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There is a widely recognized need to reduce human activity's impact on the environment. Many industries of the leather and textile sector (LTI), being aware of producing a significant amount of residues (Keßler et al. 2021; Liu et al. 2021), are adopting measures to reduce the impact of their processes on the environment, starting with a more comprehensive characterization of the chemical risk associated with the substances commonly used in LTI. The present work contributes to these efforts by compiling and toxicologically annotating the substances used in LTI, supporting a continuous learning strategy for characterizing their chemical safety. This strategy combines data collection from public sources, experimental methods and in silico predictions for characterizing four different endpoints: CMR, ED, PBT, and vPvB. We present the results of a prospective validation exercise in which we confirm that in silico methods can produce reasonably good hazard estimations and fill knowledge gaps in the LTI chemical space. The proposed protocol can speed the process and optimize the use of resources including the lives of experimental animals, contributing to identifying potentially harmful substances and their possible replacement by safer alternatives, thus reducing the environmental footprint and impact on human health.

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Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known as the first glaucoma gene. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 h post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but, remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provides in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination.

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This paper reports part of an international research project with the long-term aim of developing more sustainable asphalt mixture with crack-healing properties by the addition of recycled metallic waste from industrial sources. Specifically, this article presents an evaluation of the physical, thermophysical, and mechanical properties of asphalt mixtures with metallic fiber obtained from recycled tires for crack-healing purposes. Detailed results on the crack-healing of asphalt mixtures will be reported in a second article. Results showed a small reduction on the bulk density and increase in the air voids content was quantified with increasing fiber contents. The experimental results showed that mixing and compaction was more difficult for higher fiber contents due to less space for the bitumen to freely flow and fill the voids of the mixtures. Computed tomography (CT) results allowed to identify clustering and orientation of the fibers. The samples were electrically conductive, and the electrical resistivity decreased with the increase of the fiber content. Fiber content had a direct effect on the indirect tensile stiffness modulus (ITSM) and strength (ITS) that decreased with increasing temperature for mixtures and with increase in fiber content. However, the indirect tensile strength ratio (ITSR) was within acceptable limits. In short, results indicate that fibers from recycled tires have a potential for use within asphalt mixtures to promote crack-healing.

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Compelling data in the literature from the recent years leave no doubt about the pluridimensional nature of G protein-coupled receptor function and the fact that some ligands can couple with different efficacies to the multiple pathways that a receptor can signal through, a phenomenon most commonly known as functional selectivity or biased agonism. Nowadays, transduction coefficients (log(τ/KA)), based on the Black and Leff operational model of agonism, are widely used to calculate bias. Nevertheless, combining both affinity and efficacy in a single parameter can result in compounds showing a defined calculated bias of one pathway over other though displaying varying experimental bias preferences. In this paper, we present a novel scale (log(τ)), that attempts to give extra substance to different compound profiles in order to better classify compounds and quantify their bias. The efficacy-driven log(τ) scale is not proposed as an alternative to the affinity&efficacy-driven log(τ/KA) scale but as a complement in those situations where partial agonism is present. Both theoretical and practical approaches using µ-opioid receptor agonists are presented.

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Fluorescence resonance energy transfer (FRET) is an approach widely used to detect protein-protein interactions in live cells. This approach is based on the sensitization of an "acceptor" molecule by the energy transfer from a "donor" when there is an overlap between the emission spectrum of the "donor" and the excitation spectrum of the "acceptor" and close proximity between the two fluorophore species (in the region of 8 nm). Various methods exist to quantify FRET signals: here, we describe the application of homogeneous time-resolved FRET (htrFRET) combined with Tag-lite™ technology and its application to determine not only protein-protein interactions but also the capability of GPCR mutant variants to form homomers compared to the wild type GPCR within the plasma membrane of transfected cells.

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Los niños con enfermedades oncológicas en tratamiento convencional se ven afectados tanto emocional como físicamente por la medicina tradicional y, considerando, que la OMS ha realizado publicaciones en que se invita a los países a implementar el uso de terapias complementarias, y que el Ministerio de Salud del Gobierno de Chile ha reconocido a la acupuntura, naturopatía y homeopatía como profesiones auxiliares de salud, se realizó una investigación descriptiva, basada en la metodología cuantitativa y tomando como referencia la Teoría de los Seres Unitarios planteada por Martha Rogers, con el propósito de conocer el impacto que producen las terapias complementarias en la tolerancia al tratamiento convencional, y la participación del Profesional de Enfermería en su uso. El proceso de recolección de datos fue durante el mes de diciembre de 2014 a enero de 2015, en los Hospitales Dr. Exequiel González Cortés y Dr. Roberto del Río, en el Hospital Clínico de la Universidad Católica de Chile, en la Clínica Dávila y en la Fundación Nuestros Hijos, sede San Miguel. Se encuestó a 120 cuidadores de niños con enfermedades oncológicas, quienes voluntariamente respondieron un cuestionario autoadministrado. Al cuantificar el uso de terapias complementarias, se determinó que 56 niños (47%), utilizan este tipo de terapias y que a su vez, más de la mitad de quienes la utilizan, hacen uso de más de un tipo de éstas. Al determinar el impacto de las terapias complementarias en la tolerancia al tratamiento convencional el resultado fue de carácter positivo, con un porcentaje que fluctúa entre un 75% y un 97%. Finalmente, al establecer el grado de participación de los Profesionales de Enfermería en el uso de terapias complementarias, se evidenció que su participación es baja (18%).

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The aim of this study is to investigate psychosocial factors related to the diagnosis and treatment of patients with restless legs syndrome. Fifteen patients were interviewed at the Neuro-Sono Outpatient Clinic, Universidade Federal de São Paulo. The results were submitted to a qualitative analysis. We identified four content categories: illness description, illness history, illness experience, and relationships. Lack of control over the body and lack of recognition by professionals produce stigma and lead patients to suffering. The research underscores the relevance of psychosocial factors to the diagnosis and treatment of patients with restless legs syndrome and the importance of having interdisciplinary teams when attending patients with restless legs syndrome.

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OBJECTIVE: The use of unstructured play as an intervention to help children cope with the stress of a hospitalization period was tested in this randomized clinical trial. METHODS: Urinary cortisol (a stress marker) was examined in 53 pediatric patients hospitalized for respiratory diseases in a public hospital, divided into two groups that did or did not play. RESULTS: Boys and girls from the play group, 7-11 years old, showed a decrease in cortisol levels after participating in play activities. In younger participants (4-7 years old) the intervention did not seem as efficient, probably because in this group maturity levels may have influenced how children cognitively engaged in play as a coping strategy. CONCLUSIONS: The study showed the importance of using interventions that consider age ranges and gender in enhancing coping strategies, as well as the importance of such techniques that are employed by occupational therapists since they are professionals with expertise in the use of activities as therapeutic instruments.

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The behavioral and neurochemical adaptations related to chronic 3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this study, we assessed whether repeated administration of MDMA would induce (a) context-dependent locomotor sensitization in mice and (b) changes in serotonin 5-HT(2A) and dopamine D2 receptor functionality as measured by [³5S]GTPγS binding. Mice were treated with MDMA (10 mg/kg, intraperitoneally) or saline every other day for 11 days either in their home cages or in the environment where locomotor activity was measured. After a 10-day withdrawal period, mice were challenged with MDMA (5 and 10 mg/kg) and saline before locomotor activity measurements. During repeated MDMA treatment, locomotion was progressively enhanced, indicating the development of behavioral sensitization. The MDMA challenge at a dose of 5 mg/kg increased locomotor activity to a greater extent in mice pretreated with MDMA in the testing apparatus than in mice pretreated in the home cages, revealing that contextual cues paired with repeated drug exposure can enhance the expression of behavioral sensitization to MDMA. In contrast, a challenge administration of MDMA at 10 mg/kg induced similar locomotor sensitization in mice pretreated in both environments. An increase in the functionality of cortical 5-HT(2A) receptors was observed in mice pretreated with MDMA compared with mice pretreated with saline, but this activation was significantly greater in mice pretreated in the locomotor environment. In contrast, the functional activity of striatal D2 receptors was significantly decreased only in mice pretreated with MDMA in the testing apparatus. These results reveal neuroadaptations in cortical 5-HT(2A) and striatal D2 receptors after MDMA-induced behavioral sensitization in mice.

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OBJECTIVE: To investigate the prevalence of sleep disorders in a sample of children from a public hospital in the city of São Paulo, Brazil. METHOD: 330 children, who came to the clinical laboratory, were consecutively investigated for sleep disorders, using the sleep disturbance scale for children. Gender, age, and social/economical classification were considered. RESULTS: Sleep disordered breathing (SDB) showed higher prevalence in our sample (55%) than in data found in the literature. Prevalence of sleep hyperhydrosis (SHY) was 27% considering the whole sample. Boys and children in age range 7.1 to 11 years old showed higher prevalence for SDB as well as children belonging to lower social/economic classifications who were also more prevalent for disorders in the transition of sleep-wakefulness. CONCLUSION: Sleep disorders were highly prevailing in our study, mostly SDB and SHY which were exceedingly more prevalent in boys in relation to international literature.

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OBJECTIVE: To investigate the prevalence of sleep disorders in a sample of children from a public hospital in the city of São Paulo, Brazil. METHOD: 330 children, who came to the clinical laboratory, were consecutively investigated for sleep disorders, using the sleep disturbance scale for children. Gender, age, and social/economical classification were considered. RESULTS: Sleep disordered breathing (SDB) showed higher prevalence in our sample (55 percent) than in data found in the literature. Prevalence of sleep hyperhydrosis (SHY) was 27 percent considering the whole sample. Boys and children in age range 7.1 to 11 years old showed higher prevalence for SDB as well as children belonging to lower social/economic classifications who were also more prevalent for disorders in the transition of sleep-wakefulness. CONCLUSION: Sleep disorders were highly prevailing in our study, mostly SDB and SHY which were exceedingly more prevalent in boys in relation to international literature.

OBJETIVO: Investigar a prevalência de distúrbios do sono numa amostra de crianças de um hospital público da cidade de São Paulo, Brasil. MÉTODO: 330 crianças que compareceram ao laboratório clínico foram consecutivamente investigadas para a presença de distúrbios do sono, usando-se a Escala de Distúrbios do Sono para crianças. Foram consideradas variáveis como sexo, idade e classificação sócio econômica. RESULTADOS: Os distúrbios respiratórios do sono (DRS) mostraram alta prevalência (55 por cento) em nossa amostra em relação aos dados encontrados na literatura. A prevalência de hiper hidrose do sono (HHS) foi de 27 por cento. Meninos e crianças da faixa etária compreendida entre 7,1 e 11 anos apresentaram prevalências mais altas para distúrbios respiratórios do sono assim como crianças pertencentes às classificações sócio econômicas mais baixas, que também foram mais prevalentes para desordens da transição sono-vigília. CONCLUSÃO: Os distúrbios do sono foram altamente presentes em nosso estudo, principalmente DRS e HHS, que foram mais prevalentes nos meninos, comparados com a literatura internacional.

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