Bigger Calves from Doing Higher Resistance Training Volume?

We compared the effects of different weekly calf training sets on muscle size changes. Sixty-one untrained young women performed a calf training program for 6 weeks, 3 d·wk-1, with differences in resistance training volume. The participants were randomly assigned to one of the three groups: 6-SET, 9-SET, and 12-SET weekly calf training sets. The calf raise exercise was performed in sets of 15-20 repetitions maximum. The muscle thickness measurements of medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SOL) were taken via B-mode ultrasound. We used the sum of the three-muscle thickness as a proxy for the triceps surae (TSSUM). The 12-SET group elicited greater increases than the 6-SET in LG (6-SET=+ 8.1% vs. 12-SET=+ 14.3%; P=0.017), SOL (6-SET=+ 6.7% vs. 12-SET=+ 12.7%; P=0.024), and TSSUM (6-SET=+ 6.9% vs. 12-SET=+ 12.0%; P=0.005), but there was no significant difference in MG changes (6-SET=+ 6.6% vs. 12-SET=+ 9.9%; P=0.067). There were no significant differences when comparing 9-SET vs. 6-SET and 12-SET (P≥0.099). Although all groups experienced calf muscle hypertrophy, our results suggest that the higher dose range may optimize triceps surae muscle size gains.

ClotCatcher: a novel natural language model to accurately adjudicate venous thromboembolism from radiology reports.

INTRODUCTION: Accurate identification of venous thromboembolism (VTE) is critical to develop replicable epidemiological studies and rigorous predictions models. Traditionally, VTE studies have relied on international classification of diseases (ICD) codes which are inaccurate - leading to misclassification bias. Here, we developed ClotCatcher, a novel deep learning model that uses natural language processing to detect VTE from radiology reports. METHODS: Radiology reports to detect VTE were obtained from patients admitted to Emory University Hospital (EUH) and Grady Memorial Hospital (GMH). Data augmentation was performed using the Google PEGASUS paraphraser. This data was then used to fine-tune ClotCatcher, a novel deep learning model. ClotCatcher was validated on both the EUH dataset alone and GMH dataset alone. RESULTS: The dataset contained 1358 studies from EUH and 915 studies from GMH (n = 2273). The dataset contained 1506 ultrasound studies with 528 (35.1%) studies positive for VTE, and 767 CT studies with 91 (11.9%) positive for VTE. When validated on the EUH dataset, ClotCatcher performed best (AUC = 0.980) when trained on both EUH and GMH dataset without paraphrasing. When validated on the GMH dataset, ClotCatcher performed best (AUC = 0.995) when trained on both EUH and GMH dataset with paraphrasing. CONCLUSION: ClotCatcher, a novel deep learning model with data augmentation rapidly and accurately adjudicated the presence of VTE from radiology reports. Applying ClotCatcher to large databases would allow for rapid and accurate adjudication of incident VTE. This would reduce misclassification bias and form the foundation for future studies to estimate individual risk for patient to develop incident VTE.

Viral Micro-RNAs Are Detected in the Early Systemic Response to Injury and Are Associated With Outcomes in Polytrauma Patients.

