Search Results (2,246)

Background: Type 2 inflammatory diseases are among the most common chronic inflammatory conditions in childhood and represent a growing global health burden. Increasing evidence suggests that early-life nutritional exposures may influence immune programming and allergic disease development. This Position Paper aims to summarize the current evidence regarding the immunomodulatory role of polyunsaturated fatty acids (PUFAs), particularly omega-3 long-chain fatty acids, in the prevention of allergic diseases during early life. Methods: A scoping literature review and consensus process were conducted to map biological mechanisms and clinical evidence linking omega-3 PUFAs with allergic disease prevention. This document analyzed experimental, observational, and randomized controlled studies evaluating maternal prenatal/lactational omega-3 exposure. The clinical evidence was qualitatively appraised using study-design-specific Joanna Briggs Institute (JBI) Critical Appraisal Tools. Particular attention was given to immune modulation, inflammatory pathways, epithelial barrier function, gut microbiota interactions, and the ferroptosis–immune–metabolic axis. Results: Omega-3 PUFAs, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exert immunomodulatory and anti-inflammatory effects through multiple mechanisms, including specialized pro-resolving mediator production, regulation of T-helper cell responses, cytokine modulation, maintenance of epithelial barrier integrity, and microbiota interaction. Emerging evidence also supports their involvement in oxidative stress and ferroptosis regulation. Current clinical evidence, particularly from higher-quality prenatal randomized trials and evidence syntheses, suggests that adequate maternal omega-3 intake during pregnancy and lactation may reduce the risk of respiratory allergic outcomes, especially wheezing and asthma, in selected offspring. Conclusions: Adequate omega-3 PUFA intake, such as 2 g/die, during critical windows of immune maturation may represent a valuable strategy for the primary prevention of allergic diseases. Current evidence most strongly supports supplementation during pregnancy and lactation, particularly in populations with low dietary omega-3 intake or increased allergic risk. Omega-3 supplementation should be considered within a broader multifactorial preventive approach aimed at promoting immune tolerance and reducing the future burden of allergic diseases. Full article

Objective: Pediatric intestinal pseudo-obstruction (PIPO) is a rare, severe, and heterogeneous gastrointestinal motility disorder associated with intestinal failure, recurrent hospitalizations, and significant morbidity and mortality. This study aimed to evaluate the clinical features, management strategies, and long-term outcomes of children diagnosed with PIPO at a tertiary referral center. Methods: This retrospective single-center study included pediatric patients diagnosed with PIPO between 2011 and 2025. Diagnosis was established according to ESPGHAN consensus criteria. Demographic characteristics, clinical presentation, genetic findings, nutritional support, surgical interventions, intestinal transplantation, and long-term outcomes were retrospectively reviewed. Results: A total of 32 patients with PIPO were included, of whom 56.2% were female and 43.7% had early-onset disease. Genetic testing was performed in 22 of 32 patients; clinically significant variants were identified in 16 (50% of the total cohort), most commonly ACTG2 mutations. Prior abdominal surgery before referral was present in 84.3% of patients. During follow-up, 56% remained parenteral nutrition dependent, five patients underwent intestinal transplantation, and the overall mortality rate was 21.8%. Conclusions: PIPO is a highly heterogeneous disorder associated with substantial morbidity, prolonged nutritional support requirements, repeated surgical interventions, and significant mortality. Early diagnosis, genetic evaluation, multidisciplinary management, and timely referral to specialized intestinal failure and transplantation centres are likely to support more individualised management and may help prevent avoidable complications in affected children. Full article

