Does the Analysis of Separate Bands of Echo Intensity Strengthen the Relationship to Muscle Function?

Ultrasound echo intensity (EI) has been proposed as a method of assessing muscle quality through the use of non-invasive imaging. Traditionally, EI is assessed as the mean pixel brightness that ranges from 0-255 within an area of interest. However, it may be reasonable to consider that additional portions of the ultrasound EI signal (i.e., bands of signal) may provide novel insight to muscle function. The determination of which band of signal may be more related to a given functional outcome may increase the sensitivity of EI. Thus far, there is no research analyzing the association between EI bands and fatigue. PURPOSE: The purpose of this study was to compare relationships between mean echo intensity and unique bands of ultrasound signal of the vastus lateralis with metrics of whole muscle performance in healthy adults. METHODS: Twenty-four participants (mean ± age = 22 ± 3.9 yrs; BMI = 25.7 ± 3.4 kg/m2), completed two visits to the laboratory. On the first visit, subjects completed Brightness mode (B-mode) ultrasound imaging and were familiarized with the fatigue assessment. Between two and seven days later, subjects returned for the testing visit. B-mode ultrasound was used to image the vastus lateralis (VL) at 50% muscle length. The VL cross-sectional area was traced using the polygon tool. As much of the muscle was selected without selecting any of the surrounding fascia. Each pixel is assigned a brightness value from 0-255 based on gray scale; 0 representing true black and 255 is pure white. Mean EI was quantified from within the selected portion of the image. Echo intensity bands were calculated in pixel value intervals of 0-49, 50-99, 100-149, 150-199, 200-255. The percentage of pixels per band compared to the total number of pixels in each image was assessed by: (number of pixels in each band/ total number of pixels in the selected portion of the image)*100. For the fatigue assessment, participants completed 100 repeated, maximal, isokinetic muscle actions (120°/sec). Isokinetic peak torque was analyzed offline using custom written software by selecting individual torque peaks from each muscle action. Initial and final isokinetic peak torque were calculated by averaging the highest 3 of the first 5 and the highest 3 of the last 5 contractions. Isokinetic peak torque percent decline (%Decline) was calculated by: %Decline = (initial – PT – final - PT)/initial - PT. Pearson’s correlation coefficient (r) was used to assess the relationship between each EI band and %Decline as well as mean EI and %Decline. The Stieger’s Z procedure was used to compare the correlation coefficients between mean EI and each EI band. RESULTS: There were no significant correlation between mean EI and %Decline (r=0.03, p=0.88) or any of the EI bands and %Decline (r=-0.07-0.3, p=0.16-0.89). Additionally, there were no significant relationships between the mean EI and any of the EI bands (z=0.001-0.88, p=0.38-0.99). CONCLUSION: The findings suggest that unique bands of ultrasound signal do not offer different relationships compared to overall mean EI when assessing fatigue from repetitive isokinetic muscle actions

Bioimpedance Spectroscopy Compared to Ultrasound-derived Measures of Quadriceps Muscle Quality

Muscle quality is often measured using ultrasound-derived echo intensity (EI). Recent works have shown tissue frequency-dependent electrical impedance from bioimpedance spectroscopy may be a modality for assessing tissue quality. PURPOSE: The purpose of the project was to examine the association between ultrasound-derived EI of the quadriceps muscles (i.e., vastus lateralis [VL], vastus medialis [VM], vastus intermedius [VI], rectus femoris [RF]) and measures of thigh tissue frequency-dependent electrical impedance (i.e., R0, R1, C, a, fp). METHODS: Twenty-four participants (13 women; mean ± SD; age: 22 ± 4 years; BMI: 25.47 ± 3.26 kg/m2) were recruited. Participants completed one laboratory visit where quadriceps tissue quality was assessed via ultrasound and bioimpedance spectroscopy (BIS). Participants laid supine on a portable exam table to undergo imaging of the dominant leg VL using ultrasound in conjunction with a multi-frequency linear array probe (L4 – 12t – RS, 4.2-13 MHz, 47.1mm field of view). The VL was marked at the proximal and distal musculo-tendon junctions determined via ultrasound and the length was measured with a tape measure. Participants had cross-sectional scans of the VM, VL, VI, and RF at 25, 50, 75% of the length of the VL. Images were analyzed using the polygon tool in ImageJ to trace the muscles and provide EI values. Subcutaneous fat width was measured using the straight-line tool. Echo intensity was calculated using ImageJ gray-scale analysis and histogram function as well as corrected for subcutaneous fat. For statistical analyses, the average corrected EI for each muscle was created across scan sites. For BIS, participants were seated in a chair with Ag/AgCl electrodes placed above the patella and below the hip. Electrodes were placed 6cm apart and the Cole-impedance model was used to represent frequency-dependent thigh tissue data. Signals were analyzed using a custom-written software program. Pearson’s correlation coefficient (r) was used to determined associations between the VL, VM, VI, RF and BIS variables (R0, R1, C, a, fp). An alpha level of p ≤ 0.05 determined statistical significance. RESULTS: The results suggest that VL, VM, VI and RF echo intensity was significantly related to R0 (r = 0.65 – 0.81; p \u3c 0.01). For VI and RF, they were significantly related to a (r = -0.51 – -0.50; p = 0.01), but not for VL or VM (r = -0.39 - -0.22; p \u3e 0.06). Lastly, R1, C, and fp were not significantly correlated to the quadriceps muscles (r = -0.38 – 0.33; p \u3e 0.07). CONCLUSION: Our findings suggest that BIS-derived R0 may be a metric of muscle quality of the quadriceps as it was significantly related to ultrasound-derived measures of echo intensity of the VL, VM, VI, and RF. Further investigation of other muscle groups may be warranted

