The Impact of Serum Albumin Levels on COVID-19 Mortality.

Low serum albumin (SA) correlates with mortality in critically ill patients, including those with COVID-19. We aimed to identify SA thresholds to predict the risk of longer hospital stay, severe respiratory failure, and death in hospitalized adult patients with COVID-19 pneumonia. A prospective longitudinal study was conducted at the Infectious Diseases Unit of Trieste University Hospital (Italy) between March 2020 and June 2021. The evaluated outcomes were: (1) need of invasive mechanical ventilation (IMV); (2) length of hospital stay (LOS); and (3) 90-day mortality rate. We enrolled 864 patients. Hypoalbuminemia (<3.5 g/dL) was detected in 586 patients (67.8%). SA on admission was significantly lower in patients who underwent IMV (2.9 vs. 3.4 g/dL; p < 0.001). The optimal SA cutoff predicting the need of IMV was 3.17 g/dL (AUC 0.688; 95% CI: 0.618−0.759; p < 0.001) and this threshold appeared as an independent risk factor for the risk of IMV in multivariate Cox regression analysis. The median LOS was 12 days and a higher SA was predictive for a shorter LOS (p < 0.001). The overall 90-day mortality rate was 15%. SA was significantly lower in patients who died within 90 days from hospital admission (3.1 g/dL; IQR 2.8−3.4; p < 0.001) as compared to those who survived (3.4 g/dL; IQR 3.1−3.7). The optimal SA threshold predicting high risk of 90-day mortality was 3.23 g/dL (AUC 0.678; 95% CI: 0.629−0.734; p < 0.001). In a multivariate Cox regression analysis, SA of <3.23 g/dL appeared to be an independent risk factor for 90-day mortality. Our results suggest that low SA on admission may identify patients with COVID-19 pneumonia at higher risk of severe respiratory failure, death, and longer LOS. Clinicians could consider 3.2 g/dL as a prognostic threshold for both IMV and mortality in hospitalized COVID-19 patients.

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.

Aspirin and Infection: A Narrative Review.

Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the world. It derives from the extract of white willow bark, whose therapeutic potential was known in Egypt since 1534 BC. ASA's pharmacological effects are historically considered secondary to its anti-inflammatory, platelet-inhibiting properties; however, human studies demonstrating a pro-inflammatory effect of ASA exist. It is likely that we are aware of only part of ASA's mechanisms of action; moreover, the clinical effect is largely dependent on dosages. During the past few decades, evidence of the anti-infective properties of ASA has emerged. We performed a review of such research in order to provide a comprehensive overview of ASA and viral, bacterial, fungal and parasitic infections, as well as ASA's antibiofilm properties.

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.

Impact of lockdown on Covid-19 case fatality rate and viral mutations spread in 7 countries in Europe and North America.

BACKGROUND: Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the first coronavirus disease 2019 (COVID-19) outbreak in China and has become a public health emergency of international concern. SARS-CoV-2 outbreak has been declared a pandemic by WHO on March 11th, 2020 and the same month several Countries put in place different lockdown restrictions and testing strategies in order to contain the spread of the virus. METHODS: The calculation of the Case Fatality Rate of SARS-CoV-2 in the Countries selected was made by using the data available at https://github.com/owid/covi-19-data/tree/master/public/data . Case fatality rate was calculated as the ratio between the death cases due to COVID-19, over the total number of SARS-CoV-2 reported cases 14 days before. Standard Case Fatality Rate values were normalized by the Country-specific ρ factor, i.e. the number of PCR tests/1 million inhabitants over the number of reported cases/1 million inhabitants. Case-fatality rates between Countries were compared using proportion test. Post-hoc analysis in the case of more than two groups was performed using pairwise comparison of proportions and p value was adjusted using Holm method. We also analyzed 487 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 from January 2020 to April 2020 in Italy, Spain, Germany, France, Sweden, UK and USA. SARS-CoV-2 reference genome was obtained from the GenBank database (NC_045512.2). Genomes alignment was performed using Muscle and Jalview software. We, then, calculated the Case Fatality Rate of SARS-CoV-2 in the Countries selected. RESULTS: In this study we analyse how different lockdown strategies and PCR testing capability adopted by Italy, France, Germany, Spain, Sweden, UK and USA have influenced the Case Fatality Rate and the viral mutations spread. We calculated case fatality rates by dividing the death number of a specific day by the number of patients with confirmed COVID-19 infection observed 14 days before and normalized by a ρ factor which takes into account the diagnostic PCR testing capability of each Country and the number of positive cases detected. We notice the stabilization of a clear pattern of mutations at sites nt241, nt3037, nt14408 and nt23403. A novel nonsynonymous SARS-CoV-2 mutation in the spike protein (nt24368) has been found in genomes sequenced in Sweden, which enacted a soft lockdown strategy. CONCLUSIONS: Strict lockdown strategies together with a wide diagnostic PCR testing of the population were correlated with a relevant decline of the case fatality rate in different Countries. The emergence of specific patterns of mutations concomitant with the decline in case fatality rate needs further confirmation and their biological significance remains unclear.

