Investigating the relationships between motor skills, cognitive status, and area deprivation index in Arizona: a pilot study.

Introduction: Previous studies highlight the negative impact of adverse socioeconomic conditions throughout life on motor skills and cognitive health. Factors such as cognitive activity, physical activity, lifestyle, and socioeconomic position significantly affect general health status and brain health. This pilot study investigates the relationships among the Area Deprivation Index (ADI)-a measure of neighborhood-level socioeconomic deprivation, brain structure (cortical volume and thickness), and cognitive status in adults in Arizona. Identifying measures sensitive to ADI could elucidate mechanisms driving cognitive decline. Methods: The study included 22 adults(mean age = 56.2 ± 15.2) in Arizona, residing in the area for over 10 years(mean = 42.7 ± 15.8). We assessed specific cognitive domains using the NeuroTrax™ cognitive screening test, which evaluates memory, executive function, visual-spatial processing, attention, information processing speed, and motor function. We also measured cortical thickness and volume in 10 cortical regions using FreeSurfer 7.2. Linear regression tests were conducted to examine the relationships between ADI metrics, cognitive status, and brain health measures. Results: Results indicated a significant inverse relationship between ADI metrics and memory scores, explaining 25% of the variance. Both national and state ADI metrics negatively correlated with motor skills and global cognition (r's < -0.40, p's < 0.05). In contrast, ADI metrics generally positively correlated with motor-related volumetric and cortical thickness measures (r's > 0.40, p's < 0.05). Conclusion: The findings suggest that neighborhood-level social deprivation might influence memory and motor status, primarily through its impact on motor brain health.

Awareness of embodiment enhances enjoyment and engages sensorimotor cortices.

Whether in performing arts, sporting, or everyday contexts, when we watch others move, we tend to enjoy bodies moving in synchrony. Our enjoyment of body movements is further enhanced by our own prior experience with performing those movements, or our 'embodied experience'. The relationships between movement synchrony and enjoyment, as well as embodied experience and movement enjoyment, are well known. The interaction between enjoyment of movements, synchrony, and embodiment is less well understood, and may be central for developing new approaches for enriching social interaction. To examine the interplay between movement enjoyment, synchrony, and embodiment, we asked participants to copy another person's movements as accurately as possible, thereby gaining embodied experience of movement sequences. Participants then viewed other dyads performing the same or different sequences synchronously, and we assessed participants' recognition of having performed these sequences, as well as their enjoyment of each movement sequence. We used functional near-infrared spectroscopy to measure cortical activation over frontotemporal sensorimotor regions while participants performed and viewed movements. We found that enjoyment was greatest when participants had mirrored the sequence and recognised it, suggesting that awareness of embodiment may be central to enjoyment of synchronous movements. Exploratory analyses of relationships between cortical activation and enjoyment and recognition implicated the sensorimotor cortices, which subserve action observation and aesthetic processing. These findings hold implications for clinical research and therapies seeking to foster successful social interaction.

Upper motor neuron-predominant motor neuron disease presenting as atypical parkinsonism: A clinicopathological study.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN-dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN-predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN-predominant MND. We reviewed 24 patients with UMN-predominant MND with TDP-43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically-confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically-confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN-predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN-predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN-predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN-predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met.

New opportunities for antioxidants in amelioration of neurodegenerative diseases.

This comprehensive review elucidates the critical role of antioxidants to mitigate oxidative stress, a common denominator in an array of neurodegenerative disorders. Oxidative stress-induced damage has been linked to the development of diseases such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. This article examines a wide range of scientific literature and methodically delineates the several methods by which antioxidants exercise their neuroprotective benefits. It also explores into the complex relationship between oxidative stress and neuroinflammation, focusing on how antioxidants can alter signaling pathways and transcription factors to slow neurodegenerative processes. Key antioxidants, such as vitamins C and E, glutathione, and polyphenolic compounds, are tested for their ability to combat reactive oxygen and nitrogen species. The dual character of antioxidants, which operate as both direct free radical scavengers and regulators of cellular redox homeostasis, is investigated in terms of therapeutic potential. Furthermore, the study focuses on new antioxidant-based therapy techniques and their mechanisms including Nrf-2, PCG1α, Thioredoxin etc., which range from dietary interventions to targeted antioxidant molecules. Insights into ongoing clinical studies evaluating antioxidant therapies in neurodegenerative illnesses offer an insight into the translational potential of antioxidant research. Finally, this review summarizes our present understanding of antioxidant processes in neurodegenerative illnesses, providing important possibilities for future study and treatment development.

