Imposing compulsory rugby union on school children: An analysis of English state-funded secondary schools.

To establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk. A cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools. Rugby Union was delivered in 81% ( = 234 of 288) of state-funded secondary school physical education curricula, including 83% ( = 229 of 275) of state-funded secondary school boys' and 54% ( = 151 of 282) of girls' physical education curricular. Rugby Union was compulsory in 91% ( = 208 of 229) of state-funded secondary schools that delivered it as part of the boys' physical education curriculum and 54% ( = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls' physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum. Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education. [Abstract copyright: Copyright © 2022 White, Batten, Howarth, Magrath, Piggin, Millward, Parry, Lang, Bullingham, Pearce, Morales, Turner, Humphries, Hardwicke, Anderson, Kirkwood and Pollock.

Imposing compulsory Rugby Union on schoolchildren: an analysis of English state-funded secondary schools

Objective: to establish the extent to which Rugby Union was a compulsory physical education activity in state-funded secondary schools in England and to understand the views of Subject Leaders for Physical Education with respect to injury risk. Method: a cross-sectional research study using data obtained under the Freedom of Information Act (2000) from 288 state-funded secondary schools. Results: Rugby Union was delivered in 81% (n = 234 of 288) of state-funded secondary school physical education curricula, including 83% (n = 229 of 275) of state-funded secondary school boys’ and 54% (n = 151 of 282) of girls’ physical education curricular. Rugby Union was compulsory in 91% (n = 208 of 229) of state-funded secondary schools that delivered it as part of the boys’ physical education curriculum and 54% (n = 82 of 151) of state-funded secondary schools that delivered contact Rugby Union as part of the girls’ physical education curriculum. Subject Leaders for Physical Education also perceived Rugby Union to have the highest risk of harm of the activities they delivered in their school physical education curriculum. Conclusion: Notwithstanding discussions of appropriate measures (i.e., mandatory concussion training, Rugby Union specific qualifications and CPD) to reduce injury risk, it is recommended that Rugby Union should not be a compulsory activity given that it has a perceived high risk of injury and is an unnecessary risk for children in physical education

Next-Generation Sequencing Applications for Inherited Retinal Diseases

Inherited retinal diseases (IRDs) represent a collection of phenotypically and genetically diverse conditions. IRDs phenotype(s) can be isolated to the eye or can involve multiple tissues. These conditions are associated with diverse forms of inheritance, and variants within the same gene often can be associated with multiple distinct phenotypes. Such aspects of the IRDs highlight the difficulty met when establishing a genetic diagnosis in patients. Here we provide an overview of cutting-edge next-generation sequencing techniques and strategies currently in use to maximise the effectivity of IRD gene screening. These techniques have helped researchers globally to find elusive causes of IRDs, including copy number variants, structural variants, new IRD genes and deep intronic variants, among others. Resolving a genetic diagnosis with thorough testing enables a more accurate diagnosis and more informed prognosis and should also provide information on inheritance patterns which may be of particular interest to patients of a child-bearing age. Given that IRDs are heritable conditions, genetic counselling may be offered to help inform family planning, carrier testing and prenatal screening. Additionally, a verified genetic diagnosis may enable access to appropriate clinical trials or approved medications that may be available for the condition

Fibrotic Changes to Schlemm’s Canal Endothelial Cells in Glaucoma

Previous studies have shown that glaucomatous Schlemm’s canal endothelial cells (gSCECs) are stiffer and associated with reduced porosity and increased extracellular matrix (ECM) material compared to SCECs from healthy individuals. We hypothesised that Schlemm’s canal (SC) cell stiffening was a function of fibrotic changes occurring at the inner wall of SC in glaucoma. This study was performed in primary cell cultures isolated from the SC lumen of human donor eyes. RNA and protein quantification of both fibrotic and endothelial cell markers was carried out on both healthy and gSCECs. Functional assays to assess cell density, size, migration, proliferation, and mitochondrial function of these cells were also carried out. Indeed, we found that gSCECs deviate from typical endothelial cell characteristics and exhibit a more fibrotic phenotype. For example, gSCECs expressed significantly higher protein levels of the fibrotic markers α-SMA, collagen I-α1, and fibronectin, as well as significantly increased protein expression of TGFβ-2, the main driver of fibrosis, compared to healthy SCECs. Interestingly, we observed a significant increase in protein expression of endothelial marker VE-cadherin in gSCECs, compared to healthy SCECs. gSCECs also appeared to be significantly larger, and surprisingly proliferate and migrate at a significantly higher rate, as well as showing significantly reduced mitochondrial activity, compared to healthy SCECs

