Search Results (2,825)

Xylazine abuse is emerging as a global problem, whereas the toxic mechanisms of xylazine poisoning are seldom studied. The present study aims to assess the heart injury in xylazine poisoning and uncover the underlying mechanism. Forty male SD rats were randomly dived into four groups: control (saline), low dose (10 mg/kg xylazine), median dose (20 mg/kg xylazine) and high dose (40 mg/kg xylazine). The rats were injected with the drug intraperitoneally for 28 consecutive days, and then cardiac ultrasound examination was performed and serum and heart tissues were collected. Genomic, proteomic, and metabolic omics analyses were conducted. ELISA, RNA sequencing, histopathology examination, RT-qPCR, and Western blot were performed. Repeated injection of xylazine led to a decrease in the expression of cardiac output (CO), ventricular systole (VS), and ventricular diastole (VD), while concurrently elevating the levels of lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin T (c-TNT) in the serum. HE staining analysis showed evidence of contraction band necrosis, interstitial fibrosis, and infiltration by inflammatory cells in animals with xylazine poisoning. The modified genes, proteins, and metabolites were gathered, and the integration of transcriptomic, proteomic, and metabolic networks identified 25 overlapping pathways between the differentially expressed genes and metabolites (DEGs-DEMs) and the differentially expressed proteins and metabolites (DEPs-DEMs) joint pathways. The majority of these pathways pertained to the metabolism of sugars, amino acids, and fats. The proteins associated with fructose and mannose metabolism, as well as cholesterol metabolism, were validated, thereby substantiating their pivotal role in the development of xylazine-induced cardiac injury. Repeated injection of xylazine impaired heart function and the metabolism of fructose and mannose. Cholesterol metabolism pathways were critical in the process of xylazine-induced heart injury. Full article

Oxidative stress is a major contributor to skin aging and related disorders. This study comparatively evaluated the bioefficacy of Schinus terebinthifolius Raddi leaf extracts prepared using three extraction techniques: conventional extraction (CE), accelerated solvent extraction (ASE), and pulsed electric field (PEF) extraction, with 50% (v/v) ethanol and water as green solvents. Among all tested conditions, the CE-derived extract (C-4), obtained with 50% (v/v) ethanol for 120 min, exhibited the highest extraction yield (29.7%). It also showed the highest total phenolic (668.56 ± 11.52 mg gallic acid equivalent (GAE)/g dry material (DM)) and flavonoid content (2629.92 ± 112.61 mg quercetin equivalent (QE)/100 g DM), and potent antioxidant activity against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical (12,645.50 ± 60.31 µmol Trolox equivalent (TE)/g DM) and oxygen radical absorbance capacity assay (ORAC: 7180.27 ± 101.79 µM TE/100 g DM). Liquid Chromatography coupled with Mass Spectrometry (LC-MS) analysis revealed a diverse phytochemical profile rich in polyphenols, including gallic acid, p-coumaric acid, rutin, rosmarinic acid, caffeic acid, and epicatechin. Cellular assays in hydrogen peroxide (H₂O₂)-induced HaCaT keratinocytes demonstrated that C-4 extract significantly enhanced cell viability and upregulated endogenous antioxidant genes (superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPX)), with effects comparable to established antioxidants such as epigallocatechin gallate (EGCG) and ascorbic acid. These findings highlight the influence of extraction parameters on phytochemical yield and biological activity, supporting the potential application of CE-derived S. terebinthifolius extracts as effective, sustainable ingredients for cosmeceutical formulations targeting oxidative stress-mediated skin aging. Full article

Informed consent is a fundamental component of both the right to health and self-determination. Its violation, which occurs when the acquisition process is absent or flawed, can also lead to legal proceedings for isolated harm, regardless of the simultaneous existence of those related to biological and psychological harm. Across Europe, this remains a legal and ethical cornerstone, increasingly important in the context of cross-border care and culturally diverse healthcare settings. Many countries have enacted specific laws to ensure patients receive adequate information, while courts continue to refine its interpretation—often highlighting the inadequacy of informed consent in daily clinical practice. In Italy, in particular, recent rulings underscore the need for clear, comprehensive, and properly documented consent formats for health treatments. This review synthesizes rulings, regulations, and the scientific literature to offer practical guidance for improving informed consent practices in Italy, valuing the role of forensic experts in the integration in healthcare settings of the different interests at stake. The aim is to support both legal compliance and the delivery of high-quality, patient-centred care. Courts and legislation in Italy demand clear and tailored informative disclosure for health treatments, with indications of the treatment and outcomes, to be in written form. Yet, foreseeable risks, more common complications, and alternative treatment options are often poorly communicated in practice—frequently forming the basis of claims for compensation. Integrating team-based consultations and multimedia tools can significantly enhance patient understanding and secure the informed consent process. Those key points are summarized in a brief table, ideally suggesting the minimal requirements for an informed consent form. Investing in standardizing informed consent protocols, and also fostering the sharing of best practices with forensic medicine experts, are crucial steps in ensuring shared decision-making in healthcare and trying to reduce legal disputes. Full article

