Toxic Levels Research Articles

In silico assessment of antioxidant activity and toxicity profiling of bioactive molecules from Murraya koenigii

The antioxidant activity of curry leaves is of interest because oxidative stress is implicated in a variety of diseases, including cancer, heart disease, and neurodegenerative disorders. By scavenging free radicals and inhibiting lipid peroxidation, antioxidants can help protect cells from damage and reduce the risk of these diseases. Overall, in-silico studies suggest that curry leaves and their bioactive compounds have potent antioxidant activity. The objective of the study was to assess the antioxidant activity of the bioactive molecules from Murraya koenigii and anticipate the toxicity by in-silico research. iGEMDOCK software was used to assess the antioxidant activity. ProTox II software was used to conduct the toxicity investigations. Osthol (− 81.4863, − 81.9046 kcal/mol), mukoenineA (− 81.0417, − 78.9941 kcal/mol), murrayone(− 80.0731, − 78.9453 kcal/mol), kaempferol (− 97.0774, − 89.3534 kcal/mol), and apigenin (− 89.5291, − 108.704 kcal/mol) were found to have the highest binding energies with SOD and GPx proteins, respectively, when compared with standard (ascorbic acid; − 81.132, − 98.917 kcal/mol). All the mentioned compounds have low levels of hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. The bioactive molecules of Murraya koenigii have a potent antioxidant effect and low level of toxicity that gives valuable insight for optimizing lead molecules to combat free radical generation or oxidation.

Cysteamine dioxygenase (ADO) governs cancer cell mitochondrial redox homeostasis through proline metabolism.

2-Aminoethanethiol dioxygenase (ADO) is a thiol dioxygenase that sulfinylates cysteamine and amino-terminal cysteines in polypeptides. The pathophysiological roles of ADO remain largely unknown. Here, we demonstrate that ADO expression represents a vulnerability in cancer cells, as ADO depletion led to loss of proliferative capacity and survival in cancer cells and reduced xenograft growth. In contrast, generation of the ADO knockout mouse revealed high tolerance for ADO depletion in adult tissues. To understand the mechanism underlying ADO's essentiality in cancer cells, we characterized the cell proteome and metabolome following depletion of ADO. This revealed that ADO depletion leads to toxic levels of polyamines which can be driven by ADO's substrate cysteamine. Polyamine accumulation in turn stimulated expression of proline dehydrogenase (PRODH) which resulted in mitochondrial hyperactivity and ROS production, culminating in cell toxicity. This work identifies ADO as a unique vulnerability in cancer cells, due to its essential role in maintenance of redox homeostasis through restraining polyamine levels and proline catabolism.

Toxicity prediction based on PAHs in fruits and vegetables − A machine learning approach

This study analyses the toxicity levels of fruits and vegetables by identifying the presence of polycyclic aromatic hydrocarbons (PAHs), particularly in areas affected by industrial and vehicle pollution. The presence of PAHs on plant surfaces, caused mostly by air pollution particulate matter, raises serious concerns about the nutritional value of these foods. Traditional techniques for measuring PAH levels include Gas Chromatography/Mass Spectrometry (GC/MS) and High-Performance Liquid Chromatography (HPLC). Although successful, these procedures are expensive and time-consuming. Toxicity detection is often based on expert knowledge or experimental analysis relative to the European Food Safety Authority’s (EFSA) limits. In response to these challenges, this work uses artificial intelligence approaches to determine toxicity levels using 16 PAHs. Data on PAH concentrations in fruits and vegetables were collected from a variety of sources, classified as safe or harmful, and verified using statistical analysis. The validated dataset was subsequently classified using several machine learning techniques. The level of toxicity is scaled and compared to the expected outputs using the results obtained from the neural network. An experimental investigation validates the promising findings of level of toxicity classification using artificial intelligence approaches, which are then evaluated statistically. The study shows that machine learning algorithms obtained classification accuracies of over 90 %, including the evaluation of harmfulness. The accuracy for the two-class (Safe and Unsafe) category was 98.27 %, while the accuracy for the four-class (No harm, Low harm, Moderate Harm, and Severe harm) category was 98.68 %. These findings highlight the potential of artificial intelligence in improving food safety and public health by presenting an innovative multidisciplinary method to assessing the impacts of environmental pollutants on the edibility of fruits and vegetables in the context of climate change.

