Current Advances, Research Needs and Gaps in Mycotoxins Biomonitoring under the HBM4EU-Lessons Learned and Future Trends.

Mycotoxins are natural metabolites produced by fungi that contaminate food and feed worldwide. They can pose a threat to human and animal health, mainly causing chronic effects, e.g., immunotoxic and carcinogenic. Due to climate change, an increase in European population exposure to mycotoxins is expected to occur, raising public health concerns. This urges us to assess the current human exposure to mycotoxins in Europe to allow monitoring exposure and prevent future health impacts. The mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1) were considered as priority substances to be studied within the European Human Biomonitoring Initiative (HBM4EU) to generate knowledge on internal exposure and their potential health impacts. Several policy questions were addressed concerning hazard characterization, exposure and risk assessment. The present article presents the current advances attained under the HBM4EU, research needs and gaps. Overall, the knowledge on the European population risk from exposure to DON was improved by using new harmonised data and a newly derived reference value. In addition, mechanistic information on FB1 was, for the first time, organized into an adverse outcome pathway for a congenital anomaly. It is expected that this knowledge will support policy making and contribute to driving new Human Biomonitoring (HBM) studies on mycotoxin exposure in Europe.

Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles-A Systematic Review.

Titanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).

New Alternatives to Milk From Pulses: Chickpea and Lupin Beverages With Improved Digestibility and Potential Bioactivities for Human Health.

There is a strong demand for plant-based milk substitutes, often low in protein content (<1.5% w/v). Protein-rich pulse seeds and the right processing technologies make it possible to make relevant choices. The major objective of this study was to assess the impact of processing on the nutritional characteristics of beverages with a high impact on health, in particular on digestibility and specific bioactivities. The results suggest that pulse beverages are as high in protein content (3.24% w/v for chickpea and 4.05% w/v for lupin) as cow's milk. The anti-nutrient level characteristics of pulses have been considerably reduced by strategic processing. However, when present in small quantities, some of these anti-nutritional factors may have health benefits. Controlling processing conditions play a crucial role in this fine balance as a tool to take advantage of their health benefits. There is evidence of protein hydrolysis by in vitro digestion and limited bioaccessibility of minerals. In addition to being highly digestible, lupin and chickpea beverages have anti-inflammatory and anti-carcinogenic potential evaluated through the inhibition of metalloproteinase MMP-9.

From trihalomethanes chronic daily intake through multiple exposure routes to cancer and non-cancer health risk assessment: Evidence from public Portuguese indoor swimming pools facilities using a probabilistic approach.

This study aimed to estimate chronic daily intake (CDI) and to predict the attributable lifetime cancer risk (LCR) and hazard index (HI) from concurrent exposure to four trihalomethanes (THMs; chloroform, bromodichloromethane, dibromochloromethane and bromoform), via multiple exposure routes (oral ingestion, dermal contact and inhalation), among 238 non-competitive attendees of 10 Portuguese public indoor swimming pools (SPs), using a probabilistic approach based on Monte Carlo simulations. Exposure parameters of study participants were collected via questionnaires and THMs levels in SPs water were determined according the respective normative standards. The CDI for total THMs calculated for male and female participants considering all routes was 7.52 and 8.97 mg/kg/day, respectively. SP attendees presented higher CDI through inhalation than via the other two exposure routes, and chloroform was the compound contributing the most to total THMs CDI. The risk analysis indicated that the total LCR and HI from the targeted THMs were higher than the negligible risk levels (1 × 10-6 and 1, respectively) in the scenarios examined (central tendency exposure and reasonable maximum exposure), and the health risk for females was slightly higher than for males. This study suggests that there are possible adverse health risks, thus, to protect pool attendees, adequate mitigation measures, and comprehensive regulatory guidelines on individual THMs concentrations are needed.

Burden of osteoporosis and costs associated with human biomonitored cadmium exposure in three European countries: France, Spain and Belgium.

