Search Results (299)

Background: Electroencephalography (EEG) systems based on textile electrodes are increasingly being developed to address the need for more wearable sensor systems for brain function monitoring. Blink-related oscillations (BROs) are a new measure of brain function that corresponds to brainwave responses occurring after spontaneous blinking, and indexes neural processes as the brain evaluates new visual information appearing after eye re-opening. Prior studies have reported BRO utility as both a clinical and non-clinical biomarker of cognition, but no study has demonstrated BRO measurement using textile-based EEG devices that facilitate user comfort for real-world applications. Methods: We investigated BRO measurement using a four-channel EEG system with textile electrodes by extracting BRO responses using existing, publicly available EEG data (n = 9). We compared BRO effects derived from textile-based electrodes with those from standard dry Ag/Ag-Cl electrodes collected at the same locations (i.e., Fp1, Fp2, F7, F8) and using the same EEG amplifier. Results: Results showed that BRO effects measured using textile electrodes exhibited similar features in both time and frequency domains compared to dry Ag/Ag-Cl electrodes. Data from both technologies also showed similar performance in artifact removal and signal capture. Conclusions: These findings provide the first demonstration of successful BRO signal capture using four-channel EEG with textile electrodes, providing compelling evidence toward the development of a comfortable and user-friendly EEG technology that uses the simple activity of blinking for objective brain function assessment in a variety of settings. Full article

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks. Full article

Background and Objectives: The spontaneous reporting (SR) of adverse drug events (ADEs) is a cornerstone of pharmacovigilance and a critical mechanism for safeguarding patient safety. However, underreporting remains a persistent global challenge. In Korea, despite the widespread use of herbal medicines (HMs), adverse event reports from traditional Korean medicine doctors (KMDs) are remarkably scarce. This study aimed to assess the knowledge, attitudes, and experiences of KMDs regarding SR, identify key barriers, and suggest strategies to strengthen the safety culture within traditional Korean medicine. Materials and Methods: A cross-sectional, anonymous online survey was distributed to licensed KMDs registered with the Association of Korean Medicine. The questionnaire collected information on respondents’ sociodemographic characteristics and assessed their knowledge, attitudes, and experiences related to ADE reporting. Descriptive statistics and multivariate logistic regression were used to analyze the associations between the variables. Results: Of the 1021 KMDs who completed the survey, the vast majority acknowledged the importance of SR and recognized their role in pharmacovigilance. Nevertheless, only 5% had ever submitted an ADE report. A widespread lack of awareness about the national spontaneous reporting system (SRS), particularly its inclusion of licensed HMs, was evident. Although many respondents expressed support for expanding the scope of SR to cover all HMs, significant gaps in pharmacovigilance knowledge and limited access to relevant training were major barriers. KMDs affiliated with academic institutions or specialist groups showed higher levels of awareness, education, and reporting behavior. Conclusions: While KMDs exhibit positive attitudes toward patient safety and understand the importance of SR, their participation in it remains low due to knowledge deficits and insufficient training. Addressing these gaps through targeted education and expanding the national SRS to comprehensively include herbal medicines are essential steps toward enhancing pharmacovigilance and cultivating a proactive safety culture in Korean medicine. Full article

Backgrounds and Objectives: This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Materials and Methods: Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs. Sensitivity analysis was performed to validate the overall findings and assess the robustness of associations across subgroups defined by completeness of demographic data (age and sex), elderly age-stratification, and causality assessment. The study protocol was approved by the Kyung Hee University institutional review board. Results: Among 21,103 antidepressant-related ADEs, duloxetine was the most etiologic medication, followed by amitriptyline and escitalopram. Fluoxetine is the only agent with a high likelihood of reporting SAEs. ADEs involving vascular (extracardiac) disorders (ROR 42.42, 95% CI 13.19–136.42) and liver and biliary system disorders (ROR 7.84, 95% CI 3.77–16.29) were most likely to be SAEs. The predictors associated with substantial increased SAE risk were fluoxetine use (OR 2.71, 95% CI 1.68–4.39), male sex (OR 1.48, 95% CI 1.11–1.98), and concomitant administration of antiparkinsonian treatment (OR 8.29, 95% CI 3.61–19.06) and antidementia treatment (OR 2.94, 95% CI 1.34–6.05). Sensitivity analyses demonstrated similar and consistent findings. However, reversed trends in the association between SOC-based ADEs and sex were observed in the sensitivity analysis restricted to cases with “certain” and “probable” causality. Conclusions: The type of antidepressant, concomitant medications, and sex are major predictors for SAE risk. Further controlled studies on the impact of comorbidities and polypharmacy on antidepressant-related SAEs are warranted. Full article

Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study reviews the safety of nirsevimab through post-marketing surveillance. Material and Methods: A descriptive pharmacovigilance study was made based on spontaneous reporting data of suspected adverse events (SAEs) from the Spanish Pharmacovigilance System for Medicinal Products for Human Use (SEFV-H) and industry reports. SAEs reported between September 2023 and May 2024 were extracted from the Spanish Pharmacovigilance Adverse Reactions Data (FEDRA) database. Cases were analysed by sex, age, severity, and SAEs classification using the Preferred Terms (PT) level of the Medical Dictionary for Regulatory Activities (MedDRA). Reporting rates were estimated based on immunization coverage and birth data. Results: Sixty-seven cases reported 141 SAEs, yielding an overall rate of 23.1 cases per 100,000 doses. Common events included rash (8.51%), drug ineffectiveness (7.09%), and pyrexia (7.09%). Serious events constituted 53.70% of reports, including two fatalities (3.00%). No new safety signals or unexpected risks, such as antibody-dependent enhancement (ADE), were identified. Discussion: SAEs reported peaked early in the campaign, reflecting heightened reporting in new immunization programs. The safety profile aligns with clinical trial findings and regulatory expectations, confirming nirsevimab’s benefit–risk balance. Continued pharmacovigilance is critical for maintaining public trust in RSV prophylaxis. Nirsevimab demonstrated a favorable safety profile during Spain’s initial universal RSV immunization campaign in infants, supporting its continued use in reducing RSV-related morbidity. Full article

This case report describes a fetus diagnosed with complete atrioventricular block (CAVB) associated with positive maternal anti-Ro and anti-La antibodies, referred to our fetal cardiology unit at 25 weeks of gestation. The diagnosis of systemic lupus erythematosus (SLE) was established during the investigation of the fetal condition. Oral dexamethasone was initiated and well tolerated, with no adverse effects reported throughout the remainder of the pregnancy. The fetal heart rate (HR) remained above 50 bpm, and, therefore, no beta-sympathomimetic agents were administered. Due to progressive reduction in myocardial contractility and the appearance of early signs of endocardial fibroelastosis, intravenous immunoglobulin (IVIG) therapy was initiated. The patient was hospitalized for the infusion, which was well tolerated without complications, and a second IVIG cycle was administered four weeks later. Significant improvement in ventricular contractility and reduction in fibroelastosis were observed. As reported in the literature, no chronotropic effect was noted, and fetal HR remained stable after treatment. Weekly monitoring of cardiovascular profile score and fetal HR was maintained, with the score consistently remaining at 8 throughout gestation, supporting continued outpatient management. Delivery occurred at 36 weeks and 3 days due to spontaneous preterm labor. A male neonate weighing 3025 g was delivered with Apgar scores of 8 and 9, and an initial heart rate of 84 bpm. Neonatal electrocardiography confirmed persistent CAVB, and the newborn was monitored in the neonatal intensive care unit. At follow-up, the infant remains clinically stable and has not required permanent pacemaker implantation. Full article

Vin Santo is a passito wine produced mainly in Tuscany. In the traditional production of Vin Santo, fermentation occurs naturally. Only a few reports have explored the microbial ecology of Vin Santo. Therefore, the present study aimed to investigate the microbial ecology and its impact on the fermentative kinetics in traditional processes of Vin Santo carried out in two different Tuscan wineries. Despite the different systems used for drying the grapes, both wineries showed similar microbial ecology. Non-Saccharomyces yeasts were the dominant microbial population during grape drying in different succession, even though in the end, the dominant species (at different percentages) in both were Metschnikowia pulcherrima, Kloeckera apiculata, and Starmerella bacillaris. The spontaneous fermentations were instead both dominated by Saccharomyces cerevisiae, however in different concentration throughout the process, leading to a different ethanol content—12% (v/v) and 10.8% (v/v) in winery A and B, respectively. In both wineries, acetic bacteria and moulds did not grow. Considering the intraspecific biodiversity of S. cerevisiae populations, the vinifications of both wineries displayed very similar biodiversity indices. No single strain of S. cerevisiae dominated the entire fermentation process. The analysis identified 30 distinct genetic patterns in the fermentations of winery A and 23 in the fermentations of winery B. The work provided an insight into the microbial communities and their metabolomic interactions during Vin Santo production which could improve the management and control of the process. Full article

