The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Injuries in male and female semi-professional football (soccer) players in Nigeria: prospective study of a National Tournament

BACKGROUND: Research on the epidemiology of football injuries in Africa is very sparse despite its importance for injury prevention planning in a continent with limited sports medicine resources. The vast majority of studies available in literature were conducted in Europe and only a very few studies have prospectively reported the pattern of football injury in Africa. The purpose of this study was to evaluate the incidence and pattern of injuries in a cohort of male and female semi-professional football players in Nigeria. METHODS: A prospective cohort design was conducted, in which a total of 756 players with an age range of 18–32 years (356 males and 300 females) from 22 different teams (12 male and 10 female teams), were prospectively followed in a National Football Tournament. Physiotherapists recorded team exposure and injuries. Injuries were documented using the consensus protocol for data collection in studies relating to football injury surveillance. RESULTS: An overall incidence of 113.4 injuries/1000 h (95% CI 93.7–136.0) equivalent to 3.7 injuries/match and time-loss incidence of 15.6 injuries/1000 h were recorded for male players and 65.9 injuries/1000 h (95% CI 48.9–86.8) equivalent to 2.2 injuries/match and time-loss incidence of 7.9 injuries/1000 h were recorded for female players. Male players had a significantly higher risk of injuries [IRR = 1.72 (95% CI 1.23–2.45)]. Injuries mostly affected the lower extremity for both genders (n = 81, 70% and n = 31, 62% for males and females respectively). Lower leg contusion (n = 22, 19%) and knee sprain (n = 9, 18%) were the most common specific injury types for male and female players respectively. Most of the injuries were as a result of contact with another player (n = 102, 88%—males; n = 48, 96%—females). Time-loss injuries were mostly estimated as minimal (n = 11, 69%) for male players and severe (n = 4, 66%) for female players. CONCLUSION: The overall incidence of injuries among Nigerian semi-professional football players is high but most of the injuries do not result in time-loss. Pattern of injuries is mostly consistent with previous studies. More prospective studies are needed to establish injury prevention initiatives among African players

Frequency drift in MR spectroscopy at 3T.

PurposeHeating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites.MethodA standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC).ResultsOf the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.DiscussionThis study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed