Search Results (3,990)

Aquatic ecological issues have garnered significant attention in recent years, driving the demand for convenient, effective, and systematic assessment methods in environmental risk evaluation. This review provides a comprehensive introduction to methodologies for assessing the toxicity of chemicals toward aquatic microorganisms, which include viruses, bacteria, fungi, protozoa, and algae. Among these, microalgae are commonly used as model organisms due to their relative simplicity. The article details conventional biological methods, general chemical techniques, modern instrumental analyses, and informatics approaches, with a particular focus on algae and bacteria as model organisms for toxicity assessment. The principles, advantages, and limitations of each method are discussed, along with examples of their application in various contexts. Biological methods offer direct visualization, convenience, and rapid results, while modern instrumental techniques enable mechanistic insights at molecular and biochemical levels. Informatics methods facilitate toxicity evaluation in complex systems. While aquatic microorganisms encompass viruses, fungi, protozoa, bacteria, and algae, this review primarily focuses on bacteria and algae as model organisms due to their ecological relevance, sensitivity, and widespread use in standardized assays. Full article

Introduction: Women with breast cancer experience psychological distress, and resilience-strengthening psychosocial support may improve their quality of life (QoL). Identifying those at risk of low QoL is challenging. This study evaluated the cost-effectiveness of a machine learning-based QoL predictor to support clinical decision-making regarding psychosocial support (sample size: 660). Methods: A decision tree cost–utility model was developed to compare four decision-making strategies in offering psychosocial support: the clinician alone, the QoL predictor alone, the clinician supported by the predictor, and no prediction with no psychosocial support. QoL after one year was used as a proxy for resilience. Costs, health outcomes, and net monetary benefits (NMBs) were estimated using a one-year time horizon. Incremental cost-effectiveness ratios (ICERs) were calculated and dominance assessed. A societal scenario analysis incorporated productivity losses. A probabilistic sensitivity analysis generated cost-effectiveness acceptability curves. Results: Clinicians supported by the QoL predictor produced the highest NMB (EUR 16,349) and the greatest quality-adjusted life year (QALY) gain (0.759), with an ICER of EUR 22,892 compared with the next least costly strategy. Clinician-only prediction and predictor-only approaches were dominated or extendedly dominated. Under the societal perspective, all strategies produced negative NMB values due to productivity losses, but the overall ranking remained unchanged. The probabilistic sensitivity analysis showed that the combined clinician and predictor strategy had a 69% probability of being cost-effective at a willingness to pay threshold of EUR 30,000. Conclusions: Combining clinician judgement with the machine learning-based QoL predictor improved the targeting of psychosocial support and was the most cost-effective strategy. Further prospective and comparative studies are needed to confirm its long-term effectiveness and cost-effectiveness in clinical practice. Full article

Introduction: Patients with extremely elevated IL-6 levels remain poorly characterized, and no specific plasma concentration has been established to reliably predict mortality or guide immunomodulatory interventions. We hypothesized that extreme hypercytokinemia is associated with increased mortality in sepsis. The primary objective was to identify, in patients with hyperinflammatory endotype, an IL-6 threshold associated with a significantly elevated risk of death. Methods: We conducted a retrospective, single-center observational study based on a historical cohort of adult patients with consecutive activation of the in-hospital sepsis code, a prospective and standardized institutional care pathway, at Vall d’Hebron University Hospital between July 2018 and December 2024. Patients fulfilling Sepsis-2 diagnostic criteria and criteria for severe sepsis or septic shock were eligible. Plasma interleukin-6 (IL-6) levels were routinely determined in all patients. The analysis included patients with complete clinical and laboratory data available in the study database. To identify the IL-6 threshold associated with critical risk of death, a cumulative conditional relative frequency analysis was performed. A quantile-based analysis was conducted using predefined intervals of 1000 pg/mL and 15,000 pg/mL. A multivariable logistic regression analysis was conducted to identify clinical and laboratory parameters independently associated with IL-6 > 15,000 pg/mL and outcome. Results are presented as odds ratios (ORs). Survival differences were assessed using Kaplan–Meier analysis. Results: Overall mortality was 31% in the 1669 patients analyzed. Median IL-6 concentration was 772 pg/mL (IQR: 164–8750 pg/mL) with significantly higher levels in non-survivors (2137 pg/mL, IQR: 267–34,758). A critical IL-6 cutoff of 14,930 pg/mL was identified, which was rounded to 15,000 pg/mL for clinical applicability. IL-6 > 15,000 pg/mL was associated with increased mortality (OR 2.22, 95% CI: 1.12–5.36). Kaplan–Meier analysis revealed significantly reduced survival in patients above this IL-6 threshold (p < 0.0001). Conclusions: In this cohort of patients with severe sepsis or septic shock, plasma IL-6 levels > 15,000 pg/mL defined a critical threshold beyond which mortality risk exceeded survival probability. Critical hypercytokinemia may serve as a clinically relevant biomarker to identify patients with sepsis and multiorgan dysfunction who could benefit from precision immunomodulatory therapies. Full article

