Protein hydrolysate and oil from fish waste reveal potential as dog food ingredients.

The increased fish consumption by the growing human population in the world translates into an increase in fish waste. The reintroduction of these fish by-products into food and feed chains presents economic benefits and contributes to counteracting their negative environmental impact. Under this context, the present study aimed to evaluate the effects of the dietary inclusion of fish hydrolysate and oil obtained from fish waste (experimental diet) in substitution of shrimp hydrolysate and salmon oil (control diet) mainly imported from third countries on palatability, apparent total tract digestibility, fecal characteristics and metabolites, blood fatty acid profile, flatulence, and coat quality of adult dogs. A two-bowl test was performed to evaluate palatability by the pairwise comparison between the two diets. A feeding trial was conducted according to a crossover design with two diets (control and experimental diets), six adult Beagle dogs per diet, and two periods of 6 weeks each. The replacement of shrimp hydrolysate and salmon oil with fish hydrolysate and oil did not affect the first diet approach and taste, as well as the intake ratio. Generally, the digestibility of dry matter, nutrients, and energy was not affected by diet, but the intake of digestible crude protein (CP) and ether extract was higher, respectively, with the control and the experimental diet. The higher intake of eicosapentaenoic acid and docosahexaenoic acid with the experimental diet was reflected in a higher content of these long-chain polyunsaturated fatty acids and the omega-3 index of red blood cells, but it did not affect coat quality. The significantly higher intake of digestible CP with the control diet might have contributed to the higher fecal ammonia-N and valerate concentrations. Daily fecal output and characteristics were similar between diets. Overall, results suggest that fish hydrolysate and oil from the agrifood industry might constitute sustainable functional ingredients for dog feeding while adding value for wild fisheries, aquaculture, and fish farming under a circular economy approach and reducing dependence on imports from third countries with a high carbon footprint.

Intrinsic capacity as proposed by the World Health Organization and 30-month mortality among older adults in long-term care facilities / Capacidade Intrínseca proposta pela Organização Mundial de Saúde e mortalidade em residentes de Instituição de Longa Permanência para Idosos em 30 meses

Objetivo: Analisar o efeito da Capacidade Intrínseca na mortalidade de 30 meses em residentes idosos de Instituição de Longa Permanência. Metodologia: Estudo de coorte prospectivo realizado de julho de 2020 a dezembro de 2022 com análise de sobrevivência de idosos residentes de ILPIs brasileiras. Na avaliação inicial (M0) foram avaliados 209 idosos residentes quanto aos dados demográficos e clínicos (doenças diagnosticadas e medicações utilizadas); capacidade intrínseca segundo ICOPE nos domínios cognição, psicológico, audição, visão, vitalidade e locomotor; capacidade funcional pelas atividades básicas de vida diária (índice de Katz) e fragilidade (escala FRAIL). Após 30 meses, foi avaliada a ocorrência de óbito. Resultados: Em M0, a média da idade dos residentes era de 82 anos (±11,21), 65,07% eram do sexo feminino, 94,26% de cor branca e 88,04% tinham multimorbidade. Apresentaram alteração em quatro ou mais domínios da capacidade intrínseca 54,07% (n = 113) dos residentes, sendo o domínio mais alterado a locomoção (82,78%). Eram totalmente dependentes para as atividades básicas de vida diária 43,54% dos idosos, e 42,58% eram frágeis. Após 30 meses de acompanhamento, 33,49% (n = 70) dos idosos evoluíram para óbito. Na análise da sobrevida para óbito, houve associação estatisticamente significativa do evento com alteração em quatro ou mais domínios da capacidade intrínseca (p = 0,044). Conclusão: a alteração de quatro ou mais domínios da capacidade intrínseca está associada com óbito em residentes de ILPI. (AU)

Objective: To analyze the impact of intrinsic capacity on 30-month mortality among older adults living in long-term care facilities (LTCFs). Methods: Prospective cohort study with survival analysis conducted from July 2020 to December 2022 among older adults living in Brazilian LTCFs. At baseline (T0), 209 older residents were evaluated for demographic profile, clinical data (diagnosed diseases and current medications), intrinsic capacity according to ICOPE (cognitive capacity, psychological capacity, hearing capacity, visual capacity, vitality, and locomotor capacity domains), functional capacity (Katz Index of Independence in Activities of Daily Living), and frailty (FRAIL scale). At 30 months, mortality in the sample was assessed. Results: At T0, the mean age of residents was 82 (SD, 11.21) years; 65.07% were female, 94.26% were white, and 88.04% had multimorbidity. Overall, 54.07% (n = 113) of residents exhibited changes in four or more domains of intrinsic capacity, with locomotor capacity being the most commonly impaired domain (82.78%); 43.54% were completely dependent for basic activities of daily living, and 42.58% were frail. At 30-month follow-up, 33.49% (n = 70) of residents had died. Survival analysis revealed a statistically significant association between death and impairment in four or more domains of intrinsic capacity (p = 0.044). Conclusion: Impairment in four or more domains of intrinsic capacity is associated with death in LTCF residents. (AU)

