Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations:a scoping review

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients.Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury,but relatively less is known about the effect in pediatric populations.The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibito rs as a potential a djuvant treatment fo r neurocognitive decline in pediatric patients with traumatic brain injury.Investigators queried PubMed to identify literature published from database inception thro ugh June 2023 desc ribing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions.Based on preselected search criteria,340 unique papers we re selected for title and abstra ct screening.Thirty-two reco rds were reviewed in full after eliminating preclinical studies and pape rs outside the scope of the project.In adult traumatic brain injury,we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tole rated and shows both objective and patient-reported efficacy for reducing cognitive impairment.In children,3 pape rs report on 5 children recovering from traumatic brain injury,showing limited efficacy.An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group.Given its promise for efficacy in adults with traumatic brain injury and tole rability in pediatric patients,we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Making the case for the evolving role of social media in health professions education and a literature review on the application of some in ophthalmology

Background and Objective:Social media(SoMe)has emerged as a tool in health professions education(HPE),particularly amidst the challenges posed by the coronavirus disease 2019(COVID-19)pandemic.Despite the academia’s initial skepticism SoMe has been gaining traction in supporting learning communities,and offering opportunities for innovation in HPE.Our study aims to explore the integration of SoMe in HPE.Four key components were outlined as necessary for a successful integration,and include designing learning experiences,defining educator roles,selecting appropriate platforms,and establishing educational objectives.Methods:This article stemmed from the online Teaching Skills Series module on SoMe in education from the Ophthalmology Foundation,and drew upon evidence supporting learning theories relevant to SoMe integration and models of education.Additionally,we conducted a literature review considering Englishlanguage articles on the application of SoMe in ophthalmology from PubMed over the past decade.Key Content and Findings:Early adopters of SoMe platforms in HPE have leveraged these tools to enhance learning experiences through interaction,dialogue,content sharing,and active learning strategies.By integrating SoMe into educational programs,both online and in-person,educators can overcome time and geographical constraints,fostering more diverse and inclusive learning communities.Careful consideration is,however,necessary to address potential limitations within HPE.Conclusions:This article lays groundwork for expanding SoMe integration in HPE design,emphasizing the supportive scaffold of various learning theories,and the need of furthering robust research on examining its advantages over traditional educational formats.Our literature review underscores an ongoing multifaceted,random application of SoMe platforms in ophthalmology education.We advocate for an effective incorporation of SoMe in HPE education,with the need to comply with good educational practice.

Improving the training abilities of ophthalmic educators: the Ophthalmology Foundation’s initiatives

Our goal as medical educators is for our students to learn what they need to know and competently perform ophthalmic procedures.In addition,the students need to have good communication skills and behave professionally and ethically(1,2).Most medical educators are not taught how to teach but rather learn by role-modeling their mentors.This can be good or bad depending on the mentor!In addition,the amount of knowledge and numbers of surgical procedures is ever increasing and yet,in most countries,the amount of time to train and become competent is not changing.Thus,our goal of creating competent ophthalmologists is ever more challenging.

Key issues in water sealing performance of underground oil storage caverns: Advances and perspectives

Water sealing performance is important for underground water-sealed oil storage(UWSOS).The key issues concerning water sealing performance mainly include the permeability of fractured rock mass(FRM),water-sealed safety(WSS),water curtain performance,and prediction and control of water inflow.This paper reviews the progress of above four key issues on water sealing performances.First,the permeability of an FRM is the basis of water sealing performance,and several commonly used permeability test methods and spatial variation characteristics of permeability are outlined.Second,the current water sealing criteria are compared,and the evaluation methods of WSS are summarized.Third,the design parameters and efficiency evaluation of water curtain systems(WCSs)are introduced.The water inflow of oil storage caverns(OSCs)can reflect the water sealing effect,and the prediction methods and control measures of water inflow are also summarized.Finally,the advantages and disadvantages of the current research are discussed,and the potential research directions are pointed out,such as optimization of water sealing criteria and FRM model,quantitative evaluation of WCS efficiency,accurate prediction of water inflow,and improvement of grouting technology.

Implications of obesity in patients with foot and ankle pathology

Obesity is a growing problem defined as a body mass index of greater than 30 kg/m2.It is predicted that by 2030,48.9%of adults will be classified as obese which expands surgical risk factors to a broad population while increasing healthcare costs at the same time in different socioeconomic groups.This specific population has been widely studied in multiple surgical fields and published studies have shown the implications in each of these fields.The impact of obesity on orthopedic surgical outcomes has been previously reported in several total hip and knee arthroscopy studies,with evidence indicating that obesity is strongly associated with an increased risk of post operative complications together with higher revision rates.In line with increasing interest on the impact of obesity in orthopedics,there has been a similar output of publications in the foot and ankle literature.This review article evaluates several foot and ankle pathologies,their risk factors associated with obesity and subsequent management.It provides an updated,comprehensive analysis of the effects of obesity on foot and ankle surgical outcomes,with the ultimate aim of educating both surgeons and allied health professionals about the risks,benefits,and modifiable factors of operating on obese patients.

Multicenter evaluation of recurrence in endoscopic submucosal dissection and endoscopic mucosal resection in the colon:A Western perspective

BACKGROUND While colon endoscopic mucosal resection(EMR)is an effective technique,removal of larger polyps often requires piecemeal resection,which can increase recurrence rates.Endoscopic submucosal dissection(ESD)in the colon offers the ability for en bloc resection and is well-described in Asia,but there are limited studies comparing ESD vs EMR in the West.AIM To evaluate different techniques in endoscopic resection of large polyps in the colon and to identify factors for recurrence.METHODS The study is a retrospective comparison of ESD,EMR and knife-assisted endoscopic resection performed at Stanford University Medical Center and Veterans Affairs Palo Alto Health Care System between 2016 and 2020.Knife-assisted endoscopic resection was defined as use of electrosurgical knife to facilitate snare resection,such as for circumferential incision.Patients≥18 years of age undergoing colonoscopy with removal of polyp(s)≥20 mm were included.The primary outcome was recurrence on follow-up.RESULTS A total of 376 patients and 428 polyps were included.Mean polyp size was greatest in the ESD group(35.8 mm),followed by knife-assisted endoscopic resection(33.3 mm)and EMR(30.5 mm)(P<0.001).ESD achieved highest en bloc resection(90.4%)followed by knife-assisted endoscopic resection(31.1%)and EMR(20.2%)(P<0.001).A total of 287 polyps had follow-up(67.1%).On follow-up analysis,recurrence rate was lowest in knife-assisted endoscopic resection(0.0%)and ESD(1.3%)and highest in EMR(12.9%)(P=0.0017).En bloc polyp resection had significantly lower rate of recurrence(1.9%)compared to non-en bloc(12.0%,P=0.003).On multivariate analysis,ESD(in comparison to EMR)adjusted for polyp size was found to significantly reduce risk of recurrence[adjusted hazard ratio 0.06(95%CI:0.01-0.57,P=0.014)].CONCLUSION In our study,EMR had significantly higher recurrence compared to ESD and knife-assisted endoscopic resection.We found factors including resection by ESD,en bloc removal,and use of circumferential incision were associated with significantly decreased recurrence.While further studies are needed,we have demonstrated the efficacy of ESD in a Western population.

Porous heterostructure of graphene/hexagonal boron nitride as an efficient electrocatalyst for hydrogen peroxide generation

Compared with the traditional heteroatom doping,employing heterostructure is a new modulating approach for carbon-based electrocatalysts.Herein,a facile ball milling-assisted route is proposed to synthesize porous carbon materials composed of abundant graphene/hexagonal boron nitride(G/h-BN)heterostructures.Metal Ni powder and nanoscale h-BN sheets are used as a catalytic substrate/hard template and“nucleation seed”for the formation of the heterostructure,respectively.As-prepared G/h-BN heterostructures exhibit enhanced electrocatalytic activity toward H_(2)O_(2) generation with 86%-95%selectivity at the range of 0.45-0.75 V versus reversible hydrogen electrode(RHE)and a positive onset potential of 0.79 versus RHE(defined at a ring current density of 0.3 mA cm^(-2))in the alkaline solution.In a flow cell,G/h-BN heterostructured electrocatalyst has a H_(2)O_(2) production rate of up to 762 mmol g_(catalyst)^(-1) h^(-1) and Faradaic efficiency of over 75%during 12 h testing,superior to the reported carbon-based electrocatalysts.The density functional theory simulation suggests that the B atoms at the interface of the G/h-BN heterostructure are the key active sites.This research provides a new route to activate carbon catalysts toward highly active and selective O_(2)-to-H_(2)O_(2) conversion.

Self-adaptive bulk/surface engineering of Bi_(x)O_(y)Br_(z) towards enhanced photocatalysis:Current status and future challenges

The bulk/surface states of semiconductor photocatalysts are imperative parameters to maneuver their performance by significantly affecting the key processes of photocatalysis including light absorption,separation of charge carrier,and surface site reaction.Recent years have witnessed the encouraging progress of self-adaptive bulk/surface engineered Bi_(x)O_(y)Br_(z) for photocatalytic applications spanning various fields.However,despite the maturity of current research,the interaction between the bulk/surface state and the performance of Bi_(x)O_(y)Br_(z) has not yet been fully understood and highlighted.In this regard,a timely tutorial overview is quite urgent to summarize the most recent key progress and outline developing obstacles in this exciting area.Herein,the structural characteristics and fundamental principles of Bi_(x)O_(y)Br_(z)for driving photocatalytic reaction as well as related key issues are firstly reviewed.Then,we for the first time summarized different self-adaptive engineering processes over Bi_(x)O_(y)Br_(z)followed by a classification of the generation approaches towards diverse Bi_(x)O_(y)Br_(z)materials.The features of different strategies,the up-to-date characterization techniques to detect bulk/surface states,and the effect of bulk/surface states on improving the photoactivity of Bi_(x)O_(y)Br_(z)in expanded applications are further discussed.Finally,the present research status,challenges,and future research opportunities of self-adaptive bulk/surface engineered Bi_(x)O_(y)Br_(z)are prospected.It is anticipated that this critical review can trigger deeper investigations and attract upcoming innovative ideas on the rational design of Bi_(x)O_(y)Br_(z)-based photocatalysts.

Narrative minireview of the spatial epidemiology of substance use disorder in the United States:Who is at risk and where?

Drug overdose is the leading cause of death by injury in the United States.The incidence of substance use disorder(SUD)in the United States has increased steadily over the past two decades,becoming a major public health problem for the country.The drivers of the SUD epidemic in the United States have changed over time,characterized by an initial heroin outbreak between 1970 and 1999,followed by a painkiller outbreak,and finally by an ongoing synthetic opioid outbreak.The nature and sources of these abused substances reveal striking differences in the socioeconomic and behavioral factors that shape the drug epidemic.Moreover,the geospatial distribution of the SUD epidemic is not homogeneous.The United States has specific locations where vulnerable communities at high risk of SUD are concentrated,reaffirming the multifactorial socioeconomic nature of this epidemic.A better understanding of the SUD epidemic under a spatial epidemiology framework is necessary to determine the factors that have shaped its spread and how these patterns can be used to predict new outbreaks and create effective mitigation policies.This narrative minireview summarizes the current records of the spatial distribution of the SUD epidemic in the United States across different periods,revealing some spatiotemporal patterns that have preceded the occurrence of outbreaks.By analyzing the epidemic of SUD-related deaths,we also describe the epidemic behavior in areas with high incidence of cases.Finally,we describe public health interventions that can be effective for demographic groups,and we discuss future challenges in the study and control of the SUD epidemic in the country.

A Five-stage Evolution of Earth's Phosphorus Cycle

Phosphorus(P)is a key biological nutrient and probably the ultimate limiter of marine productivity during Earth history.In recent years,a wealth of new knowledge has revolutionized our understanding of the global P cycle,yet its longterm evolution remains incompletely documented.In this paper,we review the effects of three major controlling factors on the long-term evolution of the global P cycle,i.e.,tectonics,marine redox conditions,and bio-evolution,on the basis of which a five-stage model is proposed:StageⅠ(>~2.4 Ga),tectonic-lithogenic-controlled P cycling;StageⅡ(~2.4 Ga to 635Ma),low-efficiency biotic P cycling;StageⅢ(~635 Ma to 380 Ma),transitional biotic P cycling;StageⅣ(~380 Ma to near-modern),high-efficiency biotic P cycling;and Stage V(Anthropocene),human-influenced P cycling.This model implies that the earlier-proposed Ediacaran reorganization of the marine P cycle may represent only the start of a-250-Myr-long transition of the Earth's P cycle(StageⅢ)between the low-efficiency biotic mode of the Proterozoic(StageⅡ)and the high-efficiency biotic mode of the Phanerozoic(StageⅣ).The development of biologically-driven,high-efficiency P cycling may have been a key factor for the increasing frequency and volume of phosphorite deposits since the late Neoproterozoic.

Effectiveness of PMV-Based Controls for Commercial Buildings in the USA

Using an accurate energy model,this paper simulated existing commercial buildings to compare PMV-based comfort control with conventional thermostatic control and conduct a sensitivity analysis using the Design of Experiments method with monitored energy consumption data.This analysis was applied considering the impact of building envelope characteristics including thermal insulation level of exterior walls and air leakage rate on the ability of both control options to maintain indoor thermal comfort while minimizing cooling energy consumption.The analysis findings indicated that PMV-based comfort control is viable for striking a middle ground between thermal comfort and heating energy consumption with a PPD(predicted percentage of dissatisfied)level at 8%for any combination of walls’R-value and air infiltration rate while temperature-based controls result in an unacceptable indoor thermal comfort performance especially for low R-values regardless of the air infiltration rate with PPD level reaching over 76%.Also,the results show that in a comfort-controlled space,the average radioactive temperature and occupant-related features like metabolic rate and clothing level have a far bigger effect on energy use than other parameters like relative humidity.

Autophagy in neural stem cells and glia for brain health and diseases

Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

A Novel On-Site-Real-Time Method for Identifying Characteristic Parameters Using Ultrasonic Echo Groups and Neural Network

On-site and real-time non-destructive measurement of elastic constants for materials of a component in a in-service structure is a challenge due to structural complexities,such as ambiguous boundary,variable thickness,nonuniform material properties.This work develops for the first time a method that uses ultrasound echo groups and artificial neural network(ANN)for reliable on-site real-time identification of material parameters.The use of echo groups allows the use of lower frequencies,and hence more accommodative to structural complexity.To train the ANNs,a numerical model is established that is capable of computing the waveform of ultrasonic echo groups for any given set of material properties of a given structure.The waveform of an ultrasonic echo groups at an interest location on the surface the structure with material parameters varying in a predefined range are then computed using the numerical model.This results in a set of dataset for training the ANN model.Once the ANN is trained,the material parameters can be identified simultaneously using the actual measured echo waveform as input to the ANN.Intensive tests have been conducted both numerically and experimentally to evaluate the effectiveness and accuracy of the currently proposed method.The results show that the maximum identification error of numerical example is less than 2%,and the maximum identification error of experimental test is less than 7%.Compared with currently prevailing methods and equipment,the proposefy the density and thickness,in addition to the elastic constants.Moreover,the reliability and accuracy of inverse prediction is significantly improved.Thus,it has broad applications and enables real-time field measurements,which has not been fulfilled by any other available methods or equipment.

Microglial autophagy in neurogenesis:a new player in Alzheimer's disease

While extensive studies have illuminated the impact of Alzheimer's disease(AD) on neuronal survival,there is growing evidence that abnormal postnatal neurogenesis in early AD brains contributes to disease progression.Postnatal neurogenesis serves as a mechanism to replace dead or damaged neurons.New neurons generated from neural stem cells(NSCs) in the subgranular zone(SGZ) of the dentate gyrus integrate into the existing hippocampal circuit.

Viologen-based flexible electrochromic devices

Electrochromic technology has gained significant attention in various fields such as displays,smart windows,biomedical monitoring,military camouflage,human-machine interaction,and electronic skin due to its ability to provide reversible and fast color changes under applied voltage.With the rapid development and increasing demand for flexible electronics,flexible electrochromic devices(FECDs)that offer smarter and more controllable light modulation hold great promise for practical applications.The electrochromic material(ECM)undergoing color changes during the electrochemical reactions is one of the key components in electrochromic devices.Among the ECMs,viologens,a family of organic small molecules with 1,1'-disubstituted-4,4'-dipyridinium salts,have garnered extensive research interest,due to their well-reversible redox reactions,excellent electron acceptance ability,and the ability to produce multiple colors.Notably,viologen-based FECDs demonstrate color changes in the liquid or semisolid electrolyte layer,eliminating the need for two solid electrodes and thus simplifying the device structure.Consequently,viologens offer significant potential for the development of FECDs with high optical contrast,fast response speed,and excellent stability.This review aims to provide a comprehensive overview of the progress and perspectives of viologen-based FECDs.It begins by summarizing the typical structure and recent exciting developments in viologen-based FECDs,along with their advantages and disadvantages.Furthermore,the review discusses recent advancements in FECDs with additional functionalities such as sensing,photochromism,and energy storage.Finally,the remaining challenges and potential research directions for the future of viologen-based FECDs are addressed.