Rod Photoreceptor Loss in Rho ؊/؊ Mice Reduces Retinal Hypoxia and Hypoxia-Regulated Gene Expression

PURPOSE. This study was conducted to evaluate whether regions of the retinal neuropile become hypoxic during periods of high oxygen consumption and whether depletion of the outer retina reduces hypoxia and related changes in gene expression. METHODS. Retinas from rhodopsin knockout (Rho Ϫ/Ϫ ) mice were evaluated along with those of wild-type (WT) control animals. Retinas were also examined at the end of 12-hour dark or light periods, and a separate group was treated with L-cisdiltiazem at the beginning of a 12-hour dark period. Hypoxia was assessed by deposition of hypoxyprobe (HP) and HPprotein adducts were localized by immunohistochemistry and quantified using ELISA. Also, hypoxia-regulated gene expression and transcriptional activity were assessed alongside vascular density. RESULTS. Hypoxia was observed in the inner nuclear and ganglion cell layers in WT retina and was significantly reduced in Rho Ϫ/Ϫ mice (P Ͻ 0.05). Retinal hypoxia was significantly increased during dark adaptation in WT mice (P Ͻ 0.05), whereas no change was observed in Rho Ϫ/Ϫ or with L-cis-diltiazem-treated WT mice. Hypoxia-inducible factor (HIF)-1␣ DNA-binding and VEGF mRNA expression in Rho Ϫ/Ϫ retina was significantly reduced in unison with outer retinal depletion (P Ͻ 0.05). Retina from the Rho Ϫ/Ϫ mice displayed an extensive intraretinal vascular network after 6 months, although there was evidence that capillary density was depleted in comparison with that in WT retinas. CONCLUSIONS. Relative hypoxia occurs in the inner retina especially during dark adaptation. Photoreceptor loss reduces retinal oxygen usage and hypoxia which corresponds with attenuation of the retinal microvasculature. These studies suggest that in normal physiological conditions and diurnal cycles the adult retina exists in a state of borderline hypoxia, making this tissue particularly susceptible to even subtle reductions in perfusion. (Invest Ophthalmol Vis Sci. 2006;47:5553-5560

RNA Interference–Mediated Suppression and Replacement of Human Rhodopsin In Vivo

Mutational heterogeneity represents a significant barrier to development of therapies for many dominantly inherited diseases. For example, >100 mutations in the rhodopsin gene (RHO) have been identified in patients with retinitis pigmentosa (RP). The development of therapies for dominant disorders that correct the primary genetic lesion and overcome mutational heterogeneity is challenging. Hence, therapeutics comprising two elements—gene suppression in conjunction with gene replacement—have been investigated. Suppression is targeted to a site independent of the mutation; therefore, both mutant and wild-type alleles are suppressed. In parallel with suppression, a codon-modified replacement gene refractory to suppression is provided. Both in vitro and in vivo validation of suppression and replacement for RHO-linked RP has been undertaken in the current study. RNA interference (RNAi) has been used to achieve ∼90% in vivo suppression of RHO in photoreceptors, with use of adeno-associated virus (AAV) for delivery. Demonstration that codon-modifed RHO genes express functional wild-type protein has been explored transgenically, together with in vivo expression of AAV-delivered RHO-replacement genes in the presence of targeting RNAi molecules. Observation of potential therapeutic benefit from AAV-delivered suppression and replacement therapies has been obtained in Pro23His mice. Results provide the first in vivo indication that suppression and replacement can provide a therapeutic solution for dominantly inherited disorders such as RHO-linked RP and can be employed to circumvent mutational heterogeneity