Real-time, specific, and label-free transistor-based sensing of organophosphates in liquid.

Organophosphates (OP), commonly used in agriculture and as chemical warfare agents, pose significant environmental risks, necessitating real-time, low-cost OP detection methods. In particular, liquid-phase OP sensing with minimal sample volumes is crucial. While several methods allow rapid detection of low concentrations of OP vapors, they are effective only in the short term, while vapors are still being produced. Many OP compounds are semi-volatile, leading to the contamination of water, soil, and surfaces, posing a risk of secondary, long-term exposure. Detecting this contamination requires methods that can be directly applied to droplets of the affected medium. Currently, no method provides the desired combination of ultra-sensitivity, quantitative detection, rapid response, and low-cost for detecting OPs in liquid samples. This study aims to demonstrate quantitative, low-cost, real-time, specific, and label-free OP sensing in ultra-small samples using a transistor-based approach. The current work employs the 2-(4-Aminophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (aminophenyl-HFIP) functionalized meta-nano-channel field-effect chemical sensor (MNChem sensor) to monitor the organophosphate, diethyl cyanophosphonate (DCNP), in liquid samples. The silicon component of the MNChem is fabricated using a complementary metal-oxide semiconductor (CMOS) process, and the amine-based chemical functionalization of the sensing area is performed post-fabrication. The MNChem sensor provides electrostatic control over the source-drain current (IDS), allowing an optimized channel configuration that efficiently transduces localized OP recognition events into significant IDS variations. Sensing is performed using 0.5 µL buffer solution to simulate a miniature field-deployable sensor for on-site liquid analysis. We report the sensing of DCNP with a limit-of-detection of 100 fg/mL, a dynamic range of 9 orders of magnitude, and excellent linearity (≥0.97) and sensitivity. Control measurements confirm the specificity and reliability of the sensor's response, validating its applicability. This study introduces a novel method for OP detection in contaminated droplets using a low-cost disposable transistor technology.

Assessment of the toxic influence of locally formulated pesticides on hepatic and renal biomarkers in male Wistar rats.

Background: There is growing concern of the potential damage to vital organs after long term exposure to locally formulated pesticides in rural area of Nigeria. This study was designed to assessed the effects of the individual chemical compound and their combination on the kidney and liver of rats' model. Methodology: Fifty-four rats divided into six groups and three sub-groups were exposed to 25, 50 and 75% dose of each of the pesticide's LD50 for 4 h at 3 days interval in an inhalation chamber for 28 days. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TOT_BIL), creatinine and urea assay showed significant increase at the aforementioned doses in comparison to the control group. The red blood cell counts, hematocrit and hemoglobin concentrations were significantly altered in the rats administered varying doses of the pesticides when compared with the control. Similar result was obtained for the differential white blood cell counts. Histopathological examinations of the liver tissue of rats showed infiltrated sinusoids, traces of karypyknosis, vacuolar degeneration and microvesicular steatosis while that of the renal tissue showed glomeruli atrophy leading to widened Bowman's spaces as well as few shrunken glomeruli and varied level of degenerative tubular changes to tubular necrosis. Conclusion: This study established that individual pesticides and their mixture is toxic to the liver and kidney, as evidenced by the elevated markers of renal and liver functions and distortion of the structure of both organs as revealed by their photomicrographs. Therefore, it is a matter of public health significance to regularly monitor pesticide residues in foods and humans in order to assess the food safety risk and population exposure to pesticides.

[Distribution of 21 organic ophospesters and their metabolites in drinking water in Dongcheng District of Beijing and their health hazard assessment in 2023].