Transmembrane protein TMEM230, regulator of metalloproteins and motor proteins in gliomas and gliosis.

Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.

Single-cell transcriptomic analysis to identify endomembrane regulation of metalloproteins and motor proteins in autoimmunity.

TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.

Long-term culture of patient-derived mammary organoids in non-biogenic electrospun scaffolds for identifying metalloprotein and motor protein activities in aging and senescence.

We recently identified TMEM230 as a master regulator of the endomembrane system of cells. TMEM230 expression is necessary for promoting motor protein dependent intracellular trafficking of metalloproteins for cellular energy production in mitochondria. TMEM230 is also required for transport and secretion of metalloproteinases for autophagy and phagosome dependent clearance of misfolded proteins, defective RNAs and damaged cells, activities that decline with aging. This suggests that aberrant levels of TMEM230 may contribute to aging and regain of proper levels may have therapeutic applications. The components of the endomembrane system include the Golgi complex, other membrane bound organelles, and secreted vesicles and factors. Secreted cellular components modulate immune response and tissue regeneration in aging. Upregulation of intracellular packaging, trafficking and secretion of endosome components while necessary for tissue homeostasis and normal wound healing, also promote secretion of pro-inflammatory and pro-senescence factors. We recently determined that TMEM230 is co-regulated with trafficked cargo of the endomembrane system, including lysosome factors such as RNASET2. Normal tissue regeneration (in aging), repair (following injury) and aberrant destructive tissue remodeling (in cancer or autoimmunity) likely are regulated by TMEM230 activities of the endomembrane system, mitochondria and autophagosomes. The role of TMEM230 in aging is supported by its ability to regulate the pro-inflammatory secretome and senescence-associated secretory phenotype in tissue cells of patients with advanced age and chronic disease. Identifying secreted factors regulated by TMEM230 in young patients and patients of advanced age will facilitate identification of aging associated targets that aberrantly promote, inhibit or reverse aging. Ex situ culture of patient derived cells for identifying secreted factors in tissue regeneration and aging provides opportunities in developing therapeutic and personalized medicine strategies. Identification and validation of human secreted factors in tissue regeneration requires long-term stabile scaffold culture conditions that are different from those previously reported for cell lines used as cell models for aging. We describe a 3 dimensional (3D) platform utilizing non-biogenic and non-labile poly ε-caprolactone scaffolds that supports maintenance of long-term continuous cultures of human stem cells, in vitro generated 3D organoids and patient derived tissue. Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

Motor proteins, spermatogenesis and testis function.

The role of motor proteins in supporting intracellular transports of vesicles and organelles in mammalian cells has been known for decades. On the other hand, the function of motor proteins that support spermatogenesis is also well established since the deletion of motor protein genes leads to subfertility and/or infertility. Furthermore, mutations and genetic variations of motor protein genes affect fertility in men, but also a wide range of developmental defects in humans including multiple organs besides the testis. In this review, we seek to provide a summary of microtubule and actin-dependent motor proteins based on earlier and recent findings in the field. Since these two cytoskeletons are polarized structures, different motor proteins are being used to transport cargoes to different ends of these cytoskeletons. However, their involvement in germ cell transport across the blood-testis barrier (BTB) and the epithelium of the seminiferous tubules remains relatively unknown. It is based on recent findings in the field, we have provided a hypothetical model by which motor proteins are being used to support germ cell transport across the BTB and the seminiferous epithelium during the epithelial cycle of spermatogenesis. In our discussion, we have highlighted the areas of research that deserve attention to bridge the gap of research in relating the function of motor proteins to spermatogenesis.

A model of microtubule depolymerization by kinesin-8 motor proteins.

The dimeric kinesin-8 motors have the biological function of depolymerizing microtubules (MTs) from the plus end. However, the molecular mechanism of the depolymerization promoted by the kinesin-8 motors is still undetermined. Here, a model is proposed for the MT depolymerization by the kinesin-8 motors. Based on the model, the dynamics of depolymerization in the presence of the single motor at the MT plus end under no load and under load on the motor is studied theoretically. The dynamics of depolymerization in the presence of multiple motors at the MT plus end is also analyzed. The theoretical results explain well the available experimental data. The studies can also be applicable to other families of kinesin motors such as kinesin-13 mitotic centromere-associated kinesin motors that have the ability to depolymerize MTs.

Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Sensing, feeling and regulating: investigating the association of focal brain damage with voluntary respiratory and motor control.

Breathing is a complex, vital function that can be modulated to influence physical and mental well-being. However, the role of cortical and subcortical brain regions in voluntary control of human respiration is underexplored. Here we investigated the influence of damage to human frontal, temporal or limbic regions on the sensation and regulation of breathing patterns. Participants performed a respiratory regulation task across regular and irregular frequencies ranging from 6 to 60 breaths per minute (bpm), with a counterbalanced hand motor control task. Interoceptive and affective states induced by each condition were assessed via questionnaire, and autonomic signals were indexed via skin conductance. Participants with focal lesions to the bilateral frontal lobe, right insula/basal ganglia and left medial temporal lobe showed reduced performance relative to individually matched healthy comparisons during the breathing and motor tasks. They also reported significantly higher anxiety during the 60 bpm regular and irregular breathing trials, with anxiety correlating with difficulty in rapid breathing specifically within this group. This study demonstrates that damage to frontal, temporal or limbic regions is associated with abnormal voluntary respiratory and motor regulation and tachypnoea-related anxiety, highlighting the role of the forebrain in affective and motor responses during breathing. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Effects of structured and unstructured interventions on fundamental motor skills in preschool children: a meta-analysis.

Background: It has been suggested that higher levels of fundamental motor skills (FMS) promote the physical health of preschool-aged children. The impacts of structured and unstructured interventions on FMS in children aged 10-16 years have been widely acknowledged in previous studies. However, there is a lack of relevant studies in preschool-aged children. Objective: This meta-analysis aimed to compare the effects of structured and unstructured interventions on FMS in preschool-aged children. Methods: The PubMed, Web of Science, and Google Scholar databases were searched from inception to 1 November 2023 to identify experiments describing structured and unstructured interventions for FMS in preschool-aged children. The Downs and Black Checklist was used to assess the risk of bias. A random effects model was used for the meta-analysis to evaluate the pooled effects of interventions on FMS. Subgroup analyses based on the duration and characteristics of the intervention were conducted to identify sources of heterogeneity. Results: A total of 23 studies with 4,068 participants were included. There were 12 studies examining structured interventions, 9 studies examining unstructured interventions, and 6 studies comparing structured vs. unstructured interventions. The risk of bias in the included studies was generally low. All interventions significantly improved FMS in preschool-aged children compared to control treatments (p < 0.05). Structured interventions had more significant effects on locomotor skills (LMSs) in preschool-aged children than unstructured interventions (Hedges' g = 0.44, p = 0.04). The effects of structured interventions were strongly influenced by the total intervention duration, such that long-term interventions were more effective (Hedge's g = 1.29, p < 0.001). Conclusion: Structured interventions play a crucial role in enhancing FMS among young children, especially when considering LMSs. These interventions require consistent and repeated practice over time to reach proficiency. Systematic review registration: PROSPERO, identifier number CRD42023475088, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023475088.

Do the effects last? A comparison between internal and external focus of attention instructions on golf putting accuracy over multiple days.

Background: The role of attentional focus is a well-explored topic in exercise sciences. Studies generally indicate that external focus (EF) enhances motor performance and learning compared with internal focus (IF). However, most studies only included one or two experimental days which limits participants' exposure to the focus conditions. This raises the question of whether the superiority of EF varies over time. Methods: Accordingly, in this pre-registered within-subject study, we examined the effects of focus instructions on golf-putting performance over four days, with 48-72 h between them. On each day, participants performed 15 putts under three instructional conditions: (1) EF, (2) IF, and (3) control, in a randomized and counterbalanced order. Results: We observed trivial differences in performance between conditions but considerable improvements from day 1 to day 4. When using an exploratory analysis, we found that participants performed better under EF and control conditions compared with the IF condition on day 1, but not on subsequent days. Conclusions: Since IF instructions are more commonly used in practice, we speculate that the two other focus conditions were experienced as more novel, potentially accounting for their superiority on Day 1. Nevertheless, our results question the significance of employing EF to enhance performance.

