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.

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.

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.

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.

Potential human health risk of the emerging environmental contaminant 6-PPD quinone.

The tire antioxidant 6-PPD has been widely used to enhance tire performance and extend tire lifespan. 6-PPD quinone (6-PPDQ), a quinone derivative derived from 6-PPD in the presence of ozone, has been recognized an emerging environmental contaminant. In addition to causing acute lethality to coho salmon, 6-PPDQ exhibits toxic effects on other aquatic species and mammals. Based on the existing evidence, we provide a critical overview on the human internal exposure, potential adverse effects on health, and prediction of human health risk of 6-PPDQ. 6-PPDQ could be detected in human samples, including human urine, blood, and cerebrospinal fluid. Human exposure to 6-PPDQ in the environment is inevitable and may lead to adverse health effects, including hepatotoxicity, enterotoxicity, pulmonary toxicity, neurotoxicity, reproductive toxicity, and cardiotoxicity. Additionally, potential human health risk to 6-PPDQ through exposure routes and human samples were predicted. This review is helpful to identify the existing knowledge gaps and future research directions regarding the human health effects of 6-PPDQ.

Scientific opinion on the tolerable upper intake level for preformed vitamin A and ß-carotene.

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and ß-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether ß-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 µg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 µg RE/day (infants 4-11 months) and 2600 µg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental ß-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that ß-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing ß-carotene. The use of supplemental ß-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

Adverse human health effects of climate change: an update.

Background: The world is currently facing a process of climate change, which may adversely impact human health in many different ways. The safety of food, water and urban environments is endangered by the consequences of climate change. Sea level and temperature rise, along with more frequent and longer heat waves, represent only a few of the effects of climate change. The increased risk of extreme climate events (e.g., cyclones, droughts and floods) is another serious public health issue. These adverse effects are enhanced in areas and countries not having the capacity to effectively deal with climate change. Study design: We primarily aimed at summarizing the impacts of climate change on public health. A further aim was to identify the most concerning consequences of this phenomenon and the vulnerability factors that amplify the negative effects of climate change. Methods: PubMed and other literature databases were used as literature sources for this narrative review based on the search terms 'climate change' and 'diseases categories' up to January 2024, in order to assess the most recent and relevant scientific evidence about the relation between climate change and public health, identify knowledge gaps and priorities for future research. We also screened the websites of major agencies devoted to human health protection and environmental health. Results and Conclusions: Climate change appears to induce a broad spectrum of generally adverse effects on public health. It may increase the risk of infectious diseases, psychiatric disorders, cancer and other diseases. Currently, we are not effectively counteracting this phenomenon, since pollutant and greenhouse gas emissions have been increasing alongside temperatures. A host of measures are required in order to prevent and fight climate change and related health effects. These include the adoption of a holistic approach and the collaboration of different kinds of expertise in order to design more effective strategies. Special attention should be paid to those who live in disadvantaged countries, and those who are more vulnerable to the adverse health consequences of climate change.

Time-integrated radiation risk metrics and interpopulation variability of survival.

Task Group 115 of the International Commission on Radiological Protection is focusing on mission-related exposures to space radiation and concomitant health risks for space crew members including, among others, risk of cancer development. Uncertainties in cumulative radiation risk estimates come from the stochastic nature of the considered health outcome (i.e., cancer), uncertainties of statistical inference and model parameters, unknown secular trends used for projections of population statistics and unknown variability of survival properties between individuals or population groups. The variability of survival is usually ignored when dealing with large groups, which can be assumed well represented by the statistical data for the contemporary general population, either in a specific country or world averaged. Space crew members differ in many aspects from individuals represented by the general population, including, for example, their lifestyle and health status, nutrition, medical care, training and education. The individuality of response to radiation and lifespan is explored in this modelling study. Task Group 115 is currently evaluating applicability and robustness of various risk metrics for quantification of radiation-attributed risks of cancer for space crew members. This paper demonstrates the impact of interpopulation variability of survival curves on values and uncertainty of the estimates of the time-integrated radiation risk of cancer.

Microbial approaches for pharmaceutical wastewater recycling and management for sustainable development: A multicomponent approach.

