The role of pre-operative α-blockade in patients with normotensive phaeochromocytoma or paraganglioma: A retrospective cohort study

No abstract available

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Comparison of a novel clinical score to estimate the risk of REsidual neuromuscular block Prediction Score and the last train-of-four count documented in the electronic anaesthesia record: A retrospective cohort study of electronic data on file

BACKGROUND Residual neuromuscular block (rNMB) after surgery is not difficult to identify if proper neuromuscular monitoring is used, but many clinicians do not use quantitative neuromuscular monitoring. OBJECTIVE The aim of this study was to develop a REsidual neuromuscular block Prediction Score (REPS) to predict postoperative rNMB and compare the predictive accuracy of the prediction score with train-of-four count (TOFC) measurement at the end of a surgical case. DESIGN Retrospective cohort study of data on file. DATA SOURCE Electronic patient data and peri-operative data on vital signs, administered medications, and train-of-four ratio (TOFR) obtained in the postoperative recovery rooms [postanaesthesia care unit (PACU)] at Massachusetts General Hospital in Boston, Massachusetts, USA. PATIENTS Quantitative TOFR measurements obtained on admission to the PACU were available from 2144 adult noncardiac surgical patients. MAIN OUTCOME MEASURE Presence of rNMB at PACU admission, defined as a TOFR of less than 0.9. RESULTS In the score development cohort (n=2144), rNMB occurred in 432 cases (20.2%). Ten independent predictors for residual paralysis were identified and used for the score development. The final model included: hepatic failure, neurological disease, high-neostigmine dose, metastatic tumour, female sex, short time between neuromuscular blocking agent administration and extubation, aminosteroidal neuromuscular blocking agent, BMI more than 35, absence of nurse anaesthetist and having an experienced surgeon. The model discrimination by C statistics was 0.63, 95% confidence interval (0.60 to 0.66), and risk categories derived from the REPS had a higher accuracy than the last documented intra-operative TOFC for predicting rNMB (net reclassification improvement score 0.26, standard error 0.03, P 

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Association of pre-operative troponin levels with major adverse cardiac events and mortality after noncardiac surgery: A systematic review and meta-analysis

BACKGROUND Circulating cardiac troponin levels are powerful predictors of prognosis in many clinical settings, but their association with outcomes after noncardiac surgery is unclear. OBJECTIVES The aim of this systematic review was to summarise current evidence on the association of pre-operative troponin elevation with postoperative major adverse cardiac events (MACE) and mortality in patients undergoing noncardiac surgery. DESIGN Systematic review of observational studies with meta-analysis. DATA SOURCES PubMed, EMBASE and Science Citation Index Expanded (ISI Web of Science) from their inception to 1 October 2017. ELIGIBILITY CRITERIA Observational studies reporting the associations between pre-operative troponin levels and MACE and all-cause mortality after noncardiac surgeries were included. RESULTS Ten studies met the eligibility criteria. The entire body of evidence addressing the research question was based on a total of 10 371 patients: 4.7 to 68.3% (median 23.8%) of patients had elevated troponin levels before surgery. Elevated pre-operative troponin was significantly associated with short-term MACE (seven studies, 5180 patients: odds ratio (OR) 6.92, 95% confidence interval (CI) 3.85 to 12.42), short-term mortality (five studies, 6103 patients: OR 4.23, 95% CI 2.27 to 7.89) and long-term mortality (two studies, 760 patients: OR 2.51, 95% CI 1.47 to 4.29). The associations remained significant when only multivariate-adjusted results were analysed. Overall, the reviewers' certainty about the summary estimates of the associations was very low. CONCLUSION Current evidence suggests that pre-operative high troponin levels are significantly associated with adverse cardiac events and mortality after noncardiac surgery. TRIAL REGISTRATION This systematic review was registered in the International Prospective Register of Systematic Reviews (Centre for Reviews and Dissemination 42017077837).

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Deep vs. moderate neuromuscular blockade during laparoscopic surgery: A systematic review and meta-analysis

BACKGROUND Previous studies have reported that deep neuromuscular block (posttetanic-count 1 to 2 twitches) improves surgical conditions during laparoscopy compared with moderate block (train-of-four count: 1 to 2 twitches). However, comparisons of surgical conditions were made using different scales and assessment intervals with variable results. OBJECTIVE To explore the heterogeneity of previous comparisons between deep and moderate neuromuscular block. DESIGN Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES Medline, EMBASE and Cochrane Central Register of Controlled Trials were searched from inception to October 2017. ELIGIBILITY CRITERIA Our meta-analysis included RCTs comparing the effects of deep with moderate neuromuscular block on surgical field conditions during laparoscopic surgery. The frequency of excellent or good operating conditions on a surgical rating scale was compared. Heterogeneity was assessed by subgroup analyses. RESULTS Eleven RCTs involving 844 patients were included. On the surgical rating scale, the frequency of excellent or good operating conditions was higher with deep block compared with a moderate block (odds ratio 2.83, 95% confidence interval 1.34 to 5.99, P = 0.007, I2 = 59%). We analysed surgical rating according to the number of assessments made. There was a significant difference in surgical rating with multiple assessments, but no difference when the assessment was made on only one occasion. A significant difference in rating was noted with variable abdominal pressures; there was no significant difference with the same fixed abdominal pressure. Trial sequential analysis demonstrated that the cumulative z-curve crossed the O′Brien–Fleming significance boundary. However, required information size was not achieved. CONCLUSION Deep block was associated with excellent or good surgical rating more frequently than moderate block. However, this finding was not consistent on subgroup analyses based on frequencies of assessment of surgical conditions and abdominal pressure. Further studies are required to address the heterogeneity and power shortage demonstrated by the trial sequential analysis.

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Intra-operative cutaneous temperature monitoring with zero-heat-flux technique (3M SpotOn) in comparison with oesophageal and arterial temperature: A prospective observational study

BACKGROUND Continuous monitoring of core temperature is essential during major surgery as a way of improving patient safety. Oesophageal probes or specific arterial catheters are invasive methods used in this setting. A new noninvasive device based on zero-heat-flux (ZHF) technique (SpotOn) seems promising but has been poorly investigated during rapid core temperature changes (RCTC). OBJECTIVE To assess the accuracy of a SpotOn sensor vs. an oesophageal probe or specific arterial catheter during a slow change in core temperature of less than 1 °C within 30 min and RCTC ≥ 1 °C within 30 min. DESIGN Prospective observational study. SETTING Operating rooms at the University Hospital of Poitiers, France. PATIENTS Fifty patients scheduled for major abdominal surgery under general anaesthesia were enrolled from June 2015 to March 2016. Data from 49 patients were finally analysed. Among these, 15 patients were treated with hyperthermic intraperitoneal chemotherapy. INTERVENTION Each patient had a ZHF sensor placed on the skin surface of the forehead (TempZHF) and an oesophageal probe (TempEso) used as a reference method. Twenty-two patients also had a thermodilution arterial catheter (TempArt) placed in the axillary artery. MAIN OUTCOME MEASURES Core temperature was continuously recorded from the three devices after induction of anaesthesia. Comparison of temperature measurements between methods was made using the Bland and Altman method during two separate periods according to the speed of core temperature changes. RESULTS Compared with TempEso, bias and limits of agreement for TempZHF were 0.1 ± 0.5 °C during slow core temperature changes periods and 0.6 ± 1.8 °C during RCTC periods (P = 0.0002). Compared with TempArt, these values were −0.1 ± 0.4 and 0.5 ± 1.7 °C, respectively (P = 0.0039). The ZHF sensor was well tolerated. CONCLUSION A SpotOn sensor using the ZHF method seems reliable for core temperature monitoring during abdominal surgery when variations in core temperature are slow rather than rapid. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02869828.

