Search Results (3,014)

Background/Objectives: Major adverse cardiovascular events (MACE) are the primary cause of mortality among individuals with peripheral artery disease (PAD). Despite this, there is limited research on biomarkers that can predict MACE risk in this population. Proteins involved in angiogenesis are integral to both systemic circulation and the development of atherosclerosis, indicating their potential as prognostic markers. This study aimed to identify angiogenesis-related proteins associated with MACE risk in PAD patients. Methods: We conducted a prospective cohort study involving 250 patients diagnosed with PAD. At baseline, plasma levels of 17 angiogenesis-related proteins were measured. Participants were followed for two years, with the primary outcome being the incidence of MACE—a composite of stroke, myocardial infarction, or death. Protein concentrations were compared between those who experienced 2-year MACE and those who did not using the Mann–Whitney U test. Proteins showing significant differences were further analyzed using Cox proportional hazards modeling to assess their independent associations with MACE, adjusting for baseline demographic and clinical variables, including prior coronary and cerebrovascular disease. Kaplan–Meier survival analysis was also employed to compare MACE-free survival based on protein concentration levels. Results: The average age of participants was 69 years (SD 9), with 32% (n = 80) being female. Over the two-year follow-up, 48 patients (19.8%) experienced MACE. Among the proteins assessed, only hepatocyte growth factor (HGF) and angiopoietin-2 were significantly elevated in patients who developed MACE (HGF: 390.83 [SD 319.16] vs. 300.55 [SD 177.53] pg/mL, p < 0.001; angiopoietin-2: 23.67 [SD 17.60] vs. 19.36 [SD 12.06] pg/mL, p = 0.020). Multivariable Cox analysis confirmed that elevated levels of both HGF (adjusted HR 1.37; 95% CI 1.14–1.64; p = 0.001) and angiopoietin-2 (adjusted HR 1.27; 95% CI 1.04–1.55; p = 0.016) were independently associated with increased 2-year MACE risk. Kaplan–Meier curves demonstrated significantly reduced MACE-free survival in patients with higher levels of HGF and angiopoietin-2. Conclusions: HGF and angiopoietin-2 emerged as significant, independent predictors of 2-year MACE in patients with PAD. Measuring plasma levels of these proteins may enhance risk stratification, guiding referrals to appropriate cardiovascular specialists and informing the intensity of medical management. This biomarker-based precision medicine approach holds potential for improving cardiovascular outcomes in the PAD population. Full article

Epigenetic biomarkers offer promising potential for early identification and risk stratification of frail individuals susceptible to adverse cardiovascular outcomes. This scope review aimed to identify and evaluate epigenetic biomarkers concurrently associated with frailty and increased cardiovascular risk, potentially facilitating more precise patient stratification and treatment decisions. A two-stage literature search was performed using PubMed, Scopus, Web of Science, and Embase databases from the year 2000 through 27 December 2024. Stage 1 identified studies reporting epigenetic biomarkers associated with frailty in blood-derived human samples. Stage 2 assessed cardiovascular relevance by screening the frailty biomarkers identified in Stage 1 for their documented association with cardiovascular diseases. Two independent reviewers conducted screening, data extraction, and risk-of-bias assessments, resolving disagreements via a third reviewer. The primary outcomes were the association of biomarkers with frailty severity and cardiovascular risk. Key epigenetic biomarkers identified included microRNAs (particularly miR-21, miR-146a, miR-451, and miR-92a) and DNA methylation markers (LINE-1 methylation, epigenetic clocks like GrimAge and DunedinPACE, and possibly novel, emerging clocks like DNAmCVDscore and the Smoking Index). Due to specificity limitations, these biomarkers are most promising when used collectively as part of multimarker panels rather than individually. Future research should validate multimarker panels, explore novel biomarkers, and assess clinical integration to optimize precision medicine in frail cardiovascular populations. Full article

Three-dimensional (3D) printing has gained substantial interest among scientists and surgeons over the past decade due to its broad potential in medical applications. Its clinical utility has been increasingly recognized, demonstrating promising outcomes for patient care. Currently, 3D printing technology enables surgeons to enhance operative precision by facilitating the creation of patient-specific anatomical models, customized implants, biological tissues, and even surgical instruments. This personalization contributes to improved surgical outcomes, reduced operative times, and shorter postoperative recovery periods. Furthermore, 3D printing significantly aids in the customization of prostheses to conform closely to individual anatomical structures. Beyond therapeutic applications, 3D printing serves as a valuable educational tool in medical training. It enhances case-specific visualization, elucidates fracture mechanisms, and provides tangible models for simulation-based practice. Although the use of 3D printing might be seen as useful mostly in orthopedics, it has expanded into multiple medical specialties, including plastic surgery, dentistry, and emergency medicine. Presently, 3D-printed constructs are routinely employed for preoperative planning, prosthetic development, fracture management, and the fabrication of patient-specific surgical tools. Futuristically, the integration of 3D printing into clinical practice is expected to play a pivotal role in the advancement of personalized medicine, offering substantial benefits for both healthcare providers and patients. Full article