The Peruvian grunt, Anisotremus scapularis, is a commercially valuable coastal fish in the southeastern Pacific that is facing overexploitation. To support its aquaculture development, this study evaluated the spontaneous reproductive dynamics of a captive broodstock held under natural photoperiod and temperature conditions in a flow-through system. Eleven wild adult specimens (3 females and 8 males) with an average size of 34.9 ± 5.4 cm and a weight of 986 ± 470 g were housed in a 9 m³ tank and monitored over five consecutive spawning seasons (2016–2021). Fish were fed a semi-moist, animal-protein-based diet (37% protein and 6.6% lipid) at 2% body weight/day. A total of 214 spontaneous spawning events produced over 83 million eggs. The highest reproductive output occurred in the first season (2016–2017) with 94 spawnings and 23.3 million eggs. Fertilization, hatching, and larval survival rates averaged 94.7%, 89.7%, and 75%, respectively, but declined in later years. Spawning showed marked seasonality from October to May, with a major reproductive pause in late January. The temperature (16–20 °C) and photoperiod (>12 h daylight) appeared to influence reproductive timing, alongside diet and broodstock handling. The findings reported herein are observational in nature and provide valuable baseline data for future experimental designs aimed at optimizing broodstock management in A. scapularis aquaculture. Full article

Drug–drug interactions (DDIs) can pose significant risks in clinical practice and pharmacovigilance. Although traditional association rule mining techniques, such as the Apriori algorithm, have been applied to drug safety signal detection, their performance in DDI detection has not been systematically evaluated, especially in the Spontaneous Reporting System (SRS), which contains a large number of drugs and AEs with a complex correlation structure and unobserved latent factors. This study fills that gap through comprehensive simulation studies designed to mimic key features of SRS data. We show that latent confounding can substantially distort detection accuracy: for example, when using the reporting ratio (RR) as a secondary indicator, the area under the curve (AUC) for detecting main effects dropped by approximately 30% and for DDIs by about 15%, compared to settings without confounding. A real-world application using 2024 VAERS data further illustrates the consequences of unmeasured bias, including a potentially spurious association between COVID-19 vaccination and infection. These findings highlight the limitations of existing methods and emphasize the need for future tools that account for latent factors to improve the reliability of safety signal detection in pharmacovigilance analyses. Full article

Background/Objectives: Some product information on pregabalin suggests a potential risk for congenital anomalies (CAs), although evidence remains inconsistent and lacks clear patterns. This study aimed to provide additional safety information on pregabalin use in pregnancy by analyzing VigiBase, the World Health Organization’s global pharmacovigilance database of individual case safety reports (ICSRs). Methods: The analysis included de-duplicated ICSRs related to pregabalin exposure in pregnancy, collected up to 16 January 2024. Reporting odds ratios (RORs) with 95% confidence intervals (CIs) were calculated for CA categories reported in at least 10 ICSRs, with a statistical threshold defined as a 95% CI lower bound > 1. Results: Among 410 ICSRs, the majority originated from Europe (64.8%) and North America (26.5%). Of these, 59 (14.4%) ICSRs documented only pregabalin exposure in pregnancy, while 351 (85.6%) also reported adverse events in pregnancy. CAs occurred in 82 ICSRs (23.3%), most commonly involving heart defects (30), nervous system anomalies (18), and limb anomalies (12). No signals of disproportionate reporting were identified for these categories compared to the full database (heart defects: ROR 0.587, 95% CI 0.410–0.839; nervous system anomalies: ROR 0.588, 95% CI 0.370–0.933; limb anomalies: ROR 0.671, 95% CI 0.381–1.183). Conclusions: Future disproportionality analyses, along with pharmacovigilance and pharmacoepidemiological studies using patient registries and large-scale collaborative projects, are essential for the ongoing monitoring of pregabalin safety in pregnancy. Full article

Ferroelectric liquid crystals (FLCs) are key materials for high-speed electro-optical applications, yet achieving optimal properties over a broad temperature range down below room temperature remains a challenge. This study presents a novel series of systematically designed FLC mixtures, incorporating components with three degrees of chirality—achiral systems, with one center of chirality and with two centers of chirality—to optimize the mesomorphic stability, electro-optical response, and physicochemical properties. The strategic doping by chiral components up to a 0.2 weight fraction extends the temperature range of the ferroelectric phase while lowering the melting temperature. Notably, mixtures containing two chiral centers exhibit shorter helical pitches, while increasing chirality enhances the tilt angle of the director and spontaneous polarization. However, in a mixture containing all three types of chirality (CchM), spontaneous polarization decreases due to opposing vector contributions. Switching time analysis reveals that a system with achiral components and those with two centers of chirality (A-BchM) exhibits the fastest response, while CchM demonstrates only intermediary behavior, caused by its high rotational viscosity. Among all formulations, those containing compounds with two centers of chirality display the most favorable balance of functional properties for deformed helix ferroelectric liquid crystal (DHFLC) applications. One such mixture achieves the lowest melting temperature reported for DHFLC-compatible FLCs, enabling operation at sub-zero temperatures. These findings pave the way for next-generation electro-optical devices with enhanced performance and appropriate environmental stability. Full article