DeepOCL:A deep neural network for Object Constraint Language generation from unrestricted nature language

Object Constraint Language(OCL)is one kind of lightweight formal specification,which is widely used for software verification and validation in NASA and Object Management Group projects.Although OCL provides a simple expressive syntax,it is hard for the developers to write correctly due to lacking knowledge of the mathematical foundations of the first-order logic,which is approximately half accurate at the first stage of devel-opment.A deep neural network named DeepOCL is proposed,which takes the unre-stricted natural language as inputs and automatically outputs the best-scored OCL candidates without requiring a domain conceptual model that is compulsively required in existing rule-based generation approaches.To demonstrate the validity of our proposed approach,ablation experiments were conducted on a new sentence-aligned dataset named OCLPairs.The experiments show that the proposed DeepOCL can achieve state of the art for OCL statement generation,scored 74.30 on BLEU,and greatly outperformed experienced developers by 35.19%.The proposed approach is the first deep learning approach to generate the OCL expression from the natural language.It can be further developed as a CASE tool for the software industry.

Sickle cell retinopathy and systemic disease

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and mortality.Vascular occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and priapism.All ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell retinopathy.Proliferative sickle cell retinopathy(PSR)is the most common cause of vision loss.Untreated PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal detachment.Ophthalmic screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient outcomes.SCD patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic complications.While hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment options.Despite the United States screening all infants for SCD,there can be delays in diagnosis and treatment.This review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

Circulating microRNA expression and nonalcoholic fatty liver disease in adolescents with severe obesity

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases in children and adolescents.NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),wherein hepatocellular inflammation and/or fibrosis coexist with steatosis.Circulating microRNA(miRNA)levels have been suggested to be altered in NAFLD,but the extent to which miRNA are related to NAFLD features remains unknown.This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.AIM To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.METHODS This study included 81 adolescents diagnosed with NAFLD and 54 adolescents without NAFLD from the Teen-Longitudinal Assessment of Bariatric Surgery study.Intra-operative core liver biopsies were collected from participants and used to characterize histological features of NAFLD.Plasma samples were collected during surgery for miRNA profiling.A total of 843 plasma miRNAs were profiled using the HTG EdgeSeq platform.We examined associations of plasma miRNAs and NAFLD features using logistic regression after adjusting for age,sex,race,and other key covariates.Ingenuity Pathways Analysis was used to identify biological functions of miRNAs that were associated with multiple histological features of NAFLD.RESULTS We identified 16 upregulated plasma miRNAs,including miR-193a-5p and miR-193b-5p,and 22 downregulated plasma miRNAs,including miR-1282 and miR-6734-5p,in adolescents with NAFLD.Moreover,52,16,15,and 9 plasma miRNAs were associated with NASH,fibrosis,ballooning degeneration,and lobular inflammation,respectively.Collectively,16 miRNAs were associated with two or more histological features of NAFLD.Among those miRNAs,miR-411-5p was downregulated in NASH,ballooning,and fibrosis,while miR-122-5p,miR-1343-5p,miR-193a-5p,miR-193b-5p,and miR-7845-5p were consistently and positively associated with all histological features of NAFLD.Pathway analysis revealed that most common pathways of miRNAs associated with multiple NAFLD features have been associated with tumor progression,while we also identified linkages between miR-122-5p and hepatitis C virus and between miR-199b-5p and chronic hepatitis B.CONCLUSION Plasma miRNAs were associated with NAFLD features in adolescent with severe obesity.Larger studies with more heterogeneous NAFLD phenotypes are needed to evaluate miRNAs as potential biomarkers of NAFLD.

Indirect traumatic optic neuropathy:modeling optic nerve injury in the context of closed head trauma

Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.

Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain

Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states.It has been well-documented that,after peripheral nerve injury or inflammation,functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings,the injured or inflamed afferent fibers,the dorsal root ganglion(DRG),and the central afferent terminals in the spinal cord.Among all the changes,ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest,as such discharges doubtless contribute to the develop-ment of pathological pain states such as neuropathic pain.Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury:the injured afferent fibers(neuroma) leading to the DRG,and the DRG somata.The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain.Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation.Further,mechanisms involved in the generation of spontaneous activity are also reviewed;evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed.An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.