In vivo modeling recapitulates radiotherapy delivery and late-effect profile for childhood medulloblastoma.

Background: Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with 5-year survival rates > 70%. Cranial radiotherapy (CRT) to the whole brain, with posterior fossa boost (PFB), underpins treatment for non-infants; however, radiotherapeutic insult to the normal brain has deleterious consequences to neurocognitive and physical functioning, and causes accelerated aging/frailty. Approaches to ameliorate radiotherapy-induced late-effects are lacking and a paucity of appropriate model systems hinders their development. Methods: We have developed a clinically relevant in vivo model system that recapitulates the radiotherapy dose, targeting, and developmental stage of childhood medulloblastoma. Consistent with human regimens, age-equivalent (postnatal days 35-37) male C57Bl/6J mice received computerized tomography image-guided CRT (human-equivalent 37.5 Gy EQD2, n = 12) ±â€…PFB (human-equivalent 48.7 Gy EQD2, n = 12), via the small animal radiation research platform and were longitudinally assessed for > 12 months. Results: CRT was well tolerated, independent of PFB receipt. Compared to a sham-irradiated group (n = 12), irradiated mice were significantly frailer following irradiation (frailty index; P = .0002) and had reduced physical functioning; time to fall from a rotating rod (rotarod; P = .026) and grip strength (P = .006) were significantly lower. Neurocognitive deficits were consistent with childhood MB survivors; irradiated mice displayed significantly worse working memory (Y-maze; P = .009) and exhibited spatial memory deficits (Barnes maze; P = .029). Receipt of PFB did not induce a more severe late-effect profile. Conclusions: Our in vivo model mirrored childhood MB radiotherapy and recapitulated features observed in the late-effect profile of MB survivors. Our clinically relevant model will facilitate both the elucidation of novel/target mechanisms underpinning MB late effects and the development of novel interventions for their amelioration.

The Reported Use of Tongue-Ties and Nosebands in Thoroughbred and Standardbred Horse Racing-A Pilot Study.

This article reports on the results of a survey of racehorse trainers (n = 112) outlining the reasons for tongue-tie (TT) and noseband (NB) use by Thoroughbred trainers (TBTs) (n = 72) and Standardbred trainers (SBTs) (n = 40). The study also investigated the reported effectiveness of TTs and possible complications arising from their use. Tongue-tie use was reported by 62.5% (n = 70) of racehorse trainers. The reasons for TT use varied between TBTs and SBTs. For TBTs, the most common reason for TT use was to prevent or reduce airway obstruction (72.3%, n = 34), followed closely by to prevent or reduce airway noise (55.3%, n = 16). Standardbred trainers assigned equal importance for TT use [to prevent or reduce airway obstruction (69.6%, n = 16) and to prevent the horse from moving its tongue over the bit (69.6%, n = 16)]. Tongue-ties were considered significantly less effective at improving performance than at reducing airway obstruction and preventing the tongue from moving over the bit (t = -2.700, p = 0.0007). For respondents who used both TTs and NBs, there was a mild to moderate positive association between the reasons for using TTs and NBs. Of the 70 TT-using respondents, 51.4% (n = 36) recorded having encountered either a physical or behavioural complication due to TT use, with redness/bruising of the tongue (20.0%, n = 14) being the most common physical complication reported. Duration of use influenced the risk of observing complications. The likelihood of a respondent reporting a behavioural complication due to TT use increased with every minute of reported application and a nine-minute increment in application period doubled the odds of a respondent reporting a complication. Tightness was a risk factor for physical complications: Checking TT tightness by noting the tongue as not moving was associated with increased reporting of physical complications (OR = 6.59; CI 1.1-67.5). This pilot study provides some insight into how and why TTs are applied by some racehorse trainers, and the potential risks associated with their use. A further study of a larger cohort is recommended because these results are valid for only the 112 trainers who responded and cannot be generalized to the equine industry.

The Reported Use of Nosebands in Racing and Equestrian Pursuits.

This article reports on the results of a survey designed to explore the types of nosebands that owners, riders and trainers use in training and competition, their reasons for using nosebands, the design preferences in different disciplines and approaches to noseband tightness and monitoring, as well as the incidence of negative impacts related to noseband usage. Respondents (n = 3040) were asked to specify the type of noseband they were currently using and to rate how effective they were in achieving these stated reasons. Respondents who used nosebands (n = 2332) most commonly used Plain Cavesson (46.6%, n = 1087) and Hanoverian (24.8%, n = 579) nosebands. The reasons provided in the survey for noseband usage were grouped into three broad, mutually exclusive categories: Anatomical; Consequential and Passive. Responses across these categories were fairly evenly distributed overall: Anatomical (29.5%, n = 1501), Consequential (30.6%, n = 1560), Passive (32.9%, n = 1673) and other reasons (7.0%, n = 358). Across all respondents (n = 2332), the most common Anatomical reason given was to prevent the horse's tongue from moving over the bit (20.8%, n = 485), the most common Consequential reason was to improve the appearance of the horse (20.4%, n = 476), with aligning with the rules of the sport (30.2%, n = 705) the most popular Passive reason. Of the respondents who answered the question of checking noseband tightness (n = 2295), most reported checking noseband tightness at the bridge of the nose (62.1%, n = 1426), some (10.4%, n = 238) reported checking for tightness on the side of the face and others under the chin (21.5%, n = 496). This survey also revealed some of the potential issues associated with noseband use, with 18.6% (n = 434) reporting at least one physical or behavioural complication. The most common complication was hair loss under the noseband (39.9%, n = 173). Crank systems were reported to be used by 28.9% (n = 665) of respondents. This is of concern as these devices can be excessively tightened, minimising jaw and tongue movement and may compromise horse welfare. Indeed, the current data in our study show that these devices are associated with an increased risk of complications being reported. Against the backdrop of potential harm to horse welfare associated with restrictive nosebands, this report may serve as a guide for future regulations and research. It helps improve our understanding of noseband preferences and their use in different disciplines.