A central hypothesis on brain functioning is that plasticity regulates the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granular layer has been shown to control the gain of signals transmitted through the mossy fiber pathway. Until now, the impact of plasticity on incoming activity patterns was analyzed by combining electrophysiological recordings in acute cerebellar slices and computational modeling, unraveling a broad spectrum of different forms of synaptic plasticity in the granular layer, often along with forms of intrinsic excitability changes. Here, we attempt to provide a brief overview of the most prominent forms of plasticity at excitatory synapses formed by mossy fibers onto principal neurons (granule cells, Golgi cells and unipolar brush cells) in the granular layer. Specifically, we will highlight current understanding of the mechanisms and their functional implications of the synaptic and intrinsic plasticity, providing valuable insights into how inputs are processed and reconfigured at the cerebellar input stage.

Brain plasticity is the ability of the brain to change and adapt in response to experience or learning. Its hallmarks are developmental flexibility, complex interactions of genetic and environmental influences, and structure-functional changes comprising neurogenesis, axonal sprouting, and synaptic remodeling. Herein, we review brain plasticity association with non-coding RNAs (ncRNAs). Studies on brain plasticity have important practical implications. Numerous cerebral ncRNAs are linked with neurological disorders, which makes them putative targets for RNA-based diagnostics and therapeutics since molecular characteristics of brain plastic change may reveal disease course and rehabilitative potential of the patient. A new insight into the concept of brain plasticity will provide perspectives on functional recovery following brain damage. The knowledge of this phenomenon will enable physicians to exploit cerebral plastic potential and regulate eloquent networks with timely interventions. Future studies will provide pathophysiologic mechanisms of brain plasticity at macro- and microscopic levels to advance rehabilitation strategies and improve the quality of life in neurological disorders.

Introduction Delayed intra-operative neuro-monitoring (IOM) events can be defined as loss of responses, after baseline traces were present upon completion of instrumentation and deformity correction. This study reports this subgroup of events, assesses their incidence and evaluates potential causative factors. Methods We reviewed 1881 consecutive patients who underwent spinal deformity correction between 2011 and 2021. Surgeries were performed using a standardised anaesthetic regimen and multimodal IOM protocol. Results 44 patients (2.4%) had an IOM event. 9 patients (6F:3M) had a true positive delayed event after posterior segmental pedicle screw instrumentation. Mean age was 12.5 (2-17) years with mean thoracic Cobb angle of 78° (51-94°). Mean estimated blood loss was 28%. Titanium beam shaped rods were utilised in 3 patients and 5.5mm titanium rods in 5 patients. Motor evoked potentials were lost on average 18 (10-30) minutes after completion of instrumentation. 7 patients had bilateral loss and 2 patients had unilateral loss of MEP traces. Sensory evoked potential amplitude was preserved in all cases. There was a transient latency shift in one patient. MEPs returned within 20 minutes of rod release. The rod was re-contoured to incorporate more scoliosis in 1 patient. 2 patients had beam rods exchanged to 5.5mm titanium rods. 6 patients had rod removal with retention of pedicle screws and staged completion of instrumentation at mean 5 (1-7) days later. No patients had a postoperative neurological deficit. Conclusion Delayed IOM loss represented 15% of all events. Increased cord tension and hypo-perfusion were considered likely mechanisms. Rod release restored MEPs in all cases. The timing of events emphasises the importance of continued monitoring for minimum 30 minutes after completion of spinal instrumentation or until wound closure.

Multiple sclerosis (MS) is an immune-mediated disease characterized by inflammation, demyelination, and neurodegeneration within the central nervous system. Brain plasticity, the brain's ability to adapt its structure and function, plays a crucial role in mitigating MS's impact. This paper explores the potential benefits of lifestyle changes and nutraceuticals on brain plasticity in MS population. Lifestyle modifications, including physical activity and dietary adjustments, can enhance brain plasticity by upregulating neurotrophic factors, promoting synaptogenesis, and reducing oxidative stress. Nutraceuticals, such as vitamin D, omega-3 fatty acids, and antioxidants like alpha-lipoic acid, have shown promise in supporting brain health through anti-inflammatory and neuroprotective mechanisms. Regular physical activity has been linked to increased levels of brain-derived neurotrophic factor and improved cognitive function. Dietary interventions, including caloric restriction and the intake of polyphenols, can also positively influence brain plasticity. Integrating these lifestyle changes and nutraceuticals into the management of MS could provide a complementary approach to traditional therapies, potentially improving neurological outcomes and enhancing the quality of life for MS population.

Age-related brain deterioration and Alzheimer's disease (AD) pose major challenges as misfolded proteins are deposited in the brain, leading to a decline in cognitive abilities and disruption of neural networks crucial for memory. This article addresses the impact of disrupted spike-timing-dependent plasticity (STDP) mechanisms in Alzheimer's disease and highlights the role of Transcranial magnetic stimulation (TMS) in the study of cortico-cortical spike-timing-dependent plasticity. Amidst this adversity, the role of STDP emerges as a key player in memory formation by synchronizing neural activity. Progressive neuronal dysfunction decreases neural plasticity and impairs manual dexterity and speed, echoing more general problems in elderly people. The findings highlight the potential of neurally-driven cortico-cortical paired associative stimulation (ccPAS) to revitalize neural plasticity and improve motor performance in elderly people, bridging the gap between age-related challenges and Alzheimer's research. This work opens a door to potential rehabilitation strategies for aging populations by unlocking the aging brain's ability to improve motor performance.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

The objective of this study was to develop and evaluate artificial intelligence (AI) models for the detection and instance segmentation of vertebrae and spinal metastases in computer tomography (CT) scans. The models were trained on datasets consisting of patients with polytrauma and relatively undamaged spines, as well as patients diagnosed with spinal metastases. Our results indicate that the models achieved high performance in vertebra segmentation, with F-beta scores ranging from 0.88 to 0.96 across all vertebra classes. For spinal metastases, the model attained F-beta scores of 0.68 for lytic type and 0.57 for sclerotic type metastases. Additionally, the models demonstrated the capability to detect isolated metastatic nodes in other bones, highlighting their robustness and potential for broader clinical application. Despite these promising results, the study faced limitations including a relatively small and homogeneous dataset, variability in segmentation mask quality, and the need for real-world clinical validation. Future clinical trials are necessary to evaluate the practical utility and effectiveness of these AI models in improving patient outcomes. Our study emphasizes the potential of AI-assisted detection and segmentation models in enhancing diagnostic accuracy and efficiency in clinical practice.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Background: Injury of the spinal cord causes motor and sensory dysfunction, and pathological reflexes, leading to paraplegia or tetraplegia. The sequelae of traumatic spinal cord injury (SCI) is a significant burden and impact on healthcare systems. Despite constant progress in medicine, traumatic SCI still remains irreversible. Till now, no satisfying treatment that can enable neuronal regeneration and recovery of function at the damaged level has been found. Hundreds of experiments have been conducted on various possibilities of influencing spinal regeneration, some of them have yielded promising results, but unfortunately, the successes obtained in experimental animals have not translated into humans. Methods: This narrative review article presents the application of Extracorporeal Shock Wave Therapy (eSWT) in Spinal Cord Injury. The article has been divided into parts: 1. Use of extracorporeal Shock Wave Therapy for regeneration of the spinal cord after traumatic Spinal Cord Injury. 2. Application of extracorporeal Shock Wave Therapy in spasticity after Spinal Cord Injury. In both cases, the hypotheses of possible mechanisms of action will be described. Results and conclusions: A small number of clinical trials have demonstrated the potential of eSWT to influence the regeneration of the spine, as an innovative, safe, and cost-effective treatment option for patients with SCI. Some reports have shown that eSWT can improve spasticity, walking ability, urological function, quality of life, and independence in daily life.

Objective: This prospective study investigated the feasibility performing laparoscopic pelvic surgery in spinal anesthesia and analyzed their intraoperative side effects like pain and nausea and vomitus of 915 patients. Methods: Implementation and performance of laparoscopic surgery under local anes-thesia of 915 patients out of a total of 3212, who underwent laparoscopic pelvic surgery in spinal anesthesia, were analyzed in relation to BMI (Body Mass Index), obesity, pain during surgery and amount of intraperitoneal mmHg CO2 gas pressure and surgical complications. Results: BMI > 30, intraabdominal adhesions, increased duration of the operation, bleeding and increased intraperitoneal CO2 pressure were statistically significant as the main causes of pain during laparoscopic surgery in spinal anesthesia. Under-weight patients, on the other hand, had less pain when intra-abdominal pressure in-creased compared to those of normal weight. The appearance of pain, nausea and vomitus occurred in 10,3% and was easy to manage and treat. It did not affect the sur-geon's work and the course of the operation. Conclusion: In view of these observations, we are proposing spinal anesthesia for lap-aroscopic surgery as the first choice in those patients, who have no contraindications. In our knowledge this clinical study constitutes the largest clinical observations and dataset that applies spinal anesthesia in laparoscopic pelvic surgery.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

Presenting a rare case of adult-onset mature cystic teratoma of the spinal cord in the thoracolumbar spinal cord in a 54-year-old male whose chief complaint was lower back pain radiating to both legs while other findings were normal. X-ray images of the thoracolumbar spine showed early degenerative changes and unfused posterior elements noted in lower sacral vertebral levels. Magnetic resonance images of the lumbar spine showed a well-defined non-enhancing intramedullary altered intensity lesion noted at the level of conus at the L1-L2 vertebral level. The resected tumour was histopathologically diagnosed as a mature cystic teratoma. The patient's symptoms improved following the surgery.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

The aim of this report is to evaluate the segmental rib index (RI) from T1-T12 spinal level in mild and moderate idiopathic scoliosis (IS) curves of thoracic, thoracolumbar and lumbar type by gender. The relationship of segmental RI to the frontal plane radiological deformity presented as the Cobb angle and to the posterior truncal surface deformity presented as the scoliometric readings of Angle of Trunk Rotation (ATR) in these patients is also assessed. Any statistical significant rela-tionship of these parameters would be very important for biomechanical relations of the rib cage (RC) deformity presented as the rib hump deformity (RHD) and the deformity in the spine and it would thus provide valuable information about scoliogeny. The segmental rib index (RI) is presented in 83 boys and girls with mild and moderate IS. The measurements include the scoliometric readings for truncal asymmetry (TA), the Cobb angle assessment and the segmental RI from T1-T12. The statistical package SPSS 23 was used for statistical analysis. The TA is documented and the Cobb angle is presented by gender and curve type. The segmental RI of thoracic, thoracolumbar and lumbar curves are presented for the first time. The correlations of the segmental RI to surface deformity presented as the rib hump deformity (RHD) in all IS patients and particularly in thoracic curves, to Cobb angle by gender and age and the comparison of the segmental RI index of asymmetric but not scoliotic children to the scoliotic peers by curve (in thoracic, thoracolumbar, lumbar curves) in boys and girls are presented. The findings emphasize the significant protagonistic role of the thoracic asymmetry in relation to the spinal deformity mainly in girls for the thoracic and in boys for the thoracolumbar curves. The cut-off point of age of the examined scoliotics is 14 years, that is when the RI shows stronger correlation with the spinal deformity, namely when the thoracic deformity is decisively effective to the developing thoracic spinal deformity, in terms of Cobb angle. In summary, the results of this study provide aetiological implications for IS, as far as the role of thorax is con-cerned.

