ADAMTSL1 and mandibular prognathism

Mandibular prognathism is characterized by a prognathic or prominent mandible. The objective of this study was to find the gene responsible for mandibular prognathism. Whole exome sequencing analysis of a Thai family (family 1) identified the ADAMTSL1 c.176C>A variant as the potential defect. We cross‐checked our exome data of 215 people for rare variants in ADAMTSL1 and found that the c.670C>G variant was associated with mandibular prognathism in families 2 and 4. Mutation analysis of ADAMTSL1 in 79 unrelated patients revealed the c.670C>G variant was also found in family 3. We hypothesize that mutations in ADAMTSL1 cause failure to cleave aggrecan in the condylar cartilage, and that leads to overgrowth of the mandible. Adamtsl1 is strongly expressed in the condensed mesenchymal cells of the mouse condyle, but not at the cartilage of the long bones. This explains why the patients with ADAMTSL1 mutations had abnormal mandibles but normal long bones. This is the first report that mutations in ADAMTSL1 are responsible for the pathogenesis of mandibular prognathism.

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Recent achievements and future developments in neonatal cardiopulmonary bypass

Summary

A primary goal of improving neonatal cardiopulmonary bypass has been making the circuit smaller and reduce the blood contacting surfaces. As bypass circuit size has decreased, bloodless surgery has become possible even in neonates. Since transfusion guidelines are difficult to construct based on existing literature, these technical advances should be taken advantage of in conjunction with an individualized transfusion scheme, based on monitoring of oxygen availability to the tissues.

For the majority of neonatal heart operations, several centres have shifted towards normothermic bypass even for complex neonatal surgeries, in order to avoid the adverse effects of hypothermia. Deep hypothermic circulatory arrest is no longer a necessity but an option, and selective antegrade cerebral perfusion has become common practice; however technical uncertainties with regard to this technique have to be addressed, based on reliable neurologic monitoring.

Maintenance of patient‐specific heparin concentrations during bypass is another key goal, since neonates have lower baseline antithrombin concentrations and, therefore, a higher risk for inadequate thrombin inhibition and postoperative bleeding. Due to the immaturity of their haemostatic system, the standard coagulation tests alone are inappropriate to guide haemostatic therapy in neonates. The use of indirect heparin concentration assays and global viscoelastic assays in the operating room is likely to represent the optimal strategy, and requires validation in neonates.

Monitoring of global and regional indexes of oxygen availability and consumption on bypass have become possible, however, their use in neonates still has outstanding technical issues which should be addressed and hence needs further validation.

Due to the immaturity of the neonatal myocardium, single‐shot cold cardioplegia solutions are thought to confer the best myocardial protection; their superiority when compared to more conventional modalities, however, remains to be demonstrated.

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Manual versus pressure‐controlled facemask ventilation during the induction of general anaesthesia in children: a prospective randomised controlled study

Abstract

Background

Gastric insufflation frequently occurs during facemask ventilation in children. In the present study, we compared the incidence of gastric insufflation between pressure‐controlled facemask ventilation and manual facemask ventilation during general anaesthesia induction in children.

Methods

Children in the pressure‐controlled ventilation group (n = 76) received pressure‐controlled facemask ventilation at an inspiratory pressure of 13 cmH₂O. In the manual ventilation group (n = 75), facemask ventilation was manually performed by anaesthesiologists, who tried to maintain an inspiratory pressure of 13 cmH₂O. The adjustable pressure limiting valve was set at 13 cmH₂O. The incidence of gastric insufflation during 90 s after the initiation of ventilation was assessed using epigastric auscultation and gastric ultrasonography.

Results

The incidence of gastric insufflation was significantly higher in the MV group than in the pressure‐controlled ventilation group (48% vs. 12% respectively; odds ratio 7.78, 95% confidence interval [CI] 3.38–17.9; P < 0.001). The mean peak airway pressure during ventilation was significantly higher in the manual ventilation group than in the pressure‐controlled ventilation group [16.1 (3.0) cmH₂O vs. 13.0 (0.1) cmH₂O; 95% CI of differences, 2.36–3.71 cmH₂O; P < 0.001]. The manual ventilation group exhibited a wide peak airway pressure range (11–26 cmH₂O) and a wide variation of tidal volume (0–7.0 ml/kg) compared with those of the pressure‐controlled ventilation group (13–14 cmH₂O and 0.6–16.0 ml/kg, respectively).

