Transcranial Direct Current Stimulation in Pediatric Motor Disorders: A Systematic Review and Meta-analysis

Publication date: Available online 7 November 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Ghazala T. Saleem, Jewel E. Crasta, Beth Slomine, Gabriela Lucila Cantarero, Stacy J. Suskauer

Abstract

Objective

To systematically examine the safety and effectiveness of transcranial direct current stimulation (tDCS) interventions in pediatric motor disorders.

Data Sources

PubMed, EMBASE, Cochrane, CINAHL, Web of Science, and ProQuest databases were searched from inception to August 2018.

Study Selection

tDCS randomized controlled trials (RCTs), observational studies, conference proceedings and dissertations in pediatric motor disorders were included. Two authors independently screened articles based on predefined inclusion criteria.

Data Extraction

Data related to participant demographics, intervention, and outcomes were extracted by two authors. Quality assessment was independently performed by two authors.

Data Synthesis

Twenty-three studies involving a total of 391 participants were included. There was no difference in drop-out rates between active (1/144) and sham (1/144) tDCS groups, risk difference 0.0, 95% CI [-.05, .04]. Across studies, the most common adverse effects in the active group were tingling (17.2%), discomfort (8.02%), itching (6.79%), and skin redness (4%). Across 3 studies in children with cerebral palsy, tDCS significantly improved gait velocity (MD = .23; 95% CI [0.13, 0.34], p < .0005), stride length (MD = 0.10; 95% CI [0.05, 0.15], p< .0005), and cadence (MD = 15.7; 95% CI [9.72, 21.68], p< .0005). Mixed effects were found on balance, upper-extremity function, and overflow movements in dystonia.

Conclusion

Based on the studies reviewed, tDCS is a safe technique in pediatric motor disorders and may improve some gait measures and involuntary movements. Research to date in pediatric motor disorders shows limited effectiveness in improving balance and upper-extremity function. tDCS may serve as a potential adjunct to pediatric rehabilitation; to better understand if tDCS is beneficial for pediatric motor disorders, more well-designed RCTs are needed.

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Diagnostic efficacy of dual-focus endoscopy with narrow-band imaging using simplified dyad criteria for superficial esophageal squamous cell carcinoma

Abstract

Background

Our previous studies have shown the diagnostic utility of a newly developed dual-focus endoscope with narrow-band imaging (DF-NBI) and simplified dyad criteria for detection of superficial esophageal squamous cell carcinoma (SESCC). This clinical trial aimed to study the diagnostic efficacy of DF-NBI with dyad criteria for detecting SESCC compared to white light imaging (WLI).

Methods

This was a single-arm prospective comparative trial. We enrolled 170 consecutive high-risk patients for esophageal squamous cell carcinoma. Patients were initially examined with WLI by one independent endoscopist and then the other performed DF-NBI blinded to the WLI diagnosis to avoid a carry-over effect. Lesions showing proliferation and/or various shapes of intrapapillary capillary loops (IPCL) under DF-NBI (i.e., dyad criteria) were endoscopically diagnosed as SESCC including high-grade intraepithelial neoplasia. The primary endpoint was sensitivity of WLI and DF-NBI for detecting SESCC. The secondary endpoints were the diagnostic performance (i.e., specificity and accuracy) and inter/intra-observer concordance of DF-NBI with dyad criteria.

Results

A total 77 SESCCs were detected. The sensitivity of DF-NBI for SESCC was significantly higher than that of WLI (91% vs. 51%, P < 0.001). The specificity and accuracy of WLI and DF-NBI using dyad criteria were 100% vs. 84%, and 86% vs. 86%, respectively. Various shapes and proliferation of IPCL showed the highest value in inter-observer and intra-observer agreements (κ = 0.77 and 0.82, respectively).

Conclusion

DF-NBI combined with dyad criteria may be a promising technique with a high sensitivity for diagnosis of SESCC and high inter/intra-observer agreement.

