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Background: Cholinesterase is a classical nutritional and inflammatory marker. The aim of the present study was to evaluate the value of cholinesterase as a predictive marker for postoperative skeletal muscle loss after gastrectomy for gastric cancer., Methods: The study comprised 68 patients who had undergone gastrectomy for gastric cancer. Skeletal muscle mass was evaluated using skeletal mass index, and major skeletal muscle loss was defined as less than or equal to the median change rate (1-year postoperative/preoperative) of skeletal mass index in all patients. We explored the relationship between postoperative major skeletal muscle loss and disease-free survival and overall survival. Then we investigated the relationship between change rate of skeletal muscle index and serum cholinesterase levels after gastrectomy., Results: The median value of change rate of skeletal mass index was 0.93. Postoperative major skeletal muscle loss was significantly associated with disease-free survival after gastrectomy (P = 0.003). Although major skeletal muscle loss had worse overall survival, it was not significant (P = 0.058). The change rate of skeletal mass index and cholinesterase had a stronger positive correlation compared with other nutritional indices according to Spearman's rank correlation coefficient (r = 0.438, P ≤ 0.001)., Conclusion: Evaluation of serum cholinesterase levels may be valuable for predicting postoperative skeletal muscle loss after gastrectomy, suggesting the importance of cholinesterase in postoperative nutritional management of patients with gastric cancer., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adolescents living in agricultural communities may be at risk for the adverse effects of pesticide exposure because they are involved in agriculture either as a career or to support their families., Objective: The purpose of this study was to investigate the association of farm activities related to pesticide exposure on blood cholinesterase (ChE) levels among adolescents from farming families in the north of Thailand., Material and Methods: This cross-sectional study included 336 adolescents aged 12-19 years from farming families in Chiang Dao District, Chiang Mai Province. Data on pesticide exposure was collected using a questionnaire, and blood ChE activity was assessed using a ChE reactive paper test kit via fingerstick blood sampling., Results: Overall, 51.2% of participants had abnormal blood ChE levels. Univariable logistic regression analysis revealed that pesticide-related activities on farms associated with abnormal ChE levels were mixing/spraying (OR=10.54; 95%CI=4.63-23.99), assisting or working in areas with pesticide application (OR=5.54; 95%CI=3.45-8.89), and harvesting (OR=3.70; 95%CI=2.35-5.82). In a multivariable model (Nagelkerke R2=0.374), mixing/spraying (OR=4.90; 95%CI=2.03-11.83) and assisting or working in areas with pesticide application (OR=2.61; 95%CI=1.49-4.57) were significantly associated with abnormal ChE levels, but harvesting (OR=1.48; 95%CI=0.84-2.61) was not significant after adjusting for sex, age in years, and entering or walking through a farm., Conclusions: The findings indicated that Thai adolescents living in farming families are at risk of pesticide exposure, particularly those involved in agricultural activities such as pesticide applicators. An intervention and measure to raise awareness and reduce the risk of pesticide exposure in adolescents is required.

Chlorpyrifos is an organophosphate pesticide associated with numerous health effects including motor performance decrements. While many studies have focused on the health effects following acute chlorpyrifos poisonings, almost no studies have examined the effects on motoneurons following occupational-like exposures. The main objective of this study was to examine the broad effects of repeated occupational-like chlorpyrifos exposures on spinal motoneuron soma size relative to motor activity. To execute our objective, adult rats were exposed to chlorpyrifos via oral gavage once a day, five days a week for two weeks. Chlorpyrifos exposure effects were assessed either three days or two months following the last exposure. Three days following the last repeated chlorpyrifos exposure, there were transient effects in open-field motor activity and plasma cholinesterase activity levels. Two months following the chlorpyrifos exposures, there were delayed effects in sensorimotor gating, pro-inflammatory cytokines and spinal lumbar motoneuron soma morphology. Overall, these results offer support that subacute repeated occupational-like chlorpyrifos exposures have both short-term and longer-term effects in motor activity, inflammation, and central nervous system mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Enzymes play a pivotal role in regulating numerous bodily functions. Thus, there is a growing need for developing sensors enabling real-time monitoring of enzymatic activity and inhibition. The activity and inhibition of cholinesterase (CHE) enzymes in blood plasma are fluorometrically monitored using near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) as probes, strategically functionalized with myristoylcholine (MC)- the substrate of CHE. A significant decrease in the fluorescence intensity of MC-suspended SWCNTs upon interaction with CHE is observed, attributed to the hydrolysis of the MC corona phase of the SWCNTs by CHE. Complementary measurements for quantifying choline, the product of MC hydrolysis, reveal a correlation between the fluorescence intensity decrease and the amount of released choline, rendering the SWCNTs optical sensors with real-time feedback in the NIR biologically transparent spectral range. Moreover, when synthetic and naturally abundant inhibitors inhibit the CHE enzymes present in blood plasma, no significant modulations of the MC-SWCNT fluorescence are observed, allowing effective detection of CHE inhibition. The rationally designed SWCNT sensors platform for monitoring of enzymatic activity and inhibition in clinically relevant samples is envisioned to not only advance the field of clinical diagnostics but also deepen further understanding of enzyme-related processes in complex biological fluids., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Homocysteine (Hcy) is an independent cardiovascular disease (CVD) risk factor, whose mechanisms are poorly understood. We aimed to explore mild hyperhomocysteinemia (HHcy) effects on oxidative status, inflammatory, and cholinesterase parameters in aged male Wistar rats (365 days old). Rats received subcutaneous Hcy (0.03 μmol/g body weight) twice daily for 30 days, followed by euthanasia, blood collection and heart dissection 12 h after the last injection. Results revealed increased dichlorofluorescein (DCF) levels in the heart and serum, alongside decreased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase), reduced glutathione (GSH) content, and diminished acetylcholinesterase (AChE) activity in the heart. Serum butyrylcholinesterase (BuChE) levels also decreased. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) protein content decreased in both cytosolic and nuclear fractions, while cytosolic nuclear factor kappa B (NFκB) p65 increased in the heart. Additionally, interleukins IL-1β, IL-6 and IL-10 showed elevated expression levels in the heart. These findings could suggest a connection between aging and HHcy in CVD. Reduced Nrf2 protein content and impaired antioxidant defenses, combined with inflammatory factors and altered cholinesterases activity, may contribute to understanding the impact of Hcy on cardiovascular dynamics. This study sheds light on the complex interplay between HHcy, oxidative stress, inflammation, and cholinesterases in CVD, providing valuable insights for future research., 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. Published by Elsevier B.V.)

