Animals exhibit multimodal behavior, which means that they can behave in different motion patterns, such as crawling, running, jumping, hunting, and escaping. Quadrupeds can maintain balance and coordination in challenging terrains. Amphibians can transit on land and in water. Insects can freely fly and crawl. These innate locomotion talents are simple and natural to animals and enable them to survive in nature by efficiently exploiting their body morphology and neural control system. Thus, it is very important to investigate the mechanism and influencing factors of multimodal behavior, especially for the development of dexterous, agile, and stable robots through biologically inspired guidance.Various attempts, including the use of hybrid structure systems, neural control, and embodied intelligence, have been made to mimic such impressive multimodal behaviors for robots, e.g., the turtle robot  of quadruped robots -Hopper. The performance of the serial and parallel pneumatic artificial muscles (PAM) is evaluated with respect to four criteria: efficiency, performance, stability, and hopping robustness against perturbations. The serial PAM has a more pronounced impact than the parallel PAM on these criteria and can help to further understand the human hopping mechanism and support the design and control of legged robots and assistive devices. Strohmer et al. developed a spiking neural network capable of continuously changing amplitude, frequency, and phase online. The network is deployed to observe the meaningful role of network topology in locomotion on the Modular Robot Framework (MORF), which is both a simulated robot in V-REP and a physical hexapod robot with 18 degrees of freedom. The neural control of locomotion relates back to biology where it can provide theoretical evidence that is not currently testable on behaving insects.For bionic robots, different structures and morphology should be developed and designed according to the application scenarios. Thus, the topics of concern and unsolved problems will also vary accordingly. In this Research Topic, Bonzon defines a neural basis for such behaviors, potentially learned by bio-inspired artifacts. The stochastic decision tree that drives this behavior is then transformed into a plastic neuronal circuit. The principle of using synchronized multimodal perceptions in association with the Hebb principle of wiring together neuronal cells is induced. The emergence of behaviors allows for a strict delineation of successive complexity levels. The isolation of levels allows for simulating yet unknown processes of cognition independently of their underlying neurological grounding. Koseki et al. provide a framework that reproduces multimodal bipedal locomotion using passive dynamics through deep reinforcement learning (DRL). By carefully planning the weight parameter settings of the DRL reward function during the learning process based on a curriculum learning method, the bipedal model successfully learned to perform multimodal behaviors . These results indicate that DRL can be applied to generate various gaits with the effective use of passive dynamics.The high dynamics control strategy of the bio-inspired robot is impressive and has a history of technology, such as a non-linear program (NLP) (Jenelten et al., The Research Topic presents multimodal behavior approaches of bio-inspired robots, considering mechanical design, sensory integration systems, control strategies, and applications in different environments. The studies on this topic cover multimodal behaviors for the hopping robot, biped robot, and hexapod robot. The results from these studies confirm that the sensory system provides support for the decision-making of multimodal behaviors. Furthermore, the neural control architecture can easily realize a variety of gait patterns, while the reinforcement learning and control methods ensure the stability and reliability of the related locomotion. Given these and further studies, robots with delicate structures and systems are likely to have more complex multimodal behavior and can be more similar to the behavior mechanisms and physiological functions of animals in the future.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Atrial fibrillation (AF) is one of the most common sustained tachyarrhythmias worldwide, and its prevalence is positively correlated with aging. AF not only significantly reduces the quality of life of patients but also causes a series of complications, such as thromboembolism, stroke, and heart failure, increases the average number of hospitalizations of patients, and places a huge economic burden on patients and society. Traditional drug therapy and ablation have unsatisfactory success rates, high recurrence rates, and the risk of serious complications. Surgical treatment is highly traumatic. The nano drug delivery system has unique physical and chemical properties, and in the application of AF treatment, whether it is used to assist in enhancing the ablation effect or for targeted therapy, it provides a safer, more effective and more economical treatment strategy. Since the birth of nanotechnology, it's application in the medical field has brought appreciable enhancements in the accuracy of diagnosis and treatment of various diseases . CurrentAF is a common persistent tachyarrhythmia. The global prevalence of AF currently ranges from 2% to 4%, and if screening of long-lived individuals and undiagnosed AF in the general population is expanded, the prevalence is expected to increase by a factor of 2.3 . In prinHowever, the current treatment strategies for AF are still intravenous drugs  and long-term oral drugs  –13. In aThis review aims to summarize some technologies based on nano drug delivery systems for the treatment of AF. From three main aspects, the main mechanism of AF and its treatment status, the introduction of nano drug delivery systems, and the application examples of nano drug delivery systems in the treatment of AF.The mechanism of AF occurrence is complex and controversial, and the dominant mechanism varies among different individuals. The current core mechanisms  indicateMore than two-thirds of patients with recently diagnosed AF have a paroxysmal pattern, but between 5 and 10% per year progress to persistent AF. During 10 years of follow-up, more than half of patients with an initial diagnosis of paroxysmal AF converted to persistent AF or died .The transformation of AF from paroxysmal to persistent or even permanent requires persistent ectopic activity or reentry. The occurrence of reentry requires the support of two conditions: the “triggering” activity (including early postdepolarization and delayed postdepolarization) and the “substrate”  , 16–18. These remodeling processes promote each other and together form a substrate that is conducive to the maintenance of AF. Studies have shown that the mechanism behind the occurrence of atrial remodeling may be related to acute atrial ischemia, abnormal activation of the local renin-angiotensin-aldosterone system (RAAS) in myocardial tissue, inflammatory mediators , immune cell infiltration, cardiomyocyte apoptosis, etc. –28, and The treatment of AF is still based on long-term oral or intravenous drugs, with the goal of restoring normal sinus rhythm, controlling ventricular rate, and preventing and treating related complications , 29. SevCatheter ablation, surgical ablation, and hybrid therapy have all been proposed as treatments for AF, but they vary in efficacy and accessibility. In recent years, transvenous catheter ablation of pulmonary vein isolation (PVI) has been the treatment of choice for symptomatic patients who require rhythm control and fail antiarrhythmic drug therapy –33.Surgical ablation (SA) is often performed concurrently with other cardiac procedures by creating an electrically silent lesion group, passing electrical impulses through a narrow organized pathway or maze, interruption of major reentry, and restoration of sinus depolarization initiation –36. SincClassic antiarrhythmic drug treatment not only has poor curative effects and a high recurrence rate, but will also inevitably produce toxic side effects after long-term use , 39. AltTraditional systemic drug delivery methods are insufficient in terms of stability, solubility, and bioavailability, and have various adverse side effects. Amiodarone (AMD) is commonly used as a class III antiarrhythmic drug for the conversion of AF –55, but Nano drug delivery systems refer to a family of nanomaterials with extremely small sizes, unique shapes and surface properties. Due to its special physicochemical properties and biological properties, it has received extensive attention in the medical field.The basic structure of nanoparticles (NPs) used in drug delivery systems usually consists of a particle core, a biocompatible protective layer, and linking molecules. The drug to be delivered can be encapsulated in the particle core or bound to the particle core surface. The biocompatibility protective layer is used to improve the biocompatibility of the drug delivery system and plays the role of avoiding the inflammatory response, reducing immunogenicity, and preventing the drug from being destroyed prematurely. Linking molecules are a class of compounds with active ends, whose role is to link NPs with biologically active molecules.The definition and classification of NPs has changed as the field continues to evolve. Generally, the size of NPs is between 1 and 100 nm. The US National Nanotechnology Program and the European Commission believe that the upper limit of nanoparticles cannot be limited to 100 nanometers. In the medical field, nanoparticles range in size from 5 to 250 nanometers. There are also nanosystems that may exceed a few microns in size, such as liposomes –61.Particles commonly used to carry drugs mainly include the following: nanoparticles (NPs), liposomes (liposomes), solid lipid nanoparticles (SLNs), nanocells (NMs), microemulsions, nanosuspensions, etc. . Nano drFor oral drugs to enter the blood, they must first be dissolved in the gastrointestinal fluid. The protective layer on the surface of the carrier can prevent the drug from being destroyed by the physical and chemical environment of the body's digestive system and the action of various enzymes or recognized and destroyed by the immune system before reaching the point of action, at the same time, it can also prevent the unstable drug from being converted into active ingredients prematurely in the body, and avoid toxic reactions due to excessive active drug doses , 64. TakIn the sustained-release system, the protective layer of the drug carrier is designed in various release modes: shell that can be eroded/degraded, swelling and dissolving matrix, organic membrane permeation or inorganic porous hollow particles, etc. . It is rIn a broad sense, controlled release refers to controlling the release rate, release location and release time of the drug. In a narrow sense, controlled release refers to a controlled release formulation that releases a drug at a zero-order or near-zero-order rate within a predetermined time . The triTargeting can be divided into active targeting and passive targeting . By chanMany studies have reported the application of nano-drug delivery systems in the treatment of AF . This chCa2+ waves occur when calcium overload occurs in the sarcoplasmic reticulum and some pathological changes are combined. Such spontaneous Ca2+ waves induce cell membrane depolarization through the mechanism of Na+/Ca2+ exchange, causing arrhythmias and systolic dysfunction  act as integrative centers for afferent information and efferent outflows of perceptual stimuli and are capable of modulating cardiac electrophysiological function through cardio-cardiac reflexes. The need for targeted ablation of the atrial GP emerged as GP stimulation resulted in increased triggering activity in the PV as well as increased dispersion of action potentials, which are considered factors in the maintenance of AF. Ablation of the GP results in changes in cardiac autonomic control, which multiple studies have linked to a reduced risk of AF recurrence .Botulinum toxin (BoTN) is a neurotoxin that acts on neural synapses, blocking the release of acetylcholine-containing synaptic vesicles from the presynaptic membrane, reducing vagus-induced shortening of the atrial effective refractory period and preventing autonomic remodeling , 85. TheBoth animal experiments and human studies have shown that injection of botulinum toxin into the atrial fat pad can temporarily reduce the susceptibility of atrial tissue to AF induction and the effect of the vagus nerve on the atrial effective refractory period, potentially inhibiting the progression of autonomic remodeling. This effect can break the so-called “AF-induced AF” vicious cycle, preventing AF from progressing to persistent or even permanent AF , 87. FurThere is a certain time delay in the effect of BoNT-blocking nerve effects, and the blocking effect is temporary ; therefoin situ release, the drug is inseparable from the form of solution, while traditional linear chitosan is insoluble at physiological pH, but chitosan nanoparticles can be suspended in aqueous solution, and the resulting suspension can be assimilated into a solution  in magnetic nanoparticles, and a piece of permanent magnet was placed on the surface of the epicardium. After the drug was released to the coronary artery through catheter intervention, the external magnetic field generated by the permanent magnet pulled the magnetic nanoparticles loaded with drugs to the prepositioned GPs  formed after absorption enters the transintestinal hepatic circulation and can extend the elimination half-life to approximately 60 days. As a result, active metabolites tend to accumulate fibrosis , 56, 57.c organs , 64.Polymer hydrogels are a good medium commonly used for controlled drug release. Nanoparticle outer coatings based on polymer hydrogels can provide stable protection and can degrade under certain triggering conditions (specific pH and temperature).Poly-N-isopropylacrylamide-co-acrylamide is a temperature-sensitive polymer gel that hydrates at ambient temperatures below body temperature and becomes hydrophobic at body temperature , accordiDuring radiofrequency ablation, due to the local high temperature, the myocardial tissue at the ablation site will be inflamed, and the perioperative inflammatory response will increase the risk of early postoperative recurrence of atrial fibrillation. The budesonide is encapsulated with polylactic-co-glycolic acid (PLGA) nanoparticles. In the process of radiofrequency ablation, the nano drugs delivery system is triggered at high temperature to release the budesonide carried inside and inhibit the inflammatory response at the ablation site. In addition, some untriggered nanoparticles can provide a sustained anti-inflammatory effect on the ablation site through the sustained release effect, effectively enhance the effect of radiofrequency ablation, and reduce the risk of postoperative atrial fibrillation recurrence .Similarly, there is a nano drugs delivery system designed as a chain, with a liposomal drug carrier and a tail composed of three magnetic nanoparticles . MagnetiMagnetic nanoparticles have a hysteresis effect. When the ferrous core of the magnetic nanoparticles is exposed to the alternating magnetic field of the positive and negative electrodes, magnetic hysteresis loss will occur repeatedly, and a part of the electromagnetic energy will be irreversibly converted into heat energy . ThermalClinically, radiofrequency, ultrasound and other technologies are used to increase tissue temperature through thermal effects, thereby causing irreversible damage to the target, and are used to treat arrhythmias such as AF. MFH can also be used for ablation of AF. MFH guided by the magnetic particle imaging (MPI) technique for imaging using the properties of superparamagnetic nanoparticles is currently being investigated , 94. TheIn addition, if hyperthermic heating of cells is insufficient, polymer coatings with higher critical temperatures can also be designed to release endotoxins by heating the particles with an alternating magnetic field, thereby providing additional targeted killing for drug delivery , 97.In addition to carrying synthetic exogenous substances, nano drugs delivery systems can also be used to change the distribution of endogenous substances in the human body.Exosomes are a type of extracellular vesicles, usually 40–200 nm in size, that can carry various signaling biomolecules  inside and have the ability to mediate cell-to-cell interactions and exchange information between cells over long distances , 99.In recent years, studies have shown that exosomes are involved in some important links in the pathogenesis of AF, and some ncRNAs have also been proven to be important factors in regulating cardiac function and participating in the occurrence and development of the disease, which has the potential to be used in the treatment of cardiovascular diseases –102.Studies have shown that myocardial fibrosis in AF is associated with macrophages infiltrating into cardiac tissue, and macrophages lead to myocardial fibrosis through interactions with cardiomyocytes or fibroblasts, which in turn provide the basis for the development and maintenance of AF. Inhibition of “canonical” activated macrophage (M1) polarization and enhancement of “alternate” activated macrophage (M2) polarization improves myocardial fibrosis and alleviates myocardial remodeling .Several studies  found reCardiomyocyte apoptosis can occur before atrial remodeling, and AF can aggravate apoptosis. It can be seen that cardiomyocyte apoptosis and AF are mutually aggravating processes. Exosomes enriched in miR-210, miR-133a, and miR-19a reduce apoptosis by enhancing cardiomyocyte resistance to oxidative stress , and carAcute atrial ischemia can aggravate the vulnerability of AF, and exosomal miR-19a from MSCs can reduce the expression of inflammatory cytokines. The immune response has also been shown to be involved in the pathogenesis of AF, and exosomal miR-19a from MSCs can reduce the expression of inflammatory cytokines, inhibit the inflammatory response and prevent the progression of AF .Mechanisms based on these specific ncRNA-rich exosomes that inhibit fibrosis, resist apoptosis, suppress immune inflammatory responses, and promote angiogenesis are promising in the prevention and treatment of AF. However, insufficient retention of exosomes in the myocardium and the mechanism of endogenous manipulation of exosome biodistribution are still unclear, which are the main challenges in the clinical application of exosomes.Nano drugs delivery systems for exosome binding have been developed to enhance the enrichment and retention of exosomes in tissues of interest, which can be applied for targeted delivery of exosomes to myocardial tissue. Studies  found thThe application of nano drugs delivery system provides a new idea for the treatment of AF. Nonetheless, there are still some important limitations and challenges in the use of nano drugs delivery systems in the clinical treatment of AF.From the point of view of AF treatment, because important structures in the heart, such as blood vessels, nerves, valves, and cardiac conduction systems, are adjacent to each other, off-target effects during the treatment process will result in a serious adverse prognosis. Future research needs to take into account the potential off-target risk of the treatment process and screen for methods with high accuracy and efficiency. In the application of MFH ablation of AF, there are symptoms such as pain and muscle twitching caused by external magnetic field stimulation of peripheral nerves , which pFurthermore, due to the heterogeneity of nanodrug delivery systems in humans, some nanoparticles undergoing preclinical development have been retrospectively found to be cytotoxic or immunogenic , 122. WiFrom the perspective of nano drugs delivery system production, how to maintain a certain degree of stability in the physical and chemical properties, encapsulation rate, release rate, etc., of the nano drug drugs delivery system in the process of large-scale repeated production, that is, to ensure that the entire production process has a high degree of repeatability and reliability, how to reduce the loss of the produced nano drugs delivery system during storage and transportation, and how to reduce the economic cost and time cost of production. These questions all relate to the possibility of applying this technology to the clinic.ZW, QT, TL, and YQ prepared the manuscript. ZW, QT, and YQ wrote the main parts of the article and produced graphics. TL, QT, and YQ reviewed and edited the manuscript. ZW and YQ drafted the final version of the manuscript. All authors read and approved the final manuscript.YQ acknowledges lab support provided by grants from the Scientific Research Project of National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (No. Z2018B19), and 135 project for disciplines of excellence–Clinical Research Incubation Project, West China Hospital, Sichuan University (No. 2019HXFH029), and Technology innovation research and development project of Chengdu Science and Technology Bureau(No. 2019YF05-00183-SN), and the Major Science and Technology Project of Sichuan Province, China (No. 2021YFS0121), and the Science and Technology Project of Sichuan Province Health Commission, China (No. 21PJ035).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Lubricious polymer coatings are increasingly used on intravascular devices to facilitate application processes. Although increasing reports about the detachment and subsequent embolism of polymer particles, this iatrogenic polymer embolism has not been paid enough clinical attention for many years. This article reviews the hazard of coating separation and the difficulty to find it. Furthermore, this proposes the scientific evaluation concept and regulatory exploration to solve the problems. Since the mid-1980s, polymers have been widely used as the lubrication coating on intravascular devices in the fields of interventional heart disease, interventional neurology, interventional radiology, and vascular surgery, thus enhancing the lubricity and biocompatibility of the device surface. Lubrication coating includes hydrophilic polymers such as polyvinylpyrrolidone (PVP), polyacrylic acid, and hydrophobic polymers such as polytetrafluoroethylene (PTFE), which can effectively reduce the friction between the surface of the intravascular device and blood vessels or other intravascular instruments, reduce the risk of vascular wall damage, and prevent vasospasm and thrombosis. Therefore, the application of surface lubrication coating expands the scope of interventional instruments for surgical treatment. It reduces the surgical time and cost, enables several innovative intravascular techniques, and becomes an important tool for minimally invasive interventional therapy .It is of great concern, therefore, that the use of polymer coatings has been observed to result in poor adhesion and separation , which can potentially cause adverse events and may have a significant impact on patient turnover –7.The disadvantage of polymer coating is that the polymer coating