The porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits infiltration of cells, nutrients, and molecular signals, and the discharge of metabolic waste. Porous structures with precisely customised pore sizes, porosities, and connectivities were used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs to replace traditional nerve autografts in treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs including biodegradation, mechanical performance, and permeability were analysed. Pore structure affects the biological behaviour of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. Construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalise, summarise, and analyse the preparation methods for porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide development of medical nerve repair materials.

Despite a significant advance in the pathophysiological understanding of peripheral nerve damage, the successful treatment of large nerve defects remains an unmet medical need. In this article, axon growth guidance for peripheral nerve regeneration is systematically reviewed and discussed mainly from the engineering perspective. In addition, the common approach to surgery, bioengineering approaches to emerging technologies (i.e. optogenetic stimulation and magnetic stimulation) for functional recovery are discussed, with pros and cons. Alternatively, clear future perspectives of axon guidance and nerve regeneration are addressed.

Abstract: Imaging devices of less than 300,000 pixels are mostly used for sewage conduit exploration due to the petty nature of the survey industry in Korea. P articular ly , devices of less than 100,000 pixels are still widely used, and the environment for image processing is very bitter . Since the sewage conduit image s covered in this study ha ve a very low resolution (240 × 320 = 76,800 pixels), it is very difficult to detect cracks. Because most of the resolution of the sewe r conduit images are very low in Korea, this problem of low resolution was selected as the subject of study. Cracks were detected through a total of six steps of improving the crack in Step 2, finding the optimal threshold value in Step 3, and applying an algorithm to detect cracks in Step 5. Cracks were effectively detected by the optimal parameters in Steps 2 and 3 and the user algorithm in Step 5. Desp ite the very low resolution, the cracked image s showed 96.4% accuracy of detection, and the non cracked image s showed 94.5% accuracy . Moreover, the analysis was excellent in quality , also . It is believed that the findings of this study can be effectively u sed for crack detection with low resolution images.

Previous literature has linked working for pay while attending university with negative academic and health outcomes, yet working students are often resilient when experiencing such adverse circumstances. This makes it crucial to explore potential psychological mechanisms which transform adverse experiences into sources of motivation and persistence for working students. We explore one mechanism – social identification – and its different foci – identifying as a student, employee, working student, or as a student of one’s discipline of study – as potential predictors of important academic (academic self-efficacy, approaches to learning, and academic achievement) and social (status in society) outcomes in three cross-sectional studies. In Study 1, part-time working hours (but not identification processes) were associated with academic self-efficacy. In Study 2, discipline identification and part-time working hours were associated with using deep approaches to learning. In Study 3, student identification was associated with increased status in society. Overall, discipline identification may be solely linked to academic outcomes, yet student identification should be explored further as a potential enhancer of social and graduate outcomes. We discuss additional mechanisms which can help to transform working students’ experiences through their social identities and suggest boundary conditions which can affect the link between these identities and important outcomes.

Radial nerve palsies present a challenging clinical scenario, often leading to substantial functional impairment. This study focuses on evaluating the outcomes of tendon transfer surgeries in patients with post-traumatic radial nerve injuries. The radial nerve, vital for upper limb movements, faces various etiologies such as trauma, compression, or idiopathy. Patients with radial nerve palsy encounter difficulties in daily activities, emphasizing the need for effective management strategies. The research introduces a novel evaluation protocol, aiming to comprehensively assess tendon transfer outcomes. This protocol incorporates functional movements of wrist and finger joints, encompassing both objective and subjective parameters. The retrospective study includes eleven patients treated between 2010 and 2022, with a minimum follow-up of one year post-surgery. Tendon transfers demonstrated positive results. The evaluation protocol covers a wide range of parameters, including wrist and finger mobility, thumb function, grip strength, and patient satisfaction. The results indicate successful restoration of motor function, with an average grip strength of 70% compared to the healthy arm. The proposed evaluation protocol facilitates standardized and reproducible assessment, minimizing subjective errors in clinical evaluations. Despite the study's limitations, such as a relatively small sample size, the findings underscore the effectiveness of tendon transfers in treating radial nerve palsies. The introduced evaluation scheme provides a comprehensive and reproducible approach to assess outcomes, contributing to the global standardization of tendon transfer assessments in radial nerve injuries.

Background: Tibial shaft fractures are the most common of long bone fractures. The gold standard for management is locked intramedullary nailing. The freehand method under fluoroscopic monitoring is the most often utilized method for distal screw locking. Electromagnetic guidance-based distal screw locking methods have gained popularity recently. The study's objective is to evaluate the system using electromagnetic tracking data against the free-hand technique. Methods: Sixty-three patients who received intramedullary nailing for tibial shaft fractures at our institute between January 2018 and May 2022, were included in this study. Two groups of patients were distinguished: Group FH underwent freehand distal locking and intramedullary nailing, while Group SS underwent electromagnetically guided locking. Radiation exposure period, as well as dose area product, were noted and statistically compared. Results: In terms of dose area product, a mean value of 43.57±31.57 cGy/cm2 in group FH and a mean value of 27.62±11.20 cGy/cm2 in group SS (p < 0.05) was assessed. Concerning the duration of surgery a mean value of 128.83±26.51 minutes was reported in group FH and a mean value of 126.42±48.31 minutes in group SS (p > 0.05). Conclusions: This study confirms the use of electromagnetic-guided locking distal screws reduces the total time of exposure to ionizing radiation, with no difference in operating time.

Chronic inflammatory diseases are considered the most significant cause of death worldwide. Current treatments for inflammatory diseases are limited due to the lack of understanding of the biological factors involved in early-stage disease progression. Nerve growth factor (NGF) is a neurotrophic factor directly associated with inflammatory and autoimmune diseases like osteoarthritis, multiple sclerosis, and rheumatoid arthritis. It has been shown that NGF levels are significantly upregulated at the site of inflammation and play a crucial role in developing a robust inflammatory response. However, little is known about NGF's temporal expression profile during the initial progressive phase of inflammation. This study aimed to determine the temporal expression pattern of NGF in rat skin during Adjuvant-Induced Arthritis (AIA). Sprague Dawley rats were randomly divided into control and Complete Freund's Adjuvant (CFA) treated groups. Levels of NGF were evaluated following unilateral AIA at different time points and it was found that peripheral inflammation due to AIA significantly upregulated the expression of NGF mRNA and Protein in a biphasic pattern. These results suggest that NGF signaling is crucial for initiating and maintaining peripheral neurogenic inflammation in rats during AIA.

The vertebrate skeletal neuromuscular junction (NMJ) has long served as a model system for studying synapse structure, function and development. Over the last several decades a neuron-specific isoform of agrin, a heparan sulfate proteoglycan, has been identified as playing a central role in synapse formation at all vertebrate skeletal neuromuscular synapses. While agrin was initially postulated to be the inductive molecule that initiates synaptogenesis, this model has been modified in response to work showing that postsynaptic differentiation can develop in the absence of innervation, and that synapses can form in transgenic mice in which the agrin gene is ablated. In place of a unitary mechanism for neuromuscular synapse formation, studies in both mice and zebrafish have led to the proposal that two mechanisms mediate synaptogenesis, with some synapses being induced by nerve contact while others involve the incorporation of prepatterned postsynaptic structures. Moreover, the current model also proposes that agrin can serve two functions, to induce synaptogenesis and to stabilize new synapses, once these are formed. This review examines the evidence for these propositions, and concludes that it remains possible that a single molecular mechanism mediates synaptogenesis at all NMJs, and that agrin acts as a stabilizer, while its role as inducer is open to question. Moreover, if agrin does not act to initiate synaptogenesis, it follows that as yet uncharacterized molecular interactions are required to play this essential inductive role. Several alternatives to agrin for this function are suggested, including focal pericellular proteolysis and integrin signaling, but all require experimental validation.

Previous control methods developed by our research team cannot satisfy the high-accuracy requirements of unmanned surface vessel (USV) path-tracking during bathymetric mapping because of the excessive overshoot and slow convergence speed. For this reason, this study developed an adaptive fuzzy integral-derivative line-of-sight (AFIDLOS) guidance law for USV path-tracking control. Integral and derivative terms were added to counteract the effect of the sideslip angle, with which the USV could be quickly guided to converge to the planned path for bathymetric mapping. To obtain a high-accuracy of the look-ahead distance, a fuzzy control method was proposed. The proposed method was verified using simulations and outdoor experiments. The results demonstrate that the AFIDLOS guidance law can reduce the overshoot by 79.85%, shorten the settling time by 55.32% in simulation experiments, and reduce the average cross-track error by 10.91%, and can ensure a 30% overlap of neighboring strips of bathymetric LiDAR outdoor mapping when compared with the traditional method.

The application of space robotic manipulators and heightened autonomy for ios represents a paramount pursuit for leading space agencies, given the substantial threat posed by space debris to operational satellites and forthcoming space endeavors. This work presents a guidance algorithm based on drl to solve for the space manipulator path-planning during the motion synchronization phase with the mission target. The goal is the trajectory generation and control of a spacecraft equipped with a 7-dof robotic manipulator, such that its end effector remains stationary with respect to the target point of capture. The ppo drl algorithm is used to optimize the manipulator’s guidance law, and the autonomous agent generates the desired joints rates of the robotic arm, which are then integrated and passed to a model-based feedback linearization controller. The agent is first trained to optimize its guidance policy and then tested extensively to validate the results against a simulated environment representing the motion synchronization scenario of an ios mission.

Aim: the main aim of this study is to compare the onset of effectiveness of mental nerve block with lingual infiltration and inferior alveolar nerve block on patients visiting dental hospital for extraction of mandibular anterior teeth. Materials and methods: The study was set in a clinical setting. This was a randomized controlled double-blind cross study, where 25 subjects received two treatments at an interval of at least 1 week in a within a dental hospital.Inferior alveolar nerve block and lingual nerve block injection is given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered for the right side. Mental nerve block along with lingual infiltration of the corresponding tooth was given with 2mL lignocaine 2% with 1:2,00,000 epinephrine was administered on the left side.Visual analogue scale (VAS) was used in this study, which consists of a scale with range of 0-10 pain severity on which 0 indicated absence of pain and 10 the worst pain possible. The patients were asked to give scores corresponding to his/her pain, after IANB, mental nerve block and lingual infiltration and these scores were recorde.Results: From the results we can see that patients gave scores between 3-4, stating that they had moderate pain during extraction after administration of IANB (54%) (graph 2) and VAS scores of 0-1 were given by patients, which is suggestive of no pain during extraction after administration of Mental nerve block and lingual nerve infiltration (62%)Conclusion: Within the limits of the study we can conclude that mental nerve block along with lingual infiltration is an effective way to completely and quickly anaesthetise the central incisor to the 1st premolar region.

