Contraction intensity affects NIRS-derived skeletal muscle oxidative capacity but not its relationships to mitochondrial protein content or aerobic fitness.

To further refine the near-infrared spectroscopy (NIRS)-derived measure of skeletal muscle oxidative capacity in humans, we sought to determine whether the exercise stimulus intensity affected the τ value and/or influenced the magnitude of correlations with in vitro measures of mitochondrial content and in vivo indices of exercise performance. Males (n = 12) and females (n = 12), matched for maximal aerobic fitness per fat-free mass, completed NIRS-derived skeletal muscle oxidative capacity tests for the vastus lateralis following repeated contractions at 40% (τ40) and 100% (τ100) of maximum voluntary contraction, underwent a skeletal muscle biopsy of the same muscle, and performed multiple intermittent isometric knee extension tests to task failure to establish critical torque (CT). The value of τ100 (34.4 ± 7.0 s) was greater than τ40 (24.2 ± 6.9 s, P < 0.001), but the values were correlated (r = 0.688; P < 0.001). The values of τ40 (r = -0.692, P < 0.001) and τ100 (r = -0.488, P = 0.016) correlated with myosin heavy chain I percentage and several markers of mitochondrial content, including COX II protein content in whole muscle (τ40: r = -0.547, P = 0.006; τ100: r = -0.466, P = 0.022), type I pooled fibers (τ40: r = -0.547, P = 0.006; τ100: r = -0.547, P = 0.006), and type II pooled fibers (τ40: r = -0.516, P = 0.009; τ100: r = -0.635, P = 0.001). The value of τ40 (r = -0.702, P < 0.001), but not τ100 (r = -0.378, P = 0.083) correlated with critical torque (CT); however, neither value correlated with W' (τ40: r = 0.071, P = 0.753; τ100: r = 0.054, P = 0.812). Overall, the NIRS method of assessing skeletal muscle oxidative capacity is sensitive to the intensity of skeletal muscle contraction but maintains relationships to whole body fitness, isolated limb critical intensity, and mitochondrial content regardless of intensity.NEW & NOTEWORTHY Skeletal muscle oxidative capacity measured using near-infrared spectroscopy (NIRS) was lower following high-intensity compared with low-intensity isometric knee extension contractions. At both intensities, skeletal muscle oxidative capacity was correlated with protein markers of mitochondrial content (in whole muscle and pooled type I and type II muscle fibers) and critical torque. These findings highlight the importance of standardizing contraction intensity while using the NIRS method with isometric contractions and further demonstrate its validity.

Differences in injury and concussion rates in a cohort of Canadian female and male youth Rugby Union: a step towards targeted prevention strategies.

OBJECTIVE: To examine differences in match and training musculoskeletal injury and concussion rates and describe mechanisms of concussion while considering previous playing experience in female and male Canadian high school Rugby Union ('rugby') players. METHODS: A 2-year prospective cohort study was completed in a high school league (n=361 females, 421 player-seasons; n=429 males, 481 player-seasons) in Calgary, Canada over the 2018 and 2019 rugby playing seasons. Baseline testing was completed at the start of each season and injury surveillance and individual player participation through session attendance was documented to quantify individual-level player exposure hours. Injury incidence rates (IRs) and incidence rate ratios (IRRs) were calculated using Poisson regression, offset by player exposure hours and clustered by team. RESULTS: Overall match IR for females was 62% higher than males (overall IRR=1.62, 95% CI: 1.20 to 2.18) and the overall training IR was twice as high for females (overall IRR=2.15, 95% CI: 1.40 to 3.32). The female match concussion IR was 70% higher than the males (concussion IRR=1.70, 95% CI: 1.08 to 2.69). Females had a 75% greater tackle-related IR compared with males (IRR=1.75, 95% CI: 1.20 to 2.56). Additionally, female tacklers had a twofold greater rate of injury compared with male tacklers (IRR=2.17, 95% CI: 1.14 to 4.14). Previous playing experience was not associated with tackle-related injury or concussion IRs. CONCLUSION: The rate of injury and concussion was significantly higher in females within this Canadian high school cohort. These results emphasise the need for development, implementation and evaluation of female-specific injury and concussion prevention strategies to reduce injury and concussion in female youth rugby.