separates and falls during intervention. Mechanical abrasion and time-dependent chemical degradation are the main mechanisms causing the detachment of the polymer coating. Mechanical abrasion is a result of device interaction with the vasculature  or other devices used to access or treat a lesion. Mechanical abrasion causes incremental strain on chemical bonds within the bulk polymer structure and between the polymer and the device substrate. Upon reaching a bond-energy threshold, the chemical bonds break, resulting in coating separation (scraping or peeling) from the device. In chemical degradation over time, the bonds within the polymer-coated structure and the bond between the polymer and the substrate weaken with long-term contacting with saline or pulsatile blood. Therefore, the polymer-coating composition and coating-binding mechanism, coating thickness, product storage conditions and shelf life, endovascular operation frequency and proficiency, and the anatomical situation of the target blood vessels can all affect the stability of the coating through mechanical abrasion and time-dependent chemical degradation , 9.Histopathological observations of patients have raised further concerns about detachment of coatings during clinical procedures. A wide range of documented polymer embolism particulate sizes  and adverse reactions have been reported in the lungs, brain, heart, kidney, liver, and skin/extremities. It was reported that myocardial ischemia and infarction with polymer-coated embolization in the heart, circular enhancement of polymer particles, and surrounding edema were observed in the brain. In some cases with neurodegenerative changes, newborn polymer embolization and occlusion of dermal vessels resulted in skin damage in the lower limbs, manifested as spots and purple patches .In 2009, Rupal et al. first reported the fatal complications of iatrogenic hydrophilic polymer embolism (HPE) to the Food and Drug Administration (FDA) and the current awareness of morbidity and mortality caused by iatrogenic HPE. In fact, foreign bodies in the small arteries after use of an infusion microcatheter was reported in 1997. However, after more than 30 years of interventional coating use, the harm of coating HPE is still not being taken seriously enough. The main reason is that polymer-coated embolization is difficult to detect in the clinical setting. As these foreign bodies were not previously encountered, differences in opinion between physicians and discreet disclosure of details of unexpected negative results prevented and delayed reporting of these cases. In the absence of clinical suspicion of iatrogenic coating complications, or targeted histopathological analysis, HPE has failed to gain full clinical attention and awareness over the years –15.Identification of clinical HPE phenomena requires direct biopsies of important tissues, thorough autopsy analysis of the organs and vasculature, or histological testing of the removed thrombotic/emboli. The low autopsy rate in the hospital and the lack of autopsy procedures make the association between polymer embolism and clinical sequelae challenging. Furthermore, while the histological analysis remains the only clearly diagnostic method, the microscopic performance of endovascular polymers and the limitations of tissue sampling led to frequent false-negative interpretations and significant underreporting. Another reason is that with the same device, different surgeons have different results due to operational proficiency, and the risk of HPE associated with the HPE phenomenon may vary further in different patients due to unique anatomical and clinical considerations.Therefore, in the absence of clinical coating separation complications and the absence of targeted histopathological analysis, HPE has not been paid enough clinical attention for many years.Intravascular interventional devices such as vascular catheters or guide wires are managed as the Class III medical device in European Union and China and as the Class II device in the United States, which are regulatory products that do not need clinical trials. Currently, pre-market evaluation requirements for coated intravascular instruments include coating stability/integrity and lubricity studies and evaluating coating stability/integrity on the surface of the instrument. The applicants basically research the coating durability, friction, and stability with their own methods. The administration authorities usually recommend evaluating the substantial equivalence to the approved products.However, there are no standard methods for detection of particulates, no permissive size threshold, and strict overall permissive limits for producing particulates. The current focus on the particles is mainly about the control of production environment, process, or particles caused by products and their packaging. Presently, the particle control of products generally follows the standard for small specification injection in the national pharmacopeia. That is, particles each test product contained more than 10 μm should not exceed 6,000, and the particle more than 25 μm should not exceed 600.However, the evaluation method of the particle does not reflect the real situation of particles in the clinical application of coating products. Polymer embolism raises this issue to new concerns. Thus, the analyses of the distal vasculature, organ-related responses, and/or long-term biopolymer effects have not been specifically evaluated, and so far, their effects are unclear.via non-standardized protocols  uses particle testing as an industry standard for assessing the coating integrity of endovascular equipment, but states in Section 6 of the AAMI TIR 42 “because of the absence of comprehensive and definitive clinical data, particle size ranges and particle count limits are not recommended in this TIR. “The International Organization for Standardization 10993 Standard Series (ISO10993), entitled ”Biological evaluation of medical devices,' puts forth guidelines for preclearance evaluation of hydrophilic vascular medical device biocompatibility and safety, incorporating requirements for preclinical testing of polymeric degradation. Part 13 of the Standard provides general requirements for evaluating particulates released from polymeric medical device surfaces, when subjected to simulated clinical environments. Notably, recommended studies are performed by individual manufacturers rotocols , 17.In 2015, the FDA issued a document entitled “Safe Communications for Intravascular Medical Device lubrication coating separation” which acknowledged these concerns, reminding the potential hazards and risks of polymer lubrication coatings on vascular interventional devices and suggesting safe clinical practice. It also concluded that it will work with stakeholders to develop non-clinical testing methods, establish performance standards, and identify the gap between the current national and international equipment standards on coating integrity performance. Despite this communication and multiple case reports from physicians, pathologists, dermatologists, and other physician specialties involved, polymer-coated embolization remains clinically under-recognized. In the industry communication, the US FDA recognized the important role of hydrophilic coating of vascular device products. Although its operating difficulties and the subsequent risk, the vascular intervention provides doctors with greater operability and reduces vascular friction rupture and vasospasm. The FDA recommends that manufacturers are responsible for developing an appropriate particulate matter assessment procedure and providing an interpretation of the test data , 19.On 10 October 2019, FDA issued “Coronary, Peripheral, and Neurovascular Guidewires Performance Tests and Recommended Labeling.” It is recommended to evaluate the coating integrity and particulates and to evaluate the lubrication function of the coating. The coating integrity testing should illustrate the data collected from the device in a model representative of bending and test the particles while conducting the coating integrity test to evaluate the source, number, and size of particles that may be lost during simulation. If there are coating defects, scientific and reasonable instructions should be provided on whether these coatings have safety risks. It is recommended that the number of particles should be quantified by size and quantity in each evaluation, and the quantification method  should be confirmed  and may have a higher durability standard. On the other hand, a transcatheter aortic valve repair (TAVR) device may be prepped and inserted once or twice during a procedure and may have a lower durability standard. Accommodations for clinical, anatomical, and procedural variations are required when determining the durability standard for a device category. For products with different applications, it is recommended to develop different simulation test cycles (times) in combination with clinical practice. Therefore, it is necessary to classify the shedding risk of the product lubrication coating according to the anatomical characteristics of the clinical use and application processes.At present, an important factor of coating thickness is not considered in coating evaluation. The coating thickness is not the thicker the better; on the contrary, a thinner coating under the conditions of satisfying lubrication can reduce the risk of coating shedding within the blood vessels.Measure the amount of equipment coating (thickness) and test its durability by determining the maximum possible cycle count. Compare the cycle counts with predetermined durability criteria to assess the number of coatings on the equipment. Cycle counts significantly higher than the device durability criteria may cause the excess coating. In most cases, the manufacturer's coating application process creates a minimum and actual number of coatings applied to the device; however, some changes may occur. In this case, the maximum cycle counts relative to the minimum number of coatings allowed by using the manufacturer's coating application process can also be determined.To accurately evaluate the particulates generated during the use of device, the particles should be characterized after simulated use. The number of particulates generated at each evaluation should be quantified and characterized by size and count using a validated method  under continuous flow conditions to simulate blood flow. Coating stability evaluation also involves test cycles/times. For products with different ranges of application, the simulated test cycles/times of tests should represent the most adverse clinical situation. Therefore, it is appropriate to classify the shedding risk of the product lubrication coating according to the anatomical characteristics of the clinical application and application processes.Due to the unique anatomical and clinical considerations, the risk of HPE associated with the coating shedding phenomenon may have different clinical manifestations and outcomes in different patients. Infants and children will be more susceptible to multifocal foreign body deposition as well as inflammatory and developmental sequelae. Cumulative subclinical responses may lead to increased risk of complications throughout their lifetime. A strict treatment for pediatric devices is performed due to possible long-term effects and unique size considerations as well as the tendency for vessel occlusion in distal small vessels and developmental organs. Therefore, there should be stricter restrictions and clear vigilance in the vascular interventional devices used in