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Comparison of noninvasive and minimally invasive pulse contour analysis to measure stroke volume during major surgery: A prospective observational study

No abstract available

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Diagnostic accuracy of inferior vena caval respiratory variation in detecting fluid unresponsiveness: A systematic review and meta-analysis

BACKGROUND The accuracy of respiratory variation of the inferior vena cava (rvIVC) in predicting fluid responsiveness, particularly in spontaneously breathing patients is unclear. OBJECTIVES To consider the evidence to support the accuracy of rvIVC in identifying patients who are unlikely to benefit from fluid administration. DESIGN Systematic review and meta-analysis. DATA SOURCE We searched MEDLINE, EMBASE, Cochrane Library, KoreaMed, LILCAS and WHO Clinical Trial Registry from inception to June 2017. ELIGIBILITY CRITERIA Case–control or cohort studies that evaluated the accuracy of rvIVC in living adult humans were included. A study was included in the meta-analysis if data enabling construction of 2 × 2 tables were reported, calculated or could be obtained from authors and met the above cited criteria. RESULT A total of 23 studies including 1574 patients were included in qualitative analysis. The meta-analysis involved 20 studies and 761 patients. Pooled sensitivity and specificity of rvIVC in 330 spontaneously breathing patients were 0.80 [95% confidence interval (CI) 0.68 to 0.89] and 0.79 (95% CI 0.60 to 0.90). Pooled sensitivity and specificity of rvIVC in 431 mechanically ventilated patients were 0.79 (95% CI 0.67 to 0.86) and 0.70 (95% CI 0.63 to 0.76). CONCLUSION Decreased inferior vena caval respiratory variation is moderately accurate in predicting fluid unresponsiveness both in spontaneous and mechanically ventilated patients. The findings of this review should be used in the appropriate clinical context and in conjunction with other clinical assessments of fluid status. IDENTIFIER CRD 42017068028.

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Device or target? A paradigm shift in airway management: Implications for guidelines, clinical practice and teaching

No abstract available

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Haemodilution and head-down tilting induce functional injury in the rat optic nerve: A model for peri-operative ischemic optic neuropathy

BACKGROUND Mechanisms of peri-operative ischaemic optic neuropathy remain poorly understood. Both specific pre-operative and intra-operative factors have been examined by retrospective studies, but no animal model currently exists. OBJECTIVES To develop a rodent model of peri-operative ischaemic optic neuropathy. In rats, we performed head-down tilt and/or haemodilution, theorising that the combination damages the optic nerve. DESIGN Animal study. SETTING Laboratory. ANIMALS A total of 36 rats, in four groups, completed the functional examination of retina and optic nerve after the interventions. INTERVENTIONS Anaesthetised groups (n>8) were supine (SUP) for 5 h, head-down tilted 70° for 5 h, head-down tilted/haemodiluted for 5 h or SUP/haemodiluted for 5 h. We measured blood pressure, heart rate, intra-ocular pressure and maintained constant temperature. MAIN OUTCOME MEASUREMENTS Retinal function (electroretinography), scotopic threshold response (STR) (for retinal ganglion cells) and visual evoked potentials (VEP) (for transmission through the optic nerve). We imaged the optic nerve in vivo and evaluated retinal histology, apoptotic cells and glial activation in the optic nerve. Retinal and optic nerve function were followed to 14 and 28 days after experiments. RESULTS At 28 days in head down tilted/haemodiluted rats, negative STR decreased (about 50% amplitude reduction, P = 0.006), VEP wave N2-P3 decreased (70% amplitude reduction, P = 0.01) and P2 latency increased (35%, P = 0.003), optic discs were swollen and glial activation was present in the optic nerve. SUP/haemodiluted rats had decreases in negative STR and increased VEP latency, but no glial activation. CONCLUSION An injury partly resembling human ischaemic optic neuropathy can be produced in rats by combining haemodilution and head-down tilt. Significant functional changes were also present with haemodilution alone. Future studies with this partial optic nerve injury may enable understanding of mechanisms of peri-operative ischaemic optic neuropathy and could help discover preventive or treatment strategies.

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Deep neuromuscular blockade and surgical conditions during laparoscopic ventral hernia repair: A randomised, blinded study

BACKGROUND Laparoscopic ventral hernia repair is a common surgical procedure. However, muscle contractions and general muscle tension may impair the surgical view and cause difficulties suturing the hernial defect. Deep neuromuscular blockade (NMB) paralyses the abdominal wall muscles and may help to create better surgical conditions. OBJECTIVES The current study investigated if deep compared with no NMB improved the surgical view during laparoscopic ventral hernia repair. DESIGN Crossover study. SETTING The study was carried out at Herlev and Gentofte Hospital, University of Copenhagen, Denmark and conducted from May 2015 until February 2017. PARTICIPANTS A total of 34 patients were randomised in an investigator-initiated, assessor-blinded crossover design of deep vs. no NMB during laparoscopic ventral hernia repair. INCLUSION CRITERIA Adults scheduled for elective laparoscopic ventral hernia repair. EXCLUSION CRITERIA Known allergy to any study medication, known homozygous variants in the butyrylcholinesterase gene, severe renal disease, neuromuscular disease, lactating or pregnant women, any indication for rapid sequence induction. INTERVENTIONS Deep NMB was established with rocuronium and reversed with sugammadex. Anaesthesia was conducted with propofol and remifentanil. MAIN OUTCOME MEASURES The primary outcome was evaluation of surgical view assessed on a five-point rating scale. Other outcomes included the surgical conditions during laparoscopic suturing of the hernia defect. RESULTS We found no difference in ratings for the surgical view when comparing deep with no NMB: mean −0.1 (95% confidence interval −0.4 to 0.2) (P = 0.521, paired t test). However, deep compared with no NMB improved the rating score for surgical conditions while suturing the hernia defect (P = 0.012, Mann–Whitney U test). No differences were found in either total length of surgery (P = 0.76) or hernia suturing time (P = 0.81). CONCLUSION Deep compared with no NMB did not change the rating score of the surgical view immediately after introduction of trocars during laparoscopic ventral hernia repair, but the surgical condition were improved during suturing of the hernia. TRIAL REGISTRATION ClinicalTrials.gov, NCT02247466.

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End-tidal carbon dioxide monitoring improves patient safety during propofol-based sedation for breast lumpectomy: A randomised controlled trial

BACKGROUND The use of sedation is becoming more commonplace. Although pulse oximetry is a standard monitoring procedure during sedation, it cannot accurately detect early hypoventilation. End-tidal carbon dioxide (EtCO2) monitoring can be an earlier indicator of airway compromise; however, the existing literature is limited to a few studies with varying outcomes. OBJECTIVES To evaluate whether EtCO2 monitoring decreases the incidences of CO2 retention and apnoeic events in propofol-based sedation. DESIGN Randomised controlled study. SETTING A tertiary hospital. PATIENTS Two hundred women (aged 18 to 65 years, ASA physical status 1 or 2) who were scheduled for breast lumpectomy between June 2017 and August 2017. INTERVENTIONS Patients were allocated randomly to receive either standard monitoring or standard monitoring and EtCO2 monitoring. MAIN OUTCOME MEASURES The primary outcome was the incidence of CO2 retention. The secondary outcomes were the number of actions taken to restore ventilation, variations in PaCO2 and pH, the frequency of apnoea and the recovery time. RESULTS CO2 retention occurred significantly less often in the EtCO2 monitoring group (10 vs. 87%; P 

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Haemodynamic evaluation and optimisation of brain-dead donors with oesophageal Doppler during organ harvesting: A feasibility study

No abstract available

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Dexamethasone concentration affecting rocuronium-induced neuromuscular blockade and sugammadex reversal in a rat phrenic nerve-hemidiaphragm model: An ex vivo study

