Pilot Study of an Integrative New Tool for Studying Clinical Outcome Discrimination in Acute Leukemia.

Acute leukemia is a heterogeneous set of diseases affecting children and adults. Current prognostic factors are not accurate predictors of the clinical outcome of adult patients and the stratification of risk groups remains insufficient. For that reason, this study proposes a multifactorial analysis which integrates clinical parameters, ex vivo tumor characterization and behavioral in vivo analysis in zebrafish. This model represents a new approach to understand leukemic primary cells behavior and features associated with aggressiveness and metastatic potential. Xenotransplantation of primary samples from patients newly diagnosed with acute leukemia in zebrafish embryos at 48 hpf was used to asses survival rate, dissemination pattern, and metastatic potential. Seven samples from young adults classified in adverse, favorable or intermediate risk group were characterized. Tumor heterogeneity defined by Leukemic stem cell (LSC) proportion, was performed by metabolic and cell membrane biomarkers characterization. Thus, our work combines all these parameters with a robust quantification strategy that provides important information about leukemia biology, their relationship with specific niches and the existent inter and intra-tumor heterogeneity in acute leukemia. In regard to prognostic factors, leukemic stem cell proportion and Patient-derived xenografts (PDX) migration into zebrafish were the variables with highest weights for the prediction analysis. Higher ALDH activity, less differentiated cells and a broader and random migration pattern are related with worse clinical outcome after induction chemotherapy. This model also recapitulates multiple aspects of human acute leukemia and therefore is a promising tool to be employed not only for preclinical studies but also supposes a new tool with a higher resolution compared to traditional methods for an accurate stratification of patients into worse or favorable clinical outcome.

The Golden Activity of Lysinibacillus sphaericus: New Insights on Gold Accumulation and Possible Nanoparticles Biosynthesis.

Power struggles surrounding the increasing economic development of gold mining give rise to severe environmental and social problems. Two new strains of Lysinibacillus sphaericus were isolated from an area of active alluvial gold mining exploitation at El Bagre, Antioquia. The absorption capacity of these strains and some of the L. sphaericus Microbiological Research Center (CIMIC) collection (CBAM5, OT4b.31, III(3)7) were evaluated by spectrophotometry according to a calibration gold curve of HAuCl4- with concentrations between 0 µg/mL and 100 µg/mL. Bioassays with living biomass were carried out with an initial gold concentration of 60 µg/mL. Their sorption capacity was evident, reaching percentages of gold removal between 25% and 85% in the first 2 h and 75% to 95% after 48 h. Biosynthesis of possible gold nanoparticles (AuNPs) in assays with living biomass was also observed. Metal sorption was evaluated using scanning electron microscopy and energy-dispersive X-ray spectroscopy (EDS) analysis. The sorption and fabrication capacity exhibited by the evaluated strains of L. sphaericus converts this microorganism into a potential alternative for biomining processes, especially those related to gold extraction.

[Commitment and development of competences in clinical research in residency training programs in Chile]. / Intención y desarrollo de competencias en investigación clínica en programas de postítulo de médico especialista en Chile.

BACKGROUND: In Chile, residency training programs (RTP) take place in a stimulating academic environment for the promotion of clinical research skills. However, research is not a frequent curricular outcome. Accreditation of these programs by the National Accreditation Commission is an opportunity to improve the trainee's research competences. AIM: To analyze in the RTP curricula, the explicit intention to carry out clinical research and its correlation with the scientific productivity of professors and residents. MATERIAL AND METHODS: Fifty six training study programs corresponding to six primary specialties and six derived specialties, offered by seven universities holding accreditation tenure for RTP from the Chilean Association of Medicine Faculties (ASOFAMECH) up to 2005, were analyzed. The analysis included each academic program, courses and/or rotations and professors and residents' productivity, measured as publications accredited in the Institute for Scientific Information (ISI), between 1999 and 2007. RESULTS: RTP are based on a tutorial educational model, where the close relationship between professors and residents is essential for the expected final outcome. Simultaneously, the programs' curricula revealed a high intentionality towards clinical research. However, professors' publications of ISI indexed articles showed a low and irregular scientific productivity. CONCLUSIONS: The gap between the declared training in clinical research and the effective ISI productivity is an awareness call with respect to the contribution that RTP could provide to accreditation, to professors and residents, and in general to health improvement in the country.

