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Lower limb joint kinetics are among the most commonly reported values after instrumented gait analysis and are typically estimated via inverse dynamic calculations. These calculations require, among other things, the selection of a link-segment model that is representative of the subject being tested. In applying inverse dynamics calculations to a standard link-segment model, several assumptions are commonly made in an effort to simplify the calculations. These assumptions regarding the link-segment model are derived from conventional anatomy and physiology and therefore may not be valid when applied to individuals with lower limb loss because their unique anatomical characteristics and the design of lower limb prosthetic componentry may not be accurately accounted for. This article reviews the validity of applying these common assumptions to the analysis of individuals with lower limb loss, with the goal of enabling prosthetists to better judge the quality and accuracy of empirical research findings by furthering their understanding of inverse dynamic theory and its application to the quantitative gait analysis of individuals with lower limb loss. [ABSTRACT FROM AUTHOR]

Saxitoxin (STX) is a potent neurotoxin naturally produced by dinoflagellates and cyanobacteria. STX inhibits voltage-gated sodium channels (VGSCs), affecting the propagation of action potentials. Consumption of seafood contaminated with STX is responsible for paralytic shellfish poisoning (PSP). Humans are among the species most sensitive to PSP; neurological symptoms of exposure range from tingling of the extremities to severe paralysis. The objective of this study was to determine the effects of STX exposure on developmental processes during early embryogenesis. This study was designed to test the hypothesis that early developmental exposure to STX would disrupt key processes, particularly those related to neural development. Zebrafish embryos were exposed to STX (24 or 48pg) or vehicle (0.3mM HCl) at 6hours post fertilization (hpf) via microinjection. There was no overt toxicity but starting at 36 hpf there was a temporary lack of pigmentation in STX-injected embryos, which resolved by 72 hpf. Using high performance liquid chromatography, we found that STX was retained in embryos up to 72 hpf in a dose-dependent manner. Temporal transcriptional profiling of embryos exposed to 48pg STX per embryo revealed no differentially expressed genes (DEGs) at 24 hpf, but at 36 and 48 hpf, there were 3547 and 3356 DEGs, respectively. KEGG pathway analysis revealed significant enrichment of genes related to focal adhesion, adherens junction and regulation of actin cytoskeleton, suggesting that cell-cell and cell-extracellular matrix interactions were affected by STX. Genes affected are critical for axonal growth and the development of functional neural networks. We confirmed these findings by visualizing axonal defects in transgenic zebrafish with fluorescently labeled sensory neurons. In addition, our gene expression results suggest that STX exposure affects both canonical and noncanonical functions of VGSCs. Given the fundamental role of VGSCs in both physiology and development, these findings offer valuable insights into effects of exposure to neurotoxins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The focal radiation therapy (RT) boost technique was shown in a phase III randomized controlled trial (RCT) to improve prostate cancer outcomes without increasing toxicity. This technique relies on the accurate delineation of prostate tumors on MRI. A recent prospective study evaluated radiation oncologists' accuracy when asked to delineate prostate tumors on MRI and demonstrated high variability in tumor contours. We sought to evaluate the impact of contour variability and inaccuracy on predicted clinical outcomes. We hypothesized that radiation oncologists' contour inaccuracies would yield meaningfully worse clinical outcomes., Methods and Materials: Forty-five radiation oncologists and 2 expert radiologists contoured prostate tumors on 30 patient cases. Of these cases, those with CT simulation or diagnostic CT available were selected for analysis. A knowledge-based planning model was developed to generate focal RT boost plans for each contour per the RCT protocol. The probability of biochemical failure (BF) was determined using a model from the RCT. The primary metric evaluated was delta BF (DBF = Participant BF - Expert BF). An absolute increase in BF ≥5% was considered clinically meaningful., Results: Eight patient cases and 394 target volumes for focal RT boost planning were included in this analysis. In general, participant plans were associated with worse predicted clinical outcomes compared to the expert plan, with an average absolute increase in BF of 4.3%. Of participant plans, 37% were noted to have an absolute increase in BF of 5% or more., Conclusions: Radiation oncologists' attempts to contour tumor targets for focal RT boost are frequently inaccurate enough to yield meaningfully inferior clinical outcomes for patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa)., Methods: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75 ms and once at TE = 90 ms (TEmin 1 , TEmin 2 , and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin 1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrs TE90corr ) and uncorrected TE90 (RSIrs TE90 ) to RSIrs from reference TEmin 1 (RSIrs TEmin1 ) and repeated TEmin 2 (RSIrs TEmin2 ). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC)., Results: Scaling factors for C 1 , C 2 , C 3 , and C 4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrs TEmin2 and RSIrs TEmin1 differed by 0.27 ± 0.86SI (mean ± standard deviation), whereas RSIrs TE90 differed from RSIrs TEmin1 by 1.82 ± 1.20SI. After calibration, this bias was reduced to -0.51 ± 1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54 ± 1.98SI between RSIrs TEmin2 and RSIrs TEmin1 and 2.28 ± 2.06SI between RSIrs TE90 and RSIrs TEmin1 . After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrs TEmin1 has a sensitivity of 66% and a specificity of 72%., Conclusions: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

A diversity of chemicals are intentionally added to plastics to enhance their properties and aid in manufacture. Yet, the accumulated chemical composition of these materials is essentially unknown even to those within the supply chain, let alone to consumers or recyclers. Recent legislated and voluntary commitments to increase recycled content in plastic products highlight the practical challenges wrought by these chemical mixtures, amid growing public concern about the impacts of plastic-associated chemicals on environmental and human health. In this Perspective, we offer guidance for plastics manufacturers to collaborate across sectors and critically assess their use of added chemicals. The ultimate goal is to use fewer and better additives to promote a circular plastics economy with minimal risk to humans and the environment., Competing Interests: Competing interests The authors declare no competing interests.