BACKGROUND The concentration range of dexamethasone that inhibits neuromuscular blockade (NMB) and sugammadex reversal remains unclear. OBJECTIVE To evaluate the effects of dexamethasone on rocuronium-induced NMB and sugammadex reversal. DESIGN Ex vivo study. SETTING Asan Institute for Life Sciences, Asan Medical Center, Korea, from July 2015 to November 2015. ANIMALS One hundred sixty male Sprague–Dawley rats. INTERVENTIONS We assessed the effect of four concentrations of dexamethasone [0, 0.5, 5 (clinical concentrations) and 50 μg ml−1 (experimental concentration)] on partial NMB on 40 phrenic nerve–hemidiaphragm preparations (n=10 per concentration). Once the first twitch of train-of-four (TOF) had been depressed by 50% with rocuronium, dexamethasone was administered. To assess the effect of dexamethasone on sugammadex reversal, 120 phrenic nerve–hemidiaphragm preparations were used in three subexperiments (n=40 per experiment), using three administration regimens of rocuronium–equimolar sugammadex: a single dose, a split-dose (split 1/2 and 1/2) and a reduced split-dose (split 1/2 and 1/4). After complete NMB was achieved, dexamethasone and sugammadex were administered. MAIN OUTCOME MEASURES The change in the first twitch height, the recovery time to a TOF ratio at least 0.9, and the TOF ratio at 30 min were evaluated. RESULTS There were no significant differences in the first twitch height among groups (P = 0.532). With a single dose of sugammadex, dexamethasone did not affect the recovery time to a TOF ratio at least 0.9 (P = 0.070). After using a split-dose of sugammadex, the recovery time to a TOF ratio at least 0.9 was delayed only at a concentration of 50 μg ml−1 of dexamethasone. With a reduced split-dose of sugammadex, the TOF ratio at 30 min was lowered only by a concentration of 50 μg ml−1 of dexamethasone (P 

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Postoperative stroke: The picture is out of focus

No abstract available

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Duration of the action of rocuronium in patients with BMI of less than 25: An observational study

BACKGROUND The duration of rocuronium in patients with BMI more than 30 kg m−2 is prolonged. Whether the reverse is true when BMI is less than 18.5 kg m−2 is unclear. OBJECTIVE The objective of this study was to investigate whether a BMI less than 25 kg m−2 affects the duration of rocuronium in doses adjusted for actual body weight. DESIGN A prospective, observational, single-centre study. SETTING The operating room of a teaching hospital from 1 June 2008 to 30 June 2015. PATIENTS Thirty patients with American Society of Anesthesiologists physical status I or II who were scheduled to undergo elective surgery (BMI 

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Translational pain research: an update from European Pain Federation educational platform

No abstract available

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Highly Synergistic Effects of Melittin with Conventional Antibiotics Against Multidrug-Resistant Isolates of Acinetobacter baumannii and Pseudomonas aeruginosa

Microbial Drug Resistance, Ahead of Print.


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Early Diverging Insect-Pathogenic Fungi of the Order Entomophthorales Possess Diverse and Unique Subtilisin-Like Serine Proteases

Insect-pathogenic fungi use subtilisin-like serine proteases (SLSPs) to degrade chitin-associated proteins in the insect procuticle. Most insect-pathogenic fungi in the order Hypocreales (Ascomycota) are generalist species with a broad host-range, and most species possess a high number of SLSPs. The other major clade of insect-pathogenic fungi is part of the subphylum Entomophthoromycotina (Zoopagomycota, formerly Zygomycota) which consists of high host-specificity insect-pathogenic fungi that naturally only infect a single or very few host species. The extent to which insect-pathogenic fungi in the order Entomophthorales rely on SLSPs is unknown. Here we take advantage of recently available transcriptomic and genomic datasets from four genera within Entomophthoromycotina: the saprobic or opportunistic pathogens Basidiobolus meristosporus, Conidiobolus coronatus, C. thromboides, C. incongruus, and the host-specific insect pathogens Entomophthora muscae and Pandora formicae, specific pathogens of house flies (Muscae domestica) and wood ants (Formica polyctena), respectively. In total 154 SLSP from six fungi in the subphylum Entomophthoromycotina were identified: E. muscae (n = 22), P. formicae (n = 6), B. meristosporus (n = 60), C. thromboides (n = 18), C. coronatus (n = 36), and C. incongruus (n = 12). A unique group of 11 SLSPs was discovered in the genomes of the obligate biotrophic fungi E. muscae, P. formicae and the saprobic human pathogen C. incongruus that loosely resembles bacillopeptidase F-like SLSPs. Phylogenetics and protein domain analysis show this class represents a unique group of SLSPs so far only observed among Bacteria, Oomycetes and early diverging fungi such as Cryptomycota, Microsporidia, and Entomophthoromycotina. This group of SLSPs is missing in the sister fungal lineages of Kickxellomycotina and the fungal phyla Mucoromyocta, Ascomycota and Basidiomycota fungi suggesting interesting gene loss patterns.

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Highly Contiguous Genome Assemblies of 15 Drosophila Species Generated Using Nanopore Sequencing

The Drosophila genus is a unique group containing a wide range of species that occupy diverse ecosystems. In addition to the most widely studied species, Drosophila melanogaster, many other members in this genus also possess a well-developed set of genetic tools. Indeed, high-quality genomes exist for several species within the genus, facilitating studies of the function and evolution of cis-regulatory regions and proteins by allowing comparisons across at least 50 million years of evolution. Yet, the available genomes still fail to capture much of the substantial genetic diversity within the Drosophila genus. We have therefore tested protocols to rapidly and inexpensively sequence and assemble the genome from any Drosophila species using single-molecule sequencing technology from Oxford Nanopore. Here, we use this technology to present highly contiguous genome assemblies of 15 Drosophila species: 10 of the 12 originally sequenced Drosophila species (ananassae, erecta, mojavensis, persimilis, pseudoobscura, sechellia, simulans, virilis, willistoni, and yakuba), four additional species that had previously reported assemblies (biarmipes, bipectinata, eugracilis, and mauritiana), and one novel assembly (triauraria). Genomes were generated from an average of 29x depth-of-coverage data that after assembly resulted in an average contig N50 of 4.4 Mb. Subsequent alignment of contigs from the published reference genomes demonstrates that our assemblies could be used to close over 60% of the gaps present in the currently published reference genomes. Importantly, the materials and reagents cost for each genome was approximately $1,000 (USD). This study demonstrates the power and cost-effectiveness of long-read sequencing for genome assembly in Drosophila and provides a framework for the affordable sequencing and assembly of additional Drosophila genomes.

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An Anopheles stephensi Promoter-Trap: Augmenting Genome Annotation and Functional Genomics

The piggyBac transposon was modified to generate gene trap constructs, which were then incorporated into the genome of the Asian malaria vector, Anopheles stephensi and remobilized through genetic crosses using a piggyBac transposase expressing line. A total of 620 remobilization events were documented, and 73 were further characterized at the DNA level to identify patterns in insertion site preferences, remobilization frequencies, and remobilization patterns. Overall, the use of the tetameric AmCyan reporter as the fusion peptide displayed a preference for insertion into the 5'-end of transcripts. Notably 183 – 44882 bp upstream of the An. stephensi v1.0 ab initio gene models, which demonstrated that the promoter regions for the genes of An. stephensi are further upstream of the 5'-proximal regions of the genes in the ab inito models than may be otherwise predicted. RNA-Seq transcript coverage supported the insertion of the splice acceptor gene trap element into 5'-UTR introns for nearly half of all insertions identified. The use of a gene trap element that prefers insertion into the 5'-end of genes supports the use of this technology for the random generation of knock-out mutants, as well as the experimental confirmation of 5'-UTR introns in An. stephensi.

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Rapid Low-Cost Assembly of the Drosophila melanogaster Reference Genome Using Low-Coverage, Long-Read Sequencing

Accurate and comprehensive characterization of genetic variation is essential for deciphering the genetic basis of diseases and other phenotypes. A vast amount of genetic variation stems from large-scale sequence changes arising from the duplication, deletion, inversion, and translocation of sequences. In the past 10 years, high-throughput short reads have greatly expanded our ability to assay sequence variation due to single nucleotide polymorphisms. However, a recent de novo assembly of a second Drosophila melanogaster reference genome has revealed that short read genotyping methods miss hundreds of structural variants, including those affecting phenotypes. While genomes assembled using high-coverage long reads can achieve high levels of contiguity and completeness, concerns about cost, errors, and low yield have limited widespread adoption of such sequencing approaches. Here we resequenced the reference strain of D. melanogaster (ISO1) on a single Oxford Nanopore MinION flow cell run for 24 hr. Using only reads longer than 1 kb or with at least 30x coverage, we assembled a highly contiguous de novo genome. The addition of inexpensive paired reads and subsequent scaffolding using an optical map technology achieved an assembly with completeness and contiguity comparable to the D. melanogaster reference assembly. Comparison of our assembly to the reference assembly of ISO1 uncovered a number of structural variants (SVs), including novel LTR transposable element insertions and duplications affecting genes with developmental, behavioral, and metabolic functions. Collectively, these SVs provide a snapshot of the dynamics of genome evolution. Furthermore, our assembly and comparison to the D. melanogaster reference genome demonstrates that high-quality de novo assembly of reference genomes and comprehensive variant discovery using such assemblies are now possible by a single lab for under $1,000 (USD).