The effects of Selenium phytotoxicity on two wheat (Triticum aestivum) cultivars differing in Se tolerance and the role of antioxidant enzymes in the tolerance mechanism

Abstract Wheat seedlings were hydroponically grown in Hoagland solution containing various levels of Se. Tolerance response to Se toxicity was investigated by determining the level of thiobarbituric acid reactive substance (TBARS), proline and chlorophyll content, the growth parameters, and the activity of antioxidant enzymes. The toxic level of Se treatment significantly retarded the seedling growth. A substantial amount of proline accumulation was also observed in response to toxic Se concentration, but it was more pronounced in putative-sensitive cultivars. Chlorophyll content significantly decreased in Se-intoxicated seedlings and increased at the lowest Se dose in both cultivars. Severe and mild chlorosis was observed in putative-sensitive and tolerant cultivars at the highest Se level. Alterations in the activities of glutathione reductase (GR, 1.6.4.2), glutathione S transferase (GST, 2.5.1.18), guaiacol peroxidase (GPX, 1.11.1.7), catalase (CAT, 1.11.1.6), and ascorbate peroxidase (APX, 1.11.1.11) and superoxide dismutase (SOD, EC 1.15.1.1) were determined. TBAR level did not significantly increase in putative tolerant cultivars as an indicator of membrane lipid peroxidation. However, a significant increase was observed in putative-sensitive cultivars in response to higher selenium concentrations. In higher Se treatment groups, CAT and GST activities significantly increased in putative Se tolerant cultivars. However, excluding SOD, the activity of all the studied enzymes was increased considerably in putative-sensitive cultivars in a dose-dependent manner. Higher antioxidant enzyme activities and a substantial amount of proline accumulation did not significantly contribute to overcoming Se phytotoxicity in wheat seedlings grown in media supplemented with toxic selenium levels.

Financial toxicity screening in an urban underserved patient population with cancer.

169 Background: Cancer-related financial hardship is associated with treatment delays, non-adherence and adverse survival outcomes. Racial/ethnic minorities and low-income households are disproportionately impacted by financial toxicity. The Comprehensive Score for Financial Toxicity (COST) measure is used to measure financial toxicity in research but has not been validated in low-income, racially diverse cancer patient populations. Methods: We conducted this study at a large urban medical center from January-August 2023. We included cancer patients on systemic therapy for at least 2 months with ECOG performance status 0-2. Participants completed the COST measure, the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL to assess health-related quality of life (HRQOL). Cancer diagnosis/stage, demographic data, and social work/financial counseling interventions were abstracted. Factor analyses were conducted to determine the underlying factor structure of the COST measure responses and bivariate analyses were conducted to identify relationships between COST scores and other data. Results: 100 patients participated in the study; the average age was 65 and both sexes were equally represented. Most patients reported African American (67%) race/ethnicity. 72% of patients held less than a 4-year college degree, 22 % were unemployed and 55% reported a yearly household income of less than $35,000. Lung (46%) and gastrointestinal (38%) cancers were the most represented. 73% were enrolled in a government sponsored insurance program (Medicare, Medicaid). The average COST score among participants was 22 [range 0-44] and mean FACT-G and EORTC scores were 16.5 [range 0-28] and 59.6 [ range 0 – 100] respectively. Fifty-eight patients were referred to social work or financial counseling for financial interventions. Factor analysis revealed three predominant factors among the COST responses (Eigenvalues > 1) including Factor 1: items 3, 7, 8, 9, 10, 11; Factor 2: item 4; Factor 3: item 5. COST was weakly associated with FACT-G and EORTC (Pearson range 0.27 – 0.37). The most highly correlated value was between the COST and EORTC physical wellbeing subscale (Pearson 0.38). The COST score was significantly associated with income, with higher incomes reporting less financial toxicity (p = 0.004). No significant differences in COST scores were noted across gender, race, or level of education. Conclusions: Low levels of financial toxicity were detected using the COST measure in a diverse, low-income cancer patient population despite many patients being referred to social work/financial counseling. Compared to similar studies, we found a weaker correlation between the COST measure and HRQOL. These findings suggest that the COST measure may need to be further adapted for use in underserved populations and patients with government sponsored insurance.

Considering Safe and Sustainable by Design alternatives – Environmental Hazards of an agriculture Nano-enabled pesticide to non-target species

Nanopesticides (Npes) offer improved efficacy compared to their conventional forms while reducing the usage/application rates, hence being more sustainable options. However, there is still a knowledge gap on the Npes environmental impacts. To support the safety of nano-enabled pesticides, the present study aimed at assessing the toxicity of the commercial Npe NUCOP-M and the active substance copper oxychloride, using the ecotoxicological soil model Enchytraeus crypticus and LUFA 2.2 soil. Bioassays were performed to assess various endpoints within short- to longer-term exposures: avoidance behaviour (2 d), hatching (13 d), survival, reproduction and organisms' size (based on the standard OECD test (28 d), the OECD extension (56 d), and the Full Life Cycle test - FLCt (46 d)). Based on the standard OECD test and its extension, NUCOP-M had a similar level of toxicity as copper oxychloride without indications of increase in toxicity over time (28 versus 56 d). The shorter-term exposures (2 and 13 d) showed higher toxicity for copper oxychloride. The exposure from cocoon stage (FLCt) seemed to provide an adaptative advantage (reduced toxicity) to NUCOP-M. The differences might be related to a slower release of Cu2+ ions from NUCOP-M, which seems to account for the toxicity at longer-term. Based on the recommended application doses (ca. 1.72 mg NUCOP-M kg-1, i.e. 0.62 mg Cu kg-1 in the topsoil) there is no unacceptable risk of NUCOP-M on the enchytraeid population.

Eta-Earth Revisited I: A Formula for Estimating the Maximum Number of Earth-Like Habitats.

In this hypothesis article, we discuss the basic requirements of planetary environments where aerobe organisms can grow and survive, including atmospheric limitations of millimeter-to-meter-sized biological animal life based on physical limits and O2, N2, and CO2 toxicity levels. By assuming that animal-like extraterrestrial organisms adhere to similar limits, we define Earth-like habitats (EH) as rocky exoplanets in the habitable zone for complex life that host N2-O2-dominated atmospheres with minor amounts of CO2, at which advanced animal-like life or potentially even extraterrestrial intelligent life can in principle evolve and exist. We then derive a new formula that can be used to estimate the maximum occurrence rate of such Earth-like habitats in the Galaxy. This contains realistic probabilistic arguments that can be fine-tuned and constrained by atmospheric characterization with future space and ground-based telescopes. As an example, we briefly discuss two specific requirements feeding into our new formula that, although not quantifiable at present, will become scientifically quantifiable in the upcoming decades due to future observations of exoplanets and their atmospheres. Key Words: Eta-Earth-Earth-like habitats-oxygenation time-nitrogen atmospheres-carbon dioxide-animal-like life. Astrobiology 24, 897-915.

Derivation of ecological safety thresholds and risk assessment of new SDHI fungicides in farmland system

Succinate dehydrogenase inhibitor (SDHI) fungicides have become some of the top-selling fungicides in recent years. As the utilization of these fungicides intensifies, the corresponding potential risks to the environment proportionately increase. However, there is still limited knowledge about their toxic effects on ecosystems. In this study, acute toxicity data from laboratory assessments of the springtail Folsomia candida, alongside collected data from terrestrial and aquatic non-target species, were utilized to construct a species sensitivity distribution (SSD) model for both terrestrial and aquatic non-target organisms. Subsequently, we derived ecological baseline values for diverse scenarios within ecosystems. The results indicated that benzovindiflupyr exhibited the highest 7-day median lethal concentration (7d-LC50) to Folsomia candida at 2.0 μg cm−2, while the toxicity levels of other SDHI fungicides varied, ranging from 99 to 304 μg cm−2. In agricultural environments, the Hazard Concentration for 5 % of species (HC5) values for fluxapyroxad, boscalid, sedaxane, and isopyrazam were determined to be 8.0, 1240, 12.97, and 25.37 g ha−1, respectively. In aquatic environments, the HC5 values for benzovindiflupyr, fluxapyroxad, boscalid, sedaxane, isopyrazam, and carboxin were 0.0013, 0.022, 1.76, 0.372, 0.013, and 0.161 mg L−1, respectively. In an evaluation of typical agricultural scenarios within China, SDHI fungicides were found to exert substantial ecological risks to terrestrial non-target fauna and aquatic ecosystems around agricultural fields. Specifically, isopyrazam and fluxapyroxad were identified as posing heightened ecological risks to Typhlodromus pyri and Aphidius rhopalosiphi. Moreover, the application of benzovindiflupyr, carboxin, isopyrazam, and fluxapyroxad in paddy field environments is associated with unacceptable risks to groundwater. The findings of this study contribute significantly to the environmental risk evaluation of SDHI fungicides within farmland system, thereby informing the development of policy frameworks for their scientifically grounded application.

