic groups. They were crossed to produce 951 hybrids, evaluated for silage performances. Previously, a linkage analysis model that assumes each founder line carries a different allele was used to detect QTL involved in General and Specific Combining Abilities of hybrid value. This previously introduced model requires the estimation of numerous effects per locus, potentially affecting QTL detection power. Using the same design we compared this "Founder alleles" model to two more parsimonious models which assume that (i) identity in state at SNP alleles from the same heterotic group implies identity by descent at linked QTL ("SNP within-group" model) or (ii) identity in state implies identity by descent, regardless of population origin of the alleles ("Hybrid Genotype" model). This last model assumes biallelic QTL with equal effects in each group. It detected more QTL on average than the two other models but explained lower percentages of variance. The "SNP within-group" model appeared to be a good compromise between the two other models. These results confirm the divergence between the Dent and Flint groups. They also illustrate the need to adapt the QTL detection model to the complexity of the allelic variation, which depends on the trait, the QTL and the divergence between the heterotic groups.

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Heart rate variability: implications for perioperative anesthesia care.

Purpose of review: Heart rate variability (HRV) is a measure of the balance between both the parasympathetic and sympathetic nervous system and may provide useful information for anesthesia care providers. HRV may offer predictive information about critically ill and operative patients. Further, HRV collection provides real-time information of patient autonomic nervous system status and may allow tailoring of the analgesia for patients in the ICU and operating room. Recent findings: Reduced and abnormal resting HRV predict sudden and nonsudden cardiac death. Recent evidence shows that decreased HRV correlates with worsened outcomes in both trauma patients and patients with sepsis, as well as the risk of developing hypotension after induction of general anesthesia and placement of intrathecal local anesthesia. In addition, HRV appears to provide an accurate assessment of the nociception-analgesia balance in deeply sedated ICU patients and those under general anesthesia. Summary: No study has assessed the prognostic value of preoperative HRV in patients presenting for surgery. Use of HRV for patient risk stratification and intraoperative analgesia management may allow tailored perioperative care and improved outcomes. If intraoperative HRV data leads to decreased perioperative opioid use, opioid-related adverse events, a serious perioperative issue, may be decreased. Clinical Trials Registration: Not applicable Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Difficult airway management and training: simulation, communication, and feedback.

Purpose of review: Successful and sustainable training and learning of the management of difficult and normal airway is essential for all clinically active anesthesiologists. We emphasize the importance of a continuously updated learning and training environment based on actual knowledge, best available equipment, standardized procedures, and educational theory. Recent findings: In the past, most of the training were based on 'learning by doing' under the supervision of superiors or experienced colleagues. This has been recognized as insufficient and training has evolved to its recent level by structuring it into technical, methodological, and behavioral components. Additionally, a large part of it has been shifted away from learning on patients to simulated scenarios in designated environments. The contents, structure, components, and succession of components have been refined according to the steadily evolving and available instruments. Increasingly, team interaction and behavioral aspects gained more attention and became part of standardized education units that are tailored to the learners' clinical role and level of experience. Summary: We present the details of the Zurich Airway Training and Simulation program, which has been constantly updated to the actual state of knowledge and available equipment. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative management of cardiac rhythm assist devices in ambulatory surgery and nonoperating room anesthesia.

Purpose of review: Patients with cardiac implantable electronic devices (CIEDs) frequently undergo various surgical procedures and in the past perioperative management involved only placing magnet over the device. New programming features, development of implantable cardiac defibrillator (ICD), cardiac resynchronization therapy, and increasing complexity of the operating room equipment have led to new sources of electromagnetic interference (EMI). A comprehensive understanding of the CIED is necessary to provide a timely and optimal care to the patients. Recent findings: Technological advancements and direct implantation of the transvenous implantable cardiac defibrillators into the heart have led to less clear lines between the pacemakers and the ICD. Subcutaneous ICD as well as the leadless transcatheter deployed intracardiac pacemaker development has complicated the issue further. Summary: Rapidly developing technologies and increasing number of patients with these devices coming for noncardiac surgeries necessitate continuous education of the anesthesia team regarding perioperative management of such devices. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer.