Background: Neutrophil dysregulation drives inflammatory pathologies through mechanisms such as matrix metalloproteinase-9 (MMP-9) release. High-value bioprospecting of agro-industrial residues offers a sustainable strategy to identify novel bioactive compounds. In this study, the immunomodulatory effects of seed oils (SOs) obtained via supercritical fluid extraction from Passiflora edulis and Rubus glaucus byproducts on human neutrophil responses was evaluated. Methods: SO lipid profiles were characterized via GC-MS. Human neutrophils were isolated using Percoll gradients and treated with the SOs (10–50 µg/mL). Cytocompatibility was assessed via MTT and trypan blue assays. MMP-9 activity and ERK1/2/p38 phosphorylation were determined via zymography and Western blotting, respectively. Results of GC-MS revealed matrices rich in unsaturated lipids: R. glaucus SO was dominated by linoleic (50.02%) and α-linolenic (29.84%) acids, whereas P. edulis SO contained linoleic (58.91%) and oleic (19.75%) acids. Both oils were highly biocompatible up to 50 µg/mL. Both SOs significantly increased MMP-9 release; notably, R. glaucus induced a dose-dependent response and a potential priming effect at 10 µg/mL. Interestingly, neither oil induced the phosphorylation of ERK1/2 or p38. Conclusions: Supercritical fluid-extracted SOs from P. edulis and R. glaucus byproducts modulate early neutrophil responses by increasing MMP-9 release through pathways independent of classical MAPK phosphorylation. Further functional and in vivo validation is needed to clarify the precise regulatory roles of these specialized lipid matrices in human inflammation resolution and their potential as bioactive ingredients for nutraceutical or pharmaceutical applications. Full article

Across all kingdoms of life, ribosomes are indispensable molecular machines that translate genetic information into the proteome of living cells. The fundamental catalytic centers of the ribosome, constructed primarily from ribosomal RNA (rRNA), exhibit remarkable conservation between the major domains of life. The ribosome’s A-site deciphers the mRNA’s triplet code, while the P-site synthesizes the growing protein chain and the E-site provides exit for deacylated tRNA; a distinct tunnel facilitates nascent polypeptide export. While the conservation of ribosomal proteins is less pronounced between bacteria and eukaryotes, striking homology exists from simple eukaryotes to humans. Ribosomal proteins were traditionally viewed mainly as scaffolding agents, steering rRNA folding during ribosome biogenesis and maintaining structural stability during translation. However, since the early 2000s, advances in structural and functional ribosome analysis have ushered in a more nuanced paradigm: ribosomes are no longer considered uniform machines. Instead, an array of rRNA and ribosomal protein modifications generates a spectrum of ribosome populations capable of specialized translation. RiboScreen^TM technology leverages this regulatory potential of individual ribosomal proteins, enabling deliberate modulation of target protein output and representing a promising tool for correcting dysregulated protein expression involved in rare and common diseases. This review will first introduce relevant aspects of ribosome biology and then showcase the tools of this new technology. Finally, we report examples for the delivery of small molecules to target ribosomal proteins for tailored restoration of protein production levels in rare and prevalent diseases. Full article

This study reconsiders the meaning of the term “miqweh” in early rabbinic literature and challenges its common rendering as “immersion pool” or “ritual bath.” Surveying biblical and Second Temple texts, it demonstrates that “miqweh” originally indicated a general “gathering of water” and was not associated with purificatory bathing. Only in early rabbinic sources did the term acquire a specialized, legal-technical sense, referring to pooled water within the narrow context of ritual purification through immersion in water. This semantic shift likely derives from rabbinic interpretation of Leviticus 11:36 and reflects broader patterns of legal abstraction in rabbinic discourse. Crucially, the study shows that “miqweh” never referred to the physical installation or structure containing the water; instead, terms such as “mǝʿārâ” (“cave”) and “bêt haṭṭǝbîlâ” (“place of immersion”) were used for such spaces. These two terms, the study tentatively suggests, likely emerged before the more abstract “miqweh” was coined. Full article

Diabetic retinal disease (DRD) has classically been defined as a microvascular complication of diabetes; however, the recent evidence highlighted the key role of neuronal degeneration during the earliest stages of its pathogenesis. Therefore, neuroprotection has emerged as a promising therapeutic strategy to prevent disease progression. Topical administration via eyedrops represents a non-invasive approach to deliver neuroprotective agents directly to the retina. This review summarizes the current advances in the field of neuroprotective therapies against early DRD with a special focus on topical delivery, including preclinical and clinical evidence, while discussing the relevance of the transscleral route of absorption in all of them. In this review, the most promising neuroprotective compounds under development will be discussed, highlighting the opportunity that they represent for treating early stages of DRD. Full article

