Myotoxin-3 from the Pacific Rattlesnake Crotalus oreganus oreganus Venom Is a New Microtubule-Targeting Agent.

Microtubule targeting agents (MTA) are anti-cancer molecules that bind tubulin and interfere with the microtubule functions, eventually leading to cell death. In the present study, we used an in vitro microtubule polymerization assay to screen several venom families for the presence of anti-microtubule activity. We isolated myotoxin-3, a peptide of the crotamine family, and three isoforms from the venom of the Northern Pacific rattlesnake Crotalus oreganus oreganus, which was able to increase tubulin polymerization. Myotoxin-3 turned out to be a cell-penetrating peptide that slightly diminished the viability of U87 glioblastoma and MCF7 breast carcinoma cells. Myotoxin 3 also induced remodeling of the U87 microtubule network and decreased MCF-7 microtubule dynamic instability. These effects are likely due to direct interaction with tubulin. Indeed, we showed that myotoxin-3 binds to tubulin heterodimer with a Kd of 5.3 µM and stoichiometry of two molecules of peptide per tubulin dimer. Our results demonstrate that exogenous peptides are good candidates for developing new MTA and highlight the richness of venoms as a source of pharmacologically active molecules.

[Treatment of borderline personality disorder with opioid antagonists: buprenorphine, nalmefene, naloxone and naltrexone in the treatment of dissociative symptoms, self-mutilation and suicidal behavior]. / Tratamiento del Trastorno límite de la personalidad con antagonistas opioides: buprenorfina, nalmefeno, naloxona y naltrexona en el tratamiento de síntomas disociativos, automutilaciones y conducta suicida.

OBJECTIVE: Recent theory has proposed that a dysfunction of the opioid system modulates mood, reward and pain; seems to be unstable in people with Borderline Personality Disorder. Our purpose is to analyze the evidence on the efficacy of the use of buprenorphine, nalmefene, naloxone and naltrexone, in the treatment of dissociative symptoms, self-mutilation and suicidal behavior of these patients. METHOD: We conducted a systematic search of MEDLINE and LILACS databases, to retrieve relevant articles. Included studies were experimental and observational designs of borderline personality samples in which dissociative symptoms, self mutilation or suicidal behavior was reported as an outcome and evaluated with some impact measures. RESULTS: A total of eight studies were reviewed. These provided interesting expectations about posible treatment lines in Borderline Personality Disorder using opioid antagonists. The subgroup most benefited was the one who has analgesia and highest number of diagnostic criteria. CONCLUSIONS: Studies of higher methodological quality are needed, in larger population samples and using control of confounding variables that allow us to estimate a value power calculation, and thus be able to support firm conclusions.

Impact of the International Nosocomial Infection Control Consortium (INICC)'s Multidimensional Approach on Rates of Central Line-Associated Bloodstream Infection in 14 Intensive Care Units in 11 Hospitals of 5 Cities in Argentina.

OBJECTIVE To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Approach (IMA) and the INICC Surveillance Online System (ISOS) on central line-associated bloodstream infection (CLABSI) rates in 14 intensive care units (ICUs) in Argentina from January 2014 to April 2017. DESIGN This prospective, pre-post surveillance study of 3,940 ICU patients was conducted in 11 hospitals in 5 cities in Argentina. During our baseline evaluation, we performed outcome and process surveillance of CLABSI applying Centers for Disease Control and Prevention/National Health Safety Network (CDC/NHSN) definitions. During the intervention, we implemented the IMA through ISOS: (1) a bundle of infection prevention practice interventions, (2) education, (3) outcome surveillance, (4) process surveillance, (5) feedback on CLABSI rates and consequences, and (6) performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using a logistic regression model to estimate the effect of the intervention on the CLABSI rate. RESULTS During the baseline period, 5,118 CL days and 49 CLABSIs were recorded, for a rate of 9.6 CLABSIs per 1,000 central-line (CL) days. During the intervention, 15,659 CL days and 68 CLABSIs were recorded, for a rate of 4.1 CLABSIs per 1,000 CL days. The CLABSI rate was reduced by 57% (incidence density rate: 0.43; 95% confidence interval, 0.34-0.6; P<.001). CONCLUSIONS Implementing IMA through ISOS was associated with a significant reduction in the CLABSI rate in ICUs in Argentina. Infect Control Hosp Epidemiol 2018;39:445-451.

Human Papillomavirus Types 16 and 18 Early-expressed Proteins Differentially Modulate the Cellular Redox State and DNA Damage.