Molecular imaging and precision therapies are transforming ophthalmology, enabling earlier and more accurate diagnosis and targeted treatment of sight-threatening diseases. This review focuses on age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis, examining high-resolution imaging techniques such as optical coherence tomography (OCT), OCT angiography, MALDI-MSI, and spatial transcriptomics. Artificial intelligence supports these methods by improving image interpretation and enabling personalized analysis. The review also discusses therapeutic advances, including gene therapies (e.g., AAV-mediated RPE65 delivery), stem cell-based regenerative approaches, and biologics targeting inflammatory and neovascular processes. Targeted molecular therapies targeting specific signaling pathways, such as MAPK, are also explored. The combination of single-cell transcriptomics, proteomics, and machine learning facilitates the development of personalized treatment strategies. Although these technologies hold enormous potential, their implementation in routine clinical care requires further validation, regulatory approval, and long-term safety assessment. This review highlights the potential and challenges of integrating molecular imaging and advanced therapies in the future of precision ophthalmic medicine. Full article

Cancer cachexia is a multifactorial syndrome characterized by metabolic dysregulation, inflammation, and progressive loss of skeletal muscle mass. Frequently observed in colorectal cancer patients, it is associated with poor clinical outcomes and reduced treatment tolerance. Current therapies provide limited benefit, underscoring the need for integrative approaches. Grape seed polyphenols, particularly oligomeric proanthocyanidins, have demonstrated potential to modulate catabolic signaling, mitochondrial dysfunction, and inflammatory responses involved in cachexia pathophysiology. This review integrates preclinical and clinical evidence on the use of grape seed-derived products, highlighting their effects on NF-κB and AMPK pathways, redox homeostasis, and gut–muscle axis. Furthermore, the nutritional composition and bioactive properties of grape seed flour—rich in fiber and phenolic compounds—are discussed in the context of nutraceutical applications. A clinical trial currently underway in Brazil aims to evaluate the effects of grape seed flour supplementation in colorectal cancer patients with cachexia. Altogether, grape-derived compounds offer a safe, low-cost, and mechanistically grounded strategy for improving nutritional status and resilience in oncological care. Full article

Differentiated thyroid cancer (DTC) is the most prevalent endocrine malignancy in the world. Accurate diagnosis and prognostication are essential for optimizing its treatment and improving patient outcomes. This narrative review explores the diagnostic and prognostic histopathological, immunohistochemical, molecular, and genetic biomarkers in DTC, emphasizing their role in risk stratification and personalized management. Histopathological biomarkers, including tumor size, extrathyroidal extension, lymphovascular invasion, and aggressive subtypes (e.g., tall cell, hobnail, and insular variants), correlate with poor prognosis. Additionally, genetic alterations such as BRAF:p.V600E, RAS mutations, TERT promoter mutations, and RET/PTC rearrangements provide molecular insights into tumor progression and therapeutic response. Some of these molecular/genetic mutations have surrogate proteins that are feasible for immunohistochemical analysis, providing faster and cost-effective alternatives. Advances in next-generation sequencing have further refined risk stratification, facilitating precision medicine approaches. Future research should focus on validating novel biomarkers and developing targeted therapies to improve patient outcomes. Full article