Cadmium (Cd) is a toxic heavy metal widespread in the environment leading to human exposure in particular through diet (when smoking is excluded), as documented by recent human biomonitoring (HBM) surveys. Exposure to Cd at environmental low-exposure levels has been associated with adverse effects such as renal toxicity and more recently bone effects. The implication, even if limited, of Cd in the etiology of osteoporosis can be of high importance at the population level given the significant prevalence of osteoporosis and the ubiquitous and life-long exposure to Cd. Therefore, the osteoporosis cases attributable to Cd exposure was estimated in three European countries (Belgium, France and Spain), based on measured urinary Cd levels from HBM studies conducted in these countries. The targeted population was women over 55 years old, for which risk levels associated with environmental Cd exposure were available. Around 23% of the cases were attributed to Cd exposure. Moreover, in a prospective simulation approach of lifelong urinary Cd concentrations assuming different intakes scenarios, future osteoporosis attributable cases were calculated, based on urinary Cd levels measured in women aged under 55. Between 6 and 34% of the considered populations under 55 years were at risk for osteoporosis. Finally, the costs associated to the burden of osteoporosis-related fractures attributable to Cd for each country targeted in this paper were assessed, standing for a major contributing role of Cd exposure in the overall social costs related to osteoporosis. Absolute costs ranged between 0.12 (low estimate in Belgium) and 2.6 billion Euros (high estimate in France) in women currently over 55 years old and at risk for fractures. Our results support the importance of reducing exposure of the general population to Cd.

Drinking Green Tea: Despite the Risks Due to Mycotoxins, Is It Possible to Increase the Associated Health Benefits?

Tea has been consumed for thousands of years. Despite the different varieties, particular emphasis has been placed on green tea (GT), considering the associated health benefits following its regular consumption, some of which are due to its polyphenol constituents, such as epigallocatechin-3-gallate (EGCG). Tea is not prone to the growth of microorganisms, except fungus, when proper storage, handling, and packing conditions are compromised. Consequently, mycotoxins, secondary metabolites of fungi, could contaminate tea samples, affecting human health. In the present study, we aimed to assess the balance between risks (due to mycotoxins and high levels of EGCG) and benefits (due to moderate intake of EGCG) associated with the consumption of GT. For this, 20 GT samples (10 in bulk and 10 in bags) available in different markets in Lisbon were analyzed through a LC-MS/MS method, evaluating 38 different mycotoxins. Six samples revealed detectable values of the considered toxins. Current levels of mycotoxins and EGCG intake were not associated with health concerns. Scenarios considering an increasing consumption of GT in Portugal showed that drinking up to seven cups of GT per day should maximize the associated health benefits. The present study contributes to the future establishment of GT consumption recommendations in Portugal.

Occupational Exposure to Mycotoxins-Different Sampling Strategies Telling a Common Story Regarding Occupational Studies Performed in Portugal (2012-2020).

In occupational settings where exposure to organic dust occurs (e.g., intensive animal production, waste management, farming and many others) workers can also be exposed to mycotoxins. However, recognizing exposure to mycotoxins in workplace environments does not happen commonly and, consequently, remains as a not identified occupational risk factor. In the last decade, work developed in different occupational settings, using different sampling approaches reported that occupational exposure to mycotoxins occurs and it's of upmost importance to be seen as an occupational concern that needs to be tackled. This paper intends to discuss the several possibilities available for assessing and characterizing the occupational exposure to mycotoxins through the description of the advantages and limitations of the different sampling strategies. Overviewing the approaches and the main achievements used in several field campaigns developed in Portugal, the knowledge obtained will be used to support the identification of the main aspects to consider when designing new occupational studies. The need for additional research work will also be discussed where new directions to follow will be debated.

Food Consumption Data as a Tool to Estimate Exposure to Mycoestrogens.

