Search Results (10,634)

Temporal lobe epilepsy (TLE) is a debilitating disorder that affects millions of people worldwide and is difficult to treat with medicines. There has been little progress in the development of novel therapies for these patients because of the lack of suitable animal models. Current rodent models of TLE use chemoconvulsants or electrical stimulation to induce status epilepticus, which evolves into chronic epilepsy with spontaneous recurring seizures. These models have face validity in human TLE as they share similarities with seizure onset in the hippocampus, EEG patterns, tonic–clonic convulsions behavior, and hippocampal sclerosis. Unfortunately, seizure frequencies are so variable that they hinder drug testing. The ideal model for screening epilepsy therapies would have spontaneous seizure frequencies that are greater than two per day, little-to-no seizure-free days, and would maintain these features for more than 4 weeks. This study describes a series of improvements to the mouse pilocarpine TLE model. First, a pharmacokinetic model was developed to guide pilocarpine dosing. Second, induction was combined with EEG monitoring, allowing for real-time monitoring of pilocarpine-induced EEG discharges and electrographic seizures that precede behavioral manifestations. Third, strains of mice were identified that withstand pilocarpine-induced status epilepticus and reliably develop spontaneous recurring seizures. The pilocarpine model was improved by lowering mortality and increasing the fraction of mice that developed spontaneous seizures and had seizure frequencies that are amenable to drug screening. Future studies are required to identify the ideal mouse strain for drug screening and validate the response to known anti-epileptic drugs. Full article

Osteoarthritis involves complex interactions between articular joint tissues and the immune system, which is implicated in molecular trafficking via barrier-function modulating cytokines. The current study aims to test effects of an acute spike in TNF-α or TGF-β on vascular barrier function at multiple length scales, from the heart to tissue compartments of the knee, and cellular inhabitants of those respective compartments, in a spontaneous guinea pig model of osteoarthritis. First we quantified the intensity of a fluorescent-tagged 70 kDa tracer, similar in size to albumin, the most prevalent transporter protein in the blood, in tissue compartments of bone (periosteum, marrow space, compact bone, and epiphyseal bone) and cartilage (superficial cartilage, calcified cartilage, and the interface between, i.e., the epiphyseal line), as well as at sites of tendon attachment to bone (entheses). We then examined tracer presence and intensity in the respective pericellular and extracellular matrix zones of bone and cartilage. Acute exposure to TGF-β reduced barrier function (increased permeability) at nearest vascular interfaces in four of eight tissue compartments studied, compared to TNF-α where one of eight tissue compartments showed significant diminishment in barrier function. The increase in permeability associated with reduced barrier function was observed at both tissue compartment and cellular length scales. The observation of pericellular transport of the albumin-sized molecules to osteocytes contrasts with previous observations of barrier function in healthy, untreated animals and is indicative of increased molecular transport in pericellular regions of musculoskeletal tissues in cytokine-treated animals. Understanding age- and disease-related changes in molecular transport within musculoskeletal structures, such as the knee joint, is crucial for elucidating the etiology and pathogenesis of osteoarthritis. Full article

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Background: It has recently been proposed that the retina plays an important modulatory role in the control of motor function that is usually attributed exclusively to the function of the nigro-striatal dopamine (NSD) system. Indeed, it has been proposed further that Parkinson’s disease (PD) begins in and progresses from the retina and may be effectively treated from there. While previous intraocular work has employed intravitreal (IVIT) administration of toxins to induce experimental PD, the first study series reported here examines the effect of IVIT haloperidol on motor performance while the second study examines the effect of IVIT haloperidol on the unilateral rotation model of PD, both in a circadian context. Methods: Motor tests included open field performance and the latency to perform three motor tests after the IVIT injection of haloperidol with and without amphetamine pretreatment. In a second study, IVIT injections of the melatonin antagonist ML-23 or L-dopa were made after unilateral lesions of the NSD in rats that were placed in a rotometer examining spontaneous ipsilateral and contralateral turning. Results: IVIT haloperidol produced robust changes in several motor parameters during the light and dark phase of the LD cycle which were enhanced by amphetamine pretreatment. In the second study, while IVIT L-dopa had only a minor effect on spontaneous rotation during the light phase, IVIT haloperidol produced a robust effect upon ipsilateral turning. The reduction in spontaneous ipsilateral turning was seen after IVIT injections into the eye ipsilateral or contralateral to the hemisphere in which NSD destruction occurred. Reduced turning was seen during both the light and dark phases of the L/D cycle. Conclusions: These results illustrate that IVIT injections of DA and melatonin receptor antagonists can differentially alter motor function via the retina. This suggests that the retina may be a treatment target not only for PD but also for other DA- and melatonin-mediated disorders such as drug addiction, psychosis and schizophrenia. Full article

Recovery from aphasia is a complex process involving restoring language ability to a level comparable to an individual’s pre-aphasia state. This recovery extends beyond linguistic functions such as improved quality of life and functional communication. Understanding language recovery in PWAs is a key area in aphasia research. Thus, the current study aimed to understand the pattern of language recovery in the acute and sub-acute stages of persons with aphasia (PWAs). A total of 11 PWAs aged between 40 and 80 were recruited. The study was conducted in two phases. In the acute stage (within one week post-stroke), participants were assessed using the Western Aphasia Battery-Kannada (WAB-K). In the sub-acute stage (between seven and fifteen days post-stroke), a similar test battery was repeated. The findings of the study showed auditory verbal comprehension scores were pronounced in the acute and sub-acute stages of recovery. Further, language quotient (LQ) scores were higher in the sub-acute stage compared to the acute stage, though these differences failed to evince statistical differences. Correlation analysis revealed strong positive correlations between LQ and spontaneous speech, repetition, and naming, with moderate correlations for auditory verbal comprehension. The study’s findings highlight the importance of targeted therapeutic interventions for PWAs, emphasizing an early focus on auditory verbal comprehension to enhance overall language recovery. Full article

Background: Optic nerve sheath diameter (ONSD) and its ratio to eyeball transverse diameter (ETD; ONSD/ETD) are potential markers for elevated intracranial pressure in comatose survivors of out-of-hospital cardiac arrest (OHCA). However, their prognostic accuracy remains uncertain. We compared their predictive value via compted tomography (CT)and magnetic resonance imaging (MRI) before and after targeted temperature management (TTM) in OHCA survivors. Methods: This retrospective study included adult comatose OHCA survivors who underwent TTM and serial brain imaging. ONSD and ONSD/ETD ratios were measured on brain CT and MRI at two predefined time-points: within 6 h (pre-TTM) and at 72–96 h (post-TTM) after return of spontaneous circulation. Intra-rater reliability was assessed using intraclass correlation coefficients (ICC). Poor neurological outcome was defined as a Cerebral Performance Category score of 3–5 at 6 months. Prognostic performance was evaluated using area under the receiver operating characteristic curve (AUC). Results: Among 136 patients, 78 (57%) had poor neurological outcomes. Only ONSD (5.12 vs. 5.37 mm) and ONSD/ETD ratio (0.22 vs. 0.23) measured on post-TTM MRI were significantly higher in the poor outcome group. These results depicted modest predictive performance (AUC, 0.67 and 0.65, respectively), whereas all CT-based and early MRI measurements had AUC < 0.60. Intra-rater reliability for ONSD and ETD was higher on CT (ICC: up to 0.93) than on MRI (ICC: 0.73–0.80). Conclusions: Delayed MRI-based ONSD and ONSD/ETD showed statistically significant but modest prognostic value, with limited clinical applicability as a stand-alone tool. These findings underscore the relevance of measurement timing, supporting ONSD as an adjunctive, rather than definitive, tool in multimodal prognostication. Full article

Compulsive fantasy, often called “maladaptive daydreaming,” involves frequent engagement with immersive fantasies that can sometimes interfere with everyday life and cause distress. This paper expands on Christoff and colleagues’ Dynamic Framework of Thought (DFT) to offer a process-based analysis of compulsive fantasy as it relates to other mental phenomena such as daydreaming and creative thought. Drawing on the existing literature and posts on online forums by self-identified maladaptive daydreamers, we also propose an account of how compulsive fantasy episodes may unfold in terms of the oscillating dynamics of various constraints on thought, and how these dynamics may be related to a perceived struggle with agency. Automatic constraints, including affective salience and mental habits, may bring about a fantasy episode. During a fantasy episode, automatic constraints may be relatively high throughout, whereas deliberate constraints may be intermittently engaged to influence the fantasy. Our analysis supports the use of “compulsive fantasy” as a more accurate designation than “maladaptive daydreaming” for this phenomenon: compulsive fantasies are not daydreams, because they are more constrained in their mental dynamics. We show that fantasy and daydreaming are not inherently harmful but can become so when they are accompanied by relatively strong and sustained automatic constraints on thought. Full article