New phenanthridine-based multi-functional chemosensor for selective detection of Th4+ and Hg2+ ions in both aqueous and solid state

A new phenanthridine-based multifunctional chemosensor (L), was synthesised via a green synthetic route and characterised using FT-IR, NMR and HRMS analysis. The sensing application of L towards metal ions in both solution and solid-state was studied using UV–vis and fluorescence spectroscopy, which exhibits dual-sensing behaviour for Th4+ and Hg2+ ions with good recyclability. In aqueous acetonitrile, L showed rapid response for the detection of environmental toxic metal ions and has a very low analytical detection limit of 125.5 pM and 1.94 nM for Th4+ and Hg2+ions respectively, which is remarkably lower than the World Health Organization standard. The cation binding property of the L with Th4+ and Hg2+ions was investigated by Job plot, 1H NMR titration, HR-MS and DFT calculation. The in-situ formed ensemble L-Hg2+ was further applied in the naked-eye detection of Cys (Cystine) and His (Histidine) over other common amino acids. The utility of L for real-time detection of Hg2+ and Th4+ ions was explored in various sources of environmental water samples, test paper strips, fingerprint imaging, fluorescent ink and smartphone-assisted sensing techniques, demonstrating the promising on-site visualization of the probe in controlling the toxicity levels in wastewater sources without resorting to expensive instruments.

Environmental Biomonitoring of Heavy and Toxic Metals Using Honeybees and Their Products—An Overview of Previous Research

Humans and bees share millennia of history that have resulted in ever-increasing connection and interdependence. Thus, today, it is impossible to ignore the influence of humans on bees, particularly regarding the decrease in their numbers due to environmental contamination. Although they do not cause immediate mortality, heavy and toxic metals, along with dangers such as bee diseases, pesticides, habitat destruction, and climate change, threaten the number of bees and should not be ignored. Honeybees, their colonies, and their products are recognized as accumulators of metals and biological indicators of the presence of these metals in all environmental components. This study is an overview of prominent research from the past three decades on heavy and toxic metal levels in honeybees (Apis mellifera L.), honey, wax, and pollen. This research compares metals such as Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se, and Zn in natural environments and in an environment where anthropogenic pressure manifests. The presented studies represent a range of research using analytical methods to determine the presence of heavy and toxic metals in different segments of bees and their products, linking these findings with the state of the environment. It has been repeatedly established that if heavy and toxic metals are present in higher concentrations in components of the environment that are under anthropogenic pressure, then their concentrations in bees, honey, and wax will also be higher. By summarizing this research in one place, this study can provide guidelines for future scientific work on this subject, promoting sustainable development through safe beekeeping and healthy bees.

Оценка степени высвобождения и токсичности соединений цинка, используемых в фармацевтических и косметических средствах

