Search Results (46,698)

Oyster health is important for aquaculture productivity and sustainability. In Thailand, the white scar oyster, Crassostrea belcheri, is being promoted for cultivation, yet its health status has not been compared between research breeding and community farming sites. This study evaluated histopathological features, ultrastructure, apoptosis, and defender against apoptotic death 1 (dad1) gene expression in sexually mature C. belcheri collected from these two sites. Gill tissues were examined by histology, transmission electron microscopy, TUNEL assay, and gene expression analysis, while organ condition was assessed using a Health Assessment Index (HAI). The proportion of TUNEL-positive cells in the gills and mantle differed significantly between sites (p < 0.05), with higher levels in oysters from the farming site. In contrast, TUNEL-positive cells in the digestive gland did not differ significantly between sites, although brown cells were observed only in the digestive gland of oysters from the breeding site, suggesting possible physiological stress. To assess the expression level of dad1 in oysters cultured under different conditions, RT-qPCR revealed no significant difference between the two sites. The breeding site also had lower temperature and salinity than the farming site. Overall, these findings suggest that site-specific environmental conditions may influence gill health and stress-related responses in C. belcheri, providing baseline information for oyster health assessment and aquaculture management. Full article

Background/Objectives: Sex differences in ST-elevation myocardial infarction (STEMI) outcomes persist despite advances in primary percutaneous coronary intervention (PCI), but whether female sex independently influences early mortality remains unclear. study aimed to assess sex-based differences in clinical characteristics, management, in-hospital outcomes and to determine whether female sex independently predicts in-hospital mortality. Methods: This retrospective observational study included 512 consecutive patients with STEMI presenting within 6 h of symptom onset and treated with primary PCI. Clinical, laboratory, echocardiographic and angiographic data were analyzed. The primary endpoint was in-hospital mortality. Multivariable logistic regression identified independent predictors of mortality. Results: Women comprised 32.0% of the cohort and were older than men (median 69 vs. 59 years, p < 0.001), with a higher prevalence of diabetes and hypertension, but lower rates of smoking (all p < 0.001). Women had lower hemoglobin levels and a higher prevalence of moderate-to-severe mitral regurgitation (17.1% vs. 8.0%, p = 0.004). Procedural characteristics, including door-to-balloon time and complete revascularization, were similar between sexes. Crude in-hospital mortality was higher in women (13.4% vs. 7.5%, p = 0.047); however, female sex was not independently associated with mortality after adjustment (adjusted OR 1.07, 95% CI 0.48–2.41; p = 0.864). Lower LVEF and reduced GFR were the strongest independent predictors of death. Conclusions: Higher mortality in women is primarily driven by a more adverse clinical profile rather than sex itself, emphasizing the importance of early risk stratification and management. Full article

Background/Objectives: Microtubule-targeting agents represent a pillar of cancer chemotherapy; however, their clinical utility is constrained by significant toxicity, pharmacokinetic instability, and susceptibility to multidrug resistance transporters. This study aimed to explore the impact of replacing substituted phenyl rings with a naphthalene moiety in sulfonamide-based colchicine-site ligands, with the goal of identifying new antiproliferative candidates with improved profiles. Methods: We designed, synthesized, and evaluated a library of 35 naphthalene sulfonamides bearing varied aryl groups and sulfonamide nitrogen substituents. We assessed the antiproliferative activity against multiple cancer cell lines. Mechanistic studies, including fluorescence microscopy, cell cycle analysis, and cell death assays, were performed to evaluate the effect of these compounds on microtubule polymerization dynamics and cell fate. Molecular docking and in silico pharmacokinetic profiling were carried out to support the proposed binding mode at the colchicine site and to assess drug-likeness. Results: Exclusively, compounds bearing a trimethoxyphenyl group showed antiproliferative activity in the submicromolar range, thus identifying it as a structural requirement. The most potent compound (2) reached double-digit nanomolar IC₅₀ values (67–104 nM) across multiple cancer cell lines. Microscopy confirmed intracellular disruption of microtubule polymerization. Unlike colchicine, these compounds did not induce canonical mitotic arrest but instead triggered apoptotic cell death. In silico analyses supported binding at the colchicine site and revealed favorable predicted pharmacokinetic properties. Conclusions: The naphthalene sulfonamides described herein demonstrate potent antiproliferative activity through a distinct mechanism compared to colchicine, and their favorable in silico profiles position them as promising candidates for further development as antitumor agents. Full article