Particulate matter with a diameter less than 2.5 µm (PM_2.5) and its chemical constituents—including ammonium (NH₄⁺), sulfate (SO₄²⁻), nitrate (NO₃⁻), organic carbon (OC), soil dust, and black carbon (BC)—have been increasingly recognized for their potential impact on fetal neurodevelopment. This systematic review aimed to synthesize current evidence on the relationship between prenatal exposure to PM_2.5 and its chemical components and neurodevelopmental outcomes in neonates, focusing on diagnoses such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Following PRISMA 2020 guidelines, a comprehensive literature search was conducted on PubMed and Embase databases from April to July 2025. Twenty-five studies meeting inclusion criteria were analyzed, of which sixteen addressed PM_2.5 exposure generally, and nine assessed specific chemical constituents. The findings indicate that increased exposure to PM_2.5, particularly during the third trimester, is associated with a higher risk of ASD. Additionally, prenatal exposure may adversely affect early neurodevelopmental domains including motor skills, problem-solving, and social interactions. Certain PM_2.5 components, notably sulfate ions (SO₄²⁻), were identified as important contributors to neurological health outcomes. These results underscore the importance of reducing prenatal exposure to PM_2.5 and its harmful constituents to protect neurodevelopment. Full article

Neurodegenerative diseases are a group of disorders characterized by the progressive deterioration of the structure and function of central nervous system neurons and include, among others, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) diseases. And while all these diseases seem to have different genetic and environmental components, growing evidence shows that they share common underlying pathological features such as increased neuroinflammation and excessive oxidative stress. RAGE, the receptor for advanced glycation end-products, is a signal transduction receptor, and its activation triggers an increase in proinflammatory molecules, oxidative stressors, and cytokines. Diaph1, protein diaphanous homolog 1, is an actin modulator and an intracellular ligand of RAGE. Studies demonstrated that RAGE and Diaph1 act together, and their downstream signaling pathways play a role in neurodegeneration. Here, based on current evidence and our own research, we provide an overview of the RAGE–Diaph1 signaling and discuss the therapeutic potential of targeted therapy aimed at RAGE–Diaph1 signaling inhibition in the prevention and treatment of neurodegenerative diseases. Full article

Background and Objectives: Lung cancer (LC) remains a significant global health issue with poor prognosis. The COVID-19 pandemic has caused delays in cancer patient management worldwide. However, its impact on the incidence of LCs in Romania has not yet been discussed. We aimed to evaluate the impact of lockdown restrictions during the COVID-19 pandemic on new LC diagnoses in a Romanian cohort and the potential associations between demographic characteristics and histological features. Materials and Methods: This retrospective study analyzed 750 patients with lung tumors diagnosed in the Pathology Department, Mureș County Clinical Hospital, Romania, between 2018 and 2022. The target population was divided in two cohorts: pre-COVID-19 (1 January 2018–15 March 2020) and COVID-19 (16 March 2020–31 December 2022). Results: The temporal trend of LC diagnosis followed a descending pattern over the study period, with a significant 72% reduction (p < 0.001) in the first year of the COVID-19 pandemic (2020 vs. 2019). In terms of histology, several subtypes displayed a notable reduction in the COVID-19 cohort compared to the pre-pandemic period: squamous carcinoma (SQC) (p < 0.001), adenocarcinoma (ADK) (p < 0.001), and lung metastases (p = 0.0008). On the other hand, cases of non-small-cell lung carcinomas not otherwise specified (NSCLCs NOS) experienced a significant increase in the pandemic years (p = 0.0406). SQC was the most frequent subtype of LC and was significantly more frequent in men (p < 0.001, RR = 1.3004, 95% CI [1.1786–1.4347]). Furthermore, a notable shift in the male-to-female ratio was observed between the two cohorts, caused by a larger decrease in the incidence of LC among men compared to females in the COVID-19 period (p = 0.0002; pre-COVID-19 M/F = 4/1 versus COVID-19 M/F = 2/1). Conclusions: COVID-19-related restrictions led to a significant drop in new LC diagnoses during the first year of the pandemic, which was followed by a slight upward trend in the subsequent years. Additionally, the sharp decline in the number of cases among men narrowed the gender gap in LC patients. Full article

Psoriasis is a chronic inflammatory autoimmune skin disease with current treatments often causing significant side effects. This study systematically evaluated the therapeutic potential and mechanisms of polyphenolic compounds in psoriasis treatment. Following PRISMA guidelines, we searched PubMed, Google Scholar, and ScienceDirect databases between January 2008 and September 2023. Studies investigating polyphenolic effects on psoriasis through in vitro, animal, or clinical models were included. Twenty-five studies met inclusion criteria: nine in vitro studies, eleven animal studies, and five clinical trials. Curcumin was most extensively studied, demonstrating 30–60% reductions in inflammatory markers (TNF-alpha, IL-17, IL-22) and significant PASI score improvements. Mechanistic analysis revealed polyphenols primarily target NF-kappaB pathway inhibition and IL-17/Th17 axis suppression, addressing fundamental inflammatory processes in psoriatic pathophysiology. However, limited clinical evidence represents a significant implementation barrier. Polyphenols show potential as adjunctive therapies to conventional topical and systemic treatments. Future research should prioritize large-scale randomized controlled trials with standardized formulations and combination therapy investigations to establish clinical efficacy and overcome bioavailability challenges. Full article