In this cross-sectional study, we determined the relative impact of long-term occupational exposure to pesticides on physical performance and perception of tiredness. Experimental data was collected in locus from agricultural communities and included surveys to assess the duration of exposure to pesticides, social status, habitual physical activity levels, presence of common mental disorders (CMD), and self-reported tiredness. Plasmatic cholinesterase (PChE), body composition and traditional functional performance tests (Handgrip strength-HGS; Time up and go-TUG; and Sit-to-stand-STS) were obtained. From the 127 individuals tested, cluster analysis yielded 80 individuals divided in Direct Exposed (n = 37) and Indirect Exposed (n = 43); Tired (n = 16), and Not Tired (n = 64). PChE values were within the reference values (5209.64-13943.53 U/L). Pesticide exposure had no influence on PChE levels, CMD or fatigue (p > 0.05), while Self-reported tiredness had (p < 0.05). Principal Component Analyses showed that HGS; STS and TUG (i.e., physical performance variables) are negatively influenced by two independent factors: pesticide exposure and self-reported tiredness. We conclude that chronic pesticide exposure and tiredness can negatively impact physical performance, independently, without clinically significant changes in PChE levels that is a biomarker used to track pesticide intoxication. Functional physical tests can be a useful tool to identify chronic pesticide exposure, and help with the limitations of commonly used parameters (i.e. PChE and CMD). Self-reported tiredness is a confounding variable., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (Copyright: © 2024 Coelho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Atrial fibrillation (AF) is a very common arrhythmia with significant incidence rate and mortality. Several studies have shown a notable correlation between non-alcoholic fatty liver disease (NAFLD) and AF. It has been observed that serum cholinesterase (SChE) levels are elevated in individuals with fatty liver. However, the relationship between the SChE index and AF is still unclear. Therefore, the purpose of this study is to explore the association between the SChE index and the prevalence of AF in patients with hypertension., Method: We collected cross-sectional data from January 2018 to April 2021 based on a retrospective study of cardiovascular disease. A total of 748 patients with hypertension were included, of whom 165 had AF. We used logistic regression models to test the relationship between SChE and the prevalence of AF in hypertensive patients., Result: In hypertensive patients, the SChE index was significantly associated with AF (OR = 0.723, P < 0.001). After adjusting for potential confounding factors, this correlation was still significant (OR = 0.778, P < 0.001). The stability of the model was verified by adjusting the variable type of SChE. The data were further stratified according to whether the patient had fatty liver. In the stratified data, the correlation between SChE and atrial fibrillation was still significant (P < 0.05)., Conclusion: Our study showed that SChE was significantly negatively correlated with the occurrence of AF in patients with hypertension. And this correlation was not affected by whether the patient had fatty liver., (© 2023. The Author(s).)

Purpose: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer., Methods: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications., Results: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (P interaction  = 0.006)., Conclusion: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Measurements of blood cholinesterase (ChE) activities, including those of erythrocytes (EChE), plasma or serum (PChE), and whole blood (WBChE), are used to assess exposure to ChE-inhibiting pesticides. The purpose of this review was to report normal reference ChE activities in the blood of healthy adult humans, as determined by a modified electrometric method. We performed a systematic review following PRISMA guidelines. Single-group meta-analysis of means of PChE, EChE, and WBChE activities of adult healthy subjects was conducted using the random effects model. The programs used were Open-Meta Analyst and Meta-Essentials Version 1.5. Studies selected for analysis comprised 21, 19, and 4 reports of normal reference/baseline PChE, EChE, and WBChE activities in 690, 635, and 121 healthy adult males and/or females, respectively. The meta-analysis showed normal reference values of the means (effect sizes) with 95% CI of PChE, EChE, and WBChE activities of healthy adult subjects, which were 1.078 (1.015, 1.142), 1.075 (1.024, 1.125) and 1.331 (1.226, 1.436), respectively. By the subgroup analysis, heterogeneity (I2>89%) was considerably reduced in females to 4.4% and 30.1% for PChE and EChE, respectively. Funnel plots indicated no publication bias. However, Egger's regression confirmed the symmetry of the data points for PChE and WBChE activities with a significant effect on EChE. This meta-analysis showed normal reference values of PChE, EChE, and WBChE activities, measured by a modified electrometric method, in healthy adult humans., Competing Interests: The authors declare no conflict of interest., (©2022 JOURNAL of MEDICINE and LIFE.)

Background: Serum cholinesterase (ChE) was found to be involved in cancer initiation and progression. However, the survival association between serum ChE and non-small cell lung cancer (NSCLC) has not been extensively discussed. In the present study, we aim to elevate the role of ChE in overall survival (OS) of NSCLC patients., Methods: A total of 961 histologically confirmed NSCLC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant information, such as histological type, clinical stage, chemotherapy, smoking status, body mass index (BMI), important serum indicators (albumin, neutrophil-to-lymphocyte ratio, ChE), date of death of the patients was extracted from the computerized hospital information system. Univariate and multivariate Cox proportional hazards models were used to determine the association between baseline serum ChE measured at the diagnosis and the OS of NSCLC patients., Results: The median of baseline ChE (7700 units/liter) was used as a cut-off to dichotomize NSCLC patients. After controlling for possible confounding factors, serum ChE at diagnosis was significantly associated with OS of NSCLC: patients with higher level of ChE were observed a better prognosis (hazard ratio, HR: 0.77, 95% CI: 0.67-0.93, p = 0.006). Subgroup analysis revealed significant ChE-OS association for NSCLC patients: with lower systemic inflammation level (baseline NLR < 2.95, HR: 0.71, 95% CI: 0.56-0.89, p = 0.003), of adenocarcinoma (HR: 0.66, 95% CI: 0.54-0.80, p < 0.001), in advanced stage (HR: 0.77, 95% CI: 0.66-0.92, p < 0.01), and received chemotherapy (HR: 0.75, 95% CI: 0.59-0.96, p < 0.02)., Conclusion: Baseline ChE may have independent prognostic value for NSCLC patients. Longitudinal studies should be performed to corroborate this finding., (© 2022. The Author(s).)

This quasiexperimental study was designed to determine the effectiveness of a participatory program on pesticide use behavior and blood cholinesterase levels. The participants were 18-60 years old, living in Thung Satok subdistrict, San Pa Tong District, Chiang Mai Province. Eighty subjects, including 32 farmers and 48 consumers, were recruited to participate in the study voluntarily by a purposive sampling technique. Data concerning each individual's behaviors were collected using questionnaires, and blood cholinesterase levels were obtained from whole blood finger, providing whole blood pre and postexperiment. The data were analyzed using Fishers' exact and paired t -tests, for the problem situations were independently analyzed. The results show that the participatory process made it possible to improve methods for the prevention of the unhealthy effects of pesticides. After participating in the activities, both groups showed significantly higher scores in before and after knowledge ( P < 0.05) and a decrease in pesticide contamination in their bodies as a result of the measurement of average cholinesterase which increased significantly ( P < 0.001). In conclusion, the participatory program was applied to solve health problems from chemical hazards. The program can raise awareness about chemical toxicity, leading to the modification of the related behavior toward chemicals and reduction of the contamination of chemicals in the body. Therefore, the adoption of participatory processes can effectively solve problems related to chemical hazards that affect health., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Nootchakarn Sawarng et al.)

Purposes: An accurate assessment of preoperative malnutrition in the elderly is critically important to predicting postoperative complications. The aim of this study is to evaluate the predictive value of the preoperative serum cholinesterase levels as a risk factor for postoperative complications in the elderly who have undergone emergency surgery., Methods: The study comprised 60 elderly patients who had undergone emergency major gastroenterological surgery. We retrospectively investigated the relationship between the preoperative serum cholinesterase levels and postoperative complications (Clavien-Dindo classification ≥ II). Univariate and multivariate analyses were performed to evaluate the risk factors for postoperative complications., Results: Thirty-three patients (55%) developed postoperative complications. According to the univariate analysis, hemoglobin (P = 0.018), albumin (P = 0.0036), cholinesterase (P < 0.001), C-reactive protein (P = 0.043), prognostic nutritional index (P = 0.0050), the Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity (P < 0.001) and operation time (P = 0.042) were identified to be risk factors for postoperative complications. According to the multivariate analysis, low preoperative serum cholinesterase levels were found to be an independent risk factor for postoperative complications (P = 0.029). In the extremely elderly (80-95 years), the cholinesterase-low group had a higher complication rate compared to the cholinesterase-high group (77.8 vs 43.8%, P = 0.028)., Conclusion: The preoperative serum cholinesterase levels may be a risk factor for postoperative complications in elderly patients after emergency surgery, thus suggesting the significance of cholinesterase in evaluating the nutritional status., (© 2021. Springer Nature Singapore Pte Ltd.)

Risk stratification is of utmost importance in burn therapy. However, suitable bedside biomarkers to evaluate the emerging inflammatory response following burn injuries are missing. Serum cholinesterase (butyrylcholinesterase, BChE) has been shown to be a clinically relevant biomarker in acute inflammatory diseases including burns. In this observational cohort study BChE activity was measured by using point-of-care testing (POCT), a novel method in acute burn care. POCT measurements were performed at emergency room admission (ERA) of 35 patients and repeated 12, 24 and 48 h later. All patients or their legal designees gave informed consent. Patients with burn injuries showed sustained BChE activity reduction following hospital admission. BChE activity correlated negatively with burn injury severity, organ failure severity and intensive care unit resource requirements. BChE activity measured at ERA and 12 h later identified survivors and predicted 28-day patient outcome with noninferior efficacy compared to the abbreviated burn severity index (ABSI) scoring. Finally, POCT-measured BChE activity might complement ABSI scoring and possibly improve early risk stratification in acute burn care therapy., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

COVID-19 patients typically present with lower airway disease, although involvement of other organ systems is usually the rule. Hematological manifestations such as thrombocytopenia and reduced lymphocyte and eosinophil numbers are highly prevalent in COVID-19 and have prognostic significance. Few data, however, are available about the prevalence and significance of anemia in COVID-19. In an observational study, we investigated the prevalence, pathogenesis and clinical significance of anemia among 206 patients with COVID-19 at the time of their hospitalization in an Internal Medicine unit. The prevalence of anemia was 61% in COVID-19, compared with 45% in a control group of 71 patients with clinical and laboratory findings suggestive of COVID-19, but nasopharyngeal swab tests negative for SARS-CoV-2 RNA (p = 0.022). Mortality was higher in SARS-CoV-2 positive patients. In COVID-19, females had lower hemoglobin concentration than males and a higher prevalence of moderate/severe anemia (25% versus 13%, p = 0.032). In most cases, anemia was mild and due to inflammation, sometimes associated with iron and/or vitamin deficiencies. Determinants of hemoglobin concentration included: erythrocyte sedimentation rate, serum cholinesterase, ferritin and protein concentrations and number of chronic diseases affecting each patient. Hemoglobin concentration was not related to overall survival that was, on the contrary, influenced by red blood cell distribution width, age, lactate dehydrogenase and the ratio of arterial partial oxygen pressure to inspired oxygen fraction. In conclusion, our results highlight anemia as a common manifestation in COVID-19. Although anemia does not directly influence mortality, it usually affects elderly, frail patients and can negatively influence their quality of life.

Background: Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Methods: Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). Results: A total of 150 advanced GC patients were included and divided into serum level ≥5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141-2.243; p = 0.006), poorer OS (HR, 1.76; 95% CI, 1.228-2.515; p = 0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272-1.129; p = 0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response ( p < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28-2.57; p = 0.0002). The medium OS was 13.1 months in patients with increased post-treatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29-2.71; p = 0.0002). Conclusion: Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC., Competing Interests: JZ is employees of Shanghai 3D Medicines Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bi, Zhang, Zeng, Chen, Ye, Yang and Ling.)

The aim of this study was to explore the association between metabolizing enzyme gene polymorphisms and the decrease in cholinesterase activity induced by omethoate exposure. A total of 180 workers exposed to omethoate over an extended period were recruited along with 115 healthy controls. Cholinesterase activity in whole blood, erythrocyte, and plasma was detected using acetylthiocholine and the dithio-bis-(nitrobenzoic acid) method. Six polymorphic loci of GSTT1 (+/-), GSTM1 (+/-), GSTP1 rs1695, CYP2E1 rs6413432, CYP2E1 rs3813867, and PON2 rs12026 were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The gene-environment interactions were analyzed using the generalized linear model method. The cholinesterase activity of erythrocyte and plasma in the exposure group was significantly lower than that in the control group ( P  < 0.001) in general. The plasma cholinesterase activity in the TT + AT genotype in CYP2E1 rs6413432 was lower than that in the AA genotype in the exposure group ( P  = 0.016). Interaction between the AA genotype in CYP2E1 rs6413432 and omethoate exposure had a significant effect on plasma cholinesterase activity ( P  = 0.079). The decrease in plasma cholinesterase activity was associated with interaction between the AA genotypes in rs6413432 and omethoate exposure.

The evaluation of laboratory blood analytes is an important tool for health assessment in avian medicine. Unfortunately, there is a lack of suitable reference values for many zoo bird species. The goal of the present study was to establish reference intervals for a wide range of blood analytes in healthy black-headed ibis ( Threskiornis melanocephalus ) kept in a zoologic garden. Lithium heparinized blood samples from 15 individuals were collected, and 18 different clinical chemistry analytes were measured. New are especially the minimum and maximum values for bile acid (2.38-49.4 µmol/L), cholinesterase (439-1260 U/L), vitamin A (0.65-1.70 mg/L), vitamin E (26.3-52.5 mg/L), and capillary zone electrophoresis (prealbumin, 10.2-23.4%; albumin, 35.9-44.1%; A/G ratio, 1.07-1.69; α-, 15.7-20.0%; β-, 13.5-19.1%; γ-globulin, 6.08-11.3%). The measured values for clinical chemistry, vitamin, electrophoresis, and hematologic analytes are a basis for further studies and for diagnostics and clinical treatment in this ibis species.

Objectives: To assess pesticide exposure and understand the resultant health effects of agricultural workers in Northern Thailand., Methods: This was a cross-sectional study. We quantified exposure to pesticides, including chlorpyrifos, methomyl, and metalaxyl, by air sampling and liquid chromatography/mass spectrometry. We estimated differences in self-reported health outcomes, complete blood counts, cholinesterase activity, and serum/urine calcium and creatinine concentrations at baseline between farmworkers and comparison workers, and after pesticide spraying in farmworkers only., Results: This study included 97 men between the ages of 22 and 76 years; 70 were conventional farmworkers; and 27 did not report any prior farmwork or pesticide spraying. None of the farmworkers wore standardized personal protective equipment (PPE) for the concentrated chemicals they were working with. Methomyl (8.4-13 481.9 ng/m 3 ), ethyl chlorpyrifos (11.6-67 759 ng/m 3 ), and metalaxyl (13.9-41 191.3 ng/m 3 ) were detected via personal air sampling. When it came to reporting confidence in the ability to handle personal problems, only 43% of farmworkers reported feeling confident, which reflects higher stress levels in comparison to 78% of comparison workers (P = .028). Farmworkers also had significantly lower monocyte counts (P = .01), serum calcium (P = .01), red blood count (P = .01), white blood cell count (P = .04), and butyrylcholinesterase activity (P < .0001), relative to comparison workers. After adjusting for body mass index (BMI), age, and smoking, methomyl air concentrations were associated with a decrease in farmworker acetylcholinesterase activity (beta = -0.327, P = .016)., Conclusions: This population of farmworkers had significant alterations in stress measures and clinical biomarkers, including decreased blood cell counts and cholinesterase activity, relative to matched controls. These changes are potentially linked to occupational pesticide exposures. Improving PPE use presents a likely route for preventive intervention in this population., (© 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-κB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-κB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The aim of our study was to investigate whether serum cholinesterase (ChE) levels were associated with inflammatory bowel disease (IBD)., Materials and Methods: We conducted a retrospective case-control study to clarify the relationship between serum ChE levels and IBD that included 142 patients with ulcerative colitis (UC), 60 patients with Crohn's disease (CD), and 264 healthy controls (HCs). We used ROC curves to evaluate the diagnostic value of serum ChE levels for IBD., Results: Substantially lower serum ChE levels were detected in patients with UC than in HCs (6376 U/L versus 8418 U/L, P < 0.001) and in patients with CD than in HCs (5181 U/L versus 8418 U/L, P < 0.001). Additionally, patients with CD displayed significantly lower serum ChE levels than patients with UC (5181 U/L versus 6376 U/L, P < 0.01). We also found that there was a negative association between serum ChE levels and the Crohn's Disease Activity Index (CDAI) score of patients with CD ( P = 0.011) and the Simple Clinical Colitis Activity Index (SCCAI) score of patients with UC ( P = 0.018). The area under the curve (AUC) for serum ChE for the diagnosis of IBD was 0.826, and the AUCs of serum ChE for the diagnosis of CD and UC were 0.890 and 0.800, respectively., Conclusions: Serum ChE levels have important clinical significance in the diagnosis and assessment of clinical activity in patients with IBD, and the cholinergic anti-inflammatory pathway may provide new ideas for targeted treatment of IBD., Competing Interests: The authors declared no conflict of interest., (Copyright © 2020 Xiaona Shao et al.)

Acute organophosphorus poisoning (AOPP) is a serious public health issue, especially in the rural areas. This study was designed to establish a scoring system to assess the risk of cases with severe AOPP. A retrospective cohort study was conducted at two independent hospitals. The derivation cohort included 444 patients with AOPP and the validation cohort included 274 patients. A risk score for patients with severe AOPP was developed. The rates of severe AOPP cases were 20.7% and 20.1% in the derivation and validation cohorts, respectively. A scoring system for severe AOPP risk was developed that included: (1) age >50 years, (2) white blood cell count of >15 × 10 9 /L, (3) plasma cholinesterase of <360 U/L, (4) plasma albumin of <35 g/L, (5) blood pH <7.3, and (6) lactic acid >3.0 mmol/L. The predicted score in severe cases of AOPP had good accuracy in both the derivation (area under the receiver operating characteristic curve [AUC] 0.88, 95% confidence interval [CI], 0.85-0.92) and validation cohorts (AUC 0.83, 95% CI, 0.77-0.90). A practical bedside prediction scoring system was developed for patients with severe AOPP. The routine use of this scoring system could rapidly assist in identifying patients at higher risk who require more intensive care or transfer to a larger better-equipped hospital., (© 2020 John Wiley & Sons, Ltd.)

Kinetic and validation of the enzymatic method for the determination of fenitrothion organophosphorus based on cholinesterase inhibition were studied. A Linear relationship was obtained with a determination coefficient R 2 of 0.9989 suggesting that the noncompetitive inhibition kinetic equation is suitable to represent the enzymatic assay of fenitrothion. The value of the inhibition constant K I was 0.374 μg/ml/min. The analytical logarithmic curve for the determination of fenitrothion concentration using the percentage of cholinesterase inhibition presented good linear relations at concentrations of 0.05-2 μg/ml ( R 2 = 0.9889). The maximum inhibition 83% was observed at 2.0 μg/ml final assay concentration. The lower inhibition 3.3% was observed at 0.05 μg/ml detection limit. The experimental measurement condition was optimized. The enzymatic method exhibited detection limits (LOD) in the range of 0.05-2.0 μg/ml. The limit of quantification (LOQ) was 0.06 μg/ml with inhibition 13%. The concentration of fenitrothion that inhibited the hydrolysis of substrate by 50% (IC50 value) was 0.4 μg/ml. Standard deviations and coefficients of variation indicate a good precision of the enzymatic method for the detection of organophosphate insecticides at an incubation time of 20 min.

Background Malnutrition is one of the most important comorbidities in patients with heart failure with preserved ejection fraction. We recently reported the prognostic significance of serum cholinesterase level and superior predictive power of cholinesterase level to other objective nutritional indices such as the controlling nutritional status score, prognostic nutritional index, and geriatric nutritional risk index in patients with acute decompensated heart failure. The aim of this study was to clarify the prognostic role of cholinesterase in patients with heart failure with preserved ejection fraction/acute decompensated heart failure and investigate incremental cholinesterase value. Methods and Results We prospectively studied 274 consecutive patients from the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure With Preserved Ejection Fraction) study. During a follow-up period of 1.2±0.6 years, 56 patients reached the composite end points (cardiovascular death and readmission for worsening heart failure). In the multivariable Cox analysis, cholinesterase level was significantly associated with the composite end points after adjustment for major confounders. A Kaplan-Meier analysis revealed that patients with low cholinesterase levels (stratified by tertile) had significantly greater risk of reaching the composite end points than those with middle or high cholinesterase levels ( P =0.0025). Cholinesterase level showed the best C-statistics (0.703) for prediction of the composite end points among the objective nutritional indices. C-statistics of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score for prediction of the composite end points were improved when cholinesterase level was added (C-statistics, from 0.601 to 0.705; P =0.0408). Conclusions Cholinesterase was a useful prognostic marker for prediction of adverse outcome in patients with heart failure with preserved ejection fraction/acute decompensated heart failure.

Blood components are considered to reflect nutrient metabolism and immune activity in both humans and animals. In this study, we measured 12 blood components in Pekin ducks and performed genome-wide association analysis to identify the QTLs (quantitative trait locus) using a genotyping-by-sequencing strategy. A total of 54 QTLs were identified for blood components. One genome-wide significant QTL for alkaline phosphatase was identified within the intron-region of the OTOG gene (P = 1.31E-07). Moreover, 21 genome-wide significant SNPs for the level of serum cholinesterase were identified on six different scaffolds. In addition, for serum calcium, one genome-wide significant QTL was identified in the upstream region of gene RAB11B. These results provide new markers for functional studies in Pekin ducks, and several candidate genes were identified, which may provide additional insights into specific mechanisms for blood metabolism in ducks and their potential application for duck breeding programs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Although distigmine is known to sometimes cause severe adverse drug reactions (ADRs), such as cholinergic crisis, there are limited data on the risk factors for these ADRs. In this study, we defined a serum cholinesterase (sChE) cutoff level for early detection of ADRs to distigmine and sought to identify risk factors for these ADRs based on this value. This retrospective cohort study included all patients who were prescribed distigmine and underwent measurement of sChE over a period of 8 years at Kaetsu Hospital. Ninety-three patients were included. The sChE cutoff level below which there was an increase in risk of ADRs was defined as 129 U/L based on the levels in patients who had ADRs by receiver operating characteristic analysis. The percentage of ADRs tended to increase with advancing chronic kidney disease (CKD) stage. Multivariate logistic regression analyses showed that a distigmine dose >0.1 mg/kg/d (odds ratio 3.19, 95% confidence interval 1.24-8.19) and age >85 years (odds ratio 3.04, 95% confidence interval 1.18-7.82) were positively associated with an sChE level ≤129 U/L. An sChE cutoff level of 129 U/L is a useful predictor of the risk of an ADR to distigmine, and dose per body weight, age, and CKD progression may pose potential risk of an ADR to distigmine. Therefore, for patients taking distigmine who have these risk factors, the risk of a severe ADR to distigmine can be reduced by decreasing the dose of distigmine and close monitoring of the sChE level.

