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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.

Colorectal cancer (CRC) is the third most common cancer in the USA and worldwide. In the USA, nearly one-third of CRC cases are anatomically classified as rectal cancer. Over the past few decades, continued refinement of multimodality treatment and the introduction of new therapeutic agents have enhanced curative treatment rates and quality of life outcomes. As treatments improve and the incidence of young onset rectal cancer rises, the number of rectal cancer survivors grows each year. This trend highlights the growing importance of rectal cancer survivorship. Multimodality therapy with systemic chemotherapy, chemoradiation, and surgery can result in chronic toxicities in multiple organ systems, requiring a multi-disciplinary care model with services ranging from appropriate cancer surveillance to management of long-term toxicities and optimization of modifiable risk factors. Here, we review the evidence on these long-term toxicities and provide management considerations from consensus guidelines. Specific topics include bowel dysfunction from radiation and surgery, oxaliplatin-induced neuropathy, accelerated bone degeneration, the impact of fluoropyrimidines on long-term cardiovascular health, urinary incontinence, sexual dysfunction, and psychosocial distress. Additionally, we review modifiable risk factors to inform providers and rectal cancer survivors of various lifestyle and behavioral changes that can be made to improve their long-term health outcomes.

Diabetic mellitus (DM) is characterized by hyperglycaemia and defective macromolecular metabolism, arising from insulin resistance or lack of insulin production. The present study investigates the potential of artemisinin, a sesquiterpene lactone isolated from Artemisia annua, to exert anti-diabetic and antioxidant effects through modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. Our computational analyses demonstrated a high binding affinity of artemisinin with proteins belonging to the PI3K/AKT signalling cascade. α-Amylase and α-glucosidase studies revealed a notable increase in inhibition percentages with artemisinin treatment across concentrations ranging from 10 to 160 µM. A similar significant (p < 0.05) dose-dependent inhibition of free radicals was observed for the in vitro anti-oxidant assays. Further, toxicological profiling of artemisinin in the in vivo zebrafish embryo-larvae model from 4 to 96 h post-fertilization (hpf) did not exhibit any harmful repercussions. In addition, gene expression investigations confirmed artemisinin's potential mechanism in modulating hyperglycaemia and oxidative stress through the regulation of the PI3K/AKT pathway. Overall, our investigation suggests that artemisinin can be used as a therapeutic intervention for diabetes and oxidative stress, opening up opportunities for future investigation in clinical settings. [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]

Background: The glassy clover snail, Monacha obstructa (Pfeiffer), is considered one of the major agricultural pests that ruin many field crops, vegetables, orchards of fruits, plants of ornament as well as many other plantations. Synthesis of the Schiff base ligand, namely bis-[4-benzylidene-thiophene-2′-yl] methane (L), produced from the reaction between thiophene-2-carboxaldehyde and diaminodiphenylmethane (MDA), alongside its copper complex were conducted. The output chemical compounds were evaluated in vitro for their molluscicidal activity against the glassy clover snail, M. obstructa by performing the contact technique. Stock solutions were prepared via using (distilled water + DMF) mixture. Furthermore, the impact of these compounds on some critical biochemical indicators: cholesterol, total protein, and acetylcholinesterase (AChE), was evaluated. Results: The outcome results demonstrated the significantly higher molluscicidal activity of the Cu(II) chelate compared to its free ligand (L), which in turn reveals the importance of metal chelation in enhancing toxicity against the target species. Particularly, the LC25 and LC50 values are (27.25, 34.65) and (17.88, 25.31) ppm for the ligand (L) and its copper construction, respectively. Additionally, the data confirmed the significant effectiveness of the tested compounds on the assessed biochemical indicators of treated snails. Total protein and cholesterol levels were elevated after treatment with both the ligand (L) and its copper complex while AChE activity increased after treatment with the ligand (L) and reduced upon the exposure to the Cu(II) chelate. Conclusions: The findings established that the copper complex exhibited a markedly higher molluscicidal activity compared to the free ligand (L). Also, the results confirmed the significant effects of the investigated compounds on the assessed biochemical indicators of treated M. obstructa snails. [ABSTRACT FROM AUTHOR]

The herbicide atrazine (ATR) has been one of the most widely used herbicides worldwide. However, due to its indiscriminate use, it has been considered an environmental contaminant. Several studies have classified ATR as an endocrine disruptor, and it has been found to have neurotoxic effects on behavior, along with alterations in the dopaminergic, GABAergic, and glutamatergic systems in the basal ganglia of male rodents. These findings suggest that these neurotransmitter systems are targets of this herbicide. However, there are no studies evaluating the neurotoxicity of ATR in female rodents. Our study aimed to assess the effects of repeated IP injections of 100 mg ATR/kg or a vehicle every other day for 2 weeks (six injections) on the locomotor activity, content of monoamines, GABA, glutamate, and glutamine in the striatum, nucleus accumbens, ventral midbrain, and prefrontal cortex, and tyrosine hydroxylase (TH) protein levels in striatum and nucleus accumbens of female rats. Repeated 100 mg ATR/kg injections immediately decreased all the locomotor activity parameters evaluated, and such hypoactivity persisted for at least 48 h after the last ATR administration. The ATR administration increased dopamine and DOPAC content in the nucleus accumbens and the dopamine and DOPAC and serotonin and 5-HIAA content in the ventral midbrain. In contrast, the TH protein levels in the striatum and nucleus accumbens were similar between groups. Meanwhile, GABA, glutamine, and glutamate levels remained unaltered in all brain regions evaluated. The observed behavioral alterations could be associated with the monoamine changes presented by the rats. These data reveal that the nucleus accumbens and ventral midbrain are susceptible to repeated ATR exposure in female rats. [ABSTRACT FROM AUTHOR]