Conclusions

At an inspiratory pressure of 13 cmH₂O, pressure‐controlled ventilation may be more effective than manual ventilation in preventing gastric insufflation while providing stable ventilation in children.

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Associations between single nucleotide polymorphisms and erythrocyte parameters in humans: a systematic literature review

Publication date: Available online 2 February 2019

Source: Mutation Research/Reviews in Mutation Research

Author(s): Tiffany C. Timmer, Michael W.T. Tanck, Elisabeth M.J. Huis in' t Veld, Barbera Veldhuisen, Joost G. Daams, Wim L.A.M. de Kort, C. Ellen van der Schoot, Katja van den Hurk

Abstract

Individual variations in erythrocyte parameters are influenced by factors like sex, age, diet and season. Genetic variations have also been associated with erythrocyte parameters. The aim of this systematic review is to provide an overview of associations between single nucleotide polymorphisms (SNPs) and erythrocyte parameters in humans. A systematic review protocol was published at the international prospective register of systematic reviews (registration number CRD42016053052). Literature searches were conducted in Medline and Embase. Studies were included if: investigating a(n) causality/association/correlation; population-based; investigating a human population of Caucasian/mixed-ethnic descent; and written in English, Dutch or German. Study quality was assessed using the quality of genetic association studies tool. In total, 4,385 studies were screened on title/abstract and 194 studies were screened on full text. Inclusion criteria were met by 13 candidate gene studies (n = 126–49,488) and eight genome-wide association studies (GWASes, n = 1,664–116,666). One moderate and six good quality GWAS(s) identified 1,237 SNPs located in/near 241 genes. SNPs in/near ten genes were found to be associated with one or more erythrocyte parameter(s) by multiple GWASes, namely HIST1H2AC, MPST, SLC17A1 and SLC17A3 with mean cell hemoglobin (MCH), HIST1H1T and KCTD17 with MCH and mean cell volume (MCV), HBS1L and MYB with MCH, MCV and red cell count (RCC), HFE with MCH, MCV and hemoglobin, TMPRSS6 with MCH, MCV, hemoglobin and mean cell hemoglobin concentration (MCHC). Four genes were found across multiple erythrocyte parameters by one study in each parameter. Fourteen SNPs were associated with one or more erythrocyte parameter(s) in multiple cohorts, namely rs129128, rs17342717, rs228129 and rs5756504 (MCH), rs4895441, rs7775698, rs9376092 and rs9494145 (MCH, MCV, RCC), rs6569992 (MCH, RCC), rs1800562 (hemoglobin, MCH, MCV), rs130624 and rs198846 (MCH, MCV), rs4820268 and rs855791 (MCH, MCV, MCHC). Further research on these fourteen genes in erythropoiesis is recommended, especially eight whose role in erythropoiesis is unclear.

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Importance of root uptake of 14CO2 on 14C transfer to plants impacted by below-ground 14CH4 release