Objective: To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS)., Methods: A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation II (APACHE II) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE ≤ 4 000 U/L) and the normal SChE group (SChE > 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels., Results: A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHE II score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk (RR) = 1.444, 95% confidence interval (95%CI) was 1.090-1.914, P = 0.010], APACHE II score (RR = 2.249, 95%CI was 1.688-2.997, P = 0.000), SChE (RR = 1.469, 95%CI was 1.057-2.043, P = 0.022), and Lac (RR = 2.190, 95%CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHE II score and Lac was greater than APACHE II score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group (n = 88), the 28-day mortality of patients in the low SChE group (n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: χ 2 = 5.852, P = 0.016)., Conclusions: Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.

Bilateral symmetrical weakness of acute onset is not very uncommon and the differential varies widely from life-threatening neurological illnesses to metabolic and electrolyte derangements. We report the case of a young female with severe muscle weakness, respiratory distress and hypokalemia who required immediate intubation on arrival to emergency department. During hospital course, even after normalisation of serum potassium and some improvement in limb weakness, patient failed multiple attempts of extubation because of type II respiratory failure. Subsequently, acetyl cholinesterase antibodies were checked which came out positive, and diagnosis of myasthenia gravis and hypokalemic periodic paralysis was made. She was successfully extubated after intravenous pulse steroids, pyridostigmine and plasmapheresis. Patient was finally discharged home on oral steroids, pyridostigmine and azathioprine. In a patient presenting with hypokalemic weakness, the suspicion of a second disorder should be very high if weakness fails to resolve following correction of hypokalemia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to evaluate the seroprevalence of Neospora caninum in dairy cows, as well as to verify the risk factors for N. caninum infection and inflammatory response in dairy cows. Using the indirect immunofluorescence reaction, the seroprevalence of neosporosis was determined to be 32.82%. Based on regression analysis, the presence of dogs at a farm increased the probability of a cow testing positive for N. caninum (OR = 20.01 [5.21-123.12]). These data suggest that N. caninum has a relevant prevalence in dairy cows of the Microregion of Rio do Sul (Brazil), with elevated frequencies of anti-N. caninum IgG. The data also suggest that the parasite is widely distributed in dairy herds of the micro-region, because 94.4% of properties screened had at least one seropositive animal. The principal risk factors for disease maintenance in herds may be considered the presence of dogs and absence of a diagnostic test when introducing new animals. Blood from these cows was used to measure variables related to the inflammatory response. Serum cholinesterase activity, as well as serum levels of globulins and C-reactive protein were higher in seropositive to N. caninum than in seronegative cows. Furthermore, the infection by parasite causes an intense inflammatory process, contributing to disease pathophysiology., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Esophagectomy is a highly invasive procedure for patients aged > 70 years. Here, we compared the actual nutritional status of older and younger patients who underwent esophagectomy., Methods: A total of 118 patients who underwent radical esophagectomy between April 2013 and December 2016 were enrolled and divided into two groups based on age: group A (n = 41; ≥ 70 years) and group B (n = 77; < 70 years). Data pertaining to body mass index and nutritional variables (albumin; total cholesterol; cholinesterase; and prealbumin) were retrospectively analyzed preoperatively and at 3, 6, and 12 months postoperatively., Results: Significant preoperative between-group differences were found in the cholinesterase, albumin, and prealbumin levels. The body mass index gradually decreased over the first 12 months after surgery in both groups, without significant between-group differences. Significant differences were observed in prealbumin and cholinesterase levels at 3 months postoperatively. 1 year postoperatively, both groups showed slight improvements; however, the between-group differences were not statistically significant. Group A had a significantly lower amount of the degree of decrement of BMI and chE than group B., Conclusion: Thus, patients aged > 70 years can recover within 12 months of esophagectomy.

Background: Patients undergoing subtotal esophagectomy for esophageal cancer frequently experience postoperative pneumonia. Development of preoperatively determined predictors for postoperative pneumonia will facilitate identifying high-risk patients and will assist with informing patients about their risk of postoperative pneumonia, enabling physicians to estimate with greater accuracy, will result in tailoring perioperative management., Methods: Postoperative pneumonia was defined according to the revised Uniform Pneumonia Score. We analyzed the data for 355 patients to compare 32 potential predictive variables associated with postoperative pneumonia after subtotal esophagectomy., Results: Forty-one patients (11.5%) had postoperative pneumonia. Preoperative cholinesterase (ChE) concentrations demonstrated the greatest area under the curve value (0.662) to predict postoperative pneumonia (optimal cutoff value = 217 IU/l). Univariate analysis identified a continuous value of preoperative ChE concentration as a significant risk factor for postoperative pneumonia (P = 0.0014). Multivariable analysis using factors potentially relevant to pneumonia revealed that preoperative ChE concentration was one of independent risk factors for pneumonia after esophagectomy (P = 0.008). Patients with low ChE concentrations were at increased risk of postoperative pneumonia in most patient subgroups. Moreover, the odds ratios of low ChE concentrations were highest in patients undergoing neoadjuvant treatment. A combination of preoperative serum ChE concentrations and Brinkman index stratified patients into low, intermediate, and high risk of postoperative pneumonia., Conclusions: Our findings indicate that preoperative ChE concentrations, particularly in combination with Brinkman index, may serve simply as a determined predictor of pneumonia after subtotal esophagectomy and may facilitate physicians' efforts to reduce the incidence of postoperative pneumonia.

Background & Objectives: Chronic exposure to pesticides can damage DNA and lead to cancer, diabetes, respiratory diseases and neurodegenerative and neurodevelopment disorders. The objective of this study was to determine the frequency of DNA damage through the comet assay and micronucleus (MN) test in two groups of children, under 10 yr of age living in rural Paraguay and in relation to pesticide exposure., Methods: Two groups of 5 to 10 yr old children were formed; the exposed group (group A, n=43), born and currently living in a community dedicated to family agriculture and surrounded by transgenic soybean crops, and the control group (group B, n=41), born and living in a community dedicated to family agriculture with biological control of pests. For each child, 2000 cells were studied for the MN test and 200 cells for the comet assay., Results: The comparison between exposed and control children revealed significant differences in biomarkers studied for the measurement of genetic damage (cell death and DNA damage). The median of MN was higher in the exposed group (6 vs. 1) (P <0.001). Binucleated cells (2.9 vs. 0.5, P <0.001); broken eggs (5.5 vs. 1.0, P <0.001); karyorrhexis (6.7 vs. 0.5, P <0.001); kariolysis (14.0 vs. 1.0, P <0.001); pyknosis (7.4 vs. 1.2, P <0.001) and condensed chromatin (25.5 vs. 7.0, P <0.001) were significantly higher in the exposed group. The values of tail length (59.1 vs 37.2 μm); tail moment (TM) (32.8 vs. 14.4 μm); TM olive (15.5 vs. 6); % DNA tail (45.2 vs. 27.6) and % DNA head (54.8 vs. 72.4), were significantly different between the two groups., Interpretations & Conclusions: In children exposed to pesticides, a greater genotoxic and cytotoxic effect was observed compared to non-exposed children. Our findings suggest that monitoring of genetic toxicity in population exposed to pesticides and agrochemicals should be done., Competing Interests: None