Background/Objectives: In ketogenic therapy for children with refractory epilepsy—a special patient group—the quality of life of primary caregivers is often overlooked. This study aimed to explore the current state of primary caregivers’ quality of life and identify associated risk factors. Methods: A cross-sectional study was conducted from 21 January 2024 to 21 January 2025. A total of 117 primary caregivers of children with refractory epilepsy completed the World Health Organization Quality of Life (WHOQOL)-BREF (26 items) and Adherence questionnaire (6 items). Participants were divided into KD therapy groups (n = 51) and non-KD therapy groups (n = 66) according to the treatment. Factors associated with caregivers’ QoL in the ketogenic treatment were analyzed using the multifactor hierarchical regression. Results: There was no significant difference in QoL scores between the KD and non-KD caregiver groups (p > 0.05). KD adherence emerged as independently associated with caregivers’ QoL, particularly in the environmental domain (Model 1: β = −0.309, p = 0.022; Model 2: β = −0.306, p = 0.025). A higher KD cost was significantly associated with a lower social domain score in both models (Model 1: β = −0.285, p = 0.032; Model 2: β = −0.286, p = 0.034). Model 1 for the environmental domain demonstrated modest explanatory power (Adjusted R² = 0.246, p = 0.002). Conclusions: These findings underscore the need for clinical support systems to assess and address modifiable stressors early in treatment, including family structure, challenges with ketogenic diet therapy adherence, and financial burden. Such comprehensive evaluation is essential for developing effective and personalized interventions. Full article

Rosa damascena Mill. is a medicinal and aromatic species of major pharmacological and economic importance, widely valued for its complex profile of bioactive secondary metabolites. While extensive research has focused on field-grown plants and essential oils, comparatively little attention has been devoted to the behavior of R. damascena under in vitro conditions. Plant tissue culture systems provide controlled platforms for investigating secondary metabolism independently of environmental variability; however, their application to R. damascena has produced heterogeneous and often inconsistent results. This review examines the main in vitro culture systems developed for R. damascena, including callus, suspension, and organ-derived cultures, with emphasis on their capacity to accumulate secondary metabolites. Available evidence indicates that undifferentiated cultures generally fail to reproduce the full metabolic complexity observed in planta, particularly for volatile monoterpenes associated with tissue specialization. Nevertheless, several studies demonstrate that in vitro systems can accumulate phenolic compounds with relevant biological activities, supporting their use as experimental models for investigating metabolic regulation. By integrating early studies with recent advances in plant biotechnology, this review highlights current limitations, unresolved questions, and future perspectives for the use of R. damascena in vitro cultures in medicinal plant research. Full article

Background/Objectives: In interceptive sports like volleyball, the ability to accurately time an action relative to a moving object (Coincidence Anticipation Timing—CAT) is critical. This study investigated the effects of a structured 8-week deliberate practice intervention on CAT accuracy and its long-term retention in young female athletes. Methods: Thirty-two female volleyball players (aged 8–10 years) were randomly assigned to an Experimental Group (EG, n = 16) and a Control Group (CG, n = 16). The EG underwent a specialized 8-week training program focusing on progressive cognitive load and immediate knowledge of results, while the CG followed standard volleyball training. A single-blind assessor measured CAT at two velocities (5 mph and 10 mph) using the Bassin Anticipation Timer at three time points: pre-test, post-test, and a 2-month retention test. Results: ANCOVA revealed a significant group-by-time interaction (p < 0.001), with the EG demonstrating a substantial reduction in absolute timing error. The effect size was markedly higher at 10 mph (partial η² = 0.400) compared to 5 mph (partial η² = 0.197). Crucially, the EG maintained their performance gains during the retention test (p < 0.05), whereas the CG showed no significant improvement over time. Conclusions: Targeted deliberate practice effectively enhances temporal prediction accuracy in children, likely by facilitating a shift from reactive to predictive motor control. The robust retention of these skills underscores the significant neuroplasticity of the 8–10 age window, suggesting that early foundational timing interventions provide long-lasting benefits for athletic development. Full article