Background/Objective: Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real world. Methods: SARs to esketamine reported in the data system EudraVigilance were analyzed, and disproportionality analysis for adverse reactions indicating suicidality for esketamine, in comparison to the antidepressants fluoxetine and venlafaxine, was performed. Results: Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported SARs. The sex distribution indicates the prevalence of women, except for increased blood pressure and completed suicide, which were signaled in men, while adults (18–64 years) and elders (65–85 years) were the ages with the largest number of reported adverse reactions to esketamine. The results indicate the existence of a potential increase in the risk of suicide in depressed patients taking esketamine when compared with fluoxetine and venlafaxine. Conclusions: Apart from carefulness due to the known limitations of pharmacovigilance research conducted by using data systems of spontaneous signals for SARs, the analysis of data points toward the need for greater attention being paid to the potential risk of suicide following the prescription of esketamine in depressed subjects. In this regard, as regulatory agencies also recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to beginning treatment should receive more careful monitoring during treatment. Full article

Introduction: Kidney transplant recipients present a higher risk of developing malignancies than the general population. Malignancies represent the third leading cause of death for kidney transplant recipients. There is an increased risk of developing urothelial carcinoma among kidney transplant recipients, but it is not as high as the risk of renal cell carcinoma, which is the most common urologic malignancy. Although the bladder is the most common location for urothelial carcinoma, urothelial carcinomas of the upper tracts of the native kidneys and the allograft are also reported. The estimated incidence of urothelial carcinomas arising on kidney grafts is 0.019%. Case report: We present a case of a kidney transplant recipient who developed non-muscle-invasive bladder cancer 10 years after the transplant. This was successfully treated with TURBT (transurethral resection of the bladder tumor) and BCG (bacillus Calmette–Guerin) instillations. Two years later, this patient developed metastatic urothelial carcinoma of the allograft. Discussion: Nephroureterectomy of the transplant with bladder preservation after BCG treatment, no systemic chemotherapy, and cessation of immunotherapy were the treatments of choice in this case. Local oncologic control and spontaneous complete regression of pulmonary metastasis were obtained at a 2-year follow-up. Conclusions: With this case, we emphasize the fact that managing urothelial carcinomas in kidney transplant recipients is a provocative challenge for surgeons, nephrologists, and oncologists, as there are no treatment guidelines or protocols. Full article

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear cell RCC. The patient initially presented with right lower back pain, weight loss, and a loss of appetite. Following systemic immunotherapy with nivolumab and ipilimumab, and right radical nephrectomy, the patient was diagnosed with metastatic clear cell RCC, with new metastatic lesions detected in the liver, and on the chest wall on follow-up imaging. Second-line systemic treatment with pazopanib was initiated. Shortly thereafter, the patient developed severe systemic inflammatory syndrome, resulting in a mental stupor and acute kidney failure. Intensive care, including continuous renal replacement therapy and high-dose immunosuppressants, was administered. The patient’s condition improved significantly with the intensive care regimen, leading to unintended tumor regression. These potentially fatal side effects occurred without infection, as confirmed by negative blood and urine cultures, and were attributed to the recent introduction of pazopanib. Follow-up imaging showed a significant reduction in hepatic metastatic lesions and the disappearance of chest wall nodules. This is the first reported case of RCC tumor regression following the side effects of pazopanib, underscoring the need for further studies into the immune mechanisms involved in RCC treatment and highlighting potential therapeutic strategies that leverage innate immune responses. Full article

Enzymatic catalysis has gained significant attention in green chemistry due to its high specificity and efficiency under mild conditions. However, challenges related to enzyme immobilization and spatial control often limit its practical applications. In this work, we report a Marangoni flow-driven strategy to fabricate a biomimetic jellyfish-like hydrogel with tunable tentacle-like structures. The formation process occurs entirely in an aqueous system without organic solvents or post-treatment, enabling the construction of ultra-thin, free-standing hydrogels through spontaneous interfacial self-assembly. The resulting structure exhibits high surface-area geometry and excellent biocompatibility, providing a versatile platform for localized enzyme loading. This method offers a simple and scalable route for engineering soft materials with complex morphologies, and expands the design space for bioinspired hydrogel systems. Full article