Search Results (4,524)

Background and Objectives: The goal of this study is to assess health-related quality of life (HRQoL) using the EuroQoL (EQ-5D-5L) and identify factors that might contribute to it. Materials and Methods: This is a real-life, observational study involving 234 hypertensive patients from Sofia and Burgas, conducted between January 2024 and July 2024. Patients were interviewed during their regular outpatient examinations and completed the questionnaire independently. Results: In total, 141 out of 234 respondents reported a visual analog scale (VAS) score of 70, and 152 reported a utility score of 0.7. The average VAS scores for males and females were 77.5 and 77.0, respectively, and the utility scores were 0.848 and 0.768, respectively. With advancing age, patients’ quality of life (QoL) decreased from 0.879 to 0.652 utility. Respondents with higher levels of education had higher utility scores (0.848 for bachelor’s/master’s degrees vs. 0.542 for primary education). With an increase in the number of concomitant diseases and prescribed medications, the QoL decreased (0.848 vs. 0.623 and 0.848 vs. 0.736, respectively). Conclusions: This first study of HRQoL using EQ-5D-5L among Bulgarian hypertensive patients revealed relatively high average VAS and utility scores. These results suggest that the disease is under control and that patients are being successfully treated and monitored. Factors such as comorbidity, residence, education, disability, and disease duration significantly affected and worsened patients’ HRQoL. Full article

Background: Alzheimer’s disease (AD) is largely linked with oxidative stress, the accumulation of amyloid-β plaques, and hyperphosphorylated τ-protein aggregation. Alterations in dopaminergic and serotonergic neurotransmission have also been implicated in various AD-related symptoms. Methods: To explore new therapeutic agents, a series of bicyclic and tricyclic thieno-oxazepine derivatives were synthesized as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The resultant compounds were purified via HPLC and characterized using spectral analysis techniques. Histopathological examinations, other antioxidants, and anti-inflammatory biomarkers were evaluated, and in silico ADMET calculations were performed for synthetic hybrids. Molecular docking was utilized to validate the new drugs’ binding mechanisms. Results: The most powerful AChE inhibitors were 14 and 16, with respective values of IC₅₀ equal to 0.39 and 0.76 µM. Derivative 15 demonstrated remarkable BChE-inhibitory efficacy, on par with tacrine, with IC₅₀ values of 0.70 µM. Hybrids 13 and 15 showed greater selectivity towards BChE, despite substantial inhibition of AChE. Compounds 13 and 15 reduced escape latency and raised residence time, with almost equal activity to donepezil. Conclusions: According to these findings, the designed hybrids constitute multipotent lead compounds that could be used in the creation of novel anti-AD medications. Full article

Boa constrictor snakes represent a suitable model for studying the absorption, metabolism, and elimination of tramadol due to their distinct physiological characteristics. The objective of this work was to provide preliminary data on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol (M1), in the plasma of Boa constrictor using liquid chromatography with fluorescence detection. Ten snakes received tramadol (5 mg kg⁻¹) both into the epaxial musculature (TRIM) and into the paravertebral vein (TRIV) with a 45-day interval between the two administration methods. Blood samples were taken at specified time points to analyze the pharmacokinetics. Data were evaluated with an independent pharmacokinetic model (R software version 4.3.0). A paired Student’s t-test was used for all parametric variables, except clearance, which was analyzed with the Wilcoxon test. A significance level of 5% was applied. The mean (range) maximum concentration of tramadol, volume of distribution, clearance, and elimination half-life for the TRIM group were 2.58 µg mL⁻¹, 10.58 ± 2.91 L kg⁻¹, 0.36 L kg⁻¹ h⁻¹, and 19.96 ± 8.34 h, respectively. For the TRIV group, these values were 3.39 µg mL⁻¹, 5.60 ± 1.69 L kg⁻¹, 0.22 L kg h⁻¹, and 17.32 ± 7.55 h⁻¹, respectively. M1 achieved maximum concentration and elimination half-lives of 0.58 µg mL⁻¹ and 49.89 ± 10.8 h, respectively, for TRIM and 0.59 µg mL⁻¹ and 35.66 ± 10.85 h for TRIV. The bioavailability of intramuscular tramadol was 61%, and M1 remained at similar concentrations for 20 min after tramadol administration in both treatments. Tramadol is rapidly biotransformed into M1 in Boa constrictors, maintaining high concentrations over an extended period. The pharmacokinetic characteristics, particularly the sustained plasma concentrations of M1, suggest potential for effective analgesia in the Boa constrictor. Furthermore, the intramuscular route provides the additional advantage of ease and practicality of administration. Full article