Background: Multi-segment foot models (MFMs) provide a better understanding of the intricate biomechanics of the foot, yet it is unclear if they accurately differentiate foot type function during locomotion., Research Question: We employed an MFM to detect subtle kinematic differences between foot types, including: pes cavus, neutrally aligned, and asymptomatic and symptomatic pes planus. The study investigates how variable the results of this MFM are and if it can detect kinematic differences between pathologic and non-pathologic foot types during the stance phase of gait., Methods: Independently, three raters instrumented three subjects on three days to assess variability. In a separate cohort, each foot type was statically quantified for ten subjects per group. Each subject walked while instrumented with a four-segment foot model to assess static alignment and foot motion during the stance phase of gait. Statistical analysis performed with a linear mixed effects regression., Results: Model variability was highest for between-day and lowest for between-rater, with all variability measures being within the true sample variance. Almost all static measures (radiographic, digital scan, and kinematic markers) differed significantly by foot type. Sagittal hindfoot to leg and forefoot to leg kinematics differed between foot types during late stance, as well as coronal hallux to forefoot range of motion. The MFM had low between-rater variability and may be suitable for multiple raters to apply to a single study sample without introducing significant error. The model, however, only detected a few dynamic differences, with the most dramatic being the hallux to forefoot coronal plane range of motion., Significance: Results only somewhat aligned with previous work. It remains unclear if the MFM is sensitive enough to accurately detect different motion between foot types (pathologic and non-pathologic). A more accurate method of tracking foot bone motion (e.g., biplane fluoroscopy) may be needed to address this question., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Popularized on social media, hand-moldable plastics are formed by consumers into tools, trinkets, and dental prosthetics. Despite the anticipated dermal and oral contact, manufacturers share little information with consumers about these materials, which are typically sold as microplastic-sized resin pellets. Inherent to their function, moldable plastics pose a risk of dermal and oral exposure to unknown leachable substances. We analyzed 12 moldable plastics advertised for modeling and dental applications and determined them to be polycaprolactone (PCL) or thermoplastic polyurethane (TPU). The bioactivities of the most popular brands advertised for modeling applications of each type of polymer were evaluated using a zebrafish embryo bioassay. While water-borne exposure to the TPU pellets did not affect the targeted developmental end points at any concentration tested, the PCL pellets were acutely toxic above 1 pellet/mL. The aqueous leachates of the PCL pellets demonstrated similar toxicity. Methanolic extracts from the PCL pellets were assayed for their bioactivity using the Attagene FACTORIAL platform. Of the 69 measured end points, the extracts activated nuclear receptors and transcription factors for xenobiotic metabolism (pregnane X receptor, PXR), lipid metabolism (peroxisome proliferator-activated receptor γ, PPARγ), and oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2). By nontargeted high-resolution comprehensive two-dimensional gas chromatography (GC × GC-HRT), we tentatively identified several compounds in the methanolic extracts, including PCL oligomers, a phenolic antioxidant, and residues of suspected antihydrolysis and cross-linking additives. In a follow-up zebrafish embryo bioassay, because of its stated high purity, biomedical grade PCL was tested to mitigate any confounding effects due to chemical additives in the PCL pellets; it elicited comparable acute toxicity. From these orthogonal and complementary experiments, we suggest that the toxicity was due to oligomers and nanoplastics released from the PCL rather than chemical additives. These results challenge the perceived and assumed inertness of plastics and highlight their multiple sources of toxicity.

Children in rural communities consume more energy-dense foods relative to their urban peers. Identifying effective interventions for improving energy intake patterns are needed to address these geographic disparities. The primary aim of this study was to harness the benefits of physical activity on children's executive functioning to see if these improvements lead to acute changes in eating behaviors. In a randomized crossover design, 91 preadolescent (8-10y; M age = 9.48 ± 0.85; 50.5% female; 85.7% White, 9.9% Multiracial, 9.9% Hispanic) children (86% rural) completed a 20-minute physical activity condition (moderate intensity walking) and time-matched sedentary condition (reading and/or coloring) ~ 14 days apart. Immediately following each condition, participants completed a behavioral inhibition task and then eating behaviors (total energy intake, relative energy intake, snack intake) were measured during a multi-array buffet test meal. After adjusting for period and order effects, body fat (measured via DXA), and depressive symptoms, participants experienced significant small improvements in their behavioral inhibition following the physical activity versus sedentary condition (p = 0.04, Hedge's g = 0.198). Eating behaviors did not vary by condition, nor did improvements in behavioral inhibition function as a mediator (ps > 0.09). Thus, in preadolescent children, small improvements in behavioral inhibition from physical activity do not produce acute improvements in energy intake. Additional research is needed to clarify whether the duration and/or intensity of physical activity sessions would produce different results in this age group, and whether intervention approaches and corresponding mechanisms of change vary by individual factors, like age and degree of food cue responsivity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Mongold, SJ, Ricci, AW, Hahn, ME, and Callahan, DM. Skeletal muscle compliance and echogenicity in resistance-trained and nontrained women. J Strength Cond Res 38(4): 671-680, 2024-Noninvasive assessment of muscle mechanical properties in clinical and performance settings tends to rely on manual palpation and emphasizes examination of musculotendinous stiffness. However, measurement standards are highly subjective. The purpose of the study was to compare musculotendinous stiffness in adult women with varying resistance training history while exploring the use of multiple tissue compliance measures. We identified relationships between tissue stiffness and morphology, and tested the hypothesis that combining objective measures of morphology and stiffness would better predict indices of contractile performance. Resistance-trained (RT) women (n = 11) and nontrained (NT) women (n = 10) participated in the study. Muscle echogenicity and morphology were measured using B-mode ultrasonography (US). Vastus lateralis (VL) and patellar tendon (PT) stiffness were measured using digital palpation and US across submaximal isometric contractions. Muscle function was evaluated during maximal voluntary isometric contraction (MVIC) of the knee extensors (KEs). Resistance trained had significantly greater PT stiffness and reduced echogenicity (p < 0.01). Resistance trained also had greater strength per body mass (p < 0.05). Muscle echogenicity was strongly associated with strength and rate of torque development (RTD). Patellar tendon passive stiffness was associated with RTD normalized to MVIC (RTDrel; r = 0.44, p < 0.05). Patellar tendon stiffness was greater in RT young women. No predictive models of muscle function incorporated both stiffness and echogenicity. Because RTDrel is a clinically relevant measure of rehabilitation in athletes and can be predicted by digital palpation, this might represent a practical and objective measure in settings where RTD may not be easy to measure directly., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the National Strength and Conditioning Association.)

Microplastics and nanoplastics are found in marine biota across a wide range of trophic levels and environments. While a large portion of the information about plastic exposure comes from gastrointestinal (GI) data, the relevance of particle accumulation from an oral exposure compared with other types of exposure (e.g. dermal, respiratory) is unknown. To address this gap in knowledge, larval zebrafish (7 days post fertilization) were exposed to two different sizes of nanoplastics through either oral gavage or a waterborne exposure. Larvae were tracked for 48 h post exposure (hpe) to assess the migration and elimination of plastics. Larvae eliminated orally gavaged nanoplastics within 48 hpe. Oral gavage showed limited particle movement from the GI tract into other tissues. In contrast, waterborne nanoplastic-exposed larvae displayed notable fluorescence in tissues outside of the GI tract. The 50 nm waterborne-exposed larvae retained the particles past 48 hpe, and showed accumulation with neuromasts. For both sizes of plastic particles, the nanoplastics were eliminated from non-GI tract tissues by 24 hpe. Our results suggest that waterborne exposure leads to greater accumulation of plastic in comparison to oral exposure, suggesting that plastic accumulation in certain tissues is greater via routes of exposure other than oral consumption., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery., Design: Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross-sectional study., Setting: Eight clinical sites in the US Pelvic Floor Disorders Network., Population or Sample: Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015., Methods: The MRI (rest, strain) obtained 30-42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI-based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to create three-dimensional models placed in a morphometry algorithm to quantify and compare vaginal morphology (angulation, dimensions) and position., Main Outcome Measures: Vaginal angulation (upper, lower and upper-lower vaginal angles in the sagittal and coronal plane), dimensions (length, maximum transverse width, surface area, volume) and position (apex, mid-vagina) at rest., Results: Of the 82 women analysed, 12/41 (29%) in the hysteropexy group and 22/41 (54%) in the hysterectomy group had prolapse recurrence. After hysteropexy, women with recurrence had a more laterally deviated upper vagina (p = 0.02) at rest than women with successful surgery. After hysterectomy, women with recurrence had a more inferiorly (lower) positioned vaginal apex (p = 0.01) and mid-vagina (p = 0.01) at rest than women with successful surgery., Conclusions: Vaginal angulation and position were associated with prolapse recurrence and suggestive of vaginal support mechanisms related to surgical technique and potential unaddressed anatomical defects. Future prospective studies in women before and after prolapse surgery may distinguish these two factors., (© 2023 John Wiley & Sons Ltd.)

