Production of electrospun fast-dissolving drug delivery systems with therapeutic eutectic systems encapsulated in gelatin

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/ v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.The research leading to these results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the projects ENIGMA - PTDC/EQU-EPR/ 121491/2010 and UID/CTM/50025/2013, LAQVREQUIMTE: UID/QUI/50006/2013, UCIBIO-REQUIMTE: UID/Multi/04378/2013 (co-financed by the ERDF under the PT2020 Partnership Agreement [POCI-01-0145-FEDER- 007728]) and by FEDER through the COMPETE 2020 Programme. Marta Martins is grateful for financial support from FCT through the grant BIM/PTDC/EQUEPR/121491/ 2010/ENIGMA. This research has also received funding from the European Union Seventh Framework Programme (FP7/ 2007-2013) under grant agreement number REGPOTCT2012-316331-POLARIS and from the project BNovel smart and biomimetic materials for innovative regenerative medicine approaches^ RL1 - ABMR - NORTE-01-0124- FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries

BACKGROUND: The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe. METHODS: A cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries. RESULTS: Capture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI -12.4 to -5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease. CONCLUSIONS: Fewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral

As necessidades comunicacionais das práticas educativas na prevenção da transmissão materno-fetal do HIV Communication needs of education practices in preventing maternal-fetal HIV transmission

OBJETIVOS: elucidar a fecundidade da prática educativa centrada na prevenção da transmissão materno-fetal da AIDS para promover a comunicação usuárias-serviços. MÉTODOS: Estudo exploratório, parte de uma pesquisa sobre atenção pré-natal, realizado em 19 centros de saúde, duas maternidades e seis unidades de saúde da família da Secretaria de Saúde da cidade do Recife, de maio a julho de 1998. O processo de trabalho foi observado, equipes técnicas entrevistadas e um questionário foi aplicado às 355 mulheres em atendimento; dessas, 81 foram submetidas à sondagem. RESULTADOS: nenhum serviço faz aconselhamento, mesmo quando informam sobre o teste anti-HIV (48,1%). O trabalho educativo está focalizado no fornecimento de informações durante a consulta, pois, as atividades coletivas, nas unidades que realizam-nas (48,1%), não ocorrem em todos os horários do pré-natal. A prática educativa baseada na racionalidade estratégica subestima a importância da aproximação às decisões valorativas das mulheres, das quais somente 11,1% utilizam camisinha de modo sistemático. CONCLUSÕES: a pequena oferta de atividades educativas no pré-natal e o "monólogo tecnocrático" que predomina nas relações entre usuárias e serviços de saúde têm repercussões negativas na vulnerabilidade da população feminina e de seus filhos.<br>OBJECTIVES: to determine the efficiency of educational methods in preventing maternal-fetal AIDS transmission through communication among users and health services providers. METHODS: exploratory study, part of the survey on pre-natal care, accomplished in 19 clinics, two maternity hospitals and six family health units performed by the Health Secretariat of the city of Recife, from May to July, 1998. Procedures were observed, technical teams were interviewed and questionnaires applied to 355 women being seen, of these, 81 participated of the survey. RESULTS: healthcare providers do not perform counseling, even when informing on HIV testing (48,1%). Education work is focused on furnishing information during consultation, for, collective activities in the units doing them (48,1%) do not occur in all of the pre-natal care schedules. Education based on strategic rationality underestimates the value of women's informed choice of which only 11,1% used condoms o a systematic way. CONCLUSIONS: insufficient education during pre-natal care and a "technocratic monologue" prevailing on the relationship between users and healthcare providers have a negative impact on the vulnerability of the female population and their children

Infecção pelo HIV durante a gestação: estudo-Sentinela Parturiente, Brasil, 2002 HIV infection during pregnancy: the Sentinel Surveillance Project, Brazil, 2002

OBJETIVO: Avaliar a cobertura efetiva da detecção da infecção pelo HIV durante a gestação, em âmbito nacional. MÉTODOS: A cobertura efetiva do teste de HIV na gestação foi definida como a proporção de gestantes que teve atendimento pré-natal (pelo menos uma consulta), pedido de teste de HIV e conhecimento do resultado antes do parto, sendo estimada por processo de amostragem, utilizando-se as informações coletadas no Estudo-Sentinela Parturiente, 2002. As desigualdades da cobertura efetiva foram analisadas por: grande região; tamanho populacional do município de ocorrência do parto; e grau de instrução da mãe. RESULTADOS: A cobertura efetiva do teste de HIV durante a gestação foi estimada em 52%. As enormes desigualdades socioespaciais ficaram evidenciadas na comparação entre as regiões Nordeste (24%) e Sul (72%); entre parturientes analfabetas (19%) com as que têm o ensino fundamental completo (64%); entre as que realizaram o parto em municípios pequenos (36%) com as que o realizaram em municípios com mais de 500 mil habitantes (66%). As recomendações do Ministério da Saúde foram atendidas, completamente, por somente 27% parturientes. CONCLUSÕES: Os resultados estabelecem a necessidade de haver medidas voltadas para maior cobertura da detecção do HIV na gestação, e indicam que os programas do Programa Nacional de DST e Aids e os programas de saúde da mulher devem ser intensificados, com estratégias conjuntas entre eles.<br>OBJECTIVE: To evaluate the actual coverage of HIV infection detection during pregnancy at national level. METHODS: The actual coverage of HIV testing during pregnancy was defined as the proportion of women who attended prenatal care visits (at least one visit), ordering HIV testing and knowledge of test result before delivery. The coverage was estimated by sampling procedures based on the 2002 Sentinel Surveillance Study data. Actual coverage Inequalities were assessed by: country regions; population size of the municipality where delivery took place; and mother's schooling. RESULTS: The actual coverage of HIV testing during pregnancy was 52%. Huge sociogeographic inequalities are seen between the Northeastern (24%) and Southern regions (72%); illiterate mothers (19%) and those with complete basic education (64%); mothers who delivered in small municipalities (36%) and those who delivered in municipalities with more than 500,000 inhabitants (66%). Ministry of Health recommendations were fully followed by only 27% pregnant women. CONCLUSIONS: The study results show a need for actions aiming at increasing HIV detection coverage during pregnancy, and indicate that HIV/STD programs should be intensified with joint strategies between the National AIDS Program and infant-maternal programs

Role of the DHH1 gene in the regulation of monocarboxylic acids transporters expression in Saccharomyces cerevisiae

Previous experiments revealed that DHH1, a RNA helicase involved in the regulation of mRNA stability and translation, complemented the phenotype of a Saccharomyces cerevisiae mutant affected in the expression of genes coding for monocarboxylic-acids transporters, JEN1 and ADY2 (Paiva S, Althoff S, Casal M, Leao C. FEMS Microbiol Lett, 1999, 170:301-306). In wild type cells, JEN1 expression had been shown to be undetectable in the presence of glucose or formic acid, and induced in the presence of lactate. In this work, we show that JEN1 mRNA accumulates in a dhh1 mutant, when formic acid was used as sole carbon source. Dhh1 interacts with the decapping activator Dcp1 and with the deadenylase complex. This led to the hypothesis that JEN1 expression is post-transcriptionally regulated by Dhh1 in formic acid. Analyses of JEN1 mRNAs decay in wild-type and dhh1 mutant strains confirmed this hypothesis. In these conditions, the stabilized JEN1 mRNA was associated to polysomes but no Jen1 protein could be detected, either by measurable lactate carrier activity, Jen1-GFP fluorescence detection or western blots. These results revealed the complexity of the expression regulation of JEN1 in S. cerevisiae and evidenced the importance of DHH1 in this process. Additionally, microarray analyses of dhh1 mutant indicated that Dhh1 plays a large role in metabolic adaptation, suggesting that carbon source changes triggers a complex interplay between transcriptional and post-transcriptional effects.This study was supported by the Portuguese grant POCI/BIA-BCM/57812/2004 (Eixo 2, Medida 2.3, QCAIII - FEDER). N.V. received a FCT PhD fellowship (SFRH/BD/23503/2005). S.M. received a FCT PhD fellowship (SFRH/BD/74790/2010). F.D.'s work is supported by a grant from the Agence pour la Recherche contre le Cancer (ARC). Support to C.B.M.A. by FEDER through POFC-COMPETE and by Portuguese funds from FCT through the project PEst-OE/BIA/UI4050/2014 is also acknowledged. The authors thank Josette Banroques and Kyle Tanner for their advice regarding polysome gradients. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript