Graduação Byesiana e projeção de taxas de mortalidade aplicadas à populações de fundos de pensão do setor elétrico

Resumo: O processo de envelhecimento populacional que vem afetando a população mundial - o qual é caracterizado por quedas significativas nas taxas de mortalidade e fecundidade - tem afetado os sistemas de previdência e seguridade em todo o mundo, alertando-os a adotarem hipóteses biométricas cada vez mais conservadoras, impactando os cálculos atuariais. Essas tendências já começam a ser contempladas nos cálculos de provisões matemáticas e de benefícios através do uso de algumas ferramentas de construção de tábuas de mortalidade e projeções de taxas de mortalidade futuras. Diante disso, considerando a população de expostos ao risco de seis Entidades de Previdência Complementar Fechadas do sul do país – especificamente do setor elétrico – o objetivo deste estudo é graduar e projetar as taxas de mortalidade desta população, obtendo informações sobre seus níveis de mortalidade atuais e futuros, auxiliando na adoção da hipótese de mortalidade geral que melhor reflita a mortalidade do grupo. Para isto, aplicouse a técnica de Graduação Bayesiana de Taxas de Mortalidade utilizando simulação estocástica de Monte Carlo via Cadeias de Markov (MCMC) na população de assistidos das referidas Fundações, considerando os anos de estudo de 2000 a 2008, obtendo-se uma tábua de mortalidade para as idades entre 42 e 90 anos. Também foi utilizado o modelo demográfico de Lee-Carter para projeção das taxas de mortalidade raduadas, obtendo os respectivos fatores de melhoria a serem aplicados às mesmas, projetando-as para o futuro, tornando a tábua na forma geracional e obtendo o comportamento futuro dos níveis de mortalidade. A componente kt do modelo de Lee-Carter, que corresponde a uma série temporal que descreve a mudança na mortalidade ao longo do tempo, foi modelada por um processo ARIMA, o qual foi imulado estocasticamente utilizando bootstrap paramétrico, obtendo-se intervalos de confiança empíricos para as taxas de mortalidade observadas

Transferrin-Liposome-Mediated Systemic p53 Gene Therapy in Combination with Radiation Results in Regression of Human Head and Neck Cancer Xenografts

This is the published version, also available here: http://dx.doi.org/10.1089/10430349950016357.The use of cationic liposomes as nonviral vehicles for the delivery of therapeutic molecules is becoming increasingly prevalent in the field of gene therapy. We have previously demonstrated that the use of the transferrin ligand (Tf) to target a cationic liposome delivery system resulted in a significant increase in the transfection efficiency of the complex [Xu, L., Pirollo, K.F., and Chang, E.H. (1997). Hum. Gene Ther. 8, 467-475]. Delivery of wild-type (wt) p53 to a radiation-resistant squamous cell carcinoma of the head and neck (SCCHN) cell line via this ligand-targeted, liposome complex was also able to revert the radiation resistant phenotype of these cells in vitro. Here we optimized the Tf/liposome/DNA ratio of the complex (LipT) for maximum tumor cell targeting, even in the presence of serum. The efficient reestablishment of wtp53 function in these SCCHN tumor cells in vitro, via the LipT complex, restored the apoptotic pathway, resulting in a significant increase in radiation-induced apoptosis that was directly proportional to the level of exogenous wtp53 in the tumor cells. More significantly, intravenous administration of LipT-p53 markedly sensitized established SCCHN nude mouse xenograft tumors to radiotherapy. The combination of systemic LipT-p53 gene therapy and radiation resulted in complete tumor regression and inhibition of their recurrence even 6 months after the end of all treatment. These results indicate that this tumor-specific, ligand-liposome delivery system for p53 gene therapy, when used in concert with conventional radiotherapy, can provide a new and more effective means of cancer treatment

Food Selectivity in Children with Autism: Guidelines for Assessment and Clinical Interventions

Autisms Spectrum Disorders (ASD) are characterized by core symptoms (social communication and restricted and repetitive behaviors) and related comorbidities, including sensory anomalies, feeding issues, and challenging behaviors. Children with ASD experience significantly more feeding problems than their peers. In fact, parents and clinicians have to manage daily the burden of various dysfunctional behaviors of children at mealtimes (food refusal, limited variety of food, single food intake, or liquid diet). These dysfunctional behaviors at mealtime depend on different factors that are either medical/sensorial or behavioral. Consequently, a correct assessment is necessary in order to program an effective clinical intervention. The aim of this study is to provide clinicians with a guideline regarding food selectivity concerning possible explanations of the phenomenon, along with a direct/indirect assessment gathering detailed and useful information about target feeding behaviors. Finally, a description of evidence-based sensorial and behavioral strategies useful also for parent-mediated intervention is reported addressing food selectivity in children with ASD

