Search Results (301)

Cervical myoclonus (CM) has been associated with intervertebral disc extrusion (IVDE), with a higher prevalence in French Bulldogs. The presence of CM in other breeds and with other aetiologies has not been reported. The purpose of this study was to describe the signalment, neurological examination, neuroanatomical localisation and grade, imaging findings, diagnosis, treatment, follow-up and resolution of CM in dogs. An observational multicentred retrospective analysis identified 173 dogs with CM; of those, 113 met the inclusion criteria. French Bulldogs (n = 52/113, 46%), Beagles (n = 8/113, 7.1%), Chihuahuas and Shih-Tzus (n = 6/113 for each, 5.31%) were the most affected breeds. Apparent cervical pain was the most common finding on neurologic examination (n = 70/113, 62%). Magnetic resonance imaging (MRI) was consistent with nerve root impingement in 17% (n = 19/113) of the dogs. The most frequently diagnosed conditions were degenerative (n = 100/113, 88.5%), inflammatory (n = 8/113, 7.1%), neoplastic (n = 3/113, 2.7%), vascular (n = 1/113, 0.9%) and congenital (n = 1/113, 0.9%) in origin. Dogs with a neoplastic aetiology tended to be older than those with other causes. Follow-up was recorded in 77 dogs, and 75 of these (n = 75/77, 97.4%) had resolution of the CM. The results supported that cervical myoclonus can be caused by various underlying conditions and can affect different dog breeds. Full article

Myofascial pain syndrome (MPS) is caused by trigger points (TrPs): hypersensitive spots in taut muscle bands that impair function and cause pain. Dry needling (DN) is a common treatment in humans, but evidence in horses is limited. This prospective, controlled study evaluated the effectiveness of DN in reducing TrP-related pain in the brachiocephalic muscle of horses. Of the 98 horses enrolled, 66 were allocated to a treatment group receiving weekly DN sessions for three weeks, while 32 were assigned to a control group with no intervention. Pain and function were assessed using pressure algometry, a numerical rating scale (NRS), a functional total test score (FTTS), and behavioral indicators including jump sign (JS), equine pain face (EPF), and local twitch responses (LTRs). Assessments were performed at baseline and at 0, 4, 24, and 72 h post-intervention. Results indicate a significant increase in pressure pain thresholds (p < 0.001), especially after the second and third sessions. Both NRS and FTTS improved significantly over time (p < 0.001), and LTRs progressively decreased. EPF and JS showed minimal variation. These results support the use of DN to reduce local muscle pain and improve function in horses with TrPs. Further robust studies are warranted to refine protocols and investigate long-term effects. Full article

Acinetobacter baumannii has emerged as a major pathogen responsible for healthcare-associated infections, particularly in intensive care units, contributing to significant morbidity and mortality due to its multidrug resistance and ability to persist in clinical environments. This study aimed to investigate the phenotypic and genomic characteristics of all multidrug-resistant A. baumannii isolates collected between January and June 2022 from two tertiary care hospitals in Thessaloniki, Greece. A total of 40 isolates were included. All isolates exhibited resistance to colistin; however, none harbored the mcr-1 to mcr-9 genes, as confirmed by polymerase chain reaction (PCR). PCR-based screening for virulence-associated genes revealed high prevalence rates of basD (100%), pld (95%), csuE (87.5%), and bap (77.5%). In contrast, ompA and pglC were not detected. Twitching motility ranged from 2 to 50 mm, with 25% of the isolates classified as non-motile and 20% as highly motile. Swarming motility was observed in all strains. Additionally, all isolates demonstrated positive α-hemolysis, suggesting a potential virulence mechanism involving tissue damage and iron acquisition. Pulsed-field gel electrophoresis (PFGE) revealed significant genomic diversity among the isolates, indicating a low likelihood of patient-to-patient or clonal transmission within the hospital setting. These findings highlight the complex relationship between antimicrobial resistance and virulence in clinical A. baumannii isolates and emphasize the urgent need for robust infection control strategies and continued microbiological surveillance. Full article

