Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

COVID-19 pandemic impacts physical activity levels and sedentary time but not sleep quality in young badminton athletes

Purpose

Regular physical activity is a good strategy to maintain the health of athletes, and prevent pain and decreased joint flexibility during the pandemic. On the other hand, higher sedentary time during the pandemic period can have deleterious effects. The objective of this study was to compare physical activity levels, sedentary time, and sleep parameters during the pre-COVID period and the COVID-19 pandemic period in young badminton athletes.

Methods

Fifteen young badminton athletes were evaluated during a pre-COVID period (July 2019) and during the COVID-19 period (July 2020). Sleep parameters, physical activity level, and sedentary time were measured using a tri-axial accelerometer. Participants wore the accelerometer on their dominant wrist for 7 days consecutively. In addition, the average of each sleep parameter [time in bed and total sleep time in hours per day, sleep efficiency (%), wake after sleep onset (WASO, total per day), and sleep latency (minutes per day)] was reported over the 7-day period.

Results

Athletes presented increased sedentary time (pre-COVID?=?7.0?±?1.1 vs.COVID-19?=?8.9?±?1.9 h/day, p?=?0.004, d?=?1.30) and significant decreases in the total PA observed in counts per day (pre-COVID?=?2,967,064.4?±?671,544.1 vs. COVID-19?=?1,868,210.2?±?449,768.4 counts/day, p?=?0.001, d?=?1.99), time in vigorous PA (pre-COVID?=?7.7?±?0.9 vs. COVID-19?=?6.1?±?1.2 h/day, p?=?0.001, d?=?1.56), and time in moderate-to-vigorous PA (pre-COVID?=?8.1?±?0.9 vs. COVID-19?=?6.5?±?1.3 h/day, p?=?0.001, d?=?1.48). There were no significant differences for time in light and moderate PA or in sleep parameters (p?>?0.05).

Conclusion

Young badminton athletes presented increased sedentary time, and decreased total physical activity, time in MVPA, and time in vigorous activities during the COVID-19 pandemic compared to the pre-COVID period, however, there were no significant differences in sleep parameters.

     

Racial disparity in orbital morphology and spatial relations in unoperated Crouzon patients

The altered orbital morphology of patients with Crouzon syndrome could have an impact on the planning of treatment in diverse populations, in spite of the confounding influences of different cranial suture synostosis. This study attempted to explore the differences in orbital characteristics between Asian, Caucasian patients with Crouzon syndrome, associated pansynostosis. Eighty-six preoperative computed tomograms (CT) were included (Asian Crouzon syndrome: n=10; Asian controls: n=24; Caucasian Crouzon syndrome: n=19; Caucasian controls: n=33) and measured using Mimics software (Materialise). Unique cephalometric measurements related to orbital morphology and position were designed. Crouzon syndrome and race both have interactive effects on protrusion of the globe (p=0.009) and medial horizontal angle (p=0.012) in the assessment of orbital morphology. They also interact in the width of the ethmoid sinus (p=0.009) and influence bilateral orbital relations. The anteroposterior orbital roof in Caucasian patients with Crouzon syndrome was shortened by 4.09 mm (p=0.002) compared with Caucasian controls. However, in Asian patients this dimension developed normally. The anteroposterior orbital floor was significantly reduced to a similar extent in both Asian and Caucasian Crouzon patients (both p<0.001). The visual axes in Caucasian patients with Crouzon showed more inferior rotation, by 4.38° (p=0.031) than they did in Caucasian controls, but did not achieve a statistically significant difference in other comparisons. The effect of Crouzon syndrome on orbital malformation and placement is influenced by race, especially structures related to the ethmoid sinus. Asian patients need greater infraorbital advancement for better correction of orbital proptosis and aesthetic benefits, but may require less fronto-orbital advancement than Caucasian patients.     

Synonymous Mutations in RNASEH2A Create Cryptic Splice Sites Impairing RNase H2 Enzyme Function in Aicardi–Goutières Syndrome

Aicardi–Goutières syndrome is an inflammatory disorder resulting from mutations in TREX1, RNASEH2A/2B/2C, SAMHD1, or ADAR1. Here, we provide molecular, biochemical, and cellular evidence for the pathogenicity of two synonymous variants in RNASEH2A. Firstly, the c.69G>A (p.Val23Val) mutation causes the formation of a splice donor site within exon 1, resulting in an out of frame deletion at the end of exon 1, leading to reduced RNase H2 protein levels. The second mutation, c.75C>T (p.Arg25Arg), also introduces a splice donor site within exon 1, and the internal deletion of 18 amino acids. The truncated protein still forms a heterotrimeric RNase H2 complex, but lacks catalytic activity. However, as a likely result of leaky splicing, a small amount of full‐length active protein is apparently produced in an individual homozygous for this mutation. Recognition of the disease causing status of these variants allows for diagnostic testing in relevant families.     

A Ubiquitous Reflective E-Portfolio Architecture

BackgroundIn nurse and in medicine courses, the use of reflective portfolios as a pedagogical tool is becoming a common practice; in the last years, this practice has gradually migrated from paper-based to electronic-based portfolios. Current approaches for reflective e-portfolios, however, do not widely operate at outdoor sites, where data networks are limited or nonexistent. Considering that many of the activities related to nurse and medicine courses relate to professional practices conducted in such conditions, these network shortcomings restrict the adoption of e-portfolios.PurposeThe present study describes the requirements specification, design, implementation, and evaluation of the Ubiquitous Reflective E-Portfolio Architecture, a solution proposed to support the development of systems based on mobile and wired access for both online and offline operation.MethodsWe have implemented a prototype named Professional Practice Module to evaluate the Ubiquitous Reflective E-Portfolio Architecture; the module was based on requirements observed during the professional practice, the paper-based portfolio in use, and related learning meetings in the Medicine Course of a Brazilian University. The evaluation of the system was carried out with a learning group of 2nd year students of the medicine course, who answered to extensive evaluation questionnaires.ResultsThe prototype proved to be operational in the activities of the professional practice of the Medicine Course object of the study, including homework tasks, patient care, data sharing, and learning meetings. It also demonstrated to be versatile with respect to the availability of the computer network that, many times, was not accessible. Moreover, the students considered the module useful and easy to use, but pointed out difficulties about the keyboard and the display sizes of the netbook devices, and about their operational system. Lastly, most of the students declared preference for the electronic Professional Practice Module in internal and in group activities, and for the paper-based version while in patient attendance.ConclusionsThere is evidence that the environment where the professional practice takes place influences the usage of the e-portfolio. Mobile devices were able to support students in their professional practice; however, these devices present characteristics that must be judiciously selected, otherwise, they may limit the execution of important tasks. The main shortcoming identified during the evaluation tests was about the use of the module, and of the access device, during patient attendance. For this reason, we have envisioned a new version of the Professional Practice Module that shall follow a twofold requisite: by one side, it will include all the features of the module, to be used at the university or in the students’ homes; from the other side, it will include only the features that are essential for the practice of patient attendance.     

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.