Search Results (5,277)

Background: Shaken Baby Syndrome (SBS) is a severe form of abusive head trauma with potentially fatal consequences. Nurses and midwives play a crucial role in its prevention through early recognition and caregiver education; however, little is known about their knowledge and preparedness in the Polish context. Objectives: To assess the knowledge, perceptions, and educational experiences related to SBS among Polish nurses and midwives working with infants. Participants and Setting: A nationwide cross-sectional survey was conducted among 110 nurses and midwives employed in neonatal and pediatric care settings across Poland. Methods: An anonymous questionnaire collected demographic data and evaluated knowledge of SBS, infant crying, coping strategies, and prior training. Associations between knowledge levels and participant characteristics were analyzed using the Mann-Whitney U and Kruskal-Wallis tests. Results: Most participants (94.5%) had heard of SBS, and 78.2% correctly recognized shaking as more dangerous than a fall from a changing table. However, only 5.5% reported receiving formal training on SBS. Recognition of SBS symptoms was generally high (e.g., vomiting 100%, seizures 90.9%), but misconceptions persisted regarding coping with infant crying. More than one-quarter (27.3%) admitted experiencing a “breaking point,” and this group was more likely to acknowledge the risk of losing emotional control. Older nurses demonstrated significantly better recognition of crying patterns and colic (p = 0.0415), while SBS knowledge was positively associated with years of professional experience (p = 0.0484). Conclusions: Although general awareness of SBS is widespread, practical knowledge and training remain insufficient. Structured educational programs on SBS and infant crying management are urgently needed to better prepare healthcare professionals and reduce the risk of caregiver-related harm to infants. Full article

Cathepsin L (CatL) is a critical protease involved in cleaving the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), facilitating viral entry into host cells. Inhibition of CatL is essential for preventing SARS-CoV-2 cell entry, making it a potential therapeutic target for drug development. Six QSAR models were established to predict the inhibitory activity (expressed as IC₅₀ values) of candidate compounds against CatL. These models were developed using statistical method heuristic methods (HMs), the evolutionary algorithm gene expression programming (GEP), and the ensemble method random forest (RF), along with the kernel-based machine learning algorithm support vector regression (SVR) configured with various kernels: radial basis function (RBF), linear-RBF hybrid (LMIX2-SVR), and linear-RBF-polynomial hybrid (LMIX3-SVR). The particle swarm optimization algorithm was applied to optimize multi-parameter SVM models, ensuring low complexity and fast convergence. The properties of novel CatL inhibitors were explored through molecular docking analysis. The LMIX3-SVR model exhibited the best performance, with an $R^2$ of 0.9676 and 0.9632 for the training set and test set and RMSE values of 0.0834 and 0.0322. Five-fold cross-validation $R_{5-fold}^2$ = 0.9043 and leave-one-out cross-validation $R_{loo}^2$ = 0.9525 demonstrated the strong prediction ability and robustness of the model, which fully proved the correctness of the five selected descriptors. Based on these results, the IC₅₀ values of 578 newly designed compounds were predicted using the HM model, and the top five candidate compounds with the best physicochemical properties were further verified by Property Explorer Applet (PEA). The LMIX3-SVR model significantly advances QSAR modeling for drug discovery, providing a robust tool for designing and screening new drug molecules. This study contributes to the identification of novel CatL inhibitors, which aids in the development of effective therapeutics for SARS-CoV-2. Full article