Machine Learning-Assisted Optimization of Drug Combinations in Zeolite-Based Delivery Systems for Melanoma Therapy.

Two independent artificial neural network (ANN) models were used to determine the optimal drug combination of zeolite-based delivery systems (ZDS) for cancer therapy. The systems were based on the NaY zeolite using silver (Ag+) and 5-fluorouracil (5-FU) as antimicrobial and antineoplastic agents. Different ZDS samples were prepared, and their characterization indicates the successful incorporation of both pharmacologically active species without any relevant changes to the zeolite structure. Silver acts as a counterion of the negative framework, and 5-FU retains its molecular integrity. The data from the A375 cell viability assays, involving ZDS samples (solid phase), 5-FU, and Ag+ aqueous solutions (liquid phase), were used to train two independent machine learning (ML) models. Both models exhibited a high level of accuracy in predicting the experimental cell viability results, allowing the development of a novel protocol for virtual cell viability assays. The findings suggest that the incorporation of both Ag and 5-FU into the zeolite structure significantly potentiates their anticancer activity when compared to that of the liquid phase. Additionally, two optimal AgY/5-FU@Y ratios were proposed to achieve the best cell viability outcomes. The ZDS also exhibited significant efficacy against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus); the predicted combination ratio is also effective against S. aureus, underscoring the potential of this approach as a therapeutic option for cancer-associated bacterial infections.

Causal identification of single-cell experimental perturbation effects with CINEMA-OT.

Recent advancements in single-cell technologies allow characterization of experimental perturbations at single-cell resolution. While methods have been developed to analyze such experiments, the application of a strict causal framework has not yet been explored for the inference of treatment effects at the single-cell level. Here we present a causal-inference-based approach to single-cell perturbation analysis, termed CINEMA-OT (causal independent effect module attribution + optimal transport). CINEMA-OT separates confounding sources of variation from perturbation effects to obtain an optimal transport matching that reflects counterfactual cell pairs. These cell pairs represent causal perturbation responses permitting a number of novel analyses, such as individual treatment-effect analysis, response clustering, attribution analysis, and synergy analysis. We benchmark CINEMA-OT on an array of treatment-effect estimation tasks for several simulated and real datasets and show that it outperforms other single-cell perturbation analysis methods. Finally, we perform CINEMA-OT analysis of two newly generated datasets: (1) rhinovirus and cigarette-smoke-exposed airway organoids, and (2) combinatorial cytokine stimulation of immune cells. In these experiments, CINEMA-OT reveals potential mechanisms by which cigarette-smoke exposure dulls the airway antiviral response, as well as the logic that governs chemokine secretion and peripheral immune cell recruitment.

Optimization of iron-ZIF-8 catalysts for degradation of tartrazine in water by Fenton-like reaction.

Optimization of iron zeolitic imidazole framework-8 (FeZIF-8) nanoparticles, as heterogeneous catalysts, were synthesized and evaluated by the Fenton-like reaction for to degrade tartrazine (Tar) in aqueous environment. To achieve this, ZIF-8 nanoparticles were modified with different iron species (Fe2+ or Fe3O4), and subsequently assessed through the Fenton-like oxidation. The effect of different parameters such as the concentration of hydrogen peroxide, the mass of catalyst and the contact time of reaction on the degradation of Tar by Fenton-like oxidation was studied by using the Box-Behnken design (BBD). The BBD model indicated that the optimum catalytic conditions for Fenton-like reaction with an initial pollutant concentration of 30 ppm at pH 3.0 were T = 40 °C and 12 mM of H2O2, 2 g/L of catalyst and 4 h of reaction. The maximum Tar conversion value achieved with the best catalyst, Fe1ZIF-8, was 66.5% with high mineralization (in terms of decrease of total organic carbon - TOC), 44.2%. To assess phytotoxicity, the germination success of corn kernels was used as an indicator in the laboratory. The results show that the catalytic oxidation by Fenton-like reaction using heterogeneous iron ZIF-8 catalysts is a viable alternative for treating contaminated effluents with organic pollutants and highlighted the importance of the validation of the optimized experimental conditions by mathematical models.

