Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.

Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

Hypothalamic inflammation and the development of an obese phenotype induced by high-fat diet consumption is exacerbated in alpha7 nicotinic cholinergic receptor knockout mice.

Hypothalamic inflammation and metabolic changes resulting from the consumption of high-fat diets have been linked to low grade inflammation and obesity. Inflammation impairs the hypothalamic expression of α7 nicotinic acetylcholine receptor (α7nAChR). The α7nAChR is described as the main component of the anti-inflammatory cholinergic pathway in different inflammation models. To assess whether the reduction in α7nAChR expression exacerbates hypothalamic inflammation induced by a high-fat diet (HFD), were used male and female global α7nAChR knockout mouse line in normal or high-fat diet for 4 weeks. Body weight gain, adiposity, glucose homeostasis, hypothalamic inflammation, food intake, and energy expenditure were evaluated. Insulin sensitivity was evaluated in neuronal cell culture. Consumption of an HFD for 4 weeks resulted in body weight gain and adiposity in male Chrna7-/- mice and the hypothalamus of male Chrna7-/- mice showed neuroinflammatory markers, with increased gene expression of pro-inflammatory cytokines and dysregulation in the nuclear factor kappa B pathway. Moreover, male Chrna7-/- mice consuming an HFD showed alterations in glucose homeostasis and serum of Chrna7-/- mice that consumed an HFD impaired insulin signalling in neuronal cell culture experiments. In general, female Chrna7-/- mice that consumed an HFD did not show the phenotypic and molecular changes found in male mice, indicating that there is sexual dimorphism in the analysed parameters. Thus, receptor deletion resulted in increased susceptibility to hypothalamic inflammation and metabolic damage associated with HFD consumption in male mice.

Blimp-1 signaling pathways in T lymphocytes is essential to control the Trypanosoma cruzi infection-induced inflammation.

In many infectious diseases, the pathogen-induced inflammatory response could result in protective immunity that should be regulated to prevent tissue damage and death. In fact, in Trypanosoma cruzi infection, the innate immune and the inflammatory response should be perfectly controlled to avoid significant lesions and death. Here, we investigate the role of Blimp-1 expression in T cells in resistance to T. cruzi infection. Therefore, using mice with Blimp-1 deficiency in T cells (CKO) we determined its role in the controlling parasites growth and lesions during the acute phase of infection. Infection of mice with Blimp-1 ablation in T cells resulted failure the cytotoxic CD8+ T cells and in marked Th1-mediated inflammation, high IFN-γ and TNF production, and activation of inflammatory monocyte. Interestingly, despite high nitric-oxide synthase activation (NOS-2), parasitemia and mortality in CKO mice were increased compared with infected WT mice. Furthermore, infected-CKO mice exhibited hepatic lesions characteristic of steatosis, with significant AST and ALT activity. Mechanistically, Blimp-1 signaling in T cells induces cytotoxic CD8+ T cell activation and restricts parasite replication. In contrast, Blimp-1 represses the Th1 response, leading to a decreased monocyte activation, less NOS-2 activation, and, consequently preventing hepatic damage and dysfunction. These data demonstrate that T. cruzi-induced disease is multifactorial and that the increased IFN-γ, NO production, and dysfunction of CD8+ T cells contribute to host death. These findings have important implications for the design of potential vaccines against Chagas disease.

Hypothalamic α7 nicotinic acetylcholine receptor (α7nAChR) is downregulated by TNFα-induced Let-7 overexpression driven by fatty acids.

The α7nAChR is crucial to the anti-inflammatory reflex, and to the expression of neuropeptides that control food intake, but its expression can be decreased by environmental factors. We aimed to investigate whether microRNA modulation could be an underlying mechanism in the α7nAchR downregulation in mouse hypothalamus following a short-term exposure to an obesogenic diet. Bioinformatic analysis revealed Let-7 microRNAs as candidates to regulate Chrna7, which was confirmed by the luciferase assay. Mice exposed to an obesogenic diet for 3 days had increased Let-7a and decreased α7nAChR levels, accompanied by hypothalamic fatty acids and TNFα content. Hypothalamic neuronal cells exposed to fatty acids presented higher Let-7a and TNFα levels and lower Chrna7 expression, but when the cells were pre-treated with TLR4 inhibitor, Let-7a, TNFα, and Chrna7 were rescued to normal levels. Thus, the fatty acids overload trigger TNFα-induced Let-7 overexpression in hypothalamic neuronal cells, which negatively regulates α7nAChR, an event that can be related to hyperphagia and obesity predisposition in mice.

