How does cognitive behavior therapy for dissociative seizures work? A mediation analysis of the CODES trial.

BACKGROUND: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. METHODS: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. RESULTS: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. CONCLUSIONS: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Interleaved x-ray imaging: A method for simultaneous acquisition of quantitative and diagnostic digital subtraction angiography.

BACKGROUND: Flow altering angiographic procedures suffer from ill-defined, qualitative endpoints. Quantitative digital subtraction angiography (qDSA) is an emerging technology that aims to address this issue by providing intra-procedural blood velocity measurements from time-resolved, 2D angiograms. To date, qDSA has used 30 frame/s DSA imaging, which is associated with high radiation dose rate compared to clinical diagnostic DSA (up to 4 frame/s). PURPOSE: The purpose of this study is to demonstrate an interleaved x-ray imaging method which decreases the radiation dose rate associated with high frame rate qDSA while simultaneously providing low frame rate diagnostic DSA images, enabling the acquisition of both datasets in a single image sequence with a single injection of contrast agent. METHODS: Interleaved x-ray imaging combines low radiation dose image frames acquired at a high rate with high radiation dose image frames acquired at a low rate. The feasibility of this approach was evaluated on an x-ray system equipped with research prototype software for x-ray tube control. qDSA blood velocity quantification was evaluated in a flow phantom study for two lower dose interleaving protocols (LD1: 3.7 ± 0.02 mGy / s $3.7 \pm 0.02\ {\mathrm{mGy}}/{\mathrm{s}}$ and LD2: 1.7 ± 0.04 mGy / s $1.7 \pm 0.04{\mathrm{\ mGy}}/{\mathrm{s}}$ ) and one conventional (full dose) protocol ( 11.4 ± 0.04 mGy / s ) $11.4 \pm 0.04{\mathrm{\ mGy}}/{\mathrm{s}})$ . Dose was measured at the interventional reference point. Fluid velocities ranging from 24 to 45 cm/s were investigated. Gold standard velocities were measured using an ultrasound flow probe. Linear regression and Bland-Altman analysis were used to compare ultrasound and qDSA. RESULTS: The LD1 and LD2 interleaved protocols resulted in dose rate reductions of -67.7% and -85.5%, compared to the full dose qDSA scan. For the full dose protocol, the Bland-Altman limits of agreement (LOA) between qDSA and ultrasound velocities were [0.7, 6.7] cm/s with a mean difference of 3.7 cm/s. The LD1 interleaved protocol results were similar (LOA: [0.3, 6.9] cm/s, bias: 3.6 cm/s). The LD2 interleaved protocol resulted in slightly larger LOA: [-2.5, 5.5] cm/s with a decrease in the bias: 1.5 cm/s. Linear regression analysis showed a strong correlation between ultrasound and qDSA derived velocities using the LD1 protocol, with a R 2 ${R}^2$ of 0.96 $0.96$ , a slope of 1.05 $1.05$ and an offset of 1.9 $1.9$  cm/s. Similar values were also found for the LD2 protocol, with a R 2 ${R}^2$ of 0.93 $0.93$ , a slope of 0.98 $0.98$ and an offset of 2.0 $2.0$  cm/s. CONCLUSIONS: The interleaved method enables simultaneous acquisition of low-dose high-rate images for intra-procedural blood velocity quantification (qDSA) and high-dose low-rate images for vessel morphology evaluation (diagnostic DSA).

E-cigarettes and arrhythmogenesis: a comprehensive review of pre-clinical studies and their clinical implications.

Electronic cigarette use has grown exponentially in recent years, and while their popularity has increased, the long-term effects on the heart are yet to be fully studied and understood. Originally designed as devices to assist with those trying to quit traditional combustible cigarette use, their popularity has attracted use by teens and adolescents who traditionally have not smoked combustible cigarettes. Acute effects on the heart have been shown to be similar to traditional combustible cigarettes, including increased heart rate and blood pressure. The main components of electronic cigarettes that contribute to these arrhythmic effects are found in the e-liquid that is aerosolized and inhaled, comprised of nicotine, flavourings, and a combination of vegetable glycerin (VG) and propylene glycol (PG). Nicotine can potentially induce both ventricular and atrial arrhythmogenesis, with both the atrial and ventricular effects resulting from the interactions of nicotine and the catecholamines they release via potassium channels. Atrial arrhythmogenesis, more specifically atrial fibrillation, can also occur due to structural alterations, which happens because of nicotine downregulating microRNAs 133 and 590, both post-transcriptional growth factor repressors. Liquid flavourings and the combination of PG and VG can possibly lead to arrhythmic events by exposing users to acrolein, an aldehyde that stimulates TRPA1 that in turn causes a change towards sympathetic activation and autonomic imbalance. The design of these electronic delivery devices is constantly changing; therefore, it has proven extremely difficult to study the long-term effects on the heart caused by electronic cigarettes but will be important to understand given their rising popularity. The arrhythmic effects of electronic cigarettes appear similar to traditional cigarettes as well; however, a comprehensive review has not been compiled and is the focus of this article.

Lessons Learned in Change Management in Deploying Novel Informatics Solutions: Experience Implementing a Point-of-Care Patient Photography System with Radiography.

We describe implementation of a point-of-care system for simultaneous acquisition of patient photographs along with portable radiographs at a large academic hospital. During the implementation process, we observed several technical challenges in the areas of (1) hardware-automatic triggering for photograph acquisition, camera hardware enclosure, networking, and system server hardware and (2) software-post-processing of photographs. Additionally, we also faced cultural challenges involving workflow issues, communication with technologists and users, and system maintenance. We describe our solutions to address these challenges. We anticipate that these experiences will provide useful insights into deploying and iterating new technologies in imaging informatics.

First record of plastic ingestion by a freshwater stingray.

The abundance and dispersion of plastic particles in aquatic ecosystems has become pervasive resulting in the incorporation of these materials into food webs. Here we describe the first record of plastic ingestion by the freshwater white-blotched river stingray Potamotrygon leopoldi (Potamotrygonidae), an endemic and threatened species in the Xingu River, Amazon basin. Potamotrygonidae stingrays inhabit exclusively Neotropical rivers, occupying rocky substrate habitats and feeding mainly on benthic macroinvertebrates. The gastrointestinal tract of 24 stingrays were analyzed, 16 (66.6 %) of which contained plastic particles. In total, 81 plastic particles were recorded and consisted of microplastics (< 5 mm, n = 57) and mesoplastics (5-25 mm, n = 24). The plastic particles found were classified into fibers (64.2 %, n = 52) and fragments (35.8 %, n = 29). The predominant color was blue (33.3 %, n = 27), followed by yellow (18.5 %, n = 15), white (14.8 %, n = 12), black (13.6 %, n = 11), green (6.2 %, n = 5), transparent (4.9 %, n = 4), pink, grey and brown (2.5 %, n = 2, each) and orange (1.2 %, n = 1). No significant correlation was observed between the number of plastic particles and the body size. Eight types of polymers were identified in the plastic particles analyzed using 2D FTIR Imaging. The most frequent polymer was artificial cellulose fiber. This is the first report of plastic ingestion by freshwater elasmobranchs in the world. Plastic waste has become an emerging problem in aquatic ecosystems globally and our results provide an important datapoint for freshwater stingrays in the Neotropics.

Normative Cerebral Hemodynamics in Middle-aged and Older Adults Using 4D Flow MRI: Initial Analysis of Vascular Aging.

