Development of pH-Sensitive magnetoliposomes containing shape anisotropic nanoparticles for potential application in combined cancer therapy

Late diagnosis and systemic toxicity associated with conventional treatments make oncological therapy significantly difficult. In this context, nanomedicine emerges as a new approach in the prevention, diagnosis and treatment of cancer. In this work, pH-sensitive solid magnetoliposomes (SMLs) were developed for controlled release of the chemotherapeutic drug doxorubicin (DOX). Shape anisotropic magnetic nanoparticles of magnesium ferrite with partial substitution by calcium (Mg0.75Ca0.25Fe2O4) were synthesized, with and without calcination, and their structural, morphological and magnetic properties were investigated. Their superparamagnetic properties were evaluated and heating capabilities proven, either by exposure to an alternating magnetic field (AMF) (magnetic hyperthermia) or by irradiation with near-infrared (NIR) light (photothermia). The Mg0.75Ca0.25Fe2O4 calcined nanoparticles were selected to integrate the SMLs, surrounded by a lipid bilayer of DOPE:Ch:CHEMS (45:45:10). DOX was encapsulated in the nanosystems with an efficiency above 98%. DOX release assays showed a much more efficient release of the drug at pH = 5 compared to the release kinetics at physiological pH. By subjecting tumor cells to DOX-loaded SMLs, cell viability was significantly reduced, confirming that they can release the encapsulated drug. These results point to the development of efficient pH-sensitive nanocarriers, suitable for a synergistic action in cancer therapy with magnetic targeting, stimulus-controlled drug delivery and dual hyperthermia (magnetic and plasmonic) therapy.This work was funded by the Portuguese Foundation for Science and Technology (FCT) within the framework of the Strategic Funding of Research Units UIDB/04650/2020 (CF-UM-UP), UIDB/00319/2020 (ALGORITMI), UIDB/04077/2020 (MEtRICs), UIDB/04436/2020 (CMEMS) and UIDB/00511/2020 (LEPABE). FCT, POCI, FEDER and NORTE2020 are acknowledged for funding through research projects PTDC/QUI-QFI/28020/2017, EXPL/EMD-EMD/0650/2021, PTDC/EEI-EEE/2846/2021 and NORTE-01-0145-FEDER-000054. MINECO (Spain) is acknowledged for project MAT2016-76824-C3-2-R. B.D.C. and V.M.C. acknowledge FCT for PhD grants SFRH/BD/141936/2018 (B.D.C.) and UI/BD/151028/2021 (V.M.C.). R.O.R. thanks FCT for contract 2020.03975.CEECIND

Behavioral Profile of Children and Adolescents with Prader-Willi Syndrome and Exogenous Obesity

The objective of present study was compared the behavioral profile of two different groups of children and adolescents with obesity. Ten subjects presented diagnoses of exogenous obesity and ten Prader-Willi syndrome. The Prader-Willi syndrome is a genetic disease which the main behavioral symptom is hyperphagia. The samples were paired by sex and age, with mean age of 12 years. In the evaluation of behavioral profile was utilized Child Behavior Checklist (CBCL/6–18). In the most cases children with exogenous obesity have obtained better results than the referred with Prader-Willi Syndrome. Into the comparison by mean of ANOVA univariate identified significant differences between the groups in the scales: school (p = 0.001), social problems (p = 0.012), thought problems (p = 0.001), attention problems (p = 0.048), rule-breaking behavior (p = 0.019); aggressive behavior (p = 0.003) and conduct problems (p = 0.001). The differences suggested the need of counseling psychological strategies in the Prader-Willi syndrome group

Direitos humanos nos Centros de Atenção Psicossocial do Nordeste do Brasil: um estudo avaliativo, tendo como referência o QualityRights - WHO

O artigo pretende avaliar as práticas dos Centros de Atenção Psicossocial no respeito aos direitos humanos dos usuários, analisando suas percepções referentes às crenças, valores, hábitos, preconceitos sofridos, reivindicações atendidas ou não e à participação comunitária, como exercícios de cidadania. Através da análise de dados etno-epidemiológicos do Projeto Avaliar-Caps Nordeste (Ministério da Saúde/2013), utilizando questionários e observação direta, à luz do QualityRights, verificou-se que os Centros de Atenção Psicossocial influenciam positivamente na vida dos usuários, ao estimular-lhes a autonomia, a corresponsabilização no cuidado e o protagonismo sociocultural e político nos serviços e nas suas comunidades

Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics Revisão da eficácia do placebo nos ensaios clínicos que comparam antipsicóticos típicos e atípicos

OBJECTIVE: To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD: Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms "amisulpride", "aripiprazole", "clozapine", "olanzapine", "quetiapine", "risperidone", "sertindole", "ziprasidone" and "zotepine". Main efficacy parameters were calculated using the proportion of "events" (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale) and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS: The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS: Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.OBJETIVO: Revisar a eficácia do placebo em comparação com a dos antipsicóticos atípicos e típicos no tratamento da esquizofrenia e do transtorno esquizoafetivo, bem como avaliar a pertinência do uso do placebo nos ensaios clínicos com antipsicóticos. MÉTODO: Foram incluídos estudos nos quais os antipsicóticos atípicos foram comparados com antipsicóticos típicos e placebo simultaneamente. A pesquisa bibliográfica incluiu os termos "amisulprida", "aripiprazol", "clozapina", "olanzapina", "quetiapina", "risperidona", "sertindol", "ziprasidona" e "zotepina". Os principais parâmetros de eficácia foram a proporção de "eventos" (definidos como deterioração ou falta de melhora de pelo menos 20% na Positive and Negative Syndrome Scale ou Brief Psychiatric Rating Scale) e os riscos relativos combinados (efeitos randômicos), com seus respectivos intervalos de confiança de 95%. Foram também estimados os tamanhos de amostras nos estudos em que a droga pesquisada fosse comparada com um antipsicótico típico ou com placebo. RESULTADOS: As taxas de eficácia combinada foram de 40,8%, 34,9% e 21,3%, respectivamente, para os antipsicóticos atípicos, antipsicóticos típicos e placebo. Cento e sessenta e seis pacientes teriam de ser incluídos quando a nova droga fosse comparada com placebo se os cálculos fossem baseados na diferença de 20% encontrada entre o antipsicótico atípico e placebo, ao passo que 2.054 teriam de ser incluídos se a diferença procurada fosse aquela encontrada entre o antipsicótico atípico e o antipsicótico típico, isto é, 6%. Os insucessos terapêuticos estimados seriam de 115 entre os 166 pacientes quando a droga em estudo fosse comparada com placebo, e de 1.274 entre os 2.054 pacientes quando fosse comparada com um antipsicótico típico. CONCLUSÕES: Os estudos controlados por placebo podem reduzir o número de indivíduos expostos aos efeitos prejudiciais de drogas ineficazes