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21 pages, 6472 KB  
Article
Post-Processing Algorithm for Leg Electrical Impedance Imaging Integrating Boundary Attention Mechanism
by Luwen Zhang and Wu Wang
Sensors 2026, 26(10), 3117; https://doi.org/10.3390/s26103117 - 15 May 2026
Viewed by 344
Abstract
In impedance imaging, the incompatibility and nonlinearity of the inverse problem lead to problems such as blurred boundaries and severe artifacts in the reconstructed images, making it difficult to meet the requirements for precise identification of multi-layer tissue structures in the legs. To [...] Read more.
In impedance imaging, the incompatibility and nonlinearity of the inverse problem lead to problems such as blurred boundaries and severe artifacts in the reconstructed images, making it difficult to meet the requirements for precise identification of multi-layer tissue structures in the legs. To this end, this paper proposes a post-processing algorithm for leg EIT that integrates the boundary attention mechanism, with a Wasserstein generative adversarial network as the training framework, cyclic residual U-Net as the generator, and the boundary attention module embedded in the RecurrentBlock. This leads to adaptive enhancement of the ability to extract organizational boundary features through a three-path fusion of spatial attention, channel attention, and learnable Laplacian edge enhancement. A leg anatomy prior constraint loss function was designed, integrating six constraints—pixel loss, edge loss, hierarchical tissue constraint, total variation regularization, structural similarity loss, and histogram matching—to guide the reconstruction results to conform to the multi-layered tissue structure features of the leg. A simulation dataset of leg sections containing multiple tissues such as skin, fat, muscle, bone, blood vessels, and nerves was constructed, and the pre-reconstructed images were obtained using the hybrid total variation regularization algorithm as the network input. The simulation results show that, under noise-free and different signal-to-noise ratio conditions, the proposed BAM-R2UNet algorithm achieves the best performance in RMSE, SSIM and PSNR metrics compared with HTV, DnCNN and standard U-Net algorithms, can remove artifacts, accurately restore the boundary and conductivity distribution of leg tissues, and has stronger anti-noise robustness. Full article
(This article belongs to the Section Biomedical Sensors)
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18 pages, 2078 KB  
Article
Histological and Immunohistochemical Characterization of the Tibial ACL Remnant: Implications for Ligament Healing
by Sorin Florescu, Blidişel Iulian Alexandru, George Andrei Drăghici, Dragoş Vasile Nica, Boru Casiana and Cosmin Grațian Damian
Medicina 2026, 62(2), 407; https://doi.org/10.3390/medicina62020407 - 20 Feb 2026
Viewed by 936
Abstract
Background and Objectives: The pathways mediating the beneficial effect of tibial stump preservation for anterior cruciate ligament (ACL) reconstruction remain insufficiently clarified. This study investigated key vascular, neural, and stromal aspects of cellular remodeling processes occurring across lesion stages in tibial remnant [...] Read more.
Background and Objectives: The pathways mediating the beneficial effect of tibial stump preservation for anterior cruciate ligament (ACL) reconstruction remain insufficiently clarified. This study investigated key vascular, neural, and stromal aspects of cellular remodeling processes occurring across lesion stages in tibial remnant pre-reconstruction. Materials and Methods: Biopsies were obtained from 25 patients undergoing arthroscopic ACL reconstruction (paired free-end and tibial insertion sampling) and 10 from quasi-normal, macroscopically intact ligaments (controls). We evaluated intergroup differences in microvascular density using a t-test. Group comparisons for angiogenesis (CD34), neural components (S100, neurofilament-associated proteins—NFAPs), and stromal activation (vimentin and actin) were conducted using Chi-square or Fisher’s exact tests. Results: ACL remnants revealed a significantly higher microvascular density (37 ± 2.3 vs. 18 ± 3.2 vessels/mm2, p < 0.001), in addition to a markedly increased prevalence of synovial angiogenesis (90% vs. 20%, p < 0.001), stellate stromal cells (94% vs. 10%, p < 0.001), and CD34-positive fibrocytes (92% vs. 10%, p < 0.001) compared to control tissues. Elevated intraligamentous