Introduction: Conjunctival and eyelid lesions encompass a broad spectrum of conditions, ranging from benign entities to malignant neoplasms, and may significantly impact ocular health and quality of life. Their occurrence is influenced by environmental exposure, demographic characteristics, and access to healthcare services. In public health settings, delayed diagnosis and limited access to specialized care may contribute to disease progression. Objective: To characterize the clinical and epidemiological profile of conjunctival and eyelid lesions in patients treated at a referral ophthalmology service within the Brazilian Unified Health System (SUS). Methods: This retrospective observational study reviewed medical records of patients diagnosed with conjunctival and/or eyelid lesions during ophthalmologic screening campaigns. Clinical and demographic variables were analyzed using descriptive statistics to assess prevalence and distribution patterns. Results: A total of 66 patients were included. Conjunctival involvement predominated (78.8%), with the nasal region being the most frequently affected location (62.1%). Pterygium was the most prevalent diagnosis (31.8%), followed by racial melanosis (15.2%) and melanocytic nevus (12.1%). No statistically significant differences were observed according to sex or lesion laterality. However, a significant association was identified between lesion type and anatomical location. Conclusions: Conjunctival and eyelid lesions in this population were predominantly benign and associated with demographic and environmental factors. These findings highlight the importance of structured screening strategies and early diagnosis to improve clinical outcomes and support public health policies aimed at reducing the burden of ocular disease within the SUS. Full article

Thyroid tumors rank among the most frequently occurring endocrine cancers because early detection helps doctors deliver effective treatments that lead to better patient results. Ultrasound imaging enables the detection of thyroid nodules, yet medical professionals struggle to differentiate between benign and malignant nodules through their diagnostic tests. This study introduces a new medical framework that enables thyroid nodule diagnosis through ultrasound imaging. The proposed model combines advanced segmentation with feature extraction, classification, and reasoning components to create a complete system. The specialized segmentation method shows accurate results when it detects nodule boundaries, which leads to better analysis of specific regions. The Hybrid Vision Transformer (HVT) operates to capture detailed textural information together with complete environmental patterns, which boosts its ability to classify different elements. The proposed framework incorporates a Large Language Model (LLM), specifically Med-PaLM, to provide context-aware clinical reasoning and interpretation. The structured evaluation process uses Thyroid Imaging Reporting and Data System (TI-RADS)-based feature scoring to compare model results with designated clinical standards. The diagnostic process is enhanced through the use of a language model, which delivers contextual understanding and produces valuable information from features that have been extracted. The proposed model achieves excellent performance with accuracy at 98.5%, precision at 98.7%, recall at 98.4%, and F1-score at 98.5%, which demonstrates its capacity for accurate and equivalent performance across different classifications. The experimental results demonstrate that the model achieves better results than existing methods. The combination of multimodal data with clinical reasoning improves both the accuracy and the user experience of the system. The proposed framework provides an efficient, interpretable, and scalable solution for thyroid nodule diagnosis. Full article

Background: Unilateral progressive condylar growth (UPCG) represents a complex clinical condition characterized by abnormal enlargement of the mandibular condyle, leading to progressive facial asymmetry and functional impairment. Objectives: The aim of this review is to analyze the biological, clinical, and therapeutic factors guiding condylectomy, assess the current role and scope of proportional condylectomy, and propose an algorithm to guide its indication in patients with UPCG. Methods: A narrative review was conducted to analyze the biological, clinical, and therapeutic factors involved in the indication for condylectomy in patients with progressive unilateral condylar growth. Studies including patients diagnosed with unilateral condylar hyperplasia or condylar osteochondroma who underwent surgical treatment were considered to evaluate clinical indications, timing of intervention, and outcomes. Special attention was given to the concept of proportional condylectomy. Results: Current evidence indicates that early intervention may control disease progression, reduce the severity of residual deformity, and minimize the need for secondary orthognathic surgery. The integration of clinical findings, three-dimensional imaging, and patient-specific factors is essential for appropriate treatment planning. Conclusions: Based on these considerations, a structured clinical algorithm is proposed to guide decision-making in patients with unilateral progressive condylar growth. This approach supports individualized treatment strategies aimed at optimizing functional and esthetic outcomes. Full article