OBJECTIVE: To investigate the pollution of organophosphate esters(OPEs) and their metabolites in drinking water in Dongcheng District of Beijing, and to assess the exposure risk of adults in drinking water. METHODS: The contents of 14 OPEs and 7 metabolites in drinking water were determined by automatic solid phase extraction, isotope dilution and liquid chromatography tandem mass spectrometry. The average daily potential dose(ADD) were calculated based on the recommended intake of drinking water. RESULTS: Seventeen pieces of tap water and 30 pieces of packaged drinking water collected by supermarket were measured. OPEs and di-OPEs were widely detected in drinking water(11 kinds of OPEs and 6 kinds of di-OPEs with the detection rate of more than 50%). The ΣOPEs range was 16.8 to 177ng/L, and the Σdi-OPEs range was 0.328 to 16.3 ng/L. The average daily dose of adult population was calculated: the ADD of 14 kinds of ΣOPEs in male and female were 3.15 and 3.10 ng/(kg·BW·d), and the P95 exposure was 6.95 and 7.00 ng/(kg·BW·d), respectively. The ADD of the seven Σdi-OPEs in male and female were 0.150 and 0.147 ng/(kg·BW·d), and the P95 exposure was 0.330 and 0.332 ng/(kg·BW·d), respectively. The hazard quotient(HQ) of exposure to OPEs through drinking water, calculated using the EPA's oral reference dose assessment, was much less than 1. CONCLUSION: The current exposure of OPEs via drinking water poses a low health risk to adult residents in Dongcheng District. However, due to the lack of Health-based guidance values for the metabolites of OPEs, the exposure risk may be underestimated.

Supercharged Phosphotriesterase for improved Paraoxon activity.

Phosphotriesterases (PTEs) represent a class of enzymes capable of efficient neutralization of organophosphates (OPs), a dangerous class of neurotoxic chemicals. PTEs suffer from low catalytic activity, particularly at higher temperatures, due to low thermostability and low solubility. Supercharging, a protein engineering approach via selective mutation of surface residues to charged residues, has been successfully employed to generate proteins with increased solubility and thermostability by promoting charge-charge repulsion between proteins. We set out to overcome the challenges in improving PTE activity against OPs by employing a computational protein supercharging algorithm in Rosetta. Here, we discover two supercharged PTE variants, one negatively supercharged (with -14 net charge) and one positively supercharged (with +12 net charge) and characterize them for their thermodynamic stability and catalytic activity. We find that positively supercharged PTE possesses slight but significant losses in thermostability, which correlates to losses in catalytic efficiency at all temperatures, whereas negatively supercharged PTE possesses increased catalytic activity across 25°C-55°C while offering similar thermostability characteristic to the parent PTE. The impact of supercharging on catalytic efficiency will inform the design of shelf-stable PTE and criteria for enzyme engineering.

Drosophila melanogaster as a model organism for screening acetylcholinesterase reactivators.

The widely used insecticide chlorpyrifos (CP) is known to inhibit acetylcholinesterase (AChE) activity attributed to result in various neurological disorders and acetylcholine-dependent organ functions including heart, skeletal muscle, lung, gastrointestinal tract, and central nervous systems. Enzyme reactivators, such as oximes, are known to restore AChE activity and mitigate adverse effects. The identification of compounds that reactivate AChE constitute agents with important therapeutic beneficial effects in cases of pesticide poisoning. However, the screening of novel drugs using traditional models may raise ethical concerns. This study aimed to investigate the potential of Drosophila melanogaster as a model organism for screening AChE reactivators, with a focus on organophosphate poisoning. The efficacy of several oximes, including pralidoxime, trimedoxime, obidoxime, methoxime, HI-6, K027, and K048, against CP-induced AChE activity inhibition in D. melanogaster was determined in silico, in vitro, and in vivo experiments. Molecular docking studies indicated a strong interaction between studied oximes and the active-site gorge of AChE. Data showed that selected oximes (100 µM) are effective in the reactivation of AChE inhibited by CP (10 µM) in vitro. Finally, in vivo investigations demonstrated that selected oximes, pralidoxime and K048 (1.5 ppm), reversed the locomotor deficits, inhibition of AChE activity as well as lowered the mortality rates induced by CP (0.75 ppm). Our findings contribute to utilization of D. melanogaster as a robust model for determination of actions of identified new AChE inhibitory agents with more effective therapeutic properties that those currently in use in the clinical practice in treatment of AChE associated disorders.

Relationship between organophosphate and pyrethroid pesticides and metabolic syndrome in Korean farmers.

BACKGROUND: The global use of pesticides steadily increased until the early 2010s. Pesticides play a significant role in agriculture in Korea. Metabolic syndrome is more prevalent in rural areas than in urban areas. This study explored the potential association between organophosphate and pyrethroid pesticide exposure and metabolic syndrome. METHODS: This study enrolled 1,317 individuals who participated in the Pesticide Exposure and Intoxication Study conducted by the Dankook University Hospital Center for Farmers' Safety and Health from 2014 to 2019. Urinary levels of dimethylphosphate, dimethylthiophosphat, diethylphosphate, and diethylthiophosphate were measured to assess organophosphate pesticide exposure and urinary levels cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, and 3-phenoxybenzoic acid were measured to assess pyrethroid pesticide exposure. RESULTS: The odds ratio for the 4th quartile group of organophosphate metabolites concentration was 1.48 (95% confidence interval: 1.06-2.09) compared to the 1st quartile group after adjustment for general factors. In addition, a positive trend was observed across the quartile groups of organophosphate metabolites concentration. A positive trend was noted across the quartile groups of organophosphate metabolites in males, while no significant association was observed in females. Furthermore, no significant associations were observed between metabolic syndrome and pyrethroid metabolites concentration. CONCLUSIONS: A positive correlation was observed between the prevalence of metabolic syndrome and the concentrations of urinary organophosphate metabolites, consistent with previous research finding. This association may be attributed to the action of organophosphates as acetylcholinesterase inhibitors, stimulating beta cells in the islets of Langerhans. This can lead to alterations in lipid metabolism and insulin resistance, ultimately leading to metabolic syndrome development. Metabolic syndrome is a major contributor to cardiovascular disease; therefore, it is necessary to identify the risk factors unique to rural areas, such as pesticide exposure.

Effective parallel evaluation of molecular design, expression and bioactivity of novel recombinant butyrylcholinesterase medical countermeasures.

Current medical countermeasures (MCMs) for nerve agent poisoning have limited efficacy, and can cause serious adverse effects, prompting the requirement for new broad-spectrum therapeutics. Human plasma-derived butyrylcholinseterase (huBChE) is a promising novel bioscavenger MCM which has shown potential in animal studies, however, is economically prohibitive to manufacture at scale. This study addresses current challenges for the economical production of a bioactive and long-acting recombinant huBChE (rBChE) in mammalian cells by being the first to directly compare novel rBChE design strategies. These include co-expression of a proline rich attachment domain (PRAD) and fusion of BChE with a protein partner. Additionally, a pre-purification screening method developed in this study enables parallel comparison of the expression efficiency, activity and broad-spectrum binding to nerve agents for ten novel rBChE molecular designs. All designed rBChE demonstrated functionality to act as broad-spectrum MCMs to G, V and A series nerve agents. Expression using the ExpiCHO™ Max protocol provided greatest expression levels and activity for all constructs, with most rBChE expressing poorly in Expi293™. Fc- or hSA-fused rBChE significantly outperformed constructs designed to mimic huBChE, including PRAD-BChE, and proved an effective strategy to significantly improve enzyme activity and expression. Choice of protein partner, directionality and the addition of a linker also impacted fusion rBChE activity and expression. Overall, hSA fused rBChE provided greatest expression yield and activity, with BChE-hSA the best performing construct. The purified and characterised BChE-hSA demonstrated similar functionality to huBChE to be inhibited by GD, VX and A-234, supporting the findings of the pre-screening study and validating its capacity to assess and streamline the selection process for rBChE constructs in a cost-effective manner. Collectively, these outcomes contribute to risk mitigation in early-stage development, providing a systematic method to compare rBChE designs and a focus for future development.

Study of the Clinical Profiling and Assessment of Poisoning Cases in a Tertiary Care Hospital.

Introduction Accidental and intentional poisoning is a major cause of morbidity and mortality. Pesticide poisoning is particularly common in India, where a large percentage of the population works in agriculture. This study aims to evaluate admission profiles, management trends, and outcome status among poisoning cases in a tertiary care hospital. Methodology A prospective observational study was carried out from May to July 2022 in the medicine ward of a tertiary care hospital, which is associated with a government medical college. Demographic characteristics, history of poisoning, clinical presentation at the time of admission, and intervention for treatment were recorded once the patient was diagnosed with poisoning or when there was a suspicion. Data regarding outcomes was also collected from this section. The appropriateness of the decontamination, support, and specific treatments was assessed. The collected data was subjected to descriptive statistical analysis. Results The most common agent was pesticides, involved in 44 (43.56%) cases out of a total of 101 poisoning cases, with the predominant subtype being organophosphate. Bites accounted for 18 (17.82%) cases, mainly snake bites. Household products were responsible for eight (7.92%) cases, and medicinal products for four (3.96%) cases. Decontamination, when indicated, was properly applied in 98 (97.02%) cases; supportive treatments were administered in 95 (94.05%) cases; and specific detoxifying measures were taken in 59 (58.41%) cases. A majority of the patients (60, or 59.41%) reached the hospital within three hours of poisoning, which dramatically reduced morbidity and mortality. Conclusion In summary, the study indicates that pesticide poisoning is prevalent in rural India, and, as such, there is an urgent need for appropriate regulation of agrochemicals and behavioural education to protect farmers. On average, the appropriateness of decontamination and supportive treatments was high (i.e., >85%), reflecting adequate initial responses. In contrast, the low level of appropriateness for specific treatments highlights gaps regarding institutional medical protocols and training. There is a need to educate the public about timely medical intervention, which can help in decreasing the mortality and morbidity associated with cases of poisoning.

Isolation of Monocrotophos degrading bacterial consortium from agricultural soil for in vivo analysis of pesticide degradation.

Extensive Monocrotophos (MCP) application in agricultural soils has led to its ubiquitous accumulation in the environment. Human health can be adversely affected by chronic exposure to produce and water from such areas, causing endocrine dysfunction, birth defects, blood and nervous disorders. This study investigated the possibility of detecting Monocrotophos-degrading bacteria in soil samples taken from a cotton cultivation field in a local area. We isolated a consortium that could tolerate and neutralize Monocrotophos upto a concentration of 2000 ppm. The consortium on 16 S rRNA sequencing were identified as Micrococcus luteus SBR2, Rhodococcus SBR5, Bacillus aryabhattai SBR8, Ochrobactrum intermedium SBK2. Significant tolerance of individual strains in the range of 500-5000 ppm was observed when incubating them in vitro with Monocrotophos in minimal salt medium. An analysis of the degrading genes opdA, mpd, and opd revealed plasmid borne opdA and mpd in the O.intermedium strain and B.aryabhattai strain. All the strains indicated genomic opdA and mpd whereas opd was not detected in plasmid or genomic DNA. The HPLC showed no peak at 2.5 min, when individual strains were incubated with Monocrotophos. The HPLC analysis of soil samples incubated with the consortium for two weeks showed complete degradation of Monocrotophos. GC-MS analysis confirmed that Monocrotophos and its solvent cyclohexamide were degraded into non-toxic compounds such as cyclotrisiloxane compounds, acetic acid, and others. This study indicates that the expression of organophosphate hydrolyzing enzymes in the consortium can greatly contribute to the neutralization of organophosphorus compounds and also serve as a bioremediation method for agricultural soils.

Concentration-dependent effects of the nerve agents cyclosarin and VX on cytochrome P450 in a HepaRG cell-based liver model.

The exposure to highly toxic organophosphorus (OP) compounds, including pesticides and nerve agents, is an ongoing medical challenge. OP can induce the uncontrolled overstimulation of the cholinergic system through inhibition of the enzyme acetylcholinesterase (AChE). The cytochrome P450 (CYP) enzymes in the liver play a predominant role in the metabolism of xenobiotics and are involved in the oxidative biotransformation of most clinical drugs. Previous research concerning the interactions between OP and CYP has usually focused on organothiophosphate pesticides that require CYP-mediated bioactivation to their active oxon metabolites to act as inhibitors of AChE. Since there has been little data available concerning the effect of nerve agents on CYP, we performed a study with cyclosarin (GF) and O-ethyl-S-[2-(diisopropylamino)-ethyl]-methylphosphonothioate (VX) by using a well-established, metabolically competent in vitro liver model (HepaRG cells). The inhibitory effect of the nerve agents GF and VX on the CYP3A4 enzyme was investigated showing a low CYP3A4 inhibitory potency. Changes on the transcription level of CYP and associated oxygenases were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using the two nerve agent concentrations 250 nM and 250 µM. In conclusion, the results demonstrated various effects on oxygenase-associated genes in dependence of the concentration and the structure of the nerve agent. Such information might be of relevance for potential interactions between nerve agents, antidotes or other clinically administered drugs, which are metabolized by the affected CYP, for example, for the therapy with benzodiazepines, that are used for the symptomatic treatment of OP poisoning and that require CYP-mediated biotransformation.

Combining QSAR and SSD to predict aquatic toxicity and species sensitivity of pyrethroid and organophosphate pesticides.

The widespread use of pyrethroid and organophosphate pesticides necessitates accurate toxicity predictions for regulatory compliance. In this study QSAR and SSD models for six pyrethroid and four organophosphate compounds using QSAR Toolbox and SSD Toolbox have been developed. The QSAR models, described by the formula 48 h-EC50 or 96 h-LC50 = x + y * log Kow, were validated for predicting 48 h-EC50 values for acute Daphnia toxicity and 96 h-LC50 values for acute fish toxicity, meeting criteria of n ≥10, r2 ≥0.7, and Q2 >0.5. Predicted 48 h-EC50 values for pyrethroids ranged from 3.95 × 10-5 mg/L (permethrin) to 8.21 × 10-3 mg/L (fenpropathrin), and 96 h-LC50 values from 3.89 × 10-5 mg/L (permethrin) to 1.68 × 10-2 mg/L (metofluthrin). For organophosphates, 48 h-EC50 values ranged from 2.00 × 10-5 mg/L (carbophenothion) to 3.76 × 10-2 mg/L (crufomate) and 96 h-LC50 values from 3.81 × 10-3 mg/L (carbophenothion) to 12.3 mg/L (crufomate). These values show a good agreement with experimental data, though some, like Carbophenothion, overestimated toxicity. HC05 values, indicating hazardous concentrations for 5% of species, range from 0.029 to 0.061 µg/L for pyrethroids and 0.030 to 0.072 µg/L for organophosphates. These values aid in establishing environmental quality standards (EQS). Compared to existing EQS, HC05 values for pyrethroids were less conservative, while those for organophosphates were comparable.

Safeguarding food safety: Nanomaterials-based fluorescent sensors for pesticide tracing.

Pesticide residue contamination has emerged as a critical concern due to its potential negative effects on both public health and the natural environment. Consequently, the detection of pesticide residue is of utmost importance. Nanomaterial-based fluorescence sensors, including metal nanoparticles (MNPs), metal nanoclusters (MNCs), carbon dots (CDs), and quantum dots (QDs), are particularly effective for detecting pesticide residues. Herein, we provide a comprehensive review of the recent advances (2018-2024) in fluorescence-based sensors utilizing MNPs, MNCs, CDs and QDs and their composites for the purpose of detecting various pesticides including organophosphates, carbamates, organochlorines, and pyrethroids in food. This review delves into the evolution of nanomaterials, their corresponding fluorescence-based sensing mechanisms, including Förster resonance energy transfer (FRET), photoinduced electron transfer (PET), inner filter effect (IFE), aggregation induced emission (AIE), and the detection principle, focusing on aspects of sensitivity and specificity. We also address the challenges and future perspectives of nanomaterials-based fluorescence sensors.

Acute toxicity of chlorpyrifos to some non-target freshwater organisms: which one is more toxic-technical grade or commercial formulation?

Chlorpyrifos is among the most widely sold organophosphates in the agriculture sector worldwide. Static bioassays were performed in the laboratory to compare the acute toxicity between the technical grade (94% a.i.) and commercial formulation (20% EC) of chlorpyrifos to four freshwater organisms: the crustacean zooplankton Cyclops viridis, the oligochaete worm Branchiura sowerbyi, the gastropod Pila globosa, and tadpole larvae of Duttaphrynus melanostictus. The recovery of actual chlorpyrifos concentrations in water after 2 h of exposure to the nominal concentrations ranged from 82.98% to 88.56%. The commercial formulation (F) of chlorpyrifos was found to be 1.94 to 2.76 times more toxic than the technical grade (T). Based on 96 h LC50 values of T and F chlorpyrifos, C. viridis was found to be most sensitive (0.56 and 0.25 µg/L) and P. globosa as most tolerant (1482 and 536 µg/L) to chlorpyrifos. Changes in LC50 values of both T and F chlorpyrifos were noted in respect of exposure hours for the three aquatic invertebrates and the tadpole larvae of the toad. In conclusion, the acute toxicity of chlorpyrifos to some non-target freshwater organisms differs between technical grade and commercial formulations.

