How RNA editing keeps an I on physiology.

Adenosine deaminases acting on RNAs convert adenosines (A) to inosines (I) in structured or double-stranded RNAs. In mammals, this process is widespread. In the human transcriptome, more than a million different sites have been identified that undergo an ADAR-mediated A-to-I exchange Inosines have an altered base pairing potential due to the missing amino group when compared to the original adenosine. Consequently, inosines prefer to base pair with cytosines but can also base pair with uracil or adenine. This altered base pairing potential not only affects protein decoding at the ribosome but also influences the folding of RNAs and the proteins that can associate with it. Consequently, an A to I exchange can also affect RNA processing and turnover (Nishikura K. Annu Rev Biochem 79: 321-349, 2010; Brümmer A, Yang Y, Chan TW, Xiao X. Nat Commun 8: 1255, 2017). All of these events will interfere with gene expression and therefore, can also affect cellular and organismic physiology. As double-stranded RNAs are a hallmark of viral pathogens RNA-editing not only affects RNA-processing, coding, and gene expression but also controls the antiviral response to double-stranded RNAs. Most interestingly, recent advances in our understanding of ADAR enzymes reveal multiple layers of regulation by which ADARs can control antiviral programs. In this review, we focus on the recoding of mRNAs where the altered translation products lead to physiological changes. We also address recent advances in our understanding of the multiple layers of antiviral responses and innate immune modulations mediated by ADAR1.

IAEA survey of paediatric computed tomography practice in 40 countries in Asia, Europe, Latin America and Africa: procedures and protocols.

OBJECTIVE: To survey procedures and protocols in paediatric computed tomography (CT) in 40 less resourced countries. METHODS: Under a project of the International Atomic Energy Agency, 146 CT facilities in 40 countries of Africa, Asia, Europe and Latin America responded to an electronic survey of CT technology, exposure parameters, CT protocols and doses. RESULTS: Modern MDCT systems are available in 77 % of the facilities surveyed with dedicated paediatric CT protocols available in 94 %. However, protocols for some age groups were unavailable in around 50 % of the facilities surveyed. Indication-based protocols were used in 57 % of facilities. Estimates of radiation dose using CTDI or DLP from standard CT protocols demonstrated wide variation up to a factor of 100. CTDI(vol) values for the head and chest were between two and five times those for an adult at some sites. Sedation and use of shielding were frequently reported; immobilisation was not. Records of exposure factors were kept at 49 % of sites. CONCLUSION: There is significant potential for improvement in CT practice and protocol use for children in less resourced countries. Dose estimates for young children varied widely. This survey provides critical baseline data for ongoing quality improvement efforts by the IAEA.

IAEA survey of pediatric CT practice in 40 countries in Asia, Europe, Latin America, and Africa: Part 1, frequency and appropriateness.

OBJECTIVE: The purpose of this study was to assess the frequency of pediatric CT in 40 less-resourced countries and to determine the level of appropriateness in CT use. MATERIALS AND METHODS: Data on the increase in the number of CT examinations during 2007 and 2009 and appropriate use of CT examinations were collected, using standard forms, from 146 CT facilities at 126 hospitals. RESULTS: The lowest frequency of pediatric CT examinations in 2009 was in European facilities (4.3%), and frequencies in Asia (12.2%) and Africa (7.8%) were twice as high. Head CT is the most common CT examination in children, amounting to nearly 75% of all pediatric CT examinations. Although regulations in many countries assign radiologists with the main responsibility of deciding whether a radiologic examination should be performed, in fact, radiologists alone were responsible for only 6.3% of situations. Written referral guidelines for imaging were not available in almost one half of the CT facilities. Appropriateness criteria for CT examinations in children did not always follow guidelines set by agencies, in particular, for patients with accidental head trauma, infants with congenital torticollis, children with possible ventriculoperitoneal shunt malfunction, and young children (< 5 years old) with acute sinusitis. In about one third of situations, nonavailability of previous images and records on previously received patient doses have the potential to lead to unnecessary examinations and radiation doses. CONCLUSION: With increasing use of CT in children and a lack of use of appropriateness criteria, there is a strong need to implement guidelines to avoid unnecessary radiation doses to children.