Background/Objectives: Fibromyalgia is a chronic pain syndrome with unclear etiology, meaning that it is difficult to treat effectively. The stimulation of cannabinoid receptor 1 (CB1) suppresses neuronal excitability and synaptic transmission in nociceptive pathways via reducing activity in the calcium channel and promoting the opening of the potassium channel. Methods: In this study, we examined whether CB1 activity contributes to the antinociceptive efficacy of electroacupuncture (EA) in a mouse fibromyalgia (FM) pain model established using intermittent cold stress (ICS). The model mice demonstrated both mechanical and thermal hyperalgesia measured using the von Frey and Hargreaves tests, respectively. Results: Electroacupuncture effectively reduced both forms of hyperalgesia and enhanced CB1 expression in the dorsal root ganglia, spinal cord, hypothalamus, and periaqueductal gray. In addition, EA attenuated the fibromyalgia-associated reactive transformation of microglia and astrocytes and the activation of the pain-related TLR4–MyD88–TRAF6 signaling pathway. The effects of ICS were also mitigated by the deletion of Trpv1, the gene encoding the transient receptor potential cation channel TRPV1 (capsaicin channel) implicated in nociceptive and inflammatory signaling. Further, the antinociceptive efficacy of EA was partially recapitulated by the acupoint injection of a CB1 agonist and abolished by the injection of a CB1 antagonist, suggesting that activating CB1 is essential for this therapeutic effect. Conclusions: Electroacupuncture can effectively alleviate mechanical and thermal hyperalgesia in a mouse model affected by fibromyalgia pain by activating the CB1 pathway, highlighting the therapeutic potential of CB1 agonism as a therapeutic strategy. Full article

Acute aortic syndromes (AAS) include a spectrum of life-threatening conditions that pose considerable diagnostic challenges, particularly in emergency care settings. Clinical scores and circulating biomarkers have become essential in improving diagnostic accuracy, risk stratification, and guiding clinical decision-making. Tools such as the Aortic Dissection Detection Risk Score (ADD-RS) and the AORTAs score offer structured methods for identifying patients at elevated risk; however, their diagnostic performance can be further enhanced through integration with biomarker testing and imaging modalities. Biomarkers including D-dimer, NT-proBNP, cardiac troponins, and novel candidates such as soluble ST2 (sST2) and matrix metalloproteinase-8 and 9 (MMP-8, MMP-9), have demonstrated potential in refining diagnostic and prognostic assessments with an outstanding sensibility. ADAMTS-1 and ADAMTS-4 appear to have the best diagnostic accuracy, whereas certain non-coding DNAs (miR-15a) achieve an exceptionally high negative predictive value. These biomarkers reflect key underlying mechanisms such as inflammation, oxidative stress, and vascular injury, offering valuable insights into disease severity and progression. However, limitations related to specificity, inter-cohort variability, and assay standardization currently hinder their widespread clinical adoption. Further validation through large-scale, multi-center studies is essential to establish their role within integrated diagnostic pathways. Full article

Background: Hyperventilation Syndrome (HVS) is a well-recognized physiological consequence of acute anxiety, often resulting in respiratory alkalosis and subsequent electrolyte imbalances. Among these, a reduction in ionized calcium levels can lead to neuromuscular irritability and electrocardiographic abnormalities such as QTc prolongation. Although well-documented in specific settings, including autism spectrum disorders and drug-induced crises, such complications are rarely described in otherwise healthy pediatric patients presenting with isolated anxiety episodes. This report aims to raise awareness of anxiety-driven somatic manifestations, particularly in the context of the rising prevalence of mental health disorders among children and adolescents. Methods: We report the case of a previously healthy 10-year-old girl presenting to the emergency department with acute agitation and hyperventilation. Clinical examination revealed neuromuscular symptoms, including Trousseau’s sign and flexion posture. Initial laboratory testing and arterial blood gas analysis indicated respiratory alkalosis with decreased ionized calcium levels, and a resting ECG showed QTc prolongation (510 ms). Treatment included intravenous midazolam, a balanced electrolyte solution, and oral bromazepam during intensive observation with cardiac monitoring. Results: The patient’s symptoms progressively improved following anxiolytic and supportive therapy. Electrolyte abnormalities normalized within 48 h, with complete resolution of the prolonged QTc (430 ms). No arrhythmias or other complications occurred. Outpatient psychological follow-up was arranged upon discharge. Conclusions: This case underscores the importance of considering anxiety as a primary etiology in pediatric patients with apparent metabolic or cardiac abnormalities. Early psychiatric recognition and targeted supportive care can prevent overtreatment and reduce the burden on emergency and cardiologic resources. Full article

