Natural Pigments Recovery from Food By-Products: Health Benefits towards the Food Industry.

Given the health risks associated with synthetic colorants, natural pigments have emerged as a promising alternative. These renewable choices not only provide health benefits but also offer valuable technical and sensory properties to food systems. The effective application of natural colorants, however, requires the optimization of processing conditions, exploration of new sources, and development of novel formulations to ensure stability and maintain their inherent qualities. Several natural pigment sources have been explored to achieve the broad color range desired by consumers. The purpose of this review is to explore the current advances in the obtention and utilization of natural pigments derived from by-products, which possess health-enhancing properties and are extracted through environmentally friendly methods. Moreover, this review provides new insights into the extraction processes, applications, and bioactivities of different types of pigments.

Carotenoids and Intestinal Harmony: Exploring the Link for Health.

Carotenoids, prominent lipid-soluble phytochemicals in the human diet, are responsible for vibrant colours in nature and play crucial roles in human health. While they are extensively studied for their antioxidant properties and contributions to vitamin A synthesis, their interactions with the intestinal microbiota (IM) remain poorly understood. In this study, beta (ß)-carotene, lutein, lycopene, a mixture of these three pigments, and the alga Osmundea pinnatifida were submitted to simulated gastrointestinal digestion (GID) and evaluated on human faecal samples. The results showed varying effects on IM metabolic dynamics, organic acid production, and microbial composition. Carotenoid exposure influenced glucose metabolism and induced the production of organic acids, notably succinic and acetic acids, compared with the control. Microbial composition analysis revealed shifts in phyla abundance, particularly increased Pseudomonadota. The α-diversity indices demonstrated higher diversity in ß-carotene and the pigments' mixture samples, while the ß-diversity analysis indicated significant dissimilarity between the control and the carotenoid sample groups. UPLC-qTOF MS analysis suggested dynamic changes in carotenoid compounds during simulated fermentation, with lutein exhibiting distinct mass ion fragmentation patterns. This comprehensive research enhances our understanding of carotenoid-IM interactions, shedding light on potential health implications and the need for tailored interventions for optimal outcomes.

Safety and Efficacy of Para-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors.

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce 177Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received 177Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.

Skeletal muscle mass increases after viral eradication with direct-acting antivirals in patients with chronic hepatitis C: A longitudinal study.

BACKGROUND: Results of studies evaluating the effect of viral eradication following direct-acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. AIM: To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. METHODS: We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up-and-go (TUG) test. Mixed-effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. RESULTS: 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. CONCLUSION: HCV eradication with DAA therapy was associated with a dynamic reduction of non-invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.

Compreensão de cuidadores de pessoas idosas acamadas acerca da assistência recebida pela atenção primária à sua saúde / Understanding of caregivers of bedridden older adults about the primary assistance received to their own health care

Resumo Objetivo Identificar a compreensão de cuidadores de pessoas idosas acamadas acerca da assistência recebida pela atenção primária em relação à sua própria saúde. Método Estudo qualitativo baseado na fenomenologia de Alfred Schütz. A abordagem dos cuidadores de pessoas idosas acamadas ocorreu pelo agente comunitário em sua área de abrangência em uma unidade básica de saúde localizada no norte do Espírito Santo, Brasil. A escolha do local se deu por conveniência. A coleta de dados ocorreu entre os meses de setembro a dezembro de 2022 nos domicílios. Aplicou-se um questionário contendo questões sobre o perfil sociodemográfico dos participantes, somados a seis perguntas fenomenológicas para entender o típico vivido de cada cuidador de pessoas idosas e sua intencionalidade. Os dados foram analisados à luz da fenomenologia. Resultados Participaram 16 cuidadores de pessoas idosas acamadas, sendo 15 do sexo feminino, 15 tinham laço familiar; 15 não receberam treinamento que o qualificasse na função. 37,5% dos cuidadores apresentaram idade acima de 61 anos. Em relação ao típico vivido, emergiram das falas as seguintes categorias: 1- Impactos físicos, emocionais e sociais na saúde do cuidador; 2- Necessidade de qualificação; 3- Suporte da equipe de saúde e a subcategoria: 3.1- Ausência do profissional médico e/ou enfermeiro. Conclusão Compreendeu-se que os cuidadores são invisíveis e não recebem assistência da equipe de saúde para a sua saúde, e quando ocorre a visita domiciliar, os profissionais visam o atendimento a pessoa idosa fragmentando a assistência que deveria ser ampliada para as necessidades da comunidade familiar, incluindo o cuidador.