Objectives: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. Patients and methods: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. Results: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0x10-6), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. Conclusion: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Perissodactyla (Rhinocerotidae and Equidae) from Kanapoi

Publication date: Available online 28 September 2017
Source:Journal of Human Evolution
Author(s): Denis Geraads
The Kanapoi collection of Rhinocerotidae, first studied by Hooijer and Patterson (1972), now consists of 25 specimens and substantial reinterpretation of their affinities is made here. Kanapoi post-dates the extinction of Brachypotherium and the whole collection belongs to the Dicerotini. It is important because it includes the type-specimen of Diceros praecox, a species that remains poorly known, but looks slightly larger and more primitive than the modern 'black' rhino, Diceros bicornis. A second species is probably ancestral to the modern 'white' rhino, Ceratotherium simum; it looks identical to the Pleistocene North African Ceratotherium mauritanicum, of which Ceratotherium efficax is probably a synonym. The evolution of the Dicerotini in Africa can be regarded as an increasing divergence in diet and related morphofunctional adaptations in the two lineages. The co-occurrence at Kanapoi of both Diceros and Ceratotherium, with distinct dietary preferences, suggests some habitat heterogeneity, although the low sample size prevents robust paleoecological conclusions.The Equidae are also rare and consist mostly of isolated teeth. I take the most parsimonious option of tentatively including all of them in a single species, whose identification is left open. Dental features of eastern African Pliocene to Pleistocene hipparions may reflect increasing adaptation to grazing.



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When birds and sias fly: A neural indicator of inferring a word meaning in context

Publication date: Available online 28 September 2017
Source:International Journal of Psychophysiology
Author(s): Pablo Rodríguez-Gómez, Natalia Martínez-García, Miguel A. Pozo, José A. Hinojosa, Eva M. Moreno
Inference generation is a crucial skill in language comprehension. Recent research suggests that readers use both the contents from prior written text and their background knowledge, stored in long-term memory, to generate predictive inferences about what will come up next in a sentence. We recorded Event-Related Potentials (ERPs) to examine the reader's ability to make online inferences even in the presence of pseudowords (orthographically legal, but meaningless letter strings), that is, in the presence of referents with no a priori match to vocabulary stored knowledge. As expected, a large and sustained negativity (250–900ms) was elicited by the target word 'fly' when preceded by the pseudoword 'Sias' in the sentence 'Sias fly.' relative to when preceded by 'Birds' in the sentence 'Birds fly'. However, when readers were provided with an initial statement inviting to make an inference: 'Sias have wings', the word 'fly' in 'Sias fly' only elicited a negative voltage deflection over 100ms period (250–350), rapidly falling down to baseline. This result indicates that participants rapidly generated online inferences even with a hindered access to a referent's meaning (i.e. not knowing what 'Sias' are). Remarkably, brainwave traces to the access to a word's meaning in long-term memory (access to a well-known fact such as 'Birds fly') only diverged from ERPs for an inferred-from-reading knowledge ('Sias fly') for 100ms. We conclude that a fundamental search for across sentence coherence drives fast inference making processes in reading tasks. This pattern of brain response is critical to understand the rapid acquisition of new vocabulary when learning first and second languages.



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(Too) Anxious to help? Social support provider anxiety and cardiovascular function

Publication date: Available online 27 September 2017
Source:International Journal of Psychophysiology
Author(s): Robert G. Kent de Grey, Bert N. Uchino, Timothy W. Smith, Brian R.W. Baucom
Provider factors, such as anxiety, may be important in understanding effects of received social support (SS), which are less consistently positive than those of perceived SS. Due to the dyadic nature of support, anxiety on the part of the provider was predicted to influence the effectiveness of received SS. This laboratory study examined effects of SS provider anxiety within unacquainted dyads on cardiovascular reactivity during acute stress. 148 participants were assigned to support roles, and each dyad was randomized to low or high provider anxiety. Results include that SS provider anxiety resulted in greater blood pressure reactivity and less recovery toward baseline diastolic blood pressure within the dyad. Overall, it appears provider anxiety contributes to less effective SS for recipients and that health costs may accompany providing and receiving support under nonoptimal conditions.