AbstractPolycyclic aromatic hydrocarbons (PAHs) are a group of complex chemicals that are formed and released during incomplete combustion during industrial processes or pyrolysis of the organic matter. Human exposure to PAHs primarily occurs through food consumption. One of the possible causes of formation in food is free radicals. Also, the confirmed mechanism of their toxicity in living organisms is oxidative stress. This complication is also caused by free radicals released during their metabolism. Chronic exposure to PAHs can lead to carcinogenic, teratogenic and mutagenic effects in humans. Consequently, there is a need to minimize the presence of these compounds in food. Research suggests that antioxidants play a crucial role in reducing PAH levels in food. Therefore, formulating food products with the right combination of antioxidants could be an effective strategy to mitigate the formation of PAHs. Moreover, antioxidants have been found to alleviate the toxicity associated with PAHs in the human body. This manuscript discusses the effects and mechanisms of antioxidants in reducing PAH in food products and living organisms. [ABSTRACT FROM AUTHOR]

Cerium oxide nanoparticles (CeNPs) have emerged as a potent therapeutic agent in the realm of wound healing, attributing their efficacy predominantly to their exceptional antioxidant properties. Mimicking the activity of endogenous antioxidant enzymes, CeNPs alleviate oxidative stress and curtail the generation of inflammatory mediators, thus expediting the wound healing process. Their application spans various disease models, showcasing therapeutic potential in treating inflammatory responses and infections, particularly in oxidative stressinduced chronic wounds such as diabetic ulcers, radiation-induced skin injuries, and psoriasis. Despite the promising advancements in laboratory studies, the clinical translation of CeNPs is challenged by several factors, including biocompatibility, toxicity, effective drug delivery, and the development of multifunctional compounds. Addressing these challenges necessitates advancements in CeNP synthesis and functionalization, novel nano delivery systems, and comprehensive bio effectiveness and safety evaluations. This paper reviews the progress of CeNPs in wound healing, highlighting their mechanisms, applications, challenges, and future perspectives in clinical therapeutics. [ABSTRACT FROM AUTHOR]

This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy (RT) can be used to reduce symptoms and maintain open airways for patients with non-small cell lung cancer when systemic treatment is not sufficient. For some patients, tumor control is not achieved due to radioresistance. Concurrent inhibition of epidermal growth factor receptors has been proposed as a strategy to overcome radioresistance but may increase toxicity. We performed a randomized trial to assess the efficacy, tolerance, and quality of life of concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer. Methods: Patients were randomized 1:1 to RT alone (arm A) or in combination with erlotinib (arm B). A computed tomography (CT) scan at baseline and one at 4-12 weeks after inclusion was used to evaluate treatment response. Adverse events were registered during treatment and the subsequent 30 days. Healthrelated quality-of-life questionnaires were completed by the patients at baseline, weeks 2, 6, and 20. Results: A total of 114 patients were included. Of the 74 patients with CT scans available for evaluation of treatment effect, there were no significant differences in tumor size reduction between the two groups: median 14.5% reduction in the control arm A and 17.0% in the erlotinib arm B (p = 0.68). Overall survival was not significantly different between the two treatment arms: 7.0 and 7.8 months in arm A and arm B, respectively (log-rank p = 0.32). There was no significant increase in adverse events in the experimental arm, other than what is expected from erlotinib treatment alone. Overall, patients reported similar quality of life in both treatment arms. Conclusion: Concurrent erlotinib and palliative thoracic RT for patients with advanced non-small cell lung cancer was well tolerated but did not improve the efficacy of the RT. [ABSTRACT FROM AUTHOR]

Background: Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model. Method: Rats were exposed to cerium dioxide (CeO2, 28.4 ± 10.4 nm) and titanium dioxide (TiO2, 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m3 or a repeated exposure of 2 × 5 days to 5 mg/m3. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF). Results: Although similar lung deposited doses were obtained for both materials, exposure to CeO2 induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO2 did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure. Conclusion: We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung. [ABSTRACT FROM AUTHOR]

Abstract\nHIGHLIGHTSCardiovascular diseases (CVDs) cause 30% of deaths each year, and in 2030, around 23.6 million people will die due to CVDs. The major challenge is to obtain molecules with minimal adverse reactions that can prevent and dissolve blood clots. In this context, fibrinolytic enzymes from diverse microorganism sources have been extensively investigated due to their potential to act directly and specifically on the fibrin clot, preventing side effects and performing potential thrombolytic effects. However, most researches focus on the purification and characterization of proteases, with little emphasis on the mechanism of action and pharmacological characteristics, including toxicity assays which are essential to assess safety and side effects. Therefore, this work aims to emphasize the importance of evaluations indicating the toxicological profile of fibrinolytic proteases through in vitro and in vivo tests. Both types of assays contribute as preclinical stage in drug development and are crucial for clinical applications. This scarcity creates arbitrary barriers to further studies. This work should further encourage the development of studies to ensure the safety and effectivity of fibrinolytic proteases.Suggested pre-clinical trials aim to validate more specific methods for fibrinolytic enzymes;Current toxicity standards can be adapted to better assess the profile of fibrinolytic enzymes;The class of fibrinolytic enzymes must be carefully evaluated according to the method of application.Suggested pre-clinical trials aim to validate more specific methods for fibrinolytic enzymes;Current toxicity standards can be adapted to better assess the profile of fibrinolytic enzymes;The class of fibrinolytic enzymes must be carefully evaluated according to the method of application. [ABSTRACT FROM AUTHOR]