Background Characterizing cerebrovascular hemodynamics in older adults is important for identifying disease and understanding normal neurovascular aging. Four-dimensional (4D) flow MRI allows for a comprehensive assessment of cerebral hemodynamics in a single acquisition. Purpose To establish reference intracranial blood flow and pulsatility index values in a large cross-sectional sample of middle-aged (45-65 years) and older (>65 years) adults and characterize the effect of age and sex on blood flow and pulsatility. Materials and Methods In this retrospective study, patients aged 45-93 years (cognitively unimpaired) underwent cranial 4D flow MRI between March 2010 and March 2020. Blood flow rates and pulsatility indexes from 13 major arteries and four venous sinuses and total cerebral blood flow were collected. Intraobserver and interobserver reproducibility of flow and pulsatility measures was assessed in 30 patients. Descriptive statistics (mean ± SD) of blood flow and pulsatility were tabulated for the entire group and by age and sex. Multiple linear regression and linear mixed-effects models were used to assess the effect of age and sex on total cerebral blood flow and vessel-specific flow and pulsatility, respectively. Results There were 759 patients (mean age, 65 years ± 8 [SD]; 506 female patients) analyzed. For intra- and interobserver reproducibility, median intraclass correlation coefficients were greater than 0.90 for flow and pulsatility measures across all vessels. Regression coefficients ß ± standard error from multiple linear regression showed a 4 mL/min decrease in total cerebral blood flow each year (age ß = -3.94 mL/min per year ± 0.44; P < .001). Mixed effects showed a 1 mL/min average annual decrease in blood flow (age ß = -0.95 mL/min per year ± 0.16; P < .001) and 0.01 arbitrary unit (au) average annual increase in pulsatility over all vessels (age ß = 0.011 au per year ± 0.001; P < .001). No evidence of sex differences was observed for flow (ß = -1.60 mL/min per male patient ± 1.77; P = .37), but pulsatility was higher in female patients (sex ß = -0.018 au per male patient ± 0.008; P = .02). Conclusion Normal reference values for blood flow and pulsatility obtained using four-dimensional flow MRI showed correlations with age. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Steinman in this issue.

Automated hemodynamic assessment for cranial 4D flow MRI.

Cranial 4D flow MRI post-processing typically involves manual user interaction which is time-consuming and associated with poor repeatability. The primary goal of this study is to develop a robust quantitative velocity tool (QVT) that utilizes threshold-based segmentation techniques to improve segmentation quality over prior approaches based on centerline processing schemes (CPS) that utilize k-means clustering segmentation. This tool also includes an interactive 3D display designed for simplified vessel selection and automated hemodynamic visualization and quantification. The performances of QVT and CPS were compared in vitro in a flow phantom and in vivo in 10 healthy participants. Vessel segmentations were compared with ground-truth computed tomography in vitro (29 locations) and manual segmentation in vivo (13 locations) using linear regression. Additionally, QVT and CPS MRI flow rates were compared to perivascular ultrasound flow in vitro using linear regression. To assess internal consistency of flow measures in vivo, conservation of flow was assessed at vessel junctions using linear regression and consistency of flow along vessel segments was analyzed by fitting a Gaussian distribution to a histogram of normalized flow values. Post-processing times were compared between the QVT and CPS using paired t-tests. Vessel areas segmented in vitro (CPS: slope = 0.71, r = 0.95 and QVT: slope = 1.03, r = 0.95) and in vivo (CPS: slope = 0.61, r = 0.96 and QVT: slope = 0.93, r = 0.96) were strongly correlated with ground-truth area measurements. However, CPS (using k-means segmentation) consistently underestimated vessel areas. Strong correlations were observed between QVT and ultrasound flow (slope = 0.98, r = 0.96) as well as flow at junctions (slope = 1.05, r = 0.98). Mean and standard deviation of flow along vessel segments was 9.33e-16 ± 3.05%. Additionally, the QVT demonstrated excellent interobserver agreement and significantly reduced post-processing by nearly 10 min (p < 0.001). By completely automating post-processing and providing an easy-to-use 3D visualization interface for interactive vessel selection and hemodynamic quantification, the QVT offers an efficient, robust, and repeatable means to analyze cranial 4D flow MRI. This software is freely available at: https://github.com/uwmri/QVT.

Multiple trophic pathways support fish on floodplains of California's Central Valley.

We used compound-specific isotope analysis of carbon isotopes in amino acids (AAs) to determine the biosynthetic source of AAs in fish from major tributaries to California's Sacramento-San Joaquin river delta (i.e., the Sacramento, Cosumnes and Mokelumne rivers). Using samples collected in winter and spring between 2016 and 2019, we confirmed that algae are a critical component of floodplain food webs in California's Central Valley. Results from bulk stable isotope analysis of carbon and nitrogen in producers and consumers were adequate to characterize a general trophic structure and identify potential upstream and downstream migration into our study site by American shad Alosa sapidissima and rainbow trout Oncorhynchus mykiss, respectively. However, owing to overlap and variability in source isotope compositions, our bulk data were unsuitable for conventional bulk isotope mixing models. Our results from compound-specific carbon isotope analysis of AAs clearly indicate that algae are important sources of organic matter to fish of conservation concern, such as Chinook salmon Oncorhynchus tshawytscha in California's Central Valley. However, algae were not the exclusive source of energy to metazoan food webs. We also revealed that other sources of AAs, such as bacteria, fungi and higher plants, contributed to fish as well. While consistent with the well-supported notion that algae are critical to aquatic food webs, our results highlight the possibility that detrital subsidies might intermittently support metazoan food webs.

Moderators of cognitive behavioural therapy treatment effects and predictors of outcome in the CODES randomised controlled trial for adults with dissociative seizures.

OBJECTIVE: We explored moderators of cognitive behavioural therapy (CBT) treatment effects and predictors of outcome at 12-month follow-up in the CODES Trial (N = 368) comparing CBT plus standardised medical care (SMC) vs SMC-alone for dissociative seizures (DS). METHODS: We undertook moderator analyses of baseline characteristics to determine who had benefited from being offered CBT 12 months post-randomisation. Outcomes included: monthly DS frequency, psychosocial functioning (Work and Social Adjustment Scale - WSAS), and health-related quality of life (Mental Component Summary (MCS) and Physical Component Summary (PCS) SF-12v2 scores). When moderating effects were absent, we tested whether baseline variables predicted change irrespective of treatment allocation. RESULTS: Moderator analyses revealed greater benefits (p < 0.05) of CBT on DS frequency for participants with more (≥22) symptoms (Modified PHQ-15) or ≥ 1 current (M.I.N.I.-confirmed) comorbid psychiatric diagnosis at baseline. The effect of CBT on PCS scores was moderated by gender; women did better than men in the CBT + SMC group. Predictors of improved outcome included: not receiving disability benefits, lower anxiety and/or depression scores (PCS, MCS, WSAS); shorter duration, younger age at DS onset, employment, fewer symptoms and higher educational qualification (PCS, WSAS); stronger belief in the diagnosis and in CBT as a "logical" treatment (MCS). Some variables that clinically might be expected to moderate/predict outcome (e.g., maladaptive personality traits, confidence in treatment) were not shown to be relevant. CONCLUSION: Patient complexity interacted with treatment. CBT was more likely to reduce DS frequency in those with greater comorbidity. Other patient characteristics predicted outcome regardless of the received intervention.

Small extracellular vesicles induce resistance to anti-GD2 immunotherapy unveiling tipifarnib as an adjunct to neuroblastoma immunotherapy.

BACKGROUND: Anti-GD2 monoclonal antibody immunotherapy has significantly improved the overall survival rate for high-risk neuroblastoma patients. However, 40% of patients fail to respond or develop resistance to treatment, and the molecular mechanisms by which this occurs remain poorly understood. Tumor-derived small extracellular vesicles (sEVs) have emerged as critical regulators in modulating the response to immunotherapy. In this study, we investigated the role of neuroblastoma-derived sEVs in promoting resistance to the anti-GD2 monoclonal antibody dinutuximab. Moreover, to determine whether pharmacologic inhibition of sEV secretion sensitizes tumors to dinutuximab treatment, we combined dinutuximab with tipifarnib, a farnesyltransferase inhibitor that inhibits sEV secretion. METHODS: We investigated the role of neuroblastoma-derived sEVs in modulating the response to dinutuximab by utilizing the syngeneic 9464D-GD2 mouse model. The effect of neuroblastoma-derived sEVs in modulating the tumor microenvironment (TME) and host immune system were evaluated by RNA-sequencing and flow cytometry. Importantly, we used this mouse model to investigate the efficacy of tipifarnib in sensitizing neuroblastoma tumors to dinutuximab. The effect of tipifarnib on both the TME and host immune system were assessed by flow cytometry. RESULTS: We demonstrated that neuroblastoma-derived sEVs significantly attenuated the efficacy of dinutuximab in vivo and modulated tumor immune cell infiltration upon dinutuximab treatment to create an immunosuppressive TME that contains more tumor-associated macrophages and fewer tumor-infiltrating NK cells. In addition, we demonstrated that neuroblastoma-derived sEVs suppress splenic NK cell maturation in vivo and dinutuximab-induced NK cell-mediated antibody-dependent cellular cytotoxicity in vitro. Importantly, tipifarnib drastically enhanced the efficacy of dinutuximab-mediated inhibition of tumor growth and prevented the immunosuppressive effects of neuroblastoma-derived sEVs in vivo. CONCLUSIONS: These preclinical findings uncover a novel mechanism by which neuroblastoma-derived sEVs modulate the immune system to promote resistance to dinutuximab and suggest that tipifarnib-mediated inhibition of sEV secretion may serve as a viable treatment strategy to enhance the antitumor efficacy of anti-GD2 immunotherapy in high-risk neuroblastoma patients.

Thoracic Neuroblastoma: A Novel Surgical Model for the Study of Extra-adrenal Neuroblastoma.

BACKGROUND/AIM: Neuroblastoma is clinically and molecularly heterogeneous, with poor outcomes despite multimodal treatment strategies. The primary tumor site is an independent predictor of survival; adrenal tumors have the worst outcomes, while posterior mediastinum tumors carry a more favorable prognosis. MATERIALS AND METHODS: To elucidate the role of the primary tumor microenvironment in mediating survival outcomes, we developed a mouse model for the study of extra-adrenal neuroblastoma by injecting luciferase-tagged cells into either the subpleural space of the posterior chest or the adrenal gland. RESULTS: Solid tumors developed in the thoracic cavity at the same rate and efficiency as the adrenal as early as one week post-surgery. The survival rate following surgery was equivalent, though the physiological tolerance for large tumors was lower in the thoracic group. CONCLUSION: This novel mouse model of survivable extra-adrenal neuroblastoma will enable future investigations of the distinct tumor microenvironments between the adrenal gland and posterior mediastinum.

Impact of varying doses of omega-3 supplementation on muscle damage and recovery after eccentric resistance exercise.

BACKGROUND: Exercise-induced muscle damage (EIMD) commonly occurs following intense resistance exercise and is associated with decrements in exercise performance and delayed muscle recovery. Thus, practical methods to attenuate EIMD would prove useful to both training and athletic populations. Omega-3 (n-3) supplementation has been shown to mitigate EIMD with evidence of increasing efficacy at higher doses (up to 6 g/day). However, data of its efficacy in trained individuals is limited. Therefore, this study investigated the effects of 6 and 8 g of n-3 supplementation on markers of muscle damage and muscle recovery after eccentric resistance exercise in resistance-trained males. METHODS: Using a double-blind, randomized, placebo-controlled design, 26 resistance trained males (23 ± 4 years; 173.6 ± 20.5 cm; 81.9 ± 9.7 kg; 14.2 ± 3.7% body fat) supplemented with 6 (n=10) or 8 g (n=7) of n-3 polyunsaturated fatty acids, or placebo (n=9) for 33 days. On day 30, participants performed a lower body muscle-damaging eccentric resistance exercise bout. Measures of muscle performance, soreness, and damage were taken pre-exercise on day 30 as well as on days 31-33, including vertical jump height (VJH), perceived muscle soreness (PMS), hip and knee range of motion (ROM), repetitions to fatigue (RTF) at 70% 1-RM, and serum creatine kinase (CK) while participants continued to supplement until day 33. RESULTS: There were significant differences in VJH, PMS, and serum CK following the muscle-damaging exercise bout compared to pre-exercise (p<0.05). However, there were no significant (p>0.05) differences between supplementation groups (6 g, 8 g, and placebo) at any time point post-exercise (day 31-33). There were no changes in hip and knee ROM or RTF at any time point or between groups. Vertical jump height and PMS returned to pre-exercise levels despite CK remaining elevated post-exercise. CONCLUSIONS: Thirty-three days of 6 and 8 g of n-3 supplementation did not attenuate EIMD or enhance muscle recovery following muscle-damaging eccentric resistance exercise in resistance-trained males. Further research using various n-3 supplementation durations, doses, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations may be needed to establish its efficacy in attenuating EIMD, which may vary between trained and untrained individuals. Furthermore, while circulating CK is commonly used to assess muscle damage, elevated CK levels may not reflect muscle recovery status following muscle-damaging exercise.

Biogeochemical processes create distinct isotopic fingerprints to track floodplain rearing of juvenile salmon.

Floodplains represent critical nursery habitats for a variety of fish species due to their highly productive food webs, yet few tools exist to quantify the extent to which these habitats contribute to ecosystem-level production. Here we conducted a large-scale field experiment to characterize differences in food web composition and stable isotopes (δ¹³C, δ¹5N, δ³4S) for salmon rearing on a large floodplain and adjacent river in the Central Valley, California, USA. The study covered variable hydrologic conditions including flooding (1999, 2017), average (2016), and drought (2012-2015). In addition, we determined incorporation rates and tissue fractionation between prey and muscle from fish held in enclosed locations (experimental fields, cages) at weekly intervals. Finally, we measured δ³4S in otoliths to test if these archival biominerals could be used to reconstruct floodplain use. Floodplain-reared salmon had a different diet composition and lower δ13C and δ³4S (δ¹³C = -33.02±2.66‰, δ³4S = -3.47±2.28‰; mean±1SD) compared to fish in the adjacent river (δ¹³C = -28.37±1.84‰, δ³4S = +2.23±2.25‰). These isotopic differences between habitats persisted across years of extreme droughts and floods. Despite the different diet composition, δ¹5N values from prey items on the floodplain (δ¹5N = 7.19±1.22‰) and river (δ¹5N = 7.25±1.46‰) were similar, suggesting similar trophic levels. The food web differences in δ13C and δ³4S between habitats were also reflected in salmon muscle tissue, reaching equilibrium between 24-30 days (2014, δ¹³C = -30.74±0.73‰, δ³4S = -4.6±0.68‰; 2016, δ¹³C = -34.74 ±0.49‰, δ³4S = -5.18±0.46‰). δ³4S measured in sequential growth bands in otoliths recorded a weekly time-series of shifting diet inputs, with the outermost layers recording time spent on the floodplain (δ³4S = -5.60±0.16‰) and river (δ³4S = 3.73±0.98‰). Our results suggest that δ¹³C and δ³4S can be used to differentiate floodplain and river rearing habitats used by native fishes, such as Chinook Salmon, across different hydrologic conditions and tissues. Together these stable isotope analyses provide a toolset to quantify the role of floodplains as fish habitats.

Reconciling fish and farms: Methods for managing California rice fields as salmon habitat.

Rearing habitat for juvenile Chinook Salmon (Oncorhynchus tshawytscha) in California, the southernmost portion of their range, has drastically declined throughout the past century. Recently, through cooperative agreements with diverse stakeholders, winter-flooded agricultural rice fields in California's Central Valley have emerged as ecologically functioning floodplain rearing habitat for juvenile Chinook Salmon. From 2013 to 2016, we conducted a series of experiments examining methods to enhance habitat benefits for fall-run Chinook Salmon reared on winter-flooded rice fields in the Yolo Bypass, a modified floodplain managed for flood control, agriculture, and wildlife habitat in the Sacramento River Valley of California. Investigations included studying the effect of 1) post-harvest field substrate; 2) depth refugia; 3) duration of field drainage; and 4) duration of rearing occupancy on in-situ diet, growth and survival of juvenile salmon. Post-harvest substrate treatment had only a small effect on the lower trophic food web and an insignificant effect on growth rates or survival of rearing hatchery-origin, fall-run Chinook Salmon. Similarly, depth refugia, created by trenches dug to various depths, also had an insignificant effect on survival. Rapid field drainage yielded significantly higher survival compared to drainage methods drawn out over longer periods. A mortality of approximately one third was observed in the first week after fish were released in the floodplain. This initial mortality event was followed by high, stable survival rates for the remainder of the 6-week duration of floodplain rearing study. Across years, in-field survival ranged 7.4-61.6% and increased over the course of the experiments. Despite coinciding with the most extreme drought in California's recorded history, which elevated water temperatures and reduced the regional extent of adjacent flooded habitats which concentrated avian predators, the adaptive research framework enabled incremental improvements in design to increase survival. Zooplankton (fish food) in the winter-flooded rice fields were 53-150x more abundant than those sampled concurrently in the adjacent Sacramento River channel. Correspondingly, observed somatic growth rates of juvenile hatchery-sourced fall-run Chinook Salmon stocked in rice fields were two to five times greater than concurrently and previously observed growth rates in the adjacent Sacramento River. The abundance of food resources and exceptionally high growth rates observed during these experiments illustrate the potential benefits of using existing agricultural infrastructure to approximate the floodplain wetland physical conditions and hydrologic patterns (shallow, long-duration inundation of cool floodplain habitats in mid-winter) under which Chinook Salmon evolved and to which they are adapted.

Altered Physical Performance Following Advanced Special Operations Tactical Training.

ABSTRACT: Winters, JD, Heebner, NR, Johnson, AK, Poploski, KM, Royer, SD, Nagai, T, Randall, CA, Abt, JP, and Lephart, SM. Altered physical performance following advanced special operations tactical training. J Strength Cond Res 35(7): 1809-1816, 2021-The purpose of this study was to determine how the unique challenges of specific military tactical training phases influence overall physical performance characteristics. Broad jump, 5-10-5, 300-yd shuttle, percent body fat (%BF), anaerobic power (AP) and anaerobic capacity (AC), maximal oxygen uptake (V̇o2max), isokinetic knee extension/flexion strength, shoulder internal/external rotation strength, and trunk extension/flexion strength were collected on 73 United States Marine Corps Forces Special Operations Command (MARSOC) students (age: 27.4 ± 3.8 years, height: 178.7 ± 6.6 cm, and body mass: 85.8 ± 9.4 kg) at the beginning of (P1), in between (P2), and at the completion of 2 distinct tactical training phases (P3). Linear mixed models were used to analyze within-subject performance changes over the 3 time points, and post hoc Bonferroni pairwise comparisons analyzed performance changes between each testing time point. There were significant changes in broad jump (p < 0.0001), 5-10-5 agility time (p < 0.001), %BF (p = 0.011), AP (p < 0.0001), V̇o2max (p = 0.001), and both right and left shoulder internal rotation strength (p = 0.004 and p = 0.015, respectively) between P1 and P2. There were also significant changes in 300-yd shuttle run time (p = 0.001), AP (p < 0.0001), AC (p < 0.0001), left knee extension strength (p = 0.006), trunk flexion strength (p < 0.0001), and left shoulder external rotation strength (0.027) between P2 and P3. Identifying the effect that specific tactical training phases may have on physical performance will allow for the development of effective phase-specific evidence-based human performance programs, reducing performance deficits and thereby reducing the risk of injury.

Endochondral growth zone pattern and activity in the zebrafish pharyngeal skeleton.

BACKGROUND: Endochondral ossification is a major bone forming mechanism in vertebrates, defects in which can result in skeletal dysplasia or craniofacial anomalies in humans. The zebrafish holds great potential to advance our understanding of endochondral growth zone development and genetics, yet several important aspects of its biology remain unexplored. Here we provide a comprehensive description of endochondral growth zones in the pharyngeal skeleton, including their developmental progression, cellular activity, and adult fates. RESULTS: Postembryonic growth of the pharyngeal skeleton is supported by endochondral growth zones located either at skeletal epiphyses or synchondroses. Col2a1a and col10a1a in situ hybridization and anti-PCNA immunostaining identify resting-, hypertrophic- and proliferative zones, respectively, in pharyngeal synchondroses. Cellular hypertrophy and matrix deposition contribute little, if at all, to axial growth in most skeletal elements. Zebrafish endochondral growth zones develop during metamorphosis and arrest in adults. CONCLUSIONS: Two endochondral growth zone configurations in the zebrafish pharyngeal skeleton produce either unidirectional (epiphyses) or bidirectional (synchondroses) growth. Cell proliferation drives endochondral growth and its modulation, in contrast to mammalian long bones in which bone length depends more on cell enlargement during hypertrophy and intramembranous ossification is the default mechanism of bone growth in zebrafish adults.

Chemotherapy-Induced Upregulation of Small Extracellular Vesicle-Associated PTX3 Accelerates Breast Cancer Metastasis.

Although neoadjuvant chemotherapy is a standard component of breast cancer treatment, recent evidence suggests that chemotherapeutic drugs can promote metastasis through poorly defined mechanisms. Here we utilize xenograft mouse models of triple-negative breast cancer to explore the importance of chemotherapy-induced tumor-derived small extracellular vesicles (sEV) in metastasis. Doxorubicin (DXR) enhanced tumor cell sEV secretion to accelerate pulmonary metastasis by priming the premetastatic niche. Proteomic analysis and CRISPR/Cas9 gene editing identified the inflammatory glycoprotein PTX3 enriched in DXR-elicited sEV as a critical regulator of chemotherapy-induced metastasis. Both genetic inhibition of sEV secretion from primary tumors and pharmacologic inhibition of sEV uptake in secondary organs suppressed metastasis following chemotherapy. Taken together, this research uncovers a mechanism of chemotherapy-mediated metastasis by which drug-induced upregulation of sEV secretion and PTX3 protein cargo primes the premetastatic niche and suggests that inhibition of either sEV uptake in secondary organs or secretion from primary tumor cells may be promising therapeutic strategies to suppress metastasis. SIGNIFICANCE: These findings show that chemotherapy-induced small extracellular vesicles accelerate breast cancer metastasis, and targeted inhibition of tumor-derived vesicles may be a promising therapeutic strategy to improve the efficacy of chemotherapy treatment.

A Quantitative Digital Subtraction Angiography Technique for Characterizing Reduction in Hepatic Arterial Blood Flow During Transarterial Embolization.

OBJECTIVE: There is no standardized and objective method for determining the optimal treatment endpoint (sub-stasis) during transarterial embolization. The objective of this study was to demonstrate the feasibility of using a quantitative digital subtraction angiography (qDSA) technique to characterize intra-procedural changes in hepatic arterial blood flow velocity in response to transarterial embolization in an in vivo porcine model. MATERIALS AND METHODS: Eight domestic swine underwent bland transarterial embolizations to partial- and sub-stasis angiographic endpoints with intraprocedural DSA acquisitions. Embolized lobes were assessed on histopathology for ischemic damage and tissue embolic particle density. Analysis of target vessels used qDSA and a commercially available color-coded DSA (ccDSA) tool to calculate blood flow velocities and time-to-peak, respectively. RESULTS: Blood flow velocities calculated using qDSA showed a statistically significant difference (p < 0.01) between partial- and sub-stasis endpoints, whereas time-to-peak calculated using ccDSA did not show a significant difference. During the course of embolizations, the average correlation with volume of particles delivered was larger for qDSA (- 0.86) than ccDSA (0.36). There was a statistically smaller mean squared error (p < 0.01) and larger coefficient of determination (p < 0.01) for qDSA compared to ccDSA. On pathology, the degree of embolization as calculated by qDSA had a moderate, positive correlation (p < 0.01) with the tissue embolic particle density of ischemic regions within the embolized lobe. CONCLUSIONS: qDSA was able to quantitatively discriminate angiographic embolization endpoints and, compared to a commercially available ccDSA method, improve intra-procedural characterization of blood flow changes. Additionally, the qDSA endpoints correlated with tissue-level changes.