Search Results (121)

Tebuconazole (TBZ), a triazole-class fungicide widely used in agriculture, is frequently detected in aquatic environments due to runoff and leaching, where it poses a threat to non-target aquatic organisms. This study investigates the acute toxicity of TBZ on juvenile rainbow trout (Oncorhynchus mykiss), a commercially important cold-water fish species. The 96 h LC₅₀ value was determined to be 9.05 mg/L using probit analysis. In addition to mortality, the physiological responses of fish exposed to both LC₅₀ and maximum tolerance concentration (MTC; 6 mg/L) were evaluated through haematological and histological assessments. TBZ exposure significantly suppressed key haematological parameters, particularly WBC, RBC, HGB, HCT, and LYM, indicating immunosuppression and potential hypoxia. Histological examination revealed progressive and regressive damage in gill tissues, including epithelial lifting, hyperplasia, and hypertrophy, which were more severe in the LC₅₀ group. These alterations were quantified using a semi-quantitative scoring system. Additionally, significant changes in biochemical parameters such as ALT, AST, creatinine, total protein, and glucose levels were observed, further indicating hepatic and renal dysfunctions induced by TBZ exposure. The findings demonstrate that TBZ exposure induces substantial physiological and structural impairments in rainbow trout, highlighting the importance of assessing the ecological risks of fungicide contamination in aquatic environments. The study also provides a dose–response model that can be used to estimate mortality risk in aquaculture operations exposed to TBZ. Full article

Background: Marburg virus disease (MVD) is a highly lethal filoviral infection, yet its long-term health consequences remain poorly understood. We present one of the most temporally distant evaluations of MVD survivors, conducted 13 years post-outbreak in Uganda, offering novel insights into chronic physiological, biochemical, haematological, and psychosocial outcomes. Methods: A cross-sectional, community-based study compared ten MVD survivors with nineteen age- and sex-matched unexposed controls. Clinical evaluations included vital signs, anthropometry, mental health screening, and symptom reporting. Laboratory analyses covered electrolytes, inflammatory markers, renal and liver function tests, haematology, and urinalysis. Standardised psychological assessments measured anxiety, depression, perceived stigma, and social support. Findings: Survivors exhibited an elevated body mass index (BMI), higher systolic and diastolic blood pressure, and lower respiratory rates compared to controls, indicating ongoing cardiometabolic and autonomic changes. These trends may reflect persistent cardiometabolic stress and potential alterations in autonomic regulation, warranting further investigation. Biochemically, survivors exhibited disruptions in serum chloride, bilirubin, and total protein levels, suggesting subclinical hepatic and renal stress. Haematological analysis revealed persistent reticulocytosis despite normal haemoglobin levels, indicating long-term erythropoietic modulation. Despite these physiological changes, survivors reported minimal psychological morbidity, sharply contrasting with the post-recovery profiles of other viral haemorrhagic fevers. Stigma was prevalent during the outbreak; however, strong family support alleviated long-term psychosocial distress. Interpretation: Thirteen years post-infection, MVD survivors demonstrate multisystem physiological perturbations without marked psychological sequelae. These findings challenge assumptions of universal post-viral trauma and highlight the necessity for tailored survivor care models. Future longitudinal studies should investigate the mechanistic pathways underlying cardiometabolic and haematological reprogramming to inform intervention strategies in resource-limited settings. Full article

Background and Objectives: Blood-borne inflammatory ratios have been proposed as inexpensive prognostic tools across a range of diseases, but their role in pulmonary tuberculosis (TB) remains uncertain. In this retrospective case–control analysis, we explored whether composite indices derived from routine haematology—namely the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune–inflammation index (SII) and a novel CRP–Fibrinogen Index (CFI)—could enhance risk stratification beyond established cytokine measurements among Romanian adults with culture-confirmed pulmonary T. Materials and Methods: Data were drawn from 80 consecutive TB in-patients and 50 community controls. Full blood counts, C-reactive protein, fibrinogen, and four multiplex cytokines were extracted from electronic records, and composite indices were calculated according to standard formulas. The primary outcomes were in-hospital mortality within 90 days and length of stay (LOS). Results: Among TB patients, the median NLR was 3.70 (IQR 2.54–6.14), PLR was 200 (140–277) and SII was 1.36 × 10⁶ µL⁻¹ (0.74–2.34 × 10⁶), compared with 1.8 (1.4–2.3), 117 (95–140) and 0.46 × 10⁶ µL⁻¹ (0.30–0.60 × 10⁶) in controls. Those with SII above the cohort median exhibited more pronounced acute-phase responses (median CRP 96 vs. 12 mg L⁻¹; fibrinogen 578 vs. 458 mg dL⁻¹), yet median LOS remained virtually identical (29 vs. 28 days) and early mortality was low in both groups (8% vs. 2%). The CFI showed no clear gradient in hospital stay across its quartiles, and composite ratios—while tightly inter-correlated—demonstrated only minimal association with cytokine levels and LOS. Conclusions: Composite cell-count indices were markedly elevated but did not predict early death or prolonged admission. In low-event European cohorts, their chief value may lie in serving as cost-free gatekeepers, flagging those who should proceed to more advanced cytokine or genomic testing. Although routine reporting of NLR and SII may support low-cost surveillance, validation in larger, multicentre cohorts with serial sampling is needed before these indices can be integrated into clinical decision-making. Full article