The genetic architecture of phenotypic traits can affect the mode and tempo of trait evolution. Human-altered environments can impose strong natural selection, where successful evolutionary adaptation requires swift and large phenotypic shifts. In these scenarios, theory predicts that adaptation is due to a few adaptive variants of large effect, but empirical studies that have revealed the genetic architecture of rapidly evolved phenotypes are rare, especially for populations inhabiting polluted environments. Fundulus killifish have repeatedly evolved adaptive resistance to extreme pollution in urban estuaries. Prior studies, including genome scans for signatures of natural selection, have revealed some of the genes and pathways important for evolved pollution resistance, and provide context for the genotype-phenotype association studies reported here. We created multiple quantitative trait locus (QTL) mapping families using progenitors from four different resistant populations, and using RAD-seq genetically mapped variation in sensitivity (developmental perturbations) following embryonic exposure to a model toxicant PCB-126. We found that one to two large-effect QTL loci accounted for resistance to PCB-mediated developmental toxicity. QTLs harbored candidate genes that govern the regulation of aryl hydrocarbon receptor (AHR) signaling. One QTL locus was shared across all populations and another was shared across three populations. One QTL locus showed strong signatures of recent natural selection in the corresponding wild population but another QTL locus did not. Some candidate genes for PCB resistance inferred from genome scans in wild populations were identified as QTL, but some key candidate genes were not. We conclude that rapidly evolved resistance to the developmental defects normally caused by PCB-126 is governed by few genes of large effect. However, other aspects of resistance beyond developmental phenotypes may be governed by additional loci, such that comprehensive resistance to PCB-126, and to the mixtures of chemicals that distinguish urban estuaries more broadly, may be more genetically complex., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

While plastic pollution threatens ecosystems and human health, the use of plastic products continues to increase. Limiting its harm requires design strategies for plastic products informed by the threats that plastics pose to the environment. Thus, we developed a sustainability metric for the ecodesign of plastic products with low environmental persistence and uncompromised performance. To do this, we integrated the environmental degradation rate of plastic into established material selection strategies, deriving material indices for environmental persistence. By comparing indices for the environmental impact of on-the-market plastics and proposed alternatives, we show that accounting for the environmental persistence of plastics in design could translate to societal benefits of hundreds of millions of dollars for a single consumer product. Our analysis identifies the materials and their properties that deserve development, adoption, and investment to create functional and less environmentally impactful plastic products., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Microplastics (MPs) have been found in a diverse range of organisms across trophic levels. While a majority of the information on organismal exposure to plastics in the environment comes from gastrointestinal (GI) data, the prevalence of MP particles in other tissues is not well understood. Additionally, many studies have not been able to detect the smallest, most prevalent, MPs (1 µm - 5 mm) that are the most likely to distribute to tissues in the body. To address these knowledge gaps, MPs in the GI tract and muscle of Atlantic killifish ( Fundulus heteroclitus ) collected from two sites (Falmouth and Bourne) on Buzzards Bay, Cape Cod, MA were quantified down to 2 µm in size. Eight fish from Falmouth and 10 fish Bourne site were analyzed. Fourier-transform infrared spectroscopy and Raman spectroscopy were used to identify all particles. The mean concentrations of MPs in the GI tract and muscle from fish collected from Falmouth was 85.5 ± 70.2 and 11 ± 12.5 particles per gram wet weight, respectively. Fish collected from Bourne site had mean particle concentrations of 12.2 ± 18.1 and 1.69 ± 5.36 particles per gram wet weight. Of the 2,008 particles analyzed in various fish tissue samples, only 3.4% (69 particles) were identified as plastic; polymers included nylon, polyethylene, polypropylene, and polyurethane. MPs detected in the GI tract samples also tended to be more diverse in both size and polymer type than those found in the muscle. We found that MPs < 50 µm, which are often not analyzed in the literature, were the most common in both the GI tract and muscle samples. There was not a significant correlation between the MP content in the muscle compared to the GI tract, indicating that GI tract MP abundance cannot be used to predict non-GI tract tissue MP content; however, MP abundance in muscle correlated with fish total length, suggesting potential bioaccumulation of these small MPs., Supplementary Information: The online version contains supplementary material available at 10.1186/s43591-024-00101-w., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Postural control is one of the primary body functions for fall prevention. Unexpected perturbation-based balance training is effective for improving postural control. However, the effect of perturbation-based training using assistive devices on muscle activity and co-contraction for standing balance is still unclear. This training is also difficult to perform easily because it requires large instruments or expert guidance. The purpose of this study is to demonstrate the effect of perturbation-based balance training using a wearable balance training device (WBTD) on postural control. In this study, fourteen healthy young adult males were assigned to either a WBTD group or a sham group. In the intervention session, participants in the WBTD group were perturbed either left or right direction at random timing by the WBTD during tandem stance balance training. Participants in the Sham group did not receive external perturbation during tandem stance balance training. Before and after the intervention session, participants of both groups underwent unexpected lateral perturbation postural control testing (pre- and post-test). The normalized integral of electromyography (IEMG), co-contraction index (CCI), and center of pressure (COP) parameters were measured in the pre- and post-test. Experimental results showed that the WBTD group in the post-test significantly decreased left Gluteus Medius IEMG, CCI of both Gluteus Medius, and peak [Formula: see text] velocity, compared to those of the pre-test ( [Formula: see text], p =0.024 , p =0.031 , respectively). We conclude that balance training using WBTD could improve flexible postural control adjustment via cooperative muscle activation.

