Sexually dimorphic effects of prenatal alcohol exposure on the murine skeleton

Background: Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton. Methods: Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology.Results: Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. Conclusions: Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.<br/

Fluoxetine and thioridazine inhibitefflux and attenuate crystalline biofilm formation by Proteusmirabilis

Proteus mirabilis forms extensive crystalline biofilms on indwelling urethral catheters that block urineflow and lead to serious clinical complications. The Bcr/CflA efflux system has previously been identified as important for development of P. mirabilis crystalline biofilms, highlighting the potential for efflux pump inhibitors (EPIs) to control catheter blockage. Here we evaluate the potential for drugs already used in human medicine (fluoxetine and thioridazine) to act as EPIs in P. mirabilis, and control crystalline biofilm formation. Both fluoxetine and thioridazine inhibited efflux in P. mirabilis, and molecular modelling predicted both drugs interact strongly with the biofilm-associated Bcr/CflA efflux system.Both EPIs were also found to significantly reduce the rate of P. mirabilis crystalline biofilm formation on catheters, and increase the time taken for catheters to block. Swimming and swarming motilies inP. mirabilis were also significantly reduced by both EPIs. The impact of these drugs on catheter biofilm formation by other uropathogens (Escherichia coli, Pseudomonas aeruginosa) was also explored, and thioridazine was shown to also inhibit biofilm formation in these species. Therefore, repurposing of existing drugs with EPI activity could be a promising approach to control catheter blockage, or biofilmformation on other medical devices

Ethical dilemmas and validity issues related to the use of new cooling technologies and early recognition of exertional heat illness in sport

The Tokyo 2020 Olympic Games is expected to be among the hottest Games in modern history, increasing the chances for exertional heat stroke (EHS) incidence, especially in non-acclimatised athletes/workers/spectators. The urgent need to recognise EHS symptoms to protect all attendees'' health has considerably accelerated research examining the most effective cooling strategies and the development of wearable cooling technology and real-time temperature monitoring. While these technological advances will aid the early identification of EHS cases, there are several potential ethical considerations for governing bodies and sports organisers. For example, the impact of recently developed cooling wearables on health and performance is unknown. Concerning improving athletic performance in a hot environment, there is uncertainty about this technology''s availability to all athletes. Furthermore, the real potential to obtain real-time core temperature data will oblige medical teams to make crucial decisions around their athletes continuing their competitions or withdraw. Therefore, the aim of this review is (1) to summarise the practical applications of the most novel cooling strategies/technologies for both safety (of athletes, spectators and workers) and performance purposes, and (2) to inform of the opportunities offered by recent technological developments for the early recognition and diagnosis of EHS. These opportunities are presented alongside several ethical dilemmas that require sports governing bodies to react by regulating the validity of recent technologies and their availability to all

The potential of blood flow restriction exercise to overcome Jetlag : important implications for Tokyo 2020

The decision taken by the International Olympic Committee (IOC) to host the Olympic Games this summer brings new challenges for event organisers and athletes. One such measure taken by the IOC is to mandate that athletes may not enter the Olympic Village more than five days before competing at the Games in order to prevent the spread of COVID-19. As a result, athletes from around the globe that are unable to make alternative plans will need to travel to Tokyo and acclimatize within only 5 days before their event. Of particular concern are the adverse health and performance effects elicited by flight dysrhythmia, also known as jetlag, on those athletes travelling to the Olympic Games across multiple times zones. Blood flow restriction (BFR) is a safe exercise mode that can potentially diminish the impact of jetlag on performance through its numerous beneficial physiological adaptations that overlap with those of other jetlag mitigation strategies. Experimental data are required to confirm this intriguing possibility. The present commentary aims to encourage more research into the effects of BFR training in conjunction with other strategies to overcome the effects of jetlag prior, during and after a long-haul flight on the subsequent performance of elite athletes, particularly during these difficult times of the COVID19 pandemic.https://www.minervamedica.it/en/journals/medicina-dello-sport2022-07-17hj2021Sports Medicin