Activation of TP53 signaling during ribosome biogenesis is an essential part of erythroid development, whereas the pathologic activation of TP53 in ribosomopathies such as Diamond-Blackfan anemia (DBA) and del (5q) myelodysplastic syndrome (MDS) prevents the normal expansion of erythroid precursors. TP53 can also be linked to the pathogenesis of DBA and MDS via ferroptosis, a form of iron-mediated cell death propagated by excess polyunsaturated fatty acid-containing oxidizable phospholipids and loss of lipid peroxide repair capacity. The primary objective of this work was to establish how overexpression and mutation of the TP53 gene influences lipid composition, erythroid differentiation, and ferroptosis sensitivity in K-562 cells, an in vitro model for studying erythropoiesis. Employing a reverse genetics approach, we generated four isogenic cell lines that either lacked functional TP53 expression, expressed wild-type (WT) TP53, or expressed one of the two most common TP53 mutation types, R175H or R282W. We then utilized non-targeted lipidomics to quantify and identify changes in specific lipid species that occur with induction of WT and mutant TP53 expression. We also analyzed differences in gene expression, ferroptosis sensitivity, and hemoglobinization by qPCR, CCK-8 cytotoxicity assay, and o-dianisidine staining, respectively. The abundance of 337 distinct lipid species was impacted by induction of WT TP53 expression compared to K-562 cells expressing a nonfunctional P53 protein. Yet only 17 lipid compounds were differentially impacted between cells expressing WT TP53 and either of the mutant TP53 genes tested. Similarly, while the TP53 null K-562 cells displayed modest sensitivity to ferroptosis, cells expressing both WT and mutant TP53 genes were remarkably resistant to ferroptosis. However, terminal differentiation and hemoglobinization were significantly impacted in R175H mutant TP53-expressing K-562 cells. Findings from this work provide novel insights into the role of TP53 in lipid metabolism and terminal erythropoiesis. Full article

Background: Functional pancreatic neuroendocrine tumors (FpNETs) are extremely rare in childhood and adolescence, with an incidence of less than 0.1 per million. Since there is currently no systematic review of the literature on FpNETs in children, this study aims to summarize findings from studies focusing on clinical characteristics, diagnostics, treatment modalities, and outcomes. Methods: A systematic review was conducted following the PRISMA guidelines. A literature search was performed using three electronic databases: PubMed, Scopus, and Web of Science. An age filter was used during the search to limit results to childhood and adolescence. There was no limit set in relation to the type and the language of the article. Results: Out of 80,742 records identified, 91 studies met the inclusion criteria and were included in the review. Two studies included patients with insulinoma and gastrinomas, that is, insulinomas and glucagonoma. Of the included studies, 71 were insulinomas, 10 were gastrinomas, 3 were glucagonomas, 6 were VIPomas, and 3 were mixed FpNETs. A total of 163 children with FpNETs were analyzed, with a median age of 12 years. A total of 48 cases were reported in childhood, while 115 cases were reported in adolescence. The results indicate that FpNETs were more prevalent in males. Almost all patients presented with symptoms appropriate to the type of tumor. A significant proportion of tumors were associated with MEN1. In almost all patients, the symptomatology was accompanied by elevated levels of specific hormones. US, CT, PET-CT, MRI, and EUS were the dominant imaging modalities. Surgical approaches and types of resections, depending on the type, association with the syndrome, location, and size of the tumor, were quite heterogeneous. Grade 1 and Grade 2 tumors were nearly equally represented. There was no recurrence in most patients. Conclusions: Early suspicion based on specific clinical symptomatology is essential for timely diagnosis. Accurate localization and size based on modern radiological diagnostics, accompanied by biochemical and genetic testing, are essential for optimal management. Adequate surgical resection offers the best chance of cure, with the lowest risk of recurrence. Additional multicenter registries and studies are needed in the future to better understand tumor behavior, optimal management, and outcomes of FpNETs. Full article