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Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs

Publication date: Available online 8 November 2018

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

Author(s): Hironori Adachi, Meemanage D. De Zoysa, Yi-Tao Yu

Abstract

Pseudouridylation is a post-transcriptional isomerization reaction that converts a uridine to a pseudouridine (Ψ) within an RNA chain. Ψ has chemical properties that are distinct from that of uridine and any other known nucleotides. Experimental data accumulated thus far have indicated that Ψ is present in many different types of RNAs, including coding and noncoding RNAs. Ψ is particularly concentrated in rRNA and spliceosomal snRNAs, and plays an important role in protein translation and pre-mRNA splicing, respectively. Ψ has also been found in mRNA, but its function there remains essentially unknown. In this review, we discuss the mechanisms and functions of RNA pseudouridylation, focusing on rRNA, snRNA and mRNA. We also discuss the methods, which have been developed to detect Ψs in RNAs. This article is part of a Special Issue entitled: mRNA modifications in gene expression control edited by Dr. Soller Matthias and Dr. Fray Rupert.

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EP300-HDAC1-SWI/SNF functional unit defines transcription of some DNA repair enzymes during differentiation of human macrophages

Publication date: Available online 8 November 2018

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

Author(s): Julita Pietrzak, Tomasz Płoszaj, Łukasz Pułaski, Agnieszka Robaszkiewicz

Abstract

Differentiation of human macrophages predisposes these cells to numerous tasks, i.e. killing invading pathogens, and this entails the need for enhanced intracellular defences against stress, including conditions that may increase DNA damage. Our study shows that expression of DNA repair enzymes, such as PARP1, BRCA1 and XRCC1, are activated during macrophage development by the SWI/SNF chromatin remodelling complex, which serves as a histone acetylation sensor. It recognises and displaces epigenetically marked nucleosomes, thereby enabling transcription. Acetylation is controlled both in monocytes and macrophages by the co-operation of EP300 and HDAC1 activities. Differentiation modulates the activities of individual components of EP300-HDAC1-SWI/SNF functional unit and entails recruitment of PBAF to gene promoters. In monocytes, histone-deacetylated promoters of repressed PARP1, BRCA1 and XRCC1 respond only to HDAC inhibition, with an opening of the chromatin structure by BRM, whereas in macrophages both EP300 and HDAC1 contribute to the fine-tuning of nucleosomal acetylation, with HDAC1 remaining active and the balance of EP300 and HDAC1 activities controlling nucleosome eviction by BRG1-containing SWI/SNF. Since EP300-HDAC1-SWI/SNF operates at the level of gene promoters characterized simultaneously by the presence of E2F binding site(s) and CpG island(s), this allows cells to adjust PARP1, BRCA1 and XRCC1 transcription to the differentiation mode and to restart cell cycle progression. Thus, mutual interdependence between acetylase and deacetylase activities defines the acetylation-dependent code for regulation of histone density and gene transcription by SWI/SNF, notably on gene promoters of DNA repair enzymes.

Graphical abstract

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Detection of ribonucleoside modifications by liquid chromatography coupled with mass spectrometry

Publication date: Available online 7 November 2018

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

Author(s): Manasses Jora, Peter A. Lobue, Robert L. Ross, Brittney Williams, Balasubrahmanyam Addepalli

Abstract

A small set of ribonucleoside modifications have been found in different regions of mRNA including the open reading frame. Accurate detection of these specific modifications is critical to understanding their modulatory roles in facilitating mRNA maturation, translation and degradation. While transcriptome-wide next-generation sequencing (NGS) techniques could provide exhaustive information about the sites of one specific or class of modifications at a time, recent investigations strongly indicate cautionary interpretation due to the appearance of false positives. Therefore, it is suggested that NGS-based modification data can only be treated as predicted sites and their existence need to be validated by orthogonal methods. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an analytical technique that can yield accurate and reproducible information about the qualitative and quantitative characteristics of ribonucleoside modifications. Here, we review the recent advancements in LC-MS/MS technology that could help in securing accurate, gold-standard quality information about the resident post-transcriptional modifications of mRNA.

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Dietary Fiber and Gastrointestinal Disease: an Evolving Story

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Whipple’s Disease: A Well-Done Outcome to a Rare Disease

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