In former times, the spinal cord was considered a hard-wired network for spinal reflexes and a conduit for long-range connections. This view has changed dramatically over the past few decades. It is now recognized as a plastic device whose structures and functions adapt to changing circumstances. While such changes also occur under physiological conditions, the most dramatic alterations take place during or after various pathological events. It is astonishing what mechanisms the musculo-skeletal system has evolved to come to grips with the damages. Many of these changes are maladaptive, but some appear to help adapt to the new conditions. Although myriads of studies, using manifold methods, have been devoted to elucidating the underlying mechanisms, in humans and animal models, the etiology and pathophysiology of various diseases are still little understood, due to a number of reasons. We will here try to summarize some results and remaining problems in a selection of diseases, in particular spinal muscular atrophy (SMA), amyotrophic laterals sclerosis (ALS), and predominantly spinal cord injury (SCI) with occasional relations to stroke. Especially the changes in SCI (and stroke) depend on the cause, site and extent of the afflicted damage and are therefore multifarious. At the end, we will briefly summarize results indicating that operant, classical and instrumental conditioning can be used to produce plastic changes in healthy people, with potentials for applications to patients with spinal cord injury. In order not to overload the article, we will not delve deeply into sub-cellular processes.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysiological changes after injury. While low dose nicotine (1µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5-10µM) on locomotor networks in-vitro. Nicotine 10µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5-1µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes suggesting their response to stress. Excitotoxicity induced by kainate was contrasted by nicotine (10µM) in the dorsal area and persisted in central and ventral regions with no change basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.

Intratumoral heterogeneity is a major ongoing challenge in the effective therapeutic targeting of cancer. Accumulating evidence suggests that a fraction of cells within a tumor termed Cancer Stem Cells (CSCs) are primarily responsible for this diversity resulting in therapeutic resistance and metastasis. Adding to this complexity, recent studies have shown that there can be different subpopulations of CSCs with varying biochemical and biophysical traits resulting in varied dissemination and drug-resistance potential. Moreover, cancer cells can exhibit a high level of plasticity or the ability to dynamically switch between CSC and non-CSC states or among different subsets of CSCs. The molecular mechanisms underlying such plasticity has been under extensive investigation and the trans-differentiation process of Epithelial to Mesenchymal transition (EMT) has been identified as a major contributing factor. Besides genetic and epigenetic factors, CSC plasticity is also shaped by non-cell-autonomous effects such as the tumor microenvironment. In this review, we discuss the recent developments in understanding CSC plasticity in tumor progression at biochemical and biophysical levels, and the latest in silico approaches being taken for characterizing cancer cell plasticity with implications in improving existing therapeutic approaches.

Establishing macrometastases at distant organs is a highly challenging process for cancer cells, with extremely high attrition rates. A very small percentage of disseminated cells have the ability to dynamically adapt to their changing micro-environments through reversibly switching to another phenotype, aiding metastasis. Such plasticity can be exhibited along one or more axes – epithelial-mesenchymal plasticity (EMP) and cancer stem cells (CSCs) being the two most studied, and often tacitly assumed to be synonymous. Here, we review the emerging concepts related to EMP and CSCs across multiple cancers. Both processes are multi-dimensional in nature; for instance, EMP can be defined on morphological, molecular and functional changes, which may or may not be synchronized. Similarly, self-renewal, multi-lineage potential, and anoikis and/or therapy resistance may not all occur simultaneously in CSCs. Thus, arriving at rigorous functional definitions for both EMP and CSCs is crucial. These processes are dynamic, reversible, and semi-independent in nature; cells traverse the inter-connected high-dimensional EMP and CSC landscapes in diverse paths, each of which may exhibit a distinct EMP-CSC coupling. Our proposed model offers a potential unifying framework for elucidating the coupled decision-making along these dimensions and highlights a key set of open questions to be answered.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that “core” mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a “core” mechanism is the initiation of behavioral shifts through the modulation of a conserved “social decision-making network”, along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).

We present a high-throughput nanoindentation study of in-situ bending effects on incipient plastic deformation behavior of polycrystalline and single-crystalline pure aluminum and pure copper at ultra-nano depths (<200nm). We find that hardness displays a statistically inverse dependence on in-plane stress for indentation depths smaller than 10nm, and the dependence disappears for larger indentation depths. In addition, plastic noise in the nanoindentation force and displacement displays statistically robust noise features, independently of applied stresses. Our experimental results suggest the existence of a regime in FCC crystals where ultra-nano hardness is sensitive to residual applied stresses, but plasticity pop-in noise is insensitive to it.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

The increasing prevalence of spinal disorders and the subsequent rise in spinal fusion surgeries stress the necessity for optimizing spinal fusion cages, crucial for stabilizing the spine and supporting osseointegration. Despite the widespread attempts at material modifications and surface enhancements to improve these devices, failure rates and complications remain significant. This research explores an imaginitive approach to enhancing spinal fusion cages through the application of geometric tiling designs, a method scarcely employed . The study systematically investigates the potential of triangular, diamond, and hexagonal tiling patterns to improve the structural integrity and capability for osseointegration of spinal fusion cages. Through a finite element analysis simulation, each design's ability to withstand multi-directional loads and effectively distribute stress was tested under simulated conditions that mimic the complexities of spinal motion. Preliminary findings in fields of engineering indicate that geometric tiling can significantly enhance the load-bearing capabilities and stress distribution of spinal fusion cages, potentially reducing the likelihood of implant subsidence and failure. The triangular and hexagonal designs, in particular, demonstrate superior performance in maintaining structural stability under axial and anterior compressive forces compared to traditional cage designs. This research opens a new pathway for the development of more durable and efficient spinal fusion cages. By leveraging the structural advantages of geometric tiling, future spinal implants could achieve better clinical outcomes, leading to improved patient recovery and reduced rates of complications.

Spinal Cord Injury in children can be a devastating condition in children with profound implications for their overall health and quality of life. In this review we aim to provide a concise overview of the key aspects associated with SCI in pediatric population. Firstly, we discuss the etiology and epidemiology of SCI in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCI, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research and innovative therapies in the field and we emphasize the need for continued advancements in understanding and treating SCI in children to improve their functional independence and overall quality of life.

While some research supports utilizing plain radiography for measuring biomechanical alignment of the spine for prognosis and treatment, there are contrasting viewpoints regarding both the value and utilization of these procedures in conservative care. Evaluation of both conservative and non-conservative approaches to spinal care revealed vast differences in radiographic utilization and interpretation between orthopedic surgeons, primary care physicians, chiropractic physicians, and physical therapists, which may account for the different viewpoints and rationale in the literature. A research summary is provided regarding the various methods of spinal analysis utilized by these professions to help determine if there is any unique diagnostic or prognostic value associated with radiographic utilization that could assist in advancing conservative spinal assessment and treatment. Understanding any unique value provided through biomechanical assessment utilizing plain radiography of the spine established in the literature may help chiropractic physicians determine the appropriate use of radiographic procedures in clinical practice and how to coordinate efforts with other conservative and non-conservative professions to improve spinal healthcare.

Introduction: The COVID-19 pandemic challenged people with spinal cord injury (SCI) regarding a variety of mental and physical issues. New challenges may arise as the effects of the pandemic continue. The objective of the present study was to explore the social participation of Canadians with SCI during the second wave of COVID-19. Methods: Participants with SCI from two Canadian provinces (Quebec and British Columbia) were interviewed. Results: Eighteen participants completed interviews. Facilitators of social participation remain similar since the first wave of COVID-19, such as the use of technology, help received by relatives and the use of delivery services to obtain groceries and other essentials. Obstacles to mobility due to winter conditions and lack of considerations related to COVID-19 public health measures specific to wheelchair users were also discussed by participants. Conclusions: People with SCI perceived participation restrictions, little changes in life habits, and uncertainty about the future during the second wave of COVID-19. The unique living conditions of people with SCI, ability to adapt life habits, and the lived experiences of people with SCI may have contributed to an overall resilience during the pandemic. Adaptive families, social contacts and technology made a difference during the pandemic.

Oleuropein (OLE), a main constituent of olive, displays a pleiotropic beneficial dynamic in health and disease, based mainly on its antioxidant and hypolipidemic properties, and its capacity to protect myocardium during ischemia. Furthermore, OLE activates peroxisome proliferator-activated receptor (PPARα) in neurons and astrocytes, providing neuroprotection against noxious biological reactions that are induced following cerebral ischemia. Current study investigated the effect of OLE in the regulation of various neural plasticity indices, emphasizing the role of PPARα. For this purpose, 129/Sv wild-type (WT) and Pparα-null mice were treated with OLE for three weeks. The present findings revealed that chronic treatment with OLE up-regulated the brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the prefrontal cortex (PFC) of mice via activation of ERK1/2, AKT and PKA/CREB signaling pathways. No similar effects were observed in the hippocampus. The OLE-induced effects on BDNF and TrkB appear to be mediated by PPARα, because no similar alterations were observed in the PFC of Pparα-null mice. Notably, OLE did not affect the neurotrophic factors NT3 and NT4/5 in both brain tissues. Fenofibrate though, a selective PPARα agonist, up-regulated BDNF and NT3 in the PFC of mice, whereas the drug induced NT4/5 in both brain sites tested. Interestingly, OLE provided neuroprotection in differentiated human SH-SY5Y cells against β-amyloid and H2O2 toxicity independently from PPARα activation. In conclusion, OLE and similar drugs acting either as PPARα agonists or via PPARα independent mechanisms could improve synaptic function/plasticity mainly in the PFC and to a lesser extent in the hippocampus, thus beneficially affecting cognitive functions.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity that in turn determines the tumor cell response towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here we established a dual reporter system enabling the tracking of NGFR expression and mRNA stability, providing insights into the maintenance of NCSC-states. We observed that the transcriptional reporter that contained a 1kb fragment of the human NGFR promoter was activated only in a minor subset (0.72±0.49%, range 0.3-1.5) and ~2-4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provided insights into phenotype switching and revealed that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provided insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.

Constitutive models for plastic deformation of metals are typically based on flow rules determining the transition from elastic to plastic response of a material as function of the applied mechanical load. These flow rules are commonly formulated as a yield function, based on the equivalent stress and the yield strength of the material, and its derivatives. In this work, a novel mathematical formulation is developed that allows the efficient use of machine learning algorithms describing the elastic-plastic deformation of a solid under arbitrary mechanical loads and that can replace the standard yield functions with more flexible algorithms. By exploiting basic physical principles of elastic-plastic deformation, the dimensionality of the problem is reduced without loss of generality. The data-oriented approach inherently offers a great flexibility to handle different kinds of material anisotropy without the need for explicitly calculating a large number of model parameters. The applicability of this formulation in finite element analysis is demonstrated, and the results are compared to formulations based on Hill-like anisotropic plasticity as reference model. In future applications, the machine learning algorithm can be trained by hybrid experimental and numerical data, as for example obtained from fundamental micromechanical simulations based on crystal plasticity models. In this way, data-oriented constitutive modeling will also provide a new way to homogenize numerical results in a scale-bridging approach.

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

Exoskeleton technology has been shown to be useful for individuals with spinal cord injury (SCI), potentially facilitating their recovery of motor function and social reintegration. However, studies on the safety and usability of exoskeletons are limited. This study aimed to design a powered exoskeleton for SCI and evaluate its safety and usability. Ten healthy adults participated in this study. The prototype exoskeleton featured an adjustable frame, computer-controlled hip and knee joint actuators, and a gait-trigger sensor. The experimental actions included walking, standing, and sitting, with and without the prototype. Safety outcomes included adverse events, vital signs, numerical rating scale (NRS) scores for pain, discomfort, and fatigue, and prototype-human body clearance. Usability outcomes included donning and doffing times, subjective ratings, gait speed, stride length, and kinematic parameters of hip and knee joint angles. Safety outcomes showed no serious adverse events, stable vital signs, minimal NRS scores, and acceptable clearance. Usability outcomes showed high efficiency and received positive ratings. Kinematic parameters showed significant positive correlations between normal walking and walking with the prototype for both hip and knee joint angles, confirming its effectiveness in assisting walking. However, further device improvements and gait parameter tuning are necessary for future clinical application.

Background. Sarcopenia and spinal cord injury (SCI) often coexist, but little is known about the associations of these two pathologies. This study aimed to assess the impact of SCI on muscle and bone mass and the correlations between clinical characteristics of SCI patients and sarcopenia. Methods: 136 patients diagnosed with SCI admitted to rehabilitation hospital were included in the study. The type and severity of injury (AIS), the level of spasticity (MAS), bone mineral density and Appendicular Lean Muscle Mass (ALM) were assessed. Sarcopenia was diagnosed according to the recommended EWGSOP2 cut-off points for ALM. Results: There was a statistically significant association between the ALM value and the gender, 75% of women developing sarcopenia. Among men, 42.9% had sarcopenia. Over 55% of AIS Grades A and B cases had sarcopenia. Mean age of sarcopenic patients was 35.8 years and they had multiple comorbidities. 51.6% of the patients with osteoporosis had sarcopenia. 69.7% of MAS level 0 cases had sarcopenia, while this was diagnosed in about 40% of patients with MAS levels 1-4. Conclusions: Gender, type of injury, presence of multiple comorbidities and age were directly associated with sarcopenia, while surprisingly, spasticity level and the presence of immobilization osteoporosis were not.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

(1) Background: This study aims to investigate differences in the perspectives of exercise intensity for resistance exercise of healthcare professionals (HCPs) and adults living with spinal cord injury (SCI) in Asian countries. Also, it verifies the appropriateness of the conventional indicators for resistance exercise intensity in an Asian context; (2) Methods: 121 certified HCPs and 107 adults with SCI participated in a survey conducted in Indonesian, Japanese, Korean and Thai languages. The survey asked what principles are important for prescribing resistance exercise, and if ‘moderate’ and ‘vigorous’ were appropriate terms for indicating an intensity level. Perspective differences were examined between both groups and, further, between countries from a psychosocial perspective; (3) Results: Of the HCPs, 92% perceived that resistance exercise intensity was far more important than frequency, time or type of exercise while frequency (61%) followed by intensity (58%) was perceived as important by respondents with SCI. Only Japanese respondents with SCI agreed with HCP’s perception of intensity. Both HCPs and respondents with SCI showed unfavorable responses on the usage of ‘moderate’ and ‘vigorous’ for describing resistance exercise intensity, especially Japanese HCP and respondents with SCI from Indonesia; (4) Conclusion: Our findings suggest that non-HCPs must improve their perceptions of exercise intensity. Findings also suggest the need for more explicit and user-friendly terms or expressions indicating the level of intensity in a local (Asian) context.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score adjusted Cox regression) to a historical control group (N=266) receiving 10 x 3.0 Gy (32.5 Gy10). In the phase 2-cohort, 50 (of 62 planned) patients were evaluable for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy.

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial-mesenchymal transition (EMT). Cells in these hybrid E/M phenotypes often combine epithelial and mesenchymal features and tend to migrate collectively commonly as small clusters. Such collectively migrating cancer cells play a pivotal role in seeding metastases and their presence in cancer patients indicates an adverse prognostic factor. Moreover, cancer cells in hybrid E/M phenotypes tend to be more associated with stemness which endows them with tumor-initiation ability and therapy resistance. Most recently, cells undergoing EMT have been shown to promote immune suppression for better survival. A systematic understanding of the emergence of hybrid E/M phenotypes and the connection of EMT with stemness and immune suppression would contribute to more effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical and experimental approaches to elucidate mechanisms underlying EMT multi-stability (i.e. the existence of multiple stable phenotypes during EMT) and the properties of hybrid E/M phenotypes. Following we discuss non-cell-autonomous regulation of EMT by cell cooperation and extracellular matrix. Afterwards, we discuss various metrics that can be used to quantify EMT spectrum. We further describe possible mechanisms underlying the formation of clusters of circulating tumor cells. Last but not least, we summarize recent systems biology analysis of the role of EMT in the acquisition of stemness and immune suppression.

Background/Objectives: The primary life-threatening complication in Spinal-bulbar muscular atrophy (SBMA) is ventilatory failure, which results from the weakening of the bulbar and respiratory muscles. However, systematic studies assessing respiratory function over the long-term have not been performed. The present study analyzes the longitudinal patterns of respiratory function tests over a follow-up of 11 years, aiming to identify any potential, sustained decline during this time. Furthermore, we explored possible correlations between respiratory function tests and clinical and biochemical serum indices. Methods: We collected data from 9 genetically confirmed SBMA patients and conducted spirometric measurements twice a year for eleven years. The spirometric data included maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and forced vital capacity (FVC)]. Additionally, we measured serum biochemical indices and SBMA functional rating scale (SBMAFRS) for clinical analysis. Results: All three respiratory function tests showed a descending trend. A major decrease was observed for MEP (52%) and MIP (42%), while this was minor for FVC (25%). SBMAFRS score correlated with the three pulmonary function tests. MIP and MEP correlated with creatine phosphokinase and creatinine levels, and FVC correlated with serum level of transaminases. Conclusions: This longitudinal study shows a progressive decline of spirometric data throughout life in patients with SBMA. Spirometric measures relative to maximal strength of the respiratory muscles (MIP and MEP) may have a better predictive value for pulmonary and muscular decline than FVC.

Phenotypic switching in cancer cells has been found to be present across tumor types. Recent studies on Glioblastoma report a remarkably common architecture of four well-defined phenotypes coexisting within high levels of intra-tumour genetic heterogeneity. Tumours grown from any cell type recapitulate the original phenotypic composition. Similar dynamics have been shown to occur in breast cancer, melanoma and likely across further cancer types. Given the adaptive potential of phenotypic switching (PHS) strategies, understanding how it drives tumour evolution and how to break down these architectures is a major priority. Here we model the ecological dynamics behind PHS. The model is able to reproduce experimental results, and specific conditions for cancer progression and clearance reveal novel features of plastic tumours and its direct consequences on therapy resistance. Following our results we discuss \textit{transition} therapy as a novel scheme to target not only combined cytotoxicity but also the rates of phenotypic switching.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach could not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies including electrical stimulation, training, pharmacological treatments, or cell implantation that resulted in improvements in locomotor behaviour, rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers to classify these populations.

Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macro-phages and reactive M1 microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in a the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlight the time-dependent transformation of reactive mi-croglia (M1) and astrocytes (A1) into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide sug-gestions on how to increase functional outcome after SCI and discuss key therapeutic approaches.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, also in combination with other factors and cell transplantations, for repairing the injured spinal cord. As recent decades of studies strongly suggest combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

Typhulaceae Jülich is one of the cold-adapted fungal families in basidiomycetes. Typhula (Pers.) Fr. and Pistillaria Fr. representing the family are distinguished from the morphology of a stipe to a hymenium (Fries 1821). The hymenium of Typhula is distinguishable from the stipe, but indistinguishable and consecutive in the genus Pistillaria. This taxonomic criterion is ambiguous, and consequently the opinion of Karsten (1882) has been widely accepted; I the genus Typhula, basidiomata develop from sclerotia, while basidiomata develop directly from substrata in the genus Pistillaris. But, Corner (1970) observed basidiomata of Pistillaria petasitis S. Imai in Hokkaido, Japan, from sclerotia. We collected irregular sclerotia of Typhula hyperborea H. Ekstr. from Upernavik, West Greenland. This specimen had a stipe-like structure on a Poaceae plant, and sclerotia developed on its tip. In August, P. petasitis in Hokkaido, Japan, formed basidiomata directly from substrates on the ground. Similar phenomena were found from other Typhula spp. in Japan. All of these fungi had the potential to produce sclerotia in culture, and as well as the capacity of mycelial growth at ambient air temperatures in each locality when samples were collected. These findings suggest that Typhula spp. developed basidiomata not only from the sclerotia dispersed by the basidiospores but also mycelia generated by the spore germination formed basidiomata multiple times depending on their growth environments.

A paper recently published by eLife on forebrain cortical synaptic plasticity reports that retinoic acid (RA) alters synaptopodin-dependent metaplasticity in mouse dentate granule cells (Lenz et al., 2021). RA is the active form of vitamin A that functions as a ligand for nuclear RA receptors that directly bind genomic control regions to regulate gene expression (Chambon, 1996; Ghyselinck and Duester, 2019). However, some studies have suggested that RA may have nongenomic effects outside of the nucleus, particularly with regard to synaptic plasticity (Aoto et al., 2008; Zhang et al., 2018). The current results reported by Lenz et al. demonstrate that treatment with pharmacological levels of RA can alter synaptic plasticity which may be useful to treat neurological diseases (Lenz et al., 2021). However, the results reported here and those reported by others have not shown that endogenous RA is normally required for synaptic plasticity (or any other nongenomic effect) as there are no reports of genetic loss-of-function studies that remove endogenous RA in adult brain. The implication is that pharmacological levels of RA result in nongenomic effects, some of which may be helpful to treat certain diseases but in other cases this may cause unwanted side-effects.

Waddington’s epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of “landscape” in the context of dynamical system theory represents a high-dimensional cell state space, in which each cell phenotype is considered as an “attractor” that is determined by interactions among multiple variables (molecular players), and is buffered against environmental fluctuations. Further, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss these phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of “cancer attractors” – hidden stable states of the underlying regulatory network that are not occupied by normal cells. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of drug/hormone resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to drug/hormone treatment. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes ‘recanalization’, i.e. the exit from “cancer attractors” and re-entry into “normal attractors”, is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

Lineage plasticity, the switching of cells from one lineage to another has been recognized to be a cardinal property essential for embryonic development, tissue repair and homeostasis. However, such a highly regulated process goes awry when cancer cells exploit this inherent ability to their advantage, resulting in tumorigenesis, relapse, metastasis and therapy resistance. In this review, we summarize our current understanding on the role of lineage plasticity in tumor progression and therapeutic resistance in multiple cancers. Lineage plasticity can be triggered by treatment itself and is reported across various solid as well as liquid tumors. Here we focus on the importance of lineage switching in tumor progression and therapeutic resistance of solid tumors such as the prostate, lung, hepatocellular and colorectal carcinoma and the myeloid and lymphoid lineage switch observed in leukemias. Besides this, we also discuss the role of Epithelial-Mesenchymal Transition (EMT) in facilitating the lineage switch in biphasic cancers such as aggressive carcinosarcomas. We also discuss the mechanisms involved, current therapeutic approaches and challenges that lie ahead in taming the scourge of lineage plasticity in cancer.

In this paper, we present a comprehensive 4D study of the early stage of plastic deformation in a polycrystalline binary AlLi alloy. The entire microstructure is mapped with X-ray diffraction contrast tomography and a set of bulk grains is further studied via X-ray topotomography during mechanical loading. The observed contrast is analyzed with respect to the slip system activation and the evolution of the orientation spread is measured as a function of applied strain. The experimental observations are augmented by the mechanical response predicted by crystal plasticity finite element simulations to analyze the onset of plasticity in details. Simulation results show a general agreement of the individual slip system activation during loading and that comparison with experiments at the length scale of the grains may be used to fine tune the constitutive model parameters.

Introduction:In this study we evaluated the connivance of oxidative and antioxidative parameters in the pathogenesis of spinal cord injury (SCI). Although the etiology and pathogenesis of SCI remain to be fully understood, it has been suggested that reactive oxygen species (ROS) and oxidative stress may play a significant role in the pathophysiology of SCI. Furthermore, there is little information available in scientific literature about oxidative and antioxidative parameters in SCI patients. Methods:Oxidative stress was determined by measuring the levels of Lipid Peroxides (LPO) and Protein carbonyl in plasma and antioxidative parameters like Glutathione Reductase (GR), catalase and Glutathione peroxidase (GPx) in lysate in 40 SCI patients and 40 healthy subjects without SCI. However, pain was measured by McGill pain questionnaire. Results: Concentrations of catalase (p<0.01), GR (p<0.01) and GPx (p<0.01) were significantly lower in patients with SCI than in controls, and levels of oxidative stress parameters, LPO (p<0.01), Protein carbonyl (p<0.01) were significantly higher in patients than in controls. A significant positive correlation was found between LPO and pain score among SCI patients group. Furthermore, a significant positive correlation was also found between Protein carbonyl and pain score among SCI patients group than in control group. Conclusion: The present results indicate that SCI patients are exposed to oxidative stress and this escalated oxidative stress may play a role in the etiopathogenesis of the disease. Moreover, our results also show that increased oxidative stress parameters are more strongly amalgamated with pain in SCI patients.

As an uncommon cause of spinal cord infarction, anterior spinal cord syndrome can manifest with motor paralysis, loss of pain, and temperature sensation distal to the site of the lesion. The main pathogenesis of this syndrome is the disruption of blood flow in the anterior spinal artery. Mortality and morbidity differ with the etiology of the syndrome. So knowing the etiology of blood flow disruption is essential for patient management. This review article highlights the important clinical manifestation of Anterior spinal artery syndrome. Also describes etiology, pathogenesis, diagnosis, prognosis, possible management, and complications.

Background/Objectives: Traditional neurosurgical training involves a steep learning curve. The introduction of advanced simulation technologies, such as virtual reality (VR), provides an alternative method for skill acquisition, allowing for repeated practice and objective assessment. This study focuses on evaluating the learning curve associated with lumbar pedicle Kirschner wire insertion using a virtual fluoroscopic simulator among neurosurgical residents. Methods: Eighteen neurosurgery residents and two interns participated in this study. Participants’ initial skill levels were assessed through a questionnaire. Performance metrics, including insertion accuracy, time, and the number of virtual X-ray scans, were recorded across multiple attempts until a “practical learning plateau” was reached. Statistical analyses were conducted to model learning curves, assess the correlation between pre-training experience and performance. Results: The average number of attempts required to stabilize performance was 5.61. Learning rates varied, with some residents showing rapid improvement while others progressed more slowly. Higher accuracy in wire placement correlated with reduced usage on X-rays over time. However, experienced residents did not necessarily learn faster, indicating potential challenges in adapting to new simulation-based methods. Post-training feedback highlighted the simulator’s utility in increasing confidence and skill levels, although some limitations in anatomical accuracy were noted. Conclusions: This study demonstrates the potential of virtual simulation to enhance neurosurgical training by providing a controlled environment for repeated practice and objective feedback. Simulation-based training can effectively complement traditional methods, though individualized approaches may be necessary to accommodate varying learning rates among residents. Further refinement of simulation tools and their integration into standard training curricula are recommended.

Artificial intelligence has garnered significant attention in recent years as a rapidly advancing field of computer technology. With the continual advancement of computer hardware, deep learning has made breakthrough developments within the realm of artificial intelligence. Over the past few years, applying deep learning architecture in medicine and Industrial anomaly inspection has significantly contributed to solving numerous challenges related to efficiency and accuracy. Despite excellent results in radiological, pathological, endoscopic, ultrasonic, and biochemical examinations, this paper utilizes deep learning combined with image processing to identify spinal canal and vertebral foramen dimensions. In existing research, technologies such as corrosion and expansion in magnetic resonance image (MRI) processing have also strengthening the accuracy of results. Indicators such as area and Intersection over Union (IoU)are also provided for assessment. Among them, the mean average precision (mAP), for identifying intervertebral foramen (IVF) and intervertebral disc (IVD) through YOLOv4 is 95.6%. Resnet50 mixing U-Net was employed to identify the spinal canal and intervertebral foramen and achieved IoU scores of 79.11% and 80.89%.

Background: Prediction of neurorehabilitation outcomes after a Spinal Cord Injury (SCI) is crucial for healthcare resource management and improving prognosis and rehabilitation strategies. Arti-ficial neural networks (ANNs) have emerged as a promising alternative to conventional statistical approaches for identifying complex prognostic factors in SCI patients. Materials: a database of 1256 SCI patients admitted for rehabilitation was analyzed. Clinical and demographics data and SCI characteristics, were used to predict functional outcomes using both ANN and linear regression models. The former was structured with input, hidden, and output layers, while the linear regression identified significant variables affecting outcomes. Both ap-proaches aimed to evaluate and compare their predictive accuracy for rehabilitation outcomes measured by the Spinal Cord Independence Measure (SCIM) score. Results: Both ANN and linear regression models identified key predictors of functional outcomes, such as age, injury level, and initial SCIM scores (correlation with actual outcome: R=0.75 and 0.73, respectively). When alimented also with parameters recorded during hospitalization, the ANN highlighted the importance of these additional factors like motor completeness and compli-cations during hospitalization, showing an improvement in its predictive accuracy (R=0.87). Conclusion: ANN seemed to be not widely superior to classical statistics in general, but, taking into account complex and non-linear relationships among variables, emphasized the impact of complications during the hospitalization on recovery, particularly respiratory issues, deep vein thrombosis, and urological complications. These results suggested that the management of com-plications is crucial for improving functional recovery in SCI patients.

Keywords: Spine surgery 1; Metastatic spinal cord compression 2; Spinal metastasis 3; Cancer treatment.

Background and Objectives: C-arm free MIS techniques can offer significantly reduced rates of postoperative complications such as blood loss and hospitalization time. Another advantageous long-term aspect is the notably diminished exposure to radiation which is known to cause ma-lignant changes. This study emphasizes that, in some cases of spinal conditions which require a procedural intervention, C-arm free MIS techniques hold stronger indications than open surgeries guided by image intensifier. Materials and Methods: In this research, a retrospective analysis and review of various cervical and thoracic spinal procedures, performed in our hospital, by applying C-arm free techniques. The course of the study explains the basic steps of the procedures and demonstrating postoperative or intra-operative results. For anterior cervical surgery, we performed OPLL resection, while for posterior cervical surgery, we performed posterior fossa decompression for Chiari malformation, minimally invasive cervi-cal pedicle screw fixation (MICEPS) and modified Goel technique with C1 lateral mass screw for atlantoaxial subluxation. Re-garding the thoracic spine, we performed anterior correction for Lenke type 5 scoliosis, and transdiscal screw fixation for DISH fractures. Results: C-arm free techniques are safe procedures that offer precise and high-quality postoperative results by offering sufficient spine alignment and adequate decompression depending on the case. Blood loss, postoperative pain and wound infection are other important aspects of spine surgery that must be always taken into consideration. Conclusions: Navigated C-arm free techniques are safe and precise procedures implemented in the treatment of surgically demanding conditions. They can significantly increase accuracy while decreasing the operative time. They represent the advancement in the field spine surgery and are hailed as the future of the same

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, high-dose Cy exposure can cause nerve injury with symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor ability. Moreover, it was found that medium- and high-dose Cy exposure can cause disordered energy metabolism in hippocampal cells and an abnormal release of the neurotransmitter Glu. Second, pathological brain sections showed that the middle and high doses of Cy caused deformation, reduction and disorder of hippocampal pyramidal cells, a decrease in the number of Nissl bodies, pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, with the increase in exposure dose, the morphological changes in hippocampal synapses were more obvious, including blurred synaptic spaces, decreased synaptic vesicles and a decreased number of synapses. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus, and the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators, inflammatory factors, synaptic plasticity factors and apoptosis factors, suggesting that Cy may cause nerve damage in rats and has a close relationship with A2AR.

Background: Spinal schwannomas and meningiomas are the most common spinal cord benign tumors in adults and total excision is the goal of the treatment. The traditional surgical approach is performed by total laminectomy, but recently unilateral hemilaminectomy has been recognized as a valuable surgical alternative. We report the clinical results of patients affected by spinal schwannoma and meningioma in whom total laminectomy or unilateral hemilaminectomy were performed. Material and Methods: A retrospective study of patients who underwent resection of spinal meningioma or schwannoma by laminectomy or unilateral hemilaminectomy approaches in our Institute from January 2013 to January 2023 was made. The baseline data of these patients, operative approach and postoperative outcome were compared. Results: The study was performed on 41 patients with mean age of 62.5 ±14.6 years. Our series included 24 (59%) cases of schwannomas and 17 (41%) cases of meningiomas, with a prevalent location in the thoracic spine. The average schwannomas volume was 3,6 ±2,7 cm3, whereas the average meningiomas volume was 1.1 ±0.5 cm3. Total excision was achieved in all cases. Operative time of schwannomas was longer (p=0.001) respect to meningiomas with higher intra-operative blood loss (p=0.000). Total laminectomy approach was performed in 24 out of 41 patients (59%) and unilateral hemilaminectomy approach in 17 out of 41 (41%) patients. Unilateral hemilaminectomy was associated with shorter postoperative bed rest (p=0.003), shorter hospitalization (p=0.028) and lower postoperative pain (p=0.02) respect to total laminectomy. Conclusions: Both spinal schwannomas and spinal meningiomas in various size can be safely and effectively treated with unilateral hemilaminectomy approach. This approach grants more advantages compared with standard total laminectomy, including shorter postoperative bed rest, shorter hospitalization and reduced postoperative pain.