This study aimed to evaluate the effectiveness of decellularized nerves for promoting nerve regeneration by transplanting them from the sciatic nerve of a rabbit to that of a rat. The Sciatic nerves were harvested from New Zealand White Rabbits (n=4). A 1-cm segment of each nerve was decellularized by Sondell’s protocol and preserved at –4℃ in Roswell Park Memorial Institute (RPMI) 1640 medium for one week. Subsequently, a defect of a similar size was created in the sciatic nerves of rats. The decellularized nerves treated with detergent were then transplanted into these defects in the rats. The study included the three following groups: Group 1 (n=4) was the decellularized xenogeneic nerve group; Group 2 (n=7) was the negative control group in which the defect remained un-repaired; and Group 3 (n=5) was composed of the positive control group where the nerve was immediately transplanted from one rat to another. The sciatic functional index (SFI) was considered to evaluate the motor function by comparing it with the normal side at 1, 2, 3, and 4 weeks, and 1, 2, and 3 months postoperatively. Furthermore, electrophysiological and immunohistochemical assessments were conducted at 4 months. Immunohistochemically, at 16 weeks postoperative, the experimental group did not show statistically significant differences compared to controls in terms of schwann cell comparison, yet exhibited favorable outcomes when compared to the positive control group. Additionally, analysis of motor function test confirmed recovery of latency and nerve conduction velocity to levels similar to those of the normal side. While the nerve allograft demonstrated superior nerve regeneration in motor function test at 3 months, markedly low values were observed in all groups. When reconstructing peripheral nerves using detergent-based decellularized xenogenic nerves, analysis of immuno-histochemistry and motor nerve conduction study reveals a promising degree of nerve regeneration. However, when compared with fresh allograft group at 3 months after operation, the sciatic functional index was lower. Significantly lower values observed across all groups compared to previous assessments indicate the need for further research into potentially influential alternative factors.Histologically, at 16 weeks postoperative, the experimentally treated group did not show statistically significant differences compared to the controls in terms of a Schwann cell comparison, but exhibited favorable outcomes when compared to the positive control group. Additionally, an analysis of the motor function testing confirmed recovery of the latency and nerve conduction velocity to levels similar to those of the normal side. While the nerve allograft demonstrated superior nerve regeneration in the motor nerve examination at 3 months, notably low values were observed in all the groups. When reconstructing the peripheral nerves using detergent-based decellularized xenogeneic nerves, an analysis of immunohistochemistry and motor nerve conduction study reveals a promising degree of nerve regeneration. However, when compared with the fresh allograft group at 3 months post-operation, the sciatic functional index was lower. The significantly lower values observed across all groups compared to those of the previous assessments indicate the need for further research of potentially influential alternative factors.

Objective: There are currently no known treatment methods for ensuring complete recovery from facial nerve damage. Thus, various basic and clinical studies continue to be conducted to achieve this end. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and signifi-cance of autophagy in facial nerve injury and regeneration. Methods: A comprehensive litera-ture review was conducted to assess the induction and role of autophagy in facial nerve injury and subsequent regeneration. Results: Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in facial and sciatic nerves. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. Conclusion: This analysis indicates that autophagy is involved in the process of nerve regeneration follow-ing facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy re-sponses can result in regeneration issues after facial or sciatic nerve damage. Animal studies suggest that autophagy plays an important role in facial and sciatic nerve degeneration and re-generation.

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakens, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized.; (2) Methods: Literature review; (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies; (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

Autonomous navigation of spacecraft necessitates innovative technologies, methods, and algorithms, particularly when orbiting in proximity of other space objects. Optimization methods are useful for autonomous spacecraft navigation, guidance, and control, but their performance is hampered by noisy multi-sensor technologies and poorly modeled system equations, and real-time on-board utilization is generally computationally burdensome. Some proposed methods use noisy sensor data to learn the optimal guidance and control solutions real-time (online), where non-iterative instantiations are preferred to reduce computational burdens. This study aims to highlight efficacy and limitations of several common methods for optimizing guidance and control while proposing a few more, where all methods are applied to the full, nonlinear, coupled equations of motion including cross-products of motion from the transport theorem. Five disparate types of optimum guidance and control algorithms are presented and compared to a classical benchmark. Comparative analysis is based on tracking errors (both states and rates), fuel usage, and computational burden. Real-time optimalization with singular switching plus nonlinear transport theorem decoupling proves superior by matching open-loop solutions to the constrained optimization problem (in terms of state and rate errors and fuel usage), while robustness is validated in the utilization of mixed, noisy state and rate sensors and uniformly varying mass and mass moments of inertia. State tracking errors are reduced one-hundred ten percent. Rate tracking errors are reduced one-hundred thirteen percent. Control utilization (e.g., fuel) is reduced eighty four percent, while computational burden in reduced ten percent simultaneously.

This research work uses a simplified approach to combine location information from beacons propagation signal interaction with a mobile device with local building information to give real-time location and guidance to a user inside a building. This is an interactive process with visualisation information that can help user’s orientation inside unknown buildings and the data stored from different users can provide useful information about users movements inside a public building. Beacons installed on the building at specific pre-defined position emit signals that give a geographic position with an associated imprecision, related with Bluetooth’s range. This uncertainty is handled by building layout and users’ movement in a developed system that maps users’ position, gives guidance and store user movements. This system is based on an App (Find Me!) for Android OS (Operating System) which captures the Bluetooth Low Energy (BLE) signal coming from the beacon(s) and shows, through a map, the location of the user ‘s smartphone and guide him to the desired destination. Also, the beacons can deliver relevant context information. The application was tested by a panel of new and habitual campus users against traditional wayfinding alternatives yielding navigation times about 30% smaller, respectively.

Mitral regurgitation (MR) is a broadly diffuse valvular heart disease (VHD) with a significant impact on healthcare system and patient’s prognosis. Transcatheter mitral valve interventions (TMVI) are now well-established techniques included in the therapeutic armamentarium for managing patients with mitral regurgitation, either primary or functional MR. Even if guidelines give indications regarding the correct management of this VHD, the wide heterogeneity of patient’s clinical background, valvular and heart’s anatomy make each patient a unique case, in which the appropriate device’s selection requires a multimodality imaging evaluation and a multidisciplinary discussion. Proper pre-procedural evaluation plays a pivotal role to judge the feasibility of TMVI, as well as a cooperative works between imagers and interventionalist is crucial for procedural success. This manuscript aims to provide an exhaustive overview of the main parameters that need to be evaluated for appropriate device selection, pre-procedural planning, intraprocedural guidance and post-operative assessment in the setting of TMVI. In addition, it tries to give some insights about next perspective of structural cardiovascular imaging.

When profit-driven renewal is difficult to implement, many historic districts are “frozen protected” in China. In the social context of “building cities for the people” in recent years, the public value-oriented renewal of urban historic areas plays an important role in the transformation of cities. This study investigates the strategies of historic district regeneration in China by integrating spatial form, urban governance, and public value. We propose a novel framework to analyze the regeneration of historic districts, using Taiyuan Bell Tower Street as a case study. The framework distinguishes between two dimensions: spatial and economic-social. In the spatial dimension, we focus on the transformation of spatial form to regenerate public value, emphasizing the attribute of "publicness" as central to urban regeneration efforts. This involves a tiered approach of excavating and upgrading historic districts at macro, meso, and micro levels. In the economic-social dimension, we explore urban governance to strengthen public value, involving government, market, and societal actors in a collaborative renewal process. The analysis highlights that a public value-oriented approach to heritage regeneration offers greater sustainability and could serve as a model for other cities seeking similar outcomes.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Objectives: This study aims to explore the use of murine models in peripheral nerve transection research, evaluating and synthesizing key methods for analyzing nerve regeneration to guide future research and clinical interventions. Methodology: A systematic review was conducted in February 2024, adhering to Cochrane and PRISMA 2020 guidelines, using Medline, Scielo, and Lilacs databases. The focus was on experimental studies of nerve regeneration in animal models post-transection. Only experimental clinical trials reporting nerve regeneration outcomes were included; studies lacking a comparator group or functional evaluation methods were excluded. Results: Out of 273 studies initially identified from MEDLINE, 19 were selected for detailed analysis. The average study included 32.5 subjects, with about 10.16 subjects per intervention subgroup. The predominant model was the sciatic nerve injury with a 10mm gap. The most common intervention involved unprocessed adipose-derived stem cells, utilized in 14 articles. Conclusions: The review underscores the significant potential of current methodologies in peripheral nerve regeneration, particularly highlighting the use of murine models and thorough evaluation techniques. These studies significantly contribute to our understanding of nerve regeneration processes and inform directions for future research.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of <0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Thousands of people worldwide suffer from injuries in the peripheral nerve and deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee effective outcomes, and the development of new and effective therapeutic options requires the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. In an integrative way, this article includes a detailed description of the anatomy and functionality of the peripheral nerves of sheep’s hind limb, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options. A neurological exam protocol directed to the common peroneal nerve was also established, allowing to identify the changes and deficits related with the nerve injury and to evaluate the functional progression over time. Finally, a preliminary stereological study was carried out to establish control values for the healthy peroneal common nerves of this model and to identify preliminary differences between therapeutic methods. The ultimate goal is to demonstrate that sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in human and veterinary patients.

Aiming at the problem of hypersonic morphing vehicle avoiding no-fly zones and reaching the target, an improved predictor-corrector guidance method is proposed. Firstly, the aircraft motion model and the constraint model are established. Then, the basic algorithm is given, the Q-learning method is used to design the attack angle and sweep angle scheme to ensure that the aircraft can fly over the low-altitude zones. The B-spline curve is used to design the location of flight path points and the bank angle scheme is designed according to the predictor-corrector method, so that the aircraft can fly around to avoid high-altitude zones. Next, Monte Carlo reinforcement learning(MCRL) method is used to improve predictor-corrector method and Deep Neural Network(DNN) is used to fit reward function. The improved method can generate trajectory with better performance. Simulation results verify the effectiveness of the proposed algorithm.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

Background: The management of gestational diabetes mellitus (GDM) focuses on dietary interventions, physical activity, and pharmacological therapy. Strategies that enhance adherence to the diet could play a pivotal role in managing this population. Objective: To compare the effectiveness of outpatient nutritional guidance supplemented by digital media with exclusively standard outpatient nutritional guidance in pregnant women with GDM. Methods: This was a randomized, patient-blinded clinical trial conducted at the Diabetes and Pregnancy outpatient clinic from February 2021 to January 2023. Pregnant women with GDM were randomly allocated into two groups: the Control Group (CG) received exclusively outpatient nutritional guidance, and the Intervention Group (IG) received outpatient nutritional guidance along with reminders via WhatsApp. Dietary intake (calories, carbohydrates, lipids, proteins, and fibers) was evaluated using 24-hour dietary recalls (24HR). Glycemic control and the need for pharmacological treatment were also assessed. Mann-Whitney tests were applied to numerical variables, and Fisher's exact test or Chi-square tests were used for categorical variables. Results: 81 women were included, 34 allocated to the CG, and 47 to the IG. Patients were followed for a period of 4 to 8 weeks. Few differences were observed in glycemic control between the two groups over the follow-up period. There were no statistical differences in pharmacological therapy (p=0.498); 188 24HR were conducted in the CG and 290 in the IG. A statistically significant increase in lipid intake was observed in the IG over the follow-up period compared to the CG (p

The trigeminal nerve is responsible for innervating the periorbita. Ultrasound-guided trigeminal block is employed in humans for trigeminal neuralgia or periorbital surgery. There are no studies evaluating this block in dogs. This study aims to evaluate and compare two approaches (coronoid and temporal) of the trigeminal nerve block. We hypothesized superior staining with the coronoid approach. Thirteen dog heads were used. After a preliminary anatomical study, two ultrasound-guided injections per head (right and left, coronoid and temporal approach, randomly assigned), with an injectate volume of 0.15 mL cm-1 of cranial length were performed (iodate contrast and tissue dye mixture). The ultrasound probe was placed over the temporal region, visualizing the pterygopalatine fossa. For the temporal approach, the needle was advanced from the medial aspect of the temporal region in a dorsoventral direction. For the coronoid approach, it was advanced ventral to the zygomatic arch in a lateromedial direction. CT scans and dissections were conducted to assess and compare the position of the needle, spread of injectate, and nerve staining. No significant differences were found. Both approaches demonstrated effective interfascial distribution of injectate, with some minimal intracranial spread. Although the coronoid approach did not yield superior staining as hypothesized, it presents a viable alternative to the temporal approach. Studies in live animals are warranted to evaluate clinical efficacy and safety.

Navigating growth cones are exposed to multiple signals simultaneously and have to integrate competing cues into a coherent navigational response. Integration of guidance cues is traditionally thought to occur at the level of cytoskeletal dynamics. Drosophila studies indicate that cells exhibit a low level of continuous caspase protease activation, and that axon guidance cues can activate or suppress caspase activity. We base a model for axon guidance on these observations. By analogy with other systems in which caspase signaling has non-apoptotic functions, we propose that caspase signaling can either reinforce repulsion or negate attraction in response to external guidance cues by cleaving cytoskeletal proteins. Over the course of an entire trajectory, incorrectly navigating axons may pass the threshold for apoptosis and be eliminated, whereas axons making correct decisions will survive. These observations would also explain why neurotrophic factors can act as axon guidance cues and why axon guidance systems such as Slit/Robo signaling may act as tumor suppressors in cancer.

A common problem in education has always been to get students to achieve an adequate level of motivation and engagement. Many evidences show that gamification has the potential to make learning more engaging, motivating and effective. However, it is essential to design gamified experiences thoughtfully, ensuring that they align with educational objectives and promote meaningful learning outcomes, and so the lack of established design methodologies can lead to unintended consequences.

Photoacoustic imaging (PAI) is a cutting-edge biomedical imaging modality, providing detailed anatomical and functional information about the area beneath the skin surface. Its light energy deposition is such that PAI typically provides clear images of the skin with high signal-to-noise ratios. Specifically, the rich optical contrast of PAI allows biological information related to lesion growth, malignancy, treatment response, and prognosis to be seen. Given its significant advantages and emerging role in imaging skin lesions, we summarize and comment on representative studies of skin PAI, such as the guidance of skin cancer biopsies and surgical excisions, and the accurate diagnosis of psoriasis. We conclude with our insights about the clinical significance of skin PAI, showing how its use to identify biological characteristics in lesion microenvironments allows early diagnosis and prognosis of disease.

Iodine is essential for thyroid hormones synthesis and normal neurodevelopment; however, 60% of pregnant women do not meet the WHO recommended intake. Using a qualitative design, we explored perceptions, awareness and experiences of pregnancy nutrition, focusing on iodine. Women in the perinatal period (n=48) were interviewed and filled in a food frequency questionnaire for iodine. Almost all participants achieved the recommended 150 μg/day intake for non-pregnant adults (99%), but only 81% met the increased demands of pregnancy (250 μg/day). Most were unaware of the importance, sources and recommendations of iodine intake. Attitudes to dairy products consumption were positive (e.g. helps with heartburn; easy to increase). Increased fish consumption was considered less achievable, with barriers around taste, smell, heartburn and morning sickness. Community midwives were the main recognised provider of dietary advice. The dietary advice received focused most often on multivitamin supplements rather than food sources. Analysis highlighted a clear theme of commitment to change behaviour, motivated by pregnancy, with desired focus on user-friendly documentation and continued involvement of the health services. The study highlights the importance of redirecting advice on dietary requirements in pregnancy and offers practical suggestions from women in the perinatal period as the main stakeholder group.

We investigated the sleep-wake rhythm of nursery school children with the aim of supporting their health and balanced mental/physical development. We analyzed 4881 children from infant to 6 years of age, using 2-week sleep tables recorded by their guardians. The table contains sleep onset times, wake times, nighttime/daytime sleep duration, and the differences in these between weekdays and weekends. The total sleep decrement of children with age is due to a decrease in daytime sleep only, and nighttime sleep duration remains almost unchanged at about 10 hours, and is therefore called the nighttime basic sleep duration (NBSD). While sleep onset time stabilizes at around 9:30 pm by the age of 2, wake-up times to be before 7 am, resulted in weekdays sleep insufficiency. This lack of sleep is compensated by long naps on weekdays and by catching up sleep on weekends morning, which may be the background to future social-jet-lag. Guardians are encouraged to know their children's exact NBSD and set an ap-propriate bedtime to maintain it on weekdays, which prevent sleep dept and form a daily rhythm of waking up at the same time both on weekdays/weekends. These conditions are believed to maintain balance in mental/physical development and school-social-adaptation.

In response to the issue of vehicle escape guidance, this manuscript proposes a unified intelligent control strategy synthesizing optimal guidance and Meta Deep Reinforcement Learning (DRL). Optimal control with minor energy consumption is introduced to meet terminal latitude, longitude and altitude. Maneuvering escape is realized by adding longitudinal and lateral direction maneuver overloads. Maneuver command decision model is calculated based on Soft-Actor-Critic (SAC) networks. Meta learning is introduced to enhance autonomous escape capability, which improves generalization performance to time-varying scenarios not encountered in the training process. In order to obtain training samples at a faster speed, this manuscript uses the prediction method to solve reward values, which avoiding a large number of numerical integration. The simulation results manifest that the proposed intelligent strategy can achieve high precise guidance and effective escape.

This paper studies the integrated design problems of control and guidance with parameter uncertainties, target disturbances, input constraints and actuator faults. Firstly, based on the integrated design idea of the missile guidance and control, the auxiliary variable is used to establish and transform it into a cascade system with input constraints, actuator faults and disturbances of unknown upper bounds. Secondly, the adaptive anti-saturation dynamic surface fault-tolerant controller is designed by using the back-stepping method, adaptive control, auxiliary system and tracking differentiator. By introducing the tracking differentiator and tangent barrier Lyapunov function, the computational explosion problem in the traditional back-stepping method is avoided and the angle of attack can be guaranteed in prospective range, respectively. Finally, the theoretical proof of the designed control strategy is given to ensure that the states of the closed-loop system are bounded. At the same time, the digital simulation of the maneuvering target of different maneuvering forms is carried out, which further illustrate the effectiveness and robustness of the designed control schemes.

Abstract Background: Occipital neuralgia is a debilitating condition and traditional treatments often provide limited or temporary relief. Recently, ultrasound-guided hydrodissection of the greater occipital nerve (GON) has emerged as a promising minimally invasive approach. Objectives: To describe two novel ultrasound-guided hydrodissection with 5% dextrose for GON and discuss their advantages, disadvantages, and considerations. Methods: Two case reports are presented. Case 1 describes a lateral decubitus approach for hydrodissecting the GON between the semispinalis capitis (SSC) and obliquus capitis inferior (OCI) muscles. Case 2 details a cranial-to-caudal approach for hydrodissecting the GON within the SSC and upper trapezius (UT) muscles when the GON pass through these two muscles. Results: Both patients experienced significant and sustained pain relief with improvements in function and quality of life. Conclusions: Ultrasound-guided GON hydrodissection using 5% dextrose is a promising treatment for occipital neuralgia. The lateral decubitus and cranial to caudal approaches provide additional options to address patient-specific anatomical considerations and preferences.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

Peripheral nerve injury remains a medical challenge with no easy resolution. Over the last few decades, significant advances have been achieved in promoting peripheral nerve regeneration, and new assessment tools have been developed, both functional and imaging, to quantify the proportion and quality of nerve recovery. The exploration of new animal models, larger, more complex and with more similarities to humans, has made it possible to reduce the gap between the results obtained in classic animal models such as rodents and the application of new therapies in humans and animals of clinical interest. Ultrasonography is an imaging technique recurrently used in clinical practice to assess the peripheral nerves, allowing its anatomical and topographic characterization, and aiding in the administration of anesthesia and in the performance of nerve blocks. The use of this technique in animal models is scarce, but it could be a useful tool in monitoring the progression of nerve regeneration after the induction of controlled experimental lesions. In this work, sheep, a promising animal model in the area of peripheral nerve regeneration, were subjected to an ultrasonographic study of three peripheral nerves of the hind limb, the common peroneal, tibial and sciatic nerves, in order to establish values of dimensions and ultrasound appearance in healthy nerves and also landmarks for their identification. At the same time, an echographic evaluation of the cranial tibial muscle, an effector muscle of the common peroneal nerve, was also carried out, establishing normal values for the echographic aspect and dimensions. The results obtained will allow the use of these data as control values in future work exploring new therapeutic options for nerve regeneration after induction of common peroneal nerve injuries in sheep.

Energy use is of crucial importance for the global challenge of climate change but also an essential part of daily life. Hence, research on energy needs to be robust and valid. Other scientific disciplines have experienced a reproducibility crisis, that is, existing findings could not be reproduced in new studies, and energy research might be impacted as well. In this paper, we suggest the ‘TReQ’ approach to improve the research practices in the energy field and arrive at greater Transparency, Reproducibility, and Quality. We acknowledge the specific challenges of energy research and suggest a highly adaptable suite of tools that can be applied to research approaches across this multi-disciplinary and fast-changing field. In particular, we introduce preregistration of studies, making data and code publicly available, using preprints, and employing reporting guidelines to heighten the standard of research practices within the energy field. We argue that through wider adoption of these tools, we will be able to have greater trust in the findings of research used to inform evidence-based policy and practice in the energy field.

Biological drugs are inaccessible to more than 80% of the world population due mainly to their high costs; this is a significant concern of the World Health Organization. Biosimilars are supposed to reduce the cost burden, but their approval process is complex, including expensive and irrelevant studies. While the Stringent Regulatory Authorities (SRAs) have adopted the guidance of the FDA or EMA, such adoptions are neither necessary nor practical for the rest of the world (ROW). We present a science-driven, rational approach to formulate regulatory guidelines that will enable faster biosimilars' entry into the ROW without compromising their safety and efficacy. The key recommendations include removing animal and safety efficacy testing, making analytical assessment more robust, and cGMP compliance assured through third-party audits. The ROW countries are also recommended to initiate a rapporteur system available in the EU, to overcome the biases and assure state-of-the-science evaluation as the common understanding of the critical quality attributes evolves. It is anticipated that stronger regional agencies like those in the MENA region, with the leadership of the Kingdom of Saudi Arabia, will help propel the idea faster across the globe.

SacreBLEU, by incorporating a text normalizing step in the pipeline, has been well-received as an automatic evaluation metric in recent years. With agglutinative languages such as Korean, however, the metric cannot provide a conceivable result without the help of customized pre-tokenization. In this regard, this paper endeavors to examine the influence of diversified pre-tokenization schemes –word, morpheme, character, and subword– on the aforementioned metric by performing a meta-evaluation with manually-constructed into-Korean human evaluation data. Our empirical study demonstrates that the correlation of SacreBLEU (to human judgment) fluctuates consistently by the token type. The reliability of the metric even deteriorates due to some tokenization, and MeCab is not an exception. Guiding through the proper usage of tokenizer for each metric, we stress the significance of a character level and the insignificance of a Jamo level in MT evaluation.

Purpose: To evaluate the relationship between corneal nerve structure and function in a veteran population. Methods: 83 veterans (mean age: 55 ± 5 years) seen at the Miami Veterans Affairs (VA) eye clinic were included in the study. Each individual filled out questionnaires to evaluate ocular symptoms (5-Item Dry Eye Questionnaire, DEQ5, Ocular Surface Disease Index, OSDI) and ocular pain (Numerical Rating Scale, NRS, Neuropathic Pain Symptom Inventory modified for the Eye, NPSI-Eye). Individuals also underwent an ocular surface examination that captured functional nerve tests including corneal sensation, corneal staining, and Schirmer test for tear production. Corneal sub-basal nerve analysis was conducted using in vivo confocal microscopy (IVCM) images with corneal nerve density, length, area, width, and fractal dimension captured. IVCM and functional corneal metrics from the right eye were examined using correlational and linear regression analysis. Results: Most corneal structural metrics were not related to functional metrics, except for weak correlations between various IVCM metrics and tear production. In addition, corneal nerve fiber area was positively related to corneal sensation (r = 0.3, p = 0.01). On linear regression analyses, only corneal fractal dimension remained significantly related to tear production (β = -0.26, p = 0.02) and only corneal nerve fiber area remained significantly related to corneal sensation (β = 0.3, p = 0.01). Conclusions: Most corneal nerve structural metrics did not relate to functional metrics in our veteran population, apart from a few weak correlations between structural metrics and tear production. This highlights caution in using corneal nerve anatomy to predict corneal function.

Shoulder tendinopathies produce pain and reduce functionality. The aim of this randomized clinical trial was to analyze the effects of Percutaneous electrolysis (PE), Percutaneous peripheral Nerve Stimulation (PNS) and eccentric exercise (EE), on pain (NPRS), strength, electromyographic activity, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and functionality (DASH and SPADI) on individuals with supraspinatus tendinopathy. Participants (n=50) were divided into two groups, they received 4 treatment sessions, one per week, of PE and PNS (n=25) or 10 treatment sessions of TENS and US (n=25). Both groups performed EE program consisted of 3 sets of 10 repetitions of each of the 3 exercises, twice a day, during the 4 weeks. Follow-up was carried out at 4, 12 and 24 weeks after the start of the intervention. There are statistically significant differences in the analysis between groups (p<0.001) in the post-treatment and follow-up measurements favorable to the PE+PNS+EE treatment on pain (NPRS), strength, supraspinatus electromyographic amplitude, ultrasound characteristics of the tendon (echogenicity, thickness and hypervascularization) and DASH and SPADI questionnaires. The combined treatment PE, PNS and EE is an effective option in the clinical management of tendinopathies, with positive results in the short and long term on the variables studied.

Emotional experiences are a part of our lives. The maladaptive functioning of an individual's emotional field can lead to emotional disturbances of various kinds, such as anxiety and depression. Currently, there is an increasing prevalence of emotional disorders that cause great human suffering and high socio-economic costs. Emotional processing has a biological basis. The major neuroscientific theories of emotion are based on biological functioning, and all of them take into account the anatomy and function of the tenth cranial nerve: the vagus nerve. The vagus nerve connects the subdiaphragmatic and supradiaphragmatic areas and modulates emotional processing as the basis of interoceptive functioning. Auricular vagus nerve stimulation is a new and innovative neuromodulation technique based on the function of the vagus nerve. Several interventions have shown that this new neurostimulation technique is a very promising resource for treating emotional disorders. In this paper, we summarise three neuroscientific theories of emotion, explain what transauricular vagus nerve stimulation is, and present arguments for its use and continued research.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects both the upper and lower motor neurons in the nervous system, causing muscle weakness and severe disability. The progressive course of the disease reduces the functional capacity in the affected patients, limits daily activities and leads to complete dependence on caregivers, ultimately resulting in a fatal outcome. Respiratory dysfunction mostly occurs later in the disease and is associated with a worse prognosis. 46 participans were included in our study, with 23 patients in ALS group and 23 individuals in the control group. The ultrasound examination of the phrenic nerve (PN) was performed by two authors using a high-resolution "Philips EPIQ 7" ultrasound machine with a linear 4-18 MHz transducer. Our study revealed that the phrenic nerve is significantly smaller on both sides in ALS patients compared to the control group arba controls (p < 0.001). Only one significant study on PN ultrasound in ALS, conducted in Japan, also showed significant results (p < 0.00001). These small studies are particularly promising, as they suggest that ultrasound findings could serve as a additinioal diagnostic tool for ALS

Glaucoma is a multifactorial neurodegenerative disease, characterized by degeneration of the retinal ganglion cells (RGCs). There has been little progress in developing efficient strategies for neuroprotection in glaucoma. We profiled the retina transcriptome of Lister Hooded rats at 2 weeks after optic nerve crush (ONC) and analyzed the data from the Genomic Fabric Paradigm (GFP) to bring additional insights into the molecular mechanisms of the retinal remodeling after induction of RGC degeneration. GFP considers for the expression of each gene 3 independent characteristics: level, variability and correlation with each other gene. Thus, the 17,657 quantified genes our study generated a total of 155,911,310 values to analyze. This represents 8,830x more data per condition than a traditional transcriptomic analysis. ONC led to a 57% reduction in RGC numbers as detected by retrograde labeling with DiI. We observed a higher Relative Expression Variability after ONC. Gene expression stability was used as a measure of transcription control and disclosed a robust reduction in the number of very stably expressed genes. Predicted Protein-Protein interaction (PPI) analysis with STRING revealed axon and neuron projection as mostly decreased processes, consistent with RGC degeneration. Conversely, immune response PPIs were found among up-regulated genes. Enrichment analysis showed that Complement Cascade and Notch Signaling Pathway, as well as Oxidative Stress and Kit Receptor Pathway were affected after ONC. To expand our studies of altered molecular pathways, we examined the pair-wise coordination of gene expressions within each pathway and within the entire transcriptome using Pearson correlations. ONC increased the number of synergistically coordinated pairs of genes and the number of similar profiles mainly in Complement Cascade and Notch Signaling Pathway. This deep bioinformatic study provides novel insights beyond the regulation of individual gene expression and discloses changes in the control of expression of Complement Cascade and Notch Signaling functional pathways that may be relevant for both RGC degeneration and remodeling of the retinal tissue after ONC.

This study aims to optimize the subway platform passenger flow guidance method using Anylogic simulation software. The objective of the study is to minimize overcrowding within subway carriages, enhance transportation capacity, and augment service levels by guiding passengers on the platform to board trains in a distributed manner. The study achieves a balanced flow of passengers in each carriage by taking into consideration the number of passengers in each carriage, the number of passengers at the station, and the expected number of passengers disembarking from the trains. The standard deviation of balance is used to optimize the subway platform passenger flow guidance method. We simulated Guangzhou Metro Zhujiang New Town Line 5 platform to compare different guidance methods and evaluate their effects on the uneven distribution of passengers with passenger flows ranging from 120K to 600K people per day. Our results show that guidance method 2, relative to manual guidance, improves by 38.5% under a daily passenger flow of 240K people on Zhujiang New Town Line 5. Guidance method 3 improves by 25.7% relative to guidance method 2 and by 54.4% relative to manual guidance.

Background and Objectives: Ultrasound (US) is a non-invasive tool for the in-vivo detection of peripheral nerve alterations. Materials and Methods: In this study we applied nerve US to assist the discrimination between the spectrum of Amyotrophic Lateral Sclerosis (ALS, n=11), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n=5) and genetically confirmed Charcot-Marie-Tooth disease (CMT, n=5). All participants and n=15 controls without neurological diseases underwent high-resolution US of the bilateral tibial nerve. Nerve cross-sectional area (CSA) and nerve microvascular blood flow were compared between the groups and related to cerebrospinal fluid (CSF) measures, clinical symptoms and nerve conduction studies. Analyses are part of a larger multimodal study on the comparison between US and 7 Tesla (T) magnetic resonance neurography (MRN). Results: Patients and controls were matched with respect to their demographical data. CMT had the longest disease duration, followed by CIDP and ALS. CSA was related to age, weight and disease duration. CSA was larger in CMT and CIDP compared to ALS and controls. Blood flow was greatest in CIDP, and higher than in CMT, ALS and controls. In ALS, greater CSA was correlated with greater CSF total protein and higher albumin quotient. US measures did not correlate with clinical scores or nerve conduction studies in any of the subgroups. Conclusion: Our results point towards the feasibility of CSA and blood flow to discriminate between ALS, CIDP and CMT, even in small sample sized groups. In ALS, larger CSA could indicate an inflammatory disease subtype characterized by reduced blood-nerve barrier integrity. Our upcoming analysis will focus on the additive value of 7T MRN in combination with US to disentangle the spectrum between more inflammatory or more degenerative disease variants along the disease groups.

In 2015, the World Health Organization substantially revised its guidance for vaccination coverage cluster surveys (revisions were finalized in 2018) and has since developed a set of accompanying resources, including definitions for standardized coverage indicators and software (named the Vaccination Coverage Quality Indicators - VCQI) to calculate them. The current WHO vaccination coverage survey manual was used to design and conduct two nationally representative vaccination coverage surveys in Nigeria – one to assess routine immunization and one to measure post-measles campaign coverage. The primary analysis for both surveys was conducted using VCQI. In this paper, we describe those surveys and highlight some of the analyses that are facilitated by the new resources. In addition to calculating coverage of each vaccine-dose by age group, VCQI analyses provide insight into several indicators of program quality such as crude coverage versus valid doses, vaccination timeliness, missed opportunities for simultaneous vaccination, and, where relevant, vaccination campaign coverage stratified by several parameters, including the number of previous doses received. The VCQI software furnishes several helpful ways to visualize survey results. We show that routine coverage of all vaccines is far below targets in Nigeria and especially low in northeast and northwest zones, which also have highest rates of dropout and missed opportunities for vaccination. Coverage in the 2017 measles campaign was higher and showed less geospatial variation than routine coverage. Nonetheless, substantial improvement in both routine program performance and campaign implementation will be needed to achieve disease control goals.

This paper focuses on the integrated guidance and autopilot design with control input saturation in the end-game phase of hypersonic flight. Firstly, uncertain nonlinear integrated guidance and autopilot model is developed with third actuator dynamics, where the control surface deflection has magnitude constraint. Secondly, neural network is implemented in extended state observer (ESO) design, which is used to estimate the complex model uncertainty, nonlinearity and state coupling. Thirdly, a command filtered back-stepping controller is designed with hybrid sliding surfaces to improve the terminal performance. In the process, different command filters are implemented to avoid the influences of disturbances and repetitive derivation, meanwhile solve the problem of unknown control direction caused by saturation. The stability of closed-loop system is proved by Lyapunov theory, and the principles abided by the controller parameters are concluded through the proof. Finally, series of 6-DOF numerical simulations are presented to show the feasibility and validity of the proposed controller.