Gastric epithelial response to milk fat using the semi-dynamic INFOGEST digestion model coupled with NCI-N87 cells.

The stomach is a relevant spot of lipolysis for milk fat, but research on the effect of digested milk fat in the gastric epithelium is scarce and difficult to evaluate. In the present study, we implemented the semi-dynamic in vitro digestion model of INFOGEST, combined with gastric NCI-N87 cells, to study the effect of fat-free, whole conventional, and whole pasture-based milk on gastric epithelium. Cellular messenger ribonucleic acid (mRNA) expression of membrane fatty acids receptors (GPR41, GPR84), antioxidant enzymes (CAT, SOD, GPX), and inflammatory molecules (NF-κB p65, IL-1ß, IL-6, IL-8 and TNF-α) was assessed. No significant differences were observed in mRNA expression of GPR41, GPR84, SOD, GPX, IL-6, IL-8, and TNF-α, after exposure of the NCI-N87 cells to milk digesta samples (p > 0.05). An increase of CAT mRNA expression was observed (p < 0.05), at a similar level, for all milk types. Whole milk digested samples induced higher mRNA expression of NF-κB p65 and IL-1ß than fat-free milk (p < 0.05); while no differences were observed between whole conventional and whole pasture-based milk (p > 0.05). Moreover, the effect of milk digesta on gastric mRNA expression was studied in a scenario of subsequent stimulation of NCI-N87 monolayer with the pro-inflammatory cytokine IFN-γ. In these conditions, milk digesta samples increased CAT mRNA expression (p < 0.05), but had no effect in the expression of NF-κB p65 and IL-1ß (p > 0.05). The increase of CAT mRNA expression suggests that milk fatty acids are used for energy production by gastric epithelial cells. Cellular antioxidant response to higher milk fatty acids availability could be associated to gastric epithelial inflammation, but did not contribute to increased inflammation in case of an external contact with IFN-γ. Besides, a conventional or a pasture-based origin did not affect the impact of whole milk in the NCI-N87 monolayer. The combined model responded to differences in milk fat content, which indicates its usefulness to study effects of foods at the gastric level.

Reinke Edema: Factors that Interfere with Vocal Recovery after Surgery

Abstract Introduction Dysphonia and lower pitch after surgery of Reinke edema are common. They are caused especially due to chronic smoking but, probably, other factors should be associated. Objectives To evaluate the results of laryngeal microsurgery in patients with Reinke edema, following a standardized postoperative guidance protocol in our service. Methods Retrospective study. Thirty patients (3 males; 27 females) were included, 70% between 41 and 60 years old. The parameters analyzed in the pre- and postoperative (between 4 and 6 months) of patients undergoing laryngeal microsurgery for Reinke edema were: smoking, vocal symptoms, videolaryngostroboscopy, voice therapy, perceptual and acoustic vocal evaluation, histopathological report. Results Smoking was reported by 100% of the patients and maintained in the postoperative period by 80%. Complete improvement of symptoms in the postoperative period was reported by 43% of them, partial improvement by 40%, and maintenance by 17%. There was low adherence to voice therapy in the pre- and postsurgery. Postoperative videolaryngoscopy indicated congestion (19), atrophy and bowed vocal fold (1), subepithelial edema (2), and normal findings (8). The histological findings were subepithelial edema, enlargement of vessels, inflammation, epithelial hyperplasia, and thickening of the basement membrane. The perceptual and acoustic vocal analyzes indicated improvement of the analyzed parameters. Conclusions The maintenance of some vocal symptoms and laryngeal alterations in videolaryngoscopy after microsurgery of Reinke edema is frequent, even in patients who follow the recommendations of vocal rest and control of gastroesophageal reflux. Vocal symptoms are attributed to changes in the laryngeal mucosa caused by chronic smoking, aggravated by the maintenance of addiction in the postoperative period.

Reinke Edema: Factors that Interfere with Vocal Recovery after Surgery.