Inverse correlation between average monthly high temperatures and COVID-19-related death rates in different geographical areas.

BACKGROUND: With the aim of providing a dynamic evaluation of the effects of basic environmental parameters on COVID-19-related death rate, we assessed the correlation between average monthly high temperatures and population density, with death/rate (monthly number of deaths/1 M people) for the months of March (start of the analysis and beginning of local epidemic in most of the Western World, except in Italy where it started in February) and April 2020 (continuation of the epidemic). Different geographical areas of the Northern Hemisphere in the United States and in Europe were selected in order to provide a wide range among the different parameters. The death rates were gathered from an available dataset. As a further control, we also included latitude, as a proxy for temperature. METHODS: Utilizing a publicly available dataset, we retrieved data for the months of March and April 2020 for 25 areas in Europe and in the US. We computed the monthly number of deaths/1 M people of confirmed COVID-19 cases and calculated the average monthly high temperatures and population density for all these areas. We determined the correlation between number of deaths/1 M people and the average monthly high temperatures, the latitude and the population density. RESULTS: We divided our analysis in two parts: analysis of the correlation among the different variables in the month of March and subsequent analysis in the month of April. The differences were then evaluated. In the month of March there was no statistical correlation between average monthly high temperatures of the considered geographical areas and number of deaths/1 M people. However, a statistically significant inverse correlation became significant in the month of April between average monthly high temperatures (p = 0.0043) and latitude (p = 0.0253) with number of deaths/1 M people. We also observed a statistically significant correlation between population density and number of deaths/1 M people both in the month of March (p = 0.0297) and in the month of April (p = 0.0116), when three areas extremely populated (NYC, Los Angeles and Washington DC) were included in the calculation. Once these three areas were removed, the correlation was not statistically significant (p = 0.1695 in the month of March, and p = 0.7076 in the month of April). CONCLUSIONS: The number of COVID-19-related deaths/1 M people was essentially the same during the month of March for all the geographical areas considered, indicating essentially that the infection was circulating quite uniformly except for Lombardy, Italy, where it started earlier. Lockdown measures were implemented between the end of March and beginning of April, except for Italy which started March 9th. We observed a strong, statistically significant inverse correlation between average monthly high temperatures with the number of deaths/1 M people. We confirmed the data by analyzing the correlation with the latitude, which can be considered a proxy for high temperature. Previous studies indicated a negative effect of high climate temperatures on Sars-COV-2 spreading. Our data indicate that social distancing measure are more successful in the presence of higher average monthly temperatures in reducing COVID-19-related death rate, and a high level of population density seems to negatively impact the effect of lockdown measures.

Harnessing Effective Molarity to Design an Electrochemical DNA-based Platform for Clinically Relevant Antibody Detection.

Easy-to-use platforms for rapid antibody detection are likely to improve molecular diagnostics and immunotherapy monitoring. However, current technologies require multi-step, time-consuming procedures that limit their applicability in these fields. Herein, we demonstrate effective molarity-driven electrochemical DNA-based detection of target antibodies. We show a highly selective, signal-on DNA-based sensor that takes advantage of antibody-binding-induced increase of local concentration to detect clinically relevant antibodies in blood serum. The sensing platform is modular, rapid, and versatile and allows the detection of both IgG and IgE antibodies. We also demonstrate the possible use of this strategy for the monitoring of therapeutic monoclonal antibodies in body fluids. Our approach highlights the potential of harnessing effective molarity for the design of electrochemical sensing strategies.

Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant.

BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.

Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation.

Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of the viral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded by the host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1 IN degradation, we performed a targeted RNAi screen using a library of siRNAs against all components of the ubiquitin-conjugation machinery using high-content microscopy. Here we report that the E3 RING ligase TRIM33 is a major determinant of HIV-1 IN stability. CD4-positive cells with TRIM33 knock down show increased HIV-1 replication and proviral DNA formation, while those overexpressing the factor display opposite effects. Knock down of TRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of IN serine 57 to alanine, a mutation known to impair viral DNA integration. Thus, TRIM33 acts as a cellular factor restricting HIV-1 infection by preventing provirus formation.