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Viable Triploid Honey Bees (Apis mellifera capensis) Are Reliably Produced in the Progeny of CO2 Narcotised Queens

The haplodiploid system of sex determination of Hymenoptera acts as an exaptation for species to evolve novel forms of asexual reproduction including thelytoky (clonal offspring of the mother). During normal reproduction in Hymenoptera, three of the four products of meiosis that are present in newly-laid eggs are lost as polar bodies, while the remaining pronucleus either develops as a haploid male or fuses with a sperm nucleus to produce a diploid zygote. In contrast, in thelytokous reproduction, which is uncommon but taxonomically widespread, two of the four products of meiosis fuse, as if one acted as a sperm. Queenless workers of Apis mellifera capensis, a subspecies of honey bee from South Africa, routinely reproduce thelytokously. Unmated A. m. capensis queens can also be induced to lay thelytokously by narcosis with carbon dioxide, but mated queens are never thelytokous. We artificially inseminated A. m. capensis queens using CO₂ narcosis. Up to 1/3 of offspring workers carried two maternal alleles and an allele of one father whereas no three-allele progeny were seen in control queens of the arrhenotokous (unfertilized eggs result in males) subspecies A. m. scutellata. Flow cytometry of three-allele individuals revealed that they were triploid and arose from the fertilization of a thelytokous fusion nucleus. We then reared six queens from a narcotized A. m. capensis queen and determined the ploidy of the offspring queens based on microsatellites. One of the five daughters was triploid. Following artificial insemination, this queen produced unfertilized thelytokous diploid eggs at high frequency, and unfertilized triploid eggs at much lower frequency. If fertilized, thelytokous diploid eggs were non-viable, even though triploidy in itself does not impede normal development. In contrast, when the rarer triploid eggs were fertilized, a proportion developed into viable tetraploids. Our study highlights the extraordinary developmental flexibility of haplo-diploid systems.

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Mapping Quantitative Trait Loci for Tolerance to Pythium irregulare in Soybean (Glycine max L.)

Pythium root rot is one of the significant diseases of soybean (Glycine max (L.) Merr.) in the United States. The causal agent of the disease is a soil-borne oomycete pathogen Pythium irregulare, the most prevalent and aggressive species of Pythium in North Central United States. However, few studies have been conducted in soybean for the identification of quantitative trait loci (QTL) for tolerance to P. irregulare. In this study, two recombinant inbred line (RIL) populations (designated as POP1 and POP2) were challenged with P. irregulare (isolate CMISO2-5-14) in a greenhouse assay. POP1 and POP2 were derived from 'E09014' x 'E05226-T' and 'E05226-T' x 'E09088', and contained 113 and 79 lines, respectively. Parental tests indicated that 'E05226-T' and 'E09014' were more tolerant than 'E09088', while 'E09088' was highly susceptible to the pathogen. The disease indices, root weight of inoculation (RWI) and ratio of root weight (RRW) of both populations showed near normal distributions, with transgressive segregation, suggesting the involvement of multiple QTL from both parents contributed to the tolerance. All the lines were genotyped using Illumina Infinium BARCSoySNP6K iSelect BeadChip and yielded 1373 and 1384 polymorphic markers for POP1 and POP2, respectively. Notably, despite high density, polymorphic markers coverage was incomplete in some genomic regions. As such, 28 and 37 linkage groups were obtained in POP1 and POP2, respectively corresponding to the 20 soybean chromosomes. Using RRW, one QTL was identified in POP1 on Chromosome 20 that explained 12.7–13.3% of phenotypic variation. The desirable allele of this QTL was from 'E05226-T'. Another QTL was found in POP2 on Chromosome 11. It explained 15.4% of the phenotypic variation and the desirable allele was from 'E09088'. However, no QTL were identified using RWI in either population. These results supported that RRW was more suitable to be used to evaluate P. irregulare tolerance in soybean.

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Coping-Style Behavior Identified by a Survey of Parent-of-Origin Effects in the Rat

In this study we investigate the effects of parent of origin on complex traits in the laboratory rat, with a focus on coping style behavior in stressful situations. We develop theory, based on earlier work, to partition heritability into a component due to a combination of parent of origin, maternal, paternal and shared environment, and another component that estimates classical additive genetic variance. We use this theory to investigate the effects on heritability of the parental origin of alleles in 798 outbred heterogeneous stock rats across 199 complex traits. Parent-of-origin-like heritability was on average 2.7fold larger than classical additive heritability. Among the phenotypes with the most enhanced parent-of-origin heritability were 10 coping style behaviors, with average 3.2 fold heritability enrichment. To confirm these findings on coping behavior, and to eliminate the possibility that the parent of origin effects are due to confounding with shared environment, we performed a reciprocal F1 cross between the behaviorally divergent RHA and RLA rat strains. We observed parent-of-origin effects on F1 rat anxiety/coping-related behavior in the Elevated Zero Maze test. Our study is the first to assess genetic parent-of-origin effects in rats, and confirm earlier findings in mice that such effects influence coping and impulsive behavior, and suggest these effects might be significant in other mammals, including humans.

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Double Selection Enhances the Efficiency of Target-AID and Cas9-Based Genome Editing in Yeast

CRISPR-Cas9 loss of function (LOF) and base editing screens are powerful tools in genetics and genomics. Yeast is one of the main models in these fields, but has only recently started to adopt this new toolkit for high throughput experiments. We developed a double selection strategy based on co-selection that increases LOF mutation rates using the Target-AID base editor. We constructed the pDYSCKO vector, which is amenable to high throughput double selection experiments, and show that the improvement in Target-AID efficiency generalizes across loci. Using modeling, we show that this improvement in efficiency provides the required increased in detection power to measure the fitness effects of thousands of mutations in typical yeast pooled screens. We show that double selection can also improve Cas9 mediated LOF rates, but that this multiplex genome editing causes programmable chromosomal translocations at high frequency. This suggests that multiplex LOF editing should be performed with caution and that base-editors could be preferable tools for some screens in yeast. Base editing using double selection is simple and straightforward and provides an alternative to homology directed repair based high throughput variant strain construction methods.

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A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult Drosophila

A screen for neuroprotective genes in Drosophila melanogaster led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the brain tumor (brat) locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for brat in the adult Drosophila brain has not been described previously. The new allele, brat^cheesehead (brat^chs), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult brat^chs mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for brat that could be relevant to human cancer and neurodegenerative diseases.

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Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon Usage Bias Indices

Experimental evidence shows that synonymous mutations can have important consequences on genetic fitness. Many organisms display codon usage bias (CUB), where synonymous codons that are translated into the same amino acid appear with distinct frequency. Within genomes, CUB is thought to arise from selection for translational efficiency and accuracy, termed the translational efficiency hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels, which is widely interpreted as evidence for translational selection. However, these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important translational disruption effect found across all organisms of the tree of life. Genes that contain -1 PRF signals should cost more to express than genes without. Thus, CUB indices that do not consider -1 PRF may overestimate genes' true adaptation to translational efficiency and accuracy constraints. Here, we first investigate whether -1 PRF signals do indeed carry such translational cost. We then propose two corrections for CUB indices for genes containing -1 PRF signals. We retest the TEH in Saccharomyces cerevisiae under these corrections. We find that the correlation between corrected CUB index and protein expression remains intact for most levels of uniform -1 PRF efficiencies, and tends to increase when these efficiencies decline with protein expression. We conclude that the TEH is strengthened and that -1 PRF events constitute a promising and useful tool to examine the relationships between CUB and selection for translation efficiency and accuracy.