Introduction Dysphonia and lower pitch after surgery of Reinke edema are common. They are caused especially due to chronic smoking but, probably, other factors should be associated. Objectives To evaluate the results of laryngeal microsurgery in patients with Reinke edema, following a standardized postoperative guidance protocol in our service. Methods Retrospective study. Thirty patients (3 males; 27 females) were included, 70% between 41 and 60 years old. The parameters analyzed in the pre- and postoperative (between 4 and 6 months) of patients undergoing laryngeal microsurgery for Reinke edema were: smoking, vocal symptoms, videolaryngostroboscopy, voice therapy, perceptual and acoustic vocal evaluation, histopathological report. Results Smoking was reported by 100% of the patients and maintained in the postoperative period by 80%. Complete improvement of symptoms in the postoperative period was reported by 43% of them, partial improvement by 40%, and maintenance by 17%. There was low adherence to voice therapy in the pre- and postsurgery. Postoperative videolaryngoscopy indicated congestion (19), atrophy and bowed vocal fold (1), subepithelial edema (2), and normal findings (8). The histological findings were subepithelial edema, enlargement of vessels, inflammation, epithelial hyperplasia, and thickening of the basement membrane. The perceptual and acoustic vocal analyzes indicated improvement of the analyzed parameters. Conclusions The maintenance of some vocal symptoms and laryngeal alterations in videolaryngoscopy after microsurgery of Reinke edema is frequent, even in patients who follow the recommendations of vocal rest and control of gastroesophageal reflux. Vocal symptoms are attributed to changes in the laryngeal mucosa caused by chronic smoking, aggravated by the maintenance of addiction in the postoperative period.

Nutritional Composition and Untargeted Metabolomics Reveal the Potential of Tetradesmus obliquus, Chlorella vulgaris and Nannochloropsis oceanica as Valuable Nutrient Sources for Dogs.

The growing pet population is questioning the sustainability of the pet food system. Although microalgae may constitute a more sustainable food resource, the assessment of their potential for canine diets is almost non-existent. The present study aimed to evaluate the potential of three microalgae species (Tetradesmus obliquus, Chlorella vulgaris and Nannochloropsis oceanica) grown locally in industrial photobioreactors as alternative food resources for dogs. A detailed characterization of their nutritional composition and metabolomic profile was carried out and related to the nutritional requirements of dogs. Overall, the essential amino acid content exceeded the amounts required for dogs at all life stages, except methionine and cysteine. The three microalgae were deficient in linoleic acid, N. oceanica presented a linolenic acid content below requirements and T. obliquus and C. vulgaris were deficient in arachidonic and eicosapentaenoic acids. The fiber was mainly composed of insoluble dietary fiber. The mineral profile varied greatly with the microalgae species, demonstrating their different potential for dog feeding. Untargeted metabolomics highlighted glycolipids, glycerolipids and phospholipids as the most discriminating compounds between microalgae species. Overall, the results support the potential of T. obliquus, C. vulgaris and N. oceanica as valuable macro- and micro-nutrients sources for dog feeding.

A Novel Approach for Monitoring the Volatile Metabolome in Biological Samples from Ruminants through Miniaturized Liquid-Liquid Extraction and Multiclass Gas Chromatography Analysis.

A straightforward and versatile methodology for the extraction of volatile metabolites in biological samples from ruminants for gas chromatography analysis is proposed. The methodology was applied in the determination of multiclass metabolites (short-chain fatty acids, aldehydes, alcohols, ketones, esters, phenols, and sulfides) in different analytical matrices (rumen fluid, urine, and feces) collected from Holstein cows. The 24 multiclass volatile metabolites reported in the different biological samples and their respective concentrations were critically discussed in the context of digestive physiology. Most detected compounds are derived from the rumen and lower gut fermentation of carbohydrates, proteins, and lipids or their metabolism, being consistent with the prior state of the art. The proposed method also takes advantage of the already existing tools in animal nutrition laboratories, providing a novel methodological ground that can generate relevant bioanalytical information with a significant impact on ruminant's nutritional studies.

Surface functionalization of zeolite-based drug delivery systems enhances their antitumoral activity in vivo.

Zeolites have attractive features making them suitable carriers for drug delivery systems (DDS). As such, we loaded the anticancer drug 5-fluorouracil (5-FU), into two different zeolite structures, faujasite (NaY) and Linde Type L (LTL), to obtain different DDS. The prepared DDS were tested in vitro using breast cancer, colorectal carcinoma, and melanoma cell lines and in vivo using the chick embryo chorioallantoic membrane model (CAM). Both assays showed the best results for the Hs578T breast cancer cells, with a higher potentiation for 5-FU encapsulated in the zeolite LTL. To unveil the endocytic mechanisms involved in the internalization of the zeolite nanoparticles, endocytosis was inhibited pharmacologically in breast cancer and epithelial mammary human cells. The results suggest that a caveolin-mediated process was responsible for the internalized zeolite nanoparticles. Aiming to boost the DDS efficacy, the disc-shaped zeolite LTL outer surface was functionalized using amino (NH2) or carboxylic acid (COOH) groups and coated with poly-l-lysine (PLL). Positively functionalized surface LTL nanoparticles revealed to be non-toxic to human cells and, importantly, their internalization was faster and led to a higher tumor reduction in vivo. Overall, our results provide further insights into the mechanisms of interaction between zeolite-based DDS and cancer cells, and pave the way for future studies aiming to improve DDS anticancer activity.

