In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles [Corrigendum]

Lopes CDF, Oliveira H, Estevão I, Pires LR, Pêgo AP. Int J Nanomedicine. 2016;11:2675–2683.  On page 2680, in Figure 2B, the double asterisks that appear above the data related to the ventral roots group should have been shown relative to the dorsal root ganglia group. The corrected version of Figure 2B is shown below.Read the original article:&nbsp

In vivo targeted gene delivery to peripheral neurons mediated by neurotropic poly(ethylene imine)-based nanoparticles

Cátia DF Lopes,1–3,* Hugo Oliveira,1,* Inês Estevão,1 Liliana Raquel Pires,1 Ana Paula Pêgo1,2,4,5 1INEB – Instituto de Engenharia Biomédica, Universidade do Porto (UPorto), Porto, Portugal; 2i3S – Instituto de Investigação e Inovação em Saúde, NanoBiomaterials for Targeted Therapies Group, UPorto, Porto, Portugal; 3FMUP – Faculdade de Medicina da Universidade do Porto, Porto, Portugal; 4ICBAS – Instituto de Ciências Biomédicas Abel Salazar, UPorto, Porto, Portugal; 5FEUP – Faculdade de Engenharia da Universidade do Porto, Porto, Portugal *These authors contributed equally to this work Abstract: A major challenge in neuronal gene therapy is to achieve safe, efficient, and minimally invasive transgene delivery to neurons. In this study, we report the use of a nonviral neurotropic poly(ethylene imine)-based nanoparticle that is capable of mediating neuron-specific transfection upon a subcutaneous injection. Nanoparticles were targeted to peripheral neurons by using the nontoxic carboxylic fragment of tetanus toxin (HC), which, besides being neurotropic, is capable of being retrogradely transported from neuron terminals to the cell bodies. Nontargeted particles and naked plasmid DNA were used as control. Five days after treatment by subcutaneous injection in the footpad of Wistar rats, it was observed that 56% and 64% of L4 and L5 dorsal root ganglia neurons, respectively, were expressing the reporter protein. The delivery mediated by HC-functionalized nanoparticles spatially limited the transgene expression, in comparison with the controls. Histological examination revealed no significant adverse effects in the use of the proposed delivery system. These findings demonstrate the feasibility and safety of the developed neurotropic nanoparticles for the minimally invasive delivery of genes to the peripheral nervous system, opening new avenues for the application of gene therapy strategies in the treatment of peripheral neuropathies. Keywords: gene therapy, nonviral vector, neuron-targeted, peripheral neuron

Prevalence of cognitive and functional impairment in community-dwelling elderly: importance of evaluating activities of daily living Prevalência de comprometimento cognitivo e funcional em idosos residentes em uma comunidade: importância da avaliação das atividades de vida diária

The study aims to evaluate the prevalence of cognitive/functional impairment in community-dwelling elderly above 60 years of age (n= 870; m=297, f=573) and the relationship of age, gender, and functional impairment with cognitive impairment using Mini-Mental State Examination (MMSE) and Pfeffer Functional Activities Questionnaire (PFAQ). Chi-square and Student's tests were used to compare cognitive and functional deficits. Linear regression assessed MMSE/PFAQ relationship. Stratified analysis assessed confounding factors. Logistic regression assessed the relationship among age/gender/functional status with cognitive impairment (p<0.05). Prevalence of cognitive/functional impairment was 19.2%. Functional and cognitive impairment are negatively correlated (Pearson= 0.737), despite educational level (illiterate/literate: OR=15.60; p=0/OR = 16.40; p=0). Age and gender (female) were associated with cognitive/functional impairment. Functional impairment is highly correlated to cognitive impairment. Family/health professionals may recognize functional impairment more easily than cognitive impairment. Thus, the use in combination of cognitive and functional scales is important when screening for dementia.<br>O estudo objetivou avaliar a prevalência de comprometimento cognitivo/funcional em idosos acima de 60 anos (n= 870; m=297, f=573) residentes na comunidade e avaliar a relação entre idade, gênero e comprometimento funcional com o comprometimento cognitivo. Utilizou-se o Mini-Exame do Estado Mental (MEEM) e o Questionário de Atividades Funcionais de Pfeffer (PFAQ). Comparou-se relação de deficits cognitivo e funcional (MEEM e PFAQ). A prevalência de comprometimento cognitivo/funcional foi 19,2%. Há relação entre comprometimento cognitivo e funcional (Pearson=0,737), independente do nível educacional (analfabetos/alfabetizados: OR=15,60; p=0/ OR = 16,40; p=0). Idade e gênero são fatores associados a comprometimento cognitivo/funcional (p<0,05). A prevalência de comprometimento cognitivo/funcional é mais alta que a encontrada em outro estudo brasileiro. Idade, gênero feminino e comprometimento funcional estão diretamente associados a comprometimento cognitivo. O reconhecimento de comprometimento funcional pode ser mais fácil por familiares/profissionais de saúde. Isso reforça a idéia do uso combinado de escalas em rastreamentos de demência