Background: In recent years, padel-based interventions have been widely applied in junior and elite players of both genders concerning athletic performance, whereas evidence of their efficacy in trials that use simple randomization has not been well established. This study aimed to compare the effects of 8 weeks of padel training (PD) on the strength and power of untrained healthy children. Methods: Twenty-five children aged 11–15 years (12.36 ± 1.15 years) were randomly assigned into experimental (PD) (nine boys and five girls: 1.58 ± 0.04 m; 50.00 ± 6.75 kg; and 19.96 ± 1.95 kg/m²) and control (CT) (seven boys and four girls: 1.60 ± 0.05 m; 56.92 ± 2.75 kg; and 21.61 ± 1.02 kg/m²) groups. The PD group trained twice a week for 8 weeks, and the CT group did not follow any training program and did not participate in regular exercise or sports. Countermovement jump, medicine ball throw, handgrip, and 5 m sprint test results were measured at baseline and after the intervention in the padel sport group. Results: The results showed a significant interaction for training-induced responses in the sprint test (T5) (F = 10.55, p = 0.004, η² = 0.31). No significant interactions were observed for handgrip strength (HG) (F = 3.90, p=0.06), the medicine ball throw (MBT) (F = 0.851, p = 0.37, η² = 0.04), and the countermovement jump (F = 1.04, p =0.32, η² = 0.04), with clear improvements from pre- to post-training in the PD group. After 8 weeks of training, the PD group showed increased performance in handgrip strength (p = 0.004), while the CT group had decreased velocity post-training (p = 0.011). Conclusions: The individual results in the PD group showed an improvement, which suggests that the practice of padel seems to be a good strategy for improving one’s fitness. It is suggested that 8 weeks of PD seem to be effective in improving strength- and power-related variables in healthy, untrained children. This could be considered an alternative to traditional sports to improve the body fitness of young children and should be applied in school-based programs and the sports club community. Also, more high-quality RCTs are needed in the future. Full article

Therapy with radioactive iodine (I-131) following a total thyroidectomy has been a gold standard in the treatment of differentiated thyroid cancer (DTC) for over 80 years. Over the years, its role has shifted from routine use to a more selective, risk-adapted approach, informed by tumor biology, patient risk stratification and evolving clinical guidelines. This review examines the changing landscape of I-131 therapy, tracing its historical foundations, current indications, and future directions shaped by molecular medicine. We discuss the transition from a standardized, one-size-fits-all treatment approach to an individualized, dynamic stratification model that allows for ongoing risk reassessment and tailored treatment strategies. Key updates in clinical practice, such as the 2015 ATA Guidelines, the 2022 ETA Consensus Statement, and joint SNMMI and EANM nuclear medicine recommendations, are critically examined. We also address ongoing controversies in the management of low- and intermediate-risk patients, including the roles of I-131 whole-body scanning, activity selection, and overall treatment approach. Molecular theranostics is ushering in a new era in DTC management, enabling improved patient selection and more precise treatment. Advances in molecular profiling, imaging, and targeted therapies support a personalized treatment approach that aims to optimize therapeutic decisions while minimizing side effects and enhancing long-term safety. Full article

Background: Chronic inflammatory bowel disease significantly impacts patients’ everyday lives. Despite receiving regular medical care in gastroenterological or family medicine consultations, patients with inflammatory bowel disease (IBD) still experience a lack of information. To evaluate these deficits, we analyzed the main points of interest raised in an online consultation forum offered as a supplementary resource for patients. Methods: We analyzed 20 years of online consultation data at three time points, 2003 (launch of the forum), 2013, and 2024, and compared them against each other. A total of 681 patients participated in the consultations during these years. The clinical profiles of the participants included Crohn’s disease (CD, n = 209), ulcerative colitis (UC, n = 140), unclassified colitis (IBDU, n = 30), and individuals with no specified diagnosis (NSD, n = 303). Results: Patients with ulcerative colitis demonstrated interest in topics such as diet and nutrition, as well as treatment with biologics. Patients with Crohn’s disease expressed interest in diet, nutritional management, and treatment with biologics. Additionally, they showed interest in pain management, diagnostic imaging, and stress management. In the case of patients with unclassified colitis, a broad range of topics was addressed, with no single area emerging as particularly prominent. Patients with no specified diagnosis exhibited interest in diet and nutrition, laboratory diagnostics, and pain therapy. Conclusions: For patients with inflammatory bowel disease, online consultations represent a valuable complement to standard medical care. They provide additional support and contribute to enhancing patients’ confidence in managing their condition. A broad spectrum of disease-related topics was addressed during the consultations. Identified information gaps can be systematically discussed and subsequently reduced. Full article

