From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Mitophagy in acute central nervous system injuries:regulatory mechanisms and therapeutic potentials

Acute central nervous system injuries,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,traumatic brain injury,and spinal co rd injury,are a major global health challenge.Identifying optimal therapies and improving the long-term neurological functions of patients with acute central nervous system injuries are urgent priorities.Mitochondria are susceptible to damage after acute central nervous system injury,and this leads to the release of toxic levels of reactive oxygen species,which induce cell death.Mitophagy,a selective form of autophagy,is crucial in eliminating redundant or damaged mitochondria during these events.Recent evidence has highlighted the significant role of mitophagy in acute central nervous system injuries.In this review,we provide a comprehensive overview of the process,classification,and related mechanisms of mitophagy.We also highlight the recent developments in research into the role of mitophagy in various acute central nervous system injuries and drug therapies that regulate mitophagy.In the final section of this review,we emphasize the potential for treating these disorders by focusing on mitophagy and suggest future research paths in this area.

Football injuries of the ankle: A review of injury mechanisms, diagnosis and management

Football is the most popular sport worldwide and is associated with a high injury rate, most of which are the result of trauma from player contact. Ankle injuries are among the most commonly diagnosed injuries in the game. The result is reduced physical activity and endurance levels, lost game time, and considerable medical cost. Sports medicine professionals must employ the correct diagnostic tools and effective treatments and rehabilitation protocols to minimize the impact of these injuries on the player. This review examines the diagnosis, treatment, and postoperative rehabilitation for common football injuries of the ankle based on the clinical evidence provided in the current literature.

Acute syndesmotic injuries in ankle fractures:From diagnosis to treatment and current concepts

A stable and precise articulation of the distal tibiofibular syndesmosis maintains the tibiofibular relationship,and it is essential for normal motion of the ankle joint.The disruption of this joint is frequently accompanied by rotational ankle fracture,such as pronation-external rotation,and rarely occurs without ankle fracture.The diagnosis is not simple,and ideal management of the various presentations of syndesmotic injury remains controversial to this day.Anatomical restoration and stabilization of the disrupted tibiofibular syndesmosis is essential to improve functional outcomes.In such an injury,including inadequately treated,misdiagnosed and correctly diagnosed cases,a chronic pattern characterized by persistent ankle pain,function disability and early osteoarthritis can result.This paper reviews anatomical and biomechanical characteristics of this syndesmosis,the mechanism of its acute injury associated to fractures,radiological and arthroscopic diagnosis and surgical treatment.

What priorities should be considered for Iranian veterans with ankle-foot injuries？ A health needs assessment study, 25 years post-conflict

Despite the passage of time,a large number of veterans are still affected by injuries acquired during Iran-Iraq war.In addition to their primary injuries,the majority of veterans also experience difficulty with long-term,secondary effects.Studies have shown that the most common of these include a range of disabilities,pain,and dramatic decline in mental health and quality of life.Improving living conditions and providing rehabilitation services to veterans has always been a main priority of authorities.The goal of this study was to explain the methods and materials with which these priorities were explored.

Mental health among Iranian combat veterans with ankle-foot neuromusculoskeletal injuries

Background:Veterans with purely physical disorders,such as ankle-foot neuromusculoskeletal disorders,are often neglected in psychological assessments because mental health evaluations are usually focused on those with a psychological disturbance or with a high percentage of injury.The purpose of this study was to evaluate the psychological condition of veterans with ankle-foot neuromusculoskeletal disorders.Methods:A cross-sectional study was performed between 2014 and 2016 on veterans with war-related ankle-foot injuries living in two provinces of Iran.An information form for demographic data and injury-related factors was used.Additionally,the previously validated Persian version of the Symptom Checklist-90-Revision(SCL-90-R)questionnaire was used for data collection.Results:The respondents were 215 male veterans with a mean age of 51.7±7.5 years.The most common mental health problems were observed for the somatization(24.7%),obsessions-compulsions(14.4%),and anxiety(12.6%).Based on the Global Severity Index(GSI),48.6%of individuals had a possible psychiatric/psychological illness.According to the multivariate regression analysis,GSI scores were significantly higher among veterans who were older than 27 years at the time of injury(P=0.005),had an associated injury(P=0.002),and had a history of hospitalization within the past 12 months for reasons other than their injury(P=0.035).Conclusion:Approximately half of the combat veterans with ankle-foot neuromusculoskeletal disorders likely had psychological problems.The evaluation of the patterns and predicting factors of psychological conditions may inform strategic planning efforts and decision-making,which,in turn,may provide a better quality of life for veterans.Further studies that utilize longitudinal designs are needed to evaluate and compare the psychological status of different groups of veterans and other groups in the general population.