Alzheimer's disease (AD) is a chronic neurodegenerative disease. G protein coupled receptor 50 (GPR50) is a candidate gene for AD. The present study was designed to determine the association between GPR50 methylation and AD. The methylation levels of the GPR50 promoter in 51 patients with AD and 61 healthy controls were determined by bisulfite pyrophosphate sequencing. All participants were Han Chinese, living in Ningbo. It was identified that the GPR50 promoter methylation level was significantly decreased in the male AD group compared with the male control group (9.15 vs. 16.67%, P=0.002). In addition, it was observed that the GPR50 methylation levels of the females was significantly increased compared with that of males in both the patients with AD and the healthy control group (AD patient group: 33.00 vs. 9.15%, P<0.0001; healthy control group: 29.41 vs. 16.67%, P<0.0001). This may be explained by the fact that GPR50 is located on the X chromosome. In addition, GPR50 methylation was positively correlated with plasma cholinesterase levels in female patients with AD (r=0.489, P=0.039). The present study demonstrated that hypomethylation of the GPR50 promoter in peripheral blood may be a potential biomarker for the diagnosis of AD in Chinese Han males.

Background: Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices., Objective: The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF)., Methods: We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality., Results: During a mean ± SD follow-up period of 2.5 ± 1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, β-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P < 0.0001]. CHE showed the best area under the curve value (0.745) for the prediction of all-cause mortality compared with the other objective nutritional indices. Net reclassification improvement afforded by adding CHE to the fully adjusted multivariable model was statistically significant for all-cause mortality (0.330; 95% CI: 0.112, 0.549, P = 0.0030)., Conclusion: CHE is a simple, strong prognostic marker for the prediction of all-cause mortality in patients with ADHF., (© American Society for Nutrition 2019.)

The detrimental effects of organophosphate (OP) nerve agents have been reported but the mechanisms mediating these multiple effects are not well understood. Recent use of nerve agents in Syria and the UK illustrate their continuous threat to the modern world. Epigenetic and autophagy studies are useful to address the issues related to regulation of gene and protein expression by which nerve agents could impact on human health. These studies help to understand molecular mechanisms underlying the multiple neurotoxic effects of nerve agents. In the present study, changes in epigenetic (global DNA methylation and histone acetylation) and autophagic marker proteins were studied in the nerve agent sensitive rat brain areas (piriform cortex and hippocampus) after soman (1xLD 50 ) exposure. Global DNA methylation analysis revealed that nerve agent induced hypomethylation in the brain regions at 1 and 7 days post exposure. In contrast, DNA hypermethylation was observed at 30 days post soman exposure, demonstrating a possible compensatory mechanism. Western blot analysis showed significant increase in the histone acetylation levels after soman exposure in the piriform cortex and hippocampus. The present study observed the changes in autophagic proteins of nerve agent poisoning for the first time to the best of our knowledge. Immunoreactivity levels of autophagic proteins (LC3-II, ATG-5 and p62) were transiently increased in the rat piriform cortex and hippocampus after soman exposure. In conclusion, this study provides insight into the epigenetic and autophagic changes in the brain following soman exposure and their possible role in the neuronal damage and development of multiple neurological effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The impact evaluation of pesticide exposure is conducted using combined data from biomonitoring and environmental monitoring. Damage to the human genome is, probably, the leading cause of chronic-degenerative disorders, reproductive toxicology, and developmental problems. Although the general population is exposed to pesticides, workers in the agrochemical industry and farmers represent a high-risk group due to the occupational and environmental exposure. The aim of this study is to determine whether occupational exposure to agrochemicals in Córdoba (Argentina) constitute a factor of genotoxic damage. The study was conducted in 30 pesticide applicators from the province of Córdoba. Chromosomal aberrations (CAs), micronuclei (MN), and comet assays (CO) were performed. The current study shows that occupational exposure to pesticides increases values of CAs, MN, and DNA fragmentation biomarkers, all indicators of damage to the genetic material. Evidence suggests that chronic exposure to pesticides is a potential risk to workers health.

The role of cholinesterase in inflammatory reactions has been described in several infectious diseases. However, in Brucella spp. this has not yet been studied. Therefore, the objective of this study was to evaluate whether experimental infection by Brucella ovis alters the cholinergic activity in pro- or anti-inflammatory responses to the disease. For the study 48 mice were used, 24 infected by B. ovis and 24 non-infected. We collected samples of whole blood on days 7, 15, 30 and 60 post-infection (PI) by B. ovis. Acetylcholinesterase (AChE) activity in the blood increased on days 15 and 60 PI (P < 0.05). Butyrylcholinesterase (BChE) activity in serum increased on days 7 and 60 PI (P < 0.05). An increase in serum free radical levels occurred on days 7, 15 and 60 PI (P < 0.05), and consequently superoxide dismutase activity increased on day 15 PI (P < 0.05). A reduction in catalase activity occurred when the infection became chronic (60 PI). The increase in AChE and BChE characterized a pro-inflammatory response, since these enzymes regulate levels of acetylcholine (ACh) and butyrylcholine (BuSCh), molecules with anti-inflammatory properties. Therefore, with the increase of cholinesterase activity, there was an extracellular reduction of ACh, an inhibitor of several inflammatory mediators. This proinflammatory response of B. ovis infection leads to oxidative stress, and consequently to cellular damage., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck × mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity., (© 2019 Stichting International Foundation for Animal Genetics.)

Purpose: The aim of this study was to evaluate an association between nutritional biomarkers and prognosis in septic patients., Methods: We retrospectively searched the association between nutritional biomarkers including serum albumin (Alb), total protein (TP), total cholesterol (T-chol), and cholinesterase (ChE), and prognosis for septic patients treated in the ICU for >7 days. We used time-dependent Cox proportional hazard regression analysis to resolve the difference of the statistical weight of each day's data for all 14 consecutive days among individual sepsis patients. The covariates were based on the minimum moving values determined from 1 day, 3 days, 7 days, and 14 days of serial data. The values of these covariates and ICU survival were considered as outcomes., Results: We included 136 septic patients. The decreases in the values of Alb, TP, T-chol, and ChE were significantly associated with the risk of death in the septic patients (p < .05). Especially, the daily changes of Alb were significantly associated with mortality during the ICU stay (p < .05)., Conclusions: We found that the changes in serial data of the nutritional markers of Alb, TP, T-chol, and ChE reflected the higher risk of death in patients with prolonged sepsis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years., Results: A total of 17 children (median age at study inclusion 2.4 years, range 0-6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0-19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1-2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3-4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction., Conclusion: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.

Objectives: To evaluate the performance of a new mathematical model γ-glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus γ-glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B., Methods: A complete cohort of 2343 patients was divided into early and late cohort depending on the time of liver biopsy. With reference to the Scheuer standard, liver pathologic stage 2 or higher and stage 4 or higher were defined as significant fibrosis and cirrhosis, respectively. Receiver operating characteristic (ROC) curve was used to evaluate the performance of investigated models., Results: In the early cohort, the areas under ROC curves (AUROCs) of GCPR in predicting significant fibrosis of hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients (0.782 and 0.775) were both significantly greater than those of GPR (0.748 and 0.747) (Z = 8.198 and Z = 6.023, both p <0.0001); the AUROCs of GCPR in predicting cirrhosis of HBeAg-positive and HBeAg-negative patients (0.842 and 0.861) were both significantly greater than those of GPR (0.802 and 0.823) (Z = 6.686 and Z = 6.116, both p <0.0001). In early, late and complete cohorts, using a single cutoff of GCPR > 0.080, the specificities of GCPR in predicting significant fibrosis of HBeAg-positive patients were 83.3%, 88.2% and 85.0% and of HBeAg-negative patients were 87.6%, 87.4% and 87.6%, respectively; and the sensitivities of GCPR in predicting cirrhosis of HBeAg-positive patients were 81.9%, 88.7% and 84.2% and of HBeAg-negative patients were 83.1%, 82.1% and 82.7%, respectively., Conclusions: GCPR has higher performance than GPR in predicting significant fibrosis and cirrhosis of chronic hepatitis B., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Postoperative delirium (POD) commonly occurs in elderly patients after noncardiac surgery, resulting in increased morbidity and greater risk of death. However, its pathophysiology is currently unknown. Cholinergic dysfunction has been implicated in delirium pathophysiology, and low plasma cholinesterase activity has been reported as a risk marker of POD., Objective: Therefore, the aim of this study was to investigate the link between plasma cholinesterase activity and POD in elderly Han Chinese patients after noncardiac surgery., Method: From January 2014 to January 2016, a cohort of 206 patients aged ≥ 60years who underwent noncardiac surgery and were transferred to the surgical intensive care unit were enrolled. POD was assessed using the Confusion Assessment Method for Intensive Care Unit. Clinical data including sex, age, general comorbidities, alcohol consumption, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and type of surgery were recorded. Blood was drawn postoperatively to measure cholinesterase activity. Using multiple logistic regression analyses, the associations between cholinesterase activity and POD were examined, adjusting for potential confounding variables., Results: Delirium incidence was 22.3%. POD was associated with cholinesterase activity, age, and APACHE II score. In multiple logistic regression analyses, lower acetylcholinesterase and butyrylcholinesterase activity were independent risk factors for POD., Conclusion: Plasma cholinesterase activity may be a candidate biomarker for POD after noncardiac surgery in the elderly Chinese Han population., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background/aim: Nutritional status is strongly associated with cancer prognosis. The aim of this study was to identify the most useful combination of nutrition-related serum markers for predicting prognosis of patients with colorectal cancer (CRC)., Patients and Methods: A total of 523 patients who underwent proctocolectomies for CRC at our hospital were enrolled in this study. Serum concentrations of albumin, cholinesterase and total cholesterol, and total peripheral lymphocyte count (TLC) were used as nutrition-related markers., Results: In multivariate analysis of nutrition-related markers, serum albumin and cholinesterase levels were found to be independent prognostic indicators. Cut-off values from receiver operating characteristic analyses were used to sort patients as ChE High or ChE Low (serum cholinesterase level ≥ or <221.5), and as Alb High or Alb Low (serum albumin level ≥ or <3.85). We then sorted them into three groups: ChE High /Alb High (Group A); ChE High /Alb Low or ChE Low /Alb High (Group B); and ChE Low /Alb Low (Group C). Their 5-year overall survival rates differed significantly (Group A: 81.6%, Group B: 62.1%, Group C: 42.7%, p<0.0001); as did their 5-year disease-specific survival rates (Group A: 90.1%, Group B: 73.8%, Group C: 62.2%, p<0.0001)., Conclusion: The combination of serum cholinesterase and albumin levels is useful for predicting the prognosis of patients with CRC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Serum cholinesterase (ChE) a serine hydrolase that catalyses the hydrolysis of esters of choline, is involved in cellular proliferation and differentiation, therefore affecting carcinogenesis. The aim of this study was to understand the prognostic role of preoperative serum ChE in patients with radiation-recurrent prostate cancer (CaP) treated with salvage radical prostatectomy (SRP)., Material and Methods: This retrospective study included 214 patients with radiation-recurrent CaP treated with SRP from January 2007 to December 2015 at 5 academic centers. Patients were considered with abnormal/decreased ChE levels if <5 kU/l. Biochemical recurrence-free and metastases-free (MFS) survival analyses were performed., Results: Median serum ChE level was 6.9 (interquartile range) 6-7.7) kU/l. Serum ChE level (<5 kU/l) was decreased in 25 (11.7%) patients. Decreased serum ChE level was associated with lower body mass index (P = 0.006) and metastasis to lymph nodes (P = 0.004). In multivariable analysis, continuous ChE was an independent predictor of MFS (hazard ratio [HR] 0.48, confidence interval [CI] 0.33-0.71, P < 0.001), overall survival (HR 0.68, CI 0.48-0.96, P = 0.03) and cancer-specific survival (HR 0.41, CI 0.2-0.84, P = 0.01). Serum ChE improved the C-index (by 2.54%) to 87.8% for prediction of overall survival and (by 3%) to 92% for prediction of MFS., Conclusion: Preoperative serum ChE is associated with the development of metastasis in patients with radiation-recurrent CaP who underwent SRP. The biological underpinning of this association with the biological and clinical aggressiveness of CaP needs to be further elucidated., (Copyright © 2018. Published by Elsevier Inc.)

This study aimed to explore the risk factors for acute myocardial injury (AMI) caused by acute organophosphorus pesticide poisoning (AOPP).The clinical data of 98 patients, who were treated in our hospital due to oral AOPP from April 2013 to April 2017, were retrospectively analyzed. These patients were divided into two groups: AMI group and control group. The incidence of AMI was analyzed. Furthermore, the dosage forms and dose of the pesticide, and the interval between pesticide taking and doctor visit were compared between these two groups. Moreover, their clinical symptoms were observed; the serum cholinesterase levels, myocardial injury, and heart failure markers were detected, and the occurrence of arrhythmia and the structure and function of the heart were investigated through continuous electrocardiographic monitoring and transthoracic echocardiography.Among these 98 AOPP patients, 51 patients were complicated with AMI, and the incidence was 52.0%. The main manifestations of these 51 patients with AMI were as follows: the serum levels of myocardial injury markers (creatine kinase-Mb [CK-Mb] and cardiac troponin I [cTnI]) and heart failure markers (N-terminal pro B-type natriuretic peptide [NT-pro BNP]) were significantly higher, when compared with the control group (P < .001), and the incidence of arrhythmia (FVPB, P = .02; RAA, P = .03; RVA, P = .02; ST-T changes, P = .01) and heart failure (P = .04) was also significantly higher when compared with the control group. With regard to dosage forms of the pesticides, the number of patients taking the pesticides with solvents containing aromatic hydrocarbons was significantly higher in the AMI group than in the control group (P = .001). And the number of patients taking over 100 mL of pesticides was also significantly higher in the AMI group than in the control group (P < .001). Significantly more patients in the AMI group had an interval of over 1 h between pesticide taking and doctor visit than in the control group (P < .001).Risk factors for AMI after AOPP may include the dose and dosage form of the pesticide, and the interval between pesticide taking and doctor visit.

