Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

BACKGROUND: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. METHODS: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. RESULTS: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. CONCLUSIONS: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018.

Rapid, Cost-Effective Peptide/Nucleic Acid-Based Platform for Therapeutic Antibody Monitoring in Clinical Samples.

We demonstrate here a homogeneous assay, named NanoHybrid, for monoclonal antibody quantification directly in serum samples in a single-step format. NanoHybrid is composed of both synthetic peptide nucleic acids (PNAs) and nucleic acid strands conjugated to recognition elements and optical labels and is designed to allow fast fluorescence quantification of a therapeutic antibody. More specifically, we have characterized our analytical assay for the detection of trastuzumab (Herceptin), a monoclonal antibody (mAb) drug used for breast cancer treatment and for tumors overexpressing the HER2/neu protein. We show here that NanoHybrid is capable of performing fast drug quantification directly in blood serum. The results obtained with a pool of samples from breast cancer patients under trastuzumab treatment are compared with CE-IVD ELISA (enzyme-linked immunosorbent assay) showing a good agreement (Cohen's K = 0.729). Due to the modular nature of the NanoHybrid platform, this technology can be programmed to potentially detect and quantify any antibody for which a high-affinity recognition element has been characterized. We envision the application of NanoHybrid in a point-of-care (POC) drug monitoring system based on disposable kits for therapeutic drug management.

Revisão sistemática integrativa da literatura sobre modelos e práticas de intervenção precoce no brasil / Systematic literature review on models and practices of early childhood intervention in brazil

RESUMO Objetivo: Identificar quais práticas e modelos de Intervenção Precoce na Infância estão descritos na literatura científica brasileira. Fontes de dados: Realizou-se uma revisão sistemática integrativa da literatura indexada entre 2005 e 2015 nas bases Biblioteca Virtual em Saúde, Bielefeld Academic Search Engine, Education Resources Information Center e Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior. Foram incluídos artigos publicados em língua inglesa ou portuguesa, na íntegra e disponibilizados online que: contivessem os termos "Intervenção Precoce" ou "Estimulação Precoce" ou "Estimulação Essencial" no título, resumo ou palavras-chave; contassem como participantes crianças de 0 a 6 anos, seus cuidadores ou profissionais de serviços de Intervenção Precoce; estivessem indexados em uma revista com classificação igual ou superior a B2, segundo avaliação do WebQualis (Qualis 2014), para as áreas de Educação ou Educação Física; e descrevessem práticas de Intervenção Precoce. Síntese dos dados: Verifica-se que a Intervenção Precoce parece desenvolver-se exclusivamente aliada ao setor da saúde, com prevalência de práticas voltadas à estimulação de habilidades, com enfoque centrado na criança, estruturadas a partir de um modelo reabilitativo de cuidado e do emprego de abordagens clínicas. Conclusões: Os resultados apontam para a adoção de práticas e modelos de Intervenção Precoce distantes daqueles recomendados e reconhecidos como boas práticas pela literatura internacional. Nesse sentido, aponta-se a necessidade da atualização dos profissionais que atuam nessa área, bem como do investimento em pesquisas que incidam sobre a temática.

ABSTRACT Objective: To identify which Early Childhood Intervention practices and models are described in the Brazilian literature. Data sources: A systematic integrative review of the literature indexed in databases from Virtual Health Library, Bielefeld Academic Search Engine, Education Resources Information Center and Portal of Periodicals of the Coordination of Improvement of Higher Education Personnel was carried out, considering the period between 2005 and 2015. The following articles were analyzed: those published in English or Portuguese, fully available online, with the terms "Early Intervention", "Early Stimulation" or "Essential Stimulation" in the title, abstract or keywords; studies that enrolled children aged from 0 to 6 years, their caregivers or professionals in Early Intervention services; manuscripts published in journals classified as ≥ B2 (WebQualis; Qualis 2014) in the fields of Education or Physical Education; and studies that described Early Intervention practices. Data synthesis: Early Intervention seems to be developed exclusively related to the health sector, with prevalence of practices aimed at stimulating skills through the use of clinical approaches, whose focus is centered on the child and structured in the model of rehabilitative care. Conclusions: The adoption of Early Intervention practices and models are far from those recommended and recognized by the international literature as good practices. In this sense, the need of continuous education of professionals involved in this area is shown, as well the need for investments in research on this subject.

Redes de colaboração e intersetorialidade nas creches públicas do estado de São Paulo / Collaboration networks and intersectoriality in public daycares of São Paulo state

Introdução: A literatura indica impactos positivos no desenvolvimento infantil de crianças que frequentam creches quando, neste contexto, há boas práticas. Acredita-se que um conjunto de ações, em rede, coordenadas pelos gestores, pode impactar positivamente o desenvolvimento integral da criança. Objetivo: Embora a literatura aponte os campos de conhecimento "saúde, educação e o social" como as redes de colaboração das creches, o objetivo desta pesquisa foi identificar redes de colaboração no contexto de creches públicas do Estado de São Paulo. Método: A metodologia contemplou etapas para efetivação dos procedimentos éticos e definição do plano amostral, que resultou em 32 creches dos municípios do Estado de São Paulo. Os dados foram coletados por meio de entrevistas feitas com os dirigentes das creches que buscaram identificar os pontos da rede, a partir de situações presentes em sua prática cotidiana. Resultados: Os resultados apontaram para a presença de 75 pontos de rede de colaboração nos 32 municípios com distintas parcerias de serviços, ora contando com redes mais extensas, ora mais curtas. Confirmou-se a forte presença da intersetorialidade advinda dos campos da educação, da saúde e do social. Além destes, equipamentos municipais para ações de infraestrutura foram também identificados, bem como a presença de diversos programas governamentais oriundos da esfera federal. Conclusão: A dimensão do desenvolvimento infantil está presente de forma intensa na esfera da educação e da saúde. Os dados foram discutidos na perspectiva do apoio aos dirigentes para a resolutividade dos problemas, considerando-se o potencial das ações preventivas na primeira infância.

