Πέμπτη 31 Ιανουαρίου 2019

A novel WDR62 missense mutation in microcephaly with abnormal cortical architecture and review of the literature

Abstract

Autosomal recessive primary microcephaly (MCPH) is a group of rare neurodevelopmental diseases with severe microcephaly at birth. One type of the disorder, MCPH2, is caused by biallelic mutations in the WDR62 gene, which encodes the WD repeat–containing protein 62. Patients with WDR62 mutation may have a wide range of malformations of cortical development in addition to congenital microcephaly. We describe two patients, a boy and a girl, with severe congenital microcephaly, global developmental delay, epilepsy, and failure to thrive. MRI showed hemispherical asymmetry, diffuse pachygyria, thick gray matter, indistinct gray-white matter junction, and corpus callosum and white matter hypoplasia. Whole exome sequencing revealed the same novel homozygous missense mutation, c.668T>C, p.Phe223Ser in exon 6 of the WDR62 gene. The healthy parents were heterozygous for this mutation. The mutation affects a highly conserved region in one of the WD repeats of the WDR62 protein. Haplotype analysis showed genetic relatedness between the families of the patients. Our findings expand the spectrum of mutations randomly distributed in the WDR62 gene. A review is also provided of the brain malformations described in WDR62 mutations in association with congenital microcephaly.



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Genomic Resources for Goniozus legneri, Aleochara bilineata and Paykullia maculata, Representing Three Independent Origins of the Parasitoid Lifestyle in Insects

Parasitoid insects are important model systems for a multitude of biological research topics and widely used as biological control agents against insect pests. While the parasitoid lifestyle has evolved numerous times in different insect groups, research has focused almost exclusively on Hymenoptera from the Parasitica clade. The genomes of several members of this group have been sequenced, but no genomic resources are available from any of the other, independent evolutionary origins of the parasitoid lifestyle. Our aim here was to develop genomic resources for three parasitoid insects outside the Parasitica. We present draft genome assemblies for Goniozus legneri, a parasitoid Hymenopteran more closely related to the non-parasitoid wasps and bees than to the Parasitica wasps, the Coleopteran parasitoid Aleochara bilineata and the Dipteran parasitoid Paykullia maculata. The genome assemblies are fragmented, but complete in terms of gene content. We also provide preliminary structural annotations. We anticipate that these genomic resources will be valuable for testing the generality of findings obtained from Parasitica wasps in future comparative studies.



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Evaluation of InSeq To Identify Genes Essential for Pseudomonas aeruginosa PGPR2 Corn Root Colonization

The reciprocal interaction between rhizosphere bacteria and their plant hosts results in a complex battery of genetic and physiological responses. In this study, we used insertion sequencing (INSeq) to reveal the genetic determinants responsible for the fitness of Pseudomonas aeruginosa PGPR2 during root colonization. We generated a random transposon mutant library of Pseudomonas aeruginosa PGPR2 comprising 39,500 unique insertions and identified genes required for growth in culture and on corn roots. A total of 108 genes were identified as contributing to the fitness of strain PGPR2 on roots. The importance in root colonization of four genes identified in the TnSeq screen was verified by constructing deletion mutants in the genes and testing them for the ability to colonize corn roots singly or in competition with the wild type. All four mutants were affected in corn root colonization, displaying 5- to 100-fold reductions in populations in single inoculations, and all were outcompeted by the wild type by almost 100-fold after seven days on corn roots in mixed inoculations of the wild type and mutant. The genes identified in the screen had homology to genes involved in amino acid catabolism, stress adaptation, detoxification, signal transduction, and transport. INSeq technology proved a successful tool to identify fitness factors in P. aeruginosa PGPR2 for root colonization.



