Ultrasound-responsive microfibers promoted infected wound healing with neuro-vascularization by segmented sonodynamic therapy and electrical stimulation.

Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.

Neuro-Immune Communication at the Core of Craving-Associated Brain Structural Network Reconfiguration in Methamphetamine Users.

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.

Utilization of Remote Patient Monitoring for Neurological Disorders: A Nationwide Analysis of Administrative Claims Data.

Introduction: The use of remote patient monitoring (RPM) services for neurological disorders remains understudied, particularly in the context of newer billing codes introduced before the COVID-19 pandemic. Methods: This retrospective cohort study utilized data from commercial and Medicare employer-sponsored administrative claims between January 1, 2019, to December 31, 2021. The study population included all patients with at least one qualifying RPM-related Current Procedural Terminology (CPT) code for a neurological disorder, separated into first-generation (CPT 99091) codes and second-generation (CPT 99453, 99454, 99457, 99458) code cohorts. We compared patient and encounter characteristics between both cohorts. Results: We identified 27,756 encounters attributable to 11,326 patients who received RPM services for neurological disorders, of whom 5,785 (51.1%) received RPM via second-generation billing codes, 3,941 (34.8%) were female, 6,712 (59.3%) were between 45 and 64 years old, and 10,488 (92.6%) had a primary diagnosis of sleep-wake disorder. The second-generation cohort was significantly more likely to be female (41.5% vs. 27.8%, p < 0.001), be of age 65 or older (15.7% vs. 7.1%, p < 0.001), and reside in urban areas (93.4% vs. 87.6%, p < 0.001) than the first-generation cohort. Patients in the second-generation cohort were more likely to receive RPM in office settings (86.3% vs. 62.5%, p < 0.001), by physicians (77.0% vs. 40.3%, p < 0.001), and less likely for sleep-wake disorders (87.9% vs. 97.5%, p < 0.001) than the first-generation cohort. Patients who received RPM from physicians were most often evaluated by pulmonologists (31.4%). Discussion: In this commercially insured patient population receiving RPM for neurological disorders, we found that sleep-wake disorders and non-neurologists were over-represented.

A review article on the development of dopaminergic neurons and establishment of dopaminergic neuron-based in vitro models by using immortal cell lines or stem cells to study and treat Parkinson's disease.

The primary pathological hallmark of Parkinson's disease (PD) is the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, a critical midbrain region. In vitro models based on DA neurons provide a powerful platform for investigating the cellular and molecular mechanisms of PD and testing novel therapeutic strategies. A deep understanding of DA neuron development, including the signalling pathways and transcription factors involved, is essential for advancing PD research. This article first explores the differentiation and maturation processes of DA neurons in the midbrain, detailing the relevant signalling pathways. It then compares various in vitro models, including primary cells, immortalized cell lines, and stem cell-based models, focusing on the advantages and limitations of each. Special attention is given to the role of immortalized and stem cell models in PD research. This review aims to guide researchers in selecting the most appropriate model for their specific research goals. Ethical considerations and clinical implications of using stem cells in PD research are also discussed.

Competence of Senior Otolaryngology Residents with the Bedside Head Impulse Test-Has There Been Improvement After 5 Years of Competency By Design?

BACKGROUND: The bedside head impulse test (bHIT) is a clinical method of assessing the vestibulo-ocular reflex. It is a critical component of the bedside assessment of dizzy patients and helps differentiate acute stroke from vestibular neuritis. A previous study on senior Otolaryngology residents showed poor competence in performing and interpreting the bHIT and called for specific evaluations in the Competency By Design (CBD) curriculum to remedy this. This study aimed to assess whether those competencies have improved after full implementation of CBD in residency programs. METHODS: Thirty post-graduate year 4 Otolaryngology residents in Canada were evaluated on the use of the bHIT using a written multiple-choice question (MCQ) examination, interpretation of bHIT videos, and performance of a bHIT. Ratings of bHIT performance were completed by 2 expert examiners (DT, DL) using the Ottawa Clinic Assessment Tool. RESULTS: Only 6.7% (rater DT) and 20% (rater DL) of residents were found able to perform the bHIT independently. Inter-rater reliability was moderate (0.55, intraclass correlation). Mean scores were 70% (13.4% standard deviation) for video interpretation and 59% (20.6% standard deviation) for multiple-choice questions. Video interpretation scores did not correlate with bHIT ratings (Pearson r = 0.11), but MCQs and bHIT ratings did correlate moderately (Pearson r = 0.52).Comparing to the prior study, residents performed worse on the bHIT (3.14 average score vs 3.64, P < .01) and fewer residents performed the bHIT independently (6.7% vs 22%-rater DT, 20% vs 39%-rater DL). Residents also performed worse on MCQs (58.7% vs 70.9%, P = 0.038), though similarly on video interpretation (70% vs 65%, P = .198). CONCLUSION: Fourth year OTL-HNS residents in Canada are not competent in performing the bHIT. These findings have implications for refining competency-based curricula in the evaluation of critical physical exam skills.

3D ultrasound-augmented image guidance for surgery of high-grade gliomas - A quantitative analysis focused on the extent of resection.

Background: We have retrospectively reviewed our series of brain tumor patients operated on using 3D IntraOperative UltraSound (IOUS) to report technical advantages and areas of improvement. Methods: Clinical and radiological data of patients with a diagnosis of high-grade glioma IV operated with and without IOUS were retrieved and analyzed. Results: We have found 391 patients operated using IOUS coupled with neuronavigation and 257 using neuronavigation standalone. We have selected a pool of 60 patients with a diagnosis of GlioBlastoma (GB), comparing two equally sized groups operated with and without IOUS, respectively. The average extent of resection (EOR) in the IOUS group was 93%, while in the control group, it was 80%. IOUS was significantly associated with improved EOR (P < 0.0004), even when accounting for other factors affecting EOR. The average overall survival (OS) was 13.4 months, and the average progression-free survival (PFS) was 7.4 months. The Cox proportional hazard model showed an advantage in OS on patients operated using the IOUS. No statistically significant effect was observed on PFS. Conclusion: Intraoperative ultrasound coupled with image guidance is associated with an improved EOR and possibly an improved OS. While we are aware of several limitations related to the present analysis, these data support the routine use of IOUS as a safe and reliable technology. Larger, prospective series with updated IOUS technology are desirable to verify the accuracy of these results.

Ferroptosis and pathogenesis of neuritic plaques in Alzheimer's Disease.

Neuritic plaques are pathognomonic and terminal lesions of Alzheimer's Disease (AD). They embody AD pathogenesis because they harbor in one space critical pathologic features of the disease: amyloid deposits, neurofibrillary degeneration (NFD), neuroinflammation, iron accumulation. Neuritic plaques are thought to arise from the conversion of diffuse extracellular deposits of amyloid beta protein (Aß), and it is believed that during conversion amyloid toxicity creates the dystrophic neurites of neuritic plaques, as well as neurofibrillary tangles (NFTs). However, recent evidence from human post-mortem studies suggests a much different mechanism of neuritic plaque formation where the first step in their creation is neuronal degeneration driven by iron overload and ferroptosis. Similarly, NFTs represent corpses of iron-laden neurons that develop independent of Aß deposits. In this review, we will focus on the role of free redox-active iron in the development of typical AD pathology, as determined largely by evidence obtained in human temporal lobe during early, preclinical stages of AD. The findings have allowed construction of a scheme of AD pathogenesis where brain iron is center stage and is involved in every step of the sequence of events that produce characteristic AD pathology. We will discuss how the study of preclinical AD has produced a fresh and revised assessment of AD pathogenesis that may be important for reconsidering current therapeutic efforts and guiding future ones. Significance Statement This review offers a novel perspective on AD pathogenesis where elevated brain iron plays a central role and is involved throughout the development of lesions. We review arguments against the amyloid cascade theory and explain how recent findings in humans during early preclinical disease support iron-mediated cell death and endogenous iron containment mechanisms as critical components of neuritic plaque formation and the ensuing dementia.

Transcriptomic insights into pseudorabies virus suppressed cell death pathways in neuroblastoma cells.

Pseudorabies virus (PRV) exhibits a complex interplay of host-pathogen interactions, primarily by modulating host cell death pathways to optimize its replication and spread in Neuro-2a cells. Using high-throughput RNA sequencing, we identified 2,382 upregulated differentially expressed genes (DEGs) and 3,998 downregulated DEGs, indicating a intricate interaction between viral pathogenesis and host cellular responses. This research offers valuable insights into the molecular processes involved in PRV infection, highlighting the substantial inhibition of crucial cell death pathways in Neuro-2a cells, including necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. Cells infected with PRV exhibit decreased expression of genes critical in these pathways, potentially as a mechanism to avoid host immune reactions and ensure cell survival to support ongoing viral replication. This extensive inhibition of apoptosis and metabolic alterations highlights the sophisticated tactics utilized by PRV, enhancing our comprehension of herpesvirus biology and the feasibility of creating specific antiviral treatments. This research contributes to our understanding of how viruses manipulate host cell death and presents potential opportunities for therapeutic interventions to disrupt the virus's lifecycle.

From Diagnosis to Resolution: A Case Study of Myxopapillary Ependymoma Survival.

Myxopapillary ependymoma (MPE) is a rare, slow-growing tumor that commonly arises in the lumbosacral region of the spinal cord, within the filum terminale and cauda equina. The frequent presentation of MPE is back, sacral, or leg pain. The tumor's size, site, and extension usually influence these symptoms. MPE is usually evaluated using magnetic resonance imaging (MRI) because of its superior soft tissue contrast. The best treatment modality is total surgical resection, which improves the long-term survival rate, with follow-up imaging recommended to ensure total resolution. Here, we present the case of a 29-year-old male who presented with symptoms suggestive of severe neurological impairment. An MRI scan revealed an intradural lesion arising from the cauda equina with peripheral and intrathecal haemorrhage, consistent with MPE. He was managed with laminectomy and microsurgical resection of the tumor, which achieved total resection. Postoperative follow-up found gradual improvement in his symptoms, and routine surveillance imaging confirmed the complete resolution of the tumor.

Biophysical and Biological Mechanisms of Tumor Treating Fields in Glioblastoma.

Glioblastoma (GBM) is one of the most aggressive forms of brain cancer that presents with a median survival rate of 14-30 months and along with a discouraging five-year survival rate of 4-5%. Standard treatment of newly diagnosed GBM, also known as the Stupp protocol, includes a maximally safe surgical resection followed by radiation and chemotherapy. Despite these treatment regimens, recurrence is almost inevitable, emphasizing the need for new therapies to combat the aggressive nature of GBMs. Tumor Treating Fields (TTFs) are a relatively new application to the treatment of GBMs, and results have been promising with both progression-free survival and overall survival when TTFs have been used in combination with temozolomide. This article critically reviews the biophysical and biological mechanisms of TTFs, their clinical efficacy, and discusses the results in clinical trials, including EF-11 and EF-14. Both trials have demonstrated that TTFs can enhance progression free survival and overall survival without compromising quality of life or causing severe adverse effects. Despite the high cost associated with TTFs and the need for further analysis to determine the most effective ways to integrate TTFs into GBM treatments, TTFs represent a significant advancement in GBM therapy and offer hope for improved patient prognosis.

Blood-brain barrier damage accelerates the accumulation of micro- and nanoplastics in the human central nervous system.

The widespread use of plastics has led to increased micro- and nanoplastics (MNPs) pollution, resulting in significant environmental challenges and concerns about potential harm to human health. This study investigated whether certain types of MNPs can accumulate in the human central nervous system (CNS) and trigger inflammatory responses, particularly after CNS infection. Our analysis of 28 cerebrospinal fluid (CSF) samples from 28 patients with or without CNS infection revealed that only polystyrene (PS), polyethylene (PE), polypropylene (PP), and polyvinyl chloride (PVC) were capable of selectively entering the human CNS. Concentrations of PP and PE were positively correlated with the CSF albumin index. The levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly increased in patients with CNS infections. However, concentrations of MNPs were not significantly associated with CSF levels of IL-6 or IL-8. Overall, these findings suggest that specific MNPs can penetrate the human CNS, especially after impairment of the blood-brain barrier. Notably, MNPs derived from commonly used plastics did not significantly induce or exacerbate inflammation in the human CNS.

Preparation of new green poly (amino amide) based on cellulose nanoparticles for adsorption of Congo red and its adaptive neuro-fuzzy modeling.

In this study, a novel green poly(amino amide) nanoparticle based on cellulose nanoparticles (Cell-PAMN) was developed for the efficient adsorption of Congo Red dye. Cellulose nanocrystals obtained from acid hydrolysis of cotton linter were functionalized via Oxa-Michael addition of acrylamide on their surface hydroxyl groups, followed by transamidation with ethylenediamine. The resulting nanoparticles were characterized using FT-IR spectroscopy, SEM, and X-ray diffraction techniques. The as-prepared Cell-PAMN exhibited considerably higher adsorption capacity compared to unmodified cellulose nanoparticles due to the presence of amino and amide functional groups. The adsorption kinetics and the effects of parameters such as contact time and initial dye concentration on the adsorption capacity were investigated. An adaptive Neuro-Fuzzy model was used to study the efficiency of dye removal, accurately predicted the adsorption behavior of Cell-PAMN. The kinetic study results showed that the adsorption process followed a pseudo-second-order kinetic model, with a maximum adsorption capacity of around 40 mg/g. The results demonstrated the potential of the synthesized material for the removal of Congo Red from aqueous solutions, highlighting its applicability in wastewater treatment. This research contributes to the development of sustainable and eco-friendly materials for environmental remediation applications.

Theranostics advances in the treatment and diagnosis of neurological and neurosurgical diseases.

Theranostics represents a significant advance in the fields of neurology and neurosurgery, offering innovative approaches that combine the diagnosis and treatment of various neurological disorders. This innovation serves as a cornerstone of personalized medicine, where therapeutic strategies are closely integrated with diagnostic tools to enable precise and targeted interventions. Primary research results emphasize the profound impact of theranostics in Neuro Oncol. In this context, it has provided valuable insights into the complexity of the tumor microenvironment and mechanisms of resistance. In addition, in the field of neurodegenerative diseases (NDs), theranostics has facilitated the identification of distinct disease subtypes and novel therapeutic targets. It has also unravelled the intricate pathophysiology underlying conditions such as cerebrovascular disease (CVD) and epilepsy, setting the stage for more refined treatment approaches. As theranostics continues to evolve through ongoing research and refinement, its goals include further advancing the field of precision medicine, developing practical biomarkers for clinical use, and opening doors to new therapeutic opportunities. Nevertheless, the integration of these approaches into clinical settings presents challenges, including ethical considerations, the need for advanced data interpretation, standardization of procedures, and ensuring cost-effectiveness. Despite these obstacles, the promise of theranostics to significantly improve patient outcomes in the fields of neurology and neurosurgery remains a source of optimism for the future of healthcare.

Longitudinal management in Duchenne muscular dystrophy with exon 63 duplication.

A boy with nonambulatory Duchenne muscular dystrophy (DMD) tested positive for exon 63 duplication and exhibited intellectual disability, overweight and dyslipidaemia. The patient underwent a comprehensive multidisciplinary approach involving pharmacological and non-pharmacological interventions. Despite challenges, such as socioeconomic constraints and limited access to advanced therapies, the patient received tailored care. The management included prednisone medication, dietary modifications and psychological support. The patient's journey highlighted the complex interplay of medical and psychosocial factors affecting DMD patients in resource-limited settings. Regular monitoring and the involvement of the patient's family in a peer group were arranged to improve overall quality of life. The case underscores the need for accessible and holistic care for DMD patients, addressing both medical and psychosocial challenges.

Cajal's contributions to vestibular research.