This study investigated the presence of antibodies to human adenovirus type 36 (HAdV-D36) in horses with different metabolic statuses, including normal, overweight, and those diagnosed with equine metabolic syndrome (EMS). A total of 151 serum samples were tested, of which 47.6% were positive for anti-HAdV-D36 antibodies. Although the horses were confirmed to be susceptible to HAdV-D36 infection, there was no significant correlation between infection and blood glucose or cholesterol levels. However, the triglyceride levels showed significant differences—they were particularly elevated in the seropositive horses with EMS. These findings suggest that the virus may act by a different mechanism in horses than in other species, and highlight the need for further research to understand its role in horses. Full article

Down syndrome (DS) is one of the prevalent chromosomal disorders, representing distinctive craniofacial features and a range of developmental and medical challenges. Due to the lack of clinical expertise and high infrastructure costs, access to genetic testing is restricted to resource-constrained clinical settings. There is a demand for developing a non-invasive and equitable DS screening tool, facilitating DS diagnosis for a wide range of populations. In this study, we develop and validate a robust, interpretable deep learning model for the early detection of DS using facial images of infants. A hybrid feature extraction architecture combining RegNet X–MobileNet V3 and vision transformer (ViT)-Linformer is developed for effective feature representation. We use an adaptive attention-based feature fusion to enhance the proposed model’s focus on diagnostically relevant facial regions. Bayesian optimization with hyperband (BOHB) fine-tuned extremely randomized trees (ExtraTrees) is employed to classify the features. To ensure the model’s generalizability, stratified five-fold cross-validation is performed. Compared to the recent DS classification approaches, the proposed model demonstrates outstanding performance, achieving an accuracy of 99.10%, precision of 98.80%, recall of 98.87%, F1-score of 98.83%, and specificity of 98.81%, on the unseen data. The findings underscore the strengths of the proposed model as a reliable screening tool to identify DS in the early stages using the facial images. This study paves the foundation to build equitable, scalable, and trustworthy digital solution for effective pediatric care across the globe. Full article

Background/Objectives: Musculoskeletal disorders causing chronic pain are increasingly prevalent due to factors such as injury, overuse, and aging, leading to interest in porcine collagen injections as a potential therapeutic and conservative option. Despite promising results, evidence-based information on this treatment is scarce. To address this gap, the authors conducted an eDelphi consensus among expert Italian physicians in musculoskeletal pain to gather their perspectives on collagen injections. Methods: A Steering Committee and a Panel of 23 physicians developed the statements list (36) including the modalities, safety, and efficacy of intra- and extra-articular collagen injections. Panelists rated their agreement with each statement on a 5-point Likert scale (5 means “Strong Agreement”). Consensus was defined as when at least 75% of the panelists voted with a score of ≥4/5 after two rounds of votes. The weighted average (WA) was calculated for each statement. As control, we elaborated a Hypothetical Parametric Distribution (HPD WA equal to 3.00), where the percent of panelists is equally distributed along each Likert Scale Value (LSV). The maximum WA for 75% of the consensus is established at 3.75. Indeed, the combination of 75% having WA > 3.75 was defined as “Strong Agreement”. While, if the consensus was under 75%, the WA vs. HPD comparison was performed using the Wilcoxon Test. Significant differences among the distribution of LSVs judged the statement as “Low Level of Agreement”. Disagreement was evaluated when the WA was under the PHD. Results: The consensus was reached “Strong Agreement” after twin rounds in 29 out of 36 (8.55%). In 5 out of 36 statements (13.89%), the panelists reached the “Low Level of Agreement” by statistical tests. In the remaining two statements, there was a “Consensus of Disagreement”. All panelists unanimously agreed on crucial points, such as contraindications, non-contraindication based solely on comorbidity, and the importance of monitoring collagen’s effectiveness. Unanimous agreement was reached on recommending ultrasound guidance and associating collagen injections with therapeutic exercise and physical modalities. Substantial consensus (concordance > 90%) supported collagen injections for osteoarthritis, chondropathy, and degenerative tendinopathies, emphasizing intra- and peri-articular treatment, even simultaneously. However, areas with limited evidence, such as the combination of collagen with other injectable drugs, treatment of myofascial syndrome, and injection frequency, showed disagreement. The potential of intra-tendinous porcine collagen injections for tendon regeneration yielded mixed results. Conclusions: Clinicians experts in musculoskeletal pain agree on using collagen injections to treat pain originating from joints (e.g., osteoarthritis) and periarticular (e.g., tendinopathies). Full article

