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IntroductionPirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase inhibitor, has demonstrated promising efficacy in B-cell malignancies and is associated with low rates of discontinuation and dose reduction. Pirtobrutinib is administered until disease progression or toxicity, necessitating an understanding of the safety profile in patients with extended treatment.MethodsHere we report the safety of pirtobrutinib in patients with relapsed/refractory B-cell malignancies with extended (≥12 months) drug exposure from the BRUIN trial. Assessments included median time-to-first-occurrence of adverse events (AEs), dose reductions, and discontinuations due to treatment-emergent AEs (TEAEs) and select AEs of interest (AESIs).ResultsOf 773 patients enrolled, 326 (42%) received treatment for ≥12 months. In the extended exposure cohort, the median time-on-treatment was 19 months. The most common all-cause TEAEs were fatigue (32%) and diarrhea (31%). TEAEs leading to dose reduction occurred in 23 (7%) and discontinuations in 11 (3%) extended exposure patients. One patient had a fatal treatment-related AE (COVID-19 pneumonia). Infections (73.0%) were the most common AESI with a median time-to-first-occurrence of 7.4 months. Majority of TEAEs and AESIs occurred during the first year of therapy.ConclusionsPirtobrutinib therapy continues to demonstrate an excellent safety profile amenable to long-term administration without evidence of new or worsening toxicity signals.

ContextRotenone is a toxic chemical found in various plants, including some used as food. Rotenone poisoning can be fatal and there is no antidote. Mechanistically, rotenone inhibits mitochondrial complex I, leading to reduced ATP production, compensatory glycolytic upregulation and secondary lactate production, and oxidative stress. Our literature review examined acute rotenone poisoning in humans, including exposure scenarios, clinical presentations, and treatments.MethodsWe searched five databases for relevant literature from database inception through the search date: July 12, 2022, pairing controlled vocabulary and keywords for "rotenone" with terms relating to human exposures and outcomes, such as "ingestion," "exposure," and "poisoning." We included all peer-reviewed reports found using the search terms where the full English text was available. Data abstracted included the number, age, weight, and sex of the exposed person(s), country where exposure happened, exposure scenario, ingestion context, estimated dose, clinical features, whether hospitalization occurred, treatments, and outcomes.ResultsAfter removing non-qualifying sources from 2,631 publications, we identified 11 case reports describing 18 victims, 15 of whom were hospitalized and five died. Most cases occurred in private quarters where victims unknowingly consumed rotenone-containing plants. Vomiting and metabolic acidosis occurred most commonly. Some patients exhibited impaired cardiopulmonary function. Supportive treatment addressed symptoms and included gastric lavage and/or activated charcoal to remove rotenone from the stomach, vasopressors for hypotension, mechanical ventilation for respiratory insufficiency, and sodium bicarbonate for acidosis. Some patients received N-acetylcysteine to counter oxidative stress.ConclusionsRotenone poisoning, though rare, can be fatal. Exposure prevention is impractical since rotenone is found in some plants used as food or pesticides. Cases may be under-diagnosed because symptoms are non-specific and under-reported in English-language journals since most cases occurred in non-English speaking countries. Treatments are supportive. Exploring antioxidant therapy in animal models of rotenone poisoning may be indicated considering rotenone's mechanism of toxicity.

The leaves of Citrus deliciosa Tenore were collected in southern Brazil, dried, and subjected to the hydrodistillation process to obtain the essential oil. The extraction of essential oil yielded 0.97% ± 0.04. The chromatographic profile of this compound revealed 11 substances, being methyl N-methyl-anthranilate (75.1%), γ-terpinene (13.8%), and Limonene (7%) as major substances. The essential oil shows antifungal action against all tested yeasts, with promising action against Cryptococcus neoformans, Cryptococcus gattii, and Trichosporon asahii. This compound was also able to inhibit the biofilm production of Candida albicans, Candida glabrata, Candida parapsilosis, and T. asahii. The essential oil of tangerine showed weak antioxidant action. It did not show cytotoxicity in human mononuclear cells. It is hoped that these results may guide future studies for the production of formulations that can be used in the treatment of biofilms caused by yeasts, as well as in candidiasis, cryptococcosis, and/or trichosporonosis. [ABSTRACT FROM AUTHOR]

The n-butanol extract of Stachys arvensis (L.) L. aerial parts (BESA) was analysed by LC-HRMS/MS. 43 Polyphenols, including flavonoids, cinnamic acid derivatives, phenylethaoids, chromones, gallotannins, coumarins and chalcones with hyperoside (13.85%), panasenoside (10.31%), myricitrin (7.89%) and sayaendoside (7.16%), as the major compounds, were identified. High total phenolics (470.21 ± 1.22 mg GAE/g extract) and total flavonoids (189.05 ± 0.72 mg QE/g extract) contents were measured. In addition, the BESA exhibited a higher antioxidant effect in CUPRAC (A0.5:0.45 ± 0.03 μg/mL), DPPH (IC50:4.51 ± 0.16 μg/mL) and ABTS (IC50:7.10 ± 0.18 μg/mL) assays than the standards BHA and α-Tocopherol. Moreover the extract showed a good inhibitory effect against BChE (IC50: 145.02 ± 0.03 μg/mL) and α-amylase (IC50:2.66 ± 0.0024 mg/mL). The BESA exhibited an excellent anti-inflammatory activity (IC50:416 ± 0,056 μg/mL) which was close to that of acetylsalicylic acid, used as a control. The BESA was toxic towards T. molitor larvae and it possessed a good antibacterial activity against gram (+) and gram (-) tested strains. [ABSTRACT FROM AUTHOR]

The development of an environmentally benign method for the synthesis of nanoparticles has been facilitated by green chemistry. "Green synthesis" uses a range of biological elements like microbes, plants, and other biodegradable materials to produce NPs. Active biomolecules that are secreted by natural strains and present in the plant extracts serve as both reducing and capping/stabilizing agents. Microorganisms' intracellular enzymes can reduce metal ions, which explains how NPs might potentially nucleate. Plant-based synthesis of nanomaterials is particularly promising owing to abundant resources, simplicity of synthesis, and low cost. Silver nanoparticles (AgNPs) are attracting great attention in the research community due to their wide variety of applications in chemistry, food technology, microbiology, and biomedicine. Recent years have seen a large amount of research on the bio-genic synthesis of AgNPs employing biomaterials like plant extract and bacteria as reducing agents. Herein we discuss a thorough overview of the plant-based synthesis of silver nanoparticles (AgNPs), characterization approaches, applications, and toxicity. The review covers the green chemistry and nanotechnology elements of producing AgNPs, including a thorough discussion of the plant extract mediated synthesis, detailed formation mechanism, and a well-balanced emphasis on hazards and advantages. Based on current developments, the optimisation strategies, applications, and interdisciplinary characteristics are also covered in detail. • Plant-based synthesis of nanomaterials is particularly promising. • A comprehensive review on plant-based AgNPs synthesis. • Synthesis, characterization approaches, applications and toxicity are discussed. [ABSTRACT FROM AUTHOR]

During drug discovery, it is crucial to exclude compounds with toxic effects. The human ether-à-go-go-related gene (hERG) channel is essential for maintaining cardiac repolarization and is a critical target in drug safety evaluation due to its role in drug-induced arrhythmias. Inhibition of the hERG channel can lead to severe cardiac issues, including Torsades de Pointes tachycardia. Understanding hERG inhibition mechanisms is essential to avoid these toxicities. Several structural studies have elucidated the interactions between inhibitors and hERG. However, orientation and resolution issues have so far limited detailed insights. Here, we used digitonin to analyze the apo state of hERG, which resolved orientation issues and improved the resolution. We determined the structure of hERG bound to astemizole, showing a clear map in the pore pathway. Using this strategy, we also analyzed the binding modes of E-4031 and pimozide. These insights into inhibitor interactions with hERG may aid safer drug design and enhance cardiac safety. [Display omitted] • Binding modes of hERG inhibitors were revealed with higher resolution cryo-EM data • Preferred particle orientation issues of cryo-EM data were resolved by using digitonin • The binding modes of hERG to astemizole, E-4031, and pimozide were determined • This study provides insights into hERG-inhibitor interactions for safer drug design Miyashita et al. overcame preferred orientation issue and they obtained improved cryo-EM data, which enabled them to elucidate the binding mechanisms of the hERG inhibitors astemizole, E-4031, and pimozide. These structural data are of interest to guide safer drug design and avoid drug-induced arrhythmias. [ABSTRACT FROM AUTHOR]

Background and aims: A number of case reports have documented the occurrence of acute hepatic and renal toxicity during treatment with deferasirox (DFX). The precise mechanisms underlying these adverse events remain unclear, with the time to toxicity varying considerably between patients—some experiencing it within weeks of treatment initiation, while others after several years. Recent studies have underscored the association of pharmacogenetic variants in genes responsible for the metabolism and clearance of DFX (ABCC2 , ABCG2 , and UGT1A1) in the development of toxicity. We present the case of an 8-year-old patient with beta thalassemia major who developed acute hepatic failure years after the initiation of DFX therapy. After ruling out the most likely causes, we performed a pharmacogenetic analysis, which suggested a possible link between the patient's genotype and the development of toxicity. Methods: Sanger sequencing was performed for the most extensively studied single nucleotide polymorphisms (SNPs) studied associated with changes in transporter/enzyme function: ABCC2 rs717620 (c.-24C>T), rs2273697 (c.1249G>A), rs8187710 (c.4544G>A), rs369192412 (g.99781071delG); ABCG2 rs2231142 (c.421C>A); UGT1A1 *6 rs4148323 (c.211G>A), *28 rs3064744 (g.233760235TA[8]), *36 rs3064744 (g.233760235TA[6]) and *37 rs3064744 (g.233760235TA[9]). Results: The patient is heterozygous for two ABCC2 variants, namely rs717620 (c.-24C>T) and rs2273697 (c.1249G>A). These variants have the potential to cause a reduction in transporter function, which could in turn result in decreased drug clearance and increased toxicity. Discussion: The precise mechanism by which toxicity developed in this case remains unclear and is likely multifactorial. However, it is probable that the presence of SNPs in the gene ABCC2 played a substantial role. Our findings align with those of previously published reports of remarkably similar cases, where patients also exhibited genetic variants in the gene ABCC2. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to systematically analyze the efficacy and toxicity of lurbinectedin as a second-line or subsequent treatment for extensive-stage small cell lung cancer (ES-SCLC). Methods: Candidate studies were identified in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases up to 1 May 2024. Objective remission rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were extracted, respectively. The efficacy and toxicity of lurbinectedin in ES-SCLC were analyzed by meta-analysis. Results: Six eligible prospective studies were included in this meta-analysis, including 536 patients with ES-SCLC who received second-line or subsequent treatment. In pooled analysis, the ORR of lurbinectedin was 35% (95% confidence interval [CI] 29–41), DCR was 67% (95%CI 58–76), DOR was 5.33 months (95%CI 4.51-6.16), PFS was 3.38 months (95%CI 2.59-4.17), and OS was 7.49 months (95%CI 5.11–9.87). The incidence of AEs and severe adverse events (SAEs) was 92% (95%CI 78–100) and 37% (95%CI 19–57), respectively. The most common AEs were leukopenia, neutropenia, anemia, and thrombocytopenia, with incidences of 81% (68–91), 74% (57–88), 73% (35–98) and 57% (46–68), respectively. Conclusion: As a promising alternative for second-line treatment for ES-SCLC, lurbinectedin has a certain level of efficacy and a favorable safety profile. The integration of lurbinectedin with other therapeutic modalities presents an emerging area warranting further investigation. [ABSTRACT FROM AUTHOR]

The cotton bollworm, Helicoverpa armigera (Hübner), is one of the important insect pests of cotton throughout the world. Considering the adverse effects of chemical pesticides, it is necessary to find eco-friendly substitute agents for managing insect pests, including H. armigera. Plant-derived insecticides have been introduced as suitable candidates to replace detrimental synthetic chemicals. In this study, the toxicities of water, ethanol, and n-hexane extracts of eucalyptus and thyme, as well as their wettable powder formulations, against H. armigera larvae were investigated. The treated larvae represented different degrees of abnormalities, such as larva-pupa intermediate and pupa-adult stages in their different ages until they turned into pupae and completed the breeding cycle. The results showed that the considered formulations of extract of n-hexane and ethanol, and concentrations had significant effects on the mortality rates of the larvae (P≤0.05) but the interaction of extracts and concentrations was not significant. The mortality rates were enhanced by increasing the tested concentrations. The LC50 values (lethal concentrations to kill 50% of the tested insects) were 343.758% (water), 10.171% and 23.264% (ethanol), and 0.404% and 0.490% (n-hexane) for the eucalyptus and thyme extracts within 24 hours, respectively, indicating higher toxicities of n-hexane extracts. The LC50 values of wettable powder formulations of the thyme and eucalyptus extracts were 120.68% and 177.75% (water) and 36.17% and 74.65% (ethanol), respectively, which represented the greater toxicities of these types of formulations. Therefore, the wettable powder formulations of ethanol and water extracts of thyme were more toxic than their solution formulations. Based on the results of this study, wettable powder formulation of eucalyptus and thyme extracts had promising potential for H. armigera management. [ABSTRACT FROM AUTHOR]

As the single largest class of specialty chemicals, surfactants are consumed in huge quantities in our daily life and in many industrial areas. In the past, the attention was focused entirely on technical performance. However, starting from the 1970s and 80s, surfactant related environmental concerns have become the main driving force to upgrade surfactant production technology to make more benign or "greener" products. For this reason, environmental issues, dermatological effects, and oral toxicity are the main priorities when surfactants are considered for a specific purpose. In this paper, we present five cases to demonstrate how the surfactant industry tackles these challenges to mitigate the environmental and health effects associated with surfactant consumption. We also discuss the important role played by surfactants in a current carbon capture and storage (CCS) strategy to reduce the CO2 level in the atmosphere. Surfactant-based stable CO2 foam flooding is a well-established enhanced oil recovery technique. It has been considered to be an economically realistic procedure to sequester large amounts of CO2 in geological formations. [ABSTRACT FROM AUTHOR]

• Methanolic leaf extract of chinaberry killed 85 % H. indicola workers after 6 days. • MetOH and water extracts showed dose and time-dependent trends on non-durable wood. • GC–MS: chinaberry leaf extracts contain antifeedants like phytol and terpenoids. Hetertermes indicola Wasman (Blattodea: Rhinotermitidae) is a highly wood-destructive termite species in the urban settings of Pakistan. This study evaluated the biocidal action of Melia azedarach leaf extract in different solvents on H. indicola by conducting choice and no-choice feeding deterrence assays using impregnated palatable wood under field and laboratory conditions. Dose-dependent and time-dependent trends were observed in the leaf extracts of M. azedarach at different concentrations (500, 1000, and 1500 ppm) using solvent water and methanol with 80–100 % termite mortality after 6 days of exposure. A key outcome was the higher termiticidal efficacy of methanolic extract compared to aqueous extract under both field and laboratory conditions. The LC50 values of 358 ppm for methanol and 466 ppm for aqueous extract after 15 days in a laboratory no-choice experiment exhibit a quantitative measure of chinaberry leaf extract toxicity. A significant reduction in mean percent weight loss (8.26 %) of treated wood with 1500 ppm of M. azedarach leaf extract in methanol was observed under field conditions. In conclusion, triterpenoids and phytol present in methanolic leaf extract demonstrated higher efficacy in both lab and field conditions making a solid foundation for the further development of natural wood preservatives. Since they induced rapid lethargic conditions in termites and digestive toxicity which leads to minimum loss of treated wood. [ABSTRACT FROM AUTHOR]

• Iron oxide nanoparticles decreased the microbial activity in soil. • Nanoparticle addition caused significant shift in soil bacterial community. • Beneficial bacterial community showed decreased abundance after nanoparticle amendments. • Changes in bacterial abundance affected the plant growth and yield attributes. Although nanotechnology has the potential to revolutionize the current agriculture system, there have been a few reported studies of the impact of nanoparticles on plants, showing that nanoparticles could have adverse effects. Studies have shown that these materials can have significant adverse effects on both plants and soil microbes in agroecosystems. In this study, we evaluated the effect of Fe 2 O 3 −NPs on the soil microbial community in connection to the growth of soybean plants. Nanoparticles were added to the soil at three different concentrations (0.4 %, 0.8 %, and 1.2 %). The effect of these soil amendments on soil bacterial community and plant growth attributes was checked. Results showed that the lowest concentration of the nanoparticles (0.4 %) did not affect the soil bacterial community structure and size, while nanoparticle amendment at 0.8 % and 1.2 % significantly altered the bacterial community size and structure. Taxonomic analysis revealed that the addition of nanoparticles suppressed the abundance of beneficial microbes that play essential plant-friendly roles. Moreover, plant growth and yield was significantly affected by adding nanoparticles at 0.8 % and 1.2 % nanoparticle concentration in the soil, which was correlated with the corresponding suppression of bacterial genera in the respective groups. These results reveal the potential toxicity of Fe 2 O 3 −NPs to soil microbe, which in turn affects plant growth and suggests that the hazardous impacts of the nanoparticles should be investigated before their large-scale application. [ABSTRACT FROM AUTHOR]

Environ 10 à 15 % des patientes atteintes d'un cancer du sein seront atteintes d'une récidive locale après un traitement conservateur initial ou une mastectomie. La mastectomie totale est historiquement le traitement de référence en cas de récidive locale. Cependant, la réirradiation peut être une option en cas de second traitement conservateur en association à une segmentectomie ou en cas de récidive sur la paroi thoracique afin d'améliorer le taux de contrôle local. Différentes modalités sont disponibles : la curiethérapie, la radiothérapie externe avec ou sans hyperthermie. Bien que les résultats carcinologiques soient encourageants, cette situation complexe nécessite une sélection rigoureuse des patientes et une maîtrise technique afin d'obtenir le meilleur taux de contrôle local et de limiter la toxicité. Cet article présente une revue des données de la littérature sur les indications et différentes techniques de réirradiation des récidives homolatérales des carcinomes mammaires afin d'apporter une aide à la prise de décision en pratique clinique. Approximately 10 to 15% of patients with breast cancer will have a local recurrence after initial conservative treatment or mastectomy. Total mastectomy has historically been the standard treatment for local recurrence. However, the question of reirradiation may arise as part of a second conservative treatment in conjunction with segmentectomy or in the case of chest wall recurrence to improve local control. Different modalities are available: brachytherapy, external beam radiotherapy with or without hyperthermia. Although the carcinologic results are encouraging, this complex situation requires rigorous patient selection and technical requirements to achieve the best local control and limit toxicity events. This article presents a review of the literature on the different indications and techniques for reirradiation of ipsilateral recurrent breast cancer, with the aim of providing decision support in clinical practice. [ABSTRACT FROM AUTHOR]

Approximately one-third of Americans use healthcare approaches including herbs and botanicals, such as St. John's wort (SJW), to improve overall well-being, gain control over their health, and manage the adverse reactions of conventional therapies. This article examines the use of SJW in cancer care, discussing its pharmacokinetics, toxicity, and potential interactions with cancer treatments while emphasizing the importance of patient education and collaboration between oncology nurses and pharmacists to ensure safe and effective care. [ABSTRACT FROM AUTHOR]

Municipal wastewater may contain toxic substances that have a negative impact on biological treatment processes and receiving waters. This paper presents the wastewater toxicity test results from the Lodz hybrid sewage system. Wastewater is discharged to surface waters through a treatment plant, but also during wet weather, partially without treatment by combined sewer overflows. The research was carried out using the ToxTrakTM method with the use of the microbial community of activated sludge from the wastewater treatment plant in Lodz. The median toxicity, expressed as the degree of inhibition, ranged from 16.0% to 30.7%, but sometimes exceeded 50%. Higher toxicity was observed in wet weather than in dry weather. Seasonal variability was found but typical daily variability was not observed. In the case of sewage samples with the degree of inhibition above 40%, a significant correlation was found with chromium concentration and non-ionic surfactants (Pearson's coefficient correlation above 0.7). [ABSTRACT FROM AUTHOR]

Lead white (basic lead carbonate), before its effective ban in much of Europe from 1989 onwards, was among the most versatile and widespread but also one of the most harmful pigments available. This paper is a critical discussion of the regulation of lead white paint and its consequences from the point of view of conservation and artistic practice in Europe. It looks at who benefited from exemptions to bans, and whether there was resistance to them. Buildings and artworks are both taken into account. The paper discusses nuances in regulation in four European countries which have notable differences in approach (France, Austria, Germany, and the United Kingdom). The centralised regulatory framework of the United Kingdom allows data analysis on the authorised use of the paint since its restriction up to the present day. This dataset shows a steady decrease in the use of the paint by conservators across disciplines. The paper concludes by considering the professional and ethical implications of lead white paint for artists and conservators, in the context of varied regulation and a decline in use. [ABSTRACT FROM AUTHOR]

Perfluorooctanoic acid (PFOA) is a surfactant that is detected in small quantities across various environments away from its manufacturing zones. Despite the widespread detection of PFOA in aquatic ecosystems, the impact of this compound on phytoplankton populations remains poorly understood. This study aimed to determine the physiological effects of PFOA on Microcystis aeruginosa. The cyanobacterium was exposed to 1‒10 000 μg l‒1 PFOA for 7 days under controlled laboratory conditions. The EC50 of PFOA for the test species after 7 days of exposure was 30.03 μg l‒1. Cell density significantly decreased at all PFOA concentrations (1‒10 000 μg l‒1). Chlorophyll a and carotenoid concentrations increased on day 1 (except for 1 μg l‒1, the lowest PFOA treatment) but then decreased across all treatment concentrations on day 7 of the experiment. When M. aeruginosa was exposed to PFOA, the total lipid, protein and carbohydrate content generally increased across all treatment concentrations. The concentration of intracellular hydrogen peroxide increased with increasing surfactant concentrations. In different treatments, lipid peroxidation increased, with 100 μg l‒1 PFOA producing the highest malondialdehyde content. Peroxidase and glutathione S-transferase activities increased across all treatment concentrations, demonstrating progressive changes consistent with the increase in reactive oxygen species observed. Total microcystin concentration increased in cultures exposed to 1000 and 10 000 µg l‒1 PFOA. These findings suggest that PFOA can adversely affect the survival of M. aeruginosa populations in contaminated aquatic ecosystems, with potential cascading effects on the general health of the environment. [ABSTRACT FROM AUTHOR]

Ce-doped WO3 nanoparticles were fabricated and characterized using powder X-ray diffraction (XRD), Fourier-transform infrared (FTIR), Raman, SEM–EDX, UV–Vis, photoluminescence (PL), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS) analyses. The results revealed the formation of a highly crystalline monoclinic phase in Ce-doped WO3 photocatalyst (abbreviated WCC), confirmed by Raman spectroscopy. The bandgap was tuned by increasing the percentage of Ce dopant, where the WCC (1 mol wt% Ce-doped WO3) photocatalyst sample exhibited the highest photocatalytic activity towards synthetic methylene blue (MB) dye pollutant and biodegradation-resistant tetracycline hydrochloride (TC-HCl) antibiotic. The decomposition efficiency using the WCC photocatalyst against aqueous MB dye and TC-HCl antibiotic reached 95% and 51% after exposure to simulated sunlight irradiation for 180 min, with excellent stability after four recycling runs. The interfacial contact between Ce and WO3 effectively shortened the charge transfer carrier process, enabling redox reactions to provide the best decomposition efficiency over the investigated pollutants. The photodecomposition rate constant of WCC was 0.017 min−1 for MB dye, which is 3.6-fold higher performance than common literature photocatalysts. The results showed the significance of the environmental impact toxicity assessment by applying the treated water to finger millet plant growth. Based on the research feasibility, the synthesized photocatalyst demonstrated superior decomposition against dyes and antibiotics, making it highly suitable for applications in wastewater treatment. Moreover, the use of degraded water resulted in productive plant growth. [ABSTRACT FROM AUTHOR]