Introduction: The potential impact of vitamin D deficiency on cancer risk and oncological management remains under investigation. The study aimed to analyse vitamin D information exposure, attitudes, and practices, including the use of vitamin D and other supplements as well as serum 25-hydroxyvitamin D [(25(OH)D)] testing, among breast cancer and prostate cancer survivors in the context of patient–physician communication. Material and methods: This cross-sectional survey included 145 breast and prostate cancer survivors (mean age 62.2 ± 9.9 years) who participated using an original, validated questionnaire. Results: Between cancer diagnosis and survey completion, more than 52% of respondents reported vitamin D supplementation, and nearly 65% declared using supplements other than vitamin D in relation to their cancer. However, only 17.3% of respondents had been instructed by their physician to take vitamin D, and only 5.5% had been ordered by their physician to have their serum 25(OH)D levels tested. The majority of respondents (94%) perceived the need for physicians to routinely order vitamin D level tests for patients diagnosed with cancer. Only 39.5% of vitamin D users and 7.5% of other supplement users stated that their oncology care physicians knew about their supplement intake. The most common reason for patients not to inform their physician about taking vitamin D and/or other supplements was that the physician did not ask about this issue. Almost all aspects analysed showed greater health information exposure and better communication skills with physicians among women than among men. Conclusions: It appears reasonable to improve physician–patient communication and broaden consideration of patients’ needs, which suggests a direction for further studies on the role of routine 25(OH)D testing in the standard care of patients with breast and prostate cancer. Full article

Background: Globally, an estimated 1.4 billion people had hypertension in 2014, yet only just over 20% had controlled blood pressure, and about 580 million remained undiagnosed. Evidence indicates that salt substitutes facilitate meaningful blood-pressure reductions, yet their implementation remains restricted by social and healthcare constraints. The comparative effectiveness of alternative sodium-reduction interventions for elevated blood pressure remains unclear, limiting their introduction across diverse clinical and public health contexts. This study is registered with PROSPERO (CRD420251130153). Methods: We systematically searched PubMed, MEDLINE, and supplementary sources for randomised controlled trials (RCTs) published between 2000 and 2025. All behavioural sodium-reduction interventions among populations with elevated blood pressure, including hypertension, were included. The mean difference in systolic blood pressure (SBP) was the primary outcome, as evidence indicates that intensive control of SBP to levels below 120–130 mmHg is significantly associated with a reduced risk of major cardiovascular disease (CVD) and all-cause mortality. Network and subgroup pairwise meta-analyses were performed, with sensitivity analyses conducted to assess robustness of the findings and subgroup analyses used to explore clinical and public health factors influencing intervention effectiveness (clinical factors: blood pressure stage, trial duration, and medication status; public health factors: setting, implementation period, and country income level). Results: Of 10,404 records identified, 42 studies (46 trials, n = 46,771) were included. While the use of salt substitutes was ranked the most effective intervention in the network meta-analysis, with reductions of −6.78 mmHg (95% CI, −8.42, −5.14) compared to no intervention and −5.35 mmHg (95% CI, −7.89, −2.81) compared to conventional health education, self-monitoring devices and low-sodium diets, when combined with health education, demonstrated similar magnitudes of SBP reductions. Digital health education showed a larger point estimate for SBP reduction by −3.59 mmHg (95% CI −7.40 to 0.22) than conventional education (−1.43 mmHg; 95% CI −3.49 to 0.63), but both confidence intervals crossed zero, indicating no statistically significant difference. Subgroup analyses indicated that, except for trial duration, intervention setting, and country income level in specific intervention comparisons, clinical and public health factors did not generally account for differences in SBP reduction. No evidence of publication bias was observed, except between salt substitutes and no intervention and low-sodium diets and no intervention. Conclusions: Network meta-analysis ranked the use of salt substitutes as the most effective intervention, yet self-regulated interventions, such as low-sodium diets and self-monitoring devices, when combined with education-based sodium-reduction approaches, showed comparable point estimates for SBP reductions. Digital health education showed promise as a supportive adjunct to self-regulated interventions, although its effects were variable and require further quantification. These findings underscore the need for alternative sodium-reduction interventions supported by digital or conventional health education to improve blood pressure control. Health education on sodium reduction, including clinical counselling, should be viewed primarily as a complementary component that enhances other interventions. Full article