Zearalenone and alternariol are mycotoxins produced by Fusarium and Alternaria species, respectively, that present estrogenic activity and consequently are classified as endocrine disruptors. To estimate the exposure of the Portuguese population to these two mycotoxins at a national level, a modelling approach, based on data from 94 Portuguese volunteers, was developed considering as inputs: i) the food consumption data generated within the National Food and Physical Activity Survey; and ii) the human biomonitoring data used to assess the exposure to the referred mycotoxins. Six models of association between mycoestrogens urinary levels (zearalenone, total zearalenone and alternariol) and food items (meat, cheese, and fresh-cheese, breakfast cereals, sweets) were established. Applying the obtained models to the consumption data (n = 5811) of the general population, the median estimates of the probable daily intake revealed that a fraction of the Portuguese population might exceed the tolerable daily intake defined for zearalenone. A reference intake value for alternariol is still lacking, thus the characterization of risk due to the exposure to this mycotoxin was not possible to perform. Although the unavoidable uncertainties, these results are important contributions to understand the exposure to endocrine disruptors in Portugal and the potential Public Health consequences.

Occupational Exposure to Mycotoxins in Swine Production: Environmental and Biological Monitoring Approaches.

Swine production workers are exposed simultaneously to multiple contaminants. Occupational exposure to aflatoxin B1 (AFB1) in Portuguese swine production farms has already been reported. However, besides AFB1, data regarding fungal contamination showed that exposure to other mycotoxins could be expected in this setting. The present study aimed to characterize the occupational exposure to multiple mycotoxins of swine production workers. To provide a broad view on the burden of contamination by mycotoxins and the workers' exposure, biological (urine) samples from workers (n = 25) and 38 environmental samples (air samples, n = 23; litter samples, n = 5; feed samples, n = 10) were collected. The mycotoxins biomarkers detected in the urine samples of the workers group were the deoxynivalenol-glucuronic acid conjugate (60%), aflatoxin M1 (16%), enniatin B (4%), citrinin (8%), dihydrocitrinone (12%) and ochratoxin A (80%). Results of the control group followed the same pattern, but in general with a lower number of quantifiable results (

Climate change and the health impact of aflatoxins exposure in Portugal - an overview.

Climate change has been indicated as a driver for food safety issues worldwide, mainly due to the impact on the occurrence of food safety hazards at various stages of food chain. Mycotoxins, natural contaminants produced by fungi, are among the most important of such hazards. Aflatoxins, which have the highest acute and chronic toxicity of all mycotoxins, assume particular importance. A recent study predicted aflatoxin contamination in maize and wheat crops in Europe within the next 100 years and aflatoxin B1 is predicted to become a food safety issue in Europe, especially in the most probable scenario of climate change (+2°C). This review discusses the potential influence of climate change on the health risk associated to aflatoxins dietary exposure of Portuguese population. We estimated the burden of disease associated to the current aflatoxin exposure for Portuguese population in terms of Disability Adjusted Life Years (DALYs). It is expected that in the future the number of DALYs and the associated cases of hepatocellular carcinoma due to aflatoxins exposure will increase due to climate change. The topics highlighted through this review, including the potential impact on health of the Portuguese population through the dietary exposure to aflatoxins, should represent an alert for the potential consequences of an incompletely explored perspective of climate change. Politics and decision-makers should be involved and committed to implement effective measures to deal with climate change issues and to reduce its possible consequences. This review constitutes a contribution for the prioritisation of strategies to face the unequal burden of effects of weather-related hazards in Portugal and across Europe.

Assessment of multiple mycotoxins in breakfast cereals available in the Portuguese market.

Mycotoxins are secondary metabolites of fungi that cause toxic and carcinogenic effects. Human exposure to multiple mycotoxins constitutes an increasing health concern due to potential mycotoxins combined effects. The presence of mycotoxins mixtures in foodstuffs as cereals has been reported over the last years, but few studies are available concerning its occurrence in cereals primarily marketed for children, a particular vulnerable population group. The present study aims to assess the co-occurrence of twenty-one mycotoxins and metabolites present in breakfast cereals primarily marketed for children in Portugal. Results showed that 96% of the analysed breakfast cereal samples were contaminated with several mycotoxins. Twenty-two combinations were identified including two to seven different mycotoxins. Conclusions pointed out an urgent need to review legislative limits in food matrices consumed by children and to perform a more accurate risk assessment of children's exposure to mycotoxins mixtures in food.