Body Composition and Anthropometric Changes During a 10-week Training Academy in Police Recruits

Obesity and cardiometabolic risk factors are often present in law enforcement personnel, which may compromise physical readiness and long-term health. As such, physical fitness interventions are warranted for promoting officers\u27 performance and wellbeing. PURPOSE: To determine the body composition and anthropometric changes experienced by police recruits undergoing a departmental training academy. METHODS: Twenty-one police recruits (20 M, 1 F; age: 25.1 ± 5.0 y; BMI: 27.8 ± 4.3 kg/m2) were tested before and after a 10-week training academy in Lubbock, Texas. Supervised physical training was conducted 5 times per week and consisted of ~1–1.5 hours of high-intensity, multi-modal (i.e., running, weightlifting, calisthenics), functional training following linear periodization. Dual-energy X-ray absorptiometry (DXA; GE Lunar iDXA) and 3-dimensional optical imaging (3DO; Size Stream SS20) were performed to assess body composition and anthropometry. Paired-samples t-tests were performed to compare values before and after the training academy, and Cohen’s d effect sizes were generated. After Bonferroni correction, statistical significance was accepted at p\u3c0.003. Changes are presented as mean ± SD. RESULTS: From DXA, statistically significant decreases in total fat mass (FM; -3.3 ± 3.1 kg, p\u3c0.001, d=1.1), trunk FM (-2.1 ± 2.2 kg, p\u3c0.001, d=1.0), arms FM (-0.3 ± 0.3 kg, p=0.001, d=1.1), legs FM (-0.9 ± 0.9 kg, p\u3c0.001, d=1.1), and body fat percentage (-3.1 ± 2.5%, p\u3c0.001, d=1.2) were observed. Increases in total lean soft tissue (LST; 1.3 ± 1.3 kg, p=0.002, d=1.0) and trunk LST (0.8 ± 0.9 kg, p\u3c0.001, d=0.9) were also noted, with trends for increases in leg LST (0.2 ± 0.7 kg, p=0.096, d=0.4) and arm LST (0.2 ± 0.4, p=0.04, d=0.5). Decreases in 3DO abdomen circumference (-3.5 ± 3.8 cm, p\u3c0.001, d=0.9) and hip circumference (-2.2 ± 2.2 cm, p\u3c0.001, d=1.0) were noted, with trends for decreases in the circumferences of the waist (-2.4 ± 3.6 cm, p=0.007, d=0.7) and upper arm (-0.9 ± 1.5 cm, p=0.02, d=0.6). No significant changes in thigh circumference (-0.7 ± 1.9 cm, p=0.12, d=0.4) or calf circumference (-0.2 ± 1.5 cm, p=0.52, d=0.1) were noted. A trend for a decrease in body mass (-2.0 ± 3.1 kg, p=0.007, d=0.7) was also observed. CONCLUSION: The present study indicates that police academy training significantly improves recruits\u27 body composition, both reducing FM and increasing LST, which has the potential to positively affect operational performance. Future studies should track these changes over time to help develop ongoing health and fitness strategies for career police officers, ultimately improving their long-term wellbeing and job readiness

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial

Background Early rapid fluid resuscitation (boluses) in African children with severe febrile illnesses increases the 48-hour mortality by 3.3% compared with controls (no bolus). We explored the effect of boluses on 48-hour all-cause mortality by clinical presentation at enrolment, hemodynamic changes over the first hour, and on different modes of death, according to terminal clinical events. We hypothesize that boluses may cause excess deaths from neurological or respiratory events relating to fluid overload. Methods Pre-defined presentation syndromes (PS; severe acidosis or severe shock, respiratory, neurological) and predominant terminal clinical events (cardiovascular collapse, respiratory, neurological) were described by randomized arm (bolus versus control) in 3,141 severely ill febrile children with shock enrolled in the Fluid Expansion as Supportive Therapy (FEAST) trial. Landmark analyses were used to compare early mortality in treatment groups, conditional on changes in shock and hypoxia parameters. Competing risks methods were used to estimate cumulative incidence curves and sub-hazard ratios to compare treatment groups in terms of terminal clinical events. Results Of 2,396 out of 3,141 (76%) classifiable participants, 1,647 (69%) had a severe metabolic acidosis or severe shock PS, 625 (26%) had a respiratory PS and 976 (41%) had a neurological PS, either alone or in combination. Mortality was greatest among children fulfilling criteria for all three PS (28% bolus, 21% control) and lowest for lone respiratory (2% bolus, 5% control) or neurological (3% bolus, 0% control) presentations. Excess mortality in bolus arms versus control was apparent for all three PS, including all their component features. By one hour, shock had resolved (responders) more frequently in bolus versus control groups (43% versus 32%, P <0.001), but excess mortality with boluses was evident in responders (relative risk 1.98, 95% confidence interval 0.94 to 4.17, P = 0.06) and 'non-responders' (relative risk 1.67, 95% confidence interval 1.23 to 2.28, P = 0.001), with no evidence of heterogeneity (P = 0.68). The major difference between bolus and control arms was the higher proportion of cardiogenic or shock terminal clinical events in bolus arms (n = 123; 4.6% versus 2.6%, P = 0.008) rather than respiratory (n = 61; 2.2% versus 1.3%, P = 0.09) or neurological (n = 63, 2.1% versus 1.8%, P = 0.6) terminal clinical events. Conclusions Excess mortality from boluses occurred in all subgroups of children. Contrary to expectation, cardiovascular collapse rather than fluid overload appeared to contribute most to excess deaths with rapid fluid resuscitation. These results should prompt a re-evaluation of evidence on fluid resuscitation for shock and a re-appraisal of the rate, composition and volume of resuscitation fluids. Trial registration: ISRCTN6985659

