Search Results (4,197)

People with cystic fibrosis may experience polypharmacy, which can increase the risk of drug induced complications such as adverse events and drug–drug interactions. This study aimed to examine the prevalence of adverse events and to identify potential drug–drug interactions associated with elexacaftor/tezacaftor/ivacaftor (ETI). Three databases, the Australian Therapeutic Goods Administration Database of Adverse Event Notification (TGA DAEN), the Canada Vigilance Adverse Reaction Online Database (CVAROD), and the USA Food and Drug Administration Adverse Event Reporting System (FAERS) Database were searched for spontaneous ETI adverse events between 2019 and 2024. Descriptive analysis of the data was undertaken. The FAERS database was analysed to identify adverse events of interest such as anxiety and depression and concomitant drugs prescribed with ETI. A total of 10,628 ETI associated adverse events were identified in all system organ classes. The incidence of psychiatric adverse events ranged from 7 to 15% across the three databases. Potential drug–drug interactions with CYP 3A4/5 strong inhibitors and strong inducers were identified from the FAERS database and azole antifungals were implicated in several ETI dose modifications. The prevalence and types of ETI adverse events were varied and use of concomitant drugs with potential drug interactions was significant, requiring more research to manage them. Full article

The purpose of this article is to examine a previously unrecognized role for the vasopressin–oxytocin (VP-OT) system in mammalian “stress-response hormesis.” The current review adds hormesis to the long list of beneficial effects of OT. Hormesis, a biphasic adaptive response to low-level stressors, is introduced here to contextualize the dynamic roles of oxytocin and vasopressin. As with hormesis, the properties of the VP-OT system are context-, time-, and dose-sensitive. Here we suggest that one key to understanding hormesis is the fact that VP and OT and their receptors function as an integrated system. The VP-OT system is capable of changing and adapting to challenges over time, including challenges necessary for survival, reproduction and sociality. Prior research suggests that many beneficial effects of OT are most apparent only following stressful experiences, possibly reflecting interactions with VP, its receptors and other components of the hypothalamic–pituitary–adrenal axis. The release of OT is documented following various kinds of hormetic experiences such as birth, vigorous exercise, ischemic events and the ingestion of emetics, including psychedelics. The phasic or cyclic modulation of VP and related “stress” hormones, accompanied or followed by the release of OT, creates conditions that conform to the core principles of hormesis. This concept is reviewed here in the context of other hormones including corticotropin releasing hormone (CRH) and urocortin, as well as cytokines. In general, VP and classic “stress hormones” support an active response, helping to quickly mobilize body systems. OT interacts with all of these, and may subsequently re-establish homeostasis and precondition the organism to deal with future stressors. However, the individual history of an organism, including epigenetic modifications of classical stress hormones such as VP, can moderate the effects of OT. Oxytocin’s effects also help to explain the important role of sociality in mammalian resilience and longevity. A hormetic perspective, focusing on a dynamic VP-OT system, offers new insights into emotional and physical disorders, especially those associated with the management of chronic stress, and helps us to understand the healing power of social behavior and perceived safety. Full article

Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article

Candidiasis arises from the proliferation of Candida species in the human body, especially in individuals with compromised immune systems. Efficient therapeutic management of candidiasis is often hampered by the limited availability of potent antifungal drugs and the emergence of drug-resistant strains. We have previously identified the N-[(4-sulfamoylphenyl)methyl][1,1′-biphenyl]-4-carboxamide to have fungistatic and fungicidal properties, likely due to the hydrophobic biphenyl–chemical features affecting the structural organization of Candida spp. cell membrane. Here, we designed and synthesized a novel series of twelve 5-arylfuran-2-carboxamide derivatives bearing a new hydrophobic tail as bioisosteric replacement of the diphenyl fragment. Its antifungal effectiveness against C. albicans, C. glabrata, and C. parapsilosis, including ATCC and clinically isolated strains, was assessed for all compounds. The most active compound was N-benzyl-5-(3,4-dichlorophenyl)furan-2-carboxamide (6), with fungistatic and fungicidal effects against C. glabrata and C. parapsilosis strains (MIC = 0.062–0.125 and 0.125–0.250 mg/mL, respectively). No synergistic effects were observed when combined with fluconazole. Interestingly, fluorescent microscopy analysis after staining with SYTO 9 and propidium iodide revealed that compound 6 affected the cell membrane integrity in C. albicans strain 16. Finally, carboxamide 6 exhibited a dose-dependent cytotoxicity on erythrocytes, based on assessing the LDH release. Full article

Heavy metal contamination in freshwater ecosystems poses persistent threats to aquatic organisms and public health. This study evaluates the transgenerational toxicity of cadmium chloride and copper sulfate on Culex pipiens, focusing on development, reproduction, and midgut histopathology over two successive generations. Larval bioassays showed cadmium chloride to be more toxic than copper sulfate, with early instars exhibiting higher sensitivity (LC₅₀ = 8.66 μg/L for Cd; 175.63 μg/L for Cu). Both metals significantly delayed larval and pupal development, reduced fecundity, and decreased egg hatchability in a dose-dependent manner. Histopathological examination revealed midgut epithelial degeneration, vacuolation, and brush border loss, with copper sulfate inducing more severe cytotoxicity. These findings confirm that sublethal, chronic metal exposure can impair physiological and reproductive traits across generations. Moreover, this study highlights the utility of mosquitoes as sensitive bioindicators of aquatic pollution, and underscores the long-term ecological implications of heavy metal contamination on vector dynamics and disease transmission. Full article

Helminth parasites of wild animals represent a major threat to the health of these animals, leading to significant losses in performance, health, and zoonotic implications. In some zoos, anthelmintics have traditionally been used to control these parasites, many of which are also zoonotic. Other actions, such as the removal of organic waste, have also been adopted. Few or no control measures are applied to free-ranging wild animals. Helminthophagous fungi are a promising biological alternative. When animals ingest fungal spores, they are excreted in their feces, where they trap and destroy helminth larvae and eggs, preventing and reducing the parasite load in the environment. Another alternative is to administer fungi by spraying them directly into the environment. This review aims to examine the use of helminthophagous fungi in the control of helminthiases in wild animals, highlighting their potential to minimize dependence on chemical treatments and promote sustainable animal breeding and production. There are many challenges to making this viable, such as environmental variability, stability of formulations, and acceptance of this new technology. These fungi have been shown to reduce parasite burdens in wild animals by up to 75% and can be administered through the animals’ feeding troughs. To date, evidence shows that helminthophagous fungi can reliably curb environmental parasite loads for extended periods, offering a sustainable alternative to repeated anthelmintic dosing. Their use has been linked to tangible gains in body condition, weight, and overall welfare in various captive and free-ranging wildlife species. Full article

This study investigated the effects of reducing organic trace minerals below commercial inclusion levels and compared them with both low-dose and commercial levels of inorganic trace minerals, focusing on growth performance, carcass traits, tibia characteristics, oxidative stress (superoxide dismutase [SOD] and malondialdehyde [MDA]), and immune response (serum IgG) in broilers. A total of 384 one-day-old Ross 308 chicks were randomly assigned to three dietary treatments: (1) commercial-level inorganic trace minerals (ILI; Zn 100 ppm; Cu 15 ppm; Fe 100 ppm; Mn 80 ppm; Se 0.2 ppm; I 3 ppm); (2) low-level organic trace minerals (LLO; Zn 30 ppm; Cu 4 ppm; Fe 11 ppm; Mn 30 ppm; Se 0.225 ppm; I 3 ppm), and (3) low-level inorganic trace minerals (LLI; Zn 30 ppm; Cu 4 ppm; Fe 11 ppm; Mn 30 ppm; Se 0.2 ppm; I 3 ppm). Each treatment consisted of eight replicates with 16 birds per replicate, and diets were provided in two phases: starter (days 1–21) and grower (days 22–35). The results showed that the LLO group demonstrated a significantly improved feed conversion ratio (FCR) during the starter phase, 2.4% better than that of the ILI and LLI groups (p = 0.02). Additionally, filet and thigh muscle yields in the LLO group were higher by 11.9% (p = 0.03) and 13.9% (p = 0.02), respectively, compared to the ILI group. Other carcass traits, as well as pH and drip loss, were not significantly affected. However, tibia breaking strength at day 35 was 15.1% lower in the LLO group compared to the ILI group (p = 0.02). No significant differences were observed in oxidative stress markers or IgG levels among groups. This study demonstrated that reducing the inclusion level of inorganic trace minerals did not negatively affect broiler growth performance, whereas supplementation with low levels of organic trace minerals improved both growth performance and carcass quality. Full article

The topic of environmental pollution by petroleum products is highly relevant due to rapid urbanisation, including industrial development, road infrastructure and fuel distribution. Potential threat areas include refineries, fuel stations, pipelines, warehouses and transshipment bases, as well as sites affected by accidents or fuel spills. This study aimed to determine whether organic and mineral materials could mitigate the effects of diesel oil pollution on the soil’s trace element content. The used materials were compost, bentonite and calcium oxide. Diesel oil pollution had the most pronounced effect on the levels of Cd, Ni, Fe and Co. The levels of the first three elements increased, while the level of Co decreased by 53%. Lower doses of diesel oil (2.5 and 5 cm³ per kg of soil) induced an increase in the levels of the other trace elements, while higher doses caused a reduction, especially in Cr. All materials applied to the soil (compost, bentonite and calcium oxide) reduced the content of Ni, Cr and Fe. Compost and calcium oxide also increased Co accumulation in the soil. Bentonite had the strongest reducing effect on the Ni and Cr contents of the soil, reducing them by 42% and 53%, respectively. Meanwhile, calcium oxide had the strongest reducing effect on Fe and Co accumulation, reducing it by 12% and 31%, respectively. Inverse relationships were recorded for Cd (mainly bentonite), Pb (especially compost), Cu (mainly compost), Mn (mainly bentonite) and Zn (only compost) content in the soil. At the most contaminated site, the application of bentonite reduced the accumulation of Pb, Zn and Mn in the soil, while the application of compost reduced the accumulation of Cd. Applying various materials, particularly bentonite and compost, limits the content of certain trace elements in the soil. This has a positive impact on reducing the effect of minor diesel oil pollution on soil properties and can promote the proper growth of plant biomass. Full article

Despite growing global momentum to reduce the number of children who never received a dose of any vaccine, i.e., zero-dose (ZD) children, persistent geographic and social inequities continue to undermine progress toward universal immunization coverage. In Madagascar, where routine vaccination coverage remains below 50% in most regions, the non-governmental organization Doctors for Madagascar and public sector partners are implementing the SOAMEVA program: a targeted community-based initiative to identify and reach ZD children in sixteen underserved districts in the country’s south. This paper outlines the equity-sensitive evaluation design developed to assess the implementation and impact of SOAMEVA. It presents a forward-looking evaluation framework that integrates both quantitative program monitoring and qualitative community insights. By focusing at the fokontany level—the smallest administrative unit in Madagascar—the evaluation captures small-scale variation in ZD prevalence and program reach, allowing for a detailed analysis of disparities often masked in aggregated data. Importantly, the evaluation includes structured feedback loops with community health workers and caregivers, surfacing local knowledge on barriers to immunization access and program adoption. It also tracks real-time adaptations to implementation strategy across diverse contexts, offering insight into how routine immunization programs can be made more responsive, sustainable, and equitable. We propose eight design principles for conducting equity-sensitive evaluation of immunization programs in similar fragile settings. 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

Dye residues from the textile industry constitute a critical wastewater problem. This study aimed to evaluate the removal capacity of methylene blue (MB) in aqueous media, using an adsorbent formulated from activated and sonicated nanoclay (NC) and microatomized Nostoc sphaericum (ANS). NC was obtained by acid treatment, followed by activation with 1 M NaCl and sonication, while ANS was obtained by microatomization in an aqueous medium. NC/ANS was mixed in a 4:1 weight ratio. The NC/ANS synergistic adsorbent was characterized by the point of zero charge (PZC), zeta potential (ζ), particle size, FTIR spectroscopy, and scanning electron microscopy (SEM). NC/ANS exhibited good colloidal stability, as determined by pH_PZC, particle size in the nanometer range, and heterogeneous morphology with functional groups (hydroxyl, carboxyl, and amide), removing between 72.59 and 97.98% from an initial concentration of 10 ppm of MB, for doses of 20 to 30 mg/L of NC/ANS and pH of 5 to 8. Optimal adsorption conditions are achieved at pH 6.8 and 32.9 mg/L of adsorbent NC/ANS. It was observed that the pseudo-first-order (PFO) and pseudo-second-order (PSO) kinetic models best described the adsorption kinetics, indicating a predominance of the physisorption process, with adsorption capacity around 20 mg/g. Isotherm models and thermodynamic parameters of adsorption, ΔS, ΔH, and ΔG, revealed that the adsorption process is spontaneous, favorable, thermodynamically stable, and occurs at the monolayer level, with a regeneration capacity of 90.35 to 37.54% at the fifth cycle. The application of physical activation methods, such as sonication of the clay and microatomization of the algae, allows proposing a novel and alternative synergistic material from organic and inorganic sources that is environmentally friendly and promotes sustainability, with a high capacity to remove cationic dyes in wastewater. Full article

Soybean (Glycine max [L.] Merr.) cultivation is expanding in Central Europe due to the development of early-maturing cultivars and growing demand for plant-based protein produced without the use of genetically modified organisms. However, nitrogen (N) management remains a major challenge in temperate climates, where variable weather conditions can significantly affect nodulation and yield. This study evaluated the effects of three nitrogen fertilisation doses (0, 30, and 60 kg N·ha⁻¹), applied in the form of ammonium nitrate (34% N) and two commercial rhizobial inoculants—HiStick Soy (containing Bradyrhizobium japonicum strain 532C) and Nitragina (including a Polish strain of B. japonicum)—on nodulation, nitrogen uptake, and seed yield. A three-year field experiment (2017–2019) was conducted in southwestern Poland using a two-factor randomized complete block design. Nodulation varied significantly across years, with the highest values recorded under favourable early-season moisture and reduced during drought. In the first year, inoculation with HiStick Soy significantly increased nodule number and seed yield compared to Nitragina and the uninoculated control. Nitrogen fertilisation consistently improved seed yield, although it had no significant effect on nodulation. The highest nitrogen use efficiency was observed with moderate nitrogen input (30 kg N·ha⁻¹) combined with inoculation. These findings highlight the importance of integrating effective rhizobial inoculants with optimized nitrogen fertilisation to improve soybean productivity and nitrogen efficiency under variable temperate climate conditions. Full article

Background: Inflammation abrogates cellular organization and tissue homoeostasis, resulting in redness, swelling, heat, pain, and loss of function. A model of carrageenan-induced paw edema (CIE) is commonly utilized to test anti-inflammatory substances. Based on the ability of Lepisanthes alata (LA), a tropical plant that is rich in phytochemicals like polyphenols, this study assessed the optimal dose and the health benefits of LA in rats that had been induced with carrageenan to develop paw swelling. Methods: Twenty-four male Wistar rats were divided into four groups to which carrageenan was administered, after which, distilled water at oral dose (C + DW), sodium diclofenac 25 mg/kg (C + DS), LA extract in 250 mg/kg (C + LA250), and 500 mg/kg (C + LA500) was given, respectively. Paw edema was assessed in 24 h. Pain was assessed using the Rat Grimace Scale (RGS), cytokines, antioxidant activity, and tissue changes. Results: LA at 250 and 500 mg/kg significantly decreased paw edema and inflammatory markers in the results of both studies. Remarkably, LA 250 mg/kg significantly decreased RGS scores as well as IL-1β, TNF-α, and histological inflammation but had a positive effect on T-SOD levels. Conclusions: LA extract, especially at 250 mg/kg, shows potent anti-inflammatory, analgesic, and antioxidant properties in CIE rats. Full article

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article

Nephronophthisis (NPH) is the leading genetic cause of end-stage renal disease in children and young adults, but no effective disease-modifying therapies are currently available. Here, we identify glucagon-like peptide-1 (GLP-1) signaling as a novel therapeutic target for NPH through a systematic drug repurposing screen in zebrafish. By simultaneously depleting nphp1 and nphp4, we developed a robust zebrafish model that reproduces key features of human NPH, including glomerular cyst formation. Our screen revealed that dipeptidyl peptidase-4 (DPP4) inhibitors (Omarigliptin and Linagliptin) and GLP-1 receptor agonists (Semaglutide) significantly reduce cystogenesis in a dose-dependent manner. Genetic analysis demonstrated that GLP-1 receptor signaling is important for maintaining pronephros integrity, with gcgra and gcgrb (GLP-1 receptor genes) playing a particularly important role. Transcriptomic profiling identified adenosine receptor A2ab (adora2ab) as a key downstream effector of GLP-1 signaling, which regulates ciliary morphology and prevents cyst formation. Notably, nphp1/nphp4 double mutant zebrafish exhibited the upregulation of gcgra as a compensatory mechanism, which might explain their resistance to cystogenesis. This compensation was disrupted by the targeted depletion of GLP-1 receptors or the inhibition of adenylate cyclase, resulting in enhanced cyst formation, specifically in the mutant background. Our findings establish a signaling cascade from GLP-1 receptors to adora2ab in terms of regulating ciliary organization and preventing cystogenesis, offering new therapeutic opportunities for NPH through the repurposing of FDA-approved medications with established safety profiles. Full article