The influence of skeletal muscle mitochondria and sex on critical torque and performance fatiguability in humans.

Critical torque (CT) represents the highest oxidative steady state for intermittent knee extensor exercise, but the extent to which it is influenced by skeletal muscle mitochondria and sex is unclear. Vastus lateralis muscle biopsy samples were collected from 12 females and 12 males -matched for relative maximal oxygen uptake normalized to fat-free mass (FFM) (F: 57.3 (7.5) ml (kg FFM)-1  min-1 ; M: 56.8 (7.6) ml (kg FFM)-1  min-1 ; P = 0.856) - prior to CT determination and performance fatiguability trials. Males had a lower proportion of myosin heavy chain (MHC) I isoform (40.6 (18.4)%) compared to females (59.5 (18.9)%; P = 0.021), but MHC IIa and IIx isoform distributions and protein markers of mitochondrial content were not different between sexes (P > 0.05). When normalized to maximum voluntary contraction (MVC), the relative CT (F: 42.9 (8.3)%; M: 37.9 (9.0)%; P = 0.172) and curvature constant, W' (F: 26.6 (11.0) N m s (N m)-1 ; M: 26.4 (6.5) N m s (N m)-1 ; P = 0.962) were not significantly different between sexes. All protein biomarkers of skeletal muscle mitochondrial content, as well as the proportion of MHC I isoform, positively correlated with relative CT (0.48 < r < 0.70; P < 0.05), and the proportion of MHC IIx isoform correlated positively with relative W' (r = 0.57; P = 0.007). Indices of performance fatiguability were not different between males and females for MVC- and CT-controlled trials (P > 0.05). Greater mitochondrial protein abundance was associated with attenuated declines in potentiated twitch torque for exercise at 60% MVC (P < 0.05); however, the influence of mitochondrial protein abundance on performance fatiguability was reduced when exercise was prescribed relative to CT. Whether these findings translate to whole-body exercise requires additional research. KEY POINTS: The quadriceps critical torque represents the highest intensity of intermittent knee extensor exercise for which an oxidative steady state is attainable, but its relationship with skeletal muscle mitochondrial protein abundance is unknown. Matching males and females for maximal oxygen uptake relative to fat-free mass facilitates investigations of sex differences in exercise physiology, but studies that have compared critical torque and performance fatiguability during intermittent knee extensor exercise have not ensured equal aerobic fitness between sexes. Skeletal muscle mitochondrial protein abundance was correlated with critical torque and fatigue resistance for exercise prescribed relative to maximum voluntary contraction but not for exercise performed relative to the critical torque. Differences between sexes in critical torque, skeletal muscle mitochondrial protein abundance and performance fatiguability were not statistically significant. Our results suggest that skeletal muscle mitochondrial protein abundance may contribute to fatigue resistance by influencing the critical intensity of exercise.

Assessment of dependence potential and abuse liability of Δ8-tetrahydrocannabinol in mice.

Delta-8-tetrahydrocannabinol (Δ8-THC) is a psychotropic cannabinoid produced in low quantities in the cannabis plant. Refinements in production techniques, paired with the availability of inexpensive cannabidiol substrate, have resulted in Δ8-THC being widely marketed as a quasi-legal, purportedly milder alternative to Δ9-THC. Yet, little research has probed the behavioral and physiological effects of repeated Δ8-THC use. The present study aimed to evaluate the effects of acute and repeated exposure to Δ8-THC. We hypothesized that Δ8-THC produces effects similar to Δ9-THC, including signs of drug tolerance and dependence. Adult male and female C57BL/6J mice were treated acutely with Δ8-THC (6.25-100 mg/kg, i.p.) or vehicle and tested in the tetrad battery to quantify cannabimimetic effects (i.e., catalepsy, antinociception, hypothermia, immobility) as compared with a non-selective synthetic cannabinoid (WIN 55,212-2) and Δ9-THC. As previously reported, Δ8-THC (≥12.5 mg/kg) induced cannabimimetic effects. Pretreatment with the CB1 receptor-selective antagonist rimonabant (3 mg/kg, i.p.) blocked each of these effects. In addition, repeated administration of Δ8-THC (50 mg/kg, s.c.) produced tolerance, as well as cross-tolerance to WIN 55,212-2 (10 mg/kg, s.c.) in tetrad, consistent with downregulated CB1 receptor function. Behavioral signs of physical dependence in the somatic signs, tail suspension, and marble burying assays were also observed following rimonabant-precipitated withdrawal from Δ8-THC (≥10 mg/kg BID for 6 days). Lastly, Δ8-THC produced Δ9-THC-like discriminative stimulus effects in both male and female mice. Together, these findings demonstrate that Δ8-THC produces qualitatively similar effects to Δ9-THC, including risk of drug dependence and abuse liability.

Caught on camera: a video assessment of suspected concussion and other injury events in women's rugby union.

OBJECTIVES: The objective of this study was to identify and report the incidence and mechanisms of suspected injury and concussion in women's rugby union. DESIGN: A cross-sectional video analysis study. METHODS: Using video analysis of non-professional, single-angle footage, cases of suspected injury and concussion were identified and reported, based on content validation and consensus by eight rugby-specific researchers, therapists, and sport medicine physicians. RESULTS: There were 225 suspected injuries recorded in 48 games [Suspected injury rate (IR) = 117.5/1000 h (95 % CI;102.6-133.9) or 4.7 suspected injuries per match]. The on-field medical attention IR was 95.0/1000 h (95 % CI;81.7-109.9: 3.8 per game). Suspected concussions accounted for 26 % of injuries (30.8/1000 h: 95 % CI;23.5-39.7: 1.2 per game). The attacking team sustained 64 % of suspected injuries. Permanent removal from play was observed for 29 % of suspected injuries. The most common suspected injury locations were head/neck (28.4 %) and lower extremity (27.6 %). The tackle accounted for 67.1 % of all suspected injuries, with a propensity of 11.2/1000 tackle events (95 % CI;9.5-13.2) or 3.1 tackle-related injuries/game. Of tackle-related injuries, 63.6 % were to the ball carrier while 52.2 % of tackle-related concussions were to the ball carrier. CONCLUSION: This study adds to the growing body of literature examining women's rugby. The rate of suspected injury is high compared with other studies. It is acknowledged that these are suspected injuries not supported by prospective injury surveillance. The high proportion of suspected injuries that are tackle-related warrants specific attention to identify tackle characteristics associated with injury and concussion.

The responsiveness and validity of the Rotator Cuff Quality of Life (RC-QOL) index in a 2-year follow-up study.

Background: The Rotator Cuff Quality of Life (RC-QOL) index was developed to evaluate quality of life in patients with rotator cuff disease. This study provides additional psychometric testing in accordance with the Consensus-Based Standards for the Selection of Health Measurement Instruments guidelines. Methods: This was a 2-year follow-up study on 66 patients (mean age, 59 ± 10 years) originally presenting with chronic full-thickness rotator cuff tears to a tertiary care center. The methodology involved testing internal consistency, content validity, and criterion validity. Responsiveness was evaluated using 3 strategies: 1) standardized response mean of the raw change scores; 2) Guyatt's Responsiveness Index; and 3) Global Rating Scales of improvement correlated to a quality of life measure. Results: Content validity was confirmed with a Cronbach α of 0.92 (95% confidence interval, 0.92-0.95) and absence of floor and ceiling effects. Criterion validity was confirmed using the Western Ontario Rotator Cuff Index as a reference standard (r = 0.87, P < .001). The effect size of distribution-based methods of determining responsiveness was large (0.99-1.09) compared to that of mixed- and anchor-based methods (0.47-0.89). All responsiveness calculations met minimum requirements for acceptable thresholds. Conclusion: The RC-QOL is a valid and responsive measure of health-related quality of life in patients with chronic rotator cuff pathology. The results of this study added to the methodologic quality assessment of the RC-QOL, completing 7 of 10 Consensus-Based Standards for the Selection of Health Measurement Instruments criteria.

Time course and fibre type-dependent nature of calcium-handling protein responses to sprint interval exercise in human skeletal muscle.