This paper presents a deep learning-based multi-guidance line detection approach, enabling an autonomous four-wheeled agricultural robot to navigate strip farmland. The integration of Proportional-Integral-Derivative (PID) and Fuzzy Logic Control (FLC) systems optimizes the velocity and heading angle of robot, facilitating smooth navigation along identified guidance line. Enhance cornering maneuverability with real-time kinematics (RTK)-assisted Global Navigation Satellite System (GNSS) (RTK-GNSS) positioning. Additionally, the spraying system combined with deep learning can effectively identify weeds and crop nutrient deficiencies to achieve precise spraying. The guidance system prioritizes irrigation lines for navigation, with additional guidance from crop and furrow lines. Trigonometric analysis determines the angular deviation between the identified guidance line and the vertical line of the top view image. Experiments under diverse weather conditions demonstrate the stable navigation of robot at 12.5 cm/s, achieving up to 90% accuracy in weed and nutrient deficiency identification. The spraying accuracy for weeds and deficiencies averages 87% and 73%, respectively, underscoring the system's contribution to sustainable and precision horticulture practices.

This research used an experimental study design in which 60 subjects were randomly assigned to either an experimental (image e-book guidance) group or a control (text guidance) group after meeting the admission conditions and agreeing to participate in the study. It was proven that providing image e-book guidance before surgery significantly changed the behavior of patients and promoted relief of urinary catheter discomfort through self-efficacy to reduce urinary catheter pain after surgery. It was found that providing image e-book guidance can shorten the time for health education and provide patients with repeated medical education and familiarity with health guidance, which can help to address the important clinical service demand issue and the shortage of nursing staff.

This study aims to precisely characterize the use of magnetoelectric nanoparticles (MENPs) for stimulating peripheral nerves. Numerical methods were employed to quantify the interaction between MENPs and nervous tissue. The influence of MENPs orientation, concentration and distance was assessed in terms of the external potential distribution exerted by the MENPs, the amplification of the exerted MENPs stimulation required to excite the neural fibers and the current injected into the intracellular space. The results highlight the significance of MENPs concentration for stimulation accuracy and efficiency, the impact of MENPs orientation on the electric potential distribution sensed by the nervous tissue, as well as the importance of the MENPs distance over the fibers’ recruitment. Given the considerable variability in the interaction between MENPs and nerves, our research provides a crucial step towards understanding this interaction, offering quantitative support for the application of MENPs in nervous tissue stimulation.

Extracellular vesicles (EVs), including exosomes, microvesicles, and other lipid vesicles derived from cells, play a pivotal role in intercellular communication by transferring information between cells. EVs secreted by progenitor and stem cells have been associated with the therapeutic effects observed in cell-based therapies, and they also contribute to tissue regeneration following injury, such as in orthopedic surgery cases. This review briefly explores the involvement of EVs in tissue repair and nerve regeneration, their potential as drug carriers, and their significance in stem cell research and cell-based therapies. It underscores the importance for bioengineers to comprehend and manipulate EV activity to optimize the efficacy of tissue engineering and regenerative therapies.

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.

In this paper, to make the missile intercept the maneuvering target, the parallel approaching guidance law is developed. In order to estimate the target maneuver more accurately and reduce that’s influence on guidance accuracy, the distance-scalar disturbance observer is employed. Specifically, the estimation accuracy of the observer designed is regardless of the relative distance. The finite-time prescribed performance is employed to ensure that the line-of-sight angular rate is capable of converging to a predesigned small region in the specified finite time. All signals of interception system can guarantee ultimately uniformly boundedness proved by the Lyapunov stability theory. Finally, the availability of the parallel approaching guidance law is demonstrated by the numerical simulation.

This paper presents a combined optical imaging/artificial intelligence (OI/AI) technique for real-time analysis of tissue morphology at the tip of the biopsy needle, prior collecting a biopsy specimen. This is an important clinical problem as up to 40% of the collected biopsy cores provide low diagnostic value due to high adipose or necrotic content. Micron-scale resolution optical coherence tomography (OCT) images can be collected with a minimally invasive needle probe and automatically analyzed by a computer neural network (CNN)-based AI software. The results can be conveyed to the clinician in real-time and used to select the biopsy location more adequately. This technology was evaluated on a rabbit model of cancer. OCT images were collected with a hand-held custom-made OCT probe. Annotated OCT images were used as ground truth for AI algorithm training. The overall performance of the AI model was very close to that of the humans performing the same classification tasks. Specifically, tissue segmentation was excellent (~99% accuracy) and provided segmentation that closely mimicked ground truth provided by the human annotations, while over 83% correlation accuracy was obtained for tumor and non-tumor classification.

Target detection and segmentation in synthetic aperture radar (SAR) images are vital steps for many remote sensing applications. In the era of data-driven deep learning, this task is extremely challenging due to the limited labeled data. Few-shot Learning has the ability to learn quickly from few samples with supervised information. Inspired by this, a few-shot learning framework named MSG-FN is proposed to solve the segmentation of ship targets in heterologous SAR images with few annotated samples. The proposed MSG-FN adopts a dual-branch network consisting of a support branch and a query branch. The support branch is used to extract features with an encoder, and the query branch uses a U-shaped encoder-decoder structure to segment the target in the query image. The encoder of each branch is composed of well-designed residual blocks combined with filter response normalization to capture robust and domain-independent features. A multi-scale similarity guidance module is proposed to improve the scale adaptability of detection by applying hand-on-hand guidance of support features to query features of various scales. In addition, a SAR dataset named SARShip-4i is built to evaluate the proposed MSG-FN and the experimental results show that the proposed method achieves superior segmentation results compared with the state-of-the-arts.

Objectives: Data sharing has become a requirement of many funding bodies and is becoming a scientific standard in many disciplines. In medical research, however, data sharing can conflict with clinicians’ obligation to protect patients’ privacy. General recommendations on data sharing exist also for clinical research, but so far lack practical and Swiss-specific aspects. The objective of this document is to provide practical recommendations for all relevant aspects of data sharing in agreement with legislation in Switzerland. Methods: This document was written by members of the Swiss CTU Network, a network of academic clinical trial units. The process did not follow a formalized Delphi process. After an internal consensus round, this report is now published as pre-print for external review. A second version will incorporate external comments. We plan to publish this document as a text in progress, as we expect relevant changes in related fields such as the development of further dedicated medical repositories or methodological advances in anonymization techniques. Results: We developed principles and practical recommendations with respect to informed consent, data management plan, anonymization, data structure and format, coding of variables, metadata and documentation, version control, selection of repository, requesting and use of data. We also provide a summary of legal aspects relevant for the Swiss context. Conclusions: The intension to share data has an impact not only after a clinical trial or an observational study is completed, but also during the planning period, the conduct and the analysis phase. Clinical researchers need to be aware at the beginning of a study on how to inform patients and at least the amount of work related to preparing data for sharing, metadata, and any further documentation. This report provides details of aspects to be considered, suggests decision criteria, and provides examples and checklists, in order to support data sharing in practice.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

The aim of this review was to provide an update on the potential of cell therapies to restore or replace damaged and/or lost cells in retinal degenerative and optic nerve diseases, describing the available cell sources and the challenges involved in such treatments when these techniques are applied in real clinical practice. Sources include human fetal retinal stem cells, allogenic cadaveric human cells, adult hippocampal neural stem cells, human CNS stem cells, ciliary pigmented epithelial cells, limbal stem cells, retinal progenitor cells (RPCs), human pluripotent stem cells (PSCs) (including both human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs)) and mesenchymal stem cells (MSCs). Of these, RPCs, PSCs and MSCs have already entered early-stage clinical trials since they can all differentiate into RPE, photoreceptors or ganglion cells, and have demonstrated safety, while showing some indicators of efficacy. Stem/progenitor cell therapies for retinal diseases still have some drawbacks, such as the inhibition of proliferation and/or differentiation in vitro (with the exception of RPE) and the limited long-term survival and functioning of grafts in vivo. Some other issues remain to be solved concerning the clinical translation of cell-based therapy, including (1) the ability to enrich for specific retinal subtypes; (2) cell survival; (3) cell delivery, which may need to incorporate a scaffold to induce correct cell polarization, which increases the size of the retinotomy in surgery and, therefore, the chance of severe complications; (4) the need to induce retinal detachment to perform the subretinal placement of the transplanted cell; and (5) the evaluation of the risk of tumor formation caused by the undifferentiated stem cells and prolific progenitor cells. Despite these challenges, stem/progenitor cells represent the most promising strategy for retinal and optic nerve disease treatment in the near future, and therapeutics assisted by gene techniques, neuroprotective compounds and artificial devices can be applied to fulfil clinical needs.

Nerve hydrodissection (HD), a technique used when treating nerve entrapments, involves using an anesthetic or solution such as saline or 5% dextrose solution to separate the nerve from the surrounding tissue, fascia, or adjacent structures. This technique aims to treat neuropathic pain, or pain caused by the nerve. Ultrasound-guided HD of peripheral nerves has gained significant attention in the medical profession and pain management fields in recent years. This is due to a number of high impact publications of randomized control trials demonstrating the efficacy and safety of this technique for the treatment of carpal tunnel syndrome. Even the 20th edition of Harrison’s Principles of Internal Medicine textbook lists injection of 5% dextrose as an alternative local treatment that does not have the side effects of corticosteroids. At present, there is no review of the current literature on this technique. This manuscript will summarize and discuss the following: 1) the different approaches to doing ultrasound-guided HD of nervous structures, 2) its usages in different clinical situations, 3) its clinical pearls, 4) the solution used, and 5) the postulated mechanisms of action.

Previous studies have reported certain sex differences in motor performance precision. The aim of the present study was to analyse sex differences in fine motor precision performance for both hands in different tests conditions. 220 Spanish participants (ages: 12-95) performed fine motor tasks - tracing over the provided models – lines of 40 mm for both hands, two sensory conditions (PV – proprioceptive-visual; P – proprioceptive only) and three movement types (F – frontal, T – transversal and S - Sagittal). Differences in line length (the task focused on precision) were observed through MANOVA analysis for all test conditions, both sexes and different age groups. Sex differences in precision were observed in F and T movement types (statistically significance level and higher Cohens’ d was observed in condition with vision). No any statistically significant differences were observed in both hands and sensory conditions in sagittal type. Sex differences in fine motor precision were more frequently observed in the PV sensory condition in the frontal movement type and less in the sagittal one.

Prevention of obstetric trauma from damage to the pelvic floor is not always possible and sacral nerve stimulation (SNS) may be necessary later in life. Sacral nerve stimulation has been a promising innovation in the management of moderate to severe faecal incontinence and following sphincter repair failure. Although the indication spectrum for SNS is expanding, the success of neuromodulation for constipation is limited. Adverse events of SNS requiring re-intervention are not common but a long-term successful outcome may depend on interventions for maintenance of the device.

This work aims to develop an autonomous system for the unmanned aerial vehicle (UAV) to land on a moving platform such as the automobile or marine vessels, providing a promising solution for a long-endurance flight operation, a large mission coverage range, and a convenient recharging ground station. Different from most state-of-the-art UAV landing frameworks which rely on UAV’s onboard computers and sensors, the proposed system fully depends on the computation unit situated on the ground vehicle/marine vessel to serve as a landing guidance system. Such novel configuration can therefore lighten the burden of the UAV and computation power on the ground vehicle/marine vessel could be enhanced. In particular, we exploit a sensor fusion-based algorithm for the guidance system to perform UAV localization, whilst a control method based upon trajectory optimization is integrated. Indoor and outdoor experiments are conducted and the result shows that a precise autonomous landing on a 43 X 43 cm platform could be performed.

Axon guidance is a crucial process for growth of the central and peripheral nervous systems. In this study, 3 axon guidance related disorders, namely- Duane Retraction Syndrome (DRS) , Horizontal Gaze Palsy with Progressive Scoliosis (HGPPS) and Congenital fibrosis of the extraocular muscles type 3 (CFEOM3) were studied using various Systems Biology tools to identify the genes and proteins involved with them to get a better idea about the underlying molecular mechanisms including the regulatory mechanisms. Based on the analyses carried out, 7 significant modules have been identified from the PPI network. Five pathways/processes have been found to be significantly associated with DRS, HGPPS and CFEOM3 associated genes. From the PPI network, 3 have been identified as hub proteins- DRD2, UBC and CUL3.

Major cardiovascular events (MACE) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques is diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation the affected blood vessel diameter in order to decide if intervention with stent colocation is suitable, where small blood vessels (&lt; 2.75 mm) are majorly left untreated; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for recurrence of MACE, and there are some limitations to the use of CAG that could be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain their underuse. To address this discrepancy and identify specific cases for its use, we conducted a retrospective study in patients who underwent PCI for MACE with at least one small blood vessel affected. The affected small blood vessels’ diameter was obtained with both CAG and IVUS, additionally we underwent a multivariate analysis to identify risk factors associated with a change in diameter. We included information from 48 patients with mean + SD age of 69.1 + 11.9 years and 34% were masculine gender. We found a significant positive low correlation in diameter measurements of small blood vessels (r=0.1242 p=0.014). Mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0) the estimated difference was of 0.8 mm (95 % CI 0.7-0.9). In total 37 (77%) of patients had a reclassification of their blood vessels from a small to medium (2.75-3.00 mm) in 21 cases, or even large (&lt;3.00 mm) in 15 cases, after IVUS; this was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjusted in a multivariate analysis was DT2 (p=0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in the diabetes population, therefore at least in these cases the use of IVUS is recommended over CAG.

We report an unusual case of Terson's syndrome that resulted in the di-agnosis of a right posterior communicating artery aneurysm. Interest-ingly Terson's syndrome presented with Roth spot resembling features accompanied by third nerve palsy in a patient without any disturbance of consciousness. To our knowledge, the association of Terson's syndrome with third nerve palsy has not been described before in the absence of radiologically diagnosed subarachnoid haemorrhage. We present the case of a 48-year old woman who presented in the De-partment of Emergencies of the University Hospital of Patras with right-sided complete pupil-involving third nerve palsy combined with bilateral Terson's syndrome. More precisely, fundoscopy revealed multi-ple scattered intra- and pre-retinal haemorrhages in both eyes while some retinal haemorrhages had a white-centered pattern resembling Roth spots. Neurological examination revealed no nuchal rigidity or any other neurological signs. The Glasgow coma scale was 15/15. A cerebral computed tomography angiography revealed a 5mm aneurysm of the right posterior communicating artery and the patient underwent a mi-crovascular clipping operation after craniotomy. The significant contribution of the ophthalmological consultation to the appropriate and timely diagnosis and management of a life-threatening condition is highlighted.

The carotid body is a major peripheral chemoreceptor that senses changes in arterial blood oxygen, carbon dioxide, and pH, what is important for regulation of breathing and cardiovascular function. The mechanisms by which the carotid body senses O2 and CO2 are well known; conversely, the mechanisms by which it senses pH variations are almost unknown. Here we used immunohistochemistry to investigate how the human carotid body contributes to the detection acidosis analyzing whether it expresses acid-sensing ion channels (ASIC) ion channels, and to know if these channels are in the cells chemosensory glomic cells or in the afferent nerves. ASIC1, ASIC2 and ASIC3, and to a much lesser extent ASIC4, immunoreactivity was detected in subpopulations of type I glomus cells, as well as in the nerves of the carotid body. In addition, immunoreactivity was found for all ASIC subunits in neurons of the petrosal and superior cervical sympathetic ganglia, where afferent and efferent neurons are located, respectively, innervating the carotid body. This study reports for the fist time the occurrence of ASIC proteins in the human carotid body, demonstrating that they are present in glomus chemosensory cells (ASIC1 &lt; ASIC2 &gt; ASIC3 &gt; ASIC4) and nerves, presumably both afferent an efferent supplying the organ. These results suggest that the detection of acidosis by the carotid body can be mediated by ASIC ion channels present in the type I glomus cells or directly by sensory nerve fibers.

Hypoglossal nerve stimulator (HGNS) is a minimally invasive device used for treating obstructive sleep apnea (OSA). The conventional implantable HGNS is a device that consists of a stimuli generator, a breathing sensor, and electrodes connected to the hypoglossal nerve via leads. However, this implant is bulky and causes significant trauma. In this paper, we propose a minimally invasive HGNS based on an electrocardiogram (ECG) sensor and a wireless power transfer (WPT), consisting of a wearable breathing monitor and an implantable stimulator. The breathing external monitor utilizes an ECG sensor to identify abnormal breathing patterns associated with OSA with 88.68$\%$ accuracy, achieved through the utilization of a Convolutional Neural Network (CNN) algorithm. With a skin thickness of 5mm and a receiving coil diameter of 9mm, the power conversion efficiency was measured at 31.8$\%$. The implantable device, on the other hand, is composed of a front-end CMOS Power Management Module (PMM), a Binary Phase Shift Keying (BPSK)-based data demodulator, and a bipolar biphasic current stimuli generator. The PMM, with a silicon area of 0.06 $mm^2$ (excluding pads), demonstrates a power conversion efficiency of 77.5$\%$ when operating at a receiving frequency of 2 MHz. Furthermore, it offers three-voltage options (1.2V, 1.8V, and 3.1V). Within the data receiver component, a low-power BPSK demodulator has been ingeniously incorporated, consuming only 42 $\mu$W when supplied with a voltage of 0.7V. The performance is achieved through the implementation of the self-biased phase-locked loop (PLL) technique. The stimuli generator delivers biphasic constant currents, providing a 5-bit programmable range spanning from 0 to 2.4 mA. The functionality of proposed ECG and WPT-based HGNS was validated, representing a highly promising solution for the effective management of OSA, all while minimizing trauma and space requirements.

Colistin is used in treatment against gram-negative bacteria. It causes toxic effects due to oxidative stress in a dose-dependent manner. Naringin is a flavonoid with strong antioxidant properties found naturally in many plants, especially citrus fruits. This study aimed to determine the protective effects of NRG in CLS-induced sciatic nerve injury. Thirty-five male Spraque rats were randomly divided into five groups: control, NRG, CLS, CLS+NRG50, and CLS+NRG100. CLS was administered orally at a 15mg/kg for seven days. NRG was administered orally at 50 or 100 mg/kg for seven days. CLS caused toxic damage in sciatic nerve tissue by increasing MDA and decreasing antioxidant capacity (SOD, CAT, GPx, and GSH); increasing NF-κB, TNF-α, nNOS release; increasing apoptotic factor (Caspase-3); decreasing HO-1 and nCAM; and inducing 8-OHdG, MAPK and GFAP. NRG, on the other hand, reversed all these changes in sciatic nerve tissue and reduced CLS-induced oxidative stress damage, inflammatory damage and apoptotic damage. These effects were more effective at the 100mg/kg dose of NRG than at the 50mg/kg dose. In sciatic nerve tissue, CLS-induced sciatic nerve toxicity with increased oxidative stress, inflammation, and apoptotic damage. NRG showed a protective effect against CLS-induced sciatic nerve toxicity.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon^® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Investigations reporting positive effects of Extracorporeal Shock Wave Therapy (ESWT) on nerve regeneration are limited to the rat sciatic nerve model. The effects of ESWT on muscle-in-vein conduits (MVCs) have also not been investigated yet. This study aimed to evaluate the effects of ESWT after repair of the rat median nerve with either autografts (ANGs) or MVCs. In male Lewis rats, a 7-mm segment of the right median nerve was reconstructed either with an ANG or MVC. For each reconstructive technique, one group of animals received one application of ESWT while the other rats served as controls. Animals were observed for 12 weeks and nerve regeneration was assessed via computerized gait analysis, the grasping test, electrophysiological evaluations and histological quantification of axons, blood vessels and lymphatic vasculature. Here we provide for the first time a comprehensive analysis of ESWT effects on nerve regeneration in a rat model of median nerve injury. Furthermore, this study is among the first reporting the quantification of lymphatic vessels following peripheral nerve injury and reconstruction in vivo. While we found no significant direct positive effects of ESWT on peripheral nerve regeneration, results following nerve repair with MVCs were significantly inferior to those after ANG repair.

Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.

BACKGROUND: Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child's quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves. AIM: To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation. METHODS: Between April 2019 and October 2021, 38 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro-Wilk test. Wilcoxon test and Student's t-test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables. RESULTS: Of the 38 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported. CONCLUSION: TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation.

Background Ultrasonographic measurement of the optic nerve sheath diameter (ONSD) is helpful in the assessment of intracranial pressure. The aim of this study was to determine whether the Trendelenburg position during laparoscopic urological surgery changed the ONSD and whether changes correlated with postoperative complications. Methods In this prospective study, we measured ONSD before patients were placed in the Trendelenburg position. Then the Trendelenburg position was established by tilting the operating table to 20-25 degrees. After surgery, the patients were placed in a horizontal position, and the second measurement of ONSD was obtained. Results The study included 69 patients. The average preoperative ONSD in the right eye was 5.8 ± 0.7 mm and 5.8 ± 0.8 mm in the left eye. The average postoperative ONSD in the right eye was 6.6 ± 0.8 mm and 6.6 ± 0.7 mm in the left eye. The differences between postoperative and preoperative values in the right and left eyes were statistically significant (p <0.000001). ONSD increases above the norm did not correlate with the incidence of postoperative nausea (p = 0.94), delirium (p = 0.81), or the time to patient awakening (p = 0.29). Conclusion ONSD increased in patients who underwent surgical procedures performed in the Trendelenburg position, but the increase did not correlate with postoperative complications.

Bilateral recurrent nerve damage following total thyroidectomy in thyroid surgery represents severe complications. These complications have almost low incidence thanks also by using the Nerve Intraoperative Monitoring. The aim of this observational retrospective study is to evaluate the inception mode and the recovery time for different clinical laryngeal pictures that arise from this surgery. We enrolled 25 patients with bilateral vocal folds mobility deficit between October 2017 and October 2022, diagnosed in ENT Unit of University of Campania “L. Vanvitelli”, out of a total of 1417 patients undergoing total thyroidectomy. The 25 patients (23F,2M) aged from 24 to 78 years old (average age 51.7) presented a bilateral vocal folds motility deficit (occurring in about 0.1% of cases). All patients underwent 9 months diagnostic/therapeutic process, which started approximately 30 days after thyroid surgery. There are several outcomes of these complications with functional laryngeal defects being mainly related to respiratory and phonatory activities. These clinical manifestations evolve in different ways within a context of a wide range of possibilities, from spontaneous bilateral or monolateral recovery to functional or surgical restoration. This study allowed the acquisition of useful information about prognostic indications and an adequate therapeutic process, based on the specific clinical characteristics.

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., pro-NGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. Besides pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

The center vortex model of quantum chromodynamic states that vortices, closed color-magnetic flux, percolate the vacuum. Vortices are seen as the relevant excitations of the vacuum, causing confinement and dynamical chiral symmetry breaking. In an appropriate gauge, as direct maximal center gauge, vortices are detected by projecting onto the center degrees of freedom. Such gauges suffer from Gribov copy problems: different local maxima of the corresponding gauge functional can result in different predictions of the string tension. By using non-trivial center regions, that is, regions whose boundary evaluates to a non-trivial center element, a resolution of this issue seems possible. We use such non-trivial center regions to guide simulated annealing procedures, preventing an underestimation of the string tension in order to resolve the Gribov copy problem.

Abstract: In this comprehensive review, we delve into the significance of the mul-timodal imaging in diagnosing and managing of complications of congenital optic nerve anomalies.. While the Fundus examination is the gold standard tool in diagnosisc of these pathologies, SD OCT and OCTA could shed a light in the pathogenesis, and treatment. Moreover , this review seeks to offer a comprehensive insight into a multimodal approach of these rare congenital pathologies. In conclusion, congenital anomalies of the optic nerve represent a major challenge for ophthalmologists Further research could be clarify the pathophysiology of these diseases and define a correct and specific treatment approach. Keywords: keyword 1; ODC, ODP, MGS, OCT; OCTA, Multimodal imaging.

Organophosphorus nerve agents are amongst the most toxic chemicals known to human beings. 9 They interfere with the central nervous system, resulting in continuous muscle contractions, 10 paralysis and even death. Prohibition by many countries around the world cannot disguise the 11 remaining presence of nerve agents in stockpile storage and governmental deployment, 12 highlighting the dire need for an efficient catalyst to degrade and detoxify nerve agents by 13 hydrolysis. Metal-organic frameworks (MOFs) have raised a few eyebrows for their permanent 14 porosity, precise tunability, and lasting stability. Modern Reticular Chemistry fosters the design and 15 synthesis of well-defined crystalline MOFs with open Lewis acidic metal sites that can catalytically 16 hydrolyze nerve agents both in aqueous solution and in solid state systems, unveiling unparalleled 17 potential for MOF-based personal protection gears. In this review, a summary of the representative 18 catalytically active MOFs in nerve agent hydrolysis is discussed. MOFs are categorized by their 19 reticular structure, emphasizing the capability and mechanistic insights of each single MOF in nerve 20 agent hydrolysis. The author’s perspective on the current challenges and future directions of MOF- 21 based catalysts in real-world protection applications is also provided, which hopefully could shed some 22 light on the future development of commercially available MOF protection suits.

Tarsal tunnel syndrome is a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches. Brief mention is made in the literature of the use of corticosteroid injections for this condition. The basic technique of hydrodissection is used for other nerve entrapments and includes identifying the region of nerve compression, and the injection of a fluid medium to dissect between structures or fascial planes. We introduce our treatment protocol using a methylprednisolone/sterile water/ropivacaine hydrochloride injectate mix and peripheral nerve stimulation to a perform hydrodissection technique for tarsal tunnel syndrome.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these nervous structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these nervous structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch were measured. We found that at the greater sciatic foramen the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to it. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, has been used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than Grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan–Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, it concludes that TESS was feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region, even during CRT. Although the precise mechanism of TESS on dysphagia is not yet clear, its continued use has great potential for improving sensory disturbance.

Gene therapy is becoming increasingly prevalent, with new gene therapy medicinal products (GTMPs) being approved for use every year. Hospital pharmacists are expected to prepare and dispense these products, but there is substantial heterogeneity in the availability of up-to-date, practical guidance at a national level in Europe. Many institutions have no or very limited experience in handling GTMPs. As such, there is a need for updated, practical guidance to aid hospital pharmacy teams in developing institutional standard operating procedures (SOPs) for the safe handling of GTMPs across the entire workflow. Here, we present the European Association of Hospital Pharmacists’ updated guidance on the handling of GTMPs, developed by a team of recognised experts from around Europe. Each aspect of the GTMP handling process is addressed, including receipt and storage, dispensing and reconstitution, transportation, administration, waste disposal, decontamination of spills and accidental exposure. A series of charts are provided to aid the development of practical workflows. This guidance document is intended as a framework to help develop institutional SOPs and should always be used in conjunction with local regulations.

More than 13.5 billion COVID-19 vaccine doses have so far been delivered between 2021 and 2023 through a mix of delivery platforms, with mass vaccination campaigns being the main approach. In 2022, with the most likely scenario of continued circulation of SARS-CoV-2 and the need for periodic booster doses, there was a need for countries to plan for more sustainable approaches to provide COVID-19 vaccination. In this context of uncertainty, a global tool for integrating COVID-19 vaccines into immunization programmes and primary health care was published jointly by WHO and UNICEF to respond to country needs. The guidance leveraged existing health system frameworks, proposed four steps for the COVID-19 integration journey, and identified investment areas. The development process maximized robust global stakeholder and country engagement, and the timeframe was aligned with donor funding windows to support the integration of COVID-19 vaccination. The rapid dissemination of guidance allowed its use by countries to ascertain their readiness for integrating COVID-19 vaccination and inform the development of national plans and funding applications. While progress has been made in specific areas (e.g., optimizing cold chain and logistics leveraging COVID-19 vaccination), in the context of decreasing demand for COVID-19 vaccines, reaching adult COVID-19 vaccine high-priority-use groups and engaging and coordinating with other health programmes (beyond immunization) remains a challenge. We share the learning that despite the uncertainties of a pandemic, guidance documents can be developed and used within a short timeframe. Working in partnership with stakeholders beyond immunization towards a common objective is powerful and can allow progress to be made on integrating health services and preparing better for future pandemics.

Background : Drug treatments for gait disorders in post-stroke patients aim to reduce muscular hyperactivity. Analysis of muscle activity is essential to help clinicians understand these disorders. The aim of this study was to quantify changes in muscle synergies before (PRE) and after (POST) rectus femoris nerve block. Methods : Gait analysis of 8 post-stroke patients before and immediately after nerve block. Muscle synergies were quantified from electromyographic signals. We have selected: the account for variance indicating the robustness of the synergies, the recruitment selectivity index indicating the degree of multiplexing of the synergies, and the recruitment consistency index indicating the variability of the synergies. Results : A decrease in VAF is observed, suggesting a reduction in gait pattern robustness. We also note that spatial and temporal primitives are slightly different (IRC, IRS) in PRE vs. POST, and that their activation is more nested in POST than in PRE. Conclusions : The motor nerve block has not created new muscle synergies of the paretic limb during gait, but indicates that there is flexibility in motor organization. This method of quanti-fication may enable clinicians to assess the motor adaptation potential of their post-stroke patient.

Lower urinary tract dysfunction, such as incontinence or urinary retention, is one of the leading consequences of neurological diseases. This significantly impacts the quality of life for those affected, with implications extending not only to humans but also to clinical veterinary care. Having motor and sensory fibers, the pudendal nerve is an optimal candidate for neuromodulation therapies using bidirectional intraneural prostheses, paving the way towards the restoration of a more physiological urination cycle: bladder state can be detected from recorded neural signals, then an electrical current can be injected to the nerve based on the bladder real-time need. To develop such prostheses and investigate this novel approach, animal studies are still required since the morphology of the target nerve is fundamental to optimize the prosthesis design. This study aims to describe the porcine pudendal nerve as a model for neuromodulation studies aiming at restoring lower urinary tract dysfunction. Five male farm pigs were involved in the study. First, a surgical procedure to access the porcine pudendal nerve without muscle resection was developed. Then, an intraneural interface was implanted to confirm the presence of fibers innervating the external urethral sphincter by measuring its electromyographic activity. Finally, the morpho-physiology of the porcine pudendal nerve at the level of surgical exposure was described by using histological and immunohistochemical characterization. This analysis confirmed the nerve fasciculate nature and the presence of mixed fibers with a spatial and functional organization. These achievements pave the way for further pudendal neuromodulation studies by using a clinically relevant animal model with the potential for translating the findings into clinical applications.

Erectile dysfunction (ED) is a common and feared complication of radical prostatectomy (RP) for prostate cancer. Recently, tissue engineering is being attempted for post-prostatectomy ED, with controlled interactions between cells, growth factors, and extracellular matrix (ECM) being important for nerve regeneration's structural integrity. In this study, we evaluated the effects of biomechanical ECM patch on human bone marrow-derived mesenchymal stem cells (hBMSCs) morphology and behavior in bilateral cavernous nerve injury (BCNI) rat model. The ECM patch, made of decellularized human fibroblast-derived ECM (hFDM) and a biocompatible polyvinyl alcohol (PVA) hydrogel, was tested with human bone marrow-derived mesenchymal stem cells (hBMSCs) on a bilateral cavernous nerve injury (BCNI) rat model. In vitro analysis showed that the hFDM/PVA + hBMSCs patches significantly increased neural development markers. In vivo experiments demonstrated that the rats treated with the hFDM/PVA patch had higher ICP/MAP ratio, a higher ratio of smooth muscle to collagen, increased content of nNOS, higher levels of eNOS protein expression, and a higher cGMP level compared to the BCNI group. These results indicate that the hFDM/PVA patch is effective in promoting angiogenesis, smooth muscle regeneration, and nitrergic nerve regeneration, which could contribute to improved erectile function in post-prostatectomy ED.

Optic nerve sheath diameter (ONSD) can help predict the neurologic outcome of patients with post-cardiac arrest (CA) return of spontaneous circulation (ROSC). We aimed to investigate the effect of ONSD changes before and after CA on neurologic outcomes in patients with ROSC after CA using brain computed tomography (CT). The study included patients hospitalized after CA, who had undergone pre- and post-CA brain CT from January 2001 to September 2020. The patients were divided into good and poor neurologic outcome (GNO and PNO, respectively) groups based on the neurologic outcome at hospital discharge. We performed between-group comparisons of the amount and rate of ONSD changes on brain CT and calculated the area under the curve (AUC) to determine their predictive value for neurologic outcomes. Among the 96 enrolled patients, 25 had GNO. Compared to the GNO group, the PNO group showed significantly higher amount (0.30 vs. 0.63 mm; p=0.030) and rate of change (5.26 vs. 12.29 %; p=0.041). The AUC for predicting PNO was 0.64 (95% CI=0.53–0.73; p=0.04) and patients with a rate of ONSD change &gt;27.2% had PNO with 100% specificity and positive predictive value. Hence, ONSD changes may predict neurologic outcomes in patients with post-CA ROSC.