Intención y desarrollo de competencias en investigación clínica en programas de postítulo de médico especialista en Chile / Commitment and development of competences in clinical research in residency training programs in Chile

Background: In Chile, residency training programs (RTP) take place in a stimulating academic environment for the promotion of clinical research skills. However, research is not a frequent curricular outcome. Accreditation of these programs by the National Accreditation Commission is an opportunity to improve the trainee's research competences. Aim: To analyze in the RTP curricula, the explicit intention to carry out clinical research and its correlation with the scientific productivity of professors and residents. Material and Methods: Fifty six training study programs corresponding to six primary specialties and six derived specialties, offered by seven universities holding accreditation tenure for RTP from the Chilean Association of Medicine Faculties (ASOFAMECH) up to 2005, were analyzed. The analysis included each academic program, courses and/or rotations and professors and residents' productivity, measured as publications accredited in the Institute for Scientific Information (ISI), between 1999 and 2007. Results: RTP are based on a tutorial educational model, where the close relationship between professors and residents is essential for the expected final outcome. Simultaneously, the programs' curricula revealed a high intentionality towards clinical research. However, professors' publications of ISI indexed articles showed a low and irregular scientific productivity. Conclusions: The gap between the declared training in clinical research and the effective ISI productivity is an awareness call with respect to the contribution that RTP could provide to accreditation, to professors and residents, and in general to health improvement in the country.

Immunogenicity and tolerability of a paediatric presentation of a virosomal hepatitis A vaccine in Chilean children aged 1-16 years.

We assessed the immunogenicity of the paediatric dose of Epaxal(®) (0.25 mL) and the degrees of seroprotection achieved with the standard dose (0.5 mL) of Epaxal(®) or a dose of Havrix(®) Junior, in children in an open, randomised, controlled, multi-centre, parallel-group study conducted at 2 Chilean study centres. 360 healthy children and adolescents 12 months to <17 years of age not previously vaccinated against hepatitis A were enrolled. Subjects were randomised 2:2:1 to be vaccinated with either Epaxal(®) 0.25 mL [n=146], Epaxal(®) 0.5 mL [n=142] or Havrix(®) Junior [n=72] intramuscularly on Day 1 and after 6 months (26 weeks±14 days). Primary end point was the proportion of subjects seroprotected (anti-HAV antibody concentration ≥10 mIU/mL) in the ATP population at Month 1. All vaccines elicited high seroprotection rates at Month 1: 95.7% with Epaxal(®) 0.25 mL, 99.3% with Epaxal(®) 0.5 mL and 94.0% with Havrix(®) Junior. After the booster vaccination, all subjects demonstrated 100% seroprotection with all vaccines. Antibody concentrations were similarly high in all age groups. The paediatric presentation achieved antibody concentrations similar to those achieved with the 0.5 mL dose across the entire age range, and there were no differences across the range of body weights from 9.0 kg to 82.7 kg. All study vaccines were well tolerated and there were no AEs leading to discontinuation. Thus, the paediatric 0.25 mL dose of Epaxal(®) fulfilled the primary objective of showing non-inferiority to the adult 0.5 mL dose and to Havrix(®) Junior, in terms of seroprotection rates achieved. The results show the paediatric dose of Epaxal(®) to be an attractive option when conducting childhood-vaccination programmes.

[Hepatitis A and E virus antibodies in Chilean children of low socioeconomic status: a one year follow-up study]. / Seguimientos de anticuerpos contra hepatitis A y E en una cohorte de niños de bajo nivel socioeconómico.

BACKGROUND: The seroprevalence of antibodies against hepatitis A virus (HAV) is decreasing in many Latin American countries, along with improvements in sanitary standards. However, there is no information available about low socioeconomic status (LSE) populations. AIM: To assess the evolution of hepatitis A and E virus antibodies in a cohort of LSE Chilean children. MATERIAL AND METHODS: One hundred sixty eight children aged four years, 97 males, coming from public primary care clinics, were studied. Two blood samples were obtained with an interval of one year. Anti-HAV and anti-hepatitis E virus (HEV) antibodies, were detected by ELISA using Abbott kits. RESULTS: Anti-HAV was positive in 19 children (11.3%). After one year of follow-up, only 10 children had sustained reactivity (52.6%). Fourteen children, initially negative, became positive during the follow up (9.4%). Antibody titers to HAV were significantly higher in samples that remained positive, compared with those that lost reactivity. Anti-HEV was found positive in two children (1.2%). One remained positive and the other became negative. CONCLUSIONS: In this cohort of LSE Chilean children, the prevalence to antibodies against HAV and HEV is low. Follow-up detected loss of reactivity to HAV in nearly one half of the children, probably related to lower antibody levels.