neovascularization (with borderline significance) was also found in these tissues (38% vs. 0%, p = 0.045). Both injured and control ACLs showed widespread S100-positive neural fibers, suggesting maintained Schwann cell integrity despite ligament disruption. In contrast, control ligaments showed a substantially richer NFAP+ neural network, particularly in small-caliber fibers and free nerve endings, pointing to preferential vulnerability of small-caliber neural elements during ACL rupture. Vimentin expression changes—from homogeneous fibrocytic staining to diffuse reticular overexpression in fibrotic lesions—were accompanied by the emergence of stellate myofibroblast-like cells, supporting advanced stromal remodeling. Absent in controls, actin immunoreactivity increased with lesion severity, indicating a progressive myofibroblastic response driven by perivascular cells during ligament remodeling. Conclusions: The tibial ACL remnant is a biologically active, compartmentalized repair niche driven by coordinated vascular, neural, and stromal responses, with reparative activity concentrated at the synovial–epiligament interface. These findings support the biological rationale for preserving tibial remnant for ACL reconstruction. Full article
(This article belongs to the Section Orthopedics)
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21 pages, 2335 KB  
Article
Experimental Validation of a Battery-Free RFID-Powered Implantable Neural Sensor and Stimulator
by Luís Eduardo Pedigoni Bulisani, Marco Antonio Herculano, Carolina Chen Pauris, Luma Rissatti Borges do Prado, Lucas Jun Sakai, Francisco Martins Portelinha Júnior and Evaldo Marchi
Sensors 2026, 26(3), 954; https://doi.org/10.3390/s26030954 - 2 Feb 2026
Viewed by 667
Abstract
Introduction: Neurological injuries significantly impair quality of life by disrupting neural transmission. Traditional implantable stimulators often rely on internal batteries, which limit device longevity and necessitate repeated surgical interventions. Objective: This study presents the experimental validation of a battery-free, RFID-powered neural platform for [...] Read more.
Introduction: Neurological injuries significantly impair quality of life by disrupting neural transmission. Traditional implantable stimulators often rely on internal batteries, which limit device longevity and necessitate repeated surgical interventions. Objective: This study presents the experimental validation of a battery-free, RFID-powered neural platform for peripheral nerve signal acquisition and stimulation, targeting TRL-6 validation. Methods: The prototype incorporates an adjustable analog front-end with gains up to 93 dB and a biphasic current-controlled stimulator. Validation was performed through benchtop testing, biological tissue assessments using porcine tissue, and functional in vivo trials in adult Wistar rats (n = 3) over a three-month period. Results: Benchtop evaluation confirmed gain accuracy with errors below 2.2 dB and precise stimulation timing. The system maintained a stable 3.3 V wireless power link through 20 mm of biological tissue using RFID. In vivo experiments indicated a 100% functional success rate (51/51 trials) in eliciting gross motor responses via wireless stimulation. Thermal safety was confirmed, with a maximum operating temperature of 28 °C, remaining well below physiological limits. Conclusions: The results demonstrate the functional feasibility of a battery-free, RFID-powered neural interface for wireless signal acquisition and stimulation, supporting system-level validation of this architecture. Full article
(This article belongs to the Special Issue Sensing Technologies in Neuroscience and Brain Research)
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16 pages, 805 KB  
Article
Neck Management in Malignant Parotid Tumors: A Retrospective Analysis of Elective Neck Dissection Indications and Outcomes
by Andrea Battisti, Giulio Pagnani, Giulia Scivoletto, Marco Della Monaca, Matteo Fatiga, Andrea Cassoni and Valentino Valentini
Diagnostics 2025, 15(24), 3194; https://doi.org/10.3390/diagnostics15243194 - 14 Dec 2025
Viewed by 803
Abstract
Background/Objectives: Management of the clinically negative neck in malignant parotid tumors remains controversial. We aimed to identify clinicopathologic predictors of nodal involvement and to evaluate whether elective neck dissection (END) improves disease-free survival (DFS) versus observation in cN0 patients. Methods: We performed a [...] Read more.
