Search Results (546)

Background/Objectives: Epilepsy is a neurological disorder that severely impacts patients’ quality of life. In clinical practice, specific pharmacological and surgical interventions are tailored to distinct seizure types. The identification of the epileptogenic zone enables the implementation of surgical procedures and neuromodulation therapies. Consequently, accurate classification of seizure types and precise determination of focal epileptic signals are critical to provide clinicians with essential diagnostic insights for optimizing therapeutic strategies. Traditional machine learning approaches are constrained in their efficacy due to limited capability in autonomously extracting features. Methods: This study proposes a novel deep learning framework integrating temporal and spatial information extraction to address this limitation. Multivariate variational mode decomposition (MVMD) is employed to maintain inter-channel mode alignment during the decomposition of multi-channel epileptic signals, ensuring the synchronization of time–frequency characteristics across channels and effectively mitigating mode mixing and mode mismatch issues. Results: The Bern–Barcelona database is employed to classify focal epileptic signals, with the proposed framework achieving an accuracy of 98.85%, a sensitivity of 98.75%, and a specificity of 98.95%. For multi-class seizure type classification, the TUSZ database is utilized. Subject-dependent experiments yield an accuracy of 96.17% with a weighted F1-score of 0.962. Meanwhile, subject-independent experiments attain an accuracy of 87.97% and a weighted F1-score of 0.884. Conclusions: The proposed framework effectively integrates temporal and spatial domain information derived from multi-channel epileptic signals, thereby significantly enhancing the algorithm’s classification performance. The performance on unseen patients demonstrates robust generalization capability, indicating the potential clinical applicability in assisting neurologists with epileptic signal classification. Full article

Dystonia is defined as a movement disorder, the etiology of which may be linked to oxidative stress. The objective of this study was to evaluate the serum levels of zinc, copper, and selenium, as well as oxidative stress parameters, in patients diagnosed with focal dystonia, in comparison to a control group. The study comprised 39 patients and 30 healthy subjects. Patients demonstrated a marked decrease in Total Antioxidant Status (TAS) (p = 0.0002) and an increase in Total Oxidant Status (TOS) and Oxidative Stress Index (OSI) (both p < 0.0001), suggesting a redox imbalance. Of the elements examined, only copper exhibited a significant elevation (p = 0.0061), while zinc and selenium levels remained unchanged. The results of this study suggest that oxidative stress may play a significant role in the pathophysiology of dystonia and represent a potential target for adjunctive therapy. Full article

Background: In the evolving landscape of localized prostate cancer management, focal therapies such as high-intensity focused ultrasound (HIFU) and prostate gland cryoablation (PGC) have emerged as organ-sparing alternatives for patients with low- to intermediate-risk disease. While these strategies aim to preserve functional outcomes, comparative data against robot-assisted radical prostatectomy (RARP) remain scarce and heterogeneous. Methods: We conducted a prospective, single-center study evaluating oncologic and functional outcomes in patients with organ-confined prostate cancer (Grade Group ≤ 2) treated with HIFU (n = 49), PGC (n = 114), or RARP (n = 109). Outcomes were assessed using standardized definitions at a median follow-up of 22 months. Treatment failure was defined according to EAU guidelines, and Kaplan–Meier analysis was applied to time-to-event outcomes. Results: Focal therapy patients were older, more comorbid, and had lower baseline erectile function (each p < 0.001). RARP was associated with the longest operative time but yielded the lowest complication rate (2.75% vs. 20.4% for HIFU and 31.5% for PGC; p < 0.001). Catheter-related morbidity was disproportionately higher in the PGC group. RARP conferred a longer time to treatment failure (p < 0.001), although continence and potency recovery at follow-up were comparable across groups. Notably, erectile function returned earlier among HIFU patients. Conclusions: While focal therapies offer promising early functional results with minimal perioperative risk, they are associated with earlier treatment failure and higher catheter-related morbidity, particularly after cryoablation. These findings underscore the need for individualized treatment strategies guided by standardized, comparative outcome frameworks. Full article