[Objective] To screen out the effective pesticides against Colletotrichum gloeosporioide. [Method]Seven fungicides were selected to carry out toxicity test and field efficacy test. [Result]The toxicity test results showed that the 4 d-EC50 of 35% Difenoconazole·Pyraclostrobin SC, 30% Pyraclostrobin·Tebuconazole SC, 30% Pyraclostrobin·Flusilazole EC, 40% Difenoconazole SC, 25% Pyraclostrobin SC, 430 g / L Tebuconazole SC and 40% Flusilazole EC against Colletotrichum gloeosporioide were 0. 194 0, 0. 078 8, 0. 097 8, 0. 445 0, 0. 218 0, 0. 165 0, and 0. 146 0 mg / L, respectively;in the field efficacy test, the control effect of 7 pesticides on Colletotrichum gloeosporioide of fig leaves was as follows:30% Pyraclostrobin·Tebuconazole SC had the best control effect at 2 000 times, with a control effect of 92. 76%±2. 96%. 30% Pyraclostrobin·Flusilazole EC had the second best control effect at 2 000 times, with a control effect of 89. 54%±2. 41%. There was no significant difference between the two. The control effect of other pesticides at 2 000 times was over 80%. 30% Pyraclostrobin·Tebuconazole SC had a control effect of over 80% at 3 000 times, while the control effect of the remaining treatments was poor. The control results of 7 pesticides on Colletotrichum gloeosporioide of fig fruit were as follows:30% Pyraclostrobin·Tebuconazole SC had the best control effect at 2 000 times liquid, reaching 86. 22% ± 3. 87%, 30% Pyraclostrobin·Flusilazole EC had a control effect of 83. 69% ± 1. 59% at 2 000 times liquid, 430 g / L Tebuconazole SC had a control effect of 81. 68% ± 2. 01% at 2 000 times liquid, and the control effect in other treatments was lower than 80%. [Conclusion]The results showed that the 30% Pyraclostrobin·Tebuconazole SC and 30% Pyraclostrobin·Flusilazole EC had good control effects on fig anthracnose at a concentration of 2 000 times, and could be extended to the prevention and control of anthracnose in fig planting areas in Guangxi region. [ABSTRACT FROM AUTHOR]

As nutrient-rich water in aquaponic systems cannot supply growing plants with all the required trace elements, supplementation with specific fertilizers is performed to make up for this deficit. While chelated fertilizers such as ethylenediaminetetraacetic acid-zinc disodium complex (Zn-EDTA) are becoming more popular in this context for improving plant growth in aquaponic systems, little is known about their effects on fish. During two experiments, a total of 576 individuals of catfish fry (0.19 g) and fingerlings (220.01 g) of the African catfish (Clarias gariepinus; Burchell, 1822) were kept separately for 32 days under experimental aquarium conditions. The fry was exposed to 0.125 and 0.5 mg/L, while the fingerlings were exposed to 0.5 and 2.0 mg/L Zn-EDTA in a plantless aquaponic system. The third treatment group consisted of a control group without Zn-EDTA. The growth, mortality, and ethological indicators were assessed for all growth stages, while the leukocyte distribution and histopathological changes were additionally determined for the fingerlings. As the feed intake in the experiment was limited, the investigations were focused on the effects of Zn-EDTA and not on the growth process of a respective fish growth stage. While the growth, mortality, and behavior were not significantly different in both growing stages, the number of mature neutrophils changed significantly in all treatments in fingerlings. Zn was not detected in the histologically investigated organs at the tested concentrations using the staining method. However, morphological alterations of the gill epithelium were found on the secondary lamellae. Quantitative multiplex PCR was used to simultaneously evaluate the expression of 17 genes related to Zn metabolism and stress physiology in head kidney samples. The transcripts of several selected genes changed by up to 70-fold. Due to high individual variances, only the copy numbers of the KMT2A (lysinespecific methyltransferase 2a) gene were significantly different across treatment groups and sampling points. However, the present results indicate that the addition of Zn-EDTA at the tested concentrations can be considered relatively benign for the health and welfare of C. gariepinus, as no toxic effects of Zn-EDTAwere observed in moderately hard to hard water. [ABSTRACT FROM AUTHOR]

To increase the biodiversity of agricultural systems, aromatic plants appear particularly promising as additional perennial crops in intercropping. They produce essential oils that contain monoterpenes, for example. These compounds have antibiotic properties that make them interesting for commercialisation as medicinal or pesticide products, but also carry the risk of undesirable effects on soil microorganisms and thus on essential soil functions. To investigate this, the monoterpenes thymol and carvacrol and a set of four typical agricultural soils were selected and soil sorption batch tests and soil toxicity tests were carried out to determine dose-response relationships. Sorption followed second order kinetics and was best described at equilibrium by the non-linear BET isotherm that distinguishes between monolayer and multilayer sorption of the non-polar compounds. While the kinetics were very fast with rate constants of 1.66 × 10-4 and 0.70 × 10-4 min-1 for thymol and carvacrol, the strength of sorption remained quite low (Kd 1.93-3.69), indicating a high mobility and bioavailability of the monoterpenes. In addition, the relation to single soil properties remained low, indicating a multivariate impact of several soil properties. Although thymol and carvacrol are isomeric compounds, they differed in the rate and strength of sorption as well as in the effects on five selected soil microbiological enzyme activities. In particular, carvacrol caused inhibition of enzyme activities, whereas thymol did not produce measurable or relevant effects in all cases. The effect concentrations of 10% and 25% percent inhibition (EC10, EC25) ranged from <1 µg to several grams per Gram of soil and hormesis effects were also observed at low concentrations. On the one hand, this indicates only low toxicity; on the other hand, several of the defined effect thresholds can be reached or exceeded by expected environmental concentrations. This may harbour a risk of adverse effects, but may also have a phytosanitary effect, which requires further research. [ABSTRACT FROM AUTHOR]