Heavy metals like cadmium (Cd) are one of the main environmental pollutants, with no biological role in the human body. Cd has been well-documented to have disastrous effects on both plants and animals. It is known to accumulate in kidneys, lungs, liver, and testes and is thought to affect these organs' function over time, which is linked to a very long biological half-life and a very poor rate of elimination. According to recent researches, the testes are extremely vulnerable to cadmium. The disruption of the blood–testis barrier, seminiferous tubules, Sertoli cells, and Leydig cells caused by cadmium leads to the loss of sperm through various mechanisms, such as oxidative stress, spermatogenic cell death, testicular swelling, dysfunction in androgen-producing cells, interference with gene regulation, disruption of ionic homeostasis, and damage to the vascular endothelium. Additionally, through epigenetic control, cadmium disrupts the function of germ cells and somatic cells, resulting in infertile or subfertile males. A full grasp of the mechanisms underlying testicular toxicity caused by Cd is very important to develop suitable strategies to ameliorate male fertility. Therefore, this review article outlines cadmium's impact on growth and functions of the testicles, reviews therapeutic approaches and protective mechanisms, considers recent research findings, and identifies future research directions. [ABSTRACT FROM AUTHOR]

Since the reports of the first cases of COVID-19, in less than 5 years, a huge number of documents regarding that disease and the coronavirus (SARS-CoV-2), responsible for the infection, have been published. The tremendous number of scientific documents covers many topics on different issues directly related to COVID-19/SARS-CoV-2. The number of articles—including reviews—reporting adverse/side effects of the approved COVID-19 vaccines is considerable. A wide range of adverse/side effects have been reported in humans after COVID-19 vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, and other miscellaneous adverse effects. In contrast, information on nonclinical studies conducted to assess the potential toxicity/adverse effects of the COVID-19 vaccines in laboratory animals, is comparatively very scarce. The present review was aimed at revising the scientific literature regarding the studies in laboratory animals on the toxic/adverse effects of COVID-19 vaccines. In addition, the investigations reported in those specific toxicology journals with the highest impact factors have been examined one by one. The results of the present review indicate that most nonclinical/experimental studies on the adverse/toxic effects of the COVID-19 vaccines and/or potential candidates showed—in general terms—a good safety profile. Only in some animal studies were certain adverse effects found. However, a rather surprising result has been the limited number of available (in the databases PubMed and Scopus) nonclinical studies performed by the companies that have been the largest manufacturers of mRNA vaccines in the world. It is assumed that these studies have been conducted. However, they have not been published in scientific journals, which does not allow the judgment of the international scientific community, including toxicologists. [ABSTRACT FROM AUTHOR]

Purpose: Nivolumab is approved at various doses, including 3 mg/kg, 240 mg and 480 mg flat doses at various dosing intervals. The concept of low-dose immunotherapy is gaining traction in recent years. However, there is a need to better understand the pharmacokinetics and clinical outcomes at lower doses. Methods: Patients were either administered 40 mg flat dose or 3 mg/kg Q2W/Q3W, depending on affordability as per prevailing hospital practice. All patients were hospitalized on day 1 and pharmacokinetic samples were collected at 0, 0.5, 1.0, 6.0, 24.0, 72.0 h and day 14 following administration of the first dose of nivolumab. Plasma nivolumab levels were measured by ELISA. Patients were followed up for response and toxicity. Results: Twenty five patients were included in the study. Fourteen received nivolumab at conventional dose (3 mg/kg), while 11 patients received low-dose (40 mg flat). The geometric means of dose normalized Cmax and AUC0-t were comparable between those who received conventional dose and low-dose of nivolumab (0.28 versus 0.23 µg/mL/mg and 0.0014 versus 0.0011 d/mL respectively). Nineteen patients were evaluable for response. ORR among patients who received conventional dose was 5/11 (45.5%) whereas it was 4/9 (44.4%) in the low-dose cohort. All 14 (100%) patients in conventional dosing group and 7/11 patients (63.64%) in low-dose group had treatment emergent adverse events. Grade ≥ 3 toxicities were observed in 4/14 patients in conventional dose group and none in low-dose group. Conclusion: Low-dose nivolumab leads to lower exposure in patients as compared with conventional dose, but low-dose was better tolerated, while response rates were comparable to conventional dose. [ABSTRACT FROM AUTHOR]

BACKGROUND: The stem of Abroma augusta contains mucilaginous polysaccharides having numerous ethnomedicinal properties. The present work aimed to develop a scalable ultrasonic‐assisted aqueous Abroma augusta mucilage (AAM) extraction (UAE) method and further explores its emulsifying property and toxicity concern. RESULTS: The combination of ultrasonic power (750 W), solid‐to‐liquid ratio (1:15) and temperature (348 K) gave the highest extraction yield of 2.28% with a diffusivity value of 3.85 × 10−9 m2 s−1, which was higher than aqueous extraction method using a kinetic model based on Fick's second law of diffusion. The extracted polysaccharide showed no toxicity as measured through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assay on RAW cell line. Additionally, the polysaccharide over its critical micelle concentration (400, 500, 600 and 700 μg mL−1) offered emulsifying properties with 0.5%, 1% and 5% oil (v/v). The emulsion with a polysaccharide concentration of 600 μg mL−1 with 5% oil (v/v) provides stability against coalescence for 3 days. CONCLUSION: The overall findings indicated that UAE of AAM polysaccharide can be used for an efficient extraction method, and the obtained polysaccharide is nontoxic in nature and bears emulsifying properties. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Heavy metals (HM) and polycyclic aromatic hydrocarbons (PAHs) exposition has been associated with health problems. Therefore, this research evaluated genotoxicity induced in male mice strain CD-1 exposed to benzo[a]anthracene (B[a]A) and benzo[a]pyrene (B[a]P) and their interaction with Fe, Pb, and Al. Methods: Groups of animals were exposed intraperitoneally to HM, PAHs, and mixtures of both. Peripheral blood samples were taken from 0 to 96 h at 24 h intervals; genotoxicity was determined by micronucleus tests and comet assay. Additionally, toxicity and viability were evaluated. Results: HM and PAHs individually were genotoxic. About toxicity, only Al altered polychromatic erythrocytes number and did not change leukocytes viability. Concerning mixtures, Fe + B[a]P, Fe + B[a]A, Pb + B[a]P increased genotoxicity. There were no changes with Pb + B[a]A. Finally, Al mixtures with both PAHs damage was decreased. Conclusions: Exposure to HM and PAH caused genetic damage. Fe, Al, and B[a]A, established a genotoxic potential. Every metal can interact with PAHs in different ways. Also, the micronucleus test and the comet assay demonstrated their high capacity and reliability to determine the genotoxic potential of the compounds evaluated in this work. [ABSTRACT FROM AUTHOR]

Hamza MA, Hassan MS, Mousa RF. 2024. The role of ginseng extract green nanoparticles as an antioxidant on physiological parameters and fertility in male rats exposed to potassium dichromate. Nusantara Bioscience 16: 219-227. The toxicity of chrome ions is prevalent due to their commonly used in the industry. Some plants are useful for treating toxicity, and ginseng is one of the most known medicinal herbs worldwide and possesses numerous health benefits. The present study aims to use ginseng extract and nano ginseng particles to treat toxicity by potassium dichromate PDC in a rat's model. Therefore, the PDC-toxified rats were treated with ginseng extract and ginseng-NPs at different concentrations, and ginseng-NPs were prepared using green biosynthesis. ELISA technique was used for serum estimation of GSH, SOD, MDA, LH, FSH, and testosterone in the animals' groups. Ginseng extract and ginseng nanoparticles could alleviate the toxic effects of PDC, as indicated by lower MDA, higher levels of antioxidants (SOD and catalase), FSH, and LH-Ab compared to the PDC intoxication group. The results display the lower toxicity of MDA and Catalase parameters compared to groups 2 and 5, whereas the other parameters indicate an increase. By buffering the concentrations of the tested biomarkers in a concentration-dependent way, the nanoparticles added to the protective effects of ginseng. For PDC, ginseng extract has antioxidant and antitoxic properties. Using ginseng nanoparticles led to a concentration-dependent increase in the activity of ginseng extract. [ABSTRACT FROM AUTHOR]