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Intranasal oxytocin decreases cross-frequency coupling of neural oscillations at rest

Publication date: Available online 28 September 2017
Source:International Journal of Psychophysiology
Author(s): Helena J.V. Rutherford, Xiaoyue M. Guo, Jia Wu, Kelsey M. Graber, Nathan J. Hayes, Kevin A. Pelphrey, Linda C. Mayes
Recent research has suggested a role for the hormone oxytocin in social cognition and behavior. Administration of intranasal oxytocin modulates multiple brain regions during experimental tasks; however, the neural mechanisms that underscore the changes associated with oxytocin administration are yet to be fully elucidated. In a double-blind placebo controlled design using electroencephalography, the effects of intranasal oxytocin on neural oscillations (delta, theta, alpha, beta) and their coupling during the resting state were examined. Prior work suggested that coupling of slow and fast waves are indicative of the integration of motivational and cognitive processes. Furthermore, oxytocin has been implicated in modulating affect and cognition. While neural oscillations were unaffected by oxytocin relative to placebo administration; oxytocin decreased delta-beta, delta-alpha, theta-alpha, and theta-beta coupling. These findings suggest that one mechanism through which intranasal oxytocin may modulate brain and behavior is through affecting the cross-frequency coupling of neural oscillations, a phenomenon that has been associated with specific cognitive and motivational states.



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Expression analyzes of early factors in midbrain differentiation programs

Publication date: Available online 27 September 2017
Source:Gene Expression Patterns
Author(s): Simone Mesman, Sonja J. Krüse, Marten P. Smidt
Mesodiencephalic dopaminergic (mdDA)¹ neurons are born in the ventricular zone (VZ) of the midbrain between E10 and E12. Although these neurons all express specific DA markers like Th and Pitx3, they are subdivided into distinct subsets, each depending on a unique set of transcription factors and signaling cascades for their differentiation. How a neural progenitor commits to an mdDA neuronal cell-fate and how the specification into the different subsets is determined remains unclear.To gain more insight into the development and specification of these neurons we have previously conducted a genome-wide expression analysis, in which dissected midbrain material (E10.5-E13.5) was compared to the adult mdDA region (Chakrabarty et al., 2012). In the present study, we have compared the genome-wide expression analysis including PITX3-GFP sorted (E12.5-E15.5) neurons to available expression data to search for genes specifically expressed in the midbrain during early stages of mdDA differentiation. We have divided these genes into 3 groups: (I) genes upregulated throughout differentiation (Mest, NeuroD1, and Tcf12), (II) genes upregulated during early stages of differentiation (Hes5, and Tcf3), and (III) genes upregulated during late stages of differentiation (Enc1).Here, we show the expression profile of these genes in the embryonic midbrain during development and adult stage and compared that to the appearance of mdDA neurons via co-staining for TH. With this analysis we have identified 6 novel factors that may play a role during cell-fate commitment of neural progenitors or later during differentiation of the mdDA group of neurons.



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Clinical Report: Warsaw Breakage Syndrome with small radii and fibulae

We present two new cases of Warsaw Breakage Syndrome (WABS), an autosomal recessive cohesinopathy, in sisters aged 13 and 11 years who both had compound heterozygous mutations in DDX11. After exclusion of Fanconi anemia, Bloom syndrome and Nijmegen breakage syndrome, whole exome sequencing revealed two novel variants—c.1523T>G, predicting (p.Leu508Arg) and c.1949-1G>A (IVS19-1G>A), that were confirmed with Sanger sequencing in both affected individuals. DDX11 encodes an iron-sulfur-containing DNA helicase, and mutations in this gene have been reported in the five WABS cases previously identified to date. The sisters reported here display the distinguishing clinical features of WABS: pre- and post-natal growth restriction, microcephaly, intellectual disability, sensorineural hearing loss with cochlear abnormalities, and facial dysmorphic features. In addition, our cases had early menarche at 8 and 10 years of age, bilateral small thumbs, and the younger, more severely affected sister had small fibulae. These findings broaden the WABS phenotype and the limb malformations demonstrate further clinical overlap with Fanconi anemia and other cohesinopathies, such as Roberts Syndrome.