The review starts by highlighting the significance of nuclear power plants in contemporary world, especially its indispensable role in the global efforts to reduce CO2 emissions. Then, it describes the impact of irradiation on microstructure and mechanical properties of reactor structural materials. The main part provides the reader with a thorough overview of crystal plasticity models developed to address the irradiation effects so far. All three groups of most important materials are included. Namely, the Zr alloys used for fuel cladding, austenitic stainless steels used for reactor internals and ferritic steels used for reactor pressure vessel. Other materials, especially those considered for construction of future fission and fusion nuclear power plants, are also mentioned. The review pays also special attention to ion implantation and instrumented nanoindentation which are a common way to substitute costly and time-consuming neutron irradiation campaigns.

Single-particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here we tested the possibility of extracting from the nano-resolved (16 ms and 30 nm) population dynamics of several quantum dots, time-binned at the second time-scale, the rapid structural changes of the cell membrane surface. We used for this proof-of-concept study bright, small and stable biofunctional QD nanoconstructs recognizing the neuronal cannabinoid type 1 (CB1) receptor and a commercial point-localization microscope to reconstruct in 3D the dynamics of the plasma membrane surface of cultured cells with a spatial resolution of tens of nanometers. CB1 receptor was chosen because it’s a highly expressed and fast diffusing membrane protein. Therefore, rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allowed highly precise reconstruction of the membrane surface in less than one minute. QD nanoconstructs diffused into the membrane of synaptic clefts allowing the entire topological reconstruction of the presynaptic component. In addition, we demonstrated successful reconstruction of the remarkably high dynamics of membrane surface topology at the second time-scale both in HEK-293 cell filopodia and axons. Our results show that this novel technique, which we named nanoPaint, is a powerful precision tool for the study of the structural plasticity of cell membrane surfaces.

Keywords: spinal muscular atrophy (SMA); survival of motor neuron 1 (SMN1); SMN2; SMN protein; antisense oligonucleotide (ASO); nusinersen; gene therapy; onasemnogene; risdiplam; small molecule, combination therapy

Wear simulation aims to assess wear rates and their dependence on factors like load, kinematics, temperature, and implant orientation. Despite its significance, there's a notable gap in research concerning advancements in simulator control systems and the testing of clinically relevant waveforms. This study addresses this gap by focusing on enhancing the conventional proportional-integral-derivative (PID) controller used in joint simulators through the development of a fuzzy logic-based controller. Leveraging a single-input-multiple-output (SIMO) fuzzy logic control system, the study aimed to improve displacement control, augmenting the traditional Proportional-Integral (PI) tuning approach. Implementation and evaluation of a novel Fuzzy-PI control algorithm were conducted on the Leeds spine wear simulator. The study also included testing of daily-living (DL) profiles, particularly from the hip joint, to broaden the scope of simulation scenarios. While both the conventional PI controller and the Fuzzy-PI controller met ISO tolerance criteria for the spine flexion-extension (FE) profile at 1Hz, the Fuzzy-PI controller demonstrated superior performance at higher frequencies and with DL profiles due to its real-time adaptive tuning capability. The Fuzzy-PI controller represents a significant advancement in joint wear simulation, offering improved control functionalities and a more accurate emulation of real-world physiological dynamics.

Gamma-aminobutyric acid (GABA) and glycine act as inhibitory neurotransmitters. Three types of inhibitory neurons and terminals, GABAergic, GABA/glycine co-releasing, and glycinergic, are orchestrated in the spinal cord neural circuits and play key roles in the regulation of pain, locomotive movement, and respiratory rhythms. Herein, we first describe GABAergic and glycinergic transmission and inhibitory networks, which consist of three types of terminals, in the mature mouse spinal cord. Second, we describe the developmental formation of GABAergic and glycinergic networks, with specific focus on the differentiation of neurons, formation of synapses, maturation of removal systems, and changes in their action. GABAergic and glycinergic neurons are derived from the same domains of the ventricular zone. Initially, GABAergic neurons are differentiated and their axons form synapses. Some of these neurons remain GABAergic in lamina I and II. Many of GABAergic neurons convert to co-releasing state. The co-releasing neurons and terminals remain in the dorsal horn, whereas many of co-releasing ones ultimately become glycinergic in the ventral horn. During the development of terminals and the transformation from radial glia to astrocytes, GABA and glycine receptor subunit compositions markedly change, removal systems mature, and GABAergic and glycinergic action shifts from excitatory to inhibitory.

The aim of the study was to assess the relationship between the shape of the anterior-posterior curvature of the spine and body composition in school-children. The study included 257 children, aged 11-12. Correct spinal curvature was established in 106 (41.08%) subjects. Other types included: decreased kyphosis and correct lordosis - 40 participants (15.50%), correct kyphosis and decreased lordosis - 24 individuals (9.30%), increased kyphosis and correct lordosis - 17 subjects (6.59%), correct kyphosis and increased lordosis - 22 children (8.53%), decreased kyphosis and decreased lordosis - 32 people (12.40%), decreased kyphosis and increased lordosis - 4 of the examined subjects (1.55%), increased kyphosis and lordosis - 13 people (5.04%). In addition, 134 (51.94%) demonstrated scoliotic posture and 8 (3.10%) scoliosis. There were significant relationships between the shape of the anterior-posterior curvatures and body composition in school-children. Those with a strong body build (predominance of mesomorphs) were generally characterised by the correct formation of these curvatures. In contrast, lean people (with the predominance of ectomorphic factors) were more likely to experience abnormalities. No correlations with body composition were observed in the group with scoliotic posture or scoliosis.

Background: Drought, N deficiency and herbivory are considered the most important stressors caused by climate change in the agro- and eco-systems and varied in space and time shaping a highly dynamic and heterogeneous stressful environments. This study aims to evaluate the to-mato morpho-physiological and metabolic responses to combined abiotic and herbivory at dif-ferent within-plant spatial levels and temporal scales. Methods: Leaf-level morphological, gas exchange traits and VOC profiles were measured in to-mato plants exposed to N deficiency and drought, T. absoluta larvae and their combination. Ad-ditive, synergistic or antagonistic effects of the single stress when combined were also evaluat-ed. Morpho-physiological traits and VOC profile were also measured on leaves located at three different positions along the shoot axes. Results: The combination of the abiotic and biotic stress has been more harmful than single stress with antagonistic and synergistic but non-additive effects for the morpho-physiological and VOC tomato responses, respectively. Combined stress also determined a high within-plant phenotypic plasticity of the morpho-physiological responses. Conclusions: These results suggest that the combined stress in tomato determined a “new stress state” and a higher within-plant phenotypic plasticity which could permit an efficient use of the growth and defence resources in the heterogeneous and multiple stressful environmental condi-tions.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological; natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, also physiological nAAbs exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR; n=1739 and anti-SARS-CoV-2 IgG; n=330) and nAAbs (anti-citrate synthase IgG, IgM; n=1739) were measured by in-house and commercial ELISAs, using Croatian (Osijek) anonymous samples with documented vaccination background. Results were subsequently compared for statistical evaluation. Interestingly, IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p< 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p= 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls; vector/mRNA vaccines p= 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network.

The great pipefish Syngnathus acus is one of the most representative European syngnathid, being highly associated with seagrass and macroalgal beds. Surprisingly, the ecology of this ovoviviparous marine fish has received scanty attention. The population inhabiting three sites on Cíes Archipelago (Atlantic Islands National Park, NW Spain) was monitored in 2017-2018 for spatial and temporal changes in abundances, reproduction traits, trophic niche occupancy and dietary regimes across reproduction states through an isotopic (δ13C and δ15N) approach. Abundances were highly variable across seasons and sites, decreasing significantly from mid-autumn. The population consisted almost exclusively of large adults that migrate by the end of the breeding season, which extended from mid-spring to summer. Operational sex ratios suggest that the species is sex-role reversed. S. acus is a secondary consumer (Trophic position= 3.36 ± 0.05) preferring amphipods but displaying annual and seasonal dietary plasticity. Mature fish were less selective than immatures (especially females) with a higher preference for amphipods (36-68%) in the former. The second most preferred prey were carideans, copepods or isopods, depending on the year and reproduction state. Overall, the wider trophic niches in females and immature specimens compared to males and mature fish would indicate a higher variability in both the use of prey resources and/or their origin. The present study highlights the trophic plasticity and unique features of S. acus population in Cíes Archipelago, especially regarding the outstanding size of the fish and the exceptional occurrence of breeders.

Electrical transmission between neurons is largely mediated by gap junctions. These junctions allow the direct flow of electric current between neurons, and in mammals are mostly composed of the protein connexin (Cx)36. Circuits of electrically coupled neurons are widespread in these animals, plus, experimental and theoretical evidence supports the notion that, beyond synchronicity, these circuits are able to perform sophisticated operations like lateral excitation and inhibition, noise reduction, as well as the ability to selectively respond upon coincident excitatory inputs. Although once considered stereotyped and unmodifiable, we now know that electrical synapses are subject to modulation and, by reconfiguring neural circuits, these modulations can alter relevant operations. The strength of electrical synapses depends on gap junction conductance, as well as on its functional interaction with the electrophysiological properties of coupled neurons. In particular, voltage dependent channels of the non-synaptic membrane critically determine the efficacy of transmission at these contacts. Consistently, modulatory actions on these channels have been shown to represent relevant mechanisms of plasticity of electrical synaptic transmission. Here we review recent evidence on the regulation of electrical synapses of mammals, the underlying molecular mechanisms, and the possible ways in which they affect circuit function.

Brown-Séquard Syndrome (BSS) is a rare spinal cord injury characterized by asymmetrical motor and sensory dysfunction. Trauma to the spinal cord, particularly the hemi section, is the primary cause. Diagnosis involves a thorough medical history, physical examination, and imaging studies. Treatment focuses on stabilization, rehabilitation, and potential emerging therapies. This article provides a comprehensive overview of BSS, including its causes, symptoms, diagnosis, and treatment.