Sprint interval training (SIT) causes fragmentation of the skeletal muscle sarcoplasmic reticulum Ca2+ release channel, ryanodine receptor 1 (RyR1), 24 h post-exercise, potentially signalling mitochondrial biogenesis by increasing cytosolic [Ca2+ ]. Yet, the time course and skeletal muscle fibre type-specific patterns of RyR1 fragmentation following a session of SIT remain unknown. Ten participants (n = 4 females; n = 6 males) performed a session of SIT (6 × 30 s 'all-out' with 4.5 min rest after each sprint) with vastus lateralis muscle biopsy samples collected before and 3, 6 and 24 h after exercise. In whole muscle, full-length RyR1 protein content was significantly reduced 6 h (mean (SD); -38 (38)%; P < 0.05) and 24 h post-SIT (-30 (48)%; P < 0.05) compared to pre-exercise. Examining each participant's largest response in pooled samples, full-length RyR1 protein content was reduced in type II (-26 (30)%; P < 0.05) but not type I fibres (-11 (40)%; P > 0.05). Three hours post-SIT, there was also a decrease in sarco(endo)plasmic reticulum Ca2+ ATPase 1 in type II fibres (-23 (17)%; P < 0.05) and sarco(endo)plasmic reticulum Ca2+ ATPase 2a in type I fibres (-19 (21)%; P < 0.05), despite no time effect for either protein in whole muscle samples (P > 0.05). PGC1A mRNA content was elevated 3 and 6 h post-SIT (5.3- and 3.7-fold change from pre, respectively; P < 0.05 for both), but peak PGC1A mRNA expression was not significantly correlated with peak RyR1 fragmentation (r2  = 0.10; P > 0.05). In summary, altered Ca2+ -handling protein expression, which occurs primarily in type II muscle fibres, may influence signals for mitochondrial biogenesis as early as 3-6 h post-SIT in humans. KEY POINTS: Sprint interval training (SIT) has been shown to cause fragmentation of the sarcoplasmic reticulum calcium-release channel, ryanodine receptor 1 (RyR1), 24 h post-exercise, which may act as a signal for mitochondrial biogenesis. In this study, the time course was examined of RyR1 fragmentation in human whole muscle and pooled type I and type II skeletal muscle fibres following a single session of SIT. Full-length RyR1 protein content was significantly lower than pre-exercise by 6 h post-SIT in whole muscle, and fragmentation was detectable in type II but not type I fibres, though to a lesser extent than in whole muscle. The peak in PGC1A mRNA expression occurred earlier than RyR1 fragmentation. The increased temporal resolution and fibre type-specific responses for RyR1 fragmentation provide insights into its importance to mitochondrial biogenesis in humans.

The Impact of Concussion, Sport, and Time in Season on Saliva Telomere Length in Healthy Athletes.

To date, sport-related concussion diagnosis and management is primarily based on subjective clinical tests in the absence of validated biomarkers. A major obstacle to clinical validation and application is a lack of studies exploring potential biomarkers in non-injured populations. This cross-sectional study examined the associations between saliva telomere length (TL) and multiple confounding variables in a healthy university athlete population. One hundred eighty-three (108 male and 75 female) uninjured varsity athletes were recruited to the study and provided saliva samples at either pre- or mid-season, for TL analysis. Multiple linear regression was used to determine the associations between saliva TL and history of concussion, sport contact type, time in season (pre vs. mid-season collection), age, and sex. Results showed no significant associations between TL and history of concussion, age, or sport contact type. However, TL from samples collected mid-season were longer than those collected pre-season [ß = 231.4, 95% CI (61.9, 401.0), p = 0.008], and males had longer TL than females [ß = 284.8, 95% CI (111.5, 458.2), p = 0.001] when adjusting for all other variables in the model. These findings population suggest that multiple variables may influence TL. Future studies should consider these confounders when evaluating saliva TL as a plausible fluid biomarker for SRC.

The effect of an exertional field-test on sport concussion assessment tool 5 subcomponents in University rugby and wrestling athletes: A pilot prospective case series.