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Factors affecting quality of life in children and adolescents with hypermobile Ehlers‐Danlos syndrome/hypermobility spectrum disorders

Hypermobile Ehlers‐Danlos syndrome (hEDS) is a hereditary disorder of connective tissue, often presenting with complex symptoms can include chronic pain, fatigue, and dysautonomia. Factors influencing functional disability in the pediatric hEDS population are incompletely studied. This study's aims were to assess factors that affect quality of life in children and adolescents with hEDS. Individuals with hEDS between the ages 12–20 years and matched parents were recruited through retrospective chart review at two genetics clinics. Participants completed a questionnaire that included the Pediatric Quality of Life Inventory (PedsQL™), PedsQL Multidimentional Fatigue Scale, Functional Disability Inventory, Pain‐Frequency‐Severity‐Duration Scale, the Brief Illness Perception Questionnaire, measures of anxiety and depression, and helpful interventions. Survey responses were completed for 47 children and adolescents with hEDS/hypermobility spectrum disorder (81% female, mean age 16 years), some by the affected individual, some by their parent, and some by both. Clinical data derived from chart review were compared statistically to survey responses. All outcomes correlated moderately to strongly with each other. Using multiple regression, general fatigue and pain scores were the best predictors of the PedsQL total score. Additionally, presence of any psychiatric diagnosis was correlated with a lower PedsQL score. Current management guidelines recommend early intervention to prevent disability from deconditioning; these results may help identify target interventions in this vulnerable population.



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Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway

Abstract

An international advisory group met at the National Institutes of Health in Bethesda, Maryland in 2017, to discuss a new classification system for the ectodermal dysplasias (EDs) that would integrate both clinical and molecular information. We propose the following, a working definition of the EDs building on previous classification systems and incorporating current approaches to diagnosis: EDs are genetic conditions affecting the development and/or homeostasis of two or more ectodermal derivatives, including hair, teeth, nails, and certain glands. Genetic variations in genes known to be associated with EDs that affect only one derivative of the ectoderm (attenuated phenotype) will be grouped as non‐syndromic traits of the causative gene (e.g., non‐syndromic hypodontia or missing teeth associated with pathogenic variants of EDA "ectodysplasin"). Information for categorization and cataloging includes the phenotypic features, Online Mendelian Inheritance in Man number, mode of inheritance, genetic alteration, major developmental pathways involved (e.g., EDA, WNT "wingless‐type," TP63 "tumor protein p63") or the components of complex molecular structures (e.g., connexins, keratins, cadherins).



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Comment on: “Equity in Physical Activity: A Misguided Goal”



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Reply to Williams et al.: Comment on: “Equity in Physical Activity: A Misguided Goal”



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Comparison of Naturally Occurring Resistance-Associated Substitutions Between 2008 and 2016 in Chinese Patients with Chronic Hepatitis C Virus Infection

Microbial Drug Resistance, Ahead of Print.


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The combined effects of salivas and occlusal indicators on occlusal contact forces

Abstract

Background

Some occlusal detection products are designed for use on dry teeth, but this is not always achieved. Others are suited for dry and wet applications.

Objective

The objective of this study is to assess the combined effects, on occlusal contact forces, of two previously studied affecting variables – occlusal detection products and saliva.

Methods

We used a full arch dentiform with 3 occlusal detection products (an articulating film, an articulation paper and T‐Scan) in combination with human (HS) and an artificial saliva. The maxillary arch assembly, weighing ~54 N (the maximum bite force), was lowered onto (occlusion) and lifted off (disclusion) of the mandibular arch through 10 cycles by a mechanical testing machine. The forces and moments acting on the mandibular arch were continuously recorded by a load cell that supported it.

Results

The maximum values of Flateral (the in‐occlusal plane component of the occlusal contact force) were analyzed by occlusion/disclusion separately using one‐way ANOVA, with factor for group type to identify the significant effect of salivas on products, effect of products, effect of salivas with products, effect of human saliva. A difference in occlusion and/or in disclusion was considered different.

Statistical differences (p < 0.0001) in Flateral were found in: dry product vs. product + HS, dry product vs. product + artificial saliva (with articulating film and T‐Scan) and HS vs. product + HS (with articulation paper and T‐Scan).

Conclusion

All products were affected by the salivas, except articulation paper by artificial saliva.

This article is protected by copyright. All rights reserved.