Microplastic particles (MPs) have been detected in a variety of environmental samples, including soil, water, food, and air. Cellular studies and animal exposures reported that exposure to MPs composed of different polymers might result in adverse effects at the portal of entry (local) or throughout the body (systemic). The most relevant routes of particle uptake into the body are oral and respiratory exposure. This review describes the various processes that may contribute to the adverse effects of MPs. Only MPs up to 5 µm were found to cross epithelial barriers to a significant extent. However, MPs may also exert a detrimental impact on human health by acting at the epithelial barrier and within the lumen of the orogastrointestinal and respiratory tract. The potential for adverse effects on human health resulting from the leaching, sorption, and desorption of chemicals, as well as the impact of MPs on nutritional status and dysbiosis, are reviewed. In vitro models are suggested as a means of (1) assessing permeation, (2) determining adverse effects on cells of the epithelial barrier, (3) examining influence of digestive fluids on leaching, desorption, and particle properties, and (4) role of microbiota-epithelial cell interactions. The contribution of these mechanisms to human health depends upon exposure levels, which unfortunately have been estimated very differently. [ABSTRACT FROM AUTHOR]

Background: Gabapentin and pregabalin were originally introduced as anticonvulsant medications but are now also prescribed on- and off-label for multiple medical disorders, especially for pain management. The national opioid crisis has led to increased use of non-opioid pain medications, including gabapentinoids, which has been associated with changing patterns of adverse events associated with these medications. This study investigated the characteristics and trends of gabapentin and pregabalin exposures reported to US poison centers from 2012 to 2022. Methods: National Poison Data System data involving gabapentin and pregabalin exposures for 2012 to 2022 were analyzed. Results: There were 124,161 exposures involving gabapentin and pregabalin as the primary substance reported to US poison centers during the study period. Most exposures involved gabapentin (85.9%), females (59.4%), single-substance exposures (62.9%), or occurred at a residence (97.2%). Suspected suicides accounted for 45.2% of exposures. Most exposures were associated with a minor effect (27.4%) or no effect (34.0%), while 22.1% experienced a serious medical outcome, including 96 fatalities. The rate of gabapentin and pregabalin exposures per one million US population increased by 236.1% from 22.7 in 2012 to 76.5 in 2019 (P < 0.001), followed by a non-significant decrease to 68.5 in 2022 (P = 0.068). Conclusions: The rate of gabapentin and pregabalin exposures reported to US poison centers increased by more than 230% from 2012 to 2019 before plateauing from 2019 to 2022. The observed rate trend was driven primarily by gabapentin exposures and by cases associated with suspected suicide. Although most exposures were associated with a minor or no effect, 22% of individuals experienced a serious medical outcome, including 96 fatalities. These findings contribute to the discussion of rescheduling gabapentin as a federally controlled substance, which is the current status of pregabalin. Prevention of suicide associated with gabapentin and pregabalin merits special attention. [ABSTRACT FROM AUTHOR]

Road dust resuspension in urban environments can contribute to high human exposure to metal(loid)s, polycyclic aromatic hydrocarbons, and other potentially toxic organic compounds. However, for many regions, information on loadings, emission factors and chemical profiles is lacking to accurately apply emission inventories and source apportionment models. In the present study, PM10 samples were collected with an in situ road dust sampler from eleven representative streets of Bragança, an inland city of the Iberian Peninsula, and were analysed for organic and elemental carbon by a thermal-optical technique, elemental composition by ICP-MS and ICP-OES, and ecotoxicity by a luminescence inhibition bioassay with Allivibrio fischeri. A global emission factor of 5.36 ± 2.35 mg veh−1 km−1 was obtained but in suburban areas the values reached twice the average. Total carbon accounted for 14.9 ± 6.8% of the PM10 mass, while element oxides represented the largest share (28.6 ± 18.7%). Very high enrichments were found for typical traffic-related elements such as Cu, Zn, S, Pb and Ni. The geochemical index Igeo further confirmed that road dust of the study region is extremely contaminated by elements mainly originated from tyre and brake wear. Although the total non-carcinogenic and carcinogenic risks associated with metal exposure were found to be low for both children and adults, the bioluminescence inhibition assay showed (eco)toxic responses for all samples, indicating that road dust resuspension may pose a significant human health and ecological threat. [ABSTRACT FROM AUTHOR]

Background: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1‐2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV‐negative (HPV‐) patients. We aimed to compare outcomes of potential TOS‐candidates vs. non‐TOS candidates, among patients who underwent RT/CRT for early T‐stage HPV‐ OPSCC. Methods: For patients treated with RT/CRT for early T‐stage HPV‐negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head‐and‐neck surgeons, masked to clinical outcomes, to assess primary‐site suitability for TOS. Extracapsular extension (ECE) was assessed by a head‐and‐neck neuroradiologist. We compared outcomes based on surgical resectability relating to: (1) the primary site tumor alone, and (2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan–Meier curves for overall survival (OS), disease‐specific survival (DSS), and progression‐free survival (PFS) were compared using the log‐rank test. Results: Seventy patients were included in the analysis. The primary site was TOS‐favorable in 46/70 (66%). Based on the overall assessment, 41/70 (58.6%) were TOS‐favorable. The 3‐year OS, DSS and PFS for primary site TOS‐favorable versus unfavorable were OS: 76.9% versus 37.4%; DSS: 78.1% versus 46.2%, PFS: 69.9% versus 41.3%, (log‐rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS‐unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log‐rank test = 0.01, 0.04, 0.01; respectively). Conclusion: Patients with TOS‐favorable HPV‐negative early T‐stage OPSCC have superior survival outcomes than TOS‐unfavorable patients. [ABSTRACT FROM AUTHOR]

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Xanthobacter sp. SoF1 (SoF1) is an autotrophic hydrogen‐oxidizing bacteria that produces protein‐rich biomass and has potential to be an alternative protein source that is more environmentally sustainable than animal and plant derived proteins. A protein‐rich powder derived from SoF1 was the test material in a 90‐day repeated‐dose oral toxicity study to explore major toxic effects, demonstrate target organs, and provide an estimate of a no‐observed‐adverse‐effect level (NOAEL). Daily doses of 0 (vehicle only), 375, 750, and 1500 mg/kg bw/day of the test material were administered by gavage to 10 Han:WIST rats/sex/group. An additional group was administered 1290 mg/kg bw/day whey protein concentrate as positive control. No treatment‐related adverse effects were observed, and no target organs were determined after 90/91 days of consecutive administration of the test item. A NOAEL of 1500 mg/kg bw/day was determined. A 90‐day repeated‐dose oral toxicity study was conducted to assess the subchronic toxicity of a microbial protein powder derived from Xanthobacter sp. SoF1. Daily doses of 0 (vehicle only), 375, 750, and 1500 mg/kg bw/day of the test material and 1290 mg/kg whey protein concentrate as a positive control were administered by gavage to 10 Han:WIST rats/sex/group. A no‐observed‐adverse‐effect‐level of 1500 mg/kg bw/day was determined. [ABSTRACT FROM AUTHOR]

Apis mellifera has ecological, economic and social importance. Thus, this study aimed to compare, at a toxicological, physiological and nutritional level, the insecticidal activity of natural pesticides in comparison with synthetic ones, adding knowledge about the impacts of these products and verifying their safety for these animals. Toxicity bioassays were performed to obtain the LC50 (lethal concentration) of the products (Azamax®, Limonene, Karate® and Roundup®) through Probit analysis. The concentrations and toxicity ratios (TR) obtained, in decreasing toxicity level, were Karate® (0.0134 mL/100 mL, 53,156 times) > Limonene (1.44 mL/100 mL, 494.64 times) > Roundup® (712.29 mL/100 mL). It was not possible to obtain the LC50 for Azamax®, as concentrations above 250 mL/100 mL caused repellency and below there was no mortality. LC50 and Azamax® concentrations were used as a treatment in histological, histochemical and biochemical analyses. Although the herbicide Roundup® has shown low toxicity by ingestion, it and the Limonene were the substances that most interfered with nutritional biochemical parameters, in addition to causing histopathological changes in midgut cells. The insecticide Karate® also led to histopathological changes in cells and a reduction in important macromolecules used in biochemical functions. Despite the repellency observed in the insecticide Azamax®, A. mellifera presented morphological alterations in the digestive cells and in the absorption of nutrients. It is concluded that natural pesticides can be as harmful to A. mellifera bees as synthetic ones, and they can cause deleterious effects on the digestive physiology of these insects, which may reflect on their reproduction. [ABSTRACT FROM AUTHOR]