Transcutaneous electrical stimulation of the spinal cord is used to restore locomotion and body weight support in patients with severe motor disorders. We studied effects of this non-invasive stimulation on postural control in healthy subjects. Stimulation at the L1-L2 vertebrae was performed to activate the extensor muscles of the lower limbs. Because postural regulation depends on the cognitive style, the effects of the stimulation were analyzed separately in field-dependent (FD) and field-independent (FI) participants. During the study young adults (N=16, half FD and half FI participants, all right dominant leg) stood on a force platform in a soundproof chamber with their eyes closed. Stimulation was applied in the midline between the L1-L2 vertebrae or over the left or right dorsal roots of the spinal cord; under control condition there was no stimulation. Stimulation destabilized posture in healthy subjects, whereas patients with movement disorders usually showed an improvement in postural control. In FD participants, left dorsal root and midline stimulation increased several postural parameters by up to 30%. Dorsal root stimulation on the side of the supporting leg reduced postural control, while stimulation on the side of the dominant leg did not. No significant changes were observed in the FI participants.

Background Main treatment modality for spinal meningiomas (SM) is gross total resection (GTR). However, optimal timing of surgery, especially in cases with absent or mild neurological symptoms remains unclear. The aim of this study is to assess the impact of early-stage resection on neurological outcome, quality of life (QoL) and quality of care. The primary objective was a favorable neurological outcome (McCormick scale 1); Methods: We retrospectively analyzed data from patients operated on SM between 2011 and 2021. Patients with mild neurological symptoms preoperatively (McCormick scale 1 and 2) were compared to those with more severe neurological symptoms (McCormick scale 3-5). Disabilities and QoL were assessed according to validated questionnaires (SF36, ODI, NDI). Results: Age, spinal cord edema, thoracic localization, and spinal canal occupancy ratio were associated with more severe neurological symptoms (all p<.05). Patients presented with mild symptoms were associated with favorable neurological outcome (OR: 14.778 (95%CI 3.918-55.746, p<.001), which is associated with shorter hospitalization, better QoL and less disabilities (p<.05). Quality of care was comparable in both cohorts; Conclusions: Early surgical intervention of SM, before the development of severe neurological deficits, should be considered as it is associated with a favorable neurological outcome and quality of life.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality. Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis thus becoming the main cause of HCC incidence. NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition. Mitochondria are highly dynamic organelles which may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”). Mounting evidence highlighted that mitochondrial dysfunction due to loss of mitochondrial flexibility, may arise before overt NAFLD and since the early stages of liver injury. Mitochondrial failure not only promotes hepatocellular damage, but also release signals (mito-DAMPs) which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation. Furthermore, one of the key events in malignant hepatocytes is represented by remodeling of glucidic-lipidic metabolism combined to reprogramming of mitochondrial functions, optimized to deal with energy demand. In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.

The relative dislocation density of aluminum and copper samples is quantitatively measured using linear Resonant Ultrasound Spectroscopy (RUS). For each metallic group, four samples were prepared with different thermomechanical treatments in order to induce changes in their dislocation densities. The RUS results are compared with Nonlinear Resonant Ultrasound Spectroscopy (NRUS) as well as Second Harmonic Generation (SHG) measurements. NRUS has a higher sensitivity by a factor of two to six and SHG by 14% to 62%. The latter technique is, however, faster and simpler. As main a result we obtain a quantitative relation between the changes in the nonlinear parameters and the dislocation density variations, which in a first approximation is a linear relation between these differences. We also present a simple theoretical expression that explains the better sensitivity to dislocation content of the nonlinear parameters with respect to the linear ones. X-Ray diffraction measurements, although intrusive and less accurate, support the acoustics results.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

The interplay between Diffuse Idiopathic Skeletal Hyperostosis (DISH) and the gut microbiota represents a compelling area of research, offering insights into the relationship between spinal degenerative diseases and the gut's microbial inhabitants. This comprehensive review seeks to unravel the complex connection, shedding light on its implications for human health and potential therapeutic avenues. A crucial section dives into the world of gut microbiota (GM), exploring its impact on human health, featuring its defining characteristics, and highlighting its role in metabolism, immunomodulation, host interaction, and how its composition changes over time. The subsequent portion delves into the relationship between microbiome composition and pathological bone development, including the link between Intervertebral Disc Degeneration (IDD) and gut inflammation, emphasizing how gut inflammation and GM dysbiosis play pivotal roles. Further dissecting the interconnections, various axes of influence, including the gut-spine axis, gut-bone axis, gut-joint axis, gut-disc axis (specific to DISH), gut-ligament axis, and gut-muscle axis, are discussed. Of particular interest is the section on the impact of GM on DISH-derived pain, addressing a critical aspect of the condition's manifestation. The review discusses the potential of GM modulation as a treatment for DISH, providing hope for therapeutic advancements. Additionally, it highlights the positive impact of lifestyle interventions, such as dietary modifications, sleep optimization, and exercise regimens, in mitigating GM dysbiosis and potentially improving DISH outcomes. Lastly, the intriguing prospect of fecal microbiome transplant and its implications for DISH management is examined, opening new avenues for research and therapeutic interventions. In conclusion, this comprehensive review underscores the intricate interplay between DISH and the gut microbiota, offering a fresh perspective on the impact of GM on spinal degenerative diseases. It emphasizes the potential for innovative treatments, such as GM modulation and lifestyle interventions, and presents fecal microbiome transplant as an exciting area for future exploration.

Background: In spinal cord injury, radical treatment is still a persistent hope for patients and clinicians. Our study aimed to determine the different histological changes in central, cranial and caudal sites of compressed spinal cord as a result of neuroectodermal stem cells (NESCs) transplantation in rats. Material and methods: For extraction of NESCs, future brains were extracted from mice embryos (10-days old) and cultured. Eighty, male rats were divided randomly into control, sham (20 rats each); while 40 rats were subjected to compressed spinal cord injury (CSCI). Seven days after spinal cord injury, rats were subdivided into 2 groups (20 rats each); an untreated and treated with NESCs injected cranial and caudal to the site of the spinal cord injury. Rats were sacrificed 4 weeks after transplantations of NESCs and specimens from the spinal cord at the central, cranial and caudal to site of spinal cord injury were proceeded to be stained with haematoxylin & eosin, osmic acid and Immunohistochemistry of glial fibrillary acidic protein (GFAP). Results: Sections of CSCI revealed areas of hemorrhages, necrosis and cavitation limited by reactive astrocytosis, with upregulation of GFAP expression. Evidence of remyelination and mitigation of histopathological features, reactive astrocytosis in CSCI sections were more pronounced in cranial than in caudal region. Conclusions: NESCs transplantation ameliorated the pathological changes, promoted remyelination.

We recently reported that in the spinal cord of PPMS or SPMS patients, large areas of periplaque demyelinating lesions extend distance away from plaque borders. Such lesions are characterized by a progliotic TGF-beta 1 signature accompanied by: i) a low-grade inflammatory reaction, ii) an extensive astrocytosis and iii) a process of incomplete demyelination. It was proposed that, while efficiently dampening inflammation in MS spinal cords, TGF-beta 1 could promote astrocytosis, prevent remyelination and possibly trigger alterations of myelin synthesis. In light of these findings, a re-interpretation of two large neuropathological studies performed on MS brains and spinal cords is provided here. While results from these studies clearly showed that active plaques do not display any region-specific distribution, an important point was apparently overlooked and not discussed by the authors: a significantly higher percentage of inactive plaques was found in MS spinal cords as compared to brains and, conversely, the percentage of slowly-expanding (or smoldering) lesions was significantly lower in the spinal cord as compared to the brain. These data indicate that the spinal cord environment may be more favorable to the resolution of inflammation. Downstream of the autoimmune process leading to plaque formation, region-specific mechanisms may thus drive the outcome of active plaques. While inflammation triggers tissue destruction, inflammation may also be needed for effective tissue repair and an inappropriate dampening of inflammatory events may possibly translate into a poor level of remyelination in MS spinal cords. It is proposed here that TGF-beta 1 is involved in such a brain-spinal cord dissociation of active plaques outcome.

Study design : Technical note. Objectives: To present a new spinal shortening technique for tethered cord syndrome. Background : Tethered cord syndrome (TCS) is a debilitating condition of progressive neurological decline. Surgical detethering for TCS is a gold standard. However, symptomatic retethering of TCS has been reported in 5%–50% of patients after initial release. To solve this problem, posterior spinal shortening osteotomy has been reported. This technique has risks of massive blood loss and neurological deterioration. The authors hereby report a new safe spinal shortening technique for tethered cord syndrome. Materials and Methods : A 31-year-old man with gait disturbance was referred to our hospital. After the delivery, he underwent surgical untethering of spinal cord in another hospital. He had hyperreflexia of Achilles tendon reflex and muscle weakness of bilateral legs (MMT 3-4). He also had urinary and bowel incontinence, and total sensory loss below L5.Anteroposterior lumbar radiogram indicates partial laminectomy of L3 and L4. Lumbar MRI showed retethering of spinal cord. Results: He underwent new spinal shortening technique for tethered cord syndrome under the guidance of O-arm navigation. First, from anterior approach disectomy from T12 to L3 was performed. Second, from posterior Ponte osteotomy was done from T12 to L3, shorten the spinal column 15 mm. The patient was successfully treated surgically. Postoperative lumbar MRI showed the tension of spinal cord was released. Manual muscle testing results and sensory function of the left leg had recovered almost fully on final follow-up at one year. Conclusions/Level of Evidence: Retethered spinal cord after initial untethering was difficult to treat. This new spinal shortening technique was effective and very safe technique to release the tension of spinal cord. Level V.

The operating theatre represents a key contributor to healthcare-derived emissions. Here, we outline the carbon footprint of a lumbar microdiscectomy at our regional unit in Greater Manchester, with the use of AI technology. In doing so, we aim to define the extent of the environmental impact and identify carbon hotspots for sustainable change. Our unit of analysis covered the start of the patient journey into hospital through to the final outpatient appointment. Publicly available and locally sourced data was used. An inventory analysis of two lumbar microdiscectomies was conducted. Each item was categorised reconciled against our AI-powered ‘CO2 analysis’ database. Kilograms of carbon dioxide equivalent (kg CO2e) was chosen as the primary measure of impact. An average lumbar microdiscectomy at our trust generates 477.73kg CO2e. The operation (173.89kg CO2e, 36.40%) and the inpatient stay (144.67kg CO2e, 30.28%) constituted the biggest contributors. Single-use intraoperative equipment contributed to over three-quarters of the total emissions from the operation. By defining the environmental burden of elective spinal surgery, we have identified carbon hotspots to target for sustainable change. Substituting polluting elements for carbon-friendly alternatives and challenging the single-use culture, modern healthcare systems can help pave the way to a ‘net zero’ healthcare system.

Background: The diagnosis of metabolic syndrome (MetS) is a challenge in people with spinal cord injury (SCI). We aimed at identifying clinical risk factors or early markers of MetS in SCI that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. Methods: 168 patients with chronic (>1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Results: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in minutes/week (OR: 0.998, 95%CI: 0.996, 0.999) and more severe pain symptoms as assessed by numeral rating scale (OR: 1.353, 95%CI: 1.085, 1.793). Conclusions: In patients with SCI, intense pain symptoms and poor LTPA may suggest a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insu-lin-sensitivity and comorbidities.