Purpose: In a phase III randomized trial, adding a radiation boost to tumor(s) visible on MRI improved prostate cancer (PCa) disease-free and metastasis-free survival without additional toxicity. Radiation oncologists' ability to identify prostate tumors is critical to widely adopting intraprostatic tumor radiotherapy boost for patients. A diffusion MRI biomarker, called the Restriction Spectrum Imaging restriction score (RSIrs), has been shown to improve radiologists' identification of clinically significant PCa. We hypothesized that (1) radiation oncologists would find accurately delineating PCa tumors on conventional MRI challenging and (2) using RSIrs maps would improve radiation oncologists' accuracy for PCa tumor delineation., Methods and Materials: In this multi-institutional, international, prospective study, 44 radiation oncologists (participants) and 2 expert radiologists (experts) contoured prostate tumors on 39 total patient cases using conventional MRI with or without RSIrs maps. Participant volumes were compared to the consensus expert volumes. Contouring accuracy metrics included percent overlap with expert volume, Dice coefficient, conformal number, and maximum distance beyond expert volume., Results: 1604 participant volumes were produced. 40 of 44 participants (91%) completely missed ≥1 expert-defined target lesion without RSIrs, compared to 13 of 44 (30%) with RSIrs maps. On conventional MRI alone, 134 of 762 contour attempts (18%) completely missed the target, compared to 18 of 842 (2%) with RSIrs maps. Use of RSIrs maps improved all contour accuracy metrics by approximately 50% or more. Mixed effects modeling confirmed that RSIrs maps were the main variable driving improvement in all metrics. System Usability Scores indicated RSIrs maps significantly improved the contouring experience (72 vs. 58, p < 0.001)., Conclusions: Radiation oncologists struggle with accurately delineating visible PCa tumors on conventional MRI. RSIrs maps improve radiation oncologists' ability to target MRI-visible tumors for prostate tumor boost., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In May 2021, the M/V X-Press Pearl container ship burned for 2 weeks, leading to the largest maritime spill of resin pellets (nurdles). The disaster was exacerbated by the leakage of other cargo and the ship's underway fuel. This disaster affords the unique opportunity to study a time-stamped, geolocated release of plastic under real-world conditions. Field samples collected from beaches in Sri Lanka nearest to the ship comprised nurdles exposed to heat and combustion, burnt plastic pieces (pyroplastic), and oil-plastic agglomerates (petroplastic). An unresolved question is whether the 1600+ tons of spilled and recovered plastic should be considered hazardous waste. Due to the known formation and toxicity of combustion-derived polycyclic aromatic hydrocarbons (PAHs), we measured 20 parent and 21 alkylated PAHs associated with several types of spilled plastic. The maximum PAH content of the sampled pyroplastic had the greatest amount of PAHs recorded for marine plastic debris (199,000 ng/g). In contrast, the sampled unburnt white nurdles had two orders of magnitude less PAH content. The PAH composition varied between the types of spilled plastic and presented features typical of and conflicting with petrogenic and pyrogenic sources. Nevertheless, specific markers and compositional changes for burning plastics were identified, revealing that the fire was the main source of PAHs. Eight months after the spill, the PAH contents of sampled stray nurdles and pyroplastic were reduced by more than 50%. Due to their PAH content exceeding levels allowable for plastic consumer goods, classifying burnt plastic as hazardous waste may be warranted. Following a largely successful cleanup, we recommend that the Sri Lankans re-evaluate the identification, handling, and disposal of the plastic debris collected from beaches and the potential exposure of responders and the public to PAHs from handling it. The maritime disaster underscores pyroplastic as a type of plastic pollution that has yet to be fully explored, despite the pervasiveness of intentional and unintentional burning of plastic globally., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Sunlight transforms plastic into water-soluble products, the potential toxicity of which remains unresolved, particularly for vertebrate animals. We evaluated acute toxicity and gene expression in developing zebrafish larvae after 5 days of exposure to photoproduced (P) and dark (D) leachates from additive-free polyethylene (PE) film and consumer-grade, additive-containing, conventional, and recycled PE bags. Using a "worst-case" scenario, with plastic concentrations exceeding those found in natural waters, we observed no acute toxicity. However, at the molecular level, RNA sequencing revealed differences in the number of differentially expressed genes (DEGs) for each leachate treatment: thousands of genes (5442 P, 577 D) for the additive-free film, tens of genes for the additive-containing conventional bag (14 P, 7 D), and none for the additive-containing recycled bag. Gene ontology enrichment analyses suggested that the additive-free PE leachates disrupted neuromuscular processes via biophysical signaling; this was most pronounced for the photoproduced leachates. We suggest that the fewer DEGs elicited by the leachates from conventional PE bags (and none from recycled bags) could be due to differences in photoproduced leachate composition caused by titanium dioxide-catalyzed reactions not present in the additive-free PE. This work demonstrates that the potential toxicity of plastic photoproducts can be product formulation-specific.