Abstract\nNovelty statementThis study explores the use of algae for phycoremediation, focusing on how Chlorella sorokiniana and Anabaena laxa detoxify water contaminated with captan, a common fungicide. The efficiency of these species in absorbing captan and the associated biochemical changes were evaluated to assess their potential for environmental protection. Microalgae were exposed to captan concentrations of 15 and 30 mg/L, and various parameters, including captan uptake, chlorophyll (Chl) a, carotenoid levels, and changes in metabolic profiles (soluble carbohydrates, organic acids, amino acids, and fatty acids), were measured. Results showed Anabaena had a higher captan absorption capacity (141.7 µg/g at 15 mg/L and 239.3 µg/g at 30 mg/L) compared to Chlorella (74.43 µg/g and 162 µg/g). Increased captan uptake reduced the growth of both species, as indicated by lower Chl a levels. Both species accumulated osmo-protectants and antioxidants as defense mechanisms, with soluble sugars increasing by 83.49% in Chlorella and 68.87% in Anabaena, and carotenoids increasing by 60.42% and 46.24%, respectively. Principal component analysis revealed distinct species-level responses, with Anabaena showing greater tolerance. The study concludes that both species can effectively remediate captan, with Anabaena being more efficient, indicating their potential for mitigating agrochemical impacts in aquatic environments and promoting sustainable agriculture and water management.This study uniquely demonstrates the superior capability of Anabaena laxa over Chlorella sorokiniana in remediating captan-contaminated water, highlighting distinct biochemical responses and enhanced tolerance mechanisms. By detailing species-specific metabolic adaptations, it underscores the potential of Anabaena for more effective phycoremediation. This novel insight into the differential resilience of microalgae species offers a promising approach to mitigating agrochemical pollution, advancing sustainable agriculture, and improving water management practices. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Sunitinib exhibits considerable interindividual variability in exposure. While the target total plasma concentration of sunitinib and its active metabolite is 50–87.5 ng/mL for the intermittent dosing schedule, ~10–21% of patients experience higher exposures (>87.5 ng/mL), correlated with an increased risk for toxicity. Previous research identified single nucleotide variants (SNVs) in genes from the sunitinib pharmacokinetic pathway to be associated with efficacy and toxicity. However, significant interindividual variability in exposure remains unexplained. Our aim was to identify genetic variants associated with supratherapeutic exposure of sunitinib.This was a genome‐wide association study. Cases were identified during routine therapeutic drug monitoring and consisted of patients with dose‐normalized sunitinib plasma concentrations >87.5 ng/mL (intermittent dosing) or >75 ng/mL (continuous dosing). Controls were sampled from the historical cohort EuroTARGET who tolerated the standard dose of 50 mg in an intermittent schedule. SNVs were tested for an association with sunitinib exposure. A P‐value ≤5 × 10−8 was considered significant and a P‐value between 5 × 10−8 and 5 × 10−6 was considered suggestive.Sixty‐nine cases and 345 controls were included for association analysis. One SNV (rs6923761), located on the gene glucagon‐like peptide 1 receptor, was significantly associated with increased sunitinib exposure (P = 7.86 × 10−19). Twelve SNVs were suggestive for an association with sunitinib exposure (P ≤ 5 × 10−6).While rs6923671 is associated with high sunitinib exposure, the underlying mechanism is not yet clarified and warrants further investigation. We could not confirm the earlier found associations between SNVs in candidate genes involved in the pharmacokinetic pathway of sunitinib and its efficacy and toxicity. [ABSTRACT FROM AUTHOR]

Synthetic food antioxidants such as tert‐butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and propyl gallate (PG) have been extensively utilized in different food industries because of their high protectant activities to stop food spoilage and remove foodborne diseases in humans and animals. It would be emphasized that increasing the intake of antioxidants through intracellular may lead to cyto/genotoxicity, and their complex formation with biological molecules eventually accelerate the progress of various diseases like multiple sclerosis, diabetes, neurological disorders, cardiac vascular disease, cancer, etc. Therefore, their toxicity is one of the challenging subjects due to their extensive use in food‐related industries. TBHQ, BHA, and PG antioxidants have cytotoxic, genotoxic, and carcinogenic effects if absorbed in high doses through the gastrointestinal tract. Thermodynamic parameters presented that the hydrophobic bind plays a key role in the complexation of the TBHQ, BHA, and PG with albumin. The molecular modeling results showed that subdomain IIA plays a vital role in the interaction of TBHQ and BHA with albumin. To comprehend the mechanisms of the cyto/genotoxicity effects of these food antioxidants and conformational alterations of albumin macromolecule, we aim to overview numerous types of research that evaluated the cyto/genotoxicity effects of these antioxidants using several procedures. [ABSTRACT FROM AUTHOR]

Background: Sulphur containing natural compounds are among the most biologically relevant metabolites in vivo. Naringenin 8-sulphonate from Parinari excelsa Sabine was evaluated in a previous work, demonstrating ability to act as a natural anti-inflammatory. Although the interference of this molecule against different inflammatory mediators was described, there is no information regarding its potential toxicity and pharmacokinetics, which are essential for its capacity to reach its therapeutic targets. In fact, despite the existence of reports on naringenin ADMET properties, the influence of sulphation patterns on them remains unknown. Objectives: This work aims to assess the in vitro pharmacokinetic and toxicological behavior of naringenin 8-sulphonate, as well as to understand the importance of the presence and position of the sulphur containing group for that. Methods: Naringenin 8-sulphonate physicochemical and ADMET properties were investigated using in silico tools and cell-based in vitro models. At the same time, naringenin and naringenin 4’-O-sulphate were investigated to evaluate the impact of the sulphonate group on the results. ADMETlab 2.0 in silico tool was used to predict the compounds’ physicochemical descriptors. Pharmacokinetic properties were determined experimentally in vitro. While MRC5 lung fibroblasts and HaCaT keratinocytes were used to evaluate the cytotoxicity of samples through MTT and LDH assays, Caco-2 human intestinal epithelial cells were used for the determination of genotoxicity, through alkaline comet assay, and as a permeability model to assess the ability of compounds to cross biological barriers. Results: Experimental determinations showed that none of the compounds was cytotoxic. In terms of genotoxicity, naringenin 8-sulphonate and naringenin caused significant DNA fragmentation, whereas naringenin 4’-O-sulphate did not. When it comes to permeability, the two sulphur-containing compounds with a sulphur containing group were clearly less capable to cross the Caco-2 cell barrier than naringenin. Conclusion: In this study, we conclude that the sulphur containing group from naringenin 8-sulphonate is disadvantageous for the molecule in terms of ADMET properties, being particularly impactful in the permeability in intestinal barrier models. Thus, this work provides important insights regarding the role of flavonoids sulphation and sulphonation upon pharmacokinetics and toxicity. [ABSTRACT FROM AUTHOR]