Background/Objectives: Management of the clinically negative neck in malignant parotid tumors remains controversial. We aimed to identify clinicopathologic predictors of nodal involvement and to evaluate whether elective neck dissection (END) improves disease-free survival (DFS) versus observation in cN0 patients. Methods: We performed a retrospective cohort study of adults undergoing surgery for malignant parotid tumors at a single tertiary center (2013–2023) with ≥24 months of follow-up. Collected variables included demographics, tumor T category and histologic grade (AJCC 8th), parotidectomy type, neck management [END vs. therapeutic neck dissection (TND) vs. observation], lymph node yield, and outcomes. Associations were tested with Fisher’s exact tests; disease-free survival (DFS) was analyzed using Kaplan–Meier curves, log-rank tests and an exploratory multivariable Cox proportional hazards model. Results: Seventy-four patients were included (mean age 54.3 years; 12.2% preoperative facial nerve impairment). Parotidectomy was partial (41.9%), total (31.1%), radical (21.6%), or extended (5.4%). Neck dissection was performed in 40.5% (END 23.0%; TND 17.6%). Overall pathologic nodal positivity (pN+) was 18.9%. T3–T4 tumors had greater odds of nodal metastasis than T1–T2 (OR 10.58; p < 0.05). Among cN0 patients, occult metastasis was 17.6%; notably, all high-grade cN0 tumors that underwent END were pN+. Intraparotid nodal metastases occurred in 28.6% and always co-occurred with cervical metastases. DFS did not differ significantly between cN0 patients managed with END versus observation (log-rank p > 0.05). Patients with pN0 had superior DFS versus pN+ (p < 0.05). Lymph node yield groupings (0–17 vs. 18–40 vs. >40) were not associated with recurrences. In the exploratory multivariable Cox model, high/intermediate-grade and T3-T4 tumors and nodal positivity were associated with reduced DFS. Conclusions: Higher T category and high/intermediate grade strongly predict nodal involvement, and pN+ status portends worse DFS. Although END did not show a DFS advantage over observation in cN0 patients, the 17.6% occult metastasis rate—especially in high-grade disease—and the linkage between intraparotid and cervical metastases support a risk-adapted END strategy and intraoperative assessment of intraparotid nodes to guide neck management. Full article
(This article belongs to the Special Issue Diagnosis and Management in Oral and Maxillofacial Surgery)
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9 pages, 538 KB  
Review
What Is Inside the Sinus Tarsi? Mechanoreceptor Distribution, Typing and Clinical Relevance—A Histological and Immunohistochemical Synthesis
by Alberto Arceri, Antonio Mazzotti, Gianmarco Di Paola, Federico Sgubbi, Laura Langone, Simone Ottavio Zielli, Francesca Veronesi, Gianluca Giavaresi, Paolo Mora and Cesare Faldini
Biomedicines 2025, 13(12), 3052; https://doi.org/10.3390/biomedicines13123052 - 11 Dec 2025
Viewed by 693
Abstract
The sinus tarsi, a small osseoligamentous recess of the subtalar joint, contains multiple soft-tissue structures with a complex sensory network. However, the detailed neural architecture and clinical significance of its innervation remain incompletely defined. The aim of this study was to conduct a [...] Read more.
The sinus tarsi, a small osseoligamentous recess of the subtalar joint, contains multiple soft-tissue structures with a complex sensory network. However, the detailed neural architecture and clinical significance of its innervation remain incompletely defined. The aim of this study was to conduct a comprehensive review of histological and immunohistochemical studies on the neural structures of the sinus tarsi. Histological staining and validated immunohistochemical markers (S100, p75, PGP9.5, neurofilament, myelin basic protein) were the methods used in these studies to analyze human sinus tarsi tissue. Across all investigations, free nerve endings predominated, while Ruffini, Pacinian and Golgi-like corpuscles were variably identified, mainly near ligament insertions. The sinus tarsi exhibits a dense and heterogeneous neural network that likely contributes to both pain perception and sensorimotor control. Further standardized and quantitative research is warranted to clarify the neurofunctional role of this region. Full article
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26 pages, 1682 KB  
Review
Surgical Outcomes in Non-Transected and Partially Transected Peripheral Nerve Injuries
by Naveen Arunachalam Sakthiyendran, Karter Morris, Caroline J. Cushman, Evan J. Hernandez, Anceslo Idicula and Brendan J. MacKay
Brain Sci. 2025, 15(11), 1202; https://doi.org/10.3390/brainsci15111202 - 7 Nov 2025
Viewed by 2836
Abstract
Background: Non-transected and partially transected peripheral nerve injuries (neuromas-in-continuity) are relatively common but understudied. Their optimal surgical management and expected outcomes remain unclear. We conducted a literature review of surgical repairs in such lesions and illustrate a case to guide decision-making. Systematic searches [...] Read more.
