Variability in heart rate recovery measurements over 1 year in healthy, middle-aged adults.

This study assessed the longer-term (12-month) variability in post-exercise heart rate recovery following a submaximal exercise test. Longitudinal data was analysed for 97 healthy middle-aged adults (74 male, 23 female) from 2 occasions, 12 months apart. Participants were retrospectively selected if they had stable physical activity habits, submaximal treadmill fitness and anthropometric measurements between the 2 assessment visits. A submaximal Bruce treadmill test was performed to at least 85% age-predicted maximum heart rate. Absolute heart rate and Δ heart rate recovery (change from peak exercise heart rate) were recorded for 1 and 2 min post-exercise in an immediate supine position. Heart rate recovery at both time-points was shown to be reliable with intra-class correlation coefficient values ≥ 0.714. Absolute heart rate 1-min post-exercise showed the strongest agreement between repeat tests (r = 0.867, P < 0.001). Lower coefficient of variation (≤ 10.2%) and narrower limits of agreement were found for actual heart rate values rather than Δ heart rate recovery, and for 1-min rather than 2-min post-exercise recovery time points. Log-transformed values generated better variability with acceptable coefficient of variation for all measures (2.2-10%). Overall, 1 min post-exercise heart rate recovery data had least variability over the 12-month period in apparently healthy middle-aged adults

Anthropometric, speed and endurance characteristics of English academy soccer players: Do they influence obtaining a professional contract at 18 years of age

This study evaluated the anthropometric, speed and endurance characteristics of English academy soccer players, comparing players who obtained a ‘professional’ contract at 18 years old with those that did not (‘academy’); 443 male academy soccer players from an English professional club undertook anthropometric (height and body mass), speed (10 and 20 m sprint) and endurance (Yo-Yo intermittent endurance test level 2 [Yo-Yo]) assessments between 2005 and 2012. Significant improvements with age were found for speed and endurance at each annual age group up until U18 age category. Significant differences were only observed between ‘professional’ and ‘academy’ players for 10 m (p = 0.003, η2 = 0.01) and 20 m (p = 0.001, η2 = 0.01) speed at U16 and U18 and Yo-Yo performance (p = 0.001, η2 = 0.12) at U18 age category. Practitioners should use speed and endurance assessments for monitoring physical development of players rather than for talent identification purposes

In vivo precision of the GE Lunar iDXA for the measurement of visceral adipose tissue in adults: the influence of body mass index.

CoreScan is a new software for the GE Lunar iDXA, which provides a quantification of visceral adipose tissue (VAT). The objective of this study was to determine the in vivo precision of CoreScan for the measurement of VAT mass in a heterogeneous group of adults. Forty-five adults (aged 34.6 (8.6) years), ranging widely in body mass index (BMI 26.0 (5.2)  kg/m(2); 16.7-42.4 kg/m(2)), received two consecutive total body scans with repositioning. The sample was divided into two subgroups based on BMI, normal-weight and overweight/obese, for precision analyses. Subgroup analyses revealed that precision errors (RMSSD:%CV; root mean square standard deviation:% coefficient of variation) for VAT mass were 20.9 g:17.0% in the normal-weight group and 43.7 g:5.4% in overweight/obese groups. Our findings indicate that precision for DXA-VAT mass measurements increases with BMI, but caution should be used with %CV-derived precision error in normal BMI subjects.European Journal of Clinical Nutrition advance online publication, 15 October 2014; doi:10.1038/ejcn.2014.213

Lessons learnt from prenatal exome sequencing

BACKGROUND: Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service delivered from two laboratories. To minimise incidental findings and reduce the number of variants investigated, analysis uses a panel of 1205 genes where pathogenic variants may cause abnormalities presenting prenatally. Here we review our laboratory's early experience developing and delivering ES to identify challenges in interpretation and reporting and inform service development. METHODS: A retrospective laboratory records review from 01.04.2020 to 31.05.2021. RESULTS: Twenty-four of 116 completed cases were identified as challenging including 13 resulting in difficulties in analysis and reporting, nine where trio inheritance filtering would have missed the diagnosis, and two with no prenatal diagnosis; one due to inadequate pipeline sensitivity, the other because the gene was not on the panel. Two cases with copy number variants identified were not detectable by microarray. CONCLUSIONS: Variant interpretation requires close communication between referring clinicians, with occasional additional examination of the fetus or parents and communication of evolving phenotypes. Inheritance filtering misses ∼5% of diagnoses. Panel analysis reduces but does not exclude incidental findings. Regular review of published literature is required to identify new reports that may aid classification

Functional interaction between Sequestosome-1/p62 and Autophagy-Linked FYVE-containing protein WDFY3 in human osteoclasts

Peer reviewedPostprin

Implementing a rapid fetal exome sequencing service: What do parents and health professionals think?

OBJECTIVES: Prenatal exome sequencing (pES) for the diagnosis of fetal abnormalities is being introduced more widely in clinical practice. Here we explore parents' and professionals' views and experiences of pES, to identify perceived benefits, concerns, and support needs. METHODS: Semi-structured interviews were conducted with 11 parents and 20 health professionals (fetal medicine and clinical genetics) with experience of rapid pES prior to implementation in the English National Health Service. Interviews were transcribed verbatim and analysed thematically. RESULTS: Parents and professionals were largely positive about pES, emphasising clinical and psychosocial benefits of a timely, definitive diagnosis in pregnancy. Concerns included parental anxiety related to the timing of pES results or uncertain findings, a need for guidelines for case selection and reporting, and ensuring sufficient capacity for counselling, phenotyping and variant interpretation. Professionals were concerned non-genetics professionals may not be equipped to counsel parents on the complexities of pES. CONCLUSION: These findings highlight important issues for clinical implementation of pES. Expert counselling is required to enable parents to make informed decisions during a stressful time. To achieve this, professionals need further education and training, and fetal medicine and genetics services must work closely together to ensure parental understanding and appropriate support

Physical Activity and Sedentary Behaviour Clustering: Segmentation to Optimise Active Lifestyles.

Background: Increasingly the health impacts of physical inactivity are being distinguished from those of sedentary behaviour. Nevertheless, deleterious health prognoses occur when these behaviours combine, making it a Public Health priority to establish the numbers and salient identifying factors of people who live with this injurious combination. Method: Using an observational between-subjects design, a non-probability sample of 22,836 participants provided data on total daily activity. A 2-step hierarchical cluster analysis identified the optimal number of clusters and the subset of distinguishing variables. Univariate analyses assessed significant cluster differences. Results: High levels of sitting clustered with low physical activity. The ‘Ambulatory & Active’ cluster (n=6,254) sat for 2.5 to 5 h d-1 and were highly active. They were significantly younger, included a greater proportion of males and reported low Indices of Multiple Deprivation compared to other clusters. Conversely, the ‘Sedentary & Low Active’ cluster (n=6,286) achieved ≤60 MET.min.wk-1 of physical activity and sat for ≥8 h d-1. They were the oldest cluster, housed the largest proportion of females and reported moderate Indices of Multiple Deprivation. Conclusions: Public Health systems may benefit from developing policy and interventions that do more to limit sedentary behaviour and encourage light intensity activity in its place

Noninvasive Prenatal Diagnosis for Cystic Fibrosis: Implementation, Uptake, Outcome, and Implications

BACKGROUND: Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive NIPD for a recessive condition, cystic fibrosis (CF). // METHODS: Definitive NIPD for CF was developed using next-generation sequencing. Validation was performed on 13 cases from 10 families before implementation. All cases referred for CF NIPD were reviewed to determine turnaround times, genotyping results, and pregnancy outcomes. // RESULTS: Of 38 referrals, 36 received a result with a mean turnaround of 5.75 days (range, 3-11 days). Nine cases were initially inconclusive, with 3 reported unaffected because the low-risk paternal allele was inherited and 4 cases in which the high-risk paternal allele was inherited, receiving conclusive results following repeat testing. One case was inconclusive owing to a paternal recombination around the mutation site, and one case was uninformative because of no heterozygosity. Before 2016, 3 invasive referrals for CF were received annually compared with 38 for NIPD in the 24 months since offering a definitive NIPD service. // CONCLUSIONS: Timely and accurate NIPD for definitive prenatal diagnosis of CF is possible in a public health service laboratory. The method detects recombinations, and the service is well-received as evidenced by the significant increase in referrals. The bioinformatic approach is gene agnostic and will be used to expand the range of conditions tested for

Mir-96 and miR-183 differentially regulate neonatal and adult post-infarct neovascularisation

Following myocardial infarction (MI), the adult heart has minimal regenerative potential. Conversely, the neonatal heart can undergo extensive regeneration, and neovascularisation capacity was hypothesised to contribute to this difference. Here, we demonstrate the higher angiogenic potential of neonatal compared to adult mouse cardiac endothelial cells (MCECs) in vitro and use this difference to identify candidate microRNAs (miRs) regulating cardiac angiogenesis after MI. MiR expression profiling revealed miR-96 and miR-183 upregulation in adult compared to neonatal MCECs. Their overexpression decreased the angiogenic potential of neonatal MCECs in vitro and prevented scar resolution and neovascularisation in neonatal mice after MI. Inversely, their inhibition improved the angiogenic potential of adult MCECs, and miR-96/miR-183 knock-out mice had increased peri-infarct neovascularisation. In silico analyses identified anillin (ANLN) as a direct target of miR-96 and miR-183. In agreement, Anln expression declined following their overexpression and increased after their inhibition in vitro. Moreover, ANLN expression inversely correlated with miR-96 expression and age in cardiac ECs of cardiovascular patients. In vivo, ANLN-positive vessels were enriched in the peri-infarct area of miR-96/miR-183 knock-out mice. These findings identify miR-96 and miR-183 as regulators of neovascularisation following MI and miR-regulated genes such as anillin as potential therapeutic targets for cardiovascular disease