Background: The (ECOG) performance status (PS) is commonly used to evaluate the functional ability of patients undergoing antitumor therapy. An ECOG PS of 2, indicating patients capable of self-care but restricted strenuous activity, can complicate treatment decisions owing to concerns regarding treatment-related toxicity. We investigated whether frailty assessment could help discriminate treatment tolerance and survival outcomes in patients with an ECOG PS of 2. Methods: We prospectively included 45 consecutive patients, aged ≥65 years, with an ECOG PS of 2, and newly diagnosed solid cancer scheduled for chemotherapy. Frailty was assessed using an eight-indicator geriatric assessment. The primary outcome was overall survival (OS) based on frailty status; secondary outcomes included treatment tolerance and toxicity. Results: The median patient age was 73 years (range 65-94), and 71% had stage IV disease. Predominant frailty-related deficits were functional decline (96%), malnutrition (78%), and polypharmacy (51%). The median OS was 12.6 months (95% confidence interval [CI]: 6.8-18.4). Patients with 4-6 deficits had significantly lower OS than those with 1-3 deficits (9.9 months vs. 20.0 months, adjusted hazard ratio 2.51, 95% CI: 1.16-5.44, P =.020). Frailty significantly correlated with reduced 12-week chemotherapy competence (52% vs. 85%, adjusted odds ratio [OR].14, 95% CI:.03-.70, P =.016) and enhanced risk of unexpected hospitalization (60% vs. 20%, adjusted OR 6.80, 95% CI: 1.64-28.1, P =.008). Conclusion: Our findings highlight the multifaceted nature of patients with an ECOG PS of 2 and emphasize the importance of frailty assessment for treatment outcomes. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMaterials and methodsResultsConclusionRadiotherapy-related damage of normal tissue inevitably influences the treatment outcomes in the context of high-grade gliomas (HGGs) treatment. We reported the survival outcomes and toxicities of patients with HGG treated with helical tomotherapy (HT) and the prognostic factors were analyzed.A total of 67 patients (29 had grade III and 38 had grade IV HGGs) who received HT between January 2016 and June 2020 were analyzed. Overall survival (OS) and progression-free survival (PFS) from the beginning of HT and OS from surgery were assessed, and toxicity and disease control were described briefly.For patients with grade III HGGs, median OS (mOS) and median PFS (mPFS) from the beginning of HT were 68.933 and 62.967 months, respectively. For patients with grade IV HGGs, mOS and mPFS from the beginning of HT were 19.667 and 7.23 months, respectively. No grade ≥3 acute or late nonhematologic toxicities were observed. Multivariable Cox regression analysis showed that methylguanine methyltransferase (MGMT) methylated status, age, number of lesions, WHO grade, and monocyte count for PFS were significant. Age, monocyte count, and isocitrate dehydrogenase (IDH) status for OS.Treatment of HGGs with HT appears to be potentially effective and safe. HT is promising for glioblastomas (GBM), especially complex cases with infratentorial involvement or multiple lesions. This study highlighted the potential clinical significance of systemic inflammation indicators in predicting survival and disease progression. [ABSTRACT FROM AUTHOR]

Graphene quantum dots (GQDs), small graphene domains with lateral dimensions lower than 10 nm, are increasingly used in electronics, composites, and biomedicine. Chemical doping of GQDs allows tuning their optical properties. Immune cells are among the first cells exposed to nanomaterials entering a living body, rapidly triggering a downstream immune response. However, the assessment of the impact of chemically‐doped GQDs on the immune system remains rather limited if not absent. In this context, the effects and the biodegradability of sulfur‐doped and nitrogen‐doped GQDs (S‐GQDs and N‐GQDs) on human monocytes and macrophages are evaluated. The metabolic activity, membrane integrity, apoptosis, and intracellular reactive oxygen species (ROS) generation are studied. In parallel, the degradation of GQDs using human myeloperoxidase and a peroxynitrite‐mediated system is investigated in test tube. Their degradation in macrophages is also pursued. High‐resolution transmission electron microscopy (HRTEM), fluorescence spectroscopy, Raman, and flow cytometry are used to confirm the degradation. Overall, both GQDs exert little activation on monocytes and macrophages although they decrease the metabolic viability in a dose‐dependent manner. The loss of native GQD structure and crystal lattice provide evidence of their biodegradability. Both the safety and biodegradability of S‐GQDs and N‐GQDs ensure their potential in biomedical applications. [ABSTRACT FROM AUTHOR]

The disposal of pharmaceutical wastewater has gained increasing attention due to its potential adverse effects on the environment and public health. This study aims to assess the concentration of pharmaceutical contaminants and their toxicity to aquatic organisms. A qualitative research approach was used. Composite samples were collected from the effluent storage system. Various analytical techniques, including high‐performance liquid chromatography (HPLC), were employed to detect and quantify pharmaceutical compounds in wastewater samples. The results revealed various pharmaceutical compounds (ibuprofen 28 μg/L, diclofenac 27.20 μg/L, paracetamol 22.03 μg/L, and tramadol <0.01 μg/L) in the wastewater. The maximal environmental concentration (MEC) for all the detected pharmaceuticals was high; hence, the risk quotients (RQs) indicated potential toxicity (RO > 1). It further indicates that the effluent was more toxic to animals (daphnia and fish) than algae (plants). It can be concluded that pharmaceutical effluent was toxic to aquatic organisms. Therefore, there is a need to implement stringent regulatory measures to mitigate untreated pharmaceutical effluent in water bodies. Addressing pharmaceutical contaminants in wastewater is crucial to safeguarding the environment and public health in an increasing pharmaceutical use and production era. [ABSTRACT FROM AUTHOR]

Nanoparticulate delivery systems have been attracting attention in pharmaceutical sciences for enhanced drug bioavailability and targeted delivery. Specifically, these systems can enhance the solubility of poorly water-soluble drugs, protect therapeutic agents from degradation, prolong circulation time in the body, control drug release, and facilitate the precise targeting of drugs to specific tissues or cells. However, once administered into the body, nanoparticles often encounter significant challenges that can affect their efficacy and safety, such as issues with stability, biocompatibility, and targeting. The surface properties of nanoparticles are one of the most important features as they can greatly influence the interactions between nanoparticles themselves and between nanoparticles and biological targets. Key surface characteristics, such as charge, hydrophobicity, and the presence of functional groups, determine how nanoparticles behave in biological environments, thereby influencing their stability, cellular uptake, and ability to avoid immune clearance. Modification of the nanoparticle surface has been shown to be an effective approach to modulate the physicochemical and biological properties of nanoparticles, achieving desired therapeutic efficacy in vivo. This review aims to summarize recent advances in surface decoration of nanoparticles, with an emphasis on improved colloidal and biological stability, reduced toxicity, and enhanced drug targeting. The challenges and future perspectives of nanoparticle surface modification approaches are also discussed. [ABSTRACT FROM AUTHOR]

In recent years, overexplorations of ore and the growth of industries are the prime factors in the release of heavy metals in environments. As a result, the food crops and water bodies are contaminated with metals which may have several adverse effects on the health of humans and other living species. These metals and metalloids, such as Zn, Cu, Mn, Ni, Cr, Pb, Cd, and As, upset the biochemical pathways of metabolite synthesis in living organisms and contribute to the etiology of different diseases. Microorganisms include bacteria, archaea, viruses, and many unicellular eukaryotes, which can span three domains of life--Archaea, Bacteria, and Eukarya--and some microorganisms, such as cyanobacteria, have shown high efficiency in the biosorption rate of heavy metals. Cyanobacteria are suitable for bioremediation as they can grow in adverse environments, have a less negative impact on the surrounding environment, and are relatively cheaper to manage. The structure of cyanobacteria has shown no extensive internal-bound membranes, so it can directly employ the physiological mechanisms to uptake heavy metals from contamination sites. Such biochemical makeups are suitable for managing and bioremediating heavy metal concentrations in polluted environments. This review aims to explore the potential of cyanobacteria in the bioremediation of heavy metals and metalloids in water bodies. Additionally, we have identified the prospects for enhancing bioremediation effectiveness. [ABSTRACT FROM AUTHOR]