Background: Food addiction is a new clinical entity that is beginning to be linked to obesity and eating disorders. The present study aims to investigate the association between the risk of food addiction in children and the presence of obesity. It also explores the relationship between food addiction, the development of eating disorders, and body image dissatisfaction. Material and methods: A matched case-control study was conducted in a Spanish pediatric population (cases have obesity, and controls have normal weight). The main outcome measures were evaluation of food addiction (S-YFAS-C), child feeding attitudes (ChEAT), and evaluation of body image (CDRS). Additionally, sociodemographic and anthropometric data were gathered. Results: A total of 62 children were evaluated (31 cases with age 11 ± 0.7 years and BMI Z-score 2.89 ± 1.33; 31 controls with age 10.7 ± 0.8 years and BMI Z-score −0.05 ± 0.52). For all items on the S-YFAS-C scale, significant differences were observed between the two groups (∧ = 0.252, p = 0.002). Food addiction was diagnosed in 32.3% of cases (2.06 ± 1.7 symptoms) and 22.6% of controls (1.61 ± 1.6 symptoms), although no statistically significant differences were observed between groups. A statistically significant correlation exists between all the scores of the scales studied in the children. Conclusions: Children with obesity have a higher number of food addiction symptoms compared to those with normal weight. In general, as food addiction scores increase, higher scores are observed for the risk of developing eating disorders and body image dissatisfaction. Full article

Non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) often coexists with multivessel coronary artery disease (MVD), complicating treatment decisions. Current guidelines suggest complete revascularization (CR), yet robust evidence in hemodynamically stable patients remains insufficient. However, the comparative benefit of CR over incomplete revascularization (IR) in reducing ischemic events and improving cardiac function in this population is not well established. The aim of this study was to evaluate the impact of CR on all-cause mortality, cardiac death, and ischemic readmissions at 6 and 12 months, as the composite primary outcome, and to assess left ventricular ejection fraction (LVEF) improvement at discharge and hospital length of stay, as secondary outcomes. A total of 282 hemodynamically stable NSTE-ACS patients with MVD were included, of whom 218 (77.3%) underwent CR and 64 (22.7%) IR. The primary composite outcome occurred in 40.6% of IR patients versus 11.0% in the CR group at 6 months (p < 0.001), and 68.8% vs. 22.0% at 12 months (p < 0.001). CR was associated with significantly lower rates of all-cause and cardiac death, myocardial infarction, and unstable angina. Stroke incidence was similar. Event-free survival favored CR. Multivariable analysis identified CR and baseline LVEF as independent predictors of 12-month outcomes (HR for CR: 7.797; 95% CI: 3.961–15.348; p < 0.001; HR for LVEF: 0.959; CI: 0.926–0.994; p = 0.021). These findings strongly support CR as the preferred therapeutic strategy. Future prospective randomized studies are warranted to confirm the results. Full article

Leaves of Gentiana lutea L., traditionally used for treating heart disorders, represent a sustainable and underutilized source of bitter secoiridoids and xanthones, also found in Gentianae radix—an official herbal drug derived from the same, protected species. As root harvesting leads to the destruction of the plant, using the more readily available leaves could help reduce the pressure on this endangered natural resource. This study aimed to optimize the ultrasound-assisted extraction of the secoiridoid swertiamarin and the xanthone isogentisin from G. lutea leaves using response surface methodology (RSM). Subsequently, the stability of the bioactive compounds (swertiamarin, gentiopicrin, mangiferin, isoorientin, isovitexin, and isogentisin) in the optimized extract was monitored over a 30-day period under different storage conditions. The influence of extraction time (5–65 min), ethanol concentration (10–90% v/v), liquid-to-solid ratio (10–50 mL/g), and temperature (20–80 °C) was analyzed at five levels according to a central composite design. The calculated optimal extraction conditions for the simultaneous maximization of swertiamarin and isogentisin yields were 50 min extraction time, 30% v/v ethanol concentration, 30 mL/g liquid-to-solid ratio, and 62.7 °C extraction temperature. Under these conditions, the experimentally obtained yields were 3.75 mg/g dry weight for swertiamarin and 1.57 mg/g dry weight for isogentisin, closely matching the RSM model predictions. The stability study revealed that low-temperature storage preserved major bioactive compounds, whereas mangiferin stability was compromised by elevated temperature and light exposure. The established models support the production of standardized G. lutea leaf extracts and may facilitate the efficient separation and purification of their bioactive compounds, thereby contributing to the further valorization of this valuable plant material. Full article

Background: Uterine leiomyomas, commonly known as fibroids, are the most prevalent benign tumors in women of reproductive age and a major contributor to gynecological morbidity. Although surgery and hormonal therapies are standard treatments, their associated side effects have prompted the search for safer, non-hormonal alternatives. Oligo-fucoidan, a sulfated polysaccharide derived from brown seaweed, has demonstrated anti-fibrotic and estrogen-regulating effects in preclinical models, but its clinical potential remains largely unexplored. Methods: In this randomized, double-blind, placebo-controlled pilot trial, 16 women diagnosed with uterine leiomyomas by ultrasound were enrolled and randomly assigned to receive either oligo-fucoidan (4 g/day) or placebo for six months (n = 8 per group). The primary endpoints were changes in the number of leiomyomas and quality of life, assessed using the World Health Organization Quality-of-Life Scale (WHOQOL-BREF) and Menstrual Distress Questionnaire (MDQ). Hormonal and safety parameters were also monitored. Results: Compared with the placebo group, participants receiving oligo-fucoidan exhibited a statistically significant reduction in fibroid number and reported improvements in quality-of-life domains. No serious adverse events occurred, and no clinically significant changes were noted in safety-related laboratory parameters. Conclusions: This pilot study provides preliminary clinical evidence that oligo-fucoidan may be a safe, well-tolerated, and potentially effective functional food-based approach for managing uterine fibroids. Larger trials are warranted to confirm these findings. Full article

Background and Clinical Significance: As a common inflammatory skin disorder, acne vulgaris is classically associated with sebum overproduction, follicular hyper keratinization, and Cutibacterium acnes proliferation. Emerging evidence suggests a link between severe or treatment-resistant acne and metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension. This case series aims to explore the clinical overlap between acne and metabolic dysfunction and highlight the relevance of multidisciplinary evaluation. Case Presentation: Three patients with severe acne vulgaris and coexisting metabolic abnormalities were evaluated at a dermatology clinic in Oradea, Romania, between 2023 and 2024. Each patient underwent dermatologic examination, laboratory testing for metabolic and hormonal parameters, and individualized treatment. Management strategies included topical/systemic acne therapies combined with metabolic interventions (lifestyle modifications, metformin (in two cases), and lipid-lowering agents). Case 1 (female, 23) had obesity, insulin resistance, dyslipidemia, and polycystic ovary syndrome (PCOS). Case 2 (male, 19) presented with central obesity and atherogenic dyslipidemia. Case 3 (male, 18) showed insulin resistance, overweight status, and elevated inflammatory markers. All three showed suboptimal response to standard acne treatment. Adjunct metabolic management resulted in partial improvement within 3 months. One patient required isotretinoin after metabolic stabilization. Conclusions: These cases underscore the interplay between acne and metabolic dysfunction. Insulin resistance and systemic inflammation may contribute to therapeutic resistance in acne. Early recognition of metabolic syndrome features in patients with severe acne may improve treatment outcomes. Dermatologists should consider metabolic screening to guide comprehensive, multidisciplinary care. Full article

Tuberculosis remains a serious infectious disease that causes over 1.3 million deaths annually. Following the COVID-19 pandemic, the global incidence of tuberculosis has increased to 10.8 million cases. Pregnant women represent a particularly vulnerable population requiring tailored approaches to the prevention, diagnosis, and treatment of tuberculosis. SARS-CoV-2 infection may have impacted existing clinical protocols. Implementing updated methods of tuberculosis prevention, diagnosis, and treatment in pregnant women could help reduce adverse maternal and fetal outcomes. The aim of this review was to explore potential modifications in tuberculosis management among pregnant women in the post-COVID-19 era, including co-infection with SARS-CoV-2. Methods: A review was conducted, incorporating a systematic literature search across major international databases, including Medline, PubMed, Web of Science, Scopus, and Google Scholar. The search covered publications released between December 2019 and September 2024 and used targeted keywords such as “COVID-19” OR “SARS-CoV-2”, “tuberculosis” OR “TB” OR “latent tuberculosis infection” OR “pulmonary tuberculosis”, and “pregnancy” OR “pregnant women”. Results: Pregnant women living with HIV are at increased risk of developing tuberculosis, which can negatively affect both maternal and perinatal outcomes. Screening for tuberculosis is recommended for all HIV-positive pregnant women, even in the absence of clinical symptoms. Notably, immunological testing before and during pregnancy facilitates the timely and safe detection of tuberculosis infection, enabling preventive and therapeutic interventions during any stage of gestation and the early postpartum period, for the benefit of both mother and child. Drug–drug interactions play a significant role in tuberculosis management, both among anti-tuberculosis agents and with medications for comorbid conditions. Current knowledge of the pharmacokinetics and pharmacodynamics of antituberculosis agents, coupled with therapeutic drug monitoring, supports the development of individualized and effective treatment regimens, which are particularly critical for pregnant patients. Recommendations for managing tuberculosis in pregnant women after COVID-19 infection include measuring D-dimer levels, performing echocardiography, and consulting cardiologists to prevent treatment-related complications. Conclusions: Pregnant women represent a distinct subgroup of tuberculosis patients requiring individualized management. Changes observed in tuberculosis progression and treatment responses in pregnant women before and after SARS-CoV-2 infection should inform therapeutic choices, especially in cases of drug-resistant tuberculosis treated with bedaquiline. COVID-19 has been associated with increased cardiovascular risk, which may heighten the likelihood of adverse drug reactions in this population, especially given the limited therapeutic options. Further research is required to assess the long-term outcomes of latent tuberculosis infection in pregnant women and to evaluate the safety and efficacy of novel regimens for drug-resistant TB during pregnancy. Full article

Solvent-exchange-induced in situ forming gel (ISG) refers to a drug delivery system that transforms from a solution state into a gel or solid matrix upon administration into the body and exposure to physiological aqueous fluid. This study investigates the molecular behavior and phase inversion process of cellulose acetate butyrate (CAB)-based in situ forming gel (ISG) formulations containing moxifloxacin (Mx) or benzydamine HCl (Bz) as model drugs dissolved in N-methyl pyrrolidone (NMP) using molecular dynamics (MD) simulations and density functional theory (DFT) calculations. The simulations reveal a solvent exchange mechanism, where the diffusion of water molecules replaces NMP, driving the formation of the CAB matrix. Bz exhibited faster diffusion and a more uniform distribution compared to Mx, which aggregated into clusters due to its larger molecular size. The analysis of the root mean square deviation (RMSD) and radius of gyration confirmed the faster diffusion of Bz, which adopted a more extended conformation, while Mx remained compact. The phase transformation was driven by the disruption of CAB-NMP hydrogen bonds, while CAB–water interactions remained limited, suggesting that CAB does not dissolve in water, facilitating matrix formation. The molecular configuration revealed that drug–CAB interactions were primarily governed by hydrophobic forces and van der Waals interactions rather than hydrogen bonding, controlling the release mechanism of both compounds. DFT calculations and electrostatic potential (ESP) maps illustrated that the acetyl group of CAB played a key role in drug–polymer interactions and that differences in CAB substitution degrees influenced the stability of drug-CAB complexes. Formation energy calculations indicated that Mx-CAB complexes were more stable than Bz-CAB complexes, resulting in a more prolonged release of Mx compared to Bz. Overall, this study provides valuable insights into the molecular behavior of CAB-based Mx-, Bz-ISG formulations. Full article