pediatrics. Furthermore, embolic events should be more likely to develop symptoms in patients with impaired baseline vascular reserve or coma and should attract particular attention.via interface-initiated hydrogel polymerization. Applications of the mucosa-like conformal hydrogel coating on the endotracheal tube significantly reduced the intubation-related complications, such as invasive stimuli, mucosal lesions, laryngeal edema, inflammation, and postoperative pain. This study offers a promising prototype for surface decoration of biomedical devices.There is less advancement in the lubrication coating on intravascular medical devices, but some new technology about lubrication coating emerged recently . A novelThere is no doubt that the introduction of lubrication coating has made great progress in the application of vascular interventional devices and has greatly improved the scope of vascular interventional surgery. However, coating is a double-edged sword. How to make full use of its lubrication advantages should cause the common attention and need the joint efforts of producers, regulators, and clinical users.YX: writing the article. Z-YM: critical revision of the article. Both authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Fluctuations of sex hormones across the menstrual cycle have been linked to exacerbation of symptoms of psychiatric disorders. Women diagnosed with trauma-related disorders such as post-traumatic stress disorder (PTSD) and borderline personality disorder (BPD) have reported worsening of mood symptoms at various phases of their menstrual cycle. There is also considerable overlap between PTSD, BPD, and complex-PTSD (cPTSD) symptoms, suggesting similar biological underpinnings. This mini-review examines the influence of sex hormones and the menstrual cycle on PTSD, BPD, and cPTSD symptoms, and discusses the involvement of the hypothalamic-pituitary-adrenal (HPA) axis. We review literature showing that PTSD and BPD symptoms fluctuate with the menstrual cycle, though the effect of the menstrual cycle phase appears to be inconsistent, warranting future research. Based on the reported phasic vulnerability in individuals with PTSD and BPD, it is plausible to assume that women diagnosed with the newly introduced cPTSD may experience similar difficulties. However, no study to date has addressed this. This review highlights the importance of considering an individual's trauma history as it may influence symptom severity and diagnosis, and the phase of the menstrual cycle at the time of diagnosis. This review also highlights that additional work is needed to clarify the influence of estradiol and progesterone fluctuations on trauma-related symptoms, especially in cPTSD. Continued research on menstrual cycle vulnerability and trauma will lead to better informed management and treatment of PTSD, BPD, and cPTSD. It is well-documented that the cyclical rise and fall of sex hormones across the menstrual cycle impacts symptoms of psychiatric disorders. The menstrual cycle typically lasts 23–35 days with four stages ; menstruHealthy women have reported increased mental ill health symptoms related to depression and anxiety during the late luteal and early follicular phases . MenstruBoth PTSD and BPD are more common in women –19, suggThis mini-review will now explore the influence of sex hormones and the menstrual cycle on PTSD, BPD, and cPTSD symptoms, and discuss potential underlying mechanisms.PTSD, recently re-classified as a trauma- and stressor-related disorder, is a psychiatric disorder that develops after exposure to a traumatic event. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria list four PTSD symptom sub-categories: intrusion, avoidance, negative alterations in cognitions and mood, and marked alterations in arousal and reactivity. Similarly, the International Classification of Diseases (ICD-11) lists three PTSD symptom clusters: re-experiencing of the trauma, avoidance of trauma reminders, and heightened sense of threat.In the general population, there are higher rates of PTSD in women (10–12%) than in men (5–6%), with women being two to three times more likely to develop PTSD . In addiEstradiol and progesterone levels at the time of trauma exposure have been suggested to contribute to the development of PTSD symptoms. For example, women with PTSD who experience trauma during the mid-luteal phase of their cycle have a greater number of flashbacks . AnotherNot only do sex hormones during time of trauma exposure play a role in symptom presentation, but a recent review by Nillni et al.  observedConversely, trauma-exposed women have higher PTSD symptoms during low-estradiol phases of their cycle . In a saAn effective behavioral treatment for PTSD is exposure therapy, which involves controlled exposure to a situation or stimulus with the purpose of reducing anxiety and distress over time. Fear extinction  appears to be influenced by estradiol levels, though findings in women with PTSD are inconsistent when exploring this by menstrual cycle phase. Greater extinction retention in females in high compared to low estradiol groups have been observed in animal studies  and in hCurrent literature indicates a phasic vulnerability in women with PTSD, with different symptoms exacerbated at different points of the menstrual cycle. It remains unclear as to whether high levels of estradiol and progesterone are protective or increase vulnerability in the maintenance of PTSD symptoms in women. It should be noted that some studies have observed stability in symptoms across the menstrual cycle, and no associations between estradiol and progesterone levels and anxiety sensitivity . Again, Borderline personality disorder (BPD) is a chronic mental condition characterized by rapidly shifting emotional and behavioral symptoms, and difficulties maintaining stable interpersonal relationships. Common BPD features include low self-esteem, fear of abandonment, identity disturbances, impulsive behaviors, and maladaptive coping strategies . While BBPD is characterized by impulsivity, and cyclical changes in ovarian hormones have been associated with several impulsive-related behaviors. Earlier studies have indicated a premenstrual increase in suicidal behavior , 48 and While women with BPD often report that affective and impulsive symptoms worsen premenstrually, empirical evidence has been inconsistent. An early small prospective study of women with BPD found no association between the phase of the menstrual cycle and affective and impulsivity . HoweverAggression can be classified into reactive and proactive forms, with both types being exacerbated in different menstrual phases. A recent study examined the differential effects of menstrual cycle changes on reactive and proactive aggression in individuals with BPD . ReactivAltogether, the current literature suggests that sensitivity to gonadal hormone fluctuations in the CNS could influence the etiology and maintenance of BPD, and individuals with BPD may experience symptom changes in the type and severity of symptoms at different menstrual cycle phases. Generally, fewer BPD symptoms are experienced in the ovulatory period when CNS estradiol levels are high and BPD symptoms increase and peak around the mid-luteal and perimenstrual phases when CNS estradiol and progesterone levels are lower. There is a clear need for further research into understanding the relationship between ovarian hormones fluctuations across the menstrual cycle and BPD symptoms. Such research may well lead to more effective management of BPD with new gonadal hormone treatment strategies.As described in the ICD-11, cPTSD consists of six symptoms clusters: the three core PTSD symptoms  and one symptom from each of three disturbances of self-organization (DSO) symptom clusters .Similar to PTSD and BPD, the prevalence of cPTSD is higher in women, with all three symptom clusters also reported significantly more often . DespiteWhile there are some differences between PTSD, BPD and cPTSD, the substantial symptom overlap indicates a similar underlying mechanism for these conditions . As trauThe HPA axis links the CNS with peripheral tissues through the involvement of the hypothalamus, the pituitary, and the adrenals. This system of neuroendocrine pathways and feedback loops regulate a broad range of physiological processes, in particular mediating the stress response, and hence is consistently implicated in trauma-related conditions.There is overlap in the neurochemistry and neurostructural changes observed in PTSD, BPD and cPTSD, with no clear differentiation between the three conditions in regards to HPA axis function or subsequent alterations . For insThere is a complex bi-directional relationship between the HPA and hypothalamic-pituitary-gonadal (HPG) axes; the latter playing a key role in regulating reproduction by controlling gonadal hormones. The activation of one axis impacts the function of the other and vice versa . The HPAMany studies, such as those dealing with BPD, lacked a control group comparison, making it difficult to determine whether the patterns observed were specific to BPD or if they were attributed simply to fluctuations in the menstrual cycle, regardless of psychological functioning , 24, 54.Future studies could explore the relationship between the type, severity and frequency of trauma and the exacerbation of trauma-related symptoms across the menstrual cycle. The timing of trauma is also an important factor that should be explored, since childhood trauma experienced as a toddler or pre-schooler, may have quite different impacts compared to trauma occurring at school-age or in adolescence. In addition, as there are no studies exploring cPTSD and the menstrual cycle, future studies in this area can model existing study designs in PTSD and BPD given the overlap in biological underpinnings and symptomatology.This review provides a few practical and theoretical implications about the possible relationship between gonadal hormone fluctuations of the menstrual cycle and behavioral, emotional, and cognitive symptoms that are seen in conditions such as PTSD, BPD and cPTSD. These three psychiatric conditions are all caused, at least in part, by trauma. Hence, it is important to consider each individual's trauma history in general. We need to consider a broader definition of trauma that considers the stressful impact of poor bonding with a primary carer, emotional neglect, or invalidation, as well as actual instances of physical abuse and sexual trauma. It appears that an experience of trauma can significantly influence an individual's neurobiology. In reproductive aged women, studying the impact of both gonadal hormone fluctuations and trauma experiences on resultant psychiatric symptoms may provide new neurobiological insights. We highlight that menstrual cycle phases could influence an individuals' diagnosis, so clinicians' need to be mindful of the phase of menstrual cycle at the time of diagnosis or perform assessments at different time points to gain a better understanding of the psychiatric symptoms' presence and severity. Similarly, clinicians should consider the phase of the menstrual cycle at the time of trauma exposure as this can contribute to symptom severity.In conclusion, the present review provides evidence that in women with trauma-based disorders, the fluctuations of gonadal hormones across the menstrual cycle appear to cause changes in psychiatric symptoms at different monthly time-points. Psychiatric symptoms of PTSD and BPD appear to vary markedly across the menstrual cycle in women who have experienced early life trauma. This suggests that trauma alters the brain's sensitivity to gonadal hormone fluctuations, resulting in marked worsening of psychiatric symptoms in the low estradiol menstrual cycle phases, and some improvement in higher estradiol phases. While the literature is lacking in cPTSD, one may assume that the alteration in brain sensitivity may extend to the cPTSD population. This review also highlights that additional work is needed to clarify the influence of estradiol and progesterone fluctuations on trauma-related symptoms. Continued research on menstrual cycle vulnerability and trauma will lead to better informed management and treatment of PTSD, BPD, and cPTSD.EM and ET were equally involved in the conceptualization of the mini-review and draft of manuscript. All authors contributed to manuscript editing.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Plastic pollution is spreading worldwide and a growing number of reports point to the presence of plastic waste and microplastics in Antarctic marine ecosystems. Although the available data do not yet allow us to define the distribution of microplastics in the biotic and abiotic components of the Southern Ocean, in discussing the possible interactions with other contaminants in wastewater from scientific stations and their possible combined effects on primary producers and food webs, this review emphasizes the urgent need for standardized protocols of sampling and analysis of microplastics. Considering the unique oceanographic and biological characteristics of the Southern Ocean, we also suggest evaluating the likely cumulative stresses in Antarctic marine organisms and ecosystems due to exposure to climate-induced environmental changes, such as the recent decrease in sea-ice formation and seawater acidification.Antarctica and the Southern Ocean are the most remote regions on Earth, and their quite pristine environmental conditions are increasingly threatened by local scientific, tourism and fishing activities and long-range transport of persistent anthropogenic contaminants from lower latitudes. Plastic debris has become one of the most pervasive and ubiquitous synthetic wastes in the global environment, and even at some coastal Antarctic sites it is the most common and enduring evidence of past and recent human activities. Despite the growing scientific interest in the occurrence of microplastics (MPs) in the Antarctic environment, the lack of standardized methodologies for the collection, analysis and assessment of sample contamination in the field and in the lab does not allow us to establish their bioavailability and potential impact. Overall, most of the Southern Ocean appears to be little-affected by plastic contamination, with the exception of some coastal marine ecosystems impacted by wastewater from scientific stations and tourist vessels or by local fishing activities. Microplastics have been detected in sediments, benthic organisms, Antarctic krill and fish, but there is no clear evidence of their transfer to seabirds and marine mammals. Therefore, we suggest directing future research towards standardization of methodologies, focusing attention on nanoplastics  and considering the interactions of MPs with macro- and microalgae  and the formation of epiplastic communities. In coastal ecosystems directly impacted by human activities, the combined exposure to paint chips, metals, persistent organic pollutants (POPs), contaminants of emerging interest (CEI) and pathogenic microorganisms represents a potential danger for marine organisms. Moreover, the Southern Ocean is very sensitive to water acidification and has shown a remarkable decrease in sea-ice formation in recent years. These climate-related stresses could reduce the resilience of Antarctic marine organisms, increasing the impact of anthropogenic contaminants and pathogenic microorganisms. Antarctica is the most remote and the last major wilderness on Earth and has been designated by the Antarctic Treaty’s Protocol on Environmental Protection  as a “nature reserve, devoted to peace and science”. Geographical isolation (enhanced by the Antarctic Circumpolar Current and the Antarctic cyclonic vortex), the lower human population density in the Southern Hemisphere and environmental management (ATPEP’s annex III and IV) have contributed to relatively pristine conditions in Antarctica and the Southern Ocean. However, dichlorodiphenyltrichloroethane (DDT) and its congeners have been detected in marine organisms in the Southern Ocean since 1966 ,3, showeThe Southern Ocean biota includes many endemic species with unique ecophysiological adaptations, resulting from the extreme abiotic conditions and the long-lasting geographic isolation ,16,17,182, and 71.8 million km3, respectively), their impact would seem significant only on a local scale. However, in these hotspots of anthropogenic disturbance, the concomitant impacts of contaminants, climate and environmental changes and the possible introduction of pathogenic microorganisms and/or invasive and pre-adapted alien species can pose cumulative stresses and threats to the biodiversity and functioning of marine ecosystems [Over the past 70 years there has been a notable increase in the human presence in Antarctica, particularly on the Antarctic Peninsula, the South Shetland Islands and other islands just south of the Polar Front, such as South Georgia. In the austral summer 2019–2020, for instance, there were over 74,000 tourists and 5000 people in scientific stations ,22. Moreosystems ,29,30. Fosystems ,33,34,35osystems ,37. Howeosystems ,39. In 2osystems ,41,42,43osystems ,45.Euphausia superba) [2 concentrations [Despite the growing interest, the data acquired so far on the distribution of MPs and their potential impact in Antarctic marine ecosystems are still scarce and refer mainly to areas with coastal scientific stations and higher anthropogenic pressures, such as the Antarctic Peninsula, the South Shetland Islands, those in the Scotia Arc and the Ross Sea. In addition, different methods for sampling, quantification and characterization of MPs were used and it is difficult to compare the results of different studies. The task is made even more difficult by the heterogeneity of the polymer types and the lack of knowledge on their degradation in the cold waters of the Southern Ocean (about −1.8 °C), with high ultraviolet (UV) radiation in summer and seasonal sea-ice cover. The Southern Ocean is characterized by very dynamic conditions in which seasonal pulses of sea-ice freezing and break-up influence the development of phytoplankton, ice-algae and algae growing on the underside of the pack ice, which can play an important role in the uptake of MPs by a key species in the food web such as Antarctic krill (superba) ,16,30. Ctrations . The Anttrations . In the trations ,49,50,51trations ,26,29,52The possible combined effects of MPs and associated contaminants on marine organisms are becoming a research hotspot and although the role of MPs as vectors, relative to other routes of exposure, is largely unknown, a preliminary assessment seems particularly useful in the most-impacted Antarctic coastal ecosystems. Concentrations of MPs, POPs and CEI in these ecosystems are generally lower or in the same range as those in other seas; however, we cannot exclude possible biological effects in coastal biotic communities exposed to cumulative stresses due to interactions between MPs and other anthropogenic contaminants and the interplay of climatic and environmental changes. For example, the presence of MPs has been shown to increase the bioaccumulation and toxicity of cadmium (Cd) in zebrafish . In AntaIn summarizing the available data on the occurrence of MPs in Antarctic marine ecosystems and their potential effects on organisms and food webs with unique characteristics on Earth, this review will mainly focus on the interactions of MPs with other anthropogenic contaminants and on possible cumulative stress due to predicted changes in the Antarctic climate and marine environment. Human activities of greatest impact and the most vulnerable species and ecosystems will be highlighted, with the aim of guiding future research and contributing to the implementation of the ATPEP environmental management protocols.When the ATPEP was adopted, the potential environmental impact of MPs, personal care products, pharmaceuticals, detergents, flame retardants and other persistent contaminants was not yet well understood, and wastewater from scientific stations and vessels operating in the Southern Ocean were generally considered to be biodegradable. On the other hand, although there were some reports of the ingestion of plastic debris by seabirds, these events seemed to mainly affect animals wintering outside the Antarctic , and theDissosticus elaginoides [Long-term monitoring with standardized methodologies is required to evaluate the distribution of macro- and mesoplastics beached in the sub-Antarctic and to make comparisons between the different islands, since the results are influenced by large spatial and temporal variations in local weather and sea conditions, tide height, beach dynamics and variation in the durability and buoyancy of different groups of polymeric materials. Eriksson et al. , for insginoides .Although the available literature data from the Scotia Arc archipelagos shows that many beached plastic debris such as fishing-related materials or packaging bands are released by local or regional sources, there are also indications of plastic debris transported long distances by ocean currents ,63. In t−1). Retracing the trajectories of the air mass from the moment of sampling, they identified the items released by local sources (mainly polymers used in clothing and station equipment) and those deposited by snow after potential long-range transport. Assuming an atmospheric residence time of the fibers of 6.5 days, they estimated that the potential sources were located up to 6000 km away. According to Evangeliou et al. [−1 and 6.5 ± 2.9 Tg year−1, respectively; like POP compounds, the smallest particles can undergo a series of depositions followed by resuspension and are dispersed by wind all around the Earth. Their deposition in Antarctica is unknown; however, possible effects on the snow/ice surface albedos that favor the melting of the cryosphere and the release of contaminants deposited in the past cannot be excluded [Depending on the polymer composition, plastic litter can persist in the marine environment for decades to centuries, and exposure to ultraviolet light, waves, heat and microorganisms favors its degradation and the formation of tiny pieces (secondary MPs). Meanwhile weathering processes modify its physicochemical properties, promoting the release of dyes and plasticizing additives and the formation of functionalized oxygen moieties on their surfaces ,68,69. Iu et al. , global excluded . Airbornexcluded .p < 0.05) lower concentrations of MPs (>100 µm) in Southern than in Northern Hemisphere waters, but no significant differences between mean MP concentrations in the Barents Sea, the Central Atlantic, the Siberian Arctic, the North Atlantic and the sub-Antarctic  were higher than those reported in other less-remote sedimentary environments.A distinctive feature of the neuston samples from Southern Ocean waters is the high content of paint fragments released by research vessels ,83,84. L−1) than in Greenland firn samples (13.2 ng mL−1) [While common polymers from single-use products are widespread in most seas, in the Southern Ocean many items originate from the weathering and fragmentation of larger plastic objects and probably, there are also significant amount of plastic items of few-micrometer or sub-micrometer size (nanoplastics) deposited after long-range atmospheric transport. A recent survey reports higher concentrations of nanoplastics in a sea-ice core from Antarctica (52.3 ng mLng mL−1) . PolyethE. superba scrape algae from the underside of ice to survive the winter [The distribution and bioavailability of MPs in the Southern Ocean is affected by complex processes such as marine and atmospheric circulation and seasonal formation and melting of sea-ice. Our knowledge of the behaviour of MPs at the seawater/ice interface is poor. However, Materic et al.  found moe winter .