NKG2D promotes CD8 T cell-mediated cytotoxicity and is associated with treatment failure in human cutaneous leishmaniasis.

Cutaneous leishmaniasis exhibits a spectrum of clinical presentations dependent upon the parasites' persistence and host immunopathologic responses. Although cytolytic CD8 T cells cannot control the parasites, they significantly contribute to pathologic responses. In a murine model of cutaneous leishmaniasis, we previously found that NKG2D plays a role in the ability of cytolytic CD8 T cells to promote disease in leishmanial lesions. Here, we investigated whether NKG2D plays a role in human disease. We found that NKG2D and its ligands were expressed within lesions from L. braziliensis-infected patients and that IL-15 and IL-1ß were factors driving NKG2D and NKG2D ligand expression, respectively. Blocking NKG2D reduced degranulation by CD8 T cells in a subset of patients. Additionally, our transcriptional analysis of patients' lesions found that patients who failed the first round of treatment exhibited higher expression of KLRK1, the gene coding for NKG2D, than those who responded to treatment. These findings suggest that NKG2D may be a promising therapeutic target for ameliorating disease severity in cutaneous leishmaniasis caused by L. braziliensis infection.

Assessing color cues of development, breeding status and reproductive condition in captive golden lion tamarins (Leontopithecus rosalia).

Color signals play an important role in intraspecific communication and are well studied in catarrhine primates, which exhibit uniform trichromatic vision that is well suited to detecting such signals. Platyrrhine primates exhibit polymorphic color vision with different individuals possessing different color vision types in most species. Intriguingly, some platyrrhine species exhibit bare faces, which are convergent with those of catarrhines. However, putative functions of bare-faced color signals in platyrrhines remain largely unexplored. We measured facial skin color of five captive golden lion tamarins (Leontopithecus rosalia) using color-calibrated digital photography and modeled these colors to the visual systems of the species. Our results show that facial coloration is different between infant and older adults and varies across reproductive condition, but not between breeding and nonbreeding adults. While preliminary, our study suggests that facial coloration may be involved in sociosexual signaling in golden lion tamarins, and provides intriguing evidence that we hope might stimulate more studies of bare-faced signaling in platyrrhines.

A decade of Zoology Summer Course: impressions and impacts of the first university extension course on Zoology in Brazil / Uma década de Curso de Verão em Zoologia: impressões e impactos do primeiro curso de extensão universitária sobre Zoologia no Brasil

Although the diversity of animal groups distributed in Brazil provides countless research opportunities, the current scenario does not follow this demand. The reasons for the disconnections range from inequality in the availability of resources for teaching and research to the focus of researchers on specific groups of animals, while others remain neglected. Training new potential Brazilian researchers interested in Zoology is essential for a greater understanding of this diversity, as well as exposing those potential new researchers to new groups and different work possibilities. Thus, the Summer Course in Zoology (in Portuguese, CVZoo) promoted by the Graduate Program in Zoology at the University of São Paulo, over the last ten years, has been seeking to contribute to this training of new researchers in the field of Zoology, as well as in updating teachers through university extension activities. In order to assess the impacts caused by CVZoo on the academic and professional training of the participants, Google forms were sent to participants in the ten editions of the course, as well as compiled information available on the Lattes Platform. Qualitative and quantitative analyses showed the profile of graduates, their expectations, and perceptions about the course. Based on these data, we demonstrate the CVZoo's efficiency in popularizing Zoology throughout the country in contributing to the decentralization of knowledge as well as in meeting the urgent concerns of making access to knowledge more egalitarian and socially fair.

Embora a diversidade de grupos de animais existentes no Brasil ofereça inúmeras oportunidades de estudo, o cenário atual não acompanha essa demanda. Os motivos para essa desconexão vão desde a desigualdade na disponibilidade de recursos para ensino e pesquisa até o foco de pesquisadores em grupos específicos de animais, enquanto outros permanecem negligenciados. O treinamento de novos pesquisadores interessados em Zoologia é essencial para um maior entendimento da diversidade brasileira, assim como a exposição de tais pesquisadores a novos grupos e diferentes possibilidades de trabalho. O Curso de Verão em Zoologia (CVZoo) promovido pelo Programa de Pós-graduação em Zoologia da Universidade de São Paulo, ao longo de dez anos vem buscando contribuir para a formação de novos(as) pesquisadores(as) na área da Zoologia, bem como na atualização de docentes do Ensino Básico por meio de atividades de extensão universitária. Para avaliar os impactos causados pelo CVZoo na formação acadêmica e profissionalizante dos participantes, foram enviados formulários aos participantes das dez edições do curso, bem como compiladas informações disponíveis na Plataforma Lattes. Análises qualitativas e quantitativas evidenciaram o perfil das pessoas egressas, suas expectativas e percepções acerca do curso oferecido. Com base nesses dados, é apontada a eficiência do CVZoo na popularização da Zoologia por todo o país, contribuindo para a descentralização do conhecimento, bem como atendendo às preocupações prementes de tornar o acesso ao conhecimento mais igualitário e socialmente justo

Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways.

Sleep-related phenotypes have been frequently reported in early on-set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse-related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep-specific clusters and developmental delay versus sleep-specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.

Fate and Trophic Transfer of Rare Earth Elements in a Tropical Estuarine Food Web.

We sampled abiotic and food web components in an impacted estuarine system to assess the transfer and fate of rare earth elements (REE). REE (based on dry weight) were measured in sediments, suspended particulate matter (SPM), and organisms from different trophic levels. The highest ∑REE concentrations were measured in sediments (180 ± 4.24 mg kg-1) and SPM (163 ± 12.6 mg kg-1). Phytoplankton (45.7 ± 5.31 mg kg-1), periphyton (51.6 ± 1.81 mg kg-1), and zooplankton (68.5 ± 1.27 mg kg-1) are the major sources of exposure and transfer of REE to the food web. REE concentrations were several orders of magnitude lower in bivalves, crustaceans, and fish (6.01 ± 0.11, 1.22 ± 0.18, and 0.059 ± 0.003 mg kg-1, respectively) than in plankton. The ∑REE declined as a function of the trophic position, as determined by functional feeding groups and δ15N, indicating that REE were subject to trophic dilution. Our study suggests that the consumption of seafood is unlikely to be an important source of REE for humans. However, given the numerous sources of dietary introduction of REE, they should be monitored for a possible harmful cumulative effect. This study provides new key information on REE's baseline concentrations and trophic transfers and patterns.

Evaluating genital skin color as a putative sexual signal in wild saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarins.

Coevolution between signalers and receivers has played a significant role in the diversity of animal signals and sensory systems. Platyrrhines (monkeys in the Americas) exhibit a remarkable color vision polymorphism that may have been selected by both natural and sexual selection, but sociosexual color signaling among platyrrhines has received almost no attention. Here, we study the color of reproductive skin among different reproductive classes in free-ranging female saddleback (Leontocebus weddelli) and emperor (Saguinus imperator) tamarins, modeling color spaces, and contrasts for the different visual systems. We find that the chromatic saturation and luminance of genital color vary between reproductive classes in saddleback tamarins. Chromatic contrast between the vulva and belly is lower in the parous females (PFs) relative to adult but not currently breeding females, while achromatic contrast is higher in PFs in saddleback tamarins relative to nonparous females. However, in emperor tamarins, genital color (saturation, hue, and luminance) does not vary between reproductive classes. Overall, genital skin color variation is present in tamarins and may play a role in sexual signaling. Nevertheless, the patterns are inconsistent between species, suggesting interspecific variation. Future studies should integrate the perceiver's behavioral responses and the physical and social signaling environments into comprehensive studies of communication as well as consider the role and interaction between multiple sensory modalities.