Maternal Low-Protein Diet Deregulates DNA Repair and DNA Replication Pathways in Female Offspring Mammary Gland Leading to Increased Chemically Induced Rat Carcinogenesis in Adulthood.

Studies have shown that maternal malnutrition, especially a low-protein diet (LPD), plays a key role in the developmental mechanisms underlying mammary cancer programming in female offspring. However, the molecular pathways associated with this higher susceptibility are still poorly understood. Thus, this study investigated the adverse effects of gestational and lactational low protein intake on gene expression of key pathways involved in mammary tumor initiation after a single dose of N-methyl-N-nitrosourea (MNU) in female offspring rats. Pregnant Sprague-Dawley rats were fed a normal-protein diet (NPD) (17% protein) or LPD (6% protein) from gestational day 1 to postnatal day (PND) 21. After weaning (PND 21), female offspring (n = 5, each diet) were euthanized for histological analysis or received NPD (n = 56 each diet). At PND 28 or 35, female offspring received a single dose of MNU (25 mg/kg body weight) (n = 28 each diet/timepoint). After 24 h, some females (n = 10 each diet/timepoint) were euthanized for histological, immunohistochemical, and molecular analyses at PDN 29 or 36. The remaining animals (n = 18 each diet/timepoint) were euthanized when tumors reached ≥2 cm or at PND 250. Besides the mammary gland development delay observed in LPD 21 and 28 groups, the gene expression profile demonstrated that maternal LPD deregulated 21 genes related to DNA repair and DNA replication pathways in the mammary gland of LPD 35 group after MNU. We further confirmed an increased γ-H2AX (DNA damage biomarker) and in ER-α immunoreactivity in mammary epithelial cells in the LPD group at PND 36. Furthermore, these early postnatal events were followed by significantly higher mammary carcinogenesis susceptibility in offspring at adulthood. Thus, the results indicate that maternal LPD influenced the programming of chemically induced mammary carcinogenesis in female offspring through increase in DNA damage and deregulation of DNA repair and DNA replication pathways. Also, Cidea upregulation gene in the LPD 35 group may suggest that maternal LPD could deregulate genes possibly leading to increased risk of mammary cancer development and/or poor prognosis. These findings increase the body of evidence of early-transcriptional mammary gland changes influenced by maternal LPD, resulting in differential response to breast tumor initiation and susceptibility and may raise discussions about lifelong prevention of breast cancer risk.

Frailty and mortality in long-term care facilities for older people in Brazil: a survival analysis / Fragilidade e mortalidade em instituições de longa permanência para idosos no Brasil: estudo de sobrevivência

OBJECTIVES: To investigate the effect of frailty on 1-year mortality in long term-care facility (LTCF) residents. METHODS: This was a prospective cohort study with survival analysis of 209 participants living in 15 Brazilian LTCFs. Data on chronic diseases, age, sex, medication use, dependence in activities of daily living (ADLs; Katz index), and frailty (FRAIL scale) were collected at baseline, and death after 1 year was the outcome measure. Kaplan-Meier estimate and log-rank test were used to analyze the survival of residents. RESULTS: In the initial assessment, 65.07 of the residents were women, and the median age was 82 (interquartile range, 71­88) years, with 55% being over 80 years old. Overall, 88% had 2 or more diseases, 59.81% were using 5 or more medications, 42.11% were considered frail, 34.92% pre-frail, and 22.97% robust, and 69.94% were dependent in 3 or more ADLs. During the 12-month follow-up, 19.61% of the residents (n=41) died. In the survival analysis for death, there was a statistically significant association with frailty (p=0.03) and dependence in ADLs (p=0.04). CONCLUSIONS: In this population of LTCF residents, frailty and functional dependence were associated with death.