Correlation of stress radiographs to injuries associated with lateral ankle instability

BACKGROUND Stress radiographs have demonstrated superior efficacy in the evaluation of ankle instability.AIM To determine if there is a degree of instability evidenced by stress radiographs that is associated with pathology concomitant with ankle ligamentous instability.METHODS A retrospective review of 87 consecutive patients aged 18-74 who had stress radiographs performed at a single institution between 2014 and 2020 was performed.These manual radiographic stress views were then correlated with magnetic resonance imaging and operative findings.RESULTS A statistically significant association was determined for the mean and median stress radiographic values and the presence of peroneal pathology(P=0.008 for tendonitis and P=0.020 for peroneal tendon tears).A significant inverse relationship was found between the presence of an osteochondral defect and increasing degrees of instability(P=0.043).CONCLUSION Although valuable in the clinical evaluation of ankle instability,stress radiographs are not an independent predictor of conditions associated with ankle in-stability.

Ankle injuries in athletes:A review of the literature

Ankle injuries are commonplace in the athletic population, with lateral ligamentsprains accounting for the majority of them. The medial ligament complex, thedistal tibiofibular syndesmosis as well as any of the bones that constitute the anklejoint can also be injured. Typical mechanisms of injury include inversion-plantarflexionand external rotation on a supinated, dorsiflexed or pronated foot. Lesionsof the ankle present with similar symptoms of pain, swelling and tenderness.Therefore, a thorough history and physical examination must be obtained to makethe correct diagnosis. This is especially critical for athletes as certain injuries canlead to termination of their career if not treated accurately on time. Imaging maybe useful in some cases to confirm or rule out differential diagnoses. Most injuriescan be managed conservatively using the Protection, Rest, Ice, Compression andElevation protocol followed by a comprehensive rehabilitation programme.Surgery is reserved for grade III ligament tears that are refractory to initial nonoperativetreatment and displaced fractures that are unlikely to unite withoutsurgical intervention. The objective of this review is to discuss the common ankleinjuries encountered in the athletic population and the approaches to theirdiagnosis and management.

Application Effect of Chinese Medicine Rehabilitation in the Treatment of Adolescent Ankle Sports Injuries

Objective:To analyze the clinical effect of traditional Chinese medicine rehabilitation in treating adolescent ankle sports injuries.Methods:From December 2020 to December 2022,adolescent patients with ankle joint sports injuries admitted to our hospital were selected as observation objects,and 67 patients were divided into a control group(n=33,routine rehabilitation treatment)and an experimental group(n=34,traditional Chinese medicine rehabilitation treatment)according to the computer grouping method.Compare the treatment results.Results:(i)The treatment received in the experimental group had an efficacy of 94.11%,which was higher than that of the control group(75.75%),and statistical significance was established(P<0.05).(ii)Before treatment,there was no difference in ankle joint pain,ankle joint activity,and ankle joint function scores between the control group and the experimental group(P>0.05);after treatment,the ankle joint pain,ankle joint activity,and ankle joint function scores in the experimental group were significantly higher than those in the control group(P<0.05).(iii)The experimental group had higher scores on physiological function,physiological function,physical pain,general health status,energy,social function,emotional function,and mental health compared to the control group(P<0.05).Conclusion:Traditional Chinese medicine rehabilitation is effective in treating ankle injuries caused by sports in adolescents and improve their quality of life.Therefore,it should be popularized.