A Scientific Review of Pesticides: Classification, Toxicity, Health Effects, Sustainability, and Environmental Impact.

Over the years, the use of pesticides has risen significantly, primarily to combat undesirable organisms that threaten crucial crops. A variety of pesticides are available, each designed to protect crops from specific threats like fungi, bacteria, and other pests. Other than crop protection, pesticides are also used in controlling insect vector-borne diseases like malaria and Lyme disease in humans. However, the application of these pesticides must be carefully measured and managed to prevent adverse effects on humans, non-target animals, and the environment. This review delves into the detailed classification of pesticides, exploring their mechanisms of action, applications, benefits, and potential side effects. Understanding the different categories of pesticides, such as herbicides, insecticides, fungicides, rodenticides, and biopesticides, helps us comprehend how each function to control pests. Additionally, we discuss the advantages of pesticide use, including increased crop yields and the prevention of crop diseases, which contribute to food security and agricultural productivity. This review also addresses the significant concerns related to pesticide usage, such as the development of pest resistance, health risks to humans through exposure and residues in food, as well as the impact on biodiversity and ecosystems. The review emphasizes the importance of using pesticides responsibly and implementing integrated pest management strategies to mitigate this risk of exposure. By providing a comprehensive overview of pesticide classification, mechanisms of action, and implications, this review aims to inform and guide us to the safe and effective use of pesticides for daily agricultural practices.

Burden of chemical poisoning and contributing factors in the case of the Amhara Region, Ethiopia.

BACKGROUND: This study aimed to evaluate the burden of chemical poisoning and its associated factors at the Chemical, Biological, Radiological, and Nuclear (CBRN) pilot surveillance sites in the Amhara region, Northwest Ethiopia. The analysis of burdens and contributing factors is intended to inform targeted interventions and enhance public health strategies. METHODS: A cross-sectional study was conducted at TibebeGhionComprehensive Specialized Hospital(TGCSH) and FelegeHiwot Comprehensive Specialized Hospital(FHCSH) in the Amhara region of Ethiopia from June to November 2021. Data were collected using structured tools and analyzed with SPSS version 26. Descriptive statistics assessed the burden of chemical poisoning, while Chi-square analysis identified significant factors associated with the burden of chemical poisoning. RESULTS: The study reported a total of 184 chemical poisoning cases at TGCSH and FHCSH in the Amhara region, with a case fatality rate of 17%. The most affected age group was 16 to 25 years, and females accounted for 60% of the cases. Geographic distribution showed that Bahir Dar had the highest incidence, contributing to 64.7% of the cases, while the South Gondar zone, particularly the Fogera district, accounted for 30.88%. Organophosphates emerged as the most prevalent toxic agents, responsible for 53% of the cases. Chi-square analysis highlighted several significant associations with a higher burden of chemical poisoning, including being female (X² = 4.463, p = 0.035), being 35 years or younger (X² = 4.629, p = 0.031), ingestion of rodent poison (X² = 4.154, p = 0.042), intentional poisoning (X² = 7.488, p = 0.006), and inhalation exposure (X² = 4.154, p = 0.042) and educational level (X² = 5.764, p = 0.016). CONCLUSIONS AND RECOMMENDATIONS: The study reveals a significant burden of chemical poisoning in the Amhara Region, Ethiopia, with a 17% fatality rate, predominantly impacting young adults and females, particularly in areas with high pesticide use, such as Bahir Dar and South Gondar. Key issues include cases with no antidotes, inhalation exposure, and intentional poisoning. RECOMMENDATIONS: Implement stricter chemical regulations, limit pesticide sales, enhance community education on safe handling, and improve mental health support for high-risk groups. Develop sustained CBRN surveillance systems and conduct further research on regional disparities and chemical agent assessments.