Background: Prompt acetylcysteine treatment with standard doses (300 mg/kg over 21 h in divided doses) is almost universally effective in preventing hepatotoxicity after paracetamol (acetaminophen) overdose. However, hepatotoxicity is reported despite early treatment when paracetamol concentrations exceed 300 mg/L (1,985 μmol/L) at 4 h. Prior studies evaluating high-dose acetylcysteine to treat high-risk ingestions have shown mixed results. We compared outcomes in patients with high-risk ingestions receiving standard or high-dose acetylcysteine. Methods: Records from a single poison center were reviewed from 1 January 2017 to 31 December 2022. We included cases of acute paracetamol ingestion treated with intravenous acetylcysteine with an initial paracetamol concentration above the "300 mg/L" (1,985 μmol/L) line on the Rumack-Matthew nomogram. We compared standard and high-dose acetylcysteine groups by odds ratios and multivariable logistic regression. We defined hepatotoxicity as aminotransferase activity >1,000 U/L. Results: We included 190 cases. Fifty-six percent received standard-dose acetylcysteine while 44% received high-dose acetylcysteine. Treatment within 8 h yielded no difference in hepatotoxicity between groups (odds ratio 1.67, 95% CI 0.067–42.3). Among patients treated after 8 h, hepatoxicity was more common in the high-dose group (odds ratio 3.39, 95% CI 1.25–9.2) though odds of liver failure were similar (odds ratio 2.78, 95% CI 0.89–8.69). Eighty-eight percent of patients with hepatotoxicity had elevated aminotransferase activity at presentation. No patient died or received a liver transplant. Discussion: Rates of hepatotoxicity were low in patients treated within 8 h regardless of acetylcysteine dose. Unexpectedly, high-dose acetylcysteine treatment was associated with an increased odds of hepatoxicity in those treated after 8 h, but most had abnormal aminotransferase activities at presentation and there was no difference in rates of liver failure. Limitations include the use of retrospective, voluntarily reported poison center data. Conclusions: Prompt treatment with acetylcysteine, regardless of dose, prevented hepatotoxicity in high-risk paracetamol ingestion. [ABSTRACT FROM AUTHOR]

Background and Objectives: The most common cause of healthcare-associated diarrhea is Clostridium difficile infection (CDI), which causes severe and recurring symptoms. The increase of antibiotic-resistant C. difficile requires alternate treatments. Postbiotics, metabolites produced by probiotics, fight CDI owing to their antibacterial capabilities. This study aims to evaluate the antibacterial, antibiofilm, and anti-toxigenic potential of postbiotics in combating CDI. Materials and Methods: GC-MS evaluated postbiotics from Bifidobacterium bifidum and Lactobacillus plantarum. Disk diffusion and broth microdilution determined C. difficile antibacterial inhibition zones and MICs. Microtiter plates assessed antibiofilm activity. MTT assay evaluated postbiotics anti-viability on HEK293. ELISA testing postbiotic detoxification of toxins A and B. Postbiotics were examined for tcdA and tcdB genes expression using real-time PCR. Results: The most identified B. bifidum and L. plantarum postbiotic compounds were glycolic acid (7.2%) and butyric acid (13.57%). B. bifidum and L. plantarum displayed 13 and 10 mm inhibition zones and 2.5 and 5 mg/ml MICs against C. difficile. B. bifidum reduced biofilm at 1.25 mg/ml by 49% and L. plantarum by 31%. MTT assay showed both postbiotics had little influence on cell viability, which was over 80%. The detoxification power of postbiotics revealed that B. bifidum decreased toxin A and B production more effectively than L. plantarum, and also their related tcdA and tcdB genes expression reduction were statistically significant (p < 0.05). Conclusion: Postbiotics' ability to inhibit bacterial growth, biofilm disruption, and toxin reduction makes them a promising adjunctive for CDI treatment and a good solution to pathogens' antibiotic resistance. [ABSTRACT FROM AUTHOR]

The risk of a terrorist attack in the United States has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the United States has organized a trans‐agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure to chemical threat agents. We sought to develop and evaluate an interactive educational session that provides hands‐on instruction on how to repurpose FDA‐approved drugs as therapeutics to treat toxicity from exposure to chemical weapons. As part of the Rutgers Summer Undergraduate Research Fellowship program, 23 undergraduate students participated in a 2‐h session that included: (1) an overview of chemical weapon toxicities, (2) a primer on pharmacology principles, and (3) an interactive session where groups of students were provided lists of FDA‐approved drugs to evaluate potential mechanisms of action and suitability as countermeasures for four chemical weapon case scenarios. The interactive session culminated in a competition for the best grant "sales pitch." From this interactive training, students improved their understanding of (1) the ability of chemical weapons to cause long‐term toxicities, (2) impact of route of administration and exposure scenario on drug efficacy, and (3) re‐purposing FDA‐approved drugs to treat disease from chemical weapon exposure. These findings demonstrated that an interactive training exercise can provide students with new insights into drug development for chemical threat agent toxicities. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma and basal cell carcinoma are the most common cancers worldwide and surgical excision is the first-line treatment. Brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, represents a curative and conservative alternative in certain situations, particularly in elderly patients. Since the withdrawal of iridium wires from the market, brachytherapy has mainly been performed with high-dose-rate iridium-192 (HDR). Few studies and recommendations exist on HDR brachytherapy. Our study aims to evaluate the efficacy of HDR brachytherapy in terms of local control, survival, toxicity, and quality of life in patients with facial periorificial cutaneous squamous cell carcinoma or basal cell carcinoma treated in our center between 2015 and 2021. While treatment of localized cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is based on surgery, brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, is an alternative. Since the withdrawal of iridium wires from the market, brachytherapy has mainly been performed with high-dose-rate iridium-192 (HDR). This study evaluated the efficacy of HDR brachytherapy in terms of local control, survival, toxicity, and quality of life in patients with facial periorificial cutaneous SCC or BCC treated in our center between 2015 and 2021. Sixty-seven patients were treated for SCC (n = 49) or BCC (n = 18), on the nose (n = 29), lip (n = 28), eyelid (n = 7), or ear (n = 3). The majority had Tis or T1 tumors (73.1%). After a median follow-up of 28 months, 8 patients had a local recurrence. The local control rate at 3 years was 87.05% (95% CI 74.6–93.7). All patients developed grade 1–2 acute radio-mucositis or radiodermatitis and one experienced reversible grade 3 acute radio-mucositis. Of the 27 patients who completed the quality-of-life questionnaire, 77.8% recommended the treatment. This study confirms that HDR brachytherapy for facial cutaneous carcinomas provides good local control, good tolerance, and satisfactory functional outcome. [ABSTRACT FROM AUTHOR]