Abstract Objective To identify caregivers' understanding of healthcare assistance received from primary health care regarding their own health. Method A qualitative study based on Alfred Schütz's phenomenology was conducted. The approach to caregivers of bedridden older adults was carried out by community health agents within their coverage area in a primary health care unit located in the northern region of Espírito Santo, Brazil. The choice of location was convenience-based. Data collection took place between September and December 2022 in households. A questionnaire containing questions about the participants' sociodemographic profile, along with six phenomenological questions to understand the typical experiences of each caregiver of older adults and their intentionality, was administered. Data were analyzed using phenomenological methods. Results Sixteen caregivers of bedridden older adults participated, with fifteen being female, fifteen having a family relationship with the care recipient, and fifteen lacking training qualifying them for the caregiver role. 37.5% of caregivers were aged 61 years or older. Regarding the typical experiences, the following categories emerged from the participants' narratives: 1- Physical, emotional, and social impacts on the caregiver's health; 2- Need for qualification; 3- Support from the healthcare team, with a subcategory: 3.1- Absence of medical and/or nursing professionals. Conclusion It was understood that caregivers are invisible and do not receive healthcare assistance from the healthcare team for their own health. When home visits occur, professionals focus on attending to the older adult, fragmenting the assistance that should be extended to the needs of the family community, including the caregiver.

Sarcopenia in chronic viral hepatitis: From concept to clinical relevance.

Although the frequency of metabolic risk factors for cirrhosis and hepatocellular carcinoma (HCC) is increasing, chronic hepatitis B (CHB) and chronic hepatitis C (CHC) remain the most relevant risk factors for advanced liver disease worldwide. In addition to liver damage, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with a myriad of extrahepatic manifestations including mixed cryoglobulinaemia, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production. Recently, the list has grown to include sarcopenia. Loss of muscle mass or muscle function is a critical feature of malnutrition in cirrhotic patients and has been found in approximately 23.0%-60.0% of patients with advanced liver disease. Nonetheless, among published studies, there is significant heterogeneity in the aetiologies of hepatic diseases and measurement methods used to determine sarcopenia. In particular, the interaction between sarcopenia, CHB and CHC has not been completely clarified in a real-world setting. Sarcopenia can result from a complex and multifaceted virus-host-environment interplay in individuals chronically infected with HBV or HCV. Thus, in the present review, we provide an overview of the concept, prevalence, clinical relevance, and potential mechanisms of sarcopenia in patients with chronic viral hepatitis, with an emphasis on clinical outcomes, which have been associated with skeletal muscle loss in these patients. A comprehensive overview of sarcopenia in individuals chronically infected with HBV or HCV, independent of the stage of the liver disease, will reinforce the necessity of an integrated medical/nutritional/physical education approach in the daily clinical care of patients with CHB and CHC.

Carotenoids Diet: Digestion, Gut Microbiota Modulation, and Inflammatory Diseases.

Several epidemiologic studies have found that consuming fruits and vegetables lowers the risk of getting a variety of chronic illnesses, including several types of cancers, cardiovascular diseases (CVDs), and bowel diseases. Although there is still debate over the bioactive components, various secondary plant metabolites have been linked to these positive health benefits. Many of these features have recently been connected to carotenoids and their metabolites' effects on intracellular signalling cascades, which influence gene expression and protein translation. Carotenoids are the most prevalent lipid-soluble phytochemicals in the human diet, are found in micromolar amounts in human serum, and are very susceptible to multiple oxidation and isomerisation reactions. The gastrointestinal delivery system, digestion processes, stability, and functionality of carotenoids, as well as their impact on the gut microbiota and how carotenoids may be effective modulators of oxidative stress and inflammatory pathways, are still lacking research advances. Although several pathways involved in carotenoids' bioactivity have been identified, future studies should focus on the carotenoids' relationships, related metabolites, and their effects on transcription factors and metabolism.

Modulation of the Gut Microbiota by Tomato Flours Obtained after Conventional and Ohmic Heating Extraction and Its Prebiotic Properties.

Several studies have supported the positive functional health effects of both prebiotics and probiotics on gut microbiota. Among these, the selective growth of beneficial bacteria due to the use of prebiotics and bioactive compounds as an energy and carbon source is critical to promote the development of healthy microbiota within the human gut. The present work aimed to assess the fermentability of tomato flour obtained after ohmic (SFOH) and conventional (SFCONV) extraction of phenolic compounds and carotenoids as well as their potential impact upon specific microbiota groups. To accomplish this, the attained bagasse flour was submitted to an in vitro simulation of gastrointestinal digestion before its potential fermentability and impact upon gut microbiota (using an in vitro fecal fermentation model). Different impacts on the probiotic strains studied were observed for SFCONV promoting the B. animalis growth, while SFOH promoted the B. longum, probably based on the different carbohydrate profiles of the flours. Overall, the flours used were capable of functioning as a direct substrate to support potential prebiotic growth for Bifidus longum. The fecal fermentation model results showed the highest Bacteroidetes growth with SFOH and the highest values of Bacteroides with SFCONV. A correlation between microorganisms' growth and short-chain fatty acids was also found. This by-product seems to promote beneficial effects on microbiota flora and could be a potential prebiotic ingredient, although more extensive in vivo trials would be necessary to confirm this.

Tomato Processing By-Products Valorisation through Ohmic Heating Approach.

Tomato by-products from processing industries have a higher potential to be reused as a source of bioactive compounds. Reliable national data on tomato by-products and physicochemical characterisation that will inform and find effective planning on tomato waste management in Portugal is absent. To help obtain this knowledge, selected Portugal companies were recruited to obtain representative samples of by-products generation, and physicochemical composition was evaluated. Furthermore, an environmental-friendly method (the ohmic heating (OH) method, which allows the recovery of bioactive compounds in absence of hazardous reagents) was also used and compared with conventional methods to explore new safe value-added ingredients. Total antioxidant capacity and total and individual phenolic compounds were also evaluated by spectrophotometric and high-performance liquid chromatography (HPLC), respectively. Tomato processing by-products have revealed a higher potential since both collected samples from companies were rich in protein (between 16.3 to 19.4 g/100 g DW, with fibre content ranging from 57.8 to 59.0 g/100 g DW). In addition, these samples contain 17.0 g/100 g of fatty acids (mainly polyunsaturated, monounsaturated and saturated, such as linoleic, oleic, and palmitic acid, respectively). Also, they present mainly chlorogenic acid and rutin as phenolic compounds. After understanding its composition, the OH was applied to determine added-value solutions to tomato by-products. With extractions, two types of fractions were obtained, namely liquid fraction rich in phenols, free sugars, and carotenoids and a solid fraction rich in fibre bound to phenols and carotenoids. This treatment has been shown to have the ability to preserve carotenoids, such as lycopene relative to conventional methods. Nevertheless, new molecules were identified by LC-ESI-UHR-OqTOF-MS analysis, such as phene-di-hexane and N-acethyl-D-tryptophan. According to the results, the OH boosts the potential of tomato by-products and can be directly introduced into the process, contributing to the circular economy and zero by-products.