Background: Non-transected and partially transected peripheral nerve injuries (neuromas-in-continuity) are relatively common but understudied. Their optimal surgical management and expected outcomes remain unclear. We conducted a literature review of surgical repairs in such lesions and illustrate a case to guide decision-making. Systematic searches of PubMed and Google Scholar identified 70 eligible reports (Level I = 2, Level II = 5, Level III = 37, Level IV = 20, Level V = 4). Across studies, neurolysis of NAP-positive lesions often restored antigravity strength, while direct repair or grafting of nonconductive segments yielded meaningful recovery in ~75%. After neurolysis or reconstruction, ~77–92% of brachial plexus/axillary neuromas-in-continuity reached LSUHSC Grade ≥3. Median/ulnar lesions treated with neurolysis, biologic/vascularized coverage, or reconstruction showed reliable pain relief but variable sensory/motor recovery. Radial/PIN lesions improved in some series irrespective of NAPs. Earlier intervention, shorter gaps, distal sites, and younger age correlated with superior outcomes. Meanwhile, prolonged observation risking end-organ atrophy degraded results. Adjuncts such as electrical stimulation and wraps may aid reinnervation or reduce scarring, though high-quality evidence is limited. Conclusions: For non-transected and partially transected PNIs, a pragmatic approach emerges: Observe low-grade injuries with serial examinations. Explore early if recovery stalls (≈3–6 months). Use NAP-guided neurolysis for conductive lesions. Perform tension-free repair or grafting for nonconductive segments, adding anti-adhesive coverage when appropriate. Standardized reporting and prospective trials are needed to refine timing, technique selection, and patient-reported outcomes. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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17 pages, 8134 KB  
Article
Chronic Low Back Pain in Young Adults: Pathophysiological Aspects of Neuroinflammation and Degeneration
by Natalya G. Pravdyuk, Anastasiia A. Buianova, Anna V. Novikova, Alesya A. Klimenko, Mikhail A. Ignatyuk, Liubov A. Malykhina, Olga I. Patsap, Dmitrii A. Atiakshin, Vitaliy T. Timofeev and Nadezhda A. Shostak
Int. J. Mol. Sci. 2025, 26(15), 7592; https://doi.org/10.3390/ijms26157592 - 6 Aug 2025
Cited by 1 | Viewed by 3359
Abstract
Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] [...] Read more.
Degenerative disc disease (DDD) is a major cause of chronic low back pain (LBP), yet the molecular mechanisms driving disc degeneration and pain remain poorly understood. This study analyzed intervertebral disc (IVD) tissue from 36 young patients (median age = 36.00 [31.00, 42.50] years) with herniated discs and LBP, alongside healthy controls, to investigate changes in the extracellular matrix (ECM) and neurochemical alterations. Disc degeneration was assessed using MRI (Pfirrmann grading) and histology (Sive’s criteria). Histochemical and immunohistochemical methods were used to evaluate aggrecan content, calcification, and the expression of nerve growth factor (NGF), substance P (SP), and S-100 protein. MRI findings included Pfirrmann grades V (30.55%), IV (61.11%), III (5.56%), and II (2.78%). Severe histological degeneration (10–12 points) was observed in three patients. Aggrecan depletion correlated with longer pain duration (r = 0.449, p = 0.031). NGF expression was significantly elevated in degenerated discs (p = 0.0287) and strongly correlated with SP (r = 0.785, p = 5.268 × 10−9). Free nerve endings were identified in 5 cases. ECM calcification, present in 36.1% of patients, was significantly associated with radiculopathy (r = 0.664, p = 0.005). The observed co-localization of NGF and SP suggests a synergistic role in pain development. These results indicate that in young individuals, aggrecan loss, neurochemical imbalance, and ECM calcification are key contributors to DDD and chronic LBP. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Intervertebral Disc Disease)
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16 pages, 1505 KB  
Systematic Review
Association Between Oral Dysbiosis and Alzheimer’s Disease: A Systematic Review
by Valeria Martínez-Martínez, Francisco Javier Rodríguez-Lozano, María Pilar Pecci-Lloret and Nuria Pérez-Guzmán
J. Clin. Med. 2025, 14(10), 3415; https://doi.org/10.3390/jcm14103415 - 13 May 2025
Cited by 8 | Viewed by 2722
Abstract
Objective: The main objective of this systematic review is to select and critically synthesize the available evidence from studies that aimed to verify whether there is a relationship between dysbiosis of the oral cavity and the development of Alzheimer’s disease. Methodology: [...] Read more.