Background: Fat embolism frequently occurs as a result of trauma, such as long bone fractures and orthopedic surgeries, as well as in certain non-traumatic conditions. The formation can be attributed to mechanical or biochemical processes. According to Hullman’s biochemical hypothesis, elevated C-reactive protein levels facilitate the precipitation of very-low-density lipoproteins and chylomicrons, forming fat globules that may result in fat embolism. Based on the abovementioned hypothesis, this study aims to detect fat embolism in autopsy patients (postmortem) suffering from bronchopneumonia and determine its possible role as a cause of death. Methods: A group of autopsies of deceased individuals with bacterial purulent bronchopneumonia with confirmed or presumed elevated C-reactive protein levels was rigorously selected, excluding those with other potential causes of fat embolism such as cardiopulmonary resuscitation, hypothermia, and diabetes mellitus. Multiple organs were sampled for frozen section analysis using Oil Red O fat staining and assessed for the presence and extent of fat embolism. The Falzi score, as modified by Janssen, was employed for the lung tissue. Results: In 73% of the cases, predominantly sporadic, Grade 0 or Grade I fat embolism was observed; however, in none of the cases was fat embolism identified as the cause of death or as a significant contributing factor. Furthermore, neither fat embolism syndrome nor multiorgan fat embolism were detected. Conclusions: Although an elevated C-reactive protein level facilitates the formation of fat globules and fat embolism, its role as a direct cause of mortality remains uncertain. It may predispose individuals to such conditions and potentially interact with other factors, such as minor soft tissue trauma, to exacerbate the severity of fat embolism or its clinical manifestations. These findings underscore the necessity for further comprehensive investigations within the contexts of infection/inflammation, fat embolism, and dyslipidemia. Full article

The possible protective effect of obesity in the outcomes of chronic kidney disease (CKD) patients is an understudied field. We aimed to evaluate the prognostic value of vascular calcification (VC) on long-term outcomes in obese and non-obese CKD patients. We conducted a single-centre, prospective observational study of 150 CKD patients. Patients were divided into two groups using body mass index (BMI) scores (BMI ≥ 30 kg/m² and BMI < 30 kg/m²). Lateral lumbar X-rays (Kauppila score), the ankle–brachial index (ABI), and echocardiography were used for assessing VC. By the 11.2-year follow-up, 70 patients had died (47%). Twenty-four patients had had CV complications: stroke, myocardial infarction, decompensated heart failure, amputation caused by atherosclerosis, and aortic rupture. Among obese patients (BMI ≥ 30 kg/m²), only LVH was a significant predictor of CV complications (p = 0.01) and mortality (p = 0.004). In patients with BMI < 30 kg/m², predictors of CV complications and mortality were ABI (p = 0.03; p = 0.009), LVH (p = 0.02 for CV complications) and heart valve lesions (p = 0.009; p = 0.004). There were no differences in the measured parameters of VC between the obese and non-obese groups. Moreover, no significant differences were found comparing patients with and without obesity according to the studied parameters; we found no significant differences in complications and mortality. VC in patients with CKD is a significant complication that negatively impacts outcomes. Obesity does not have a protective effect in long-term outcomes in CKD patients. Full article