Publication date: May 2019

Source: Journal of Environmental Radioactivity, Volume 201

Author(s): Masakazu Ota, Taku Tanaka

Abstract

¹⁴C-labelled methane (¹⁴CH₄) released from deep underground radioactive waste disposal facilities can be a below-ground source of ¹⁴CO₂ owing to microbial oxidation of ¹⁴CH₄ to ¹⁴CO₂ in soils. Environmental ¹⁴C models assume that the transfer of ¹⁴CO₂ from soil to plant occurs via foliar uptake of ¹⁴CO₂. Nevertheless, the importance of ¹⁴CO₂ root uptake is not well understood. In the present study, below-ground transport and oxidation of ¹⁴CH₄ were modeled and incorporated into an existing land-surface ¹⁴CO₂ model (SOLVEG-II) to assess the relative importance of root uptake and foliar uptake on ¹⁴CO₂ transfer from soil to plants. Performance of the model in calculating the below-ground dynamics of ¹⁴CH₄ was validated by simulating a field experiment of ¹³CH₄ (as a substitute for ¹⁴CH₄) injection into subsoil in a wheat field in the UK. The proposed model simulation was then applied to ¹⁴C transfer in a hypothetical ecosystem impacted by continuous ¹⁴CH₄ input from the water table (bottom of 1-m thick soil), which simulated continuous release of ¹⁴CH₄ from a deep underground radioactive waste disposal facility. The contrast between the results obtained from the model calculation that assumed different distributions of roots (rooting depths of 11 cm, or 97 cm) and methane oxidation (characterized by e-folding depths of 5 cm, 20 cm, or 80 cm) in the soil provided insight into the relative importance of root uptake and foliar uptake pathways. In the shallowly rooted ecosystem with rooting depth of 11 cm, foliar uptake of ¹⁴CO₂ was significant, accounting for 80% of the ¹⁴C accumulation (as organic ¹⁴C) in the plant (leaf compartment). By contrast, in a deeply rooted ecosystem (rooting depth of 97 cm), where the root penetrated to depths close to the water-table, more than half (63%) the ¹⁴C accumulated in the plant was transferred via the root uptake pathway. We found that ¹⁴CO₂ root uptake (thus ¹⁴C accumulation in the plant) in this ecosystem depended on the distribution of methane oxidation in the soil; all ¹⁴C accumulated in the plant was transferred by the root uptake pathway when methane oxidation occurred at considerable depths (e-folding depths of 20 cm, or 80 cm) in the soil. The high level of ¹⁴CO₂ root uptake was ascribed to the oxidation of added ¹⁴CH₄ (i.e., production of ¹⁴CO₂) in the deep part of the soil and the subsequent high level of root uptake of the deep soil-water containing ¹⁴CO₂. These results indicate that ¹⁴CO₂ root uptake contributes significantly to ¹⁴CO₂ transfer to plants if ¹⁴CH₄ oxidation occurs at great depths and roots penetrate deeply into the soil. It is recommended that current environmental ¹⁴C models must be refined to consider the importance of the root uptake pathway to ensure that dose estimates of ¹⁴CH₄ release from deep underground waste disposal facilities are accurate.

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The Impact of Increased Allocation Priority for Children Awaiting Liver Transplant: A Liver Simulated Allocation Model (LSAM) Analysis

Objective: To investigate the impact of prioritizing infants, children, adolescents and the sickest adults (Status 1) for deceased donor livers. We compared outcomes under two "SharePeds" allocation schema, which prioritize children and Status 1 adults for national sharing and enhanced access to (1) pediatric donors or (2) all donors

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Association of FAM65B, AGBL4, and CUX2 genetic polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity: validation study in a Chinese Han population

Objective Antituberculosis (anti-TB) drug-induced hepatotoxicity (ATDH) is a serious adverse drug reaction, and its pathogenic mechanism has not been elucidated thoroughly to date. A recent genome-wide association study reported that seven single-nucleotide polymorphisms (SNPs) in the family with sequence similarity 65, member B gene (FAM65B), ATP/GTP-binding protein-like 4 gene (AGBL4), and cut-like homeobox 2 gene (CUX2) were associated strongly with ATDH in Ethiopian patients. We validated this relationship in a Chinese Han anti-TB treatment population. Patients and methods A 1 : 2 matched case–control study was carried out of 235 ATDH cases and 470 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATDH by odds ratios with 95% confidence intervals, and weight and hepatoprotectant use were used as covariates. Results Patients with a polymorphism at rs10946737 in the FAM65B gene were at an increased risk of moderate and severe liver injury under the dominant model (adjusted odds ratio=2.147, 95% confidence interval: 1.067–4.323, P=0.032). No other genotypes or genetic risk scores were found to be significantly related to ATDH. Conclusion This is the first study to explore and validate the relationships between seven SNPs in the FAM65B, AGBL4, and CUX2 genes and ATDH in a Chinese population. On the basis of this case–control study, SNP rs10946737 in FAM65B may be associated with susceptibility to ATDH in Chinese Han anti-TB treatment patients. Further research is warranted to explain the role of the FAM65B gene and its contribution toward individual differences in susceptibility to ATDH. * Hongqiu Pan and Miaomiao Yang contributed equally to the writing of this article. Correspondence to Shaowen Tang, MD, PhD, Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China Tel: +86 25 8686 8224; fax: +86 25 8686 8499; e-mail: tomswen@njmu.edu.cn Received October 14, 2018 Accepted January 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of SULT1A3/SULT1A4 genetic polymorphisms on the sulfation of phenylephrine and salbutamol by human SULT1A3 allozymes

Objectives Phenylephrine and salbutamol are drugs that are used widely to treat diseases/disorders, such as nasal congestion, hypotension, and asthma, in individuals of different age groups. Human cytosolic sulfotransferase (SULT) SULT1A3 has been shown to be critically involved in the metabolism of these therapeutic agents. This study was carried out to investigate the effects of single nucleotide polymorphisms of human SULT1A3 and SULT1A4 genes on the sulfation of phenylephrine and salbutamol by SULT1A3 allozymes. Materials and methods Wild-type and SULT1A3 allozymes, prepared previously by site-directed mutagenesis in conjunction with bacterial expression and affinity purification, were analyzed for sulfating activity using an established assay procedure. Results Purified SULT1A3 allozymes, in comparison with the wild-type enzyme, showed differential sulfating activities toward phenylephrine and salbutamol. Kinetic studies showed further significant variations in their substrate-binding affinity and catalytic activity toward phenylephrine and salbutamol. Conclusion The results obtained showed clearly the differential enzymatic characteristics of SULT1A3 allozymes in mediating the sulfation of phenylephrine and salbutamol. This information may contribute toward a better understanding of the pharmacokinetics of these two drugs in individuals with distinct SULT1A3 and/or SULT1A4 genotypes. Correspondence to Ming-Cheh Liu, PhD, Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614, USA Tel: +1 419 383 1918; fax: +1 419 383 1909; e-mail: ming.liu@utoledo.edu Received June 13, 2018 Accepted December 24, 2018 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Pediatric Anesthesia: A Problem-Based Learning Approach

No abstract available

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How does upper extremity Fugl-Meyer motor score relate to resting-state EEG in chronic stroke? A power spectral density analysis

Publication date: Available online 2 February 2019

Source: Clinical Neurophysiology

Author(s): M. Saes, C.G.M. Meskers, A. Daffertshofer, J.C. de Munck, G. Kwakkel, E.E.H. van Wegen, on behalf of the 4D-EEG consortium

Abstract

Objective

We investigated the potential added value of high-density resting-state EEG by addressing differences with healthy individuals and associations with Fugl-Meyer motor assessment of the upper extremity (FM-UE) scores in chronic stroke.

Methods

Twenty-one chronic stroke survivors with initial upper limb paresis and eleven matched controls were included. Group differences regarding resting-state EEG parameters (delta/alpha ratio (DAR) and pairwise-derived Brain Symmetry Index (BSI)) and associations with FM-UE were investigated, as well as lateralization of BSI and the value of different frequency bands.

Results

Chronic stroke survivors showed higher BSI compared to controls (p<.001), most pronounced in delta and theta frequency bands (p<.0001; p<.001). In the delta and theta band, BSI was significantly negatively associated with FM-UE (both p=.008) corrected for confounding factors. DAR showed no differences between groups nor association with FM-UE. Directional BSI showed increased power in the affected versus the unaffected hemisphere.

Conclusions

Asymmetry in spectral power between hemispheres was present in chronic stroke, most pronounced in low frequencies and related to upper extremity motor function deficit.

Significance

BSI is related to motor impairment and higher in chronic stroke patients compared to healthy controls, suggesting that BSI may be a marker of selective motor control.

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Dynamic Ultrasound Imaging for the Diagnosis of Superior Labrum Anterior to Posterior (SLAP) Lesion

No abstract available

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Sepsis - What's new in 2019?

Purpose of review Sepsis-3 guidelines have implications in a deeper understanding of the biopathology of the disease. Further, the review focuses on timely topics and new literature on fluid resuscitation, the value of steroids in sepsis, and new therapeutic options such as angiotensin II, vitamin C, and thiamine as well as the emerging role of procalcitonin (PCT) in managing antibiotics. Recent findings Traditional therapies such as type of crystalloid fluid administration and steroid therapy for sepsis are currently under re-evaluation. Angiotensin II is investigated for reversing vasodilatory shock. The role of capillary endothelium leak and cellular metabolism can be affected by vitamin C and thiamine levels. Biomarker level trends, specifically PCT, can aid clinical suspicion of infection. Summary Sepsis-3 shifts the focus from a noninfectious inflammatory process and an emphasis on a dysregulated host response to infection. Hyperchloremic crystalloid resuscitation is associated with poor clinical outcomes. Steroid administration can reverse shock physiology; however, mortality benefits remain uncertain. Angiotensin II, vitamin C, and thiamine are novel treatment options that need further validation. PCT assays can help discern between infectious and noninfectious inflammation. Correspondence to Mark E. Nunnally, MD, Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Langone Health, NYU Langone Medical Center, 550 1st Ave, New York, NY 10016, USA. Tel: +1 (212) 263 5072; e-mail: Mark.Nunnally@nyulangone.org Copyright © 2019 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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