Background/Objectives: Spasticity is a common and disabling sequela of stroke that limits voluntary movement and functional recovery. Vibration therapy (VT) has been proposed as a non-invasive neuromodulatory intervention, but the existing studies report inconsistent outcomes due to methodological heterogeneity. This study aimed to evaluate the overall effectiveness of VT in reducing post-stroke spasticity and to identify optimal stimulation parameters via meta-analytic and meta-regression approaches. Methods: A systematic review and meta-analysis were conducted following the PRISMA 2020 guidelines. Standardized effect sizes (Hedges’ g) were calculated based on the within-group pre–post changes and compared across the groups. Meta-regression and subgroup analyses explored seven potential moderators, including the vibration frequency, amplitude, and time since stroke onset. Results: Thirteen randomized controlled trials (RCTs) involving whole-body or focal vibration interventions in stroke populations were included. Vibration therapy significantly reduced spasticity, yielding a moderate overall effect size (Hedges’ g = −0.50; 95% CI: −0.65 to −0.34; p < 0.001). The greatest treatment effects were observed when VT was applied during the late subacute to early chronic phase (6–12 months post-stroke), with low-frequency (<20 Hz) and low-amplitude (≤0.5 mm) stimulation. The frequency, amplitude, and stroke onset emerged as significant moderators (p < 0.05). Conclusions: Vibration therapy is an effective and clinically meaningful intervention for post-stroke spasticity, particularly when delivered with low-intensity parameters during the optimal recovery window. These findings support the development of individualized VT protocols and provide evidence to guide future rehabilitation strategies. Full article

Focal therapy for prostate cancer (PCa) provides approaches to treat PCa patients in a less invasive manner than traditional whole-gland surgical or radiation modalities. This manuscript provides a case series of high-intensity focused ultrasound (HIFU), cryoablation, and irreversible electroporation (IRE) for PCa at a single institution and cost analysis with a review of the literature. All patients who underwent HIFU, cryoablation, or IRE for localized PCa were retrospectively reviewed, excluding patients who received whole-gland therapy. Functional outcomes were erectile dysfunction and lower urinary tract symptoms. Cost data were collected. A total of 45 patients were included in the study with focal therapy ranging from 2023 to 2025 (4 HIFU, 20 cryoablation, 21 IRE). A total of 30 patients had focally treated lesions, and 15 patients had hemi-gland treatment. The mean preoperative PSA was 7.7 ng/mL. On the paired sample t-test, there was no significant difference between pre-focal and post-focal therapy PSA. Three patients experienced biochemical recurrence requiring prostate biopsy after focal treatment. Mean cost was USD 3804.50 and not significantly different by focal treatment. No metastatic events occurred nor deaths at a median follow-up of 6 months. Patients in this series had largely unaltered functional outcomes. Cost analysis in contemporary publications is lacking. Although follow-up was short, cancer control was adequate. Full article

Liver sinusoidal endothelial cells (LSECs) are essential for preserving liver homeostasis. Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a category of hepatic disorders characterized by excessive fat accumulation in the liver, known as steatosis. Over time, accumulated hepatic fat can induce inflammation of the liver (hepatitis). MASLD is among the most prevalent types of chronic liver disease. Obesity and Type 2 diabetes mellitus (T2DM) are frequent etiological factors of MASLD. In the absence of therapy, MASLD can lead to more severe hepatic conditions, which can be life-threatening. MASLD is noteworthy due to its potential progression to MASH and further severe liver impairment, including cirrhosis and hepatocellular carcinoma (HCC), a neoplastic progression. This narrative review examines the distinctive functions of LSECs in regulating immunologic responses, collagenization, and drug-sensitive bioreactivity in healthy livers, MASLD, and metabolic dysfunction-associated steatohepatitis (MASH), as well as in a human primary 3D model. We found that LSECs serve as crucial regulators of immunological equilibrium in the liver by inhibiting disproportionate immunologic activation, concurrently filtering tissue antigens, and engaging with immunologic cells, such as Kupffer cells (KCs) and T lymphocytes. In chronic diseases of the liver, LSECs experience cellular dysfunction, resulting in capillarization (focal to diffuse), loss of fenestrations (fenestrae), and the activation of pro-fibrotic signaling pathways, including transforming growth factor-beta (TGF-β). Indeed, TGF-β is crucial in activating hepatic stellate cells (HSCs), a process that facilitates the progression of liver disease toward fibrosis. In addition to examining the dynamic interplay between LSECs, specifically HSCs, and other liver cells throughout the progression of fatty liver–MASH, we suggest that LSECs may become a potential therapeutic target for modifying immune responses and averting fibrosis in hepatic disorders. The limitations of animal models are also highlighted and discussed. Full article