OBJECTIVES: To evaluate early activation of latent viruses in polytrauma patients and consider prognostic value of viral micro-RNAs in these patients. DESIGN: This was a subset analysis from a prospectively collected multicenter trauma database. Blood samples were obtained upon admission to the trauma bay (T0), and trauma metrics and recovery data were collected. SETTING: Two civilian Level 1 Trauma Centers and one Military Treatment Facility. PATIENTS: Adult polytrauma patients with Injury Severity Scores greater than or equal to 16 and available T0 plasma samples were included in this study. Patients with ICU admission greater than 14 days, mechanical ventilation greater than 7 days, or mortality within 28 days were considered to have a complicated recovery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Polytrauma patients (n = 180) were identified, and complicated recovery was noted in 33%. Plasma samples from T0 underwent reverse transcriptase-quantitative polymerase chain reaction analysis for Kaposi's sarcoma-associated herpesvirus micro-RNAs (miR-K12_10b and miRK-12-12) and Epstein-Barr virus-associated micro-RNA (miR-BHRF-1), as well as Luminex multiplex array analysis for established mediators of inflammation. Ninety-eight percent of polytrauma patients were found to have detectable Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus micro-RNAs at T0, whereas healthy controls demonstrated 0% and 100% detection rate for Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, respectively. Univariate analysis revealed associations between viral micro-RNAs and polytrauma patients' age, race, and postinjury complications. Multivariate least absolute shrinkage and selection operator analysis of clinical variables and systemic biomarkers at T0 revealed that interleukin-10 was the strongest predictor of all viral micro-RNAs. Multivariate least absolute shrinkage and selection operator analysis of systemic biomarkers as predictors of complicated recovery at T0 demonstrated that miR-BHRF-1, miR-K12-12, monocyte chemoattractant protein-1, and hepatocyte growth factor were independent predictors of complicated recovery with a model complicated recovery prediction area under the curve of 0.81. CONCLUSIONS: Viral micro-RNAs were detected within hours of injury and correlated with poor outcomes in polytrauma patients. Our findings suggest that transcription of viral micro-RNAs occurs early in the response to trauma and may be associated with the biological processes involved in polytrauma-induced complicated recovery.

A-Mode Ultrasound Reliability in Fat and Muscle Thickness Measurement.

ABSTRACT: Ribeiro, G, de Aguiar, RA, Penteado, R, Lisbôa, FD, Raimundo, JAG, Loch, T, Meira, Â, Turnes, T, and Caputo, F. A-mode ultrasound reliability in fat and muscle thickness measurement. J Strength Cond Res 36(6): 1610-1617, 2022-This study aimed to verify the reliability of the BodyMetrix portable A-mode ultrasound in measuring fat and muscle tissue thickness. Thirty physically active men participated in daily body composition evaluations. The evaluations comprised 2 techniques: (a) graphic technique (GTBM), which measured the fat thickness at 9 body sites (abdomen, axillary, biceps brachii, calf, chest, subscapular, suprailiac, thigh, and triceps brachii), and (b) imaging technique (ITBM), which simultaneously measured the fat and muscle thickness of 6 body surfaces (abdomen, biceps brachii, chest, thigh, trapezius, and triceps brachii). Regarding GTBM, relative reliability was moderate to excellent (intraclass correlation coefficient [ICC]: 0.81-0.98), whereas absolute reliability was acceptable for abdomen, calf, chest, subscapular, suprailiac, and triceps brachii (coefficient of variation [CV]: 6.9-8.8%) but high for axillary, biceps brachii, and thigh (CV: 12.0-17.4%) in measuring fat thicknesses. Concerning ITBM, relative reliability was good to excellent (ICC: 0.93-0.99 and 0.90-0.98), whereas absolute reliability was acceptable (CV: 3.0-9.2% and 3.5-5.9%) in measuring fat and muscle thickness, respectively. These findings suggest that the, GTBM was only reliable in measuring fat thickness of abdomen, calf, chest, subscapular, suprailiac, and triceps brachii, whereas ITBM was reliable in measuring both fat and muscle thickness in all regions, but showed better reliability values in measuring muscle than fat thickness.

Effects of Time of Day on Race Splits, Kinematics, and Blood Lactate During a 50-m Front Crawl Performance.