The Spanish neurohistologist Santiago Ramón y Cajal (1852-1934) is widely regarded as the father of modern Neuroscience. In addition to identifying the individuality of cells in the nervous system (the neuron theory) or the direction followed by nerve impulses (the principle of dynamic polarization), he described numerous details regarding the organization of the different structures of the nervous system. This task was compiled in his magnum opus, "Textura del Sistema Nervioso del Hombre y los Vertebrados," first published in Spanish between 1899 and 1904, and later revised and updated in French as "Histologie du système nerveux de l'homme et des vertébrés" between 1909 and 1911 for wider distribution among the international scientific community. Some of Cajal's findings are fundamental to our understanding of the anatomy and histology of the vestibular system. He depicted the nerve endings in the sensory epithelia, the structure of the vestibular nerve and Scarpa ganglion, afferent vestibular fibers, vestibular nuclei, lateral vestibulospinal tract, vestibulocerebellar connections, and the fine structure of the cerebellum. However, most of these pioneering descriptions were published years earlier in Spanish journals with limited circulation. Our study aimed to gather Cajal's findings on the vestibular system and identify his original publications. After this endeavor, we claim a place for Cajal among the founders of anatomy and histology of the vestibular system.

Landscape and impact of mind-body, cognitive-behavioral, and physical activity interventions in adolescent and adult brain tumor patients: A systematic review.

Background: The use of mind-body, cognitive-behavioral, and physical activity interventions have shown efficacy for improving symptom burden and functional limitations in other cancers; however, these strategies have not been widely implemented within neuro-oncology. This systematic review describes the current landscape and the impact of these interventions on adolescent and adult patients with brain tumors, which may guide the development of future interventions. Methods: A systematic search of PubMed, Embase, and Web of Science was performed using preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines with predefined eligibility criteria. Twenty-nine studies met the inclusion criteria and were selected for review. Results: There was promising evidence for the feasibility and efficacy of mind-body and physical activity interventions for improving mood and quality of life, as well as enhanced physical functioning following aerobic and strength-based interventions. Results were mixed for cognitive-behavioral interventions, likely due to underpowered analyses. Interventions tested in pediatric patients also showed improvements in fatigue, mood, and quality of life, though these individuals represented a small proportion of the pooled sample. Conclusions: Findings suggest that mind-body and physical activity interventions can improve both physical and psychological health for patients with brain tumors, though additional well-designed clinical trials are needed to better establish efficacy.

Axillary lesion in a young adult ends up to a peculiar diagnosis: primitive neuro-ectodermal tumor (PNET) of ulnar nerve: a rare case report.

Introduction and importance: Primitive neuro-ectodermal tumor (PNET) is a highly aggressive tumor composed of small round blue cells, mostly developing in children and young adults. Being a member of Ewing's Sarcoma Family of Tumors (ESFT); it has been discussed in two subcategories of central and peripheral PNET. PNETs of peripheral nerves are very uncommon pathologic findings, as to the best of our knowledge only 12 well-documented cases have been yet reported. Case presentation: A 30-year-old male presented with progressive paresthesia of his right hand's little finger and painless swelling of the right axilla. Magnetic resonance (MR) neurography demonstrated a heterogeneous, high-signal, round mass within the right axilla fossa in proximity to the medial aspect of brachial plexus branches. The clinical and radiological study failed to an accurate diagnosis, thus surgical resection of the tumor was done for tissue evaluation. Histopathologic study of the lesion revealed a neoplasm comprising sheets of small, round, blue cells (Hematoxylin and Eosin stain), which immunohistochemically consisted with the diagnosis of PNET. Clinical discussion: The differential diagnosis of axillary fossa masses, focusses on peripheral nerve tumors like Schwannoma and PNET. MR neurography aids in evaluation, but tissue diagnosis remains crucial. Treatment involves surgical resection, chemotherapy, and radiotherapy tailored to individual patients. Conclusion: Although pPNET is not apparently the first differential diagnosis coming to mind when encountering a rapidly growing mass in the axillary fossa with peripheral nerve origin, its highly malignant behavior, makes it crucial to be considered in the differential diagnoses.