The degree of release from ointments and the toxicity of three zinc compounds were assessed to establish their minimum sufficient concentration in antibacterial pharmaceutical and cosmetic products. The properties of zinc oxide (ZnO), zinc pyrrolidone carboxylate (ZnРСА) and zinc salicylate (Zn(Sal)2·2H2О) were compared. The release rate of active substances from petrolatum-based ointments (the mass fraction of zinc compounds is 1%) was determined by the Kruvchinsky method. A cellophane film for dialysis served as a semipermeable membrane, which was fixed on a glass tube (length 15 cm, cross section 20 mm2). A sample of ointment (2.00 g) was applied to the inner surface of the membrane. The dialysis tube was inserted into a beaker with dialysis medium and immersed to a depth of no more than 3 mm. The toxicity of aqueous solutions (distilled water) of zinc compounds was determined in a bioluminescent biotest using “Ecolume” bacterial preparation based on a non-pathogenic strain of Escherichia coli. It was found that a high level of toxicity of is achieved at 10-5 mol/dm3 zinc salts in a solution, zinc oxide – 10-4 mol/dm3. A similar amount of Zn2+ diffuses from ointments through a semipermeable cellophane membrane used for the study of dialysis into a 50% aqueous alcohol solution. Zinc ion release from ointment with ZnO was only 0.31%, as well as from ointments with ZnPCA and Zn(Sal)2·2H2О – 1.59% and 1.87% respectively. Thus, the tested approach is economically and environmentally effective, as it allows you to determine the lowest effective concentration of active substances, reducing the burden on the human microbiome and the environment.

Clitoria Ternatea: A Comprehensive Study on Extraction, Phytochemical Characterization, Antioxidant & Antimicrobial Properties, and Inorganic Elemental Analysis

North-eastern India is having rich biodiversity. Phytochemical are non-nutritive, chemical compounds occurs naturally on plants during metabolic processes and they have diverse proactive properties or disease preventive properties. Plants are known to produce these chemicals to protect them. While recent research demonstrates that they can also play an important role in protecting humans against diseases. Even some of these plants are in use as traditional medicine for centuries. Methanol extract showed the presence of most phytochemicals. Distilled water and acidified water extracts showed moderate phytochemical diversity. Ether extract showed presence of lipophilic phytochemicals like lipids, steroids, terpenoids, and triterpenoids. The TPC values for Clitoria ternatea range from 50-350 mg GAE/g. The methanolic extract of Clitoria ternatea showed higher total phenolic content of 209.2 mg GAE/g compared to the aqueous extract, which shows 122.1 mg GAE/g. The results indicate that methanol is a more efficient solvent for extracting phenolic compounds from Clitoria ternatea. The inorganic composition of plants, in a solid state, was determined using ED-XRF. The amount of silver, barium, cadmium, chromium, iron, nickel, lead, zinc, calcium, potassium, sodium, magnesium in plants were determined using ICP-OES. The most significant findings in this section include high concentrations of Potassium (K) in Asian pigeonwings followed by Calcium (Ca). According to the toxicity level, Cadmium (Cd) and Lead (Pb) levels are within safe limits. Hence, further research should be carried out to identify the active biomolecules or Phyto-molecules from the plants and determine the effects of them in vitro as well as in vivo.

Radiation-induced Esophagitis in Breast Cancer Patients Treated With Supraclavicular Field Irradiation.

The objective of this research was to assess the frequency and intensity of radiation-induced esophagitis in breast cancer patients treated with supraclavicular radiotherapy field irradiation. This study involved 100 patients with positive lymph nodes receiving radiotherapy to the breast or chest wall along with supraclavicular field irradiation, with toxicity levels assessed weekly. Treatment utilized the 3D conformal technique, and variables, such as mean and maximum dose to the cervical esophagus, mean dose to the entire esophagus, and length of the esophagus within the treated area were recorded. The occurrence of grade 2 or higher esophagitis was 48%, with patients facing the risk of developing such esophagitis at an average dose of 13 Gy. The probability of grade 2 esophagitis occurring at doses exceeding 13 Gy was statistically significantly higher (p<0.001) with an odds ratio of 24.4. Limiting the mean cervical esophagus dose to <13 Gy could help reduce the frequency and severity of grade 2 or higher toxicity.

Molecular characterization of a phytomelatonin receptor and its overexpression as a ‘one-stop’ solution to nullify the toxic effects of hazardous inorganic agro-pollutants