Kidney transplantation remains the ultimate treatment option for patients with end-stage renal disease. However, the global shortage in donor kidneys, exacerbated by challenges such as ischemia–reperfusion injury (IRI), reduces renal graft viability and negatively impacts post-transplant outcomes. Static cold storage, the gold standard of organ preservation, reduces metabolic demand but increases the risk of cold-induced mitochondrial dysfunction and IRI, especially in marginal kidneys. The introduction of machine perfusion techniques allows renal grafts and other solid organ grafts to be preserved at a wider range of temperatures. Organ preservation temperatures play an important role in determining post-transplant outcomes in the transplantation of the kidney and other transplantable solid organs. Therefore, determining the optimal preservation temperature may help increase organ utilization by avoiding unnecessary graft discards and increasing the safe use of marginal organs. This review discusses the impact of various preservation temperatures and methods of preservation on post-transplant outcomes in renal grafts and other organ grafts. Drawing from preclinical, clinical, and meta-analytic studies, we compare hypothermic (0–4 °C), moderate hypothermic (10 °C), subnormothermic (20–32 °C), normothermic (35–37 °C), and subzero preservation strategies, and cellular and molecular changes that occur in renal grafts and other solid organ grafts during preservation at these temperatures. Overall, temperature-controlled machine perfusion outperforms static preservation of renal grafts and other solid organ grafts from marginal and deceased donors, potentially expanding donor pools and improving long-term graft survival, and suggests the need for future research to determine optimal preservation temperature for renal grafts and other solid organ grafts to improve viability and post-transplant outcomes. Full article

Introduction: Telomeres, which protect chromosome ends, are important in cell replication and are altered by ageing. In the realm of organ transplantation, telomere length has emerged as a potential biomarker for predicting both graft survival and recipient longevity. This study explores the correlation of telomere length with transplant outcomes to assess whether longer telomere length is associated with better long-term graft function and patient survival. Methods: Telomere length (TL) was analysed in 274 European renal transplant pairs (donors/recipients). Recipient DNA was collected before and after kidney transplantation, and donor DNA just prior to transplant surgery. Results: Donor TL was not significantly associated with graft survival. Donor age was a significant predictor of graft failure (1.02, 95% CI: 1.01–1.03, p < 0.01). Post-transplant recipient TL had a significant association with graft survival. Longer TL was associated with an up to 90% reduction in risk of graft failure (HR = 0.10, 95% CI: 0.015–0.71, p = 0.02). Conclusions: In this study, kidney transplant recipients with longer telomere length demonstrated significantly better long-term graft survival. If validated in additional kidney transplant cohorts, recipient telomere length could serve as a valuable biomarker for improving graft failure risk stratification and enhancing the long-term care of transplant recipients. Full article

Introduction: Alcohol consumption is a significant risk factor for hypertension (HTN), a prevalent condition that substantially affects cardiovascular health. In Peru, where various traditional alcoholic beverages exist, the relationship between alcohol consumption and HTN has not been fully explored. Objective: To determine the association between different patterns of alcohol consumption, types of beverages, and various types of HTN. Methods: This cross-sectional analytical study utilized data from the Peruvian Demographic and Family Health Survey (2018–2023), including 236,243 adults (55.95% male; mean age: 41.06 years). General HTN, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH) were evaluated. Alcohol consumption was assessed through self-reported questionnaires evaluating consumption pattern (non-excessive vs. excessive), intensity (light, moderate, heavy), consistency (intermittent vs. consistent), and primary beverage type, including both commercial and traditional Peruvian drinks. Results: Excessive alcohol consumption was significantly associated with an increased risk of HTN (aPR: 1.19, 95% CI: 1.07–1.31), IDH (aPR: 1.61, 95% CI: 1.20–2.16), and SDH (aPR: 1.45, 95% CI: 1.18–1.78). Excessive alcohol consumption was significantly associated with an increased risk of HTN (aPR: 1.19, 95% CI: 1.07–1.31), IDH (aPR: 1.61, 95% CI: 1.20–2.16), and SDH (aPR: 1.45, 95% CI: 1.18–1.78). Consumption of traditional beverages such as chicha and Masato was associated with an elevated risk of various types of HTN. In contrast, wine consumption demonstrated a protective association against general HTN and IDH. Conclusions: Alcohol consumption patterns and beverage types have differential effects on HTN risk in the Peruvian population. These findings underscore the need for culturally adapted prevention strategies and more nuanced public health recommendations regarding alcohol consumption in Peru. Full article

Introduction: Smoking is a known risk factor for cardiovascular diseases, but its specific relationship with blood pressure remains a topic of debate. Recent studies suggest that different aspects of smoking behavior, such as intensity and duration, may have distinct effects on blood pressure. Objective: To evaluate the association between different measures of smoking behavior and blood pressure in the Peruvian population. Methodology: A cross-sectional analysis was conducted using data from the Peruvian Demographic and Family Health Survey (DHS) from 2018 to 2023. Multiple aspects of smoking were assessed, including current smoking status, intensity, duration, and the global tobacco index. Multiple linear regression models were used to examine the association between these measures and systolic (SBP) and diastolic (DBP) blood pressure, adjusting for sociodemographic and health variables. Results: A significant association was found between smoking intensity and elevated blood pressure. Smokers of 20 or more cigarettes per day showed an increase of 6.82 mmHg in SBP (95% CI: 2.90, 10.75) and 5.07 mmHg in DBP (95% CI: 2.44, 7.70) compared to non-smokers. The global tobacco index and smoking duration showed weaker and more variable associations with blood pressure. Conclusions: Smoking intensity, rather than other measures of smoking behavior, is more strongly associated with blood pressure levels. These findings highlight the importance of considering smoking intensity in cardiovascular risk assessment and suggest that prevention strategies should focus not only on cessation but also on reducing smoking intensity. Full article

The introduction of direct oral anticoagulants (DOACs), particularly factor Xa (FXa) inhibitors, has transformed the prevention and treatment of thromboembolic events. These agents have largely replaced vitamin K antagonists across most indications due to their predictable pharmacokinetics, reduced rates of intracranial bleeding, and overall ease of use. Nevertheless, a substantial residual bleeding risk remains, particularly gastrointestinal bleeding and clinically relevant non-major bleeding in elderly, frail, or polymedicated patients. Furthermore, the management of patients with severe renal dysfunction, active cancer, especially gastrointestinal or genitourinary malignancies and those requiring complex pharmacological regimens, continues to pose significant challenges. These limitations have intensified interest in targeting earlier steps of the coagulation cascade, specifically factor XI (FXI) and its activated form (FXIa). FXI occupies a unique mechanistic position: it contributes substantially to pathological thrombosis while playing only a limited role in physiological hemostasis. Genetic, observational, and mechanistic evidence consistently demonstrates that FXI deficiency confers protection against venous thromboembolism and cardiovascular events while causing minimal spontaneous bleeding. This biological paradigm has catalyzed the development of novel FXI/FXIa inhibitors, including small-molecule agents (asundexian, milvexian) and biological therapies (abelacimab). Clinical trials such as AXIOMATIC-TKR, PACIFIC-AF, and OCEANIC-AF, and ongoing programmes including ASTER and MAGNOLIA suggest that FXI inhibition may preserve antithrombotic efficacy while substantially reducing bleeding risk. This review summarizes the current landscape of oral FXa inhibitors, outlines the biological rationale for FXI/FXIa inhibition, and discusses the evolving clinical evidence supporting what may represent the next major advance in anticoagulant therapy. Full article

Fetal acidemia, caused by impaired gas exchange between the fetus and the mother, is a leading cause of stillbirth and neurologic complications. Early prediction is therefore essential to guide timely clinical intervention. Several strategies rely on cardiotocography (CTG), which combines fetal heart rate (fHR) with uterine contractions and has led to development of clinical guidelines for CTG interpretation and the introduction of different fHR features. Additionally, ST event analysis, investigating changes in the ST segments of the fetal electrocardiogram (fECG), has been proposed as a complementary tool. This narrative review adopts a systematic approach, with comprehensive searches in Embase and PubMed to ensure full coverage of the available literature, and summarizes findings from 30 studies. Clinical guidelines for CTG interpretation frequently lead to intermediate risk level annotations, leaving the final decision regarding fetal management to clinical experience. In contrast, various fHR features can successfully discriminate between fetuses developing acidemia and healthy controls. Evidence regarding the added value of ST events derived from the scalp electrode remains conflicting, due to concerns about invasiveness. Recent studies on machine learning models highlight their ability to integrate multiple fHR features and improve predictive performance, suggesting a promising direction for enhancing acidemia prediction during labor. Full article

The management of rheumatoid arthritis (RA) has undergone several practice-defining evolutions, beginning with the approval of low-dose methotrexate and continuing through the introduction of numerous disease-modifying antirheumatic drugs (DMARDs). With increasing capability to target pro-inflammatory pathways, successive therapeutics have carried the promise of improved disease control for patients with RA; however, many patients still fail to meet treatment objectives, leading to the recognition of clinical phenotypes that remain therapeutically challenging under the current treat-to-target standard of care, including preclinical inflammatory arthritis, late-onset RA, and treatment-resistant RA. Precision medicine approaches are beginning to characterize the pathogenesis of RA in such populations, and to inform effective tailoring of DMARD therapy to individual patients. Simultaneously, observational data derived from clinical practice are increasingly being used to understand the risks and benefits of long-term DMARD therapy under real-world conditions of use, with registries and other observational sources confirming long-term effectiveness, revising safety profiles, and estimating the costs of treatment for approved therapies. Together, these strategies offer opportunities to address unmet needs in the care of patients with RA. In this review of peer-reviewed clinical and translational research in RA, we identify several clinical phenotypes that demonstrate inadequate response to guideline-directed therapy and review frontiers in clinical research in RA emerging over the last decade, highlighting the use of precision medicine and real-world evidence-based approaches to advance individualized, patient-centered care. Full article

Introduction: Mounting evidence indicates that the p53 Pro72Arg single-nucleotide polymorphisms (SNPs) may play a role in modulating hepatocarcinogenesis in the setting of chronic HBV infection. However, there is currently a lack of studies focusing on this genetic variant in Indonesia, a country characterized by its diverse genetic landscape comprising over 1300 distinct ethnic groups. We aimed to investigate the association between the p53 Pro72Arg polymorphism and the risk of hepatocellular carcinoma (HCC) among Indonesian patients with chronic HBV infection. Methods: A total of 140 patients with chronic hepatitis B (CHB) were recruited, including 79 with HCC and 61 without HCC serving as controls. We used direct sequencing of DNA extracted from peripheral blood to analyze the SNPs of p53 codon 72. Results: The distribution of p53 Pro72Arg genotypes among Indonesian CHB patients was 12.9% for proline homozygotes (Pro/Pro), 31.4% for arginine homozygotes (Arg/Arg), and 55.7% for proline/arginine heterozygotes (Pro/Arg). Despite the lack of association between the SNPs and HCC risk in the overall population, both the Pro/Arg and Arg/Arg genotypes demonstrate an increased susceptibility to HCC compared to Pro/Pro genotypes exclusively in the Madurese ethnic group. Additionally, we discovered that in those with decompensated cirrhosis, the heterozygote Pro/Arg was more likely to develop HCC than the homozygous Pro/Pro. No significant association was found between the SNPs of p53 Pro72Arg and the clinicopathological characteristics of HCC. Conclusions: The p53 Pro72Arg polymorphism might contribute to hepatocarcinogenesis in Indonesian chronic hepatitis B patients, particularly Madurese and those with liver decompensation. Full article

Introduction: Gestational hypoxia (GH) increases the risk of cardiovascular diseases by inducing oxidative stress and vascular dysfunction. This study investigates whether prenatal melatonin can mitigate these effects in guinea pigs. Methods: Pregnant guinea pigs were exposed to normoxia or hypoxia and treated with melatonin (1 mg/kg/day). Echocardiography, vascular reactivity, and molecular assays were used to assess cardiovascular structure, function, and redox balance in neonates. Results: GH reduced neonatal birth weight and altered left ventricular (LV) development, resulting in increased LV systolic function and aortic blood flow velocity. Melatonin treatment reversed these effects, restoring endothelial-dependent vasodilation and decreasing oxidative stress in the LV and thoracic aorta. Catalase antioxidant enzyme activity was elevated in melatonin-treated hypoxic neonates. Unexpectedly, melatonin treatment altered cardiac structure in normoxic pregnancies, increasing LV length and decreasing LV myocardial nuclei density. Conclusions: Prenatal melatonin partially modulates GH-induced endothelial dysfunction and oxidative stress, offering potential therapeutic value. However, its effects under normoxic conditions deserve caution, emphasizing the need for targeted use only in pregnancies with evident hypoxic and oxidative stress conditions. Full article

Background and Objectives: The increase in rates of cirrhosis and hepatocellular carcinoma (HCC) due to HCV infection supported the implementation of screening programs for control of this infection in Italy. The HepCoVe network has collected cases with chronic hepatitis C (CHC) in the Veneto region of North-East Italy since the 2000s. This platform allowed us to (a) compare the characteristics of the HCV cohort exposed to parenteral risk before or after 1995 (introduction of mandatory HCV testing), and (b) track the changes induced by IFN-based therapy and the novel direct-acting antivirals (DAA). Methods: From January 2000 to December 2005, 2703 prospectively recruited cases with CHC were analyzed and followed up for 16.2 ± 8.4 years, by a per protocol analysis. Results: Two epidemic waves occurred; the first, related to blood transfusions and infection with the HCV-1b and 2a/2c genotypes, affecting an elderly population, and the second, spread through drug addiction, among young people and with a prevalence of HCV-1a, 3a/3b and 4c/4d. Patients treated with DAA had more advanced liver disease; despite this, they achieved the highest SVR rate, compared to those who received an IFN-based regimen (95.1% vs. 61.5%; p < 0.01). The 10-year HCC incidence rate by KM was 0.81, 3.75, and 1.26 per 100 person-years (p-y) in cases with or without SVR and in the untreated group, respectively (p < 0.001). Conclusions: The period of exposure to HCV in Italy (born from 1939 to 1989) was supported by two epidemic waves. Unknowing cases of HCV infection are disappearing, particularly those included in the first cohort, among the “boomers”. Despite the eradication of HCV in all treated cases, antiviral therapy does not completely eliminate the risk of HCC onset. Full article