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Deletion of GIT1 Impacts eNOS Activity To Aggravate sFlt-1-Induced Preeclampsia Phenotype in Mice

Preeclampsia, a serious multisystem disorder specific to human pregnancy, remains a considerable burden of disease worldwide. Reduced nitric oxide bioavailability is proved to be crucial in the maternal and fetal pathophysiology of preeclampsia. G-protein-coupled Receptor Kinase Interactor-1 (GIT1) is a novel endothelial nitric oxide synthases (eNOS) interactor mediator. The aim of this paper is to investigate the effect of GIT1 on preeclampsia. Blood pressure (BP) was measured using a carotid catheter-calibrated eight-chamber tail-cuff system (CODA) at the same time daily. Urinary albumin excretion (UAE) was determined using Albuwell-M kits (Exocell Inc) and creatinine clearance (CCr) was determined by measuring urinary creatinine concentration with tandem liquid chromatography–mass spectrometry. The release of nitrite was analyzed to detect nitric oxide (NO) production using a Sievers Chemiluminescence NO Analyzer. NOS activity was examined by measuring the conversion of ³H-labeled l-arginine to ³H-labeled l-citrulline. BP was significantly increased in GIT1^–/– mice with or without sFIT-1 treatment. In addition, GIT1–/– mice possessed higher UAE and lower CCr. Depletion of GIT1 impedes the NO production and placenta eNOS activity. Additional GIT1 attenuates sFlt-1-induced preeclampsia phenotypes. Our findings suggest that GIT1 significantly extenuates the sFlt-1-induced preeclampsia phenotypes by inhibiting eNOS activity, indicating a crucial role of GIT1 in the progression of preeclampsia.

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Linkage Disequilibrium and Evaluation of Genome-Wide Association Mapping Models in Tetraploid Potato

Genome-wide association studies (GWAS) have become a powerful tool for analyzing complex traits in crop plants. The current study evaluates the efficacy of various GWAS models and methods for elucidating population structure in potato. The presence of significant population structure can lead to detection of spurious marker-trait associations, as well as mask true ones. While appropriate statistical models are needed to detect true marker-trait associations, in most published potato GWAS, a 'one model fits all traits' approach has been adopted. We have examined various GWAS models on a large association panel comprising diverse tetraploid potato cultivars and breeding lines, genotyped with single nucleotide polymorphism (SNP) markers. Phenotypic data were generated for 20 quantitative traits assessed in different environments. Best Linear Unbiased Estimates (BLUEs) for these traits were obtained for use in assessing GWAS models. Goodness of fit of GWAS models, derived using different combinations of kinship and population structure for all traits, was evaluated using Quantile-Quantile (Q-Q) plots and genomic control inflation factors (_GC). Kinship was found to play a major role in correcting population confounding effects and results advocate a 'trait-specific' fit of different GWAS models. A survey of genome-wide linkage disequilibrium (LD), one of the critical factors affecting GWAS, is also presented and our findings are compared to other recent studies in potato. The genetic material used here, and the outputs of this study represent a novel resource for genetic analysis in potato.

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Genomic Signatures of Adaptation to a Precipitation Gradient in Nigerian Sorghum

Evolution of plants under climatic gradients may lead to clinal adaptation. Understanding the genomic basis of clinal adaptation in crops species could facilitate breeding for climate resilience. We investigated signatures of clinal adaptation in the cereal crop sorghum (Sorghum bicolor L. [Moench]) to the precipitation gradient in West Africa using a panel (n = 607) of sorghum accessions from diverse agroclimatic zones of Nigeria. Significant correlations were observed between common-garden phenotypes of three putative climate-adaptive traits (flowering time, plant height, and panicle length) and climatic variables. The panel was characterized at >400,000 single nucleotide polymorphisms (SNPs) using genotyping-by-sequencing (GBS). Redundancy analysis indicated that a small proportion of SNP variation can be explained by climate (1%), space (1%), and climate collinear with space (3%). Discriminant analysis of principal components identified three genetic groups that are distributed differently along the precipitation gradient. Genome-wide association studies were conducted with phenotypes and three climatic variables (annual mean precipitation, precipitation in the driest quarter, and annual mean temperature). There was no overall enrichment of associations near a priori candidate genes implicated in flowering time, height, and inflorescence architecture in cereals, but several significant associations were found near a priori candidates including photoperiodic flowering regulators SbCN12 and Ma6. Together, the findings suggest that a small (3%) but significant proportion of nucleotide variation in Nigerian sorghum landraces reflects clinal adaptation along the West African precipitation gradient.

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Estimating Genetic Relatedness in Admixed Populations

Estimating genetic relatedness, and inbreeding coefficients is important to the fields of quantitative genetics, conservation, genome-wide association studies (GWAS), and population genetics. Traditional estimators of genetic relatedness assume an underlying model of population structure. Each individual is assigned to a population, depending on a priori assumptions about geographical location of sampling, proximity, or genetic similarity. But often, this population assignment is unknown and assumptions about assignment can lead to erroneous estimates of genetic relatedness. I develop a generalized method of estimating relatedness in admixed populations, to account for (1) multi-allelic genomic data, (2) including all nine Identity By Descent (IBD) states, and implement a maximum likelihood based estimator of pairwise genetic relatedness in structured populations, part of the software, InRelate. Replicated estimations of genetic relatedness between admixed full sib (FS), half sib (HS), first cousin (FC), parent-offspring (PO) and unrelated (UR) dyads in simulated and empirical data from the HGDP-CEPH panel show considerably low bias and error while using InRelate, compared to several previously developed methods. I also propose a bootstrap scheme, and a series of Wald Tests to assign relatedness categories to pairs of individuals.

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Functional Interactions Between rsks-1/S6K, glp-1/Notch, and Regulators of Caenorhabditis elegans Fertility and Germline Stem Cell Maintenance

The proper accumulation and maintenance of stem cells is critical for organ development and homeostasis. The Notch signaling pathway maintains stem cells in diverse organisms and organ systems. In Caenorhabditis elegans, GLP-1/Notch activity prevents germline stem cell (GSC) differentiation. Other signaling mechanisms also influence the maintenance of GSCs, including the highly-conserved TOR substrate ribosomal protein S6 kinase (S6K). Although C. elegans bearing either a null mutation in rsks-1/S6K or a reduction-of-function (rf) mutation in glp-1/Notch produce half the normal number of adult germline progenitors, virtually all these single mutant animals are fertile. However, glp-1(rf) rsks-1(null) double mutant animals are all sterile, and in about half of their gonads, all GSCs differentiate, a distinctive phenotype associated with a significant reduction or loss of GLP-1 signaling. How rsks-1/S6K promotes GSC fate is unknown. Here, we determine that rsks-1/S6K acts germline-autonomously to maintain GSCs, and that it does not act through Cyclin-E or MAP kinase in this role. We found that interfering with translation also enhances glp-1(rf), but that regulation through rsks-1 cannot fully account for this effect. In a genome-scale RNAi screen for genes that act similarly to rsks-1/S6K, we identified 56 RNAi enhancers of glp-1(rf) sterility, many of which were previously not known to interact functionally with Notch. Further investigation revealed at least six candidates that, by genetic criteria, act linearly with rsks-1/S6K. These include genes encoding translation-related proteins, cacn-1/Cactin, an RNA exosome component, and a Hedgehog-related ligand. We found that additional Hedgehog-related ligands may share functional relationships with glp-1/Notch and rsks-1/S6K in maintaining germline progenitors.

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Null Mutation of the Fascin2 Gene by TALEN Leading to Progressive Hearing Loss and Retinal Degeneration in C57BL/6J Mice

Fascin2 (FSCN2) is an actin cross-linking protein that is mainly localized in retinas and in the stereocilia of hair cells. Earlier studies showed that a deletion mutation in human FASCIN2 (FSCN2) gene could cause autosomal dominant retinitis pigmentosa. Recent studies have indicated that a missense mutation in mouse Fscn2 gene (R109H) can contribute to the early onset of hearing loss in DBA/2J mice. To explore the function of the gene, Fscn2 was knocked out using TALEN (transcription activator-like effector nucleases) on the C57BL/6J background. Four mouse strains with deletions of 1, 4, 5, and 41 nucleotides in the target region of Fscn2 were developed. F1 heterozygous (Fscn2^+/–) mice carrying the same deletion of 41 nucleotides were mated to generate the Fscn2^–/– mice. As a result, the Fscn2^–/– mice showed progressive hearing loss, as measured in the elevation of auditory brainstem-response thresholds. The hearing impairment began at age 3 weeks at high-stimulus frequencies and became most severe at age 24 weeks. Moreover, degeneration of hair cells and loss of stereocilia were remarkable in Fscn2^–/– mice, as revealed by F-actin staining and scanning electron microscopy. Furthermore, compared to the controls, the Fscn2^–/– mice displayed significantly lower electroretinogram amplitudes and thinner retinas at 8, 16, and 24 weeks. These results demonstrate that, in C57BL/6Jmice, Fscn2 is essential for maintaining ear and eye function and that a null mutation of Fscn2 leads to progressive hearing loss and retinal degeneration.