OBJETIVOS: Investigar o efeito da fragilidade na mortalidade em 1 ano em residentes de instituições de longa permanência para idosos (ILPIs). METODOLOGIA: Estudo de coorte prospectivo com análise de sobrevivência de 209 participantes residentes em 15 ILPIs brasileiras. Dados sobre doenças crônicas, idade, sexo, uso de medicamentos, dependência nas atividades da vida diária (AVDs; índice de Katz) e fragilidade (escala FRAIL) foram coletados no início do estudo, e morte após 1 ano foi a medida de desfecho. A estimativa de Kaplan-Meier e o teste de log-rank foram usados para analisar a sobrevida dos residentes.. RESULTADOS: Na avaliação inicial, 65,07% dos residentes eram mulheres e a mediana da idade era de 82 (intervalo interquartil, 71­88) anos, 55% com mais de 80 anos. Em geral, 88% tinham 2 ou mais doenças, 59,81% usavam 5 ou mais medicamentos, 42,11% foram considerados frágeis, 34,92% pré-frágeis e 22,97% robustos e 69,91% eram dependentes em 3 ou mais AVDs. No decorrer do seguimento de 12 meses, 19,61% dos residentes (n =41) evoluíram para óbito. Na análise de sobrevivência para evento morte, houve associação estatisticamente significativa com fragilidade (p=0,03) e dependência para AVDs (p=0,04). CONCLUSÕES: Nesta população de residentes de ILPIs, fragilidade e dependência funcional estiveram associadas ao óbito.

Environmental exposure to benzene: evaluation of urinary S-PMA and polymorphism (CYP2E1-1293G>C and NQO1 609C>T) in Campos Elíseos residents, Duque de Caxias, Rio de Janeiro State, Brazil.

Benzene is one of the most important substances for assessment, due to its significant use, the environmental contamination resulting from its emission and the effects on human health. It is classified by the International Agency for Research on Cancer (IARC) as a known carcinogen to humans (group 1) and associated with the development of leukemia. In general, the population is exposed to this substance by inhaling contaminated air, which varies according to the location and intensity of its potential sources. The petrochemical industry is one of the most important sources of this compound. The municipality of Duque de Caxias, specifically the Campos Elíseos district, in Rio de Janeiro State, Brazil, houses the Industrial Complex of Campos Elíseos (PICE), a grouping of over 25 industries, which includes the second largest oil refinery in Brazil. Environmental contamination from the PICE has been recognized, but there is a lack of studies concerning its impact on the health of the surrounding population. S-phenylmercapturic acid (S-PMA) concentrations ranging from 0.80 to 8.01µg.g-1 creatinine were observed in the local population, apparently related to hematological changes also observed in exposed population. The quantifiable presence of urinary S-PMA from the benzene metabolism is associated with the fact that 60% of the participants present specific hematological changes, which may be due to the environmental benzene exposure. The allele and genotype frequencies of the CYP2E1 and NQO1 enzymes observed in the study population were similar to those reported in other studies. The presence of the variant allele in the NQO1 genotype may be a risk factor for the observed hematological changes.

Environmental Assessment and Evaluation of Oxidative Stress and Genotoxicity Biomarkers Related to Chronic Occupational Exposure to Benzene.

Environmental and occupational exposure to benzene from fuels is a major cause for concern for national and international authorities, as benzene is a known carcinogen in humans and there is no safe limit for exposure to carcinogens. The objective of this study was to evaluate the genotoxic effects of chronic occupational exposure to benzene among two groups of workers: filling station workers (Group I) and security guards working at vehicles entrances (Group II), both on the same busy highway in Rio de Janeiro, Brazil. Sociodemographic data on the workers were evaluated; the concentration of benzene/toluene (B/T) in atmospheric air and individual trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) were measured; oxidative stress was analyzed by catalase (CAT), glutathione S-transferase (GST), superoxide dismutase (SOD), thiol groups (THIOL) and malondialdehyde (MDA); genotoxicity was measured by metaphases with chromosomal abnormalities (MCA) and nuclear abnormalities, comet assay using the enzyme formamidopyrimidine DNA glycosylase (C-FPG), and methylation of repetitive element LINE-1, CDKN2B and KLF6 genes. Eighty-six workers participated: 51 from Group I and 35 from Group II. The B/T ratio was similar for both groups, but Group I had greater oscillation of benzene concentrations because of their work activities. No differences in ttMA and S-PMA, and no clinical changes were found between both groups, but linearity was observed between leukocyte count and ttMA; and 15% of workers had leukocyte counts less than 4.5 × 109 cells L-1, demanding close worker's attention. No differences were observed between the two groups for THIOL, MDA, MCA, or nuclear abnormalities. A multiple linear relationship was obtained for the biomarkers MCA and C-FPG. A significant correlation was found between length of time in current job and the biomarkers C-FPG, MCA, GST, and MDA. Although both populations had chronic exposure to benzene, the filling station workers were exposed to higher concentrations of benzene during their work activities, indicating an increased risk of DNA damage.

Functional Ontogeny of Hypothalamic Agrp Neurons in Neonatal Mouse Behaviors.

Hypothalamic Agrp neurons regulate food ingestion in adult mice. Whether these neurons are functional before animals start to ingest food is unknown. Here, we studied the functional ontogeny of Agrp neurons during breastfeeding using postnatal day 10 mice. In contrast to adult mice, we show that isolation from the nursing nest, not milk deprivation or ingestion, activated Agrp neurons. Non-nutritive suckling and warm temperatures blunted this effect. Using in vivo fiber photometry, neonatal Agrp neurons showed a rapid increase in activity upon isolation from the nest, an effect rapidly diminished following reunion with littermates. Neonates unable to release GABA from Agrp neurons expressed blunted emission of isolation-induced ultrasonic vocalizations. Chemogenetic overactivation of these neurons further increased emission of these ultrasonic vocalizations, but not milk ingestion. We uncovered important functional properties of hypothalamic Agrp neurons during mouse development, suggesting these neurons facilitate offspring-to-caregiver bonding.

Unravelling the phytonutrients and antioxidant properties of European Vicia faba L. seeds.

For the first time, seven European varieties of Vicia faba L. seeds were investigated for (1) their phytonutrients profile by HPLC-DAD-MS/MS, (2) total phenolic content (TPC), and (3) antioxidant capacity (DPPH and FRAP assays). A wide range of compounds were identified, namely alkaloids, organic acids, terpenoids, jasmonates, and phenolics; these two latter being the most abundant. TPC ranged between 2.62 and 4.3 mg (gallic acid equivalent) g-1 dry weight, for V. faba major variety Belshi and V. faba minor variety Bauska, respectively. The DPPH radical scavenging capacity showed poor correlation (r = 0.550, P = .041) with TPC, suggesting the presence of other antioxidant sources than phenolics. Still, FRAP was positively correlated with TPC (r = 0.709, P < .01) and DPPH (r = 0.819, P < .01). These results elucidated the phytonutrients and antioxidant properties of V. faba L. seeds as functional food sources.

Fim das utopias? A cidadede São Paulo e a discussão do urbanismo contemporâneo / End of utopias? The city of São Paulo and the discussion of contemporary urbanism

O texto discute a cidade em sua condição pós-moderna, entendendo seu corpo material e simbólico a partir do estudo da utopia geradora da cidade moderna do século XX até a construção de novo ideário da cidade contemporânea. Essa trajetória que gerou espaços riquíssimos será a base doutrinária em que urbanistas de todos os matizes gerarão os espaços urbanos do amanhã. A noção de utopia perpassa todo o texto, porque é argumento essencial para a superação dos nossos problemas urbanos atuais.

The text discusses the city in its postmodern condition, understanding its material and symbolic body through the study of the utopia that generated the modern city of the twentieth century and the construction of new corpus of ideas of the contem-porary city. This trajectory, which has generated very rich spaces, will be the doctrinal basis by which urbanists of all stripes will generate the urban spaces of tomorrow. The notion of utopia weaves through the entire text because it is an essential argument for overcoming our current urban problems.

Environmental exposure to benzene: evaluation of urinary S-PMmorphism (CYP2E1-129A and poly3G>C and NQO1 609C> T) in Campos Elíseos residents, Duque de Caxias, Rio de Janeiro State, Brazil / Exposição ambiental ao benzeno: avaliação do S-PMA urinário e de polimorfismos (CYP2E1-1293G>C e NQO1 609C> T) em residentes de Campos Elíseos, Duque de Caxias, Rio de Janeiro, Brasil / Exposición ambiental al benceno: análisis del S-PMA en la orina y polimorfismo (CYP2E1-1293G>C y NQO1 609C> T) en residentes de Campos Elíseos, Duque de Caxias, Río de Janeiro, Brasil