Mineral and Trace Elements in Nutritious Flours: Total Contents, In Vitro Bioaccessibility and Contribution to Dietary Intake.

The consumption of fruits, vegetables, and cereals in the form of flour has been an alternative for the intake of nutrients, currently seen in a society that seeks a healthier diet. Thus, the assessment of total contents and bioaccessibility is important to better understand the actual intake of nutrients or contaminants present in foods. The objective of this study was to determine the total content and estimate the bioaccessible fraction of Cu, Fe, and Zn in nutritious flours by inductively coupled plasma optical emission spectrometry (ICP OES) after microwave acid digestion. Bioaccessibility was assessed using the in vitro method, taking into account the entire gastrointestinal tract (Unified Bioaccessibility Method (UBM)). The following concentration ranges, in µg g-1, were found: Ca (341-6275), K (2984-13,953), P (476-6110), Na (< 0.39-2995), Fe (1.4-167), Cu (< 0.01-59.6), and Zn (< 0.07-30.3). Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed a tendency towards the formation of three groups. The bioaccessible fractions for Cu, Fe, and Zn were considered low, ranging from 0.96 to 40% in the gastrointestinal phase and from 4.1 to 100% in the gastric phase.

Occurrence and contents of trace metals and rare earth elements on plastic pellets.

We determined the occurrence of pellets (2-5 mm) and their composition in terms of trace metals and rare earth elements (REE) on nine sandy beaches of the coast of Bahia, northeastern Brazil. We compared the occurrence of pellets between oceanic and sheltered beaches and the effect of fluvial contribution on the occurrence of these microplastics. The number of pellets found was surprisingly low (i.e., max 45 pellets per m2 in an oceanic beach without fluvial river inputs). Thus, the studied beaches exhibited a very low pollution index. Concentrations of ∑REE in pellets varied between 0.36 and 1.74 mg kg-1 and were ~5-fold higher in white/transparent pellets than in brown pellets. The sum of trace metals (i.e., Fe, Cd, Cu, Ni, Pb, and Zn) was also highest in the white pellets (357 ± 12 mg kg-1). Plastic pellets are a potentially important vector of REE exposition to biota.

Functional Analysis of the Cortical Transcriptome and Proteome Reveal Neurogenesis, Inflammation, and Cell Death after Repeated Traumatic Brain Injury In vivo.

The pathological effects of repeated traumatic brain injuries (TBIs) are largely unknown. To gain a detailed understanding of the cortical tissue acute biological response after one or two TBIs, we utilized RNA-sequencing and protein mass spectrometry techniques. Using our previously validated C57Bl/6 weight-drop model, we administered one or two TBIs of a mild or moderate severity. Double injury conditions were spaced 7 days apart, and cortical tissue was isolated 24 h after final injury. Analysis was carried out through functional gene annotation, utilizing Gene Ontology, for both the proteome and transcriptome. Major themes across the four different conditions include: neurogenesis; inflammation and immune response; cell death; angiogenesis; protein modification; and cell communication. Proteins associated with neurogenesis were found to be upregulated after single injuries. Transcripts associated with angiogenesis were upregulated in the moderate single, mild double, and moderate double TBI conditions. Genes associated with inflammation and immune response were upregulated in every condition, with the moderate single condition reporting the most functional groups. Proteins or genes involved in cell death, or apoptosis, were upregulated in every condition. Our results emphasize the significant differences found in proteomic and transcriptomic changes in single versus double injuries. Further, cortical omics analysis offers important insights for future studies aiming to deepen current knowledge on the development of secondary injuries and neurobehavioral impairments after brain trauma.

Environmental settings of seagrass meadows control rare earth element distribution and transfer from soil to plant compartments.