An 89-year-old male developed a persistent high fever (around 39 °C) approximately two weeks following endoscopic reduction of sigmoid volvulus. He had no history of hypercalcemia but was using diuretics and proton pump inhibitors. Renal and thyroid status were normal. He was largely bedridden and asymptomatic except for fever. Laboratory tests demonstrated elevated C-reactive protein (4.75 mg/dL), but some tumor markers (including CEA, CA19-9, and CA125), anti-nuclear antibodies, MPO-ANCA, PR3-ANCA, β-D-glucan, and interferon-gamma release assay were all negative. Urinalysis was unremarkable. Blood cultures obtained from two sets were negative. Chest–abdomen–pelvis contrast-enhanced computed tomography (CT), and echocardiography did not reveal any evident neoplastic lesions or focal sites of infection. Despite various antibiotic therapies, the patient’s spike fever persisted for nearly one month, leading to a diagnosis of fever of unknown origin (FUO). The patient experienced partial symptomatic relief with corticosteroid therapy, though mild fever continued. Two months after the volvulus onset, diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) was performed, revealing hyperintensities at the right sternoclavicular joint, leading to a diagnosis of sternoclavicular arthritis. Neck CT revealed calcification in this joint. Despite difficulty in joint fluid analysis, low infection risk and the patient’s prolonged bedridden state and advanced age led to suspicion of pseudogout. Nonsteroidal anti-inflammatory drugs relieved fever and normalized inflammatory markers. DWIBS may be a valuable tool for detecting potential focus sites in FUO. Full article

Background: This study aimed to optimize low-intensity extracorporeal shockwave therapy (Li-ESWT) for the treatment of penile indications through the addition of a secondary reflector. The therapeutic potential of Li-ESWT is well-established, but its efficiency is limited by uncontrolled wave propagation and reflection resulting in regions of increased tensile pressures. The objective is to manage and reduce high tensile pressure and enhance treatment efficacy by reflecting applied shockwaves back into the treatment zone using a novel reflector design. Methods: A comprehensive investigation, including numerical modeling and phantom measurements, exploring a range of improvements to traditional shockwave application by reflecting applied therapeutic shockwaves back into the treatment zone. Computational optimization was employed to identify the most suitable secondary reflector shape for potential future clinical use. Subsequent hydrophone phantom reference measurements were extended to volumetric fields using 3D simulations. Results: Traditional treatment resulted in high tensile pressures in the treatment zone, which was mitigated by introducing an impedance-matched layer (IML) while preserving the initial shockwave’s therapeutic function. The addition of the secondary reflector enabled controlled refocusing of the therapeutic shockwave back into the initial focal zone, thus either increasing the treatment volume or achieving a rapid secondary application. Choice of the reflector’s impedance allowed for the secondary refocusing of either a tensile or positive pressure wave. Conclusions: The combined modifications of employing an IML and secondary reflector eliminate uncontrolled tensile waves and reflections, provide better control over consecutive reflections, and enable repeated shockwave signals with a single applicator shot, potentially reducing the number of required shots per session. Full article

Paediatric Focal Segmental Glomerulosclerosis (FSGS) is a leading cause of steroid-resistant nephrotic syndrome and progressive kidney failure in children. Early subclassification into primary, secondary, genetic, or undetermined forms is crucial for guiding appropriate management. Primary FSGS typically necessitates immunosuppressive therapy, whereas secondary FSGS benefits from supportive measures and treatment of the underlying cause. Emerging treatments—including SGLT2 inhibitors, endothelin receptor antagonists, and APOL1-targeted agents—show promise in reducing proteinuria and preserving kidney function. Insights into podocyte biology, including TRPC channel dysregulation and fibrotic signalling pathways, are opening new therapeutic avenues. As research continues to evolve, the future of paediatric FSGS management lies in individualised, pathophysiology-driven therapies that may significantly improve clinical outcomes. Full article

Objective: Several strategies have been described for stroke prevention, and the most commonly used medication is aspirin. Cilostazol, which is a substance with a pleiotropic effect, is still not well investigated. In this study, we aimed to delineate the effects of mono- and combinatorial pre-treatment upon neurological status and biomarkers, namely protein S100b, GFAP, procalcitonin, and galectin-3, following stroke. Methods: Twelve-week-old Sprague–Dawley rats were randomly assigned to four groups, each containing six rats: control group (normal saline), cilostazol group (30 mg/kg/daily), aspirin group (10 mg/kg/daily), and aspirin/cilostazol group. Each substance was administered by gavage for four weeks. All animals were subjected to cerebral ischemia for 2 h using intraluminal middle cerebral artery occlusion. A neurological examination was performed, serum concentrations of biomarkers were determined, and the animals were then sacrificed. Results: All treatment groups exhibited variations in the severity of immediate neurological presentation. Unlike the control group, where all rats presented with severe focal neurology or mortality, most rats in the treatment groups displayed no to moderate focal neurology. Moreover, the aspirin/cilostazol group consistently exhibited significantly lower levels in the studied biomarkers compared to other groups. Conclusions: Co-administration of cilostazol and aspirin significantly ameliorates the immediate expression of the studied biomarkers. Further large-scale studies are needed to investigate the effect of combined therapy for primary and secondary prevention of stroke, using not only serum biomarkers but other specific clinical and laboratory endpoints. Full article

Background and Clinical Significance: Anaerococcus tetradius (A. tetradius) and Gardnerella vaginalis (G. vaginalis) are rare etiological factors for postpartum endometritis and are typically associated with bacterial vaginosis. However, in some cases, G. vaginalis and A. tetradius can cause serious postpartum endometritis with complications such as sepsis. Case Presentation: 26-year-old pregnant woman expecting monochorionic diamniotic twins presented to the hospital at 35 weeks and 3 days of gestation and two male infants were delivered via the Cesarean section. On the fifth day after delivery, the patient began to complain of intense abdominal pain, a fever of 37.9 °C, and overall weakness. Blood tests revealed neutrophilic leukocytosis, increased C-reactive protein (CRP) of 225.4 mg/L. Upon examination, abdominal distension, tenderness on palpation, and positive symptoms of peritoneal irritation were present and the site of the abdominal incision was inflamed with flowing foul-smelling greenish pus. Ultrasound examination revealed free fluid collection in the peritoneal cavity, under the liver, and around the uterus. Later, the condition of the patient worsened with progressing hypotension and respiratory distress. As a result, suppurative peritonitis and sepsis was suspected and the patient underwent urgent total hysterectomy without oophorectomy. Acute endometritis, focal myometritis, and chronic cervicitis were concluded from histopathological examination of the removed uterus. Microbiological tests showed the most abundant growth of A. tetradius in the wound cultures and great abundance of G. vaginalis in the abdominal cavity cultures. After trying three different treatment schemes and difficulties with determining the antibiotic sensitivity tests for pathogens, the antibacterial therapy was escalated to Meropenem, which was found to be effective, and the patient was discharged home. Conclusions: This case report highlights the severity of complications of postpartum endometritis that can be caused by rare pathogens (such as G. vaginalis and A. tetradius), and strategies for how to manage it. The clinical presentation of a patient should be monitored closely for several days after Cesarean section and if endometritis is suspected, microbiological cultures are necessary to determine the cause of infection and implement an appropriate treatment. Full article

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. Full article

Gaultherin [methyl salicylate 2-O-β-D-xylopyranosyl-(1→6)-β-D-glucopyranoside] is a natural salicylate found in some plant species belonging primarily to the Ericaceae and Rosaceae families. Biological studies conducted since the beginning of the 21st century have suggested the potential use of gaultherin in treating various diseases related to inflammation and oxidative stress, including rheumatoid arthritis, sciatica, neuralgia, and muscular pain. The accumulated results indicated a targeted range of biological effects, particularly anti-inflammatory, antipyretic, and anti-rheumatic properties associated with reduced adverse outcomes. The molecular mechanisms involve the influence on several signalling pathways, including NF-κB, MAPK, and potentially AMPK, as well as the inhibition of critical pro-inflammatory enzymes, such as COX-2. This inhibition is achieved without affecting the COX-1 isoform, thereby preventing side effects such as bleeding ulcers or intracranial haemorrhage. This overview summarises the current knowledge about pharmacokinetics, molecular mechanisms, pharmacology, and biocompatibility of gaultherin. Additionally, four methods for isolating gaultherin from plant material and its distribution within the plant kingdom were the focal points of review and discussion. The paper also describes significant differences between synthetic aspirin and natural gaultherin in their biological potential and side effects, resulting from their different mechanisms of action. As a prodrug of salicylic acid, gaultherin releases salicylic acid gradually through enzymatic hydrolysis in the gastrointestinal tract. This controlled release minimises direct gastric irritation and accounts for its superior gastrointestinal safety profile compared to aspirin. Unlike aspirin, which irreversibly inhibits COX-1 and can lead to serious side effects with chronic use, gaultherin selectively inhibits COX-2 while sparing COX-1. These properties position gaultherin as a compelling natural alternative for patients requiring long-term anti-inflammatory therapy with reduced risk of gastrointestinal or bleeding complications. Full article

Background: Hypometabolism of the thalamus has been reported in epilepsy patients. This study aimed to investigate the prognostic value of thalamic metabolic activity in children with epilepsy. Methods: A total of 200 children with epilepsy and 237 children without epilepsy (sex- and age-matched control group) underwent 18F-FDG PET/CT in this study. Localization of the interictal hypometabolic epileptic focus was performed visually. Bilateral thalamic metabolic activity was evaluated qualitatively (thalamic FDG uptake in relation to the cerebral cortex) and semi-quantitatively (SUV max, normalized SUV (ratio to ipsilateral cerebellum), and absolute asymmetric index (AAI). Results: A total of 133 patients (66.5%) with epilepsy showed cerebral cortical hypometabolism in the interictal 18F-FDG PET study; there were 76 patients on the right side, 55 patients on the left side, and two patients on both sides. Of these 133 patients, 45 also had visually observed asymmetric hypometabolism in the thalamus. Semi-quantitatively, asymmetry was more prominent in epileptic patients. AAI was a more sensitive variable than other variables. Average AAIs were 3.89% and 7.36% in the control and epilepsy patients, respectively. Metabolic activity in the thalami was significantly reduced in epileptic patients compared to the control group. Associated hypometabolism of the ipsilateral thalamus was observed in 66.5% of epileptic patients with a focal cortical defect semi-quantitatively. Overall, 61 out of 200 patients showed thalamus hypometabolism. Some 51 out of 61 patients (83.6%) with thalamus hypometabolism showed refractory disease; however, the refractory disease was noted in 90 out of 139 (64.7%) patients without thalamus hypometabolism. Brain surgery was performed in 86 epileptic patients (43%). Some 35 out of 86 patients had thalamus hypometabolism. Recurrence of epilepsy was observed more in patients with thalamus hypometabolism (48% vs. 25%), with p ≤ 0.01. Conclusion: This study suggests that patients with thalamus metabolic abnormalities may be more medically resistant to therapy and less responsive to surgical treatments. Therefore, the thalamus metabolic abnormality could be used as a prognostic sign in pediatric epilepsy. Recent studies have also suggested that incorporating thalamic metabolic data into clinical workflows may improve the stratification of treatment-resistant epilepsy in children. Full article

Botulinum neurotoxin-A (BoNT-A) injections are effective in reducing focal limb spasticity; however, their impact on strength and active function needs to be established. This review was a secondary analysis aimed at evaluating changes to active function in the context of muscle strength changes following BoNT-A intramuscular injection for adult upper and lower limb spasticity. The original review searched eight databases (CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Google Scholar, MEDLINE, PEDro, PubMed, Web of Science) and was conducted with methodology that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as described in section 6.2 of Gill et al. For this secondary analysis, no databases were searched; only further data were extracted. The current and preceding review were registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Twenty studies were screened for inclusion, and three studies were excluded because active function was not assessed in all participants. Seventeen studies (677 participants) met the inclusion criteria for analysis. Quality was examined using the PEDro scale and modified Downs and Black checklist and rated as fair to good. Pre- and post-BoNT-A injection strength (agonist, antagonist, and global), active function (activity), participation, and quality-of-life outcomes at short-, mid-, and long-term time points were extracted and analysed. Significant heterogeneity and limited responsiveness in strength and active function outcome measures limited the ability to determine whether changes in strength mediate an effect on active function. Further, variability in BoNT-A type and dose, adjunctive therapies provided, and variability in reporting limited analyses. Overall, no clear relationship existed between the change in muscle strength and active function following BoNT-A injections to the upper and lower limbs for focal spasticity in adult-onset neurological conditions. Full article