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Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study

Cloacal exstrophy (CE) and persistent cloaca (PC) (alternatively termed urorectal septum malformation sequence [URSMS]), represent two major cloacal defects (CDs). Clinical characteristics and risk factors often are studied for both defects combined, rather than exploring if these defects have different etiologies. We enumerated clinical features for 47 CE and 54 PC (inclusive of URSMS) cases from the National Birth Defects Prevention Study. Thirty-three CE cases were classified as isolated and 14 as multiple (presence of unassociated major defects); respective totals for PC cases were 26 and 28. We compared selected child and maternal characteristics between 11,829 non-malformed controls and CE and PC cases using chi-square or Fisher's exact tests. Compared to controls, CE and PC cases were statistically more likely (p < 0.05) to be preterm; CE cases were more likely to be multiple births. We conducted logistic regression analysis to estimate odds ratios and 95% confidence intervals for any CD, CE, and PC with selected self-reported maternal prepregnancy and periconceptional (one month prior to 3 months following conception) exposures. In crude and adjusted analyses, we observed significant positive associations for any CD, CE, and PC with use of any fertility medication or assisted reproductive technology procedure. Significant positive associations observed only in crude analyses were any CD with maternal obesity or use of progesterone, any CD and CE with any x-ray, and any CD and PC with use of folate antagonist medications. Our findings provide some of the first insights into potential differing etiologies for CE and PC.

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Gene editing in T cell therapy

Publication date: Available online 28 September 2017
Source:Journal of Genetics and Genomics
Author(s): Yongping Zhang, Wei Mu, Haoyi Wang




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Bioinformatic prediction and analysis of glucolipid metabolic regulation by miR-34a in Megalobrama amblycephala

Abstract

The objective of this study was to analyze the target genes and regulatory function of miR-34a in Megalobrama amblycephala using second-generation high-throughput sequencing and bioinformatic tools. Functional enrichment analysis was performed by gene ontology. MiR-34a and target gene expression levels were measured in M. amblycephala fed normal and high-carbohydrate diets. The results revealed that miR-34a was highly conserved in several species, and miR-34a of M. amblycephala has a close evolutionary relationship to that of zebrafish and common carp. miRanda, TargetScan, RNAhybrid predicted 5,185, 6,282 and 2,168 target genes, respectively, and 645 target genes were in common. According to annotation information, the target genes were enriched in phosphate metabolism, glycerophospholipid metabolism, Golgi vesicle transport, cell division, and other biological processes (P < 0.05). Pathway enrichment analysis revealed that these target genes were mainly enriched in alpha-linolenic acid and linoleic acid metabolism, ether lipid metabolism, VEGF signaling pathway, Fc epsilon RI signaling pathway, GnRH signaling pathway, and MAPK signaling pathway (P < 0.05). The regulatory role of miR-34a was more significant in the liver than in the brain of M. amblycephala. MiR-34a regulates glucose lipid homeostasis induced by high glucose diets by upregulating hepatic PI3K/Akt, FOXO, and TOR signaling pathways.

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Cloning and analysis of the molecularly characterized chitinase genes of Daphnia carinata and Simocephalus vetulus

Abstract

Daphniidae plays an important role in maintaining the integrity and sustainability of food chains of freshwater ecosystems. However, studies on the intact genes of chitinase in Daphniidae have not been carried out till date. In this study, we obtained the full-length complementary DNA (cDNA) from Daphnia carinata and Simocephalus vetulus, members of the Family Daphniidae, by rapid amplification of cDNA ends and polymerase chain reaction. The two cDNAs were named DcChi and SvChi, respectively. The result showed that DcChi and SvChi were 1404 and 1319 bp in length and they encoded 383 and 382 amino acids, respectively. Based on their cDNA sequences, the genomic structures of the two chitinases were characterized. Sequence analysis revealed that DcChi was composed of three exons and two introns, while SvChi had four exons and three introns. Based on the presence of conserved catalytic domain sequences, the two chitinases could be clustered within the same phylogenetic group. Homology analysis showed that the two deduced proteins had a high similarity (65–88%) to those from published species in Family Daphniidae and a low similarity to those from the species in Class Malacostraca Subclass Copepoda (38–42%) and those from the species in Class Insecta Order Diptera (33–38%). Based on the results of multiple alignments of chitinases, we designed peptides that were specific to chitinases from the Family Daphniidae. The quantitative real time PCR analysis indicated that the transcript level of the chitinase gene increased with the growth of the two species.