ABSTRACT: Lisbôa, FD, Raimundo, JAG, Pereira, GS, Ribeiro, G, de Aguiar, RA, and Caputo, F. Effects of time of day on race splits, kinematics, and blood lactate during a 50-m front crawl performance. J Strength Cond Res 35(3): 819-825, 2021-This study aimed to investigate the performance, race splits, metabolic, and stroke parameters during 2 successive 50-m front crawl under conditions simulating a competition. Eleven competitive male swimmers (20 ± 3 years, 182 ± 5 cm, and 77 ± 5 kg) performed 2 successive 50-m front crawl trials in a 50-m swimming pool at 10 am and 5 pm. Block time (tB), 15-m performance (t.15-m), and 50-m performance (t.50-m) were measured. Velocity (V), stroke rate (SR), stroke length (SL), and stroke index (SI) were measured at 3 time points during the trials. Pre-trial and post-trial blood samples were taken to determine blood lactate accumulation (Δ[Lac]). For t.50-m, the relative difference between 10 am and 5 pm reached 0.1% (p = 0.7; effect size [ES] = 0.02). Furthermore, no differences in tB (p = 0.12; ES = -0.28) and t.15-m (p = 0.39; ES = -0.16) were observed between periods. Both V (p = 0.11; ES = -0.14) and SI (p = 0.16; ES = 0.15) were also similar. Higher values of SR were recorded at 10 am (p = 0.03; ES = -0.32), whereas the morning values of SL were lower (p = 0.04; ES = 0.3). Δ[Lac] was not significantly different between periods (p = 0.07; ES = -0.27). Although time of the day did not impact performance in 2 successive 50-m front crawl performances, different stroke parameters profiles were observed during these trials. This may help coaches design specific warm-up exercises to enhance performance at different times of the day.

Correction to: Advanced Modeling to Predict Pneumonia in Combat Trauma Patients.

In the original article, the units indicated on the y-axes of Fig. 3 are incorrectly labelled. The correct label is pg/mL. Following is the corrected Fig. 3.

Advanced Modeling to Predict Pneumonia in Combat Trauma Patients.

BACKGROUND: Tools to assist clinicians in predicting pneumonia could lead to a significant decline in morbidity. Therefore, we sought to develop a model in combat trauma patients for identifying those at highest risk of pneumonia. METHODS: This was a retrospective study of 73 primarily blast-injured casualties with combat extremity wounds. Binary classification models for pneumonia prediction were developed with measurements of injury severity from the Abbreviated Injury Scale (AIS), transfusion blood products received before arrival at Walter Reed National Military Medical Center (WRNMMC), and serum protein levels. Predictive models were generated with leave-one-out-cross-validation using the variable selection method of backward elimination (BE) and the machine learning algorithms of random forests (RF) and logistic regression (LR). BE was attempted with two predictor sets: (1) all variables and (2) serum proteins alone. RESULTS: Incidence of pneumonia was 12% (n = 9). Different variable sets were produced by BE when considering all variables and just serum proteins alone. BE selected the variables ISS, AIS chest, and cryoprecipitate within the first 24 h following injury for the first predictor set 1 and FGF-basic, IL-2R, and IL-6 for predictor set 2. Using both variable sets, a RF was generated with AUCs of 0.95 and 0.87-both higher than LR algorithms. CONCLUSION: Advanced modeling allowed for the identification of clinical and biomarker data predictive of pneumonia in a cohort of predominantly blast-injured combat trauma patients. The generalizability of the models developed here will require an external validation dataset.

Utilizing Precision Medicine to Estimate Timing for Surgical Closure of Traumatic Extremity Wounds.

BACKGROUND: Both the frequency and high complication rates associated with extremity wounds in recent military conflicts have highlighted the need for clinical decision support tools (CDST) to decrease time to wound closure and wound failure rates. METHODS: Machine learning was used to estimate both successful wound closure (based on penultimate debridement biomarker data) and the necessary number of surgical debridements (based on presentation biomarkers) in 73 service members treated according to military guidelines based on clinical data and the local/systemic level of 32 cytokines. Models were trained to estimate successful closure including an additional 8 of 80 civilian patients with similar injury patterns. Previous analysis has demonstrated the potential to reduce the number of operative debridements by 2, with resulting decreases in ICU and hospital LOS, while decreasing the rate of wound failure. RESULTS: Analysis showed similar cytokine responses when civilians followed a military-like treatment schedule with surgical debridements every 24 to 72 hours. A model estimating successful closure had AUC of 0.89. Model performance in civilians degraded when these had a debridement interval > 72 hours (73 of the 80 civilians). A separate model estimating the number of debridements required to achieve successful closure had a multiclass AUC of 0.81. CONCLUSION: CDSTs can be developed using biologically compatible civilian and military populations as cytokine response is highly influenced by surgical treatment. Our CDSTs may help identify who may require serial debridements versus early closure, and precisely when traumatic wounds should optimally be closed.

Acute Cardiopulmonary, Metabolic, and Neuromuscular Responses to Severe-Intensity Intermittent Exercises.

Lisbôa, FD, Raimundo, JAG, Salvador, AF, Pereira, KL, Turnes, T, Diefenthaeler, F, Oliveira, MFMd, and Caputo, F. Acute cardiopulmonary, metabolic, and neuromuscular responses to severe-intensity intermittent exercises. J Strength Cond Res 33(2): 408-416, 2019-The purpose of this study was to compare cardiopulmonary, neuromuscular, and metabolic responses to severe-intensity intermittent exercises with variable or constant work rate (CWR). Eleven cyclists (28 ± 5 years; 74 ± 7 kg; 175 ± 5 cm; 63 ± 4 ml·kg·min) performed the following tests until exhaustion on separate days: (a) an incremental test; (b) in random order, 2 CWR tests at 95 and 110% of the peak power for the determination of critical power (CP); (c) 2-4 tests for the determination of the highest power that still permits the achievement of maximal oxygen uptake (PHIGH); and (d) 2 random severe-intensity intermittent exercises. The last 2 sessions consisted of a CWR exercise performed at PHIGH or a decreasing work rate (DWR) exercise from PHIGH until 105% of CP. Compared with CWR, DWR presented higher time to exhaustion (635 ± 223 vs. 274 ± 65 seconds), time spent above 95% of V[Combining Dot Above]O2max (t95% V[Combining Dot Above]O2max) (323 ± 227 vs. 98 ± 65 seconds), and O2 consumed (0.97 ± 0.41 vs. 0.41 ± 0.11 L). Electromyography amplitude (root mean square [RMS]) decreased for DWR but increased for CWR during each repetition. However, RMS and V[Combining Dot Above]O2 divided by power output (RMS/PO and V[Combining Dot Above]O2/PO ratio) increased in every repetition for both protocols, but to a higher extent and slope for DWR. These findings suggest that the higher RMS/PO and V[Combining Dot Above]O2/PO ratio in association with the longer exercise duration seemed to have been responsible for the higher t95% V[Combining Dot Above]O2max observed during severe DWR exercise.

Impact of ischaemia-reperfusion cycles during ischaemic preconditioning on 2000-m rowing ergometer performance.

PURPOSE: Although ischaemic preconditioning (IPC), induced by cycles of transient limb ischaemia and reperfusion, seems to improve exercise performance, the optimal duration of ischaemia-reperfusion cycles is not established. The present study investigated the effect of ischaemia-reperfusion duration within each IPC cycle on performance in a 2000-m rowing ergometer test. METHODS: After incremental and familiarization tests, 16 trained rowers (mean ± SD: age, 24 ± 11 years; weight, 74.1 ± 5.9 kg; [Formula: see text] peak, 67.2 ± 7.4 mL·kg-1·min-1) were randomly submitted to a 2000-m rowing test preceded by intermittent bilateral cuff inflation of the lower limbs with three cycles of ischaemia-reperfusion, lasting 5 min (IPC-5) or 10 min (IPC-10) at 220 or 20 mmHg (control). Power output, [Formula: see text], heart rate, blood lactate concentration, pH, ratings of perceived exertion (RPE), and near-infrared spectroscopy-derived measurements of the vastus lateralis muscle were continuously recorded. RESULTS: No differences among treatments were found in the 2000-m test (control: 424 ± 17; IPC-5: 425 ± 16; IPC-10: 424 ± 17 s; P = 0.772). IPC-10 reduced the tissue saturation index and oxy-haemoglobin concentration during exercise compared with control. The power output during the last 100-m segment was significantly lower with IPC-10. The IPC treatments increased the heart rate over the first 500 m and decreased the pH after exercise. No alterations were observed in [Formula: see text], blood lactate, or RPE among the trials. CONCLUSION: In conclusion, IPC does not improve the 2000-m rowing ergometer performance of trained athletes regardless of the length of ischaemia-reperfusion cycles.

Short-term interval training at both lower and higher intensities in the severe exercise domain result in improvements in V̇O2 on-kinetics.

PURPOSE: Although high-intensity interval training (HIT) seems to promote greater improvements in aerobic parameters than continuous training, the influence of exercise intensity on [Formula: see text] on-kinetics remains under investigation. METHODS: After an incremental test, twenty-one recreationally trained cyclists performed several time-to-exhaustion tests to determine critical power (CP), and the highest intensity (I HIGH), and the lowest exercise duration (T LOW) at which [Formula: see text] is attained during constant exercise. Subjects also completed a series of step transitions to moderate- and heavy-intensity work rates to determine pulmonary [Formula: see text] on-kinetics. Surface electromyography (EMG) of vastus lateralis muscle and blood lactate accumulation (∆BLC) was measured during heavy exercise. Subjects were assigned to one of two 4-week work-matched training groups: the lower [105 % CP: n = 11; 4 × 5 min at 105 % CP (218 ± 39 W), 1 min recovery] or the upper [I HIGH: n = 10; 8 × 100 % I HIGH (355 ± 60 W), 1:2 work:recovery ratio] intensity of the severe exercise domain. RESULTS: The two interventions were similarly effective in reducing the phase II [Formula: see text] time constant during moderate (105 % CP: 34 ± 13 to 25 ± 8 s; I HIGH: 31 ± 9 to 23 ± 6 s) and heavy exercise (105 % CP: 25 ± 7 to 18 ± 5 s; I HIGH: 27 ± 7 to 16 ± 5 s) and in reducing the amplitude of [Formula: see text] slow component, EMG amplitude, and ∆BLC during heavy exercise. CONCLUSION: In conclusion, the short-term adjustments in response to step transitions to moderate and heavy exercise were independent of training intensity within the severe exercise domain.

Decreasing Power Output Increases Aerobic Contribution During Low-Volume Severe-Intensity Intermittent Exercise.

High-intensity interval training applied at submaximal, maximal, and supramaximal intensities for exercising at V[Combining Dot Above]O2max (t95V[Combining Dot Above]O2max) has shown similar adaptation to low-volume sprint interval training among active subjects. Thus, the aim of the present study was to investigate t95V[Combining Dot Above]O2max during 2 different intermittent exercises in the severe-intensity domain (e.g., range of power outputs over which V[Combining Dot Above]O2max can be elicited during constant-load exercise) and to identify an exercise protocol that reduces the time required to promote higher aerobic demand. Eight active men (22 ± 2 years, 72 ± 5 kg, 174 ± 4 cm, 47 ± 8 ml·kg·min) completed the following protocols on a cycle ergometer: (a) incremental test, (b) determination of critical power (CP), (c) determination of the highest constant intensity (IHIGH) and the lowest exercise duration (TLOW) in which V[Combining Dot Above]O2max is attained, and (d) 2 exercise sessions in a randomized order that consisted of a constant power output (CPO) session at IHIGH and a decreasing power output (DPO) session that applied a decreasing work rate profile from IHIGH to 110% of CP. Time to exhaustion was significantly longer in DPO (371 ± 57 seconds vs. 225 ± 33 seconds). Moreover, t95V[Combining Dot Above]O2max (186 ± 72 seconds vs. 76 ± 49 seconds) and O2 consumed (29 ± 4 L vs. 17 ± 3 L) were higher in DPO when compared with the CPO protocol. In conclusion, data suggest that the application of a DPO protocol during intermittent exercise increases the time spent at high percentages of V[Combining Dot Above]O2max.

Derivation and Validation of Generalized Sepsis-induced Acute Respiratory Failure Phenotypes Among Critically Ill Patients: A Retrospective Study.

Background: Septic patients who develop acute respiratory failure (ARF) requiring mechanical ventilation represent a heterogenous subgroup of critically ill patients with widely variable clinical characteristics. Identifying distinct phenotypes of these patients may reveal insights about the broader heterogeneity in the clinical course of sepsis. We aimed to derive novel phenotypes of sepsis-induced ARF using observational clinical data and investigate their generalizability across multi-ICU specialties, considering multi-organ dynamics. Methods: We performed a multi-center retrospective study of ICU patients with sepsis who required mechanical ventilation for ≥24 hours. Data from two different high-volume academic hospital systems were used as a derivation set with N=3,225 medical ICU (MICU) patients and a validation set with N=848 MICU patients. For the multi-ICU validation, we utilized retrospective data from two surgical ICUs at the same hospitals (N=1,577). Clinical data from 24 hours preceding intubation was used to derive distinct phenotypes using an explainable machine learning-based clustering model interpreted by clinical experts. Results: Four distinct ARF phenotypes were identified: A (severe multi-organ dysfunction (MOD) with a high likelihood of kidney injury and heart failure), B (severe hypoxemic respiratory failure [median P/F=123]), C (mild hypoxia [median P/F=240]), and D (severe MOD with a high likelihood of hepatic injury, coagulopathy, and lactic acidosis). Patients in each phenotype showed differences in clinical course and mortality rates despite similarities in demographics and admission co-morbidities. The phenotypes were reproduced in external validation utilizing an external MICU from second hospital and SICUs from both centers. Kaplan-Meier analysis showed significant difference in 28-day mortality across the phenotypes (p<0.01) and consistent across both centers. The phenotypes demonstrated differences in treatment effects associated with high positive end-expiratory pressure (PEEP) strategy. Conclusion: The phenotypes demonstrated unique patterns of organ injury and differences in clinical outcomes, which may help inform future research and clinical trial design for tailored management strategies.

The influence of microbial colonization on inflammatory versus pro-healing trajectories in combat extremity wounds.

A combination of improved body armor, medical transportation, and treatment has led to the increased survival of warfighters from combat extremity injuries predominantly caused by blasts in modern conflicts. Despite advances, a high rate of complications such as wound infections, wound failure, amputations, and a decreased quality of life exist. To study the molecular underpinnings of wound failure, wound tissue biopsies from combat extremity injuries had RNA extracted and sequenced. Wounds were classified by colonization (colonized vs. non-colonized) and outcome (healed vs. failed) status. Differences in gene expression were investigated between timepoints at a gene level, and longitudinally by multi-gene networks, inferred proportions of immune cells, and expression of healing-related functions. Differences between wound outcomes in colonized wounds were more apparent than in non-colonized wounds. Colonized/healed wounds appeared able to mount an adaptive immune response to infection and progress beyond the inflammatory stage of healing, while colonized/failed wounds did not. Although, both colonized and non-colonized failed wounds showed increasing inferred immune and inflammatory programs, non-colonized/failed wounds progressed beyond the inflammatory stage, suggesting different mechanisms of failure dependent on colonization status. Overall, these data reveal gene expression profile differences in healing wounds that may be utilized to improve clinical treatment paradigms.

Acute Effects of a Practical Blood Flow Restriction Device During Swimming Exercise.

Purpose: The present study aimed to analyze: 1) the reliability of the tissue saturation index (TSI) and ratings of perceived discomfort (RPD) responses wearing a neoprene practical cuff (PrC), comparing with the responses from traditional (TrC) pneumatic cuffs (study I); 2) the effects of PrC on metabolic (blood lactate concentration, BLC), perceptual (rate of perceived effort, RPE) and kinematic responses at sub-maximal swimming velocities (study II). Methods: Study I; 1) PrC test-retest at rest and during swimming ergometer exercise; 2) BFR at rest with TrC inflated to different percentages of the minimum arterial occlusion pressure (MAOP; 60, 80, 100, 120 and 140%). Test-retest reliability of TSI and RPD was assessed by the intraclass correlation coefficient (ICC) and comparisons among conditions were analyzed by one-way repeated-measures ANOVA. Study II; 1) 50, 200 and 400 m swimming performances; 2) sub-maximal incremental swimming protocol with and without PrC. Two-way repeated measures ANOVA was used to compare all variables during sub-maximal velocities. Results: TSI (ICC = 0.81; 95%CI 0.62-0.91) and RPD (ICC = 0.97; 95%CI 0.94-0.99) were reliable under restricted exercise using PrC. TSI during restricted exercise was lower (p <.001) compared to unrestricted exercise (6.8 ± 6.1% vs. 21.6 ± 8.2% of physiological normalization). PrC showed higher BLC only at or above 91% of critical velocity (p < .03), while stroke rate and RPE were higher (p < .005), and stroke length was lower (p < .03) during all swimming velocities. Conclusion: This easy-to-handle and affordable practical BFR device increased physiological stress at sub-maximal efforts which could be an additional training tool for swimmers.

Central role for neurally dysregulated IL-17A in dynamic networks of systemic and local inflammation in combat casualties.

Dynamic Network Analysis (DyNA) and Dynamic Hypergraphs (DyHyp) were used to define protein-level inflammatory networks at the local (wound effluent) and systemic circulation (serum) levels from 140 active-duty, injured service members (59 with TBI and 81 non-TBI). Interleukin (IL)-17A was the only biomarker elevated significantly in both serum and effluent in TBI vs. non-TBI casualties, and the mediator with the most DyNA connections in TBI wounds. DyNA combining serum and effluent data to define cross-compartment correlations suggested that IL-17A bridges local and systemic circulation at late time points. DyHyp suggested that systemic IL-17A upregulation in TBI patients was associated with tumor necrosis factor-α, while IL-17A downregulation in non-TBI patients was associated with interferon-γ. Correlation analysis suggested differential upregulation of pathogenic Th17 cells, non-pathogenic Th17 cells, and memory/effector T cells. This was associated with reduced procalcitonin in both effluent and serum of TBI patients, in support of an antibacterial effect of Th17 cells in TBI patients. Dysregulation of Th17 responses following TBI may drive cross-compartment inflammation following combat injury, counteracting wound infection at the cost of elevated systemic inflammation.

Targeted metagenomic assessment reflects critical colonization in battlefield injuries.

IMPORTANCE: Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.

Pregnancy-specific glycoprotein 1 induces endothelial tubulogenesis through interaction with cell surface proteoglycans.

Pregnancy-specific ß1 glycoproteins (PSGs) are the most abundant fetal proteins in the maternal bloodstream in late pregnancy. They are secreted by the syncytiotrophoblast and are detected around day 14 postfertilization. There are 11 human PSG genes, which encode a family of proteins exhibiting significant conservation at the amino acid level. We and others have proposed that PSGs have an immune modulatory function. In addition, we recently postulated that they are proangiogenic due to their ability to induce the secretion of VEGF-A and the formation of tubes by endothelial cells. The cellular receptor(s) for human PSGs remain unknown. Therefore, we conducted these studies to identify the receptor for PSG1, the highest expressed member of the family. We show that removal of cell surface glycosaminoglycans (GAGs) by enzymatic or chemical treatment of cells or competition with heparin completely inhibited binding of PSG1. In addition, PSG1 did not bind to cells lacking heparan or chondroitin sulfate on their surface, and binding was restored upon transfection with all four syndecans and glypican-1. Importantly, the presence of GAGs on the surface of endothelial cells was required for the ability of PSG1 to induce tube formation. This finding indicates that the PSG1-GAG interaction mediates at least some of the PSG1 proposed functions.

Modeling the expenditure and reconstitution of distance above critical speed during two swimming interval training sessions.

In swimming, the speed-time relationship provides the critical speed (CS) and the maximum distance that can be performed above CS (D'). During intermittent severe intensity exercise, a complete D' depletion coincides with task failure, while a sub-CS intensity is required for D' reconstitution. Therefore, determining the balance D' remaining at any time during intermittent exercise (D'BAL) could improve training prescription. This study aimed to 1) test the D'BAL model for swimming; 2) determine an equation to estimate the time constant of the reconstitution of D' (τD'); and 3) verify if τD' is constant during two interval training sessions with the same work intensity and duration and recovery intensity, but different recovery duration. Thirteen swimmers determined CS and D' and performed two high-intensity interval sessions at a constant speed, with repetitions fixed at 50 m. The duration of passive recovery was based on the work/relief ratio of 2:1 (T2:1) and 4:1 (T4:1). There was a high variability between sessions for τD' (coefficient of variation of 306%). When τD' determined for T2:1 was applied in T4:1 and vice versa, the D'BAL model was inconsistent to predict the time to exhaustion (coefficient of variation of 29 and 28%). No linear or nonlinear relationships were found between τD' and CS, possibly due to the high within-subject variability of τD'. These findings suggest that τD' is not constant during two high-intensity interval sessions with the same recovery intensity. Therefore, the current D'BAL model was inconsistent to track D' responses for swimming sessions tested herein.

Cellular microRNAs correlate with clinical parameters in multiple injury patients.

INTRODUCTION: The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may modulate the inflammatory response. The authors hypothesize that the expression of microRNAs would correlate to complicated recoveries in polytrauma patients (PtPs). METHODS: Polytrauma patients enrolled in the prospective observational Tissue and Data Acquisition Protocol with Injury Severity Score of >15 were selected for this study. Polytrauma patients were divided into complicated recoveries and uncomplicated recovery groups. Polytrauma patients' blood samples were obtained at the time of admission (T0). Established biomarkers of systemic inflammation, including cytokines and chemokines, were measured using multiplexed Luminex-based methods, and novel microRNAs were measured in plasma samples using multiplex RNA hybridization. RESULTS: Polytrauma patients (n = 180) had high Injury Severity Score (26 [20-34]) and complicated recovery rate of 33%. MicroRNAs were lower in PtPs at T0 compared with healthy controls, and bivariate analysis demonstrated that variations of microRNAs correlated with age, race, comorbidities, venous thromboembolism, pulmonary complications, complicated recovery, and mortality. Positive correlations were noted between microRNAs and interleukin 10, vascular endothelial growth factor, Acute Physiology and Chronic Health Evaluation, and Sequential Organ Failure Assessment scores. Multivariable Lasso regression analysis of predictors of complicated recovery based on microRNAs, cytokines, and chemokines revealed that miR-21-3p and monocyte chemoattractant protein-1 were predictive of complicated recovery with an area under the curve of 0.78. CONCLUSION: Systemic microRNAs were associated with poor outcomes in PtPs, and results are consistent with previously described trends in critically ill patients. These early biomarkers of inflammation might provide predictive utility in early complicated recovery diagnosis and prognosis. Because of their potential to regulate immune responses, microRNAs may provide therapeutic targets for immunomodulation. LEVEL OF EVIDENCE: Diagnostic Tests/Criteria; Level II.