Whether pattern or amount of daily activity determines neuromuscular properties is the focus of this review. The fast-to-slow conversion of many properties of fast-twitch muscles, by stimulating their nerves electrically with the continuous low-frequency pattern typical of slow motoneurons, argued that muscle properties are determined by their pattern of activity. However, the composition of the motor units (MUs) in almost all muscles is heterogeneous, with the MUs grouped into slow, fast-fatigue-resistant and fast-fatigable types that match corresponding histochemical fiber types. Nonetheless, their contractile forces lie on a continuum, with MUs recruited into activity in order of their size. This ‘size principle’ of MU organization and function applies in normally innervated and reinnervated muscles and, importantly, begs the question of whether it is the amount rather than the pattern of the MU activation that determines their properties. Experimental evidence that uniform daily amounts of ~<0.5, 5%, and 50% ES, converted motoneuron, nerve, and muscle properties to one physiological and histochemical type, argued in favor of the amount of activity determining MU properties. Yet, that the properties were not confined to the expected narrow range argued that factors other than the pattern and/or amount of neuromuscular activity must be considered. These include the progressive increase in the synaptic inputs onto motoneurons. The range of the effects of endurance and intermittent exercise programs on healthy subjects and those suffering nerve injuries and disease is also consistent with the argument that factors other than pattern or amount of neuromuscular activity should be investigated. Full article

Pseudomonas aeruginosa biofilm formation is critical to antibiotic resistance and persistence. Targeting cyclic di-GMP (c-di-GMP) signaling, a master biofilm formation and virulence regulator, presents a promising strategy to combat resistant bacterial infections. Myricetin, a natural polyphenolic flavonoid with documented antimicrobial and anti-biofilm activities, may enhance antibiotic efficacy against Pseudomonas aeruginosa. This study evaluated the synergistic effects of myricetin combined with azithromycin, ciprofloxacin, or cefdinir against both standard and drug-resistant Pseudomonas aeruginosa strains. Antibacterial activity, biofilm disruption, and motility inhibition were experimentally assessed, while molecular dynamic (MD) simulations elucidated myricetin’s molecular mechanism of action. Our results suggested that myricetin synergistically potentiated all three antibiotics, reducing c-di-GMP synthesis by 28% (azithromycin), 57% (ciprofloxacin), and 30% (cefdinir). It enhanced bactericidal effects, suppressed biofilm formation, and impaired swimming, swarming, and twitching motility. Computational analyses revealed that myricetin binds allosterically to FimX very well, a key regulator in the c-di-GMP signaling pathway. Hence, myricetin may act as a c-di-GMP inhibitor, reversing biofilm-mediated resistance in Pseudomonas aeruginosa and augmenting antibiotic efficacy. This integrated experimental and computational approach provides a framework for developing anti-virulence and antibiotic combination therapies against recalcitrant Gram-negative pathogens. Full article

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm²) from routine human cardiac surgery specimens and compared them with medium (10–30 mm²) and large (>30 mm²) slices. Size effects on biomechanical properties were examined with mathematical modeling, and viability, contraction profiles, and histological integrity were followed for 14 days. In total, 34 mini-, 25 medium, and 30 large LMS were maintained viable, the smallest measuring only 2 mm². Peak twitch force proved to be size-independent, whereas time-to-peak shortened as slice area decreased. Downsized LMSs displayed excellent contractile behavior for five to six days, after which a gradual functional decline and micro-architectural changes emerged. These findings confirm, for the first time, that mini-LMSs are feasible and viable, enabling short-term, patient-specific functional studies and pharmacological testing when tissue is scarce. Full article