Antibody-Mediated Small Molecule Detection Using Programmable DNA-Switches.

The development of rapid, cost-effective, and single-step methods for the detection of small molecules is crucial for improving the quality and efficiency of many applications ranging from life science to environmental analysis. Unfortunately, current methodologies still require multiple complex, time-consuming washing and incubation steps, which limit their applicability. In this work we present a competitive DNA-based platform that makes use of both programmable DNA-switches and antibodies to detect small target molecules. The strategy exploits both the advantages of proximity-based methods and structure-switching DNA-probes. The platform is modular and versatile and it can potentially be applied for the detection of any small target molecule that can be conjugated to a nucleic acid sequence. Here the rational design of programmable DNA-switches is discussed, and the sensitive, rapid, and single-step detection of different environmentally relevant small target molecules is demonstrated.

Programmable Nucleic Acid Nanoswitches for the Rapid, Single-Step Detection of Antibodies in Bodily Fluids.

Antibody detection plays a pivotal role in the diagnosis of pathogens and monitoring the success of vaccine immunization. However, current serology techniques require multiple, time-consuming washing and incubation steps, which limit their applicability in point-of-care (POC) diagnostics and high-throughput assays. We developed here a nucleic acid nanoswitch platform able to instantaneously measure immunoglobulins of type G and E (IgG and IgE) levels directly in blood serum and other bodily fluids. The system couples the advantages of target-binding induced colocalization and nucleic acid conformational-change nanoswitches. Due to the modular nature of the recognition platform, the method can potentially be applied to the detection of any antibody for which an antigen can be conjugated to a nucleic acid strand. In this work we show the sensitive, fast and cost-effective detection of four different antibodies and demonstrate the possible use of this approach for the monitoring of antibody levels in HIV+ patients immunized with AT20 therapeutic vaccine.

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.

SYSTEMATIC LITERATURE REVIEW ON MODELS AND PRACTICES OF EARLY CHILDHOOD INTERVENTION IN BRAZIL. / REVISÃO SISTEMÁTICA INTEGRATIVA DA LITERATURA SOBRE MODELOS E PRÁTICAS DE INTERVENÇÃO PRECOCE NO BRASIL.

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.

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.

Better together: Strategies based on magnetic particles and quantum dots for improved biosensing.

Novel technologies and strategies for sensitive detection of biological responses in healthcare, food and environmental monitoring continue to be a priority. The present review focuses on bioassay development based on the simultaneous use of quantum dots and magnetic beads. Due to the outstanding characteristics of both particles for biosensing applications and the large number of publications using a combined approach, we aim to provide a comprehensive overview of the literature on different bioassays, the most recent advances and innovative strategies on the topic, together with an analysis of the main drawbacks encountered and potential solutions offered, with a special emphasis on the requirements that the transfer of technologies from the laboratory to the market will demand for future commercialization of biodevices. Several procedures used in immunoassays and nucleic acid-based bioassays for the detection of pathogens and biomarkers are discussed. The improvement of current approaches together with novel multiplex detection systems and nanomaterials-based research, including the use of multimodal nanoparticles, will contribute to simpler and more sensitive bioanalyses.

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.

Nuclear architecture dictates HIV-1 integration site selection.

Long-standing evidence indicates that human immunodeficiency virus type 1 (HIV-1) preferentially integrates into a subset of transcriptionally active genes of the host cell genome. However, the reason why the virus selects only certain genes among all transcriptionally active regions in a target cell remains largely unknown. Here we show that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore. This region contains a series of cellular genes, which are preferentially targeted by the virus, and characterized by the presence of active transcription chromatin marks before viral infection. In contrast, the virus strongly disfavours the heterochromatic regions in the nuclear lamin-associated domains and other transcriptionally active regions located centrally in the nucleus. Functional viral integrase and the presence of the cellular Nup153 and LEDGF/p75 integration cofactors are indispensable for the peripheral integration of the virus. Once integrated at the nuclear pore, the HIV-1 DNA makes contact with various nucleoporins; this association takes part in the transcriptional regulation of the viral genome. These results indicate that nuclear topography is an essential determinant of the HIV-1 life cycle.

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.

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.(AU)

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.(AU)