Background: The incidence of early-onset colorectal cancer (EOCRC) has increased worldwide and now represents approximately 10% of colorectal cancers in high-income countries. EOCRC is frequently associated with advanced pathological features, although its clinical behavior and optimal management remain incompletely defined. Methods: We performed a retrospective single-center study including 88 consecutive patients aged ≤50 years who underwent curative-intent colorectal cancer resection between January 2019 and December 2023 at a tertiary referral center. Perioperative outcomes, pathological characteristics, and recurrence patterns were analyzed. Results: The median age was 44 years, and 67% of tumors were located in the colon. Pathological nodal involvement (pN+) was observed in 47.7% of patients, with a high prevalence of adverse features including perineural invasion (62.5%), tumor budding (17.0%), and tumor deposits (15.9%). Minimally invasive surgery was performed in 79% of patients and was associated with shorter hospital stay without increased postoperative morbidity (19.3%). During a median follow-up of 31.3 months [IQR 21.6–44.6], recurrence occurred in 40 patients (45.5%) and was predominantly distant (75.0%). Among patients with recurrence, 21 (52.5%) underwent surgical reintervention, most commonly hepatic and pulmonary resections. Rectal cancer was associated with higher rates of stoma formation and major postoperative complications compared to colon cancer. Conclusions: EOCRC is characterized by a high prevalence of adverse pathological features and a substantial rate of distant recurrence. However, a relevant proportion of recurrences remains amenable to surgical treatment in selected patients. Management in a specialized tertiary center allows achievement of high-quality surgical outcomes and supports an aggressive multidisciplinary approach. Full article

Nowadays, numerical simulation methods are advanced and widely used in industry, enabling the modeling of complex systems from printed circuit boards (PCBs) to full power converters. Among many isolated topologies, the phase-shift full-bridge (PSFB) topology is a well-established solution for isolated DC–DC conversion in electric vehicles. Therefore, this paper proposes a broadband electromagnetic compatibility (EMC) modeling methodology for a custom-designed 1 kW gallium nitride (GaN)-based PSFB converter intended for an electric vehicle (EV) DC powertrain. Moreover, the approach combines full-wave electromagnetic simulation with circuit-level simulation, including parasitic effects from PCB layout, power harnesses, and discrete components. Thus, the virtual prototype is assessed within a complete virtual test bench compliant with the standard Comité International Spécial des Perturbations Radioélectriques (CISPR) 25 over the 150 kHz–108 MHz range to capture common-mode (CM) and differential-mode (DM) conducted electromagnetic interference (EMI). Results show that the converter achieves efficiencies of 97.26% in standalone mode and 97.03% when integrated into the full DC powertrain. However, the conducted EMI assessment reveals that both CM and DM emissions exceed CISPR 25 Class 2 limits across the entire spectrum, with excess levels reaching up to 72 dBµV. Therefore, power harnesses significantly increase EMI levels at low frequencies due to the distributed inductance and stray capacitance. Finally, this study demonstrates the value of virtual prototyping for simulation-based EMI prediction in early-stage power converter design. Full article

Background/Objectives: Colorectal cancer is a leading cause of cancer-related mortality worldwide, and early detection of gastrointestinal (GI) polyps through endoscopy is critical for improving patient outcomes. However, access to specialist gastroenterology care remains severely limited in Federal Health Professional Shortage Areas (HPSAs), particularly for high-acuity geriatric patients. This study proposes GeriAIGastroNet, a clinically oriented deep learning framework designed to support AI-assisted tele-gastroenterology workflows in resource-limited settings, with the primary objective of enabling AI-powered risk stratification and colonoscopy referral triage for elderly patients who lack on-site gastroenterology access. Methods: The framework integrates an EfficientNet-B4 backbone with multi-scale attention fusion and a geriatric severity-aware classification head to enable accurate GI polyp segmentation and automated clinical risk stratification from endoscopic images. Patients identified as high-risk are referred to colonoscopy-capable centers; such centers typically offer diagnostic colonoscopy with polypectomy capability for smaller and intermediate-complexity polyps, while patients with larger, sessile, or morphologically complex lesions requiring advanced endoscopic resection (e.g., endoscopic mucosal resection or endoscopic submucosal dissection) are further referred to tertiary endoscopy centers with specialized expertise. The model was trained and evaluated on the publicly available HyperKvasir dataset (1000 annotated polyp images). Results: GeriAIGastroNet achieved a classification accuracy of 96.77%, F1-score of 96.90%, Dice coefficient of 89.18%, and Intersection over Union (IoU) of 80.80%, outperforming established baselines, including U-Net, Attention U-Net, TransUNet, and Hybrid CNN-Transformer architectures. The integrated tele-gastroenterology decision support layer enables severity-based patient triage and automated referral triggering. Conclusions: These results demonstrate the potential of AI-powered polyp analysis to strengthen equitable access to GI care by facilitating risk stratification and specialist referral in HPSAs where direct endoscopy is unavailable, making the system deployable in telehealth infrastructures serving underserved elderly populations. Full article