Objective: The main objective of this systematic review is to select and critically synthesize the available evidence from studies that aimed to verify whether there is a relationship between dysbiosis of the oral cavity and the development of Alzheimer’s disease. Methodology: A search was conducted on 30 November 2024 and updated on 9 January 2025, in the PubMed, SciELO Scopus, and Web of Science databases, limiting the search to the last 5 years. The review was carried out under the criteria of the PRISMA 2020 guide for systematic reviews and has been accepted into the PROSPERO registry (CRD42025636275). We analyzed the risk of bias of studies using the JBI guidelines. Results: Initially, 2009 articles were obtained. After eliminating duplicates, we obtained 1716; of these, following the inclusion and exclusion criteria, 185 articles were reviewed by title and abstract, discarding 171. Of the remaining 14 articles, 12 final articles were selected. In the results obtained, it has been observed that there is a relationship between inflammation derived from oral dysbiosis caused by periodontal disease and its extension to the neuronal tissue via the hematogenous blood–brain barrier (BBB) and nerve (V pair). Among the most frequently found oral microbiota are Veillonella, Fusobacteria, Prevotella, Porphyromonas, Lactobacillus, and Streptococcus. Conclusions: Oral dysbiosis gives rise to the establishment of inflammatory processes that lead to neurological degeneration, either through its passage across the blood–brain barrier or by a direct connection between the free nerve endings of the periodontium and the proprioceptors found in the central nervous system. Therefore, the chronic inflammation caused by oral dysbiosis and its role in systemic inflammation could be associated with the onset and progression of Alzheimer’s disease (AD); however, more studies are needed to show the association between oral dysbiosis and Alzheimer’s disease. Full article
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9 pages, 5234 KB  
Brief Report
Immunohistochemical Detection of Tentonin-3/TMEM150C in Human Dorsal Root Ganglion, Cutaneous End-Organ Complexes, and Muscle Spindles
by Iván Suazo, Yolanda García-Mesa, José Martín-Cruces, Patricia Cuendias, Teresa Cobo, Olivia García-Suárez and José A. Vega
Brain Sci. 2025, 15(4), 337; https://doi.org/10.3390/brainsci15040337 - 24 Mar 2025
Cited by 1 | Viewed by 1041
Abstract
Background/Objectives: Tentonin-3/TMEM150C is a pore-forming protein of a mechanically activated channel recently identified that typically displays rapid activation followed by slow inactivation. It has been detected in murine dorsal root ganglia, nodose ganglion baroreceptors, and muscle spindles. Nevertheless, primary sensory neurons expressing tentonin-3/TMEM150C [...] Read more.
Background/Objectives: Tentonin-3/TMEM150C is a pore-forming protein of a mechanically activated channel recently identified that typically displays rapid activation followed by slow inactivation. It has been detected in murine dorsal root ganglia, nodose ganglion baroreceptors, and muscle spindles. Nevertheless, primary sensory neurons expressing tentonin-3/TMEM150C fall into the categories of nociceptors, mechanoreceptors, and proprioceptors. Methods: We used immunohistochemistry and image analysis (examining the size of the neuronal bodies in the dorsal root ganglia) to investigate the distribution of tentonin-3/TMEM150C in human cervical dorsal root ganglia, sensory nerve formations in the glabrous skin, especially cutaneous end-organ complexes or sensory corpuscles, and muscle spindles. Results: In dorsal root ganglia, 41% of neurons were tentonin-3/TMEM150C-positive, with a distribution of small (12.0%), intermediate (18.1%), and large (10.9%). In the glabrous skin, tentonin-3/TMEM150C was observed in the axon of Meissner, Pacinian, and Ruffini corpuscles as well as in the axon of the Merkel cell–axon complexes. Furthermore, tentonin-3/TMEM150C-positive axons were observed in muscle spindles. No free nerve endings displaying immunoreactivity were found. Conclusions: This is the first report on the distribution of tentonin-3/TMEM150C immunoreactivity in the human peripheral somatosensory system, and although it is a brief preliminary study, it opens new perspectives for the study of this new mechano-gated ion channel. Full article
(This article belongs to the Section Neurosurgery and Neuroanatomy)
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16 pages, 4723 KB  
Review
An Emerging Perspective on the Role of Fascia in Complex Regional Pain Syndrome: A Narrative Review
by Carmelo Pirri, Nina Pirri, Lucia Petrelli, Caterina Fede, Raffaele De Caro and Carla Stecco
Int. J. Mol. Sci. 2025, 26(6), 2826; https://doi.org/10.3390/ijms26062826 - 20 Mar 2025
Cited by 12 | Viewed by 12793
Abstract
Complex Regional Pain Syndrome (CRPS) is a debilitating pain disorder involving chronic inflammation, neural sensitization and autonomic dysfunction. Fascia, a highly innervated connective tissue, is increasingly recognized for its role in pain modulation, yet its contribution to CRPS remains underexplored. This narrative review [...] Read more.