A microbial-driven approach for effluent treatment, recycling, and management of Pharmaceutical and Personal Care Products (PPCPs) has been undertaken to mitigate the menace of water contamination. Bioremediation processes are mainly considered the first preference in pharmaceutical wastewater recycling and management. PPCPs are reported as one of the primary sources of emerging contaminants in various water matrices, which raises concern and requires efficient management. Their widespread utilization, persistently high level, and resistance to breaking down make them one of the potentially dangerous compounds causing harm to the ecosystem. Continually increasing PPCPs level PPCPs contaminants in water bodies raised concern for human health as they can produce potential risks with harmful and untoward impacts on our health. PPCPs are composed of multiple diverse compounds used by humans and animals, which include biopharmaceuticals, vitamins and nutritional supplements, antibiotics, counter-prescription drugs, cosmetics products, and unused pharmaceutical products. Personal care products are found to be bioaccumulative, reduce water quality and potentially impact ecological health. However, continual exposure to PPCPs in aquatic organisms, impacts their endocrine function disruption, gene toxicity, and antibiotic resistance. Decreased water quality may result in an outbreak of various water-borne diseases, which could have acute or long-term health complications and may result in an outbreak of various water-borne diseases, which could have acute or long-term effects on public and community health. Polluted water consumption by humans and animals produces serious health hazards and increased susceptibility to water-borne diseases such as carcinogenic organic or inorganic contaminants and infectious pathogens present in water bodies. Many water resource recovery facilities working on various conventional and advanced methods involve the utilization of microbes for filtration and advanced oxidation processes. Therefore, there is an immense need for bioremediation techniques facilitated by mixed cultures of bacteria, algae, and other microbes that can be used as an alternative approach for removing pharmaceutical content from effluent. This review highlights the various sources of PPCPs and their impacts on soil and water bodies, resulting in bioaccumulation. Different techniques are utilized to detect PPCPs, and various control strategies imply controlling, recycling, and managing waste.

Effects of aircraft noise cessation on blood pressure, cardio- and cerebrovascular endothelial function, oxidative stress, and inflammation in an experimental animal model.

Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects of noise may persist in response to a noise-off period. We investigated the effects of acute aircraft noise exposure (mean sound level of 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction and increased blood pressure in male C57BL/6 J mice. 1, 2 or 4d of noise cessation after a 4d continuous noise exposure period completely normalized noise-induced endothelial dysfunction of the aorta (measured by acetylcholine-dependent relaxation) already after a 1d noise pause. Vascular oxidative stress and the increased blood pressure were partially corrected, while markers of inflammation (VCAM-1, IL-6 and leukocyte oxidative burst) showed a normalization within 4d of noise cessation. In contrast, endothelial dysfunction, oxidative stress, and inflammation of the cerebral microvessels of noise-exposed mice did not improve at all. These data demonstrate that the recovery from noise-induced damage is more complex than expected demonstrating a complete restoration of large conductance vessel function but persistent endothelial dysfunction of the microcirculation. These findings also imply that longer noise pauses are required to completely reverse noise-induced vascular dysfunction including the resistance vessels.

Counseling Patients with Chronic Obstructive Pulmonary Disease Traveling to High Altitude.

Bloch, Konrad E., Talant M. Sooronbaev, Silvia Ulrich, Mona Lichtblau, and Michael Furian. Clinician's corner: counseling patients with chronic obstructive pulmonary disease traveling to high altitude. High Alt Med Biol. 24:158-166, 2023.-Mountain travel is increasingly popular also among patients with chronic obstructive pulmonary disease (COPD), a highly prevalent condition often associated with cardiovascular and systemic manifestations. Recent studies have shown that nonhypercapnic and only mildly hypoxemic lowlanders with moderate to severe airflow obstruction owing to COPD experience dyspnea, exercise limitation, and sleep disturbances when traveling up to 3,100 m. Altitude-related adverse health effects (ARAHE) in patients with COPD include severe hypoxemia, which may be asymptomatic but expose patients to the risk of excessive systemic and pulmonary hypertension, cardiac arrhythmia, and even myocardial or cerebral ischemia. In addition, hypobaric hypoxia may impair postural control, psycho-motor, and cognitive performance in patients with COPD during altitude sojourns. Randomized, placebo-controlled trials have shown that preventive treatment with oxygen at night or with acetazolamide reduces the risk of ARAHE in patients with COPD while preventive dexamethasone treatment improves oxygenation and altitude-induced excessive sleep apnea, and lowers systemic and pulmonary artery pressure. This clinical review provides suggestions for pretravel assessment and preparations and measures during travel that may reduce the risk of ARAHE and contribute to pleasant mountain journeys of patients with COPD.

Occurrence of meso/micro/nano plastics and plastic additives in food from food packaging.

This chapter focuses on the occurrence of plastic constituents in food due to the contact with different types of plastic packaging, films and coatings. The type of mechanisms occurring during the contamination of food by different packaging materials are described, as well as how the type of food and packaging may influences the extent of contamination. The main types of contaminants phenomena are considered and comprehensively discussed, along with the regulations in force for the use of plastic food packaging. In addition, the types of migration phenomena and factors that may influence such migration are comprehensively highlighted. Moreover, migration components related to the packaging polymers (monomers and oligomers) and the packaging additives are individually discussed in terms of chemical structure, adverse effects on foodstuffs, health, migration factors, as well as regulated residual values of such components.

Adverse health effects of emerging contaminants on inflammatory bowel disease.

Inflammatory bowel disease (IBD) is becoming increasingly prevalent with the improvement of people's living standards in recent years, especially in urban areas. The emerging environmental contaminant is a newly-proposed concept in the progress of industrialization and modernization, referring to synthetic chemicals that were not noticed or researched before, which may lead to many chronic diseases, including IBD. The emerging contaminants mainly include microplastics, endocrine-disrupting chemicals, chemical herbicides, heavy metals, and persisting organic pollutants. In this review, we summarize the adverse health effect of these emerging contaminants on humans and their relationships with IBD. Therefore, we can better understand the impact of these new emerging contaminants on IBD, minimize their exposures, and lower the future incidence of IBD.

Comprehensive insight into triclosan-from widespread occurrence to health outcomes.

Humans are exposed to the variety of emerging environmental pollutant in everyday life. The special concern is paid to endocrine disrupting chemicals especially to triclosan which could interfere with normal hormonal functions. Triclosan could be found in numerous commercial products such as mouthwashes, toothpastes and disinfectants due to its antibacterial and antifungal effects. Considering the excessive use and disposal, wastewaters are recognized as the main source of triclosan in the aquatic environment. As a result of the incomplete removal, triclosan residues reach surface water and even groundwater. Triclosan has potential to accumulate in sediment and aquatic organisms. Therefore, the detectable concentrations of triclosan in various environmental and biological matrices emerged concerns about the potential toxicity. Triclosan impairs thyroid homeostasis and could be associated with neurodevelopment impairment, metabolic disorders, cardiotoxicity and the increased cancer risk. The growing resistance of the vast groups of bacteria, the evidenced toxicity on different aquatic organisms, its adverse health effects observed in vitro, in vivo as well as the available epidemiological studies suggest that further efforts to monitor triclosan toxicity at environmental levels are necessary. The safety precaution measures and full commitment to proper legislation in compliance with the environmental protection are needed in order to obtain triclosan good ecological status. This paper is an overview of the possible negative triclosan effects on human health. Sources of exposure to triclosan, methods and levels of detection in aquatic environment are also discussed.

Effect of altitude and acetazolamide on postural control in healthy lowlanders 40 years of age or older. Randomized, placebo-controlled trial.

Background: Hypoxia and old age impair postural control and may therefore enhance the risk of accidents. We investigated whether acetazolamide, the recommended drug for prevention of acute mountain sickness, may prevent altitude-induced deterioration of postural control in older persons. Methods: In this parallel-design trial, 95 healthy volunteers, 40 years of age or older, living <1,000 m, were randomized to preventive therapy with acetazolamide (375 mg/d) or placebo starting 24 h before and during a 2-day sojourn at 3,100 m. Instability of postural control was quantified by a balance platform with the center of pressure path length (COPL) as primary outcome while pulse oximetry (SpO2) was monitored. Effects of altitude and treatment on COPL were evaluated by ordered logistic regression. www.ClinicalTrials.gov NCT03536429. Results: In participants taking placebo, ascent from 760 m to 3,100 m increased median COPL from 25.8 cm to 27.6 cm (odds ratio 3.80, 95%CI 2.53-5.70) and decreased SpO2 from 96% to 91% (odds ratio 0.0003, 95%CI 0.0002-0.0007); in participants taking acetazolamide, altitude ascent increased COPL from 24.6 cm to 27.3 cm (odds ratio 2.22, 95%CI 1.57-3.13), while SpO2 decreased from 96% to 93% (odds ratio 0.007, 95%CI 0.004-0.012). Altitude-induced increases in COPL were smaller with acetazolamide vs. placebo (odds ratio 0.58, 95%CI 0.34-0.99) while drops in SpO2 were mitigated (odds ratio 19.2, 95%CI 9.9-37.6). Conclusion: In healthy individuals, 40 years of age or older, postural control was impaired after spending a night at 3,100 m. The altitude-induced deterioration of postural control was mitigated by acetazolamide, most likely due to the associated improvement in oxygenation.