Optimal Ranges of Training Load and Recovery Status Prior to the Game to Maximize Game-day Performance in Soccer

Identifying ideal ranges of training load (TL) and recovery status before soccer games is essential to maximize game-day performance. PURPOSE: To determine how accumulative TL and subjective fatigue affect performance during the game. METHODS: Twenty-one male semi-professional soccer players (mean ± standard deviation; age: 22 ± 2 years; mass: 77.3 ± 6.9 kg) wore a player tracking device to monitor TL during each practice and game. A 7-day accumulation of high speed running and sprinting (HSR+Sprint, ³12.30 mph), total distance (TD), low acceleration (LowACC: 0.50-1.99 m×s-2), and high acceleration (HighACC: 2.00-50.00 m×s-2) was calculated. Also, 7-day average fatigue and pre-game fatigue was monitored using a 0 to 10 Likert scale. Game-day performance was defined as the percent changes in average HR and velocity between 1st and 2nd halves. Standard least square regression analysis was performed to determine if TL metrics and fatigue predicted game-day performance. Then, a predictive modeling decision tree was used to establish optimal ranges for each variable and corresponding probability of positive game-day performance. RESULTS: TD, LowACC,HighACC,HSR+Sprint, and game-day fatigue predicted game-day performance in HR (pnd half compared to 1st half. Similarly, achieving LowACC between 0.8 ≤ 1.6 miles and HighACC between 0.1 ≤ 0.2 miles had a 74% and 82% probability maintaining performance in the 2nd half. Additionally, HSR+Sprint between 0.1 ≤ 0.9 miles in practice had a 77% probability and game-day fatigue within 2-4 (small-somewhat fatigued) had an 80% probability. For velocity, TD, LowACC, HighACC, and 7-day average fatigue predicted game-day performance (pnd half. CONCLUSION: In order to achieve better game-day performance, players need to follow the designated ranges of TL, specifically for TD, LowACC,HighACC,and HSR+Sprint. Also, maintaining low levels of fatigue can lead to better game-day performance. Based on these findings, coaches can create individualized training and recovery plans for their players during practice to optimize performance in the game

Identification of Positive Allosteric Modulators of the D1 Dopamine Receptor That Act at Diverse Binding Sites

The D1 dopamine receptor is linked to a variety of neuropsychiatric disorders and represents an attractive drug target for the enhancement of cognition in schizophrenia, Alzheimer disease, and other disorders. Positive allosteric modulators (PAMs), with their potential for greater selectivity and larger therapeutic windows, may represent a viable drug development strategy, as orthosteric D1 receptor agonists possess known clinical liabilities. We discovered two structurally distinct D1 receptor PAMs, MLS6585 and MLS1082, via a high-throughput screen of the NIH Molecular Libraries program small-molecule library. Both compounds potentiate dopamine-stimulated G protein- and β-arrestin-mediated signaling and increase the affinity of dopamine for the D1 receptor with low micromolar potencies. Neither compound displayed any intrinsic agonist activity. Both compounds were also found to potentiate the efficacy of partial agonists. We tested maximally effective concentrations of each PAM in combination to determine if the compounds might act at separate or similar sites. In combination, MLS1082 + MLS6585 produced an additive potentiation of dopamine potency beyond that caused by either PAM alone for both β-arrestin recruitment and cAMP accumulation, suggesting diverse sites of action. In addition, MLS6585, but not MLS1082, had additive activity with the previously described D1 receptor PAM "Compound B," suggesting that MLS1082 and Compound B may share a common binding site. A point mutation (R130Q) in the D1 receptor was found to abrogate MLS1082 activity without affecting that of MLS6585, suggesting this residue may be involved in the binding/activity of MLS1082 but not that of MLS6585. Together, MLS1082 and MLS6585 may serve as important tool compounds for the characterization of diverse allosteric sites on the D1 receptor as well as the development of optimized lead compounds for therapeutic use