Complex Regional Pain Syndrome (CRPS) is a debilitating pain disorder involving chronic inflammation, neural sensitization and autonomic dysfunction. Fascia, a highly innervated connective tissue, is increasingly recognized for its role in pain modulation, yet its contribution to CRPS remains underexplored. This narrative review synthesizes the current evidence on fascia’s involvement in CRPS pathophysiology and potential therapeutic strategies. A literature search was conducted in PubMed, Scopus and Web of Science, selecting studies on fascia, CRPS, inflammation, oxidative stress and autonomic dysfunction, with emphasis on recent experimental, anatomical and clinical research. Fascia contributes to CRPS through neuroinflammation, fibrosis and autonomic dysregulation. Its rich innervation facilitates peripheral and central sensitization, while inflammatory mediators drive fibrosis, reducing elasticity and exacerbating pain. Autonomic dysfunction worsens hypoxia and oxidative stress, fueling chronic dysfunction. Advances in sonoelastography provide new insights, while fascial manipulation and targeted therapies show promise in early studies. Fascia plays a key role in CRPS pathophysiology, yet its clinical relevance remains underexplored. Future research integrating imaging, molecular profiling and clinical trials is needed to develop evidence-based fascia-targeted interventions, potentially improving CRPS diagnosis and treatment. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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8 pages, 2180 KB  
Case Report
A Case Report of Median Nerve Entrapment in a Supracondylar Humeral Fracture: Diagnosis, Treatment, and Results After 5 Years of Follow-Up
by Carlo Colonna, Joil Ramazzotti, Francesco Locatelli, Alessandro Crosio and Pierluigi Tos
Reports 2025, 8(1), 23; https://doi.org/10.3390/reports8010023 - 18 Feb 2025
Cited by 1 | Viewed by 3190
Abstract
Background and Clinical Significance: Neurological complications in extension-type-III supracondylar humeral fractures (SCHFs) in children represent 11% of cases. An extension-type-III SCHF with posterolateral displacement of the distal fragment is commonly associated with damage to the median nerve and the anterior interosseous nerve [...] Read more.
Background and Clinical Significance: Neurological complications in extension-type-III supracondylar humeral fractures (SCHFs) in children represent 11% of cases. An extension-type-III SCHF with posterolateral displacement of the distal fragment is commonly associated with damage to the median nerve and the anterior interosseous nerve (AIN). Neurological complications are often unnoticed, and their immediate postoperative diagnosis is difficult, particularly in young children. Neurapraxia, the most common complication, usually undergoes spontaneous nerve recovery. Case Presentation: We report a case of a 7-year-old patient with postoperative median nerve palsy after an SCHF (Gartland type III) who was referred to our unit from another hospital due to a lack of spontaneous recovery. In addition, motor and sensory functions were absent. As ultrasound (US) indicated nerve kinking at the fracture site, an exploration was performed. The nerve was trapped within the fracture and the callus. It was surgically extracted, and intraoperative examination with US indicated that resecting the kinked nerve, freeing the two stumps, and attempting a primary end-to-end suture represented the best course of action. We present this case with a 5-year follow-up surgery, which showed a good clinical outcome. Conclusions: This case is noteworthy because of its diagnostic and therapeutic pathways, and it is complemented by surgical and ultrasound images that can assist other surgeons in similar circumstances. Full article
(This article belongs to the Section Orthopaedics/Rehabilitation/Physical Therapy)
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15 pages, 2241 KB  
Article
NELL2-PAX7 Transcriptional Cascade Suggests Activation Mechanism for RAD52-Dependent Alternative Lengthening of Telomeres During Malignant Transformation of Malignant Peripheral Nerve Sheath Tumors: Elongation of Telomeres and Poor Survival
by Jungwoo Lee, Eunji Choi, Hyoju Kim, Young-Joon Kim and Seung Hyun Kim
Biomedicines 2025, 13(2), 281; https://doi.org/10.3390/biomedicines13020281 - 23 Jan 2025
Cited by 2 | Viewed by 2173
Abstract
Background: In eukaryotes with a double-stranded linear DNA genome, the loss of terminal DNA during replication is inevitable due to an end-replication problem; here, telomeres serve as a buffer against DNA loss. Thus, the activation of the telomere maintenance mechanism (TMM) is [...] Read more.