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Comparative Genomics Approaches Accurately Predict Deleterious Variants in Plants

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

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Recursive Algorithms for Modeling Genomic Ancestral Origins in a Fixed Pedigree

The study of gene flow in pedigrees is of strong interest for the development of quantitative trait loci (QTL) mapping methods in multiparental populations. We developed a Markovian framework for modeling ancestral origins along two homologous chromosomes within individuals in fixed pedigrees. A highly beneficial property of our method is that the size of state space depends linearly or quadratically on the number of pedigree founders, whereas this increases exponentially with pedigree size in alternative methods. To calculate the parameter values of the Markov process, we describe two novel recursive algorithms that differ with respect to the pedigree founders being assumed to be exchangeable or not. Our algorithms apply equally to autosomes and sex chromosomes, another desirable feature of our approach. We tested the accuracy of the algorithms by a million simulations on a pedigree. We demonstrated two applications of the recursive algorithms in multiparental populations: design a breeding scheme for maximizing the overall density of recombination breakpoints and thus the QTL mapping resolution, and incorporate pedigree information into hidden Markov models in ancestral inference from genotypic data; the conditional probabilities and the recombination breakpoint data resulting from ancestral inference can facilitate follow-up QTL mapping. The results show that the generality of the recursive algorithms can greatly increase the application range of genetic analysis such as ancestral inference in multiparental populations.

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Identification of Candidate Genes Controlling Black Seed Coat and Pod Tip Color in Cowpea (Vigna unguiculata [L.] Walp)

Seed coat color is an important part of consumer preferences for cowpea (Vigna unguiculata [L.] Walp). Color has been studied in numerous crop species and has often been linked to loci controlling the anthocyanin biosynthesis pathway. This study makes use of available resources, including mapping populations, a reference genome, and a high-density single nucleotide polymorphism genotyping platform, to map the black seed coat and purple pod tip color traits, with the gene symbol Bl, in cowpea. Several gene models encoding MYB domain protein 113 were identified as candidate genes. MYB domain proteins have been shown in other species to control expression of genes encoding enzymes for the final steps in the anthocyanin biosynthesis pathway. PCR analysis indicated that a presence/absence variation of one or more MYB113 genes may control the presence or absence of black pigment. A PCR marker has been developed for the MYB113 gene Vigun05g039500, a candidate gene for black seed coat color in cowpea.

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Genomic Structural Variations Within Five Continental Populations of Drosophila melanogaster

Chromosomal structural variations (SV) including insertions, deletions, inversions, and translocations occur within the genome and can have a significant effect on organismal phenotype. Some of these effects are caused by structural variations containing genes. Large structural variations represent a significant amount of the genetic diversity within a population. We used a global sampling of Drosophila melanogaster (Ithaca, Zimbabwe, Beijing, Tasmania, and Netherlands) to represent diverse populations within the species. We used long-read sequencing and optical mapping technologies to identify SVs in these genomes. Among the five lines examined, we found an average of 2,928 structural variants within these genomes. These structural variations varied greatly in size and location, included many exonic regions, and could impact adaptation and genomic evolution.

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Orofacial pain and its potential oral causes in older people with Mild Cognitive Impairment or dementia

Journal of Oral Rehabilitation, Volume 0, Issue ja, -Not available-.


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A comparison of growth among growth friendly systems for scoliosis: a systematic review

The optimal method for surgical treatment of early onset scoliosis is currently unknown. Although the aim of growth-friendly systems is to reduce the curve and maintain growth, there is no consensus on how to measure spinal growth during and after the treatment. Different measurements of different segments (T1-S1, T1-T12, instrumented length) are used for different time points to evaluate growth. The aim of this review is to assess what measurements are used and to compare the growth-friendly systems based on spinal growth during treatment.

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Clinical Predictors of Delayed Discharges in Inpatient Mental Health Settings Across Ontario

Abstract

Delayed discharges constitute an ongoing issue in psychiatric facilities. This study examined clinical predictors of 30-day delayed discharges in all designated inpatient mental health units within Ontario, Canada. Data for 76,184 inpatient episodes were obtained from 68 psychiatric facilities between 2011 and 2013. Risk factors for delayed discharges were analyzed using multivariate logistic regression. Indicators of functional, social, and cognitive impairment positively predicted delayed discharges, while symptoms of mental illness were inversely related. Policy makers and mental health care practitioners may utilize early predictors of delayed discharges to introduce treatment interventions and policies that reduce the risk of delays in mental health settings.

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APD teams up with RapidDeploy to offer complete hosted solution to critical control operations

Software pioneer APD Communications has announced an alliance with fellow technology market leader RapidDeploy to provide a complete hosted solution for control room operations globally. The collaboration brings together complementary, cloud-based technologies to enhance the efficiency and effectiveness of critical control operations. It offers an unrivalled combination of APD's Cortex...

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Logistical concerns surrounding an overdose mass casualty incident

Overdose cases can create numerous logistical problems when there are multiple overdose cases around the same time in different locations

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Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities: Current Challenges and New Approaches: Report of the Symposium Held at the 63rd Annual Meeting of the Radiation Research Society, 15–18 October 2017; Cancun, Mexico

Radiation Research, Volume 190, Issue 4, Page 350-360, October 2018.


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John Tompkins Lyman; (May 25, 1932 – May 30, 2018)

Radiation Research, Volume 190, Issue 4, Page 445-447, October 2018.


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The importance of genetic counselling in genome-wide sequencing

The importance of genetic counselling in genome-wide sequencing

The importance of genetic counselling in genome-wide sequencing, Published online: 03 October 2018; doi:10.1038/s41576-018-0057-3

Genome-wide sequencing (GWS) is the most sensitive test available for detecting pathogenic genetic variants but it generates complex results. It is important, therefore, that individuals undergoing GWS are offered both pre-test and post-test genetic counselling.

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Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data

Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data

Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data, Published online: 03 October 2018; doi:10.1038/s41576-018-0058-2

Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data

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Towards quantitative and multiplexed in vivo functional cancer genomics

Towards quantitative and multiplexed in vivo functional cancer genomics

Towards quantitative and multiplexed in vivo functional cancer genomics, Published online: 28 September 2018; doi:10.1038/s41576-018-0053-7

CRISPR–Cas genome editing and next-generation sequencing are driving advances in cancer modelling and functional cancer genomics. Their application to autochthonous mouse models of human cancer to generate and analyse multiplexed and/or combinatorial alterations in vivo is reviewed here.

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Determination of the minimal alveolar concentration of sevoflurane associated with isoelectric electroencephalogram in children: A prospective, randomized, double‐blind study

Pediatric Anesthesia, EarlyView.


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A randomized controlled trial of oral chloral hydrate vs intranasal dexmedetomidine plus buccal midazolam for auditory brainstem response testing in children

Pediatric Anesthesia, EarlyView.


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Perioperative respiratory adverse event risk assessment in children with upper respiratory tract infection: Validation of the COLDS score

Pediatric Anesthesia, EarlyView.


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Anesthetic management of thoracoscopic resection of lung lesions in small children

Pediatric Anesthesia, EarlyView.


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Diagnosis and perioperative management in pediatric sleep‐disordered breathing

Pediatric Anesthesia, EarlyView.