Demonstration of a very dense or hyper-attenuated liver on the pre-contrast CT images of the abdomen can be an unexpected finding. It may present as a diagnostic challenge if the underlying cause of it is not apparent from the provided clinical history. There are about 12 different pathologic conditions that are associated with deposition of radiopaque elements within the hepatic parenchyma, resulting in diffuse or multi-lobar hyperdense appearance of the liver on abdominal radiographs and CT. Most of them are drug-induced or iatrogenic in nature, while others are the sequelae of genetic disorders like thalassemia, Wilson's disease, and primary hemochromatosis. This pictorial essay will present the CT appearance and etiology of hyper-attenuated liver in various clinical entities., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest, The authors declare that they have no disclosure relevant to the subject matter of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Plastics have conveyed great benefits to humanity and made possible some of the most significant advances of modern civilization in fields as diverse as medicine, electronics, aerospace, construction, food packaging, and sports. It is now clear, however, that plastics are also responsible for significant harms to human health, the economy, and the earth's environment. These harms occur at every stage of the plastic life cycle, from extraction of the coal, oil, and gas that are its main feedstocks through to ultimate disposal into the environment. The extent of these harms not been systematically assessed, their magnitude not fully quantified, and their economic costs not comprehensively counted., Goals: The goals of this Minderoo-Monaco Commission on Plastics and Human Health are to comprehensively examine plastics' impacts across their life cycle on: (1) human health and well-being; (2) the global environment, especially the ocean; (3) the economy; and (4) vulnerable populations-the poor, minorities, and the world's children. On the basis of this examination, the Commission offers science-based recommendations designed to support development of a Global Plastics Treaty, protect human health, and save lives., Report Structure: This Commission report contains seven Sections. Following an Introduction, Section 2 presents a narrative review of the processes involved in plastic production, use, and disposal and notes the hazards to human health and the environment associated with each of these stages. Section 3 describes plastics' impacts on the ocean and notes the potential for plastic in the ocean to enter the marine food web and result in human exposure. Section 4 details plastics' impacts on human health. Section 5 presents a first-order estimate of plastics' health-related economic costs. Section 6 examines the intersection between plastic, social inequity, and environmental injustice. Section 7 presents the Commission's findings and recommendations., Plastics: Plastics are complex, highly heterogeneous, synthetic chemical materials. Over 98% of plastics are produced from fossil carbon- coal, oil and gas. Plastics are comprised of a carbon-based polymer backbone and thousands of additional chemicals that are incorporated into polymers to convey specific properties such as color, flexibility, stability, water repellence, flame retardation, and ultraviolet resistance. Many of these added chemicals are highly toxic. They include carcinogens, neurotoxicants and endocrine disruptors such as phthalates, bisphenols, per- and poly-fluoroalkyl substances (PFAS), brominated flame retardants, and organophosphate flame retardants. They are integral components of plastic and are responsible for many of plastics' harms to human health and the environment.Global plastic production has increased almost exponentially since World War II, and in this time more than 8,300 megatons (Mt) of plastic have been manufactured. Annual production volume has grown from under 2 Mt in 1950 to 460 Mt in 2019, a 230-fold increase, and is on track to triple by 2060. More than half of all plastic ever made has been produced since 2002. Single-use plastics account for 35-40% of current plastic production and represent the most rapidly growing segment of plastic manufacture.Explosive recent growth in plastics production reflects a deliberate pivot by the integrated multinational fossil-carbon corporations that produce coal, oil and gas and that also manufacture plastics. These corporations are reducing their production of fossil fuels and increasing plastics manufacture. The two principal factors responsible for this pivot are decreasing global demand for carbon-based fuels due to increases in 'green' energy, and massive expansion of oil and gas production due to fracking.Plastic manufacture is energy-intensive and contributes significantly to climate change. At present, plastic production is responsible for an estimated 3.7% of global greenhouse gas emissions, more than the contribution of Brazil. This fraction is projected to increase to 4.5% by 2060 if current trends continue unchecked., Plastic Life Cycle: The plastic life cycle has three phases: production, use, and disposal. In production, carbon feedstocks-coal, gas, and oil-are transformed through energy-intensive, catalytic processes into a vast array of products. Plastic use occurs in every aspect of modern life and results in widespread human exposure to the chemicals contained in plastic. Single-use plastics constitute the largest portion of current use, followed by synthetic fibers and construction.Plastic disposal is highly inefficient, with recovery and recycling rates below 10% globally. The result is that an estimated 22 Mt of plastic waste enters the environment each year, much of it single-use plastic and are added to the more than 6 gigatons of plastic waste that have accumulated since 1950. Strategies for disposal of plastic waste include controlled and uncontrolled landfilling, open burning, thermal conversion, and export. Vast quantities of plastic waste are exported each year from high-income to low-income countries, where it accumulates in landfills, pollutes air and water, degrades vital ecosystems, befouls beaches and estuaries, and harms human health-environmental injustice on a global scale. Plastic-laden e-waste is particularly problematic., Environmental Findings: Plastics and plastic-associated chemicals are responsible for widespread pollution. They contaminate aquatic (marine and freshwater), terrestrial, and atmospheric environments globally. The ocean is the ultimate destination for much plastic, and plastics are found throughout the ocean, including coastal regions, the sea surface, the deep sea, and polar sea ice. Many plastics appear to resist breakdown in the ocean and could persist in the global environment for decades. Macro- and micro-plastic particles have been identified in hundreds of marine species in all major taxa, including species consumed by humans. Trophic transfer of microplastic particles and the chemicals within them has been demonstrated. Although microplastic particles themselves (>10 µm) appear not to undergo biomagnification, hydrophobic plastic-associated chemicals bioaccumulate in marine animals and biomagnify in marine food webs. The amounts and fates of smaller microplastic and nanoplastic particles (MNPs <10 µm) in aquatic environments are poorly understood, but the potential for harm is worrying given their mobility in biological systems. Adverse environmental impacts of plastic pollution occur at multiple levels from molecular and biochemical to population and ecosystem. MNP contamination of seafood results in direct, though not well quantified, human exposure to plastics and plastic-associated chemicals. Marine plastic pollution endangers the ocean ecosystems upon which all humanity depends for food, oxygen, livelihood, and well-being., Human Health Findings: Coal miners, oil workers and gas field workers who extract fossil carbon feedstocks for plastic production suffer increased mortality from traumatic injury, coal workers' pneumoconiosis, silicosis, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer. Plastic production workers are at increased risk of leukemia, lymphoma, hepatic angiosarcoma, brain cancer, breast cancer, mesothelioma, neurotoxic injury, and decreased fertility. Workers producing plastic textiles die of bladder cancer, lung cancer, mesothelioma, and interstitial lung disease at increased rates. Plastic recycling workers have increased rates of cardiovascular disease, toxic metal poisoning, neuropathy, and lung cancer. Residents of "fenceline" communities adjacent to plastic production and waste disposal sites experience increased risks of premature birth, low birth weight, asthma, childhood leukemia, cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer.During use and also in disposal, plastics release toxic chemicals including additives and residual monomers into the environment and into people. National biomonitoring surveys in the USA document population-wide exposures to these chemicals. Plastic additives disrupt endocrine function and increase risk for premature births, neurodevelopmental disorders, male reproductive birth defects, infertility, obesity, cardiovascular disease, renal disease, and cancers. Chemical-laden MNPs formed through the environmental degradation of plastic waste can enter living organisms, including humans. Emerging, albeit still incomplete evidence indicates that MNPs may cause toxicity due to their physical and toxicological effects as well as by acting as vectors that transport toxic chemicals and bacterial pathogens into tissues and cells.Infants in the womb and young children are two populations at particularly high risk of plastic-related health effects. Because of the exquisite sensitivity of early development to hazardous chemicals and children's unique patterns of exposure, plastic-associated exposures are linked to increased risks of prematurity, stillbirth, low birth weight, birth defects of the reproductive organs, neurodevelopmental impairment, impaired lung growth, and childhood cancer. Early-life exposures to plastic-associated chemicals also increase the risk of multiple non-communicable diseases later in life., Economic Findings: Plastic's harms to human health result in significant economic costs. We estimate that in 2015 the health-related costs of plastic production exceeded $250 billion (2015 Int$) globally, and that in the USA alone the health costs of disease and disability caused by the plastic-associated chemicals PBDE, BPA and DEHP exceeded $920 billion (2015 Int$). Plastic production results in greenhouse gas (GHG) emissions equivalent to 1.96 gigatons of carbon dioxide (CO 2 e) annually. Using the US Environmental Protection Agency's (EPA) social cost of carbon metric, we estimate the annual costs of these GHG emissions to be $341 billion (2015 Int$).These costs, large as they are, almost certainly underestimate the full economic losses resulting from plastics' negative impacts on human health and the global environment. All of plastics' economic costs-and also its social costs-are externalized by the petrochemical and plastic manufacturing industry and are borne by citizens, taxpayers, and governments in countries around the world without compensation., Social Justice Findings: The adverse effects of plastics and plastic pollution on human health, the economy and the environment are not evenly distributed. They disproportionately affect poor, disempowered, and marginalized populations such as workers, racial and ethnic minorities, "fenceline" communities, Indigenous groups, women, and children, all of whom had little to do with creating the current plastics crisis and lack the political influence or the resources to address it. Plastics' harmful impacts across its life cycle are most keenly felt in the Global South, in small island states, and in disenfranchised areas in the Global North. Social and environmental justice (SEJ) principles require reversal of these inequitable burdens to ensure that no group bears a disproportionate share of plastics' negative impacts and that those who benefit economically from plastic bear their fair share of its currently externalized costs., Conclusions: It is now clear that current patterns of plastic production, use, and disposal are not sustainable and are responsible for significant harms to human health, the environment, and the economy as well as for deep societal injustices.The main driver of these worsening harms is an almost exponential and still accelerating increase in global plastic production. Plastics' harms are further magnified by low rates of recovery and recycling and by the long persistence of plastic waste in the environment.The thousands of chemicals in plastics-monomers, additives, processing agents, and non-intentionally added substances-include amongst their number known human carcinogens, endocrine disruptors, neurotoxicants, and persistent organic pollutants. These chemicals are responsible for many of plastics' known harms to human and planetary health. The chemicals leach out of plastics, enter the environment, cause pollution, and result in human exposure and disease. All efforts to reduce plastics' hazards must address the hazards of plastic-associated chemicals., Recommendations: To protect human and planetary health, especially the health of vulnerable and at-risk populations, and put the world on track to end plastic pollution by 2040, this Commission supports urgent adoption by the world's nations of a strong and comprehensive Global Plastics Treaty in accord with the mandate set forth in the March 2022 resolution of the United Nations Environment Assembly (UNEA).International measures such as a Global Plastics Treaty are needed to curb plastic production and pollution, because the harms to human health and the environment caused by plastics, plastic-associated chemicals and plastic waste transcend national boundaries, are planetary in their scale, and have disproportionate impacts on the health and well-being of people in the world's poorest nations. Effective implementation of the Global Plastics Treaty will require that international action be coordinated and complemented by interventions at the national, regional, and local levels.This Commission urges that a cap on global plastic production with targets, timetables, and national contributions be a central provision of the Global Plastics Treaty. We recommend inclusion of the following additional provisions:The Treaty needs to extend beyond microplastics and marine litter to include all of the many thousands of chemicals incorporated into plastics.The Treaty needs to include a provision banning or severely restricting manufacture and use of unnecessary, avoidable, and problematic plastic items, especially single-use items such as manufactured plastic microbeads.The Treaty needs to include requirements on extended producer responsibility (EPR) that make fossil carbon producers, plastic producers, and the manufacturers of plastic products legally and financially responsible for the safety and end-of-life management of all the materials they produce and sell.The Treaty needs to mandate reductions in the chemical complexity of plastic products; health-protective standards for plastics and plastic additives; a requirement for use of sustainable non-toxic materials; full disclosure of all components; and traceability of components. International cooperation will be essential to implementing and enforcing these standards.The Treaty needs to include SEJ remedies at each stage of the plastic life cycle designed to fill gaps in community knowledge and advance both distributional and procedural equity.This Commission encourages inclusion in the Global Plastic Treaty of a provision calling for exploration of listing at least some plastic polymers as persistent organic pollutants (POPs) under the Stockholm Convention.This Commission encourages a strong interface between the Global Plastics Treaty and the Basel and London Conventions to enhance management of hazardous plastic waste and slow current massive exports of plastic waste into the world's least-developed countries.This Commission recommends the creation of a Permanent Science Policy Advisory Body to guide the Treaty's implementation. The main priorities of this Body would be to guide Member States and other stakeholders in evaluating which solutions are most effective in reducing plastic consumption, enhancing plastic waste recovery and recycling, and curbing the generation of plastic waste. This Body could also assess trade-offs among these solutions and evaluate safer alternatives to current plastics. It could monitor the transnational export of plastic waste. It could coordinate robust oceanic-, land-, and air-based MNP monitoring programs.This Commission recommends urgent investment by national governments in research into solutions to the global plastic crisis. This research will need to determine which solutions are most effective and cost-effective in the context of particular countries and assess the risks and benefits of proposed solutions. Oceanographic and environmental research is needed to better measure concentrations and impacts of plastics <10 µm and understand their distribution and fate in the global environment. Biomedical research is needed to elucidate the human health impacts of plastics, especially MNPs., Summary: This Commission finds that plastics are both a boon to humanity and a stealth threat to human and planetary health. Plastics convey enormous benefits, but current linear patterns of plastic production, use, and disposal that pay little attention to sustainable design or safe materials and a near absence of recovery, reuse, and recycling are responsible for grave harms to health, widespread environmental damage, great economic costs, and deep societal injustices. These harms are rapidly worsening.While there remain gaps in knowledge about plastics' harms and uncertainties about their full magnitude, the evidence available today demonstrates unequivocally that these impacts are great and that they will increase in severity in the absence of urgent and effective intervention at global scale. Manufacture and use of essential plastics may continue. However, reckless increases in plastic production, and especially increases in the manufacture of an ever-increasing array of unnecessary single-use plastic products, need to be curbed.Global intervention against the plastic crisis is needed now because the costs of failure to act will be immense., Competing Interests: In addition to the adjunct positions at the Nigerian Institute of Medical Research and Lead City University in Nigeria, AM works for Shell Nigeria Exploration & Production Company but did not receive any support from the company for her research and for this study, and the company is not in any way involved in this study. MB, DC, AG, YM, BJS, CS, and SD are employed by the Minderoo Foundation, an independent not-for-profit philanthropic organization. The contributions of the following authors were supported by the Minderoo Foundation: MC, MH, RH, AL, AM, MP, YP, MS, JJS, HT & RCT. JJS’s work was also supported by the Woods Hole Center for Oceans and Human Health (NIH grant P01ES028938 and National Science Foundation grant OCE-1840381). MEH’s work was also supported by the Minderoo Foundation as well as by grants from Woods Hole Sea Grant (Award No. NA18OAR4170104, project R/P–89) and the March Marine Initiative, a program of March Limited, Bermuda. BDJ was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution (WHOI), with funding provided by the Weston Howland Jr. Postdoctoral Scholarship. JAP was supported by the US National Science Foundation (NSF) Graduate Research Fellowship Program as well as by a grant from Woods Hole Sea Grant (Award No. NA180AR4170104, project R/P-89). ZW gratefully acknowledges funding by the European Union under the Horizon 2020 Research and Innovation Programme (grant agreement number 101036756). No other authors have conflicts of interest., (Copyright: © 2023 The Author(s).)

Harmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, a GLI1/2 inhibitor that reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes., (© 2023. The Author(s).)

In laboratory experiments, biomechanical data collections with wearable technologies and machine learning have been promising. Despite the development of lightweight portable sensors and algorithms for the identification of gait events and estimation of kinetic waveforms, machine learning models have yet to be used to full potential. We propose the use of a Long Short Term Memory network to map inertial data to ground reaction force data gathered in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience: novice to highly trained runners (<15 min 5 km race), and ages ranging from 18 to 64 years old. Force sensing insoles were used to measure normal foot-shoe forces, providing the standard for identification of gait events and measurement of kinetic waveforms. Three inertial measurement units (IMUs) were mounted to each participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant's waistband, approximating their sacrum. Data input into the Long Short Term Memory network were from the three IMUs and output were estimated kinetic waveforms, compared against the standard of the force sensing insoles. The range of RMSE for each stance phase was from 0.189-0.288 BW, which is similar to multiple previous studies. Estimation of foot contact had an r 2  = 0.795. Estimation of kinetic variables varied, with peak force presenting the best output with an r 2  = 0.614. In conclusion, we have shown that at controlled paces over level ground a Long Short Term Memory network can estimate 4 s temporal windows of ground reaction force data across a range of running speeds., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Donahue and Hahn.)

Wearable sensors and machine learning algorithms are becoming a viable alternative for biomechanical analysis outside of the laboratory. The purpose of this work was to estimate gait events from inertial measurement units (IMUs) and utilize machine learning for the estimation of ground reaction force (GRF) waveforms. Sixteen healthy runners were recruited for this study, with varied running experience. Force sensing insoles were used to measure normal foot-shoe forces, providing a proxy for vertical GRF and a standard for the identification of gait events. Three IMUs were mounted on each participant, two bilaterally on the dorsal aspect of each foot and one clipped to the back of each participant's waistband, approximating their sacrum. Participants also wore a GPS watch to record elevation and velocity. A Bidirectional Long Short Term Memory Network (BD-LSTM) was used to estimate GRF waveforms from inertial waveforms. Gait event estimation from both IMU data and machine learning algorithms led to accurate estimations of contact time. The GRF magnitudes were generally underestimated by the machine learning algorithm when presented with data from a novel participant, especially at faster running speeds. This work demonstrated that estimation of GRF waveforms is feasible across a range of running velocities and at different grades in an uncontrolled environment., (© 2023. The Author(s).)

Purpose To develop a multicompartmental signal model for whole-body diffusion-weighted imaging (DWI) and apply it to study the diffusion properties of normal tissue and metastatic prostate cancer bone lesions in vivo. Materials and Methods This prospective study ( ClinicalTrials.gov : NCT03440554) included 139 men with prostate cancer (mean age, 70 years ± 9 [SD]). Multicompartmental models with two to four tissue compartments were fit to DWI data from whole-body scans to determine optimal compartmental diffusion coefficients. Bayesian information criterion (BIC) and model-fitting residuals were calculated to quantify model complexity and goodness of fit. Diffusion coefficients for the optimal model (having lowest BIC) were used to compute compartmental signal-contribution maps. The signal intensity ratio (SIR) of bone lesions to normal-appearing bone was measured on these signal-contribution maps and on conventional DWI scans and compared using paired t tests (α = .05). Two-sample t tests (α = .05) were used to compare compartmental signal fractions between lesions and normal-appearing bone. Results Lowest BIC was observed from the four-compartment model, with optimal compartmental diffusion coefficients of 0, 1.1 × 10 -3 , 2.8 × 10 -3 , and >3.0 ×10 -2 mm 2 /sec. Fitting residuals from this model were significantly lower than from conventional apparent diffusion coefficient mapping ( P < .001). Bone lesion SIR was significantly higher on signal-contribution maps of model compartments 1 and 2 than on conventional DWI scans ( P < .008). The fraction of signal from compartments 2, 3, and 4 was also significantly different between metastatic bone lesions and normal-appearing bone tissue ( P ≤ .02). Conclusion The four-compartment model best described whole-body diffusion properties. Compartmental signal contributions from this model can be used to examine prostate cancer bone involvement. Keywords: Whole-Body MRI, Diffusion-weighted Imaging, Restriction Spectrum Imaging, Diffusion Signal Model, Bone Metastases, Prostate Cancer Clinical trial registration no. NCT03440554 Supplemental material is available for this article. © RSNA, 2023 See also commentary by Margolis in this issue.

Background: Multiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSI rs )., Objective: To evaluate RSI rs for automated patient-level detection of csPCa., Design Setting and Participants: We retrospectively studied all patients ( n  = 151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI., Intervention: We calculated the maximum RSI rs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records., Outcome Measurements and Statistical Analysis: We compared the performance of RSI rs , ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α  = 0.05. We also explored whether the combination of PI-RADS and RSI rs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones., Results and Limitations: AUC values for ADC, RSI rs , and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSI rs and PI-RADS were each superior to ADC for patient-level detection of csPCa ( p  < 0.0001). RSI rs alone was comparable with PI-RADS ( p  = 0.8). The combination of PI-RADS and RSI rs had an AUC of 0.85 (0.78, 0.91) and was superior to either PI-RADS or RSI rs alone ( p  < 0.05). Similar patterns were seen in the peripheral and transition zones., Conclusions: RSI rs is a promising quantitative marker for patient-level csPCa detection, warranting a prospective study., Patient Summary: We evaluated a rapid, advanced prostate magnetic resonance imaging technique called restriction spectrum imaging to see whether it could give an automated score that predicted the presence of clinically significant prostate cancer. The automated score worked about as well as expert radiologists' interpretation. The combination of the radiologists' scores and automated score might be better than either alone., (© 2022 The Authors.)

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD) 1 -a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity 2 . However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Zero-velocity assumption has been used for estimation of foot trajectory and stride length during running from the data of foot-mounted inertial measurement units (IMUs). Although the assumption provides a reasonable initialization for foot trajectory and stride length estimation, the other source of errors related to the IMU's orientation still remains. The purpose of this study was to develop an improved foot trajectory and stride length estimation method for the level ground running based on the displacement of the foot. Seventy-nine runners performed running trials at 5 different paces and their running motions were captured using a motion capture system. The accelerations and angular velocities of left and right feet were measured with two IMUs mounted on the dorsum of each foot. In this study, foot trajectory and stride length were estimated using zero-velocity assumption with IMU data, and the orientation of IMU was estimated to calculate the mediolateral and vertical distance of the foot between two consecutive midstance events. Calculated foot trajectory and stride length were compared with motion capture data. The results show that the method used in this study can provide accurate estimation of foot trajectory and stride length for level ground running across a range of running speeds.

In late May 2021, the M/V X-Press Pearl container ship caught fire while anchored 18 km off the coast of Colombo, Sri Lanka and spilled upward of 70 billion pieces of plastic or "nurdles" (∼1680 tons), littering the country's coastline. Exposure to combustion, heat, chemicals, and petroleum products led to an apparent continuum of changes from no obvious effects to pieces consistent with previous reports of melted and burned plastic (pyroplastic) found on beaches. At the middle of this continuum, nurdles were discolored but appeared to retain their prefire morphology, resembling nurdles that had been weathered in the environment. We performed a detailed investigation of the physical and surface properties of discolored nurdles collected on a beach 5 days after the ship caught fire and within 24 h of their arrival onshore. The color was the most striking trait of the plastic: white for nurdles with minimal alteration from the accident, orange for nurdles containing antioxidant degradation products formed by exposure to heat, and gray for partially combusted nurdles. Our color analyses indicate that this fraction of the plastic released from the ship was not a continuum but instead diverged into distinct groups. Fire left the gray nurdles scorched, with entrained particles and pools of melted plastic, and covered in soot, representing partial pyroplastics, a new subtype of pyroplastic. Cross sections showed that the heat- and fire-induced changes were superficial, leaving the surfaces more hydrophilic but the interior relatively untouched. These results provide timely and actionable information to responders to reevaluate cleanup end points, monitor the recurrence of these spilled nurdles, gauge short- and long-term effects of the spilled nurdles to the local ecosystem, and manage the recovery of the spill. These findings underscore partially combusted plastic (pyroplastic) as a type of plastic pollution that has yet to be fully explored despite the frequency at which plastic is burned globally., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Introduction: Loading of a residual limb within a prosthetic socket can cause tissue damage such as ulceration. Computational simulations may be useful tools for estimating tissue loading within the socket, and thus provide insights into how prosthesis designs affect residual limb-socket interface dynamics. The purpose of this study was to model and simulate residual limb-socket interface dynamics and evaluate the effects of varied prosthesis stiffness on interface dynamics during gait. Methods: A spatial contact model of a residual limb-socket interface was developed and integrated into a gait model with a below-knee amputation. Gait trials were simulated for four subjects walking with low, medium, and high prosthesis stiffness settings. The effects of prosthesis stiffness on interface kinematics, normal pressure, and shear stresses were evaluated. Results: Model-predicted values were similar to those reported previously in sensor-based experiments; increased stiffness resulted in greater average normal pressure and shear stress ( p < 0.05). Conclusions: These methods may be useful to aid experimental studies by providing insights into the effects of varied prosthesis design parameters or gait conditions on residual limb-socket interface dynamics. The current results suggest that these effects may be subject-specific., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Michael McGeehan, Kieran Nichols, and Michael Hahn declare no conflicts of interest for this work. Peter Adamczyk was a partner in Intelligent Prosthetic Systems, LLC, which created the Variable Stiffness Prosthesis used in this project., (© The Author(s) 2022.)

Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b -value range (up to 3000 s/mm 2 ) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C 1 compartment and product of the restricted and intermediate diffusion compartments ( C 1 and C 2 ). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast.

The development of lightweight portable sensors and algorithms for the identification of gait events at steady-state running speeds can be translated into the real-world environment. However, the output of these algorithms needs to be validated. The purpose of this study was to validate the identification of running gait events using data from Inertial Measurement Units (IMUs) in a semi-uncontrolled environment. Fifteen healthy runners were recruited for this study, with varied running experience and age. Force-sensing insoles measured normal foot-shoe forces and provided a standard for identification of gait events. Three IMUs were mounted to the participant, two bilaterally on the dorsal aspect of the foot and one clipped to the back of each participant’s waistband, approximating their sacrum. The identification of gait events from the foot-mounted IMU was more accurate than from the sacral-mounted IMU. At running speeds <3.57 m s−1, the sacral-mounted IMU identified contact duration as well as the foot-mounted IMU. However, at speeds >3.57 m s−1, the sacral-mounted IMU overestimated foot contact duration. This study demonstrates that at controlled paces over level ground, we can identify gait events and measure contact time across a range of running skill levels.