Background: In eukaryotes with a double-stranded linear DNA genome, the loss of terminal DNA during replication is inevitable due to an end-replication problem; here, telomeres serve as a buffer against DNA loss. Thus, the activation of the telomere maintenance mechanism (TMM) is a prerequisite for malignant transformation. Methods: We compared neurofibroma (NF, benign) and malignant peripheral nerve sheath tumors (MPNSTs) occurring in the same patient with type 1 neurofibromatosis, where each NF–MPNST pair shared the same genetic background and differentiation lineage; this minimizes the genetic bias and contrasts only those changes that are related to malignant transformation. A total of 20 NF–MPNST pairs from 20 NF1 patients were analyzed. Whole-transcriptome sequencing (WTS) was conducted to profile the transcriptional relationship, and whole-genome sequencing (WGS) was performed to measure the telomere length. Results: We identified 22 differentially expressed genes (DEGs) during the malignant transformation of MPNSTs. Among them, NELL2 activated PAX7, which sequentially activated RAD52, the recombinase of RAD52-dependent alternative lengthening of telomeres (ALT). RAD52 elongated MPNSTs–telomeres (p = 0.017). Otherwise, neither NELL2 nor PAX7 affected telomere length (p = 0.647 and p = 0.354, respectively). RAD52 increased MPNSTs–telomeres length, independently of NELL2 and PAX7 in multiple analyses (p = 0.021). The group with increased telomere length during the malignant transformation showed inferior overall survival (OS) (HR = 3.809, p = 0.038) to the group without increased telomere length. Accordingly, the group with increased PAX7 showed inferior OS (HR = 4.896, p = 0.046) and metastasis-free survival (MFS) (HR = 9.129, p = 0.007) in comparison to the group without increased PAX7; the group with increased RAD52 showed inferior MFS (HR = 8.669, p = 0.011) in comparison to the group without increased RAD52. Conclusions: We suggest that the NELL2-PAX7 transcriptional cascade activates RAD52-dependent ALT to increase telomere length during the malignant transformation of MPNSTs, resulting in a poor prognosis. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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16 pages, 1469 KB  
Article
Enteric Nervous System and Its Relationship with Neurological Diseases
by María José Luesma, Liberto López-Marco, Marta Monzón and Sonia Santander
J. Clin. Med. 2024, 13(18), 5579; https://doi.org/10.3390/jcm13185579 - 20 Sep 2024
Cited by 14 | Viewed by 7690
Abstract
The enteric nervous system (ENS) is a fundamental component of the gastrointestinal system, composed of a vast network of neurons and glial cells. It operates autonomously but is interconnected with the central nervous system (CNS) through the vagus nerve. This communication, known as [...] Read more.
The enteric nervous system (ENS) is a fundamental component of the gastrointestinal system, composed of a vast network of neurons and glial cells. It operates autonomously but is interconnected with the central nervous system (CNS) through the vagus nerve. This communication, known as the gut–brain axis, influences the bidirectional communication between the brain and the gut. Background/Objectives: This study aimed to review neurological pathologies related to the ENS. Methods: To this end, a comprehensive literature search was conducted in the “PubMed” database. Articles available in “free format” were selected, applying the filters “Humans” and limiting the search to publications from the last ten years. Results: The ENS has been linked to various neurological diseases, from autism spectrum disorder to Parkinson’s disease including neurological infection with the varicella zoster virus (VZV), even sharing pathologies with the CNS. This finding suggests that the ENS could serve as an early diagnostic marker or therapeutic target for neurological diseases. Gastrointestinal symptoms often precede CNS symptoms, and the ENS’s accessibility aids in diagnosis and treatment. Parkinson’s patients may show intestinal lesions up to twenty years before CNS symptoms, underscoring the potential for early diagnosis. However, challenges include developing standardized diagnostic protocols and the uneven distribution of dopaminergic neurons in the ENS. Continued research is needed to explore the ENS’s potential in improving disease prognosis. Conclusions: The ENS is a promising area for early diagnosis and therapeutic development. Nevertheless, it is essential to continue research in this area, especially to gain a deeper understanding of its organization, function, and regenerative capacity. Full article
(This article belongs to the Section Epidemiology & Public Health)
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19 pages, 9880 KB  
Article
Vitamin B12 Ameliorates Pesticide-Induced Sociability Impairment in Zebrafish (Danio rerio): A Prospective Controlled Intervention Study
by Madalina Andreea Robea, Ovidiu Dumitru Ilie, Mircea Nicusor Nicoara, Gheorghe Solcan, Laura Ecaterina Romila, Dorel Ureche and Alin Ciobica
Animals 2024, 14(3), 405; https://doi.org/10.3390/ani14030405 - 26 Jan 2024
Cited by 8 | Viewed by 3742
Abstract
Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component plays an important part in determining [...] Read more.