Background: Quality of life (QoL) in oncology patients is shaped by the interplay of biological, psychological and treatment-related factors. While prior studies have addressed the independent effects of treatment toxicity and psychological distress, little is known about the interaction between depressive–anxious disorders, kidney failure and haematological toxicity on QoL among patients with head and neck cancer undergoing chemoradiotherapy. Objective: This study aims to examine the combined effect of haematological toxicity, depressive–anxious disorders and chronic renal disease on the total QLQ-H&N43 score, a validated measure of QoL in patients with head and neck cancer. Methods: A total of 93 patients were included in an observational study. PROCESS macro for SPSS was used to test the three-way interaction between haematological toxicity (X), depressive–anxious disorders (W) and kidney failure (Z) on QoL (Y). Results: The three-way interaction was statistically significant (β = 31.04, p = 0.032), accounting for 18.9% of the variance in QLQ-H&N43 scores (R² = 0.1888). Patients presenting both depressive–anxious disorders and renal comorbidities reported higher QoL scores, indicating poorer quality of life in the presence of severe treatment toxicity. Conclusions: Psychological distress and kidney failure may synergistically exacerbate the negative effects of chemoradiotherapy toxicity on quality of life. These findings underscore the need for integrated care models addressing both psychological vulnerability and medical comorbidities in oncology. Full article

Objectives: This study aimed to analyse the haematological parameters in relation to subjective tinnitus. We hypothesise that abnormal haematological findings may correlate with increased severity and chronicity of tinnitus. This research could lead to improved diagnostic methods and more targeted treatments. Material and Methods: A total of 439 patients with primary subjective tinnitus and 274 individuals without tinnitus were enrolled. These participants underwent comprehensive laboratory testing, which included haematological parameters. Results: When comparing the white blood cell levels between the tinnitus group and the control group, no statistically significant differences were found (p = 0.743). Similarly, comparisons of red blood cell levels (p = 0.250), haemoglobin levels (p = 0.087), and haematocrit levels (p = 0.066) also revealed no significant differences. The platelet levels showed no significant difference between the two groups (p = 0.782). According to a logistic regression model, lower levels of haemoglobin (p = 0.000) and platelets (p = 0.000) significantly predicted higher scores on the Tinnitus Handicap Inventory, indicating self-reported tinnitus severity. Furthermore, lower haemoglobin levels were significant predictors (p = 0.04) of developing bilateral tinnitus. Using Spearman’s correlation test, a statistically significant negative correlation (p = 0.029) was observed between red blood cell levels and the onset of tinnitus. The frequency of tinnitus demonstrated a significant positive correlation with haemoglobin levels (p = 0.04) and haematocrit levels (p = 0.043). Conversely, platelet levels showed a significant negative correlation with both tinnitus intensity (p = 0.002) and the onset of tinnitus (p = 0.033). Conclusions: While the haematological parameters showed no significant differences between the tinnitus and control groups, further analyses indicated that certain parameters, such as haemoglobin and haematocrit levels, could potentially influence tinnitus, necessitating further investigation. Full article

Background: Oral mucositis (OM) is a painful inflammation resulting from chemotherapy. It is dependent on factors such as age, gender, chemotherapy regimen, oral health, immunological and nutritional status, and genetics. Objectives: The aim of the study was to conduct a narrative review to compile studies on the contribution of genetic and epigenetic aspects to the pathogenesis of OM in children with haematological malignancies undergoing chemotherapy treatment. Methods: The literature search was performed in Pubmed, Scopus, Web of Science, Cochrane, Lilacs, and grey literature databases covering articles published since 2010. Results: Twenty-two studies investigating polymorphisms and four studies investigating DNA methylation were included. Polymorphisms in the MTHFR, ABCB1, ABCC2, ABCG2, SLCO1B, miR-1206, miR-3683, CAT, and VDR genes were associated as risk factors for OM and polymorphisms in the TYMS and miR-4268 genes were associated as protective factors. With regard to DNA methylation, associations such as protection or susceptibility to OM have not yet been proven. However, studies have shown that DNMT1 methylation and hypomethylation in total DNA and in the TNF-α gene are associated with recovery of the oral mucosa. Conclusions: Genetic variants are associated with OM in various biological pathways, such as folate metabolism, transport proteins, epigenetic machinery, oxidative stress, and vitamin D metabolism. The DNA methylation profile, which is still poorly understood in the pathogenesis of OM, is associated with mucosal recovery (inflammation and epigenetic machinery). Genetic and epigenetic markers may be tools to indicate a patient’s susceptibility to developing OM, and epigenetic markers may be a target for therapies. Full article

Introduction: The consumption of systemic antifungals is on the rise. However, a significant proportion of systemic antifungal prescriptions is inappropriate. Inappropriately prescribed antifungals are problematic, but there has been minimal emphasis on ensuring the appropriate prescription of systemic antifungals. Local studies regarding the patterns and appropriateness of antifungal prescriptions are also lacking. Materials and Methods: In this retrospective, single-centre, observational study, every in-patient prescription order of systemic antifungals in a regional hospital in Hong Kong between 1 May and 31 July 2023 was reviewed via electronic patient records. The appropriateness of a systemic antifungal prescription was assessed by its indication, dosage, duration and antifungal–concomitant drug interactions by a single reviewer. Results: A total of 177 prescriptions orders were collected. Itraconazole, micafungin and fluconazole were the most prescribed systemic antifungals. The haematology team, infectious disease team and ICU were the major systemic antifungal prescribers in this study. The overall appropriateness of systemic antifungal prescriptions was 27.7% (49/177), with an appropriateness of 72.9% (129/177) for indications, 57.1% (101/177) for dosage, 91.5% (162/177) for duration and 71.6% (127/177) for antifungal–concomitant drug interactions. Triazole antifungals had an overall prescription appropriateness of only 15% and were more likely to be prescribed inappropriately than non-triazole antifungals (p < 0.001). Common prescription pitfalls include (i) starting a systemic antifungal for sputum culture that grew Candida spp., (ii) debatable prophylaxis with itraconazole capsules, (iii) overlooking potentially serious antifungal–drug interactions. Conclusions: Inappropriate systemic antifungal prescription is not uncommon in Hong Kong. Establishing an antifungal stewardship programme in public hospitals may be beneficial. Full article

This study investigates the relationship between methane emissions and physiological, behavioural, and haematological parameters in dairy cows during the transition period. Methane emissions were monitored alongside variations in rumination, feeding behaviour, and blood markers three weeks before calving, on calving day, and three weeks post-calving. Cows were retrospectively classified into low, medium, and high rumination groups according to their average daily rumination duration to investigate the effects of behavioural influences. During the prepartum period, the methane concentration was moderately positively correlated with drinking time (r = 0.41, p < 0.01) and weakly negatively correlated with chews per minute (r = −0.358, p < 0.05). Significant negative correlations were noted with chloride (r = −0.42, p < 0.01) and glucose levels (r = −0.41, p < 0.01). Following calving, methane emissions showed a positive correlation with haematocrit (r = 0.41, p < 0.01) and a negative correlation with haemoglobin (r = −0.47, p < 0.01). A haematological analysis revealed a notable negative correlation with platelets during calving (r = −0.64, p < 0.05). Individual dry matter intake (DMI) was recorded for each period, showing a significant drop on calving day. This intake fluctuation coincided with a significant rise in methane yield on calving day (p < 0.001). In the low rumination time group, methane was moderately negatively correlated with rumination chews (r = −0.52, p < 0.05), while in the high rumination group, a moderate negative correlation was observed with drinking gulps (r = −0.42, p < 0.05), and a weak negative correlation was observed with bolus events (r = −0.37, p < 0.05). Despite behavioural variations, methane emissions showed no substantial differences among groups with low, medium, and high rumination times, suggesting a minimal direct influence on rumination duration. These findings emphasise the complex interactions between feed intake, metabolism, and methane emissions, underscoring the importance of integrating behavioural and physiological indicators to develop targeted strategies for enteric methane mitigation while providing baseline data from healthy cows that could guide future research on methane emissions in cows undergoing postpartum metabolic disorders. Full article

The traditional horse industry has undergone a remarkable evolution, with horse racing emerging as a prominent and pivotal economic driver within the sector. Among the various breeds, Mongolian horses, renowned for their exceptional endurance and speed, occupy a significant position in the horse industry. To investigate their homeostasis mechanisms during and after a 20 km endurance exercise and identify novel oxidative-imbalance markers, we selected 12 two-year-old horses and collected blood samples at various time points before, during (at 5, 10, 15, and 20 km), and after the exercise (at 1, 2, 4, and 6 h post-exercise). These samples were analyzed for haematology, blood biochemistry, antioxidant enzyme activities, and liquid chromatography–mass spectrometry (LC-MS) metabolomics. Our results revealed significant changes in heart rate, speed, blood cells, and biochemical markers throughout the exercise. Antioxidant indicators decreased, while malondialdehyde increased, indicating oxidative imbalance post-exercise. Metabolomics analysis identified 122 differential metabolites, including uric acid and L-tyrosine, which were enriched in pathways related to energy metabolism. Uric acid and tyrosine correlated positively with serum creatine kinase, suggesting their potential as markers of oxidative-imbalance injury. These findings elucidate the mechanisms of endurance adaptability in Mongolian horses and provide a theoretical basis for mitigating oxidative imbalance, enhancing horse performance, and promoting the sustainable development of the equine industry. Full article

The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders. Full article

Background: Despite the development of advanced cancer therapies, achieving cancer eradication remains challenging. Radioimmunotherapy (RIT) is an innovative approach that combines radionuclides with monoclonal antibodies targeting tumour-associated antigens or those expressed by the tumour microenvironment. Over the past two decades, RIT has been extensively researched, along with two RIT products—⁹⁰Y-ibritumomab tiuxetan and ¹³¹I-tositumomab. However, despite its demonstrated efficacy in non-solid tumours, RIT’s clinical use remains limited, and its effectiveness in solid tumours is inconclusive. This study aimed to analyse randomised controlled trials (RCTs) to evaluate the overall clinical effectiveness of RIT across different cancer types and its impact on treatment outcomes. Methods: A systematic search of PubMed, EMBASE, Scopus, CENTRAL, and Google Scholar was conducted from January 2000 to October 2024 in accordance with PRISMA guidelines and the PICOS framework. Studies were included if they were RCTs evaluating RIT for cancer treatment and reported treatment outcomes such as overall survival (OS), progression-free survival (PFS), disease-free survival, or time to progression (TTP). Data extraction was performed using a standardised Excel form, and study quality was assessed with the Joanna Briggs Institute Critical Appraisal Tool for RCTs. A narrative synthesis of the data was complemented by meta-analyses where feasible, particularly for progression- and survival-related endpoints. Results: Out of 2241 records identified, 20 RCTs encompassing approximately 3562 patients were included. The majority of trials focused on non-solid tumours, particularly non-Hodgkin’s lymphoma (NHL), while a smaller subset evaluated solid tumours such as lung, pancreatic, ovarian, and prostate cancers. Most non-solid tumour studies employed ⁹⁰Y-ibritumomab tiuxetan or ¹³¹I-tositumomab, targeting the CD20 antigen, whereas limited evidence exists for RIT efficacy in solid tumours. Meta-analysis of progression-related outcomes yielded a pooled hazard ratio (HR) of 0.48 (95% CI: 0.39–0.59), indicating a 52% reduction in the risk of progression. In contrast, overall survival outcomes were more variable, with a pooled OS HR of 0.80 (95% CI: 0.60–1.07). Adverse events, predominantly haematological and nonhaematological toxicities, were common yet generally reversible. The findings suggest that RIT, especially when used as part of combination regimens, significantly improves treatment outcomes in non-solid tumours but has an inconsistent effect in solid tumour settings. Conclusions: The results underscore the clinical promise of RIT in treating non-solid tumours like NHL, where combination regimens yield superior outcomes compared to monotherapy. However, the inconclusive evidence in solid tumours highlights the need for further large-scale, well-designed RCTs to define the optimal use, dosing, and patient selection for RIT in these settings. Additionally, standardisation in outcome reporting and longer follow-up periods are essential for more accurate economic and clinical assessments. Overall, RIT represents a valuable therapeutic modality, yet its integration into cancer treatment regimens should be guided by further research aimed at mitigating toxicity and optimising combination strategies. Full article

Efficient and fair allocation of donated blood depends on multiple factors, like medical urgency, donor/recipient compatibility, blood availability, geographic location, limited shelf life, etc. Due to the limited supply of blood and its critical role in healthcare, fair distribution protocols are essential. This study builds upon previous authors’ research that proposed a general mathematical model for fair blood allocation, taking as inputs the universal blood compatibility chart and the assumption of allocating equal shares of the donated blood from each blood type to recipients with respectively compatible blood types. The sum normalization technique was performed (twice, first per recipients and then per donors) for the purpose of balancing between donation needs and options. The result was an indicative blood allocation reference framework in support of the decision making in transfusion haematology. In the present paper, we tailor that general model by introducing as model variables the actual blood group frequencies of a given population. Additional customization is proposed by adding weight coefficients to the values along the framework’s main diagonal that represent ABO-identical transfusions, preferred to non-identical transfusions for minimizing the risks of hemolytic reactions. The model is further elaborated via intervalization of the estimations in the resultant blood allocation framework, thus making the model more flexible and usable. While demonstrated with Bulgarian blood group distributions from 2023, the model can be adapted to other populations and contexts. Full article

B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds 2a–2t, 3a–3j and 4a–4g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds 2a exhibited the best antiproliferative activity (IC₅₀ = 0.276, 0.159, 0.312 and 0.271 µM to U937, K562, K562R and KG-1, respectively). In addition, 2a induced apoptosis in K562 and markedly arrested the cell cycle G2/M phase of K562. The Western blot assay showed that 2a is a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that 2a had firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of 2a indicated its potential as an anti-leukemia drug lead in the future. Full article

Chronic lymphocytic leukaemia (CLL) is a haematological malignancy primarily affecting older adults, characterised by the proliferation of functionally impaired B lymphocytes with abnormal expression of CD5, a typical T cell marker. The current study investigates the expression of cytotoxicity-related receptors (CD16, CD56, CD57, CD69) and a checkpoint (LAG-3) on γδ T cells in CLL patients. Sixty-nine treatment-naive CLL patients and fourteen healthy controls were recruited. Flow cytometry analysis revealed that the CLL patients had higher expressions of CD56 and LAG-3 and lower CD16 on their γδ T cells compared to the healthy controls. Subgroup analysis showed that ZAP-70-negative patients exhibited increased CD69, while CD38-negative patients showed higher CD16 expression. Additionally, CD16 expression was inversely correlated with serum LDH levels, a marker of disease progression. Bioinformatic analysis of the LAG-3 ligand mRNA in a CLL dataset indicated higher expression of HLA-DQA2 and HLA-DRB5 in patients with unmutated IGVH. Our findings highlight the altered expression of key cytotoxicity markers on γδ T cells in CLL, suggesting their potential role in disease progression and as a therapeutic target. In particular, the use of anti-LAG-3 antibodies seems promising. Full article

Background and Objectives: Gallbladder cancer (GBC) is a biologically aggressive malignancy characterised by poor survival outcomes often attributed to delayed diagnosis due to nonspecific clinical presentations. Paraneoplastic syndromes (PNSs), atypical symptoms caused by cancer itself, may serve as valuable indicators for timely diagnosis, particularly in malignancies with nonspecific features. Understanding the manifestations of PNSs in GBC is, therefore, critical. This systematic review collates case studies documenting the association of PNS with GBC, including subsequent management and clinical outcomes. Materials and Methods: A comprehensive search of PubMed, Embase, CINAHL, Web of Science, and Cochrane Library databases yielded 49 relevant articles. Upon searching other information sources, two more relevant articles were identified via citation sources. Results: The paraneoplastic syndromes were classified according to haematological (leukocytosis), dermatological (inflammatory myositis like dermatomyositis and polymyositis, acanthosis nigricans, Sweet’s syndrome, exfoliative dermatitis), neurological, metabolic (hypercalcemia, hyponatremia), and others (chorea). The analysis included the age, sex, and country of origin of the patient, as well as the time of PNS diagnosis relative to GBC diagnosis. Furthermore, common presenting complaints, investigations, and effectiveness of treatment modalities using survival time were assessed. Conclusions: While PNS management can offer some benefits, oncologic outcomes of GBC are largely poor. The majority of PNS in GBC are reported in advanced stages, and, hence, PNS has a minimal role in early diagnosis. PNS management can improve a patient’s quality of life, and thus recognition and treatment are important considerations in the holistic management of GBC patients. Full article