Proteomic insights from extracellular vesicles into the molecular mechanisms of health effects induced by Per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFASs) can induce a range of adverse health effects, with the precise molecular mechanisms remaining elusive. Extracellular vesicles (EVs) have demonstrated their potential to elucidate unknown molecular mechanisms. Building upon the close alignment of their biological functions with the observed health effects of PFASs, this study innovatively focuses on proteomic insights from EVs into the molecular mechanisms underlying the systemic health effects of PFASs. Through rat exposure experiments and proteomics technology, it not only demonstrated the occurrence of PFASs in EVs but also revealed the alterations in the serum EVs and the expression of their protein cargos following mixed exposure to PFASs, leading to changes in related pathways. These changes encompass various biological processes, including proteasome activity, immune response, cytoskeletal organization, oxidative stress, cell signaling, and nervous system function. Particularly noteworthy is the uncovering of the activation of the proteasome pathway, highlighting significant key contributing proteins. These novel findings provide a new perspective for exploring the molecular mechanism underlying the systemic health effects of PFASs and offer reliable screening for potential biomarkers. Additionally, comparisons with serum confirmed the potential of serum EVs as biological responders and measurable endpoints for evaluating PFASs-induced toxicity.

CRISPR/Cas: a powerful tool for designing and improving oil crops.

Improving oil yield and quality is a major goal for crop breeding, and CRISPR/Cas-mediated genome editing has opened a new era for designing oil crops with enhanced yield and quality. CRISPR/Cas technology can not only increase oil production but also enhance oil quality, including enhancing pharmaceutical and health components, improving oil nutrients, and removing allergic and toxic components. As new molecular targets for oil biosynthesis are discovered and the CRISPR/Cas system is further improved, CRISPR/Cas will become a better molecular tool for designing new oil crops with higher oil production, enhanced nutrients, and improved health components. 'CRISPRized' oil crops will have broad applications both in industry (e.g., as biofuels) and in daily human life.

Sex Differences in the Development of an Opioid Addiction-Like Phenotype: A Focus on the Telescoping Effect.

Background: Women develop addiction and drug-related health consequences after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed clinically for multiple drugs, including opioids. Preclinical studies indicate that this is a biologically based phenomenon; however, these studies have focused exclusively on cocaine, and none have considered health effects. Methods: In this study, we used a rat (Sprague Dawley) model to determine sex differences in the time course for the development of an opioid addiction-like phenotype, as defined by the development of physical dependence (withdrawal-induced weight loss) and an increase in motivation for fentanyl (under a progressive-ratio schedule). Effects were determined following either 10 days (optimized, experiment 1) or 3 days (threshold, experiment 2) of extended-access fentanyl self-administration (24 hours/day, fixed ratio 1, 2- to 5-minute trials/hour) or following short-access fentanyl self-administration (subthreshold, experiment 3; fixed ratio 1, up to 40 infusions/day). Opioid-related adverse health effects were also determined (experiment 4). Results: Motivation for fentanyl was similarly increased in males and females following 10 days of extended-access self-administration (experiment 1), was transiently increased in females, but not males, following 3 days of extended-access self-administration (experiment 2) and was not increased in either sex following short-access self-administration (experiment 3). Females developed fentanyl-associated adverse health effects more readily than males (experiment 4), with particularly robust differences during extended-access self-administration and withdrawal. Conclusions: As with findings in humans, female rats developed opioid addiction-like features and adverse health consequences more readily than male rats. These data provide support for a biologically based telescoping effect in females for opioids, particularly for opioid-related adverse health consequences.

In this issue, we explore how female rats develop signs of opioid addiction and related health issues faster than male rats, a phenomenon known as the telescoping effect. This study expands on previous research by using a rat model to assess addiction-like behaviors and health consequences following different withdrawal period and durations of fentanyl self-administration. The findings underline the biological underpinnings of sex differences in addiction trajectories, previously demonstrated in humans but not yet studied in opioids until now.

Cross-cutting studies of per- and polyfluorinated alkyl substances (PFAS) in Arctic wildlife and humans.

This cross-cutting review focuses on the presence and impacts of per- and polyfluoroalkyl substances (PFAS) in the Arctic. Several PFAS undergo long-range transport via atmospheric (volatile polyfluorinated compounds) and oceanic pathways (perfluorinated alkyl acids, PFAAs), causing widespread contamination of the Arctic. Beyond targeting a few well-known PFAS, applying sum parameters, suspect and non-targeted screening are promising approaches to elucidate predominant sources, transport, and pathways of PFAS in the Arctic environment, wildlife, and humans, and establish their time-trends. Across species, concentrations were dominated by perfluorooctanesulfonic acid (PFOS), followed by perfluorononanoic acid (PFNA); highest concentrations were present in mammalian livers and bird eggs. Time trends were similar for East Greenland ringed seals (Pusa hispida) and polar bears (Ursus maritimus). In polar bears, PFOS concentrations increased from the 1980s to 2006, with a secondary peak in 2014-2021, while PFNA increased regularly in the Canadian and Greenlandic ringed seals and polar bear livers. Human time trends vary regionally (though lacking for the Russian Arctic), and to the extent local Arctic human populations rely on traditional wildlife diets, such as marine mammals. Arctic human cohort studies implied that several PFAAs are immunotoxic, carcinogenic or contribute to carcinogenicity, and affect the reproductive, endocrine and cardiometabolic systems. Physiological, endocrine, and reproductive effects linked to PFAS exposure were largely similar among humans, polar bears, and Arctic seabirds. For most polar bear subpopulations across the Arctic, modeled serum concentrations exceeded PFOS levels in human populations, several of which already exceeded the established immunotoxic thresholds for the most severe risk category. Data is typically limited to the western Arctic region and populations. Monitoring of legacy and novel PFAS across the entire Arctic region, combined with proactive community engagement and international restrictions on PFAS production remain critical to mitigate PFAS exposure and its health impacts in the Arctic.

Effects of website-based risk communication of radio-frequency electromagnetic fields on general public.

Background: Radio-frequency electromagnetic fields (RF-EMFs) are utilized in communications and appliances and are indispensable in daily life. However, some people have concerns about the adverse health effects of RF-EMFs; therefore, effective risk communication (RC) is needed in this field. Objective: In this study, we investigate public attitudes towards RF-EMFs and examine the impact of RC via a website on these attitudes and objective knowledge. Methods: Three web surveys were conducted over 10 weeks with the same participants. The questionnaires were conducted at three different time points with 5-week intervals: baseline survey (T1), RC evaluation survey (T2), and follow-up survey (T3). Participants of T2 were randomly recruited from among those of T1, and participants of T3 were randomly selected from among the T2 respondents. Approximately half of the respondents in each of T2 and T3 were assigned to the control group. Twelve items regarding attitudes toward RF-EMFs and objective knowledge were evaluated in all surveys (T1-T3). After removing low-engagement data, the number of valid answers was 782 in T3. Differences between T1 and T2 (Sub T1-T2) and T1 and T3 (Sub T1-T3) were analyzed. Participant selection was randomized and the authors were blind to this selection until analysis. Results: Four clusters were identified: Cluster 1 (Non-anxious, 25.0%), Cluster 2 (Anxious, 16.0%), Cluster 3 (Low-interest, 40.5%), and Cluster 4 (High-interest, 18.5%). A decrease in subjective RF-EMF exposure levels was noted in Cluster 2 immediately after website viewing. Temporary increases and decreases in health concerns about RF-EMF usage activities were observed in Clusters 1 and 2, respectively, immediately after viewing. Clusters 1 and 3 showed a temporal decrease in needs for RF-EMF usage activities at T2 but it returned to the baseline level 5 weeks later. Cluster 4 was less responsive to the risk communication. Subanalysis stratified by gender and age showed fluctuations in responses, especially in Clusters 1 and 2. Conclusion: We demonstrate the effectiveness of RF-EMF risk communication via websites, particularly for Cluster 2. The results of this study showed that offering objective and comprehensible information through a website can significantly reduce concerns and perceived risks related to RF-EMFs.

Health Risk Assessment of Residents' Exposure to Air Pollutants around the Sinpyeong-Jangrim Industrial Complex in Busan.

In this study, we aimed to evaluate the health effects of heavy metals and volatile organic compounds (VOCs) in fine particulate matter (PM2.5) in the air around the Sinpyeong-Jangrim Industrial Complex, Busan, and the necessity of reduction measures. We measured the concentrations of heavy metals and VOCs in PM2.5 in five areas with dense population around the Sinpyeong-Jangrim Industrial Complex. A health risk assessment was conducted, and the spatial risk distribution for the entire Saha-gu area was predicted using inverse distance weighting (IDW). Our results indicated that the carcinogens benzene, As, and Cr6+, and the non-carcinogen m,p-xylene, have the potential to adversely affect health. In particular, As was found to have the potential to express health effects at all measurement points. Additionally, based on the IDW results, the minimum values of benzene, arsenic, and m,p-xylene exceeded the threshold level, potentially affecting the health of residents across the entire Saha-gu area. In contrast, Cr6+ could potentially impact health only in some parts of Saha-gu as only its maximum value exceeded the threshold level. We demonstrated the importance of reducing air pollutant emissions from general industrial complexes. Our results will be useful in establishing more systematic mitigation measures to protect the health of residents near the Sinpyeong-Jangrim Industrial Complex and developing air pollutant management systems.

Adverse health effects of exposure to plastic, microplastics and their additives: environmental, legal and policy implications for Israel.

BACKGROUND: Israel is a regional "hotspot" of plastic pollution, with little discussion of potential adverse health effects from exposure to plastic. This review aims to stimulate discussion and drive policy by focusing on these adverse health effects. MAIN BODY: Plastics are synthetic polymers containing additives which can leach from food- and beverage-contact plastic into our food and beverages, and from plastic textiles onto our skin. Plastics persist in the environment for generations, fragmenting into MNPs: Micro (1 micron-5 mm)-Nano (1 nm-1 micron)-Plastic, which contaminate our atmosphere, water, and food chain. MNP can enter the human body through ingestion, inhalation and touch. MNP < 10 microns can cross epithelial barriers in the respiratory and gastrointestinal systems, and fragments < 100 nm can cross intact skin, enabling entry into body tissues. MNP have been found in multiple organs of the human body. Patients with MNP in atheromas of carotid arteries have increased risk of a combined measure of stroke, cardiovascular disease, and death. Toxic additives to plastics include bisphenols, phthalates, and PFAS, endocrine-disrupting chemicals (EDCs) which cause dysregulation of thyroid function, reproduction, and metabolism, including increased risk of obesity, diabetes, endometriosis, cancer, and decreased fertility, sperm count and quality. Fetal exposure to EDCs is associated with increased rates of miscarriages, prematurity and low birth weight. There is likely no safe level of exposure to EDCs, with increasing evidence of trans-generational and epigenetic effects. There are several existing Israeli laws to reduce plastic use and waste. Taxes on single-use plastic (SUP) were recently cancelled. There are many gaps in regulatory standards for food-, beverage- and child- safe plastic. Existing standards are poorly enforced. CONCLUSION: Reduction in production and use of plastic, promotion of recycling and reduction of leaching of toxic additives into our food and beverages are essential policy goals. Specific recommendations: Periodic monitoring of MNP in bottled beverages, food, indoor air; Strengthen enforcement of standards for food-, beverage-, and child-safe plastic; Renew tax on SUPs; National ban on SUP at public beaches, nature reserves and parks; Ban products manufactured with MNP; Increase research on sources and health outcomes of exposure to MNP and EDCs.