Obesity is reaching global epidemic proportions worldwide, posing a significant burden on individual health and society. Altered gut microbiota is considered a key factor in the pathogenesis of many diseases, producing metabolites that contribute to the health-beneficial properties of postbiotics. Postbiotics, bioactive microbial components derived from probiotics, are emerging as a valuable strategy in modern medicine and a promising alternative for managing obesity without the need for live bacteria. This work provides a comprehensive overview of the potential health benefits of postbiotics, particularly in relation to obesity, which represents an important health challenge. Despite the encouraging insights into the health benefits of postbiotics, we highlight the need for further research to clarify the mechanisms and the specific roles of different postbiotic components. Integrating postbiotics into health interventions has the potential to enhance preventive care and significantly improve health outcomes in at-risk populations. Full article

Chronic endometritis (CE) is a persistent, often asymptomatic inflammatory condition of the endometrium, increasingly recognized as a potential contributor to infertility and recurrent implantation failure. Despite its clinical significance, CE remains underdiagnosed due to a lack of standardized diagnostic criteria and its subtle clinical presentation. Objective: This review aims to synthesize the current evidence on the pathophysiology, diagnosis, and treatment of CE, highlighting its impact on reproductive outcomes and the effectiveness of therapeutic interventions. A comprehensive literature review was conducted, analyzing 85 peer-reviewed studies published in the last decade, of which 65 were deemed relevant and retained for further analysis. These studies were selected based on their relevance to the pathophysiology, diagnostic methodologies, and treatment outcomes for CE, focusing on their implications for fertility and assisted reproductive technologies (ARTs). The findings suggest that CE is associated with impaired endometrial receptivity, increased inflammatory markers, and reduced implantation and pregnancy rates with ARTs. Histopathological assessment using CD138 immunostaining remains the gold standard for diagnosis, while hysteroscopy and molecular microbiological techniques provide complementary diagnostic value. Antibiotic treatment has been shown to significantly improve implantation rates and pregnancy outcomes, particularly in women with recurrent implantation failure. Emerging therapies, including probiotics and regenerative medicine approaches, are being explored as potential adjuncts to the conventional treatment. Early and accurate diagnosis of CE is essential for optimizing reproductive outcomes. Standardized diagnostic protocols and individualized treatment strategies are crucial for improving implantation success and pregnancy rates in affected women. Future research should focus on refining the diagnostic methods and exploring novel therapeutic options to enhance endometrial health and fertility outcomes. Full article

Endometrial organoids (EOs) have emerged as a powerful three-dimensional (3D) model for studying the human endometrium, offering new insights into infertility and reproductive disorders. These self-organizing miniature structures closely mimic the cellular composition, hormonal responsiveness, and functional characteristics of the endometrium, making them valuable preclinical tools for investigating implantation failure, endometrial receptivity, and disease pathophysiology. This review explores the role of EOs in reproductive medicine, with a focus on their applications in infertility research, environmental toxicology, and regenerative therapies. Traditional 2D cell cultures fail to capture the complexity of these physiological and pathological interactions, whereas organoids provide a physiologically relevant system for studying implantation mechanisms. Additionally, co-culture models incorporating stromal and immune cells have further enhanced our understanding of the maternal–fetal interface. Beyond modeling infertility, EOs hold significant promise for therapeutic applications. Advances in organoid transplantation have demonstrated potential for treating endometrial dysfunction-related infertility, including conditions such as Asherman’s syndrome and thin endometrium. Moreover, these models serve as a platform for drug screening and biomarker discovery, paving the way for personalized reproductive medicine. Despite their transformative potential, limitations remain, including the need for improved extracellular matrices, vascularization, and immune system integration. This review emphasizes the significant contributions of EOs to the field of infertility treatment and reproductive biology by examining recent advancements and emerging research. The continued refinement of these models would offer a paradigm for improving assisted reproductive technologies (ARTs) and regenerative medicine outcomes, offering new hope for individuals facing infertility challenges. Full article

Glucagon-like peptide-1 receptor agonists, originally developed for the treatment of metabolic disorders, have recently emerged as promising candidates for the management of substance use disorders. This review synthesizes preclinical, clinical, and translational evidence on the effects of glucagon-like peptide-1 receptor agonists across addiction models involving alcohol, nicotine, psychostimulants, and opioids. In animal studies, glucagon-like peptide-1 receptor agonists consistently reduce drug intake, attenuate dopamine release in reward circuits, and decrease relapse-like behavior. Clinical and observational studies provide preliminary support for these findings, particularly among individuals with comorbid obesity or insulin resistance. However, several translational barriers remain, including limited blood–brain barrier penetration, species differences in pharmacokinetics, and variability in treatment response due to genetic and metabolic factors. Ethical considerations and methodological heterogeneity further complicate clinical translation. Future directions include the development of central nervous system penetrant analogues, personalized medicine approaches incorporating pharmacogenomics, and rigorously designed trials in diverse populations. Glucagon-like peptide-1 receptor agonists may offer a novel therapeutic strategy that addresses both metabolic and neuropsychiatric dimensions of addiction, warranting further investigation to define their role in the evolving landscape of substance use disorder treatment. Full article

Colon cancer is the second leading cause of cancer-related deaths in the world. This is commonly observed among older adults, and the occurrence of colon cancer is mainly influenced by unhealthy lifestyle factors. Edible medicinal mushrooms have been demonstrated to have anti-colon cancer effects both individually and in combination with conventional therapies, including synergistically enhancing the efficacy of chemotherapy medications such as 5-fluorouracil in preclinical models. Medicinal mushrooms such as Lentinus edodes, Phellinus linteus, Ganoderma lucidum, Inonotus obliquus, Pleurotus ostreatus, Hericium erinaceus, Pleurotus eryngii, Gloeostereum incarnatum, and Termitomyces heimii are emerging as promising candidates, not only because conventional treatments for colon cancer face significant limitations, including side effects, psychological impacts on patients, high cost, limited specificity toward cancer and healthy cells, and the development of drug resistance, but also due to the diverse array of bioactive compounds present within them. Therefore, there is a strong demand for innovative, affordable, and minimally invasive treatments such as medicinal mushrooms. Their bioactive compounds, including terpenoids, sterols, phenols, polysaccharides, acids, sesquiterpenes, alkaloids, lactones, metal-chelating agents, nucleotide analogs, glycoproteins, β-glucan, cerebrosides, steroids, terpenes, quinolones, anthraquinones, benzoic acid derivatives, linoleic acid, ascorbic acid, glycosides, organic acids, flavonoids, grifolin, tocopherols, proteins, indoles, lectin, and laccases, exert anti-colon cancer activities through various mechanisms, including anti-proliferative effects, cell cycle arrest, anti-inflammatory effects, antioxidant effects, induction of apoptosis, cytotoxic effects, and antimigratory effects. Further research is needed to elucidate the molecular mechanisms and confirm the safety and efficacy of medicinal mushrooms as a holistic anti-colon cancer treatment. Full article

Ineffective treatment and side effects are associated with high burdens for the patient and society. We investigated the application of graph representation learning (GRL) for predicting medication usage based on individual genetic data in the United Kingdom Biobank (UKBB). A graph convolutional network (GCN) was used to integrate interconnected biomedical entities in the form of a knowledge graph as part of a machine learning (ML) prediction model. Data from The Pharmacogenomics Knowledgebase (PharmGKB) was used to construct a biomedical knowledge graph. Individual genetic data (n = 485,754) from the UKBB was obtained and preprocessed to match with pharmacogenetic variants in the PharmGKB. Self-reported medication usage labels were obtained from UKBB data field 20003. We hypothesize that pharmacogenetic variants can predict the impact of medications on individuals. We assume that an individual using a medication on a regular basis experiences a net benefit (vs. side-effects) from the medication. ML models were trained to predict medication usage for 264 medications. The GCN model significantly outperformed both a baseline logistic regression model (p-value: 1.53 × 10⁻⁹) and a deep neural network model (p-value: 8.68 × 10⁻⁸). The GCN model also significantly outperformed a GCN model trained using a random graph (GCN-random) (p-value: 5.44 × 10⁻⁹). A consistent trend of medications with higher sample sizes having better performance was observed, and for several medications, a high relative rank of the medication (among multiple medications) was associated with greater than 2-fold higher odds of usage of the medication. In conclusion, a graph-based ML approach could be useful in advancing precision medicine by prioritizing medications that a patient may need based on their genetic data. However, further research is needed to improve the quality and quantity of genetic data and to validate our approach using more reliable medication labels. Full article

Musk, a dried secretion from the sac gland near the urethral foramen of adult male forest musk deer (Moschus berezovskii), has significant economic value and is extensively utilized as a valuable component in traditional Chinese medicine. In the practice of forest musk deer breeding, musk with different colors and varying moisture contents is observed during the season when the musk reaches maturity. For many years, researchers have focused mainly on musk composition and symbiotic bacteria. However, the influence of fecal fungi on the production and quality of musk is unknown. In this study, internal transcribed spacer (ITS) analysis was employed to explore the relationships between the fungal composition of musk deer fecal and the quality and production of musk produced by each individual. The results indicate that fungal genera known to cause diseases, such as Colletotrichum and Apiotrichum, are prevalent in the feces of musk deer that produce abnormal musk. Furthermore, the fecal microbiota health index (GMHI) is lower and the intestinal microbiota dysbiosis index (MDI) is greater in musk deer producing white musk than in normal individuals. Additionally, by correlating musk production with fecal fungi, we also found that Dolichousnea and Scolecoleotia were significantly positively correlated with musk production. Moreover, Metschnikowia, Ganodermataceae_gen_Incertae_sedis, Hypoxylon, Neovaginatispora, Didymella, Dothidea, and Trichoderma were negatively correlated with musk production. This study is the first to investigate gut fungi in relation to musk production/quality, establish gut health and fungal dysbiosis links, and identify candidate fungi tightly associated with musk traits. This exploratory approach is critical for exploring uncharted territories like gut fungi in musk deer and musk traits. Full article

This study aimed to evaluate the antinociceptive effect of Salvia hispanica L. seeds, Citrus × latifolia (Lime) juice, and the interaction of their combination in rats using the writhing test. Dose–response curves were constructed for an n-hexane extract of S. hispanica seeds (100–300 mg/kg; p.o.) and C. × latifolia juice (10–300 mg/kg; p.o.) administered individually or in combination to rats subjected to 1% acetic acid-induced writhing. Isobolographic analysis was used to assess the interaction between the combinations. Results showed that both medicinal plants exhibited dose-dependent antinociceptive effects. The antinociceptive effect of C. × latifolia (ED₅₀ = 43.95 ± 1.9 mg/kg) exhibited greater potency than S. hispanica (ED₅₀ = 112.9 ± 2.0 mg/kg). Their combination (1:1 ratio) showed a synergistic antinociceptive effect (Z_exp = 4.9 ± 0.6 mg/kg vs. Z_add = 83.5 ± 1.7 mg/kg). Both extracts were non-toxic, according to the OECD-423 test. Antioxidant activity may have contributed to the observed antinociceptive synergy. This study demonstrates that the synergistic antinociceptive effects suggest that combining S. hispanica and C. × latifolia may be a promising therapeutic approach for managing inflammatory and visceral pain with potential clinical utility. Full article

Background and Objectives: this study aimed to evaluate the prognostic significance of systemic immune-inflammatory markers, particularly the pan-immune-inflammation value (PIV) and systemic immune-inflammation Index (SII), in predicting overall survival among patients with hematologic malignancies. Materials and Methods: This retrospective cohort study included 300 patients diagnosed with various hematologic malignancies between January 2020 and January 2025 at the Department of Hematology, Faculty of Medicine, Mersin University. Baseline laboratory data, including neutrophil, lymphocyte, platelet, and monocyte counts, were collected to calculate SII, NLR, PLR, and PIV. Patients were stratified into high and low groups based on the median values of these markers. Overall survival was analyzed using Kaplan–Meier curves and Cox proportional hazards models, adjusted for age, sex, malignancy type, and disease stage. Results: High levels of PIV and SII were significantly associated with poorer overall survival. In univariate analysis, high PIV (HR: 2.35, 95% CI: 1.68–3.28, p < 0.001) and high SII (HR: 2.12, 95% CI: 1.53–2.95, p < 0.001) were strong predictors of mortality. After multivariate adjustment, PIV (adjusted HR: 2.14, 95% CI: 1.47–3.11, p < 0.001) and SII (adjusted HR: 1.88, 95% CI: 1.32–2.67, p = 0.001) remained independent prognostic factors. Subgroup analyses demonstrated that the predictive power of PIV and SII was consistent across different malignancy types, particularly in acute myeloid leukemia and multiple myeloma patients. Conclusions: Our findings indicated that systemic immune-inflammatory markers, particularly PIV and SII, are valuable prognostic tools in hematologic malignancies. These markers, derived from routine blood counts, offer a simple cost-effective means for improving risk stratification. Incorporating these indices into clinical practice could enhance individualized management strategies. Further prospective studies are warranted to validate these findings. Full article