Patulin and ochratoxin A co-occurrence and their bioaccessibility in processed cereal-based foods: A contribution for Portuguese children risk assessment.

Patulin (PAT) and ochratoxin A (OTA) are well known enteropathogenic mycotoxins that are present in several foodstuffs. Processed cereal-based foods are among the first solid foods eaten by children, a particularly vulnerable population group. There is a lack of knowledge related to the co-occurrence of PAT and OTA in food intended for children consumption and their potential interactions during the digestion process. The present study aims to evaluate, for the first time, the co-occurrence of PAT and OTA in processed cereal-based foods for children consumption, the bioaccessibility of these two mycotoxins, and the contribution of the bioaccessibility data for human health risk assessment. PAT and OTA incidence were 75% and 50%, respectively. These mycotoxins co-occurred in 40% of analysed samples. Bioaccessibility assays revealed mean values of 52% and 56% for PAT, alone and combined with OTA; and 100% and 106% for OTA, alone and combined with PAT. Considering the human health risk assessment, and taking into account the co-occurrence and the bioaccessibility results, this study indicates a tolerable exposure to these mycotoxins representing a low risk for Portuguese children. The present work reinforces the importance of a holistic approach for risk assessment which gathers data from occurrence, exposure and bioaccessibility.

Applicability of in vitro methods to study patulin bioaccessibility and its effects on intestinal membrane integrity.

In human health risk assessment, ingestion of food is considered a major route of exposure to many contaminants, although the total amount of an ingested contaminant (external dose) does not always reflect the quantity available for the body (internal dose). In this study, two in vitro methods were applied to study bioaccessibility and intestinal membrane integrity of cells exposed to patulin, a mycotoxin with significant public health risk. Seven artificially contaminated fruit juices were assayed in the presence or absence of a standard meal, showing a significant difference for bioaccessibility values between contaminated samples alone (mean 27.65 ± 13.50%) and combinations with a standard meal (mean 7.89 ± 4.03%). Different concentrations of patulin (PAT) and cysteine (CYS) (protector agent) were assayed in Caco-2 cells monolayers. At 95 µM, PAT produced a marked decrease in transepithelial electrical resistance (TEER). This effect was significantly reduced when 400 µM and 4000 µM CYS was added to the cells. Combined use of in vitro digestion models with other techniques using intestinal cell lines, such as in vitro intestinal absorption models that use Caco-2 cells, may offer a more comprehensive model of what is occurring during digestion and absorption processes. The study of beneficial effects of protective agents would also be enhanced.

Uso de próteses em cirurgia ginecológica: o estado da arte / Use of protheses in gynecological surgery: state of the art

A escolha de materiais biocompatíveis sintéticos sofreu grande evolução. Os tecidos encontrados hoje no mercado são extremamente atraentes porque reduzem tanto o tempo de operação quanto o desconforto do paciente. Não há incisão adicional, e o tempo de internação hospitalar também é reduzido. Os resultados de operações mostram-se muito promissores utilizando-se estes materiais. São comparáveis aos resultados de cirurgias clássicas em seguimento de curto e longo prazo

Ligadura da artéria hipogástrica: alternativa nas hemorragias ginecológicas incontroláveis / Hypogastric artery ligation: alternative in the uncontrollable gynecological hemorrhages

O objetivo deste trabalho é mostrar a importância da ligadura da artéria hipogástrica no tratamento das hemorragias ginecológicas incontroláveis. Os autores fazem uma revisão da base anatômica, fisiopatológica e técnica do método. Além disso, são explicadas as situações nas quais este procedimento deve ser realizado