Sickle cell disease (SCD) is a hereditary hemoglobin disorder characterized by chronic hemolysis and recurrent vaso-occlusive crises, leading to a wide spectrum of complications. While common SCD manifestations have well-established management protocols, rare and atypical complications pose significant diagnostic and therapeutic challenges. A critical barrier is diagnostic overshadowing, where common SCD symptoms (pain, fever, respiratory distress) mask infrequent but life-threatening conditions, resulting in delayed recognition and suboptimal outcomes. This narrative review synthesizes the literature from 2000–2025 on rare SCD complications, including atypical neurological events (e.g., spontaneous epidural or subdural hematoma, central retinal artery occlusion, cerebral arteriovenous malformations, posterior reversible encephalopathy syndrome), uncommon hematologic syndromes (acute leukemia, extramedullary hematopoiesis in unusual sites, hemophagocytic lymphohistiocytosis), severe cardiopulmonary emergencies (acute multiorgan failure and fat embolism syndromes), unusual hepatic crises (acute hepatic sequestration, intrahepatic cholestasis), and others (e.g., compartment syndrome). Key insights underscore the need for high clinical suspicion and prompt use of advanced diagnostics (e.g., MRI, specialized laboratory tests) when patients present with atypical or disproportionate symptoms. Clinical implications: Heightening clinician awareness of these rare complications and implementing structured diagnostic strategies can facilitate earlier intervention, improving outcomes and reducing the high morbidity and mortality associated with these infrequent but severe events. Full article

Mucopolysaccharidosis (MPS) type II, or Hunter syndrome, is an X-linked lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase. Glycosaminoglycan (GAG) accumulation leads to progressive multisystemic involvement, with coarse facial features, hepatosplenomegaly, short stature, recurrent upper respiratory infections, hearing loss, hernias, dysostosis multiplex, joint contractures, and cardiac valve disease. Individuals with the neuronopathic form of the disease also have central nervous system (CNS) involvement with developmental delay and progressive cognitive decline. Enzyme replacement therapy (ERT), idursulfase, is the only FDA-approved treatment for MPS II. MPS II was added to the Recommended Uniform Screening Panel (RUSP) in the United States in 2022, and screening is ongoing in several other countries, including Taiwan. Here, we report seven individuals from four families identified through newborn screening sharing the same IDS variant: c.817C>T, p.Arg273Trp. Confirmatory testing demonstrated low iduronate-2-sulfatase activity level and elevated GAGs in every individual, but they had no signs or symptoms of MPS II. They were aged 8 months to 60 years old according to the most recent assessment and all remained asymptomatic. ERT was not initiated for any of them. Our findings suggest that the IDS c.817C>T variant is associated with abnormal biochemical findings but no clinical phenotype of MPS II. Newborn screening will likely identify additional cases and provide a better understanding of the clinical significance of this variant. Full article