To reduce severe fluoropyrimidine-related toxicity, pharmacogenetic guidelines recommend a dose reduction for carriers of four high-risk variants in the DPYD gene (*2A, *13, c.2846A>T, HapB3). The polymorphism in the MIR27A gene has been shown to enhance the predictive value of these variants. Our study aimed to explore whether rs895819 in the MIR27A gene modifies the effect of five common DPYD variants: c.1129-5923C>G (rs75017182, HapB3), c.2194G>A (rs1801160, *6), c.1601G>A (rs1801158, *4), c.496A>G (rs2297595), and c.85T>C (rs1801265, *9A). The study included 370 Caucasian patients with gastrointestinal tumors who received fluoropyrimidine-containing chemotherapy. Genotyping was performed using high-resolution melting analysis. The DPYD*6 allele was associated with overall severe toxicity and neutropenia with an increased risk particularly pronounced in patients carrying the MIR27A variant. All carriers of DPYD*6 exhibited an association with asthenia regardless of their MIR27A status. The increased risk of neutropenia in patients with c.496G was only evident in those co-carrying the MIR27A variant. DPYD*4 was also significantly linked to neutropenia risk in co-carriers of the MIR27A variant. Thus, we have demonstrated the predictive value of the *6, *4, and c.496G alleles of the DPYD gene, considering the modifying effect of the MIR27A polymorphism. [ABSTRACT FROM AUTHOR]

The exopolymer (ESPp) was obtained from Bacillus licheniformis IDN-EC, composed of a polyglutamic acid and polyglycerol phosphate chain O-substituted with αGal moieties (αGal/αGlcNH2 3:1 molar ratio) and with a 5000 Da molecular weight. The cytotoxicity activity of EPSp was determined by reducing the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) to formazan on HeLa cells. This EPS did not show cytotoxicity against the tested cell line. The ESPp presented great advantages as an antioxidant with free radical scavenging activities (1,1-diphenyl-2-picryl-hydrazyl radical (DPPH),hydroxyl radical (OH), and superoxide anion (O2−)) (65 ± 1.2%, 98.7 ± 1.9%, and 97 ± 1.7%), respectively. Moreover, EPSp increased the enzyme activity for catalase (CAT) and glutathione peroxidase (GSH-Px) in HeLa cells (CAT, 2.6 ± 0.24 U/mL; and GSH-Px, 0.75 ± 0.3 U/L). The presence of ESPp showed a significant protective effect against H2O2 in the cell line studied, showing great viability (91.8 ± 2.8, 89.9 ± 2.9, and 93.5 ± 3.6%). The EPSp presented good emulsifying activity, only for vegetable oils, olive oil (50 ± 2.1%) and sesame (72 ± 3%). Sesame was effective compared to commercials products, Triton X-100 (52.38 ± 1.6%), Tween 20 (14.29 ± 1.1%), and sodium dodecyl sulphate (SDS) (52.63 ± 1.6%). Furthermore, the EPS produced at 0.6 M has potential for environmental applications, such as the removal of hazardous materials by emulsification whilst resulting in positive health effects such as antioxidant activity and non-toxicity. EPSp is presented as a good exopolysaccharide for various applications. [ABSTRACT FROM AUTHOR]

Nanoparticles are structures that possess unique properties with high surface area-to-volume ratio. Their small size, up to 100 nm, and potential for surface modifications have enabled their use in a wide range of applications. Various factors influence the properties and applications of NPs, including the synthesis method and physical attributes such as size and shape. Additionally, the materials used in the synthesis of NPs are primary determinants of their application. Based on the chosen material, NPs are generally classified into three categories: organic, inorganic, and carbon-based. These categories include a variety of materials, such as proteins, polymers, metal ions, lipids and derivatives, magnetic minerals, and so on. Each material possesses unique attributes that influence the activity and application of the NPs. Consequently, certain NPs are typically used in particular areas because they possess higher efficiency along with tenable toxicity. Therefore, the classification and the base material in the NP synthesis hold significant importance in both NP research and application. In this paper, we discuss these classifications, exemplify most of the major materials, and categorize them according to their preferred area of application. This review provides an overall review of the materials, including their application, and toxicity. [ABSTRACT FROM AUTHOR]

Engaging the thinking of Georges Bataille, this article examines the international politics of poison as a category of death-dealing that defies distinctions between war/not war and weapon/not weapon. Refraining from splitting poison into pesticides and chemical weapons, the article analyses political ecologies and affective economies of poison both historically and today, to illuminate which desires and strategies poison, as a technology of death, lends itself to. Taking its departure in Bataille's writing on fascism and ending with his main theory of a general economy, the article weaves through nerve agent assassinations, fumigation, and ideas about gardening, to arrive at the conclusion that poison is not so much an excessive response as it is a response to excess. Following Bataille in viewing ecology as economies of consumption and competition, the article develops a rubric of martial economies of poison to encapsulate how poison, as mode of martial expenditure, makes spaces vacant by death, and room for organisms deemed worthy. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) have played a pivotal role in various biomedical applications, spanning from sensing to drug delivery, imaging and anti-viral therapy. The therapeutic utilisation of NPs in clinical trials was established in the early 1990s. Silver nanoparticles (AgNPs) possess anti-microbial, anti-cancer and anti-viral properties, which make them a possible anti-viral drug to combat the COVID-19 virus. Free radicals and reactive oxygen species are produced by AgNPs, which causes apoptosis induction and prevents viral contamination. The shape and size of AgNPs can influence their interactions and biological activities. Therefore, it is recommended that silver nanoparticles (AgNPs) be used as a valuable tool in the management of COVID-19 pandemic. These nanoparticles possess strong anti-microbial properties, allowing them to penetrate and destroy microbial cells. Additionally, the toxicity level of nanoparticles depends on the administered dose, and surface modifications are necessary to reduce toxicity, preventing direct interaction between metal surfaces and cells. By utilising silver nanoparticles, drugs can be targeted to specific areas in the body. For example, in the case of COVID-19, anti-viral drugs can be stimulated as nanoparticles in the lungs to accelerate disease recovery. Nanoparticle-based systems have the capability to transport drugs and treat specific body parts. This review offers an examination of silver nanoparticle-based drug delivery systems for combatting COVID-19, with the objective of boosting the bioavailability of existing medications, decreasing their toxicity and raising their efficiency. [ABSTRACT FROM AUTHOR]