Self-Assembly of a Virus-Mimicking Nanostructure System for Efficient Tumor-Targeted Gene Delivery

This is the published version, also available here: http://dx.doi.org/10.1089/10430340252792594.Molecular therapy, including gene therapy, is a promising strategy for the treatment of human disease. However, delivery of molecular therapeutics efficiently and specifically to the target tissue remains a significant challenge. A human transferrin (Tf)-targeted cationic liposome-DNA complex, Tf-lipoplex, has shown high gene transfer efficiency and efficacy with human head and neck cancer in vitro and in vivo (Xu, L., Pirollo, K.F., Tang, W.H., Rait, A., and Chang, E.H. Hum. Gene Ther. 1999;10:2941-2952). Here we explore the structure, size, formation process, and structure-function relationships of Tf-lipoplex. We have observed Tf-lipoplex to have a highly compact structure, with a relatively uniform size of 50-90 nm. This nanostructure is novel in that it resembles a virus particle with a dense core enveloped by a membrane coated with Tf molecules spiking the surface. More importantly, compared with unliganded lipoplex, Tf-lipoplex shows enhanced stability, improved in vivo gene transfer efficiency, and long-term efficacy for systemic p53 gene therapy of human prostate cancer when used in combination with conventional radiotherapy. On the basis of our observations, we propose a multistep self-assembly process and Tf-facilitated DNA cocondensation model that may provide an explanation for the resultant small size and effectiveness of our nanostructural Tf-lipoplex system

Case Report A New Case of Prenatally Diagnosed Pentasomy X: Review of the Literature

Pentasomy X is a rare chromosomal abnormality probably due to a nondisjunction during the meiosis. Only four cases prenatally diagnosed were described until now. Our case is the fifth one prenatally diagnosed at 20 weeks of gestational age in a 39-yearsold woman. She underwent invasive prenatal diagnosis for her advanced maternal age without any other known risk factor. Amniocentesis performed at 17 weeks showed a female 49, XXXXX karyotype. The ultrasonographic examination revealed nonspecific signs of a mild early fetal growth retardation and no significant increased nuchal fold. The fetal autopsy and the Xray excluded major malformations. Prenatal diagnosis is often difficult due to the lack of indicative ultrasonographic findings and the rarity of described cases. The influence of the mother's age on the occurrence of penta-X syndrome has not been determined. Considering the lack of correlation between advanced maternal age and increased risk for pentasomy X, as well as the absence of typical echographic signs, evaluation of the inclusion of a noninvasive prenatal test (NIPT) that expands clinical coverage to include the X and Y chromosomes in routine prenatal diagnosis should be considered as well as three-dimensional ultrasound to detect any helpful indicative prognostic signs

Production and characterization of a recombinant single-chain antibody against Hantaan virus envelop glycoprotein

Hantaan virus (HTNV) is the type of Hantavirus causing hemorrhagic fever with renal syndrome, for which no specific therapeutics are available so far. Cell type-specific internalizing antibodies can be used to deliver therapeutics intracellularly to target cell and thus, have potential application in anti-HTNV infection. To achieve intracellular delivery of therapeutics, it is necessary to obtain antibodies that demonstrate sufficient cell type-specific binding, internalizing, and desired cellular trafficking. Here, we describe the prokaryotic expression, affinity purification, and functional testing of a single-chain Fv antibody fragment (scFv) against HTNV envelop glycoprotein (GP), an HTNV-specific antigen normally located on the membranes of HTNV-infected cells. This HTNV GP-targeting antibody, scFv3G1, was produced in the cytoplasm of Escherichia coli cells as a soluble protein and was purified by immobilized metal affinity chromatography. The purified scFv possessed a high specific antigen-binding activity to HTNV GP and HTNV-infected Vero E6 cells and could be internalized into HTNV-infected cells probably through the clathrin-dependent endocytosis pathways similar to that observed with transferrin. Our results showed that the E. coli-produced scFv had potential applications in targeted and intracellular delivery of therapeutics against HTNV infections

Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid–polyethylene glycol/gadolinium–diethylenetriamine-pentaacetic acid (PLA–PEG/Gd–DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA–PEG/Gd–DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA–PEG nanoparticles and the commercial contrast agent, Gd–DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA–PEG/Gd–DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was −12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA–PEG/Gd–DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed (r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd–DTPA. PLA–PEG/Gd–DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA–PEG/Gd–DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent