Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported

Mass spectrometry imaging of cassette-dosed drugs for higher throughput pharmacokinetic and biodistribution analysis

Cassette dosing of compounds for preclinical drug plasma pharmacokinetic analysis has been shown to be a powerful strategy within the pharmaceutical industry for increasing throughput while decreasing the number of animals used. Presented here for the first time is data on the application of a cassette dosing strategy for label-free tissue distribution studies. The aim of the study was to image the spatial distribution of eight nonproprietary drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxifloxacin) in multiple tissues after oral and intravenous cassette dosing (four compounds per dose route). An array of mass spectrometry imaging technologies, including matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), liquid extraction surface analysis tandem mass spectrometry (LESA-MS/MS), and desorption electrospray ionization mass spectrometry (DESI-MS) was used. Tissue analysis following intravenous and oral administration of discretely and cassette-dosed compounds demonstrated similar relative abundances across a range of tissues indicating that a cassette dosing approach was applicable. MALDI MSI was unsuccessful in detecting all of the target compounds; therefore, DESI MSI, a complementary mass spectrometry imaging technique, was used to detect additional target compounds. In addition, by adapting technology used for tissue profiling (LESA-MS/MS) low spatial resolution mass spectrometry imaging (∼1 mm) was possible for all targets across all tissues. This study exemplifies the power of multiplatform MSI analysis within a pharmaceutical research and development (R&D) environment. Furthermore, we have illustrated that the cassette dosing approach can be readily applied to provide combined, label-free pharmacokinetic and drug distribution data at an early stage of the drug discovery/development process while minimizing animal usage

Sport, sex and age increase risk of illness at the Rio 2016 Summer Paralympic Games: a prospective cohort study of 51 198 athlete days

OBJECTIVETo describe the epidemiology of illness at the Rio 2016 Summer Paralympic Games. METHODS A total of 3657 athletes from 78 countries, representing 83.5% of all athletes at the Games, were monitored on the web-based injury and illness surveillance system (WEB-IISS) over 51 198 athlete days during the Rio 2016 Summer Paralympic Games. Illness data were obtained daily from teams with their own medical support through the WEB-IISS electronic data capturing systems. RESULTSThe total number of illnesses was 511, with an illness incidence rate (IR) of 10.0 per 1000 athlete days (12.4%). The highest IRs were reported for wheelchair fencing (14.9), para swimming (12.6) and wheelchair basketball (12.5) (p<0.05). Female athletes and older athletes (35–75 years) were also at higher risk of illness (both p<0.01). Illnesses in the respiratory, skin and subcutaneous and digestive systems were the most common (IRs of 3.3, 1.8 and 1.3, respectively). CONCLUSION (1) The rate of illness was lower than that reported for the London 2012 Summer Paralympic Games; (2) the sports with the highest risk were wheelchair fencing, para swimming and wheelchair basketball; (3) female and older athletes (35–75 years) were at increased risk of illness; and (4) the respiratory system, skin and subcutaneous system and digestive system were most affected by illness. These results allow for comparison at future Games

Risk of injuries in Paralympic track and field differs by impairment and event discipline A prospective cohort study at the London 2012 Paralympic Games

Background: The incidence rates (IRs) and factors associated with injuries in the sport of Paralympic athletics (track and field) have not been comprehensively and prospectively studied. Purpose: To determine injury IRs, characteristics of injuries, and associated factors in the sport of athletics at the London 2012 Paralympic Games. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 977 athletes competing in the sport of athletics were followed over a total 10-day competition period of the Paralympic Games. Daily injury data were obtained via 2 databases: (1) a custom-built, web-based injury and illness surveillance system (WEB-IISS), maintained by team medical personnel; and (2) the organizing committee database, maintained by medical providers in the medical stations operated by the London Organising Committee of the Olympic and Paralympic Games. Athlete impairment and event discipline were obtained via the International Paralympic Committee athlete database. IRs (injuries per 1000 athlete-days) by impairment, event discipline, sex, and age were examined. Results: The overall IR was 22.1 injuries per 1000 athlete-days (95% CI, 19.5-24.7). In track disciplines, ambulant athletes with cerebral palsy experienced a lower incidence of injuries (IR, 10.2; 95% CI, 4.2-16.2) when compared with ambulant athletes from other impairment categories. Athletes in seated throwing experienced a higher incidence of injuries (IR, 23.7; 95% CI, 17.5-30.0) when compared with athletes in wheelchair racing (IR, 10.6; 95% CI, 5.5-15.6). In both track and field disciplines, the majority of injuries did not result in time loss from competition or training. Ambulant athletes experienced the greatest proportion of injuries to the thigh (16.4% of all injuries; IR, 4.0), observed predominantly in track athletes. Wheelchair or seated athletes experienced the greatest proportion of injuries to the shoulder/clavicle (19.3% of all injuries; IR, 3.4), observed predominantly in field athletes. Conclusion: This is the first prospective cohort study examining injury IRs and associated factors in the sport of athletics at the Paralympic Games. Injury patterns were specific to the event discipline and athlete impairment. The majority of injuries occurred to the thigh (ambulant athletes) or shoulder/clavicle (wheelchair or seated athletes) and did not result in time loss. </jats:sec

Poor reproducibility of compression elastography in the Achilles tendon: same day and consecutive day measurements.

OBJECTIVE To determine the reproducibility of compression elastography (CE) when measuring strain data, a measure of stiffness of the human Achilles tendon in vivo, over consecutive measures, consecutive days and when using different foot positions. MATERIALS AND METHODS Eight participants (4 males, 4 females; mean age 25.5 ± 2.51 years, range 21-30 years; height 173.6 ± 11.7 cm, range 156-189 cm) had five consecutive CE measurements taken on one day and a further five CE measures taken, one per day, at the same time of day, every day for a consecutive 5-day period. These 80 measurements were used to assess both the repeatability and reproducibility of the technique. Means, standard deviations, coefficient of variation (CV), Pearson correlation analysis (R) and intra-class correlation coefficients (ICC) were calculated. RESULTS For CE data, all CVs were above 53%, R values indicated no-to-weak correlations between measures at best (range 0.01-0.25), and ICC values were all classified in the poor category (range 0.00-0.11). CVs for length and diameter measures were acceptably low indicating a high level of reliability. CONCLUSIONS Given the wide variation obtained in the CE results, it was concluded that CE using this specific system has a low level of reproducibility for measuring the stiffness of the human Achilles tendon in vivo over consecutive days, consecutive measures and in different foot positions

Reproducibility of shear wave elastography measuresof the Achilles tendon.

OBJECTIVE To assess the reproducibility of shear wave elastography (SWE) measures in the Achilles tendon (AT) in vivo. MATERIALS AND METHODS Shear wave velocity (SWV) of 14 healthy volunteers [7 males, 7 females; mean age 26.5 ± 3.8 years, mean height 171.6 ± 10.9 cm, mean Victorian Institute of Sports Assessment Achilles questionnaire (VISA-A) score 99.4 ± 1.2] was measured with the foot relaxed and fixed at 90°. Data were collected over five consecutive measures and 5 consecutive days. RESULTS Mean SWV values ranged from 7.91 m/s-9.56 m/s ± 0.27-0.50 m/s. Coefficient of variation (CV), correlations and intra-class correlation coefficient (ICC) scores ranged from 2.9%-6.3%, 0.4-0.7 and 0.54-0.85 respectively. No significant differences were noted for longitudinal or transverse data with respect to protocol or time and no significant differences were noted for foot position in transverse data. Significant differences in SWV values were noted between foot positions for longitudinal scanning (p = <0.05), with a relaxed foot position providing SWV values on average 0.47 m/s faster than a fixed position. Increased reproducibility was obtained with the foot relaxed. ICC between operators was 0.70 for transverse and 0.80 for longitudinal scanning. CONCLUSIONS Reproducible SWE measures were obtained over a 1-h period as well as a period of 5 consecutive days with more reliable measures obtained from a longitudinal plane using a relaxed foot position. SWE also has a high level of agreement between operators making SWE a reproducible technique for quantitatively assessing the mechanical properties of the human AT in vivo

The Epidemiology of Injuries in Football at the London 2012 Paralympic Games

BACKGROUND : The epidemiology of injury in Paralympic football has received little attention. A study of all sports at the London 2012 Paralympic Games identified football 5-a-side as the sport with the highest injury rate, meriting further detailed analysis, which may facilitate the development of strategies to prevent injuries. OBJECTIVE : To examine the injury rates and risk factors associated with injury in Paralympic football. DESIGN : Secondary analysis of a prospective cohort study of injuries to football 5-a-side and football 7-a-side athletes. SETTING : London 2012 Paralympic Games. Participants: Participants included 70 football 5-a-side athletes and 96 football 7-a-side athletes. Athletes from all but one country chose to participate in this study. METHODS : The Paralympic Injury and Illness Surveillance System was used to track injuries during the Games, with data entered by medical staff. MAIN OUTCOME MEASURMENTS : Injury incidence rate (IR) and injury incidence proportion (IP). RESULTS : The overall IR for football 5-a-side was 22.4 injuries/1000 athlete-days (95% confidence interval [CI], 14.1-33.8) with an IP of 31.4 injuries per 100 athletes (95% CI, 20.9- 43.6). In 5-a-side competition, 62.5% of injuries were associated with foul play. The overall IR for football 7-a-side was 10.4 injuries/1000 athlete-days (95% CI, 5.4-15.5), with an IP of 14.6 injuries per 100 athletes (95% CI, 7.5-21.6). The most commonly injured body region in both sports was the lower extremity. CONCLUSIONS : To our knowledge, this study is the first to examine IR and risk factors associated with injury in Paralympic football. Future studies are needed to determine mechanisms of injury and independent risk factors for injury, thus informing prevention strategies.http://www.pmrjournal.org2017-06-30hb2016Sports Medicin