Long-term effects of caesarean delivery on health and behavioural outcomes of the mother and child in Bangladesh.

BACKGROUND: Medically unnecessary caesarean section (CS) is now an ongoing concern worldwide including in Bangladesh. This intensifies the occurrence of adverse maternal and child health outcomes. We investigated the associations of CS with some basic health and behavioural outcomes of the mothers and their children in Bangladesh. METHODS: We conducted a community-based case-control study from May to August 2019. A total of 600 mother-child dyads were interviewed using a structured questionnaire, 300 of them had CS, and 300 had vaginal delivery (VD) in their most recent live births. The exposure variable was the mode of delivery, classified as 1 if mothers had CS and 0 if mothers had VD. The outcome variables were a group of health and behavioural problems of the mothers and their children. Multivariate or multiple logistic regression model, separately for each health and behavioural outcome, was used to determine the effect of exposure variable on outcome variable after adjusting for possible confounders. RESULTS: The mean age and weight of mothers were 25.1 years and 53.1 kg, respectively. Likelihoods of headache, after delivery hip pain, problem of daily activities, and breastfeeding problem were reported higher among mothers who had CS in their most recent live birth than mothers who had VD. Similarly, children who were born through the CS operation were more likely to report breathing problem, frequent illness, lower food demand and lower hours of sleeping. CONCLUSION: The use of CS increases the risks of health and behavioural problems of the mothers and their children. Policies and programs to avoid medically unnecessary CS and increase awareness over its adverse effects are important.

Designing a Surveillance System to Monitor the Adverse Health Effect of Environmental Disasters: A Case Study of Drying Lake Urmia-Iran.

Background: Through designing a surveillance system, steps to policy making and designing measures needed to reduce the potential risks of environmental disasters on human health could be taken. Therefore, this study aimed to develop a model for Environmental Disasters Diseases Surveillance System (EDDS) to monitor Adverse Health Effects (AHEs) of Environmental Disasters (AHEEDs). Methods: As the first step, the literature review was conducted to identify the AHEEDs. Then, using the results of the first step and analyzing the existing documents, the AHEEDs were identified, and, based on the experts' opinions, high-priority effects were included in the EDDS. Then, using semi-structured interviews, 20 experts' views on the appropriate model of EDDS were investigated. To design the initial model, a panel of experts was formed with six participants. Finally, the Delphi technique was used for expert opinion and model finalization. Results: As a result of the literature review and document analysis, 41 hazards/diseases were identified. Finally, ten diseases were suggested to enter the EDDS. In the experts' view, it is better that communicable diseases be reported actively and urgently and Non-Communicable Diseases (NCD) actively and non-urgently. From the participants' point of view, the most significant achievements of the EDDS can be organizational and managerial, health promotion, and economic achievements. Conclusion: Developing a dedicated EDDS for AHEEDs can be very helpful for better management of these effects. To this end, the model proposed in this study can serve as a guide for national and local policymakers to implement surveillance systems for AHEEDs.

Clinician's Corner: Counseling Patients with Pulmonary Vascular Disease Traveling to High Altitude.