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Interoceptive accuracy predicts nonplanning trait impulsivity

Abstract

Influential theories concerning personality argue that many impulsive individuals show physiological underarousal at rest. This interoceptive state is proposed to be egodystonic, motivating impulsive maladaptive actions to enhance arousal. However, there is little empirical research on this matter. The current study tested the relationship between physiological markers of arousal, measures of interoceptive (in)sensitivity, and trait impulsivity in a nonclinical sample of young adults. Experiment 1 investigated whether individuals (N = 31) with high trait impulsivity show decreased resting measures of arousal (indexed from heart rate, heart rate variability, and sympathetic electrodermal activity). Experiment 2 assessed whether trait impulsivity is linked to interoceptive abilities (N = 60). Overall, our results do not provide any compelling support for the underarousal theory of impulsivity. However, impaired interoceptive (cardiac discrimination) accuracy predicted the degree of Barratt nonplanning impulsivity, such that individuals with a better ability to distinguish between internal (bodily) and external signals manifest lower levels of nonplanning trait impulsivity. These findings open an avenue for potential novel interventions aimed at improving planning abilities via better interoceptive discrimination.



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Electroencephalography-based endogenous brain–computer interface for online communication with a completely locked-in patient

Brain–computer interfaces (BCIs) have demonstrated the potential to provide paralyzed individuals with new means of communication, but an electroencephalography (EEG)-based endogenous BCI has never been succes...

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Exploring the relationship between social deprivation and domestic radon levels in the East Midlands, UK

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Antony R. Denman, Robin G.M. Crockett, Christopher J. Groves-Kirkby, Paul S. Phillips, Gavin K. Gillmore

Abstract

The natural radioactive gas radon is widely present in the built environment and at high concentrations is associated with enhanced risk of lung-cancer. This risk is significantly enhanced for habitual smokers. Although populations with higher degrees of social deprivation are frequently exposed to higher levels of many health-impacting pollutants, a recent study suggests that social deprivation in the UK is associated with lower radon concentrations.

The analysis reported here, based on published data on social deprivation and domestic radon in urban and rural settings in the English East Midlands, identifies a weak association between increasing deprivation and lower radon areas. This is attributed to the evolution of the major urban centres on low-permeability, clay-rich alluvial soils of low radon potential. In addition, the predominance of high-rise dwellings in towns and cities will further reduce average exposure to radon in populations in those areas.



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The Accuracy of Acquiring Heart Rate Variability from Portable Devices: A Systematic Review and Meta-Analysis

Abstract

Background

Advancements in wearable technology have provided practitioners and researchers with the ability to conveniently measure various health and/or fitness indices. Specifically, portable devices have been devised for convenient recordings of heart rate variability (HRV). Yet, their accuracies remain questionable.

Objective

The aim was to quantify the accuracy of portable devices compared to electrocardiography (ECG) for measuring a multitude of HRV metrics and to identify potential moderators of this effect.

Methods

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles published before July 29, 2017 were located via four electronic databases using a combination of the terms related to HRV and validity. Separate effect sizes (ESs), defined as the absolute standardized difference between the HRV value recorded using the portable device compared to ECG, were generated for each HRV metric (ten metrics analyzed in total). A multivariate, multi-level model, incorporating random-effects assumptions, was utilized to quantify the mean ES and 95% confidence interval (CI) and explore potential moderators.

Results

Twenty-three studies yielded 301 effects and revealed that HRV measurements acquired from portable devices differed from those obtained from ECG (ES = 0.23, 95% CI 0.05–0.42), although this effect was small and highly heterogeneous (I2 = 78.6%, 95% CI 76.2–80.7). Moderator analysis revealed that HRV metric (p <0.001), position (p = 0.033), and biological sex (β = 0.45, 95% CI 0.30–0.61; p <0.001), but not portable device, modulated the degree of absolute error. Within metric, absolute error was significantly higher when expressed as standard deviation of all normal–normal (R–R) intervals (SDNN) (ES = 0.44) compared to any other metric, but was no longer significantly different after a sensitivity analysis removed outliers. Likewise, the error associated with the tilt/recovery position was significantly higher than any other position and remained significantly different without outliers in the model.

Conclusions

Our results suggest that HRV measurements acquired using portable devices demonstrate a small amount of absolute error when compared to ECG. However, this small error is acceptable when considering the improved practicality and compliance of HRV measurements acquired through portable devices in the field setting. Practitioners and researchers should consider the cost–benefit along with the simplicity of the measurement when attempting to increase compliance in acquiring HRV measurements.



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mTOR-S6K1 pathway mediates cytoophidium assembly

Publication date: Available online 31 January 2019

Source: Journal of Genetics and Genomics

Author(s): Zhe Sun, Ji-Long Liu

Abstract

CTP synthase (CTPS), the rate-limiting enzyme in de novo CTP biosynthesis, has been demonstrated to assemble into evolutionarily conserved filamentous structures, termed cytoophidia, in Drosophila, bacteria, yeast and mammalian cells. However, the regulation and function of the cytoophidium remain elusive. Here, we provide evidence that the mechanistic target of rapamycin (mTOR) pathway controls cytoophidium assembly in mammalian and Drosophila cells. In mammalian cells, we find that inhibition of mTOR pathway attenuates cytoophidium formation. Moreover, CTPS cytoophidium assembly appears to be dependent on the mTOR complex 1 (mTORC1) mainly. In addition, knockdown of the mTORC1 downstream target S6K1 can inhibit cytoophidium formation, while overexpression of the constitutively active S6K1 reverses mTOR knockdown-induced cytoophidium disassembly. Finally, reducing mTOR protein expression results in a decrease of the length of cytoophidium in Drosophila follicle cells. Therefore, our study connects CTPS cytoophidium formation with the mTOR signaling pathway.



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Treatment of Veterans with Psychiatric Diagnoses Nationally in the Veterans Health Administration: A Comparison of Service Delivery by Mental Health Specialists and Other Providers

Abstract

Patients with psychiatric disorders are treated by both mental health specialists and non-specialists. We use national data from the Veterans Health Administration to evaluate changing proportions of patients seen exclusively by non-specialists during the study year (FY 2012) limit as well as differences in socio-demographic, clinical and service use characteristics. There has been a five-fold increase in veterans with mental disorders seen by non-specialists over 20 years from 7 to 38%, findings similar to those in non-VA settings. Veterans treated by mental health specialists were younger, more likely to have been homeless and disabled, and had more severe and more numerous psychiatric diagnoses. There is a need to maintain specialty services and to strengthen non-specialty care through education and research.



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Allocation Concealment And Intention-To-Treat Analysis Do Not Influence The Treatment Effects Of Physical Therapy Interventions In Low Back Pain Trials: A Meta-Epidemiological Study

Publication date: Available online 31 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Matheus Oliveira de Almeida, Bruno Tirotti Saragiotto, Chris Maher, Leonardo Oliveira Pena Costa

Abstract
Objective

To evaluate if allocation concealment and intention-to-treat (ITT) analysis influence the treatment effects of physical therapy interventions in low back pain trials.

Data sources

We searched on PubMed, Embase, Cochrane Database of Systematic Reviews, PEDro and CINAHL up to February 2017.

Study selection

We included low back pain trials that compared physical therapy interventions to placebo or no intervention or minimal intervention with pain or disability outcomes.

Data extraction

Information about allocation concealment and ITT analysis was extracted from PEDro and pain and disability outcomes converted to a 0-100 scale. A meta-regression was performed to evaluate the influence of these methodological features of interest on treatment effects. Other covariates included in the meta-regression were sample size and sequence generation.

Data Synthesis

We identified 128 eligible trials (pooled n = 20555 participants). A total of 44.5% of the trials achieved allocation concealment, while 32% performed ITT analysis. Meta regression analyses showed no influence of allocation concealment on treatment effects for pain (regression coefficient 0.009; 95% CI -2.91 to 2.91) and disability (regression coefficient 1.13; 95% CI -1.35 to 3.62), and no influence of ITT analysis for pain (regression coefficient 1.38; 95% CI -1.73 to 4.50) or disability (regression coefficient 1.27; 95% CI -1.39 to 3.64). For the other covariates, there was also no clinically significant influence on the treatment effects.

Conclusion

There is no influence of allocation concealment and/or ITT analysis on treatment effects of physical therapy interventions for pain and disability in low back pain trials.



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Returning to Activity After a Concussion

Publication date: Available online 30 January 2019

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Nick Reed, Noah D. Silverberg, Mary Alexis Iaccarino, Michael McCrea, Karen L. McCulloch, William Panenka, Emma Gregory, Kristen Dams-O'Connor, Grant L. Iverson, Chris Weyer Jamora, Heather Belanger, Gary McKinney, Alison M. Cogan, Christine Provvidenza



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Aging, effort, and stereotyping: The evidence for the moderating role of self-involvement

Publication date: Available online 30 January 2019

Source: International Journal of Psychophysiology

Author(s): Gabriela Czarnek, Małgorzata Kossowska, Michael Richter

Abstract

A study with young and older adults (N = 91) investigated the effect of self-involvement on stereotyping tendency and effort mobilization. We hypothesized that the impact of self-involvement varies as a function of age: increased self-involvement should lead older adults to engage in more effortful information processing and decreased stereotyping, whereas increased self-involvement should have no impact on effort mobilization and stereotyping tendency in younger adults. Young and older adults read narratives under low and high-self-involvement conditions before performing a recognition test that measured their stereotyping tendency. Effort was assessed as cardiovascular responses. We found that older adults in the high-self-involvement condition presented low stereotyping tendency (similar to that of young people) in comparison to older adults in the low-self-involvement condition. Furthermore, older adults in the high-self-involvement condition had decreased high-frequency heart rate variability in comparison to the other conditions, but only during the recognition test; this suggests increased effort mobilization. These findings indicate that self-involvement decreases older adults' stereotyping tendency, possibly through effort mobilization.



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Preventing Nerve Injury with Pedicle Screw Testing

Publication date: Available online 31 January 2019

Source: Clinical Neurophysiology

Author(s): Marc R. Nuwer



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Neuronal spiking activity highlights a gradient of epileptogenicity in human tuberous sclerosis lesions

Publication date: Available online 30 January 2019

Source: Clinical Neurophysiology

Author(s): Elodie Despouy, Jonathan Curot, Marie Denuelle, Martin Deudon, Jean-Christophe-Sol, Jean-Albert Lotterie, Leila Reddy, Lionel G. Nowak, Jérémie Pariente, Simon J. Thorpe, Luc Valton, Emmanuel J. Barbeau

Abstract
Objective

The mechanisms underlying epileptogenicity in tuberous sclerosis complex (TSC) are poorly understood.

Methods

We analysed neuronal spiking activity (84 neurons), fast ripples (FRs), local field potentials and intracranial electroencephalogram during interictal epileptiform discharges (IEDs) in the tuber and perituber of a patient using novel hybrid electrodes equipped with tetrodes.

Results

IEDs were recorded in the tuber and perituber. FRs were recorded only in the tuber and only with the microelectrodes. A larger proportion of neurons in the tuber (57%) than in the perituber (17%) had firing-rates modulated around IEDs.

Conclusions

A multi-scale analysis of neuronal activity, FRs and IEDs indicates a gradient of epileptogenicity running from the tuber to the perituber.

Significance

We demonstrate, for the first time in vivo, a gradient of epileptogenicity from the tuber to the perituber, which paves the way for future models of epilepsy in TSC. Our results also question the extent of the neurosurgical resection, including or not the perituber, that needs to be made in these patients.



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Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI

Publication date: Available online 30 January 2019

Source: Clinical Neurophysiology

Author(s): Tomohiro Yamazoe, Nicolás von Ellenrieder, Hui Ming Khoo, Yao-Hsien Huang, Natalja Zazubovits, François Dubeau, Jean Gotman

Abstract
Objective

We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI.

Methods

157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient.

Results

The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ.

Conclusions

The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ.

Significance

Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.



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