Fast resolution of mild midvetricular takotsubo syndrome triggered by blunt chest trauma: case study.

Blunt chest trauma (BCT) may rarely trigger stress-induced takotsubo syndrome (TTS) which requires dif f erential diagnosis with myocardial contusion and BCT-induced myocardial infarction. So far reported cases have been presented as apical ballooning or inverted (reverse) TTS forms but not as a midventricular variant. The authors described a case of a 53-year-old female admitted to Intensive Care Unit after motor vehicle accident with BCT and airbag deployment during car roll over. For some time after the accident, she was trapped in a car with her head bent to the chest. After being pulled out from the car, she had impaired consciousness and therefore was intubated by the rescue team. Trauma computed tomography scan did not reveal any injuries. However, ECG showed ST-segment depression in II, III, aVF, V4-6, and discrete ST-segment elevation in aVR. Troponin I and NTpro-BNP increased to 2062 ng/l and 6413 pg/ml, respectively. Echocardiography revealed mild midventricular dysfunction of the left ventricle with ejection fraction (EF) and global longitudinal strain (GLS) reduced to 45% and -17.6%, respectively. On day two, the patient's general condition improved and stabilized, so she was extubated. Normalization of ECG, EF and GLS (but not regional LS) was observed on day three. She was discharged home on day fi ve. Post-hospital examinations documented that segmental longitudinal strain remained abnormal for up to 4 weeks. The authors conclude that fast ECG and echocardiographic evolution may result in underestimation of the posttraumatic TTS diagnosis, especially if it takes atypical form and its course is mild. Longitudinal strain evaluation can be helpful in cardiac monitoring of trauma patients.

Reliability of the Test of Gross Motor Development Third Edition Among Children with Developmental Coordination Disorder.

AIM: The Test of Gross Motor Development Third Edition (TGMD-3) is used to assess the development of fundamental movement skills in children from 3 to 10 years old. This study aimed to evaluate the intra-rater, inter-rater, and test-retest reliability and to determine the minimal detectable change (MDC) value of the TGMD-3 in children with developmental coordination disorder (DCD). METHODS: The TGMD-3 was administered to 20 children with DCD. The child's fundamental movement skills were recorded using a digital video camera. Reliability was assessed at two occasions by three raters using the generalizability theory. RESULTS: The TGMD-3 demonstrates good inter-rater reliability for the locomotor skills subscale, the ball skills subscale, and the total score (φ = 0.77 - 0.91), while the intra-rater reliability was even higher (φ = 0.94 - 0.97). Test-retest reliability was also shown to be good (φ = 0.79-0.93). The MDC95 was determined to be 10 points. CONCLUSION: This study provides evidence that the TGMD-3 is a reliable test when used to evaluate fundamental movement skills in children with DCD and suggests that an increase of 10 points represents a significant change in the motor function of a child with DCD.

Explicit Instruction May Impair the Transfer of Motor Adaptation in an Upper Extremity Motor Task.

This study focused on explicit instruction and evaluated the differences in task performance between participants who were instructed to employ the change and those who were not. Ninety-three healthy young adults were assigned to the accurate information group (AG; n = 31), misinformation group (MG; n = 31), and non-information group (NG; n = 31). All participants manipulated a mouse to track a moving target on a screen with a cursor. The cursor was rotated to 60° in the clockwise direction from the actual mouse position during the 1st to 5th blocks (i.e., motor adaptation task). Subsequently, in the 6th block (i.e., transfer task), we gradually changed the angle of rotation from 60° to 80° to prevent from noticing the change. Participants in the AG were instructed accurate experimental information. Participants in the MG were instructed that the angle of rotation was 60° during the 1st to 6th blocks. Participants in the NG were instructed to manipulate the cursor movement only. The results indicated that an average error distance in the AG was significantly lower than that in the NG in the 6th block. This study suggested that explicit instruction may impair the transfer of motor adaptation in this setting.