Peripheral nerve injury (PNI) is a complex clinical challenge affecting quality of life. Neurological recovery does not always ensure functional recovery as extracellular matrix (ECM) alterations affecting muscle function. This study evaluates hyaluronan (HA) and collagen concentration in gastrocnemius muscle and thoracolumbar fascia (TLF) in unilateral lower limb PNI rats to ex-plore systemic ECM alterations following PNI and their impacts on functional recovery. Eighteen 8-week-old male Sprague-Dawley rats were divided into experimental (n=12 with left sciatic nerve transection injury repaired by nerve conduit) and control (n=6) groups. After six weeks, motor function was evaluated. Muscle and TLF samples were analyzed for HA and collagen concentrations using Purple-Jelley HA Assay and Total-Collagen Assay kit. HA and collagen distribution was assessed using Alcian Blue and immunohistochemistry, and Picrosirius Red staining. In PNI rats, SFI and gait analysis were -87±9.12 and 1.32±0.29. Both sides of muscles showed significantly lower HA concentration than that in healthy rats (left p

Background: Trigeminal neuralgia associated to vascular compression, by aberrant or ectopic arterial or venous vessels, is a frequent condition in clinical practice. Management with microvascular decompression through a Minimal invasive retrosigmoidal has shown high rates of pain control, with low complication rates and excellent therapeutic results. Objective: To describe the surgical technique and clinical outcomes in terms of pain relief after microvascular decompression for trigeminal nerve, through a minimal invasive retrosigmoidal parasterional burr-hole technique. Methods: A group of patients with trigeminal neuralgia refractory to medical management who underwent microvascular decompression considering outcomes based on Visual Analogue Scale (VAS), and Barrow Neurological Institute Pain Scale (BNIPS). Added to a technical note of the surgical technique for a minimal invasive retrosigmoidal parasterional burr-hole. Results: Twenty-two patients were evaluated, clinical assessment after surgical intervention showed a decrease pain according to VAS, resulting from an average preoperative state of 9.5 ± 0.37 to a postoperative condition of 1.32 ± 1.28, exhibiting statistically significant changes (p < 0.0001, d = 9.356). On the other hand, in relation to the BNIPS scale, a decrease from an average preoperative status of 4.55 ± 0.25, to a postoperative status at 12 months of 1.73 ± 0.54 was also demonstrated, showing significant changes (p < 0.0001, d = 3.960). Conclusion: Microvascular decompression of the trigeminal nerve through a minimal invasive retrosigmoidal parasterional burr-hole is feasible and can be a safe and effective technique for the management of pain.

Axonal degeneration resulting from optic nerve damage can lead to the progressive death of retinal ganglion cells (RGCs), culminating in irreversible vision loss. We contrasted two methods for inducing optic nerve damage: optic nerve compression (ONCo) and optic nerve crush (ONCr). These were assessed for their respective merits in simulating traumatic optic neuropathies and neurodegeneration. We also administered neural progenitor cells (NPCs) into the subtenon space to validate their potential in mitigating optic nerve damage. Our findings indicate that both ONCo and ONCr successfully induced optic nerve damage, as shown by increased ischemia and expression of genes linked to neuronal regeneration. Post NPCs injection, recovery in the expression of neuronal regeneration-related genes was more pronounced in the ONCo model than in the ONCr model, while inflammation-related gene expression saw a better recovery in ONCr. In addition, proteomic analysis of R28 cells in hypoxic conditions identified Vps35 and Syntaxin12 genes. Vps35 preserved mitochondrial function in ONCo, while Syntaxin12 appeared to restrain inflammation via the Wnt/β-catenin signaling pathway in ONCr. NPCs managed to restore damaged RGCs by elevating neuroprotection factors and controlling inflammation through mitochondrial homeostasis and Wnt/β-catenin signaling in hypoxia-injured R28 cells and in both animal models. Our results suggest that ischemic injury and crush injury cause optic nerve damage via different mechanisms, which can be effectively simulated using ONCo and ONCr, respectively. Moreover, cell-based therapies such as NPCs may offer promising avenues for treating various optic neuropathies, including ischemic and crush injuries.

The measurement of sP4 often varies due to different laboratory methodologies and individual canine characteristics. In this investigation, sP4 outcomes obtained from a commercial POC analyzer, designed for efficient sP4 assessment in bitches, were compared with results derived from CMIA, the reference laboratories in Thailand. Thorough documentation encompassed various parameters: mean, standard deviation (SD), 95% confidence interval (CI), minimum and maximum sP4 concentration values. Additionally, we meticulously recorded the Pearson’s correlation coefficient, Lin’s concordance correlation coefficient, and the bias correction factor. Interestingly, there was no significant difference (p &gt; 0.05) in the means obtained by the POC and CMIA. The Pearson’s correlation coefficient between POC and CMIA stood at 0.957, with Lin’s concordance correlation coefficient for POC recorded as 0.949. Furthermore, the bias correction factor was established at 0.991. This investigation followed established CMIA guidelines, modified to incorporate the mean and 95% CI as criteria for optimal breeding time using the POC analyzer. In conclusion, the commercial POC immunologic analyzer emerges as a valuable tool, aiding in precisely determining the optimal timing for natural mating or artificial insemination in bitches.

The in silico studies were performed in order to assess the binding affinity of selected organophosphorus compounds towards the acetylcholinesterase enzyme (AChE). Quantum mechanical calculations, molecular docking and molecular dynamics (MD) with molecular mechanics Generalized-Born surface area (MM/GBSA) were applied to assess quantitatively differences between the binding energies of acetylcholine (ACh; the natural agonist of AChE) and neurotoxic, synthetic correlatives (so-called “Novichoks”, and selected compounds from the G- and V-series). Several additional quantitative descriptors like root mean square fluctuation (RMSF) and the solvent accessible surface area (SASA) were briefly discussed to give – to the best of our knowledge – the first quantitative in silico description of AChE – Novichok non-covalent binding process and thus facilitate the search for an efficient and effective treatment for Novichok intoxication and in a broader sense - intoxication with other warfare nerve agents as well.

Brain stem cells (neural stem cells or NSCs) and neurons of a chosen kind reprogramming is a potential technique for cell therapy. It is possible to reprogram non-neuronal cells, for example, by using a predetermined group of factors, nuclear transfer, and the induced transcriptional factors (TFs) expression in a related lineage of cells, and non-coding microRNAs (miRNAs). Researchers have additionally been attempting to improve reprogramming methods, whether it is by employing unique sets of biomolecules and particular TFs or by delivering relevant miRNA and Biomolecules. The technique of miRNA mediated is intriguing for its capability to quickly create a range of biologically desirable cell types for therapy from different lineages of cells. Current findings have made significant advancements towards changing the somatic cells to diverse particular neuronal subgroups with greater efficiency, using reprogramming of miRNA-mediated neural cells, despite the fact that the precise processes need to be discovered. To further understand how miRNAs might direct somatic cells to become neural, we need to look at the latest research on their function in neural reprogramming over the differentiated cells. Recent findings on the role of miRNAs in the initiation of cell reprogramming and the determination of the neuronal subtype's destiny are the primary focus of this comprehensive overview. Furthermore, we cover the far more latest results concerning certain miRNAs' activity in controlling different phases of neuronal differentiation, which contributes in comprehending the interaction network of miRNAs and their receptors.

Background: Distal sensory polyneuropathy (DSP) and distal neuropathic pain (DNP) remain significant challenges for older people with HIV (PWH), necessitating enhanced clinical attention. HIV and certain antiretroviral therapies (ART) can compromise mitochondrial function and impact mitochondrial DNA (mtDNA) replication, which is linked to DSP in ART-treated PWH. Methods: This study investigated mtDNA, mt fission and fusion protein, and mt electron transport chain protein changes in the dorsal root ganglion (DRG) and sural nerve (SuN) from 11 autopsied PWH. In antemortem standardized assessments, six had no or one sign of DSP, while five exhibited two or more DSP signs. Digital droplet polymerase chain reaction (ddPCR) measured mtDNA quantity and the common deletion (CD) in isolated DNA. Results: We found lower mtDNA copy numbers in DSP+ donors. SuN exhibited a higher proportion of mtDNA CD than DRGs in both groups. Mitochondrial electron transport chain (ETC) proteins were altered in DRG of DSP+ compared to DSP- donors, particularly complex I. Conclusion: These findings suggest reduced mtDNA quantity and increased CD abundance may contribute to DSP in PWH, indicating diminished mitochondrial activity in sensory neurons. Accumulated ETC proteins in the DRG imply impaired mitochondrial transport to the sensory neuron's distal portion. Identifying molecules to safeguard mitochondrial integrity could aid in treating or preventing HIV-associated peripheral neuropathy.

This study aimed to verify the effects of an acute increase in blood pressure (BP) and/or renal sympathetic nerve activity (rSNA) on the renal excretion of sodium and water and its potential effect on the regulation of NHE3 activity. Uninephectomized anesthetized male Wistar rats were divided into three experimental groups: 1) Sham, the rats had their BP and rSNA recorded, and urine was collected for 2 h; 2) bicuculline (Bic) paraventricular nucleus of the hypothalamus (PVN), rat BP, and rSNA were recorded, and urine was collected for 1 h at baseline conditions and 1 h after bicuculline injection into the PVN; 3) RNS + Bicuculine injection into the PVN, BP, and rSNA were recorded, and urine was collected 1h after RNS and 1 h after bicuculline injection into the PVN. Renal nerve stimulation (RNS) decreased sodium and water excretion independent of changes in BP. However, after Bic in the PVN during RNS stimulation, BP and rSNA increased up to 30% and 60%, respectively, increasing diuresis (5-fold) and natriuresis (2.3-fold), accompanied by a significant reduction in the NHE3 activity independent of GFR changes. In conclusion, an acute increase in BP overcomes such effects, generating diuresis, natriuresis, and NHE3 activity inhibition.

This review describes and discusses unusual axonal structural details and evidence for unmasking of sulfhydryl groups (-SH) in axoplasmic membranes resulting from electrical stimulation or asphyxia. Crayfish axons contain fenestrated septa (FS) that in phase contrast micrographs appear as repeated striations. In the electron microscope each septum is made of two cross-sectioned membranes containing ~550 Å pores, each occupied by a microtubule. Thin filaments, likely to be made of kinesin, bridge the microtubule to the edge of the pore. FS are believed to play a role in axoplasmic flow. The axons also display areas in which axon and sheath-glial cell plasma membranes are sharply curved and project into the axoplasm. In freeze-fractures, the protoplasmic leaflet (P-face) of the projections appears as elongated indentations containing parallel chains of particles. The sheath-glial cell plasma membrane also contains particles, but they are irregularly aggregated. The axons also display areas where axonal and glial plasma membranes fuse, creating intercellular pores. In axons fixed during electrical stimulation the plasma membrane, the outer membrane of mitochondria, membranes of other cytoplasmic organelles and gap junctions increase in electron opacity and thickness, resulting from unmasking of sulfhydryl groups (-SH). Similar changes occur in asphyxiated nerve cords.

Neuropathic pain is initiated by a malfunction of the somatosensory cortex system. Acupuncture had been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We used electroacupuncture (EA) to treat mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetic techniques. Both me-chanical and thermal pain were found in SNI mice till four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Hyperalgesia was attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g; ther-mal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), sug-gesting EA’s specificity. In addition, animals with transient receptor potential V1 (Trpv1) deletion showed no significant induction of neuropathic pain (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-β), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in EA and Trpv1-/- group rather than sham group. Western blot and immunofluorescence analysis showed similar tendency in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity showed an analgesic effect through TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as beneficial targets for neuropathic pain.

The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often over a prolonged duration, the symptoms resemble migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a possible solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible stenosis of the aqueduct. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and considering that the patient had not a total response, bilateral parietal stimulation was added. Three months after the combined PNS she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus associated headache.