Experiences and Translatability of In Vitro and In Vivo Models to Evaluate Caprate as a Permeation Enhancer.

Transient permeation enhancers (PEs) have been widely used to improve the oral absorption of macromolecules. During pharmaceutical development, the correct selection of the macromolecule, PE, and the combination needs to be made to maximize oral bioavailability and ensure successful clinical development. Various in vitro and in vivo methods have been investigated to optimize this selection. In vitro methods are generally preferred by the pharmaceutical industry to reduce the use of animals according to the "replacement, reduction, and refinement" principle commonly termed "3Rs," and in vitro methods typically have a higher throughput. This paper compares two in vitro methods that are commonly used within the pharmaceutical industry, being Caco-2 and an Ussing chamber, to two in vivo models, being in situ intestinal instillation to rats and in vivo administration via an endoscope to pigs. All studies use solution formulation of sodium caprate, which has been widely used as a PE, and two macromolecules, being FITC-dextran 4000 Da and MEDI7219, a GLP-1 receptor agonist peptide. The paper shares our experiences of using these models and the challenges with the in vitro models in mimicking the processes occurring in vivo. The paper highlights the need to consider these differences when translating data generated using these in vitro models for evaluating macromolecules, PE, and combinations thereof for enabling oral delivery.

Factors Associated with the Oral Health-Related Quality of Life in Children with Intellectual Disabilities / Factores asociados con la calidad de vida relacionada con la salud bucal en niños con discapacidad intelectual

Abstract: Different factors can influence the perception of quality of life in individuals with intellectual disabilities. This study investigated the factors associated with quality of life related to oral health in children with intellectual disabilities from the perspective of their parents. A cross-sectional study was carried out with Brazilian children from specialized institutions and their respective guardians. Data were collected through medical records, application of instruments and oral clinical examination (n=92). Most children had poor oral hygiene (64.10%) and a high caries experience (59.8%). The mothers' perception of quality of life related to oral health was low, however there was an association of greater perception when they had low education, female child, less brushing frequency and history of breastfeeding (p≤0.05). Although the perception of quality of life was low, the oral condition found evidences the need to promote oral health education actions with children with intellectual disabilities and their respective guardians.

Resumen: Diferentes factores pueden influir en la calidad de vida de personas con discapacidad intelectual. Este estudio investigó los factores asociados con la calidad de vida relacionada con la salud oral en niños con discapacidades intelectuales desde la perspectiva de sus cuidadores. Se realizó un estudio transversal con niños brasileños institucionalizados, que fueron evaluados clínicamente y sus respectivos tutores, quienes respondieron cuestionarios. Los datos fueron recolectados a través de registros médicos, aplicación de instrumentos de evaluación y examen clínico oral (n=92). La mayoría de los niños presentaban una higiene oral deficiente (64,10%) y una experiencia de caries alta (59,8%). Si bien la percepción específicamente de las madres respecto del impacto de las condiciones de la salud oral en la calidad de vida fue baja, mostró una tendencia a aumentar en cuanto disminuía el nivel educacional, la frecuencia de cepillado y la historia de lactancia materna (p≤0.05). El hecho de que la percepción del impacto en la calidad de vida por parte de los tutores no se condiga con las precarias condiciones de salud oral exhibida por los niños con discapacidad intelectual, no sólo demuestra el desconocimiento respecto de la importancia de la salud oral en un contexto general, sino que también evidencia la necesidad de promover acciones que incentiven el cuidado y educación en relación con este aspecto, tanto en los tutores como en los niños afectados.

Multiplicando saberes: ampliando os cuidados em saúde bucal. Relato de experiência de um projeto de extensão universitária / Multiplying knowledge: extending oral health care. Experience report of a university extension project / Multiplicar el conocimiento: extender la atención de la salud bucal. Informe de experiencia de un proyecto de extensión universitaria

A extensão universitária é uma atividade que engrandece a vivência acadêmica, implementando melhorias na qualidade de saúde bucal da comunidade. Esse escopo teve como objetivo mostrar o desenvolvimento de práticas educativas e promoção de saúde no projeto de Extensão Multiplicando Saberes o qual é vinculado ao Programa de Pós-Graduação em Odontologia (PRODONTO) da UFS. A ação de extensão envolveu atividades educativas voltadas à cidadania e promoção de saúde bucal, com orientação e avaliação odontológica a crianças e adolescentes com deficiência e seus cuidadores, professores e orientadores educacionais. Participaram 162 crianças e adolescentes com deficiência das quais 22 com paralisia cerebral, 36 com transtorno do espectro autista, 13 com síndrome de Down e 91 com retardo mental. Dos 44 cuidadores participantes, 92% eram mulheres. A faixa etária da maioria foi de 30 a 40 anos (54.5%), casados (38.6%),tendo 2 a 3 filhos (63.6%),e ensino médio completo (72.7%) e são cuidadores integrais 79.5%. Cerca de 68.2% não possuem renda formal. Dos 4 educadores participantes, 3 são do gênero feminino e apresentam ensino médio completo. Foi possível observar a materialização de noções básicas de saúde, o autocuidado e a capacitação de cuidadores, elevados à condição de agentes ativos e multiplicadores das ações de promoção de saúde em nível individual e coletivo. (AU)