The effects of reward and punishment on the performance of ping-pong ball bouncing.

Introduction: Reward and punishment modulate behavior. In real-world motor skill learning, reward and punishment have been found to have dissociable effects on optimizing motor skill learning, but the scientific basis for these effects is largely unknown. Methods: In the present study, we investigated the effects of reward and punishment on the performance of real-world motor skill learning. Specifically, three groups of participants were trained and tested on a ping-pong ball bouncing task for three consecutive days. The training and testing sessions were identical across the three days: participants were trained with their right (dominant) hand each day under conditions of either reward, punishment, or a neutral control condition (neither). Before and after the training session, all participants were tested with their right and left hands without any feedback. Results: We found that punishment promoted early learning, while reward promoted late learning. Reward facilitated short-term memory, while punishment impaired long-term memory. Both reward and punishment interfered with long-term memory gains. Interestingly, the effects of reward and punishment transferred to the left hand. Discussion: The results show that reward and punishment have different effects on real-world motor skill learning. The effects change with training and transfer readily to novel contexts. The results suggest that reward and punishment may act on different learning processes and engage different neural mechanisms during real-world motor skill learning. In addition, high-level metacognitive processes may be enabled by the additional reinforcement feedback during real-world motor skill learning. Our findings provide new insights into the mechanisms underlying motor learning, and may have important implications for practical applications such as sports training and motor rehabilitation.

Corrigendum: High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study.

[This corrects the article DOI: 10.3389/fnhum.2023.1286238.].

Peripheral Nerve Stimulation for Treating Acute Pain Following Traumatic Fracture: A Case Report of Rapid-Onset Analgesia Without Motor Blockade.

Analgesia following acute traumatic fracture remains a clinical challenge. Pain relief via peripheral nerve stimulation (PNS) is a promising treatment modality due to its opioid-sparing effects and rapid, reversible sensory blockade without motor blockade. We present the case of a patient who suffered a traumatic tibial plateau fracture. A popliteal sciatic PNS device was placed on postoperative day 1 following inadequate pain control. The patient reported marked pain relief, a significant reduction in morphine milligram equivalent (MME) utilization, and improved early functional recovery. The PNS lead was removed at the patient's 2-month follow-up visit without any adverse events.

Development of a mouse model of chronic ventral spinal cord compression: Neurobehavioral, radiological, and pathological changes.

Objectives: The main objective of this study was to establish a mouse model of spinal ligament ossification to simulate the chronic spinal cord compression observed in patients with ossification of the posterior longitudinal ligament (OPLL). The study also aimed to examine the mice's neurobiological, radiological, and pathological changes. Methods: In the previous study, a genetically modified mouse strain was created using Crispr-Cas9 technology, namely, Enpp1 flox/flox /EIIa-Cre (C57/B6 background), to establish the OPLL model. Wild-type (WT) mice without compression were used as controls. Functional deficits were evaluated through motor score assessment, inclined plate testing, and gait analysis. The extent of compression was determined using CT imaging. Hematoxylin and eosin staining, luxol fast blue staining, TUNEL assay, immunofluorescence staining, qPCR, and Western blotting were performed to evaluate levels of apoptosis, inflammation, vascularization, and demyelination in the study. Results: The results demonstrated a gradual deterioration of compression in the Enpp1 flox/flox /EIIa-Cre mice group as they aged. The progression rate was more rapid between 12 and 20 weeks, followed by a gradual stabilization between 20 and 28 weeks. The scores for spinal cord function and strength, assessed using the Basso Mouse Scale and inclined plate test, showed a significant decline. Gait analysis revealed a noticeable reduction in fore and hind stride lengths, stride width, and toe spread. Chronic spinal cord compression resulted in neuronal damage and activated astrocytes and microglia in the gray matter and anterior horn. Progressive posterior cervical compression impeded blood supply, leading to inflammation and Fas-mediated neuronal apoptosis. The activation of Bcl2 and Caspase 3 was associated with the development of progressive neurological deficits (p < 0.05). Conclusions: The study presents a validated model of chronic spinal cord compression, enabling researchers to explore clinically relevant therapeutic approaches for OPLL.