Crosstalk among mitophagy,pyroptosis,ferroptosis,and necroptosis in central nervous system injuries

Central nervous system injuries have a high rate of resulting in disability and mortality;however,at present,effective treatments are lacking.Programmed cell death,which is a genetically determined fo rm of active and ordered cell death with many types,has recently attra cted increasing attention due to its functions in determining the fate of cell survival.A growing number of studies have suggested that programmed cell death is involved in central nervous system injuries and plays an important role in the progression of brain damage.In this review,we provide an ove rview of the role of programmed cell death in central nervous system injuries,including the pathways involved in mitophagy,pyroptosis,ferroptosis,and necroptosis,and the underlying mechanisms by which mitophagy regulates pyroptosis,ferroptosis,and necro ptosis.We also discuss the new direction of therapeutic strategies to rgeting mitophagy for the treatment of central nervous system injuries,with the aim to determine the connection between programmed cell death and central nervous system injuries and to identify new therapies to modulate programmed cell death following central nervous system injury.In conclusion,based on these properties and effects,interventions targeting programmed cell death could be developed as potential therapeutic agents for central nervous system injury patients.

Chronic Ankle Instability: Therapeutic Exercise and Data Analysis

Background and Objectives: Ankle injuries are the most common type of injury in healthy active individuals. If not treated properly, recurrent sprains can lead to a condition of chronic ankle instability (CAI). The present paper examines some subjects with a previous history of acute inversion ankle sprain who have developed a subsequent condition of instability, grouping them according to inclusion criteria and analyzing them through four field tests considered objective by the scientific literature: SEBT test, BEES test, TIBT test, SHT test. The data obtained were stored in order to compare them following a re-education protocol aimed at improving proprioception, balance, walking and strengthening the extrinsic and intrinsic muscles of the foot. per year. The subjects were then divided into two categories: subjects with CAI > 1 year and subjects with CAI ≤ 1 year. A protocol lasting 6 weeks was administered to both groups, trying to work on improving balance in single stance, improving static and dynamic stability, strengthening the gluteus medius and maximus (pelvis stabilizers) and strengthening of the intrinsic muscles of the foot. At the end of the protocol the subjects were all re-evaluated with the same field tests used previously and the data obtained were compared both with the pre-protocol data and with the data measured by the control subjects.

Analysis of a passive ankle exoskeleton for reduction of metabolic costs during walking

Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational readiness.Several exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday usability.This article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target population.Based on the 6-min walk test,twenty-nine subjects participated in the study using three different force elements.The results indicate that it is possible to reduce metabolic expenditure while using the developed exoskeleton.Additionally,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended periods.Nevertheless,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.

Ambulance Records as an Information Source to Document and Prevent Fall Injuries in Sweden

In Sweden, there has been only limited documentation for injuries requiring ambulance responses. The main objective of this study is, through the use of historic data, to assess the suitability of ambulance records to describe circumstances with fall injuries. Methods: The injury events data around patients were sourced from the ambulance data register. Descriptive statistics were used to describe injured patients based on age group, type of injury, place of injury, injury mechanism and consequence of an injury event. Two-group comparison was performed with Pearson’s chi-squared. Predictors of transport to hospital were identified using logistic regression analyses. Result: Ambulance provides unique data on all injury events, with direct implications for translational research, public policy and clinical practice (safety promotion). In 2002 ambulance attended 3964 injured people which represents 14% of ambulance attended workload in Värmland county, Sweden. The most common trauma location was the traffic area followed by residential area and nursing home. These three injury sites account for 2320 cases (61.6%). The most common cause of injury was falls (63.9%) followed by contact with another person (26.5%). Contact with another person is the most common site of injury in the traffic area (79.5%), and men aged 25-66 years are overrepresented. Conclusion: Logistic regression found that, age-group and place code were significant predictor for being attended by ambulance. Traffic, home and nursing homes were over-represented injury environments (61.6%) that require special attention. Most injury cases occur in the home and nursing homes among people over 67 years of age. Surprisingly, most of the injury events in the traffic environment are about hitting another person. Paramedics can provide rich and valuable data on injury events. Registration of such data is entirely possible and desirable, and can be used in preventive work.

Functional assessment and influencing factors after staged functional training in patients with ankle fractures

BACKGROUND The recovery of limb function after ankle fracture surgery is a gradual process.The main purpose of implementing early functional exercise,joint mobility,muscle contraction function,passive ankle flexion and extension exercises,or physical factor therapy techniques is to achieve the rapid recovery of normal physiological limb function.However,currently the most effective rehabilitation training method is staged limb functional exercise,which promotes rapid recovery of limb function while preventing adverse consequences caused by overwork or insufficient training.Staged limb functional exercise divides the rehabilitation process into multiple stages,each of which has specific training objectives and contents.This method helps patients gradually restore limb function.Nevertheless,some patients still exhibit poor limb function after standardized exercise.Therefore,a functional evaluation should be performed to analyze the impact of staged functional training after ankle fracture surgery.AIM To perform a functional evaluation and determine the influencing factors of staged functional training in patients with ankle fracture.METHODS A retrospective study enrolled 150 patients who underwent surgical treatment for ankle fracture from May 2020 to May 2022 at our hospital.Univariate and multivariate linear regression analyses were performed on general data,functional exercise compliance scale for orthopedic patients,Social Support Rating Scale(SSRS),American Orthopedic Foot and Ankle Score(AOFAS)Ankle-Hindfoot Score,and pain factors[serum bradykinin(BK),prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)].RESULTS Based on the AOFAS Ankle-Hindfoot Scale,the cases were divided into the excellent function(n=111)and ordinary function(n=39)groups.Univariate analysis revealed that monthly family income,education level,diabetes mellitus,functional exercise compliance scale of orthopedic patients score,SSRS,BK,PGE2,and 5-HT significantly influenced limb function after ankle fracture(P<0.05);Multiple linear regression analysis showed that the functional exercise compliance scale score,SSRS,BK,PGE2,and 5-HT were independent risk factors affecting functional performance after staged functional exercise(P<0.05).CONCLUSION Exercise compliance,SSRS,and pain level are the independent risk factors affecting functional performance after staged functional training following ankle surgery.Clinical nursing care after ankle surgery should include analgesic and health education measures to ensure optimal recovery of limb function.

Configuration and Kinematics of a 3-DOF Generalized Spherical Parallel Mechanism for Ankle Rehabilitation

The kinematic equivalent model of an existing ankle-rehabilitation robot is inconsistent with the anatomical structure of the human ankle,which influences the rehabilitation effect.Therefore,this study equates the human ankle to the UR model and proposes a novel three degrees of freedom(3-DOF)generalized spherical parallel mechanism for ankle rehabilitation.The parallel mechanism has two spherical centers corresponding to the rotation centers of tibiotalar and subtalar joints.Using screw theory,the mobility of the parallel mechanism,which meets the requirements of the human ankle,is analyzed.The inverse kinematics are presented,and singularities are identified based on the Jacobian matrix.The workspaces of the parallel mechanism are obtained through the search method and compared with the motion range of the human ankle,which shows that the parallel mechanism can meet the motion demand of ankle rehabilitation.Additionally,based on the motion-force transmissibility,the performance atlases are plotted in the parameter optimal design space,and the optimum parameter is obtained according to the demands of practical applications.The results show that the parallel mechanism can meet the motion requirements of ankle rehabilitation and has excellent kinematic performance in its rehabilitation range,which provides a theoretical basis for the prototype design and experimental verification.

Type Synthesis of Self-Alignment Parallel Ankle Rehabilitation Robot with Suitable Passive Degrees of Freedom

The current parallel ankle rehabilitation robot(ARR)suffers from the problem of difficult real-time alignment of the human-robot joint center of rotation,which may lead to secondary injuries to the patient.This study investigates type synthesis of a parallel self-alignment ankle rehabilitation robot(PSAARR)based on the kinematic characteristics of ankle joint rotation center drift from the perspective of introducing"suitable passive degrees of freedom(DOF)"with a suitable number and form.First,the self-alignment principle of parallel ARR was proposed by deriving conditions for transforming a human-robot closed chain(HRCC)formed by an ARR and human body into a kinematic suitable constrained system and introducing conditions of"decoupled"and"less limb".Second,the relationship between the self-alignment principle and actuation wrenches(twists)of PSAARR was analyzed with the velocity Jacobian matrix as a"bridge".Subsequently,the type synthesis conditions of PSAARR were proposed.Third,a PSAARR synthesis method was proposed based on the screw theory and type of PSAARR synthesis conducted.Finally,an HRCC kinematic model was established to verify the self-alignment capability of the PSAARR.In this study,93 types of PSAARR limb structures were synthesized and the self-alignment capability of a human-robot joint axis was verified through kinematic analysis,which provides a theoretical basis for the design of such an ARR.