Objectives: We performed an observational, retrospective, cohort study to assess changes in insulin sensitivity after a switch from dolutegravir/lamivudine (DOL/3TC) or bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) to doravirine/tenofovir disoproxil fumarate/3TC (DOR/TDF/3TC) in virologically suppressed people living with HIV with recent significant weight gain. Methods: All non‐diabetic patients with HIV treated with DOL/3TC or BIC/F/TAF for ≥12 months, with HIV RNA <20 copies/mL, and with a weight increase ≥3 kg in the last year, who underwent a switch to DOR/TDF/3TC were enrolled into the study. Serum levels of glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA‐IR) index were evaluated every 6 months during a 12‐month follow‐up. Results: Overall, 81 patients were enrolled: 41 were treated with DOL/3TC and 40 with BIC/F/TAF. At baseline, median HOMA‐IR index was 3.18 and insulin resistance (HOMA‐IR index >2.5) was present in 49 subjects (60%). At 12 months after the switch to DOR/TDF/3TC, change in mean serum glucose concentration was not significant, but the reduction in median concentration of insulin was significant (−3.54 mcrUI/L [interquartile range −4.22 to −2.87]; p = 0.012), associated with a significant reduction in mean HOMA‐IR index (−0.54 [interquartile range −0.91 to −0.18]; p = 0.021). A significant reduction in total and low‐density lipoprotein cholesterol was also reported, whereas decreases in mean body weight and mean body mass index were not significant. Conclusions: In our retrospective study in virologically suppressed people living with HIV treated with DOL/3TC or BIC/F/TAF and with recent weight gain, the switch to DOR/TDF/3TC led to a significant improvement in insulin sensitivity and plasma lipids, with a trend to decreased body weight. [ABSTRACT FROM AUTHOR]

Gambierdiscus is a marine benthic dinoflagellate genus that currently contains 19 species; some of them are toxigenic, producing ciguatoxins, maitotoxins, and other toxic compounds. The objective of this study was to document the morphological and molecular identification (ITS, 5.8S and 28S of the rDNA) of two strains of Gambierdiscus from La Gaviota Island, Gulf of California, Mexico, and a toxicity test. The shape of the 2′ plate varied between hatchet-shaped and rectangular, that complicated the differentiation between G. carpenteri and G. toxicus. Molecular markers of the three rDNA regions allowed confirmation of the taxonomic identity of G. carpenteri, separating this species from other congeners with high phylogenetic affinity, such as G. excentricus, G. toxicus and G. caribaeus. Studies of the morphological taxonomy of G. carpenteri are scarce; therefore, due to the similarity between species, the combination of morphological and molecular tools is recommended for the identification of species, such as G. carpenteri, G. excentricus, G. toxicus and G. caribaeus. The mouse bioassay showed that the examined isolate was toxic, and it is a potential etiology of ciguatera fish poisoning cases in the region. This study provides the first reliable report and ribosomal sequences of G. carpenteri for the Gulf of California, as well as data on mouse bioassay toxicity. [ABSTRACT FROM AUTHOR]

Background: Due to the close proximity of the prostate and rectum, rectal toxicity remains a major problem in patient treated by radiotherapy for prostate adenocarcinoma. One method of increasing the distance between the prostate and the rectum is to use a spacer implanted into the rectoprostatic space. This report describes the long-term outcomes obtained with a new ballon spacer. Methods: Patients treated with curative radiotherapy for low- or intermediate-risk prostate adenocarcinoma, who underwent insertion of the ProSpace® (BioProtect Ltd, Tzur Yigal, Israel) rectal-prostate balloon spacer, were included. The main objective was to evaluate the dosimetric benefit of the spacer for OARs. The secondary objectives were to evaluate the feasibility and tolerability of ProSpace® balloon placement and to evaluate its long-term therapeutic efficacy and tolerance. Results: Between October 2013 and March 2015, 16 patients were enrolled in the Pasteur Clinic, Toulouse, France. The median follow-up was 85.5 months. From top to bottom, the space created was a mean of 16.3 mm (range: 11–20.5 mm) at the base of the prostate, 12.1 mm (range: 4–16 mm) at the middle and 8.9 mm at the apex (range: 5–15 mm). On average, rectal volumes receiving a dose of 70 Gy, 60 Gy and 50 Gy were significantly lower after balloon implantation: -4.81 cc (1.5 vs. 6.3; p < 0.0005), -8.08 cc (6.4 vs. 14.5; p = 0.002) and -9.06 cc (16.7 vs. 25.7; p = 0.003), respectively. There were significant differences in coverage after balloon implantation: Median V95% (p < 0.0005), median Dmin (p = 0.01) and median V98% (p < 0.001) were higher after balloon implantation. At 5 years, cumulative gastrointestinal toxicity was grade 1 in 6% (1/16 patients). No toxicity of grade 2 or higher was found. At 5 years, no urinary toxicity grade 3 or 4 toxicity was found. The QoL was not deteriorated. Conclusions: The use of the ProSpace® balloon seems to be well accepted by patients, allowing a double dosimetric gain: a decrease in doses received by the rectum and an improvement in the coverage of the high-risk PTV. The long-term gastrointestinal toxicity remains low and QoL is preserved in all treated patients. [ABSTRACT FROM AUTHOR]

Background: We report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT). Methods: A total of 124 patients (median age: 74 y, 46–84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5–7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76–78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2–3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation. Results: A total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups. Conclusion: These results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy. [ABSTRACT FROM AUTHOR]

