Search Results (12,693)

Nanotechnologies bring a rapid paradigm shift in hard and soft bone tissue regeneration (BTR) through unprecedented control over the nanoscale structures and chemistry of biocompatible materials to regenerate the intricate architecture and functional adaptability of bone. This review focuses on the transformative analyses and prospects of current and next-generation nanomaterials in designing bioactive bone scaffolds, emphasizing hierarchical architecture, mechanical resilience, and regenerative precision. Mainly, this review elucidated the innovative findings, new capabilities, unmet challenges, and possible future opportunities associated with biocompatible inorganic ceramics (e.g., phosphates, metallic oxides) and the United States Food and Drug Administration (USFDA) approved synthetic polymers, including their nanoscale structures. Furthermore, this review demonstrates the newly available approaches for achieving customized standard porosity, mechanical strengths, and accelerated bioactivity to construct an optimized nanomaterial-oriented scaffold. Numerous strategies including three-dimensional bioprinting, electro-spinning techniques and meticulous nanomaterials (NMs) fabrication are well established to achieve radical scientific precision in BTR engineering. The contemporary research is unceasingly decoding the pathways for spatial and temporal release of osteoinductive agents to enhance targeted therapy and prompt healing processes. Additionally, successful material design and integration of an osteoinductive and osteoconductive agents with the blend of contemporary technologies will bring radical success in this field. Furthermore, machine learning (ML) and artificial intelligence (AI) can further decode the current complexities of material design for BTR, notwithstanding the fact that these methods call for an in-depth understanding of bone composition, relationships and impacts on biochemical processes, distribution of stem cells on the matrix, and functionalization strategies of NMs for better scaffold development. Overall, this review integrated important technological progress with ethical considerations, aiming for a future where nanotechnology-facilitated bone regeneration is boosted by enhanced functionality, safety, inclusivity, and long-term environmental responsibility. Therefore, the assimilation of a specialized research design, while upholding ethical standards, will elucidate the challenge and questions we are presently encountering. Full article

Background: Metastatic melanoma is a highly aggressive malignancy with poor prognoses and frequent resistance to conventional chemotherapy. Approximately 40% of melanoma cases carry the BRAF^V600E mutation, for which vemurafenib, a selective BRAF^V600E inhibitor, is approved. Despite initial clinical benefits, vemurafenib often leads to drug resistance and relapse, highlighting the need for improved therapeutic strategies. Objectives, methods: In this study, we designed, synthesized, and characterized five novel vemurafenib analogs—RF-86A, RF-87A, RF-94A, RF-94B, and RF-96B—with the aim of enhancing anti-proliferative and anti-metastatic effects against human melanoma cells. Results: All compounds induced apoptosis in BRAF^V600E-mutated A375 cells, with RF-86A displaying the lowest IC₅₀ value among the series, comparable to that of vemurafenib. Moreover, RF-86A exhibited the highest selectivity index, as determined using HEK293T cells as a non-tumorigenic control. Additionally, migration assays and gelatin zymography demonstrated that the analogs, unlike vemurafenib, significantly inhibited matrix metalloproteinases MMP-2 and MMP-9, key enzymes involved in tumor invasion and metastasis. Conclusions: These findings suggest that structural modifications to the vemurafenib scaffold may improve therapeutic efficacy and offer a promising strategy to overcome acquired resistance. Full article

The objective of this study was to evaluate the efficacy of selected herbicides permitted for use in sustainable agriculture, specifically targeting spring rye and spring barley in a no-till farming system. The application of chemical herbicide protection in the cultivation of spring rye and barley significantly increased the yield and improved the quality parameters of the harvested grain, with the most pronounced effect observed in spring barley. The effectiveness of the herbicide treatment in reducing the number of weeds was 99.4% for spring rye and 82.39% for spring barley. The study demonstrated that the application of chemical herbicide protection had a positive impact on the quality parameters of spring barley grain. Both the thousand-grain weight and protein content were significantly higher in the grain collected from protected plots compared to the control plots. By utilizing herbicides permitted for use in integrated production (IP) in a sustainable manner, we protect the environment while minimizing the impact on crop yields and maintaining the quality of the harvested produce. Full article

Background/Objectives: The social importance of health literacy (HL) is widely understood, and its measurement is the subject of various studies. Due to the recent pandemic, several instruments for measuring HL about COVID-19 have been proposed in different countries, including the HLS-COVID-Q22 questionnaire. The diversity of cultures and languages necessitates the cross-cultural adaptation of this instrument. Thus, the present study translates, adapts, and validates the psychometric properties of the HLS-COVID-Q22 questionnaire to provide its cross-cultural adaptation from English to Spanish (Peru). Methods: As part of ensuring that the final questionnaire accommodates the cultural nuances and idiosyncrasies of the target language, the following activities were carried out: (a) a survey of 40 respondents; and (b) a focus group with 10 participants, followed by expert approval. In addition, the validity and reliability of the health instrument have been ascertained through a further pilot test administered to 490 people in the city of Tacna in southern Peru. Results: The resulting questionnaire helps measure HL in Peru, aiding better-informed decision-making for individual health choices. Conclusions: The presence of such a tool is advantageous in case of similar global health emergencies, when the questionnaire can be made readily available to support a promotion of strategies towards better self-care. Moreover, it encourages other Latin American stakeholders to adjust the instrument to their own cultural, language, and socio-economic contexts, thus invigorating the regional and global expansion of the HL study network. Full article

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η²_p = 0.188–0.197), LH (η²_p = 0.061–0.068), and FSH (η²_p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article

Background: The rationale for strict fluid fasting for pediatric and adult patients has been questioned recently. Point-of-care tools for the evaluation of gastric content have evolved over time, often using gastric ultrasound. Usually, the gastric antral cross-sectional area (CSA) is determined. A liberal fluid fasting regimen, that is, ingestion of liquid fluids until the call for theatre, does not delay gastric emptying compared to midnight fasting, as evaluated with gastric ultrasound. Anesthesia is safe, and no adverse events result from a liberal regimen. Methods: The ethics committee of LMU Munich approved the study (21-0903). Liberal fluid fasting in a geriatric orthopedic surgery department (LFFgertrud) is a sub-study within a project investigating perioperative neurocognitive disorders (Study Registration: DRKS00026801). After obtaining informed consent from 134 geriatric patients 70 years or older, we investigated the gastric antral cross-sectional area (CSA) prior to and postimplementation of liberal fluid management, respectively. Results: After the implementation of liberal fluid fasting, fasting times for solid food and liquids decreased from 8.8 (±5.5) to 1.8 (±1.8) hours (p < 0.0001). In 39 patients where CSA was obtained, a slight increase in fluid was encountered. No critical amount of gastric content was observed, and no adverse events occurred. Conclusions: A liberal fluid fasting concept was safe even for comorbid elderly patients in orthopedic surgery. Applying a gastric ultrasound may be helpful to increase safety. According to the incidence of complications encountered in our study, it seems indispensable. Full article

This article analyzes the work of Fr. Elias Friedman, whose legacy of theological work on Jewish identity and Jewish conversion to Catholicism serves as the foundation of the Association of Hebrew Catholics, of which he is the founder. Friedman frames his work as a sensitive approach to Jewish identity and Catholic faith, but as this paper demonstrates, his work reveals a reiteration of some of the most entrenched and historically devastating tropes of Christian anti-Judaism, as well as racial antisemitism. This article presents three main arguments. First, it demonstrates that Friedman’s work evidences a theological anti-Judaism characteristic of Catholicism prior to the Second Vatican Council, which he maintained firmly even after the theological revision of Vatican II rejected such views; and furthermore, that his work also expresses an antisemitism that reflects the modern racial antisemitism adopted by the Nazi regime. Second, this article examines the positive reception of Friedman’s work, as evidenced not only in the revered position he holds within the Association for Hebrew Catholics, but also by the nihil obstat and imprimatur on both of Friedman’s monographs, that is, the official stamp of ecclesiastical approval within the Catholic Church, which declares that the work is “free of doctrinal and moral error.” It proposes that these factors evidence the uncritical reception of his work not only within the Association of Hebrew Catholics, but also on behalf of the institutional Catholic Church. Third, it raises the question of the extent to which Friedman’s identity as a Jewish convert to Catholicism is relevant in the analysis and reception of his work. It argues that his Jewish identity makes his concoction of religious anti-Judaism and racial antisemitism particularly potent, rendering anodyne even the most virulently antisemitic of his statements. Full article

Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such effects remain largely unstudied in non-target predatory carabid beetles. The carabid beetle Platynus assimilis was subjected to repeated oral and continuous contact exposure to low doses of prothioconazole (20 g ha⁻¹), lambda-cyhalothrin (0.4 g ha⁻¹), or their combination over a 64-day period. The food consumption rate, body mass, locomotor activity, and mortality were monitored throughout the experiment. All pesticide-treated groups showed significantly increased final mortality, with median lethal times (LT₅₀) of 51.6 days for prothioconazole, 60.3 days for lambda-cyhalothrin, and 12.2 days for their combination. A significant synergistic effect on mortality was observed in the combined treatment group, with the highest synergistic ratio detected 20 days after the first exposure. Pesticide-treated beetles exhibited significant abnormalities in locomotor activity and body mass compared to the untreated group. These findings demonstrate that both time-cumulative mortality and potential synergistic interactions, reflecting field-realistic conditions, must be considered in ERA. Failure to do so may lead to an underestimation of pesticide toxicity to predatory carabids. Full article

Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more pregnancy losses before 20 weeks of gestation. RPL is a common medical condition among reproductive-age women, with approximately 23 million cases reported annually worldwide. Up to 5% of pregnant women may experience two or more consecutive pregnancy losses. Previous studies have investigated risk factors for RPL, including maternal age, uterine pathology, genetic anomalies, infectious agents, endocrine disorders, thrombophilia, and immune dysfunction. However, RPL is a disease caused by a complex interaction of genetic factors, environmental factors (e.g., diet, lifestyle, and stress), epigenetic factors, and the immune system. In addition, due to the lack of research on genetics research related to RPL, the etiology remains unclear in up to 50% of cases. Platelets play a critical role in pregnancy maintenance. This study examined the associations of platelet receptor and ligand gene variants, including integrin subunit beta 3 (ITGB3) rs2317676 A > G, rs3809865 A > T; fibrinogen gamma chain (FGG) rs1049636 T > C, rs2066865 T > C; glycoprotein 1b subunit alpha (GP1BA) rs2243093 T > C, rs6065 C > T; platelet endothelial cell adhesion molecule 1 (PECAM1) rs2812 C > T; and platelet endothelial aggregation receptor 1 (PEAR1) rs822442 C > A, rs12137505 G > A, with RPL prevalence. In total, 389 RPL patients and 375 healthy controls (all Korean women) were enrolled. Genotyping of each single nucleotide polymorphism was performed using polymerase chain reaction–restriction fragment length polymorphism and the TaqMan genotyping assay. All samples were collected with approval from the Institutional Review Board at Bundang CHA Medical Center. The ITGB3 rs3809865 A > T genotype was strongly associated with RPL prevalence (pregnancy loss [PL] ≥ 2: adjusted odds ratio [AOR] = 2.505, 95% confidence interval [CI] = 1.262–4.969, p = 0.009; PL ≥ 3: AOR = 3.255, 95% CI = 1.551–6.830, p = 0.002; PL ≥ 4: AOR = 3.613, 95% CI = 1.403–9.307, p = 0.008). The FGG rs1049636 T > C polymorphism was associated with a decreased risk in women who had three or more pregnancy losses (PL ≥ 3: AOR = 0.673, 95% CI = 0.460–0.987, p = 0.043; PL ≥ 4: AOR = 0.556, 95% CI = 0.310–0.997, p = 0.049). These findings indicate significant associations of the ITGB3 rs3809865 A > T and FGG rs1049636 T > C polymorphisms with RPL, suggesting that platelet function influences RPL in Korean women. Full article

Background: Disease-modifying drugs (DMDs) for multiple sclerosis (MS) slightly increase the risk of tuberculosis (TB) disease. The QuantiFERON-TB-Plus (QFT-Plus) test is approved for TB infection (TBI) screening. Currently, there are no data available regarding the characterization of QFT-Plus response in patients with MS. Objectives: This study aimed to compare the magnitude of QFT-Plus responses between patients with MS and TBI (MS-TBI) and TBI subjects without MS (NON-MS-TBI). Additionally, discordant responses to TB1/TB2 stimulation were documented. Results were evaluated considering demographic and clinical data, particularly the impact of DMDs and the type of TB exposure. Methods: Patients with MS (N = 810) were screened for TBI (2018–2023). Thirty (3.7%) had an MS-TBI diagnosis, and 20 were recruited for the study. As a control group, we enrolled 106 NON-MS-TBI. Results: MS-TBI showed significantly lower IFN-γ production in response to TB1 (p = 0.01) and TB2 stimulation (p = 0.02) compared to NON-MS-TBI. The 30% of TB2 results of MS-TBI fell into the QFT-Plus grey zone (0.2–0.7 IU/mL). Only 7% of NON-MS-TBI showed this profile (p = 0.002). Conclusions: MS-TBI had a lower QFT-Plus response and more borderline results compared to NON-MS-TBI. Future studies should clarify the significance of the borderline results in this vulnerable population to improve QFT-Plus accuracy regarding sensitivity, specificity, and TB prediction. Full article

Prostate cancer accounts for approximately 1.5 million new diagnoses and 400,000 deaths every year worldwide, and demographic projections indicate a near-doubling of both figures by 2040. Despite existing treatments, 10–20% of patients eventually progress to metastatic castration-resistant disease (mCRPC). The median overall survival (OS) after progression to mCPRC drops to 24 months, and efficacy drops severely after each additional line of treatment. Omics platforms have reached advanced levels and enable the acquisition of high-resolution large datasets that can provide insights into the molecular mechanisms underlying PCa pathology. Genomics, especially DDR (DNA damage response) gene alterations, detected via tissue and/or circulating tumor DNA, efficiently guides therapy in advanced prostate cancer. Given recent developments, we have performed a comprehensive literature search to cover recent research and clinical trial reports (over the last five years) that integrate omics along three converging trajectories in therapeutic development: (i) predicting response to approved agents with demonstrated survival benefits, (ii) stratifying patients to receive therapies in clinical trials, (iii) guiding drug development as part of drug repurposing frameworks. Collectively, this review is intended to serve as a comprehensive resource of recent advancements in omics-guided therapies for advanced prostate cancer, a clinical setting with existing clinical needs and poor outcomes. Full article

The evidence for photobiomodulation in reducing postoperative pain after endodontic instrumentation is classified as low or very low certainty, indicating a need for further research. Longitudinal pain assessments over 24 h are crucial, and studies should explore these pain periods. Background/Objectives: This double-blind, randomized controlled clinical trial evaluated the effect of PBM on pain following single-visit endodontic treatment of maxillary molars at 4, 8, 12, and 24 h. Primary outcomes included pain at 24 h; secondary outcomes included pain at 4, 8, and 12 h, pain during palpation/percussion, OHIP-14 analysis, and frequencies of pain. Methods: Approved by the Research Ethics Committee (5.598.290) and registered in Clinical Trials (NCT06253767), the study recruited adults (21–70 years) requiring endodontic treatment in maxillary molars. Fifty-eight molars were randomly assigned to two groups: the PBM Group (n = 29), receiving conventional endodontic treatment with PBM (100 mW, 333 mW/cm², 9 J distributed at 3 points near root apices), and the control group (n = 29), receiving conventional treatment with PBM simulation. Pain was assessed using the Visual Analog Scale. Results: Statistical analyses used chi-square and Mann–Whitney tests, with explained variance (η²). Ten participants were excluded, leaving 48 patients for analysis. No significant differences were observed in postoperative pain at 24, 4, 8, or 12 h, or in palpation/percussion or OHIP-14 scores. Pain frequencies ranged from 12.5% to 25%. Conclusions: PBM does not influence post-treatment pain in maxillary molars under these conditions. These results emphasize the importance of relying on well-designed clinical trials to guide treatment decisions, and future research should focus on personalized dosimetry adapted to the anatomical characteristics of the treated dental region to enhance the accuracy and efficacy of therapeutic protocols. Full article

Chronic kidney disease (CKD) remains a global health burden, with limited therapeutic options that effectively target the underlying pathophysiology. Nuclear factor erythroid 2-related factor 2 (NRF2), a key regulator of oxidative stress and inflammation, has garnered significant attention as a potential therapeutic target in CKD. Despite encouraging preclinical results, no NRF2-targeted agents have achieved clinical approval for CKD treatment. This review synthesizes emerging evidence showing substantial heterogeneity in NRF2 activity across CKD subtypes, influenced by disease etiology, CKD stage, and rate of disease progression. We elucidate the key therapeutic implications across diverse CKD etiologies and highlight that the therapeutic efficacy of NRF2 activation depends on precise modulation tailored to disease context. Although NRF2 overactivation and the need for stage-dependent modulation are increasingly recognized, this review further delineates the consequences of indiscriminate NRF2 activation, demonstrating that its effects diverge across CKD etiologies and cellular contexts. These insights support a nuanced, context-specific approach to NRF2-targeted strategies and provide a framework to guide future drug development in CKD. Full article

Background: Statins exhibit pleiotropic anti-inflammatory, antioxidant, and immunomodulatory effects, suggesting their potential in non-cardiovascular conditions. However, evidence supporting their repurposing remains limited, and off-label prescribing policies vary globally. Objective: To systematically review evidence on statin repurposing in oncology and infectious diseases, and to assess Hungarian regulatory practices regarding off-label statin use. Methods: A systematic literature search (PubMed, Web of Science, Scopus, ScienceDirect; 2010–May 2025) was conducted using the terms “drug repositioning” OR “off-label prescription” AND “statin” NOT “cardiovascular,” following PRISMA guidelines. Hungarian off-label usage data from the NNGYK (2008–2025) were also analyzed. Results: Out of 205 publications, 12 met the inclusion criteria—75% were oncology-focused, and 25% focused on infectious diseases. Most were preclinical (58%); only 25% offered strong clinical evidence. Applications included hematologic malignancies, solid tumors, Cryptococcus neoformans, SARS-CoV-2, and dengue virus. Mechanisms involved mevalonate pathway inhibition and modulation of host immune responses. Hungarian data revealed five approved off-label statin uses—three dermatologic and two pediatric metabolic—supported by the literature and requiring post-treatment reporting. Conclusions: While preclinical findings are promising, clinical validation of off-label statin use remains limited. Statins should be continued in cancer patients with cardiovascular indications, but initiation for other purposes should be trial-based. Future directions include biomarker-based personalization, regulatory harmonization, and cost-effectiveness studies. Full article

Cystic fibrosis produces viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in cystic fibrosis patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX), which functions to inhibit bacterial replication but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled therapy due to enhanced targeting and delivery. The extracellular matrix (ECM) has been shown to possess pro-regenerative and non-toxic properties in vitro, making it a promising delivery agent. The combination of LVX and ECM formed into nanoparticles may overcome barriers to lung delivery to effectively treat cystic fibrosis bacterial infections. Our goal is to advance CF care by providing a combined treatment option that has the potential to address both bacterial infections and lung damage. Two hybrid formulations of a 10:1 and 1:1 ratio of LVX to ECM have shown neutral surface charges and an average size of ~525 nm and ~300 nm, respectively. The neutral charge and size of the particles may suggest their ability to attract toward and penetrate through the mucus barrier in order to target the bacteria. The NPs have also been shown to slow the drug dissolution, are non-toxic to human airway epithelial cells, and are effective in inhibiting Pseudomonas aeruginosa and Staphylococcus aureus. LVX-ECM NPs may be an effective treatment for pulmonary CF bacterial treatments. Full article