Inorganic toxicants like arsenic, copper, lead, nickel and fluoride are notorious agro-pollutants, impeding plant-productivity due to high bioaccumulation. Consumption of such contaminated plant-parts causes irreversible health hazards. We identified a G-protein coupled receptor, serving as melatonin receptor (MelR) in Nicotiana tabacum (NtMelR), that relayed downstream-signaling after binding melatonin, a potent growth regulator and antioxidant. Using inhibitors against G-protein-α and NADPH oxidase (NOX), and by supplementing epidermal strips with exogenous melatonin and H2O2, we established that NtMelR acted upstream of reactive oxygen species (ROS) production in guard cells. Transgenic lines of N. benthamiana overexpressing NtMelR maintained constitutive melatonin-signaling via MelR, leading to efficient stomatal closure for preventing desiccation during oxidative stress. Melatonin biosynthesis was stimulated in the transgenic lines, exposed to different agro-pollutant stress, providing a steady-abundance of ligand for NtMelR binding and activating the defence machinery, comprising of enzymatic-antioxidants like superoxide dismutase, catalase, peroxidases and glyoxalases. Due to increased antioxidant capacity, the transgenics exhibited less molecular injuries (electrolyte leakage, methylglyoxal accumulation and NOX activity), generated less ROS and bioaccumulated significantly lower levels of toxicants. Unlike the wild-type counterparts, the transgenics maintained high relative water content, photosynthetic efficiency, could flower abundantly and even produce seeds. Overall, we established that overexpression of NtMelR is a single-window strategy to generate multiple-stress tolerant genotypes.

Recién nacida con litemia en rango tóxico. ¿Debemos retirar la lactancia materna?

Lithium is a common part of the treatment for bipolar disorder. It is excreted through breast milk, and traditionally, mothers undergoing this treatment were advised to discontinue breastfeeding due to the potential serious adverse effects of this medication on the infant. More recently, it has been demonstrated that plasma lithium levels in exposed children are generally low and well tolerated, so, in selected cases, breastfeeding can be maintained, and close clinical and analytical monitoring of the child can be conducted, including measurement of thyroid and renal function, and serial lithium levels. We present a clinical case of a full-term newborn, born to a mother with bipolar disorder receiving lithium treatment, exclusively breastfed on demand, who in the second week of life showed toxic levels of lithium in plasma with no symptoms. Careful investigation of the case revealed that the elevated lithium levels were falsely elevated due to incorrect collection of the blood sample in a container containing lithium-heparin as an anticoagulant. The circumstances of the case will be reviewed as well as current recommendations on lithium intake by mothers and breastfeeding of their children.

Spatial distribution, ecological and ecotoxicity evaluation of heavy metals in agricultural soils along Lala-Manjo Highway, Cameroon Volcanic Line

This study aims at assessing the spatial distribution, ecological and toxicity levels of heavy metals in agricultural soils of Lala-Manjo Highway in Cameroon. The soil samples were collected and analyzed by inductively coupled plasma-mass spectrometry. The result shows that Co, Cr, Cu, Hg, Mn, Ni, Sr, V and Zn concentrations are higher than those of the upper continental crust reference values except those of As, Cd and Pb. Correlation coefficient indicate similar input sources governed by same geochemical characteristics. Spatial distribution maps show high concentration of heavy metals in east, south and western part of the study area. Pollution indicators show that enrichment factor varied from moderate to high enrichment of heavy metals. The contamination degree (27.12–35.59), geo-accumulation index (0.01–4.94), and potential ecological risk index (RI = < 150) revealed a low to moderate levels of metallic pollution. The majority of stations have pollution load index and Nemerow integrated pollution index values greater than one, indicating serious pollution. Modified hazard quotient and toxic risk index suggest significant severity of pollution and low toxicity risk of heavy metals, pointing low toxicity effects of heavy metals to fauna and flora in the soil ecosystem. Considering the factors governing soils accumulation such as geology, climate and anthropogenic activities as well as the correlation with commonly used environmental background, it is proposed that the data from this study can be considered as a baseline of pollution to plan major agricultural developments in the area. The study underlines the importance of continuous monitoring and adaptive management for the preservation of soil ecosystem. The results may assist companies and local population in setting realistic targets for monitoring and remediation programs.