Dosimetric comparison of different inhomogeneity correction algorithms for external photon beam dose calculations.

Dose calculation algorithm is one of the main sources of uncertainty in the radiotherapy sequences. The aim of this study was to compare the accuracy of different inhomogeneity correction algorithms for external photon beam dose calculations. The methodology was based on International Atomic Energy Agency TEC-DOC 1583. The phantom was scanned in every center, using computed tomography and seven tests were planned on three-dimensional treatment planning systems (TPSs). The doses were measured with ion chambers and the deviation between measured and TPS calculated dose was reported. This methodology was tested in five different hospitals which were using six different algorithms/inhomogeneity correction methods implemented in different TPSs. The algorithms in this study were divided into two groups: Measurement-based algorithms (type (a)) and model-based algorithms (type (b)). In type (a) algorithms, we saw 7.6% and 11.3% deviations out of agreement criteria for low- and high-energy photons, respectively. While in type (b) algorithms, these values were 4.3% and 5.1%, respectively. As a general trend, the numbers of measurements with results outside the agreement criteria increase with the beam energy and decrease with advancement of TPS algorithms. More advanced algorithm would be preferable and therefore should be implanted in clinical practice, especially for calculation in inhomogeneous medias like lung and bone and for high-energy beams calculation at low depth points.

Does concrete composition affect photoneutron production inside radiation therapy bunkers?

PURPOSE: Different types of concretes are used for bunker construction for radiation therapy. As neutron production occurs in high-energy photon beams, the purpose of this study was to investigate the effect of different concretes on photoneutron doses at an isocenter and maze entrance door. MATERIALS AND METHODS: The 18-MV photon beam of a Varian 2100 C/D linear accelerator and a radiation therapy bunker were simulated using the MCNPX Monte Carlo code. Different commercially available concretes were used in photoneutron calculations for the simulated bunker. RESULTS: Higher neutron doses of the water phantom were seen for barytes and galena concretes, while there was no significant (less than 1%) difference between the neutron dose of the phantom for all other concretes. Also, the neutron fluence at the inner and outer maze entrance varied up to 36% depending on the concretes' atomic compositions. CONCLUSION: It can be concluded that application of high-density concretes in order to use limited space or for other purposes may cause higher neutron doses in the maze entrance door and consequently may impose stricter requirements for neutron shielding of maze entrance doors.

Radiation protection of patients in diagnostic and interventional radiology in Asian countries: impact of an IAEA project.

Recognizing the lack of information on image quality and patient doses in most countries in Asia, the International Atomic Energy Agency (IAEA) initiated a project to assess the status of imaging technology, practice in conventional radiography, mammography, computed tomography (CT) and interventional procedures, and to implement optimisation actions. A total of 20 countries participated. Obsolete practices of use of fluoroscopy for positioning, photofluorography, chest fluoroscopy and conventional tomography were reported by 4 out of 7 countries that provided this information. Low-kV technique for chest radiography is in use in participating countries for 20-85% of cases, and manual processing is in 5-85% of facilities in 5 countries. Instances of the use of adult CT protocol for children in three participating countries were observed in 10-40% of hospitals surveyed. After implementation of a Quality Control programme, the image quality in conventional radiography improved by zero to 13 percentage points in certain countries and dose reduction was from 10% to 85%. In mammography, poor quality, ranging from 10 to 29% of images in different countries was observed. The project increased attention to dose quantities and dose levels in computed tomography, although doses in most cases were not higher than reference levels. In this study 16-19% of patients in interventional cardiology received doses that have potential for either stochastic risk or tissue reaction. This multi-national study is the first of its kind in the Asia, and it provided insight into the situation and opportunities for improvement.