Background/Objectives: Subarachnoid cysts in children, while often linked to trauma, can also rupture spontaneously without any apparent injury. Their etiology remains complex, involving congenital, traumatic, and infectious factors. This article explores the risks, pathophysiology, and management strategies related to spontaneous rupture in pediatric cases reported in the literature through the means of a systematic review. Materials and Methods: A systematic review of Web of Science, Scopus, PubMed and the Virtual Health Library (BVS, for its acronym in Spanish) was conducted; the online software Ryyan was used to manage the references and conduct the filtering process. The National Heart, Lung, and Blood Institute (NHLBI) quality assessment tool was used to assess bias for each type of study. Results: We analyzed the data of 101 articles; in total we found that 331 pediatric patients with arachnoid cyst were diagnosed with intracranial hemorrhage and 1030 patients had an unruptured arachnoid cyst. The most common cyst diameter was between 5–7 cm in the bleeding group vs. 3–4.5 cm in the non-bleeding group. A head trauma trigger was identified in 36.25% of cases of bleeding and 10.6% were sports related. Most of the hemorrhages were subdural, followed by a mixed pattern between subdural and intracystic. In both groups the arachnoid cyst was mostly located in the middle cranial fossa in the left side. The bleeding arachnoid cysts were mostly treated with surgery, but conservative treatment was also effective; the outcome was good in the majority of cases. Conclusions: Further research is required to elucidate the pathophysiological mechanisms underlying hemorrhage associated with arachnoid cysts in the pediatric population. Nevertheless, upon identification of an arachnoid cyst, neurosurgical follow-up is warranted. Bleeding tends to occur only in the presence of high-risk features and can be precipitated by traumatic events. Full article

Tumor necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins that transmit signals from immunoregulatory receptors—such as TNF receptors, Toll-like receptors, and interleukin receptors—to coordinate immune and inflammatory responses. Among them, TRAF5 is highly expressed in lymphocytes and implicated in obesity-associated inflammation, but its role in secondary lymphoid organs during chronic low-grade inflammation remains unclear. We examined splenic B and T cell phenotypes in wild-type (WT) and Traf5-deficient (KO) mice fed a high-fat diet (HFD). Although lymphocyte composition was broadly comparable, KO mice showed reduced spontaneous immunoglobulin G2c (IgG2c) production ex vivo—about 1.5-fold lower than WT. Notably, despite elevated TNF-α and CD40 ligand (CD40L) expression in HFD-fed KO splenocytes, IgG2c production remained diminished—about 1.9-fold lower than WT—upon soluble CD40L stimulation, indicating impaired CD40-mediated class-switch recombination (CSR). Consistently, B cells from KO mice on a normal diet exhibited reduced activation-induced cytidine deaminase (AID) expression—about 4.4-fold lower than WT—after CD40L stimulation, and decreased IgG2c secretion—about 6.6-fold lower—upon CD40L and IFN-γ co-stimulation in vitro. Collectively, these findings suggest that TRAF5 is involved in CD40-dependent CSR in B cells under inflammatory conditions and may contribute to sustaining adaptive immune responses during obesity-associated chronic inflammation. Full article

Shilajit, a natural herbo-mineral compound with potent antioxidant, anti-inflammatory, and osteogenic properties, has been traditionally used to promote tissue repair. However, limited experimental data exist on its localized application in bone regeneration. This study aimed to evaluate the combined effect of Shilajit and bovine-derived xenograft on bone healing in a rat tibial defect model. Twenty-eight male Sprague–Dawley rats were randomly assigned to four groups (n = 7): Control (defect left to heal spontaneously), Graft-only, Graft + Shilajit 150 mg/kg, and Graft + Shilajit 250 mg/kg. Standardized 3 mm tibial defects were created and filled with xenograft in all groups except the Control. Shilajit was administered intraperitoneally on days 0–3 postoperatively. After 4 weeks, serum total oxidant status (TOS), total antioxidant status (TAS), and TNF-α levels were measured. Tibial specimens underwent histopathological, histomorphometric, and TNF-α immunohistochemical analysis. High-dose Shilajit significantly increased TAS and reduced TOS compared with the Control and Graft-only groups (p < 0.001). Median TNF-α concentrations decreased in a dose-dependent manner, with the lowest values in the high-dose group (15.7 [14.3–17.1] pg/mL, p < 0.001). Histomorphometry revealed the highest new bone area percentage (78.1% [74.9–81.2]) and lowest fibrous tissue content (9.8% [8.1–11.6]) in the high-dose group. Immunohistochemistry confirmed marked suppression of TNF-α expression in Shilajit-treated groups, particularly at high doses. The combination of Shilajit and bovine-derived xenograft significantly enhanced bone regeneration in a dose-dependent manner, likely through antioxidative, anti-inflammatory, and osteogenic mechanisms. These findings suggest that Shilajit may serve as a promising adjunct in bone grafting procedures. Full article