Classifying spinal tumors can be challenging due to nonspecific clinical and radiological qualities, and a precise biopsy is crucial for an accurate diagnosis and treatment planning. This study aimed to enhance the accuracy and efficiency of spinal biopsies integrating Cone Beam Computed Tomography (CBCT) and magnetic resonance imaging (MRI) modalities using an O-arm CT navigation system. Eighteen patients with diverse spinal lesions underwent 18 biopsies following the Stealth Station navigation system Spine 8 protocol. Preoperative MRI scans were merged with intraoperative CT navigation systems for continuous monitoring during the biopsy process. The combined imaging technique accurately identified the diseased lesion type in all biopsies, demonstrating 100% sensitivity and specificity. In conclusion, combining MRI and CT imaging modalities significantly improved spinal biopsy accuracy and efficiency, differentiating between pathological entities. However, large-scale studies are desired to validate these findings and investigate potential benefits in different clinical scenarios. Although this method requires general anesthesia, its potential profits in avoiding misdiagnosed lesions and decreasing the need for further invasive procedures make it a promising approach for improving spinal biopsy accuracy and efficiency.

Background/Objectives: The aim of the project is a longitudinal assessment of body image and mental health in scoliosis females pre-, postoperatively and in a follow-up, and implementation (one group-CBT scoliosis sample, CBTSS) or not (second group-control scoliosis sample, CSS) of CBT interventions. A healthy female sample (HFS) was also selected for comparative purposes. Methods. 36 in total AIS patients participated in the 1st and 2nd study phases, whereas 23 were eligible in the follow-up. Regarding HFS, 18 participants were included in the study. The CBT intervention took place pre- and postoperatively, during the patients' stay in hospital. Participants completed the Spinal Appearance Questionnaire (SAQ), Body Esteem Scale (BES) and Strengths and Difficulties Questionnaire-25 (SDQ-25). Body image was also assessed using a virtual reality-based application “Avatar Scoliosis 3D”. Results: The difference between the desired and objective, actual body shape is significant preoperatively both in the CBTSS and CSS at p

The pivotal role of the basolateral amygdala (BLA) in the emotional modulation of hippocampal plasticity and memory consolidation is well established. Specifically, multiple studies have demonstrated that the activation of the noradrenergic (NA) system within BLA governs these modulatory effects. However, most of the current evidence has been obtained by direct infusion of synthetic NA or beta-adrenergic agonists. In the present study, we aimed to investigate the effect of endogenous NA release in the BLA, induced by a natural aversive stimulus (coyote urine), on memory consolidation for a neutral hippocampal-dependent task. We combined a weak version of the object location task (OLT) with mild predator odor exposure (POE) for our experiments. To investigate the role of the BLA in memory modulation, a subset of the animals (Wistar rats) were treated with the non-selective beta-blocker propranolol at the end of the behavioral procedures. Hippocampal tissue was collected either 90 minutes after drug infusion or 24 hours after the OLT test. The samples were used to determine the levels of phosphorylated CREB (pCREB) and activity-regulated cytoskeleton-associated protein (Arc) - two molecular markers of experience-dependent changes in neuronal activity. The result suggests that POE is a behavioral paradigm suitable for studying the interaction between BLA and the hippocampus in memory prioritization and selectivity.

The paper describes an application of machine learning approach for parameter optimization. The method is demonstrated for the elasto-viscoplastic model with both isotropic and kinematic hardening. It is shown that the proposed method based on long-short term memory networks enabled to obtain reasonable agreement of stress-strain curves for cyclic deformation in low-cycle fatigue regime. The main advantage of the proposed approach over traditional optimization schemes lies in the possibility to get parameters for a new material without the necessity to conduct any further optimizations. As the power and robustness of the developed method was demonstrated on the very challenging problem (cyclic deformation, crystal plasticity, self-consistent model, isotropic and kinematic hardening), it is directly applicable to other experiments and models.

This article presents a novel computational approach to visualizing memristor dynamics within a simulated neural network. Memristors, known for their ability to emulate synaptic plasticity due to their variable resistance characteristics, are key components in neuromorphic computing and hold potential for advancing our understanding of neural processes. Our study introduces a sophisticated memristor model that incorporates non-linear resistance changes, simulating the complex behavior of synaptic connections in a neural network.The neural network, consisting of multiple interconnected neurons with memristor-based synapses, is subjected to a series of electrical stimuli. Each memristor's resistance is modulated in response to the applied voltage, mimicking the synaptic weight adjustments that occur during learning and memory formation in biological neural networks. To effectively illustrate these changes, we employ a high-contrast color mapping scheme, where the varying resistance of each memristor is represented by distinct colors, providing a clear and intuitive visualization of synaptic modifications over time.Our simulation runs through multiple iterations, demonstrating how synaptic weights evolve in response to different input patterns. The use of an extended voltage range and increased scaling factors ensures pronounced changes in memristance, enhancing the visibility of synaptic adaptations. The resulting visualizations offer a compelling representation of how memristors can mimic the dynamic nature of biological synapses, contributing to the field of neuromorphic engineering and deepening our comprehension of neural mechanisms underlying learning and memory.This work not only showcases the potential of memristors in simulating neural behavior but also provides a valuable educational tool for illustrating complex concepts in neuroscience and neuromorphic computing. The insights gained from this study pave the way for further exploration into the development of advanced neural network models and the design of memristor-based computing systems.

The classification of tumors in subtypes, characterized by phenotypes determined by specific differentiation pathways, aids diagnosis and directs therapy towards targeted approaches. However, with the advent and explosion of next-generation sequencing, cancer phenotypes are turning out to be far more heterogenous than initially thought, and the classification is continually being updated to include more subtypes. Tumors are indeed highly dynamic and they can evolve and undergo various changes in their characteristics during disease progression. The picture becomes even more complex when tumor responds to a therapy. In all these cases, cancer cells acquire the ability to trans-differentiate, changing subtype, and adapt to changing microenvironments. These modifications affect the tumor's growth rate, invasiveness, response to treatment, and overall clinical behavior. Studying tumor subtype transitions is crucial for understanding tumor evolution, predicting disease outcomes, and developing personalized treatment strategies. We discuss this emerging hallmark of cancer and the molecular mechanisms involved at the crossroads between tumor cells and their microenvironment, focusing on four different human cancers in which tissue plasticity causes a subtype switch: breast cancer, prostate cancer, glioblastoma and pancreatic adenocarcinoma.

Plants exhibit the capacity for adaptation through their metabolic processes to various changes in environmental conditions. Investigating these adaptations in current and future climatic scenarios is of great importance for ensuring productive agricultural crops. This adaptative potential is commonly employed as an indicator of genotypes with higher potential in breeding programs. However, the complexity and interaction of plant metabolic parameters pose a challenge to selection strategies. In this context, the aim of this study was to explore phenotypic plasticity within the germplasm of Hybrid Timor coffee. Additionally, we assessed the utility of the Phenotypic Plasticity Index (MVPi) as a promising tool to predict genotype performance across diverse climatic conditions. To achieve this, we evaluated the performance of seven accessions from the Hybrid Timor germplasm in comparison to the Rubi and IPR 100 cultivars, known for their susceptibility and resistance to drought, respectively. The experiment was conducted at greenhouse conditions, with two treatments: a control scenario, maintaining soil moisture near its maximum water-holding capacity, and a water deficit scenario involving irrigation cessation followed by rehydration. Data encompassing physiological, biochemical, and growth aspects were collected during three distinct stages: pre-application of water deficit, its imposition, and subsequent rehydration. Furthermore, field evaluations of the productivity of the same genotypes were carried out over two consecutive seasons. Based on physiological and biochemical assessments, the MVPi was computed, employing Euclidean distance between principal component multivariate analysis scores. Subsequently, this index was correlated with growth and productivity data through linear regressions. Our findings reveal that the more plastic genotypes, capable of significantly altering physiological and biochemical parameters in response to environmental stimuli, exhibited reduced biomass loss in both aerial and root parts, consequently positively influencing their productivity. Enhanced plasticity was particularly prominent in accessions from the MG Germplasm Collection: MG 311 - Hybrid Timor UFV 428-02, MG 270 - Hybrid Timor UFV 377-21, and MG 279 - Hybrid Timor UFV 376-31, alongside the Rubi MG 1192 cultivar. The MVPi emerged as a valuable instrument to assess genotype adaptability and predict their performance under varying climatic scenarios.

Attention Deficit-Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with high incidence in children and adolescents characterized by motor hyperactivity, impulsivity, and inattention. MRI-based evidences support that neuroanatomical abnormalities as the volume reduction of neocortex and hippocampus are shared by several neuropsychiatric diseases as schizophrenia, autism spectrum disorder and ADHD. In addition, it is well documented the abnormal development and postnatal pruning of dendritic spines of neocortical neurons in schizophrenia, autism spectrum disorder and intellectual disability. A recent report using the prenatal nicotine exposure murine model of ADHD support a delay in spine maturation in CA1 neurons correlated with impaired working memory and hippocampal long-term potentiation (LTP). In vivo spine imaging show that dendritic spines are dynamic structures exhibiting Hebbian and homeostatic plasticity triggering intracellular cascades involving glutamate receptors, calcium influx and remodeling of F-actin network. The LTP-induced insertion of postsynaptic glutamate receptors is associated to the enlargement of spine head and long-term depression (LTD) to the spine shrinkage. In this review, we summarize recent evidence emerged from meta-analysis of brain imaging data from ADHD patients, risk loci from global genome-wide analysis and new reports focused on spine molecular structure and dynamics using in vivo imaging in neocortex and hippocampus.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

Working memory (WM) is a brain system for short-term storage and manipulation of information and plays an important role in complex cognitive tasks. In the synaptic theory of WM memorized elements are stored in the form of short-term potentiated connections in a sample population of neurons. In this paper, we show that such populations can be formed due to the mechanisms of spike-timing-dependent plasticity (STDP) – the phase dependence associated with the ratio of the pulse times of the interacting neurons. We propose a WM model considering two types of plasticity: short-term plasticity and STDP. We have shown formation of neuronal clusters encoding items in the WM model, that can be formed by external stimulation of a group of neurons due to the mechanisms of STDP and hold and reactivated by short-term plasticity mechanisms. The dynamic formation of neuronal clusters instead of pre-formed clusters gives additional flexibility to the model.

Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.

