Serum N-Glycan Changes in Rats Chronically Exposed to Glyphosate-Based Herbicides.

Glyphosate, the active ingredient in many herbicides, has been widely used in agriculture since the 1970s. Despite initial beliefs in its safety for humans and animals due to the absence of the shikimate pathway, recent studies have raised concerns about its potential health effects. This study aimed to identify glycomic changes indicative of glyphosate-induced toxicity. Specifically, the study focused on profiling N-glycosylation, a protein post-translational modification increasingly recognized for its involvement in various disorders, including neurological conditions. A comprehensive analysis of rat serum N-glycomics following chronic exposure to glyphosate-based herbicides (GBH) was conducted using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed significant changes in the N-glycan profile, particularly in sialylated and sialofucosylated N-glycans. The analysis of N-glycans across gender subgroups provided insights into gender-specific responses to GBH exposure, with the male rats exhibiting a higher susceptibility to these N-glycan changes compared to females. The validation of significantly altered N-glycans using parallel reaction monitoring (PRM) confirmed their expression patterns. This study provides novel insights into the impact of chronic GBH exposure on serum N-glycan composition, with implications for assessing glyphosate toxicity and its potential neurological implications.

Neuroglycome alterations of hippocampus and prefrontal cortex of juvenile rats chronically exposed to glyphosate-based herbicide.

Introduction: Glyphosate-based herbicides (GBHs) have been shown to have significant neurotoxic effects, affecting both the structure and function of the brain, and potentially contributing to the development of neurodegenerative disorders. Despite the known importance of glycosylation in disease progression, the glycome profile of systems exposed to GBH has not been thoroughly investigated. Methods: In this study, we conducted a comprehensive glycomic profiling using LC-MS/MS, on the hippocampus and prefrontal cortex (PFC) of juvenile rats exposed to GBH orally, aiming to identify glyco-signature aberrations after herbicide exposure. Results: We observed changes in the glycome profile, particularly in fucosylated, high mannose, and sialofucosylated N-glycans, which may be triggered by GBH exposure. Moreover, we found major significant differences in the N-glycan profiles between the GBH-exposed group and the control group when analyzing each gender independently, in contrast to the analysis that included both genders. Notably, gender differences in the behavioral test of object recognition showed a decreased performance in female animals exposed to GBH compared to controls (p < 0.05), while normal behavior was recorded in GBH-exposed male rats (p > 0.05). Conclusion: These findings suggest that glycans may play a role in the neurotoxic effect caused by GBH. The result suggests that gender variation may influence the response to GBH exposure, with potential implications for disease progression and specifically the neurotoxic effects of GBHs. Understanding these gender-specific responses could enhance knowledge of the mechanisms underlying GBH-induced toxicity and its impact on brain health. Overall, our study represents the first detailed analysis of N-glycome profiles in the hippocampus and PFC of rats chronically exposed to GBH. The observed alterations in the expression of N-glycan structures suggest a potential neurotoxic effect associated with chronic GBH exposure, highlighting the importance of further research in this area.

O-Glycome Profiling of Breast Cancer Cell Lines to Understand Breast Cancer Brain Metastasis.

Breast cancer is the second leading cause of cancer-related death among women and a major source of brain metastases. Despite the increasing incidence of brain metastasis from breast cancer, the underlying mechanisms remain poorly understood. Altered glycosylation is known to play a role in various diseases including cancer metastasis. However, profiling studies of O-glycans and their isomers in breast cancer brain metastasis (BCBM) are scarce. This study analyzed the expression of O-glycans and their isomers in human breast cancer cell lines (MDA-MB-231, MDA-MB-361, HTB131, and HTB22), a brain cancer cell line (CRL-1620), and a brain metastatic breast cancer cell line (MDA-MB-231BR) using nanoLC-MS/MS, identifying 27 O-glycan compositions. We observed significant upregulation in the expression of HexNAc1Hex1NeuAc2 and HexNAc2Hex3, whereas the expression of HexNAc1Hex1NeuAc1 was downregulated in MDA-MB-231BR compared to other cell lines. In our isomeric analysis, we observed notable alterations in the isomeric forms of the O-glycan structure HexNAc1Hex1NeuAc1 in a comparison of different cell lines. Our analysis of O-glycans and their isomers in cancer cells demonstrated that changes in their distribution can be related to the metastatic process. We believe that our investigation will contribute to an enhanced comprehension of the significance of O-glycans and their isomers in BCBM.

Metabolomic Changes in Rat Serum after Chronic Exposure to Glyphosate-Based Herbicide.

Glyphosate-based herbicides (GBHs) have gained extensive popularity in recent decades. For many years, glyphosate has been regarded as harmless or minimally toxic to mammals due to the absence of its primary target, the shikimic acid pathway in humans. Nonetheless, mounting evidence suggests that glyphosate may cause adverse health effects in humans via other mechanisms. In this study, we described the metabolomic changes in the serum of experimental rats exposed to chronic GBH using the highly sensitive LC-MS/MS technique. We investigated the possible relationship between chronic exposure to GBH and neurological disorders. Our findings suggest that chronic exposure to GBH can alter spatial learning memory and the expression of some important metabolites that are linked to neurophysiological disorders in young rats, with the female rats showing higher susceptibility compared to the males. This indicates that female rats are more likely to show early symptoms of the disorder on exposure to chronic GBH compared to male rats. We observed that four important metabolites (paraxanthine, epinephrine, L-(+)-arginine, and D-arginine) showed significant changes and involvement in neurological changes as suggested by ingenuity pathway analysis. In conclusion, our results indicate that chronic exposure to GBH can increase the risk of developing neurological disorders.

Effects of the COVID-19 Outbreak on Elder Mistreatment and Response in New York City: Initial Lessons.

New York City is currently experiencing an outbreak of COVID-19, a highly contagious and potentially deadly virus, which is particularly dangerous for older adults. This pandemic has led to public health policies including social distancing and stay-at-home orders. We explore here the impact of this unique crisis on victims of elder mistreatment and people at risk of victimization. The COVID-19 outbreak has also had a profound impact on the organizations from many sectors that typically respond to protect and serve victims of elder mistreatment. We examine this impact and describe creative solutions developed by these organizations and initial lessons learned in New York City to help inform other communities facing this pandemic and provide guidance for future crises.

Methodological approaches to the analyses of elder abuse screening measures: Application of latent variable measurement modeling to the WC-RAPS.

While several elder abuse screens exist, few measure risk and none target long-term support services. The aims were to examine the psychometric properties of the Weinberg Center Risk and Abuse Prevention Screen (WC-RAPS), comparing approaches to modeling self-reported risk and abuse in relation to reported Adult Protective Services contacts. METHODS: The sample (n = 7,035), admissions to managed long-term care (79%) and short-term rehabilitation (20%), was primarily (66%) female, with mean age 77.6 (SD = 9.10); 7% each were African American and Latino and 12% Asian. Latent variable models were used to examine measurement properties of six indicators of abuse and five of risk. RESULTS: Good model fit and stable subscale measurement models were observed across analyses. Reliability was >0.80 across methods, and concurrent criterion validity estimates were as expected. CONCLUSION: Evidence supported the reliability and concurrent criterion validity of the risk and abuse subscales in an ethnically diverse cohort.

Development and Spanish translation of the Weinberg Center Risk and Abuse Prevention Screen (WC-RAPS).

Barriers for enhanced detection, identification, and reporting of elder abuse include the paucity of appropriate, valid, easily administered screening tools. This article describes the qualitative methods used in the development of the Weinberg Center Risk and Abuse Prevention Screen (WC-RAPS), and of its Spanish version. Focus groups and cognitive interviews were instrumental in identifying problematic items, underscoring potential response errors, and informing about putative causes for divergent interpretations of item-intent. Seven of the 11 original items were modified, a double-barreled item was segregated into two, one item deleted, and three additional items included to create the final 13 WC-RAPS items. The multi-step approach implemented for the Spanish conversion evidenced deviation from the original intended meaning for one item. The readability for English and Spanish versions was also assessed. Screening for elder abuse, if implemented systematically can be instrumental in identifying unrecognized abuse and preventing reoccurrence.