−2) in two stations close to the continent than in offshore ones [A preliminary survey on the occurrence of MPs carried out in 2016 throughout the Southern Ocean reported much higher concentrations  [Neobuccinum eatoni) [−1) were three to five times higher in filter-feeders  and benthic grazers than in predators or omnivorous invertebrates. Although this accumulation pattern seemed to exclude the transfer of MPs through the Antarctic benthic food web, Bottari et al. [Trematomus bernacchii, an opportunistic and generalized feeder on benthic organisms, small fishes and zooplankton, collected in 1998 near the Italian station. The similar polymer composition recorded in sediments, benthic organisms and T. bernacchii confirms that although the Mario Zucchelli station has a wastewater treatment plant and is only open from mid-October to mid-February, it is a source of local MP contamination. According to Caruso et al. [Fibers from cloth washing are among the most common MPs in coastal marine ecosystems affected by scientific stations’ wastewater, and their concentrations in waters and sediments can be comparable to those reported in other coastal environments outside Antarctica. At Admiralty Bay (King George Island) microfibers were found to be entangled in various species of zooplankton  and MP c−2 day−1 . Althoug2 day−1) . Anyhow,2 day−1)  and Zhan2 day−1)  found hi2 day−1) . In the  eatoni) , and in  eatoni)   from Bird Island and Signy Island and identified seven different polymer types in 20% of the samples (Aptenodytes patagonicus) scats at South Georgia (Pygoscelis adeliae), chinstrap (Pygoscelis antarcticus) and gentoo penguin colonies (Aptenodytes forsteri) is the only penguin species breeding around Antarctica during the austral winter. Golubev [Apex predators, and especially those consuming their whole prey, act as integrators of MPs ingested by a diversity of species and their scats could reflect the availability of plastic debris in the marine environment. After the discovery in the 1980s of plastic debris having been ingested by seabirds from the Southern Hemisphere ,112, in  samples . A highe Georgia . Incubatcolonies . In the  Golubev  reported Golubev  found noArctocephalus gazella) on Macquarie Island (north of the APF) has been reported since 2003 [A. australis) in Northern Patagonia and plastic fragments and fibers also in scats from different species of pinnipeds living on the Peruvian and Chilean coasts. However, as reported for emperor penguins at Atka Bay [The occurrence of plastic particles in scats of the Antarctic fur seal .Although few diatom taxa, such as stigated ,120. Somstigated ,121; howstigated  indicatestigated . Sea-icestigated , and thestigated . Smallerstigated  and can stigated . The forstigated , for insPalmaria, Desmaretia and Himanthothallus reaching down to 90–100 m depths [Ice scouring severely limits the extent and biodiversity of biotic communities on the Antarctic shores; however, starting from depths of 3–5 m, most of substrata are covered by a vertical succession of many different macroalgae, with the genera m depths . Macroalm depths . Thus, iDue to their persistent and hydrophobic nature, buoyant plastic fragments of a few millimeters or hundreds of micrometers can be colonized by microalgae and many other organisms such as viruses, bacteria, fungi and invertebrates  ,131. Epi2 of seasonal sea-ice grow and melt around Antarctica each year; however, this extensive sea-ice cover shows wide inter-annual variations. After a few years of great extension, a rapid decline in Antarctic sea-ice has begun since 2016  [As reported above, sea-ice intercepts and accumulates MPs from atmospheric deposition and seawater and probably contributes to their ad/absorption by primary producers and Antarctic krill ,121,129. Arctic) . This ma Arctic) , for ins2 by the oceans is lowering seawater pH and carbonate ion concentrations. Due to the higher solubility of CO2 at lower temperatures, naturally low concentrations of calcium carbonate and the upwelling of CO2-rich deep waters, Antarctic marine organisms are likely to be most exposed to the potentially damaging effects of seawater acidification [2 concentrations increase the nutrient uptake and growth of Antarctic sea-ice diatoms of the genus Nitzschia [Nacella concinna [Sterechinus neumayeri appears to be resilient to the near-future ocean warming and acidification [E. superba, also appears not to be affected by exposure for one year to near-future levels of ocean acidification (1000–2000 µatm ρCO2) [E. superba at a simulated concentration of 2000 µatm ρCO2. Biological effects were also observed in experiments with multi-stress treatments. Rowland et al. [E. superba embryos when exposed to the combined effects of different nanoplastics and water acidification and this treatment had negative effects on the survival of the sub-Antarctic pteropod Limacina retroversa, even with short-term exposure (48 h) [The absorption of anthropogenic COfication . Calcifyfication  suggesteitzschia ; low pH concinna ; and thefication . Adult Atm ρCO2) . Howevertm ρCO2) , and Kawtm ρCO2)  found and et al.  found a e (48 h) . Since tPuffinus gravis), found a positive relationship between plastic and PCB content and hypothesized that the ingestion of plastic debris may contribute to the absorption of toxic chemicals by seabirds. Micro- and nanoplastics have a large specific surface and, depending on the characteristics of the polymers, their surfaces can provide an ecological niche for microorganisms with the formation of biofilms , which can enhance the adsorption of metals and organic pollutants [Ingested MPs particles can act as vectors for microorganisms and persistent organic pollutants, and the concomitant impact of pathogens and chemicals is undoubtedly far more severe than internal abrasion or other direct effects of MPs alone. As early as 1998, Ryan et al. , analyzillutants ,148,149.One main finding in MP research in surface and sub-surface waters of the Southern Ocean was the widespread occurrence of paint fragments derived from vessels. These particles can adsorb contaminants and, if ingested, can also release toxic chemicals in paint and dyes ,84, whicSeveral kinetic models have been used to study the adsorption of metals and POPs by MPs, and among the parameters tested  there is evidence that the aging of particles, by increasing their specific surface and the oxygen-containing functional groups, plays an important role . Being uRegardless of the relative importance of MPs as carriers of contaminants for the biota compared to other absorption routes, in Antarctic coastal marine ecosystems near scientific stations, chronic co-exposure even to low concentrations of a range of contaminants and pathogenic microorganisms can give rise to synergistic or additive biological effects. Most personal Antarctic equipment is made from synthetic polymers, which are often treated with water-repellent and flame-retardant compounds. Thus, wastewater from scientific stations is a source of these contaminants and of fibers from clothing, chemicals from detergents, personal care products or pharmaceuticals, and pathogenic microorganisms ,25,26,27E. superba is due to species-specific physiological and behavioral characteristics, such as adaptation to the Southern Ocean environment, synchronization with the seasonal sea-ice cycle and the ability to exploit whatever food is available. The huge decrease in Antarctic sea-ice in recent years is likely giving krill less food and shelter from predation, and many other threats are putting the conservation of E. superba populations at risk. For over a century, krill biomass has declined in parts of the Atlantic sector of the Southern Ocean . The fishing industry and krill catches are concentrated around the South Orkney Islands and the Antarctic Peninsula and the increasing demand for fish feed and for the production of pharmaceuticals and nutraceuticals from krill could increase the pressure on the krill fishery, placing further threats on this fundamental resource for Southern Ocean food webs [The biological implications for Antarctic organisms from simultaneous exposure to MPs, metals, organic compounds and microorganisms remain to be explored. Moreover, the resilience and responses of communities and ecosystems could be exacerbated by the concomitant impact of climate-related stressors and other anthropogenic disturbances. Just think of the pressures on Antarctic krill, the keystone species of the Southern Ocean trophic web, with the largest biomass (300 to 500 million tonnes) of all multicellular organisms. The success of ood webs .-the standardization of sampling and analytical procedures, paying greater attention to nanoplastics and adopting universally accepted methods for the assessment of MP contamination of samples in the field and in the lab.-the study of possible interactions of MPs with macro- and microalgae  for their potential role in the transfer of contaminants to Antarctic krill and along the food web.-the adsorption on plastic debris of potentially toxic anthropogenic contaminants and the composition of epiplastic biotic communities, which can be sources of pathogenic microorganisms.-the responses of keystone species under environmentally realistic conditions to combined exposure to MPs, paint chips, metals, POPs and CEI, which are quite common in Antarctic coastal ecosystems impacted by human activities.The Antarctic continent and the Southern Ocean are linked to global processes and receive anthropogenic persistent contaminants released worldwide through long-range atmospheric and marine transport. Moreover, the number of persons visiting Antarctica for scientific, tourism and fishing activities is increasing and can directly affect the Antarctic environment through fuel combustion, accidental oil spills, sewage outfalls, waste production and the introduction of pre-adapted and invasive alien species. Plastic debris is one of the most pervasive and ubiquitous synthetic wastes in the global environment and in recent years there has been growing concern about its occurrence in Antarctic marine ecosystems. However, despite the extraordinary increase in the number of surveys, it is still impossible to establish the distribution of MPs in the Southern Ocean and their potential impact on biotic communities. Overall, plastic contamination appears to be significant, especially in coastal marine areas of the Antarctic Peninsula, sub-Antarctic islands and the Ross Sea that receive wastewater from scientific stations and/or with rather intense research, fishing or tourism activities. The Southern Ocean has specific biotic communities and food webs and to evaluate the possible biological effects of MPs it is advisable to direct future research towards:In fact, these cumulative stresses could likely reduce the resilience of Antarctic marine organisms and ecosystems, thereby increasing the impact of anthropogenic contaminants and pathogenic microorganisms.Regarding the implementation of environmental management protocols, it seems appropriate to raise awareness of all people visiting Antarctica about the potential impact of MPs, personal care products, pharmaceuticals and inadvertently introduced alien organisms. National Antarctic Research Programs and tour operators should be encouraged to equip scientific stations and vessels with suitable wastewater treatment facilities to reduce/prevent the discharge of MPs, contaminants and microorganisms into Southern Ocean waters.


Esophagogastric variceal bleeding (EGVB) is one of the main complications of portal hypertension, especially in patients with liver cirrhosis, and has a very high fatality rate. At present, the treatment methods for rupture and bleeding of gastroesophageal varices (GV) include drug therapy, compression hemostasis with three-lumen and two-balloon tube, endoscopic therapy, and interventional and surgical operations. Endoscopy and intervention or their combined application is the mainstream treatment modes in clinical practice, especially their combined application has been increasingly recognized by front-line clinicians. This article intends to discuss the application characteristics of the two treatment methods. With the development of endoscopic treatment technology, active intervention through endoscopic gastric fundus, esophageal variceal ligation, sclerosing agent injection, and other methods has greatly improved the therapeutic effect of venous rupture and bleeding compared with the single use of drugs in internal medicine. Endoscopic sclerotherapy (EIS) is a method of treating gastric fundus esophageal varices through endoscopic injection of lauryl alcohol  to achieve hemostasis and prevent rebleeding. The mechanism is to inject sclerosant into the varicose veins to cause aseptic inflammation of the varicose veins, resulting in varicose vein contracture, thrombosis, fibrous scarring, and eventually occlusion. The Japanese clinical guidelines for liver cirrhosis , 2 recomEndoscopic ligation therapy (EVL) is to ligate the lower esophageal varices to occlude the veins, so as to relieve the varices and reduce the risk of rebleeding. EVL needs to be performed in several times, every 2 to 4 weeks, until the varicose veins are eliminated, so as to achieve the purpose of hemostasis and prevention of rebleeding. However, in the postoperative period of necrosis and scab removal, there is a risk of massive bleeding, and complications such as pain, esophageal ulceration, and perforation may occur.Both EVL and EIS directly treat submucosal varicose veins under endoscope to effectively control EVB in patients with liver cirrhosis , 4. EndoThere are many treatment methods for variceal bleeding, which are described in detail in the guidelines . Among tPercutaneous transhepatic and gastric coronary vein embolization (PTVE) refers to percutaneous puncture of intrahepatic portal vein branches under the guidance of ultrasound and then superselected into varicose vein branches such as gastric coronary vein/short gastric vein and injected with embolic materials to block bleeding, esophagus, gastric varices, to achieve the purpose of treatment and prevention of variceal bleeding. Commonly used embolic materials include hardeners (polyurethane), gelatin sponges, and spring steel rings. As a minimally invasive treatment method, it has achieved good therapeutic effect and low complication rate , and theBRTO refers to inserting a balloon catheter into the outflow end of the gastrorenal or gastric shunt via the femoral vein or internal jugular vein, inflating the balloon to stop blood flow, and injecting a sclerosing agent to eliminate varicose veins . As earlPartial splenic embolization (PSE) is to infarct part of the spleen by embolizing the internal splenic artery and reduce the damage of splenic parenchyma to peripheral blood cells and is mainly used to relieve clinical symptoms of hypersplenism . At the TIPS is to establish a shunt channel in the liver parenchyma between the hepatic vein and the portal vein through the internal jugular vein so that the blood flow of the portal venous system can be directly returned to the systemic circulation through the shunt channel, thereby reducing the portal pressure. Complications due to treatment of portal hypertension are reported . Early sThe following studies have compared the clinical efficacy of TIPS and endoscopic tissue glue injection in the treatment of GV bleeding. One retrospective study found that endoscopic injection of tissue glue for GV had a higher rate of rebleeding than TIPS (30% vs. 15%). In addition, the TIPS group had longer hospital stays and higher treatment costs, suggesting that endoscopic therapy may be more cost-effective . The resInterventional therapy is an important treatment method for esophagogastric variceal bleeding in cirrhotic portal hypertension, and some surgical methods may vary according to the specific conditions of different patients. Interventional therapy is only part of the comprehensive treatment of esophageal variceal bleeding in cirrhotic portal hypertension. How to rationally use the existing treatment methods for these bleeding patients needs to be carefully analyzed clinically to maximize the benefits of the patients. Even in patients after TIPS, in addition to the necessary anticoagulation therapy, the treatment of the cause is also very important.Interventional procedures can significantly reduce portal pressure by TIPS or reduction of splenic artery blood flow (PSE/SATE). Clinical studies , 48 haveLimited by the lack of high-quality clinical studies, there is currently no widely accepted consensus on GV treatment strategies. For secondary prevention of GV, the American Academy of Liver Diseases recommends interventional therapy as first-line therapy and endoscopic therapy as second-line therapy . BritishIn conclusion, endoscopy (EIS and EVL) and interventional therapy  are minimally invasive treatments that can effectively control and prevent GV bleeding. However, a large number of clinical studies are needed to distinguish the risks, pros, and cons of different surgical procedures and their application value in different populations. We should choose an individualized treatment strategy according to the specific situation of the patient: (1) whether it is used for the control of acute bleeding or mainly for the primary and secondary prevention of GV; (2) the diameter of the portal vein, whether there is portal vein thrombosis; (3) whether there is a large amount of ascites, shunt encephalopathy, hepatocellular carcinoma, etc.; (4) whether the patient's vital signs are stable and the liver function reserve; and (5) whether the hospital has technical means and equipment. All of these factors may influence the choice of treatment regimen. Both gastroscopy and interventional therapy have their own advantages and disadvantages. The ideal strategy is the combined application of gastroscopy and interventional therapy to learn from each other's strengths. We look forward to exploring the best treatment strategies for GV patients through rigorously designed prospective clinical studies.


Background: Rapid technological developments enable the immediate transmission of armed conflict events through a variety of media channels, inducing mass anxiety, fear, and helplessness. Youth are particularly vulnerable and face new challenges as a result of this exposure. The effects of media exposure to such events on psychological distress and post-traumatic symptoms were examined. Methods: A total of 161 participants aged 13–18 years completed a questionnaire battery that included measures of media exposure to armed conflict events, previous direct exposure to armed conflict events, psychological distress, post-traumatic symptoms, dispositional optimism, and self-mastery. A structural equation model (SEM) approach was employed for data analysis. Results: The extent of media exposure to armed conflict was directly associated with psychological distress and post-traumatic symptoms. Dispositional optimism moderated the association between media exposure and psychological distress, while self-mastery moderated the association between media exposure and post-traumatic symptoms. The effects of the Internet factor of media exposure, which included social media, were particularly disturbing as neither of the resilience factors moderated negative outcomes. Conclusions: The findings suggest that clinical interventions to enhance dispositional optimism and self-mastery as well as other potential resilience factors can protect adolescents from the severe effects of media exposure to violent armed conflict events. Developmental and public health implications related to vulnerabilities and resilience during adolescence are discussed. Social media have become a central focus in the life of adolescents , with reIn addition, the increasing incidence of war, armed conflict, and terrorism has become a global problem, reaching deep into societies and communities, targeting civilians and inducing mass anxiety, fear, a continuous sense of threat, and helplessness ,10,11. MAmong the population groups affected by war and terrorism, the youth are particularly vulnerable . The devAdolescents can be deeply affected by the images viewed across the various media platforms following armed conflict events and acts of terrorism. Studies have shown that realistic violence has greater effects on children and adolescents than fictional violence ,23. MoreThe effects of viewing these frightening scenes range across symptoms of anxiety, sadness, isolation, and general psychological distress ,26,27 toResearch suggests that for adolescents, the frequency, duration, and type of media exposure predict the psychological effects of media exposure to armed conflict events. For example, greater media exposure, either in duration measured as longer hours or intensity reflected in highly gruesome images, has been associated with a higher prevalence of distress symptoms ,26,33. MSocial media and other Internet platforms have been embraced by military organizations and terrorists for the same reasons as they have been engaged by other organizations, namely, their capacity to expand their reach and influence and their efficiency in the dissemination of propaganda . Media cThe feasibility of uploading and publishing any information, with no need for monitoring or approval from authorities, is an immense advantage ,16,41,42theater of terror”, an expression that is extremely relevant today , see In order to examine whether media exposure and previous direct armed conflict event exposure predicted both psychological distress and post-traumatic symptoms as a function of dispositional optimism and self-mastery, a structural equation model (SEM) approach was employed using AMOS 4 with the maximum likelihood estimation. The model controlled for age and gender. Overall, the model demonstrated good fit . As in the previous model, both psychological distress and post-traumatic symptoms were predicted by self-mastery and dispositional optimism. In addition, the extent of use of Internet media exposure predicted psychological distress , and the extent of use of video media exposure predicted post-traumatic symptoms . Finally, two significant interactions were found. First, an interaction effect of video media exposure and self-mastery on post-traumatic symptoms was found . In addition, an interaction between conventional media exposure and dispositional optimism in predicting post-traumatic symptoms emerged . Simple slope analyses indicated that the extent of media exposure of both video and conventional platforms was associated with more severe post-traumatic symptoms, but only for low levels of self-mastery and dispositional optimism, respectively , and not for high levels Results of the path model again indicated a good fit [χ2(25) = 31.44, This study examined the effects of adolescent media exposure to armed conflict events on post-traumatic symptoms and psychological distress as well as possible interactive factors including previous direct armed conflict event exposure, self-mastery, and dispositional optimism. The results showed that the extent of media exposure to armed conflict was directly associated with psychological distress and post-traumatic symptoms. Previous direct exposure to armed conflict events was not associated with post-traumatic symptoms or with psychological distress. In addition, dispositional optimism moderated the association between the extent of general media exposure to armed conflict events and psychological distress, while self-mastery moderated the association between the extent of general media exposure to armed conflict events and post-traumatic symptoms. The exploratory question related to the moderating role of self-mastery and dispositional optimism for the extent of the usage of each of the different categories of media exposure on psychological distress and post-traumatic symptoms. The first hypothesis stated that the extent of general media exposure to armed conflict events, operationalized as the extent of usage of all types of media, will be directly related to psychological distress and post-traumatic symptoms. This hypothesis was confirmed. In addition, a moderate correlation was found between psychological distress and post-traumatic symptoms, indicating that each made a unique contribution to the exposure outcomes. This indicates that the exposure outcomes can present as post-traumatic symptoms or as more specific symptoms of anxiety, depression, and somatization, as measured by the BSI. These findings are congruent with previous studies ,101 and The second hypothesis, which stated that the severity of previous direct exposure to armed conflict events will be directly associated with psychological distress and post-traumatic symptoms, was not confirmed. Correlations between the previous direct armed conflict exposure and post-traumatic symptoms and psychological distress were not significant. This is a surprising finding considering the widely documented relation between the exposure to terrorism and armed conflict events and post-traumatic symptoms ,102,103.The third hypothesis predicted that self-mastery and dispositional optimism will moderate the association between the exposure variables  and the outcome variables of psychological distress and post-traumatic symptoms. This hypothesis was partially confirmed. A significant negative correlation was found between dispositional optimism and self-mastery and psychological distress and post-traumatic symptoms. This finding corroborates the existing research literature ,67,71,72The significant association between the extent of general media exposure to armed conflict events and psychological distress was only found among participants with low levels of dispositional optimism and not among participants with high levels of dispositional optimism. This finding suggests that dispositional optimism acts as a resilience factor in mitigating general psychological distress, which presents as anxiety, depression, and somatization after media exposure to armed conflict events. Additionally, a significant association between the extent of general media exposure to armed conflict events and post-traumatic symptoms was found only among the participants with low levels of self-mastery and not among the participants with high levels of self-mastery, suggesting that self-mastery acts as a resilience factor in the association between media exposure and post-traumatic symptoms. The moderating function of dispositional optimism and self-mastery has been well-established ,69,71,72The finding that dispositional optimism and self-mastery function as resilience factors against media exposure to armed conflict events has not been shown previously. It is important to note that this finding pertains to the media exposure of armed conflict events and terrorism among adolescents. With the advent of different, easily accessible media platforms, notorious for their amenability, adolescents have become particularly avid consumers of the media coverage of war, armed conflict, and terrorism events ,34,107. The exploratory question examined the moderating role of self-mastery and dispositional optimism for the extent of usage of each of the different categories of media exposure to armed conflict events on psychological distress and post-traumatic symptoms, for which a directional hypothesis could not be formulated. Three categories of media exposure emerged in this analysis—Internet media exposure, conventional media exposure, and video media exposure. The Internet factor of media exposure, which included social media, Internet news channels, and phone alerts, showed a direct association with psychological distress levels, which presented as anxiety, depression, somatization, and general distress. This finding is particularly disturbing given that the Internet has become a major means of media distribution among adolescents, especially via social media platforms such as Facebook, Instagram, Twitter, Tik-Tok, etc. Youth can be exposed to uncensored and highly troubling scenes that are associated with increases in psychological distress including, anxiety, depression, and somatization. These findings emphasize the need to direct public attention to the dire effects to adolescents of uncensored, disturbing, and easily available materials. This study also showed that dispositional optimism and self-mastery did not moderate the association between Internet exposure to armed conflict events and psychological distress and post-traumatic symptoms. Hopefully, there are other variables that moderate the association between Internet exposure to war, armed conflict and terrorism events, and psychological distress. Other such variables should be explored in future research, considering the impact such variables can have on future interventions. Even though self-mastery did not moderate the negative effects of Internet media exposure, it was found to moderate the impact of both conventional and video media exposure on post-traumatic symptoms. Dispositional optimism, on the other hand, only moderated the effects of conventional media exposure on general psychological distress, as reflected in the GSI.Despite the aforementioned findings that suggest the complex effects of different types of media exposure and resilience factors on psychological symptoms and post-traumatic symptoms, this study has several limitations that should be addressed in further research. First, this study was based on questionnaires completed on the Internet and therefore may have been susceptible to response bias. Second, this study made use of single-agent, self-reported questionnaires, which would be better complemented with multi-agent reports or behavioral measures. Third, the media exposure to the armed conflict variable was difficult to operationalize, making it necessary to categorize the many platforms of media exposure to armed conflict  and create measures of usage and the extent of consumption of each of these different platforms. Therefore, this variable was then measured as the sum of consumption of each of the listed platforms. This measurement was unable to distinguish between the extensive consumption of a few favored platforms versus the light consumption of many different platforms. Finally, the sample was comprised of Jewish adolescents, and therefore did not represent the Arab population in Israel. Attention to these limitations in future studies would increase the generalization of these findings.The present study advances many suggestions for public policy regarding the mental health of adolescents. The developmental implications relate to our comprehension of the vulnerabilities and resilience during the period of adolescence. Adolescents are commonly exposed to the rapid media distribution of violent scenes, war, armed conflict events, and terrorist acts, and thus are particularly susceptible to significant negative psychological effects. The period of adolescence is characterized by the search for autonomy and the tendency to seek new and adventurous experiences, which could eventuate in high risk-taking behaviors. This, alongside the adolescents’ proficiency in exploiting new media platforms, accessibility to violent materials, and immaturity to cope with these disturbing stimuli, could produce a potent combination that heightens their vulnerability to psychological symptoms. Parents are a pivotal factor in supporting an adolescent’s mental health, particularly in an insecure and threatening environment. Thus, public health stakeholders should address ways to inform parents of the potential harmful effects of uncensored and unsupervised media exposure to war, armed conflict, and terrorism events as well as the resilience factors that can mitigate negative outcomes and strategies for reducing exposure. Education and counseling for parents are essential, since the monitoring of adolescents is particularly difficult due to the complexities of the developmental period including the high value placed on protecting privacy and autonomy . The present study also provides specific findings regarding the role of dispositional optimism and self-mastery as moderators of the negative effects of media exposure to armed conflict. The findings showed that dispositional optimism moderates psychological distress and that self-mastery moderates post-traumatic symptoms. These findings suggest the possibility of clinically manipulating the levels of dispositional optimism and self-mastery. However, it is important to identify the specific media platforms for which these resilience factors serve as moderators. Despite the partial effectivity of these particular moderating factors, the findings of this study hold promise for the detection of additional resilience factors that could inform the development of interventions for mitigating the negatives effects of media exposure to armed conflict events and terrorism among adolescents.On a broader level, this study has important consequences for the development and examination of the efficacy of intervention programs to inform, monitor, and treat youth exposed through the media to shocking and violent war, armed conflict, and terrorism events. As several screening and intervention programs have been developed for children exposed to the Israeli–Palestinian conflict in particular ,110, thePublic policy implications suggest that authorities and media stakeholders should consider the trade-off between freedom of information and the adverse effects of media exposure to war, armed conflict, and terrorism on the mental health of the youth. It could be useful to alert new social media propagators of the adverse effects of this uncensored material, which may encourage the development of appropriate strategies to monitor and limit exposure.This study highlights the complex ethical and regulatory dilemmas involved in relations between the media distribution of violent armed conflict related material and public mental health. This relation has become even more complicated with the development of diverse and ever-increasing social media platforms with which today’s youth are extremely proficient. Mental health practitioners should be informed about the effects and risks to youth, leading to careful consideration of the strategies to limit negative outcomes.