Background: Onconephrology is an emerging field addressing renal and cardiovascular complications in patients with cancer. Kidney disease and cardiovascular risk frequently coexist and may significantly affect oncological outcomes. Methods: We conducted a single-center, prospective, observational study including adult oncological patients. Patients were evaluated at baseline and after 1, 3, and 12 months. Renal outcomes (Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), AKI on CKD, Acute Kidney Disease (AKD)), cardiovascular risk assessment scores (using the SCORE/SCORE2 systems), and major adverse kidney events (MAKEs) were recorded. Results: Eighty-three patients were enrolled (mean age 69.8 ± 11.6 years, 60.2% male). At baseline, AKI was present in 30.4%, CKD in 27.8%, and AKI on CKD in 16.5% of patients. Overall, 96.7% of the cohort was classified as having a high or very high cardiovascular risk. During follow-up, 18.1% experienced new AKI, and MAKEs occurred in 30.4% of patients, driven primarily by mortality. Male sex emerged as the main predictor of death. Conclusions: Onconephrology patients suffer from a high burden of renal disease and cardiovascular risk. Integrated nephrological and cardiovascular assessment may represent a key component of personalized cancer care. Full article

Troponin T is a molecular marker of cardiomyocyte injury, whereas left ventricular ejection fraction (LVEF) and tricuspid regurgitation velocity (TRV) reflect downstream ventricular and cardiopulmonary measures. This study evaluated whether synchronized troponin T and echocardiographic data can identify mortality risk in critically ill patients with heart failure, while separating statistical association from clinically meaningful incremental discrimination. Adult intensive care unit admissions with heart failure diagnoses were identified from MIMIC-IV and MIMIC-IV-ECHO. The primary endpoint was 28-day all-cause mortality; one-year mortality was secondary. Multivariable Cox models were adjusted for demographics, comorbidity, illness severity, organ support, and laboratory covariates. Restricted cubic splines, proportional hazards diagnostics, variance inflation factors, prespecified subgroup interaction tests, complete-case analyses, and multiple imputation sensitivity analyses were performed. The final cohort included 4362 patients, and 1072 patients (24.6%) died within 28 days. In the primary complete-case Cox model (n = 2087; 659 deaths), higher log-transformed troponin T was associated with higher 28-day mortality (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.03–1.15; p = 0.003), and higher LVEF was associated with lower mortality (HR per percentage point, 0.99; 95% CI, 0.99–1.00; p = 0.004). After severity and organ-support covariates were entered, troponin T and LVEF produced statistically detectable but very small C-statistic gains. Measurable TRV was available in 1546 patients and was associated with mortality in that subset (HR, 1.28; 95% CI, 1.08–1.52; p = 0.005). Troponin T, LVEF, and TRV were associated with mortality in ICU heart failure. Their contribution was best interpreted as risk enrichment within a clinical severity framework rather than a stand-alone decision rule. Full article

Sudden death syndrome (SDS) and soybean cyst nematode (SCN) are major yield-limiting diseases in North American soybean production, with limited effective management options. Long-term soybean monoculture has been reported to suppress SDS and SCN, but the mechanisms, onset, and persistence of such suppression remain poorly understood. To study these mechanisms, a six-year field study (2018–2023) was conducted at two Ontario sites with contrasting disease histories: Chatham (conducive) and Essex (suppressive). We evaluated suppression development and resilience across soybean monoculture (SSSSSS) and corn–soybean rotations (SCSCSC/CSCSCS), using eight cultivars differing in SDS and SCN resistance across two maturity groups. In Chatham, disease index (DX) progressively declined under monoculture; the most susceptible cultivar, HS11RY07, declined from a mean DX of 89 to 43 by year six, with corresponding yield increases, and rotational yield advantages diminished. In Essex, introducing corn rotation increased SDS symptoms during soybean phases; monoculture yields became comparable to rotation in later years. Importantly, suppression developed without corresponding reductions in Fusarium virguliforme and SCN populations, which remained variable across years, suggesting that monoculture may disrupt pathogen effectiveness rather than eliminating it. This decoupling of pathogen abundance and disease severity is consistent with soil-mediated biological suppression; the microbial drivers are addressed in subsequent work. Full article

Background/Objectives: Spinal ependymoma is the most common intramedullary spinal cord tumor in adults, and maximal safe resection is the cornerstone of treatment. Patients aged 75 years and older are underrepresented in surgical neuro-oncology cohorts. We sought to characterize treatment patterns and identify predictors of overall survival in very elderly patients with spinal ependymoma. Methods: We performed a retrospective cohort study of patients aged 65 years or older with spinal ependymoma using the National Cancer Database. The primary cohort was patients aged 75 years or older (very elderly); patients aged 65–74 years served as a comparison cohort. Multivariable Cox proportional-hazards models were fit within each cohort, and a surgery-by-age-cohort interaction was tested. Results: Of 1497 eligible patients aged 65 years or older with spinal ependymoma, 422 patients (28.2%) met criteria for the final analytic cohort. Intramedullary versus extramedullary tumor status was not available in the NCDB PUF and therefore could not be characterized. Very elderly patients were less likely to undergo surgery than the comparison cohort (70% vs. 85%; p < 0.001) despite similar tumor characteristics. Among very elderly patients, median overall survival was 59.7 months without surgery and 106.0 months with surgery, an approximately 46-month difference favoring surgery. Surgery was independently associated with lower mortality (HR 0.46; 95% CI, 0.24–0.89; p = 0.021). Increasing age (HR 1.15 per year; 95% CI, 1.07–1.22; p < 0.001), Charlson–Deyo score ≥ 2 (HR 4.41; 95% CI, 1.65–11.79; p = 0.003), and increasing tumor size (HR 1.02 per mm; 95% CI, 1.01–1.04; p < 0.001) were also independently associated with worse survival. In the 65–74 cohort, no significant association between surgery and overall survival was detected (HR 1.23; 95% CI, 0.54–2.81; p = 0.623), though statistical power was limited by only 7 deaths in the no-surgery arm. The surgery-by-age-cohort interaction was significant (HR 0.37; p = 0.043). Conclusions: Surgical resection was independently associated with improved overall survival in very elderly patients with spinal ependymoma despite lower utilization. Chronological age alone may be an imperfect basis for excluding older adults from surgical consideration. Full article

Objectives: To evaluate associations between social vulnerability and rheumatoid arthritis (RA)-related mortality in the United States, with emphasis on domain-specific effects of the Social Vulnerability Index (SVI). Methods: We conducted a county-level ecological study of RA-related mortality from 2010 to 2019 using age-adjusted mortality rates and the Centers for Disease Control and Prevention SVI. Gamma regression models examined associations between RA mortality and overall SVI and four thematic domains, including socioeconomic status, household composition and disability, minority status and language, housing type and transportation by using both continuous and quartile-based measures. Results: Between 2010 and 2019, 354,280 deaths occurred among individuals with RA, corresponding to a mean age-adjusted mortality rate of 9.7 per 100,000 population. In multivariable analyses adjusting for all SVI domains, household composition and disability vulnerability demonstrated the strongest and most consistent positive association with mortality, with a dose–response relationship across quartiles. Housing type and transportation vulnerability showed a modest positive association. Minority status and language vulnerability was inversely associated with mortality, whereas socioeconomic vulnerability was not significant in continuous models but demonstrated an inverse association with mortality in quartile-based analyses. Conclusions: RA mortality is differentially associated with specific domains of social vulnerability rather than overall vulnerability burden. Household composition and disability represent clinically salient risk factors, demonstrating the relevance of functional status and caregiving context in RA outcomes. Domain-specific assessment of social vulnerability may enhance clinical risk stratification and inform more targeted, patient-centered RA management. Full article

In 2025, the Democratic Republic of the Congo (DRC) experienced its 16th Ebola Virus Disease (EVD) outbreak, centered in the Bulape Health Zone of Kasai Province, amid multiple concurrent epidemics and limited health infrastructure. Genomic sequencing revealed a novel zoonotic spillover genetically related to the 1976 Yambuku strain. A Root Cause Analysis (RCA) using the “5 Whys” framework, integrating epidemiological data, genomic analysis, and surveillance reports, identified key contributors to delayed detection and response, with comparative insights drawn from the 2018–2020 North Kivu outbreak. The Mweka outbreak resulted in 28 confirmed, probable, or suspected cases and 15 deaths, including four healthcare workers. Root causes included inadequate ecological surveillance, weak community alert systems, diagnostic delays due to reliance on centralized laboratories, health system overload from concurrent outbreaks, and structural underfunding of preparedness and coordination. Unlike North Kivu, where security issues drove response delays, systemic and ecological vulnerabilities predominated in Mweka. These findings highlight how ecological and structural weaknesses facilitate novel Ebola spillovers and their escalation, emphasizing the need for sustained investment in One Health surveillance, decentralized diagnostics, and resilient public health governance to strengthen outbreak response capacity. Full article

The prevalence of diabetes and heart failure rises sharply with age, and their coexistence amplifies cardiovascular and renal risk. Elderly patients display unique clinical and biological profiles characterised by frailty, multimorbidity, and pharmacodynamic variability that challenge conventional treatment strategies. Sodium–glucose co-transporter-2 inhibitors (SGLT2i) have emerged as a cornerstone of cardio–renal–metabolic protection, with the most consistent cardiovascular benefit being the reduction in heart failure hospitalisation, whereas effects on cardiovascular death and major adverse cardiovascular events vary according to baseline cardiovascular risk, heart failure phenotype, diabetic status, and trial design. However, real-world use among the elderly remains limited due to concerns about tolerability, polypharmacy, and cost. This review analyses the pharmacological rationale and evidence base for SGLT2i therapy in older adults, highlighting mechanisms beyond glucose control, quantitative data from pivotal trials, and practical issues for geriatric implementation. Full article

Background/Objectives: Recognizing and managing grief is particularly important in nursing, especially from the perspective of family caregivers. In this qualitative study, we aim to understand the grieving process of family caregivers, focusing on what happens before the death of an adult family member due to chronic illness, and to identify the factors influencing the grieving process in this context. Methods: This study is an outcome of a broader study which aimed to understand how family caregivers grieve during the first year following the death of an adult family member due to a chronic illness. This article will only address the influencing conditions that emerged from data related to events that occurred prior to the person’s death. A theoretical sample was gathered through semi-structured interviews with 20 bereaved family caregivers. Data were collected and then analyzed independently by the research team using the three stages and principles of Strauss and Corbin’s grounded theory. Results: Adaptation was identified as the central category. Before death, the family caregiver undergoes two adaptive processes: adapting to their new role and preparing for the imminent loss. As they adapt to this loss, they become aware of the seriousness of the illness and the inevitability of death, opening the possibility for the grieving process to begin. The process is influenced by personal and contextual factors as well as interaction-related factors, including access to information, satisfaction with the care provided, recognition of their efforts, and feelings of abandonment or interaction with healthcare professionals. A wide range of emotions and feelings are experienced. This experience is colored by hope and anticipatory grief. The meaning of the dying process is explored and expectations are redefined. Conclusions: The grieving process experienced by family caregivers is an adaptive process that begins before the patient’s death. Some conditions can be modified before the patient’s death; in this case, nurse interventions can enhance the experience of family caregivers. Full article

Invasive cervical cancer is a very common cause of cancer death in women worldwide, primarily due to late detection of this cancer. The clinical manifestations of cervical cancer vary significantly and are difficult to predict. Finding new effective biomarkers for the early detection of cervical cancer is essential to reducing mortality. Small microRNA molecules have also recently emerged as potential biomarker candidates in the diagnosis of cervical cancer. Despite analytical limitations in microRNA assays and the lack of automated and standardized tests, validated and prospective systematic evaluation of this new parameter in cervical cancer deserves further development. This review describes the importance and potential usefulness of microRNAs in detecting cervical cancer at an early stage, monitoring the course of the disease, and assessing the effectiveness of treatment. The diagnostic importance of microRNAs is well documented in many publications, suggesting that, as microRNA research progresses, they may become a useful diagnostic tool for cervical cancer. Full article

Lipid peroxidation (LPO) is a process where polyunsaturated fatty acids (PUFA) in cellular membranes are oxidized. This process is mediated by reactive oxygen species (ROS) and leads to the formation of reactive products, including 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), and oxidized phospholipids. At low concentrations these products act as second messengers in adaptive redox signalling and metabolic homeostasis, whereas at higher concentrations they compromise membrane integrity and promote cell death. Lipid peroxidation plays a crucial role in anticancer therapies. Here we focus on three mechanistically complementary drugs—sorafenib, cisplatin, and olaparib—because each converges, directly or indirectly, on the redox/LPO axis (system xc−/GPX4 modulation, mitochondrial ROS, and SLC7A11 regulation, respectively), modulating tumor cell responses by inducing PUFA oxidation, mitochondrial dysfunction, and membrane damage. However, tumor cells have several protective pathways against oxidative stress, such as increased expression of glutathione peroxidase 4 (GPX4), the SLC7A11 system Xc, and detoxification of reactive aldehydes. Enrichment of membranes with PUFA increases susceptibility to lipid peroxidation and ferroptosis, thereby sensitizing tumor cells to therapy, whereas enrichment with monounsaturated fatty acids (MUFA), driven by the SREBP1–SCD1 axis, limits peroxidation and confers resistance. Among regulated cell death modalities, ferroptosis is strictly dependent on lipid peroxidation, whereas apoptosis, necrosis, necroptosis, pyroptosis, and immunogenic cell death can be modulated by lipid peroxidation but do not universally require it. Collectively, these mechanisms indicate that lipid peroxidation is an important—though not exclusive—determinant of anticancer drug sensitivity and resistance, and that its dual, context-dependent role (tumor-suppressive at high flux, tumor-promoting under chronic, sub-lethal exposure) must be considered when designing LPO-based therapeutic strategies. Full article

As liver cancer is a leading cause of death all over the world, there is a need to explore new therapeutic strategies. This study presents an in silico analysis of the genes Caspase₃ (CASP₃), Caspase₉ (CASP₉), and BCL-2-associated X protein (BAX) in liver cancer cells to evaluate the apoptosis profile following exposure to green-synthesized plant extract. We assessed the modulatory effects of phytochemicals on the apoptotic pathway by means of bioinformatics tools and a publicly available gene expression dataset. Our findings revealed the possible mechanistic basis of the pro-apoptotic activity observed in vitro, utilizing a structure-based molecular docking method. The biologically synthesized AgNPs at a concentration of 50 µg/mL induced an approximately 4-fold increase in the mRNA expression levels of CASP3, CASP9, and BAX compared with chemically synthesized AgNPs, as determined by qPCR. Rutin was the compound with the highest binding affinities toward all three proteins, with ΔG values of −9.3 kcal/mol (Caspase₃), −9.1 kcal/mol (Caspase₉), and −9.0 kcal/mol (BAX). These findings offer new insights about the molecular mechanisms that support the cytotoxicity of phytochemicals, and simultaneously highlight the potential of green nanotechnology for the development of therapeutic strategies for liver cancer. Full article

Background: mRNA vaccines, first approved in December 2020, have been used globally to prevent infectious diseases, and those for treating cancers are being developed. Safety-related labelling changes of Comirnaty and Spikevax were made in June 2025; however, concerns remain. This study assessed the potential risks associated with mRNA vaccines on the indications previously approved, utilizing Real-World Data (RWD) of Adverse Events Following Immunization (AEFIs) derived from the Vaccine Adverse Event Reporting System (VAERS) and Academic Literature Databases (ALD). Methods: A Disproportionality Analysis (DPA) was performed using the Reporting Odds Ratio (ROR) and the Bayesian Confidence Propagation Neural Network (BCPNN) algorithm on spontaneous case reports from VAERS. Statistical positive signals were cross-validated with literature case reports from ALD to provide more comprehensive medical descriptions and clearer causal assessments, and compared with safety information documented in clinical trials and on vaccine labelling. Time-to-onset, stratified, and immunization schedule analyses were conducted to characterize the safety profiles of mRNA vaccines. Results: In total, 5,040,725 spontaneous case reports and 4,387 literature case reports were analyzed. In both VAERS and ALD, new signals involving blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) and ear and labyrinth disorders (e.g., deafness) were detected from Comirnaty as Designated Medical Events (DMEs), while blood and lymphatic system disorders (e.g., thrombotic thrombocytopenic purpura) from Spikevax in ALD only. No new signals were detected from other vaccines on the DMEs list. In VAERS, Serious Adverse Events (SAEs) were more common in females, while death risk was higher in males. In ALD, SAEs were more common in males for most mRNA vaccines, except Comirnaty. Medical history emerged as a key risk factor for SAEs, particularly among older adults. Conclusions: Statistically significant safety signals were detected across all mRNA vaccines based on five-year cumulative RWD, indicating the need of intensified monitoring of specific populations, including older adults and individuals with medical histories, alongside further optimization of vaccination strategies. Full article