Benzene is one of the most important substances for assessment, due to its significant use, the environmental contamination resulting from its emission and the effects on human health. It is classified by the International Agency for Research on Cancer (IARC) as a known carcinogen to humans (group 1) and associated with the development of leukemia. In general, the population is exposed to this substance by inhaling contaminated air, which varies according to the location and intensity of its potential sources. The petrochemical industry is one of the most important sources of this compound. The municipality of Duque de Caxias, specifically the Campos Elíseos district, in Rio de Janeiro State, Brazil, houses the Industrial Complex of Campos Elíseos (PICE), a grouping of over 25 industries, which includes the second largest oil refinery in Brazil. Environmental contamination from the PICE has been recognized, but there is a lack of studies concerning its impact on the health of the surrounding population. S-phenylmercapturic acid (S-PMA) concentrations ranging from 0.80 to 8.01μg.g-1 creatinine were observed in the local population, apparently related to hematological changes also observed in exposed population. The quantifiable presence of urinary S-PMA from the benzene metabolism is associated with the fact that 60% of the participants present specific hematological changes, which may be due to the environmental benzene exposure. The allele and genotype frequencies of the CYP2E1 and NQO1 enzymes observed in the study population were similar to those reported in other studies. The presence of the variant allele in the NQO1 genotype may be a risk factor for the observed hematological changes.

O benzeno é uma das substâncias mais importantes para a biomonitorização, em função do uso disseminado, da contaminação ambiental que resulta da emissão e dos efeitos sobre a saúde humana. O benzeno é classificado pela Agência Internacional de Pesquisa em Câncer (IARC) como carcinógeno conhecido em seres humanos (grupo 1) e está associado ao desenvolvimento de leucemias. Em geral, a população fica exposta a essa substância através da inalação do ar contaminado, que varia de acordo com a localização e a intensidade das fontes potenciais. A indústria petroquímica é uma das fontes mais importantes desse composto. O Município de Duque de Caxias, especificamente o Distrito de Campos Elíseos, no Estado do Rio de Janeiro, Brasil, é sede do Polo Industrial de Campos Elíseos (PICE), um conjunto de mais de 25 indústrias que inclui a segunda maior refinaria de petróleo no Brasil. A contaminação ambiental produzida pelo PICE já é conhecida, mas faltam estudos sobre o impacto na saúde da população local. Foram observadas concentrações de ácido S-fenilmercaptúrico (S-PMA) entre 0,80 e 8,01μg.g-1 creatinina na população local, aparentemente implicadas nas alterações hematológicas também observadas na população exposta. A presença quantificável do S-PMA urinário do metabolismo do benzeno está associada ao fato de 60% dos participantes apresentarem alterações hematológicas específicas, o que pode ser devido à exposição ambiental ao benzeno. As frequências alélicas e genotípicas das enzimas CYP2E1 e NQO1, observadas na população do estudo, foram semelhantes àquelas relatadas em outros estudos. A presença da variante alélica do genótipo NQO1 pode ser um fator de risco para as alterações hematológicas observadas.

El benceno es una de las sustancias más importantes susceptibles de estudio, debido a su uso significativo, la contaminación ambiental resultante de sus emisiones y sus efectos sobre la salud humana. Está clasificado por el Centro Internacional de Investigaciones sobre el Cáncer (IARC) como un conocido carcinógeno para los humanos (grupo 1) y está asociado con el desarrollo de leucemias. En general, la población está expuesta a esta sustancia por inhalación de aire contaminado, que varía según el lugar y la intensidad de las emisiones. La industria petroquímica es un de las fuentes emisoras más importantes de este compuesto. La municipalidad de Duque de Caxias, específicamente el distrito de Campos Elíseos, en Río de Janeiro, Brasil, alberga el Complejo Industrial de Campos Elíseos (PICE), un conglomerado de más de 25 industrias, que incluye la segunda mayor refinería de petróleo en Brasil. La contaminación ambiental procedente del PICE ya ha sido reconocida, pero es notable la falta de estudios respecto a su impacto en la salud de la población circundante. Se observaron en la población local concentraciones de ácido s-fenilmercaptúrico (SPMA por sus siglas en inglés) que oscilan entre los 0,80 a 8,01μg.g-1 creatinina, aparentemente relacionadas con cambios hematológicos también hallados en la población expuesta. La presencia cuantificable de SPMA en la orina, procedente del metabolismo del benceno, está asociada con el hecho de que un 60% de los participantes presenta cambios específicos hematológicos, los cuales tal vez se deben a la exposición ambiental al benceno. Las frecuencias alélicas y genotípicas del CYP2E1 y enzimas NQO1 observadas en el estudio fueron similares a las reportadas en otros estudios. La presencia de la variante alélica en el genotipo NQO1 podría ser un factor de riesgo para los cambios hematológicos observados.