OBJECTIVES: To evaluate how an exertional field-test impacts the Sport Concussion Assessment Tool 5 (SCAT5) subcomponents in uninjured athletes. DESIGN: Prospective case-series. SETTING: Sports medicine setting. PARTICIPANTS: A total of 37 rugby and wrestling athletes (76% female) with a median age of 19 years (range: 18-23). Twenty-one (57%) had a history of concussion. MAIN OUTCOME MEASURES: The SCAT5 was administered prior-to and following a volitionally fatiguing, field-based 30-15 Intermittent Fitness Test. The primary outcome measures included: total symptom scores and severity, standardized assessment of concussion, neurological screening, and balance errors during the modified balance error scoring system. Wilcoxon signed-rank tests examined differences in ordinal data between pre- and post-exertion with Bonferroni corrections (alpha = 0.006). Data were also stratified into time to SCAT5 administration post-exertion and compared via Cliff's Delta (d). RESULTS: The SCAT5 was administered a median of 20-min (interquartile range: 14-26-min) following exertion. No differences were found pre- and post-exertion across all SCAT5 metrics (p > 0.048). Within the post-exertion 0-10-min stratification, total symptoms and severity scores appeared to be elevated with a large effect size (d ≥ 0.64). CONCLUSIONS: While SCAT5 metrics were not statistically altered when quantified a median of 20-min following high-intensity exertion; greater symptom reporting may occur 10-min following exertion.

One-year stability of preseason Sport Concussion Assessment Tool 5 (SCAT5) values in university level collision and combative sport athletes.

OBJECTIVES: To determine the stability of the Sport Concussion Assessment Tool (SCAT) 5 between consecutive seasons in uninjured collision and combative varsity athletes. METHODS: Thirty-six athletes (19 females) were recruited to participate (wrestling [n = 12], rugby [n = 14], and hockey [n = 10]). The SCAT5 was administration at the start of the 2017 and 2018 seasons. Median baseline demographics for 2017 were as follows: age (19 years [range: 17-24 years]), height (174 cm [range: 149-195 cm]), and weight (76 kg [range: 57-118 kg]). Outcome metrics included subcomponents of the SCAT5: symptom reporting, standardized assessment of concussion (SAC), neurological screening, and balance performance measured with the modified balance error scoring system (mBESS). Wilcoxon signed-rank tests and Cronbach's alpha (α) values were calculated to determine the stability between consecutive years for the SCAT5 variables in the same cohort of athletes. Bonferroni corrections were applied for Wilcoxon signed-rank tests, where alpha = 0.006 (0.05/9). RESULTS: Between the 2017 and 2018 seasons, no differences were noted in symptom reporting (p = 0.14), SAC (p = 0.32), neurological screening (p = 0.98), and balance performance on the mBESS (p = 0.01). The Cronbach's alpha displayed unacceptable to questionable levels of within-subject stability (range: α = 0.34-0.70) for all subcomponents, except months in reverse order (α = 0.92). CONCLUSIONS: While no statistical differences were present for all SCAT5 subcomponent metrics between 2017 and 2018 baselines, all but one displayed unacceptable to questionable stability (α ≤ 0.70) when retested one year later. Further research is needed to understand the appropriate time duration baseline SCAT5 values can reliably be utilized within longitudinal studies; as well as the normal variation of SCAT5 reporting/scoring.

The effect of high-intensity physical exertion on measures of cervical spine, vestibular/ocular-motor screening, and vestibulo-ocular reflex function in university level collision and combative sport athletes.

OBJECTIVES: To examine how high-intensity physical exertion affects clinical measures of cervical spine (CSp), vestibular/ocular motor screen (VOMS), and vestibulo-ocular reflex (VOR) function. DESIGN: Case series. SETTING: Sports Medicine Centre. PARTICIPANTS: A total of 37 athletes consented to participate (22 rugby, 15 wrestling; 9 men, 28 women; median age = 19 years [range 17-23 years]). MAIN OUTCOME MEASURES: Outcome measures included tests of CSp (cervical flexor endurance, head perturbation test, cervical flexion rotation test and anterolateral strength), VOR (head thrust test and dynamic visual acuity [DVA]), and a quantified version of the VOMS. These metrics were assessed prior to and after completing the 30-15 Intermittent Fitness Test. Bland-Altman plots and Wilcoxon signed-rank tests were utilized to analyze the data using an alpha of p < 0.004. RESULTS: Cervical anterolateral strength (kg) was reduced post-exertion on the left (z = 3.87; p < 0.001), but not on the right between conditions (z = -1.49; p = 0.14). Athletes reported increased dizziness (z = -3.55; p = 0.004) and had reduced DVA following exertion (z = -2.78; p < 0.001). All other metrics were not significantly different following exertion (p > 0.011). CONCLUSION: Reduced performance on DVA, decreased left-anterolateral strength, and increased dizziness occurred following high-intensity exertion in varsity collision and combative athletes, which has implications for sideline screening for sport-related concussion.

Uncovering Survivorship Bias in Longitudinal Mental Health Surveys During the COVID-19 Pandemic.

AIMS: Markedly elevated adverse mental health symptoms were widely observed early in the coronavirus disease 2019 (COVID-19) pandemic. Unlike the U.S., where cross-sectional data indicate anxiety and depression symptoms have remained elevated, such symptoms reportedly declined in the U.K., according to analysis of repeated measures from a largescale longitudinal study. However, nearly 40% of U.K. respondents (those who did not complete multiple follow-up surveys) were excluded from analysis, suggesting that survivorship bias might partially explain this discrepancy. We therefore sought to assess survivorship bias among participants in our longitudinal survey study as part of The COVID-19 Outbreak Public Evaluation (COPE) Initiative. METHODS: Survivorship bias was assessed 4,039 U.S. respondents who completed surveys including the assessment of mental health as part of The COPE Initiative in April 2020 and were invited to complete follow-up surveys. Participants completed validated screening instruments for symptoms of anxiety, depression, and insomnia. Survivorship bias was assessed for (1) demographic differences in follow-up survey participation, (2) differences in initial adverse mental health symptom prevalences adjusted for demographic factors, and (3) differences in follow-up survey participation based on mental health experiences adjusted for demographic factors. RESULTS: Adjusting for demographics, individuals who completed only one or two out of four surveys had higher prevalences of anxiety and depression symptoms in April 2020 (e.g., one-survey versus four-survey, anxiety symptoms, adjusted prevalence ratio [aPR]: 1.30, 95% confidence interval [CI]: 1.08-1.55, P=0.0045; depression symptoms, aPR: 1.43, 95% CI: 1.17-1.75, P=0.00052). Moreover, individuals who experienced incident anxiety or depression symptoms had higher odds of not completing follow-up surveys (adjusted odds ratio [aOR]: 1.68, 95% CI: 1.22-2.31, P=0.0015, aOR: 1.56, 95% CI: 1.15-2.12, P=0.0046, respectively). CONCLUSIONS: Our findings revealed significant survivorship bias among longitudinal survey respondents, indicating that restricting analytic samples to only respondents who provide repeated assessments in longitudinal survey studies could lead to overly optimistic interpretations of mental health trends over time. Cross-sectional or planned missing data designs may provide more accurate estimates of population-level adverse mental health symptom prevalences than longitudinal surveys.

Influence of landscape management practices on urban greenhouse gas budgets.

BACKGROUND: With a lack of United States federal policy to address climate change, cities, the private sector, and universities have shouldered much of the work to reduce carbon dioxide (CO2) and other greenhouse gas emissions. This study aims to determine how landcover characteristics influence the amount of carbon (C) sequestered and respired via biological processes, evaluating the role of land management on the overall C budget of an urban university. Boston University published a comprehensive Climate Action Plan in 2017 with the goal of achieving C neutrality by 2040. In this study, we digitized and discretized each of Boston University's three urban campuses into landcover types, with C sequestration and respiration rates measured and scaled to provide a University-wide estimate of biogenic C fluxes within the broader context of total University emissions. RESULTS: Each of Boston University's three highly urban campuses were net sources of biogenic C to the atmosphere. While trees were estimated to sequester 0.6 ± 0.2 kg C m-2 canopy cover year-1, mulch and lawn areas in 2018 emitted C at rates of 1.7 ± 0.4 kg C m-2 year-1 and 1.4 ± 0.4 kg C m-2 year-1, respectively. C uptake by tree canopy cover, which can spatially overlap lawn and mulched landcovers, was not large enough to offset biogenic emissions. The proportion of biogenic emissions to Scope 1 anthropogenic emissions on each campus varied from 0.5% to 2%, and depended primarily on the total anthropogenic emissions on each campus. CONCLUSIONS: Our study quantifies the role of urban landcover in local C budgets, offering insights on how landscaping management strategies-such as decreasing mulch application rates and expanding tree canopy extent-can assist universities in minimizing biogenic C emissions and even potentially creating a small biogenic C sink. Although biogenic C fluxes represent a small fraction of overall anthropogenic emissions on urban university campuses, these biogenic fluxes are under active management by the university and should be included in climate action plans.

Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts.

A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.

Pulmonary mucormycosis with extensive bronchial necrosis and bronchomediastinal fistula: A case report and review.

Mucormycosis is a life-threatening infection caused by fungi in the Mucorales species. It most often affects immunocompromised hosts, including diabetics patients. It can affect a variety of organ systems with pulmonary manifestations being the second most common. In severe cases, significant bronchial necrosis and angioinvasion can be seen. Due to its rarity, such extensive cases are not often reported in literature. We present a case of a 32-year-old man who presented with severe bronchial necrosis, including bronchomediastinal fistula, due to Rhizopus. Despite prompt treatment, he developed massive hemoptysis from invasion of the pulmonary vasculature and died. We also provide a brief review of mucormycosis.

Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines.

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 µM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.

Exploring the Business Case for Improving Quality of Care for Patients With Chronic Rotator Cuff Tears.

BACKGROUND AND OBJECTIVES: Currently, management of patients presenting with chronic rotator cuff tears in Alberta is in need of quality improvements. This article explores the potential impact of a proposed care pathway whereby all patients presenting with chronic rotator cuff tears in Alberta would adopt an early, conservative management plan as the first stage of care; ultrasound investigation would be the preferred tool for diagnosing a rotator cuff tear; and only patients are referred for surgery once conservative measures have been exhausted. METHODS: We evaluate evidence in support of surgery and conservative management, compare care in the current state with the proposed care pathway, and identify potential solutions in moving toward optimal care. RESULTS: A literature search resulted in an absence of indications for either surgical or conservative management. Conservative management has the potential to reduce utilization of public health care resources and may be preferable to surgery. The proposed care pathway has the potential to avoid nearly Can $87 000 in public health care costs in the current system for every 100 patients treated successfully with conservative management. CONCLUSION: The proposed care pathway is a low-cost, first-stage treatment that is cost-effective and has the potential to reduce unnecessary, costly surgical procedures.

Clostridium scindens ATCC 35704: Integration of Nutritional Requirements, the Complete Genome Sequence, and Global Transcriptional Responses to Bile Acids.

In the human gut, Clostridium scindens ATCC 35704 is a predominant bacterium and one of the major bile acid 7α-dehydroxylating anaerobes. While this organism is well-studied relative to bile acid metabolism, little is known about the basic nutrition and physiology of C. scindens ATCC 35704. To determine the amino acid and vitamin requirements of C. scindens, the leave-one-out (one amino acid group or vitamin) technique was used to eliminate the nonessential amino acids and vitamins. With this approach, the amino acid tryptophan and three vitamins (riboflavin, pantothenate, and pyridoxal) were found to be required for the growth of C. scindens In the newly developed defined medium, C. scindens fermented glucose mainly to ethanol, acetate, formate, and H2. The genome of C. scindens ATCC 35704 was completed through PacBio sequencing. Pathway analysis of the genome sequence coupled with transcriptome sequencing (RNA-Seq) under defined culture conditions revealed consistency with the growth requirements and end products of glucose metabolism. Induction with bile acids revealed complex and differential responses to cholic acid and deoxycholic acid, including the expression of potentially novel bile acid-inducible genes involved in cholic acid metabolism. Responses to toxic deoxycholic acid included expression of genes predicted to be involved in DNA repair, oxidative stress, cell wall maintenance/metabolism, chaperone synthesis, and downregulation of one-third of the genome. These analyses provide valuable insight into the overall biology of C. scindens which may be important in treatment of disease associated with increased colonic secondary bile acids.IMPORTANCEC. scindens is one of a few identified gut bacterial species capable of converting host cholic acid into disease-associated secondary bile acids such as deoxycholic acid. The current work represents an important advance in understanding the nutritional requirements and response to bile acids of the medically important human gut bacterium, C. scindens ATCC 35704. A defined medium has been developed which will further the understanding of bile acid metabolism in the context of growth substrates, cofactors, and other metabolites in the vertebrate gut. Analysis of the complete genome supports the nutritional requirements reported here. Genome-wide transcriptomic analysis of gene expression in the presence of cholic acid and deoxycholic acid provides a unique insight into the complex response of C. scindens ATCC 35704 to primary and secondary bile acids. Also revealed are genes with the potential to function in bile acid transport and metabolism.