Endocrine Disruptors in Pregnancy: Effects on Mothers and Fetuses-A Review.

Background/Objectives: Endocrine disruptors are ubiquitous agents in the environment and are present in everyday consumer products. These agents can interfere with the endocrine system, and subsequently the reproductive system, especially in pregnancy. An increasing number of studies have been conducted to discover and describe the health effects of these agents on humans, including pregnant women, their fetuses, and the placenta. This review discusses prenatal exposure to various endocrine disruptors, focusing on bisphenols, phthalates, organophosphates, and perfluoroalkyl substances, and their effects on pregnancy and fetal development. Methods: We reviewed the literature via the PubMed and EBSCO databases and included the most relevant studies. Results: Our findings revealed that several negative health outcomes were linked to endocrine disruptors. However, despite the seriousness of this topic and the abundance of research on these agents, it remains challenging to draw strong conclusions about their effects from the available studies. This does not allow for strong, universal guidelines and might result in poor patient counseling and heterogeneous approaches to regulating endocrine disruptors. Conclusions: The seriousness of this matter calls for urgent efforts, and more studies are needed in this realm, to protect pregnant patients, and ultimately, in the long term, society.

Pesticide levels in shrimp on Mexican coasts.

The present review aimed to evaluate the current situation of pesticide residues detected in shrimp (commercial species) on the Mexican coasts. The organochlorine pesticides (OC), α-endosulfan (210.01 ng g-1), endosulfan sulfate (127.5 ng g-1), heptachlor (126.04 ng g-1 and γ-HCH (121.04 ng g-1) are identified as the most common pesticides in shrimp tissues, with the Northwest area reporting the highest concentrations of these OC. Given that there is an under-evaluation of pesticide residue levels, there was a greater contribution of studies directed at the Northwest of the country considering that there are states that are among the main shrimp-producing and consumers entities. The concentrations and types of pesticides banned nationally and globally, due to their toxic effects on the population, were reported. Therefore, since the most current information is 19 years out of date, it is necessary to perform recent evaluations with sensible and precise methods.

Dietary Exposure to Pesticide and Veterinary Drug Residues and Their Effects on Human Fertility and Embryo Development: A Global Overview.

Drug residues that contaminate food and water represent a serious concern for human health. The major concerns regard the possible irrational use of these contaminants, since this might increase the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact.

Real time monitoring of nerve agent mimics: Novel solid state emitter for enhanced precision and reliability.

Chemical nerve agents are hazardous compounds that terrorists can exploit to pose a significant threat to public safety and national security. The nucleophilic behaviour of these agents enables their interaction with acetyl cholinesterase in the body, leading to paralysis and potentially fatal consequences. Therefore, developing robust and efficient detection methods for these agents is crucial for preventing their misuse. In this manuscript, (E)-12-(1-hydrazineylideneethyl)benzo[f]pyrido[1,2-a]indole-6,11-dione (HBID) is developed as a novel colorimetric and fluorometric probe for the detection of specific chemical nerve agent simulants in both liquid and vapor phase. HBID reacts rapidly with diethyl chlorophosphate (DCP), a common nerve agent simulant, leading to a significant increase in the fluorescence intensity. Under optimized conditions, HBID exhibits high sensitivity, good recyclability, fast response and low limit of detection (0.092 µM). NMR and mass spectral studies suggest that the reaction involves the nucleophilic addition of HBID to DCP, forming a phosphate ester. Additionally, the developed sensor demonstrates viscosity-sensitive AIE phenomena thus greatly expanding its potential applications in biological systems. This sensitivity enables precise detection and visualization of viscosity changes within cellular environments, making the sensor an invaluable tool for studying complex biological processes. The developed probe also detects pH within biologically relevant range (4-6). In practical applications, the probe-treated strips efficiently detected DCP vapor in real time, showing a noticeable fluorescence response. Further, the probe has a strong potential to detect the presence of DCP in the soil samples.

Alterations in GABAA receptor-mediated inhibition triggered by status epilepticus and their role in epileptogenesis and increased anxiety.

The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic "bursts" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.