Background/Objectives: The term ‘cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID)’ refers to patients with positive screening tests but without a final diagnosis of Cystic Fibrosis (CF). Intestinal Current Measurement (ICM) is a novel diagnostic technique that may document the abnormal function of the cystic fibrosis transmembrane conductance regulator. Our study aims to compare the cumulative chloride secretory response in the ICM study in the Polish population of CF patients, CRMS/CFSPID, and in a control group. Methods: Forceps rectal biopsies were taken from 40 patients (CF; n = 17 mean age 9.10 ± 4.18 (0.7–17.20); CRMS/CFSPID: n = 16, mean age 6.66 ± 4.83 (0.6–18.0); healthy controls (HC): n = 7, mean age 23.7 ± 9.5 (7.8–34.6). ICM tests were performed in the Ussing Chamber according to standard protocol version 2.7 of the European Cystic Fibrosis Society Diagnostic Network Working Group. Delta short circuit-current (ΔIsc) was measured after carbachol (ΔIsc_carbachol), 3-isobutyl-1-methylxanthine with forskolin (ΔIsc_{IBMX/forskolin}), and histamine (Δisc_histamine) stimulation. Cumulative secretion was calculated for each study group. Results: We obtained statistically significant differences in cumulative chloride secretory response between CF and CRMS/CFSPID (CF ΔIsc_{carbachol+IBMX/forskolin+histamine} 15.32 ± 15.47 µA/cm² vs. CRMS/CFSPID ΔIsc_{carbachol+IBMX/forskolin+histamine} 86.84 ± 37.84 µA/cm²; p < 0.001), and between CF and healthy controls (CF ΔIsc_{carbachol+IBMX/forskolin+histamine} 15.32 ± 15.47 µA/cm² vs. HC ΔIsc_{carbachol+IBMX/forskolin+histamine} 80.16 ± 48.54 µA/cm²; p = 0.005). No differences in cumulative chloride secretion were observed between the CRMS/CFSPID and HC groups. Conclusions: The conducted study suggests that ICM may offer diagnostic value, especially in cases where sweat test results are equivocal. Full article

Background/Objectives: Frailty syndrome favors the deterioration of health; therefore, identifying associated factors is essential for establishing preventive measures. Oral candidiasis is a factor that may be related to the onset of frailty. Our objective was to evaluate the association between frailty and oral candidiasis in institutionalized participants. Methods: We conducted a cross-sectional study involving 589 institutionalized individuals aged 65 years or older. A diagnosis of candidiasis was established clinically and with a microbiological study (potassium hydroxide (KOH) test and culture for candidiasis). Assessments of salivary flow and the use of dental prostheses were also performed. Frailty was classified according to Fried’s phenotype criteria. Results: Frailty and prefrailty were found in 28.9% and 66.7% of the participants, respectively. Oral candidiasis was diagnosed in 39.05% of cases and was more frequent among individuals with dental prostheses (49.13%) and hyposalivation (47.54%). Conclusions: Our findings suggest that frailty in institutionalized older adults is associated with the presence of subprosthetic stomatitis associated with candidiasis and hyposalivation, indicating the need for integrated oral health strategies in geriatric care. Full article

Schmallenberg virus (SBV) is a negative-sense RNA virus transmitted by insect vectors, causing arthrogryposis-hydranencephaly syndrome in newborn ruminants. Since its discovery in Germany and the Netherlands in 2011, SBV has rapidly spread across multiple European countries, resulting in significant economic losses in the livestock industry. With the increasing global animal trade and the expanded range of insect transmission, the risk of SBV introduction into non-endemic regions is also rising. As the gold standard for serological testing, the virus neutralization test (VNT) is crucial for tracking the spread of SBV and evaluating the efficacy of vaccines. However, in non-endemic regions, the lack of local viral strains and the biosafety risks associated with introducing foreign strains pose challenges to the implementation of VNT. In this study, we employed reverse genetics techniques using vesicular stomatitis virus (VSV) to substitute the VSV G protein with the envelope glycoproteins of SBV, thereby successfully generating and rescuing the recombinant virus rVSVΔG-eGFP-SBVGPC. The recombinant virus was then thoroughly characterized in terms of SBV Gc protein expression, viral morphology, and growth kinetics. Importantly, rVSVΔG-eGFP-SBVGPC exhibited SBV-specific cell tropism and was capable of reacting with SBV-positive serum, enabling the measurement of neutralizing antibody titers. The results suggest that this recombinant virus can serve as a feasible alternative for SBV neutralization tests, with promising potential for application in serological screening and vaccine evaluation. Full article