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Development: Epigenome dynamics from seed to seedling

Nature Reviews Genetics. doi:10.1038/nrg.2017.78

Author: Linda Koch

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Demographic history, selection and functional diversity of the canine genome

Nature Reviews Genetics. doi:10.1038/nrg.2017.67

Authors: Elaine A. Ostrander, Robert K. Wayne, Adam H. Freedman & Brian W. Davis

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The power of frontal midline theta and post-error slowing to predict performance recovery: Evidence for compensatory mechanisms

Abstract

Past studies utilizing cognitive control tasks have noted that trials following errors are characterized by slowed reaction time. Despite the assumption long held by researchers that this slowing is compensatory (in the service of post-error performance recovery), studies consistently show that post-error trials are no more accurate than post-correct trials. As a result, it has recently been proposed that post-error slowing (PES) is merely part of an orienting response that serves no task-relevant cognitive control purpose. Frontal midline theta (FMθ) oscillations represent another potential compensatory mechanism serving cognitive control processes, yet past studies relying on ERPs have failed to find an association between FMθ and post-error accuracy. The present study investigated the potentially adaptive role of PES and FMθ oscillations during a flanker task using trial-by-trial comparisons. Results indicated that error-related FMθ oscillations signal the need for enhanced top-down cognitive control and that PES supports cognitive control by providing the added time needed to achieve greater confidence in judgment. Overall, findings provide convergent evidence that both error-related FMθ and PES predict performance recovery following errors.

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Temporal dynamics of reactive cognitive control as revealed by event-related brain potentials

Abstract

Reactive cognitive control refers to a complementary set of cognitive operations by which individuals monitor for and detect the presence of goal-interfering conflict (i.e., conflict monitoring/evaluation) and, subsequently, initiate attention-focusing and response selection processes to bolster goal-directed action in the face of such conflict (regulative control). The purpose of the current study was to characterize the nature of conflict adaptation in both components of this dynamic process across sequences of trials and, more broadly, across time as participants complete a cognitive control task. Fifty-two young adults completed a standard arrow flanker task while behavioral and ERP data were recorded. Multilevel modeling of sequences of compatible and incompatible trials over time showed that, whereas response time data demonstrated a typical conflict adaptation effect throughout the task, N2 and frontal slow wave (FSW) indices of conflict monitoring and regulative control, respectively, demonstrated significant conflict adaptation only during the early part of the task. Moreover, although differential change in N2 and FSW over time suggested that conflict monitoring and regulative control were dissociable, a reciprocal relation between them was maintained throughout the task and was not present in a component theoretically unrelated to conflict adaptation (visual attention-related N1). Findings are discussed in terms of compensatory processes that help to maintain goal-directed performance even as control-related neural responses become fatigued.

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Interplay of upper and lower motor neuron degeneration in amyotrophic lateral sclerosis

Publication date: November 2017
Source:Clinical Neurophysiology, Volume 128, Issue 11
Author(s): Mamede de Carvalho, Artiom Poliakov, Cristiano Tavares, Michael Swash
ObjectiveWe studied motor unit recruitment to test a new method to identify motor unit firing rate (FR) variability.MethodsWe studied 68 ALS patients, with and without upper neuron signs (UMN) in lower limbs, 24 patients with primary lateral sclerosis (PLS), 13 patients with spinal cord lesion and 39 normal subjects. All recordings were made from tibialis anterior muscles of normal strength. Subjects performed a very slight contraction in order to activate 2 motor units in each recording. 5–7 motor unit pairs were recorded in each subject. Mean consecutive differences (MCD) were calculated for each pair of potentials. The mean MCD for each muscle was estimated as the mean from the total number of pairs recorded. Ap value<0.01 was accepted as significant.ResultsMCD of FR frequency was less in the subjects with spinal cord lesion and PLS. In addition, the FR frequency of the 1st motor unit in a pair of units was markedly reduced in PLS, and in subjects with spinal cord lesions.ConclusionThese results support a lower threshold and reduced FR fluctuation in spinal motor neurons of spastic patients.SignificanceThis method can be developed for detection of UMN lesions.



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