The aryl hydrocarbon receptor (AHR) is a member of the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family of transcription factors and has broad biological functions. Early after the identification of the AHR, most studies focused on its roles in regulating the expression of drug-metabolizing enzymes and mediating the toxicity of dioxins and dioxin-like compounds (DLCs). Currently, more diverse functions of AHR have been identified, indicating that AHR is not just a dioxin receptor. Dioxins and DLCs occur ubiquitously and have diverse health/ecological risks. Additional research is required to identify both shared and compound-specific mechanisms, especially for emerging DLCs such as polyhalogenated carbazoles (PHCZs), polychlorinated diphenyl sulfides (PCDPSs), and others, of which only a few investigations have been performed at present. Many of the toxic effects of emerging DLCs were observed to be predominantly mediated by the AHR because of their structural similarity as dioxins, and the in vitro TCDD-relative potencies of certain emerging DLC congeners are comparable to or even greater than the WHO-TEFs of OctaCDD, OctaCDF, and most coplanar PCBs. Due to the close relationship between AHR biology and environmental science, this review begins by providing novel insights into AHR signaling (canonical and non-canonical), AHR's biochemical properties (AHR structure, AHR-ligand interaction, AHR-DNA binding), and the variations during AHR transactivation. Then, AHR ligand classification and the corresponding mechanisms are discussed, especially the shared and compound-specific, AHR-mediated effects and mechanisms of emerging DLCs. Accordingly, a series of in vivo and in vitro toxicity evaluation methods based on the AHR signaling pathway are reviewed. In light of current advances, future research on traditional and emerging DLCs will enhance our understanding of their mechanisms, toxicity, potency, and ecological impacts., (Copyright © 2021. Published by Elsevier B.V.)

Crude oil released into the environment undergoes weathering processes that gradually change its composition and toxicity. Co-exposure to petroleum mixtures and other stressors, including ultraviolet (UV) radiation, may lead to synergistic effects and increased toxicity. Laboratory studies should consider these factors when testing the effects of oil exposure on aquatic organisms. Here, we study transcriptomic responses of the estuarine sea anemone Nematostella vectensis to naturally weathered oil, with or without co-exposure to environmental levels of UV radiation. We find that co-exposure greatly enhances the response. We use bioinformatic analyses to identify molecular pathways implicated in this response, which suggest phototoxicity and oxidative damage as mechanisms for the enhanced stress response. Nematostella's stress response shares similarities with the vertebrate oxidative stress response, implying deep conservation of certain stress pathways in animals. We show that exposure to weathered oil along with surface-level UV exposure has substantial physiological consequences in a model cnidarian., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To report the radiological features of intestinal ascariasis and to review the clinical implications of this re-emerging disease for adult population of the USA. This retrospective observational study involved 12 adult patients, whose radiological examinations disclosed unsuspected presence of ascaris in their intestinal tract. They were evaluated by computed tomography of the abdomen with oral contrast, small bowel series with barium, and magnetic resonance enterography. This series included 7 men and 5 women, who ranged in age from 19 to 72 years (mean age 48 years). The typical configuration of ascaris within the bowel loops was demonstrated on CT of the abdomen in 5 patients, small bowel examination with barium in 3, and by MR enterography in another 4 cases. Our study highlights the radiological appearances of intestinal ascariasis and the clinical implications of this resurging disease. The practicing radiologists should be aware of these findings, particularly when examining patients who have immigrated from or traveled to the endemic regions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Burnsed-Torres, ML, Wichmann, TK, Clayton, ZS, and Hahn, ME. Comparison of the Gauntlet test with standard laboratory measures of aerobic fitness. J Strength Cond Res 36(2): 386-391, 2022-The purpose of this study was to validate whether the Gauntlet test (GT) can accurately estimate individual aerobic endurance performance compared with standard laboratory-based physiological tests. The GT required athletes to complete 5 maximal effort running stages, with a 1-minute break between each stage, with the goal of achieving the best overall time. Eighteen men (n = 9) and women (n = 9) (age, 23.5 ± 4.13 years; body mass index, 23.1 ± 7.62 kg·m-2; 5k time, 22 ± 7 minutes; 10k time, 47 ± 15 minutes; V̇o2max, 52.3 ± 8 ml·kg-1·min-1) completed a lactate threshold test and V̇o2max test (laboratory measures). Four to 14 days later, subjects completed the GT on an outdoor track. Blood lactate (bLa), V̇o2max, and heart rate (HR) were recorded during the laboratory session. Blood lactate, HR, stage completion time, and overall completion time were recorded during the GT. Linear regression correlation analyses revealed a significant inverse association between V̇o2max (mL·kg-1·min-1) and GT completion time (r = -0.88, P < 0.0001). In addition, there were significant correlations between V̇o2max maximum HR and GT maximum HR (r = 0.89, P < 0.0001) and V̇o2max 3-minute post bLa and GT 3-minute post bLa (r = 0.63, P = 0.0029). Sex-specific analysis showed significant inverse associations between female and male GT completion time and V̇o2max (r = -0.70, P = 0.0352; r = -0.94, P < 0.0002). Bland-Altman plots were used to evaluate concordance between GT completion time, V̇o2max, maximum HR, and 3-minute post bLa. Results suggest the GT is a valid assessment to accurately estimate aerobic endurance performance similar to standard laboratory methods., (Copyright © 2021 National Strength and Conditioning Association.)

Diffusion-weighted magnetic resonance imaging (DWI) of the musculoskeletal system has various applications, including visualization of bone tumors. However, DWI acquired with echo-planar imaging is susceptible to distortions due to static magnetic field inhomogeneities. This study aimed to estimate spatial displacements of bone and to examine whether distortion corrected DWI images more accurately reflect underlying anatomy. Whole-body MRI data from 127 prostate cancer patients were analyzed. The reverse polarity gradient (RPG) technique was applied to DWI data to estimate voxel-level distortions and to produce a distortion corrected DWI dataset. First, an anatomic landmark analysis was conducted, in which corresponding vertebral landmarks on DWI and anatomic T 2 -weighted images were annotated. Changes in distance between DWI- and T 2 -defined landmarks (i.e., changes in error) after distortion correction were calculated. In secondary analyses, distortion estimates from RPG were used to assess spatial displacements of bone metastases. Lastly, changes in mutual information between DWI and T 2 -weighted images of bone metastases after distortion correction were calculated. Distortion correction reduced anatomic error of vertebral DWI up to 29 mm. Error reductions were consistent across subjects (Wilcoxon signed-rank p < 10 -20 ). On average (± SD), participants' largest error reduction was 11.8 mm (± 3.6). Mean (95% CI) displacement of bone lesions was 6.0 mm (95% CI 5.0-7.2); maximum displacement was 17.1 mm. Corrected diffusion images were more similar to structural MRI, as evidenced by consistent increases in mutual information (Wilcoxon signed-rank p < 10 -12 ). These findings support the use of distortion correction techniques to improve localization of bone on DWI., (© 2022. The Author(s).)

The purpose of this study was to compare a heuristic feature identification algorithm with output from the Beta Process Auto Regressive Hidden Markov Model (BP-AR-HMM) utilizing minimally sampled (≤ 100 Hz) human locomotion data for identification of gait events prior to their occurrence. Data were collected from 16 participants (21-64 years) using a single gyroscopic sensor in an inertial measurement unit on the dorsum of the foot, across multiple locomotion modes, including level ground walking and running (across speeds 0.8 m s -1 - 3.0 m s -1 ), ramps and stairs. Identification of gait events, initial contact (IC) and toe off (TO) with the heuristic algorithm, was 94% across locomotion modes. The features identified prior to initial contact had a lead time of 186.32 ± 86.70 ms, while TO had a lead time of 63.96 ± 46.30 ms. The BP-AR-HMM identified features that indicated an impending IC and TO with 99% accuracy, with a lead time of 59.41 ± 54.41 ms for IC and 90.79 ± 35.51 ms for TO. These approaches are consistent in their identification of gait events and have the potential to be utilized for classification and prediction of locomotion mode.