Association between toxicity-index of diquat and in-hospital mortality in patients with acute diquat poisoning: a retrospective cohort study

Background This study investigates the impact of diquat toxicity levels on in-hospital mortality rates among patients with acute diquat poisoning. It aims to clarify the relationship between diquat toxicity scores and the likelihood of death during hospitalization. Methods A retrospective cohort study was conducted on 98 individuals with acute diquat poisoning. Data on post-ingestion time, initial diquat plasma concentration, and clinical outcomes were systematically collected for all participants. The toxicity-index of diquat was calculated based on post-ingestion time and initial diquat plasma concentration. Logistic regression analysis was utilized to assess the association between the toxicity-index of diquat and in-hospital mortality rates, adjusting for potential confounding variables such as age, comorbidities, and treatment interventions. Results The study found that the overall prevalence of in-hospital mortality was 34.7%, with 58.2% in males. The multivariable-adjusted regression coefficient for in-hospital mortality associated with the toxicity-index was 1.09, with a 95% confidence interval (CI) of 1.01–1.17. Subsequent exploratory subgroup analysis indicated that there were no significant interactions (all p values for interaction were >0.05). Conclusions The study found that higher diquat toxicity-index values correlate with increased in-hospital mortality in acute diquat poisoning cases, indicating that the toxicity-index could be a useful biomarker for assessing mortality risk.

Evaluation of a New In Chemico Skin Corrosion Test

The purpose of this study is to evaluate a novel macromolecular test method for the identification of dermal corrosives. The simple in chemico test procedure involves allowing the material to be tested to interact with a skin biomarker for corrosivity and then adding a detection reagent. The corrosivity of the test substance is predicted based on the measured macromolecular damage, which results in reduced optical density of the detection reagent as compared with controls. This study aims to determine if such an extremely simple, cell-free test method can accurately identify dermal corrosives. To determine predictivity and repeatability, we tested 60 chemicals (30 in vivo dermal corrosives and 30 in vivo dermal noncorrosives; all tested in triplicate) representative of a broad range of chemical classes, functional groups, mixtures, and levels of toxicity. Validation results indicate the GHS multicategory and packing group assignment accuracy is on par with that of the Reconstructed Human Epidermis test method and the Membrane Barrier test method and for the global identification of corrosives, the method has a considerably higher accuracy (98 % vs. ∼80 %).

Association Between Exposure to Heavy Metals and Dyslexic Risk Among Children: A Narrative Review

Context: Developmental dyslexia (DD) is a learning disorder characterized by difficulties in reading due to challenges in sound identification and letter-word association. This study aimed to evaluate the correlation between exposure to heavy metals (HMs) and the risk of dyslexia in children through a narrative review. Evidence Acquisition: The study adopted a narrative review approach, utilizing keywords to search reputable databases like Google Scholar, Scopus, PubMed, and Web of Science. Relevant research meeting specific criteria were selected for analysis. Results: In most studies, metals were measured in children's urine. The results indicated that children with DD had lower levels of essential metals such as zinc (Zn), selenium (Se), and cobalt (Co). In contrast, toxic metals like mercury (Hg), cadmium (Cd), silver (Ag), and lead (Pb) were significantly higher compared to the control group. Based on the results of previous studies, no significant variations were observed in other essential and toxic metals between the case and control groups. Conclusions: Essential metals like Zn, Se, and Co may protect against DD in children, whereas toxic metals such as Pb, Ag, Cd, and Hg could exacerbate the disorder. It is recommended to evaluate essential and toxic metal levels in parents before and during pregnancy and in infants to mitigate dyslexia risk in children.

Clinical use of Abemaciclib a cyclin-dependent kinase (CDK) 4/6 inhibitor in patients with breast cancer — literature review

Breast cancer is the most common neoplasma affecting women. Over, the past few years, the incidence of breast cancer has significantly increased, including among young women. Hormone receptor-positive (HR+) Her2 negative (HER2-) early stage breast cancer can be successfully treated using the currently available treatment methods based on endocrine theraphy (ET). However, if we consider early stage breast cancer with high risk of recurrence or metastatic disease, endocrine therapy alone may be insufficient. Unfortunately, resistance to drugs is observed in both adjuvant and palliative endocrine therapy, therefore there is a need for new treatments that are both effective and less toxic than conventional chemotherapy. One of the most successful applications of this strategy has been the use of cyclin-dependent kinase (CDK) 4 and 6 inhibitors alongside endocrine therapy significantly enhance its effectiveness. This combination has been shown to substantially increase progression-free survival while maintaining relatively low levels of toxicity. One of them is abemaciclib, whose efficacy will be shown in this research work.