Health Impacts of Pre-eclampsia: A Comprehensive Analysis of Maternal and Neonatal Outcomes.

Background and Objectives: Hypertensive disorders, particularly pre-eclampsia, pose significant risks during pregnancy, affecting both maternal and neonatal health. The study aims to analyze short- and long-term health implications for mothers and their children, comparing those with pre-eclampsia to those without, to improve understanding of risk factors, diagnostic markers, and outcomes. Materials and Methods: This retrospective observational study involved 235 patients, 98 with pre-eclampsia and 137 without, monitored from 2015 to 2018 at the Obstetrics and Gynecology Department of the "Pius Brînzeu" Emergency County Clinical Hospital in Timișoara, Romania. Results: Women with pre-eclampsia were older, had higher BMIs, and more frequently had a family history of pre-eclampsia, hypertension, and diabetes. They also had lower educational and socioeconomic levels and fewer prenatal visits. Biochemical markers such as higher proteinuria, elevated sFlt-1, and lower PlGF were significant in diagnosing pre-eclampsia. Short-term maternal complications like eclampsia, HELLP syndrome, and acute kidney injury were more prevalent in the pre-eclampsia group. Neonatal outcomes included higher rates of preterm birth, low birth weight, and NICU admissions. Long-term mothers with a history of pre-eclampsia had higher incidences of chronic hypertension, cardiovascular disease, kidney problems, diabetes, and mental health disorders. Their children faced increased risks of neuropsychological delays, chronic respiratory issues, behavioral disorders, learning difficulties, and frequent infections. Conclusions: The study highlights the significant short- and long-term health impacts of pre-eclampsia on both mothers and their children. Early monitoring, intervention, and comprehensive management are crucial in mitigating these risks. These findings underscore the need for personalized care strategies to improve health outcomes for affected individuals.

Unveiling the development trends of environmental and human health concerns for pesticides: Integrating an intelligent approach and data mining across diverse databases.

The impact of pesticide use on environmental and human health has been a persistent global concern. In the era of big data, the scientific literature concerning big data is a significant source of information; however, it is difficult to construct an optimal policy based on traditional insight using keyword searches or a single static-specialized database. In this study, we constructed a new path for data mining across multiple databases to provide a comprehensive picture of the major issues concerning environmental pollution and human health as a result of pesticide use at the global scale. This approach uses a classic unsupervised learning algorithm, Latent Dirichlet Allocation (LDA), in combination with a newly developed dataset of pesticide-associated human health outcomes (PAHHO), including 618 health outcomes classified into 14 types of toxic effects. Our data visualization revealed a shift in the scientific center for pesticide research over the past five decades. The major issues concerning environmental pollutants and health outcomes varied among different countries and in different periods, which was verified in our analysis of several organochlorine pesticides (OCPs) about which people are particularly concerned. A cooccurrence network of adverse health outcomes has gradually increased, suggesting that the impact of pesticides on human health is persistent and cumulative. Our work not only provides a promising research direction related to the most concerning issues in a systematic and visualized way but also provides valuable references to formulate optimal strategies for the goal of the global "One Health" objective in pesticide regulation.

The Dairy Matrix: Its Importance, Definition, and Current Application in the Context of Nutrition and Health.

Nutrition research has shifted from single nutrients to examining the association of foods and dietary patterns with health. This includes recognizing that food is more than the sum of the individual nutrients and relates to the concept of the food matrix. Like other foods, dairy foods are characterized by their unique matrices and associated health effects. Although the concepts of the food matrix and/or dairy matrix are receiving increasing attention in the nutrition and health literature, there are different terms and definitions that refer to it. This article aims to provide insights into the application of the concepts of the food matrix and dairy matrix and to provide a current overview of the definitions and terminology surrounding the food matrix and dairy matrix. By analysing these aspects, we aim to illustrate the practical implications of the food matrix and dairy matrix on nutrition and health outcomes and evaluate their roles in shaping evidence-based policies for the benefit of public health. There is a need for harmonized definitions within the literature. Therefore, the International Dairy Federation put forward harmonized terms to be internationally applicable: the "dairy matrix" describes the unique structure of a dairy food, its components (e.g., nutrients and non-nutrients), and how they interact; "dairy matrix health effects" refers to the impact of a dairy food on health that extend beyond its individual components.

Machine learning-ready mental health datasets for evaluating psychological effects and system needs in Mexico city during the first year of the COVID-19 pandemic.

The prevalence of mental health problems constitutes an open challenge for modern societies, particularly for low and middle-income countries with wide gaps in mental health support. With this in mind, five datasets were analyzed to track mental health trends in Mexico City during the pandemic's first year. This included 33,234 responses to an online mental health risk questionnaire, 349,202 emergency calls, and city epidemiological, mobility, and online trend data. The COVID-19 mental health risk questionnaire collects information on socioeconomic status, health conditions, bereavement, lockdown status, and symptoms of acute stress, sadness, avoidance, distancing, anger, and anxiety, along with binge drinking and abuse experiences. The lifeline service dataset includes daily call statistics, such as total, connected, and abandoned calls, average quit time, wait time, and call duration. Epidemiological, mobility, and trend data provide a daily overview of the city's situation. The integration of the datasets, as well as the preprocessing, optimization, and machine learning algorithms applied to them, evidence the usefulness of a combined analytic approach and the high reuse potential of the data set, particularly as a machine learning training set for evaluating and predicting anxiety, depression, and post-traumatic stress disorder, as well as general psychological support needs and possible system loads.

Clinical Patterns and Factors Contributing to Ophthalmic and Otologic Events Associated With Immune Checkpoint Inhibitors: A Narrative Review.

Immune checkpoint inhibitors, which are a type of cancer immunotherapy, have been associated with the development of adverse events related to an overactive immune system caused by the effect of this type of therapy. It affects a wide range of organs, including the ear and eye. Ophthalmic toxicity related to immune checkpoint inhibitors usually occurs bilaterally. Corneal toxicity (mainly dry eye disease) and uveitis are the most commonly reported patterns of toxicity. Other patterns of involvement include optic neuritis, serous retinal detachment, keratitis, ophthalmoplegia, and ocular myasthenia, but are not limited to them. Potential factors contributing to the development of toxicity are age, previous history of ocular immune disease, type, doses, and duration of treatment, and race. Ototoxicity is also reported in the literature, usually manifesting as bilateral, symmetrical/asymmetrical hearing loss. Ear toxicity presenting as ear fullness, tinnitus, and vertigo has also been mentioned in the literature. Hearing loss is often associated with word/speech recognition. An audiogram usually shows a pattern of sensorineural hearing loss. Otitis media has also been reported to be a potential cause of ear toxicity. Immune checkpoint inhibitor toxicity was present more commonly when used along with other anti-neoplastic agents. Ear toxicity, which presumably results from damage to the melanocytes in the ear, often presents with other melanocytotic manifestations, like uveitis and vitiligo. According to the literature, some agents (ipilimumab, nivolumab, atezolizumab, and pembrolizumab) were more commonly associated with toxic effects on the eye and ear and more when combined with each other.

Air pollution, viral spread and health outcomes evidence from strikes in France.

To evidence the impact of air pollution on the health of urban populations, several studies use natural experiments that shift commuting from public transport to cars (or vice-versa). However, as public transport use declines, reduced interpersonal contact may lead to slower virus spread and thus lower respiratory morbidity. Using a difference-in-differences strategy, we show that respiratory hospitalisations are both positively affected by air pollution and negatively affected by viral spread following partial unavailability of public transport due to strikes in the ten most populated French cities during the period 2010-2015. Our results are in line with studies in other countries that have found a significant increase in urgent respiratory hospitalisations following a public transport strike, most likely due to car pollution, but we also find a detectable interaction with viral spread, which should not be overlooked when interpreting these studies.

Dietary glycation compounds - implications for human health.

The term "glycation compounds" comprises a wide range of structurally diverse compounds that are formed endogenously and in food via the Maillard reaction, a chemical reaction between reducing sugars and amino acids. Glycation compounds produced endogenously are considered to contribute to a range of diseases. This has led to the hypothesis that glycation compounds present in food may also cause adverse effects and thus pose a nutritional risk to human health. In this work, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) summarized data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and systematically assessed potential associations between dietary intake of defined glycation compounds and disease, including allergy, diabetes, cardiovascular and renal disease, gut/gastrotoxicity, brain/cognitive impairment and cancer (Part B). A systematic search in Pubmed (Medline), Scopus and Web of Science using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet retrieved 253 original publications relevant to the research question. Of these, only 192 were found to comply with previously defined quality criteria and were thus considered suitable to assess potential health risks of dietary glycation compounds. For each adverse health effect considered in this assessment, however, only limited numbers of human, animal and in vitro studies were identified. While studies in humans were often limited due to small cohort size, short study duration, and confounders, experimental studies in animals that allow for controlled exposure to individual glycation compounds provided some evidence for impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to dicarbonyl compounds, albeit at dose levels by far exceeding estimated human exposures. The overall database was generally inconsistent or inconclusive. Based on this systematic review, the SKLM concludes that there is at present no convincing evidence for a causal association between dietary intake of glycation compounds and adverse health effects.

Considering the implication of endogenous glycation compounds in aging and disease, dietary exposure via consumption of an "AGE (advanced glycation end product) rich diet" is increasingly suggested to pose a potential health risk. However, studies attempting to assess an association between dietary glycation compounds and adverse health effects frequently suffer from insufficient chemical analysis of glycation compounds, including inadequate structural characterization and limited quantitative data. The Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) previously defined quality criteria for studies designed to assess the effects of dietary glycation compounds on human health. The aim of the present work is to summarize data on formation, occurrence, exposure and toxicity of glycation compounds (Part A) and to systematically evaluate if the currently available scientific database allows for a conclusive assessment of potential health effects of defined glycation compounds (Part B).The term "glycation compounds" comprises a wide range of structurally diverse compounds that derive from the Maillard reaction, a chemical reaction between reducing carbohydrates and amino compounds that occurs during food processing. In the first stage of the Maillard reaction, reducing sugars such as glucose and fructose react for instance with the ε-amino group of lysine, which is most abundant in food ("glycation" of lysine). Subsequently, these primary reaction products undergo Amadori rearrangement to yield products (ARP) such as fructosyllysine (FL) from glucose and also Heyns rearrangement products (HRPs) such as glucosyl- and mannosyllysine from fructose. While ARPs are rapidly formed during food processing, they are not stable and undergo degradation reactions, predominantly to 1,2-dicarbonyl compounds such as glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3-DG), which are highly reactive. The last stage of the Maillard reaction is characterized predominantly by the reaction of these dicarbonyl compounds with nucleophilic groups of proteins. The side-chains of lysine and arginine residues as well as the N-termini of proteins are important reaction sites. Carboxyalkylated amino acids such as N-ε-carboxymethyllysine (CML) and N-ε-carboxyethyllysine (CEL) result from reaction of the ε-amino group of lysine with the dicarbonyl compounds GO and MGO. Dicarbonyl compounds with C5 or C6 chains can form cyclic pyrrole derivatives at the ε-amino group of lysine. The most important example for this reaction is pyrraline, which is formed from reaction of 3-DG and lysine. The reaction of dicarbonyl compounds with the guanidino group of arginine mainly leads to hydroimidazolones, of which the MGO-derived hydroimidazolone 1 (MG-H1) is best described in food systems.ARPs are the most abundant glycation products found in food. Up to 55% of the lysine residues in food may be modified to ARPs at the side-chain. Food items particularly rich in ARPs include bread, rusk, biscuits, chocolate, and powdered infant formulas. Exposure estimates range between 0.6­1.6 mg/kg body weight (bw), although exposure may be as high as 14.3 mg/kg bw in individuals consuming foods with extreme ARP concentrations. Foods particularly rich in dicarbonyl compounds include heat-treated or long-term stored items rich in reducing sugars such as jams, alternative sweeteners, soft drinks, honey, candies, cookies, and vinegars, especially balsamico-type vinegars. The main contributors to the daily intake of MGO, GO, and 3-DG are coffee and bread. Dietary exposure to dicarbonyl compounds has been estimated to range between 0.02­0.29 mg/kg bw/d for MGO, 0.04­0.16 mg/kg bw/d for GO, 0.14­2.3 mg/kg bw/d for 3-DG, and 0.08­0.13 mg/kg bw/d for 3-deoxygalactosone (3-DGal). Dietary intake of 5-hydroxymethylfurfural (HMF), which can be formed from 3-DG, is estimated to range between 0.0001­0.9 mg/kg bw/d. Exposure estimates for individual glycated amino acids range from 0.03­0.35 mg/kg bw/d for CML, 0.02­0.04 mg/kg bw/d for CEL and 0.19­0.41 mg/kg bw/d for MG-H1. From a model diet consisting of 1 L milk, 500 g bakery products and 400 mL coffee, an intake of pyrraline corresponding to 0.36 mg/kg bw/d for a 70 kg person was estimated.Quantitative analysis of individual glycation compounds or their metabolites in tissues or body fluids as well as their reaction products with amino acids, proteins or DNA may serve to monitor exposure to glycation compounds. However, since glycation compounds are also formed endogenously, these biomarkers reflect the totality of the exposure, making it inherently difficult to define the body burden due to dietary intake against the background of endogenous formation.Information on the toxicokinetics and toxicity of glycation compounds is scarce and mostly limited to the reactive dicarbonyl compounds GO, MGO, 3-DG, HMF, and individual glycated amino acids such as CML and CEL. Acute toxicity of dicarbonyl compounds is low to moderate. There are some data to suggest that rapid detoxification of dicarbonyls in the gastrointestinal tract and liver may limit their oral bioavailability. Biotransformation of GO and MGO occurs predominantly via the glutathione (GSH)-dependent glyoxalase system, and to a lesser extent via glutathione-independent aldo-keto-reductases, which are also responsible for biotransformation of 3-DG. GO, MGO and 3-DG readily react with DNA bases in vitro, giving rise to DNA adducts. There is clear evidence for genotoxicity of GO, MGO and 3-DG. Repeated dose toxicity studies on GO consistently reported reduced body weight gain concomitant with reduced food and water consumption but did not identify compound related changes in clinical chemistry and hematology or histopathological lesions. There is also no evidence for systemic carcinogenicity of GO and MGO based on the available studies. However, initiation/promotion studies indicate that oral exposure to GO may exhibit genotoxic and tumor promoting activity locally in the gastrointestinal tract. From a 2-year chronic toxicity and carcinogenicity study in rats, a NOAEL for systemic toxicity of GO administered via drinking water of 25 mg/kg bw was reported based on reduced body weight and erosions/ulcer in the glandular stomach. Other non-neoplastic and neoplastic lesions were not observed. Acute toxicity of HMF is also low. From a 90-day repeated dose toxicity study in mice, a NOAEL of 94 mg/kg bw was derived based on cytoplasmic alterations of proximal tubule epithelial cells of the kidney. HMF was mostly negative in in vitro genotoxicity tests, although positive findings for mutagenicity were obtained under conditions that promote formation of the chemically reactive sulfuric acid ester 5-sulfoxymethylfurfural. There is some evidence of carcinogenic activity of HMF in female B6C3F1 mice based on increased incidences of hepatocellular adenoma, but not in male mice and rats of both sexes. Although data on oral bioavailability of glycated amino acids are mostly limited to CML, it appears that glycated amino acids may be absorbed from the gastrointestinal tract after oral exposure to their free and protein bound form. Glycated amino acids that are not absorbed in the intestine may be subject to metabolism by the gut microbiome. Glycated amino acids present in the systemic circulation are rapidly eliminated via the urine. Acute oral toxicity of CML is low. Studies in mice and rats reported changes in clinical chemistry parameters indicative of impaired renal and hepatic function. However, these changes were not dose-related and not supported by histopathological evaluation.Previous risk assessments of individual glycation compounds did not identify a health concern at estimated human exposures (GO, HMF) but also noted the lack of data to draw firm conclusions on health risks associated with exposure to MGO.To identify potential associations between dietary intake of defined glycation compounds and disease a systematic review was carried out according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) model, applying the quality criteria previously defined by the SKLM. Using a combination of keywords defining individual glycation compounds and relevant disease patterns linked to the subject area of food, nutrition and diet, a systematic search in Pubmed (Medline), Scopus and Web of Science was performed. Although the present systematic review identified numerous studies that investigated an association between an "AGE-rich diet" and adverse health effects, only a subset of studies was found to comply with the quality criteria defined by the SKLM and was thus considered suitable to assess potential health risks of dietary glycation compounds.For each adverse health effect considered in this assessment, only limited numbers of human studies were identified. Although studies in humans offer the advantage of investigating effects at relevant human exposures, these studies did not provide compelling evidence for adverse effects of dietary glycation compounds. Animal studies identified in this systematic review provide some evidence for induction of impaired glucose tolerance, insulin resistance, cardiovascular effects and renal injury in response to oral exposure to GO and MGO as representatives of dicarbonyl compounds. Only limited evidence points to a link between high intake of glycated amino acids and metabolic disorders. However, these effects were typically reported to occur at dose levels that exceed human dietary exposure, often by several orders of magnitude. Unfortunately, most studies employed only one dose level, precluding characterization of dose-response and derivation of a point of departure for riskassessment. While in vitro studies provide some evidence for a potential mechanistic link between individual glycation compounds and presumed adverse health effects, the clinical and toxicological relevance of the in vitro findings is often limited by the use of high concentrations of glycation compounds that by far exceed human dietary exposure and by insufficient evidence for corresponding adverse effects in vivo. A key question that has not been adequately considered in most studies investigating systemic effects of glycation compounds is the extent of oral bioavailability of dietary glycation compounds, including the form in which MRPs may be taken up (e.g. free vs. peptide bound glycated amino acids). Understanding how much dietary glycation compounds really add to the significant endogenous background is critical to appraise the relevance of dietary MRPs for human health.While it appears mechanistically plausible that glycation of dietary allergens may affect their allergenic potential, the currently available data do not support the hypothesis that dietary glycation compounds may increase the risk for diet-induced allergies. There are no human studies addressing the immunological effects of dietary AGEs. Accordingly, there are no data on whether dietary AGEs promote the development of allergies, nor whether existing allergies are enhanced or attenuated. In numerous in vitro studies, the IgG/E binding ability of antigens and therefore their allergenic potential has been predominantly reported to be reduced by glycation. However, some in vitro studies showed that glycated proteins bind to receptors of immunological cells, and thus may have promoting effects on immune response and inflammation.Although experimental data from animal studies provide some evidence that high doses of individual glycation compounds such as MGO and protein-bound CML may produce certain adverse health effects, including diabetogenic, cardiovascular, metabolic and renal effects, the doses required to achieve these effects by far exceed human dietary exposures. Of note, in the only long-term study identified, a high dose of MGO administered via drinking water to mice for 18 months had no adverse effects on the kidneys, cardiovascular system, or development of diabetes.Experimental data from animal studies provide evidence that high doses of defined glycation compounds such as MGO or protein-bound CML may affect glucose homeostasis. However, the doses required to produce these effects markedly exceed human dietary exposure. Results from human studies are inconclusive: Three short-term intervention studies suggested that diets rich in AGEs may impair glucose homeostasis, whereas one recent intervention study and two observational studies failed to show such an effect.For the cardiovascular system, there is some evidence from in vitro and in vivo studies that high concentrations of MRPs, well above the dietary exposure of humans, may enhance inflammation in the cardiovascular system, induce endothelial damage, increase blood pressure and increase the risk of thrombosis. Only a limited number of human intervention studies investigated potential effects of short-term exposure and longer-term effects of glycation compounds on the cardiovascular system, and yielded inconsistent results. The few observational studies available either found no association between dietary MRP intake and cardiovascular function or even reported beneficial effects. Therefore, currently no definitive conclusion on potential acute and chronic effects of dietary MRPs on inflammation and cardiovascular function can be drawn. However, there is currently also no convincing evidence that potential adverse effects on the cardiovascular system are triggered by dietary MRP intake.Furthermore, human studies did not provide evidence for an adverse effect of dietary MRPs on kidney function. In animal studies with high levels of oral intake, MGO was reported to cause structural and functional effects in the kidney. Several studies show that the concentration of modified proteins and amino acids, such as CML, increases significantly in kidney tissue after oral intake. One study showed a negative effect of a high-temperature-treated diet containing increased CML concentrations on kidney structure integrity and impaired glomerular filtration. The causative relationship of accumulation of dietary MRPs and a functional decline of the kidneys, however, needs further confirmation.With regard to gut health, there is some evidence for alterations in gut microflora composition and the production of individual short-chain fatty acids (SCFAs) upon dietary exposure to glycation compounds. However, this has not been linked to adverse health effects in humans and may rather reflect adaptation of the gut microbiota to changing nutrients. In particular, a human observational study and several animal studies did not find a correlation between the intake of glycation compounds and increased intestinal inflammation. In animal studies, positive effects of glycation compounds on gut tissue damage and dysbiosis during colitis were described.Considering clear evidence for DNA reactivity and genotoxicity of the dicarbonyl compounds GO, MGO and 3-DG, it is plausible to suspect that dicarbonyl compounds may induce mutations and cancer. Although there is some evidence for tumor promoting activity of GO locally in the gastrointestinal tract, the only guideline-compatible chronic rodent bioassays reported erosions and ulcer in the glandular stomach but no treatment-related neoplastic lesions. A recent multinational cohort study with focus on CEL, CML, and MG-H1 found no evidence to support the hypothesis that dietary AGEs are linked to cancer risk.Evidence for an association between human exposure to dietary glycation compounds and detrimental effects on the brain and on cognitive performance is far from being compelling. No human studies fully complying with the defined quality criteria were identified. A few experimental studies reported neuroinflammation and cognitive impairment following dietary MRP exposure, but these can be considered indicative at best and do not support firm conclusions for human health. In addition to utilizing exceedingly high dosages of individual agents like CML, harsh processing conditions causing a multitude of major process-related changes do not allow to convincingly reconcile effects observed with measured/supposed contents of free and protein-bound CML alone.Overall, although dietary glycation compounds have been claimed to contribute to a wide range of adverse health effects, the present critical evaluation of the literature allows the conclusion that the available data are insufficient, inadequate or inconclusive and do not compellingly support the hypothesis of human health risks being related to the presence of glycation compounds in food. The study limitations detailed above, together with the fact that a large number of studies did not comply with the defined quality criteria and therefore had to be excluded highlight the importance of performing adequately designed human or animal studies to inform scientifically reliable health risk assessment.To achieve this, high quality, dependable scientific cooperation within various disciplines is pivotal.

Direct health implications of e-cigarette use: a systematic scoping review with evidence assessment.

Background: E-cigarettes are often marketed as a less harmful alternative to traditional tobacco cigarettes. Despite their popularity, the evidence regarding their effects on human health remains unclear and is filled with complexities. Objectives: This systematic review aims to elucidate the direct effects of electronic cigarette use on human health, carefully distinguishing between the specific characteristics of the populations studied. Methodology: Adhering to the PRISMA guidelines, we conducted a comprehensive search in PubMed/Medline, Web of Science, Scopus, and Google Scholar databases without date restrictions, including articles in both Spanish and English. This approach enabled the identification and analysis of primary studies to understand the direct effect of electronic cigarettes on human health. Results: A total of 33 studies were included that evaluated cardiovascular, pulmonary, renal, weight and fertility effects. Only five studies analyzed e-cigarettes in healthy populations and seven studies compared healthy individuals against smokers. The effects evaluated on smokers or former tobacco smokers were apparently positive, however, among healthy individuals, increased heart rate, mean arterial pressure, oxidative stress, alteration of respiratory epithelial cells and increased airflow resistance were found. Conclusion: Smokers or former smokers who switch to e-cigarettes may reduce their exposure to carcinogens and lower their risk of developing severe health issues associated with conventional smoking. However, in healthy individuals who have never smoked traditional cigarettes, the use of e-cigarettes introduces several cardiovascular and respiratory adverse effects. These findings suggest that while e-cigarettes can be a strategic harm reduction tool for smokers, they are not a safe option for non-smokers.

Longitudinal association of exclusive and dual use of cigarettes and cigars with asthma exacerbation among US adults: a cohort study.

BACKGROUND: Cigar use among adults in the United States has remained relatively stable in the past decade and occupies a growing part of the tobacco marketplace as cigarette use has declined. While studies have established the detrimental respiratory health effects of cigarette use, the effects of cigar use need further characterization. In this study, we evaluate the prospective association between cigar use, with or without cigarettes, and asthma exacerbation. METHODS: We used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study to run generalized estimating equation models examining the association between time-varying, one-wave-lagged cigarette and cigar use and self-reported asthma exacerbation among US adults (18+). We defined our exposure as non-established (reference), former, exclusive cigarette, exclusive cigar, and dual use. We defined an asthma exacerbation event as a reported asthma attack in the past 12 months necessitating oral or injected steroid medication or asthma symptoms disrupting sleep at least once a week in the past 30 days. We adjusted for age, sex, race and ethnicity, household income, health insurance, established electronic nicotine delivery systems use, cigarette pack-years, secondhand smoke exposure, obesity, and baseline asthma exacerbation. RESULTS: Exclusive cigarette use (incidence rate ratio (IRR): 1.26, 95% confidence interval (CI): 1.03-1.54) and dual use (IRR: 1.41, 95% CI: 1.08-1.85) were associated with a higher rate of asthma exacerbation compared to non-established use, while former use (IRR: 1.01, 95% CI: 0.80-1.28) and exclusive cigar use (IRR: 0.70, 95% CI: 0.42-1.17) were not. CONCLUSION: We found no association between exclusive cigar use and self-reported asthma exacerbation. However, exclusive cigarette use and dual cigarette and cigar use were associated with higher incidence rates of self-reported asthma exacerbation compared to non-established use. Studies should evaluate strategies to improve cigarette and cigar smoking cessation among adults with asthma who continue to smoke.

An overview of traditional smoking cessation interventions and E-cigarettes.

Many people still struggle with quitting smoking despite available treatment options, making it one of the most significant public health challenges that our society faces. The use of electronic cigarettes (E-cigarettes) has become increasingly popular among people who are seeking to quit smoking. The objective of this review paper is to present a comprehensive analysis of the mechanisms, several types, and impact of E-cigarettes, along with supporting evidence indicating their efficacy in aiding smokers to quit tobacco usage. Additionally, the review discusses recent developments in the treatment of smoking cessation, which include conventional smoking cessation methods. Also, the review discusses the challenges, potential risks, ethical considerations, and controversies surrounding the use of E-cigarettes. The present review presents a comprehensive examination of the existing methods and approaches employed in smoking cessation, including the emerging utilization of E-cigarettes as an effective option in smoking cessation. It explores their efficacy as a valuable instrument in promoting smoking cessation.

Secondhand cannabis smoke exposure and respiratory symptoms among adults living in a state with legalized medical cannabis with limited smoke-free protections.

Background: Little is known about the demographic and health correlates of secondhand cannabis smoke (SHCS) exposure, despite increased availability and use of cannabis across the U.S. This study examined the prevalence and correlates of SHCS exposure in a sample of N=5,410 adults living in Oklahoma and the association of SHCS exposure with self-reported respiratory problems. Methods: Data were from a repeated cross-sectional online survey of adults ages 18 and older who completed measurements of past 30-day SHCS exposure in the respondent's home, in a vehicle, and/or in an indoor setting; harm perceptions of SHCS exposure; frequency of current respiratory symptoms; past 30-day use of cannabis, alcohol, and cigarettes. Results: Almost half (42 %) reported past 30-day SHCS exposure. In bivariate tests, those exposed were male, younger, non-Hispanic (NH) black or Hispanic, reported lower educational and financial attainment, had lower harm perceptions of SHCS exposure, endorsed more respiratory symptoms, and reported past 30-day cannabis and cigarette use (all p's < 0.01). In an adjusted regression model, young adulthood (ages 18-24), NH black race (vs NH White), and past 30-day cigarette smoking and cannabis use emerged as the strongest correlates of SHCS exposure. In interaction models, respiratory symptoms were highest among those reporting past 30-day SHCS exposure and past 30-day cannabis use. Conclusion: SHCS exposure is common and associated with more frequent respiratory symptoms, particularly among cannabis users. Those exposed were more socially and economically vulnerable.

Spatial source, simulating improvement, and short-term health effect of high PM2.5 exposure during mutation event in the key urban agglomeration regions in China.

Air quality in China has significantly improved owing to the effective implementation of pollution control measures. However, mutation events caused by short-term spikes in PM2.5 in urban agglomeration regions continue to occur frequently. Identifying the spatial sources and influencing factors, as well as improving the prediction accuracy of high PM2.5 during mutation events, are crucial for public health. In this study, we firstly introduced discrete wavelet transform (DWT) to identify the mutation events with high PM2.5 concentration in the four key urban agglomerations, and evaluated the spatial sources for the polluted scenario using Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model. Additionally, DWT was combined with a widely used artificial neural network (ANN) to improve the prediction accuracy of PM2.5 concentration seven days in advance (seven-day forecast). Results indicated that mutation events commonly occurred in the northern regions during winter time, which were under the control of both short-range transportation of dirty airmass as well as negative meteorology conditions. Compared with the ANN model alone, the average band errors decreased by 9% when using DWT-ANN model. The average correlation coefficient (R) and root mean square error (RMSE) obtained using the DWT-ANN improved by 10% and 12% compared to those obtained using the ANN, indicating the efficiency and accuracy of simulating PM2.5, by combining the DWT and ANN. The short-term mortality during mutation events was then calculated, with the total averted all-cause, cardiovascular, and respiratory deaths in the four regions, being 4751, 2554, and 582 persons, respectively. A declining trend in prevented deaths from 2018 to 2020 demonstrated that the pollution intensity during mutation events gradually decreased owing to the implementation of the Three-Year Action Plan to Win the Blue Sky Defense War. The method proposed in this study can be used by policymakers to take preventive measures in response to a sudden increase in PM2.5, thereby ensuring public health.

Recent advances of 3-fucosyllactose in health effects and production.

Human milk oligosaccharides (HMOs) have been recognized as gold standard for infant development. 3-Fucosyllactose (3-FL), being one of the Generally Recognized as Safe HMOs, represents a core trisaccharide within the realm of HMOs; however, it has received comparatively less attention in contrast to extensively studied 2'-fucosyllactose. The objective of this review is to comprehensively summarize the health effects of 3-FL, including its impact on gut microbiota proliferation, antimicrobial effects, immune regulation, antiviral protection, and brain maturation. Additionally, the discussion also covers the commercial application and regulatory approval status of 3-FL. Lastly, an organized presentation of large-scale production methods for 3-FL aims to provide a comprehensive guide that highlights current strategies and challenges in optimization.