Foot and ankle surgery:Tourniquet placement site to cause as little postoperative pain as possible

There is controversy in the literature on where to place the tourniquet(thigh,calf,ankle)for foot and ankle surgery.While some authors prefer the ankle tourniquet to the calf tourniquet,others state that the surgeon can decide between using the thigh tourniquet or the ankle tourniquet,since there was no difference in postoperative pain between them.Where to place the tourniquet during foot and ankle surgery to cause the least possible postoperative pain to the patient as a result of the tourniquet is a common question in clinical practice.The reality is that,unfortunately,there is no consensus on this issue.Perhaps the only possible way to answer this question would be to conduct a comparative study with sufficient statistical power to reach scientifically sound conclusions.It does not seem easy to carry out such a study,but it would be important to be able to answer the question posed in the title of this Editorial once and for all.

Use of induced pluripotent stem cell-derived brain cells,organoids,assembloids,and blood-brain barrier models in understanding alcohol and anesthetic-induced brain injuries:an emerging perspective

Neurological disorders,including developmental disorders,Alzheimer’s disease(AD),and psychiatric conditions,have significant social and economic impacts globally.Despite extensive research into the underlying mechanisms of these disorders,effective treatments remain elusive,partly due to the complexity of the brain,the limited availability of human brain tissue,and the blood-brain barrier(BBB)’s impermeability to certain drugs.This perspective article discusses the potential of human induced pluripotent stem cell(iPSC)-based models of brain cells,organoids,assembloids,and BBB to advance our understanding of the etiology,progression,and mechanisms of brain injuries induced by alcohol consumption and general anesthesia.These models could also be used to develop protective and therapeutic approaches.

Bone marrow edema in a postpartum female following ankle sprain: a case report

Bone marrow edema(BME)is characterized by an accumulation of interstitial fluid within the bone marrow,the cancellous,hematopoietic compartment within bones.[1]BME is divided into two principal categories:idiopathic or primary BME,with an unknown etiology,and secondary BME,which occurs as a result of an identifiable underlying pathology.[2]Although the prevalence of BME is not limited to specific demographic parameters,it shows a predilection for males or individuals assigned male at birth,predominantly aged between the ages of 30 and 60 years,especially in cases of bone marrow edema syndrome(BMES),a rare idiopathic variant.[3]The etiological spectrum of BME is diverse,including oncological entities(such as acute myeloid leukemia and osteosarcoma),degenerative diseases(such as osteoarthritis),infectious processes(osteomyelitis),ischemic conditions(avascular necrosis),metabolic dysfunctions(osteoporosis),inflammatory disorders(rheumatoid arthritis),and traumatic injuries(such as stress fractures).[1,2]Clinically,BME primarily manifests as localized pain,often accompanied by joint effusion and warmth near the affected joint.Diagnostic protocols typically include physical examination,serological assays,bone marrow biopsies,dual-energy X-ray absorptiometry(DEXA)scans,magnetic resonance imaging(MRI),and ultrasonography,with computed tomography(CT)scans and radiographs being less effective.

The Role of Age as a Risk Factor for Pickleball-Related Injuries

Pickleball is a popular sport that includes players from many different demographics. The popularity has resulted in not only increases in participation but also in activity related injuries. The purpose of this study was to identify risk factors along with potential mechanisms for injuries related to pickleball and identify effective countermeasures. Methods included the identification of pickleball related injuries from a US National Emergency Room database (NEISS). A narrative section of the database was used to identify and categorize potential mechanisms of injury. Results indicated that the types and mechanisms of injury relate to three specific age groups: younger, middle age, and older players. Injuries to younger players under the age of 26 are likely the result of misuse of sport equipment. Middle aged players from 26 to 50 sustained injuries more related activity overuse. However, there were more concerns with players over 50 years of age with a great percentage resulting in cardia arrest or symptoms leading to more severe cardiovascular conditions. While pickleball activity should be encouraged as it is a beneficial form of physical activity, there should be specific age-group interventions to reduce injury. It should be highly recommended that doctors approve the activity for individual at risk for heart conditions and supervision for adults in that age group.