Several experimental evidences and field data documented that zooplankton may alter its behavioral response in the presence of toxic phytoplankton, reducing its consumption to the point of starvation. This paper is devoted to the mathematical study of such interactions of toxic phytoplankton with grazer zooplankton. The non-toxic phytoplankton is assumed to adopt a density-dependent refuge strategy to avoid over-predation by zooplankton. Both groups of phytoplankton are assumed to suffer direct harm from anthropogenic toxicants, while zooplankton is affected indirectly by ingesting contaminated phytoplankton. We calibrate the proposed model with the field data from Talsari and Digha Mohana, India, and estimate some crucial model parameters consistent with the behavior of the observed data. Our results demonstrate that zooplankton grazing on toxic phytoplankton plays a key role in the emergence or mitigation of plankton blooms. We also highlight the system's potential to exhibit multiple stable configurations under the same ecological conditions. The plankton system experiences significant regime shifts, which are explored through various bifurcation scenarios, such as transcritical and saddle-node bifurcations. These shifts are influenced by changes in refuge capacity, species growth rates, and environmental carrying capacity. Furthermore, we incorporate environmental variations due to seasonal periodic or almost periodic changes, allowing the refuge parameter to be time-dependent. We observe that the forced system exhibits double periodic solutions. Moreover, stronger seasonal variations in the refuge pattern lead to irregular chaotic blooms. In conclusion, the results offer valuable insights into the sustainability of biodiversity, potentially shedding light on the origin of diverse plankton bloom phenomena. [ABSTRACT FROM AUTHOR]

Introduction: The use of anti-retroviral therapy (ART) has made HIV a manageable condition, but there are risks associated with medications like reverse transcriptase inhibitors (RTIs) and integrase strand transfer inhibitors (INSTIs), such as liver and renal toxicity. It is essential to understand these risks for effective treatment and case management. Investigating liver toxicity related to RTIs and INSTIs in Nigeria is crucial for optimizing HIV treatment. This study aimed to assess the impact of tenofovir lamivudine dolutegravir (TLD) on the liver function of HIV patients at Nigerian Navy Hospital (NNH)-Warri. Methods: The liver function of 170 participants was assessed, with 120 on ART and the remainder being HIV-negative attendees at NNH-Warri. The study used a cross-sectional design and selected participants through random sampling. We collected data using a semi-structured questionnaire. Blood samples were taken through venipuncture and stored at – 20 °C before analysis. Ethical approval was obtained, and data analysis was conducted using SPSS Statistical Software Version 23, with significance set at p < 0.05. Results: The study found significant differences in AST, TP, Alb, and GST levels between HIV-positive subjects receiving TLD and HIV-negative individuals. HIV-positive subjects had lower AST and Alb levels but higher TP and GST levels. Further analysis revealed correlations between age, gender, and liver enzymes, highlighting the complex relationship between HIV, liver function, and treatment outcomes. Conclusion: The study suggests that decreased AST levels may have a protective effect, while ALT activity had minimal impact. Changes in TP, Alb, and GSTs emphasize the importance of monitoring hepatic synthetic function and detoxification pathways in HIV patients taking TLD. [ABSTRACT FROM AUTHOR]

Background:Moringa oleifera leaf is used for diabetes due to its pharmacologic effects. Patients with hyperglycemia experience beta cell destruction. However, no research on risk awareness has been done to ascertain its safety. The present study describes the antidiabetic effect of Moringa oleifera leaf, such as the protection of pancreatic beta cells and the induction of glycogen synthesis, before addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Methods: Forty‐five Wistar rats weighed 160 ± 10 g were divided into nine groups. All animal operations complied with the National Institute of Health (NIH) guidelines for the care and use of laboratory animals as approved by the Animal Ethical Committee, University of Jos. Group I was normal control and Group II was diabetic animals induced with alloxan. Insulin and extract doses of 200, 400, and 800 mg/kg were given to diabetic Groups III‐VI. Normal animals in Groups VII–IX were given extract at doses of 200, 400, and 800 mg/kg for 28 days. Tissues were retrieved for biochemical and histological investigations using standard techniques. Results: There was decrease relative body weight of diabetic animals (95.50 ± 5.50) when compared to normal control (142.75 ± 20.08) with increased levels of urea (control 6.13 ± 0.523 and diabetes 29.23 ± 1.267) and creatinine (control 0.70 ± 0.057 and diabetes 2.13 ± 0.185). Histology of the liver and pancreas also points to organ damage due to hyperglycemia. However, oral administration of extract showed antidiabetic effect with protection of pancreatic beta cells and the induction of glycogen synthesis, no glycogen was deposited in the liver, addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Further discovery revealed that extract elevated antioxidant enzyme expression. Conclusion: Leaf extract from Moringa oleifera reduces blood sugar and lessens the damage caused by hyperglycemia in the pancreas and liver. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) causes a systemic illness that can result in various manifestations. In addition to severe acute respiratory syndrome, patients often exhibit complications unrelated to the respiratory system. Potential liver damage can occur in 14.8 to 53.0% of the affected patients. Liver impairment in COVID-19 can also occur because of the use of polypharmacy during disease management. It is essential to be aware of drug-induced liver injury (DILI) in patients diagnosed with COVID-19, especially when considering the off-label usage of medications in both preventative and therapeutic regimens used on a wide scale. This review aims to give pertinent information regarding drugs utilized thus far in COVID-19 patients and their potential toxicity to the liver. We also present a suggested management approach to DILI in COVID-19 patients and lessons learned from the pharmacological management of this pandemic. [ABSTRACT FROM AUTHOR]

Introduction: This study seeks to compare expectations regarding systemic cancer treatment for advanced lung cancer from the perspectives of both patient and medical oncologist. Methods: A cross-sectional study involving 17 medical oncologists from 13 Spanish hospitals between 2021 and 2022. Patients with advanced, unresectable lung cancer were recruited prior to initiating systemic cancer treatment. Both patients and oncologists completed the NEOetic-EIT and the STAR. Results: Seventeen medical oncologists specializing in lung cancer participated, with a mean age of 36.2 years (range 28-56); 65% were female. The study included 298 patients with advanced, unresectable lung cancer, predominantly non-small cell type (72%), and most at stage IV (77%). Most patients were retired or unemployed (71%), and married or partnered (77%). Treatment approaches varied, with 44% based on biomarkers. Oncologists had greater expectations of positive outcomes for participants with better baseline prognosis, such as ECOG 0, newly diagnosed, locally advanced, unresectable non-small cell lung cancer, and those receiving biomarker-based treatments. In contrast, patients' treatment expectations did not vary based on sociodemographic or clinical factors. Generally, patients had high expectations of cure, in contrast to oncologists' lower expectations, though both anticipated similar quality-of-life improvements. Patients anticipated more side effects than oncologists. Among oncologists, expectations varied by gender and decreased with age and experience, with no differences detected among patients based on gender, age, or doctor-patient relationship. Conclusion: This study reveals the complex expectations of patients and oncologists in advanced lung cancer treatment. It underscores the need for effective communication in oncology to align patient expectations with clinical realities. [ABSTRACT FROM AUTHOR]

Introduction: Melittin is a potent antimicrobial peptide from bee venom that is effective against both Gram-positive and Gram-negative bacteria. However, it is extremely toxic to mammalian cells and, as yet, has no clinical use. Modifications to its amino acid sequence, cyclization, truncation, and dimerization have been attempted in order to reduce its toxicity whilst maintaining its antimicrobial activity. Methods: In this study, we targeted the three lysine residues present in melittin and substituted them with lysine homologs containing shorter side chains (ornithine, Orn, diaminobutyric acid, Dab, and diaminopropanoic acid, Dap) and made both parallel and antiparallel melittin dimers to observe how lysine substitution and dimerization affects its activity and toxicity. The antibacterial activity of melittin and its analogs was tested against S. aureus (Gram-positive bacteria) and E. coli (Gram-negative bacteria), and cytotoxicity was tested against the mammalian cell lines HEK293 and H4IIE. Results: Overall, dimerization and lysine substitution exhibited improved antimicrobial activity toward E. coli and limited improvement toward S. aureus. However, mammalian cell toxicity was only marginally reduced compared to native melittin. Interestingly, the parallel dimer was found to be marginally more active than the antiparallel dimer, indicating orientation maybe important for activity, although both dimers were less effective than the native and Lys-analog peptides toward S. aureus. Of the Lys substitutions, Dab and Dap improved melittin's activity toward E. coli. Discussion: Dimerization and Lys substitution of melittin improved the antimicrobial activity toward Gram-negative bacteria but did not significantly improve its activity toward Gram-positive bacteria. Some analogs also displayed reduced toxicity toward HEK293 and H4IIE cells but overall remained toxic at bactericidal concentrations. Our data indicates that although highly antibacterial, melittin's toxicity is the major drawback in its potential use. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSMesoporous bioactive glass, with its versatile characteristics and morphology, holds significant potential as an ideal hemostatic material. However, limited data is available regarding its toxicity levels. Consequently, this research intends to assess the acute and repeated dose dermal toxicity of Mesoporous antibacterial bioactive glass microsphere impregnated nonwoven surgical cotton gauze (MABGmscg) dressing in albino Wistar rats, following the standards set by the Organization for Economic Cooperation and Development. In the acute dermal toxicity study, the impact of MABG (@2000mg/kg BW) mscg dressing was assessed following a single dermal application in both male and female Wistar rats (n = 10). Mortality, clinical signs, body weight fluctuations and gross observations were consistently monitored over a14 day period following the single dose. The results indicated that, MABG (@2000mg/kg BW) mscg dressing upon dermal exposure did not cause any adverse effect in acute dermal toxicity study in Wistar rats compared to control group. Given that 2000 mg/kg BW of MABG was deemed a nontoxic dose, a repeated dose dermal toxicity study of MABGmscg dressing was subsequently conducted at three dose levels (@200, 500, 1000 mg/kg BW) over 28 consecutive days in Wistar rats. During the study period, no unscheduled deaths occurred, and there were no clinical signs associated with treatment, body weight variations or abnormal gross findings at necropsy in any groups. The analysis concluded that, MABGmscg dressing is safe to be considered as a hemostatic dressing at the various tested dose levels in Wistar rats.A dressing composed of mesoporous antibacterial bioactive glass impregnated into nonwoven surgical cotton gauze (MABGmscg) has been developed to serve as an effective hemostatic material.The acute and repeated dose dermal toxicity study of MABGmscg dressing has been performed in Wistar ratsNo visible changes or systemic effects were observed after applying the MABGmscg dressing at different doses for 28 consecutive days in Wistar rats.Therefore, the MABGmscg dressing is considered safe for use as a hemostatic gauze.A dressing composed of mesoporous antibacterial bioactive glass impregnated into nonwoven surgical cotton gauze (MABGmscg) has been developed to serve as an effective hemostatic material.The acute and repeated dose dermal toxicity study of MABGmscg dressing has been performed in Wistar ratsNo visible changes or systemic effects were observed after applying the MABGmscg dressing at different doses for 28 consecutive days in Wistar rats.Therefore, the MABGmscg dressing is considered safe for use as a hemostatic gauze. [ABSTRACT FROM AUTHOR]

In this study, the impact of exposure to a glyphosate-based herbicide (GBH) and a trifloxystrobin-based fungicide (TBF) on Daphnia magna in diverse feeding environments was assessed through the analysis of morphological and biochemical markers. The test organisms selected for analysis were Chlorella vulgaris and D. magna. First, the 48-hour median lethal concentrations (LC50) of GBH and TBF for D. magna were determined to be 253.1 mg/L and 20.7 µg/L, respectively. Secondly, the lethality, length, width, and spin length of D. magna were evaluated following exposure to sublethal pesticide concentrations, selected based on the LC50 values, in different feeding environments. Thirdly, the activities of glutathione S-transferase (GST), glutathione reductase, catalase (CAT), carboxylesterase, and acetylcholinesterase, as well as the levels of reduced glutathione, were measured in D. magna exposed to sublethal pesticide concentrations in different feeding environments. Both pesticides caused an increase in CAT activity, while GBH also caused an increase in GST activity in the unfed and mixed-fed groups. Conversely, it can be concluded that feeding with C. vulgaris reduces oxidative stress and toxic effects since there was a lesser increase in GST and CAT activities in the C. vulgaris-fed group for both pesticides, similar to the lethality. [ABSTRACT FROM AUTHOR]

We study the prevalence and characteristics of toxic speech on Twitter in the run-up to the 2022 Italian General election. We analyzed over 8.5 M tweets shared by 450k unique users and employed a machine learning classifier to estimate the toxicity score of their messages. We found that supporters of different political coalitions exhibit varying levels of toxic speech, sending between 6-8% of toxic messages overall. Notably, Centre-Left politicians received more toxic messages on average, with the largest target of hate receiving over 15,000 toxic replies. We employed Generalized Linear Models to study factors that drive hate speech to political targets, finding that, importantly, politicians employing more abusive and harmful language are also more likely to attract more inflammatory speech. Our findings underscore the critical need for targeted interventions to address hate speech online, fostering healthier dialogue and safeguarding democratic discourse. [ABSTRACT FROM AUTHOR]

Laboratory tests and semi-field evaluation were carried out to examine the acaricidal effect of four concentrations of diatomaceous earth (DE) and sulfur against four mites: Tetranychus urticae (Tetranychidae), Rhizoglyphus echinopus (Acaridae), Tyrophagus putrescentiae (Schrank) (Acaridae), and Amblyseius swirskii (Phytoseiidae). Results revealed that mortality increased as both time and concentration increased. Tetranychus urticae was the most affected mite; LC50 values were 70.4 and 92.0 for immature and adult stages, respectively, after 7 days. For the LC50 concentrations examined, a significant decrease in the total number of immature and adult stages of all mites during seven days was noticed. Under semi-field conditions, the LC50s were calculated for (DE) and sulfur against T. urticae on cucumber plants. The reduction percentage of T. urticae was 66.67 and 50% for (DE) and sulfur, respectively, after seven days of application, with significant differences. [ABSTRACT FROM AUTHOR]

Bacterial nanocellulose (BNC) is considered a promising alternative to microcrystalline cellulose, as well as an ingredient in low-calorie dietary products. However, the risks of BNC when consumed with food are not well characterized. The aim of this study is to investigate the impact of BNC on immune function, the intestinal microbiome, intestinal barrier integrity, and allergic sensitization in subacute experiments on rats. Male Wistar rats received BNC with a diet for eight weeks in a dose range of 1–100 mg/kg of body weight. The measurements of serum levels of cytokines, adipokines, iFABP2, indicators of cellular immunity, composition of the intestinal microbiome, and a histological study of the ileal mucosa were performed. In a separate four-week experiment on a model of systemic anaphylaxis to food antigen, BNC at a dose of 100 mg/kg of body weight did not increase the severity of the reaction or change the response of IgG antibodies. Based on dose–response effects on immune function, the non-observed adverse effect level for BNC was less than 100 mg/kg of body weight per day. The effects of BNC on the gut microbiome and the intestinal mucosal barrier were not dose-dependent. Data on the possible presence of prebiotic effects in BNC have been obtained. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (NPs) have become highly promising agents in the field of biomedical science, offering wide therapeutic potential due to their unique physicochemical properties. The unique characteristics of silver NPs, such as their higher surface-area-to-volume ratio, make them ideal for a variety of biological applications. They are easily processed thanks to their large surface area, strong surface plasmon resonance (SPR), stable nature, and multifunctionality. With an emphasis on the mechanisms of action, efficacy, and prospective advantages of silver NPs, this review attempts to give a thorough overview of the numerous biological applications of these particles. The utilization of silver NPs in diagnostics, such as bioimaging and biosensing, as well as their functions in therapeutic interventions such as antimicrobial therapies, cancer therapy, diabetes treatment, bone repair, and wound healing, are investigated. The underlying processes by which silver NPs exercise their effects, such as oxidative stress induction, apoptosis, and microbial cell membrane rupture, are explored. Furthermore, toxicological concerns and regulatory issues are discussed, as well as the present difficulties and restrictions related to the application of silver NPs in medicine. [ABSTRACT FROM AUTHOR]