In the present study three composite materials based on iron in combination with bismuth, copper or lithium carbonates FeNO₃@Li₂CO₃ (SFL), FeNO₃@CuCO₃ (SFC), and FeNO₃@(BiO)₂CO₃ (SFB) were synthesized by coprecipitation. The purpose was to obtain materials that possess targeted adsorbent properties for the recovery of silver ions from aqueous solutions. After synthesis, to emphasize the adsorptive qualities of materials for the recovery of silver ions, the synthesized composite materials, as well as those doped with silver ions following the adsorption process (SFL-Ag, SFC-Ag, and SFB-Ag), were characterized and several adsorption-specific parameters were examined, including temperature, contact time, pH, adsorbent dose, and the initial concentration of silver ions in solution. Subsequently, the ideal adsorption conditions were determined to be as follows: pH > 4, contact time 60 min, temperature 298 K, and solid–liquid ratio (S–L) of 0.1 g of adsorbent to 25 mL of Ag (I) solution for all three materials. The Langmuir model properly fits the experimental equilibrium data of the adsorption process; however, the Ho–McKay model closely represents the adsorption kinetics. The maximum adsorption capacities of the materials, 19.7 mg Ag(I)/g for SFC, 19.3 mg Ag(I)/g for SFB, and 19.9 mg Ag(I)/g for SFL, are comparable. The adsorption mechanism is physical in nature, as evidenced by the activation energies of 1.6 kJ/mol for SFC, 4.15 kJ/mol for SFB, and 1.32 kJ/mol for SFL. The highest Ag(I) concentration used for doping all three materials in the study was 150 mg Ag(I)/L. The process is endothermic, spontaneous, and takes place at the interface between the adsorbent and the adsorbate, according to thermodynamic theory. Subsequently, the antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans microorganisms was evaluated by rate of inhibition assessment. The SFC-Ag material showed a percentage of 100% inhibition with respect to the positive control for each microorganism. All synthetized materials have better efficiency as antifungal agents. Full article

The Baikouquan Oilfield edge expansion wells suffer from poor reservoir properties and limited connectivity, leading to low waterflooding sweep efficiency and insufficient reservoir energy. While oil displacement agents (ODAs) are currently employed in huff-and-puff flooding to enhance recovery, there is a lack of a solid basis for selecting these ODAs, and the dominant mechanisms of enhanced oil recovery (EOR) remain unclear. To address this issue, this study combines experimental work and reservoir numerical simulation to investigate the mechanisms of EOR by ODAs, optimize the selection of ODAs, and fine-tune the huff-and-puff flooding parameters. The results show that the selected nanoemulsion ODA (Nano ODA) significantly reduces the oil–water interfacial tension (IFT) by 97%, thereby increasing capillary number. Additionally, the ODA induces a shift from water–wet to neutral–wet conditions on rock surfaces, reducing capillary forces and weakening spontaneous imbibition. The Nano ODA demonstrates strong emulsification and oil-carrying ability, with an emulsification efficiency of 75%. Overall, the ODA increases the relative permeability of the oil phase, reduces residual oil saturation, and achieves a recovery improvement of more than 10% compared with conventional waterflooding. The injection volume and shut-in time were optimized for the target well, and the recovery enhancement from multiple cycles of huff-and-puff flooding was predicted. The research in this paper is expected to provide guidance for the design of huff-and-puff flooding schemes in low-permeability reservoirs. Full article

