Search Results (43)

Peripheral nerve injuries, particularly those involving the sciatic nerve, remain a major clinical challenge due to incomplete functional recovery and the limited translation of preclinical advances into effective therapies. This review synthesizes current evidence on the phase-specific evaluation of sciatic nerve regeneration in preclinical models, integrating behavioral, sensory, electrophysiological, and morphological approaches across the acute, subacute (Wallerian degeneration), early regenerative, and late regenerative phases. By mapping functional readouts onto the underlying biological events of each phase, we highlight how tools such as the Sciatic Functional Index, Beam Walk test, Rotarod test, nerve conduction studies, and nociceptive assays provide complementary and often non-interchangeable information about motor, sensory, and neuromuscular recovery. We further examine emerging therapeutic strategies, including intraoperative electrical stimulation, immunomodulation, platelet-rich plasma, bioengineered scaffolds, conductive and piezoelectric conduits, exosome-based hydrogels, tacrolimus delivery systems, and small molecules, emphasizing the importance of aligning their mechanisms of action with the dynamic microenvironment of peripheral nerve repair. Despite substantial advancements in experimental models, an analysis of publication trends and registries reveals a persistent translational gap, with remarkably few clinical trials relative to the high volume of preclinical studies. To illustrate how mechanistic insights can be complemented by molecular-level characterization, we also present a targeted computational analysis of alpha-lipoic acid (ALA,) including frontier orbital energies, physicochemical descriptors, and docking interactions with IL-6, TGF-β, and a growth-factor receptor—performed solely for this molecule due to its documented structural availability and relevance. By presenting an integrated, phase-specific framework for functional assessment and therapeutic evaluation, this review underscores the need for standardized, biologically aligned methodologies to improve the rigor, comparability, and clinical relevance of future studies in sciatic nerve regeneration. Full article

This study investigates the practical value of angular-velocity measurements in the dynamic identification of pedestrian footbridges, addressing the need for reliable yet cost-effective diagnostics for slender civil structures. A comprehensive experimental campaign on a steel footbridge in Gdynia combined ambient vibration tests, forced excitation (light and heavy shakers), and controlled pedestrian loading. Synchronous translational accelerations and rotational velocities from MEMS sensors enabled evaluation of both bending and torsional responses. Three identification techniques—Peak Picking (PP), Frequency Domain Decomposition (FDD), and Stochastic Subspace Identification (SSI)—were applied and compared with a validated beam–shell FEM developed in SOFiSTiK. The results show that rotational data improve mode-shape interpretation and classification, notably resolving a coupled torsional–vertical mode (VT₂) that was ambiguous in acceleration-only analyses. The fundamental frequency of 3.1 Hz places the bridge in a resonance-prone range; field tests confirmed predominantly vertical response, with horizontal accelerations < 0.05 m/s² and peak vertical accelerations exceeding comfort class CL3 during synchronised walking of six pedestrians (≈2.55 m/s²) and jumping (up to 3.61 m/s²). Overall, the outcomes highlight that low-cost gyroscopic sensing offers substantial benefits for structural system identification and mode-shape characterization, enriching acceleration-based diagnostics and strengthening the basis for subsequent analyses. By reducing the financial and material demands of vibration testing, the proposed approach contributes to more sustainable assessment and maintenance of pedestrian bridges, aligning with resource-efficient monitoring strategies in civil infrastructure. Full article

The Crested Porcupine Optimizer (CPO), as a newly emerging swarm intelligence algorithm, demonstrates advantages in balancing global exploration and local exploitation but still suffers from limitations in convergence speed and local exploitation precision. To address these issues, this paper proposes an enhanced variant, the Butterfly Search and Triangular Walk Crested Porcupine Optimizer (BTCPO). The method achieves a dynamic balance between exploration and exploitation by combining triangular walk to boost local exploitation and butterfly search to increase global variety. Experimental results on 23 classical benchmark functions and the CEC2021 test suite show that BTCPO outperforms CPO as well as seven state-of-the-art algorithms (DBO, HBA, BKA, HHO, GWO, GOOSE, and SSA). Specifically, BTCPO achieves the best performance on more than 80% of CEC2021 functions, with convergence speed improved by approximately 25% compared to CPO. Furthermore, BTCPO exhibits higher efficiency and usefulness in engineering design problems such as trusses, welded beams, and cantilever beams. These findings demonstrate the theoretical and practical advantages of BTCPO, making it a workable approach to solving difficult optimization problems. Full article

Extracellular vesicles (EVs) have emerged as potential therapeutic agents for neurological disorders. Their molecular cargo may reflect the clinical status of the donor and has been identified as a biomarker for the cellular damage and repair processes underlying intracerebral hemorrhage (ICH). It has been shown that EVs from patients with favorable outcomes carry a distinct proteomic signature, compared to those from poor outcome patients, which may promote recovery in preclinical models of ICH. We investigated whether intravenously administered EVs isolated from patients with poor outcomes after ICH provide any benefit in a preclinical ICH model. No significant differences were observed in lesion volume between the placebo and treatment groups at 24 h, 72 h, or 28 days post-ICH. Functional assessments using the Rogers and tapered beam walking tests revealed no improvement in motor performance in the treatment group at 24 h, 72 h, 7 d, 14 d and 28 d. Histological analysis at 28 days showed no significant differences in immunofluorescence markers of myelin preservation (MOG, Olig-2), astroglial activation (GFAP), or angiogenesis (VEGF) between groups. In conclusion, EVs derived from patients with poor outcomes after ICH failed to promote functional recovery or modulate markers of injury and repair in a rat model, suggesting few endogenous repair mechanisms. Full article

Spastic paraplegia 80 (SPG80), caused by mutations in ubiquitin-associated protein 1 (UBAP1), is a pure form of juvenile-onset hereditary spastic paraplegia (HSP) and leads to progressive motor dysfunction. Despite recent advances in the molecular analyses of HSP, disease-modifying therapy has not been established for HSP including SPG80. In the present study, we evaluated the therapeutic potential of 4-phenylbutyric acid (4-PBA), a chemical chaperone and histone deacetylase inhibitor, in Ubap1 knock-in (KI) mice expressing a disease-associated truncated UBAP1 variant. We found that 4-PBA administration significantly improved the motor performance of KI mice in the rotarod and beam walk tests, with maximal benefits achieved when given during pre- or early-symptomatic stages. Partial efficacy was also observed when treatment began after symptom onset in KI mice. Furthermore, 4-PBA attenuated spinal microglial activation and partially restored microglial morphology, although astrocytic reactivity remained unchanged. These findings support 4-PBA as a candidate therapeutic compound for SPG80 and highlight the potential of proteostasis-targeted interventions in HSPs. Full article

Assessing the fall risk of a patient in a busy clinical setting is challenging. Tests such as the timed-up-and-go test and narrow beam walking are difficult to perform due to space restrictions. Moreover, it is not easy to directly connect the results of these tests to fundamental biomechanical principles of gait stability, which emphasize the interplay between the movements of the body’s center of mass (CoM) and its base of support (BoS). Herein, we show how a 1.2 m-long treadmill and a single “time-of-flight” Azure Kinect camera can capture the CoM-BoS interplay within 5 min. The CoM was calculated by dividing the body into 14 segments determined from 20 joint positions measured by the Kinect camera’s body tracking SDK. By tracking the CoM and joint positions from stride to stride, we can evaluate different gait stability metrics using a markerless, contactless, space-efficient approach. A large digital database of CoM movements relative to foot placement will be useful for the future development of statistical and machine learning techniques for identifying subjects at higher risk of falling. Full article

Kernicterus spectrum disorder is the permanent and highly disabling neurologic sequel of neonatal exposure to hyperbilirubinemia, presenting, among other symptoms, variable and untreatable motor disabilities. To search for potential biomolecular explanations, we used a Gunn rat colony exhibiting spontaneous hyperbilirubinemia and a large variability of motor deficits on a beam-walking test. Histological and microscopic analyses confirmed worsening damage in the cerebellum (Cll; hypoplasia, increased death of neurons, and disrupted astroglial structures) and parietal motor cortex (hCtx; increased cell sufferance and astrogliosis). Clustering and network analyses of transcriptomic data reveal rearrangement of the physiological expression patterns and signaling pathways associated with bilirubin neurotoxicity. Bilirubin content among hyperbilirubinemic (jj) animals is overlapped, which suggests that the amount of bilirubin challenge does not fully explain the tissue, transcriptomic, proteomic, and neurobehavioral alterations. The expression of nine genes involved in key postnatal brain development processes is permanently altered in a phenotype-dependent manner. Among them, Grm1, a metabotropic glutamatergic receptor involved in glutamate neurotoxicity, is consistently downregulated in both brain regions both at the transcriptomic and proteomic levels. Our results support the role of Grm1 and glutamate as biomolecular markers of ongoing bilirubin neurotoxicity, suggesting the possibility to improve diagnosis by ¹H-MR spectroscopy. Full article

Current treatments fail to prevent long-term consequences induced by a severe traumatic brain injury (TBI). This study aimed to evaluate the efficacy of repetitive intranasal administration of NeuroEPO (a derivative of erythropoietin) on long-term alterations after a severe TBI induced by the application of a lateral fluid percussion in male rats. A otal of 30–31 days after the trauma, TBI+vehicle group showed sensorimotor dysfunction (Neuroscore, p < 0.0009; beam walking test, p < 0.0001 vs. Sham+vehicle group) and depressive-like behavior suggested by increased immobility (p = 0.0009 vs. baseline) during the forced swim test. Rats also showed increased production of malondialdehyde (a marker of oxidative damage), increased catalase activity (an antioxidant enzyme), and atrophy of brain areas evaluated with Magnetic Resonance Imaging 31 days after the trauma. TBI+NeuroEPO group received intranasal administration of NeuroEPO (0.136 mg/kg) starting 3 h post-TBI and continued every 8 h for four days. This group showed less sensorimotor dysfunction (Neuroscore, p = 0.020; beam walking test, p = 0.001, vs. TBI+vehicle group) and normal immobility behavior (p = 0.998 vs. Sham+vehicle group). Levels of malondialdehyde and catalase as well as the volume of brain structures of this group were like the Sham+vehicle group. These findings support the potential of NeuroEPO as a therapeutic agent to reduce long-term consequences of TBI. Full article

The piperazine derivative N-(2,6-difluorophenyl)-2-(4-phenylpiperazin-1-yl)propanamide (cmp2) has emerged as a potential transient receptor potential cation channel, subfamily C, member 6 (TRPC6) modulator, offering a promising pathway for Alzheimer’s disease (AD) therapy. Our recent findings identify cmp2 as a novel compound with synaptoprotective effects in primary hippocampal cultures and effective blood–brain barrier (BBB) penetration. In vivo studies demonstrate that cmp2 (10 mg/kg, intraperitoneally) restores synaptic plasticity deficits in 5xFAD mice. This study further shows cmp2’s selectivity towards tetrameric TRPC6 channel in silico. Acute administration of cmp2 is non-toxic, with no indications of chronic toxicity, and Ames testing confirms its lack of mutagenicity. Behavioral assays reveal that cmp2 improves cognitive functions in 5xFAD mice, including increased novel object recognition, better passing of the Morris water maze, and improved fear memory, as well as upregulation of motor function in beam walking tests. These findings suggest that cmp2 holds promise as a candidate for AD treatment. Full article

Timing measurements are critical for the detectors at the future HL-LHC, to resolve reconstruction ambiguity when the number of simultaneous interactions reaches up to 200 per bunch crossing. The ATLAS collaboration therefore builds a new High-Granularity Timing detector for the forward region. A customized ASIC, called ALTIROC, has been developed, to read out fast signals from low-gain avalanche detectors (LGADs), which has 50 ps time-resolution for signals from minimum-ionizing particles. To meet these requirements, a custom-designed pre-amplifier, a discriminator, and TDC circuits with minimal jitter have been implemented in a series of prototype ASICs. The latest version, ALTIROC3, is designed to contain full functionality. Hybrid assemblies with ALTIROC3 ASICs and LGAD sensors have been characterized with charged-particle beams at CERN-SPS and with laser-light injection. The time-jitter contributions of the sensor, pre-amplifier, discriminator, TDC, and digital readout are evaluated. Full article

Urban renewal and improving the structural resilience of infrastructure are the hotspots of attention in all walks of life. The structural resilience of existing infrastructure and engineering structures is deteriorating with the increase in service life. In order to quickly improve the structural resilience and service life of existing engineering structures, a new method of rapid reinforcement for in-service concrete beams is proposed in this paper, which is the external prestressed reinforcement method of the side façade. The specific procedure involves creating a penetration hole at each end of the side surface of the concrete beam, inserting a prestressed support rod into the hole and subsequently installing a prestressed long bolt within the support rod. External prestress is applied to the side façade of the concrete beam through prestressed bolts. A total of 21 reinforced concrete beams were designed and manufactured, including 3 contrast beams of ordinary concrete, 9 concrete beams reinforced with traditional external prestressing steel and 9 concrete beams reinforced with externally prestressed steel on side façades. Different initial prestressing forces were applied to the reinforced beams, and flexural shear tests and numerical analyses were carried out on the concrete beams. The failure modes and shear resistances were analyzed. This research demonstrates that, in comparison with the control beam, the ultimate bearing capacity of the traditionally externally prestressed concrete beams increased by 137.8% to 140.8%, depending on the initial prestress difference. For the externally prestressed concrete beams applied to the side façade, these increases range from 42.6% to 52.0%. Furthermore, the cracking load and yield load of the reinforced concrete beams are significantly enhanced, thereby improving their operational performance. Additionally, the numerical results confirm that the theoretical calculations align well with the experimental findings. Full article

Spinal cord injury (SCI) affects millions of people worldwide. One of the main challenges of rehabilitation strategies is re-training and enhancing the plasticity of the spinal circuitry that was preserved or rebuilt after the injury. The serotonergic system appears to be crucial in these processes, since recent studies have reported the capability of serotonergic (5-HT) axons for axonal sprouting and regeneration in response to central nervous system (CNS) trauma or neurodegeneration. We took advantage of tryptophan hydroxylase 2 knockout (TPH2 KO) rats, lacking serotonin specifically in the brain and spinal cord, to study the role of the serotonergic system in the recovery of sensorimotor function after SCI. In the present work, we compared the rate of sensorimotor recovery of TPH2 KO and wild-type (WT) female rats after SCI (lateral hemisection at the T8 spinal level). SCI caused severe motor impairments in the ipsilateral left hindlimb, the most pronounced in the first week after the hemisection with gradual functional recovery during the following 3 weeks. The results demonstrate that TPH2 KO rats have less potential to recover motor functions since the degree of sensorimotor deficit in the tapered beam walking test (TBW) and ladder walking test (LW) was significantly higher in the TPH2 KO group in comparison to the WT animals in the 3rd and 4th weeks after SCI. The recovery dynamics of the hindlimb muscle tone and voluntary movements was in agreement with the restoration of motor performance in TBW and LW. Compound muscle action potential analysis in the gastrocnemius (GM) and tibialis (TA) muscles of both hindlimbs after electrical stimulation of the sciatic nerve or lumbar region (L5–L6) of the spinal cord indicated slower recovery of sensorimotor pathways in the TPH2 KO group versus their WT counterparts. In general, the observed results confirm the significance of central serotonergic mechanisms in the recovery of sensorimotor functions in rats and the relevance of the TPH2 KO rat model in studying the role of the 5-HT system in neurorehabilitation. Full article

Heating steel charges is essential for proper charge formation. At the same time, it is a highly energy-intensive process. Limiting the scale formed is critical for reducing heat consumption in this process. This paper applies fuzzy logic to model heating and scale formation in industrial re-heating furnaces. Scale formation depends on the temperature of the initial charge, heating time, excess air coefficient value, and initial scale thickness. These parameters were determined based on experimental tests, which are also the inputs in the model of the analyzed process. The research was carried out in walking beam furnaces operating in hot rolling mill departments. To minimize the excess energy consumption for heating a steel charge in an industrial furnace before forming, a heating and scale formation (HSF) model was developed using the fuzzy logic-based approach. The developed model allows for the prediction of the outputs, i.e., the charge’s final surface temperature and the scale layer’s final thickness. The comparison between the measured and calculated results shows that the model’s accuracy is acceptable. Full article

Background: Ceftriaxone upregulates GLT1 glutamate transporter in the brain and may have anti-CFC and anti-OCD effects. Methods: Twenty WZ-5HT rats were used to investigate the effects of ceftriaxone on obsessive–compulsive (OCD)-like behaviour in the marble-burying (MB) test, freezing behaviour in contextual fear conditioning (CFC) and expression of GLT1 protein in the hippocampus or amygdala using immunoblots. Fifteen DBA/2J mice were used in the MB test. We also compared diazepam with ceftriaxone in open-field, beam-walking, and wire-hanging tests on 47 DBA/2J mice. Ceftriaxone (200 mg/kg) and saline were applied intraperitoneally, once daily for 7 (rats) or 5 (mice) consecutive days. A single dose of diazepam (1.5–3.0 mg/kg) or saline was injected 30 min before the behavioural tests. Results: Ceftriaxone significantly diminished OCD-like behaviour (↓ number of marbles buried) and freezing behaviour in CFC context session (↑ latencies, ↓ total duration, ↓ duration over four 2 min periods of the session) but increased GLT1 protein expression in the amygdala and hippocampus of rats. Diazepam induced sedation, ataxia and myorelaxation in mice. Ceftriaxone did not have these side effects. Conclusions: The results of this study confirm the anti-CFC and anti-OCD effects of ceftriaxone, which did not produce the unwanted effects typical of diazepam. Full article

Previous research has proven that the balance of autistic children is poor. However, the reliability of assessing balance in this cohort has been inadequately researched. This study therefore aimed to examine if field-based static and dynamic balance tests can be reliably assessed in autistic children, to determine the number of familiarisation sessions required and whether autistic severity impacts on the reliability of these balance tests. The balance of eighteen primary school-aged autistic children was assessed three times a week over five weeks, using the flamingo balance test, a modified version of the balance error scoring system (BESS), the low beam walking test, and the heel to toe walking test. Reliability criteria included an intraclass correlation coefficient (ICC) level of ≥0.75 and a coefficient of variance (CV%) of ≤46% for the low beam walking test, the heel to toe walking test, and the BESS, and a CV% of ≤82% or the flamingo balance test. Inter-session reliability was achieved and required the least number of familiarisation sessions for the flamingo balance test, compared to the low beam walking test, which required a greater number of familiarisation sessions to achieve inter-session reliability. The heel to toe walking test and the BESS achieved inter-session reliability and familiarisation in an acceptable time frame. Due to the large CV% values reported in the current study, practitioners need to be aware that balance interventions need to achieve improvements greater than the CV% in this cohort. Full article