Diisopropyl fluorophosphate (DFP), a surrogate of nerve agent sarin, is an organophosphorus (OP) compound which inhibits neuronal enzyme acetylcholinesterase (AChE). Exposure of this compound leads to a wide range of toxic symptoms and survivors may exhibit long term neurotoxicity related to cognitive and memory defects. Due to ease of availability and similar mechanism of action to other highly toxic nerve agent, DFP is widely used as model compound to trace changes associated with nerve agent exposures. Proximal fluids are widely used for the elucidation of biomarkers for exposure to toxic substances and to study the mechanism of toxicity. Using a rat model of OP intoxication, the present study was carried out to elucidate proteomic changes in plasma associated with DFP intoxication. Rats were exposed to a single dose (0.5 LD 50 ) of DFP and their plasma proteome was studied, one day post exposure by two dimensional gel electrophoresis - mass spectrometry (2DE-MS). Some of the milestone changes were validated by Western blot analysis. A total 15 proteins showed significant fold changes in expression with respect to control after 1 day of DFP intoxication. Most of the proteins showing changes in expression at initial stages were related to immunogenic function, acute phase response, blood coagulation, and stress response. Experiments reported here demonstrate that 0.5 LD 50 DFP intoxication leads to AChE inhibition, modulation of immunogenic function, and generation of stress at an early stage. Although, some proteins and their putative functional ramifications indicated similarity with those observed in our previous plasma proteome study, neurodegenerative changes were not observed in plasma of 0.5 LD 50 DFP treated animals., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Exposure to organophosphate (OP) compounds leads to behavioral alterations. To determine whether paraoxon has effects on anxiety, anxiety-like behaviors were assessed in paraoxon-exposed rats. Protein expression of glutamate transporters has also been measured in hippocampus and prefrontal cortex. Three doses of paraoxon (0.3, 0.7, or 1 mg/kg) or corn oil (vehicle) were intraperitoneally injected to adult male rats. At 14 or 28 days after exposure, behavioral tests were done using elevated plus-maze (EPM) or open field tests. Thereafter, animals were sacrificed and both hippocampi and prefrontal cortices were extracted for cholinesterase assay and western blotting. Animals treated with convulsive doses of paraoxon (0.7 and 1 mg/kg) showed an increase in percentage of time spent in open arms and percentage of open arm entries in the EPM. In the open field test, an increase in the time spent in central area was observed in rats treated with the same doses of paraoxon. These effects of paraoxon were independent of any changes in locomotor activity. There was an increase in both astrocytic glutamate transporter proteins (GLAST and GLT-1) in the hippocampus of animals treated with 0.7 and 1 mg/kg of paraoxon. In the prefrontal cortex, protein levels of the GLAST and GLT-1 increased in 0.7 and decreased in 1 mg/kg groups. Only a significant decrease in EAAC1 protein was observed in the prefrontal cortex at 14 days following exposure to 1 mg/kg of paraoxon. Collectively, this study showed that exposure to convulsive doses of paraoxon induced anxiolytic-like behaviors in both behavioral tests. This effect may be attributed to alterations of glutamate transporter proteins in the rat hippocampus and prefrontal cortex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Vaspin, as a newly discovered adipocytokine, can modulate obesity with insulin-sensitizing effects. This study mainly focused on the plasma level of vaspin in insulin resistant rats, which received high-fat diet (HFD) and diazinon (DZN) (70 mg/kg). Upon 30-day experiment, related oxidative stress and inflammatory markers of plasma, the toxic effects of DZN and HFD on the histological structure of the liver, as well as the expression levels of potential genes associated with insulin resistance, phosphatase and tensin homolog (PTEN) and Forkhead box protein O1 (FoxO1) were evaluated. Metabolic parameters implicated to the glucose and insulin statues such as homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were determined. DZN significantly inhibited almost 50% of the plasma cholinesterase (ChE) activity. A remarkable increase of MDA level was observed in groups that received DZN and DZN + HFD. Animals treated with DZN or DZN + HFD showed significant changes in reactive oxygen species (ROS) level. The level of plasma tumor Necrosis Factor alpha (TNF-α) was noticeably elevated in the exposed groups. The highest elevation in vaspin level was observed in HFD group followed by DZN treated animals. In all treated groups, insulin level significantly increased and also, the area under the curve (AUC0-180) values of plasma glucose heightened considerably. The histopathological micrographs of HFD + DZN treated group indicated a severe fatty change. The plasma concentration of DZN was significantly higher in the DZN-treated group in comparison to the DZN + HFD group. FoxO1 and PTEN mRNA levels were significantly overexpressed in the DZN and HFD exposed groups. In HFD treated group, PTEN expression significantly increased compared with the DZN and DZN + HFD groups. Consequently, in contrast to oxidative stress and inflammatory biomarkers, vaspin level would be a more reliable diagnostic factor when it comes to the insulin resistance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Perfluorooctanoic acid (PFOA) is a widespread organic pollutant with various toxicological impacts on the liver. Members of the miR-34 family are P53-targeted growth suppressors. We found that PFOA exposure (5 mg/kg/d PFOA for 28 d) resulted in a significant increase of miR-34a in the livers of mice but had no effect on either miR-34b or miR-34c. We knocked out miR-34a in mice to explore the role of elevated miR-34a in PFOA-induced liver toxicity. Compared with the corresponding untreated control, significant increases in liver weight as well as serum alanine transaminase, aspartate aminotransferase, and cholinesterase levels were observed in miR-34a -/- and wild-type mice after PFOA exposure. Hepatic cells showed similar swelling in both miR-34a -/- and wild-type mice after PFOA treatment. Hepatic RNA-sequencing (RNA-seq) showed that PFOA led to significant alteration in lipid metabolism genes, especially those involved in the peroxisome proliferator-activated receptor pathway, in both wild-type and miR-34a null mice. With or without PFOA treatment, relatively fewer genes were altered in miR-34a -/- livers compared to wild-type livers. Among the changed genes by miR-34a, the most dominant were metabolism-related genes, such as Fabp3, Cyp7a1, and Apoa4. Our in vivo study indicated that miR-34a mainly exerts a metabolic regulation role, rather than the pro-apoptosis and cell cycle arrest role reported previously by many in vitro studies. In addition, although hepatic P53 was unchanged, the active type of P53 (acetylated P53 (acetyl-p53, Lys379)) was markedly altered under PFOA treatment. Therefore, the increase in acetylated P53 may have activated the transcription of miR-34a in mouse livers after PFOA treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Hepatic encephalopathy is a common consequence of liver cirrhosis, but diagnosis can be difficult as it is based on clinical criteria alone. We hypothesised that serum prealbumin, cholinesterase and retinol binding protein (RBP) can help support the diagnosis of hepatic encephalopathy., Methods: We enrolled 306 cirrhotic patients (110 with encephalopathy), 100 chronic hepatitis B patients and 50 healthy controls, measuring routine liver function tests (ALT, AST, GGT, ALP, and bilirubin), albumin, prothrombin time, prealbumin, cholinesterase and RBP by routine methods. Logistic regression analysis and areas under the receiver operating characteristic curves (AUCs) were used to find predictive factors for hepatic encephalopathy., Results: There were differences in all laboratory indices between the three groups (all p < 0.001). In univariate analysis, albumin, prothrombin time, prealbumin, cholinesterase and RBP were significantly altered in those with encephalopathy (p < 0.01), but only prealbumin, cholinesterase and RBP levels were significant predictors in multivariate analysis, and each was linked to the severity of liver fibrosis defined by the Child-Pugh score (all p < 0.001). The AUCs (95% CI) of prealbumin, cholinesterase and RBP for diagnosing liver cirrhosis with hepatic encephalopathy were comparable at 0.85 (81-90), 0.81 (0.76-0.85) and 0.81 (0.76-0.86), respectively (all p < 0.01)., Conclusions: Serum prealbumin, cholinesterase and RBP levels are of potential clinical value in diagnosis of liver cirrhosis complicated by encephalopathy.