Herein, nanoscale MgAl₂O₄ (MOA), 10%CuO@MgAl₂O₄ (10Cu@MOA), 10%NiO@MgAl₂O₄ (10Ni@MOA), and 10%CoO@MgAl₂O₄ (10Co@MOA) were synthesized employing butylated hydroxytoluene (the food additive BHT) as a capping agent. The SEM images illustrated average sizes of 38.8, 30.0, 40.8, and 32.7 nm for MOA, 10Cu@MOA, 10Ni@MOA, and 10Co@MOA, respectively, and their BET surface area were 84.4, 141.8, 126.7, and 105.3, respectively. Doxycycline DXC removal was studied employing the MOA, 10Cu@MOA, 10Ni@MOA, and 10Co@MOA, which resulted in q_t values of 57.3, 106.1, 97.7, and 73.9 mg g⁻¹, respectively. The pseudo-second order model best described the DXC sorption onto MOA, 10Cu@MOA, 10Ni@MOA, and 10Co@MOA, and both film diffusion models influenced the DXC sorptions onto the sorbents. The DXC sorption onto the 10Cu@MOA fitted the Freundlich model. The thermodynamics implied endothermic-spontaneous DXC sorption onto the10Cu@MOA. The pH study exposed that the DXC removal by 10Cu@MOA was more effective in a mildly acidic medium (pH = 6.0). Furthermore, the 10Cu@MOA effectiveness in treating surface water contaminated by 5.0 and 10.0 mg L⁻¹ DXC was 99.9% and 98.1%, respectively, while it was 94.7% and 92.5% in treating the concentrations above in seawater, respectively. The reusability study showed a 10% reduction in the 10Cu@MOA’s removal efficiency at the fourth cycle, which is encouraging for real-life applications. Full article

Background/Objectives: Childbirth is a natural and joyfully anticipated life event for parents and relatives. Yet, in some cases, it can be a medical emergency requiring immediate intervention, i.e., neonatal resuscitation. The majority of newborns breathe spontaneously; a small number, though, may receive basic life support (assisted transition), and an even smaller but clinically significant number require advanced life support (resuscitation). Within the context of family-centered care, the presence of parents during resuscitation has emerged as a factor with potential implications for emotional adjustment, communication with healthcare providers, and early parent–infant bonding. However, the presence of family members during neonatal resuscitation remains a subject of ongoing debate among healthcare professionals (HCPs). Despite increasing recognition of its potential benefits, HCPs’ views on parental presence during such critical procedures have not been extensively investigated in Greece. This study aims at developing and validating a tool to assess healthcare professionals’ views on parental presence during neonatal resuscitation. Methods: A preliminary questionnaire was developed based on the principles of family-centered care and adapted to the Greek population. The first phase included expert assessment of validity, clarity, and relevance using a modified Delphi method. Item Content Validity Index (I-CVI) and Scale CVI (S-CVI) were calculated. Pilot testing was conducted to assess test–retest reliability. Reliability was assessed using the Intraclass Correlation Coefficient (ICC) and Bland–Altman analyses. The study followed the principles of the Declaration of Helsinki, ensuring anonymity, informed consent, and confidentiality. Results: The questionnaire includes 37–50 items allocated in four sections. It demonstrated excellent content validity (CVI = 1.00) and good test–retest reliability (ICC = 0.86). Qualitative feedback indicated that the tool is user-friendly and comprehensive. Interestingly, participants expressed genuine concerns regarding the implementation of parental presence in neonatal resuscitation. Conclusions: The questionnaire development process led to a comprehensive tool, ready for large-scale testing in order to further establish its validity and internal consistency. Full article

Sarcoidosis is a chronic inflammatory disease of unknown etiology that can involve virtually any organ, with pulmonary involvement seen in over 90% of cases. Although many patients experience spontaneous remission, approximately 10–30% develop progressive pulmonary disease, which may lead to fibrocystic changes, respiratory failure, and death. Oral glucocorticoids remain the cornerstone of treatment for symptomatic patients with pulmonary infiltrates and abnormal pulmonary function tests, with typical starting doses ranging from 20 to 40 mg/day followed by a slow taper over 6–18 months based on clinical and radiographic response. However, prolonged glucocorticoid therapy is associated with significant toxicity, and many patients require additional immunosuppressive agents for disease control or steroid-sparing purposes. Antimetabolites such as methotrexate, azathioprine, mycophenolate mofetil, and leflunomide are commonly used second-line therapies. For refractory disease, particularly in those with metabolically active lesions on FDG-PET, anti-tumor necrosis factor (TNF) agents like infliximab may be effective but carry risks of serious adverse effects. In select cases, newer strategies—including RCI, rituximab, JAKi or investigational regimens—are being explored. Management must also account for non-inflammatory complications such as sarcoidosis-associated pulmonary hypertension and bronchiectasis, which can mimic disease progression and require distinct therapeutic approaches. Given the heterogeneity of sarcoidosis and lack of robust clinical trial data, a stepwise and individualized approach to immunosuppression remains essential in optimizing outcomes while minimizing treatment-related harm. Full article