Ulrich, Silvia, Mona Lichtblau, Simon R. Schneider, Stéphanie Saxer, and Konrad E. Bloch, Clinician's corner: counseling patients with pulmonary vascular disease traveling to high altitude. High Alt Med Biol. 23:201-208, 2022.-Pulmonary vascular diseases (PVDs) with precapillary pulmonary hypertension (PH), such as pulmonary arterial or chronic thromboembolic PH, impair exercise performance and survival in patients. Vasodilators and other treatments improve quality of life and prognosis to an extent in patients who have PVDs as chronic disorders. Obviously, patients with PVD wish to participate in usual daily activities, including travel to popular settlements and mountainous regions located at high altitude. However, the pulmonary hemodynamic impairment due to PVD leads to blood and tissue hypoxia, particularly during exercise and sleep. It is thus of concern that alveolar hypoxia at higher altitude may exacerbate patients' symptoms and lead to decompensation. Current PH guidelines discourage high-altitude exposure for fear of altitude-related adverse health effects. However, several recent well-designed prospective and randomized trials show that despite altitude-induced hypoxemia, pulmonary hemodynamic changes and impairment of exercise performance in patients with PVD are similar to the responses in healthy people or in patients with mild chronic obstructive pulmonary disease. The vast majority of patients with PVD can tolerate short-term exposure to moderate altitudes up to 2,500 m. For the roughly 10% of patients with stable disease who develop severe hypoxemia when ascending to 2,500 m, they respond well to low-level supplemental oxygen support. The best low-altitude predictors for adverse health effects at high altitude are the known clinical risk factors for PVD such as symptoms, functional class, exercise capacity, and exertional oxygen desaturation, whereas hypoxia altitude simulation testing is of little additive value. In any case, patients should be instructed that altitude-related adverse health effects may be difficult to predict and that in case of worsening symptoms, immediate accompanied descent to lower altitude and oxygen therapy are required. Patients with severe hypoxemia near sea level may safely visit high-altitude regions up to 1,500-2,000 m while continuing oxygen therapy and avoiding strenuous exercise. All PH patients should be counseled before any high-altitude sojourn by doctors with experience in PVD and high-altitude medicine and have an action plan for the occurrence of severe hypoxemia and other altitude-related conditions such as acute mountain sickness.

1,3-Butadiene: a ubiquitous environmental mutagen and its associations with diseases.

1,3-Butadiene (BD) is a petrochemical manufactured in high volumes. It is a human carcinogen and can induce lymphohematopoietic cancers, particularly leukemia, in occupationally-exposed workers. BD is an air pollutant with the major environmental sources being automobile exhaust and tobacco smoke. It is one of the major constituents and is considered the most carcinogenic compound in cigarette smoke. The BD concentrations in urban areas usually vary between 0.01 and 3.3 µg/m3 but can be significantly higher in some microenvironments. For BD exposure of the general population, microenvironments, particularly indoor microenvironments, are the primary determinant and environmental tobacco smoke is the main contributor. BD has high cancer risk and has been ranked the second or the third in the environmental pollutants monitored in most urban areas, with the cancer risks exceeding 10-5. Mutagenicity/carcinogenicity of BD is mediated by its genotoxic metabolites but the specific metabolite(s) responsible for the effects in humans have not been determined. BD can be bioactivated to yield three mutagenic epoxide metabolites by cytochrome P450 enzymes, or potentially be biotransformed into a mutagenic chlorohydrin by myeloperoxidase, a peroxidase almost specifically present in neutrophils and monocytes. Several urinary BD biomarkers have been developed, among which N-acetyl-S-(4-hydroxy-2-buten-1-yl)-L-cysteine is the most sensitive and is suitable for biomonitoring BD exposure in the general population. Exposure to BD has been associated with leukemia, cardiovascular disease, and possibly reproductive effects, and may be associated with several cancers, autism, and asthma in children. Collectively, BD is a ubiquitous pollutant that has been associated with a range of adverse health effects and diseases with children being a subpopulation with potentially greater susceptibility. Its adverse effects on human health may have been underestimated and more studies are needed.

Shifting the Paradigm on Cannabis Safety.

The global movement toward legalization of cannabis is resulting in an ever-increasing public perception that cannabis is safe. Cannabis is not the first drug to be available for nonmedical use, nor is it the first to have such an unfounded safety profile. The safety of long-term exposure to phytocannabinoids is misunderstood by, and under reported to, the general public. There is evidence to suggest that long-term use of recreational cannabis may be associated with an increased risk of undesirable side effects. This evidence warrants both appropriate caution from the general public and investment in further research by government and industry sectors that are profiting from the sale of these potent psychoactive agents. There is no doubt that these compounds have medical potential. However, in addition to the medical potential, we must also remain aware of the adverse health effects that are becoming synonymous with recreational cannabis use. This perspective highlights the privileged role that cannabis has as a perceived "safe drug" in society and summarizes some concerning side effects that are becoming associated with regular nonprescribed cannabis use.