We have previously developed several successful decellularization strategies yielding porcine cardiac extracellular matrices (pcECMs), which exhibit tissue-specific bioactivity and bioinductive capacity when cultured with various pluri- and multipotent stem cells. Here, we studied the tissue-specific effects of the pcECM on seeded human mesenchymal stem cells (hMSCs) phenotype using reverse transcribed quantitative polymerase chain reaction (RT-qPCR) arrays for cardio-vascular related genes. We further corroborated interesting findings at the protein level (flow cytometry and immunological stains) as well as bioinformatically using several mRNA sequencing and protein databases of normal and pathologic adult tissue expression, as well as during human embryonic organogenesis. We discovered that upon seeding of human mesenchymal stem cells (hMSCs) on the pcECM they displayed partial MET toward endothelial phenotypes (CD31+) and morphologies, which were preceded by an early spike (~day 3 onward after seeding) in HAND2 expression at both the mRNA and protein levels compared to plate controls. CRISPR-Cas9 knockout (KO) of HAND2 and its associated antisense long non-coding RNA (HAND2-AS1) regulatory region resulted in proliferation arrest, hypertrophy, and senescent-like morphology. Bioinformatic analyses revealed that HAND2 and HAND2-AS1 are highly correlated in expression, are expressed in many different tissue types albeit at distinct yet tightly regulated expression levels. Deviation (down or up regulation) from these basal tissue expression levels are associated with a long list of pathologies. We thus suggest that HAND2 expression levels may finetune cell plasticity possibly affecting senescence and mesenchymal-to-epithelial transition states, through yet unknown mechanisms. Targeting this pathway may represent a promising new therapeutic approach for a wide range of diseases, including cancer, degenerative disorders, and aging. Nevertheless, further investigations are required to better understand the molecular players involved, potential inducers and inhibitors of this pathway, and eventually potential therapeutic applications.

Adipose tissue (AT) is a remarkably plastic and active organ with functional pleiot-ropism and high remodeling capacity. Although the expansion of fat mass, by defini-tion, represents the hallmark of obesity, the dysregulation of the adipose organ emerges as the forefront of the link between adiposity and its associated metabolic and cardio-vascular complications. The dysfunctional fat displays distinct biological signatures, which include enlarged fat cells (i.e., adipocyte hypertrophy), low-grade inflammation, impaired redox homeostasis, and cellular senescence. While these events are orches-trated in a cell-type, context-dependent and temporal manner, the failure of the adipose precursor cells to form new mature adipocytes appears the main instigator of the adi-pose dysregulation, which, ultimately, poses a deleterious milieu either by promoting ectopic lipid overspill in non-adipose targets (i.e., lipotoxicity) or by inducing an al-tered secretion of different adipose-derived hormones (i.e., adipokines and lipokines). This novel paradigm (“expandability hypothesis”) challenges and extends previous “adipocentric view”, which implies a reduced plasticity of the adipose organ at the nexus between “unhealthy” fat expansion and the development of obesity-associated comorbidities. In this review, we will briefly summarize the potential mechanisms by which adaptive changes to variations of energy balance may impair adipose plasticity and promote fat organ dysfunction. We will also highlight the conundrum with the perturbation of the adipose microenvironment and the development of cardio-metabolic complications by focusing on adipose lipoxidation and cellular senescence. Finally, we discuss the sci-entific rationale for proposing adipose organ plasticity as a target to curb/prevent adi-posity-linked cardio-metabolic complications.

Minimally invasive surgery for adult spinal deformities (MIS deformity surgery) utilizes MIS lumbar interbody fusion and percutaneous pedicle screw fixation (PPSF) without posterior corrective osteotomy. While MIS reduces issues associated with open deformity surgery, it has limitations in correcting sagittal imbalance. This review discusses the limitations and solutions of lateral lumbar interbody fusion (LLIF) and introduces our experience in addressing marked sagittal deformities. We reviewed the literature and incorporated our clinical experience to evaluate the efficacy of recent MIS techniques, particularly focusing on oblique lumbar interbody fusion (OLIF) at L1-5 and L5-S1. The use of higher profile and greater angle cages and the application of PPSF with curved rods and percutaneous rod compression were discussed. Advances in MIS techniques, such as OLIF, have enabled significant improvements in increasing disc height and angle. Combining these new techniques and concepts, we successfully corrected marked sagittal deformities using MIS deformity surgery. Early onset of proximal junctional kyphosis was identified as a notable complication. Although recent advancements in MIS deformity surgery have shown promise in correcting sagittal deformities, further clinical experience and data are necessary to enhance outcomes and mitigate complications such as proximal junctional kyphosis.

Background: Neuromuscular electrical stimulation (NMES) has beneficial effects on physical functions in Multiple Sclerosis (MS) patients. However, the neurophysiological mechanisms underlying these functional improvements are still unclear. This study aims at comparing acute responses in spinal excitability, as measured by soleus Hoffmann reflex (H-reflex), between MS patients and healthy individuals, following three experimental conditions involving the ankle planta flexor muscles: 1) passive NMES (pNMES); 2) NMES superimposed to isometric voluntary contraction (NMES+); and 3) isometric voluntary contraction (ISO). Methods: 20 MS patients (MSp) and 20 healthy individuals as control group (CG) took part in a single experimental session. During each condition, participants performed 15 repetitions of 6 seconds at 20% of maximal voluntary isometric contraction, with 6 seconds of recovery between repetitions. Before and after each condition, H-reflex amplitudes were recorded. Results: In MSp, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.506; pNMES: p = 0.068; NMES+: p = 0.126). In CG, H-reflex amplitude significantly increased following NMES+ (p = 0.01), decreased after pNMES (p = 0.000) and was unaltered following ISO (p = 0.829). Conclusion: the different H-reflex responses between MS and CG might reflect a reduced ability of MS patients in modulating spinal excitability.

Degenerative spinal cord (SC) compression is a frequent pathological condition with increasing prevalence throughout aging. Initial non-myelopathic cervical SC compression (NMDC) might progress over time into potentially irreversible degenerative cervical myelopathy (DCM). While quantitative MRI (qMRI) techniques demonstrated the ability to depict intrinsic tissue properties, longitudinal in-vivo biomarkers to identify NMDC patients who will eventually develop DCM are still missing. Thus, we aim to review the ability of qMRI techniques (such as diffusion MRI, diffusion tensor imaging (DTI), magnetization transfer (MT) imaging, magnetic resonance spec-troscopy (1H-MRS)) to serve as prognostic markers in NMDC. While DTI in NMDC patients con-sistently detected lower fractional anisotropy and higher mean diffusivity at compressed levels caused by demyelination and axonal injury, MT and 1H-MRS along with advanced and tract-specific diffusion MRI recently revealed microstructural alterations also rostrally pointing to Wallerian degeneration. Recent studies also disclosed significant relationship between micro-structural damage and functional deficits, assessed by qMRI and electrophysiology, respectively. Thus, tract-specific qMRI in combination with electrophysiology critically extend our under-standing of the underlying pathophysiology of degenerative SC compression and may provide predictive markers of DCM development for accurate patient management. However, the prog-nostic value must be validated in longitudinal studies.

Implantable drug-delivery systems provide new means for achieving therapeutic drug concentration over a prolonged time to achieve better tissue protection and enhanced recovery. The hypothesis of the current study was to test the antioxidant and anti-inflammatory effects of genistein and nanofibers on the spinal cord tissue following experimental spinal cord injury (SCI). Rats were treated post SCI with genistein loaded on chitosan/polyvinyl alcohol (CS/PVA) nanofibers as an implantable drug-delivery system. SCI caused marked oxidative damage and inflammation as evident by the reduction in the super oxide dismutase (SOD) activity and the level of interleukin-10 (IL-10) in injured spinal cord tissue, as well as, the significant increase in the levels of nitric oxide (NO), malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α). Treatment of rats post SCI with genistein and CS/PVA nanofibers improved most of the above mentioned biochemical parameters and shifted them toward the control group values. Genistein induced an increase in the activity of SOD and the level of IL-10, while causing a decrease in the levels of NO, MDA and TNF-α in injured spinal cord tissue. Genistein and CS/PVA nanofibers provide a novel combination for treating inflammatory nervous tissue conditions, especially when combined as an implantable drug-delivery system.

Zebrafish have been found to be the premier model organism in biological and biomedical research, specifically offering many advantages in developmental biology and genetics. This unique aquatic species has been found to have the capacity to regenerate their spinal cord after injury. However, the complete molecular and cellular mechanisms behind glial bridge formation in the central and peripheral nervous systems upon glial cell injury remains unclear. This review paper focuses on the molecular mechanisms and cellular processes that underlie spinal cord regeneration in four initial phases: proliferation and initial migration; migration and differentiation; glial bridge formation; and remodeling. We propose that within these four phases the cellular mechanisms that underlie spinal cord regeneration each express a terminating signal that aborts one step of the process and initiates the next. Specifically, future studies would be devoted to investigate transmitting signals in the spinal cord injury micro-environment in hope to contribute to the understanding of underlying cellular mechanisms by connecting each process of spinal cord regeneration in zebrafish.

(1) Background: Hepatoblastoma is the most common primary liver cancer in children. Nowadays, poor outcome occurs essentially for patients with distant metastases; (2) Methods: Starting from Mammalian Metabolic Enzyme Database over expression of metabolic enzymes was searched in hepatoblastoma tumors as compared to noncancerous liver tissue in transcriptome dataset GSE131329. With overexpressed enzymes, Elasticnet machine learning tuning was performed according to metastasis status outcome. With significant enzymes a metabolic expression score was computed and integrated in multivariate clinical-biological logistic model; (3) Results: Forty-one overexpressed enzymes discriminate hepatoblastoma tumors and noncancerous liver tissues. Eighteen of them predict metastasis status (AUC 0.90) with 85.7% of sensibility and 92.3% of specificity. Elasticnet machine learning model tuning highlighted major importance of DNMT3B and PFKFB4 expression to predict metastasis. Role of these two enzymes was confirmed by univariate analyses with respective p-values: 0.0058 and 0.0091. Metabolic score computed with combined expression of DNMT3B and PFKFB4 discriminates metastasis status and high-risk CHIC score by univariate analysis (p-value=0.005). Meta.score was found more sensitive than C1/C2 classifier to predict metastasis status (accuracy: 0.72 versus 0.55). Integration of meta.score (DNMT3B, PFKFB4) with epidemiological parameters: gender, age at diagnosis, histological types, and clinical PRETEXT stages in a multivariate model confirmed independent adverse role of meta.score to predict metastasis status (multivariate p-value=0.003, odds ratio: 2.12); (4) Conclusions: Based on metabolic enzyme expression program of hepatoblastoma, we characterized a dual overexpression of PFKFB4 and DNMT3B in samples of patients at risk of metastasis (High risk CHIC stratification). With combined tumor expression of DNMT3B and PFKFB4 a meta.score was computed and this parameter was confirmed as an independent adverse score to predict metastatic status during hepatoblastoma.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of type 2 diabetes that affects a significant proportion of diabetic patients worldwide. Although the pathogenesis of DPN involves axonal atrophy and demyelination, the exact mechanisms remain elusive. Current research has predominantly focused on neuronal damage, overlooking the potential contributions of Schwann cells, which are the predominant glial cells in the peripheral nervous system. Schwann cells play a critical role in neurodevelopment, neurophysiology, and nerve regeneration. This review highlights the emerging understanding of the involvement of Schwann cells in DPN pathogenesis. This review explores the potential role of Schwann cell plasticity as an underlying cellular and molecular mechanism in the development of DPN. Understanding the interplay between Schwann cell plasticity and diabetes could reveal novel strategies for the treatment and management of DPN.