Arsenic (As) is one of the most important water pollutant of global concern due to its extreme hazard. In the present study, B. subtilis synthesized iron oxide nanoparticles (Fe3O4 NPs) were used for mitigation of harmful metalloid As from the aqueous solution. Initially, the arsenic removal efficiency was tested in a batch culture experiment across various concentrations (5, 10 and 15 ppm) of B. subtilis synthesized Fe3O4 NPs at different pH, time interval and agitation speed. Optimal removal efficiency of As by using B. subtilis synthesized Fe3O4 NPs was observed at pH 7, after 80 min, and with agitation at 200 rpm. Additionally, hydroponic culture experiment was designed to assess B. subtilis synthesized Fe3O4 NPs efficiency in removal of As from As-contaminated water used to irrigate rice plants. Results revealed that B. subtilis synthesized Fe3O4 NPs effectively removed As from the contiminated water and reduced its uptake by the different parts of rice plants (root, shoot and leaf). Furthermore, these B. subtilis synthesized Fe3O4 NPs also reduced the bioaccumulation and enhanced plant tolerance to As, suggesting their potential in mitigating heavy metal toxicity, especially As and promoting plant growth. Thus, this study proposes B. subtilis synthesized Fe3O4 NPs as nano-adsorbents in reducing arsenic toxicity in rice plants. [ABSTRACT FROM AUTHOR]

It is crucial to investigate the effects of mixtures of contaminants on aquatic organisms, because they reflect what occurs in the environment. Cadmium (Cd) and nickel (Ni) are metals that co‐occur in aquatic ecosystems, and information is scarce on their joint toxicity to Chlorophyceae using multiple endpoints. We evaluated the effects of isolated and combined Cd and Ni metals on multiple endpoints of the chlorophycean Raphidocelis subcapitata. The results showed that Cd inhibited cell density, increased reactive oxygen species (ROS) production (up to 308% at 0.075 mg L−1 of Cd), chlorophyll a (Chl a) fluorescence (0.050–0.100 mg L−1 of Cd), cell size (0.025–0.100 mg L−1 of Cd), and cell complexity in all concentrations evaluated. Nickel exposure decreased ROS production by up to 25% at 0.25 mg L−1 of Ni and Chl a fluorescence in all concentrations assessed. Cell density and oxygen‐evolving complex (initial fluorescence/variable fluorescence [F0/Fv]) were only affected at 0.5 mg L−1 of Ni. In terms of algal growth, mixture toxicity showed antagonism at low doses and synergism at high doses, with a dose level change greater than the median inhibitory concentration. The independent action model and dose‐level–dependent deviation best fit our data. Cadmium and Ni mixtures resulted in a significant increase in cell size and cell complexity, as well as changes in ROS production and Chl a fluorescence, and they did not affect the photosynthetic parameters. Environ Toxicol Chem 2024;43:1855–1869. © 2024 SETAC [ABSTRACT FROM AUTHOR]

The results of a Fourier-transform IR spectroscopic study of polypropylene (PP) subjected to gamma-irradiation and post-irradiation high-temperature shear grinding are presented. The IR spectra of PP granules irradiated in air exhibited absorption peaks of hydroxyl and oxygen-containing groups, the intensity of which noticeably decreased in the powder obtained by grinding the irradiated polymer granules. The toxic properties of PP obtained by high-temperature shear grinding of irradiated polymer granules were investigated. It was found that gamma-irradiation of polymer granules in air did not affect the toxic properties of polymer powder obtained by grinding granules irradiated with a dose of 700−4500 kGy. It was established that PP powder obtained from unirradiated and irradiated granules was a moderately toxic substance when administered intragastrically to BDF1 mice. [ABSTRACT FROM AUTHOR]

To investigate the transdentinal effects of surface reaction-type pre-reacted glass-ionomer (S-PRG) fillers on odontoblast-like cells. An eluate of S-PRG fillers was obtained by dissolving the particles in distilled water (1:1 m/v). Dentin discs with similar permeability were mounted into artificial pulp chambers and MDPC-23 cells were seeded on their pulpal surface. The occlusal surface was treated with (n = 10): ultrapure water (negative control – NC), hydrogen peroxide (positive control – PC), S-PRG eluate exposure for 1 min (S-PRG 1 min), or S-PRG filler eluate exposure for 30 min (S-PRG 30 min). After 24 h, cell viability (alamarBlue) and morphology (SEM) were evaluated. The extract obtained from transdentinal diffusion was applied to MDPC-23 pre-cultured in plates for another 24 h to evaluate viability (alamarBlue, 1, 3, and 7 days), gene expression of Col1a1 , Alpl , Dspp , and Dmp1 (RT-qPCR, 1 and 7 days), and mineralization (Alizarin Red, 7 days). Data were analyzed with ANOVA (α = 5 %). While S-PRG 1 min did not differ from NC, S-PRG 30 min reduced 17.9 % viability of cells from discs. S-PRG treatments resulted in low cell detaching from dentin, and the remaining cells exhibited typical morphology or minor cytoplasmic contraction. S-PRG 30 min slightly increased cell viability (6 %) 1 day after contact with the extract. S-PRG treatments upregulated the expression of the investigated genes, especially after 1 day. S-PRG 30 min stimulated mineralization activity by 39.7 %. S-PRG filler eluate does not cause transdentinal cytotoxicity on odontoblast-like cells, and long-term exposure can stimulate their dentinogenic-related mineralization activity. The transdentinal elution of ions from S-PRG fillers is not expected to be harmful to the dental pulp and may exert bioactive effects by inducing dentin matrix deposition through the metabolism of underlying odontoblasts. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) are a typical group of persistent contaminants and have arisen public concern for their close correlation with health risks. Dietary exposure is the principal source of PAHs. They can be formed through the degradation, integration and cyclization of nutrients in foods during high-temperature food processing. Precursors in foodstuffs and processing conditions have a remarkable influence on the formation of PAHs, which can be modified to diminish their production. Moreover, the addition of exogenous active compounds, especially natural antioxidants is an effective approach to decrease PAHs in foods. Deleterious effects of PAHs, including immunotoxicity, carcinogenicity and teratogenicity have been revealed to have a strong relevance with human diseases. In this review, reported data on PAHs in various foods and maximum limit standards are provided. Also, based on a comprehensive understanding of the formation mechanisms, the mitigation strategies for their generation are summarized to diminish human exposure. Furthermore, potential intervention by phenolic compounds and various natural plant extracts are proposed to restrain PAHs toxicity, hence decreasing detrimental health effects. [ABSTRACT FROM AUTHOR]