Introduction: University extension is an activity that enhances the academic experience, implementing improvements in the oral health quality of the community. Objective: This scope aimed to show the development of educational practices and health promotion in the Extension Multiplicando Saberes project, which is linked to the Postgraduate Program in Dentistry (PRODONTO) of UFS. Material and Method: The extension action involved educational activities focused on citizenship and oral health promotion, with orientation and dental assessment to children and adolescents with disabilities and their caregivers, teachers and educational counselors. RESULTS: A total of 162 children and adolescents with a disability participated, 22 of them with cerebral palsy, 36 with autism spectrum disorder, 13 with Down syndrome and 91 with mental retardation. Of the 44 participating caregivers, 92% were women. The majority age group was between 30 and 40 years old (54.5%), married (38.6%), having 2 to 3 children (63.6%), and complete secondary education (72.7%). About 68.2% have no formal income. Of the 4 participating educators, 3 are female and have completed high school. Conclusion: It was possible to observe the materialization of basic concepts of health, self-care and the training of caregivers, elevated to the condition of active agents and multipliers of actions of health promotion at individual and collective level. (AU)

La extensión universitaria es una actividad que mejora la experiencia académica, implementando mejoras en la calidad de la salud oral de la comunidad. Este alcance tuvo como objetivo mostrar el desarrollo de las prácticas educativas y la promoción de la salud en el proyecto de Extensión del Conocimiento Multiplicador que está vinculado al Programa de Postgrado en Odontología de UFS (PRODONTO). La acción de extensión incluyó actividades educativas dirigidas a la ciudadanía y la promoción de la salud bucal, con orientación y evaluación dental para niños y adolescentes con discapacidades y sus cuidadores, maestros y consejeros educativos. Participaron 162 niños y adolescentes con discapacidad, 22 con parálisis cerebral, 36 con trastorno del espectro autista, 13 con síndrome de Down y 91 con retraso mental. De los 44 cuidadores participantes, el 92% eran mujeres. El grupo de edad mayoritario fue de 30 a 40 años (54.5%), casados (38.6%), con 2 a 3 hijos (63.6%) y completar la escuela secundaria (72.7%) y cuidadores completos 79.5%. Alrededor del 68.2% no tiene ingresos formales. De los 4 educadores participantes, 3 son mujeres y han completado la escuela secundaria. Fue posible observar la materialización de los conceptos básicos de salud, autocuidado y capacitación de cuidadores, elevada a la condición de agentes activos y multiplicadores de acciones de promoción de la salud a nivel individual y colectivo. (AU)

Aproximação às condições de saúde bucal de catadores de materiais recicláveis cooperados em Aracaju/SE / Approach to the oral health conditions of Aracaju/SE cooperated recycling materials / Enfoque de las condiciones de salud oral de los materiales de reciclaje cooperados de Aracaju/SE

Evidencia-se que na área de saúde bucal a pobreza e a exclusão sócio sanitária tem uma das suas mais evidentes manifestações, tendo em vista que pessoas pobres, que possuem baixa escolaridade e uma menor inserção no mercado de trabalho trazem consigo marcas dentárias que são reflexo de uma realidade objetiva e uma outra subjetiva. Assim foi realizada uma descrição e analise das condições de saúde bucal dos trabalhadores cooperados evidenciando os acometimentos mais prevalentes e a opinião sobre tal situação por parte dos cooperados. A avaliação foi feita por meio de uma ficha de identificação com nome, idade, sexo, em seguida os participantes responderam um questionário que trazia perguntas relacionadas ao cotidiano dos mesmos, envolvendo temas relativos à sua rotina de trabalho, saúde geral e saúde odontológica. Pode ser observado que a maior preocupação dos trabalhadores é estar apto ao trabalho, devido à necessidade de manter o seu sustento, sendo que quadros variáveis de sintomatologia dolorosa são suportados, até o limite que se possa continuar a labuta diária. É fato evidente, que o presente estudo feito na cooperativa, observando uma fração da rotina desses trabalhadores, dentro da sua realidade e segundo o seus relatos não deve encerrar-se em si devendo, por sua vez, provocar um novo olhar, com uma característica mais analítica e com uma sensibilidade a sua realidade para que os catadores de materiais recicláveis não vivam com o descaso, tendo em vista a rotina penosa que tem de enfrentar todos os dias. (AU)

It is evident that in the area of oral health to poverty and social exclusion Health has one of its most obvious manifestations, given that poor people, who have lower education and lower insertion in the labor market brings with tooth marks that are reflective of an objective reality and subjective another. This paper presents a description and analysis of the oral health status of workers cooperative bouts highlighting the most prevalent and opinion about this situation on the part of members. The evaluation was made by means of a form with name, age, sex, then the participants answered a questionnaire featured questions related to daily thereof, involving issues related to routine work, general health and dental health. It can be observed that the greatest concern of employees is being able to work because of the need to maintain their livelihood, and variable frame of painful symptoms are supported, to the extent that it can continue to toil daily. It is indeed evident that the present study the cooperative observing a fraction of the routine of these workers, into your reality and according to their reports should not end in itself and should, in turn, cause a new look, with a characteristic more analytical sensitivity and your reality for the waste pickers do not live with neglect, with a view to routine painful to have to face every day. (AU)