Introduction: The literature indicates positive impacts on child development for those children attending day care centers, when this context includes good practices. It is believed that a set of actions, networking, coordinated by managers can positively to impact the children development. Objective: Although the literature indicate the fields of knowledge "health, education and social" as the daycare collaborative networks, this study evaluated are the points that allow connections in these networks today, and the possible existence of other networks describing their characteristics. Method: The methodology included ethical procedures and definition of the sampling plan, which resulted in 32 daycare schools in the municipalities of São Paulo. Data were collected through interviews with the daycares directors seeking to identify the network points, from situations present in their daily practice. Results: The results showed the presence of 75 points of the cooperation network in 32 municipalities with different service partnerships, sometimes with more extensive networks, or shorter. We highlight the strong presence of intersectorality arising from the fields of education, health and social. Municipal equipment for infrastructure actions were identified, as well as the presence of various government programs from the federal level. Conclusion: The scale of child development is present in an intense way in the sphere of education and health. The data are discussed from the perspective of supporting leaders for solving the problems considering the potential of preventive action in early childhood.

Grupo de mães de bebês prematuros hospitalizados: experiência de intervenção de Terapia Ocupacional no contexto hospitalar / Group of mothers of hospitalized premature newborns: experience of Occupational Therapy intervention in hospital context

The hospitalization of newborns implies fragility for the infants and their families, because they are exposed to the stress and tensions of this delicate moment. The support offered to the family, especially to mothers of hospitalized infants, may reflect in the future care provided to these children, strengthening the bond and creating a favorable environment for their healthy development. The objective of this study is to report the experience of occupational therapy in a group of mothers of hospitalized neonates. The aim of this activity was to provide information and guidance on the care and interaction of these mothers with their hospitalized babies. This practice was developed through an Extension Project in Occupational Therapy carried out in a hospital of a countryside city of the state of São Paulo. The Group of Mothers was joined weekly, and dynamics of artisanal, plastic and artistic activities were offered based on the demands observed or reported verbally by the mothers in meetings at the baby nursery before the group was joined. As a result of these group meetings, improvement of the emotional condition of the mothers was observed in the day they participated in the group. We believe that this project can not only facilitate the access to information and guidance to this population, but also minimize the stress experienced by families in the hospital context, which is strange and adverse to a natural birth condition.

A hospitalização do recém-nascido implica em fragilidade para o bebê e para a família, uma vez que ela fica exposta ao estresse e tensões desse momento delicado. O auxílio que se oferece aos familiares, em especial às mães dos bebês internados, pode refletir nos cuidados futuros à criança, fortalecendo o vínculo e criando um ambiente propício para seu desenvolvimento saudável. Objetiva-se explicitar por meio deste artigo uma experiência junto ao grupo de mães de neonatos hospitalizados. A realização dessa atividade visou promover informação e orientação sobre cuidados e interação dessas mães com seus bebês hospitalizados, prática vivenciada por meio da realização de um Projeto de Extensão em Terapia Ocupacional numa Santa Casa de Misericórdia do interior do estado de São Paulo. Tal atividade, Grupo de Mães, ocorre semanalmente, com o oferecimento de dinâmicas, atividades artesanais, artísticas e plásticas, selecionadas a partir das demandas observadas ou relatadas verbalmente pelas próprias mães nos momentos de encontro no berçário, antes da realização do encontro do Grupo. Como resultado desses encontros grupais, observou-se melhora na condição emocional das mães quando elas participavam do Grupo. Acredita-se que atividades dessa natureza possam facilitar o acesso à informação e orientação para esse público, bem como minimizar o estresse vivenciado pela família diante do contexto hospitalar: estranho e adverso a uma condição natural de nascimento.

Proximity to PML nuclear bodies regulates HIV-1 latency in CD4+ T cells.

Nuclear bodies (NBs), characterized by the presence of the promyelocytic leukemia (PML) protein, are important components of the nuclear architecture, contributing to genetic and epigenetic control of gene expression. In investigating the mechanisms mediating HIV-1 latency, we determined that silenced but transcriptionally competent HIV-1 proviruses reside in close proximity to PML NBs and that this association inhibits HIV-1 gene expression. PML binds to the latent HIV-1 promoter, which coincides with transcriptionally inactive facultative heterochromatic marks, notably H3K9me2, at the viral genome. PML degradation and NB disruption result in strong activation of viral transcription as well as release of G9a, the major methyltransferase responsible for H3K9me2, and loss of facultative heterochromatin marks from the proviral DNA. Additionally, HIV-1 transcriptional activation requires proviral displacement from PML NBs by active nuclear actin polymerization. Thus, nuclear topology and active gene movement mediate HIV-1 transcriptional regulation and have implications for controlling HIV-1 latency and eradication.