The role of seagrass meadows in the cycling and accumulation of rare earth elements and yttrium (REEY) is unknown. Here, we measured the concentration of REEY in the different compartments of Halodule wrightii (shoots, rhizomes, and roots) and soils in seagrass meadows near sandy beaches, mangroves, and coral reefs in the Todos os Santos Bay, Brazil. We provide data on the accumulation dynamics of REEY in seagrass compartments and demonstrate that plant compartments and soil properties determine accumulation patterns. The ∑REEY in soils were ~1.7-fold higher near coral reefs (93.0 ±â€¯5.61 mg kg-1) than near mangrove sites (53.9 ±â€¯31.5 mg kg-1) and were slightly higher than in sandy beaches (81.7 ±â€¯49.1 mg kg-1). The ∑REEY in seagrasses varied between 35.4 ±â€¯28.1 mg kg-1 near coral reefs to 59.2 ±â€¯21.3 mg kg-1 near sandy beaches, respectively. The ∑REE bioaccumulation factor (BAF) was highest in seagrass roots near sandy beaches (BAF = 0.67 ±â€¯0.48). All values of ∑REE translocation are <1, indicating inefficient translocation of REE from roots to rhizome to shoot. PAAS normalized REE was enriched in light REE (LREE) over heavy REE (HREE). The REEY accumulation in Halodule wrightii revealed a low potential of the seagrass to act as a sink for these elements. However, their bioavailability and potential uptake may change with soil properties. Our results serve as a basis for a better understanding of REE biogeochemical cycling and its fate in the marine environment. REE have experienced increased use as they are central to new technologies revealing an urgent need for further investigations of potential impacts on coastal ecosystems.

Hepatic Epigenetic Reprogramming After Liver Resection in Offspring Alleviates the Effects of Maternal Obesity.

Obesity has become a public health problem in recent decades, and during pregnancy, it can lead to an increased risk of gestational complications and permanent changes in the offspring resulting from a process known as metabolic programming. The offspring of obese dams are at increased risk of developing non-alcoholic fatty liver disease (NAFLD), even in the absence of high-fat diet consumption. NAFLD is a chronic fatty liver disease that can progress to extremely severe conditions that require surgical intervention with the removal of the injured tissue. Liver regeneration is necessary to preserve organ function. A range of pathways is activated in the liver regeneration process, including the Hippo, TGFß, and AMPK signaling pathways that are under epigenetic control. We investigated whether microRNA modulation in the liver of the offspring of obese dams would impact gene expression of Hippo, TGFß, and AMPK pathways and tissue regeneration after partial hepatectomy (PHx). Female Swiss mice fed a standard chow or a high-fat diet (HFD) before and during pregnancy and lactation were mated with male control mice. The offspring from control (CT-O) and obese (HF-O) dams weaned to standard chow diet until day 56 were submitted to PHx surgery. Prior to the surgery, HF-O presented alterations in miR-122, miR-370, and Let-7a expression in the liver compared to CT-O, as previously shown, as well as in its target genes involved in liver regeneration. However, after the PHx (4 h or 48 h post-surgery), differences in gene expression between CT-O and HF-O were suppressed, as well as in microRNA expression in the liver. Furthermore, both CT-O and HF-O presented a similar regenerative capacity of the liver within 48 h after PHx. Our results suggest that survival and regenerative mechanisms induced by the partial hepatectomy may overcome the epigenetic changes in the liver of offspring programmed by maternal obesity.

Withalutin, a new cytotoxic withanolide from Athenaea velutina (Sendtn.) D'Arcy.

Bioassay-guided fractionation of dichloromethane extract from Athenaea velutina leaves led to the isolation of three withanolides, all being reported for the first time in this species. They were identified as withacnistin (1), withacnistin acetate (2) and a new withanolide, designated as withalutin (3). The structures were established by spectral data analysis, including MS, 1D and 2D NMR. In addition, in silico ADMET studies were employed to understand the pharmacokinetic properties of these withanolides. The withanolides isolated from A. velutina reduced cancer cell viability with IC50 values ranging from 1.52 to 5.39 µM. In silico prediction revealed that withanolides have good gastrointestinal absorption or oral bioavailability properties; and are not likely to be mutagenic or hepatotoxic. These findings revealed that A. velutina is an important source of cytotoxic withanolides.