Background: Bicycles constitute a primary means of transportation, particularly within the scope of urban micromobility. However, the use of this mode of transport is associated with the risk of traffic accidents and subsequent maxillofacial trauma. Cyclists are classified as vulnerable road users, among whom the assessment of injury patterns is a significant issue. This study aimed to identify the most common maxillofacial fractures resulting from bicycle-related traffic accidents. Methods: A retrospective analysis was conducted on the medical records of patients treated at the Clinic of Maxillofacial Surgery at the University Clinical Hospital in Poznan, who sustained maxillofacial injuries as a result of bicycle-related accidents between 2019 and 2023. Results: A total of 99 patients met the inclusion criteria. Most of the study population was males (70.7%), with a median age of 38. Accidents most frequently occurred during the summer months and on Fridays and weekends. The most common fracture site was the mandible (40.4%), with double fractures being the predominant type. Additionally, zygomatic-orbital fractures were frequently observed (30.3%). In terms of treatment, surgical intervention was predominant, and the mean duration of hospitalisation was 6 days. Only 5.1% of patients were under the influence of alcohol at the time of the incident. Furthermore, it was found that isolated mandibular fractures occurred more frequently in younger patients, whereas midface fractures of the Le Fort II and III types were more commonly observed in individuals under the influence of alcohol at the time of the event. Moreover, accidents involving alcohol consumption were associated with a higher incidence of concomitant cranio-cerebral injuries. Conclusions: Defining the profile of maxillofacial fractures resulting from bicycle accidents constitutes a clinically relevant issue. Additionally, identifying the main risk factors and developing preventive measures is of critical importance. Full article

Background/Objectives: Childhood obesity represents a pressing global health challenge, demanding coordinated, long-term strategies. Schools and families are pivotal environments for shaping children’s lifestyle behaviors. The LIVELY project aimed to assess overweight/obesity prevalence and associated factors in primary school children, and to implement a multidimensional educational intervention promoting healthy, sustainable lifestyles. Methods: This single-arm study was conducted from October 2023 to October 2024 in a primary school in Milan. The intervention included age and culturally tailored lessons, games, and activities. Anthropometric measures, dietary adherence, and lifestyle habits were assessed before and after the intervention. Satisfaction surveys were administered to children, families, and teachers. Results: The project involved 227 children across 14 classes (mean age 8.9, SD 1.2 years). The prevalence of overweight/obesity was 23.4%. Adherence to the Mediterranean Diet was moderate, limited by low intake of vegetables, nuts, and dairy. Physical activity was low, screen time excessive, and sleep insufficient. No statistically significant improvements in anthropometrics or diet adherence were observed post-intervention, but positive trends emerged for physical activity, sleep, and hydration. Over half of the children passed the nutritional knowledge test. Despite these challenges, high satisfaction levels have been shared by children, parents, and teachers. Conclusions: The limited duration of the intervention and challenges engaging families in a low socio-economic context may have constrained the impact of the program, and caution is advised in generalizing the findings. The LIVELY project highlights the complexity of tackling childhood obesity in multicultural settings and emphasizes the need for longer, continuous, and culturally tailored programs that actively involve families to promote sustainable healthy behaviors. Full article

(1) Background: COVID-19 sepsis, marked by hyperinflammation and cardiac injury, poses significant challenges in high-comorbidity populations. This prospective cohort study evaluates the prognostic value of IL-6, troponin, NT-proBNP, and radiological findings for mortality and unfavorable outcomes in a post-2022 Eastern European cohort. (2) Methods: At “Victor Babes” Hospital, Timisoara, Romania (September 2022–December 2024), 207 adults with COVID-19 sepsis (Sepsis-3 criteria) were enrolled. Baseline IL-6, troponin, NT-proBNP, CRP, PCT, D-dimers, and chest CT lung involvement were measured. Unfavorable outcomes (in-hospital death, ICU transfer, mechanical ventilation, or vasopressor use) were analyzed using logistic and linear regression. (3) Results: Among 207 patients (mean age: 68.7 years, 54.1% male), 52 (25.1%) experienced unfavorable outcomes. Multivariable analysis identified IL-6 (OR 1.016 per pg/mL, p = 0.013), troponin (OR 1.013 per ng/L, p = 0.017), NT-proBNP (OR 1.009 per pg/mL, p = 0.049), >50% lung involvement (OR 1.835, p = 0.011), unvaccinated status (OR 2.312, p = 0.002), and higher BMI (OR 1.112 per kg/m², p = 0.005) as independent predictors of unfavorable outcomes. Tocilizumab use (n = 12) was associated with reduced mortality (p = 0.041). IL-6 (cut-off 39.0 pg/mL, AUC = 0.91) and troponin (cut-off = 111.3 ng/L, AUC = 0.88) showed strong predictive accuracy. (4) Conclusions: Elevated IL-6, troponin, NT-proBNP, severe lung involvement, unvaccinated status, and higher BMI predict adverse outcomes in COVID-19 sepsis. Tocilizumab may offer survival benefits, warranting larger trials. These findings support targeted risk stratification in high-comorbidity populations. Full article