Oxidative stress has been proposed as a risk factor for cervical cancer development. However, few studies have evaluated the redox state associated with human papillomavirus (HPV) infection. The aim of this work was to determine the role of the early expressed viral proteins E1, E2, E6 and E7 from HPV types 16 and 18 in the modulation of the redox state in an integral form. Therefore, generation of reactive oxygen species (ROS), concentration of reduced glutathione (GSH), levels and activity of the antioxidant enzymes catalase and superoxide dismutase (SOD) and deoxyribonucleic acid (DNA) damage, were analysed in epithelial cells ectopically expressing the viral proteins. Our research shows that E6 oncoproteins decreased GSH and catalase protein levels, as well as its enzymatic activity, which was associated with an increase in ROS production and DNA damage. In contrast, E7 oncoproteins increased GSH, as well as catalase protein levels and its activity, which correlated with a decrease in ROS without affecting DNA integrity. The co-expression of both E6 and E7 oncoproteins neutralized the effects that were independently observed for each of the viral proteins. Additionally, the combined expression of E1 and E2 proteins increased ROS levels with the subsequent increase in the marker for DNA damage phospho-histone 2AX (γH2AX). A decrease in GSH, as well as SOD2 levels and activity were also detected in the presence of E1 and E2, even though catalase activity increased. This study demonstrates that HPV early expressed proteins differentially modulate cellular redox state and DNA damage.

Impact of the International Nosocomial Infection Control Consortium's multidimensional approach on rates of ventilator-associated pneumonia in 14 intensive care units in 11 hospitals of 5 cities within Argentina.

BACKGROUND: To analyze the impact of the International Nosocomial Infection Control Consortium (INICC) multidimensional approach (IMA) on ventilator-associated pneumonia (VAP) rates in 11 hospitals within 5 cities of Argentina from January 2014-April 2017. METHODS: A multicenter, prospective, before-after surveillance study was conducted through the use of International Nosocomial Infection Control Consortium Surveillance Online System. During baseline, we performed outcome surveillance of VAP applying the definitions of the Centers for Disease Control andPrevention's National Healthcare Safety Network. During intervention, we implemented the IMA, which included a bundle of infection prevention practice interventions, education, outcome surveillance, process surveillance, feedback on VAP rates and consequences, and performance feedback of process surveillance. Bivariate and multivariate regression analyses were performed using a logistic regression model to estimate the effect of the intervention. RESULTS: We recorded 3,940 patients admitted to 14 intensive care units. At baseline, there were 19.9 VAPs per 1,000 mechanical ventilator (MV)-days-with 2,920 MV-days and 58 VAPs, which was reduced during intervention to 9.4 VAPs per 1,000 MV-days-with 9,261 MV-days and 103 VAPs. This accounted for a 52% rate reduction (incidence density rate, 0.48; 95% confidence interval, 0.3-0.7; P .001). CONCLUSIONS: Implementing the IMA was associated with significant reductions in VAP rates in intensive care units within Argentina.

Oportunidades ganadas en vacunación de los adultos. Implementación de una estrategia combinada para superar barreras / Gained opportunities in adult vaccination. Performing a combined strategy to overcome barriers

El Programa Nacional de Inmunizaciones en Argentina es-tablece la administración universal y obligatoria de las vacunas doble adultos (dT) y hepatitis B (HB) y las vacunas antigripal y antineumocó-cica para poblaciones especiales y mayores de 65 años. Son gratuitas y, excepto las vacunas antigripal y antineumocócica en personas en-tre 2-64 años, no requieren prescripción para su administración. Sin embargo, las tasas de vacunación en los adultos son bajas. Mejorar las coberturas vacunales en adultos es un desafío. Realizamos un estu-dio prospectivo de corte transversal para evaluar la implementación de una estrategia de vacunación combinada para aumentar la vacunación de los adultos de una institución. Esta se basó en el requerimiento obli-gatorio de dT en las cirugías programadas junto con el consejo médico en el vacunatorio y el acceso inmediato a la vacunación. Como resulta-do de esta estrategia se administraron 2.946 dosis extra que represen-tan un aumento de 312 % sobre las dosis sin intervención. Esta estrate-gia simple podría ser replicada fácilmente en otros centros

The National Immunization Program in Argentina recom-mends tetanus and diphtheria vaccine [Td] and hepatitis B for all healthy adults and influenza and pneumococcal vaccines for special populations. Despite the fact that these vaccines are free and without requirement for prescription, rates of vaccination remain low in adults.Improving vaccina-tion coverage among adults remains a major challenge. We performed a prospective cross-sectional study to assess a combined vaccination strat-egy in order to enhance compliance in a single institution. It was based on institutional requirement of Td vaccine for all elective surgery plus med-ical counseling provided by a trained physician at the Vaccination Room and immediate access to vaccination. As a result of this strategy, 2946 extra doses of vaccines were given. These doses represent an increase of 312% from the doses estimated without our intervention. This simple strategy may be easily replicated in other centers