Background/Objectives: Advances in understanding immune checkpoint pathways and tumor immune biology have enabled the development of immune checkpoint inhibitors (ICIs), particularly targeting the PD-1/PD-L1 axis, which has transformed cancer immunotherapy. While they have shown remarkable success in various cancer types, including melanoma, non-small cell lung cancer, and gastrointestinal malignancies, variability in patient response, immune-related adverse events (irAEs), and resistance mechanisms remain significant. This review aims to evaluate clinical pharmacology, mechanisms of action, resistance pathways, and pharmacogenomic influences shaping interindividual responses to ICIs. Methods: This comprehensive review synthesizes current literature on FDA-approved ICIs, exploring their clinical use, underlying biological mechanisms, and emerging pharmacogenomic data. It also assesses key biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), HLA diversity, and epigenetic factors influencing ICI efficacy and safety. Results: We outline key mechanisms contributing to ICI resistance, including T cell dysfunction, altered antigen presentation, and immunosuppressive tumor microenvironment components. Furthermore, we highlight promising pharmacogenomic findings, including single-nucleotide polymorphisms (SNPs) in PD-1/PD-L1 and immune-regulatory genes, offering predictive and prognostic utility. Variability in PD-L1 expression and the role of epigenetic modifications are also addressed as challenges in treatment optimization. Conclusions: Interindividual variability in ICI response underscores the need for biomarker-driven strategies. By integrating pharmacogenomic insights with clinical pharmacology, future approaches may support more personalized and effective use of ICIs. Combination therapies and novel modalities hold promise for overcoming resistance, enhancing therapeutic efficacy, and enabling precision oncology. Full article

Croton tiglium L. seeds, a component of many recipes of Thai traditional medicine (TTM), had to undergo the Thai traditional detoxification process (TDP) before being used. However, this detoxification process has never been scientifically proven for its effectiveness. Thus, this research aimed to investigate the effects of TDP on purgative effect and acute toxicity, as well as the identification of some chemical constituents in C. tiglium seeds before (CB) and after (CA) treatment. The purgative effect and acute toxicity of CB and CA powders were evaluated using Wistar rats. The amounts of phorbol-12-myristate-13-acetate (PMA) and crotonic acid in the CB and CA powders were determined using HPLC. The results showed no acute toxicity in the rats administered CB and CA powders at doses of 300–2000 mg/kg of body weight (BW). However, CB and CA caused a dose-dependent increase in the number of fecal pellets as well as an increase in the amount of wet and dry feces. Interestingly, only CB, at the dose of 100 mg/kg, caused a significant purgative effect. The TDP was also found to affect the amounts of PMA and crotonic acid. While the amount of PMA in C. tiglium seed powder decreased from 1.59 mg/g in CB to 1.26 mg/g in CA, the amount of crotonic acid decreased from 0.001 mg/g in CB to an undetectable level in CA. This investigation demonstrated that TDP not only reduced the purgative effect and toxicity of croton seeds but also the amounts of PMA and crotonic acid. Full article

In folk medicine, species of the genus Melampyrum (Orobanchaceae) have traditionally been used to treat dermatological conditions, neuralgia, rheumatism, and wounds. M. nemorosum L. possesses a diverse chemical profile that supports its therapeutic potential. This study aimed to investigate its principal biologically active compounds and to evaluate the antimicrobial, anti-inflammatory, haemostatic, and wound-healing activities of aqueous-ethanolic extracts (40% ethanol (MN40) and 70% ethanol (MN70)) of M. nemorosum herb. Nineteen phenolic compounds were identified in the extracts, including phenolic acids, hydroxycinnamic acids, flavonoids, and tannin metabolites. At a dose of 100 mg/kg, the extracts exhibited anti-inflammatory activity in the formalin-induced paw oedema model. Haemostatic effects were demonstrated by reductions in bleeding time by 38.5% (MN40) and 45.5% (MN70). Both extracts significantly accelerated wound healing, with MN70 showing the most pronounced effect: achieving 97.8% wound closure by day 11 and complete healing by day 13. Additionally, both extracts demonstrated antimicrobial activity, with MN70 being the most effective across all tested parameters. These findings reported here for the first time for this plant support the potential of M. nemorosum herb extracts for further preclinical and clinical development as a multifunctional phytotherapeutic agent. Full article

Background/Objectives: Inflammation plays a key role in acute coronary syndromes (ACS). The systemic immune-inflammation index (SII), which integrates immune and inflammatory markers, may serve as a valuable prognostic tool. This study aimed to evaluate the utility of SII as a short-term predictor of mortality and major adverse cardiovascular and cerebral events (MACCE) in ACS patients. Methods: A retrospective analysis was conducted on 964 ACS patients admitted in 2023. SII was calculated from admission hematological parameters. Primary and secondary outcomes were 30-day mortality and MACCE, respectively. Results: SII levels differed significantly across ACS subtypes (p < 0.001), highest in ST-segment elevation myocardial infarction (STEMI) and lowest in unstable angina. SII was markedly higher in deceased patients (2003.79 ± 1601.17) vs. survivors (722.04 ± 837.25; p < 0.001) and remained an independent predictor of mortality (OR = 1.038, p < 0.001). Similarly, SII was elevated in MACCE cases (1717 ± 1611.32) vs. non-MACCE (664.68 ± 713.11; p < 0.001) and remained predictive in multivariate analysis (OR = 1.080, p < 0.001). Predictive accuracy for MACCE was moderate (AUC = 0.762), improved when combined with GRACE 2, especially in specificity (p = 0.07). In STEMI, SII had excellent accuracy (AUC = 0.874), outperforming neutrophil–lymphocyte ratio and C-reactive protein. SII rose at 24 h and declined at 48 h in STEMI, with a slower decline in MACCE patients. Conclusions: SII proved to be a cost-effective biomarker reflecting inflammation, immunity, and thrombosis. Elevated SII predicted short-term MACCE and mortality in ACS, with improved prognostic power when combined with GRACE 2. Persistent elevation may signal ongoing inflammation and increased MACCE risk. Full article

SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study aimed to investigate the expression of Angiotensin-converting enzyme 2 (ACE2), spike protein, and CD68+ markers in placental tissue to demonstrate a possible correlation with the level of systemic oxidative stress biomarkers in patients who were infected with SARS-CoV-2 during pregnancy. A prospective clinical cohort study was designed to investigate the presence of CD68+ macrophages, ACE2, and spike proteins in placental tissue using immunohistochemical methods and to compare these results with oxidative stress from our previous study. Spike and CD68+ macrophages’ immunoreactivity were more pronounced in the placental tissue of patients from the SARS-CoV-2 group. Placental tissue spike protein and CD68+ immunoreactivity correlate with maternal and fetal Thiobarbituric Acid Reactive (TBARS) levels. This study has confirmed that spike protein expression in placental tissue is associated with the newborn’s stay in intensive neonatal care. Therefore, immunoreactivity analysis for the Spike antigen is important in detecting newborns at risk of early neonatal complications. Full article