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Parabens are preservatives widely used in personal care products, pharmaceuticals, and foodstuffs. However, they are still unregulated chemical compounds. Given their extensive use and presence in different environmental compartments, parabens can adversely affect animal health. Thus, the current study aimed to summarize and critically analyze the bioaccumulation and ecotoxicity of parabens in aquatic species. Studies have been mostly conducted in laboratory conditions (75%), using mainly fish and crustaceans. Field studies were carried out across 128 sampling sites in six countries. Paraben bioaccumulation was predominantly detected in fish muscle, liver, brain, gills, ovary, and testes. Among the parent parabens, methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) have been detected frequently and more abundantly in tissues of marine and freshwater specimens, as well as the metabolite 4-hydroxybenzoic acid (4-HB). Parabens can induce lethal and sublethal effects on aquatic organisms, such as oxidative stress, endocrine disruption, neurotoxicity, behavioral changes, reproductive impairment, and developmental abnormalities. The toxicity of parabens varied according to species, taxonomic group, developmental stage, exposure time, and concentrations tested. This study highlights the potential bioaccumulation and ecotoxicological impacts of parabens and their metabolites on aquatic invertebrates and vertebrates. Additionally, future research recommendations are provided to evaluate the environmental risks posed by paraben contamination more effectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. However, long-term disease-free survival is still a challenge to overcome. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimulatory CAR domains, as well as manufacturing conditions, cellular product type, doses, patient's age, and tumor types on the clinical outcomes of patients with B cell cancers treated with CD19 CAR T cells. The primary outcome was defined as the best complete response (BCR), and the secondary outcomes were the best objective response (BOR) and 12-month overall survival (OS). The covariates considered were the type of hinge, TM, and costimulatory domains in the CAR, CAR T cell manufacturing conditions, cell population transduced with the CAR, the number of CAR T cell infusions, amount of CAR T cells injected/Kg, CD19 CAR type (name), tumor type, and age. Fifty-six studies (3493 patients) were included in the systematic review and 46 (3421 patients) in the meta-analysis. The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS. The presence of CD28 in the CAR's hinge, TM, and costimulatory domains improved all outcomes evaluated. Doses from one to 4.9 million cells/kg resulted in better clinical outcomes. Our data also suggest that regardless of whether patients have had high objective responses, they might have survival benefits from CD19 CAR T therapy. This meta-analysis is a critical hypothesis-generating instrument, capturing effects in the CD19 CAR T cells literature lacking randomized clinical trials and large observational studies., (© 2024. The Author(s).)

Thimerosal, a preservative commonly used in the pharmaceutical and cosmetic industry, has raised concerns regarding its potentially toxic effects as an organic mercury compound. Within this context, using an NMR-based metabolomics profile and chemometric analysis, zebrafish embryos were used as an in vivo model to study the effects of thimerosal in metabolic profiles after exposure to sublethal concentrations of the mercury compound. The thimerosal concentrations of 40 and 80 nM were employed, corresponding to 40% and 80% of the LC 50 , respectively, for zebrafish embryos. The most significant alterations in the metabolic profile included changes in carbohydrates, amino acids, nucleotides, trimethylamine-N-oxide, ethanolamine, betaine, and ethanol. Furthermore, thimerosal exposure affects various metabolic pathways, impairing the nervous system, disrupting protein metabolism, and potentially causing oxidative damage. Therefore, adopting a metabolomics approach in this investigation provided insights into the potentially implicated metabolic pathways contributing to the deleterious effects of thimerosal in biological systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The present work identified and compared intracellular metabolites and metabolic networks in mycelial cultures of Lasiodiplodia theobromae grown under 12 natural light and 24 hours' dark using a 1  H NMR-based metabolomics approach., Materials and Methods: Fungal cultures were grown in potato dextrose media, and metabolites were extracted by sonication with sodium phosphate-buffered saline (pH = 6.0, 10% D 2 O, 0.1 mM TSP) from mycelium samples collected every week over four weeks., Results: Multivariate analyses revealed that the light exposure group showed a positive correlation within beta-hydroxybutyrate, acetoacetate, acetone, betaine, choline, glycerol, and phosphocholine. On the other hand, phenyl acetate, leucine, isoleucine, valine, and tyrosine were positively correlated with dark conditions. Light favored the oxidative degradation of valine, leucine, and isoleucine, leading to the accumulation of choline, phosphocholine, betaine, and ketone bodies (ketogenesis). Ketogenesis, gluconeogenesis, and the biosynthesis of choline, phosphocholine, and betaine, were considered discriminatory routes for light conditions. The light-sensing pathways were interlinked with fungal development, as verified by the increased production of mycelia biomass without fruiting bodies and stress signaling, as demonstrated by the increased production of pigments., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Morita-Baylis-Hillman adducts are polyfunctionalized compounds that result from a three-component reaction involving an electrophilic sp 2 carbon (aldehyde, ketone or imine) and the α-position of an activated alkene, catalyzed by a tertiary amine. These adducts exhibit a wide range of biological activities and act as valuable starting materials for developing drug candidates, pesticides, polymers, and other applications. In this regard, the present review aimed to explore the biological potential of Morita-Baylis-Hillman adducts and their derivatives as documented in patent literature. Additionally, the review delves into the synthetic methodologies employed in their preparation.