Educational material production and validity: educational instrument for home care for premature newborns.

OBJECTIVE: to produce and validate a booklet, based on Jean Watson's Theory, on home care for premature newborns, based on caregivers' experiences. METHOD: a methodological study, developed in the following stages: diagnosis of knowledge needs about home care; survey of scientific content; educational material production; and validity by judges/experts. RESULTS: the literature review resulted in 19 articles. The main themes (breastfeeding, bath care, bond building, infection prevention and support network) were listed for producing the booklet "Booklet for Premature Newborns: Demystifying Home Care". The booklet content and appearance received the overall Content Validity Index of 0.85, considered suitable within the scientific rigor of validity. FINAL CONSIDERATIONS: the booklet produced and validated is an educational material whose main role is to provide knowledge and awaken caregivers' autonomy in providing home care to newborns.

Educational material production and validity: educational instrument for home care for premature newborns / Producción y validación de material educativo: instrumento educativo para el cuidado domiciliario del recién nacido prematuro / Produção e validação de material educativo: instrumento educativo para o cuidado domiciliar ao recém-nascido prematuro

ABSTRACT Objective: to produce and validate a booklet, based on Jean Watson's Theory, on home care for premature newborns, based on caregivers' experiences. Method: a methodological study, developed in the following stages: diagnosis of knowledge needs about home care; survey of scientific content; educational material production; and validity by judges/experts. Results: the literature review resulted in 19 articles. The main themes (breastfeeding, bath care, bond building, infection prevention and support network) were listed for producing the booklet "Booklet for Premature Newborns: Demystifying Home Care". The booklet content and appearance received the overall Content Validity Index of 0.85, considered suitable within the scientific rigor of validity. Final considerations: the booklet produced and validated is an educational material whose main role is to provide knowledge and awaken caregivers' autonomy in providing home care to newborns.

RESUMEN Objetivo: producir y validar una cartilla, basada en la Teoría de Jean Watson, sobre el cuidado domiciliario del recién nacido prematuro, a partir de las experiencias de los cuidadores. Método: estudio metodológico, desarrollado en las siguientes etapas: diagnóstico de las necesidades de conocimiento sobre el cuidado domiciliario; encuesta de contenido científico; producción de material educativo; y validación por jueces/expertos. Resultados: la revisión de la literatura resultó en 19 artículos. Se enumeraron los temas principales (lactancia materna, cuidado del baño, creación de vínculos, prevención de infecciones y red de apoyo) para la producción del folleto "Cuaderno para Recién Nacidos Prematuros: Desmitificando el Cuidado Domiciliario". El contenido y apariencia del cuadernillo recibió el Índice de Validez de Contenido Global de 0,85, considerado adecuado dentro del rigor científico de la validez. Consideraciones finales: la cartilla producida y validada es un material educativo que tiene como función principal proporcionar conocimientos y despertar la autonomía de los cuidadores en la atención domiciliaria al recién nacido.

RESUMO Objetivo: produzir e validar cartilha, baseado na Teoria de Jean Watson, sobre os cuidados domiciliares ao recém-nascido prematuro, a partir de vivências de cuidadores. Método: estudo metodológico, desenvolvido nas etapas: diagnóstico das necessidades de conhecimento sobre os cuidados domiciliares; levantamento dos conteúdos científicos; produção de material educativo; e validação por juízas/experts. Resultados: a revisão da literatura resultou em 19 artigos. Elencaram-se os principais temas (amamentação, cuidados com o banho, construção de vínculo, prevenção de infecções e rede de apoio), para produção da cartilha intitulada "Cartilha de Cuidados com o Recém-Nascido Prematuro: Desmistificando o Cuidar no Domicílio". O conteúdo e aparência da cartilha recebeu o Índice de Validade de Conteúdo Global de 0,85, considerado adequado dentro do rigor científico de validade. Considerações finais: a cartilha produzida e validada é um material educativo cujo papel principal é proporcionar conhecimento e despertar a autonomia dos cuidadores na prestação dos cuidados domiciliares ao recém-nascido.

Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B.

BACKGROUND: Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease, there is a paucity of data evaluating body composition in patients with chronic hepatitis B (CHB). Beyond virus-related factors, nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded. AIM: To evaluate the association between components of sarcopenia and demographic, clinical, lifestyle, nutritional, and biochemical variables in CHB patients. METHODS: Dual-energy X-ray absorptiometry (DXA) was used to assess muscle mass by quantifying appendicular lean mass (ALM) adjusted for body mass index (ALMBMI). Muscle function was evaluated by hand grip strength (HGS) and the timed up and go test. Metabolic-associated fatty liver disease (MAFLD) was defined according to the criteria proposed by an international expert panel. A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level, respectively. RESULTS: This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre (mean age, 48.5 ± 12.0 years; 58.1% males; 76.2% without cirrhosis; 23.8% with compensated cirrhosis). The DXA-derived fat mass percentage was inversely correlated with the ALMBMI (r = - 0.87) and HGS (r = - 0.63). In the multivariable analysis, MAFLD, sedentarism and central obesity were positively and independently associated with low ALMBMI. MAFLD and central obesity were independently associated with low HGS. CONCLUSION: MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B, independent of the liver disease stage.

Evaluation of Microbial-Fructo-Oligosaccharides Metabolism by Human Gut Microbiota Fermentation as Compared to Commercial Inulin-Derived Oligosaccharides.

The prebiotic potential of fructo-oligosaccharides (microbial-FOS) produced by a newly isolated Aspergillus ibericus, and purified by Saccharomyces cerevisiae YIL162 W, was evaluated. Their chemical structure and functionality were compared to a non-microbial commercial FOS sample. Prebiotics were fermented in vitro by fecal microbiota of five healthy volunteers. Microbial-FOS significantly stimulated the growth of Bifidobacterium probiotic strains, triggering a beneficial effect on gut microbiota composition. A higher amount of total short-chain fatty acids (SCFA) was produced by microbial-FOS fermentation as compared to commercial-FOS, particularly propionate and butyrate. Inulin neoseries oligosaccharides, with a degree of polymerization (DP) up to 5 (e.g., neokestose and neonystose), were identified only in the microbial-FOS mixture. More than 10% of the microbial-oligosaccharides showed a DP higher than 5. Differences identified in the structures of the FOS samples may explain their different functionalities. Results indicate that microbial-FOS exhibit promising potential as nutraceutical ingredients for positive gut microbiota modulation.

Bioactivity and Bioaccessibility of Bioactive Compounds in Gastrointestinal Digestion of Tomato Bagasse Extracts.

A nutrient-rich diet is a key to improving the chemical signals, such as antioxidants, which modulate pathogens' resistance in the gut and prevent diseases. A current industrial problem is the generation of undervalued by-products, such as tomato bagasse, which are rich in bioactive compounds and of commercial interest (carotenoids and phenolic compounds). This work analyzed the effect of gastrointestinal digestion on the bioactivity and bioaccessibility of carotenoids and phenolic compounds from tomato bagasse extracts. Thus, the extraction by ohmic heating (OH) technology was compared with conventional (organic solvents). The results showed that the main phenolic compounds identified by UPLC-qTOF-MS were p-coumaric acid, naringenin, and luteolin. A higher recovery index for total phenolic compounds throughout the gastrointestinal digestion was observed for OH while for carotenoids, a strong reduction after stomach conditions was observed for both extracts. Furthermore, colon-available fraction exhibited a prebiotic effect upon different Bifidobacterium and Lactobacillus, but a strain-dependent and more accentuated effect on OH. Thus, the extraction technology highly influenced bioaccessibility, with OH demonstrating a positive impact on the recovery of bioactive compounds and related health benefits, such as antioxidant, anti-hypertensive, prebiotic, and anti-inflammatory properties. Of these properties, the last is demonstrated here for the first time.

Participation of adolescents from the Quilombola community in the creation of an educational game about alcohol consumption.

OBJECTIVE: To describe and discuss the participation of adolescents from a quilombola community in the transformation of the comic "Possible Story" ("Uma História Possível"), from the Comic on alcohol, into an educational game. METHOD: Implementation of the creative and sensitive method of art-based research, with adolescents from a quilombola community in the state of Espírito Santo, for the development of a board game. RESULTS: The democratic and interactive space favored the problematization of images and narratives about alcohol consumption mediated in the comic book. The group selected scenes, reordered the story, devised questions and riddles, formulated true and false assertions in a 17-card composition of the board game. The potential of the game as a content mediating tool to promote learning, reinforcement, and fixation of scientific content was evaluated. CONCLUSION: The active and dynamic participation of adolescents took place from conception to evaluation of the board game, encouraging them to reflect on a community context of cultural permissiveness of alcohol use.

NADPH Oxidase 3 Deficiency Protects From Noise-Induced Sensorineural Hearing Loss.

The reactive oxygen species (ROS)-generating NADPH oxidase NOX3 isoform is highly and specifically expressed in the inner ear. NOX3 is needed for normal vestibular development but NOX-derived ROS have also been implicated in the pathophysiology of sensorineural hearing loss. The role of NOX-derived ROS in noise-induced hearing loss, however, remains unclear and was addressed with the present study. Two different mouse strains, deficient in NOX3 or its critical subunit p22phox, were subjected to a single noise exposure of 2 h using an 8-16 kHz band noise at an intensity of 116-120 decibel sound pressure level. In the hours following noise exposure, there was a significant increase in cochlear mRNA expression of NOX3 in wild type animals. By using RNAscope in situ hybridization, NOX3 expression was primarily found in the Rosenthal canal area, colocalizing with auditory neurons. One day after the noise trauma, we observed a high frequency hearing loss in both knock-out mice, as well as their wild type littermates. At day seven after noise trauma however, NOX3 and p22phox knockout mice showed a significantly improved hearing recovery and a marked preservation of neurosensory cochlear structures compared to their wild type littermates. Based on these findings, an active role of NOX3 in the pathophysiology of noise-induced hearing loss can be demonstrated, in line with recent evidence obtained in other forms of acquired hearing loss. The present data demonstrates that the absence of functional NOX3 enhances the hearing recovery phase following noise trauma. This opens an interesting clinical window for pharmacological or molecular intervention aiming at post prevention of noise-induced hearing loss.

Participation of adolescents from the Quilombola community in the creation of an educational game about alcohol consumption / Participación de adolescentes de comunidad Quilombola en la creación de juego educativo sobre consumo de alcohol / Participação de adolescentes de comunidade Quilombola na criação de jogo educativo sobre o consumo de álcool

ABSTRACT Objective: To describe and discuss the participation of adolescents from a quilombola community in the transformation of the comic "Possible Story" ("Uma História Possível"), from the Comic on alcohol, into an educational game. Method: Implementation of the creative and sensitive method of art-based research, with adolescents from a quilombola community in the state of Espírito Santo, for the development of a board game. Results: The democratic and interactive space favored the problematization of images and narratives about alcohol consumption mediated in the comic book. The group selected scenes, reordered the story, devised questions and riddles, formulated true and false assertions in a 17-card composition of the board game. The potential of the game as a content mediating tool to promote learning, reinforcement, and fixation of scientific content was evaluated. Conclusion: The active and dynamic participation of adolescents took place from conception to evaluation of the board game, encouraging them to reflect on a community context of cultural permissiveness of alcohol use.