A Withanolide-rich Fraction of Athenaea velutina Induces Apoptosis and Cell Cycle Arrest in Melanoma B16F10 Cells.

Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.

Abusive advertising of food and drink products on Brazilian television.

In Brazil, any advertising strategies that take advantage of the child's judgment or induce consumers to make harmful health choices are considered abusive. However, the efficacy of restrictions on their use on television (TV) food advertising remains poorly understood. This study analysed the extent and nature of abusive techniques according to national regulations and patterns in their use in food-related ads. Cross-sectional studyrecorded the programming of the three most popular TV channels (6 am-12 am), during eight non-consecutive days, in April 2018. Data collection was based on the INFORMAS protocol and two national regulations. Descriptive analyses were used to describe the types of food ads and abusive techniques used in ultra-processed products (UPP) ads. Principal component analysis was applied to identify patterns of abusive marketing techniques and to relate them to specific food groups. More than 90% of food ads included at least one UPP. Overall, 10.1% of UPP ads targeted children and 57.7% used some kind of abusive technique directed to children and adolescents. Most ads contained messages inducing harmful health choices did not present adequate and clear information about the product and contained more than one type of abusive technique. Four out of five patterns in the use of abusive techniques in UPP ads were specifically directed to children, and fast-food meals were associated with three out of five patterns. The high abusiveness of food advertising in UPP ads should be considered a public health concern given their impact on children's food choices and health.

Assessing urinary odours across the oestrous cycle in a mouse model using portable and benchtop gas chromatography-mass spectrometry.

For female mammals, communicating the timing of ovulation is essential for reproduction. Olfactory communication via volatile organic compounds (VOCs) can play a key role. We investigated urinary VOCs across the oestrous cycle using laboratory mice. We assessed the oestrous stage through daily vaginal cytology and analysed urinary VOCs using headspace gas chromatography-mass spectrometry (GC-MS), testing a portable GC-MS against a benchtop system. We detected 65 VOCs from 40 samples stored in VOC traps and analysed on a benchtop GC-MS, and 15 VOCs from 90 samples extracted by solid-phase microextraction (SPME) and analysed on a portable GC-MS. Only three compounds were found in common between the two techniques. Urine collected from the fertile stages of the oestrous cycle had increased quantities of a few notable VOCs compared with urine from non-fertile stages. These VOCs may be indicators of fertility. However, we did not find significant differences in chemical composition among oestrous stages. It is possible that changes in VOC abundance were too small to be detected by our analytical methods. Overall, the use of VOC traps combined with benchtop GC-MS was the more successful of the two methods, yet portable GC-MS systems may still have utility for some in situ applications.

Evidence of high bioaccessibility of gadolinium-contrast agents in natural waters after human oral uptake.

Considering the large occurrence of anthropogenic Gd concentrations in natural waters, its continuous usage increase in technology developments and products and the lack of data on potential Gd human exposure due to ingestion of contaminated waters, it is urgently needed to understand how gadolinium contrast agents (Gd-CAs) reacts in the human digestive system. Here, we aimed to identify through in vitro bioaccessibility tests whether Gd-CAs can be potentially assimilated by humans after oral uptake and if there is a significant difference between contrast agents. We also roughly estimated the potential bioaccessibility of anthropogenic Gd for tap waters worldwide. Gd-CAs are highly bioaccessible (77 to 112%). The macrocyclic complexes pose the highest potential risk, because there are more stable than linear complexes in the gastrointestinal tract and, as such, tend to remain in solution and thus might bring Gd at the intestinal barrier making it potentially bioavailable. The estimated range of potential intake of Gd varied from 13 to 4839 µg in a lifespan of 70 years. The high bioaccessibility of anthropogenic Gd in tap waters calls for appropriate actions to develop better practices to treat wastewater contaminated by Gd-CAs in order to safeguard population and ecosystem health.