Metabolomics is an innovative approach used in the medical, toxicological, and biological sciences. As an interdisciplinary topic, metabolomics and its relation with the environment and toxicological research are extensive. The use of substances, such as drugs and pesticides, contributes to the continuous releasing of xenobiotics into the environment, harming organisms and their habitats. In this context, fish are important bioindicators of the environmental condition and have often been used as model species. Among them, zebrafish (Danio rerio) presents itself as a versatile and straightforward option due to its unique attributes for research. Zebrafish proves to be a valuable model for toxicity assays and also for metabolomics profiling by analytical tools. Thus, NMR-based metabolomics associated with statistical analysis can reasonably assist researchers in critical factors related to discovering and validating biomarkers through accurate diagnosis. Therefore, this review aimed to report the studies that applied zebrafish as a model for (eco)toxicological assays and essentially utilized NMR-based metabolomics analysis to assess the biochemical profile and thus suggest the potential biological marker., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The carbonic anhydrase isoform IX (CAIX) enzyme is constitutively overexpressed in the vast majority of clear cell renal cell carcinoma (ccRCC) and can also be induced in hypoxic microenvironments, a major hallmark of most solid tumors. CAIX expression is restricted to a few sites in healthy tissues, positioning this molecule as a strategic target for cancer immunotherapy. In this review, we summarized preclinical and clinical data of immunotherapeutic strategies based on monoclonal antibodies (mAbs), fusion proteins, chimeric antigen receptor (CAR) T, and NK cells targeting CAIX against different types of solid malignant tumors, alone or in combination with radionuclides, cytokines, cytotoxic agents, tyrosine kinase inhibitors, or immune checkpoint blockade. Most clinical studies targeting CAIX for immunotherapy were performed using G250 mAb-based antibodies or CAR T cells, developed primarily for bioimaging purposes, with a limited clinical response for ccRCC. Other anti-CAIX mAbs, CAR T, and NK cells developed with therapeutic intent presented herein offered outstanding preclinical results, justifying further exploration in the clinical setting.

Although the public's view of healthcare facilities is that they are inherently safe and secure, administrators and staff members in hospitals are very aware that they could be vulnerable to an episode of violence at any time, according to the author. Today, crimes, including homicide, are an ever-present reality in healthcare facilities, they report, citing recent studies which attempt to explain why this is so. The article is based on the introduction to the IAHSS and IHSS Foundation 2012 Crime and Security Trends Survey. The complete survey is accessible to members in the Reference Section of the IAHSS web page.

The 2011 Prisoner Escape Study, funded by the International Healthcare Security and Safety Foundation (IHSSF), investigates 99 reported forensic prisoner escapes from hospitals which took place from April, 2010 to April, 2011. A cross-sectional, exploratory study of prisoner escapes, the study follows up findings from the 2010 IHSSF Crime Study which indicated that members were concerned about the risks to hospital campuses and healthcare facilities that are en-gaged in the medical treatment of prisoner/forensics populations.

According to the findings of this 2010 survey, the overall number of crimes in hospitals reported in 2009 was significantly higher, in most instances, than the number of crimes reported the last time the survey was conducted in 2004. The new survey, funded by the IAHSS Foundation, also added new questions to establish baseline data on current and emerging trends in crime-related and other major security issues that challenge security professionals. For the first time, the IAHSS survey collected in formation about patient elopements and forensic and psychiatric patients. The 2010 IAHSS survey has now provided baseline data to compare the number of such patients treated in subsequent years to establish trends over time in this critical security area.