RESUMEN Objetivo: Describir y discutir la participación de adolescentes de una comunidad quilombola en la transformación de cómics de "Una Historia Posible" (Uma História Possível), del Almanaque sobre alcohol en juego educativo. Método: Implementación del método creativo y sensible de investigación basada en arte, con adolescentes de una comunidad quilombola de Espírito Santo, Brasil, en el desarrollo de un juego de mesa. Resultados: El espacio democrático e interactivo favoreció la problematización de imágenes y narrativas sobre el consumo de alcohol mediado en los cómics. El grupo seleccionó escenas, reordenó la historia, elaboró preguntas y charadas, formuló aserciones de mito o verdad en una composición de 17 fichas del juego de mesa. Se evaluó el potencial del juego como herramienta mediadora de contenido para promover el aprendizaje, el repaso y la memorización de contenidos científicos. Conclusión: La participación activa y dinámica de adolescentes ocurrió desde la concepción hasta la evaluación del juego de mesa, estimulándolos a la reflexión sobre un contexto comunitario de permisividad cultural de uso del alcohol.

RESUMO Objetivo: Descrever e discutir a participação de adolescentes de uma comunidade quilombola na transformação de quadrinhos de "Uma História Possível", do Almanaque sobre o álcool, em jogo educativo. Método: Implementação do método criativo e sensível de pesquisa baseada em arte, com adolescentes de uma comunidade quilombola do Espírito Santo, no desenvolvimento de um jogo de tabuleiro. Resultados: O espaço democrático e interativo favoreceu a problematização de imagens e narrativas sobre o consumo de álcool mediadas na história em quadrinhos. O grupo selecionou cenas, reordenou a história, elaborou perguntas e charadas, formulou asserções de verdadeiro e falso numa S composição de 17 cartas do jogo de tabuleiro. Avaliou-se o potencial do jogo como ferramenta mediadora de conteúdo para promover a aprendizagem, o reforço e fixação de conteúdos científicos. Conclusão: A participação ativa e dinâmica de adolescentes deu-se desde a concepção até a avaliação do jogo de tabuleiro, estimulando-os à reflexão sobre um contexto comunitário de permissividade cultural de uso do álcool.

Local Cisplatin Delivery in Mouse Reliably Models Sensorineural Ototoxicity Without Systemic Adverse Effects.

Cisplatin is a lifesaving chemotherapeutic drug with marked ototoxic adverse effects. Cisplatin-induced hearing loss affects a significant part of cancer-surviving patients and is an unmet clinical need with important socioeconomic consequences. Unfortunately, in current preclinical animal models of cisplatin ototoxicity, which are mainly based on systemic delivery, important morbidity is observed, leading to premature death. This methodology not only raises obvious animal welfare concerns but also increases the number of animals used in ototoxicity studies to compensate for dropouts related to early death. To overcome these important limitations, we developed a local delivery model based on the application of a cisplatin solution directly into the otic bulla through a retroauricular approach. The local delivery model reliably induced significant hearing loss with a mean threshold shift ranging from 10 to 30 dB, strongly affecting the high frequencies (22 and 32 kHz). Importantly, mice did not show visible stress or distress indicators and no significant morbidity in comparison with a traditional systemic delivery control group of mice injected intraperitoneally with 10 mg/kg cisplatin, where significant weight loss >10% in all treated animals (without any recovery) led to premature abortion of experiments on day 3. Mass spectrometry confirmed the absence of relevant systemic uptake after local delivery, with platinum accumulation restricted to the cochlea, whereas important platinum concentrations were detected in the liver and kidney of the systemic cisplatin group. A clear correlation between the cochlear platinum concentration and the auditory threshold shift was observed. Immunohistochemistry revealed statistically significant loss of outer hair cells in the basal and apical turns of the cochlea and an important and statistically significant loss of auditory neurons and synapses in all cochlear regions. In conclusion, local cisplatin delivery induces robust hearing loss with minimal morbidity, thereby offering a reliable rodent model for human cisplatin ototoxicity, reducing the number of animals required and showing improved animal welfare compared with traditional systemic models.