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Texas EMS providers to receive body armor

Fort Bend County EMS purchased 32 ballistic vests and helmets, enough to equip every working crew

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QRICH1 Mutations cause a Chondrodysplasia with Developmental Delay

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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The m6A‑methylase complex and mRNA export

Publication date: Available online 2 October 2018

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

Author(s): Simon Lesbirel, Stuart A. Wilson

Abstract

During synthesis, mRNA undergoes a number of modifications such as capping, splicing and polyadenylation. These processes are coupled with the orderly deposition of the TREX complex on the mRNA and subsequent recruitment of the NXF1-P15 heterodimer which stimulates the nuclear export of mature mRNAs. mRNAs also undergo a number of internal modifications, the most common of which is the N⁶‑methyladenosine (m⁶A) modification. In this review we discuss the recent evidence of coupling between the m⁶A modification, RNA processing and export.

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Research Progress on the Relationship Between Acute Pancreatitis and Calcium Overload in Acinar Cells

Abstract

Acute pancreatitis is a human disease with multiple causes that leads to autodigestion of the pancreas. There is sufficient evidence to support the key role of sustained increase in cytosolic calcium concentrations in the early pathogenesis of the disease. To clarify the mechanism of maintaining calcium homeostasis in the cell and pathological processes caused by calcium overload would help to research directly targeted therapeutic agents. We will specifically review the following: intracellular calcium homeostasis and regulation, the occurrence of calcium overload in acinar cells, the role of calcium overload in the pathogenesis of AP, the treatment strategy proposed for calcium overload.

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Delayed Bleeding After Colorectal Endoscopic Submucosal Dissection: When Is Emergency Colonoscopy Needed?

Abstract

Background

Endoscopic submucosal dissection (ESD) is an effective treatment for early-colorectal cancer. Although delayed bleeding is a serious potential complication, there is no consensus on the optimal protocol to determine which cases require emergency colonoscopy.

Aims

This study aimed to assess the risk factors for delayed bleeding after ESD and evaluate the "watch and wait" strategy for delayed bleeding. The "watch and wait" strategy was used for delayed bleeding, unless the shock index was ≥ 1 and/or a moderate amount of hematochezia occurred more than five occurrences.

Methods

This study included 404 patients who had undergone endoscopic resection for 439 lesions between April 2012 and February 2018. Patients were classified into the bleeding group or the no-bleeding group to investigate the risk factors for delayed bleeding, and to assess the necessity of emergency colonoscopy.

Results

Twenty-seven patients into the bleeding group and 412 into the no-bleeding group were classified. However, no case required emergency colonoscopy for hemostasis under "watch and wait strategy." Multivariate analysis revealed the risk factors for bleeding were rectal lesion (OR 5.547, 95% CI 1.456–21.130; P = 0.012) and lesion size ≥ 40 mm (OR 3.967, 95% CI 1.003–15.696; P = 0.05).

Conclusions

Risk factors for delayed bleeding are rectal lesions and lesion size ≥ 40 mm. This watch and wait strategy resulted in no requirements for emergency colonoscopy or blood transfusion, and no serious conditions caused by delayed bleeding.

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Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain

Abstract

Background

Widespread opioid use has led to increase in opioid-related adverse effects like constipation. We examined the impact of study endpoints on reported treatment benefits.

Methods

Using MEDLINE, EMBASE, and ClinicalTrials.gov, we searched for randomized control trials targeting chronic opioid-induced constipation (OIC) and subjected them to meta-analysis. Data are given with 95% confidence intervals.

Results

Thirty trials met our inclusion criteria. Combining all dichotomous definitions of responders, active drugs were consistently more effective than placebo, with an odds ratio (OR): 2.30 [2.01–2.63; 15 studies], independent of the underlying drug mechanism. The choice of endpoints significantly affected the therapeutic gain. When time from drug administration to defecation was used, the OR decreased from 4.74 [2.71–4.74] at 6 h or less to 2.46 [1.80–3.30] at 24 h (P < 0.05). Using other response definitions, the relative benefit over placebo was 2.10 [1.77–2.50; 12 studies] for weekly bowel frequency, 2.03 [1.39–2.95; 9 studies] for symptom scores, 2.21 [1.25–3.90; 4 studies] for global assessment scales, and 1.27 [0.79–2.03; 7 studies] for rescue laxative use.

Conclusion

While treatment of OIC with active drugs is more effective than placebo, the relative gain depends on the choice of endpoints. The commonly used time-dependent response definition is associated with the highest response rate but is of questionable relevance in a chronic disorder. The limited data do not clearly demonstrate a unique advantage of the peripherally restricted opioid antagonists, suggesting that treatment with often cheaper agents should be optimized before shifting to these novel expensive agents.

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Resveratrol Improves Recovery and Survival of Diet-Induced Obese Mice Undergoing Extended Major (80%) Hepatectomy

Abstract

Introduction

Loss of hepatic epidermal growth factor receptor (EGFR) expression is a cause for the increased perioperative risk for complications and death in patients with obesity and fatty liver undergoing liver resection. Herein, we set out to identify agents that might increase EGFR expression and improve recovery for patients with fatty liver undergoing resection. Using the diet-induced obese (DIO) mouse model of fatty liver, we examined resveratrol as a therapy to induce EGFR expression and improve outcomes following 80% partial hepatectomy (PH) in a murine model.

Methods

DIO mice were fed resveratrol or carrier control by gavage. EGFR expression and the response to major (80%) PH were examined.

Results

Based on an Illumina analysis, resveratrol was identified as increasing EGFR gene expression in A549 cells. Resveratrol was observed to also increase EGFR protein expression in A549 cells. DIO mice fed resveratrol by gavage (75 mg/kg) demonstrated an increased EGFR expression without the identified hepatic toxicity. Resveratrol and control mice subjected to 80% PH, a model of high mortality hepatectomy in DIO mice, demonstrated macroscopically decreased fatty liver and fewer liver hemorrhagic petechiae. Resveratrol pretreatment ameliorated liver injury and accelerated regeneration of the hepatic remnant after 80% PH including decreasing serum ALT and bilirubin, while increasing hepatic PCNA expression. Resveratrol increased induction of p-STAT3 and p-AKT after 80% hepatectomy. Resveratrol pretreatment significantly improved survival rates in DIO mice undergoing extended 80% PH.

Conclusions

Oral resveratrol restores EGFR expression in fatty liver. Resveratrol may be a promising protective agent in instances where extensive hepatic resection of fatty liver is required.

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Complex effects of laminopathy mutations on nuclear structure and function

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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GRIN2D variants in three cases of developmental and epileptic encephalopathy

Clinical Genetics, Volume 0, Issue ja, -Not available-.


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The importance of genetic counselling in genome-wide sequencing

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Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data

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Towards quantitative and multiplexed in vivo functional cancer genomics

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Evaluation of screening for celiac disease in children with juvenile idiopathic arthritis

Acta Pediatrica

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Clinical predictors of pathologically response after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma: Long term outcomes of a phase II study

Journal of Thoracic Disease

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Fruit and vegetable intake and pancreatic cancer risk in a population-based cohort study in Japan

International Journal of Cancer

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Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population

Clinical Nutrition

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Outcomes of surgical intervention for refractory gastroparesis: A systematic review

Journal of Surgical Research

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Antagonist muscle architecture and aponeurosis/tendon strain of biceps femoris long head during maximal isometric efforts

Abstract

Introduction

Examination of the mechanical behavior of the hamstrings when acting as antagonists provides information about loading of this muscle group and its role for joint stability during forceful quadriceps contractions. The aim of this study was to quantify biceps femoris long head fascicle length (FL), angle of pennation (PA) and distal tendon/aponeurosis strain during maximum voluntary contraction efforts of the knee extensors using real-time ultrasound.

Methods

Fourteen participants performed passive joint movements and maximum voluntary knee extension and flexion efforts of the knee flexors at 0°, 45° and 90° of knee flexion. An ultrasound probe was used to visualize FL, PA and tendon/aponeurosis strain from the distal part of the muscle.

Results

Two-way analysis of variance designs indicated that: (a) antagonist BFlh tendon/aponeurosis strain increased significantly up to 2.77 ± 1.25% relative to rest (p < 0.05). The FL increased non-significantly (2.86 ± 6.81%) while the PA was unaltered during isometric MVC efforts of the knee extensors (p > 0.05) (b) FL, PA and tendon/aponeurosis strain of the BFlh when acting as antagonist were not significantly affected by knee joint angular position (p > 0.05).

Conclusions

Antagonist hamstring function takes the form of a lengthened tendon/aponeurosis, no fascicle shortening and submaximal neural activation. Future research could examine whether exercise interventions that aim to alter tendon/aponeurosis mechanical properties of the hamstrings when acting as antagonists are beneficial for injury prevention and rehabilitation.

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The relationship between naturalistic sleep variation and error monitoring in young adults: An event-related potential (ERP) study

Publication date: Available online 2 October 2018

Source: International Journal of Psychophysiology

Author(s): Simone Nicole Fueggle, Romola S. Bucks, Allison M. Fox

Abstract

Sleep deprivation studies have highlighted the importance of adequate sleep for optimal daytime functioning. However, there is limited research exploring whether variations in natural sleep patterns produce similar difficulties to those seen in sleep deprivation studies. The aim of the current study was to explore whether naturalistic reductions in sleep duration and/or sleep quality were associated with behavioural and electrophysiological measures of cognitive control. Sixty undergraduate students were asked to wear an actigraph for 7 consecutive nights before completing a hybrid Flanker-Go/NoGo task whilst continuous EEG data were recorded. Participants were assigned to high or low sleep quality and short or long sleep duration groups using the National Sleep Foundation guidelines. Results indicated that individuals who, on average, slept <7 h each night showed inefficiencies in error-monitoring, as reflected by a reduction in amplitude of the error-related negativity (ERN) in comparison to those with longer sleep duration. These findings suggest that natural variations in sleep quantity are associated with atypical error detection.

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Detection of gastritis by a deep convolutional neural network from double-contrast upper gastrointestinal barium X-ray radiography

Abstract

Background

Deep learning has become a new trend of image recognition tasks in the field of medicine. We developed an automated gastritis detection system using double-contrast upper gastrointestinal barium X-ray radiography.

Methods

A total of 6520 gastric X-ray images obtained from 815 subjects were analyzed. We designed a deep convolutional neural network (DCNN)-based gastritis detection scheme and evaluated the effectiveness of our method. The detection performance of our method was compared with that of ABC (D) stratification.

Results

Sensitivity, specificity, and harmonic mean of sensitivity and specificity of our method were 0.962, 0.983, and 0.972, respectively, and those of ABC (D) stratification were 0.925, 0.998, and 0.960, respectively. Although there were 18 false negative cases in ABC (D) stratification, 14 of those 18 cases were correctly classified into the positive group by our method.

Conclusions

Deep learning techniques may be effective for evaluation of gastritis/non-gastritis. Collaborative use of DCNN-based gastritis detection systems and ABC (D) stratification will provide more reliable gastric cancer risk information.

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Increased sensitivity of the circadian system to light in delayed sleep‐wake phase disorder

The Journal of Physiology, Volume 0, Issue ja, -Not available-.


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Rehabilitation approach after surgical repair of spontaneous bilateral quadriceps tendon rupture in a healthy mason – a case report.

Quadriceps tendon rupture is a rare lesion, occurring most frequently in males over 60 years following a fall or trauma and associated with systemic diseases and risk factors. Bilateral injury is even more uncommon and disabling. The authors report a case of spontaneous bilateral quadriceps tendon rupture, non-simultaneous (8 days apart), in a healthy 54-year-old Black male mason, that may be work-related. The patient was included in a 6-month rehabilitation program after surgical repair. Pain control and gait reacquisition were particularly difficult. Following the customized and phased rehabilitation program, the patient achieved the 6-month functional outcomes reported for unilateral rupture. The authors highlight the rehabilitation specificities and challenges of the bilateral lesion and discuss the pathophysiological role of prolonged periods of working in repetitive quadriceps overuse postures on quadriceps tendon rupture. Corresponding author: Diogo Manuel Portugal, Physical and Rehabilitation Medicine Department, Prof. Doutor Fernando Fonseca Hospital, IC 19, 2720-276, Amadora, Portugal. Phone number: +351918939162. E-mail: diogoportugal@campus.ul.pt. Author Disclosures: Conflicts of interest. The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. Funding and Financial benefits. The authors have no funding or financial benefits to report. Authors' contributions. All authors have made substantial contributions, drafting the article and revising it critically. All authors have approved the manuscript and this submission. Previous presentation. This case report was presented as an oral presentation at the XVIII Congress of the Portuguese Society of Physical and Rehabilitation Medicine, 1st March 2018, and won the Case Reports honorable mention. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Effectiveness of Group-based Physiotherapy-led Behavioral Psychological Interventions on Adults With Chronic Low Back Pain: A Systematic Review and Meta-analysis

Group-based physiotherapy-led behavioral psychological interventions (GPBPIs) are an emerging treatment for chronic low back pain (CLBP), but the efficacy of these interventions is uncertain. A review of relevant randomized controlled trials and a meta-analysis was conducted to evaluate the effectiveness of GPBPIs on pain relief in adults with CLBP. Literature databases, Google Scholar, bibliographies, and other relevant sources were searched. Thirteen (13) intervention studies published from 1998 to 2013 were included. The meta-analysis was conducted using RevMan software in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. In reviewing the short term (

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Trifid Median Nerve-A Rare Variant in a Patient with Carpal Tunnel Syndrome

No abstract available

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An Unusual Pattern of Muscular Atrophy In A Case of GNE Myopathy Presenting with Low Back Pain

No abstract available

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Visual Vignette: Isolated lesion of the fourth digit extensor muscle belly fascicle

No abstract available

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Utilizing a Workshop Format for Physiatry Trainees in the Management of Acute Sports-Related Concussion

Select residency and medical student training programs have developed and researched skill-based workshops, focusing on mastering a surgical or communication skill, however they are less frequently studied in physiatry residency programs. Given the importance of concussion care in physiatric practice, this study sought to measure the effectiveness of a novel sports-related concussion workshop. Based on the 5th International Consensus Statement on Concussion in Sport, a six-hour concussion workshop was developed. Participants were administered a pre- and post-workshop questionnaire to gauge level of comfort managing various aspects of concussion, case-based questions to assess participant knowledge, and questions regarding satisfaction with workshop-based training sessions. 16 participants, ranging from PGY-2 to PGY-5, were included in the analyses, with significant gains (p

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Letter to the Editor regarding Bilgilisoy Felix M, Kilic Z, Uckum A, et al: Mechanical Traction for Lumbar Radicular Pain Supine or Prone? A Randomized Control Trial. Am J Phys Med Rehabil 2018;97:433-439

No abstract available

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The struggle for evidence in physical and rehabilitation medicine: publication rate of randomized controlled trials and systematic reviews is growing more than in other therapeutic fields

Objective To evaluate the rate of publication of randomized controlled trials (RCTs), systematic reviews and meta-analysis in Physical and Rehabilitation Medicine (PRM) and its variation over time. Design We performed a bibliometric study and searched PubMed from inception to 2017, using National Library of Medicine 3rd level MeSH terms ("Rehabilitation", "Physical Therapy Modalities" and "Drug Therapy") and filters ("Randomized Controlled Trial", "Systematic Reviews" and "Meta-Analysis"). We used descriptive statistics and we calculated the best fitting regression model for all data considered. Results The absolute number of published papers is growing in rehabilitation as much as in other treatment fields such as drug therapy. While the rate of growth of publications for all studies relative to PubMed is bigger for drug therapies than for rehabilitation and physical therapy, the rate of growth of RCTs, systematic reviews and meta-analysis is significantly greater for rehabilitation and physical therapy (P

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Ultrasound Imaging for Complete Injury of the Posterior Interosseous Nerve After Forearm Surgery

No abstract available

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Size does matter: when a large plastic biliary stent ends up in the root of the mesentery

Abstract

Duodenal perforations due to biliary stenting migration, although rare, can occur. We report a unique case of duodenal perforation due to a large in length plastic stent with no (or marginal) migration, which ended up in the root of the mesentery, explaining the normal laboratory values and minimal imaging findings observed. Any clinical symptom during the postprocedural period should raise the suspicion of a major complication and prompt quick management decisions.

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