The rapid expansion of virtual education has highlighted both its opportunities and limitations. Conventional virtual learning environments tend to lack flexibility, often applying standardized methods that do not account for individual learning differences. In contrast, Artificial Intelligence (AI) empowers the creation of customized educational experiences that address specific student needs. Such personalization is essential to mitigate educational inequalities, particularly in areas with limited infrastructure, scarce access to trained educators, and varying levels of digital literacy. This study explores the role of AI in advancing virtual education, with particular emphasis on supporting differentiated learning. It begins by selecting an appropriate pedagogical model to guide personalization strategies and proceeds to investigate the application of AI techniques across three key areas: the characterization of educational resources, the detection of learning styles, and the recommendation of tailored content. The primary contribution of this research is the development of a scalable framework that can be adapted to a variety of educational contexts, with the goal of enhancing the effectiveness and personalization of virtual learning environments through AI. Full article

5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA are three potent indazole-carboxamide synthetic cannabinoids (SCs) that have been widely abused in recent years. However, the pharmacological research on these compounds remains limited, especially in vivo research data. The purpose of the present study was to investigate the pharmacological effects of 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA in mice, comparing their in vivo effects with those caused by Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the main psychoactive substance in cannabis. We evaluated the cannabinoid-specific pharmacological effects of 5F-ADB, MDMB-4en-PINACA and ADB-4en-PINACA using the tetrad assay (locomotion inhibition, hypothermia, analgesia and catalepsy). Then we conducted conditioned place preference (CPP) and precipitated withdrawal assay to assess the rewarding effect and physical dependence, with Δ⁹-THC as a positive control. The results showed that all of the three SCs exhibited potential tetrad effects in a dose-dependent manner, with median effective dose (ED₅₀) values ranging from 0.03 to 0.77 mg/kg. In the CPP tests, they all exhibited a significant biphasic effect of conditioned place preference (CPP) and conditioned place aversion (CPA). A significant increase in paw tremors and head twitches was observed in the rimonabant-precipitated withdrawal assay, indicating that the repeated administration of these SCs can lead to potential physical dependence. All effective doses were lower than Δ⁹-THC. These findings strongly suggested that the three SCs exhibited similar but stronger cannabinoid-specific tetrad effects, rewarding effect and physical dependence compared with Δ⁹-THC, indicating their high abuse potential and possible threats to human health. The rank order of abuse potential for these drugs was 5F-ADB > MDMB-4en-PINACA > ADB-4en-PINACA > Δ⁹-THC. Full article

Skeletal muscle fiber type composition critically influences lamb meat quality. This study examined the relationships between muscle fiber types and key quality traits, including tenderness, color, lipid and amino acid profiles, and volatile flavor compounds. MyHC I (slow-twitch oxidative fibers) positively correlated with desirable traits such as increased redness, water-holding capacity, unsaturated fatty acids, and essential amino acids. Conversely, MyHC IIb (fast glycolytic fibers) was linked to reduced tenderness and higher levels of off-flavor compounds. MyHC IIa and IIx showed minimal effects. Untargeted metabolomics comparing muscles with high versus low slow-twitch fiber proportions revealed differential metabolites enriched in sphingolipid and arginine-proline metabolism pathways. These results suggest that a higher proportion of oxidative fibers enhances both the sensory and nutritional qualities of lamb meat by modulating lipid metabolism, amino acid availability, and flavor formation. Full article

Although some GABA_A receptor subtypes are involved in both the passive permeability of anions and the ATP-dependent recovery of neuronal anion concentrations, the molecular mechanisms that ensure the coordination of passive and active transport processes remain unclear. Here we used fluorescence measurements to investigate the role of genistein (tyrosine kinase inhibitor) and vanadate (tyrosine phosphatase and ATPase inhibitor) in modulating GABA_AR-mediated [Cl⁻]_i/[HCO₃⁻]_i changes and ATPase activity in rat cortical neurons and HEK 293FT cells expressing the heteropentameric α2β3γ2 GABA_AR isoform. We found that genistein plays an important role in the inhibition of passive GABA_AR-mediated Cl⁻ influx and Cl⁻ATPase activity, whereas vanadate plays an important role in the inhibition of Cl⁻, HCO₃⁻ATPase activity and ATP-dependent recovery of [HCO₃⁻]_i via changes in the formation of the phosphorylated intermediate. The effect of blockers was significantly restored in the presence of phenol. In behavioral experiments, the administration of phenol has been established to induce tremors and head twitching in rats, with the involvement of GABA_AR/ATPase in these behavioral responses. Genistein can reduce the adverse effects of phenol, thereby confirming the interaction of these chemicals when binding to binding receptor sites. While our data demonstrate the opposing roles of genistein and vanadate in modulating GABA_AR/ATPase function in a bicarbonate-dependent manner. Such multidirectional systems are considered to be bistable elements involved in the regulatory mechanisms of synaptic plasticity. Full article

Diabetic muscular atrophy is a complication of diabetes mellitus that can decrease quality of life. Its complex mechanisms include alterations in proteolytic pathways, oxidative stress, and intracellular lipid accumulation. NADPH oxidase enzymes (NOX) play a key role in the production of ROS, contributing to oxidative damage and insulin resistance. Apocynin, a NOX inhibitor, has antioxidant and anti-inflammatory effects, suggesting its therapeutic potential in various diabetic complications. This study evaluated the impact of apocynin on the mechanisms of muscle atrophy in slow- and fast-twitch muscles of diabetic rats. Diabetes was induced in male Wistar rats by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Apocynin treatment (3 mg/kg/day) was administered for 8 weeks. Fasting blood glucose levels, lipid profile, and weight gain were measured. Both slow-twitch (soleus) and fast-twitch (extensor digitorum longus, EDL) skeletal muscles were weighed and used to assess triglycerides (TG) content, histological analysis, lipid peroxidation levels, and gene expression evaluated by qRT-PCR. Apocynin reduced blood glucose levels, improved body weight, and exhibited hypolipidemic effects. It significantly increased muscle weight in EDL and soleus, especially in EDL muscle, lowering triglycerides, lipid peroxidation, and increasing fiber size. Additionally, it decreased mRNA expression levels of MuRF-1, atrogin-1, myostatin and p47phox mRNA and upregulated PGC-1α and follistatin mRNA. Apocynin exerted a myoprotective effect by mitigating muscle atrophy in diabetic rats. Its effects were differentially mediated on TG accumulation and muscle fiber size, reducing oxidative stress, atrogene expression, and positively regulating PGC-1α. Full article

Myosin-binding protein C (MyBP-C) comprises a family of myofilament proteins that maintain sarcomeric structure and regulate actomyosin crossbridge cycling. Pathogenic variants in MYBPC1, the gene encoding the slow skeletal isoform (sMyBP-C), lead to a dominant congenital myopathy, termed Myotrem, characterized by muscle weakness, hypotonia, and a distinctive tremor of myogenic origin, in the absence of neuropathy. However, the molecular mechanism(s) of myogenic tremorgenesis is largely unknown. One potential mechanism is aberrant myofilament stretch activation, which is defined as a delayed increase in force after a rapid stretch. We utilized the Myotrem murine model harboring the pathogenic MYBPC1 E248K variant to test the hypothesis that stretch activation is augmented in permeabilized Myotrem E248K soleus fibers. We found that stretch activation was significantly increased in E248K soleus muscle fibers. Interestingly, once submaximally Ca²⁺ activated, a subpopulation of slow-twitch E248K fibers exhibited spontaneous pulsatile sarcomere oscillations. This pulsing behavior generated a sinusoidal waveform pattern in sarcomere length, which often persisted on a timescale of minutes. These results align with sMyBP-C as key regulator of the synchronous activation of myofilaments by dampening both spontaneous oscillatory activity and stretch-dependent activation. We propose that the presence of sMyBP-C-E248K disrupts this regulation, thereby driving pathogenic myogenic tremors. Full article

Researchers have extensively explored learning analytics in online courses, primarily focusing on linear course structures where students progress sequentially through lessons and assessments. However, non-linear courses, which allow students to complete tasks in any order, present unique challenges for learning analytics due to the variability in course progression among students. This study proposes a method for applying learning analytics to non-linear, self-paced MOOC-style courses, addressing early performance prediction and online learning pattern detection. The novelty of our approach lies in introducing a personalized feature aggregation that adapts to each student’s progress rather than being defined at fixed timelines. We evaluated three types of features—engagement, behavior, and performance—using data from a non-linear large-scale Moodle course designed to prepare high school students for a public university entrance exam. Our approach predicted early student performance, achieving an F1-score of 0.73 at a 20% cumulative weight assessment. Feature importance analysis revealed that performance and behavior were the strongest predictors, while engagement features, such as time spent on educational resources, also played a significant role. In addition to performance prediction, we conducted a clustering analysis that identified four distinct online learning patterns recurring across various cumulative weight assessments. These patterns provide valuable insights into student behavior and performance and have practical implications, enabling educators to deliver more personalized feedback and targeted interventions to meet individual student needs. Full article

Background: Three-dimensional skeletal muscle organoids (3D SkMO) are becoming of increasing interest for preclinical studies in Duchenne muscular dystrophy (DMD), provided that the used platform demonstrates the possibility to form functional and reproducible 3D SkMOs, to investigate on potential patient-related phenotypic differences. Methods: In this study, we employed fibrin-based 3D skeletal muscle organoids derived from immortalized myogenic precursors of DMD patients carrying either a stop codon mutation in exon 59 or a 48–50 deletion. We compared dystrophic lines with a healthy wild-type control (HWT) by assessing microtissue formation ability, contractile function at multiple timepoints along with intracellular calcium dynamics via calcium imaging, as well as expression of myogenic markers. Results: We found patient-specific structural and functional differences in the early stages of 3D SkMO development. Contractile force, measured as both single twitch and tetanic responses, was significantly lower in dystrophic 3D SkMOs compared to HWT, with the most pronounced differences observed at day 7 of differentiation. However, these disparities diminished over time under similar culturing conditions and in the absence of continuous nerve-like stimulation, suggesting that the primary deficit lies in delayed myogenic maturation, as also supported by gene expression analysis. Conclusions: Our results underline that, despite the initial maturation delay, DMD muscle precursors retain the capacity to form functional 3D SkMOs once this intrinsic lag is overcome. This suggests a critical role of dystrophin in early myogenic development, while contraction-induced stress and/or an inflammatory microenvironment are essential to fully recapitulate dystrophic phenotypes in 3D SkMOs. Full article

Background/Objectives: Studies of the effects of anchor schemes (perceived intensity vs. relative intensity) on muscular performance have reported mixed findings. Therefore, the present study examined the effects of different anchor schemes on time-to-task failure (TTF), muscular performance, neuromuscular responses, and potentiated twitch torque (PTT). Methods: On separate days, 15 men (age = 21.5 ± 2.3 yrs) performed forearm flexion maximal voluntary isometric contractions (MVICs) before and after sustained tasks anchored to a rating of perceived exertion of 6 (RPEFT) and with the torque at RPE = 6 (TRQFT). Electromyographic amplitude (EMG AMP) and mean power frequency (EMG MPF) were recorded from the biceps brachii (BB). Supramaximal stimuli were delivered to the motor nerve of the BB following the MVICs to quantify the PTT. Repeated measures ANOVAs assessed the mean differences between anchor schemes for MVIC, neuromuscular, and PTT responses. Paired t-tests compared the magnitude of percent changes for the dependent variables. Results: The TTF for the RPEFT was longer (p < 0.001) than the TRQFT, but the MVIC decreased similarly (12.7 ± 9.5% vs. 20.3 ± 7.9%, p = 0.054). Electromyographic AMP did not change (p = 0.288), while EMG MPF decreased (15.7 ± 10.2%, p < 0.011) for the TRQFT only. Mean decreases in PTT were comparable for both tasks (p < 0.003), although the percent change was greater for the TRQFT (49.6 ± 16.1%, p < 0.001). Conclusions: The differences in TTF, but similar decreases in MVIC suggested that participants reached a sensory tolerance limit. Based on EMG MPF and PTT, the TRQFT caused greater peripheral perturbations to contractile function than the RPEFT. Full article