Validation of a tool to assess patient satisfaction, waiting times, healthcare utilization, and cost.

AIM: Patients' experience of the quality of care received throughout their continuum of care can be used to direct quality improvement efforts in areas where they are most needed. This study aims to establish validity and reliability of the Healthcare Access and Patient Satisfaction Questionnaire (HAPSQ) - a tool that collects patients' experience that quantifies aspect of care used to make judgments about quality from the perspective of the Alberta Quality Matrix for Health (AQMH). BACKGROUND: The AQMH is a framework that can be used to assess and compare the quality of care in different healthcare settings. The AQMH provides a common language, understanding, and approach to assessing quality. The HAPSQ is one tool that is able to assess quality of care according to five of six AQMH's dimensions. METHODS: This was a prospective methodologic study. Between March and October 2015, a convenience sample of patients presenting with chronic full-thickness rotator cuff tears was recruited prospectively from the University of Calgary Sport Medicine Centre in Calgary, Alberta, Canada. Reliability of the HAPSQ was assessed using test-retest reliability [interclass correlation coefficient (ICC)>0.70]. Validity was assessed through content validity (patient interviews, floor and ceiling effects), criterion validity (percent agreement >70%), and construct validity (hypothesis testing). FINDINGS: Reliability testing was completed on 70 patients; validity testing occurred on 96 patients. The mean duration of symptoms was three years (SD: 5.0, range: 0.1-29). Only out-of-pocket utilization possessed an ICC<0.70. Patients reported that items were relevant and appropriate to measuring quality of care. No floor or ceiling effects were present. Criterion validity was reached for all items assessed. A priori hypotheses were confirmed. The HAPSQ represents an inexpensive, reliable, and valid approach toward collecting clinical information across a patient's continuum of care.

Robotic Assessment of Motor, Sensory, and Cognitive Function in Acute Sport-Related Concussion and Recovery.

There is a need for better tools to objectively, reliably, and precisely assess neurological function after sport-related concussion (SRC). The aim of this study was to use a robotic device (Kinesiological Instrument for Normal and Altered Reaching Movements; KINARM) to quantify neurological impairments in athletes acutely and when clinically asymptomatic post-SRC. Robotic assessments included five KINARM standard tasks that evaluate aspects of motor, sensory, and cognitive function. We hypothesized that acutely concussed athletes would demonstrate significant rates of impairment on the robotic assessment, and that impairments would be associated with acute symptom severity. Pre-season assessments were conducted from 2011 to 2016 on 1051 athletes. Eighty-four athletes were reassessed acutely (≤10 days post-injury) and while symptomatic post-SRC and 89 when clinically asymptomatic. Forty-four parameters were measured from the KINARM assessment to characterize neurological function. Reliable change indices (80% confidence interval) identified impairments in healthy and concussed individuals for each parameter. In concussed individuals, impairment rate varied across parameters from 4% to 27% at the acute time point and from 2% to 18% when clinically asymptomatic. Healthy athlete impairment rates were between 2% and 16% across all testing time points. We identified relationships between acute symptom severity and task performance for only two parameters, both of which evaluated attributes of motor function. Overall, the KINARM identified impairments in motor, sensory, and cognitive function in athletes with SRC; however, impairment rates were low and largely did not relate to symptom severity. More complex tasks may be necessary to identify potentially subtle neurological impairments post-SRC.