Search Results (4,382)

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Microplastics (MPs) can affect fish health by inducing oxidative stress, but their impact on structural coloration remains poorly understood. This study investigated the effects of environmentally relevant concentrations (16 and 160 μg/L) of MPs and nanoplastics (NPs) exposure on growth, oxidative stress and structural coloration in blue strain guppy fish (Poecilia reticulata). Results showed exposure to 160 μg/L MPs significantly reduced specific growth rate of fish compared to controls. Plastic accumulation followed a dose-dependent pattern, especially within gut concentrations. Oxidative stress responses differed between MPs and NPs: 160 μg/L MPs decreased SOD activity in skin and reduced GSH levels, while 160 μg/L NPs increased MDA levels in gut tissues, indicating severe lipid peroxidation. Structural coloration analysis revealed exposure to 160 μg/L MPs decreased lightness and increased yellowness, demonstrating reduced blue coloration. This was accompanied by an increase in skin uric acid content, suggesting that guanine conversion might occur to combat oxidative stress. These findings demonstrate that MPs, particularly at high concentrations, impair growth and induce oxidative stress in guppies. To counteract stress, guanine in iridophores may be converted into uric acid, leading to a decline in structural coloration. This study is the first to reveal that MPs disrupt structural coloration of fish, providing new insights into the ecological risks of plastic pollution on aquatic organisms. Full article

Behavioral issues in domestic dogs represent a significant welfare concern affecting both canines and their caregivers, with prevalence rates reported to range from 34 to 86% across the population. Current treatment options, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, often present limitations including adverse effects and delayed efficacy. This randomized, placebo-controlled (maltodextrin) study investigated the effects of a novel Lactiplantibacillus plantarum strain (LP815^TM) on canine behavioral concerns through gut–brain axis modulation. Home-based dogs (n = 40) received either LP815^TM (n = 28) or placebo (n = 12) daily for 4 weeks, with behavioral changes assessed using the comprehensive Canine Behavioral Assessment & Research Questionnaire (C-BARQ) and continuous activity monitoring. After the intervention period, dogs receiving LP815^TM showed significant improvements in aggression (p = 0.0047) and anxiety (p = 0.0005) compared to placebo controls. These findings were corroborated by objective activity data, which demonstrated faster post-departure settling, reduced daytime sleep, and improved sleep consistency in the treatment group. Throughout >1120 administered doses, no significant adverse events were reported, contrasting favorably with pharmaceutical alternatives. The concordance between our findings and previous research using different L. plantarum strains suggests a consistent biological mechanism, potentially involving GABA production and vagal nerve stimulation. These results indicate that LP815^TM represents a promising, safe alternative for addressing common canine behavioral concerns with potential implications for improving both canine welfare and the human–animal bond. Full article

Environmental risk assessment (ERA) for pesticide approval in the context of predatory insects remains inadequate as it often overlooks the influence of agricultural practices. An increasing number of studies have shown that prolonged and synergistic pesticide exposure can elevate insect mortality. However, such effects remain largely unstudied in non-target predatory carabid beetles. The carabid beetle Platynus assimilis was subjected to repeated oral and continuous contact exposure to low doses of prothioconazole (20 g ha⁻¹), lambda-cyhalothrin (0.4 g ha⁻¹), or their combination over a 64-day period. The food consumption rate, body mass, locomotor activity, and mortality were monitored throughout the experiment. All pesticide-treated groups showed significantly increased final mortality, with median lethal times (LT₅₀) of 51.6 days for prothioconazole, 60.3 days for lambda-cyhalothrin, and 12.2 days for their combination. A significant synergistic effect on mortality was observed in the combined treatment group, with the highest synergistic ratio detected 20 days after the first exposure. Pesticide-treated beetles exhibited significant abnormalities in locomotor activity and body mass compared to the untreated group. These findings demonstrate that both time-cumulative mortality and potential synergistic interactions, reflecting field-realistic conditions, must be considered in ERA. Failure to do so may lead to an underestimation of pesticide toxicity to predatory carabids. Full article

This study investigated pesticide residues in 580 vegetable samples collected from markets in Serbia, encompassing potatoes, carrots, celery, radishes, horseradish, ginger, onions, and leeks. In total, 33 distinct pesticides were detected using validated HPLC-MS/MS and GC-MS/MS analytical methods. Multiple residues were identified in 19 samples, while 29 samples exceeded established maximum residue levels (MRLs). Acute and chronic dietary risks were assessed for both adults and children. Although individual hazard quotients (HQs) for adults and children remained below the threshold of concern (HQ < 1), the cumulative acute risk reached up to 63.1% of the Acute Reference Dose (ARfD) for children and 51.1% ARfD for adults, with ginger and celery posing the highest risks. Similarly, cumulative chronic risks remained below the safety threshold, with the Acceptable Daily Intake (ADI) percentages reaching a maximum of 5.9% ADI for adults and increased vulnerability of 11.0% ADI among children. Monte Carlo simulations were applied to account for variability and uncertainty in chronic exposure estimates. The hazard index (HI) results showed that adverse health effects for both population groups remained within acceptable safety limits (HI < 1), although higher susceptibility was observed in children. Sensitivity analysis identified body weight and vegetable consumption rates as the most influential factors affecting chronic risk variability. Full article

Objectives: To investigate how the FLASH effect modulates radiation response on multiple developmental endpoints of zebrafish embryos under normoxic and hypoxic conditions, after irradiation with proton beams at a conventional and an ultra-high dose rate (UHDR). Methods: Embryos were obtained from adult zebrafish and irradiated with a 228 MeV proton beam 24 h post-fertilization (hpf) at a dose rate of 0.6 and 317 Gy/s. For the hypoxic group, samples were kept inside a hypoxic chamber prior to irradiation, while standard incubation was adopted for the normoxic group. After irradiation, images of single embryos were acquired, and radiation effects on larval length, yolk absorption, pericardial edema, head size, eye size, and spinal curvature were assessed at specific time points. Results: Data indicate a general trend of significantly reduced toxicity after exposure to a UHDR compared to conventional regimes, which is maintained under both normoxic and hypoxic conditions. Differences are significant for the levels of pericardial edema induced by a UHDR versus conventional irradiation in normoxic conditions, and for eye and head size in hypoxic conditions. The toxicity scoring analysis shows a tendency toward a protective effect of the UHDR, which appears to be associated with a lower percentage of embryos in the high score categories. Conclusions: A radioprotective effect at a UHDR is observed both for normoxic (pericardial edema) and hypoxic (head and eye size) conditions. These results suggest that while the UHDR may preserve a potential to reduce radiation-induced damage, its protective effects are endpoint-dependent; the role of oxygenation might also be dependent on the tissue involved. Full article

One of the advantages of the EPR spectroscopy method in assessing structural defects caused by irradiation is the fact that using this method it is possible to determine not only the concentration dependences of the defect structure but to also establish their type, which is not possible with methods such as X-ray diffraction or scanning electron microscopy. Based on the data obtained, the role of variation in the ratio of components in Li₄SiO₄–Li₂TiO₃ ceramics on the processes of softening under high-dose irradiation with protons simulating the accumulation of hydrogen in the damaged layer, as well as the concentration of structural defects in the form of oxygen vacancies and radiolysis products on the processes of high-temperature degradation of ceramics, was determined. It was found that the main changes in the defect structure during the prolonged thermal exposure of irradiated samples are associated with the accumulation of oxygen vacancies, the density of which was estimated by the change in the intensity of singlet lithium, characterizing the presence of E-centers. At the same time, it was found that the formation of interphase boundaries in the structure of Li₄SiO₄–Li₂TiO₃ ceramics leads to the inhibition of high-temperature degradation processes in the case of post-radiation thermal exposure for a long time. Also, during the conducted studies, the role of thermal effects on the structural damage accumulation rate in Li₄SiO₄–Li₂TiO₃ ceramics was determined in the case when irradiation is carried out at different temperatures. During the experiments, it was determined that the main contribution of thermal action in the process of proton irradiation at a fluence of 5 × 10¹⁷ proton/cm² is an increase in the concentration of radiolysis products, described by changes in the intensities of spectral maxima, characterized by the presence of defects such as ≡Si–O, SiO₄³⁻ and Ti³⁺ defects. Full article

In the present study, we evaluated the potential use of a humic substance (HS)-based biostimulant in mitigating drought stress in lettuce (Lactuca sativa L.) by comparing both root and foliar modes of application. To achieve this, lettuce plants were grown in a growth chamber on a solid substrate composed of vermiculite and perlite (3:1). Plants were exposed to drought conditions (50% of Field Capacity, FC) and 50% FC + HS applied as radicular (‘R’) and foliar (‘F’) at concentrations: R-HS 0.40 and 0.60 mL/L, respectively, and 7.50 and 10.00 mL/L, respectively, along with a control (100% FC). HSs were applied three times at 10-day intervals. Plant growth, nutrient concentration, lipid peroxidation, reactive oxygen species (ROS), and enzymatic and non-enzymatic antioxidants were estimated. Various photosynthetic and chlorophyll fluorescence parameters were also analyzed. The results showed that HS applications alleviated drought stress, increased plant growth, and reduced lipid peroxidation and ROS accumulation. HSs also improved the net photosynthetic rate, carboxylation efficiency, electron transport flux, and water use efficiency. Although foliar HSs showed a greater tendency to enhance shoot growth and photosynthetic capacity, the differences between the application methods were not significant. Hence, in this preliminary work, the HS-based product evaluated in this study demonstrated potential for alleviating drought stress in lettuce plants at the applied doses, regardless of the mode of application. This study highlights HS-based biostimulants as an effective and sustainable tool to improve crop resilience and support sustainable agriculture under climate change. However, further studies under controlled growth chamber conditions are needed to confirm these results before field trials. Full article

Soil salinization severely limits plant growth and productivity. Mulberry (Morus alba L.), an economically and ecologically important tree, is widely cultivated, yet its salt-tolerance mechanisms at the seedling stage remain insufficiently understood. This study investigated the physiological and biochemical responses of two-year-old mulberry (‘Tailai Sang’) seedlings subjected to six NaCl treatments (0, 50, 100, 150, 200, and 300 mmol L⁻¹) for 28 days. Results showed that growth parameters and photosynthetic gas exchange exhibited dose-dependent declines. The reduction in net photosynthetic rate (Pn) was attributed to both stomatal limitations (decreased stomatal conductance) and non-stomatal limitations, as evidenced by a significant decrease in the maximum quantum efficiency of photosystem II (Fv/Fm) under high salinity. To cope with osmotic stress, seedlings accumulated compatible solutes, including soluble sugars, proteins, and proline. Critically, mulberry seedlings demonstrated effective ion homeostasis by sequestering Na⁺ in the roots to maintain a high K⁺/Na⁺ ratio in leaves, a mechanism that was compromised above 150 mmol L⁻¹. Concurrently, indicators of oxidative stress—malondialdehyde (MDA) and H₂O₂—rose significantly with salinity, inducing the activities of antioxidant enzymes (SOD, CAT, APX, and GR), which peaked at 150 mmol L⁻¹ before declining under extreme stress. A biomass-based LC₅₀ of 179 mmol L⁻¹ NaCl was determined. These findings elucidate that mulberry salt tolerance is a coordinated process involving three key mechanisms: osmotic adjustment, selective ion distribution, and a robust antioxidant defense system. This study establishes an indicative tolerance threshold under controlled conditions and provides a physiological basis for further field-based evaluations of ‘Tailai Sang’ mulberry for cultivation on saline soils. Full article

This research examined the impact of dietary supplementation with Phlogacanthus pulcherrimus extract (PPE) on the growth, disease resistance, and expression of immune-, growth-, and antioxidant-related genes in Labeo chrysophekadion. Over 150 days, 90 fish from each group were fed diets with 0 (control), 0.25, 0.50, or 0.75 g/kg of PPE. Phytochemical analysis revealed phenolics (96.00 mg GAE/g), flavonoids (17.55 mg QE/g), anthraquinones, and triterpenoids, along with moderate antioxidant activity (IC₅₀ = 1314.08 μg/mL). One-way ANOVA of growth indices, including weight gain, specific growth rate, feed conversion ratio, and survival rate, revealed no significant differences (p > 0.05); however, PPE supplementation significantly enhanced immune and antioxidant gene expression. IL-1β was significantly (p < 0.05) upregulated at all doses, with the highest expression observed at 0.50 g/kg, showing a fivefold increase compared to the control. In addition, the highest relative expressions of IGF-1 and CAT were found at 0.75 g/kg, with 4.5-fold and 3.5-fold increases compared to the control, respectively. PPE at 0.75 g/kg decreased the cumulative mortality rate (CMR) by 20% compared to the control group, which had a CMR of 50% following exposure to Aeromonas hydrophila. PPE acted as an effective immunostimulant and antioxidant, supporting reduced antibiotic reliance in aquaculture. Full article

Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned meat rabbits (n = 450) were randomly assigned to five groups, Groups A, B, C, D, and E, and fed 0, 50, 100, 150, and 200 mg/kg CA diets, respectively, for 47 days. Biological samples including serum (antioxidants), duodenal/caecal content (enzymes), intestinal tissue (morphology), and caecal digesta (microbiota) were collected at day 47 postweaning for analysis. Groups C and D showed significantly higher final body weights than Group A, with Group D (150 mg/kg CA) demonstrating superior growth performance including 11.73% longer duodenal villi (p < 0.05), 28.6% higher microbial diversity (p < 0.01), and 62% lower diarrhoea rate versus controls. Digestive enzyme activity as well as serum antioxidant capacity increased with increasing CA dose, Microbiota analysis revealed CA increased fibre-fermenting Oscillospiraceae (+38%, p < 0.01) while reducing Ruminococcaceae (−27%, p < 0.05). Thus, dietary CA supplementation at 150 mg/kg was identified as the optimal CA dose for improving meat rabbit production. These findings highlight CA as a functional feed additive for promoting sustainable rabbit production. Full article

Introduction: Medication adherence is essential for treatment and recovery following hematopoietic stem cell transplantation (HSCT). However, limited data exist on the most effective methods to measure adherence and the factors influencing it in HSCT patients. Materials and Methods: A prospective longitudinal study assessed immunosuppressant medication adherence in 150 patients with hematologic malignancies undergoing allogeneic HSCT. Adherence was assessed using pill counts, immunosuppressant medication levels, patient-reported medication logs, and the Medication Adherence Response Scale-5 (MARS-5) at 30, 100, and 180 days post-HSCT. We evaluated adherence rates, agreement between methods, and sociodemographic and clinical predictors. From patient-reported logs, we calculated dose adherence (comparing reported doses to expected doses) and timing adherence (comparing medication intake within ±3 h of the prescribed time). Kappa analysis assessed agreement among methods. Results: Of 190 eligible patients, 150 (78.9%) enrolled. The mean age was 57.5 years (SD = 13.5); 41.3% (n = 62) were female, 85.3% (n = 128) were non-Hispanic White, and 73.3% (n = 110) were married or living with a partner. Medication adherence varied across the three timepoints and by measurement type: 52–64% (pill counts), 18–24% (medication levels), 96–98% (medication log dose adherence), 83–84% (medication log timing adherence), and 97–98% (MARS−5). There was minimal agreement between measures (Kappa range: 0.008–0.12). Conclusions: Despite the feasibility of leveraging objective and patient-reported measures to assess medication adherence in HSCT patients, there was little agreement between these measures. Patient-reported measures showed high adherence, while objective measures like pill counts and medication levels revealed more modest adherence. The complexity of medication regimens likely contributes to this discrepancy. A rigorous approach to understanding medication adherence in the HSCT population may entail both objective and subjective measures of medication adherence. Full article

Hydrogels are widely known for their ability to increase soil water retention and for their potential slow nutrient release mechanism. They have been constantly improved to meet the growing demand for sustainability in agriculture. Research focused on the development of biodegradable hydrogels, produced from industrial cellulose waste, are an ecological and efficient alternative soil ameliorant for the improvement of agricultural land. The objective of this study was to evaluate the impacts of two types of hydrogel (processed in a glass reactor versus a twin-screw extruder) on soils with different textures (clay and sandy loam), testing their water retention capacity, nitrogen leaching, and effects on seed germination. The methodology included the evaluation of water retention capacity at different pressures with different hydrogel addition rates in the soil, leaching tests in columns filled with soil and hydrogel layers, and germination tests of sorghum and corn. The results indicated that the addition of hydrogel significantly improved water retention, especially in sandy loam soils. The hydrogels also reduced nitrogen leaching, acting as nitrification inhibitors and limiting the conversion of ammonium to nitrate, with greater effectiveness in clayey soils. In the tested formulations, it was observed that the hydrogel doses applied to the columns favored nitrogen retention in the region close to the roots, directly influencing the initial stages of germination. This behavior highlights the potential of hydrogels as tools for directing nutrients in the soil profile, indicating that adjustments to the C:N ratio, nutrient release rate, and applied doses can optimize their application for different crops. Full article

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article

Introduction: Long COVID syndrome is defined as persistent or new symptoms that appear after an acute SARS-CoV-2 infection and last at least three months without explanation. It is estimated that between 10% and 20% of those infected develop long COVID; however, data is not precise in Latin America. Although high immunization rates have reduced acute symptoms and the pandemic’s impact, there is a lack of evidence of its efficacy in preventing long COVID in the region. Methods: This scoping review followed PRISMA-ScR guidelines. Studies on vaccinated adults with long COVID from Central and South America and the Caribbean were included (Mexico was also considered). A comprehensive search across multiple databases was conducted. Data included study design, participant characteristics, vaccine type, and efficacy outcomes. Results are presented narratively and in tables. Results: Out of 3466 initial records, 8 studies met the inclusion criteria after rigorous selection processes. These studies encompassed populations from Brazil, Mexico, Latin America, and Bonaire, with 11,333 participants, 69.3% of whom were female. Vaccination, particularly with three or more doses, substantially reduces the risk and duration of long COVID. Variability was noted in the definitions and outcomes assessed across studies. Conclusions: This scoping review highlights that SARS-CoV-2 vaccination exhibits potential in reducing the burden of long COVID in the Americas. However, discrepancies in vaccine efficacy were observed depending on the study design, the population studied, and the vaccine regimen employed. Further robust, region-specific investigations are warranted to delineate the effects of vaccination on long COVID outcomes. Full article