Es evidente que enel área de lasalud oral, la pobreza y laexclusión social y de saludtienen una de sus manifestaciones más obvias, teniendoencuenta que las personas pobres, que tienenpocaeducación y una menor inserciónenel mercado laboral, traen consigo marcas dentales que reflejan de una realidad objetiva y una subjetiva. Por lo tanto, se realizó una descripción y análisis de las condiciones de salud bucal de lostrabajadores cooperativos, destacando lostrastornosmás frecuentes y laopinión de losmiembros de la cooperativa sobre dichasituación. La evaluación se realizó mediante unformulario de identificaciónconnombre, edad, sexo, luegolos participantes respondieronuncuestionario que hacía preguntas relacionadas consu vida diaria, que involucraba temas relacionados consu rutina laboral, salud general y salud dental. Se puede observar que la principal preocupación de lostrabajadores es poder trabajar, debido a lanecesidad de mantenersu sustento, y se admitensíntomasvariables de síntomas dolorosos, hasta ellímite que puede continuar eltrabajodiario. Esunhecho evidente que el presente estudio realizado enla cooperativa, observando una fracción de la rutina de estostrabajadores, dentro de surealidad y según sus informes, no debe terminar ensímismo y, a su vez, provocar una nueva mirada, con una característica más analítico y sensible a surealidad para que losrecolectores de materialesreciclables no vivancon negligencia, dada la dolorosa rutina que tienen que enfrentar todos losdías. (AU)

Updated European Consensus Statement on diagnosis and treatment of adult ADHD.

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.

Complete Genome Sequence of Sporisorium scitamineum and Biotrophic Interaction Transcriptome with Sugarcane.

Sporisorium scitamineum is a biotrophic fungus responsible for the sugarcane smut, a worldwide spread disease. This study provides the complete sequence of individual chromosomes of S. scitamineum from telomere to telomere achieved by a combination of PacBio long reads and Illumina short reads sequence data, as well as a draft sequence of a second fungal strain. Comparative analysis to previous available sequences of another strain detected few polymorphisms among the three genomes. The novel complete sequence described herein allowed us to identify and annotate extended subtelomeric regions, repetitive elements and the mitochondrial DNA sequence. The genome comprises 19,979,571 bases, 6,677 genes encoding proteins, 111 tRNAs and 3 assembled copies of rDNA, out of our estimated number of copies as 130. Chromosomal reorganizations were detected when comparing to sequences of S. reilianum, the closest smut relative, potentially influenced by repeats of transposable elements. Repetitive elements may have also directed the linkage of the two mating-type loci. The fungal transcriptome profiling from in vitro and from interaction with sugarcane at two time points (early infection and whip emergence) revealed that 13.5% of the genes were differentially expressed in planta and particular to each developmental stage. Among them are plant cell wall degrading enzymes, proteases, lipases, chitin modification and lignin degradation enzymes, sugar transporters and transcriptional factors. The fungus also modulates transcription of genes related to surviving against reactive oxygen species and other toxic metabolites produced by the plant. Previously described effectors in smut/plant interactions were detected but some new candidates are proposed. Ten genomic islands harboring some of the candidate genes unique to S. scitamineum were expressed only in planta. RNAseq data was also used to reassure gene predictions.

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group.

The role of hippocampal commissures in the interhemispheric transfer of epileptiform afterdischarges in the rat: a study using linear and non-linear regression analysis.

The role of the forebrain commissures and the septal area in the interhemispheric transfer of hippocampal afterdischarges (ADs) was investigated in the rat under halothane anesthesia. Electrical seizures were elicited from the dorsal hippocampus before and after commissurotomy. The degree of relatedness between EEG signals recorded from homologous sites of both hippocampi was quantified using two approaches: (i) a time domain analysis considering an AD as a succession of discrete bursts; the onset times of such bursts were measured and used to estimate interhemispheric onset delays; (ii) using signal analysis the linear (r2) and non-linear (h2) regression coefficients between pairs of EEG signals were computed as a function of time shift between the two signals. In this way the values of association (linear and non-linear) and the corresponding time delays were measured. In general a tetanus applied unilaterally to the dorsal CA3 field resulted in bilaterally synchronous ADs. The estimated interhemispheric time delay was in most cases zero. This bilateral synchrony disappeared after section of a specific part of the ventral hippocampal commissure (VHC), the dorso-caudal third, but was not affected by section of other commissural fibers or by a lesion of the septal area. This study also allowed evaluation of different methods of quantification of the association between EEG signals, namely the linear (r2) and the non-linear (h2) regression coefficients. The latter was shown to be a more robust measure than the former and to yield values of association even in cases in which r2 was at noise level. The experimental findings allow the conclusion that ADs elicited from an epileptogenic focus spread to homologous sites in the contralateral hemisphere following commissural systems that may be strong enough to ensure the forming of one bilateral oscillating system.