Constant exposure to a variety of environmental factors has become increasingly problematic. A variety of illnesses are initiated or aided by the presence of certain perturbing factors. In the case of autism spectrum disorder, the environmental component plays an important part in determining the overall picture. Moreover, the lack of therapies to relieve existing symptoms complicates the fight against this condition. As a result, animal models have been used to make biomedical research easier and more suited for disease investigations. The current study used zebrafish as an animal model to mimic a real-life scenario: acute exposure to an increased dose of pesticides, followed by prospective intervention-based therapy with vitamin B12 (vit. B12). It is known that vit. B12 is involved in brain function nerve tissue, and red blood cell formation. Aside from this, the role of vit. B12 in the redox processes is recognized for its help against free radicals. To investigate the effect of vit. B12, fish were divided into four different groups and exposed to a pesticide mixture (600 μg L−1 fipronil + 600 μg L−1 pyriproxyfen) and 0.24 μg L−1 vit. B12 for 14 days. The impact of the compounds was assessed daily with EthoVision XT 11.5 software for behavioral observations, especially for sociability, quantified by the social interaction test. In addition, at the end of the study, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured. The results showed significant improvements in locomotor activity parameters and a positive influence of the vitamin on sociability. Regarding the state of oxidative stress, high activity was found for SOD and GPx in the case of vit. B12, while fish exposed to the mixture of pesticides and vit. B12 had a lower level of MDA. In conclusion, the study provides new data about the effect of vit. B12 in zebrafish, highlighting the potential use of vitamin supplementation to maintain and support the function of the organism. Full article
(This article belongs to the Special Issue Perspectives in Veterinary Toxicology and Pharmacology)
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10 pages, 4270 KB  
Case Report
Surgical Treatment of Saphenous Nerve Injury Assisted by Plasma Rich in Growth Factors (PRGF): Lessons from a Case Report
by Homid Fahandezh-Saddi Díaz, Antonio Ríos Luna, Manuel Villanueva Martínez, María Elena Cantero Yubero, Roberto Prado, Sabino Padilla and Eduardo Anitua
Clin. Pract. 2023, 13(5), 1090-1099; https://doi.org/10.3390/clinpract13050097 - 6 Sep 2023
Cited by 2 | Viewed by 4915
Abstract
The infrapatellar branch of the saphenous nerve (SN) is a widely described anatomic and functional structure; however, its relevance in daily clinical practice is underestimated. All surgical procedures performed on the anteromedial aspect of the knee are associated with a risk of iatrogenic [...] Read more.
The infrapatellar branch of the saphenous nerve (SN) is a widely described anatomic and functional structure; however, its relevance in daily clinical practice is underestimated. All surgical procedures performed on the anteromedial aspect of the knee are associated with a risk of iatrogenic injury to this nerve, including knee arthroscopy, knee arthroplasty, tibial nailing, etc. We present the case of a saphenous nerve neuroma after treatment with radiofrequency thermal ablation due to a knee pain problem. After conducting an anaesthetic suppression test, we decided to perform a denervation of the medial saphenous nerve in Hunter’s canal. We performed surgery on the anteromedial aspect of the knee. The distal end of the medial SN was coagulated with a bipolar scalpel. The proximal end of the nerve was released proximally, and a termino-lateral suture was made at the free end of the nerve after creating an epineural window to inhibit its growth. A double crush was produced proximally to the suture site to create a grade II-III axonal injury. Autologous plasma rich in growth factors (PRGF) was used to reduce potential post-surgical adhesions and to stimulate regeneration of the surgical lesions. One year after surgery, the patient was living a completely normal life. Full article
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